PET-Detected Response to Chemo Means Better Prognosis in Esophagogastric Junction Cancer

Patients with locally advanced adenocarcinoma of the esophagogastric junction have a better prognosis if their cancer shows an early metabolic response to preoperative chemotherapy, as detected by positron emission tomography, new data show.

In a prospective study known as MUNICON-2 that was conducted in Germany, 59% of patients had a PET-detected response after 2 weeks of chemotherapy, investigators said in a press briefing in advance of a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.

Even though the nonresponders were then given intensified treatment with chemoradiation, the responders were still more likely to be able to undergo curative resection and had a 4-year rate of progression-free survival that was twice as high as that of the nonresponders.

"Early metabolic response assessment, after only 2 weeks of preoperative chemotherapy, performed with fluorodeoxyglucose (FDG)-PET, is a feasible approach and allows for a response-guided treatment," lead investigator Dr. Florian Lordick said in the press briefing.

"Unfortunately, we found that survival is still poorer in PET nonresponders, despite the addition of radiation," he continued. "Therefore, we can conclude that early metabolic response assessment by FDG-PET allows us to identify patients with a very poor tumor biology."

The investigators studied 56 patients with locally advanced, nonmetastatic adenocarcinoma of the esophagogastric junction of types I and II (cT3/4,Nx,M0). The patients underwent FDG-PET imaging before and after 2 weeks of platinum- and 5-fluorouracil-based chemotherapy.

They were defined as having a response if the tumor’s standardized uptake value decreased by at least 35%, according to Dr. Lordick, director of the department of hematology and oncology at Klinikum Braunschweig in Brunswick, Germany, and a senior lecturer at Hannover Medical School.

Responders received more of the same chemotherapy for a total duration of 3 months and then underwent surgery. Nonresponders were given salvage chemoradiation consisting of 32 Gy of external beam radiation therapy plus daily cisplatin, and then underwent surgery.

"The expectation was that by adding radiation therapy to those patients not responding to chemotherapy, we might improve their prognosis, we might improve local control, we might improve survival compared to historic controls," he commented.

The 56 patients studied had a median age of 62 years; 91% were male, and 77% had an ECOG Performance Status score of 0. In terms of disease characteristics, 70% of patients had type I tumors, 93% had an ultrasound T3 stage, and 100% had clinically node-positive disease.

A PET-detected response to chemotherapy was found in 59% (33 patients). Responders were more likely than were nonresponders (23 patients) to be able to be able to undergo curative resection (82% vs 70%, respectively), although the difference was not statistically significant.

The rate of major histologic remission, defined as having less than 10% residual tumor, was also higher for responders (36% vs 26%).

After a median follow-up of 38 months, the 4-year Kaplan-Meier estimate of progression-free survival was about 60% for PET responders, compared with 30% for PET nonresponders.

Responders fared much better in terms of median event-free survival (not reached, vs 15.4 months) and median duration of overall survival (not reached, vs 18.3 months).

"The addition of radiation therapy has some local effect, as we saw in the resection specimens" from the nonresponders, Dr. Lordick commented. "But it seems that it was not strong enough to change the tumor biology of these patients."

"The next step that we want to take now on a multicenter level within the EORTC (European Organisation for Research and Treatment of Cancer) is to ... study different alterations of treatment in PET nonresponders by adding an alternative chemotherapy regimen and new biologically targeted therapies," concluded Dr. Lordick.

The study’s findings exemplify the use of predictors to individualize therapy, according to Dr. Jennifer C. Obel, moderator of the press briefing and a medical oncologist with the NorthShore University HealthSystem in Evanston, Ill.

"This approach allows us to either stop therapies that have minimal benefit or continue those that are likely helping patients live longer," she commented.

"Really, this study is quite intriguing because it demonstrates that patients with no response on PET scan after limited chemotherapy have a poor outcome," said Dr. Obel. "Hopefully, in the future, we can use this technology to quickly move to other therapies and evaluate whether they are helping the patient or not."

