IASLC 2011

AMSTERDAM – Management of advanced non–small cell lung cancer now demands molecular profiling and personalized treatment. This new era has just begun, but it will quickly transform the field over the next 4 years, Dr. David R. Gandara said in a talk on the state of lung cancer medical oncology.

Increased molecular profiling – Dr. Gandara called for routine molecular profiling for every patient with advanced NSCLC – will mean a "culture change" for the field, and a sharp turn toward "ungrouping" the universe of NSCLC patients into individuals, he told attendees at the World Conference on Lung Cancer, which was sponsored by the International Association for the Study of Lung Cancer.

"We shouldn’t even talk about non–small cell lung cancer" as though it were a single entity, said Dr. Gandara, professor and director of the thoracic oncology program at the University of California, Davis, Cancer Center in Sacramento.

He also recommended new paradigms of drug development to reflect the complex, underlying biology and the inter- and intrapatient heterogeneity of lung cancer. "Transition from empiric to rationally selected and personalized therapy is challenging," Dr. Gandara conceded. But the transition is underway and accelerating.

Until about a year ago, the only lung cancer genes undergoing routine profiling at cancer centers were those for the epidermal growth factor receptor (EGFR) and, at fewer locations, for the oncogene KRAS. Dr. Bruce Johnson, a professor of medicine at Harvard Medical School and the Dana Farber Cancer Institute, both in Boston, takes credit for starting both; his EGFR program began 7 years ago and KRAS testing has been going for 5 years, he said.

Today, testing at several major U.S. cancer centers has added investigational tests for genes such as HER2, PIK3CA, ALK, MET, MEK, BRAF, AKTI, and NRAS. The Lung Cancer Mutation Consortium is in the midst of profiling 10 genes in 1,000 patients.

"Progress has been so dramatic. All but EGFR and KRAS came in the past year," said Marileila Varella Garcia, Ph.D., professor of medical oncology at the University of Colorado in Denver and a leader of the consortium. "At the University of Colorado, it took us 18 months to optimize the test [for 10 mutations], but now we have it and it can only improve. We test for 10 mutations for the same cost as testing for one."

At the Yale Cancer Center, the routine-profiling list stands at 13 genes, said Dr. Roy S. Herbst, chief of medical oncology at Yale in New Haven, Conn. "Right now, the only test that [insurers] pay for is the EGFR mutation test. Once the ALK story is more validated, they will probably pay to find ALK translocations, but with a chip, for the same money you can also test for other mutations for research," Dr. Herbst said.

"In the United States, testing for EGFR mutations is standard of care at most top cancer centers. EGFR is an actionable mutation, with patients considered for erlotinib treatment."

Dr. Varella Garcia, Dr. Johnson, and their collaborators from the consortium reported on the first 516 patients with advanced lung cancer who were tested with the 10-gene panel. The results showed that 280 of the tumors (54%) carried at least one mutation in at least one of the 10 genes that the consortium tested.

KRAS mutations were most prevalent, in 22% of the patients, followed by EGFR mutations in 17%, ALK rearrangement in 10%, MET amplifications in 4%, and a smaller number of genetic changes in each of the other six genes tested. Most mutations were mutually exclusive, with only 3% of tumors having mutations in two different genes, and no tumors with mutations in three or more genes.

"It was surprising that they found actionable mutations in more than half of the tumors they have tested so far. That is very promising," Dr. Gandara said.

Over the next 3-4 years, further studies will likely validate additional genes and mutations, perhaps encompassing about 90% of patients with advanced-stage lung cancer by 2015, Dr. Varella Garcia said in an interview. It’s also likely that a small percentage of these cancers won’t link with any single, identifiable gene mutation and will instead depend on changes in several pathways, something much harder to sort out.

The number of "actionable" gene mutations (mutations that, once found, can receive a targeted treatment) also remains limited but growing. Until recently, the list had a single gene, EGFR. Patients with EGFR mutations are candidates for treatment with erlotinib (Tarceva) or gefitinib (Iressa, which was not approved for routine U.S. use), both drugs from the tyrosine kinase inhibitor class.

A second, recent success story for targeted treatment involves the ALK fusion mutation, a genetic profile of tumors responsive to crizotinib. Results from phase I and II studies showed that crizotinib improved progression-free survival and overall survival in patients with tumors that had an ALK mutation; phase III studies are in progress.

"Patients with tumors that depend on these drivers have significantly better clinical outcomes when treated with specific inhibitors," Dr. Varella Garcia said.

This year’s meeting featured three main themes for patient management, but ultimately all three boil down to molecular biomarkers and molecularly directed treatment, Dr. Gandara said. One main theme – histologic profiles of advanced lung cancer – has been an important focus, but "histology is a transient selection method," he said. "At best, histology is a crude molecular selection device" superseded by molecular profiling itself.

Another important, recent focus has been maintenance therapy, but "the real questions are who gets further treatment after platinum-based induction, and when should they get it," questions best answerable by molecular profiling, he added.

"We have many ‘druggable’ molecular targets," Dr. Gandara noted.

"For almost every mutation [of the 10 genes that] the consortium is testing, we have phase I treatment trials underway," said Dr. Varella Garcia. Patients with tumors that carry KRAS and MEK mutations receive an investigational MEK inhibitor. Patients with tumors that contain HER2 mutations receive trastuzumab (Herceptin) as an investigational agent. Patients with MET mutations receive a MET monoclonal antibody.

Despite success so far, and pervasive optimism that current studies will validate new treatments, researchers cautioned that the management of advanced lung cancer also has some critical, unavoidable limitations.

"We will never cure advanced lung cancer; we can make it a chronic disease," Dr. Varella Garcia said. Effective treatment means that patients’ quality of life improves, and their disease comes under control for several years. But "it is almost universal that these patients with eventually progress again. We cannot cure advanced lung cancer. We can control it with new, targeted treatments that use oral drugs with low toxicity."

Dr. Gandara, Dr. Johnson, and Dr. Herbst disclosed relationships with numerous pharmaceutical and biotechnology companies. Among these, Dr. Johnson listed stock in Celgene and a patent for EGFR testing by Genzyme. Dr. Varella Garcia said that she has been a consultant to Abbott.

AMSTERDAM – Management of advanced non–small cell lung cancer now demands molecular profiling and personalized treatment. This new era has just begun, but it will quickly transform the field over the next 4 years, Dr. David R. Gandara said in a talk on the state of lung cancer medical oncology.

Increased molecular profiling – Dr. Gandara called for routine molecular profiling for every patient with advanced NSCLC – will mean a "culture change" for the field, and a sharp turn toward "ungrouping" the universe of NSCLC patients into individuals, he told attendees at the World Conference on Lung Cancer, which was sponsored by the International Association for the Study of Lung Cancer.

"We shouldn’t even talk about non–small cell lung cancer" as though it were a single entity, said Dr. Gandara, professor and director of the thoracic oncology program at the University of California, Davis, Cancer Center in Sacramento.

He also recommended new paradigms of drug development to reflect the complex, underlying biology and the inter- and intrapatient heterogeneity of lung cancer. "Transition from empiric to rationally selected and personalized therapy is challenging," Dr. Gandara conceded. But the transition is underway and accelerating.

Until about a year ago, the only lung cancer genes undergoing routine profiling at cancer centers were those for the epidermal growth factor receptor (EGFR) and, at fewer locations, for the oncogene KRAS. Dr. Bruce Johnson, a professor of medicine at Harvard Medical School and the Dana Farber Cancer Institute, both in Boston, takes credit for starting both; his EGFR program began 7 years ago and KRAS testing has been going for 5 years, he said.

Today, testing at several major U.S. cancer centers has added investigational tests for genes such as HER2, PIK3CA, ALK, MET, MEK, BRAF, AKTI, and NRAS. The Lung Cancer Mutation Consortium is in the midst of profiling 10 genes in 1,000 patients.

"Progress has been so dramatic. All but EGFR and KRAS came in the past year," said Marileila Varella Garcia, Ph.D., professor of medical oncology at the University of Colorado in Denver and a leader of the consortium. "At the University of Colorado, it took us 18 months to optimize the test [for 10 mutations], but now we have it and it can only improve. We test for 10 mutations for the same cost as testing for one."

At the Yale Cancer Center, the routine-profiling list stands at 13 genes, said Dr. Roy S. Herbst, chief of medical oncology at Yale in New Haven, Conn. "Right now, the only test that [insurers] pay for is the EGFR mutation test. Once the ALK story is more validated, they will probably pay to find ALK translocations, but with a chip, for the same money you can also test for other mutations for research," Dr. Herbst said.

"In the United States, testing for EGFR mutations is standard of care at most top cancer centers. EGFR is an actionable mutation, with patients considered for erlotinib treatment."

Dr. Varella Garcia, Dr. Johnson, and their collaborators from the consortium reported on the first 516 patients with advanced lung cancer who were tested with the 10-gene panel. The results showed that 280 of the tumors (54%) carried at least one mutation in at least one of the 10 genes that the consortium tested.

KRAS mutations were most prevalent, in 22% of the patients, followed by EGFR mutations in 17%, ALK rearrangement in 10%, MET amplifications in 4%, and a smaller number of genetic changes in each of the other six genes tested. Most mutations were mutually exclusive, with only 3% of tumors having mutations in two different genes, and no tumors with mutations in three or more genes.

"It was surprising that they found actionable mutations in more than half of the tumors they have tested so far. That is very promising," Dr. Gandara said.

Over the next 3-4 years, further studies will likely validate additional genes and mutations, perhaps encompassing about 90% of patients with advanced-stage lung cancer by 2015, Dr. Varella Garcia said in an interview. It’s also likely that a small percentage of these cancers won’t link with any single, identifiable gene mutation and will instead depend on changes in several pathways, something much harder to sort out.

The number of "actionable" gene mutations (mutations that, once found, can receive a targeted treatment) also remains limited but growing. Until recently, the list had a single gene, EGFR. Patients with EGFR mutations are candidates for treatment with erlotinib (Tarceva) or gefitinib (Iressa, which was not approved for routine U.S. use), both drugs from the tyrosine kinase inhibitor class.

A second, recent success story for targeted treatment involves the ALK fusion mutation, a genetic profile of tumors responsive to crizotinib. Results from phase I and II studies showed that crizotinib improved progression-free survival and overall survival in patients with tumors that had an ALK mutation; phase III studies are in progress.

"Patients with tumors that depend on these drivers have significantly better clinical outcomes when treated with specific inhibitors," Dr. Varella Garcia said.

This year’s meeting featured three main themes for patient management, but ultimately all three boil down to molecular biomarkers and molecularly directed treatment, Dr. Gandara said. One main theme – histologic profiles of advanced lung cancer – has been an important focus, but "histology is a transient selection method," he said. "At best, histology is a crude molecular selection device" superseded by molecular profiling itself.

Another important, recent focus has been maintenance therapy, but "the real questions are who gets further treatment after platinum-based induction, and when should they get it," questions best answerable by molecular profiling, he added.

"We have many ‘druggable’ molecular targets," Dr. Gandara noted.

"For almost every mutation [of the 10 genes that] the consortium is testing, we have phase I treatment trials underway," said Dr. Varella Garcia. Patients with tumors that carry KRAS and MEK mutations receive an investigational MEK inhibitor. Patients with tumors that contain HER2 mutations receive trastuzumab (Herceptin) as an investigational agent. Patients with MET mutations receive a MET monoclonal antibody.

Despite success so far, and pervasive optimism that current studies will validate new treatments, researchers cautioned that the management of advanced lung cancer also has some critical, unavoidable limitations.

"We will never cure advanced lung cancer; we can make it a chronic disease," Dr. Varella Garcia said. Effective treatment means that patients’ quality of life improves, and their disease comes under control for several years. But "it is almost universal that these patients with eventually progress again. We cannot cure advanced lung cancer. We can control it with new, targeted treatments that use oral drugs with low toxicity."

Dr. Gandara, Dr. Johnson, and Dr. Herbst disclosed relationships with numerous pharmaceutical and biotechnology companies. Among these, Dr. Johnson listed stock in Celgene and a patent for EGFR testing by Genzyme. Dr. Varella Garcia said that she has been a consultant to Abbott.

AMSTERDAM – Management of advanced non–small cell lung cancer now demands molecular profiling and personalized treatment. This new era has just begun, but it will quickly transform the field over the next 4 years, Dr. David R. Gandara said in a talk on the state of lung cancer medical oncology.

Increased molecular profiling – Dr. Gandara called for routine molecular profiling for every patient with advanced NSCLC – will mean a "culture change" for the field, and a sharp turn toward "ungrouping" the universe of NSCLC patients into individuals, he told attendees at the World Conference on Lung Cancer, which was sponsored by the International Association for the Study of Lung Cancer.

"We shouldn’t even talk about non–small cell lung cancer" as though it were a single entity, said Dr. Gandara, professor and director of the thoracic oncology program at the University of California, Davis, Cancer Center in Sacramento.

He also recommended new paradigms of drug development to reflect the complex, underlying biology and the inter- and intrapatient heterogeneity of lung cancer. "Transition from empiric to rationally selected and personalized therapy is challenging," Dr. Gandara conceded. But the transition is underway and accelerating.

Until about a year ago, the only lung cancer genes undergoing routine profiling at cancer centers were those for the epidermal growth factor receptor (EGFR) and, at fewer locations, for the oncogene KRAS. Dr. Bruce Johnson, a professor of medicine at Harvard Medical School and the Dana Farber Cancer Institute, both in Boston, takes credit for starting both; his EGFR program began 7 years ago and KRAS testing has been going for 5 years, he said.

Today, testing at several major U.S. cancer centers has added investigational tests for genes such as HER2, PIK3CA, ALK, MET, MEK, BRAF, AKTI, and NRAS. The Lung Cancer Mutation Consortium is in the midst of profiling 10 genes in 1,000 patients.

"Progress has been so dramatic. All but EGFR and KRAS came in the past year," said Marileila Varella Garcia, Ph.D., professor of medical oncology at the University of Colorado in Denver and a leader of the consortium. "At the University of Colorado, it took us 18 months to optimize the test [for 10 mutations], but now we have it and it can only improve. We test for 10 mutations for the same cost as testing for one."

At the Yale Cancer Center, the routine-profiling list stands at 13 genes, said Dr. Roy S. Herbst, chief of medical oncology at Yale in New Haven, Conn. "Right now, the only test that [insurers] pay for is the EGFR mutation test. Once the ALK story is more validated, they will probably pay to find ALK translocations, but with a chip, for the same money you can also test for other mutations for research," Dr. Herbst said.

