title: Late Side Effects After Image Guided Intensity Modulated Radiation Therapy Compared to 3D-Conformal Radiation Therapy for Prostate Cancer: Results From 2 Prospective Cohorts.
abstract: Technical developments in the field of external beam radiation therapy (RT) enabled the clinical introduction of image guided intensity modulated radiation therapy (IG-IMRT), which improved target conformity and allowed reduction of safety margins. Whether this had an impact on late toxicity levels compared to previously applied three-dimensional conformal radiation therapy (3D-CRT) is currently unknown. We analyzed late side effects after treatment with IG-IMRT or 3D-CRT, evaluating 2 prospective cohorts of men treated for localized prostate cancer to investigate the hypothesized reductions in toxicity.
  
  
  
  Patients treated with 3D-CRT (n=189) or IG-IMRT (n=242) to 78 Gy in 39 fractions were recruited from 2 Dutch randomized trials with identical toxicity scoring protocols. Late toxicity (>90 days after treatment) was derived from self-assessment questionnaires and case report forms, according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG-EORTC) scoring criteria. Grade ≥2 endpoints included gastrointestinal (GI) rectal bleeding, increased stool frequency, discomfort, rectal incontinence, proctitis, and genitourinary (GU) obstruction, increased urinary frequency, nocturia, urinary incontinence, and dysuria. The Cox proportional hazards regression model was used to compare grade ≥2 toxicities between both techniques, adjusting for other modifying factors.
  
  
  
  The 5-year cumulative incidence of grade ≥2 GI toxicity was 24.9% for IG-IMRT and 37.6% following 3D-CRT (adjusted hazard ratio [HR]: 0.59, P=.005), with significant reductions in proctitis (HR: 0.37, P=.047) and increased stool frequency (HR: 0.23, P<.001). GU grade ≥2 toxicity levels at 5 years were comparable with 46.2% and 36.4% following IG-IMRT and 3D-CRT, respectively (adjusted HR: 1.19, P=.33). Other strong predictors (P<.01) of grade ≥2 late toxicity were baseline complaints, acute toxicity, and age.
  
  
  
  Treatment with IG-IMRT reduced the risk of late grade ≥2 complications, whereas GU toxicities remained comparable. This clinically relevant observation demonstrates that IMRT and image-guidance should therefore be the preferred treatment option, provided that margin reduction is implemented with caution.
authors.affiliation: Department of Radiation Oncology, Erasmus Medical Center Cancer Institute, Rotterdam, The Netherlands.
authors.forename: Ruud C
authors.initials: RC
authors.lastname: Wortel
authors.affiliation: Department of Radiation Oncology, Erasmus Medical Center Cancer Institute, Rotterdam, The Netherlands.
authors.forename: Luca
authors.initials: L
authors.lastname: Incrocci
authors.affiliation: Department of Radiation Oncology, Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
authors.forename: Floris J
authors.initials: FJ
authors.lastname: Pos
authors.affiliation: Department of Radiation Oncology, Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
authors.forename: Uulke A
authors.initials: UA
authors.lastname: van der Heide
authors.affiliation: Department of Radiation Oncology, Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
authors.forename: Joos V
authors.initials: JV
authors.lastname: Lebesque
authors.affiliation: Department of Radiation Oncology, Erasmus Medical Center Cancer Institute, Rotterdam, The Netherlands.
authors.forename: Shafak
authors.initials: S
authors.lastname: Aluwini
authors.affiliation: Department of Radiation Oncology, Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
authors.forename: Marnix G
authors.initials: MG
authors.lastname: Witte
authors.affiliation: Department of Radiation Oncology, Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands. Electronic address: w.heemsbergen@nki.nl.
authors.forename: Wilma D
authors.initials: WD
authors.lastname: Heemsbergen
mesh_terms: D000368:Aged; D015331:Cohort Studies; D041981:Gastrointestinal Tract / Q000528:radiation effects; D006801:Humans; D008297:Male; D000071066:Patient Reported Outcome Measures; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000532:radiotherapy*; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal / Q000009:adverse effects*; D061089:Radiotherapy, Image-Guided / Q000009:adverse effects*; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects*; D014566:Urogenital System / Q000528:radiation effects