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Published on: March 18, 2020
Treatment of Locally Advanced Layngohypopharyngeal Cancers: A Network Meta-Analysis
Vincenzo Capriotti1, Elisa Dal Cin2, Agostina De Stefani3
1Otorhinolaryngology Unit, Portogruaro Hospital, Portogruaro, Italy.
Objective:
To compare the efficacy of non-surgical organ-preservation strategies for locally advanced or resectable laryngeal and hypopharyngeal squamous cell carcinoma (SCC).
Data Sources:
Randomized controlled trials (RCTs) published through June 30, 2025, identified via systematic database and trial-registry searches and reference screening.
Review Methods:
We performed a systematic review and Bayesian random-effects network meta-analysis of RCTs enrolling adults with locally advanced/resectable laryngeal/hypopharyngeal SCC. Treatments included surgery plus postoperative radiotherapy (RT), RT alone, concurrent cisplatin-based chemoradiotherapy (CTRT), induction chemotherapy followed by RT/CTRT, altered-fractionation RT, dose-modified CTRT, and RT ± cetuximab. Effect estimates were synthesized as hazard ratios (HRs) and odds ratios (ORs). Treatments were ranked using surface under the cumulative ranking curve (SUCRA).
Results:
Fifteen RCTs (n = 4395; 13 strategies) were included. For laryngeal preservation, cisplatin-based CTRT ranked highest (SUCRA 0.73), followed by induction TPF → RT (0.72) and RT + cetuximab (0.61). All non-surgical strategies outperformed surgery plus postoperative RT for laryngeal preservation (HR 0.34; 95% CI, 0.20-0.58). For overall survival, induction PF → RT showed the highest probability of benefit (SUCRA 0.68), with overlapping credible intervals across leading regimens. For locoregional control, induction TPF → RT ranked best (SUCRA 0.94). Sensitivity analyses supported robustness.
Conclusion:
Concurrent cisplatin-based CTRT remains the most consistent organ-preservation strategy. Induction PF → RT may offer modest overall survival benefit, whereas sequential TPF → RT appears superior for locoregional control. Treatment should be individualized by comorbidity, functional goals, and institutional expertise; head-to-head trials and incorporation of immunotherapy/targeted agents are needed.
Level Of Evidence:
N/A.
Insights
Concurrent cisplatin-based chemoradiotherapy (CTRT) is the most effective organ-preservation strategy for laryngeal cancer. Induction chemotherapy followed by radiotherapy shows promise for survival and locoregional control.
Area of Science:
- Oncology
- Head and Neck Cancer Research
- Clinical Trials and Meta-Analysis
Background:
- Laryngeal and hypopharyngeal squamous cell carcinoma (SCC) require effective organ-preservation strategies.
- Non-surgical approaches are increasingly investigated to improve patient outcomes and quality of life.
Purpose of the Study:
- To compare the efficacy of various non-surgical organ-preservation strategies for locally advanced or resectable laryngeal and hypopharyngeal SCC.
- To identify the optimal treatment strategy based on available evidence from randomized controlled trials (RCTs).
Main Methods:
- Systematic review and Bayesian random-effects network meta-analysis of 15 RCTs (n=4395).
- Inclusion of treatments such as surgery plus postoperative radiotherapy (RT), RT alone, concurrent cisplatin-based chemoradiotherapy (CTRT), induction chemotherapy followed by RT/CTRT, and others.
- Synthesis of effect estimates using hazard ratios (HRs) and odds ratios (ORs), with treatment ranking via surface under the cumulative ranking curve (SUCRA).
Main Results:
- Concurrent cisplatin-based CTRT demonstrated the highest efficacy for laryngeal preservation (SUCRA 0.73).
- Induction TPF-RT (docetaxel, cisplatin, 5-fluorouracil followed by RT) ranked highest for locoregional control (SUCRA 0.94) and showed potential for overall survival benefit (SUCRA 0.68).
- All non-surgical strategies outperformed surgery plus postoperative RT for laryngeal preservation.
Conclusions:
- Concurrent cisplatin-based CTRT is the most consistent organ-preservation strategy.
- Induction chemotherapy regimens may offer survival and locoregional control advantages.
- Individualized treatment selection based on patient factors and future head-to-head trials incorporating novel agents are recommended.