Induction Chemotherapy and Ablative Stereotactic Magnetic Resonance Image-Guided Adaptive Radiation Therapy for Inoperable Pancreas Cancer

Abstract

BackgroundRadiation therapy (RT) dose for inoperable pancreatic ductal adenocarcinoma (PDAC) has historically been non-ablative to avoid injuring gastrointestinal (GI) organs at risk (OARs). Accruing data suggest that dose escalation, in select patients, may significantly improve clinical outcomes. Early results of ablative stereotactic magnetic resonance image-guided adaptive radiation therapy (A-SMART) have been encouraging, although long-term outcomes are not well understood.MethodsA single institution retrospective analysis was performed of inoperable non-metastatic PDAC patients who received induction chemotherapy then 5-fraction A-SMART on a 0.35T-MR Linac from 2018-2021.ResultsSixty-two patients were evaluated with a median age of 66 years (range 35-91) and nearly all achieved Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (96.8%). Locally advanced disease was common (72.6%), otherwise borderline resectable (22.6%), or medically inoperable (4.8%). All received induction chemotherapy for a median 4.2 months (range, 0.2-13.3) most commonly FOLFIRINOX (n=43; 69.4%). Median prescribed dose was 50 Gy (range 40-50); median biologically effective dose (BED10) was 100 Gy10. The median local control (LC), progression-free survival (PFS), and overall survival (OS) from diagnosis were not reached, 20 months, and 23 months, respectively. Also, 2-year LC, PFS, and OS were 68.8%, 40.0%, and 45.5%, respectively. Acute and late grade 3+ toxicity rates were 4.8% and 4.8%, respectively.ConclusionsTo our knowledge, this is the largest series of induction chemotherapy followed by ablative 5-fraction SMART delivered on an MR Linac for inoperable PDAC. The potential for this novel treatment strategy is to achieve long-term LC and OS, compared to chemotherapy alone, and warrants prospective evaluation.

Inflammatory Cytokines and Radiotherapy in Pancreatic Ductal Adenocarcinoma

“…Dose delivery to the intended target(s) is thus maximized for cancer control while minimizing toxicities to the surrounding luminal gastrointestinal organs. Chuong et al [ 28 ] demonstrated 1-year local control, progression-free survival, and overall survival of 87.8%, 52.4%, and 58.9%, respectively, in patients with inoperable PDAC who received induction chemotherapy followed by SABR to a total dose of 50 Gy in five fractions (biological equivalent dose or BED = 100 Gy) delivered using MRI-guided adaptive radiation therapy; updated results by the same authors recently reported median progression-free survival of 20 months and median overall survival of 23 months; and 2-year local control, progression-free survival, and overall survival of 68.8%, 40%, and 45.5%, respectively, in this cohort of PDAC patients [ 29 ]. Acute and late grade 3 or higher toxicity rates were both 4.8% [ 29 ].…”

“…Chuong et al [ 28 ] demonstrated 1-year local control, progression-free survival, and overall survival of 87.8%, 52.4%, and 58.9%, respectively, in patients with inoperable PDAC who received induction chemotherapy followed by SABR to a total dose of 50 Gy in five fractions (biological equivalent dose or BED = 100 Gy) delivered using MRI-guided adaptive radiation therapy; updated results by the same authors recently reported median progression-free survival of 20 months and median overall survival of 23 months; and 2-year local control, progression-free survival, and overall survival of 68.8%, 40%, and 45.5%, respectively, in this cohort of PDAC patients [ 29 ]. Acute and late grade 3 or higher toxicity rates were both 4.8% [ 29 ]. Furthermore, in locally advanced PDAC patients who received induction chemotherapy followed by ablative, escalated-dose radiotherapy to a total dose of 75 Gy in 25 fractions (BED = 97.5 Gy) or 67.5 Gy in 15 fractions (BED = 97.88 Gy), median overall survival from diagnosis and radiotherapy were reported to be 26.8 months and 18.4 months, respectively; 1-year and 2-year overall survival from radiotherapy were 74% and 38%, respectively; 1-year and 2-year cumulative incidence of locoregional failure were 17.6% and 32.8%, respectively; grade 3 upper gastrointestinal bleeding occurred in 8% of treated patients with no grade 4 to 5 toxicity [ 30 ].…”

Initial clinical experience with magnetic resonance-guided radiotherapy in pediatric patients: Lessons learned from a single institution with proton therapy

“…MRgRT is a relatively new modality in radiation oncology, which is growing in utilization as more systems are brought online. Early results suggest that MRgRT may lead to clinical benefits in selected adults across several disease sites, including inoperable pancreatic cancer treated with SABR with survival rates that compared favorably to historical controls ( 1 ) and prostate SABR with improved toxicity rates compared to cone-beam CT-based delivery ( 10 ). The current experience for pediatric cancers, however, remains particularly limited ( 4 , 5 ).…”

“…Additional benefits include improvements in daily setup accuracy, the ability to reduce planning target volume (PTV) margins for some disease sites, use of continuous cine tumor motion tracking and beam gating, and application of respiratory breath-hold techniques to abrogate tumor motion. In adults, MRgRT has been applied in stereotactic ablative radiotherapy (SABR) for inoperable pancreatic carcinoma and oligometastatic lesions in the abdomen, pelvis, liver, and adrenal glands with favorable early outcomes ( 1 , 2 ).…”

Emergence of MR-Linac in Radiation Oncology: Successes and Challenges of Riding on the MRgRT Bandwagon

“…The most difficult disease site, pancreas, with poor outcome, has been the main theme for MR-Linac, as it can provide better visualization, targeting, and adaptive therapy to minimize normal tissue toxicities. Chuong et al [ 56 ] showed 2 years’ follow-up data in pancreatic cancer with an overall survival of 45.5% and with grade 3 toxicity of a mere 4.8%.…”