title: Fat composition changes in bone marrow during chemotherapy and radiation therapy.
abstract: OBJECTIVE
  To quantify changes in bone marrow fat fraction and determine associations with peripheral blood cell counts.
  
  
  METHODS
  In this prospective study, 19 patients received either highly myelotoxic treatment (radiation therapy plus cisplatin, 5-fluorouracil mitomycin C [FU/MMC], or cisplatin/5-FU/cetuximab) or less myelotoxic treatment (capecitabine-radiation therapy or no concurrent chemotherapy). Patients underwent MR imaging and venipuncture at baseline, midtreatment, and posttreatment visits. We performed mixed effects modeling of the mean proton density fat fraction (PDFF[%]) by linear time, treatment, and vertebral column region (lumbar [L]4-sacral [S]2 vs thoracic [T]10-L3 vs cervical[C]3-T9), while controlling for cumulative mean dose and other confounders. Spearman rank correlations were performed by white blood cell (WBC) counts versus the differences in PDFF(%) before and after treatment.
  
  
  RESULTS
  Cumulative mean dose was associated with a 0.43% per Gy (P=.004) increase in PDFF(%). In the highly myelotoxic group, we observed significant changes in PDFF(%) per visit within L4-S2 (10.1%, P<.001) and within T10-L3 (3.93%, P=.01), relative to the reference C3-T9. In the less myelotoxic group, we did not observe significant changes in PDFF(%) per visit according to region. Within L4-S2, we observed a significant difference between treatment groups in the change in PDFF(%) per visit (5.36%, P=.04). Rank correlations of the inverse log differences in WBC versus the differences in PDFF(%) overall and within T10-S2 ranged from 0.69 to 0.78 (P<.05). Rank correlations of the inverse log differences in absolute neutrophil counts versus the differences in PDFF(%) overall and within L4-S2 ranged from 0.79 to 0.81 (P<.05).
  
  
  CONCLUSIONS
  Magnetic resonance imaging fat quantification is sensitive to marrow composition changes that result from chemoradiation therapy. These changes are associated with peripheral blood cell counts. This study supports a rationale for bone marrow-sparing treatment planning to reduce the risk of hematologic toxicity.
authors.affiliation: Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California.
authors.forename: Ruben
authors.initials: R
authors.lastname: Carmona
authors.affiliation: Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California.
authors.forename: Jakub
authors.initials: J
authors.lastname: Pritz
authors.affiliation: Department of Radiology, University of California San Diego Medical Center, San Diego, California.
authors.forename: Mark
authors.initials: M
authors.lastname: Bydder
authors.affiliation: Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California.
authors.forename: Sachin
authors.initials: S
authors.lastname: Gulaya
authors.affiliation: Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California.
authors.forename: He
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California.
authors.forename: Casey W
authors.initials: CW
authors.lastname: Williamson
authors.affiliation: Department of Radiology, University of California San Diego Medical Center, San Diego, California.
authors.forename: Christian S
authors.initials: CS
authors.lastname: Welch
authors.affiliation: Biostatistics and Bioinformatics, Department of Family and Preventive Medicine, University of California San Diego Medical Center, San Diego, California.
authors.forename: Florin
authors.initials: F
authors.lastname: Vaida
authors.affiliation: Department of Radiology, University of California San Diego Medical Center, San Diego, California.
authors.forename: Graeme
authors.initials: G
authors.lastname: Bydder
authors.affiliation: Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California. Electronic address: lmell@ucsd.edu.
authors.forename: Loren K
authors.initials: LK
authors.lastname: Mell
mesh_terms: D000273:Adipose Tissue / Q000033:anatomy & histology / Q000187:drug effects* / Q000528:radiation effects*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001005:Anus Neoplasms / Q000628:therapy; D001772:Blood Cell Count; D001853:Bone Marrow / Q000033:anatomy & histology / Q000187:drug effects* / Q000528:radiation effects*; D001854:Bone Marrow Cells / Q000187:drug effects / Q000528:radiation effects; D000069287:Capecitabine; D002574:Cervical Vertebrae / Q000033:anatomy & histology / Q000187:drug effects / Q000528:radiation effects; D000068818:Cetuximab; D059248:Chemoradiotherapy / Q000009:adverse effects* / Q000379:methods; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D016889:Endometrial Neoplasms / Q000628:therapy; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000031:analogs & derivatives; D006801:Humans; D008159:Lumbar Vertebrae / Q000033:anatomy & histology / Q000187:drug effects / Q000528:radiation effects; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage; D017239:Paclitaxel / Q000008:administration & dosage; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000628:therapy; D011879:Radiotherapy Dosage; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects; D012004:Rectal Neoplasms / Q000628:therapy; D013131:Spine / Q000033:anatomy & histology / Q000187:drug effects* / Q000528:radiation effects*; D013904:Thoracic Vertebrae / Q000033:anatomy & histology / Q000187:drug effects / Q000528:radiation effects; D002583:Uterine Cervical Neoplasms / Q000628:therapy
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D003841:Deoxycytidine; D016685:Mitomycin; D000069287:Capecitabine; D017239:Paclitaxel; D000068818:Cetuximab; D002945:Cisplatin; D005472:Fluorouracil