Full-Dose Gemcitabine and Concurrent Radiotherapy for Unresectable Pancreatic Cancer

• Published in: International journal of radiation oncology, biology, physics Vol. 68; no. 3; pp. 801 - 808
• Main Authors: Murphy, James D., B.S, Adusumilli, Saroja, M.D, Griffith, Kent A., M.P.H., M.S, Ray, Michael E., M.D., Ph.D, Zalupski, Mark M., M.D, Lawrence, Theodore S., M.D., Ph.D, Ben-Josef, Edgar, M.D
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2007
• Subjects: Adult; Aged; Antimetabolites, Antineoplastic - administration & dosage; CARCINOMAS; Comorbidity; COMPUTERIZED TOMOGRAPHY; Deoxycytidine - administration & dosage; Deoxycytidine - analogs & derivatives; FAILURES; Female; Gastrointestinal Diseases - epidemiology; Gemcitabine; Hematology, Oncology and Palliative Medicine; Humans; Incidence; IRRADIATION; LYMPH NODES; Male; Michigan - epidemiology; Middle Aged; Neoplasm Recurrence, Local - mortality; Neoplasm Recurrence, Local - prevention & control; PANCREAS; Pancreatic cancer; Pancreatic Neoplasms - mortality; Pancreatic Neoplasms - surgery; Pancreatic Neoplasms - therapy; PATIENTS; Pattern of failure; PLANNING; Prognosis; RADIATION DOSES; Radiation Injuries - epidemiology; Radiation-Sensitizing Agents - administration & dosage; Radiology; RADIOLOGY AND NUCLEAR MEDICINE; RADIOTHERAPY; Radiotherapy, Adjuvant - mortality; Risk Assessment - methods; Risk Factors; Survival Analysis; Survival Rate; TIME DEPENDENCE; TOXICITY; Treatment Outcome; Michigan; Pattern of failure; Gemcitabine; Radiotherapy; Pancreatic cancer
• ISSN: 0360-3016; 1879-355X
• DOI: 10.1016/j.ijrobp.2006.12.053

Purpose: Full-dose gemcitabine and concurrent radiotherapy is a promising treatment approach in unresectable pancreatic cancer. This study was conducted to assess the pattern of failure and toxicity associated with the use of conformal treatment volumes, omitting prophylactic lymph node irradiation. Methods and Materials: Seventy-four patients with locally advanced pancreatic cancer were treated between 1997 and 2005 with full-dose (1000 mg/m2 , Days 1, 8, and 15) gemcitabine and concurrent radiotherapy (36 Gy [median] in 15 daily fractions). The planning target volume (PTV) was limited to the gross tumor volume (GTV) plus 1-cm margin. Patient computed tomography (CT) scans were systematically reviewed to determine the pattern of failure. Kaplan-Meier and Cox-regression models were used to analyze freedom from local progression (FFLP), distant failure, overall survival (OS), and toxicity. Results: With a median follow-up of 10.6 months (20.6 months in living patients), the 1-year and 2-year FFLP rates were 64% and 38%, respectively. Four patients (5%) failed in the peripancreatic lymph nodes (3 in-field and 1 marginal failure). Median OS was 11.2 months. Analyzed as a time-dependent covariate, local failure was a significant predictor of OS ( p = 0.0074). Sixteen patients (22%) had significant gastrointestinal (GI) toxicity (≥ Grade 3). PTV correlated with significant GI toxicity ( p = 0.007). Conclusions: Freedom from local progression in unresectable pancreatic cancer is suboptimal. In conjunction with full-dose gemcitabine, the use of conformal fields encompassing only the GTV helps reduce toxicity and does not result in marginal failures. Our findings provide rationale for intensification of local therapy in conjunction with more effective systemic therapy.