title: [(18)F]FDG-PET standard uptake value as a metabolic predictor of bone marrow response to radiation: impact on acute and late hematological toxicity in cervical cancer patients treated with chemoradiation therapy.
abstract: OBJECTIVE
  To quantify the relationship between bone marrow (BM) response to radiation and radiation dose by using (18)F-labeled fluorodeoxyglucose positron emission tomography [(18)F]FDG-PET standard uptake values (SUV) and to correlate these findings with hematological toxicity (HT) in cervical cancer (CC) patients treated with chemoradiation therapy (CRT).
  
  
  METHODS
  Seventeen women with a diagnosis of CC were treated with standard doses of CRT. All patients underwent pre- and post-therapy [(18)F]FDG-PET/computed tomography (CT). Hemograms were obtained before and during treatment and 3 months after treatment and at last follow-up. Pelvic bone was autosegmented as total bone marrow (BMTOT). Active bone marrow (BMACT) was contoured based on SUV greater than the mean SUV of BMTOT. The volumes (V) of each region receiving 10, 20, 30, and 40 Gy (V10, V20, V30, and V40, respectively) were calculated. Metabolic volume histograms and voxel SUV map response graphs were created. Relative changes in SUV before and after therapy were calculated by separating SUV voxels into radiation therapy dose ranges of 5 Gy. The relationships among SUV decrease, radiation dose, and HT were investigated using multiple regression models.
  
  
  RESULTS
  Mean relative pre-post-therapy SUV reductions in BMTOT and BMACT were 27% and 38%, respectively. BMACT volume was significantly reduced after treatment (from 651.5 to 231.6 cm(3), respectively; P<.0001). BMACT V30 was significantly correlated with a reduction in BMACT SUV (R(2), 0.14; P<.001). The reduction in BMACT SUV significantly correlated with reduction in white blood cells (WBCs) at 3 months post-treatment (R(2), 0.27; P=.04) and at last follow-up (R(2), 0.25; P=.04). Different dosimetric parameters of BMTOT and BMACT correlated with long-term hematological outcome.
  
  
  CONCLUSIONS
  The volumes of BMTOT and BMACT that are exposed to even relatively low doses of radiation are associated with a decrease in WBC counts following CRT. The loss in proliferative BM SUV uptake translates into low WBC nadirs after treatment. These results suggest the potential of intensity modulated radiation therapy to spare BMTOT to reduce long-term hematological toxicity.
authors.affiliation: Department of Radiation Oncology, Lausanne University Hospital, Lausanne, Switzerland.
authors.forename: Olgun
authors.initials: O
authors.lastname: Elicin
authors.affiliation: Velocity Medical Solutions, Atlanta, Georgia.
authors.forename: Sharon
authors.initials: S
authors.lastname: Callaway
authors.affiliation: Department of Nuclear Medicine, Lausanne University Hospital, Lausanne, Switzerland.
authors.forename: John O
authors.initials: JO
authors.lastname: Prior
authors.affiliation: Department of Radiation Oncology, Lausanne University Hospital, Lausanne, Switzerland.
authors.forename: Jean
authors.initials: J
authors.lastname: Bourhis
authors.affiliation: Department of Radiation Oncology, Lausanne University Hospital, Lausanne, Switzerland. Electronic address: mahmut.ozsahin@chuv.ch.
authors.forename: Mahmut
authors.initials: M
authors.lastname: Ozsahin
authors.affiliation: Department of Radiation Oncology, Lausanne University Hospital, Lausanne, Switzerland. Electronic address: fernanda.herrera@chuv.ch.
authors.forename: Fernanda G
authors.initials: FG
authors.lastname: Herrera
mesh_terms: D000208:Acute Disease; D000230:Adenocarcinoma / Q000000981:diagnostic imaging / Q000628:therapy; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001772:Blood Cell Count; D001853:Bone Marrow / Q000000981:diagnostic imaging / Q000378:metabolism / Q000528:radiation effects*; D001854:Bone Marrow Cells / Q000000981:diagnostic imaging / Q000378:metabolism / Q000528:radiation effects*; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging / Q000628:therapy; D059248:Chemoradiotherapy / Q000009:adverse effects / Q000379:methods*; D002945:Cisplatin / Q000008:administration & dosage; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D006801:Humans; D008875:Middle Aged; D064847:Multimodal Imaging; D049268:Positron-Emission Tomography / Q000379:methods; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D011879:Radiotherapy Dosage; D050397:Radiotherapy, Intensity-Modulated / Q000379:methods; D012044:Regression Analysis; D012189:Retrospective Studies; D014057:Tomography, X-Ray Computed / Q000379:methods; D002583:Uterine Cervical Neoplasms / Q000000981:diagnostic imaging / Q000628:therapy*
chemical_list: D011838:Radiation-Sensitizing Agents; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D002945:Cisplatin