Pretreatment Tracheostomy Research Articles

Induction Chemotherapy and Toripalimab for Larynx Preservation in Resectable Locally Advanced Laryngeal/Hypopharyngeal Carcinoma: Preliminary Results of INSIGHT Study

Previous studies have demonstrated excellent pathological response of induction PD-1 inhibitor with chemotherapy for locally advanced head and neck cancer. To our knowledge, there is scarce evidence on induction chemotherapy (ICT) and PD-1 inhibitor in organ preservation for patients (pts) with laryngeal/hypopharyngeal carcinoma. Hence, the aim of this study is to evaluate the efficacy and toxicities of ICT and PD-1inhibitor (Toripalimab) followed by radiotherapy or surgery, for pts with resectable locally advanced laryngeal/hypopharyngeal carcinoma. This isa single-arm phase II study. Pts with histopathologic confirmed, resectable locally advanced laryngeal/hypopharyngeal squamous cell carcinoma and ECOG PS 0-1 were eligible. Three cycles of ICT (paclitaxel 175 mg/m d1, cisplatin 25 mg/m d1-3) combined with PD-1 inhibitor (Toripalimab 240 mg d0) were given. Response assessment (RECIST 1.1) was performed post-ICT. Patients with complete response (CR)/partial response (PR) of primary tumor received concurrent chemoradiation, followed by maintenance therapy of Toripalimab for eight cycles. Otherwise, patients were referred to surgery, followed by adjuvant radiation (RT)/chemoradiation (CRT), and then maintenance therapy of Toripalimab. The primary endpoint is larynx-preservation (LP) rate at 3 months post-RT. Forty-two patients were planned. Based on a two-stage Fleming design (one-sided α:10%, power: 80%), if at least 22 patients attained LP of the first 27 patients in stage I or at least thirty-two pts attained LP of the 42 patients at the end of stage II, the null hypothesis would be rejected. The cohort would enroll 15 more pts in stage II if 19-21 pts in stage I observed LP, and the study would be terminated if the number of pts with LP were less than 18 in stage I. A total of 27 pts were enrolled. By the cut-off date Feb 8, 2023, all reached at least 3 months of follow-up post-RT. Median age was 63 (53-74) years with 92.6% male. Hypopharyngeal cancer accounted for 66.7%. There were 74.1% who were T3 to T4, and 77.7% were N2 to N3. Six cases had primary invasion of esophagus and five pts underwent pretreatment tracheostomy. ORR of ICT was 85.2%. Afterward, 21 pts were treated with concurrent CRT, while 6 pts received surgery of primary tumor. At 3 months post-RT, 23 pts attained organ preservation and the LP rate was 85.2%. With a median follow-up of 13.5 months, 1-year OS rate, PFS rate and LP survival rate was 83.1%, 79.5% and 79.4%, respectively. During ICT, 22.2% of pts experienced grade 3-4 treatment-related AEs (TRAEs). The most common grade 3-4 TRAEs were nausea and neutrophil count decreased. The primary endpoint LP rate was met. In this cohort of extensive locally advanced laryngeal/hypopharyngeal carcinoma, ICT and Toripalimab followed by radiotherapy or surgery resulted in satisfactory short-term LP rate and encouraging survival.

Induction chemotherapy and toripalimab for larynx preservation in resectable locally advanced laryngeal/hypopharyngeal carcinoma: Preliminary results of INSIGHT study.

