Causes of Death Among Patients With Initially Inoperable Pancreas Cancer After Induction Chemotherapy and Ablative 5-fraction Stereotactic Magnetic Resonance Image Guided Adaptive Radiation Therapy

Michael D Chuong; Roberto Herrera; Antonio Ucar; Santiago Aparo; Fernando De Zarraga; Horacio Asbun; Ramon Jimenez; Domenech Asbun; Govindarajan Narayanan; Sarah Joseph; Rupesh Kotecha; Matthew D Hall; Kathryn M Mittauer; Diane Alvarez; James McCulloch; Tino Romaguera; Alonso Gutierrez; Adeel Kaiser

doi:10.1016/j.adro.2022.101084

Causes of Death Among Patients With Initially Inoperable Pancreas Cancer After Induction Chemotherapy and Ablative 5-fraction Stereotactic Magnetic Resonance Image Guided Adaptive Radiation Therapy

Adv Radiat Oncol. 2022 Sep 25;8(1):101084. doi: 10.1016/j.adro.2022.101084. eCollection 2023 Jan-Feb.

Authors

Michael D Chuong^{1

2}, Roberto Herrera¹, Antonio Ucar³, Santiago Aparo³, Fernando De Zarraga³, Horacio Asbun⁴, Ramon Jimenez⁴, Domenech Asbun⁴, Govindarajan Narayanan⁵, Sarah Joseph³, Rupesh Kotecha^{1

2}, Matthew D Hall^{1

2}, Kathryn M Mittauer^{1

2}, Diane Alvarez^{1

2}, James McCulloch^{1

2}, Tino Romaguera^{1

2}, Alonso Gutierrez^{1

2}, Adeel Kaiser^{1

2}

Affiliations

¹ Department of Radiation Oncology, Miami Cancer Institute, Miami, Florida.
² Herbert Wertheim College of Medicine, Florida International University, Miami, Florida.
³ Department of Medical Oncology, Miami Cancer Institute, Miami, Florida.
⁴ Department of Surgical Oncology, Miami Cancer Institute, Miami, Florida.
⁵ Department of Interventional Oncology, Miami Cancer Institute, Miami, Florida.

Abstract

Purpose: Nearly all patients with pancreatic ductal adenocarcinoma (PDAC) eventually die of progressive cancer after exhausting treatment options. Although distant metastases (DMs) are a common cause of death, autopsy studies have shown that locoregional progression may be directly responsible for up to one-third of PDAC-related deaths. Ablative stereotactic magnetic resonance-guided adaptive radiation therapy (A-SMART) is a novel treatment strategy that appears to improve locoregional control compared with nonablative radiation therapy, potentially leading to improved overall survival.

Methods and materials: A single-institution retrospective analysis was performed of patients with nonmetastatic inoperable PDAC treated between 2018 to 2020 using the MRIdian Linac with induction chemotherapy, followed by 5-fraction A-SMART. We identified causes of death that occurred after A-SMART.

Results: A total of 62 patients were evaluated, of whom 42 (67.7%) had died. The median follow-up time was 18.6 months from diagnosis and 11.0 months from A-SMART. Patients had locally advanced (72.6%), borderline resectable (22.6%), or resectable but medically inoperable PDAC (4.8%). All patients received induction chemotherapy, typically leucovorin calcium (folinic acid), fluorouracil, irinotecan hydrochloride, and oxaliplatin (69.4%) or gemcitabine/nab-paclitaxel (24.2%). The median prescribed dose was 50 Gy (range, 40-50), corresponding to a median biologically effective dose of 100 Gy₁₀. Post-SMART therapy included surgery (22.6%), irreversible electroporation (9.7%), and/or chemotherapy (51.6%). Death was attributed to locoregional progression, DMs, cancer-related cachexia/malnutrition, surgery/irreversible electroporation complications, other reasons not due to cancer progression, or unknown causes in 7.1%, 45.2%, 11.9%, 9.5%, 11.9%, and 14.3% of patients, respectively. Intra-abdominal metastases of the liver and peritoneum were responsible for 84.2% of deaths from DMs.

Conclusions: To our knowledge, this is the first contemporary evaluation of causes of death in patients with PDAC receiving dose-escalated radiation therapy. We demonstrated that the predominant cause of PDAC-related death was from liver and peritoneal metastases; therefore novel treatment strategies are indicated to address occult micrometastatic disease at these sites.