title: Induction chemotherapy followed by radiotherapy for larynx preservation in advanced laryngeal and hypopharyngeal cancer: Outcome prediction after one cycle induction chemotherapy by a score based on clinical evaluation, computed tomography-based volumetry and18F-FDG-PET/CT.
abstract: Long-term laryngectomy-free (LFS), tumour-specific (TSS) and overall survival (OS) is achieved by non-surgical larynx preservation (LP) only in a proportion of patients with locally advanced laryngeal or hypopharyngeal cancer. A score facilitating decision-making after 1 cycle induction chemotherapy (IC-1) may improve LFS and TSS.
  
  
  
  Early response to IC-1 with TPF ± cetuximab was assessed in 52 patients using endoscopic tumour staging for selecting total laryngectomy for non-responders with endoscopic tumour surface shrinkage <30% versus induction chemotherapy plus radiotherapy (IC + RT) for responders. Computed tomography (CT)-based volumetry was used to assess volumes of primary tumour, neck nodes and their sum; maximum and mean standardised uptake value (SUVmax, SUVmean) were measured by18F-FDG-PET/CT. Baseline and residual values after IC-1 were calculated and correlated with LFS, TSS and OS.
  
  
  
  After IC-1, 39/52 patients (75%) were early responders. Early response predicted complete response to IC + RT (p = 8.48 × 10-9). Early laryngectomised non-responders and responders with endoscopic tumour surface shrinkage > 70% had best OS. Significant independent predictors for LFS in responders are number of CT-staged suspect positive neck nodes (N+), residual primary tumour volume, residual total tumour volume and the ratio of residual SUVmaxand SUVmean(resSUVmax/resSUVmean). Our LFS-score combines >2N+, residual primary tumour volume > 20%, residual total tumour volume > 5.6 mL and resSUVmax/resSUVmean> 1.51 weighted by their hazard ratio (12, 6, 5 and 4); LFS-score ≤ 16 predicts increased LFS, OS and TSS (p < 0.05).
  
  
  
  LFS-score ≤ 16 identifies in responders to IC-1 the patients with maximum benefit of non-surgical LP achieving long-term LFS. Even more importantly, a LFS-score > 16 defines patients unsuitable for LP applying the TPF/TP IC + RT protocol.
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, University of Leipzig, Germany. Electronic address: gunnar.wichmann@medizin.uni-leipzig.de.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Wichmann
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, University of Leipzig, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Krüger
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, University of Leipzig, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Boehm
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, University of Leipzig, Germany.
authors.forename: Marlen
authors.initials: M
authors.lastname: Kolb
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, University of Leipzig, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Hofer
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, University of Leipzig, Germany.
authors.forename: Milos
authors.initials: M
authors.lastname: Fischer
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, University of Leipzig, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Müller
authors.affiliation: Department of Nuclear Medicine, University of Leipzig, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Purz
authors.affiliation: Department of Diagnostic and Interventional Radiology, University of Leipzig, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Stumpp
authors.affiliation: Department of Nuclear Medicine, University of Leipzig, Germany.
authors.forename: Osama
authors.initials: O
authors.lastname: Sabri
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, University of Leipzig, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Dietz
authors.affiliation: Department of Nuclear Medicine, University of Leipzig, Germany.
authors.forename: Regine
authors.initials: R
authors.lastname: Kluge
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D000068818:Cetuximab / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007012:Hypopharyngeal Neoplasms / Q000188:drug therapy / Q000532:radiotherapy; D060828:Induction Chemotherapy / Q000379:methods*; D007822:Laryngeal Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D008875:Middle Aged; D059351:Organ Sparing Treatments / Q000379:methods; D011446:Prospective Studies; D016879:Salvage Therapy / Q000379:methods*; D016019:Survival Analysis; D043823:Taxoids / Q000008:administration & dosage; D014057:Tomography, X-Ray Computed
chemical_list: D043823:Taxoids; D000068818:Cetuximab; D002945:Cisplatin; D005472:Fluorouracil
keywords: (18)F-FDG; Decision-making; Early response evaluation; HNSCC; Head and neck cancer; Hypopharyngeal cancer; Induction chemotherapy; Laryngeal cancer; Larynx preservation; PET/CT