"In the United States, testing for EGFR mutations is standard of care at most top cancer centers. EGFR is an actionable mutation, with patients considered for erlotinib treatment."

Dr. Varella Garcia, Dr. Johnson, and their collaborators from the consortium reported on the first 516 patients with advanced lung cancer who were tested with the 10-gene panel. The results showed that 280 of the tumors (54%) carried at least one mutation in at least one of the 10 genes that the consortium tested.

KRAS mutations were most prevalent, in 22% of the patients, followed by EGFR mutations in 17%, ALK rearrangement in 10%, MET amplifications in 4%, and a smaller number of genetic changes in each of the other six genes tested. Most mutations were mutually exclusive, with only 3% of tumors having mutations in two different genes, and no tumors with mutations in three or more genes.

"It was surprising that they found actionable mutations in more than half of the tumors they have tested so far. That is very promising," Dr. Gandara said.

Over the next 3-4 years, further studies will likely validate additional genes and mutations, perhaps encompassing about 90% of patients with advanced-stage lung cancer by 2015, Dr. Varella Garcia said in an interview. It’s also likely that a small percentage of these cancers won’t link with any single, identifiable gene mutation and will instead depend on changes in several pathways, something much harder to sort out.

The number of "actionable" gene mutations (mutations that, once found, can receive a targeted treatment) also remains limited but growing. Until recently, the list had a single gene, EGFR. Patients with EGFR mutations are candidates for treatment with erlotinib (Tarceva) or gefitinib (Iressa, which was not approved for routine U.S. use), both drugs from the tyrosine kinase inhibitor class.

A second, recent success story for targeted treatment involves the ALK fusion mutation, a genetic profile of tumors responsive to crizotinib. Results from phase I and II studies showed that crizotinib improved progression-free survival and overall survival in patients with tumors that had an ALK mutation; phase III studies are in progress.

"Patients with tumors that depend on these drivers have significantly better clinical outcomes when treated with specific inhibitors," Dr. Varella Garcia said.

This year’s meeting featured three main themes for patient management, but ultimately all three boil down to molecular biomarkers and molecularly directed treatment, Dr. Gandara said. One main theme – histologic profiles of advanced lung cancer – has been an important focus, but "histology is a transient selection method," he said. "At best, histology is a crude molecular selection device" superseded by molecular profiling itself.

Another important, recent focus has been maintenance therapy, but "the real questions are who gets further treatment after platinum-based induction, and when should they get it," questions best answerable by molecular profiling, he added.

"We have many ‘druggable’ molecular targets," Dr. Gandara noted.

"For almost every mutation [of the 10 genes that] the consortium is testing, we have phase I treatment trials underway," said Dr. Varella Garcia. Patients with tumors that carry KRAS and MEK mutations receive an investigational MEK inhibitor. Patients with tumors that contain HER2 mutations receive trastuzumab (Herceptin) as an investigational agent. Patients with MET mutations receive a MET monoclonal antibody.

Despite success so far, and pervasive optimism that current studies will validate new treatments, researchers cautioned that the management of advanced lung cancer also has some critical, unavoidable limitations.

"We will never cure advanced lung cancer; we can make it a chronic disease," Dr. Varella Garcia said. Effective treatment means that patients’ quality of life improves, and their disease comes under control for several years. But "it is almost universal that these patients with eventually progress again. We cannot cure advanced lung cancer. We can control it with new, targeted treatments that use oral drugs with low toxicity."

Dr. Gandara, Dr. Johnson, and Dr. Herbst disclosed relationships with numerous pharmaceutical and biotechnology companies. Among these, Dr. Johnson listed stock in Celgene and a patent for EGFR testing by Genzyme. Dr. Varella Garcia said that she has been a consultant to Abbott.

AMSTERDAM – An experimental combination of PET scanning and a positron-emitting form of erlotinib appeared to work as a noninvasive way of identifying patients with advanced non–small cell lung cancer tumors that have the right genotype to receive erlotinib therapy.

"[¹¹C]erlotinib PET shows promise as a noninvasive, in vivo means of selecting patients who may benefit from thymidine kinase inhibitor therapy," Dr. Idris Bahce said, reporting on a pilot study of 10 patients. Erlotinib (Tarceva) is from the thymidine kinase inhibitor drug class.

In his study, uptake of ¹¹C-labeled erlotinib was significantly linked to the patients’ having an activating mutation in their epidermal growth factor receptor (EGFR) gene, specifically an exon 19 deletion.

Patients positive for erlotinib uptake on the PET scan also showed a tendency for better clinical responses to a therapeutic erlotinib regimen, reported Dr. Bahce, a pulmonologist at VU University, Amsterdam, during the World Conference on Lung Cancer.

Until now, the only way to identify advanced non–small cell lung cancer (NSCLC) tumors that are candidates for treatment with a tyrosine kinase inhibitor has been to biopsy the tumor and run an in vitro genetic analysis on the tumor cells. That can be challenging in some patients, such as when the tumor is not easy to biopsy, a limited amount of tissue is available, or the tumor is genetically heterogeneous. To get a reliable result from biopsy and testing, at least 30% of the specimen must contain malignant cells, Dr. Bahce said at the conference, sponsored by the International Association for the Study of Lung Cancer.

"It is a very early study, but ... it’s important because personalized treatment [for cancer] has gone to the next level, where we use new agents and match them to the right patients by doing biopsies," commented Dr. Roy S. Herbst, chief of medical oncology at the Yale Cancer Center in New Haven. "The PET method also allows physicians to assess the volume of cancer carrying the EGFR mutation following treatment, a way to track treatment efficacy," said Dr. Herbst in an interview.

"Instead of getting tissue at one point in time, you can image more frequently. It’s a way to track the course of treatment noninvasively," and in real time, he said.

He also predicted that the [¹¹C]erlotinib PET test will become commercialized, although currently Dr. Bahce’s studies do not have any commercial funding.

"This is a proof of concept study," commented Dr. Luis Paz-Ares, chief of medical oncology at University Hospital Virgin del Rocio in Seville, Spain. "We need to define the positive predictive value and the negative predictive value" of the test, he added. The long-term future of a test like this may also be limited because future testing will probably need to look at multiple biomarkers, Dr. Paz-Ares said.

The study enrolled five patients with advanced NSCLC who had exon 19 deletion EGFR mutations, and five advanced NSCLC patients with wild-type EGFR genes. Each patient underwent a pair of [¹¹C]erlotinib PET scans, each preceded by a [¹⁵O]water PET scan to assess blood perfusion of the tumors. A 4-hour interval separated the two sets of scans.

The scan results showed that the volume of distribution of the tagged erlotinib in the patients with EGFR mutations ran about 50% higher than in the patients with wild-type tumors, a difference that was significant (P = .03).

Clinically, two of the five wild-type patients had nonetheless received erlotinib treatment prior to testing, and neither patient responded, with both showing progressive disease.

Three of the five patients with an EGFR mutation began receiving erlotinib treatment after testing and responded. In one of these patients, the tumor remained in check for 13 months. In a second patient, the tumor began to progress after 17 months of no progression on treatment. In the third patient, the tumor began to progress again after about 4 weeks of no progression on erlotinib treatment, Dr. Bahce said. A fourth patient went on erlotinib treatment before testing, and did not respond and continued to have progressive disease.

The two patient subgroups showed no difference in blood perfusion into the tumors, or in EGFR expression in cell membranes.

Dr. Bahce said he had no disclosures.

AMSTERDAM – An experimental combination of PET scanning and a positron-emitting form of erlotinib appeared to work as a noninvasive way of identifying patients with advanced non–small cell lung cancer tumors that have the right genotype to receive erlotinib therapy.

"[¹¹C]erlotinib PET shows promise as a noninvasive, in vivo means of selecting patients who may benefit from thymidine kinase inhibitor therapy," Dr. Idris Bahce said, reporting on a pilot study of 10 patients. Erlotinib (Tarceva) is from the thymidine kinase inhibitor drug class.

In his study, uptake of ¹¹C-labeled erlotinib was significantly linked to the patients’ having an activating mutation in their epidermal growth factor receptor (EGFR) gene, specifically an exon 19 deletion.

Patients positive for erlotinib uptake on the PET scan also showed a tendency for better clinical responses to a therapeutic erlotinib regimen, reported Dr. Bahce, a pulmonologist at VU University, Amsterdam, during the World Conference on Lung Cancer.

Until now, the only way to identify advanced non–small cell lung cancer (NSCLC) tumors that are candidates for treatment with a tyrosine kinase inhibitor has been to biopsy the tumor and run an in vitro genetic analysis on the tumor cells. That can be challenging in some patients, such as when the tumor is not easy to biopsy, a limited amount of tissue is available, or the tumor is genetically heterogeneous. To get a reliable result from biopsy and testing, at least 30% of the specimen must contain malignant cells, Dr. Bahce said at the conference, sponsored by the International Association for the Study of Lung Cancer.

"It is a very early study, but ... it’s important because personalized treatment [for cancer] has gone to the next level, where we use new agents and match them to the right patients by doing biopsies," commented Dr. Roy S. Herbst, chief of medical oncology at the Yale Cancer Center in New Haven. "The PET method also allows physicians to assess the volume of cancer carrying the EGFR mutation following treatment, a way to track treatment efficacy," said Dr. Herbst in an interview.

"Instead of getting tissue at one point in time, you can image more frequently. It’s a way to track the course of treatment noninvasively," and in real time, he said.

He also predicted that the [¹¹C]erlotinib PET test will become commercialized, although currently Dr. Bahce’s studies do not have any commercial funding.

"This is a proof of concept study," commented Dr. Luis Paz-Ares, chief of medical oncology at University Hospital Virgin del Rocio in Seville, Spain. "We need to define the positive predictive value and the negative predictive value" of the test, he added. The long-term future of a test like this may also be limited because future testing will probably need to look at multiple biomarkers, Dr. Paz-Ares said.

The study enrolled five patients with advanced NSCLC who had exon 19 deletion EGFR mutations, and five advanced NSCLC patients with wild-type EGFR genes. Each patient underwent a pair of [¹¹C]erlotinib PET scans, each preceded by a [¹⁵O]water PET scan to assess blood perfusion of the tumors. A 4-hour interval separated the two sets of scans.

The scan results showed that the volume of distribution of the tagged erlotinib in the patients with EGFR mutations ran about 50% higher than in the patients with wild-type tumors, a difference that was significant (P = .03).

Clinically, two of the five wild-type patients had nonetheless received erlotinib treatment prior to testing, and neither patient responded, with both showing progressive disease.

Three of the five patients with an EGFR mutation began receiving erlotinib treatment after testing and responded. In one of these patients, the tumor remained in check for 13 months. In a second patient, the tumor began to progress after 17 months of no progression on treatment. In the third patient, the tumor began to progress again after about 4 weeks of no progression on erlotinib treatment, Dr. Bahce said. A fourth patient went on erlotinib treatment before testing, and did not respond and continued to have progressive disease.

The two patient subgroups showed no difference in blood perfusion into the tumors, or in EGFR expression in cell membranes.

Dr. Bahce said he had no disclosures.

AMSTERDAM – An experimental combination of PET scanning and a positron-emitting form of erlotinib appeared to work as a noninvasive way of identifying patients with advanced non–small cell lung cancer tumors that have the right genotype to receive erlotinib therapy.

"[¹¹C]erlotinib PET shows promise as a noninvasive, in vivo means of selecting patients who may benefit from thymidine kinase inhibitor therapy," Dr. Idris Bahce said, reporting on a pilot study of 10 patients. Erlotinib (Tarceva) is from the thymidine kinase inhibitor drug class.

In his study, uptake of ¹¹C-labeled erlotinib was significantly linked to the patients’ having an activating mutation in their epidermal growth factor receptor (EGFR) gene, specifically an exon 19 deletion.

Patients positive for erlotinib uptake on the PET scan also showed a tendency for better clinical responses to a therapeutic erlotinib regimen, reported Dr. Bahce, a pulmonologist at VU University, Amsterdam, during the World Conference on Lung Cancer.

Until now, the only way to identify advanced non–small cell lung cancer (NSCLC) tumors that are candidates for treatment with a tyrosine kinase inhibitor has been to biopsy the tumor and run an in vitro genetic analysis on the tumor cells. That can be challenging in some patients, such as when the tumor is not easy to biopsy, a limited amount of tissue is available, or the tumor is genetically heterogeneous. To get a reliable result from biopsy and testing, at least 30% of the specimen must contain malignant cells, Dr. Bahce said at the conference, sponsored by the International Association for the Study of Lung Cancer.

"It is a very early study, but ... it’s important because personalized treatment [for cancer] has gone to the next level, where we use new agents and match them to the right patients by doing biopsies," commented Dr. Roy S. Herbst, chief of medical oncology at the Yale Cancer Center in New Haven. "The PET method also allows physicians to assess the volume of cancer carrying the EGFR mutation following treatment, a way to track treatment efficacy," said Dr. Herbst in an interview.

"Instead of getting tissue at one point in time, you can image more frequently. It’s a way to track the course of treatment noninvasively," and in real time, he said.

He also predicted that the [¹¹C]erlotinib PET test will become commercialized, although currently Dr. Bahce’s studies do not have any commercial funding.

"This is a proof of concept study," commented Dr. Luis Paz-Ares, chief of medical oncology at University Hospital Virgin del Rocio in Seville, Spain. "We need to define the positive predictive value and the negative predictive value" of the test, he added. The long-term future of a test like this may also be limited because future testing will probably need to look at multiple biomarkers, Dr. Paz-Ares said.

The study enrolled five patients with advanced NSCLC who had exon 19 deletion EGFR mutations, and five advanced NSCLC patients with wild-type EGFR genes. Each patient underwent a pair of [¹¹C]erlotinib PET scans, each preceded by a [¹⁵O]water PET scan to assess blood perfusion of the tumors. A 4-hour interval separated the two sets of scans.

The scan results showed that the volume of distribution of the tagged erlotinib in the patients with EGFR mutations ran about 50% higher than in the patients with wild-type tumors, a difference that was significant (P = .03).

Clinically, two of the five wild-type patients had nonetheless received erlotinib treatment prior to testing, and neither patient responded, with both showing progressive disease.

Three of the five patients with an EGFR mutation began receiving erlotinib treatment after testing and responded. In one of these patients, the tumor remained in check for 13 months. In a second patient, the tumor began to progress after 17 months of no progression on treatment. In the third patient, the tumor began to progress again after about 4 weeks of no progression on erlotinib treatment, Dr. Bahce said. A fourth patient went on erlotinib treatment before testing, and did not respond and continued to have progressive disease.

