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 and 18F-FDG-PET/CT.
BACKGROUND
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.


METHODS
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 by 18F-FDG-PET/CT. Baseline and residual values after IC-1 were calculated and correlated with LFS, TSS and OS.


RESULTS
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 SUVmax and 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).


CONCLUSION
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.
['Wichmann|Gunnar|G|', 'Krüger|Anne|A|', 'Boehm|Andreas|A|', 'Kolb|Marlen|M|', 'Hofer|Mathias|M|', 'Fischer|Milos|M|', 'Müller|Stefan|S|', 'Purz|Sandra|S|', 'Stumpp|Patrick|P|', 'Sabri|Osama|O|', 'Dietz|Andreas|A|', 'Kluge|Regine|R|']
D000328:Adult D000368:Aged D000971:Antineoplastic Combined Chemotherapy Protocols D000068818:Cetuximab D002945:Cisplatin D005260:Female D005472:Fluorouracil D006801:Humans D007012:Hypopharyngeal Neoplasms D060828:Induction Chemotherapy D007822:Laryngeal Neoplasms D008198:Lymph Nodes D008297:Male D008875:Middle Aged D059351:Organ Sparing Treatments D011446:Prospective Studies D016879:Salvage Therapy D016019:Survival Analysis D043823:Taxoids D014057:Tomography, X-Ray Computed
Induction chemotherapy Larynx preservation Hypopharyngeal cancer Decision-making (18)F-FDG Early response evaluation HNSCC Head and neck cancer Laryngeal cancer PET/CT