title: Long-Term Bone Marrow Suppression During Postoperative Chemotherapy in Rectal Cancer Patients After Preoperative Chemoradiation Therapy.
abstract: OBJECTIVE
  To quantify ensuing bone marrow (BM) suppression during postoperative chemotherapy resulting from preoperative chemoradiation (CRT) therapy for rectal cancer.
  
  
  METHODS
  We retrospectively evaluated 35 patients treated with preoperative CRT followed by postoperative 5-Fluorouracil and oxaliplatin (OxF) chemotherapy for locally advanced rectal cancer. The pelvic bone marrow (PBM) was divided into ilium (IBM), lower pelvis (LPBM), and lumbosacrum (LSBM). Dose volume histograms (DVH) measured the mean doses and percentage of BM volume receiving between 5-40 Gy (i.e.: PBM-V5, LPBM-V5). The Wilcoxon signed rank tests evaluated the differences in absolute hematologic nadirs during neoadjuvant vs. adjuvant treatment. Logistic regressions evaluated the association between dosimetric parameters and ≥ grade 3 hematologic toxicity (HT3) and hematologic event (HE) defined as ≥ grade 2 HT and a dose reduction in OxF. Receiver Operator Characteristic (ROC) curves were constructed to determine optimal threshold values leading to HT3.
  
  
  RESULTS
  During OxF chemotherapy, 40.0% (n=14) and 48% (n=17) of rectal cancer patients experienced HT3 and HE, respectively. On multivariable logistic regression, increasing pelvic mean dose (PMD) and lower pelvis mean dose (LPMD) along with increasing PBM-V (25-40), LPBM-V25, and LPBM-V40 were significantly associated with HT3 and/or HE during postoperative chemotherapy. Exceeding ≥36.6 Gy to the PMD and ≥32.6 Gy to the LPMD strongly correlated with causing HT3 during postoperative chemotherapy.
  
  
  CONCLUSIONS
  Neoadjuvant RT for rectal cancer has lasting effects on the pelvic BM, which are demonstrable during adjuvant OxF. Sparing of the BM during preoperative CRT can aid in reducing significant hematologic adverse events and aid in tolerance of postoperative chemotherapy.
authors.affiliation: Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey.
authors.forename: Neil B
authors.initials: NB
authors.lastname: Newman
authors.affiliation: Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey.
authors.forename: Manpreet K
authors.initials: MK
authors.lastname: Sidhu
authors.affiliation: Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey.
authors.forename: Rekha
authors.initials: R
authors.lastname: Baby
authors.affiliation: Division of Medical Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Moss
authors.affiliation: Division of Medical Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Nissenblatt
authors.affiliation: Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey.
authors.forename: Ting
authors.initials: T
authors.lastname: Chen
authors.affiliation: Department of Biostatistics, School of Public Health, Rutgers University, Piscataway, New Jersey.
authors.forename: Shou-En
authors.initials: SE
authors.lastname: Lu
authors.affiliation: Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey. Electronic address: jabbousk@cinj.rutgers.edu.
authors.forename: Salma K
authors.initials: SK
authors.lastname: Jabbour
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects; D001853:Bone Marrow / Q000187:drug effects* / Q000528:radiation effects*; D001855:Bone Marrow Diseases / Q000209:etiology*; D000069287:Capecitabine / Q000008:administration & dosage / Q000009:adverse effects; D059248:Chemoradiotherapy / Q000009:adverse effects*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007085:Ilium / Q000528:radiation effects; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D007970:Leukopenia / Q000209:etiology; D016015:Logistic Models; D008159:Lumbar Vertebrae / Q000528:radiation effects; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000209:etiology; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D000077150:Oxaliplatin; D010384:Pelvic Bones / Q000528:radiation effects; D011300:Preoperative Care; D012372:ROC Curve; D012004:Rectal Neoplasms / Q000473:pathology / Q000628:therapy*; D012189:Retrospective Studies; D012447:Sacrum / Q000528:radiation effects; D018709:Statistics, Nonparametric; D013921:Thrombocytopenia / Q000209:etiology
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000069287:Capecitabine; D002955:Leucovorin; D005472:Fluorouracil