A Phase 1 Study of Stereotactic Body Radiation Therapy Dose Escalation for Borderline Resectable Pancreatic Cancer After Modified FOLFIRINOX (NCT01446458)

• Published in: International journal of radiation oncology, biology, physics Vol. 96; no. 2; pp. 296 - 303
• Main Authors: Shaib, Walid L., MD, Hawk, Natalyn, MD, Cassidy, Richard J., MD, Chen, Zhengjia, PhD, Zhang, Chao, PhD, Brutcher, Edith, NP, Kooby, David, MD, Maithel, Shishir K., MD, Sarmiento, Juan M., MD, Landry, Jerome, MD, El-Rayes, Bassel F., MD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2016
• Subjects: Aged; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Camptothecin - administration & dosage; Camptothecin - adverse effects; Camptothecin - analogs & derivatives; Chemoradiotherapy - adverse effects; Chemoradiotherapy - methods; CITROVORUM FACTOR; CLINICAL TRIALS; Dose Fractionation; Female; Fluorouracil - administration & dosage; Fluorouracil - adverse effects; GY RANGE 01-10; GY RANGE 10-100; Hematology, Oncology and Palliative Medicine; Humans; Leucovorin - administration & dosage; Leucovorin - adverse effects; Longitudinal Studies; Male; Middle Aged; NEOPLASMS; Organoplatinum Compounds - administration & dosage; Organoplatinum Compounds - adverse effects; PANCREAS; Pancreatectomy; Pancreatic Neoplasms - diagnosis; Pancreatic Neoplasms - therapy; PATIENTS; RADIATION DOSES; Radiation Injuries - diagnosis; Radiation Injuries - etiology; Radiology; RADIOLOGY AND NUCLEAR MEDICINE; Radiosurgery - adverse effects; Radiosurgery - methods; RADIOTHERAPY; Radiotherapy, Adjuvant - methods; Treatment Outcome
• ISSN: 0360-3016; 1879-355X
• DOI: 10.1016/j.ijrobp.2016.05.010

Purpose A challenge in borderline resectable pancreatic cancer (BRPC) management is the high rate of positive posterior margins (PM). Stereotactic body radiation therapy (SBRT) allows for higher radiation delivery dose with conformity. This study evaluated the maximal tolerated dose with a dose escalation plan level up to 45 Gy using SBRT in BRPC. Methods and Materials A single-institution, 3 + 3 phase 1 clinical trial design was used to evaluate 4 dose levels of SBRT delivered in 3 fractions to the planning target volume (PTV) with a simultaneous in-field boost (SIB) to the PM. Dose level (DL) 1 was 30 Gy to the PTV, and for dose levels 2 through 4 (DL2-DL4) the dose was 36 Gy. The SIB dose to the PM was 6, 6, 7.5, and 9 Gy for DL-1, DL-2, DL-3, and DL-4, respectively. All patients received 4 treatments of modified FOLFIRINOX (fluorouracil, leucovorin, irinotecan, oxaliplatin) before SBRT. Results Thirteen patients with a median age of 64 years were enrolled. The median follow-up time was 18 months. The locations of the cancer were head (n=12) and uncinate/neck (n=1). One patient did not undergo SBRT. There were no grade 3 or 4 toxicities. Five patients did not undergo resection because of disease progression (1 local, 4 distant); 8 had R0 resection in the PM, and 5 of 8 had vessel reconstruction. Two patients had disease downstaged to T1 and T2 from T3 disease. Four patients are still alive, and 3 are disease free. The median overall survival for resected patients was not reached (9.3: not reached). Conclusion The SBRT dose of 36 Gy with a 9-Gy SIB to the PM (total 45 Gy) delivered in 3 fractions is safe and well tolerated. The dose-limiting toxicity for a 45-Gy dose was not reached, and further dose escalations are needed in future trials.