Does post-operative radiation therapy offer a survival advantage in pancreatic cancer?

From the Guidelines

Post-operative radiation therapy in pancreatic cancer offers limited survival advantage for most patients. The standard of care for resectable pancreatic cancer is surgery followed by adjuvant chemotherapy, typically with modified FOLFIRINOX (oxaliplatin, irinotecan, fluorouracil, and leucovorin) or gemcitabine plus capecitabine for 6 months, as supported by the NCCN guidelines 1. Radiation therapy is generally not routinely recommended in the adjuvant setting as multiple randomized trials have failed to demonstrate a consistent overall survival benefit, including the ESPAC-1 trial which showed no benefit for chemoradiotherapy but a probable survival advantage for prolonged chemotherapy after resection 1. However, radiation may be considered in specific situations such as positive surgical margins (R1 resection) or locally advanced disease where it might help with local control. When radiation is used, it's typically delivered as 45-54 Gy in 1.8-2 Gy fractions over 5-6 weeks, sometimes with concurrent chemotherapy like capecitabine or 5-FU as a radiosensitizer. The limited benefit of radiation likely stems from pancreatic cancer's propensity for early systemic spread, making local therapies less impactful on overall survival compared to systemic treatments that address micrometastatic disease.

Some key points to consider in the management of pancreatic cancer include:

• The importance of adjuvant chemotherapy in improving overall survival, with options including gemcitabine plus capecitabine or modified FOLFIRINOX 1
• The role of clinical trials in providing the best management options for patients with pancreatic cancer, as emphasized by the NCCN guidelines 1
• The need for individualized treatment decisions through multidisciplinary tumor board discussions, considering the patient's specific disease characteristics, performance status, and treatment goals.

In terms of specific treatment recommendations, the use of adjuvant chemotherapy with gemcitabine plus capecitabine is supported by the ESPAC-4 study, which demonstrated superiority compared to gemcitabine alone (HR, 0.82; 95% CI, 0.68,0.98; P = .032) 1. This study provides high-quality evidence for the use of adjuvant chemotherapy in pancreatic cancer, and its findings should be considered in treatment decisions.

From the Research

Post-Operative Radiation in Pancreatic Cancer

• The use of post-operative radiation in pancreatic cancer is a topic of ongoing debate, with some studies suggesting a potential survival advantage in certain cases 2.
• A meta-analysis of prospective randomized studies found that adjuvant radiotherapy was not beneficial in treating all patients with pancreatic cancer, but may be beneficial for a subset of cases with potential residual local disease 2.
• The role of radiation therapy in resected pancreatic cancer is controversial, but it is used routinely to treat positive margins after pancreatic cancer surgery 3.
• Chemoradiation may improve the survival of patients with incompletely resected tumors (R1), although this remains to be confirmed by a prospective trial 4.
• Neoadjuvant chemoradiation is a promising treatment, especially for patients with borderline resectable tumors 4.

Survival Advantage

• A retrospective study of 63 patients with stage I/II pancreatic cancer found that concurrent chemoradiation using capecitabine as a radiosensitizer in the adjuvant setting was completed by the vast majority of patients, with a median survival of 23.5 months and 1-, 2-, and 3-year survival rates of 80%, 35%, and 25%, respectively 5.
• A review of the literature found that the current role of radiation in pancreatic cancer is highly debated, with emerging concepts such as dose-escalated radiation, magnetic resonance-guided radiation therapy, and particle therapy potentially changing the role of radiation in the future 6.
• The use of radiation therapy in pancreatic cancer is evolving, with advancements in treatment modalities, delivery techniques, and combination approaches 3.

Clinical Scenarios

• The role of radiation in the neoadjuvant, definitive, and adjuvant settings for pancreatic cancer is reviewed in the context of historical and modern clinical studies 6.
• Intensity modulated radiation therapy and stereotactic body radiation therapy are modern techniques that may improve outcomes for patients with pancreatic cancer 6.
• The treated volumes have been reduced to improve tolerance, and tumor movements induced by breathing should be taken into account 4.