The symptoms of burnout include emotional exhaustion, depersonalization, and reduced personal efficacy, and burnout is a widespread problem among hospitalists; recent data suggest that half of physicians are experiencing at least one such symptom.

Health care leaders are increasingly concerned that these levels of physician burnout pose a threat to patient quality and safety. “As a result, some health care systems are shifting emphasis from the Triple Aim – population health, reduced costs, and patient satisfaction – to the Quadruple Aim, which incorporates health care provider wellness,” according to a recent abstract.

The authors began their own attempt to address the problem when Penn State Health in Dauphin County, Pa., built a stand-alone children’s hospital and experienced bed demands that exceeded bed availability, creating decreased organizational efficiency, high stress, and elevated physician burnout.

The LEAN principles offer a process-focused, customer-centered methodology that improves efficiency and quality. “We redesigned our service line using LEAN principles, such as ‘staff to demand’ and ‘standardize work,’ ” the authors wrote. “To ‘staff to demand,’ we hired three additional FTE [full-time equivalent employees]. This allowed creation of two rounding teams ([up] from one) and reduced our patient-to-attending ratio from 15:1 to 8:1. Workflow was resequenced and standardized, which enabled teams to see discharges at the start of rounds. We also provided in-house evening and overnight resident supervision. Our model permitted flexibility in physicians’ schedules, deemphasized reliance on RVUs, and heightened purpose and efficiency in work as determinants of providers’ value-adding capacity.”

As a result, both service line and hospital efficiency improved and faculty stress decreased in their hospital. “Mean stress scores decreased from 23 (preintervention) to 15 over the first 2 years, and has remained steady for a period of 3 years. Our divisional work-life balance measurement 2 years after the intervention was 85%, well above the reported average of 41%. We have maintained a low physician turnover rate at 3.5% over the last 3 years.”
 

Reference

Keefer L et al. LEAN in: Our secrets to decreasing provider stress, maximizing efficiency on a pediatric hospitalist service [abstract]. Accessed April 6, 2018.


 

The symptoms of burnout include emotional exhaustion, depersonalization, and reduced personal efficacy, and burnout is a widespread problem among hospitalists; recent data suggest that half of physicians are experiencing at least one such symptom.

Health care leaders are increasingly concerned that these levels of physician burnout pose a threat to patient quality and safety. “As a result, some health care systems are shifting emphasis from the Triple Aim – population health, reduced costs, and patient satisfaction – to the Quadruple Aim, which incorporates health care provider wellness,” according to a recent abstract.

The authors began their own attempt to address the problem when Penn State Health in Dauphin County, Pa., built a stand-alone children’s hospital and experienced bed demands that exceeded bed availability, creating decreased organizational efficiency, high stress, and elevated physician burnout.

The LEAN principles offer a process-focused, customer-centered methodology that improves efficiency and quality. “We redesigned our service line using LEAN principles, such as ‘staff to demand’ and ‘standardize work,’ ” the authors wrote. “To ‘staff to demand,’ we hired three additional FTE [full-time equivalent employees]. This allowed creation of two rounding teams ([up] from one) and reduced our patient-to-attending ratio from 15:1 to 8:1. Workflow was resequenced and standardized, which enabled teams to see discharges at the start of rounds. We also provided in-house evening and overnight resident supervision. Our model permitted flexibility in physicians’ schedules, deemphasized reliance on RVUs, and heightened purpose and efficiency in work as determinants of providers’ value-adding capacity.”

As a result, both service line and hospital efficiency improved and faculty stress decreased in their hospital. “Mean stress scores decreased from 23 (preintervention) to 15 over the first 2 years, and has remained steady for a period of 3 years. Our divisional work-life balance measurement 2 years after the intervention was 85%, well above the reported average of 41%. We have maintained a low physician turnover rate at 3.5% over the last 3 years.”
 

Reference

Keefer L et al. LEAN in: Our secrets to decreasing provider stress, maximizing efficiency on a pediatric hospitalist service [abstract]. Accessed April 6, 2018.


 

The symptoms of burnout include emotional exhaustion, depersonalization, and reduced personal efficacy, and burnout is a widespread problem among hospitalists; recent data suggest that half of physicians are experiencing at least one such symptom.

Health care leaders are increasingly concerned that these levels of physician burnout pose a threat to patient quality and safety. “As a result, some health care systems are shifting emphasis from the Triple Aim – population health, reduced costs, and patient satisfaction – to the Quadruple Aim, which incorporates health care provider wellness,” according to a recent abstract.

The authors began their own attempt to address the problem when Penn State Health in Dauphin County, Pa., built a stand-alone children’s hospital and experienced bed demands that exceeded bed availability, creating decreased organizational efficiency, high stress, and elevated physician burnout.

The LEAN principles offer a process-focused, customer-centered methodology that improves efficiency and quality. “We redesigned our service line using LEAN principles, such as ‘staff to demand’ and ‘standardize work,’ ” the authors wrote. “To ‘staff to demand,’ we hired three additional FTE [full-time equivalent employees]. This allowed creation of two rounding teams ([up] from one) and reduced our patient-to-attending ratio from 15:1 to 8:1. Workflow was resequenced and standardized, which enabled teams to see discharges at the start of rounds. We also provided in-house evening and overnight resident supervision. Our model permitted flexibility in physicians’ schedules, deemphasized reliance on RVUs, and heightened purpose and efficiency in work as determinants of providers’ value-adding capacity.”

As a result, both service line and hospital efficiency improved and faculty stress decreased in their hospital. “Mean stress scores decreased from 23 (preintervention) to 15 over the first 2 years, and has remained steady for a period of 3 years. Our divisional work-life balance measurement 2 years after the intervention was 85%, well above the reported average of 41%. We have maintained a low physician turnover rate at 3.5% over the last 3 years.”
 

Reference

Keefer L et al. LEAN in: Our secrets to decreasing provider stress, maximizing efficiency on a pediatric hospitalist service [abstract]. Accessed April 6, 2018.


 

The Internet has been a transformative means of transmitting information. Alas, the information is often not vetted, so the effects on science, truth, and health literacy have been mixed. Unfortunately, Facebook spawned a billion dollar industry that transmits gossip. Twitter distributes information based on celebrity rather than intelligence or expertise.

Listservs and Google groups have allowed small communities to form unrestricted by the physical locations of the members. A listserv for pediatric hospitalists, with 3,800 members, provides quick access to a vast body of knowledge, an extensive array of experience, and insightful clinical wisdom. Discussions on this listserv resource have inspired several of my columns, including this one. The professionalism of the listserv members ensures the accuracy of the messages. Because many of the members work nights, it is possible to post a question and receive five consults from peers, even at 1 a.m. When I first started office practice in rural areas, all I had available was my memory, Rudolph’s Pediatrics textbook, and The Harriet Lane Handbook.

Misinformation has led to vaccine hesitancy and the reemergence of diseases such as measles that had been essentially eliminated. Because people haven’t seen these diseases, they are prone to believing any critique about the risk of vaccines. More recently, parents have been refusing the vitamin K shot that is provided to all newborns to prevent hemorrhagic disease of the newborn, now called vitamin K deficiency bleeding. The incidence of this bleeding disorder is relatively rare. However, when it occurs, the results can be disastrous, with life-threatening gastrointestinal bleeds and disabling brain hemorrhages. As with vaccine hesitancy, the corruption of scientific knowledge has led to bad outcomes that once were nearly eliminated by modern health care.

Part of being a professional is communicating in a manner that helps parents understand small risks. I compare newborn vitamin K deficiency to the risk of driving the newborn around for the first 30 days of life without a car seat. The vast majority of people will not have an accident in that time and their babies will be fine. But emergency department doctors would see so many preventable cases of injury that they would strongly advocate for car seats. I also note that if the baby has a stroke due to vitamin K deficiency, we can’t catch it early and fix it.

eldemir/iStock/Getty Images

Physicians themselves have contributed to this diminished credibility of scientists. Recommendations have been published and later withdrawn in areas such as dietary cholesterol, salt, and saturated fats, estrogen replacement therapy, and screening for prostate and breast cancers. In modern America, even small inconsistencies and errors get blown up into conspiracy plots.

The era of expecting patients to blindly follow a doctor’s orders has long since passed. Parents will search the Internet for answers. The modern physician needs to guide them to good ones.

Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis. Email him at pdnews@mdedge.com.

References

1. Pediatrics. 2016 Aug. doi: 10.1542/peds.2016-2146.

2. “Doubt is Their Product,” by David Michaels, Oxford University Press, 2008, and “Merchants of Doubt,” by Naomi Oreskes and Erik M. Conway, Bloomsbury Press, 2011.

The Internet has been a transformative means of transmitting information. Alas, the information is often not vetted, so the effects on science, truth, and health literacy have been mixed. Unfortunately, Facebook spawned a billion dollar industry that transmits gossip. Twitter distributes information based on celebrity rather than intelligence or expertise.

Listservs and Google groups have allowed small communities to form unrestricted by the physical locations of the members. A listserv for pediatric hospitalists, with 3,800 members, provides quick access to a vast body of knowledge, an extensive array of experience, and insightful clinical wisdom. Discussions on this listserv resource have inspired several of my columns, including this one. The professionalism of the listserv members ensures the accuracy of the messages. Because many of the members work nights, it is possible to post a question and receive five consults from peers, even at 1 a.m. When I first started office practice in rural areas, all I had available was my memory, Rudolph’s Pediatrics textbook, and The Harriet Lane Handbook.

Misinformation has led to vaccine hesitancy and the reemergence of diseases such as measles that had been essentially eliminated. Because people haven’t seen these diseases, they are prone to believing any critique about the risk of vaccines. More recently, parents have been refusing the vitamin K shot that is provided to all newborns to prevent hemorrhagic disease of the newborn, now called vitamin K deficiency bleeding. The incidence of this bleeding disorder is relatively rare. However, when it occurs, the results can be disastrous, with life-threatening gastrointestinal bleeds and disabling brain hemorrhages. As with vaccine hesitancy, the corruption of scientific knowledge has led to bad outcomes that once were nearly eliminated by modern health care.

