ImportanceThe association of primary tumor volume with outcomes in T3 glottic cancers treated with radiotherapy with concurrent chemotherapy remains unclear, with some evidence suggesting worse locoregional control in larger tumors.ObjectiveTo evaluate the association of primary tumor volume with oncologic outcomes in patients with T3 N0-N3 M0 glottic cancer treated with primary (chemo)radiotherapy in a large multi-institutional study.Design, Setting, and ParticipantsThis multi-institutional retrospective cohort study involved 7 Canadian cancer centers from 2002 to 2018. Tumor volume was measured by expert neuroradiologists on diagnostic imaging. Clinical and outcome data were extracted from electronic medical records. Overall survival (OS) and disease-free survival (DFS) outcomes were assessed with marginal Cox regression. Laryngectomy-free survival (LFS) was modeled as a secondary analysis. Patients diagnosed with cT3 N0-N3 M0 glottic cancers from 2002 to 2018 and treated with curative intent intensity-modulated radiotherapy (IMRT) with or without chemotherapy. Overall, 319 patients met study inclusion criteria.ExposuresTumor volume as measured on diagnostic imaging by expert neuroradiologists.Main Outcomes and MeasuresPrimary outcomes were OS and DFS; LFS was assessed as a secondary analysis, and late toxic effects as an exploratory analysis determined before start of the study.ResultsThe mean (SD) age of participants was 66 (12) years and 279 (88%) were men. Overall, 268 patients (84%) had N0 disease, and 150 (47%) received concurrent systemic therapy. The mean (SD) tumor volume was 4.04 (3.92) cm3. With a mean (SD) follow-up of 3.85 (3.04) years, there were 91 (29%) local, 35 (11%) regional, and 38 (12%) distant failures. Increasing tumor volume (per 1-cm3 increase) was associated with significantly worse adjusted OS (hazard ratio [HR], 1.07; 95% CI, 1.03-1.11) and DFS (HR, 1.04; 95% CI, 1.01-1.07). A total of 62 patients (19%) underwent laryngectomies with 54 (87%) of these within 800 days after treatment. Concurrent systemic therapy was associated with improved LFS (subdistribution HR, 0.63; 95% CI, 0.53-0.76).Conclusions and RelevanceIncreasing tumor volumes in cT3 glottic cancers was associated with worse OS and DFS, and systemic therapy was associated with improved LFS. In absence of randomized clinical trial evidence, patients with poor pretreatment laryngeal function or those ineligible for systemic therapy may be considered for primary surgical resection with postoperative radiotherapy.
e18044 Background: Organ preservation approaches to treatment of locally advanced larynx cancers are widely used and consist of radiotherapy (RT) with or without concurrent systemic therapy (CRT). Analyses of the National Cancer Database point to decreasing survival as CRT became widely adopted in place of total laryngectomy (TL). Tumor volume in T3 laryngeal tumors has been postulated as one variable to explain this finding, with higher volume associated with lower local control based on small sample size studies largely in pre-intensity modulated radiotherapy (IMRT) era, and low volume T3 tumors being associated with improved local control with CRT. We sought to validate these findings in a contemporary cohort of T3 larynx patients treated with IMRT. Methods: This was a national, multicentre retrospective cohort study of patients diagnosed with American Joint Committee on Cancer (AJCC) T3 N0-3 M0 glottic and supraglottic cancers who underwent curative intent IMRT with or without systemic treatment from 2002-2018. Tumor volumes were calculated using a validated standardized approach by a Neuroradiologist. Primary predictor was tumor volume, primary outcome was local control (LC), and secondary outcomes included overall survival (OS), as well as late grade 3+ toxicities. Kaplan Meier estimates and log-rank tests were used for survival analyses, with Cox proportional hazards used for univariable analyses. Results: 246 patients met inclusion criteria, 147 glottic and 99 supraglottic cancers. At baseline, glottic patients were more likely to be male (p < 0.01), have a fixed vocal cord (p < 0.01), not have pre-epiglottic space invasion ( < 0.01), be cN0 (p < 0.01), and have lower grade tumors (p < 0.01). Mean tumor volumes for glottic and supraglottic tumors were 5.0 (4.2-5.8) cc and 13.0 (10.3–15.6) cc respectively. Univariable analysis showed systemic therapy was associated with improved local failure (HR 0.49, 95%CI 0.24 – 0.99, p = 0.05). Within the glottic cohort, tumor volume was not associated with local failure (HR 1.09, 95%CI 0.71 – 1.67, p = 0.38), however having a local failure event was associated with increased feeding tube dependence (HR 2.52, 95%CI 1.05 – 6.02, p = 0.04). Median local failure free survival in the overall cohort was 28.5 months, with median OS 23.2 months. There was a trend towards improved local control in the supraglottic cohort compared to glottic patients (log-rank p = 0.08), but the supraglottic cohort had significantly worse overall survival (log-rank p = 0.02). Conclusions: In this retrospective cohort study, there were baseline and outcome differences between patients with T3 glottic and supraglottic larynx cancer, with worse overall survival in supraglottic patients. Tumor volume was not associated with local control in the glottic cohort. These findings are pending further validation in a larger cohort and will be analyzed separately for supraglottic tumors.
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