6068 Background: Previous studies have demonstrated excellent pathological response of induction PD-1 inhibitor with chemotherapy for locally advanced head and neck cancer. To our knowledge, there is scarce evidence on induction chemotherapy (ICT) and PD-1 inhibitor in organ preservation for patients (pts) with laryngeal/hypopharyngeal carcinoma. Hence, the aim of this study is to evaluate the efficacy and toxicities of ICT and PD-1 inhibitor (Toripalimab) followed by radiotherapy or surgery, for pts with resectable locally advanced laryngeal/hypopharyngeal carcinoma. Methods: This is a single-arm phase II study. Pts with histopathologic confirmed, resectable locally advanced laryngeal/hypopharyngeal squamous cell carcinoma and ECOG PS 0-1 were eligible. Three cycles of ICT (paclitaxel 175mg/m2 d1, cisplatin 25mg/m2 d1-3) combined with PD-1 inhibitor (Toripalimab 240mg d0) were given. Response assessment (RECIST 1.1) was performed post-ICT. Pts with complete response (CR)/partial response (PR) of primary tumor received concurrent chemoradiation, followed by maintenance therapy of Toripalimab for eight cycles. Otherwise, pts were referred to surgery, followed by adjuvant radiation (RT)/chemoradiation (CRT), and then maintenance therapy of Toripalimab. The primary endpoint is larynx-preservation (LP) rate at 3 months post-RT. Forty-two pts were planned. Based on a two-stage Fleming design (one-sided α:10%, power: 80%), if at least 22 pts attained LP of the first 27 pts in stage I or at least 32 pts attained LP of the 42 pts at the end of stage II, the null hypothesis would be rejected. The cohort would enroll 15 more pts in stage II if 19-21 pts in stage I observed LP, and the study would be terminated if the number of pts with LP were less than 18 in stage I. Results: A total of 27 pts were enrolled. By the cut-off date Feb 8th, 2023, all reached at least 3 months of follow-up post-RT. Median age was 63 (53-74) years with 92.6% male. Hypopharyngeal cancer accounted for 66.7%. 74.1% were T3 to T4, and 77.7% were N2 to N3. Six cases had primary invasion of esophagus and five pts underwent pretreatment tracheostomy. ORR of ICT was 85.2%. Afterwards, 21 pts were treated with concurrent CRT, while 6 pts received surgery of primary tumor. At 3 months post-RT, 23 pts attained organ preservation and the LP rate was 85.2%. With a median follow-up of 13.5 months, 1-year OS rate, PFS rate and LP survival rate was 83.1%, 79.5% and 79.4%, respectively. During ICT, 22.2% of pts experienced grade 3-4 treatment-related AEs (TRAEs). The most common grade 3-4 TRAEs were nausea and neutrophil count decreased. Conclusions: The primary endpoint LP rate was met. In this cohort of extensive locally advanced laryngeal/hypopharyngeal carcinoma, ICT and Toripalimab followed by radiotherapy or surgery resulted in satisfactory short-term LP rate and encouraging survival. Clinical trial information: NCT04995120 .

Risk Factors for Functional Outcomes in Advanced Laryngeal Squamous Cell Carcinoma.

Chemoradiation for patients with laryngeal squamous cell carcinoma (SCC) may achieve organ preservation, but appropriate patient selection remains unknown. This study investigates pre-treatment risk factors associated with functional and survival outcomes after radiation-based therapy in patients with advanced laryngeal SCC. A retrospective cohort study was performed on 75 adult patients with stage III or IV laryngeal SCC receiving definitive radiation-based therapy from 1997 to 2016 at a tertiary care center. Tracheostomy and gastrostomy dependence were the primary functional outcomes. Multivariable logistic regressions were performed to evaluate relationships between pre-treatment factors and tracheostomy and gastrostomy dependence. Time-to-event analyses were performed to determine risk factors associated with overall survival. Among 75 patients included in the analysis, 30 (40%) patients were tracheostomy dependent and 31 (41%) were gastrostomy tube dependent. The median length of follow-up was 31 months (range=1 to 142 months). Pre-treatment tracheostomy was a significant predictor of post-treatment tracheostomy (aOR=13.9, 95% CI=3.35 to 57.5) and moderate-severe comorbidity was a significant predictor of post-treatment gastrostomy dependence (aOR=2.96, 95% CI=1.04 to 8.43). The five-year overall survival was 51% (95% CI=38 to 64%). Pre-treatment gastrostomy tube dependence was associated with an increased risk of death (aHR=2.45, 95% CI=1.09 to 5.53). Baseline laryngeal functional status and overall health in advanced laryngeal SCC are associated with poor functional outcomes after radiation-based therapy, highlighting the importance of patient selection when deciding between surgical and non-surgical treatment plans. Laryngoscope, 133:594-600, 2023.

Organ Function Preservation Failure after (Chemo)Radiotherapy in Head and Neck Cancer: A Retrospective Cohort Analysis.