Part of being a professional is communicating in a manner that helps parents understand small risks. I compare newborn vitamin K deficiency to the risk of driving the newborn around for the first 30 days of life without a car seat. The vast majority of people will not have an accident in that time and their babies will be fine. But emergency department doctors would see so many preventable cases of injury that they would strongly advocate for car seats. I also note that if the baby has a stroke due to vitamin K deficiency, we can’t catch it early and fix it.

eldemir/iStock/Getty Images

Physicians themselves have contributed to this diminished credibility of scientists. Recommendations have been published and later withdrawn in areas such as dietary cholesterol, salt, and saturated fats, estrogen replacement therapy, and screening for prostate and breast cancers. In modern America, even small inconsistencies and errors get blown up into conspiracy plots.

The era of expecting patients to blindly follow a doctor’s orders has long since passed. Parents will search the Internet for answers. The modern physician needs to guide them to good ones.

Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis. Email him at pdnews@mdedge.com.

References

1. Pediatrics. 2016 Aug. doi: 10.1542/peds.2016-2146.

2. “Doubt is Their Product,” by David Michaels, Oxford University Press, 2008, and “Merchants of Doubt,” by Naomi Oreskes and Erik M. Conway, Bloomsbury Press, 2011.

The Internet has been a transformative means of transmitting information. Alas, the information is often not vetted, so the effects on science, truth, and health literacy have been mixed. Unfortunately, Facebook spawned a billion dollar industry that transmits gossip. Twitter distributes information based on celebrity rather than intelligence or expertise.

Listservs and Google groups have allowed small communities to form unrestricted by the physical locations of the members. A listserv for pediatric hospitalists, with 3,800 members, provides quick access to a vast body of knowledge, an extensive array of experience, and insightful clinical wisdom. Discussions on this listserv resource have inspired several of my columns, including this one. The professionalism of the listserv members ensures the accuracy of the messages. Because many of the members work nights, it is possible to post a question and receive five consults from peers, even at 1 a.m. When I first started office practice in rural areas, all I had available was my memory, Rudolph’s Pediatrics textbook, and The Harriet Lane Handbook.

Misinformation has led to vaccine hesitancy and the reemergence of diseases such as measles that had been essentially eliminated. Because people haven’t seen these diseases, they are prone to believing any critique about the risk of vaccines. More recently, parents have been refusing the vitamin K shot that is provided to all newborns to prevent hemorrhagic disease of the newborn, now called vitamin K deficiency bleeding. The incidence of this bleeding disorder is relatively rare. However, when it occurs, the results can be disastrous, with life-threatening gastrointestinal bleeds and disabling brain hemorrhages. As with vaccine hesitancy, the corruption of scientific knowledge has led to bad outcomes that once were nearly eliminated by modern health care.

Part of being a professional is communicating in a manner that helps parents understand small risks. I compare newborn vitamin K deficiency to the risk of driving the newborn around for the first 30 days of life without a car seat. The vast majority of people will not have an accident in that time and their babies will be fine. But emergency department doctors would see so many preventable cases of injury that they would strongly advocate for car seats. I also note that if the baby has a stroke due to vitamin K deficiency, we can’t catch it early and fix it.

eldemir/iStock/Getty Images

Physicians themselves have contributed to this diminished credibility of scientists. Recommendations have been published and later withdrawn in areas such as dietary cholesterol, salt, and saturated fats, estrogen replacement therapy, and screening for prostate and breast cancers. In modern America, even small inconsistencies and errors get blown up into conspiracy plots.

The era of expecting patients to blindly follow a doctor’s orders has long since passed. Parents will search the Internet for answers. The modern physician needs to guide them to good ones.

Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis. Email him at pdnews@mdedge.com.

References

1. Pediatrics. 2016 Aug. doi: 10.1542/peds.2016-2146.

2. “Doubt is Their Product,” by David Michaels, Oxford University Press, 2008, and “Merchants of Doubt,” by Naomi Oreskes and Erik M. Conway, Bloomsbury Press, 2011.

SAN DIEGO – Patients with newly diagnosed multiple myeloma who were ineligible for transplant had a 44% reduction in the risk of disease progression or death when they were treated with the anti-CD38 monoclonal antibody daratumumab (Darzalex) added to lenalidomide (Revlimid) and dexamethasone, compared with lenalidomide-dexamethasone alone, an interim analysis from the MAIA trial showed.

Among 737 patients in a phase 3 trial, median progression-free survival – the primary endpoint – had not been reached after a median follow-up of 28 months for patients randomized to daratumumab, lenalidomide, and dexamethasone (DRd), versus 31.9 months for patients randomized to lenalidomide and dexamethasone (Rd).

The 30-month PFS rate in the DRd arm was 71%, compared with 56% for the Rd arm. This difference translated into a hazard ratio (HR) for progression of 0.56 (P less than .0001), reported Thierry Facon, MD, of Hôpital Claude Huriez and the University of Lille, France.

“These results support DRd as a new standard of care for elderly patients with myeloma who are ineligible for transplant,” he said at the annual meeting of the American Society of Hematology.

Dr. Facon and his colleagues had previously shown in the FIRST trial that in newly diagnosed transplant-ineligible patients, continuous treatment with lenalidomide and low-dose dexamethasone was associated with significant overall survival and PFS benefits, compared with melphalan-prednisone-thalidomide.

In the POLLUX trial, investigators reported that in patients with multiple myeloma that was refractory or had relapsed after at least one prior line of therapy, the DRd combination was associated with a 63% reduction in the risk for disease progression or death, compared with Rd alone.
 

MAIA details

The MAIA trial is a pivotal, phase 3 study pitting DRd against Rd in transplant-ineligible patients with newly diagnosed multiple myeloma.

Patients with untreated disease who had Eastern Cooperative Oncology Group (ECOG) status of 0-2 and creatinine clearance rates of at least 30 mL/min were enrolled. Patients were randomly assigned to either DRd, with intravenous daratumumab 16 mg/kg weekly for cycles 1 and 2, every other week for cycles 3 through 6, and every 4 weeks from cycle 7 until disease progression, plus lenalidomide 25 mg orally per day on days 1-21 until disease progression, and dexamethasone 40 mg orally or intravenously weekly until disease progression; or to the same regimen without daratumumab.

The median patient age was 73 years and 99% of all patients were aged 65 years or older. Demographic and clinical characteristics were well balanced between the treatment arms.

The primary endpoint of progression-free survival was superior with DRd.

DRd also was associated with a significantly higher overall response rate (93% vs. 81%), complete response rate (48% vs. 25%), very good partial response or better rate (79% vs. 53%), and minimal residual disease (MRD) negativity rate (24% vs. 7%; P less than .0001 for all comparisons).

The DRd combination was associated with infusion-related reactions in 41% of patients, but only 3% were grade 3 or 4 in severity.

Hematologic treatment-emergent adverse events (TEAE) grade 3 or greater that were more common with DRd included neutropenia (50% vs. 35%) and lymphopenia (15% vs. 11%). Conversely, thrombocytopenia (7% vs. 9%, grade 3 or 4) and anemia (12% vs. 20%) were more frequent with Rd.

Nonhematologic TEAEs that were more frequent with DRd included diarrhea, constipation, fatigue, peripheral edema, and pneumonia. Rates of asthenia, back pain, nausea, and deep vein thrombosis/pulmonary embolism were similar between the study arms.

Janssen funded the study. Dr. Facon reported speakers bureau and advisory board participation for Celgene, Janssen, and Takeda; and advisory board participation for Sanofi, Amgen, Karyopharm, and Oncopeptides.

SOURCE: Facon T et al. ASH 2018, Abstract LBA-2.

SAN DIEGO – Patients with newly diagnosed multiple myeloma who were ineligible for transplant had a 44% reduction in the risk of disease progression or death when they were treated with the anti-CD38 monoclonal antibody daratumumab (Darzalex) added to lenalidomide (Revlimid) and dexamethasone, compared with lenalidomide-dexamethasone alone, an interim analysis from the MAIA trial showed.

Among 737 patients in a phase 3 trial, median progression-free survival – the primary endpoint – had not been reached after a median follow-up of 28 months for patients randomized to daratumumab, lenalidomide, and dexamethasone (DRd), versus 31.9 months for patients randomized to lenalidomide and dexamethasone (Rd).

The 30-month PFS rate in the DRd arm was 71%, compared with 56% for the Rd arm. This difference translated into a hazard ratio (HR) for progression of 0.56 (P less than .0001), reported Thierry Facon, MD, of Hôpital Claude Huriez and the University of Lille, France.

“These results support DRd as a new standard of care for elderly patients with myeloma who are ineligible for transplant,” he said at the annual meeting of the American Society of Hematology.

Dr. Facon and his colleagues had previously shown in the FIRST trial that in newly diagnosed transplant-ineligible patients, continuous treatment with lenalidomide and low-dose dexamethasone was associated with significant overall survival and PFS benefits, compared with melphalan-prednisone-thalidomide.

In the POLLUX trial, investigators reported that in patients with multiple myeloma that was refractory or had relapsed after at least one prior line of therapy, the DRd combination was associated with a 63% reduction in the risk for disease progression or death, compared with Rd alone.
 

MAIA details

The MAIA trial is a pivotal, phase 3 study pitting DRd against Rd in transplant-ineligible patients with newly diagnosed multiple myeloma.

Patients with untreated disease who had Eastern Cooperative Oncology Group (ECOG) status of 0-2 and creatinine clearance rates of at least 30 mL/min were enrolled. Patients were randomly assigned to either DRd, with intravenous daratumumab 16 mg/kg weekly for cycles 1 and 2, every other week for cycles 3 through 6, and every 4 weeks from cycle 7 until disease progression, plus lenalidomide 25 mg orally per day on days 1-21 until disease progression, and dexamethasone 40 mg orally or intravenously weekly until disease progression; or to the same regimen without daratumumab.

The median patient age was 73 years and 99% of all patients were aged 65 years or older. Demographic and clinical characteristics were well balanced between the treatment arms.

The primary endpoint of progression-free survival was superior with DRd.

DRd also was associated with a significantly higher overall response rate (93% vs. 81%), complete response rate (48% vs. 25%), very good partial response or better rate (79% vs. 53%), and minimal residual disease (MRD) negativity rate (24% vs. 7%; P less than .0001 for all comparisons).

The DRd combination was associated with infusion-related reactions in 41% of patients, but only 3% were grade 3 or 4 in severity.

