medwireNews: Ablative radiation therapy (A-RT) provides local tumor control and favorable overall survival (OS) for patients with localized, resectable pancreatic ductal adenocarcinoma (PDAC) who are deemed at high risk for surgery due to advanced age and comorbidities, suggests a retrospective study.
The patients had a median OS of 21.7 months from treatment, with 1- and 2-year rates of 65.5% and 43.7%, respectively. Local progression, characterized by a minimum increase of 20% in the longest diameter of the primary tumor and at least a 5-mm increase from baseline, was seen in 16.4% of patients at 1 year and 20.8% at 2 years.
The researchers note that the “durable control of the primary tumor” and “favorable survival” with A-RT occurred despite the patients being aged a median of 80 years, the majority (80%) scoring 80 points or lower on the Karnofsky Performance Status score, a measure of functional impairment that ranges from 0 (dead) to 100 (no evidence of disease), and only 68% receiving induction chemotherapy.
Moreover, there were only a few severe toxic effects potentially linked to A-RT, with two grade 3 incidents of upper gastrointestinal bleeding and one gastric outlet obstruction, and no events of grade 4 or higher.
Having a treatment option for PDAC with less risk for morbidity and mortality than surgery “would meet a major clinical need” in older patients with comorbidities, write Marsha Reyngold (Memorial Sloan Kettering Cancer Center, New York, USA) and colleagues in JAMA Oncology. They add that, “[i]n this regard, A-RT may be a promising alternative.”
The researchers assessed data on 25 patients (52% men) with histologically confirmed, radiographically resectable PDAC who were treated with A-RT at Memorial Sloan Kettering Cancer Center. Most (80%) of the primary tumors were in the pancreatic head and were a median of 2.5 cm in size, with 60% T2 tumors and 16% node positive.
The patients received A-RT with linear accelerators in 25, 15, 10 or 5 fractions with daily computed tomography or magnetic resonance imaging guidance, motion management, and daily or selective adaptation of the dose distribution. A biologically effective dose of at least 97.5 Gy was delivered to the tumor at the point of greatest disease volume, while up to 53.1 Gy was delivered to areas at risk for disease spread.
The best overall radiographic responses were complete response in 8% of patients, partial response in 20%, stable disease in 48%, and progressive disease in 4%, while the response could not be assessed for 20% of patients.
The median progression-free survival was 7.9 months with rates of 40.0% and 20.0% at 1 and 2 years, respectively. The patients also had a median distant metastasis-free survival of 8.0 months, with corresponding rates of 44.0% and 20.0%.
“These data provide, to our knowledge, the first clinical signal that A-RT may be a promising local therapy option for frail or functionally compromised patients with technically resectable disease, but who may also be at high risk of complications,” the authors say.
In a commentary related to the article, Douglas Evans and colleagues, from Medical College of Wisconsin in Milwaukee, USA, observe that “[p]atients with medically inoperable pancreatic cancer have not been the focus of clinical trials but deserve attention.”
They continue: “Those with frailty due to age or other medical comorbidities are common,” and “A-RT is certainly a viable option if these patients can return for daily radiation for up to 5 weeks and tolerate concurrent chemotherapy.”
However, the commentators highlight: “No therapy is possible without a secure cytologic diagnosis, the successful management of biliary and gastric outlet obstruction and patient comorbidities, as well as attending to individual social/personal challenges.
“For those who make it past this gauntlet, the benefit of local disease control will be realized most by those with responding disease—the assessment of which is currently within the grasp of all of us.”
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JAMA Oncol 2025; doi:10.1001/jamaoncol.2025.0460
JAMA Oncol 2025; doi:10.1001/jamaoncol.2025.0156