Comparison of the results of regional chemotherapy alone and in combination with conform radiotherapy in patients with curable pancreatic head cancer and high surgical risk

Rationale: Curative surgery with subsequent adjuvant chemotherapy is the main combination treatment for pancreatic cancer (PC). However, there is the group of patients with resectable tumors who cannot be resected due to severe comorbidities and as such are subjects for palliative anti-tumor treatment. Aim: To evaluate safety and efficacy of regional chemotherapy (RCT) combined with distant radiation therapy (DRT) at daily dose split regimen, compared to RCT alone in PC patients assessed as inoperable. Methods: This retrospective analysis included 71 patients with a resectable ductal adenocarcinoma of the pancreatic head without distant metastases (T2–3N0–2M0), with American Society of Anesthesiologists (ASA) physical status III (a patient with severe systemic disease, inoperable), Eastern Cooperative Oncology Group performance status (ECOG) 1 to 2, who had received RCT alone from 2010 to 2015 (n = 38) or in combination with conform DRT from 2016 to 2024 (n = 33). The subsequent follow-up was censored at February 1, 2025. All patients have received RCT as chemoembolization of the pancreatic head with suspension of gemcitabine and lipiodol followed by intra-arterial infusion of gemcitabine and oxaliplatin during at least 2 cycles. At the 2nd step of treatment, the patients of the main study group received 3D conform daily split-dose DRT (single dose 2 Gy, 4 Gy daily, up to a total physical dose of 50 Gy). Results: The mean age of the patients in the combination chemoradiation therapy group (n = 33) was 70 years, in the RCT alone group (n = 38) 66.5 years (p = 0.8). The study groups were comparable for the ECOG status (p = 0.6), CA 19-9 (p = 0.6), and disease stage (p = 0.6). There were no deaths and adverse events above NCI CTCAE, v. 5.0 grade 2 in both study groups. CTCAE v. 5.0 grade 1–2 toxicities were seen in 31 (93.9%) patients in the RCT + DRT group and in (84.2%) patients of the RCT alone group (p = 0.27), and did not affect the time schedule and dose of treatments. The median time to progression was 7.8 (95% confidence interval [CI] 6.9–8.4) months in the RCT + DRT group and 6.0 (95% CI 5.2–6.3) months in the RCT alone group (p 0.05). The median overall survival was 12.4 (95% CI 10.5–17.8) months and 10.2 (95% CI 8.9–12.2) months, respectively (p = 0.006), and one year survival, 50% and 29%, respectively (p = 0.006). Conclusion: The palliative combination of RCT with daily split-dose DRT is safe and relatively effective treatment and can be viewed as an alternative to surgery in the patients with high surgical risk.