Impact of Previous Tracheotomy as a Prognostic Factor in Patients with Locally Advanced Squamous Cell Carcinoma of the Larynx Submitted to Concomitant Chemotherapy and Radiation

Abstract

Hypothesis: The combination of chemotherapy and radiotherapy is a standard nonsurgical treatment for locally advanced laryngeal cancer. Nevertheless, there are no validated markers to predict the outcome of nonsurgical therapies. The impact of previous tracheotomy is not clear in patients submitted to concomitant chemoradiotherapy. Study Design: A non-randomized prospective study. Prognostic factors such as stage, age, performance status, number of chemotherapy cycles, radiotherapy dose, stage VIb disease, and previous tracheotomy were analyzed using the Cox’s proportional hazard model. The Kaplan-Meier and log rank tests were used to evaluate the progression-free and overall survival. Patients and Methods: Patients with stage III/IV laryngeal carcinoma were prospectively selected. Treatment consisted of cisplatin 100 mg/m² every 3 weeks for 3 cycles, radiotherapy to a total dose of 70.2 Gy and salvage surgery. Results: Forty-nine patients were analyzed; tracheotomy was performed in 12 patients (24.5%) before therapy. Patients who had previous tracheotomy had a lower rate of complete response (41.7 vs. 75%, p = 0.034, HR 0.55, CI 95% 0.27–1.11), shorter progression free-survival (HR 2.83, CI 95% 1.60–4.88, p < 0.001), and median overall survival (12 vs. 56 months, HR 2.37, CI 95% 1.43–3.93, p < 0.001), in comparison to those without a tracheotomy. Moreover a significant difference was observed in 3-year survival rates (6 vs. 61%, p = 0.001), in favor of the group without tracheotomy. Interestingly, the impact of previous tracheotomy was not altered when adjusted by other prognostic factors (HR 8.7, CI 95% 3.1–24.0, p < 0.001). Conclusions: Previous tracheotomy is a negative prognostic factor for patients submitted to chemotherapy combined with radiotherapy and should be considered as a negative clinical prognostic factor in the selection of patients for more aggressive treatment strategies.

A genetic view of laryngeal cancer heterogeneity

“…15 Moreover, PS, 12,16 node invasion 16,17 and localization 12 are prognostic factors for disease-free survival in conjunction with pathologic stage (pT), 17 surgical resection margins 16 and pretreatment tracheotomy. 18 Moreover, T4 primary extension and more than 2 cm tumoral invasion of the base of the tongue were shown to be associated with increased salvage laryngectomy in the Veterans study. 19 …”

Histopathological factors influencing results of combined treatment in patients with laryngeal cancer

“…Meredith et al [22] suggest irradiation of the pre-existing tracheostomy region. In the literature reports, the recurrence rates in patients who have undergone emergency tracheostomy range between 27% and 71% [7,43,46,47,48]. Prognostic significance of this factor is controversial, as it is most frequently related to higher tumour stage as well as poorer overall performance status of patients and thus may not be an independent prognostic factor.…”

Effects of tumour stage, comorbidity and therapy on survival of laryngeal cancer patients: a systematic review and a meta-analysis

“…In the former, the rates differed only marginally in the two treatment groups (total laryngectomy with voice prosthesis and postoperative radiotherapy compared with those receiving concurrent chemoradiation for laryngeal preservation); however, the quality of life score was better in patients treated by chemoradiation [17]. The latter showed that previous tracheotomy was a prognostic factor for a shorter survival time rate (6 vs. 61%); however, as tracheotomy is mandatory in patients with a very advanced tumour stage, the advanced tumour stage is responsible for the poor prognosis [60]. Figure 1 displays the results of all studies where the estimate for 5-year survival is given, together with the result of our meta-analysis using cancer registry studies only [34,35], which yielded an overall rate for 5-year relative survival of 64.2% (95% confidence interval 63.7-64.7%).…”

“…Studies evaluating the effectiveness of different therapeutic approaches on survival of laryngeal cancer patients are presented in Table 3 [17,[42][43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60]. In the group involving laser surgery, three studies consisted of a mixture of different stages and tumour locations [42][43][44], of which two [45,46] and one assessed advanced laryngeal cancer cases only [47].…”

“…Only the 3-year survival rates were given by BoscoloRizzo et al and Herchenhorn et al [17,60]. In the former, the rates differed only marginally in the two treatment groups (total laryngectomy with voice prosthesis and postoperative radiotherapy compared with those receiving concurrent chemoradiation for laryngeal preservation); however, the quality of life score was better in patients treated by chemoradiation [17].…”