Dr. Lordick and Dr. Obel both reported that they did not have any relevant conflicts of interest.

Patients with locally advanced adenocarcinoma of the esophagogastric junction have a better prognosis if their cancer shows an early metabolic response to preoperative chemotherapy, as detected by positron emission tomography, new data show.

In a prospective study known as MUNICON-2 that was conducted in Germany, 59% of patients had a PET-detected response after 2 weeks of chemotherapy, investigators said in a press briefing in advance of a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.

Even though the nonresponders were then given intensified treatment with chemoradiation, the responders were still more likely to be able to undergo curative resection and had a 4-year rate of progression-free survival that was twice as high as that of the nonresponders.

"Early metabolic response assessment, after only 2 weeks of preoperative chemotherapy, performed with fluorodeoxyglucose (FDG)-PET, is a feasible approach and allows for a response-guided treatment," lead investigator Dr. Florian Lordick said in the press briefing.

"Unfortunately, we found that survival is still poorer in PET nonresponders, despite the addition of radiation," he continued. "Therefore, we can conclude that early metabolic response assessment by FDG-PET allows us to identify patients with a very poor tumor biology."

The investigators studied 56 patients with locally advanced, nonmetastatic adenocarcinoma of the esophagogastric junction of types I and II (cT3/4,Nx,M0). The patients underwent FDG-PET imaging before and after 2 weeks of platinum- and 5-fluorouracil-based chemotherapy.

They were defined as having a response if the tumor’s standardized uptake value decreased by at least 35%, according to Dr. Lordick, director of the department of hematology and oncology at Klinikum Braunschweig in Brunswick, Germany, and a senior lecturer at Hannover Medical School.

Responders received more of the same chemotherapy for a total duration of 3 months and then underwent surgery. Nonresponders were given salvage chemoradiation consisting of 32 Gy of external beam radiation therapy plus daily cisplatin, and then underwent surgery.

"The expectation was that by adding radiation therapy to those patients not responding to chemotherapy, we might improve their prognosis, we might improve local control, we might improve survival compared to historic controls," he commented.

The 56 patients studied had a median age of 62 years; 91% were male, and 77% had an ECOG Performance Status score of 0. In terms of disease characteristics, 70% of patients had type I tumors, 93% had an ultrasound T3 stage, and 100% had clinically node-positive disease.

A PET-detected response to chemotherapy was found in 59% (33 patients). Responders were more likely than were nonresponders (23 patients) to be able to be able to undergo curative resection (82% vs 70%, respectively), although the difference was not statistically significant.

The rate of major histologic remission, defined as having less than 10% residual tumor, was also higher for responders (36% vs 26%).

After a median follow-up of 38 months, the 4-year Kaplan-Meier estimate of progression-free survival was about 60% for PET responders, compared with 30% for PET nonresponders.

Responders fared much better in terms of median event-free survival (not reached, vs 15.4 months) and median duration of overall survival (not reached, vs 18.3 months).

"The addition of radiation therapy has some local effect, as we saw in the resection specimens" from the nonresponders, Dr. Lordick commented. "But it seems that it was not strong enough to change the tumor biology of these patients."

"The next step that we want to take now on a multicenter level within the EORTC (European Organisation for Research and Treatment of Cancer) is to ... study different alterations of treatment in PET nonresponders by adding an alternative chemotherapy regimen and new biologically targeted therapies," concluded Dr. Lordick.

The study’s findings exemplify the use of predictors to individualize therapy, according to Dr. Jennifer C. Obel, moderator of the press briefing and a medical oncologist with the NorthShore University HealthSystem in Evanston, Ill.

"This approach allows us to either stop therapies that have minimal benefit or continue those that are likely helping patients live longer," she commented.

"Really, this study is quite intriguing because it demonstrates that patients with no response on PET scan after limited chemotherapy have a poor outcome," said Dr. Obel. "Hopefully, in the future, we can use this technology to quickly move to other therapies and evaluate whether they are helping the patient or not."

Dr. Lordick and Dr. Obel both reported that they did not have any relevant conflicts of interest.

Patients with locally advanced adenocarcinoma of the esophagogastric junction have a better prognosis if their cancer shows an early metabolic response to preoperative chemotherapy, as detected by positron emission tomography, new data show.

In a prospective study known as MUNICON-2 that was conducted in Germany, 59% of patients had a PET-detected response after 2 weeks of chemotherapy, investigators said in a press briefing in advance of a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.

Even though the nonresponders were then given intensified treatment with chemoradiation, the responders were still more likely to be able to undergo curative resection and had a 4-year rate of progression-free survival that was twice as high as that of the nonresponders.

"Early metabolic response assessment, after only 2 weeks of preoperative chemotherapy, performed with fluorodeoxyglucose (FDG)-PET, is a feasible approach and allows for a response-guided treatment," lead investigator Dr. Florian Lordick said in the press briefing.

"Unfortunately, we found that survival is still poorer in PET nonresponders, despite the addition of radiation," he continued. "Therefore, we can conclude that early metabolic response assessment by FDG-PET allows us to identify patients with a very poor tumor biology."

The investigators studied 56 patients with locally advanced, nonmetastatic adenocarcinoma of the esophagogastric junction of types I and II (cT3/4,Nx,M0). The patients underwent FDG-PET imaging before and after 2 weeks of platinum- and 5-fluorouracil-based chemotherapy.

They were defined as having a response if the tumor’s standardized uptake value decreased by at least 35%, according to Dr. Lordick, director of the department of hematology and oncology at Klinikum Braunschweig in Brunswick, Germany, and a senior lecturer at Hannover Medical School.

Responders received more of the same chemotherapy for a total duration of 3 months and then underwent surgery. Nonresponders were given salvage chemoradiation consisting of 32 Gy of external beam radiation therapy plus daily cisplatin, and then underwent surgery.

"The expectation was that by adding radiation therapy to those patients not responding to chemotherapy, we might improve their prognosis, we might improve local control, we might improve survival compared to historic controls," he commented.

The 56 patients studied had a median age of 62 years; 91% were male, and 77% had an ECOG Performance Status score of 0. In terms of disease characteristics, 70% of patients had type I tumors, 93% had an ultrasound T3 stage, and 100% had clinically node-positive disease.

A PET-detected response to chemotherapy was found in 59% (33 patients). Responders were more likely than were nonresponders (23 patients) to be able to be able to undergo curative resection (82% vs 70%, respectively), although the difference was not statistically significant.

The rate of major histologic remission, defined as having less than 10% residual tumor, was also higher for responders (36% vs 26%).

After a median follow-up of 38 months, the 4-year Kaplan-Meier estimate of progression-free survival was about 60% for PET responders, compared with 30% for PET nonresponders.

Responders fared much better in terms of median event-free survival (not reached, vs 15.4 months) and median duration of overall survival (not reached, vs 18.3 months).

"The addition of radiation therapy has some local effect, as we saw in the resection specimens" from the nonresponders, Dr. Lordick commented. "But it seems that it was not strong enough to change the tumor biology of these patients."

"The next step that we want to take now on a multicenter level within the EORTC (European Organisation for Research and Treatment of Cancer) is to ... study different alterations of treatment in PET nonresponders by adding an alternative chemotherapy regimen and new biologically targeted therapies," concluded Dr. Lordick.

The study’s findings exemplify the use of predictors to individualize therapy, according to Dr. Jennifer C. Obel, moderator of the press briefing and a medical oncologist with the NorthShore University HealthSystem in Evanston, Ill.

"This approach allows us to either stop therapies that have minimal benefit or continue those that are likely helping patients live longer," she commented.

"Really, this study is quite intriguing because it demonstrates that patients with no response on PET scan after limited chemotherapy have a poor outcome," said Dr. Obel. "Hopefully, in the future, we can use this technology to quickly move to other therapies and evaluate whether they are helping the patient or not."

Dr. Lordick and Dr. Obel both reported that they did not have any relevant conflicts of interest.