title: Genital invasion or perigenital spread may pose a risk of marginal misses for Intensity Modulated Radiotherapy (IMRT) in anal cancer.
abstract: BACKGROUND
  While intensity modulated radiotherapy (IMRT) in anal cancer is feasible and improves high-dose conformality, the current RTOG/AGITG contouring atlas and planning guidelines lack specific instructions on how to proceed with external genitalia. Meanwhile, the RTOG-Protocol 0529 explicitly recommends genital sparing on the basis of specific genital dose constraints. Recent pattern-of-relapse studies based on conventional techniques suggest that marginal miss might be a potential consequence of genital sparing. Our goal is to outline the potential scope and increase the awareness for this clinical issue.
  
  
  METHODS
  We present and discuss four patients with perigenital spread in anal cancer in both early and advanced stages (three at time of first diagnosis and one in form of relapse). Genital/perigenital spread was observed once as direct genital infiltration and thrice in form of perigenital lymphatic spread.
  
  
  RESULTS
  We review the available data regarding the potential consequences of genital sparing in anal cancer. Pattern-of-relapse studies in anal cancer after conventional radiotherapy and the current use of IMRT in anal cancer are equivocal but suggest that genital sparing may occasionally result in marginal miss. An obvious hypothesis suggested by our report is that perigenital lymphovascular invasion might be associated with manifest inguinal N+ disease.
  
  
  CONCLUSIONS
  Local failure has low salvage rates in recent anal cancer treatment series. Perigenital spread may pose a risk of marginal misses in IMRT in anal cancer. To prevent marginal misses, meticulous pattern-of-relapse analyses of controlled IMRT-series are warranted. Until their publication, genital sparing should be applied with caution, PET/CT should be used when possible and meeting genital dose constraints should not be prioritized over CTV coverage, especially (but not only) in stage T3/4 and N+ disease.
authors.affiliation: Department of Radiation Oncology, University Medical Center Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68135, Mannheim, Germany. julia_koeck@gmx.net.
authors.forename: Julia
authors.initials: J
authors.lastname: Koeck
authors.affiliation: Department of Radiation Oncology, University Medical Center Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68135, Mannheim, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Lohr
authors.affiliation: Department of Radiation Oncology, University Medical Center Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68135, Mannheim, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Buergy
authors.affiliation: Department of Clinical Radiology and Nuclear Medicine, University Medical Center Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Karen
authors.initials: K
authors.lastname: Büsing
authors.affiliation: Institute of Pathology, University Medical Center Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Marcus J
authors.initials: MJ
authors.lastname: Trunk
authors.affiliation: Department of Radiation Oncology, University Medical Center Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68135, Mannheim, Germany.
authors.forename: Frederik
authors.initials: F
authors.lastname: Wenz
authors.affiliation: Department of Radiation Oncology, University Medical Center Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68135, Mannheim, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Mai
mesh_terms: D000368:Aged; D001005:Anus Neoplasms / Q000473:pathology*; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000000981:diagnostic imaging* / Q000532:radiotherapy*; D000072078:Positron Emission Tomography Computed Tomography; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods; D050397:Radiotherapy, Intensity-Modulated / Q000379:methods*; D012008:Recurrence; D016879:Salvage Therapy; D012611:Scrotum / Q000473:pathology; D013736:Testicular Neoplasms / Q000556:secondary*; D016896:Treatment Outcome; D014566:Urogenital System / Q000473:pathology; D014846:Vulvar Neoplasms / Q000556:secondary*
keywords: Anal carcinoma; Genital sparing; Intensity Modulated Radiotherapy (IMRT); Lymphatic spread; Marginal miss; Perigenital spread; Vulvar relapse