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. 2016 Dec;38(12):1739-1751.
doi: 10.1002/hed.24532. Epub 2016 Jul 28.

Long-term outcomes after multidisciplinary management of T3 laryngeal squamous cell carcinomas: Improved functional outcomes and survival with modern therapeutic approaches

Clifton D Fuller  1 , Abdallah S R Mohamed  1   2 , Adam S Garden  1 , G Brandon Gunn  1 , Collin F Mulcahy  1 , Mark Zafereo  3 , Jack Phan  1 , Stephen Y Lai  3 , Jan S Lewin  3 , Katherine A Hutcheson  3 , Steven J Frank  1 , Beth M Beadle  1 , William H Morrison  1 , Adel K El-Naggar  4 , Esengul Kocak-Uzel  1   5 , Lawrence E Ginsberg  6 , Merril S Kies  7 , Randal S Weber  3 , David I Rosenthal  1
Affiliations

Long-term outcomes after multidisciplinary management of T3 laryngeal squamous cell carcinomas: Improved functional outcomes and survival with modern therapeutic approaches

Clifton D Fuller et al. Head Neck. 2016 Dec.

Erratum in

  • Erratum.
    [No authors listed] [No authors listed] Head Neck. 2017 Jul;39(7):1484-1496. doi: 10.1002/hed.24753. Epub 2017 Apr 7. Head Neck. 2017. PMID: 28608443 No abstract available.

Abstract

Background: The purpose of this study was to evaluate the long-term outcomes after initial definitive or adjuvant radiotherapy (RT) for T3 laryngeal cancers.

Methods: We reviewed 412 patients treated for T3 laryngeal squamous cell cancer from 1985 to 2011.

Results: The 10-year overall survival (OS) was 35%; disease-specific-survival (DSS) was 61%; locoregional control was 76%; and freedom from distant metastasis was 83%. Chemotherapy, age, performance status <2, node-negative status, and glottic subsite were associated with improved survival (all p < .03). Larynx preservation with induction and/or concurrent chemoradiotherapy (LP-CRT) had better laryngectomy-free survival than RT alone (LP-RT; hazard ratio [HR] = 0.62; 95% confidence interval [CI] = 0.47-0.81; p = .0005); 10-year laryngectomy-free survival rates of the LP-CRT cohort (37%) were higher than those of the LP-RT cohort (18%). The 5-year DSS and OS rates of the LP-CRT cohort (79% and 67%) were better after total laryngectomy with postoperative RT (TL-PORT; 61% and 50%) and LP-RT (64% and 46%; p < .006 for all).

Conclusion: In patients with T3 laryngeal cancers, LP-CRT provides better functional, oncologic, and survival outcomes than historical TL-PORT or LP-RT does. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1739-1751, 2016.

Keywords: T3; outcomes; radiotherapy; survival; total laryngectomy.