Hematologic treatment-emergent adverse events (TEAE) grade 3 or greater that were more common with DRd included neutropenia (50% vs. 35%) and lymphopenia (15% vs. 11%). Conversely, thrombocytopenia (7% vs. 9%, grade 3 or 4) and anemia (12% vs. 20%) were more frequent with Rd.

Nonhematologic TEAEs that were more frequent with DRd included diarrhea, constipation, fatigue, peripheral edema, and pneumonia. Rates of asthenia, back pain, nausea, and deep vein thrombosis/pulmonary embolism were similar between the study arms.

Janssen funded the study. Dr. Facon reported speakers bureau and advisory board participation for Celgene, Janssen, and Takeda; and advisory board participation for Sanofi, Amgen, Karyopharm, and Oncopeptides.

SOURCE: Facon T et al. ASH 2018, Abstract LBA-2.

SAN DIEGO – Patients with newly diagnosed multiple myeloma who were ineligible for transplant had a 44% reduction in the risk of disease progression or death when they were treated with the anti-CD38 monoclonal antibody daratumumab (Darzalex) added to lenalidomide (Revlimid) and dexamethasone, compared with lenalidomide-dexamethasone alone, an interim analysis from the MAIA trial showed.

Among 737 patients in a phase 3 trial, median progression-free survival – the primary endpoint – had not been reached after a median follow-up of 28 months for patients randomized to daratumumab, lenalidomide, and dexamethasone (DRd), versus 31.9 months for patients randomized to lenalidomide and dexamethasone (Rd).

The 30-month PFS rate in the DRd arm was 71%, compared with 56% for the Rd arm. This difference translated into a hazard ratio (HR) for progression of 0.56 (P less than .0001), reported Thierry Facon, MD, of Hôpital Claude Huriez and the University of Lille, France.

“These results support DRd as a new standard of care for elderly patients with myeloma who are ineligible for transplant,” he said at the annual meeting of the American Society of Hematology.

Dr. Facon and his colleagues had previously shown in the FIRST trial that in newly diagnosed transplant-ineligible patients, continuous treatment with lenalidomide and low-dose dexamethasone was associated with significant overall survival and PFS benefits, compared with melphalan-prednisone-thalidomide.

In the POLLUX trial, investigators reported that in patients with multiple myeloma that was refractory or had relapsed after at least one prior line of therapy, the DRd combination was associated with a 63% reduction in the risk for disease progression or death, compared with Rd alone.
 

MAIA details

The MAIA trial is a pivotal, phase 3 study pitting DRd against Rd in transplant-ineligible patients with newly diagnosed multiple myeloma.

Patients with untreated disease who had Eastern Cooperative Oncology Group (ECOG) status of 0-2 and creatinine clearance rates of at least 30 mL/min were enrolled. Patients were randomly assigned to either DRd, with intravenous daratumumab 16 mg/kg weekly for cycles 1 and 2, every other week for cycles 3 through 6, and every 4 weeks from cycle 7 until disease progression, plus lenalidomide 25 mg orally per day on days 1-21 until disease progression, and dexamethasone 40 mg orally or intravenously weekly until disease progression; or to the same regimen without daratumumab.

The median patient age was 73 years and 99% of all patients were aged 65 years or older. Demographic and clinical characteristics were well balanced between the treatment arms.

The primary endpoint of progression-free survival was superior with DRd.

DRd also was associated with a significantly higher overall response rate (93% vs. 81%), complete response rate (48% vs. 25%), very good partial response or better rate (79% vs. 53%), and minimal residual disease (MRD) negativity rate (24% vs. 7%; P less than .0001 for all comparisons).

The DRd combination was associated with infusion-related reactions in 41% of patients, but only 3% were grade 3 or 4 in severity.

Hematologic treatment-emergent adverse events (TEAE) grade 3 or greater that were more common with DRd included neutropenia (50% vs. 35%) and lymphopenia (15% vs. 11%). Conversely, thrombocytopenia (7% vs. 9%, grade 3 or 4) and anemia (12% vs. 20%) were more frequent with Rd.

Nonhematologic TEAEs that were more frequent with DRd included diarrhea, constipation, fatigue, peripheral edema, and pneumonia. Rates of asthenia, back pain, nausea, and deep vein thrombosis/pulmonary embolism were similar between the study arms.

Janssen funded the study. Dr. Facon reported speakers bureau and advisory board participation for Celgene, Janssen, and Takeda; and advisory board participation for Sanofi, Amgen, Karyopharm, and Oncopeptides.

SOURCE: Facon T et al. ASH 2018, Abstract LBA-2.

At the 2018 Pelvic Anatomy and Gynecologic Surgery Symposium meeting in Las Vegas, Nevada, Tommaso Falcone, MD, Chief of Staff, Chief Academic Officer, and Medical Director at Cleveland Clinic London, England, addressed the status of tissue morcellation in hysterectomy and myomectomy after several years’ controversy—noting that the specialty’s professional societies all support use of the technique, with precautions and in selected patients.

Morcellation history

Should electromechanical (‘power’) morcellation of tissue be a tool for performing minimally invasive hysterectomy and myomectomy? If so, what are the risks and benefits of using this tool, first approved by the US Food and Drug Administration (FDA) in 1995?

The matter came under intense scrutiny and debate in 2014 as concerns rose about the potential of power morcellation to disseminate intraperitoneal malignancy in women with occult cancer (an estimated 1 in 370 women who undergo power morcellation during a minimally invasive hysterectomy have uterine cancer¹). Early that year, the FDA moved to strongly discourage use of power morcellators for removing uterine fibroids.²

The aftermath, however, was that there were problems with the FDA’s [2014] statement, Dr. Falcone pointed out. In a study by Siedhoff and colleagues of a hypothetical cohort of 100,000 women with fibroids, for example, an abdominal approach resulted in more hysterectomy-related deaths and surgery-related complications than did a laparoscopic procedure with morcellation.³

Balancing risks and benefits of MIS

After continuing study of the risks presented by morcellation, the question today is: How do we balance preventing dissemination of cancer against diminishing the significant benefits of minimally invasive surgery, as surgical technique has been modified to avoid morcellation—including, Dr. Falcone said, by increased use of mini lap (i.e., extending the laparoscopy incision) tissue extraction, decreased use of supracervical hysterectomy, and a move to open approaches.

In fact, Dr. Falcone noted, power morcellation is banned in many institutions, having been replaced by scalpel, extraperitoneal, or in-bag morcellation. Last year, after further analysis, the FDA reiterated its recommendation against use of power morcellators to remove fibroids in most women.⁴
 

Continue to: Morcellation decisions

Dr. Falcone pointed out that, at the Cleveland Clinic, morcellation is not performed in postmenopausal women, and for several other contraindications, including a history of >2 years of tamoxifen therapy; history of pelvic radiation; history of childhood retinoblastoma; personal history of hereditary leiomyomatosis or renal cell carcinoma; and the presence of a cancer-positive tissue specimen. Morcellation is not performed unless endometrial adenocarcinoma has been ruled out. The decision-making process when electing to use tissue extraction includes whether to use contained or noncontained morcellation; whether to favor knife excision over power morcellation; and, when using a mini lap approach, whether to proceed via the umbilicus or suprapubically.

Complications of morcellation include direct injury by the morcellator; dissemination, as noted, of tissue; ‘upstaging’ of uterine sarcoma, with a worsening prognosis; seeding of parasitic fibroids; and reoperation with laparotomy and extensive multi-organ resection to clear disease (3 patients in a published report).⁵

An important advancement in the use of morcellation in minimally invasive hysterectomy or myomectomy has been the development of contained systems for morcellating—generally a plastic specimen bag, sometimes pulled through the port and insufflated. Dr. Falcone’s presentation included video presentations of this important, and still evolving, technology. Whether these contained systems improve survival, and whether using them in a vaginal approach makes any difference, remain uncertain, however. Furthermore, some spillage from bags is inevitable—although how much spillage is clinically significant is open to question.

Takeaways

Dr. Falcone concluded with key points to guide the surgeon’s decision on whether to proceed with morcellation:

• There are no comparative data on which technique [of tissue removal] is best.
• Tissue spill will occur in uncontained morcellation—this is intrinsic to the device.
• Even with the current generation of tissue bags, leakage is common and puncture is possible.

If you choose to continue to use power morcellation, your decision is supported by the fact that all the professional societies still support it, Dr. Falcone noted. Furthermore, he pointed out that it is important to look to the standard of care in your community regarding risks and benefits before proceeding.

Last, the advantages and risks of morcellation in hysterectomy and myomectomy should be part of an in-depth discussion between patient and surgeon prior to the procedure. And you must, Dr. Falcone emphasized, obtain specific informed consent.

At the 2018 Pelvic Anatomy and Gynecologic Surgery Symposium meeting in Las Vegas, Nevada, Tommaso Falcone, MD, Chief of Staff, Chief Academic Officer, and Medical Director at Cleveland Clinic London, England, addressed the status of tissue morcellation in hysterectomy and myomectomy after several years’ controversy—noting that the specialty’s professional societies all support use of the technique, with precautions and in selected patients.

Morcellation history

Should electromechanical (‘power’) morcellation of tissue be a tool for performing minimally invasive hysterectomy and myomectomy? If so, what are the risks and benefits of using this tool, first approved by the US Food and Drug Administration (FDA) in 1995?

The matter came under intense scrutiny and debate in 2014 as concerns rose about the potential of power morcellation to disseminate intraperitoneal malignancy in women with occult cancer (an estimated 1 in 370 women who undergo power morcellation during a minimally invasive hysterectomy have uterine cancer¹). Early that year, the FDA moved to strongly discourage use of power morcellators for removing uterine fibroids.²

The aftermath, however, was that there were problems with the FDA’s [2014] statement, Dr. Falcone pointed out. In a study by Siedhoff and colleagues of a hypothetical cohort of 100,000 women with fibroids, for example, an abdominal approach resulted in more hysterectomy-related deaths and surgery-related complications than did a laparoscopic procedure with morcellation.³

Balancing risks and benefits of MIS

After continuing study of the risks presented by morcellation, the question today is: How do we balance preventing dissemination of cancer against diminishing the significant benefits of minimally invasive surgery, as surgical technique has been modified to avoid morcellation—including, Dr. Falcone said, by increased use of mini lap (i.e., extending the laparoscopy incision) tissue extraction, decreased use of supracervical hysterectomy, and a move to open approaches.

