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TOPLINE
In a retrospective cohort study, patients with pancreatic ductal adenocarcinoma (PDAC) who received neoadjuvant chemotherapy (NAC) plus radiotherapy showed improved pathological response compared with those who received NAC alone. But their recurrence rates and overall survival were no better.
METHODOLOGY
- The role of radiotherapy in the neoadjuvant treatment of patients with resectable or borderline-resectable PDAC remains controversial. Most trials have evaluated multimodal neoadjuvant approaches vs upfront surgery or included treatment arms with differing chemotherapy regimens or use of radiotherapy — making it difficult to discern the incremental benefit of radiotherapy.
- Researchers conducted a retrospective propensity score-matched cohort study of 800 patients (median age, 65 years) who underwent pancreatic cancer resection between 2015 and 2023 at two referral centers in the US and Italy, with a median follow-up of 44 months.
- All patients were treated with combined folinic acid, fluorouracil, irinotecan, and oxaliplatin or gemcitabine/nab-paclitaxel, with or without preoperative radiation.
- Treatment groups were matched in a 1:1 ratio on the basis of age, sex, comorbidity, tumor characteristics, baseline CA19-9 level, resectability status, and chemotherapy exposure, resulting in 226 patients per group for analysis. The main outcomes were event-free survival, recurrence patterns, and overall survival.
TAKEAWAY
- The addition of radiotherapy was associated with higher rates of pathological complete response (6.6% vs 4.4%), node-negative disease (61.5% vs 33.6%), and R0 resection (85% vs 52.2%) than with NAC alone.
- However, radiotherapy was not associated with improved event-free survival (hazard ratio [HR], 1.10; P = .38) or overall survival (HR, 1.02; P = .84). Median event-free survival was 19 months vs 22 months with chemotherapy plus radiation vs NAC alone. Median overall survival was 42 months in both groups.
- Recurrence patterns were also similar between groups, with distant recurrence as the predominant first site of failure in both. Cumulative incidence of locoregional recurrence did not differ (subdistribution HR, 0.90; P = .71).
- In patients with a baseline CA19-9 level ≥ 500 U/mL, the addition of radiotherapy was associated with worse event-free survival (HR, 2.14; P = .002) and overall survival (HR, 1.80; P = .02) than with NAC alone.
IN PRACTICE
“These findings suggest that improving locoregional control is unlikely to meaningfully alter the natural history of this disease in the absence of more effective treatment of micrometastatic disease,” the study authors wrote. Future research, they added, should look at whether selective use of radiotherapy increases resectability of PDAC and whether certain patient subgroups benefit from the addition of radiotherapy, either before or after surgery.
SOURCE
The study, led by Federico De Stefano, MD, of Massachusetts General Hospital and Harvard Medical School in Boston, was published online in JAMA Surgery.
LIMITATIONS
Treatment strategies were inherently linked to the institution, and institution-specific factors may have affected the results. Although propensity-score matching was used, unmeasured confounding cannot be excluded. Only patients who underwent surgical resection were included, limiting the ability to evaluate the impact of radiotherapy across the entire treatment pathway.
DISCLOSURES
Several co-authors reported financial relationships with companies including Bayer, GE HealthCare, and Sirtex Medical, outside of the submitted work. Full disclosures are noted in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
