Assessment of the efficacy of fractionation regimes in chemoradiotherapy for inoperable locally advanced pancreatic cancer

The purpose of the study was to improve radiotherapy efficacy by optimizing fractionation regimens in patients with inoperable stage llb-lll locally advanced pancreatic cancer.

Material and Methods. Treatment outcomes of 60 patients with inoperable stage llb-lll locally advanced pancreatic cancer were analyzed in a single-center comparative study with a retrospective analysis of prospectively collected clinical data. All patients received chemoradiotherapy, including 3 or more cycles of polychemotherapy (PCT) with FOLFlRlNOX or GEMCAP regimen in combination with daily split-dose radiation therapy (RT) (group A) or stereotactic radiotherapy (STRT) (group B).

Results. The efficacy of daily split-dose RT was found to be higher than that of stereotactic RT Early radiation reactions corresponded to grade l-ll and were observed in both groups. lncreased levels of transaminases were the most common: in 36.7 % of patients in group A and in 46.7 % in group B (p=0.59). Nausea/vomiting was observed in 23.3 % and 40.0 %, respectively (p=0.18). An analysis of the immediate results showed that the overall rate of objective response was significantly higher in group A compared with group B (93.3 vs 70.0 %; p=0.03). However, disease progression was observed more frequently in group B than in group A patients (30.0 vs 6.7 %; p=0.042). The daily split-course regimen demonstrated significantly higher one-year (73 vs 48 %) and two-year (39 vs 15 %) overall survival rates than stereotactic RT (p<0.05).

Conclusion. Our study demonstrated the use of combination therapy in a carefully selected group of patients with inoperable stage llb-lll locally advanced pancreatic cancer. This type of therapy allows for increased life expectancy, overall survival, and objective response rates. Moreover, continuous improvements in radiation therapy techniques help reduce the incidence of early systemic radiation reactions. Thus, the daily split-dose dose RT is more effective and can be considered the preferred RT regimen for the treatment of inoperable patients with locally advanced pancreatic cancer.

1. Cancer care for the population of Russia in 2023. Ed. by A.D. Kaprin, V.V. Starinsky, A.O. Shakhzadova. Moscow, 2024. 262 p. (in Russian). ISBN: 978-5-85502-297-1.

2. Siegel R.L., Giaquinto A.N., Jemal A. Cancer statistics, 2024. CA Cancer J Clin. 2024; 74(1): 12-49. doi: 10.3322/caac.21820.

3. Pancreatic cancer Clinical guidelines of the Ministry of Health of the Russian Federation. 2024]. [Internet]. [cited 06.04.2026. URL: https://cr.minzdrav.gov.ru/preview-cr/355_5.

4. McGuigan A., Kelly P., Turkington R.C., Jones C., Coleman H.G., McCain R.S. Pancreatic cancer: A review of clinical diagnosis, epidemiology, treatment and outcomes. World J Gastroenterol. 2018; 24(43): 4846-61. doi: 10.3748/wjg.v24.i43.4846.

5. Stas D., Vandamme T, Roeyen G., Reynders D., Demey W., Stellamans K., Bussels B., Hutsebaut I.,Maurissen I., Bouchart C., Berbée M., Lallemand F., Poels H., Thomas M., Cuyle P.J., Bulens P., Verboven K., Martens M., Weytjens R., Joye I. Stereotactic body radiation therapy for inoperable non-metastasized pancreatic adenocarcinoma: a randomised phase II study (TORPEDO). BMC Cancer. 2025; 25(1): 1671. doi: 10.1186/s12885-025-15041-8.

6. Huan L., Yu F., Cao D., Zhou H., Qin M., Cao Y. Comparison of neoadjuvant treatment and surgery first for resectable or borderline resectable pancreatic carcinoma: A systematic review and network meta-analysis of randomized controlled trials. PLoS One. 2024; 19(3): e0295983. doi: 10.1371/journal.pone.0295983.

7. Finan J.M., Guo Y., Goodyear SM., Brody J.R. Challenges and Opportunities in Targeting the Complex Pancreatic Tumor Microenvironment. JCO Oncol Adv. 2024; 1: e2400050. doi: 10.1200/OA-24-00050.

8. Krishnan S., Chadha A.S., Suh Y, Chen H.C., Rao A., Das P., Minsky B.D., Mahmood U., Delclos M.E., Sawakuchi G.O., Beddar S., Katz M.H., Fleming J.B., Javle M.M., Varadhachary G.R., Wolff RA., Crane C.H. Focal Radiation Therapy Dose Escalation Improves Overall Survival in Locally Advanced Pancreatic Cancer Patients Receiving Induction Chemotherapy and Consolidative Chemoradiation. Int J Radiat Oncol Biol Phys. 2016; 94(4): 755-65. doi: 10.1016/j.ijrobp.2015.12.003.

9. Schwartz L.H., Litiere S., de Vries E., Ford R., Gwyther S., Mandrekar S., Shankar L., Bogaerts J., Chen A., Dancey J., Hayes W, Hodi F.S., Hoekstra O.S., Huang E.P., Lin N., Liu Y, Therasse P., Wolchok J.D., Seymour L. RECIST 1.1-Update and clarification: From the RECIST committee. Eur J Cancer. 2016; 62: 132-37. doi: 10.1016/j.ejca.2016.03.081.

10. Freites-Martinez A., Santana N.,Arias-Santiago S., Viera A. Using the Common Terminology Criteria for Adverse Events (CTCAE - Version 5.0) to Evaluate the Severity of Adverse Events of Anticancer Therapies. Actas Dermosifiliogr (Engl Ed). 2021; 112(1): 90-92. doi: 10.1016/j.ad.2019.05.009.

11. Masui T, Takaori K., Anazawa T., Sato A., Nakano K., Uchida Y, Yogo A., Goto Y, Matsumoto S., Kodama Y, Kanai M., Isoda H., Mizumoto M., Kawaguchi Y, Shibuya K., Itasaka S., Uemoto S. A Prospective Study of Intensity-modified Radiation Therapy in Comparison with Conventional 3D-RT for BR Pancreatic Cancer Patients with Arterial Involvement. Anticancer Res. 2017; 37(12): 7023-30. doi: 10.21873/anticanres.12172.

12. Nazarenko A.V, Znatkova Ya.R., Sagaydak I.V, Tkachev S.I., Alieva S.B. Use of stereotactic radiation therapy to relieve pain in patients with unresectable pancreatic cancer. Journal of Experimental and Clinical Surgery. 2018; 11(3): 208-12. doi: 10.18499/2070-478X-2018-11-3-208-212. EDN: YKZIGT.

13. Mukherjee S., Qi C., Shaw R., Jones CM., Bridgewater JA., Radhakrishna G., Patel N., Holmes J., Virdee P.S., Tranter B., Parsons P., Falk S., Wasan H.S., Ajthkumar T.V, Holyoake D., Roy R., Scott-Brown M., Hurt C.N., O ’Neill E., Sebag-Montefiore D., Maughan T.S., HawkinsMA., Corrie P. Standard or high dose chemoradiotherapy, with or without the protease inhibitor nelfinavir, in patients with locally advanced pancreatic cancer: The phase 1/randomised phase 2 SCALOP-2 trial. Eur J Cancer. 2024; 209: 114236. doi: 10.1016/j.ejca.2024.114236.