The two patient subgroups showed no difference in blood perfusion into the tumors, or in EGFR expression in cell membranes.

Dr. Bahce said he had no disclosures.

AMSTERDAM – Initial endosonographic assessment of mediastinal lymph node metastases in patients with resectable non–small cell lung cancer surpassed initial surgical staging not just in clinical outcomes but also with lower cost and better quality of life in a controlled, head-to-head comparison of the two staging approaches.

"Given that assessment of lymph nodes by the endoscopic approach was more effective [and] better tolerated by patients, and seems cheaper than the surgical approach, we recommend that endoscopic tests be used, reserving surgical tests as a backup if endoscopy does not show evidence of cancer," Dr. Robert C. Rintoul said in presenting the results of a follow-up analysis at the World Conference on Lung Cancer.

"We think this is the way forward, and that this will change practice globally," said Dr. Rintoul, lead physician for thoracic oncology at Papworth Hospital in Cambridge, England.

He reported new data and addressed implications of the totality of evidence now available from ASTER (Assessment of Surgical Staging vs. Endoscopic Ultrasound in Lung Cancer: A Randomized Clinical Trial) that was conducted in patients with potentially resectable NSCLC.

Although the overall weight of evidence now in from ASTER uniformly favors endosonography first, perhaps the most noteworthy findings from the study were those included in a report in JAMA last November: Endosonography first cut the rate of unnecessary thoracotomies to 7% compared with an 18% rate in patients assessed by mediastinoscopy first (P = .02). In addition, 45% of patients evaluated by endosonography first had positive lymph nodes and so avoided mediastinoscopy (JAMA 2010;304:2245-52).

"A few years ago, people said all these patients need mediastinoscopy. What we’ve learned [from ASTER] is that about half never need mediastinoscopy. That is practice changing," commented Dr. Richard Gralla, chief of hematology oncology at North Shore–Long Island Jewish Health System in New Hyde Park, N.Y. "As a rule, patients find EBUS [endobronchial ultrasound–guided transbronchial needle aspiration] and EUS [transesophageal ultrasound-guided fine-needle aspiration] much simpler procedures," compared with mediastinoscopy, he noted at the meeting, which was sponsored by the International Association for the Study of Lung Cancer.

The ASTER results that were published last year proved so compelling that many surgeons and thoracic oncologists have already switched to endosonography first, noted Dr. Jouke T. Annema, a thoracic surgeon at Leiden (the Netherlands) University and lead ASTER investigator.

"EBUS is the new standard," he said in an interview, noting that earlier this year the Dutch agency responsible for setting medical policy adopted endosonography as the preferred initial method for lymph node assessment in patients with resectable NSCLC. The National Institute for Health and Clinical Excellence (NICE), which sets U.K. health policies, did not name endosonography as the preferred initial staging method for lung cancer in its revised guidelines last April because the cost-effectiveness findings reported at the meeting had not yet been published, Dr. Rintoul said.

ASTER randomized 118 patients to initial mediastinoscopy staging and 123 to initial endosonographic staging at four medical centers in the United Kingdom, the Netherlands, and Belgium. The initial results reported last November also showed that initial endosonography followed by surgical staging in patients who were initially found to be node negative produced 94% sensitivity for finding positive lymph nodes, which was significantly better than the 79% sensitivity rate using mediastinoscopy first (P = .02).

The additional analyses reported by Dr. Rintoul used patient quality of life assessment by the EQ-5D (EuroQol five-domain) instrument at baseline, immediately after staging, and again at 2 and 6 months after staging. Researchers ran EQ-5D assessments on 144 of the study’s 241 patients at baseline, and on 124 patients after 6 months. The results showed similar, average EQ-5D levels at baseline and after 2 and 6 months in the two arms of the trial; however, immediately after staging, the endosonography-first patients had a statistically significant edge in average quality of life of 0.117 EQ-5D units, compared with patients who were staged by mediastinoscopy first (P = .003).

Average medical costs rung up by patients over the 6 months of treatment after baseline were about £746 (about $1,200) less per patient using endosonography first, a difference that was not statistically significant but suggested that initial endosonographic staging produced better cost-effectiveness, Dr. Rintoul said. He also reported that initial endosonography led to an average gain per patient of 0.015 quality-adjusted life-years, an advantage over initial surgical staging that just missed statistical significance (P = .052).

ASTER received no commercial support, and Dr. Rintoul said that he had no disclosures. He said that Papworth Hospital has received unrestricted educational grants and equipment loans from Olympus. Dr. Gralla and Dr. Annema had no disclosures.

AMSTERDAM – Initial endosonographic assessment of mediastinal lymph node metastases in patients with resectable non–small cell lung cancer surpassed initial surgical staging not just in clinical outcomes but also with lower cost and better quality of life in a controlled, head-to-head comparison of the two staging approaches.

"Given that assessment of lymph nodes by the endoscopic approach was more effective [and] better tolerated by patients, and seems cheaper than the surgical approach, we recommend that endoscopic tests be used, reserving surgical tests as a backup if endoscopy does not show evidence of cancer," Dr. Robert C. Rintoul said in presenting the results of a follow-up analysis at the World Conference on Lung Cancer.

"We think this is the way forward, and that this will change practice globally," said Dr. Rintoul, lead physician for thoracic oncology at Papworth Hospital in Cambridge, England.

He reported new data and addressed implications of the totality of evidence now available from ASTER (Assessment of Surgical Staging vs. Endoscopic Ultrasound in Lung Cancer: A Randomized Clinical Trial) that was conducted in patients with potentially resectable NSCLC.

Although the overall weight of evidence now in from ASTER uniformly favors endosonography first, perhaps the most noteworthy findings from the study were those included in a report in JAMA last November: Endosonography first cut the rate of unnecessary thoracotomies to 7% compared with an 18% rate in patients assessed by mediastinoscopy first (P = .02). In addition, 45% of patients evaluated by endosonography first had positive lymph nodes and so avoided mediastinoscopy (JAMA 2010;304:2245-52).

"A few years ago, people said all these patients need mediastinoscopy. What we’ve learned [from ASTER] is that about half never need mediastinoscopy. That is practice changing," commented Dr. Richard Gralla, chief of hematology oncology at North Shore–Long Island Jewish Health System in New Hyde Park, N.Y. "As a rule, patients find EBUS [endobronchial ultrasound–guided transbronchial needle aspiration] and EUS [transesophageal ultrasound-guided fine-needle aspiration] much simpler procedures," compared with mediastinoscopy, he noted at the meeting, which was sponsored by the International Association for the Study of Lung Cancer.

The ASTER results that were published last year proved so compelling that many surgeons and thoracic oncologists have already switched to endosonography first, noted Dr. Jouke T. Annema, a thoracic surgeon at Leiden (the Netherlands) University and lead ASTER investigator.

"EBUS is the new standard," he said in an interview, noting that earlier this year the Dutch agency responsible for setting medical policy adopted endosonography as the preferred initial method for lymph node assessment in patients with resectable NSCLC. The National Institute for Health and Clinical Excellence (NICE), which sets U.K. health policies, did not name endosonography as the preferred initial staging method for lung cancer in its revised guidelines last April because the cost-effectiveness findings reported at the meeting had not yet been published, Dr. Rintoul said.

ASTER randomized 118 patients to initial mediastinoscopy staging and 123 to initial endosonographic staging at four medical centers in the United Kingdom, the Netherlands, and Belgium. The initial results reported last November also showed that initial endosonography followed by surgical staging in patients who were initially found to be node negative produced 94% sensitivity for finding positive lymph nodes, which was significantly better than the 79% sensitivity rate using mediastinoscopy first (P = .02).

The additional analyses reported by Dr. Rintoul used patient quality of life assessment by the EQ-5D (EuroQol five-domain) instrument at baseline, immediately after staging, and again at 2 and 6 months after staging. Researchers ran EQ-5D assessments on 144 of the study’s 241 patients at baseline, and on 124 patients after 6 months. The results showed similar, average EQ-5D levels at baseline and after 2 and 6 months in the two arms of the trial; however, immediately after staging, the endosonography-first patients had a statistically significant edge in average quality of life of 0.117 EQ-5D units, compared with patients who were staged by mediastinoscopy first (P = .003).

Average medical costs rung up by patients over the 6 months of treatment after baseline were about £746 (about $1,200) less per patient using endosonography first, a difference that was not statistically significant but suggested that initial endosonographic staging produced better cost-effectiveness, Dr. Rintoul said. He also reported that initial endosonography led to an average gain per patient of 0.015 quality-adjusted life-years, an advantage over initial surgical staging that just missed statistical significance (P = .052).

ASTER received no commercial support, and Dr. Rintoul said that he had no disclosures. He said that Papworth Hospital has received unrestricted educational grants and equipment loans from Olympus. Dr. Gralla and Dr. Annema had no disclosures.

AMSTERDAM – Initial endosonographic assessment of mediastinal lymph node metastases in patients with resectable non–small cell lung cancer surpassed initial surgical staging not just in clinical outcomes but also with lower cost and better quality of life in a controlled, head-to-head comparison of the two staging approaches.

"Given that assessment of lymph nodes by the endoscopic approach was more effective [and] better tolerated by patients, and seems cheaper than the surgical approach, we recommend that endoscopic tests be used, reserving surgical tests as a backup if endoscopy does not show evidence of cancer," Dr. Robert C. Rintoul said in presenting the results of a follow-up analysis at the World Conference on Lung Cancer.

"We think this is the way forward, and that this will change practice globally," said Dr. Rintoul, lead physician for thoracic oncology at Papworth Hospital in Cambridge, England.

He reported new data and addressed implications of the totality of evidence now available from ASTER (Assessment of Surgical Staging vs. Endoscopic Ultrasound in Lung Cancer: A Randomized Clinical Trial) that was conducted in patients with potentially resectable NSCLC.

Although the overall weight of evidence now in from ASTER uniformly favors endosonography first, perhaps the most noteworthy findings from the study were those included in a report in JAMA last November: Endosonography first cut the rate of unnecessary thoracotomies to 7% compared with an 18% rate in patients assessed by mediastinoscopy first (P = .02). In addition, 45% of patients evaluated by endosonography first had positive lymph nodes and so avoided mediastinoscopy (JAMA 2010;304:2245-52).

"A few years ago, people said all these patients need mediastinoscopy. What we’ve learned [from ASTER] is that about half never need mediastinoscopy. That is practice changing," commented Dr. Richard Gralla, chief of hematology oncology at North Shore–Long Island Jewish Health System in New Hyde Park, N.Y. "As a rule, patients find EBUS [endobronchial ultrasound–guided transbronchial needle aspiration] and EUS [transesophageal ultrasound-guided fine-needle aspiration] much simpler procedures," compared with mediastinoscopy, he noted at the meeting, which was sponsored by the International Association for the Study of Lung Cancer.

The ASTER results that were published last year proved so compelling that many surgeons and thoracic oncologists have already switched to endosonography first, noted Dr. Jouke T. Annema, a thoracic surgeon at Leiden (the Netherlands) University and lead ASTER investigator.

"EBUS is the new standard," he said in an interview, noting that earlier this year the Dutch agency responsible for setting medical policy adopted endosonography as the preferred initial method for lymph node assessment in patients with resectable NSCLC. The National Institute for Health and Clinical Excellence (NICE), which sets U.K. health policies, did not name endosonography as the preferred initial staging method for lung cancer in its revised guidelines last April because the cost-effectiveness findings reported at the meeting had not yet been published, Dr. Rintoul said.

ASTER randomized 118 patients to initial mediastinoscopy staging and 123 to initial endosonographic staging at four medical centers in the United Kingdom, the Netherlands, and Belgium. The initial results reported last November also showed that initial endosonography followed by surgical staging in patients who were initially found to be node negative produced 94% sensitivity for finding positive lymph nodes, which was significantly better than the 79% sensitivity rate using mediastinoscopy first (P = .02).

The additional analyses reported by Dr. Rintoul used patient quality of life assessment by the EQ-5D (EuroQol five-domain) instrument at baseline, immediately after staging, and again at 2 and 6 months after staging. Researchers ran EQ-5D assessments on 144 of the study’s 241 patients at baseline, and on 124 patients after 6 months. The results showed similar, average EQ-5D levels at baseline and after 2 and 6 months in the two arms of the trial; however, immediately after staging, the endosonography-first patients had a statistically significant edge in average quality of life of 0.117 EQ-5D units, compared with patients who were staged by mediastinoscopy first (P = .003).

Average medical costs rung up by patients over the 6 months of treatment after baseline were about £746 (about $1,200) less per patient using endosonography first, a difference that was not statistically significant but suggested that initial endosonographic staging produced better cost-effectiveness, Dr. Rintoul said. He also reported that initial endosonography led to an average gain per patient of 0.015 quality-adjusted life-years, an advantage over initial surgical staging that just missed statistical significance (P = .052).

ASTER received no commercial support, and Dr. Rintoul said that he had no disclosures. He said that Papworth Hospital has received unrestricted educational grants and equipment loans from Olympus. Dr. Gralla and Dr. Annema had no disclosures.

AMSTERDAM – Wide adoption of stereotactic ablative radiation as radiotherapy for elderly patients with stage 1 non–small cell lung cancer in the Netherlands produced a dramatic rise in overall survival during the 2000s.

Dutch national data showed that median overall survival in patients aged 75 year or older with stage I NSCLC that was treated with radiation therapy jumped from 17 months in 2001-2003 to 26 months in 2007-2009 (P = .001), an improvement largely attributable to substantially increased use of sterotactic ablative radiation therapy (SABR), Dr. Cornelis J.A. Haasbeek said at the World Conference on Lung Cancer, which was sponsored by the International Association for the Study of Lung Cancer.

Dutch radiation oncologists began using SABR in 2003, and by 2009 more than 75% of early-stage NSCLC patients who received radiation therapy had it in the form of SABR.

"Our study provides high-level evidence to support the efficacy of modern SABR," said Dr. Haasbeek, a radiation oncologist at Vrije Universiteit Medische Centrum, Amsterdam.

SABR cut the number of treatments needed, compared with conventional radiation therapy, by 5- to 10-fold while also boosting efficacy, and it offers a better option for patients who are too old and frail to undergo surgical resection of their cancer. SABR is also a reasonable option for selected operable patients, said Dr. Suresh Senan, professor and vice-chairman of radiation oncology at Vrije Universiteit Amsterdam and senior investigator of the new report.