The aim of the current study was to determine the incidence of organ function preservation failure (OFPF) in patients with head and neck squamous cell carcinoma (HNSCC) treated by (chemo)radiotherapy and to identify its risk factors. Retrospective cohort analysis. Tertiary cancer care center. A single-center retrospective cohort analysis was done (n = 703) in which OFPF after (chemo)radiotherapy was assessed. OFPF was defined as local failure or pure functional failure in the absence of local failure because of major surgical intervention (total laryngectomy, commando resection, permanent tracheostomy) or feeding tube dependence >2 years. OFPF occurred in 153 patients (21.8%). Reasons for OFPF were local failure in 103 patients (14.6%) and functional failure in 50 patients (7.2%). Evidence of functional failure included need for total laryngectomy (n = 9, 1.3%), commando resection (n = 2, 0.3%), permanent tracheostomy (n = 16, 2.3%), and/or long-term feeding tube for functional reasons (n = 23, 3.3%). In a Cox proportional hazards model, OFPF was worse for patients with T4 tumors (hazard ratio [HR] <0.5 and P < .001 for all other stages), for laryngeal vs oropharyngeal cancer (HR, 1.83; 95% confidence interval [CI], 1.20-2.79, P = .005, hypopharyngeal not significant), and for smokers (HR, 1.68; 95% CI, 1.10-2.56, P = .015). Exploratory multivariate analysis by tumor site showed that T4 tumor and pretreatment tracheostomy were the strongest predictive factors for OFPF in laryngeal and hypopharyngeal carcinoma while T4 tumor and smoking were predictive for poor OFPF in oropharyngeal carcinoma. This work shows a detrimental effect of smoking on functional outcomes after (chemo-)radiotherapy for HNSCC. Moreover, T4 tumor, laryngeal subsite, and pretreatment tracheostomy are strong predictors of OFPF.

Oncologic and functional outcomes of pretreatment tracheotomy in advanced laryngeal squamous cell carcinoma: A multi-institutional analysis

ObjectivesDescribe the influence of pretreatment tracheotomy and treatment modality (surgical versus non-surgical) on oncologic and functional outcomes. Materials and methodsRetrospective study of previously untreated advanced-stage laryngeal squamous cell carcinoma patients at two academic tertiary care institutions from 1995 to 2014. ResultsPrimary outcomes evaluated were disease-free survival, disease-specific survival, and overall survival of pretreatment tracheotomy versus no pretreatment tracheotomy cohorts. Functional status, measured by tracheotomy decannulation and gastrostomy tube placement/removal, was assessed. Of the 226 patients, 31.4% underwent pretreatment tracheotomy. Five-year disease-specific survival was 72.9%, and overall survival was 48.8% for entire cohort. There was a statistically significant decrease in overall survival (p = .03) and disease-free survival (p = .02) for the pretreatment tracheotomy group compared to no pretreatment tracheotomy, which was largely explained by primary tumor stage. Pretreatment tracheotomy was associated with gastrostomy tube placement and was an independent predictor of worse odds of gastrostomy tube removal. Disease stage, distant metastasis, and age independently conferred worse odds of gastrostomy tube removal. ConclusionPatients undergoing pretreatment tracheotomy for primary T4 laryngeal cancer had decreased overall survival compared to patients without pretreatment tracheotomy. There was no difference in local recurrence rates based on tracheotomy status. Organ preservation with chemotherapy and radiation did not result in better functional outcomes than surgery in the pretreatment tracheotomy group as nearly half of patients treated with organ preservation remained tracheotomy dependent. Based on this data, pretreatment tracheotomy may impact oncologic and functional outcomes in advanced disease, and it should be a consideration in an informed decision-making process.

Predictors and outcomes for chronic tracheostomy after chemoradiation for advanced laryngohypopharyngeal cancer.

After concurrent chemoradiation for head and neck squamous cell cancer, patients with laryngeal incompetence may not recover function. We assessed variables predicting tracheostomy dependence as a measure of poor laryngeal function after chemoradiation. Retrospective Analysis of 109 patients treated with chemoradiation for locoregionally advanced laryngohypopharyngeal squamous cell cancers between 1992 and 2013. Median follow-up was 17.0 and 17.2 months for tracheostomy and nontracheostomy dependent patients, respectively. For all patients, multivariate analysis demonstrated persistent tracheostomy was associated with pretreatment tracheostomy, subglottic extension, three-dimensional conformal radiotherapy (3DCRT) and postradiotherapy lymphadenectomy. When analyzed by primary site, tracheostomy dependence was associated with pretreatment tracheostomy, subglottic extension, and 3DCRT in larynx primaries, and with pretreatment tracheostomy and feeding tube dependency in hypopharynx primaries. Tracheostomy dependence did not impact local control, progression-free survival or overall survival on univariate analysis. After curative chemoradiation, long-term tracheostomy was associated with pretreatment tracheostomy, subglottic extension, postradiotherapy lymphadenectomy, and 3DCRT but did not impact outcomes. These factors may inform treatment decision making regarding organ preservation approaches for locally advanced laryngeal and hypopharyngeal cancers. 4.

