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Resectability increased almost fourfold in patients with pancreatic cancer after neoadjuvant therapy that included intensity-modulated radiation therapy (IMRT), results of three small trials showed.

Initially, 14 of 81 patients (17%) had resectable disease. After neoadjuvant treatment, 51 patients (63%) underwent surgery, according to a report at the Gastrointestinal Cancers Symposium.

Almost 80% of patients with borderline-resectable cancer could have surgery after neoadjuvant therapy that included IMRT.

"IMRT is well tolerated and should be considered as part of a neoadjuvant treatment strategy for pancreatic adenocarcinoma," lead researcher Martin Palmeri, MD, of Dartmouth-Hitchcock Medical Center in Lebanon, N.H., said in an interview.

"A significant percentage of borderline patients were rendered resectable with neoadjuvant therapy, and they had an overall survival comparable to that of patients who were resectable at presentation. A randomized study is needed to compare the neoadjuvant approach with conventional postoperative treatment for patients with pancreatic cancer."

Though long-term diagnosis for pancreatic cancer remains poor, surgical resection offers the best chance for a favorable outcome. Unfortunately, most patients have advanced disease or otherwise unfavorable characteristics that rule out surgery.

Encouraging results with neoadjuvant therapy have increased interest in evaluation of strategies to downstage or convert unresectable and borderline-resectable cancer to resectable disease. A growing number of strategies includes IMRT, which permits delivery of high radiation doses to the tumor and spares exposure to surrounding normal tissue.

Palmeri reported data from a retrospective analysis of three small trials of neoadjuvant IMRT paired with a cytotoxic radiosensitizer to improve resectability of pancreatic adenocarcinoma. The trials employed three different regimens:

• Gemcitabine-docetaxel (Taxotere) followed by concurrent gemcitabine and IMRT
• Concurrent cetuximab (Erbitux), gemcitabine, and IMRT
• Concurrent gemcitabine-IMRT

All three regimens employed a total radiation dose of 54 Gy administered in 28 fractions.

After completion of neoadjuvant therapy, patients were restaged by CT, and a gastrointestinal tumor board evaluated the cancer's suitability for resection. Patients who underwent surgery received additional radiation intraoperatively.

Before neoadjuvant therapy and restaging, 14 patients had resectable cancer, 38 had borderline resectable disease, and 29 had unresectable cancer.

After treatment, 30 (78%) of 38 borderline tumors were removed, as were 11 (39%) of the 29 initially unresectable cancers.

Median overall survival for the 81 patients was 22 months. The population survival included a median of 23 months for patients with initially resectable cancer, 28 months for borderline-resectable disease, and 14 months for the patients with unresectable tumors (P=0.002 for both the resectable and borderline-resectable groups vs. the unresectable group).

Patients with no evidence of residual disease after surgery had a median overall survival of 28 months, compared with 24.3 months for patients with positive surgical margins and 11.7 months for unresectable disease (P<0.001).

With respect to the different neoadjuvant regimens, the gemcitabine-cetuximab-IMRT regimen was associated with the best median survival (27 months), but that did not differ significantly from the 18-month median survival with the other two regimens.

"These results reemphasize the importance of resectability," said Palmeri. "If we can convert more borderline and unresectable disease to resectable, we can offer a better diagnosis for more patients with pancreatic cancer."

Source: Gastrointestinal Cancers Symposium