In fact, Dr. Falcone noted, power morcellation is banned in many institutions, having been replaced by scalpel, extraperitoneal, or in-bag morcellation. Last year, after further analysis, the FDA reiterated its recommendation against use of power morcellators to remove fibroids in most women.⁴
 

Continue to: Morcellation decisions

Dr. Falcone pointed out that, at the Cleveland Clinic, morcellation is not performed in postmenopausal women, and for several other contraindications, including a history of >2 years of tamoxifen therapy; history of pelvic radiation; history of childhood retinoblastoma; personal history of hereditary leiomyomatosis or renal cell carcinoma; and the presence of a cancer-positive tissue specimen. Morcellation is not performed unless endometrial adenocarcinoma has been ruled out. The decision-making process when electing to use tissue extraction includes whether to use contained or noncontained morcellation; whether to favor knife excision over power morcellation; and, when using a mini lap approach, whether to proceed via the umbilicus or suprapubically.

Complications of morcellation include direct injury by the morcellator; dissemination, as noted, of tissue; ‘upstaging’ of uterine sarcoma, with a worsening prognosis; seeding of parasitic fibroids; and reoperation with laparotomy and extensive multi-organ resection to clear disease (3 patients in a published report).⁵

An important advancement in the use of morcellation in minimally invasive hysterectomy or myomectomy has been the development of contained systems for morcellating—generally a plastic specimen bag, sometimes pulled through the port and insufflated. Dr. Falcone’s presentation included video presentations of this important, and still evolving, technology. Whether these contained systems improve survival, and whether using them in a vaginal approach makes any difference, remain uncertain, however. Furthermore, some spillage from bags is inevitable—although how much spillage is clinically significant is open to question.

Takeaways

Dr. Falcone concluded with key points to guide the surgeon’s decision on whether to proceed with morcellation:

• There are no comparative data on which technique [of tissue removal] is best.
• Tissue spill will occur in uncontained morcellation—this is intrinsic to the device.
• Even with the current generation of tissue bags, leakage is common and puncture is possible.

If you choose to continue to use power morcellation, your decision is supported by the fact that all the professional societies still support it, Dr. Falcone noted. Furthermore, he pointed out that it is important to look to the standard of care in your community regarding risks and benefits before proceeding.

Last, the advantages and risks of morcellation in hysterectomy and myomectomy should be part of an in-depth discussion between patient and surgeon prior to the procedure. And you must, Dr. Falcone emphasized, obtain specific informed consent.

At the 2018 Pelvic Anatomy and Gynecologic Surgery Symposium meeting in Las Vegas, Nevada, Tommaso Falcone, MD, Chief of Staff, Chief Academic Officer, and Medical Director at Cleveland Clinic London, England, addressed the status of tissue morcellation in hysterectomy and myomectomy after several years’ controversy—noting that the specialty’s professional societies all support use of the technique, with precautions and in selected patients.

Morcellation history

Should electromechanical (‘power’) morcellation of tissue be a tool for performing minimally invasive hysterectomy and myomectomy? If so, what are the risks and benefits of using this tool, first approved by the US Food and Drug Administration (FDA) in 1995?

The matter came under intense scrutiny and debate in 2014 as concerns rose about the potential of power morcellation to disseminate intraperitoneal malignancy in women with occult cancer (an estimated 1 in 370 women who undergo power morcellation during a minimally invasive hysterectomy have uterine cancer¹). Early that year, the FDA moved to strongly discourage use of power morcellators for removing uterine fibroids.²

The aftermath, however, was that there were problems with the FDA’s [2014] statement, Dr. Falcone pointed out. In a study by Siedhoff and colleagues of a hypothetical cohort of 100,000 women with fibroids, for example, an abdominal approach resulted in more hysterectomy-related deaths and surgery-related complications than did a laparoscopic procedure with morcellation.³

Balancing risks and benefits of MIS

After continuing study of the risks presented by morcellation, the question today is: How do we balance preventing dissemination of cancer against diminishing the significant benefits of minimally invasive surgery, as surgical technique has been modified to avoid morcellation—including, Dr. Falcone said, by increased use of mini lap (i.e., extending the laparoscopy incision) tissue extraction, decreased use of supracervical hysterectomy, and a move to open approaches.

In fact, Dr. Falcone noted, power morcellation is banned in many institutions, having been replaced by scalpel, extraperitoneal, or in-bag morcellation. Last year, after further analysis, the FDA reiterated its recommendation against use of power morcellators to remove fibroids in most women.⁴
 

Continue to: Morcellation decisions

Dr. Falcone pointed out that, at the Cleveland Clinic, morcellation is not performed in postmenopausal women, and for several other contraindications, including a history of >2 years of tamoxifen therapy; history of pelvic radiation; history of childhood retinoblastoma; personal history of hereditary leiomyomatosis or renal cell carcinoma; and the presence of a cancer-positive tissue specimen. Morcellation is not performed unless endometrial adenocarcinoma has been ruled out. The decision-making process when electing to use tissue extraction includes whether to use contained or noncontained morcellation; whether to favor knife excision over power morcellation; and, when using a mini lap approach, whether to proceed via the umbilicus or suprapubically.

Complications of morcellation include direct injury by the morcellator; dissemination, as noted, of tissue; ‘upstaging’ of uterine sarcoma, with a worsening prognosis; seeding of parasitic fibroids; and reoperation with laparotomy and extensive multi-organ resection to clear disease (3 patients in a published report).⁵

An important advancement in the use of morcellation in minimally invasive hysterectomy or myomectomy has been the development of contained systems for morcellating—generally a plastic specimen bag, sometimes pulled through the port and insufflated. Dr. Falcone’s presentation included video presentations of this important, and still evolving, technology. Whether these contained systems improve survival, and whether using them in a vaginal approach makes any difference, remain uncertain, however. Furthermore, some spillage from bags is inevitable—although how much spillage is clinically significant is open to question.

Takeaways

Dr. Falcone concluded with key points to guide the surgeon’s decision on whether to proceed with morcellation:

• There are no comparative data on which technique [of tissue removal] is best.
• Tissue spill will occur in uncontained morcellation—this is intrinsic to the device.
• Even with the current generation of tissue bags, leakage is common and puncture is possible.

If you choose to continue to use power morcellation, your decision is supported by the fact that all the professional societies still support it, Dr. Falcone noted. Furthermore, he pointed out that it is important to look to the standard of care in your community regarding risks and benefits before proceeding.

Last, the advantages and risks of morcellation in hysterectomy and myomectomy should be part of an in-depth discussion between patient and surgeon prior to the procedure. And you must, Dr. Falcone emphasized, obtain specific informed consent.

SAN ANTONIO – Circulating tumor cell (CTC) counts could serve as a standalone biomarker for determining which patients with newly diagnosed estrogen receptor–positive, HER2-negative metastatic breast cancer are at high risk and should receive first-line chemotherapy and which are at low risk and could safely receive upfront hormonal therapy.

In the phase 3 STIC CTC trial, there were no significant differences in the primary endpoint of progression-free survival (PFS) or a secondary endpoint of overall survival (OS) between patients whose treatments were assigned according to the clinicians’ judgment and those whose treatments were chosen based on CTC count, reported Francois-Clement Bidard, MD, PhD, from Institut Curie in St. Cloud, France.

“CTC count should or may be included in the decision algorithm for hormone receptor–positive, HER2-negative metastatic breast cancer patients,” he said at the San Antonio Breast Cancer Symposium.

The CTC investigators sought to compare CTC-driven clinical decisions with the clinicians choice for first-line therapy in 778 patients with hormone receptor–positive, HER2-negative breast cancer.

Patients were stratified by performance status (0-3), treatment center, and disease-free interval and were randomly assigned to receive therapy based on either the clinician’s judgment of the best course of therapy for each patient or to CTC count, with a cutoff of less than 5 CTC/7.5 mL indicating hormonal therapy and 5 CTC/7.5 mL or above indicating higher-risk disease requiring chemotherapy. In the clinician’s choice arm, the CTC reading was recorded but not implemented, and in the CTC arm, the clinician’s choice was dismissed.

The trial protocol did not specify a chemotherapy regimen, and patients initially assigned to chemotherapy were allowed to have maintenance hormonal therapy.

At 42 months of follow-up, median PFS in the CTC arm was 15.6 months, compared with 14.0 months in the clinician choice arm. The hazard ratio for PFS was 0.92 (90% confidence interval, 0.80-1.06), and the trial met its primary noninferiority endpoint with a prespecified noninferiority margin of 1.25.

The OS rate at 24 months in the CTC group was 82.1%, and in the clinician choice arm was 81.4% (nonsignificant).

Planned subgroup analyses in which the two decision methods were in agreement on whether a patient was at either low or high risk found no significant differences in either PFS or OS, showing that the CTC count complemented the prognostic estimate and isolated patients with either excellent or poor outcomes.


However, when the clinician rated the risk as low but the CTC count rated it as high (196 patients), PFS was significantly higher with CTC (HR, 0.62; P = .002). OS did not differ in this circumstance.

In an exploratory analysis combining all patients with discordant findings (clinician low/CTC high or vice versa), the investigators determined that chemotherapy would offer a significant advantage for both PFS (HR, 0.66; adjusted P = .001) and OS (HR, 0.65; adjusted P = .04).

Virginia Kaklamani, MD, leader of the breast cancer program at the University of Texas, San Antonio, who moderated a briefing where Dr. Bidard discussed the findings prior to presentation in a general session, said that she is not fully convinced that CTC counts can substitute for the clinician’s discretion. “I would probably want to see another study or some more data.”

She noted that for the patient population in this study clinicians today often prescribe cyclin-dependent kinase (CDK) 4/6 inhibitors in the first-line setting over conventional chemotherapy.

“But it is true that CDK 4/6 inhibitors, besides their cost, $10,000 a month, also are toxic to our patients. They cause neutropenias, increase infections, some diarrhea, so if there is a group I can potentially save from taking a CDK 4/6 inhibitor in the first-line setting I’d love to do that. In the metastatic setting what we’re trying to do for years is deescalate therapy, so the idea of giving chemotherapy instead of endocrine therapy is a little foreign to us,” Dr. Kaklamani said.

