title: Dose-volume effects for pelvic bone marrow in predicting hematological toxicity in prostate cancer radiotherapy with pelvic node irradiation.
abstract: OBJECTIVE
  To prospectively identify clinical/dosimetric predictors of acute/late hematologic toxicity (HT) in chemo-naÏve patients treated with whole-pelvis radiotherapy (WPRT) for prostate cancer.
  
  
  METHODS
  Data of 121 patients treated with adjuvant/salvage WPRT were analyzed (static-field IMRT n=19; VMAT/Rapidarc n=57; Tomotherapy n=45). Pelvic bone marrow (BM) was delineated as ilium (IL), lumbosacral, lower and whole pelvis (WP), and the relative DVHs were calculated. HT was graded both according to CTCAE v4.03 and as variation in percentage relative to baseline. Logistic regression was used to analyze association between HT and clinical/DVHs factors.
  
  
  RESULTS
  Significant differences (p<0.005) in the DVH of BM volumes between different techniques were found: Tomotherapy was associated with larger volumes receiving low doses (3-20 Gy) and smaller receiving 40-50 Gy. Lower baseline absolute values of WBC, neutrophils and lymphocytes (ALC) predicted acute/late HT (p ⩽ 0.001). Higher BM V40 was associated with higher risk of acute Grade3 (OR=1.018) or late Grade2 lymphopenia (OR=1.005). Two models predicting lymphopenia were developed, both including baseline ALC, and BM WP-V40 (AUC=0.73) and IL-V40+smoking (AUC=0.904) for acute/late respectively.
  
  
  CONCLUSIONS
  Specific regions of pelvic BM predicting acute/late lymphopenia, a risk factor for viral infections, were identified. The 2-variable models including specific constraints to BM may help reduce HT.
authors.affiliation: Department of Medical Physics, San Raffaele Scientific Institute, Milan, Italy. Electronic address: sini.carla@hsr.it.
authors.forename: Carla
authors.initials: C
authors.lastname: Sini
authors.affiliation: Department of Medical Physics, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Fiorino
authors.affiliation: Department of Medical Physics, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Perna
authors.affiliation: Department of Radiotherapy, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Noris Chiorda
authors.affiliation: Department of Radiotherapy, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Chiara Lucrezia
authors.initials: CL
authors.lastname: Deantoni
authors.affiliation: Department of Urology, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Bianchi
authors.affiliation: Department of Radiotherapy, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Sacco
authors.affiliation: Department of Urology, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Briganti
authors.affiliation: Department of Urology, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Montorsi
authors.affiliation: Department of Medical Physics, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Calandrino
authors.affiliation: Department of Radiotherapy, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Nadia
authors.initials: N
authors.lastname: Di Muzio
authors.affiliation: Department of Radiotherapy, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Cesare
authors.initials: C
authors.lastname: Cozzarini
mesh_terms: D000368:Aged; D001853:Bone Marrow / Q000528:radiation effects*; D059248:Chemoradiotherapy / Q000009:adverse effects; D006402:Hematologic Diseases / Q000209:etiology*; D006801:Humans; D015182:Lymphatic Irradiation / Q000009:adverse effects / Q000379:methods; D008231:Lymphopenia / Q000209:etiology; D008297:Male; D008875:Middle Aged; D010384:Pelvic Bones / Q000528:radiation effects; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000532:radiotherapy*; D011832:Radiation Injuries / Q000209:etiology; D011874:Radiometry; D011879:Radiotherapy Dosage; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects / Q000379:methods; D020266:Radiotherapy, Conformal / Q000009:adverse effects / Q000379:methods; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects / Q000379:methods; D016879:Salvage Therapy / Q000009:adverse effects / Q000379:methods
keywords: Bone marrow; Hematologic toxicity; Intensity-modulated radiotherapy; Prostate cancer