Could Primary Chemoradiotherapy in T2 Glottic Cancers Yield Results Comparable to Primary Radiotherapy in T1? Considerations from 531 German Early Stage Patients

Abstract

T1 glottic cancer is a highly treatable disease with local control (LC) rates over 90% by either primary radiotherapy (pRT) or transoral laser microsurgery (TLM). LC of T2 glottic cancers is 15 percent points poorer on average. However, salvage after pRT entails more than 50% total laryngectomy. Therefore, there is a need for enhanced LC. Altered fractionation regimens improved LC in T1 but not in T2. For this reason, for T2, alternative strategies must be considered. In a large observational cohort study including 531 early-stage laryngeal cancers, a small number of patients were treated with primary chemoradiotherapy (pCRT). In multivariable analysis, factors associated with significantly poorer outcomes included age, comorbidities, supraglottic localization, and T category. While there was a significant difference between pRT and surgery (HR 1.79; 95%-CI: 1.15–2.79), there was none between pCRT and surgery (HR 0.70; 95%-CI: 0.33–1.51). There is evidence from the literature that pCRT in early glottic cancers could yield results that surpass the limits so far experienced in radiotherapy alone with acceptable toxicity. Thus, prospective randomized studies with larger numbers of patients are warranted.

Chemoradiotherapy but Not Radiotherapy Alone for Larynx Preservation in T3. Considerations from a German Observational Cohort Study

“…The demographic and clinical characteristics of the whole study cohort in the different treatment arms are presented in overview in Table 1 and are described in detail elsewhere [ 22 ]. The adjuvant treatment of T3 patients is specifically indicated in Table 2 .…”

“…Together with healthcare providers, the patient should ideally be able to approximately assess his/her individual risk of failure. To this end, it would be valuable to establish a larynx preservation failure risk score (LPFRS) analogous to the total dysphagia risk score (TDRS) published by Langendijk et al [ 65 ] (see modification for practical use in [ 22 ]). This risk score could be calculated by summation of the independent prognostic factors as categories and their respective feature expression as variables (a. tumor volume: <6 ccm, 6 ccm ≤ x ≤ 12 ccm, or >12 ccm; b. cartilage infiltration: non, minimal, or gross/multiple; c. vocal cord fixation: none, Succo pattern I/II or III/IV; d. N stage: N0–1, N2–3, the latter indicative of pCRT; e. pretreatment laryngeal dysfunction with feeding tube, tracheostomy, or recurring pneumonia in the preceding 12 months = indicative for considering TL instead of LP) multiplied by risk points that would be derived from the regression coefficients from a multivariate model.…”

“…The study was approved by the ethics committee of the Medical University of Heidelberg (Ethics Commission S-141/2008 Medical Faculty). As reported previously [ 21 , 22 , 23 ], all index laryngeal cancer patients were recruited from the five academic tertiary referral centers in the Rhein-Neckar-Odenwald region in southwest Germany between 5 January 1998 and 31 December 2004. Patients in this study either participated in a previous prospective case-control study between 1998 and 2000 or were identified retrospectively through patient records (2001–2004).…”

“…Comorbidity conditions were determined using the Charlson Comorbidity Index (CCI) [ 24 ]. Details can be found in [ 22 ].…”

“…The proportional hazards assumption was assessed by adding a time-dependent version of all the variables in the model [ 25 ]. Details can be found elsewhere [ 22 ]. In cases of TL, standardized bilateral neck dissection was performed, in cases of TLM or OPL, neck dissection depended on positive nodal disease.…”