ASTRO Issues Updated Clinical Practice Guideline on RT for Pancreatic Cancer

The American Society for Radiation Oncology (ASTRO) has released an updated clinical practice guideline on the use of radiation therapy (RT) for pancreatic cancer, with revised recommendations spanning resectable, borderline resectable, locally advanced, recurrent, and metastatic disease. Developed by a multidisciplinary task force with the American Society of Clinical Oncology, the European Society for Radiotherapy and Oncology, and the Society of Surgical Oncology, the guideline replaces ASTRO's prior version and incorporates evidence from randomized trials completed since.^1,2

Surgical resection remains the only potentially curative option, yet fewer than 20% of patients are candidates at diagnosis, and even nonmetastatic tumors often harbor occult micrometastatic spread. Several randomized trials since ASTRO's 2019 guideline, including CONKO-007, PREOPANC, PREOPANC-2, and the RT randomization of NRG Oncology/RTOG 0848, have clarified how RT should be sequenced with chemotherapy and surgery.^2,3

For resectable disease, preoperative chemoradiation is conditionally recommended based on the phase 3 PREOPANC trial, in which neoadjuvant chemoradiation improved 5-year OS vs upfront surgery (20.5% vs 6.5%) in the combined resectable and borderline resectable population.⁴ Postoperative chemoradiation after multiagent chemotherapy is conditionally recommended for node-negative patients who did not receive preoperative therapy, based on the RT randomization of NRG Oncology/RTOG 0848, which showed an OS and disease-free survival benefit in that subgroup but not overall.⁶

For borderline resectable disease, preoperative chemoradiation or RT is strongly recommended based on PREOPANC and PREOPANC-2, the latter showing no significant OS difference between preoperative chemoradiation and induction FOLFIRINOX, supporting either approach.^4,5 For locally advanced disease, chemoradiation or RT after multiagent chemotherapy is recommended even though LAP07 and CONKO-007 showed no OS benefit, because both demonstrated significantly improved local control, preventing morbidity and mortality from uncontrolled progression.^7,8 For medically inoperable patients or those who decline surgery, chemoradiation or RT after chemotherapy is recommended, based largely on expert opinion given the lack of prospective trials in that population.²

On dosing, the guideline conditionally recommends moderate hypofractionation (3600 cGy in 15 fractions) for preoperative chemoradiation in resectable disease, while conventional fractionation (5000 to 5040 cGy in 25 to 28 fractions) is recommended postoperatively. For locally advanced disease, conventionally fractionated chemoradiation or non-dose-escalated stereotactic body radiation therapy (SBRT) delivered in 5 fractions is recommended, and the task force said emerging evidence now also supports dose-escalated regimens, such as 7500 cGy in 25 fractions or up to 5000 cGy in 5 fractions of SBRT, when appropriate technology is available.²

The guideline also recommends elective coverage of anatomic regions at risk for microscopic disease, including the perineural “triangle volume” bordered by the celiac and superior mesenteric arteries and the portal vein, citing high locoregional recurrence rates when only gross tumor is targeted. The task force also recommends intensity modulated RT with daily image guidance and adaptive planning for dose-escalated SBRT to protect nearby organs.²

For recurrent disease, the guideline recommends definitive chemoradiation or RT for isolated locoregional recurrence in patients with no prior RT, and conditionally recommends reirradiation, ideally 6 to 12 months after an initial course, for those previously treated. For oligometastatic disease, typically defined as 5 or fewer metastatic lesions, the task force conditionally recommends definitive RT to metastatic sites and the primary tumor as part of multidisciplinary care, citing the phase 2 EXTEND trial, which found that adding local therapy to systemic therapy improved progression-free survival vs systemic therapy alone.⁹ A similar recommendation, grounded in expert opinion rather than randomized data, applies to oligoprogressive disease. Palliative RT is recommended for bleeding or pain, with single-fraction celiac plexus radiosurgery (2500 cGy) shown to relieve pain in a phase 2 trial, while regimens such as 3000 cGy in 10 fractions remain widely used.²

