title: Normal tissue complication probability modeling of acute hematologic toxicity in cervical cancer patients treated with chemoradiotherapy.
abstract: OBJECTIVE
  To test the hypothesis that increased pelvic bone marrow (BM) irradiation is associated with increased hematologic toxicity (HT) in cervical cancer patients undergoing chemoradiotherapy and to develop a normal tissue complication probability (NTCP) model for HT.
  
  
  METHODS
  We tested associations between hematologic nadirs during chemoradiotherapy and the volume of BM receiving≥10 and 20 Gy (V10 and V20) using a previously developed linear regression model. The validation cohort consisted of 44 cervical cancer patients treated with concurrent cisplatin and pelvic radiotherapy. Subsequently, these data were pooled with data from 37 identically treated patients from a previous study, forming a cohort of 81 patients for normal tissue complication probability analysis. Generalized linear modeling was used to test associations between hematologic nadirs and dosimetric parameters, adjusting for body mass index. Receiver operating characteristic curves were used to derive optimal dosimetric planning constraints.
  
  
  RESULTS
  In the validation cohort, significant negative correlations were observed between white blood cell count nadir and V10 (regression coefficient (β)=-0.060, p=0.009) and V20 (β=-0.044, p=0.010). In the combined cohort, the (adjusted) β estimates for log (white blood cell) vs. V10 and V20 were as follows: -0.022 (p=0.025) and -0.021 (p=0.002), respectively. Patients with V10≥95% were more likely to experience Grade≥3 leukopenia (68.8% vs. 24.6%, p<0.001) than were patients with V20>76% (57.7% vs. 21.8%, p=0.001).
  
  
  CONCLUSIONS
  These findings support the hypothesis that HT increases with increasing pelvic BM volume irradiated. Efforts to maintain V10<95% and V20<76% may reduce HT.
authors.affiliation: Department of Radiation Oncology and Center for Advanced Radiotherapy Technologies, University of California, San Diego, La Jolla, CA 92093-0843, USA.
authors.forename: Brent S
authors.initials: BS
authors.lastname: Rose
authors.forename: Bulent
authors.initials: B
authors.lastname: Aydogan
authors.forename: Yun
authors.initials: Y
authors.lastname: Liang
authors.forename: Mete
authors.initials: M
authors.lastname: Yeginer
authors.forename: Michael D
authors.initials: MD
authors.lastname: Hasselle
authors.forename: Virag
authors.initials: V
authors.lastname: Dandekar
authors.forename: Rounak
authors.initials: R
authors.lastname: Bafana
authors.forename: Catheryn M
authors.initials: CM
authors.lastname: Yashar
authors.forename: Arno J
authors.initials: AJ
authors.lastname: Mundt
authors.forename: John C
authors.initials: JC
authors.lastname: Roeske
authors.forename: Loren K
authors.initials: LK
authors.lastname: Mell
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D015992:Body Mass Index; D001853:Bone Marrow / Q000187:drug effects / Q000528:radiation effects*; D002945:Cisplatin / Q000008:administration & dosage / Q000627:therapeutic use; D003131:Combined Modality Therapy / Q000009:adverse effects / Q000379:methods; D005260:Female; D006441:Hemoglobin A / Q000032:analysis; D006801:Humans; D007958:Leukocyte Count; D008875:Middle Aged; D015233:Models, Statistical; D009504:Neutrophils / Q000187:drug effects / Q000528:radiation effects; D058958:Organs at Risk / Q000528:radiation effects*; D010388:Pelvis; D010976:Platelet Count; D011336:Probability; D011832:Radiation Injuries / Q000150:complications*; D011879:Radiotherapy Dosage; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects; D002583:Uterine Cervical Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000532:radiotherapy*
chemical_list: D000970:Antineoplastic Agents; D006441:Hemoglobin A; D002945:Cisplatin
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