Organ preservation with chemoradiation in advanced laryngeal cancer: The problem of generalizing results from randomized controlled trials

Sanábria, Álvaro; Chaves, Aline Lauda Freitas; Kowalski, Luiz Paulo; Wolf, Gregory T.; Saba, Nabil F.; Forastiere, Arlene A.; Beitler, Jonathan J.; Nibu, Ken ichi; Bradford, Carol R.; Suárez, Carlos; Rodrigo, Juan P.; Strojan, Primož; Rinaldo, Alessandra; Bree, Remco de; Haigentz, Missak; Takes, Robert P.; Ferlito, Alfio

doi:10.1016/j.anl.2016.06.005

Cited by 32 publications

(35 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Characteristics of initial treatment in 100 patients with laryngeal squamous cell carcinoma. concurrent CRT vs. induction following CRT (1)(2)(3)(4)(5). We have also shown the efficacy of ACRT with early assessment for laryngeal squamous cell carcinoma and that of chemoselection for several cancer sites, including the hypopharynx and cervical esophagus (6,(11)(12)(13).…”

Section: Discussionmentioning

confidence: 85%

“…Total laryngectomy (TL) ± radiotherapy (RT) had been the classical treatment for resectable locally-advanced laryngeal squamous cell carcinoma (LALSCC), which is classified as clinical T3-T4a disease (1). Various organ-preserving treatment modalities, including partial laryngectomy (PL), concurrent chemoradiotherapy (CRT), chemoselection from induction chemotherapy have been performed for resectable LALSCC (1)(2)(3)(4)(5). We have also showed the efficacy of alternating chemoradiotherapy (ACRT) with early assessment following induction of CRT and salvage surgery for residual tumors in resectable LALSCC (6).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Treatment package time predicts cancer‑specific survival and distant metastasis in laryngeal cancer

et al. 2018

View full text Add to dashboard Cite

We investigated whether treatment package time was significantly associated with survival outcomes of resectable locally-advanced laryngeal squamous cell carcinoma in patients who consecutively underwent various treatments, including surgery alone and salvage surgery for residual tumor. A total of 100 patients with clinical T3-T4 resectable laryngeal squamous cell carcinoma were enrolled in this study. The treatment package time was calculated in days between the start of any treatment and the end of all treatments, including postoperative radiotherapy and salvage surgery for residual tumors. Using a log-rank test, a treatment package time of ≥68 days showed significantly shorter cancer-specific (P= 0.0013) and distant metastasis-free survival (P= 0.0017), compared with a treatment package time of <68 days. Multivariate survival analyses of two Cox's hazards proportional models was conducted. In both model-1, which adjusted for cT3/cT4, cN0-1/cN2-3 and total laryngectomy/non-total laryngectomy, and model-2, which adjusted for cT3/cT4, cN0-1/cN2-3 and induction therapy/non-induction therapy, the cancer-specific survival and distant metastasis-free survival, according to treatment package time, were significantly longer with <68 days compared with ≥68 days (P<0.01). The present study demonstrated that a prolonged treatment package time is a prognostic factor for shorter cancer-specific and distant metastasis-free survival after various treatments for resectable locally-advanced laryngeal cancer.

show abstract

Section: Discussionmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Treatment package time predicts cancer‑specific survival and distant metastasis in laryngeal cancer

et al. 2018

View full text Add to dashboard Cite

show abstract

“…There are also concerns that long term toxicity, cost, and treatment related deaths may be greater compared to total laryngectomy 10,11 . Additionally, survival results of patients enrolled in carefully controlled clinical trials of chemoradiation may not be generalizable to a non-select population of patients or reproduced outside of clinical trial settings 12,32 .…”

Section: Discussionmentioning

confidence: 99%

Survival Rates Using Individualized Bioselection Treatment Methods in Patients With Advanced Laryngeal Cancer