The guideline also addresses health disparities, noting that older adults, non-white patients, and those with lower socioeconomic status or no insurance are less likely to receive multimodality therapy and have worse OS even after accounting for comorbidities. The task force called for expanded referral pathways, virtual tumor boards, and greater trial enrollment of underrepresented populations to close these gaps.²

“Indications for the use of radiation therapy in treating pancreatic cancer have changed notably in the last several years. New clinical evidence helps clarify which patients can benefit from radiation therapy, while technological advances such as image guidance, motion management and adaptive radiation therapy allow us to deliver that care with greater precision,” Daniel Chang, MD, FASTRO, chair of the guideline task force and professor and chair of radiation oncology at the University of Michigan, stated in a news release.¹

Looking ahead, the task force cited recent results with the RAS inhibitor daraxonrasib, which doubled median OS vs chemotherapy in previously treated metastatic pancreatic cancer, as a signal that evolving systemic therapies could further reshape the role of RT.^2,10 The guideline calls for further randomized trials to clarify optimal RT sequencing with systemic therapy and surgery, identify patients most likely to benefit from dose escalation, and define the comparative effectiveness of different fractionation strategies.

REFERENCES

1. American Society for Radiation Oncology. ASTRO updates guideline on radiation therapy for pancreatic cancer. News release. Published August 13, 2026. Accessed August 14, 2026. https://tinyurl.com/44hxvbxf

2. Chuong MD, Jethwa KR, Ludmir E, et al. Radiation therapy for pancreatic cancer: an ASTRO clinical practice guideline. Pract Radiat Oncol. Published online August 13, 2026. doi:10.1016/j.prro.2026.07.002

3. Palta M, Godfrey D, Goodman KA, et al. Radiation therapy for pancreatic cancer: executive summary of an ASTRO clinical practice guideline. Pract Radiat Oncol. 2019;9(5):322-332. doi:10.1016/j.prro.2019.06.016

4. Versteijne E, van Dam JL, Suker M, et al. Neoadjuvant chemoradiotherapy versus upfront surgery for resectable and borderline resectable pancreatic cancer: long-term results of the Dutch randomized PREOPANC trial. J Clin Oncol. 2022;40(11):1220-1230. doi:10.1200/JCO.21.02233.

5. Janssen QP, van Dam JL, van Bekkum ML, et al. Neoadjuvant FOLFIRINOX versus neoadjuvant gemcitabine-based chemoradiotherapy in resectable and borderline resectable pancreatic cancer (PREOPANC-2): a multicentre, open-label, phase 3 randomised trial. Lancet Oncol. 2025;26(10):1346-1356. doi:10.1016/S1470-2045(25)00363-8

6. Abrams RA, Winter KA, Goodman KA, et al. Adjuvant chemotherapy with or without chemoradiotherapy for adenocarcinoma of the pancreatic head: results of the radiotherapy randomization of NRG Oncology/RTOG 0848. J Clin Oncol. Published online 2026. doi:10.1200/JCO-25-02520

7. Fietkau R, Ghadimi M, Grutzmann R, et al. Benefit of chemoradiotherapy versus chemotherapy after induction therapy for conversion of unresectable into resectable pancreatic cancer: the randomized CONKO-007 trial. J Clin Oncol. 2025;43(30):3266-3278. doi:10.1200/JCO-24-01502

8. Hammel P, Huguet F, van Laethem JL, et al. Effect of chemoradiotherapy vs chemotherapy on survival in patients with locally advanced pancreatic cancer controlled after 4 months of gemcitabine with or without erlotinib: the LAP07 randomized clinical trial. JAMA. 2016;315(17):1844-1853. doi:10.1001/jama.2016.4324

9. Ludmir EB, Sherry AD, Fellman BM, et al. Addition of metastasis-directed therapy to systemic therapy for oligometastatic pancreatic ductal adenocarcinoma (EXTEND): a multicenter, randomized phase II trial. J Clin Oncol. 2024;42(32):3795-3805. doi:10.1200/JCO.24.00081

10. O'Reilly EM, Wainberg ZA, Hendifar AE, et al. Daraxonrasib or chemotherapy in previously treated metastatic pancreatic cancer. N Engl J Med. Published online 2026. doi:10.1056/NEJMoa2605555