"The emerging data say that SABR is an option in patients who do not want to accept the risks of surgery, or for patients told by their surgeons that they have a significantly increased surgical risk. SABR is curative treatment for a frail group, producing excellent local control with very low toxicity," Dr. Senan said in an interview. "Elderly patients who could undergo open surgery should also be informed about SABR as an alternative curative, outpatient modality."

The main drawback of SABR compared with surgery is less-extensive long-term experience. "We have no track record of more than 5 years in a substantial number of patients, so there may still be surprises on recurrences," he said.

"What is important is that patients make a [treatment] decision, and are not told that they are too old for treatment. Surgery has the advantages of allowing for accurate tissue diagnosis and intraoperative staging, and in patients with emphysema, removal of the affected lung can improve lung function," commented Dr. David A. Waller, a thoracic surgeon at Glenfield Hospital in Leicester, England. "The risk [from surgery] is the general anesthesia, especially in patients with existing cardiovascular morbidity. It’s the patients with comorbidities who might do best with radiation therapy."

Speaking as a discussant of the Dutch report, Dr. Hak Choy said that the new findings and prior results make SABR a clear choice for elderly, inoperable patients, but existing data did not yet adequately support substituting SABR for surgery in operable patients. The definitive role for SABR in operable patients will grow clearer with results from two randomized studies now underway that compare SABR and surgery in high-risk operable patients, said Dr. Choy, a professor of radiation oncology at the University of Texas Southwestern Medical Center in Dallas.

To assess the impact that SABR had on stage I NSCLC in elderly patients in the Netherlands during the 2000s, Dr. Senan, Dr. Haasbeek, and their associates analyzed data from the Netherlands Cancer Registry. The registry had 4,605 patients aged 75 or older with stage I NSCLC during 2001-2009. This included 1,678 patients who were treated with surgery (37%), 1, 570 treated with radiotherapy (34%), and 1,337 treated by neither method (29%). During the 9 years reviewed, the percentage of patients undergoing radiotherapy increased from 31% of patients in 2001-2003 to 38% in 2007-2009. This paralleled a drop in untreated patients from 32% to 25%. Surgery use stayed flat over the period.

Median overall survival for all patients rose from 16 months in 2001-2003 to 24 months in 2007-2009 (P = .001), a change linked to survival increases in both radiation-treated patients and those who got surgery. Patients with surgical resections had a median overall survival of 36 months in 2001-2003, and median survival not yet occurred in patients with surgery in 2007-2009.

The better median survival in the surgery patients in part depends on the superior physical status of patients eligible for surgery. Other factors that may have boosted postsurgical survival include improved perioperative care, reduced numbers of higher-risk patients treated with surgery as radiation use increased, improved surgical techniques such as video assistance, and a trend toward more surgery being done in specialized centers, Dr. Haasbeek said.

Patients who had neither surgery nor radiation therapy had a similar, poor median survival of about 7 months during both periods.

Dr. Senan said that he has received honoraria as a speaker for Varian Medical Systems, and that his department received research support from Varian. Dr. Haasbeek said he had no disclosures. Dr. Waller had no disclosures.

AMSTERDAM – Wide adoption of stereotactic ablative radiation as radiotherapy for elderly patients with stage 1 non–small cell lung cancer in the Netherlands produced a dramatic rise in overall survival during the 2000s.

Dutch national data showed that median overall survival in patients aged 75 year or older with stage I NSCLC that was treated with radiation therapy jumped from 17 months in 2001-2003 to 26 months in 2007-2009 (P = .001), an improvement largely attributable to substantially increased use of sterotactic ablative radiation therapy (SABR), Dr. Cornelis J.A. Haasbeek said at the World Conference on Lung Cancer, which was sponsored by the International Association for the Study of Lung Cancer.

Dutch radiation oncologists began using SABR in 2003, and by 2009 more than 75% of early-stage NSCLC patients who received radiation therapy had it in the form of SABR.

"Our study provides high-level evidence to support the efficacy of modern SABR," said Dr. Haasbeek, a radiation oncologist at Vrije Universiteit Medische Centrum, Amsterdam.

SABR cut the number of treatments needed, compared with conventional radiation therapy, by 5- to 10-fold while also boosting efficacy, and it offers a better option for patients who are too old and frail to undergo surgical resection of their cancer. SABR is also a reasonable option for selected operable patients, said Dr. Suresh Senan, professor and vice-chairman of radiation oncology at Vrije Universiteit Amsterdam and senior investigator of the new report.

"The emerging data say that SABR is an option in patients who do not want to accept the risks of surgery, or for patients told by their surgeons that they have a significantly increased surgical risk. SABR is curative treatment for a frail group, producing excellent local control with very low toxicity," Dr. Senan said in an interview. "Elderly patients who could undergo open surgery should also be informed about SABR as an alternative curative, outpatient modality."

The main drawback of SABR compared with surgery is less-extensive long-term experience. "We have no track record of more than 5 years in a substantial number of patients, so there may still be surprises on recurrences," he said.

"What is important is that patients make a [treatment] decision, and are not told that they are too old for treatment. Surgery has the advantages of allowing for accurate tissue diagnosis and intraoperative staging, and in patients with emphysema, removal of the affected lung can improve lung function," commented Dr. David A. Waller, a thoracic surgeon at Glenfield Hospital in Leicester, England. "The risk [from surgery] is the general anesthesia, especially in patients with existing cardiovascular morbidity. It’s the patients with comorbidities who might do best with radiation therapy."

Speaking as a discussant of the Dutch report, Dr. Hak Choy said that the new findings and prior results make SABR a clear choice for elderly, inoperable patients, but existing data did not yet adequately support substituting SABR for surgery in operable patients. The definitive role for SABR in operable patients will grow clearer with results from two randomized studies now underway that compare SABR and surgery in high-risk operable patients, said Dr. Choy, a professor of radiation oncology at the University of Texas Southwestern Medical Center in Dallas.

To assess the impact that SABR had on stage I NSCLC in elderly patients in the Netherlands during the 2000s, Dr. Senan, Dr. Haasbeek, and their associates analyzed data from the Netherlands Cancer Registry. The registry had 4,605 patients aged 75 or older with stage I NSCLC during 2001-2009. This included 1,678 patients who were treated with surgery (37%), 1, 570 treated with radiotherapy (34%), and 1,337 treated by neither method (29%). During the 9 years reviewed, the percentage of patients undergoing radiotherapy increased from 31% of patients in 2001-2003 to 38% in 2007-2009. This paralleled a drop in untreated patients from 32% to 25%. Surgery use stayed flat over the period.

Median overall survival for all patients rose from 16 months in 2001-2003 to 24 months in 2007-2009 (P = .001), a change linked to survival increases in both radiation-treated patients and those who got surgery. Patients with surgical resections had a median overall survival of 36 months in 2001-2003, and median survival not yet occurred in patients with surgery in 2007-2009.

The better median survival in the surgery patients in part depends on the superior physical status of patients eligible for surgery. Other factors that may have boosted postsurgical survival include improved perioperative care, reduced numbers of higher-risk patients treated with surgery as radiation use increased, improved surgical techniques such as video assistance, and a trend toward more surgery being done in specialized centers, Dr. Haasbeek said.

Patients who had neither surgery nor radiation therapy had a similar, poor median survival of about 7 months during both periods.

Dr. Senan said that he has received honoraria as a speaker for Varian Medical Systems, and that his department received research support from Varian. Dr. Haasbeek said he had no disclosures. Dr. Waller had no disclosures.

AMSTERDAM – Wide adoption of stereotactic ablative radiation as radiotherapy for elderly patients with stage 1 non–small cell lung cancer in the Netherlands produced a dramatic rise in overall survival during the 2000s.

Dutch national data showed that median overall survival in patients aged 75 year or older with stage I NSCLC that was treated with radiation therapy jumped from 17 months in 2001-2003 to 26 months in 2007-2009 (P = .001), an improvement largely attributable to substantially increased use of sterotactic ablative radiation therapy (SABR), Dr. Cornelis J.A. Haasbeek said at the World Conference on Lung Cancer, which was sponsored by the International Association for the Study of Lung Cancer.

Dutch radiation oncologists began using SABR in 2003, and by 2009 more than 75% of early-stage NSCLC patients who received radiation therapy had it in the form of SABR.

"Our study provides high-level evidence to support the efficacy of modern SABR," said Dr. Haasbeek, a radiation oncologist at Vrije Universiteit Medische Centrum, Amsterdam.

SABR cut the number of treatments needed, compared with conventional radiation therapy, by 5- to 10-fold while also boosting efficacy, and it offers a better option for patients who are too old and frail to undergo surgical resection of their cancer. SABR is also a reasonable option for selected operable patients, said Dr. Suresh Senan, professor and vice-chairman of radiation oncology at Vrije Universiteit Amsterdam and senior investigator of the new report.

"The emerging data say that SABR is an option in patients who do not want to accept the risks of surgery, or for patients told by their surgeons that they have a significantly increased surgical risk. SABR is curative treatment for a frail group, producing excellent local control with very low toxicity," Dr. Senan said in an interview. "Elderly patients who could undergo open surgery should also be informed about SABR as an alternative curative, outpatient modality."

The main drawback of SABR compared with surgery is less-extensive long-term experience. "We have no track record of more than 5 years in a substantial number of patients, so there may still be surprises on recurrences," he said.

"What is important is that patients make a [treatment] decision, and are not told that they are too old for treatment. Surgery has the advantages of allowing for accurate tissue diagnosis and intraoperative staging, and in patients with emphysema, removal of the affected lung can improve lung function," commented Dr. David A. Waller, a thoracic surgeon at Glenfield Hospital in Leicester, England. "The risk [from surgery] is the general anesthesia, especially in patients with existing cardiovascular morbidity. It’s the patients with comorbidities who might do best with radiation therapy."

Speaking as a discussant of the Dutch report, Dr. Hak Choy said that the new findings and prior results make SABR a clear choice for elderly, inoperable patients, but existing data did not yet adequately support substituting SABR for surgery in operable patients. The definitive role for SABR in operable patients will grow clearer with results from two randomized studies now underway that compare SABR and surgery in high-risk operable patients, said Dr. Choy, a professor of radiation oncology at the University of Texas Southwestern Medical Center in Dallas.

To assess the impact that SABR had on stage I NSCLC in elderly patients in the Netherlands during the 2000s, Dr. Senan, Dr. Haasbeek, and their associates analyzed data from the Netherlands Cancer Registry. The registry had 4,605 patients aged 75 or older with stage I NSCLC during 2001-2009. This included 1,678 patients who were treated with surgery (37%), 1, 570 treated with radiotherapy (34%), and 1,337 treated by neither method (29%). During the 9 years reviewed, the percentage of patients undergoing radiotherapy increased from 31% of patients in 2001-2003 to 38% in 2007-2009. This paralleled a drop in untreated patients from 32% to 25%. Surgery use stayed flat over the period.

Median overall survival for all patients rose from 16 months in 2001-2003 to 24 months in 2007-2009 (P = .001), a change linked to survival increases in both radiation-treated patients and those who got surgery. Patients with surgical resections had a median overall survival of 36 months in 2001-2003, and median survival not yet occurred in patients with surgery in 2007-2009.

The better median survival in the surgery patients in part depends on the superior physical status of patients eligible for surgery. Other factors that may have boosted postsurgical survival include improved perioperative care, reduced numbers of higher-risk patients treated with surgery as radiation use increased, improved surgical techniques such as video assistance, and a trend toward more surgery being done in specialized centers, Dr. Haasbeek said.

Patients who had neither surgery nor radiation therapy had a similar, poor median survival of about 7 months during both periods.

Dr. Senan said that he has received honoraria as a speaker for Varian Medical Systems, and that his department received research support from Varian. Dr. Haasbeek said he had no disclosures. Dr. Waller had no disclosures.

AMSTERDAM – Crizotinib treatment boosted overall survival of selected patients with advanced non–small cell lung cancer by about a year compared with patients on standard chemotherapy in a historical control analysis, adding to the growing body of evidence for the efficacy of this novel targeted therapy.

"Crizotinib may prolong overall survival and fundamentally alter the natural history" of NSCLC that features alterations in the anaplastic lymphoma kinase (ALK) gene, Dr. Alice T. Shaw said at the World Conference on Lung Cancer. Results from several recent studies indicated that about 7% of patients with advanced NSCLC have ALK-positive tumors in which the gene is rearranged.

Results from Dr. Shaw’s new analysis also indicated that the overall survival of patients with ALK-positive NSCLC closely tracked the survival rate of patients with normal ALK genes and advanced NSCLC, suggesting that the presence of ALK mutation does not change prognosis.

"ALK-positive patients do not intrinsically do better on their own, but you can make them live a lot longer if you give them this targeted therapy, crizotinib," said Dr. Shaw, an oncologist at Harvard Medical School and Massachusetts General Hospital, both in Boston.

In May, the Food and Drug Administration began a priority review of crizotinib, an ALK inhibitor, for an indication to treat patients with advanced, ALK-positive NSCLC.

"For regulatory approval, people look at overall survival, but you’ll never get [overall survival] from the large randomized studies because it would be unethical not to let patients [who were initially randomized to not receive crizotinib] cross over. That’s why this analysis is important, even with its flaws, because it shows – or at least strongly suggests – that this drug improves overall survival, that we are really making a difference for these patients," Dr. Shaw said in an interview. Prior reports from crizotinib studies in ALK-positive patients documented a response rate of 50%-60%, and a median progression-free survival of 10 months.

Dr. Shaw and her associates used data on patients who were treated with crizotinib from the first, phase I study of the drug, because those patients have had the longest follow-up on the drug, a median of 18 months for those who remained alive (N. Engl. J. Med. 2010;363:1693-703).

The phase I crizotinib study included 82 ALK-positive patients who received the drug. To better match these patients with a control group of ALK-positive patients who never got crizotinib, the researchers focused on the 56 patients who came from study centers in the United States and Australia, and specifically on the 30 patients within this subgroup who received crizotinib as their second or third chemotherapy agent.

They compared overall survival of these 30 patients with 21 ALK-positive patients from the United States or Australia who had been assessed for potential enrollment in the phase I study but never received crizotinib. In addition, during follow-up all of these control patients remained on second-line chemotherapy.

The new analysis showed that the 30 crizotinib-treated patients had an overall 1-year survival rate of 74%, and a 2-year rate of 54%, with median survival not yet reached during the median 18-month follow-up. The 21 matched control patients had a 1-year survival rate of 44% and a 2-year rate of 12%, and median survival duration of 6 months. Calculations showed a hazard ratio for overall survival of 0.36 for the patients who did not get crizotinib compared with those who did (P = .004).