The strength of the study, however, is that it’s the first to show a survival benefit using CTCs as a diagnostic aid, she added.

Lisa A. Carey, MD, from the University of North Carolina at Chapel Hill, who was not involved in the study, said in an interview that the technology is promising, but not ready for prime time.

“To be honest, it didn’t appear to me that it helped very much, so that particular approach I don’t think is likely to have much benefit for patients. But the concept is an excellent one, and I do think that’s something we need to take home, that this is an area of an unmet need,” she said.

The study was funded by the National Cancer Institute of France, Institut Curie, and Menarini. Dr. Bidard reported receiving research funding and travel grants from Menarini. Dr. Kaklamani and Dr. Carey reported having no relevant conflicts of interest.

SOURCE: Bidard F-C et al. SABCS 2018, Abstract GS3-07.

SAN ANTONIO – Circulating tumor cell (CTC) counts could serve as a standalone biomarker for determining which patients with newly diagnosed estrogen receptor–positive, HER2-negative metastatic breast cancer are at high risk and should receive first-line chemotherapy and which are at low risk and could safely receive upfront hormonal therapy.

In the phase 3 STIC CTC trial, there were no significant differences in the primary endpoint of progression-free survival (PFS) or a secondary endpoint of overall survival (OS) between patients whose treatments were assigned according to the clinicians’ judgment and those whose treatments were chosen based on CTC count, reported Francois-Clement Bidard, MD, PhD, from Institut Curie in St. Cloud, France.

“CTC count should or may be included in the decision algorithm for hormone receptor–positive, HER2-negative metastatic breast cancer patients,” he said at the San Antonio Breast Cancer Symposium.

The CTC investigators sought to compare CTC-driven clinical decisions with the clinicians choice for first-line therapy in 778 patients with hormone receptor–positive, HER2-negative breast cancer.

Patients were stratified by performance status (0-3), treatment center, and disease-free interval and were randomly assigned to receive therapy based on either the clinician’s judgment of the best course of therapy for each patient or to CTC count, with a cutoff of less than 5 CTC/7.5 mL indicating hormonal therapy and 5 CTC/7.5 mL or above indicating higher-risk disease requiring chemotherapy. In the clinician’s choice arm, the CTC reading was recorded but not implemented, and in the CTC arm, the clinician’s choice was dismissed.

The trial protocol did not specify a chemotherapy regimen, and patients initially assigned to chemotherapy were allowed to have maintenance hormonal therapy.

At 42 months of follow-up, median PFS in the CTC arm was 15.6 months, compared with 14.0 months in the clinician choice arm. The hazard ratio for PFS was 0.92 (90% confidence interval, 0.80-1.06), and the trial met its primary noninferiority endpoint with a prespecified noninferiority margin of 1.25.

The OS rate at 24 months in the CTC group was 82.1%, and in the clinician choice arm was 81.4% (nonsignificant).

Planned subgroup analyses in which the two decision methods were in agreement on whether a patient was at either low or high risk found no significant differences in either PFS or OS, showing that the CTC count complemented the prognostic estimate and isolated patients with either excellent or poor outcomes.


However, when the clinician rated the risk as low but the CTC count rated it as high (196 patients), PFS was significantly higher with CTC (HR, 0.62; P = .002). OS did not differ in this circumstance.

In an exploratory analysis combining all patients with discordant findings (clinician low/CTC high or vice versa), the investigators determined that chemotherapy would offer a significant advantage for both PFS (HR, 0.66; adjusted P = .001) and OS (HR, 0.65; adjusted P = .04).

Virginia Kaklamani, MD, leader of the breast cancer program at the University of Texas, San Antonio, who moderated a briefing where Dr. Bidard discussed the findings prior to presentation in a general session, said that she is not fully convinced that CTC counts can substitute for the clinician’s discretion. “I would probably want to see another study or some more data.”

She noted that for the patient population in this study clinicians today often prescribe cyclin-dependent kinase (CDK) 4/6 inhibitors in the first-line setting over conventional chemotherapy.

“But it is true that CDK 4/6 inhibitors, besides their cost, $10,000 a month, also are toxic to our patients. They cause neutropenias, increase infections, some diarrhea, so if there is a group I can potentially save from taking a CDK 4/6 inhibitor in the first-line setting I’d love to do that. In the metastatic setting what we’re trying to do for years is deescalate therapy, so the idea of giving chemotherapy instead of endocrine therapy is a little foreign to us,” Dr. Kaklamani said.

The strength of the study, however, is that it’s the first to show a survival benefit using CTCs as a diagnostic aid, she added.

Lisa A. Carey, MD, from the University of North Carolina at Chapel Hill, who was not involved in the study, said in an interview that the technology is promising, but not ready for prime time.

“To be honest, it didn’t appear to me that it helped very much, so that particular approach I don’t think is likely to have much benefit for patients. But the concept is an excellent one, and I do think that’s something we need to take home, that this is an area of an unmet need,” she said.

The study was funded by the National Cancer Institute of France, Institut Curie, and Menarini. Dr. Bidard reported receiving research funding and travel grants from Menarini. Dr. Kaklamani and Dr. Carey reported having no relevant conflicts of interest.

SOURCE: Bidard F-C et al. SABCS 2018, Abstract GS3-07.

SAN ANTONIO – Circulating tumor cell (CTC) counts could serve as a standalone biomarker for determining which patients with newly diagnosed estrogen receptor–positive, HER2-negative metastatic breast cancer are at high risk and should receive first-line chemotherapy and which are at low risk and could safely receive upfront hormonal therapy.

In the phase 3 STIC CTC trial, there were no significant differences in the primary endpoint of progression-free survival (PFS) or a secondary endpoint of overall survival (OS) between patients whose treatments were assigned according to the clinicians’ judgment and those whose treatments were chosen based on CTC count, reported Francois-Clement Bidard, MD, PhD, from Institut Curie in St. Cloud, France.

“CTC count should or may be included in the decision algorithm for hormone receptor–positive, HER2-negative metastatic breast cancer patients,” he said at the San Antonio Breast Cancer Symposium.

The CTC investigators sought to compare CTC-driven clinical decisions with the clinicians choice for first-line therapy in 778 patients with hormone receptor–positive, HER2-negative breast cancer.

Patients were stratified by performance status (0-3), treatment center, and disease-free interval and were randomly assigned to receive therapy based on either the clinician’s judgment of the best course of therapy for each patient or to CTC count, with a cutoff of less than 5 CTC/7.5 mL indicating hormonal therapy and 5 CTC/7.5 mL or above indicating higher-risk disease requiring chemotherapy. In the clinician’s choice arm, the CTC reading was recorded but not implemented, and in the CTC arm, the clinician’s choice was dismissed.

The trial protocol did not specify a chemotherapy regimen, and patients initially assigned to chemotherapy were allowed to have maintenance hormonal therapy.

At 42 months of follow-up, median PFS in the CTC arm was 15.6 months, compared with 14.0 months in the clinician choice arm. The hazard ratio for PFS was 0.92 (90% confidence interval, 0.80-1.06), and the trial met its primary noninferiority endpoint with a prespecified noninferiority margin of 1.25.

The OS rate at 24 months in the CTC group was 82.1%, and in the clinician choice arm was 81.4% (nonsignificant).

Planned subgroup analyses in which the two decision methods were in agreement on whether a patient was at either low or high risk found no significant differences in either PFS or OS, showing that the CTC count complemented the prognostic estimate and isolated patients with either excellent or poor outcomes.


However, when the clinician rated the risk as low but the CTC count rated it as high (196 patients), PFS was significantly higher with CTC (HR, 0.62; P = .002). OS did not differ in this circumstance.

In an exploratory analysis combining all patients with discordant findings (clinician low/CTC high or vice versa), the investigators determined that chemotherapy would offer a significant advantage for both PFS (HR, 0.66; adjusted P = .001) and OS (HR, 0.65; adjusted P = .04).

Virginia Kaklamani, MD, leader of the breast cancer program at the University of Texas, San Antonio, who moderated a briefing where Dr. Bidard discussed the findings prior to presentation in a general session, said that she is not fully convinced that CTC counts can substitute for the clinician’s discretion. “I would probably want to see another study or some more data.”

She noted that for the patient population in this study clinicians today often prescribe cyclin-dependent kinase (CDK) 4/6 inhibitors in the first-line setting over conventional chemotherapy.

“But it is true that CDK 4/6 inhibitors, besides their cost, $10,000 a month, also are toxic to our patients. They cause neutropenias, increase infections, some diarrhea, so if there is a group I can potentially save from taking a CDK 4/6 inhibitor in the first-line setting I’d love to do that. In the metastatic setting what we’re trying to do for years is deescalate therapy, so the idea of giving chemotherapy instead of endocrine therapy is a little foreign to us,” Dr. Kaklamani said.

The strength of the study, however, is that it’s the first to show a survival benefit using CTCs as a diagnostic aid, she added.

Lisa A. Carey, MD, from the University of North Carolina at Chapel Hill, who was not involved in the study, said in an interview that the technology is promising, but not ready for prime time.

“To be honest, it didn’t appear to me that it helped very much, so that particular approach I don’t think is likely to have much benefit for patients. But the concept is an excellent one, and I do think that’s something we need to take home, that this is an area of an unmet need,” she said.

The study was funded by the National Cancer Institute of France, Institut Curie, and Menarini. Dr. Bidard reported receiving research funding and travel grants from Menarini. Dr. Kaklamani and Dr. Carey reported having no relevant conflicts of interest.

SOURCE: Bidard F-C et al. SABCS 2018, Abstract GS3-07.

SAN DIEGO – A couple years ago, hematologist-oncologist Norman E. “Ned” Sharpless, MD, was gobsmacked by a groundbreaking study into treatments for acute myeloid leukemia. While the findings offered valuable new insight into the best drug options, they left Dr. Sharpless quaking, and not with delight. “I can recall that my knees buckled,” he said.

Courtesy University of North Carolina

Why? Because the findings, he told colleagues at the annual meeting of the American Society of Hematology, came too late for many patients to benefit. “One could say that’s great news, this is medical progress,” he said. “But I saw this as a clear failure of data aggregation.”

