Hypofractionated Image-Guided IMRT in Advanced Pancreatic Cancer With Simultaneous Integrated Boost to Infiltrated Vessels Concomitant With Capecitabine: A Phase I Study

• Published in: International journal of radiation oncology, biology, physics Vol. 87; no. 5; pp. 1000 - 1006
• Main Authors: Passoni, Paolo, MD, Reni, Michele, MD, Cattaneo, Giovanni M., PhD, Slim, Najla, MD, Cereda, Stefano, MD, Balzano, Gianpaolo, MD, Castoldi, Renato, MD, Longobardi, Barbara, PhD, Bettinardi, Valentino, PhD, Gianolli, Luigi, MD, Gusmini, Simone, MD, Staudacher, Carlo, MD, Calandrino, Riccardo, PhD, Di Muzio, Nadia, MD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2013
• Subjects: Adenocarcinoma - blood supply; Adenocarcinoma - drug therapy; Adenocarcinoma - pathology; Adenocarcinoma - radiotherapy; Aged; Antimetabolites, Antineoplastic - therapeutic use; Blood Vessels - drug effects; Blood Vessels - radiation effects; Capecitabine; CARCINOMAS; Chemoradiotherapy - adverse effects; Chemoradiotherapy - methods; CHEMOTHERAPY; CT-GUIDED RADIOTHERAPY; Deoxycytidine - analogs & derivatives; Deoxycytidine - therapeutic use; Dose Fractionation; Duodenum - radiation effects; Feasibility Studies; Female; FLUORODEOXYGLUCOSE; Fluorouracil - analogs & derivatives; Fluorouracil - therapeutic use; Gastric Mucosa - radiation effects; Hematology, Oncology and Palliative Medicine; Humans; Induction Chemotherapy - adverse effects; Induction Chemotherapy - methods; Intestinal Mucosa - radiation effects; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Staging - methods; Organs at Risk - radiation effects; PANCREAS; Pancreatic Neoplasms - blood supply; Pancreatic Neoplasms - mortality; Pancreatic Neoplasms - pathology; Pancreatic Neoplasms - therapy; PLANNING; POSITRON COMPUTED TOMOGRAPHY; RADIATION DOSES; Radiology; RADIOLOGY AND NUCLEAR MEDICINE; Radiotherapy, Image-Guided - methods; Radiotherapy, Intensity-Modulated - adverse effects; Radiotherapy, Intensity-Modulated - methods; TOXICITY; Tumor Burden; ULCERS
• ISSN: 0360-3016; 1879-355X
• DOI: 10.1016/j.ijrobp.2013.09.012

Purpose To determine the maximum tolerated radiation dose (MTD) of an integrated boost to the tumor subvolume infiltrating vessels, delivered simultaneously with radical dose to the whole tumor and concomitant capecitabine in patients with pretreated advanced pancreatic adenocarcinoma. Methods and Materials Patients with stage III or IV pancreatic adenocarcinoma without progressive disease after induction chemotherapy were eligible. Patients underwent simulated contrast-enhanced four-dimensional computed tomography and fluorodeoxyglucose-labeled positron emission tomography. Gross tumor volume 1 (GTV1), the tumor, and GTV2, the tumor subvolume 1 cm around the infiltrated vessels, were contoured. GTVs were fused to generate Internal Target Volume (ITV)1 and ITV2. Biological tumor volume (BTV) was fused with ITV1 to create the BTV+Internal Target Volume (ITV) 1. A margin of 5/5/7 mm (7 mm in cranium-caudal) was added to BTV+ITV1 and to ITV2 to create Planning Target Volume (PTV) 1 and PTV2, respectively. Radiation therapy was delivered with tomotherapy. PTV1 received a fixed dose of 44.25 Gy in 15 fractions, and PTV2 received a dose escalation from 48 to 58 Gy as simultaneous integrated boost (SIB) in consecutive groups of at least 3 patients. Concomitant chemotherapy was capecitabine, 1250 mg/m2 daily. Dose-limiting toxicity (DLT) was defined as any treatment-related G3 nonhematological or G4 hematological toxicity occurring during the treatment or within 90 days from its completion. Results From June 2005 to February 2010, 25 patients were enrolled. The dose escalation on the SIB was stopped at 58 Gy without reaching the MTD. One patient in the 2nd dose level (50 Gy) had a DLT: G3 acute gastric ulcer. Three patients had G3 late adverse effects associated with gastric and/or duodenal mucosal damage. All patients received the planned dose of radiation. Conclusions A dose of 44.25 Gy in 15 fractions to the whole tumor with an SIB of 58 Gy to small tumor subvolumes concomitant with capecitabine is feasible in chemotherapy-pretreated patients with advanced pancreatic cancer.