Efficacy of Non-Surgical Larynx-Preservation Comprehensive Treatment in Advanced Laryngeal Carcinoma

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Efficacy of Non-Surgical Larynx-Preservation Comprehensive Treatment in Advanced Laryngeal Carcinoma

Introduction

Advanced laryngeal carcinoma presents a significant clinical challenge, balancing oncological control with preservation of laryngeal function. Traditional approaches in China have included radical surgery followed by adjuvant radiotherapy or non-surgical comprehensive treatment for organ preservation. While landmark trials established the feasibility of laryngeal preservation in advanced disease, debates persist regarding optimal strategies. This study evaluates the efficacy of a non-surgical, multidisciplinary approach aimed at preserving laryngeal function while achieving durable disease control.

Patient Cohort and Inclusion Criteria

The study included 67 patients with advanced laryngeal squamous cell carcinoma treated between November 2007 and September 2018 at a tertiary referral center. Exclusion criteria encompassed distant metastasis or secondary primary cancers. Patients exhibited a strong preference for laryngeal preservation and declined radical surgery despite being informed of its feasibility. The cohort comprised 61 males and 6 females, with a mean age of 59.1 years (range: 26–80 years). Tumor distribution included supraglottic (39 patients), glottic (25 patients), and subglottic (3 patients) primary lesions. Staging revealed 30 stage III and 37 stage IV cases under the TNM classification system.

Treatment Protocols

Multidisciplinary Strategy

A collaborative team designed individualized protocols based on tumor characteristics and patient factors:

  1. Induction Chemotherapy (ICT) + Concurrent Chemoradiotherapy (CRT) ± EGFR Inhibitors: Preferred for most T4 tumors.
  2. Concurrent CRT ± EGFR Inhibitors: Applied to select T2-T3 cases.
  3. CRT + EGFR Inhibitors Monotherapy: Reserved for elderly patients (>75 years) or those with comorbidities.

EGFR inhibitors were selected based on receptor status: cetuximab (10 patients) and nimotuzumab (22 patients). The first EGFR inhibitor dose coincided with radiotherapy initiation.

Radiotherapy Specifications

Three advanced techniques delivered 6 MV photon beams:

  • Helical Tomotherapy (HT): 11 patients
  • Volumetric-Modulated Arc Therapy (VMAT): 44 patients
  • Intensity-Modulated Radiotherapy (IMRT): 12 patients

Dosimetric parameters standardized across modalities:

  • Planning Gross Tumor Volume (PGTV): 70 Gy to D95 (dose covering 95% volume)
  • Planning Target Volume 1 (PTV1): 60 Gy
  • Planning Target Volume 2 (PTV2): 54 Gy
    Total dose delivered in 33 fractions (5 sessions/week).

Response Assessment and Salvage

Midterm evaluation occurred after 20 fractions (42.2 Gy). Partial response (PR) mandated treatment cessation and surgical referral. Post-treatment recurrences prompted salvage surgery recommendations, though all 8 local recurrence patients declined further intervention.

Clinical Outcomes

Treatment Efficacy

All patients achieved at least PR during midterm assessment, with 52 (77.6%) attaining complete response (CR). Remarkably, the 15 PR cases converted to CR within one month post-treatment, yielding 100% ultimate CR rate.

Survival Metrics (Kaplan-Meier Analysis)

  • Overall Survival (OS): 81.3% at 3 years, 65.7% at 5 years
  • Larynx-Preservation Survival (LPS): 89.9% at 3 years, 87.2% at 5 years
  • Progression-Free Survival (PFS): 80.1% at 3 years, 73.8% at 5 years
  • Local Control Survival (LCS): 85.2% at 3 years, 80.7% at 5 years

Recurrence Patterns

  • Local Recurrence: 8 cases (40–109 months post-treatment), all involving T3/T4 tumors. Concurrent lymph node recurrence occurred in 1 T4aN2M0 case.
  • Nodal Recurrence: 4 cases (10–29 months).

Mortality Analysis

Among 24 deaths at final follow-up (October 2019):

  • Tumor-Related (12): Pulmonary metastasis (4), local recurrence (6), mediastinal metastasis (1), hemorrhagic bone metastasis (1).
  • Non-Tumor (10): Comorbidities (8), unspecified causes (2).

Functional Outcomes

  • Tracheostomy Management: 13 required pretreatment tracheostomy. Decannulation succeeded in 10 patients (6 months post-treatment). Two T3/T4 glottic cases retained permanent cannulas. One patient required recannulation after self-removal due to laryngeal edema.
  • Voice/Swallowing: No permanent gastrostomy dependence or severe dysphonia reported.

Toxicity Profile

Acute Effects

Predominant grade 3 oropharyngeal mucositis, managed effectively without treatment interruption.

Late Effects

  • Grade 1 xerostomia: 44 patients (65.7%)
  • Grade 1 laryngeal edema: 43 patients (64.2%)
  • Anterior glottic web adhesion: 2 patients (3.0%)

Discussion

LPS Superiority

The 5-year LPS (87.2%) surpasses historical benchmarks (66–84%), attributed to:

  1. Mucositis Control: Prevented radiotherapy interruptions, maintaining dose intensity.
  2. Precision Radiotherapy: IMRT/VMAT/HT minimized toxicity while ensuring target coverage.
  3. EGFR Inhibitor Integration: Enhanced radiosensitivity without compounding toxicity.

Survival Comparisons

The 5-year OS (65.7%) aligns with prior organ-preservation studies (42–58%), suggesting comparable oncologic efficacy to radical surgery while preserving laryngeal function.

Functional Preservation

Absence of severe dysphagia or permanent voice impairment contrasts favorably with surgical series. Temporary tracheostomy requirements (19.4% overall) primarily reflected pretreatment airway compromise rather than treatment sequelae.

Limitations and Future Directions

While demonstrating LPS superiority, this single-center experience highlights the need for:

  • Standardized organ preservation protocols
  • Biomarker-driven EGFR inhibitor selection
  • Long-term quality-of-life metrics

The optimal balance between laryngeal preservation and disease control remains undefined, particularly for T4 lesions. Ongoing investigations must address personalized treatment algorithms and novel therapeutic combinations.

Conclusion

This study establishes non-surgical comprehensive therapy as a viable strategy for advanced laryngeal carcinoma, achieving exceptional laryngeal preservation rates without compromising survival. Critical success factors include meticulous toxicity management, advanced radiotherapy techniques, and tailored systemic therapy integration. The paradigm shift toward functional preservation redefines therapeutic goals in laryngeal oncology, emphasizing quality of life alongside traditional survival endpoints.

doi.org/10.1097/CM9.0000000000000639

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