Now, Dr. Sharpless is in a position to do more than fume and speak out. He became the director of the National Cancer Institute in 2017 and he’s made “big data” one of his four priorities for the NCI under his leadership.

“While data security is crucial, there are also costs to not aggregating data and sharing it,” he said. “It means giving patients the wrong drug, it means patients having to die.”

While Dr. Sharpless said he’s disappointed by the progress on data in medicine, he had praise to offer, too. In conversations over his first year-plus on the job, he said, he’s learned that “it’s a great time to be a cancer scientist and a cancer doctor in the United States. ... It’s undeniably a great time to be a blood doctor or blood scientist. We’re making progress at a rate that is faster and greater than at any point in my career as an oncologist. Just look at all the new stuff we’ve got!”

In hematology, great strides are being made in areas such as the treatment of leukemia and lymphoma, he said. Progress is also boosting treatment in areas such as melanoma and lung, breast, ovarian, and head and neck cancer.

“Some of you will correctly point out that this progress is not enough. In some cases, treatments are moderately effective and not curative. These are singles or even doubles, but we still need home runs. We still have too many patients dying of cancer, including blood cancer,” he said. “From my perspective, it’s important to be very clear-eyed. While we have a long way to go to end suffering in all patients, we have to be willing to admit that progress has been impressive.”

Dr. Sharpless touted the Cancer Moonshot, which will allocate $1.8 billion in federal funds for cancer research over 7 years. And he mentioned his four priority areas at NCI: Workforce development, basic science, big data, and clinical trials. Initiatives in these areas include prioritization of research by early-career investigators and increased funding for trials, he said.

As for data, he said, “I’ve been trying to explain to congressional leaders why getting control of our data is important.”

Dr. Sharpless likes to point to his own encounter in his kitchen in 2016 – the one that buckled his knees – with an issue of the New England Journal of Medicine. There he found a study that examined molecular determinants of response to decitabine in acute myeloid leukemia and myelodysplastic syndromes (N Engl J Med. 2016 Nov 24;375[21]:2023-36).

“I can still close my eyes now and literally see the faces of patients whom I gave ... a very toxic regimen, some of whom had very bad outcomes,” he said. “I know in retrospect, based on certain statistics, I probably used the wrong drug in some of these patients. If we’d been aggregating data in a deliberate way, from the get-go of AML, a result like this would have fallen out immediately. I’m concerned we’re still making these types of mistakes for other cancer subtypes today.”

Moving forward, he said, the goal is “to create large, multimodal data sets ... And put them in the cloud and make them available to the research community in the most useful format possible, in a way that’s safe and secure. We have to do these things because the costs of not harnessing data are too great.”

Dr. Sharpless reported several past financial relationships with G1 Therapeutics, Healthspan Diagnostics, and Unity Biotechnology.

SAN DIEGO – A couple years ago, hematologist-oncologist Norman E. “Ned” Sharpless, MD, was gobsmacked by a groundbreaking study into treatments for acute myeloid leukemia. While the findings offered valuable new insight into the best drug options, they left Dr. Sharpless quaking, and not with delight. “I can recall that my knees buckled,” he said.

Courtesy University of North Carolina

Why? Because the findings, he told colleagues at the annual meeting of the American Society of Hematology, came too late for many patients to benefit. “One could say that’s great news, this is medical progress,” he said. “But I saw this as a clear failure of data aggregation.”

Now, Dr. Sharpless is in a position to do more than fume and speak out. He became the director of the National Cancer Institute in 2017 and he’s made “big data” one of his four priorities for the NCI under his leadership.

“While data security is crucial, there are also costs to not aggregating data and sharing it,” he said. “It means giving patients the wrong drug, it means patients having to die.”

While Dr. Sharpless said he’s disappointed by the progress on data in medicine, he had praise to offer, too. In conversations over his first year-plus on the job, he said, he’s learned that “it’s a great time to be a cancer scientist and a cancer doctor in the United States. ... It’s undeniably a great time to be a blood doctor or blood scientist. We’re making progress at a rate that is faster and greater than at any point in my career as an oncologist. Just look at all the new stuff we’ve got!”

In hematology, great strides are being made in areas such as the treatment of leukemia and lymphoma, he said. Progress is also boosting treatment in areas such as melanoma and lung, breast, ovarian, and head and neck cancer.

“Some of you will correctly point out that this progress is not enough. In some cases, treatments are moderately effective and not curative. These are singles or even doubles, but we still need home runs. We still have too many patients dying of cancer, including blood cancer,” he said. “From my perspective, it’s important to be very clear-eyed. While we have a long way to go to end suffering in all patients, we have to be willing to admit that progress has been impressive.”

Dr. Sharpless touted the Cancer Moonshot, which will allocate $1.8 billion in federal funds for cancer research over 7 years. And he mentioned his four priority areas at NCI: Workforce development, basic science, big data, and clinical trials. Initiatives in these areas include prioritization of research by early-career investigators and increased funding for trials, he said.

As for data, he said, “I’ve been trying to explain to congressional leaders why getting control of our data is important.”

Dr. Sharpless likes to point to his own encounter in his kitchen in 2016 – the one that buckled his knees – with an issue of the New England Journal of Medicine. There he found a study that examined molecular determinants of response to decitabine in acute myeloid leukemia and myelodysplastic syndromes (N Engl J Med. 2016 Nov 24;375[21]:2023-36).

“I can still close my eyes now and literally see the faces of patients whom I gave ... a very toxic regimen, some of whom had very bad outcomes,” he said. “I know in retrospect, based on certain statistics, I probably used the wrong drug in some of these patients. If we’d been aggregating data in a deliberate way, from the get-go of AML, a result like this would have fallen out immediately. I’m concerned we’re still making these types of mistakes for other cancer subtypes today.”

Moving forward, he said, the goal is “to create large, multimodal data sets ... And put them in the cloud and make them available to the research community in the most useful format possible, in a way that’s safe and secure. We have to do these things because the costs of not harnessing data are too great.”

Dr. Sharpless reported several past financial relationships with G1 Therapeutics, Healthspan Diagnostics, and Unity Biotechnology.

SAN DIEGO – A couple years ago, hematologist-oncologist Norman E. “Ned” Sharpless, MD, was gobsmacked by a groundbreaking study into treatments for acute myeloid leukemia. While the findings offered valuable new insight into the best drug options, they left Dr. Sharpless quaking, and not with delight. “I can recall that my knees buckled,” he said.

Courtesy University of North Carolina

Why? Because the findings, he told colleagues at the annual meeting of the American Society of Hematology, came too late for many patients to benefit. “One could say that’s great news, this is medical progress,” he said. “But I saw this as a clear failure of data aggregation.”

Now, Dr. Sharpless is in a position to do more than fume and speak out. He became the director of the National Cancer Institute in 2017 and he’s made “big data” one of his four priorities for the NCI under his leadership.

“While data security is crucial, there are also costs to not aggregating data and sharing it,” he said. “It means giving patients the wrong drug, it means patients having to die.”

While Dr. Sharpless said he’s disappointed by the progress on data in medicine, he had praise to offer, too. In conversations over his first year-plus on the job, he said, he’s learned that “it’s a great time to be a cancer scientist and a cancer doctor in the United States. ... It’s undeniably a great time to be a blood doctor or blood scientist. We’re making progress at a rate that is faster and greater than at any point in my career as an oncologist. Just look at all the new stuff we’ve got!”

In hematology, great strides are being made in areas such as the treatment of leukemia and lymphoma, he said. Progress is also boosting treatment in areas such as melanoma and lung, breast, ovarian, and head and neck cancer.

“Some of you will correctly point out that this progress is not enough. In some cases, treatments are moderately effective and not curative. These are singles or even doubles, but we still need home runs. We still have too many patients dying of cancer, including blood cancer,” he said. “From my perspective, it’s important to be very clear-eyed. While we have a long way to go to end suffering in all patients, we have to be willing to admit that progress has been impressive.”

Dr. Sharpless touted the Cancer Moonshot, which will allocate $1.8 billion in federal funds for cancer research over 7 years. And he mentioned his four priority areas at NCI: Workforce development, basic science, big data, and clinical trials. Initiatives in these areas include prioritization of research by early-career investigators and increased funding for trials, he said.

As for data, he said, “I’ve been trying to explain to congressional leaders why getting control of our data is important.”

Dr. Sharpless likes to point to his own encounter in his kitchen in 2016 – the one that buckled his knees – with an issue of the New England Journal of Medicine. There he found a study that examined molecular determinants of response to decitabine in acute myeloid leukemia and myelodysplastic syndromes (N Engl J Med. 2016 Nov 24;375[21]:2023-36).

“I can still close my eyes now and literally see the faces of patients whom I gave ... a very toxic regimen, some of whom had very bad outcomes,” he said. “I know in retrospect, based on certain statistics, I probably used the wrong drug in some of these patients. If we’d been aggregating data in a deliberate way, from the get-go of AML, a result like this would have fallen out immediately. I’m concerned we’re still making these types of mistakes for other cancer subtypes today.”

Moving forward, he said, the goal is “to create large, multimodal data sets ... And put them in the cloud and make them available to the research community in the most useful format possible, in a way that’s safe and secure. We have to do these things because the costs of not harnessing data are too great.”

Dr. Sharpless reported several past financial relationships with G1 Therapeutics, Healthspan Diagnostics, and Unity Biotechnology.

Single neurons in the human medial frontal cortex appear to be involved in the signaling of self-monitored errors, and this activity can be tracked through a scalp EEG pattern called error-related negativity, according to findings from experiments carried out during intracranial EEG recordings of candidates for surgical treatment of epilepsy.

Epifantsev/Thinkstock

“Our results suggest that coordinated neural activity can serve as a substrate for information routing that enables the performance-monitoring system to communicate the need for behavioral control to other brain regions, including those that maintain flexible goal information, such as the lateral prefrontal cortex and the frontal polar cortex,” first author Zhongzheng Fu, a PhD student at the California Institute of Technology in Pasadena, Calif., and Cedars-Sinai Medical Center, Los Angeles, and his colleagues reported in Neuron.

The findings offer insights that could lead to treatments for conditions in which the important executive function task of error self-monitoring is unbalanced, such as obsessive-compulsive disorder and schizophrenia, the authors noted in a press release.

