Multi-institutional outcomes of patients aged 75 years and older with pancreatic ductal adenocarcinoma treated with ablative 5-fraction stereotactic magnetic resonance image-guided adaptive radiation therapy (SMART).
Authors: Chuong Michael David , Palm Russell , Herrera Roberto , Rubens Muni , Bryant John Michael , Hoffe Sarah E. , Kim Dae Won , Kaiser Adeel , Ucar Antonio , Fleming Jason B. , De Zarraga Fernando I. , Hodul Pamela Joy , Aparo Santiago , Asbun Horacio , Malafa Mokenge Peter , Jimenez Ramon , Denbo Jason , Frakes Jessica M. 
Published: January 2022

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Background: Dose escalated radiation therapy (RT) may improve long-term clinical outcomes compared to standard radiation dose for patients with initially inoperable pancreatic ductal adenocarcinoma (PDAC). Favorable outcomes have recently been reported of ablative stereotactic magnetic resonance image-guided adaptive radiation therapy (SMART) delivered in 5 fractions. The appropriateness of ablative SMART inoperable PDAC patients with advanced age (>75 years) is not well understood. Methods: A retrospective analysis was performed of inoperable non-metastatic PDAC patients aged 75 year or older treated on a 0.35T-MR Linac at two institutions. Patients were excluded who did not have at least 3 months follow up after SMART. Fiducial markers were not used. Treatment delivery was typically in breath hold. Most (65.3%) were treated to gross disease only without elective coverage. On-table adaptive replanning was performed for each fraction if needed, primarily to account for interfraction anatomic changes and ensure all organ-at-risk (OAR) constraints were met. Treatment response was defined using RECIST 1.1 criteria and CTCAE v5 criteria was used to assess toxicity. Results: 49 patients were evaluated with median age of 81 years (range 75-91). ECOG performance status (PS) was 0-1 in 89.8%. PDAC was locally advanced (46.9%), borderline resectable (36.7%), or medically inoperable (16.3%). Median CA19-9 at diagnosis was 235.8 U/mL. Most received induction chemotherapy (83.7%), usually gemcitabine/nab-paclitaxel (63.3%) and rarely FOLFIRINOX (12.2%), for a median 3.2 months. Median prescribed dose was 50 Gy (range, 40-50 Gy). Surgery was performed in 18.4% after a median 10 weeks from SMART, all having negative margins. Median follow-up was 14 months from diagnosis. Median and 1-year local control (LC) was 29 months and 88.9%, respectively. Median and 1-year progression free survival (PFS) was 13 months and 53.8%, respectively. Median and 1-year estimated overall survival (OS) was 23 months and 78.9%, respectively. ECOG PS < 2 was the only significant predictor of improved OS on multivariate analysis with a trend towards significance for induction chemotherapy >3 months. Acute and late grade 3+ toxicity rates were 8.2% and 4.1%, respectively. Conclusions: Ablative 5-fraction SMART is associated with encouraging long-term LC and OS among elderly patients with PDAC. This novel treatment strategy is noninvasive, does not require anesthesia, is remarkably well tolerated among patients with advanced age despite the high prescription dose, and therefore should be strongly considered especially among older patients who have limited treatment options.