title: Multi-variable models of large International Prostate Symptom Score worsening at the end of therapy in prostate cancer radiotherapy.
abstract: OBJECTIVE
  Prospectively assessing clinical/dosimetry factors affecting the acute worsening of urinary functionality after radiotherapy for prostate cancer.
  
  
  METHODS
  DUE01 population was considered, including patients treated with conventional or moderate hypo-fractionation (2.2-2.7 Gy/fr). Relevant clinical factors were collected, urinary symptoms were self-reported through the International Prostate Symptom Score (IPSS) before and at the end of radiotherapy; while absolute weekly dose-surface histograms (DSHw) were chosen as dosimetry descriptors. An IPSS increase of at least 10 and 15 points (ΔIPSS ⩾ 10 and ΔIPSS ⩾ 15) were chosen as endpoints. Patients with baseline IPSS>20 were excluded. Relevant factors were chosen through a bootstrap-based in silico methodology.
  
  
  RESULTS
  Complete information was available for 380 patients: 77/380 (20%) and 28/380 (7%) with ΔIPSS ⩾ 10 and ΔIPSS ⩾ 15, respectively. Neoadjuvant hormone was protective (OR=0.49 and 0.69). DSHw at 8.5 Gy/week and 12 Gy/week were risk factors, with additional risk for patients who use cardiovascular drugs and anti-hypercholesterolemia drugs. In the hypo-fractionated subgroup (n=209) the role of cardiovascular drugs (OR=2.16) for ΔIPSS ⩾ 10 and anti-hypercholesterolemia drugs (OR=2.80) for ΔIPSS⩾15, together with DSHw (10 Gy/week and 12.5 Gy/week, respectively), was confirmed.
  
  
  CONCLUSIONS
  Current study shows a dose-surface/volume effect for acute large worsening of urinary functionality; several clinical variables largely impact the risk and especially all the factors related with vascular diseases.
authors.affiliation: Medical Physics, San Raffaele Scientific Institute, Milano, Italy. Electronic address: palorini.federica@hsr.it.
authors.forename: Federica
authors.initials: F
authors.lastname: Palorini
authors.affiliation: Prostate Cancer Program, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Rancati
authors.affiliation: Radiotherapy, San Raffaele Scientific Institute, Milano, Italy.
authors.forename: Cesare
authors.initials: C
authors.lastname: Cozzarini
authors.affiliation: Medical Physics, San Raffaele Scientific Institute, Milano, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Improta
authors.affiliation: Medical Physics, San Raffaele Scientific Institute, Milano, Italy.
authors.forename: Viviana
authors.initials: V
authors.lastname: Carillo
authors.affiliation: Radiation Oncology 1, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Avuzzi
authors.affiliation: Medical Physics, Ospedale ASL9, Ivrea, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Casanova Borca
authors.affiliation: Medical Physics, Arcispedale S.M. Nuova - IRCCS, Reggio Emilia, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Botti
authors.affiliation: Radiotherapy, Ospedale Bellaria, Bologna, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Degli Esposti
authors.affiliation: Radiotherapy, Ospedale Regionale U. Parini-AUSL Valle d'Aosta, Aosta, Italy.
authors.forename: Pierfrancesco
authors.initials: P
authors.lastname: Franco
authors.affiliation: Radiotherapy, Istituto di Candiolo - Fondazione del Piemonte per l'Oncologia IRCCS, Candiolo, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Garibaldi
authors.affiliation: Radiotherapy, Ospedale ASL9, Ivrea, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Girelli
authors.affiliation: Radiotherapy, Arcispedale S. M. Nuova - IRCCS, Reggio Emilia, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Iotti
authors.affiliation: Medical Physics, Istituto di Candiolo - Fondazione del Piemonte per l'Oncologia IRCCS, Candiolo, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Maggio
authors.affiliation: Medical Physics, Ospedale Bellaria, Bologna, Italy.
authors.forename: Marcella
authors.initials: M
authors.lastname: Palombarini
authors.affiliation: Medical Physics, Cliniche Gavazzeni-Humanitas, Bergamo, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: Pierelli
authors.affiliation: Medical Physics, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Pignoli
authors.affiliation: Radiotherapy, Cliniche Gavazzeni-Humanitas, Bergamo, Italy.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Vavassori
authors.affiliation: Prostate Cancer Program, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy; Radiation Oncology 1, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Valdagni
authors.affiliation: Medical Physics, San Raffaele Scientific Institute, Milano, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Fiorino
mesh_terms: D000368:Aged; D001918:Brachytherapy / Q000009:adverse effects / Q000379:methods; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D008297:Male; D020360:Neoadjuvant Therapy / Q000009:adverse effects; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000532:radiotherapy*; D011832:Radiation Injuries / Q000209:etiology*; D011874:Radiometry; D012307:Risk Factors; D012720:Severity of Illness Index; D014555:Urination Disorders / Q000209:etiology*
chemical_list: D017430:Prostate-Specific Antigen
keywords: Dose–volume effects; Prostate cancer; Radiotherapy; Urinary toxicity