Late Gastrointestinal Tissue Effects After Hypofractionated Radiation Therapy of the Pancreas

Elhammali, Adnan; Patel, Mukund; Weinberg, Benjamin D.; Verma, Vipin; Liu, J.; Olsen, Jeffrey R.

doi:10.1016/j.ijrobp.2015.07.1969

Cited by 6 publications

(6 citation statements)

References 28 publications

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“…In cooperative group trials using modest dose (40-50.4 Gy) chemoradiation after resection of pancreatic cancer, severe toxicities (grade 3 or higher) occurred in w50% of patients. 22 This high rate of severe toxicity has historically limited the radiation dose in abdominal radiation therapy to a lower dose that, not surprisingly, has limited the efficacy or utility of these regimens. In the postoperative setting for pancreatic cancer, local failure rates often exceed 50%.…”

Section: Discussionmentioning

confidence: 99%

Design, Implementation, and in Vivo Validation of a Novel Proton FLASH Radiation Therapy System

Diffenderfer

Verginadis

Kim

et al. 2020

International Journal of Radiation Oncology*Biology*Physics

348

396

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In this article, we describe a novel RT apparatus that delivers FLASH proton RT (PRT) using double scattered protons with CT guidance and provide the first report of proton FLASH RT-mediated normal tissue radioprotection. Purpose: Recent studies suggest that ultrahigh-dose-rate, "FLASH," electron radiation therapy (RT) decreases normal tissue damage while maintaining tumor response compared with conventional dose rate RT. Here, we describe a novel RT apparatus that delivers FLASH proton RT (PRT) using double scattered protons with computed tomography guidance and provide the first report of proton FLASH RT-mediated normal tissue radioprotection. Methods and Materials: Absolute dose was measured at multiple depths in solid water and validated against an absolute integral charge measurement using a Faraday cup. Real-time dose rate was obtained using a NaI detector to measure prompt gamma rays. The effect of FLASH versus standard dose rate PRT on tumors and normal tissues was measured using pancreatic flank tumors (MH641905) derived from the KPC autochthonous PanCa model in syngeneic C57BL/6J mice with analysis of fibrosis and stem cell repopulation in small intestine after abdominal irradiation.

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Section: Discussionmentioning

confidence: 99%

Design, Implementation, and in Vivo Validation of a Novel Proton FLASH Radiation Therapy System

Diffenderfer

Verginadis

Kim

et al. 2020

International Journal of Radiation Oncology*Biology*Physics

348

396

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“…Radiation-induced intestinal injury is the most important toxicity in clinical abdominal radiotherapy. In a review of 1,160 patients treated with hypofractionated radiotherapy for pancreatic cancer, serious gastrointestinal toxicities consisted of ulcers, hemorrhages, obstructions, structures, and perforations (18). The median late grade 3 or greater GI toxicity was 7.4% (but up to 32.7% in one report).…”

Section: Discussionmentioning

confidence: 99%

A Novel Mouse Model to Study Image-Guided, Radiation-Induced Intestinal Injury and Preclinical Screening of Radioprotectors

et al. 2017

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Radiation is an important treatment modality for gastrointestinal tumors, but intestinal injury is a common side effect. Here we describe a physiologically relevant model for studying the molecular determinants of radiation-induced intestinal damage and testing novel radioprotectors. The model employs a radiopaque marker implanted into the surface of the mouse jejunum, serving as a fiducial marker for precise radiation targeting. Mice were imaged with Cone-Beam CT (CBCT) and irradiated (IR) to the marked area using the Small Animal Radiation Research Platform (SARRP). IR-induced damage was acute but reversible and largely restricted to the area of the marker, leaving the surrounding tissues intact. Although whole gut irradiation with these doses caused lethal GI syndrome, focal (5 mm) radiation of the intestine did not cause any weight loss or lethality. However, fibrosis and collagen deposition 4 months post-IR indicated chronic intestinal damage. A separate cohort of mice was treated daily with curcumin, a clinically tested radioprotector, prior to and post-IR. Curcumin-treated mice showed significant decreases in both local and systemic inflammatory cytokine levels and in fibrosis, suggesting it is an effective radioprotector of the intestine. Our results indicate that this model, which emulates clinically relevant intestinal radiation-induced injury, can be used to assess radioprotectors prior to testing in the clinic. .

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“…The timing of final chemotherapy before resection, 78 examining late effects of CRT in pancreatic cancer survivors, 79 and correlating postoperative complications with the radiation dose to organsat-risk 80,81 are a few such examples. Outcomes, toxicity, and postoperative complications of SRT-based neoadjuvant CRT also need further assessment.…”

Section: Discussionmentioning

confidence: 99%

Neoadjuvant Therapy for Pancreatic Cancer

Verma

Lin

2016

American Journal of Clinical Oncology

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The purpose of this review was to assess whether neoadjuvant chemotherapy and chemoradiotherapy (CRT) result in differential postoperative morbidity and mortality as compared with pancreatic tumor resection surgery alone. Using PRISMA guidelines and the PubMed search engine, we reviewed all prospective phase II trials of neoadjuvant chemotherapy and CRT for pancreatic cancer that examined postoperative morbidities and mortalities. A total of 30 articles were identified, collated, and analyzed. Risks of postoperative complications vary based on trial. With surgery alone, the most common postoperative complications included delayed gastric emptying (DGE) (17% to 24%), pancreatic fistula (10% to 20%), anastomotic leaks (0% to 15%), postoperative bleeding (2% to 13%), and infections/sepsis (17% to 20%). With surgery alone, the mortality was <5%. Neoadjuvant chemotherapy showed comparable fistula rates (3% to 4%), leaks (3% to 11%), infection (3% to 7%), with mortality 0% to 4% in all but 1 study. CRT for resectable/borderline resectable patients also showed comparable complication rates: DGE (6% to 15%), fistulas (2% to 3%), leaks (3% to 7%), bleeding/hemorrhage (2% to 13%), infections/sepsis (3% to 19%), with 9/13 studies showing a mortality of ≤4%. As compared with initially borderline/resectable tumors, CRT for initially unresectable tumors (despite less data) showed higher complication rates: DGE (13% to 33%), fistulas (3% to 25%), infections/sepsis (3% to 16%). However, the confounding factor of the potentially higher tumor burden as an associative agent remains. The only parameters slightly higher than historical surgery-only complication rates were leaks and bleeding/hemorrhage (13% to 20%). Mortality rates in these patients were consistently 0%, with 2 outliers. Hence, neoadjuvant chemotherapy/CRT is safe from a postoperative complication standpoint, without significant increases in complication rates compared with surgery alone. Resectable and borderline resectable patients have fewer complications as compared with unresectable patients, although data for the latter are lacking.

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Late Gastrointestinal Tissue Effects After Hypofractionated Radiation Therapy of the Pancreas

Cited by 6 publications

References 28 publications

Design, Implementation, and in Vivo Validation of a Novel Proton FLASH Radiation Therapy System

Design, Implementation, and in Vivo Validation of a Novel Proton FLASH Radiation Therapy System

A Novel Mouse Model to Study Image-Guided, Radiation-Induced Intestinal Injury and Preclinical Screening of Radioprotectors

Neoadjuvant Therapy for Pancreatic Cancer

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