title: Modeling early haematologic adverse events in conformal and intensity-modulated pelvic radiotherapy in anal cancer.
abstract: OBJECTIVE
  To determine if there are differences between dose to pelvic bone marrow (PBM) using intensity modulated radiotherapy (IMRT) under UK guidance versus conformal radiotherapy (CRT) per ACT II protocol and if differences translate to rates of early haematological adverse events grade 3 or greater (HT3+).
  
  
  METHODS
  Two groups of 20+ patients, treated under IMRT and CRT regimes respectively, were identified. All patients underwent weekly blood cell count: haemoglobin (HgB), white cell count (WCC), absolute neutrophil count (ANC) and platelets (plats). Percent volume of PBM and sub structures receiving 5-25 Gy were tested for statistical significance. Regression models were used to test for correlation to blood counts. NTCP modeling was also performed.
  
  
  RESULTS
  PMB dose metrics showed a significant increase in the IMRT group. Regression analysis showed iliac and lumbosacral PBM dose metrics to associate with reduced nadir ANC and WCC. NTCP at HT3+ was 0.13 using IMRT relative to 0.07 using CRT (p<0.05).
  
  
  CONCLUSIONS
  Whilst this is a relatively small retrospective study and lacks information on the distribution of active PBM, IMRT treatment has been shown to significantly increase PMB irradiation. PBM dose metrics have been shown to be predictive of WCC and ANC suppression. NTCP modeling predicts much high risk of HT3+. Paradoxically, actual rates of HT3+ were comparable suggesting that differences in the distributions of dose metrics maybe a significant factor and/or that there are insufficiency in the NTCP modeling.
authors.affiliation: Department of Oncology, University of Oxford, UK.
authors.forename: Maxwell
authors.initials: M
authors.lastname: Robinson
authors.affiliation: Department of Clinical Oncology, Oxford University Hospitals NHS Trust, UK.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Sabbagh
authors.affiliation: Department of Oncology, University of Oxford, UK.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Muirhead
authors.affiliation: Department of Oncology, University of Oxford, UK.
authors.forename: Lisa
authors.initials: L
authors.lastname: Durrant
authors.affiliation: Department of Oncology, University of Oxford, UK.
authors.forename: Frank
authors.initials: F
authors.lastname: Van den Heuvel
authors.affiliation: Department of Oncology, University of Oxford, UK.
authors.forename: Maria
authors.initials: M
authors.lastname: Hawkins
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001005:Anus Neoplasms / Q000532:radiotherapy*; D001772:Blood Cell Count; D001853:Bone Marrow / Q000528:radiation effects; D005260:Female; D006402:Hematologic Diseases / Q000209:etiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D010384:Pelvic Bones / Q000528:radiation effects; D011829:Radiation Dosage; D011832:Radiation Injuries / Q000209:etiology*; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal / Q000009:adverse effects* / Q000379:methods; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects* / Q000379:methods; D012044:Regression Analysis; D012189:Retrospective Studies
keywords: Haematological toxicity; Intensity modulated radiotherapy; Normal tissue complication probability modeling; Pelvic bone marrow