"These results suggest that crizotinib may significantly improve survival outcomes in patients with advanced ALK-positive NSCLC," Dr. Shaw said.

To confirm that ALK positivity itself played no role in overall survival, Dr. Shaw and her associates compared overall survival in the 21 control patients who never received crizotinib vs. 48 patients who had advanced NSCLC without any ALK mutations, who never received crizotinib, and who had been treated with standard, second-line chemotherapy. In addition, all 48 control patients and all 21 ALK-positive patients had tumors with adenocarcinoma histology, and they all had a history of being never or light smokers. The two groups had virtually identical overall survival rates, Dr. Shaw reported at the meeting, which was sponsored by the International Association for the Study of Lung Cancer.

The crizotinib study that provided much of the data used in this analysis was funded by Pfizer, the company developing the drug. Dr. Shaw said that she has been a consultant to Pfizer, Ariad, Chugai, and Millennium. She has received research support from Novartis and AstraZeneca.

AMSTERDAM – Crizotinib treatment boosted overall survival of selected patients with advanced non–small cell lung cancer by about a year compared with patients on standard chemotherapy in a historical control analysis, adding to the growing body of evidence for the efficacy of this novel targeted therapy.

"Crizotinib may prolong overall survival and fundamentally alter the natural history" of NSCLC that features alterations in the anaplastic lymphoma kinase (ALK) gene, Dr. Alice T. Shaw said at the World Conference on Lung Cancer. Results from several recent studies indicated that about 7% of patients with advanced NSCLC have ALK-positive tumors in which the gene is rearranged.

Results from Dr. Shaw’s new analysis also indicated that the overall survival of patients with ALK-positive NSCLC closely tracked the survival rate of patients with normal ALK genes and advanced NSCLC, suggesting that the presence of ALK mutation does not change prognosis.

"ALK-positive patients do not intrinsically do better on their own, but you can make them live a lot longer if you give them this targeted therapy, crizotinib," said Dr. Shaw, an oncologist at Harvard Medical School and Massachusetts General Hospital, both in Boston.

In May, the Food and Drug Administration began a priority review of crizotinib, an ALK inhibitor, for an indication to treat patients with advanced, ALK-positive NSCLC.

"For regulatory approval, people look at overall survival, but you’ll never get [overall survival] from the large randomized studies because it would be unethical not to let patients [who were initially randomized to not receive crizotinib] cross over. That’s why this analysis is important, even with its flaws, because it shows – or at least strongly suggests – that this drug improves overall survival, that we are really making a difference for these patients," Dr. Shaw said in an interview. Prior reports from crizotinib studies in ALK-positive patients documented a response rate of 50%-60%, and a median progression-free survival of 10 months.

Dr. Shaw and her associates used data on patients who were treated with crizotinib from the first, phase I study of the drug, because those patients have had the longest follow-up on the drug, a median of 18 months for those who remained alive (N. Engl. J. Med. 2010;363:1693-703).

The phase I crizotinib study included 82 ALK-positive patients who received the drug. To better match these patients with a control group of ALK-positive patients who never got crizotinib, the researchers focused on the 56 patients who came from study centers in the United States and Australia, and specifically on the 30 patients within this subgroup who received crizotinib as their second or third chemotherapy agent.

They compared overall survival of these 30 patients with 21 ALK-positive patients from the United States or Australia who had been assessed for potential enrollment in the phase I study but never received crizotinib. In addition, during follow-up all of these control patients remained on second-line chemotherapy.

The new analysis showed that the 30 crizotinib-treated patients had an overall 1-year survival rate of 74%, and a 2-year rate of 54%, with median survival not yet reached during the median 18-month follow-up. The 21 matched control patients had a 1-year survival rate of 44% and a 2-year rate of 12%, and median survival duration of 6 months. Calculations showed a hazard ratio for overall survival of 0.36 for the patients who did not get crizotinib compared with those who did (P = .004).

"These results suggest that crizotinib may significantly improve survival outcomes in patients with advanced ALK-positive NSCLC," Dr. Shaw said.

To confirm that ALK positivity itself played no role in overall survival, Dr. Shaw and her associates compared overall survival in the 21 control patients who never received crizotinib vs. 48 patients who had advanced NSCLC without any ALK mutations, who never received crizotinib, and who had been treated with standard, second-line chemotherapy. In addition, all 48 control patients and all 21 ALK-positive patients had tumors with adenocarcinoma histology, and they all had a history of being never or light smokers. The two groups had virtually identical overall survival rates, Dr. Shaw reported at the meeting, which was sponsored by the International Association for the Study of Lung Cancer.

The crizotinib study that provided much of the data used in this analysis was funded by Pfizer, the company developing the drug. Dr. Shaw said that she has been a consultant to Pfizer, Ariad, Chugai, and Millennium. She has received research support from Novartis and AstraZeneca.

AMSTERDAM – Crizotinib treatment boosted overall survival of selected patients with advanced non–small cell lung cancer by about a year compared with patients on standard chemotherapy in a historical control analysis, adding to the growing body of evidence for the efficacy of this novel targeted therapy.

"Crizotinib may prolong overall survival and fundamentally alter the natural history" of NSCLC that features alterations in the anaplastic lymphoma kinase (ALK) gene, Dr. Alice T. Shaw said at the World Conference on Lung Cancer. Results from several recent studies indicated that about 7% of patients with advanced NSCLC have ALK-positive tumors in which the gene is rearranged.

Results from Dr. Shaw’s new analysis also indicated that the overall survival of patients with ALK-positive NSCLC closely tracked the survival rate of patients with normal ALK genes and advanced NSCLC, suggesting that the presence of ALK mutation does not change prognosis.

"ALK-positive patients do not intrinsically do better on their own, but you can make them live a lot longer if you give them this targeted therapy, crizotinib," said Dr. Shaw, an oncologist at Harvard Medical School and Massachusetts General Hospital, both in Boston.

In May, the Food and Drug Administration began a priority review of crizotinib, an ALK inhibitor, for an indication to treat patients with advanced, ALK-positive NSCLC.

"For regulatory approval, people look at overall survival, but you’ll never get [overall survival] from the large randomized studies because it would be unethical not to let patients [who were initially randomized to not receive crizotinib] cross over. That’s why this analysis is important, even with its flaws, because it shows – or at least strongly suggests – that this drug improves overall survival, that we are really making a difference for these patients," Dr. Shaw said in an interview. Prior reports from crizotinib studies in ALK-positive patients documented a response rate of 50%-60%, and a median progression-free survival of 10 months.

Dr. Shaw and her associates used data on patients who were treated with crizotinib from the first, phase I study of the drug, because those patients have had the longest follow-up on the drug, a median of 18 months for those who remained alive (N. Engl. J. Med. 2010;363:1693-703).

The phase I crizotinib study included 82 ALK-positive patients who received the drug. To better match these patients with a control group of ALK-positive patients who never got crizotinib, the researchers focused on the 56 patients who came from study centers in the United States and Australia, and specifically on the 30 patients within this subgroup who received crizotinib as their second or third chemotherapy agent.

They compared overall survival of these 30 patients with 21 ALK-positive patients from the United States or Australia who had been assessed for potential enrollment in the phase I study but never received crizotinib. In addition, during follow-up all of these control patients remained on second-line chemotherapy.

The new analysis showed that the 30 crizotinib-treated patients had an overall 1-year survival rate of 74%, and a 2-year rate of 54%, with median survival not yet reached during the median 18-month follow-up. The 21 matched control patients had a 1-year survival rate of 44% and a 2-year rate of 12%, and median survival duration of 6 months. Calculations showed a hazard ratio for overall survival of 0.36 for the patients who did not get crizotinib compared with those who did (P = .004).

"These results suggest that crizotinib may significantly improve survival outcomes in patients with advanced ALK-positive NSCLC," Dr. Shaw said.

To confirm that ALK positivity itself played no role in overall survival, Dr. Shaw and her associates compared overall survival in the 21 control patients who never received crizotinib vs. 48 patients who had advanced NSCLC without any ALK mutations, who never received crizotinib, and who had been treated with standard, second-line chemotherapy. In addition, all 48 control patients and all 21 ALK-positive patients had tumors with adenocarcinoma histology, and they all had a history of being never or light smokers. The two groups had virtually identical overall survival rates, Dr. Shaw reported at the meeting, which was sponsored by the International Association for the Study of Lung Cancer.

The crizotinib study that provided much of the data used in this analysis was funded by Pfizer, the company developing the drug. Dr. Shaw said that she has been a consultant to Pfizer, Ariad, Chugai, and Millennium. She has received research support from Novartis and AstraZeneca.

AMSTERDAM – The International Association for the Study of Lung Cancer has issued a call for physicians to discuss lung cancer screening with patients who match the high-risk smoking history of the people enrolled in the landmark National Lung Screening Trial.

The National Lung Screening Trial (NLST) showed that an annual, low-dose CT chest scan can lead to significant reductions in lung cancer deaths and overall mortality in patients aged 55-74 years who smoked for at least 30 pack-years and, if former smokers, quit within the prior 15 years (New Engl. J. Med. 2011 [doi: 364:10.1056/NEJMoa1102873).

Based on these unprecedented findings, the International Association for the Study of Lung Cancer (IASLC)’s position-writing committee issued a call for physicians to discuss the data and its implications with such patients.

"It is appropriate for heavy smokers ages 55 to 74 to discuss relevant lung cancer screening information with their physicians to assist them in deciding whether to undergo spiral CT screening," said the statement, issued as IASLC started its world conference

Although some committee members, including the chairman, urged caution when routinely discussing screening with the target population before the cost effectiveness of this approach is proven, two of the Americans on the 10-member position-statement writing committee endorsed immediately offering screening to fully informed people who match the study’s screening profile.

"For patients with metastatic lung cancer the cure rate is essentially zero. Finding lung cancer early is the best way to deal with this disease, and that’s why this is such an extraordinary result," said Dr. Roy S. Herbst, a member of the task force and chief of medical oncology at Yale University in New Haven, Conn.

"Even with all the cautions, I think that in the United States at least you’ll see screening, especially since the NLST was largely sponsored by the National Cancer Institute. Assuming that the CMS [Centers for Medicare and Medicaid Services] and insurers will pick this up, I think [screening] is something we’re going to see. I think there will be great pressure in the United States for this to be covered, at a cost of about $300-$400 per scan.

"At Yale, we’ll start screening people who meet the enrollment criteria for the trial, as will several other U.S. centers. We’ll offer screening with all the caveats," including informing patients about the risks they will face from screening, their need to stop smoking, their need for ongoing screening, and the need to have a multidisciplinary team in place at the screening site to deal with all the possible consequences of screening, Dr. Herbst said.

"We know there is effectiveness from screening, but is there cost effectiveness? Is there value?" asked Dr. Richard Gralla, another member of the statement-writing committee and chief of hematology-oncology at North Shore University Medical Center and Long Island Jewish Medical Center in New Hyde Park, N.Y.

"My prediction is that screening will not only be shown to be cost effective, but it will be very cost effective. It will also be very expensive" to run annual screens on the millions of middle-aged smokers who meet the trial’s screening profile, he added. The NLST report estimated that 7 million Americans match the age and smoking history of the people enrolled in the trial.

By thrusting medicine into a new era of routine lung cancer screening, these developments will trigger creation of a new system of quality oversight for lung cancer screening that will likely follow the model of breast cancer screening.

"There is a laundry list of requirements that will need to be established by the institutions that want to do CT screening," said Dr. Denise R. Aberle, professor of radiology at the University of California, Los Angeles, and a collaborator on the NLST. "That will likely evolve into a form of accreditation to better guarantee quality assurance, as with breast cancer screening." Dr. Aberle also noted that the NLST researchers collected cost-effectiveness data, and that they will soon release a report on their analysis of those data.

Routine lung cancer screening will also place new responsibilities on the thoracic surgeons who follow up on suspicious lung lesions found though screening, most of which will not be cancers.

"For surgeons it will be a very large challenge to offer correct treatment to patients with very small cancers," said Dr. Jesper Pedersen, a thoracic surgeon at Copenhagen University Hospital. "We’re planning on writing guidelines for surgeons, because they will be at risk by operating on so many patients without lung cancer." The NLST results showed that 96% of suspicious lesions identified by CT screening were not cancers.

"There is potential for physical and psychiatric harm from cancer screening, but the results from many studies of breast cancer screening have shown that the benefits of screening outweigh its harms," said IASLC president David R. Gandara, professor of medicine and director of the thoracic oncology program at the University of California, Davis, in Sacramento.

"We’re in the early days of screening for lung cancer, and we must do everything to make sure that screening is done appropriately and that follow-up is appropriate. But our message to patients about screening is positive. We can’t overemphasize that," Dr. Gandara said.

Dr. Herbst said that he has been a consultant to Genentech, Agennix, Allos Therapeutics, Boehringer Ingelheim, and OSI Pharmaceuticals. He has been on the advisory boards of Amgen, Biothera, Genetics Squared (now Everist Genomics), MedTrust, N-of-One, SunDev, Targeted Molecular Diagnostics, and DiaTech. He has received research grants from Genentech, Amgen, Bristol-Myers Squibb, AstraZeneca, Novartis, OSI, Oncothyreon, Geron, Sanofi-Aventis, Pfizer, and ImClone.

Dr. Gralla and Dr. Aberle had no relevant disclosures. Dr. Pedersen said that he has been on the speakers bureau for Eli Lilly and Roche and received grant support from AstraZeneca. Dr. Gandara said that he has been a consultant to Amgen, AstraZeneca, Biodesix, Bristol-Myers Squibb/ImClone, GlaxoSmithKline, Genentech, Merck, Novartis, Sanofi-Aventis, and Response Genetics; he has received research support from Abbott, Bristol-Myers Squibb/ImClone, Genentech, Lilly, Merck, Novartis, and Pfizer.

AMSTERDAM – The International Association for the Study of Lung Cancer has issued a call for physicians to discuss lung cancer screening with patients who match the high-risk smoking history of the people enrolled in the landmark National Lung Screening Trial.

The National Lung Screening Trial (NLST) showed that an annual, low-dose CT chest scan can lead to significant reductions in lung cancer deaths and overall mortality in patients aged 55-74 years who smoked for at least 30 pack-years and, if former smokers, quit within the prior 15 years (New Engl. J. Med. 2011 [doi: 364:10.1056/NEJMoa1102873).

