Lumbosacral spine and marrow cavity modeling of acute hematologic toxicity in patients treated with intensity modulated radiation therapy for squamous cell carcinoma of the anal canal.
OBJECTIVE
To identify various dosimetric parameters of bone marrow cavity that correlate with acute hematologic toxicity (HT) in patients with anal squamous cell carcinoma treated with definitive chemoradiation therapy (CRT).


METHODS
We analyzed 32 patients receiving CRT. The whole pelvic bone marrow (PBM) and the lumbosacral spine (LSS) subregion were contoured for each patient. Marrow cavities were contoured using the Hounsfield units (HUs) of 100, 150, 200, and 250 as maximum density threshold levels. The volume of each region receiving at least 5, 10, 15, 20, 30, and 40 Gy was calculated. The endpoint was grade ≥3 HT (HT3+). Normal-tissue complication probability (NTCP) was evaluated with the Lyman-Kutcher-Burman (LKB) model. Maximal likelihood estimate was used to compare the parameter set. Logistic regression was used to test associations between HT and both dosimetric and clinical parameters.


RESULTS
Ten patients (31%) experienced HT3+. While dose to both LSS and PBM significantly predicted for HT3+, LSS was superior to PBM by logistic regression and LKB modeling. Constrained optimization of the LKB model for HT3+ yielded the parameters m = 0.21, n = 1, and TD50 = 32 Gy for LSS. The NTCP fits were better with the whole bone than with marrow cavity using any HU threshold. Mean LSS doses of 21 Gy and 23.5 Gy result in a 5% and 10% risk of HT3+, respectively. Mean dose and low-dose radiation parameters (V5, V10, V15, V20) of whole bone or bone cavities of LSS were correlated most significantly with HT3+.


CONCLUSIONS
For predicting the risk of HT3+, whole-bone contours were superior to marrow cavity and LSS was superior to PBM by LKB modeling. The results confirm PBM and LSS as parallel organs when predicting hematologic toxicity. Recommended dose constraints to the LSS are V10 ≤80%. An LSS mean dose of 23.5 Gy is associated with a 10% risk of HT.
Department of Radiation Oncology, Stanford University, Stanford, California; Division of Radiation Oncology, Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
Jason Chia-Hsien
JC
Cheng
Department of Radiation Oncology, Stanford University, Stanford, California.
Jose G
JG
Bazan
Division of Radiation Oncology, Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan; Institute of Electro-Optical Science and Technology, National Taiwan Normal University, Taipei, Taiwan.
Jian-Kuen
JK
Wu
Department of Radiation Oncology, Stanford University, Stanford, California.
Albert C
AC
Koong
Department of Radiation Oncology, Stanford University, Stanford, California. Electronic address: dtchang@stanford.edu.
Daniel T
DT
Chang
D000208:Acute Disease; D000368:Aged; D000369:Aged, 80 and over; D001005:Anus Neoplasms / Q000188:drug therapy / Q000532:radiotherapy*; D001855:Bone Marrow Diseases / Q000209:etiology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000532:radiotherapy*; D059248:Chemoradiotherapy; D005260:Female; D006402:Hematologic Diseases / Q000209:etiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011832:Radiation Injuries / Q000097:blood / Q000209:etiology*; D011880:Radiotherapy Planning, Computer-Assisted