title: Impact of bone marrow radiation dose on acute hematologic toxicity in cervical cancer: principal component analysis on high dimensional data.
abstract: OBJECTIVE
  To study the effects of increasing pelvic bone marrow (BM) radiation dose on acute hematologic toxicity in patients undergoing chemoradiotherapy, using a novel modeling approach to preserve the local spatial dose information.
  
  
  METHODS
  The study included 37 cervical cancer patients treated with concurrent weekly cisplatin and pelvic radiation therapy. The white blood cell count nadir during treatment was used as the indicator for acute hematologic toxicity. Pelvic BM radiation dose distributions were standardized across patients by registering the pelvic BM volumes to a common template, followed by dose remapping using deformable image registration, resulting in a dose array. Principal component (PC) analysis was applied to the dose array, and the significant eigenvectors were identified by linear regression on the PCs. The coefficients for PC regression and significant eigenvectors were represented in three dimensions to identify critical BM subregions where dose accumulation is associated with hematologic toxicity.
  
  
  RESULTS
  We identified five PCs associated with acute hematologic toxicity. PC analysis regression modeling explained a high proportion of the variation in acute hematologicity (adjusted R(2), 0.49). Three-dimensional rendering of a linear combination of the significant eigenvectors revealed patterns consistent with anatomical distributions of hematopoietically active BM.
  
  
  CONCLUSIONS
  We have developed a novel approach that preserves spatial dose information to model effects of radiation dose on toxicity, which may be useful in optimizing radiation techniques to avoid critical subregions of normal tissues. Further validation of this approach in a large cohort is ongoing.
authors.affiliation: Department of Radiation Oncology, Center for Advanced Radiotherapy Technologies, University of California San Diego, La Jolla, California, USA.
authors.forename: Yun
authors.initials: Y
authors.lastname: Liang
authors.forename: Karen
authors.initials: K
authors.lastname: Messer
authors.forename: Brent S
authors.initials: BS
authors.lastname: Rose
authors.forename: John H
authors.initials: JH
authors.lastname: Lewis
authors.forename: Steve B
authors.initials: SB
authors.lastname: Jiang
authors.forename: Catheryn M
authors.initials: CM
authors.lastname: Yashar
authors.forename: Arno J
authors.initials: AJ
authors.lastname: Mundt
authors.forename: Loren K
authors.initials: LK
authors.lastname: Mell
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D001853:Bone Marrow / Q000000981:diagnostic imaging / Q000187:drug effects / Q000528:radiation effects*; D001854:Bone Marrow Cells; D002945:Cisplatin / Q000627:therapeutic use; D003131:Combined Modality Therapy / Q000009:adverse effects / Q000379:methods; D005260:Female; D006801:Humans; D007958:Leukocyte Count; D007962:Leukocytes / Q000187:drug effects / Q000528:radiation effects; D007970:Leukopenia / Q000209:etiology* / Q000473:pathology; D016014:Linear Models; D008875:Middle Aged; D010384:Pelvic Bones / Q000000981:diagnostic imaging* / Q000528:radiation effects; D010388:Pelvis; D025341:Principal Component Analysis / Q000379:methods*; D011859:Radiography; D011879:Radiotherapy Dosage; D050397:Radiotherapy, Intensity-Modulated / Q000379:methods; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin
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