“We discovered that the activity of error neurons correlates with the size of the ERN [error-related negativity],” Mr. Fu said. “This identifies the brain area that causes the ERN and helps explain what it signifies. This new insight might allow doctors to use the ERN as a standard tool to diagnose mental diseases and monitor responses to treatment.”

Error neuron firing and intracranial ERN occurred first in pre-supplementary motor area (pre-SMA), then in the dorsal anterior cingulate cortex (dACC) about 50 ms later, with significant correlations between firing and intracranial ERN in both locations. In dACC, this activity, with error-integrating neuron responses, correlated with magnitude of post-error slowing (PES).

Previous research suggested a link between “the detection of self-generated errors, as reflected in the ERN, with changes in cognitive control, as exhibited behaviorally in PES,” the investigators wrote. “However, several electroencephalogram (EEG) studies have failed to find a significant relationship between PES and ERN.”

The present study involved intracranial EEG of 29 candidates for surgical treatment of epilepsy and scalp EEG of 12 control participants, with each modality measuring activity in the frontal cortex. Both cohorts performed a rapid version of the color-word Stroop task, in which the words “red,” “green,” or “blue” were printed either in corresponding or noncorresponding colors of red, green, or blue. Subjects were presented various color-word combinations while being asked to click one of three buttons indicating the color of the word as quickly as possible. The investigators monitored neuronal activity throughout, discarding responses that were too slow.

As found in previous trials, the subjects demonstrated the “Stroop effect,” which refers to a slower response when word and color are incongruent (224.9 ms difference; P less than .001). As anticipated, correct responses following correct responses were faster than were correct responses following erroneous responses, which defines PES.

In the intracranial EEG group, the investigators isolated 1,171 neurons, of which 618 were located in dACC and 553 in pre-SMA. Using a Poisson regression model and correlations with erroneous responses, the investigators identified 99 “type I” error neurons in dACC and 118 in pre-SMA, based on higher frequency of firing during erroneous responses than during correct responses. At a single-cell level, error neuron mean spike rates were highest when intracranial ERN amplitude was greatest, such that error neuron firing in dACC and pre-SMA had maximal likelihood ratios of 7.9 (P = .01) and 15.1 (P less than .001), respectively. The strength of correlation between intracranial ERN and error neuron firing rate was directly related to PES magnitude exclusively in the dACC (maximum likelihood ratio of 13.9; P = .015). In post-error trials, faster error-integrating neuron firing rates in dACC predicted greater PES (maximal likelihood ratio of 18.3; P less than .001).

The study was funded by the National Institutes of Health, the McKnight Endowment for Neuroscience, and the National Science Foundation. The authors declared no conflicts of interest.

SOURCE: Fu Z et al. Neuron. 2018 Dec 4. doi: 10.1016/j.neuron.2018.11.016

Single neurons in the human medial frontal cortex appear to be involved in the signaling of self-monitored errors, and this activity can be tracked through a scalp EEG pattern called error-related negativity, according to findings from experiments carried out during intracranial EEG recordings of candidates for surgical treatment of epilepsy.

Epifantsev/Thinkstock

“Our results suggest that coordinated neural activity can serve as a substrate for information routing that enables the performance-monitoring system to communicate the need for behavioral control to other brain regions, including those that maintain flexible goal information, such as the lateral prefrontal cortex and the frontal polar cortex,” first author Zhongzheng Fu, a PhD student at the California Institute of Technology in Pasadena, Calif., and Cedars-Sinai Medical Center, Los Angeles, and his colleagues reported in Neuron.

The findings offer insights that could lead to treatments for conditions in which the important executive function task of error self-monitoring is unbalanced, such as obsessive-compulsive disorder and schizophrenia, the authors noted in a press release.

“We discovered that the activity of error neurons correlates with the size of the ERN [error-related negativity],” Mr. Fu said. “This identifies the brain area that causes the ERN and helps explain what it signifies. This new insight might allow doctors to use the ERN as a standard tool to diagnose mental diseases and monitor responses to treatment.”

Error neuron firing and intracranial ERN occurred first in pre-supplementary motor area (pre-SMA), then in the dorsal anterior cingulate cortex (dACC) about 50 ms later, with significant correlations between firing and intracranial ERN in both locations. In dACC, this activity, with error-integrating neuron responses, correlated with magnitude of post-error slowing (PES).

Previous research suggested a link between “the detection of self-generated errors, as reflected in the ERN, with changes in cognitive control, as exhibited behaviorally in PES,” the investigators wrote. “However, several electroencephalogram (EEG) studies have failed to find a significant relationship between PES and ERN.”

The present study involved intracranial EEG of 29 candidates for surgical treatment of epilepsy and scalp EEG of 12 control participants, with each modality measuring activity in the frontal cortex. Both cohorts performed a rapid version of the color-word Stroop task, in which the words “red,” “green,” or “blue” were printed either in corresponding or noncorresponding colors of red, green, or blue. Subjects were presented various color-word combinations while being asked to click one of three buttons indicating the color of the word as quickly as possible. The investigators monitored neuronal activity throughout, discarding responses that were too slow.

As found in previous trials, the subjects demonstrated the “Stroop effect,” which refers to a slower response when word and color are incongruent (224.9 ms difference; P less than .001). As anticipated, correct responses following correct responses were faster than were correct responses following erroneous responses, which defines PES.

In the intracranial EEG group, the investigators isolated 1,171 neurons, of which 618 were located in dACC and 553 in pre-SMA. Using a Poisson regression model and correlations with erroneous responses, the investigators identified 99 “type I” error neurons in dACC and 118 in pre-SMA, based on higher frequency of firing during erroneous responses than during correct responses. At a single-cell level, error neuron mean spike rates were highest when intracranial ERN amplitude was greatest, such that error neuron firing in dACC and pre-SMA had maximal likelihood ratios of 7.9 (P = .01) and 15.1 (P less than .001), respectively. The strength of correlation between intracranial ERN and error neuron firing rate was directly related to PES magnitude exclusively in the dACC (maximum likelihood ratio of 13.9; P = .015). In post-error trials, faster error-integrating neuron firing rates in dACC predicted greater PES (maximal likelihood ratio of 18.3; P less than .001).

The study was funded by the National Institutes of Health, the McKnight Endowment for Neuroscience, and the National Science Foundation. The authors declared no conflicts of interest.

SOURCE: Fu Z et al. Neuron. 2018 Dec 4. doi: 10.1016/j.neuron.2018.11.016

Single neurons in the human medial frontal cortex appear to be involved in the signaling of self-monitored errors, and this activity can be tracked through a scalp EEG pattern called error-related negativity, according to findings from experiments carried out during intracranial EEG recordings of candidates for surgical treatment of epilepsy.

Epifantsev/Thinkstock

“Our results suggest that coordinated neural activity can serve as a substrate for information routing that enables the performance-monitoring system to communicate the need for behavioral control to other brain regions, including those that maintain flexible goal information, such as the lateral prefrontal cortex and the frontal polar cortex,” first author Zhongzheng Fu, a PhD student at the California Institute of Technology in Pasadena, Calif., and Cedars-Sinai Medical Center, Los Angeles, and his colleagues reported in Neuron.

The findings offer insights that could lead to treatments for conditions in which the important executive function task of error self-monitoring is unbalanced, such as obsessive-compulsive disorder and schizophrenia, the authors noted in a press release.

“We discovered that the activity of error neurons correlates with the size of the ERN [error-related negativity],” Mr. Fu said. “This identifies the brain area that causes the ERN and helps explain what it signifies. This new insight might allow doctors to use the ERN as a standard tool to diagnose mental diseases and monitor responses to treatment.”

Error neuron firing and intracranial ERN occurred first in pre-supplementary motor area (pre-SMA), then in the dorsal anterior cingulate cortex (dACC) about 50 ms later, with significant correlations between firing and intracranial ERN in both locations. In dACC, this activity, with error-integrating neuron responses, correlated with magnitude of post-error slowing (PES).

Previous research suggested a link between “the detection of self-generated errors, as reflected in the ERN, with changes in cognitive control, as exhibited behaviorally in PES,” the investigators wrote. “However, several electroencephalogram (EEG) studies have failed to find a significant relationship between PES and ERN.”

The present study involved intracranial EEG of 29 candidates for surgical treatment of epilepsy and scalp EEG of 12 control participants, with each modality measuring activity in the frontal cortex. Both cohorts performed a rapid version of the color-word Stroop task, in which the words “red,” “green,” or “blue” were printed either in corresponding or noncorresponding colors of red, green, or blue. Subjects were presented various color-word combinations while being asked to click one of three buttons indicating the color of the word as quickly as possible. The investigators monitored neuronal activity throughout, discarding responses that were too slow.

As found in previous trials, the subjects demonstrated the “Stroop effect,” which refers to a slower response when word and color are incongruent (224.9 ms difference; P less than .001). As anticipated, correct responses following correct responses were faster than were correct responses following erroneous responses, which defines PES.

In the intracranial EEG group, the investigators isolated 1,171 neurons, of which 618 were located in dACC and 553 in pre-SMA. Using a Poisson regression model and correlations with erroneous responses, the investigators identified 99 “type I” error neurons in dACC and 118 in pre-SMA, based on higher frequency of firing during erroneous responses than during correct responses. At a single-cell level, error neuron mean spike rates were highest when intracranial ERN amplitude was greatest, such that error neuron firing in dACC and pre-SMA had maximal likelihood ratios of 7.9 (P = .01) and 15.1 (P less than .001), respectively. The strength of correlation between intracranial ERN and error neuron firing rate was directly related to PES magnitude exclusively in the dACC (maximum likelihood ratio of 13.9; P = .015). In post-error trials, faster error-integrating neuron firing rates in dACC predicted greater PES (maximal likelihood ratio of 18.3; P less than .001).

The study was funded by the National Institutes of Health, the McKnight Endowment for Neuroscience, and the National Science Foundation. The authors declared no conflicts of interest.

SOURCE: Fu Z et al. Neuron. 2018 Dec 4. doi: 10.1016/j.neuron.2018.11.016

While patients with renal cell carcinoma (RCC) brain metastases are traditionally thought of as having a grim prognosis, a subset of patients may experience durable long-term survival with cytoreductive nephrectomy, authors of a retrospective study have reported.