Based on these unprecedented findings, the International Association for the Study of Lung Cancer (IASLC)’s position-writing committee issued a call for physicians to discuss the data and its implications with such patients.

"It is appropriate for heavy smokers ages 55 to 74 to discuss relevant lung cancer screening information with their physicians to assist them in deciding whether to undergo spiral CT screening," said the statement, issued as IASLC started its world conference

Although some committee members, including the chairman, urged caution when routinely discussing screening with the target population before the cost effectiveness of this approach is proven, two of the Americans on the 10-member position-statement writing committee endorsed immediately offering screening to fully informed people who match the study’s screening profile.

"For patients with metastatic lung cancer the cure rate is essentially zero. Finding lung cancer early is the best way to deal with this disease, and that’s why this is such an extraordinary result," said Dr. Roy S. Herbst, a member of the task force and chief of medical oncology at Yale University in New Haven, Conn.

"Even with all the cautions, I think that in the United States at least you’ll see screening, especially since the NLST was largely sponsored by the National Cancer Institute. Assuming that the CMS [Centers for Medicare and Medicaid Services] and insurers will pick this up, I think [screening] is something we’re going to see. I think there will be great pressure in the United States for this to be covered, at a cost of about $300-$400 per scan.

"At Yale, we’ll start screening people who meet the enrollment criteria for the trial, as will several other U.S. centers. We’ll offer screening with all the caveats," including informing patients about the risks they will face from screening, their need to stop smoking, their need for ongoing screening, and the need to have a multidisciplinary team in place at the screening site to deal with all the possible consequences of screening, Dr. Herbst said.

"We know there is effectiveness from screening, but is there cost effectiveness? Is there value?" asked Dr. Richard Gralla, another member of the statement-writing committee and chief of hematology-oncology at North Shore University Medical Center and Long Island Jewish Medical Center in New Hyde Park, N.Y.

"My prediction is that screening will not only be shown to be cost effective, but it will be very cost effective. It will also be very expensive" to run annual screens on the millions of middle-aged smokers who meet the trial’s screening profile, he added. The NLST report estimated that 7 million Americans match the age and smoking history of the people enrolled in the trial.

By thrusting medicine into a new era of routine lung cancer screening, these developments will trigger creation of a new system of quality oversight for lung cancer screening that will likely follow the model of breast cancer screening.

"There is a laundry list of requirements that will need to be established by the institutions that want to do CT screening," said Dr. Denise R. Aberle, professor of radiology at the University of California, Los Angeles, and a collaborator on the NLST. "That will likely evolve into a form of accreditation to better guarantee quality assurance, as with breast cancer screening." Dr. Aberle also noted that the NLST researchers collected cost-effectiveness data, and that they will soon release a report on their analysis of those data.

Routine lung cancer screening will also place new responsibilities on the thoracic surgeons who follow up on suspicious lung lesions found though screening, most of which will not be cancers.

"For surgeons it will be a very large challenge to offer correct treatment to patients with very small cancers," said Dr. Jesper Pedersen, a thoracic surgeon at Copenhagen University Hospital. "We’re planning on writing guidelines for surgeons, because they will be at risk by operating on so many patients without lung cancer." The NLST results showed that 96% of suspicious lesions identified by CT screening were not cancers.

"There is potential for physical and psychiatric harm from cancer screening, but the results from many studies of breast cancer screening have shown that the benefits of screening outweigh its harms," said IASLC president David R. Gandara, professor of medicine and director of the thoracic oncology program at the University of California, Davis, in Sacramento.

"We’re in the early days of screening for lung cancer, and we must do everything to make sure that screening is done appropriately and that follow-up is appropriate. But our message to patients about screening is positive. We can’t overemphasize that," Dr. Gandara said.

Dr. Herbst said that he has been a consultant to Genentech, Agennix, Allos Therapeutics, Boehringer Ingelheim, and OSI Pharmaceuticals. He has been on the advisory boards of Amgen, Biothera, Genetics Squared (now Everist Genomics), MedTrust, N-of-One, SunDev, Targeted Molecular Diagnostics, and DiaTech. He has received research grants from Genentech, Amgen, Bristol-Myers Squibb, AstraZeneca, Novartis, OSI, Oncothyreon, Geron, Sanofi-Aventis, Pfizer, and ImClone.

Dr. Gralla and Dr. Aberle had no relevant disclosures. Dr. Pedersen said that he has been on the speakers bureau for Eli Lilly and Roche and received grant support from AstraZeneca. Dr. Gandara said that he has been a consultant to Amgen, AstraZeneca, Biodesix, Bristol-Myers Squibb/ImClone, GlaxoSmithKline, Genentech, Merck, Novartis, Sanofi-Aventis, and Response Genetics; he has received research support from Abbott, Bristol-Myers Squibb/ImClone, Genentech, Lilly, Merck, Novartis, and Pfizer.

AMSTERDAM – The International Association for the Study of Lung Cancer has issued a call for physicians to discuss lung cancer screening with patients who match the high-risk smoking history of the people enrolled in the landmark National Lung Screening Trial.

The National Lung Screening Trial (NLST) showed that an annual, low-dose CT chest scan can lead to significant reductions in lung cancer deaths and overall mortality in patients aged 55-74 years who smoked for at least 30 pack-years and, if former smokers, quit within the prior 15 years (New Engl. J. Med. 2011 [doi: 364:10.1056/NEJMoa1102873).

Based on these unprecedented findings, the International Association for the Study of Lung Cancer (IASLC)’s position-writing committee issued a call for physicians to discuss the data and its implications with such patients.

"It is appropriate for heavy smokers ages 55 to 74 to discuss relevant lung cancer screening information with their physicians to assist them in deciding whether to undergo spiral CT screening," said the statement, issued as IASLC started its world conference

Although some committee members, including the chairman, urged caution when routinely discussing screening with the target population before the cost effectiveness of this approach is proven, two of the Americans on the 10-member position-statement writing committee endorsed immediately offering screening to fully informed people who match the study’s screening profile.

"For patients with metastatic lung cancer the cure rate is essentially zero. Finding lung cancer early is the best way to deal with this disease, and that’s why this is such an extraordinary result," said Dr. Roy S. Herbst, a member of the task force and chief of medical oncology at Yale University in New Haven, Conn.

"Even with all the cautions, I think that in the United States at least you’ll see screening, especially since the NLST was largely sponsored by the National Cancer Institute. Assuming that the CMS [Centers for Medicare and Medicaid Services] and insurers will pick this up, I think [screening] is something we’re going to see. I think there will be great pressure in the United States for this to be covered, at a cost of about $300-$400 per scan.

"At Yale, we’ll start screening people who meet the enrollment criteria for the trial, as will several other U.S. centers. We’ll offer screening with all the caveats," including informing patients about the risks they will face from screening, their need to stop smoking, their need for ongoing screening, and the need to have a multidisciplinary team in place at the screening site to deal with all the possible consequences of screening, Dr. Herbst said.

"We know there is effectiveness from screening, but is there cost effectiveness? Is there value?" asked Dr. Richard Gralla, another member of the statement-writing committee and chief of hematology-oncology at North Shore University Medical Center and Long Island Jewish Medical Center in New Hyde Park, N.Y.

"My prediction is that screening will not only be shown to be cost effective, but it will be very cost effective. It will also be very expensive" to run annual screens on the millions of middle-aged smokers who meet the trial’s screening profile, he added. The NLST report estimated that 7 million Americans match the age and smoking history of the people enrolled in the trial.

By thrusting medicine into a new era of routine lung cancer screening, these developments will trigger creation of a new system of quality oversight for lung cancer screening that will likely follow the model of breast cancer screening.

"There is a laundry list of requirements that will need to be established by the institutions that want to do CT screening," said Dr. Denise R. Aberle, professor of radiology at the University of California, Los Angeles, and a collaborator on the NLST. "That will likely evolve into a form of accreditation to better guarantee quality assurance, as with breast cancer screening." Dr. Aberle also noted that the NLST researchers collected cost-effectiveness data, and that they will soon release a report on their analysis of those data.

Routine lung cancer screening will also place new responsibilities on the thoracic surgeons who follow up on suspicious lung lesions found though screening, most of which will not be cancers.

"For surgeons it will be a very large challenge to offer correct treatment to patients with very small cancers," said Dr. Jesper Pedersen, a thoracic surgeon at Copenhagen University Hospital. "We’re planning on writing guidelines for surgeons, because they will be at risk by operating on so many patients without lung cancer." The NLST results showed that 96% of suspicious lesions identified by CT screening were not cancers.

"There is potential for physical and psychiatric harm from cancer screening, but the results from many studies of breast cancer screening have shown that the benefits of screening outweigh its harms," said IASLC president David R. Gandara, professor of medicine and director of the thoracic oncology program at the University of California, Davis, in Sacramento.

"We’re in the early days of screening for lung cancer, and we must do everything to make sure that screening is done appropriately and that follow-up is appropriate. But our message to patients about screening is positive. We can’t overemphasize that," Dr. Gandara said.

Dr. Herbst said that he has been a consultant to Genentech, Agennix, Allos Therapeutics, Boehringer Ingelheim, and OSI Pharmaceuticals. He has been on the advisory boards of Amgen, Biothera, Genetics Squared (now Everist Genomics), MedTrust, N-of-One, SunDev, Targeted Molecular Diagnostics, and DiaTech. He has received research grants from Genentech, Amgen, Bristol-Myers Squibb, AstraZeneca, Novartis, OSI, Oncothyreon, Geron, Sanofi-Aventis, Pfizer, and ImClone.

Dr. Gralla and Dr. Aberle had no relevant disclosures. Dr. Pedersen said that he has been on the speakers bureau for Eli Lilly and Roche and received grant support from AstraZeneca. Dr. Gandara said that he has been a consultant to Amgen, AstraZeneca, Biodesix, Bristol-Myers Squibb/ImClone, GlaxoSmithKline, Genentech, Merck, Novartis, Sanofi-Aventis, and Response Genetics; he has received research support from Abbott, Bristol-Myers Squibb/ImClone, Genentech, Lilly, Merck, Novartis, and Pfizer.

AMSTERDAM – The International Association for the Study of Lung Cancer has issued a call for physicians to discuss lung cancer screening with patients who match the high-risk smoking history of the people enrolled in the landmark National Lung Screening Trial.

The National Lung Screening Trial (NLST) showed that an annual, low-dose CT chest scan can lead to significant reductions in lung cancer deaths and overall mortality in patients aged 55-74 years who smoked for at least 30 pack-years and, if former smokers, quit within the prior 15 years (New Engl. J. Med. 2011 [doi: 364:10.1056/NEJMoa1102873).

Based on these unprecedented findings, the International Association for the Study of Lung Cancer (IASLC)’s position-writing committee issued a call for physicians to discuss the data and its implications with such patients.

"It is appropriate for heavy smokers ages 55 to 74 to discuss relevant lung cancer screening information with their physicians to assist them in deciding whether to undergo spiral CT screening," said the statement, issued as IASLC started its world conference

Although some committee members, including the chairman, urged caution when routinely discussing screening with the target population before the cost effectiveness of this approach is proven, two of the Americans on the 10-member position-statement writing committee endorsed immediately offering screening to fully informed people who match the study’s screening profile.

"For patients with metastatic lung cancer the cure rate is essentially zero. Finding lung cancer early is the best way to deal with this disease, and that’s why this is such an extraordinary result," said Dr. Roy S. Herbst, a member of the task force and chief of medical oncology at Yale University in New Haven, Conn.

"Even with all the cautions, I think that in the United States at least you’ll see screening, especially since the NLST was largely sponsored by the National Cancer Institute. Assuming that the CMS [Centers for Medicare and Medicaid Services] and insurers will pick this up, I think [screening] is something we’re going to see. I think there will be great pressure in the United States for this to be covered, at a cost of about $300-$400 per scan.

"At Yale, we’ll start screening people who meet the enrollment criteria for the trial, as will several other U.S. centers. We’ll offer screening with all the caveats," including informing patients about the risks they will face from screening, their need to stop smoking, their need for ongoing screening, and the need to have a multidisciplinary team in place at the screening site to deal with all the possible consequences of screening, Dr. Herbst said.

"We know there is effectiveness from screening, but is there cost effectiveness? Is there value?" asked Dr. Richard Gralla, another member of the statement-writing committee and chief of hematology-oncology at North Shore University Medical Center and Long Island Jewish Medical Center in New Hyde Park, N.Y.

"My prediction is that screening will not only be shown to be cost effective, but it will be very cost effective. It will also be very expensive" to run annual screens on the millions of middle-aged smokers who meet the trial’s screening profile, he added. The NLST report estimated that 7 million Americans match the age and smoking history of the people enrolled in the trial.

By thrusting medicine into a new era of routine lung cancer screening, these developments will trigger creation of a new system of quality oversight for lung cancer screening that will likely follow the model of breast cancer screening.

"There is a laundry list of requirements that will need to be established by the institutions that want to do CT screening," said Dr. Denise R. Aberle, professor of radiology at the University of California, Los Angeles, and a collaborator on the NLST. "That will likely evolve into a form of accreditation to better guarantee quality assurance, as with breast cancer screening." Dr. Aberle also noted that the NLST researchers collected cost-effectiveness data, and that they will soon release a report on their analysis of those data.

Routine lung cancer screening will also place new responsibilities on the thoracic surgeons who follow up on suspicious lung lesions found though screening, most of which will not be cancers.

"For surgeons it will be a very large challenge to offer correct treatment to patients with very small cancers," said Dr. Jesper Pedersen, a thoracic surgeon at Copenhagen University Hospital. "We’re planning on writing guidelines for surgeons, because they will be at risk by operating on so many patients without lung cancer." The NLST results showed that 96% of suspicious lesions identified by CT screening were not cancers.

"There is potential for physical and psychiatric harm from cancer screening, but the results from many studies of breast cancer screening have shown that the benefits of screening outweigh its harms," said IASLC president David R. Gandara, professor of medicine and director of the thoracic oncology program at the University of California, Davis, in Sacramento.

"We’re in the early days of screening for lung cancer, and we must do everything to make sure that screening is done appropriately and that follow-up is appropriate. But our message to patients about screening is positive. We can’t overemphasize that," Dr. Gandara said.

Dr. Herbst said that he has been a consultant to Genentech, Agennix, Allos Therapeutics, Boehringer Ingelheim, and OSI Pharmaceuticals. He has been on the advisory boards of Amgen, Biothera, Genetics Squared (now Everist Genomics), MedTrust, N-of-One, SunDev, Targeted Molecular Diagnostics, and DiaTech. He has received research grants from Genentech, Amgen, Bristol-Myers Squibb, AstraZeneca, Novartis, OSI, Oncothyreon, Geron, Sanofi-Aventis, Pfizer, and ImClone.