Wolf

Bellile

Eisbruch

et al. 2017

JAMA Otolaryngol Head Neck Surg

Self Cite

View full text Add to dashboard Cite

The introduction of chemoradiation for advanced laryngeal cancer led to a major paradigm shift in treatment as an alternative to laryngectomy. Despite widespread adoption, survival rates have not improved and the original premise of matching neoadjuvant chemotherapy tumor response to determine subsequent treatment has not been followed. A unique approach incorporating a single cycle of neoadjuvant chemotherapy to select patients with advanced disease for either laryngectomy or concurrent chemoradiation was studied to determine if improved survival could be achieved. Design From 2002–2012, we treated an unselected cohort of 247 patients with laryngeal cancer in an academic institution. Interventions Limited disease patients (n=94) underwent endoscopic resection (n=33; 35%), radiation (n=50; 53%) or chemoradiation for deeply invasive T2 lesions (n=11; 12%). For advanced disease (n=153), neoadjuvant chemotherapy for treatment selection (n=71; 46%), concurrent chemoradiation (n=50; 33%) or primary surgery (n=32; 21%) was recommended. Outcomes Propensity for treatment selection in advanced patients was modeled using logistic regression. Overall (OS) and disease specific survival (DSS) were analyzed with Cox proportional hazards models stratified by propensity score. Median follow was 48 months. Results Five-year OS and DSS was 75% (95% C.I. 68–81%) and 83% (77–88%), respectively for the entire cohort. DSS was 92% (83–97%) for patients with Stage I, II and 78% (69–84%) for patients with Stage III, IV disease. For advanced disease patients, 5-year OS (and DSS) ranged from 78% (91%) for surgery to 76% (79%) for neoadjuvant bioselection and 61% (66%) for primary chemoradiation. Propensity-adjusted multivariable Cox models controlling for known prognostic factors showed DSS was significantly improved in the neoadjuvant group compared to definitive chemoradiation [Hazard ratio 0.48, 95%CI: (0.29, 0.80), p=0.005]. DSS for the definitive surgery group was significantly better compared to the neoadjuvant bioselection group, [Hazard ratio 0.34, 95%CI: (0.14, 0.82), p=0.02]. Larynx preservation was achieved in 65% of advanced patients. Conclusions Exceptional survival rates were achieved with a bioselective treatment approach utilizing a single cycle of neoadjuvant chemotherapy. Excellent survival rates were also achieved in patients selected for primary surgery and both were better than with concurrent chemoradiation suggesting that the optimal individualized treatment approach for patients with advanced laryngeal cancer has not yet been defined.

show abstract

“…“These patients would be downstaged to T3 lesions by today’s standard” [ 26 ]. The exclusion of patients with a low Karnofsky index, the inclusion of more supraglottic tumors, and the consequent restriction to T4 tumors, e.g., those with “minimal thyroid cartilage invasion or suspicion of invasion on imaging” per protocol in RCTs constitute “selection bias” [ 27 ]. Sanabria critically states that the results of the randomized controlled LP studies are more favorable than those of observational cohort studies and may not generally be extrapolated to standard practice [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

A change in the study evaluation paradigm reveals that larynx preservation compromises survival in T4 laryngeal cancer patients

2017

View full text Add to dashboard Cite

BackgroundLarynx preservation (LP) is recommended for up to low-volume T4 laryngeal cancer as an evidence-based treatment option that does not compromise survival. However, a reevaluation of the current literature raises questions regarding whether there is indeed reliable evidence to support larynx preservation for T4 tumor patients.MethodsIn an observational cohort study of 810 laryngeal cancer patients, we evaluated the outcomes of all T4 tumor patients treated with primary chemo-radiotherapy (CRT) or primary radiotherapy alone (RT) compared with upfront total laryngectomy followed by adjuvant (chemo)radiotherapy (TL + a[C]RT). Additionally, we reevaluated the studies that form the evidence base for the recommendation of LP for patients with up to T4 tumors (Pfister et al., J Clin Oncol 24:3693–704, 2006).ResultsThe evaluation of all 288 stage III and IV patients together did not show a significant difference in overall survival (OS) between CRT-LP and TL + a(C)RT (hazard ratio (HR) 1.23; 95% confidence interval (CI): 0.82–1.86; p = 0.31) using a multivariate proportional hazard model. However, a subgroup analysis of T4 tumor patients alone (N = 107; 13.9%) revealed significantly worse OS after CRT compared with TL + a(C)RT (HR 2.0; 95% CI: 1.04–3.7; p = 0.0369). A reevaluation of the subgroup of T4 patients in the 5 LP studies that led to the ASCO clinical practice guidelines revealed that only 21–45 T4 patients had differential data on survival outcome. These data, however, showed a markedly worse outcome for T4 patients after LP.ConclusionsT4 laryngeal cancer patients who reject TL as a treatment option should be informed that their chance of organ preservation with primary conservative treatment is likely to result in a significantly worse outcome in terms of OS. Significant loss of survival in T4 patients after LP is also confirmed in recent literature.

show abstract

Organ preservation with chemoradiation in advanced laryngeal cancer: The problem of generalizing results from randomized controlled trials

Cited by 32 publications

References 49 publications

Treatment package time predicts cancer‑specific survival and distant metastasis in laryngeal cancer

Treatment package time predicts cancer‑specific survival and distant metastasis in laryngeal cancer

Survival Rates Using Individualized Bioselection Treatment Methods in Patients With Advanced Laryngeal Cancer

A change in the study evaluation paradigm reveals that larynx preservation compromises survival in T4 laryngeal cancer patients

Contact Info

Product

Resources

About