Specifically, patients with brain lesions and no additional metastatic disease sites who underwent cytoreduction had a 2-year survival rate of 52%, according to the researchers’ analysis of data from the Surveillance, Epidemiology, and End Results (SEER) Program. 

By contrast, these patients with brain-only metastases who did not undergo the procedure had a 2-year survival of 14%, reported Gennady Bratslavsky, MD, of State University of New York, Syracuse, and his associates.

The findings are at odds with “previously accepted dogma” that surgery is inadvisable in patients with RCC with brain metastases, which is traditionally thought of as a poor-risk feature, according to Dr. Bratslavsky and his colleagues.

“These patients seem to benefit from cytoreductive nephrectomy and may potentially be excellent candidates for clinical trials,” they wrote in Urologic Oncology.

However, patient selection likely drove survival outcomes in this retrospective cohort, the authors acknowledged, adding that they did not intend to argue “for or against” the role of cytoreductive nephrectomy.

In their analysis, they identified 6,403 patients with metastatic RCC and complete information on sites of metastasis; of these, 775 (12.1%) had brain metastases.

Patients with brain metastases generally fared worse than did patients with other, non-brain metastases, with 2-year survival rates of 14.9% and 28.6%, respectively (P less than .0001); however, patients with brain-only metastases had a 2-year survival of 31% overall in this analysis.

Cytoreductive nephrectomy was performed in 40.8% of patients with brain-only metastases, versus 20.8% of patients with synchronous metastases (P less than .0001).

Brain-only metastases patients who underwent cytoreductive nephrectomy had 1-year survival of 67%, 2-year survival of 52%, and median survival of 33 months, the data show. In contrast, brain-only metastases patients who did not undergo the procedure had 1-year survival of 26%, 2-year survival of 14%, and median survival of just 5 months.

Even when the researchers included patients with brain metastases in addition to other sites, cytoreduction was associated with superior outcomes, compared with patients with non-brain metastases who did not undergo cytoreduction, the investigators said. The reported 2-year survival rates in that analysis were 34.1% for brain metastasis and cytoreduction versus 14.4% for non-brain metastasis and no cytoreduction.

While this study was retrospective and was based on limited patient data, these findings nevertheless suggest that patients with RCC and isolated brain metastases might benefit from the procedure, Dr. Bratslavsky and his coauthors said.

“We anticipate that this work will be helpful for patient counseling and for modifying future exclusion criteria in clinical trials,” they concluded.

Dr. Bratslavsky and his coauthors listed no disclosures related to their research.

SOURCE: Daugherty M et al. Urol Oncol. 2018 Dec 5. doi: 10.1016/j.urolonc.2018.10.021.

While patients with renal cell carcinoma (RCC) brain metastases are traditionally thought of as having a grim prognosis, a subset of patients may experience durable long-term survival with cytoreductive nephrectomy, authors of a retrospective study have reported.

Specifically, patients with brain lesions and no additional metastatic disease sites who underwent cytoreduction had a 2-year survival rate of 52%, according to the researchers’ analysis of data from the Surveillance, Epidemiology, and End Results (SEER) Program. 

By contrast, these patients with brain-only metastases who did not undergo the procedure had a 2-year survival of 14%, reported Gennady Bratslavsky, MD, of State University of New York, Syracuse, and his associates.

The findings are at odds with “previously accepted dogma” that surgery is inadvisable in patients with RCC with brain metastases, which is traditionally thought of as a poor-risk feature, according to Dr. Bratslavsky and his colleagues.

“These patients seem to benefit from cytoreductive nephrectomy and may potentially be excellent candidates for clinical trials,” they wrote in Urologic Oncology.

However, patient selection likely drove survival outcomes in this retrospective cohort, the authors acknowledged, adding that they did not intend to argue “for or against” the role of cytoreductive nephrectomy.

In their analysis, they identified 6,403 patients with metastatic RCC and complete information on sites of metastasis; of these, 775 (12.1%) had brain metastases.

Patients with brain metastases generally fared worse than did patients with other, non-brain metastases, with 2-year survival rates of 14.9% and 28.6%, respectively (P less than .0001); however, patients with brain-only metastases had a 2-year survival of 31% overall in this analysis.

Cytoreductive nephrectomy was performed in 40.8% of patients with brain-only metastases, versus 20.8% of patients with synchronous metastases (P less than .0001).

Brain-only metastases patients who underwent cytoreductive nephrectomy had 1-year survival of 67%, 2-year survival of 52%, and median survival of 33 months, the data show. In contrast, brain-only metastases patients who did not undergo the procedure had 1-year survival of 26%, 2-year survival of 14%, and median survival of just 5 months.

Even when the researchers included patients with brain metastases in addition to other sites, cytoreduction was associated with superior outcomes, compared with patients with non-brain metastases who did not undergo cytoreduction, the investigators said. The reported 2-year survival rates in that analysis were 34.1% for brain metastasis and cytoreduction versus 14.4% for non-brain metastasis and no cytoreduction.

While this study was retrospective and was based on limited patient data, these findings nevertheless suggest that patients with RCC and isolated brain metastases might benefit from the procedure, Dr. Bratslavsky and his coauthors said.

“We anticipate that this work will be helpful for patient counseling and for modifying future exclusion criteria in clinical trials,” they concluded.

Dr. Bratslavsky and his coauthors listed no disclosures related to their research.

SOURCE: Daugherty M et al. Urol Oncol. 2018 Dec 5. doi: 10.1016/j.urolonc.2018.10.021.

While patients with renal cell carcinoma (RCC) brain metastases are traditionally thought of as having a grim prognosis, a subset of patients may experience durable long-term survival with cytoreductive nephrectomy, authors of a retrospective study have reported.

Specifically, patients with brain lesions and no additional metastatic disease sites who underwent cytoreduction had a 2-year survival rate of 52%, according to the researchers’ analysis of data from the Surveillance, Epidemiology, and End Results (SEER) Program. 

By contrast, these patients with brain-only metastases who did not undergo the procedure had a 2-year survival of 14%, reported Gennady Bratslavsky, MD, of State University of New York, Syracuse, and his associates.

The findings are at odds with “previously accepted dogma” that surgery is inadvisable in patients with RCC with brain metastases, which is traditionally thought of as a poor-risk feature, according to Dr. Bratslavsky and his colleagues.

“These patients seem to benefit from cytoreductive nephrectomy and may potentially be excellent candidates for clinical trials,” they wrote in Urologic Oncology.

However, patient selection likely drove survival outcomes in this retrospective cohort, the authors acknowledged, adding that they did not intend to argue “for or against” the role of cytoreductive nephrectomy.

In their analysis, they identified 6,403 patients with metastatic RCC and complete information on sites of metastasis; of these, 775 (12.1%) had brain metastases.

Patients with brain metastases generally fared worse than did patients with other, non-brain metastases, with 2-year survival rates of 14.9% and 28.6%, respectively (P less than .0001); however, patients with brain-only metastases had a 2-year survival of 31% overall in this analysis.

Cytoreductive nephrectomy was performed in 40.8% of patients with brain-only metastases, versus 20.8% of patients with synchronous metastases (P less than .0001).

Brain-only metastases patients who underwent cytoreductive nephrectomy had 1-year survival of 67%, 2-year survival of 52%, and median survival of 33 months, the data show. In contrast, brain-only metastases patients who did not undergo the procedure had 1-year survival of 26%, 2-year survival of 14%, and median survival of just 5 months.

Even when the researchers included patients with brain metastases in addition to other sites, cytoreduction was associated with superior outcomes, compared with patients with non-brain metastases who did not undergo cytoreduction, the investigators said. The reported 2-year survival rates in that analysis were 34.1% for brain metastasis and cytoreduction versus 14.4% for non-brain metastasis and no cytoreduction.

While this study was retrospective and was based on limited patient data, these findings nevertheless suggest that patients with RCC and isolated brain metastases might benefit from the procedure, Dr. Bratslavsky and his coauthors said.

“We anticipate that this work will be helpful for patient counseling and for modifying future exclusion criteria in clinical trials,” they concluded.

Dr. Bratslavsky and his coauthors listed no disclosures related to their research.

SOURCE: Daugherty M et al. Urol Oncol. 2018 Dec 5. doi: 10.1016/j.urolonc.2018.10.021.

In this episode, Roberto Lewis-Fernandez, MD, joins MDedge Psychiatry Editor-in-Chief, Lorenzo Norris, MD, to talk about how cultural assessments work and why they’re imperative to person-centered care. More from Dr. Lewis-Fernandez, Curbside Consult: Chinese American man with high risk of psychosis.

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In this episode, Roberto Lewis-Fernandez, MD, joins MDedge Psychiatry Editor-in-Chief, Lorenzo Norris, MD, to talk about how cultural assessments work and why they’re imperative to person-centered care. More from Dr. Lewis-Fernandez, Curbside Consult: Chinese American man with high risk of psychosis.

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In this episode, Roberto Lewis-Fernandez, MD, joins MDedge Psychiatry Editor-in-Chief, Lorenzo Norris, MD, to talk about how cultural assessments work and why they’re imperative to person-centered care. More from Dr. Lewis-Fernandez, Curbside Consult: Chinese American man with high risk of psychosis.

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Spotify
 

According to a scientific statement by the AHA on Arteriosclerosis, Thrombosis, and Vascular Biology, the benefits of statins highly offset the associated risks in appropriate patients. Also today, acute stroke thrombolysis worked safely despite GI bleed or malignancy, legal advice on what to do if a patient sues you, and the link between childhood asthma and obesity.

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Apple Podcasts
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Spotify
 

According to a scientific statement by the AHA on Arteriosclerosis, Thrombosis, and Vascular Biology, the benefits of statins highly offset the associated risks in appropriate patients. Also today, acute stroke thrombolysis worked safely despite GI bleed or malignancy, legal advice on what to do if a patient sues you, and the link between childhood asthma and obesity.

Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
 

According to a scientific statement by the AHA on Arteriosclerosis, Thrombosis, and Vascular Biology, the benefits of statins highly offset the associated risks in appropriate patients. Also today, acute stroke thrombolysis worked safely despite GI bleed or malignancy, legal advice on what to do if a patient sues you, and the link between childhood asthma and obesity.

Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify