In the Journals

Clinical factors predict response to therapy for pancreatic cancer

Researchers identified young age, low baseline cancer antigen 19-9 and use of gemcitabine as a radiosensitizer as clinical factors associated with a major pathologic response following preoperative therapy for pancreatic ductal adenocarcinoma, according to results of a retrospective review.

Results also showed few patients with pancreatic ductal adenocarcinoma experienced a complete response, but those who did had significantly improved prognosis.

“Importantly, we identified a patient-related factor, tumor-related factor and treatment-related factor that were each independently associated with development of a major pathologic response,” Matthew H.G. Katz, MD, FACS, associate professor in the department of surgical oncology at The University of Texas MD Anderson Cancer Center, and colleagues wrote. “[These factors] may define a group of patients most likely to experience a significant response to preoperative therapy.”

Clinical features predictive of a pathologic response to therapy have been observed for breast, rectal and esophageal cancers. However, researchers have lacked complete understanding of which factors lead to complete response for localized pancreatic ductal adenocarcinoma.

Researchers used a prospectively maintained database to identify 583 patients (mean age, 63.7 years; 53% men) with confirmed pancreatic ductal adenocarcinoma treated with preoperative therapy prior to pancreatectomy at MD Anderson between 1990 and 2015.

Of these, 36.5% received systemic chemotherapy alone, 44.8% received chemoradiation alone, and 48.7% received chemotherapy with chemoradiation prior to pancreatoduodenectomy (n = 514), distal pancreatectomy (n = 62) or total pancreatectomy (n = 7).

Logistic regression evaluated clinical variables associated with a major pathologic response, defined as presence of less than 5% of residual cancer cells.

Seventy-seven patients (13.2%) experienced a major pathologic response, which included 23 patients (3.9%) with a complete pathologic response.

Patients who experienced a major response demonstrated longer median OS than patients who did not (73.4 months vs. 32.2 months; P < .001).

Compared with patients who did not have a major response, patients who did were younger (mean age, 61.5 years vs. 64.1 years; P = .02), had cancer antigen 19-9 levels less than 200 U/mL (70.1% vs. 56.9%; P = .03) and appeared less likely to have received postoperative chemotherapy (18.2% vs. 37%; P = .001).

Multivariate logistical regression showed younger age, baseline serum cancer antigen 19-9 levels less than 200 U/mL and gemcitabine as a radiosensitizer were associated with a major response.

The rate of major pathologic response increased with the number of predictive factors (no factors, 7.5%; one factor, 12.7%; two factors, 16.9%; three factors, 35.7%; P = .009), the researchers wrote.

“Given [pathologic response’s] association with long-term survival, better predictors of response and more effective preoperative regimens should be aggressively sought,” the researchers wrote.

The study results suggest the importance of discouraging extensive use of neoadjuvant treatment outside of clinical trials for primary resectable pancreatic cancer, Marco Del Chiaro, MD, PhD, of the division of surgery at Center for Digestive Disease at Karolinska University Hospital in Sweden, and colleagues wrote in a related editorial.

“To further stress the concept, considering the low clinical response rate associated even with the best medical treatment available for [pancreatic ductal adenocarcinoma], it would not be unlikely that most patients undergoing neoadjuvant treatment will progress under the therapy,” they wrote. “It could be ethically and practically very challenging to enroll patients for specific clinical trials on this issue.” – by Melinda Stevens

Disclosures: The authors report no relevant financial disclosures.

Researchers identified young age, low baseline cancer antigen 19-9 and use of gemcitabine as a radiosensitizer as clinical factors associated with a major pathologic response following preoperative therapy for pancreatic ductal adenocarcinoma, according to results of a retrospective review.

Results also showed few patients with pancreatic ductal adenocarcinoma experienced a complete response, but those who did had significantly improved prognosis.

“Importantly, we identified a patient-related factor, tumor-related factor and treatment-related factor that were each independently associated with development of a major pathologic response,” Matthew H.G. Katz, MD, FACS, associate professor in the department of surgical oncology at The University of Texas MD Anderson Cancer Center, and colleagues wrote. “[These factors] may define a group of patients most likely to experience a significant response to preoperative therapy.”

Clinical features predictive of a pathologic response to therapy have been observed for breast, rectal and esophageal cancers. However, researchers have lacked complete understanding of which factors lead to complete response for localized pancreatic ductal adenocarcinoma.

Researchers used a prospectively maintained database to identify 583 patients (mean age, 63.7 years; 53% men) with confirmed pancreatic ductal adenocarcinoma treated with preoperative therapy prior to pancreatectomy at MD Anderson between 1990 and 2015.

Of these, 36.5% received systemic chemotherapy alone, 44.8% received chemoradiation alone, and 48.7% received chemotherapy with chemoradiation prior to pancreatoduodenectomy (n = 514), distal pancreatectomy (n = 62) or total pancreatectomy (n = 7).

Logistic regression evaluated clinical variables associated with a major pathologic response, defined as presence of less than 5% of residual cancer cells.

Seventy-seven patients (13.2%) experienced a major pathologic response, which included 23 patients (3.9%) with a complete pathologic response.

Patients who experienced a major response demonstrated longer median OS than patients who did not (73.4 months vs. 32.2 months; P < .001).

Compared with patients who did not have a major response, patients who did were younger (mean age, 61.5 years vs. 64.1 years; P = .02), had cancer antigen 19-9 levels less than 200 U/mL (70.1% vs. 56.9%; P = .03) and appeared less likely to have received postoperative chemotherapy (18.2% vs. 37%; P = .001).

Multivariate logistical regression showed younger age, baseline serum cancer antigen 19-9 levels less than 200 U/mL and gemcitabine as a radiosensitizer were associated with a major response.

The rate of major pathologic response increased with the number of predictive factors (no factors, 7.5%; one factor, 12.7%; two factors, 16.9%; three factors, 35.7%; P = .009), the researchers wrote.

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“Given [pathologic response’s] association with long-term survival, better predictors of response and more effective preoperative regimens should be aggressively sought,” the researchers wrote.

The study results suggest the importance of discouraging extensive use of neoadjuvant treatment outside of clinical trials for primary resectable pancreatic cancer, Marco Del Chiaro, MD, PhD, of the division of surgery at Center for Digestive Disease at Karolinska University Hospital in Sweden, and colleagues wrote in a related editorial.

“To further stress the concept, considering the low clinical response rate associated even with the best medical treatment available for [pancreatic ductal adenocarcinoma], it would not be unlikely that most patients undergoing neoadjuvant treatment will progress under the therapy,” they wrote. “It could be ethically and practically very challenging to enroll patients for specific clinical trials on this issue.” – by Melinda Stevens

Disclosures: The authors report no relevant financial disclosures.