Dr. Gralla and Dr. Aberle had no relevant disclosures. Dr. Pedersen said that he has been on the speakers bureau for Eli Lilly and Roche and received grant support from AstraZeneca. Dr. Gandara said that he has been a consultant to Amgen, AstraZeneca, Biodesix, Bristol-Myers Squibb/ImClone, GlaxoSmithKline, Genentech, Merck, Novartis, Sanofi-Aventis, and Response Genetics; he has received research support from Abbott, Bristol-Myers Squibb/ImClone, Genentech, Lilly, Merck, Novartis, and Pfizer.

AMSTERDAM – The International Association for the Study of Lung Cancer has issued a call for physicians to discuss lung cancer screening with patients who match the high-risk smoking history of the people enrolled in the landmark National Lung Screening Trial.

The National Lung Screening Trial (NLST) showed that an annual, low-dose CT chest scan can lead to significant reductions in lung cancer deaths and overall mortality in patients aged 55-74 years who smoked for at least 30 pack-years and, if former smokers, quit within the prior 15 years (New Engl. J. Med. 2011 [doi: 364:10.1056/NEJMoa1102873).

Based on these unprecedented findings, the International Association for the Study of Lung Cancer (IASLC)’s position-writing committee issued a call for physicians to discuss the data and its implications with such patients.

"It is appropriate for heavy smokers ages 55 to 74 to discuss relevant lung cancer screening information with their physicians to assist them in deciding whether to undergo spiral CT screening," said the statement, issued as IASLC started its world conference

Although some committee members, including the chairman, urged caution when routinely discussing screening with the target population before the cost effectiveness of this approach is proven, two of the Americans on the 10-member position-statement writing committee endorsed immediately offering screening to fully informed people who match the study’s screening profile.

"For patients with metastatic lung cancer the cure rate is essentially zero. Finding lung cancer early is the best way to deal with this disease, and that’s why this is such an extraordinary result," said Dr. Roy S. Herbst, a member of the task force and chief of medical oncology at Yale University in New Haven, Conn.

"Even with all the cautions, I think that in the United States at least you’ll see screening, especially since the NLST was largely sponsored by the National Cancer Institute. Assuming that the CMS [Centers for Medicare and Medicaid Services] and insurers will pick this up, I think [screening] is something we’re going to see. I think there will be great pressure in the United States for this to be covered, at a cost of about $300-$400 per scan.

"At Yale, we’ll start screening people who meet the enrollment criteria for the trial, as will several other U.S. centers. We’ll offer screening with all the caveats," including informing patients about the risks they will face from screening, their need to stop smoking, their need for ongoing screening, and the need to have a multidisciplinary team in place at the screening site to deal with all the possible consequences of screening, Dr. Herbst said.

"We know there is effectiveness from screening, but is there cost effectiveness? Is there value?" asked Dr. Richard Gralla, another member of the statement-writing committee and chief of hematology-oncology at North Shore University Medical Center and Long Island Jewish Medical Center in New Hyde Park, N.Y.

"My prediction is that screening will not only be shown to be cost effective, but it will be very cost effective. It will also be very expensive" to run annual screens on the millions of middle-aged smokers who meet the trial’s screening profile, he added. The NLST report estimated that 7 million Americans match the age and smoking history of the people enrolled in the trial.

By thrusting medicine into a new era of routine lung cancer screening, these developments will trigger creation of a new system of quality oversight for lung cancer screening that will likely follow the model of breast cancer screening.

"There is a laundry list of requirements that will need to be established by the institutions that want to do CT screening," said Dr. Denise R. Aberle, professor of radiology at the University of California, Los Angeles, and a collaborator on the NLST. "That will likely evolve into a form of accreditation to better guarantee quality assurance, as with breast cancer screening." Dr. Aberle also noted that the NLST researchers collected cost-effectiveness data, and that they will soon release a report on their analysis of those data.

Routine lung cancer screening will also place new responsibilities on the thoracic surgeons who follow up on suspicious lung lesions found though screening, most of which will not be cancers.

"For surgeons it will be a very large challenge to offer correct treatment to patients with very small cancers," said Dr. Jesper Pedersen, a thoracic surgeon at Copenhagen University Hospital. "We’re planning on writing guidelines for surgeons, because they will be at risk by operating on so many patients without lung cancer." The NLST results showed that 96% of suspicious lesions identified by CT screening were not cancers.

"There is potential for physical and psychiatric harm from cancer screening, but the results from many studies of breast cancer screening have shown that the benefits of screening outweigh its harms," said IASLC president David R. Gandara, professor of medicine and director of the thoracic oncology program at the University of California, Davis, in Sacramento.

"We’re in the early days of screening for lung cancer, and we must do everything to make sure that screening is done appropriately and that follow-up is appropriate. But our message to patients about screening is positive. We can’t overemphasize that," Dr. Gandara said.

Dr. Herbst said that he has been a consultant to Genentech, Agennix, Allos Therapeutics, Boehringer Ingelheim, and OSI Pharmaceuticals. He has been on the advisory boards of Amgen, Biothera, Genetics Squared (now Everist Genomics), MedTrust, N-of-One, SunDev, Targeted Molecular Diagnostics, and DiaTech. He has received research grants from Genentech, Amgen, Bristol-Myers Squibb, AstraZeneca, Novartis, OSI, Oncothyreon, Geron, Sanofi-Aventis, Pfizer, and ImClone.

Dr. Gralla and Dr. Aberle had no relevant disclosures. Dr. Pedersen said that he has been on the speakers bureau for Eli Lilly and Roche and received grant support from AstraZeneca. Dr. Gandara said that he has been a consultant to Amgen, AstraZeneca, Biodesix, Bristol-Myers Squibb/ImClone, GlaxoSmithKline, Genentech, Merck, Novartis, Sanofi-Aventis, and Response Genetics; he has received research support from Abbott, Bristol-Myers Squibb/ImClone, Genentech, Lilly, Merck, Novartis, and Pfizer.

AMSTERDAM – The International Association for the Study of Lung Cancer has issued a call for physicians to discuss lung cancer screening with patients who match the high-risk smoking history of the people enrolled in the landmark National Lung Screening Trial.

The National Lung Screening Trial (NLST) showed that an annual, low-dose CT chest scan can lead to significant reductions in lung cancer deaths and overall mortality in patients aged 55-74 years who smoked for at least 30 pack-years and, if former smokers, quit within the prior 15 years (New Engl. J. Med. 2011 [doi: 364:10.1056/NEJMoa1102873).

Based on these unprecedented findings, the International Association for the Study of Lung Cancer (IASLC)’s position-writing committee issued a call for physicians to discuss the data and its implications with such patients.

"It is appropriate for heavy smokers ages 55 to 74 to discuss relevant lung cancer screening information with their physicians to assist them in deciding whether to undergo spiral CT screening," said the statement, issued as IASLC started its world conference

Although some committee members, including the chairman, urged caution when routinely discussing screening with the target population before the cost effectiveness of this approach is proven, two of the Americans on the 10-member position-statement writing committee endorsed immediately offering screening to fully informed people who match the study’s screening profile.

"For patients with metastatic lung cancer the cure rate is essentially zero. Finding lung cancer early is the best way to deal with this disease, and that’s why this is such an extraordinary result," said Dr. Roy S. Herbst, a member of the task force and chief of medical oncology at Yale University in New Haven, Conn.

"Even with all the cautions, I think that in the United States at least you’ll see screening, especially since the NLST was largely sponsored by the National Cancer Institute. Assuming that the CMS [Centers for Medicare and Medicaid Services] and insurers will pick this up, I think [screening] is something we’re going to see. I think there will be great pressure in the United States for this to be covered, at a cost of about $300-$400 per scan.

"At Yale, we’ll start screening people who meet the enrollment criteria for the trial, as will several other U.S. centers. We’ll offer screening with all the caveats," including informing patients about the risks they will face from screening, their need to stop smoking, their need for ongoing screening, and the need to have a multidisciplinary team in place at the screening site to deal with all the possible consequences of screening, Dr. Herbst said.

"We know there is effectiveness from screening, but is there cost effectiveness? Is there value?" asked Dr. Richard Gralla, another member of the statement-writing committee and chief of hematology-oncology at North Shore University Medical Center and Long Island Jewish Medical Center in New Hyde Park, N.Y.

"My prediction is that screening will not only be shown to be cost effective, but it will be very cost effective. It will also be very expensive" to run annual screens on the millions of middle-aged smokers who meet the trial’s screening profile, he added. The NLST report estimated that 7 million Americans match the age and smoking history of the people enrolled in the trial.

By thrusting medicine into a new era of routine lung cancer screening, these developments will trigger creation of a new system of quality oversight for lung cancer screening that will likely follow the model of breast cancer screening.

"There is a laundry list of requirements that will need to be established by the institutions that want to do CT screening," said Dr. Denise R. Aberle, professor of radiology at the University of California, Los Angeles, and a collaborator on the NLST. "That will likely evolve into a form of accreditation to better guarantee quality assurance, as with breast cancer screening." Dr. Aberle also noted that the NLST researchers collected cost-effectiveness data, and that they will soon release a report on their analysis of those data.

Routine lung cancer screening will also place new responsibilities on the thoracic surgeons who follow up on suspicious lung lesions found though screening, most of which will not be cancers.

"For surgeons it will be a very large challenge to offer correct treatment to patients with very small cancers," said Dr. Jesper Pedersen, a thoracic surgeon at Copenhagen University Hospital. "We’re planning on writing guidelines for surgeons, because they will be at risk by operating on so many patients without lung cancer." The NLST results showed that 96% of suspicious lesions identified by CT screening were not cancers.

"There is potential for physical and psychiatric harm from cancer screening, but the results from many studies of breast cancer screening have shown that the benefits of screening outweigh its harms," said IASLC president David R. Gandara, professor of medicine and director of the thoracic oncology program at the University of California, Davis, in Sacramento.

"We’re in the early days of screening for lung cancer, and we must do everything to make sure that screening is done appropriately and that follow-up is appropriate. But our message to patients about screening is positive. We can’t overemphasize that," Dr. Gandara said.

Dr. Herbst said that he has been a consultant to Genentech, Agennix, Allos Therapeutics, Boehringer Ingelheim, and OSI Pharmaceuticals. He has been on the advisory boards of Amgen, Biothera, Genetics Squared (now Everist Genomics), MedTrust, N-of-One, SunDev, Targeted Molecular Diagnostics, and DiaTech. He has received research grants from Genentech, Amgen, Bristol-Myers Squibb, AstraZeneca, Novartis, OSI, Oncothyreon, Geron, Sanofi-Aventis, Pfizer, and ImClone.

Dr. Gralla and Dr. Aberle had no relevant disclosures. Dr. Pedersen said that he has been on the speakers bureau for Eli Lilly and Roche and received grant support from AstraZeneca. Dr. Gandara said that he has been a consultant to Amgen, AstraZeneca, Biodesix, Bristol-Myers Squibb/ImClone, GlaxoSmithKline, Genentech, Merck, Novartis, Sanofi-Aventis, and Response Genetics; he has received research support from Abbott, Bristol-Myers Squibb/ImClone, Genentech, Lilly, Merck, Novartis, and Pfizer.

AMSTERDAM – A commercially available gene-expression test significantly improved discrimination between low- and high-risk stage I and IIa lung cancer patients in a pair of validation tests, leading investigators to propose routine use of the test to identify early-stage patients who should get adjuvant chemotherapy.

"The multigene assay can outperform conventional risk factors and staging, and may lead to personalized therapies for patients with early-stage nonsquamous non–small cell lung cancer," Dr. Johannes Kratz said at the World Conference on Lung Cancer.

Dr. Kratz conceded that no prospective, randomized study has yet tested whether identification of high-risk stage I patients singled out a subgroup that would definitely benefit from adjuvant chemotherapy. But the prognostic information that the genetic test already provides justifies its routine use in stage I and II patients, said Dr. Kratz, a surgeon who performed this study while at the University of California, San Francisco (UCSF), but who is now at Massachusetts General Hospital in Boston.

"I think [the test] is certainly ready for prognosis, to give patients information," he said in an interview. "We’ll start using it routinely for prognosis at UCSF. We believe the strength of the results show it’s ready for prime time. Whether it should also be used to guide treatment, especially for stage I patients, is up to each health care provider, but it opens an interesting possibility before anything is proven in a randomized, controlled trial. The hope is that by identifying high-risk patients, you’ll improve their survival by giving them adjuvant chemotherapy. And in some of the low-risk stage II patients, you can avoid some of the toxicities of adjuvant chemotherapy."

Although several different genetic tests for stage I lung cancer have been studied over the past decade, none have wound up as marketed tests. Dr. Kratz and his associates set out to develop a practical and commercially viable test. They worked in collaboration with Pinpoint Genomics, the company that has now begun marketing the test.

The test they developed uses polymerase chain reaction–based gene expression assays for 11 different genes, based on results from prior studies that identified genes critical to key causal pathways leading to lung cancer. "We took a truly blinded, one-shot approach" in putting together the genetic test panel, without any tinkering during the validation phase to boost the prognostic strength of the test, he explained at the conference sponsored by the International Association for the Study of Lung Cancer. They also focused on tests that use paraffin-embedded specimens.

"I don’t think a prospective validation study is needed" before routine prognostic use of the test begins, he said. The validation studies "were done retrospectively, but in a very controlled way that was equivalent to prospective validation. I think we have powerful evidence that these markers provide additional prognostic information. We’re not saying to abandon traditional staging, but this adds useful prognostic information."

The initial test development cohort consisted of 361 stage I, II, and III patients treated and followed at UCSF. Validation used two independent cohorts, 433 stage I patients treated by physicians from Kaiser Permanente of Northern California, and a second cohort of 1,006 patients with stage I, II, or II disease treated at hospitals affiliated with the China Clinical Trials Consortium. Median follow-up in the three cohorts ranged from just over 3 years to just short of 6 years. Five-year mortality was about 42% in each of the three cohorts. About 80% of the nonsquamous non–small cell lung cancer patients in the three cohorts had adenocarcinomas.

