title: Correlation between radiation dose to ¹⁸F-FDG-PET defined active bone marrow subregions and acute hematologic toxicity in cervical cancer patients treated with chemoradiotherapy.
abstract: OBJECTIVE
  To test the hypothesis that radiation dose to (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG-PET)-defined active bone marrow (BM(ACT)) subregions is correlated with hematologic toxicity in cervical cancer patients treated with chemoradiotherapy.
  
  
  METHODS
  The conditions of 26 women with cervical cancer who underwent (18)F-FDG-PET before treatment with concurrent cisplatin and intensity-modulated radiation therapy were analyzed. BM(ACT) was defined as the subregion of total bone marrow (BM(TOT)) with a standardized uptake value (SUV) equal to or above the mean for that individual. Inactive bone marrow (BM(INACT)) was defined as BM(TOT) - BM(ACT). Generalized linear modeling was used to test the correlation between BM(ACT) and BM(INACT) dose-volume metrics and hematologic nadirs, particularly white blood cell count (WBC) and absolute neutrophil count (ANC).
  
  
  RESULTS
  Increased BM(ACT) mean dose was significantly associated with decreased log(WBC) nadir (β = -0.04; 95% CI, -0.07 to -0.01; p = 0.009), decreased log(ANC) nadir (β = -0.05; 95% CI, -0.08 to -0.02; p = 0.006), decreased hemoglobin nadir (β = -0.16; 95% CI, -0.27 to -0.05; p = 0.010), and decreased platelet nadir (β = -6.16; 95% CI, -9.37 to -2.96; p < 0.001). By contrast, there was no association between BM(INACT) mean dose and log(WBC) nadir (β = -0.01; 95% CI, -0.06 to 0.05; p = 0.84), log(ANC) nadir (β = -0.03; 95% CI, -0.10 to 0.04; p = 0.40), hemoglobin nadir (β = -0.09; 95% CI, -0.31 to 0.14; p = 0.452), or platelet nadir (β = -3.47; 95% CI, -10.44 to 3.50; p = 0.339).
  
  
  CONCLUSIONS
  Irradiation of BM subregions with higher (18)F-FDG-PET activity was associated with hematologic toxicity, supporting the hypothesis that reducing dose to BM(ACT) subregions could mitigate hematologic toxicity. Future investigation should seek to confirm these findings and to identify optimal SUV thresholds to define BM(ACT).
authors.affiliation: Department of Radiation Oncology and Center for Advanced Radiotherapy Technologies, Rebecca and John Moores Comprehensive Cancer Center, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Brent S
authors.initials: BS
authors.lastname: Rose
authors.forename: Yun
authors.initials: Y
authors.lastname: Liang
authors.forename: Steven K
authors.initials: SK
authors.lastname: Lau
authors.forename: Lindsay G
authors.initials: LG
authors.lastname: Jensen
authors.forename: Catheryn M
authors.initials: CM
authors.lastname: Yashar
authors.forename: Carl K
authors.initials: CK
authors.lastname: Hoh
authors.forename: Loren K
authors.initials: LK
authors.lastname: Mell
mesh_terms: D000230:Adenocarcinoma / Q000000981:diagnostic imaging / Q000628:therapy; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D001853:Bone Marrow / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000528:radiation effects*; D018196:Carcinoma, Adenosquamous / Q000000981:diagnostic imaging / Q000628:therapy; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging / Q000628:therapy; D059248:Chemoradiotherapy / Q000009:adverse effects* / Q000379:methods; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D006402:Hematologic Diseases / Q000000981:diagnostic imaging* / Q000209:etiology / Q000517:prevention & control; D006801:Humans; D007958:Leukocyte Count; D016014:Linear Models; D008875:Middle Aged; D009504:Neutrophils; D010976:Platelet Count; D049268:Positron-Emission Tomography / Q000379:methods*; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage / Q000009:adverse effects; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D002583:Uterine Cervical Neoplasms / Q000628:therapy*
chemical_list: D000970:Antineoplastic Agents; D011838:Radiation-Sensitizing Agents; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D002945:Cisplatin