Addition of Chemoradiation to Adjuvant Systemic Therapy: Differences in Node-Negative vs Node-Positive Pancreatic Cancer

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Researchers have examined whether adding chemoradiation to adjuvant systemic therapy may improve survival outcomes in patients with resected periampullary pancreatic adenocarcinoma, according to recent findings presented by Abrams et al at the 2024 ASCO Annual Meeting (Abstract 4005).

Study Methods and Results

In the NRG-RTOG 0848 trial, researchers compared the efficacy of adjuvant chemotherapy with or without chemoradiation in patients with resected periampullary pancreatic adenocarcinoma. These most recent findings were from the second step of the trial.

“This trial was initially designed to address the need for a more effective and tolerable adjuvant systemic therapy for pancreatic [adenocarcinoma]. When this study was developed, gemcitabine was the only effective treatment available, and this treatment commonly corresponds with distant and local failures for this patient population. Therefore, we designed NRG-RTOG 0848 to evaluate the role of adjuvant radiation with [capecitabine or] fluorouracil following surgical resection and adjuvant systemic [therapy] to see if this additional treatment would further improve survival outcomes for patients,” emphasized lead study author Ross A. Abrams, MD, of the Rush University Medical Center.

In the first step of the trial, the researchers initiated treatment with five cycles of systemic therapy. Patients were randomly assigned to receive either gemcitabine alone (arm 1) or in combination with erlotinib (arm 2). However, following the results of the recent LAP07 trial, the randomization was stopped, and all patients were registered at the first step to receive gemcitabine alone. After 2 years, the trial was amended to allow oxaliplatin-based combination chemotherapy regimens.

Following the first step, the patients were evaluated to confirm whether they had no disease progression, and those whose cancer didn’t progress were stratified by nodal status, CA 19-9, surgical margins, and adjuvant systemic therapy. The researchers then randomly assigned 354 patients to receive radiotherapy for 1 month on one of two treatment arms: gemcitabine or combination chemotherapy (arm 3) or gemcitabine or combination chemotherapy followed by chemoradiation with either capecitabine or fluorouracil (arm 4).

The researchers noted that the median follow-up was 2.2 years for all patients (0.02–12.8 years) and 7.4 years for living patients (0.02–12.8 years). The primary endpoint of the trial was overall survival.

The researchers discovered that the addition of chemoradiation to adjuvant systemic therapy did not improve overall survival among all patients involved in the trial; however, overall survival was improved among patients with node-negative disease. Among the patients with node-negative disease, compared with those who received chemotherapy alone, patients who received chemotherapy plus chemoradiation had a 5-year overall survival rate of 48.1% vs 28.6%. The researchers found no statistically significant differences in the overall survival rates between the treatment arms among patients with node-positive pancreatic adenocarcinoma. Further, the addition of chemoradiation to adjuvant systemic therapy improved disease-free survival, particularly among patients with node-negative disease. For node-negative disease, the patients given chemotherapy plus chemoradiation experienced a 5-year disease-free survival rate of 21.4% vs 15.2% among those given chemotherapy alone.

The researchers reported that grade 4 or 5 adverse events were similar between those who received chemotherapy plus chemoradiation and those who received chemotherapy alone (6% vs 5%, respectively).


The researchers indicated that future research may be needed to assess an alternative method to improve disease-free survival and overall survival in patients with node-positive pancreatic adenocarcinoma who are at high risk of disease progression. Additionally, they proposed that it may be valuable to investigate whether adjuvant therapy could yield more benefit in these patient populations if it were combined with a more effective systemic therapy.

“The results of NRG-RTOG 0848 suggests that, with the appropriate planning and considerations, chemoradiation could be utilized in further testing for future adjuvant and neoadjuvant trials,” Dr. Abrams concluded.

Disclosure: The research in this study was supported by grants from the National Cancer Institute of the National Institutes of Health. For full disclosures of the study authors, visit

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