title: Dosimetric predictors of hematologic toxicity in patients undergoing concurrent gemcitabine-based chemoradiation for localized pancreatic cancer.
abstract: OBJECTIVE
  This study was undertaken to identify parameters associated with hematologic toxicity or chemotherapy dose modification in patients undergoing concurrent chemoradiation (CRT) with gemcitabine for localized pancreatic cancer.
  
  
  METHODS
  We reviewed patients with localized pancreatic cancer undergoing CRT between 2006 and 2012. Exclusion criteria included receipt of nongemcitabine therapy, chemotherapy before CRT, or abnormal baseline hematologic indices. The T11-L3 vertebrae were contoured as bone marrow region at risk. Linear and logistic regression models were used to test associations between dosimetric parameters and gemcitabine dose modification or hematologic toxicity during or within 3 months following CRT. Receiver operator curves were generated to identify threshold doses for hematologic toxicity.
  
  
  RESULTS
  Forty-nine patients were included. During CRT, the maximum thoracolumbar dose was associated with grade 2+ neutropenia during CRT (P = .017) and the volume receiving 5 Gy (V5) was associated with grade 2+ leukopenia (P = .041). Post-CRT, thoracolumbar mean dose (P = .015), V5 (P = .01), and V10 (P = .012) were associated with increased grade 2+ neutropenia. On multivariable analysis, the thoracolumbar maximum dose (P = .045) and V5 (P = .045) were associated with grade 2+ neutropenia and grade 2+ leukopenia during CRT, respectively. Post-CRT, the mean dose (P = .046), V5 (P = .019), and V10 (P = .037) were associated with increased grade 2+ neutropenia. A maximum dose of 48.02 Gy and V5 of 57.6% were identified as predictors of toxicity during CRT. A V5 of 56.6%, V10 of 47.05%, and mean dose of 11.67 Gy were identified as predictors of post-CRT hematologic toxicity. Post-CRT, there was a trend toward increased dose modifications with increased V5 (P = .065).
  
  
  CONCLUSIONS
  In our dataset, the thoracolumbar mean dose, maximum dose, V5, and V10 correlated with hematologic toxicity during CRT and post-CRT in patients with localized pancreatic cancer. Because of the high rates of distant failure and importance of systemic therapy in these patients, this may be an important consideration during treatment planning.
authors.affiliation: Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
authors.forename: Talha
authors.initials: T
authors.lastname: Shaikh
authors.affiliation: Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
authors.forename: Lora S
authors.initials: LS
authors.lastname: Wang
authors.affiliation: Department of Biostatistics, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
authors.forename: Brian
authors.initials: B
authors.lastname: Egleston
authors.affiliation: Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
authors.forename: Meher
authors.initials: M
authors.lastname: Burki
authors.affiliation: Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
authors.forename: John P
authors.initials: JP
authors.lastname: Hoffman
authors.affiliation: Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Cohen
authors.affiliation: Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania. Electronic address: Joshua.Meyer@fccc.edu.
authors.forename: Joshua E
authors.initials: JE
authors.lastname: Meyer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006402:Hematologic Diseases / Q000209:etiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D011874:Radiometry / Q000009:adverse effects*; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D000093542:Gemcitabine