Association between bone marrow dosimetric parameters and acute hematologic toxicity in anal cancer patients treated with concurrent chemotherapy and intensity-modulated radiotherapy.
OBJECTIVE
To test the hypothesis that the volume of pelvic bone marrow (PBM) receiving 10 and 20 Gy or more (PBM-V(10) and PBM-V(20)) is associated with acute hematologic toxicity (HT) in anal cancer patients treated with concurrent chemoradiotherapy.


METHODS
We analyzed 48 consecutive anal cancer patients treated with concurrent chemotherapy and intensity-modulated radiation therapy. The median radiation dose to gross tumor and regional lymph nodes was 50.4 and 45 Gy, respectively. Pelvic bone marrow was defined as the region extending from the iliac crests to the ischial tuberosities, including the os coxae, lumbosacral spine, and proximal femora. Endpoints included the white blood cell count (WBC), absolute neutrophil count (ANC), hemoglobin, and platelet count nadirs. Regression models with multiple independent predictors were used to test associations between dosimetric parameters and HT.


RESULTS
Twenty patients (42%) had Stage T3-4 disease; 15 patients (31%) were node positive. Overall, 27 (56%), 24 (50%), 4 (8%), and 13 (27%) experienced acute Grade 3-4 leukopenia, neutropenia, anemia, and thrombocytopenia, respectively. On multiple regression analysis, increased PBM-V(5), V(10), V(15), and V(20) were significantly associated with decreased WBC and ANC nadirs, as were female gender, decreased body mass index, and increased lumbosacral bone marrow V(10), V(15), and V(20) (p < 0.05 for each association). Lymph node positivity was significantly associated with a decreased WBC nadir on multiple regression analysis (p < 0.05).


CONCLUSIONS
This analysis supports the hypothesis that increased low-dose radiation to PBM is associated with acute HT during chemoradiotherapy for anal cancer. Techniques to limit bone marrow irradiation may reduce HT in anal cancer patients.
Mell
Loren K
LK
Department of Radiation and Cellular Oncology, University of Chicago and University of Illinois at Chicago, Chicago, IL 60637, USA. lmell@radonc.uchicago.edu
Schomas
David A
DA
Salama
Joseph K
JK
Devisetty
Kiran
K
Aydogan
Bulent
B
Miller
Robert C
RC
Jani
Ashesh B
AB
Kindler
Hedy L
HL
Mundt
Arno J
AJ
Roeske
John C
JC
Chmura
Steven J
SJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000209:etiology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001005:Anus Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D001853:Bone Marrow / Q000528:radiation effects*; D003131:Combined Modality Therapy / Q000379:methods; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007970:Leukopenia / Q000209:etiology; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage; D009503:Neutropenia / Q000209:etiology; D010388:Pelvis; D011879:Radiotherapy Dosage; D050397:Radiotherapy, Intensity-Modulated; D012044:Regression Analysis; D012189:Retrospective Studies; D013921:Thrombocytopenia / Q000209:etiology
D016685:Mitomycin; D005472:Fluorouracil