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Figures

Figure 1
Figure 1
Kaplan-Meier curves calculated for all patients (n=412) showing (A) local control (LC), locoregional control (LRC), freedom from distant disease (FDD), (B) relapse free survival (RFS), cancer-event free survival (EFS), and (C) disease specific survival (DSS), non-cancer cause specific survival (NCCSS), and Overall survival (OS).
Figure 1
Figure 1
Kaplan-Meier curves calculated for all patients (n=412) showing (A) local control (LC), locoregional control (LRC), freedom from distant disease (FDD), (B) relapse free survival (RFS), cancer-event free survival (EFS), and (C) disease specific survival (DSS), non-cancer cause specific survival (NCCSS), and Overall survival (OS).
Figure 1
Figure 1
Kaplan-Meier curves calculated for all patients (n=412) showing (A) local control (LC), locoregional control (LRC), freedom from distant disease (FDD), (B) relapse free survival (RFS), cancer-event free survival (EFS), and (C) disease specific survival (DSS), non-cancer cause specific survival (NCCSS), and Overall survival (OS).
Figure 2
Figure 2
Results of a multivariate analysis for all survival endpoints. The vertical white lines on the colored boxplots represent hazard ratios (HRs); the colored boxplots themselves represent 95% confidence intervals (CIs). Statistical significance is indicated if a boxplot does not encroach upon a risk ratio of 1.0 (indicated by vertical dashed lines); red boxplots represent increased risk of endpoint occurrence, green boxplots indicate increased reduced risk and grey boxplots indicate no statistically significant difference. Abbreviations: Local control (LC), locoregional control (LRC), ultimate LRC, freedom from distant disease (FDD), relapse-free survival (RFS), disease-specific survival (DSS), cancer event–free survival (EFS), non–cancer cause–specific survival (NCCSS), and overall survival (OS).
Figure 3
Figure 3
Kaplan-Meier curves calculated for all patients (n=412) showing (A) locoregional control (LRC), (B) ultimate LRC, (C) freedom from distant disease (FDD), (D) relapse-free survival (RFS), (E) disease-specific survival (DSS), and (F) overall survival (OS) in patients who underwent larynx preservation with induction and/or concurrent chemoradiotherapy (LP-CRT) versus larynx preservation with definitive radiotherapy alone (LP-RT) versus total laryngectomy and post-operative radiotherapy (TL-PORT). Shaded colors represent 95% confidence intervals, short vertical lines represent censored data, and asterisk indicates significant log-rank p values.
Figure 4
Figure 4
Results of a multivariate Cox model for survival endpoints for cohorts of patients with T3 larynx cancer who underwent total laryngectomy followed by post-operative radiotherapy (TL-PORT), larynx preservation with definitive radiotherapy alone (LP-RT), or larynx preservation with induction and/or concurrent chemoradiotherapy (LP-CRT). The vertical white lines on the colored boxplots represent hazard ratios (HRs); the colored boxplots themselves represent 95% confidence intervals (CIs). Statistical significance is indicated if a boxplot does not encroach upon a risk ratio of 1.0 (indicated by vertical dashed lines); red boxplots represent increased probability of endpoint occurrence, whereas green boxplots indicate reduced risk of endpoint occurrence. Overall survival (OS), local control (LC), locoregional control (LRC), ultimate LRC, freedom from distant disease (FDD), recurrence-free survival (RFS), cancer event–free survival (EFS), disease-specific survival (DSS), and non–cancer cause–specific survival (NCCSS) HRs were assessed for all patients (n=412).
Figure 5
Figure 5
Competing risk analysis for patients with T3 larynx cancer who underwent (a,d) larynx preservation with induction and/or concurrent chemoradiotherapy (LP-CRT), (b,e) larynx preservation with definitive radiotherapy alone (LP-RT), or (c,f) total laryngectomy followed by post-operative radiotherapy (TL-PORT).Patterns of failure are presented in the upper panels (a, b, and c); patterns of competing risk of demise by cause are presented in the lower panels (d, e, and f). Black dots represent aggregated data points and dashed lines represent confidence intervals.
Figure 6
Figure 6
Kaplan-Meier curves calculated for patients treated with larynx preservation approaches (n=287) showing (A) Freedom from laryngectomy (FFL), (B) laryngectomy-free survival (LFS), and (C) laryngoesophageal dysfunction–free survival (LEDFS) in patients who underwent larynx preservation with induction and/or concurrent chemoradiotherapy (LP-CRT) versus larynx preservation with definitive radiotherapy alone (LP-RT). Shaded colors represent 95% confidence intervals, short vertical lines represent censored data, and asterisk indicates significant log-rank p values.
Figure 6
Figure 6
Kaplan-Meier curves calculated for patients treated with larynx preservation approaches (n=287) showing (A) Freedom from laryngectomy (FFL), (B) laryngectomy-free survival (LFS), and (C) laryngoesophageal dysfunction–free survival (LEDFS) in patients who underwent larynx preservation with induction and/or concurrent chemoradiotherapy (LP-CRT) versus larynx preservation with definitive radiotherapy alone (LP-RT). Shaded colors represent 95% confidence intervals, short vertical lines represent censored data, and asterisk indicates significant log-rank p values.
Figure 6
Figure 6
Kaplan-Meier curves calculated for patients treated with larynx preservation approaches (n=287) showing (A) Freedom from laryngectomy (FFL), (B) laryngectomy-free survival (LFS), and (C) laryngoesophageal dysfunction–free survival (LEDFS) in patients who underwent larynx preservation with induction and/or concurrent chemoradiotherapy (LP-CRT) versus larynx preservation with definitive radiotherapy alone (LP-RT). Shaded colors represent 95% confidence intervals, short vertical lines represent censored data, and asterisk indicates significant log-rank p values.
Figure 7
Figure 7
Kaplan-Meier plots of actuarial survival endpoints, including (a) locoregional control (LRC), (b) relapse-free survival (RFS), (c) event-free survival (EFS), and (d) overall survival (OS), for patients who underwent 2- or 3-dimensional conventional radiotherapy (2D/3DCRT) or intensity-modulated radiotherapy (IMRT) for larynx preservation. Short vertical lines represent censored data, and asterisk indicates significant log-rank p values.
Figure 8
Figure 8
Kaplan-Meier plots of (a) Locoregional control (LRC), (b) recurrence-free survival (RFS), and (c) overall survival (OS) in different chemotherapy cohorts treated using larynx preservation approaches (n=287). Short vertical lines represent censored data, and asterisk indicates significant log-rank p values.
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