The genetic test used to discriminate among three risk levels in the UCSF cohort identified a low-risk group with a calculated 5-year survival of 78%, an intermediate group with a 5-year survival of 60%, and a high-risk group with a survival rate of 30%. Between-group differences were statistically significant (P = .00005). The U.S. and Chinese validation cohorts each led to identification of three very similar prognostic subgroups, "suggesting that the assay was based on principles of lung cancer biology that are fundamental to the disease and remain constant despite the diverse genetic backgrounds of the populations studied," Dr. Kratz said.

In a multivariate analysis that controlled for age, sex, tumor size, and smoking history, high-risk identification using the genetic test led to a near doubling of the mortality risk in the Kaiser cohort (hazard ratio = 1.93, P = .010) and a more than tripling of the mortality risk in the Chinese cohort, compared with the low-risk tertile (HR = 3.25, P less than .001).

On the basis of their findings, Dr. Kratz and his associates proposed a new variation on the conventional tumor size, lymph node status, metastases (TNM) staging system that they called TNMM; the second M stands for multigene assay.

Their revised system designates patients judged stage Ia or Ib by TNM who have a low-risk gene test result as a new class Ia. Patients who had been classified Ia or Ib by the old system who have intermediate- or high-risk gene test results form a new stage Ib, a stage that also includes old IIa patients by TNM who had a low-risk gene test outcome. Finally, the new stage IIa consists of patients scored as IIa by the TNM system who also score as intermediate or high risk on the genetic test.

To further assess the prognostic value of adding the gene test, the researchers ran receiver-operator curves for the standard and revised staging methods in each of the two validation cohorts, and found that adding the gene test led to statistically significant increases in the area under the curve for prognostic accuracy.

In commenting on the study, Dr. Giorgio V. Scagliotti, the designated discussant, said the prognostic factors in current use – tumor size, differentiation, vascular invasion, and surgical margins – are not enough. Additional prognostic factors are needed to identify the completely resected stage I patients who might benefit from adjuvant chemotherapy. "We also need to better identify the stage II patients who have a low risk of recurrence and will not benefit from adjuvant chemotherapy," he said.

Previously reported genetic tests for early-stage non–small cell lung cancer involved complicated microarray test methods and a need for fresh tissue. They lacked reproducibility and validation, and had other problems as well. "The new study avoided these pitfalls, but despite its advances, it remains a set of post hoc analyses that lack prospective, randomized testing. Additional study must prospectively establish the medical utility of the prognostic information before routine use begins. Do patients identified by the test as high risk get any benefit from systemic treatment? Is the genetic test significant in the context of tumor stage, patient age, and treatment with adjuvant chemotherapy? Adjuvant therapy has so far not been included in the analysis," said Dr. Scagliotti, professor of medicine at the University of Torino (Italy).

He said he has been a consultant to Eli Lilly, and has been on the speakers bureaus of AstraZeneca, Eli Lilly, and Roche. Dr. Kratz said that he has been a consultant to and has an equity interest in Pinpoint Genomics, the company that developed the genetic test used in the study.

AMSTERDAM – A commercially available gene-expression test significantly improved discrimination between low- and high-risk stage I and IIa lung cancer patients in a pair of validation tests, leading investigators to propose routine use of the test to identify early-stage patients who should get adjuvant chemotherapy.

"The multigene assay can outperform conventional risk factors and staging, and may lead to personalized therapies for patients with early-stage nonsquamous non–small cell lung cancer," Dr. Johannes Kratz said at the World Conference on Lung Cancer.

Dr. Kratz conceded that no prospective, randomized study has yet tested whether identification of high-risk stage I patients singled out a subgroup that would definitely benefit from adjuvant chemotherapy. But the prognostic information that the genetic test already provides justifies its routine use in stage I and II patients, said Dr. Kratz, a surgeon who performed this study while at the University of California, San Francisco (UCSF), but who is now at Massachusetts General Hospital in Boston.

"I think [the test] is certainly ready for prognosis, to give patients information," he said in an interview. "We’ll start using it routinely for prognosis at UCSF. We believe the strength of the results show it’s ready for prime time. Whether it should also be used to guide treatment, especially for stage I patients, is up to each health care provider, but it opens an interesting possibility before anything is proven in a randomized, controlled trial. The hope is that by identifying high-risk patients, you’ll improve their survival by giving them adjuvant chemotherapy. And in some of the low-risk stage II patients, you can avoid some of the toxicities of adjuvant chemotherapy."

Although several different genetic tests for stage I lung cancer have been studied over the past decade, none have wound up as marketed tests. Dr. Kratz and his associates set out to develop a practical and commercially viable test. They worked in collaboration with Pinpoint Genomics, the company that has now begun marketing the test.

The test they developed uses polymerase chain reaction–based gene expression assays for 11 different genes, based on results from prior studies that identified genes critical to key causal pathways leading to lung cancer. "We took a truly blinded, one-shot approach" in putting together the genetic test panel, without any tinkering during the validation phase to boost the prognostic strength of the test, he explained at the conference sponsored by the International Association for the Study of Lung Cancer. They also focused on tests that use paraffin-embedded specimens.

"I don’t think a prospective validation study is needed" before routine prognostic use of the test begins, he said. The validation studies "were done retrospectively, but in a very controlled way that was equivalent to prospective validation. I think we have powerful evidence that these markers provide additional prognostic information. We’re not saying to abandon traditional staging, but this adds useful prognostic information."

The initial test development cohort consisted of 361 stage I, II, and III patients treated and followed at UCSF. Validation used two independent cohorts, 433 stage I patients treated by physicians from Kaiser Permanente of Northern California, and a second cohort of 1,006 patients with stage I, II, or II disease treated at hospitals affiliated with the China Clinical Trials Consortium. Median follow-up in the three cohorts ranged from just over 3 years to just short of 6 years. Five-year mortality was about 42% in each of the three cohorts. About 80% of the nonsquamous non–small cell lung cancer patients in the three cohorts had adenocarcinomas.

The genetic test used to discriminate among three risk levels in the UCSF cohort identified a low-risk group with a calculated 5-year survival of 78%, an intermediate group with a 5-year survival of 60%, and a high-risk group with a survival rate of 30%. Between-group differences were statistically significant (P = .00005). The U.S. and Chinese validation cohorts each led to identification of three very similar prognostic subgroups, "suggesting that the assay was based on principles of lung cancer biology that are fundamental to the disease and remain constant despite the diverse genetic backgrounds of the populations studied," Dr. Kratz said.

In a multivariate analysis that controlled for age, sex, tumor size, and smoking history, high-risk identification using the genetic test led to a near doubling of the mortality risk in the Kaiser cohort (hazard ratio = 1.93, P = .010) and a more than tripling of the mortality risk in the Chinese cohort, compared with the low-risk tertile (HR = 3.25, P less than .001).

On the basis of their findings, Dr. Kratz and his associates proposed a new variation on the conventional tumor size, lymph node status, metastases (TNM) staging system that they called TNMM; the second M stands for multigene assay.

Their revised system designates patients judged stage Ia or Ib by TNM who have a low-risk gene test result as a new class Ia. Patients who had been classified Ia or Ib by the old system who have intermediate- or high-risk gene test results form a new stage Ib, a stage that also includes old IIa patients by TNM who had a low-risk gene test outcome. Finally, the new stage IIa consists of patients scored as IIa by the TNM system who also score as intermediate or high risk on the genetic test.

To further assess the prognostic value of adding the gene test, the researchers ran receiver-operator curves for the standard and revised staging methods in each of the two validation cohorts, and found that adding the gene test led to statistically significant increases in the area under the curve for prognostic accuracy.

In commenting on the study, Dr. Giorgio V. Scagliotti, the designated discussant, said the prognostic factors in current use – tumor size, differentiation, vascular invasion, and surgical margins – are not enough. Additional prognostic factors are needed to identify the completely resected stage I patients who might benefit from adjuvant chemotherapy. "We also need to better identify the stage II patients who have a low risk of recurrence and will not benefit from adjuvant chemotherapy," he said.

Previously reported genetic tests for early-stage non–small cell lung cancer involved complicated microarray test methods and a need for fresh tissue. They lacked reproducibility and validation, and had other problems as well. "The new study avoided these pitfalls, but despite its advances, it remains a set of post hoc analyses that lack prospective, randomized testing. Additional study must prospectively establish the medical utility of the prognostic information before routine use begins. Do patients identified by the test as high risk get any benefit from systemic treatment? Is the genetic test significant in the context of tumor stage, patient age, and treatment with adjuvant chemotherapy? Adjuvant therapy has so far not been included in the analysis," said Dr. Scagliotti, professor of medicine at the University of Torino (Italy).

He said he has been a consultant to Eli Lilly, and has been on the speakers bureaus of AstraZeneca, Eli Lilly, and Roche. Dr. Kratz said that he has been a consultant to and has an equity interest in Pinpoint Genomics, the company that developed the genetic test used in the study.

AMSTERDAM – A commercially available gene-expression test significantly improved discrimination between low- and high-risk stage I and IIa lung cancer patients in a pair of validation tests, leading investigators to propose routine use of the test to identify early-stage patients who should get adjuvant chemotherapy.

"The multigene assay can outperform conventional risk factors and staging, and may lead to personalized therapies for patients with early-stage nonsquamous non–small cell lung cancer," Dr. Johannes Kratz said at the World Conference on Lung Cancer.

Dr. Kratz conceded that no prospective, randomized study has yet tested whether identification of high-risk stage I patients singled out a subgroup that would definitely benefit from adjuvant chemotherapy. But the prognostic information that the genetic test already provides justifies its routine use in stage I and II patients, said Dr. Kratz, a surgeon who performed this study while at the University of California, San Francisco (UCSF), but who is now at Massachusetts General Hospital in Boston.

"I think [the test] is certainly ready for prognosis, to give patients information," he said in an interview. "We’ll start using it routinely for prognosis at UCSF. We believe the strength of the results show it’s ready for prime time. Whether it should also be used to guide treatment, especially for stage I patients, is up to each health care provider, but it opens an interesting possibility before anything is proven in a randomized, controlled trial. The hope is that by identifying high-risk patients, you’ll improve their survival by giving them adjuvant chemotherapy. And in some of the low-risk stage II patients, you can avoid some of the toxicities of adjuvant chemotherapy."

Although several different genetic tests for stage I lung cancer have been studied over the past decade, none have wound up as marketed tests. Dr. Kratz and his associates set out to develop a practical and commercially viable test. They worked in collaboration with Pinpoint Genomics, the company that has now begun marketing the test.

The test they developed uses polymerase chain reaction–based gene expression assays for 11 different genes, based on results from prior studies that identified genes critical to key causal pathways leading to lung cancer. "We took a truly blinded, one-shot approach" in putting together the genetic test panel, without any tinkering during the validation phase to boost the prognostic strength of the test, he explained at the conference sponsored by the International Association for the Study of Lung Cancer. They also focused on tests that use paraffin-embedded specimens.

"I don’t think a prospective validation study is needed" before routine prognostic use of the test begins, he said. The validation studies "were done retrospectively, but in a very controlled way that was equivalent to prospective validation. I think we have powerful evidence that these markers provide additional prognostic information. We’re not saying to abandon traditional staging, but this adds useful prognostic information."

The initial test development cohort consisted of 361 stage I, II, and III patients treated and followed at UCSF. Validation used two independent cohorts, 433 stage I patients treated by physicians from Kaiser Permanente of Northern California, and a second cohort of 1,006 patients with stage I, II, or II disease treated at hospitals affiliated with the China Clinical Trials Consortium. Median follow-up in the three cohorts ranged from just over 3 years to just short of 6 years. Five-year mortality was about 42% in each of the three cohorts. About 80% of the nonsquamous non–small cell lung cancer patients in the three cohorts had adenocarcinomas.

The genetic test used to discriminate among three risk levels in the UCSF cohort identified a low-risk group with a calculated 5-year survival of 78%, an intermediate group with a 5-year survival of 60%, and a high-risk group with a survival rate of 30%. Between-group differences were statistically significant (P = .00005). The U.S. and Chinese validation cohorts each led to identification of three very similar prognostic subgroups, "suggesting that the assay was based on principles of lung cancer biology that are fundamental to the disease and remain constant despite the diverse genetic backgrounds of the populations studied," Dr. Kratz said.

In a multivariate analysis that controlled for age, sex, tumor size, and smoking history, high-risk identification using the genetic test led to a near doubling of the mortality risk in the Kaiser cohort (hazard ratio = 1.93, P = .010) and a more than tripling of the mortality risk in the Chinese cohort, compared with the low-risk tertile (HR = 3.25, P less than .001).

On the basis of their findings, Dr. Kratz and his associates proposed a new variation on the conventional tumor size, lymph node status, metastases (TNM) staging system that they called TNMM; the second M stands for multigene assay.

Their revised system designates patients judged stage Ia or Ib by TNM who have a low-risk gene test result as a new class Ia. Patients who had been classified Ia or Ib by the old system who have intermediate- or high-risk gene test results form a new stage Ib, a stage that also includes old IIa patients by TNM who had a low-risk gene test outcome. Finally, the new stage IIa consists of patients scored as IIa by the TNM system who also score as intermediate or high risk on the genetic test.

To further assess the prognostic value of adding the gene test, the researchers ran receiver-operator curves for the standard and revised staging methods in each of the two validation cohorts, and found that adding the gene test led to statistically significant increases in the area under the curve for prognostic accuracy.

In commenting on the study, Dr. Giorgio V. Scagliotti, the designated discussant, said the prognostic factors in current use – tumor size, differentiation, vascular invasion, and surgical margins – are not enough. Additional prognostic factors are needed to identify the completely resected stage I patients who might benefit from adjuvant chemotherapy. "We also need to better identify the stage II patients who have a low risk of recurrence and will not benefit from adjuvant chemotherapy," he said.

Previously reported genetic tests for early-stage non–small cell lung cancer involved complicated microarray test methods and a need for fresh tissue. They lacked reproducibility and validation, and had other problems as well. "The new study avoided these pitfalls, but despite its advances, it remains a set of post hoc analyses that lack prospective, randomized testing. Additional study must prospectively establish the medical utility of the prognostic information before routine use begins. Do patients identified by the test as high risk get any benefit from systemic treatment? Is the genetic test significant in the context of tumor stage, patient age, and treatment with adjuvant chemotherapy? Adjuvant therapy has so far not been included in the analysis," said Dr. Scagliotti, professor of medicine at the University of Torino (Italy).

He said he has been a consultant to Eli Lilly, and has been on the speakers bureaus of AstraZeneca, Eli Lilly, and Roche. Dr. Kratz said that he has been a consultant to and has an equity interest in Pinpoint Genomics, the company that developed the genetic test used in the study.