Speech-language pathology care and short- and long-term outcomes of laryngeal cancer treatment in the elderly

To examine associations between speech-language pathology (SLP) care and pretreatment variables, swallowing and airway impairment, and survival in elderly patients treated for laryngeal cancer. Retrospective analysis of surveillance, epidemiology, and end results (SEER)-Medicare data. We evaluated longitudinal data from 2,370 patients diagnosed with laryngeal cancer from 2004 to 2007 using cross-tabulations, multivariate logistic regression, and survival analysis. Initial treatment with total laryngectomy (odds ratio [OR] = 3.3 [1.6-6.8]), and dysphagia during treatment (OR = 4.0 [2.2-7.2]) were the only significant predictors of SLP care during the initial treatment period. Speech-language pathology care was more likely during the first year (OR = 4.1 [2.7-6.0]) and second year (OR = 1.6 [1.1-2.3]) following initial treatment; however, only 23.7% of patients ever received SLP care. Pretreatment tracheostomy tube placement (OR = 2.8 [1.1-7.0]), initial treatment with total laryngectomy (OR = 3.4 [2.0-5.6]), dysphagia (OR = 7.6 [5.5-10.4]), stricture (OR = 1.9 [1.1-3.1]), interval tracheostomy tube placement (OR = 3.5 [2.4-5.2]), and salvage surgery (OR = 3.1 [1.6-5.8]) were significantly associated with long-term SLP care. After controlling for relevant variables, SLP care was associated with significant relative attenuation of the OR for dysphagia (50%), stricture (26%), weight loss (20%), and pneumonia (21%). Hazards ratio for death, if under SLP care, was 0.83 (0.70-0.99). SLP care is underutilized in elderly laryngeal cancer patients and is largely reserved for select patients in anticipation of total laryngectomy or after the onset of impaired airway and swallowing function, but is associated with improved outcomes. These data suggest a need for treatment guidelines that incorporate the routine use of SLP care during the initial treatment period and beyond. 2c.

MAP17 (PDZKIP1) as a novel prognostic biomarker for laryngeal cancer.

Larynx cancer organ preservation treatments with chemo and radiotherapy have substantially improved laryngoesophageal dysfunction-free survival. However, both of them lead to a high incidence of acute and chronic toxicities and a significant number of patients relapse. To date, there is no evidence available to establish the group of patients that may benefit from preservation approaches and clinical criteria such as primary tumor extension or pretreatment tracheotomy are not validated. MAP17 is a small non-glycosylated membrane protein overexpressed in carcinomas. The tumoral behavior induced by MAP17 is associated with reactive oxygen species production in which SGLT1 seems involved. In this study we found that the levels of MAP17 were related to clinical findings and survival in a cohort of 58 patients with larynx cancer. MAP17 expression is associated with overall survival (p<0.001) and laryngoesophageal dysfunction-free survival (p=0.002). Locoregional control in patients with high MAP17 showed better outcomes than those with low MAP17 (p=0.016). Besides, a positive correlation was observed between MAP17 expression and SGLT (p=0.022) and the combination of high levels of MAP17/SGLT also led to an increased overall survival (p=0,028). These findings suggest that MAP17, alone or in combination with SGLT1, may become a novel predictive biomarker for laryngeal carcinoma.

Persistent tracheostomy after primary chemoradiation for advanced laryngeal or hypopharyngeal cancer

Despite the demonstrated survival equivalence between chemoradiation and ablative surgery as primary treatment for advanced laryngeal and hypopharyngeal cancers, a subset of patients who undergo organ-preservation therapy have persistent tracheostomy requirement after completion of treatment. Patients who received primary chemoradiation for advanced laryngeal or hypopharyngeal cancer in a 3-year interval were identified. Rate of persistent posttreatment tracheostomy requirement was evaluated. The 12-month overall mortality rate was compared between patients who did and did not receive a tracheostomy before treatment. In 60 patients identified for this study, T3/T4 status and hemilarynx fixation at the time of presentation were associated with persistent tracheostomy requirement 6 and 12 months posttreatment (p = .022; p < .001; and p = .032; p = .0495, respectively). Twelve-month mortality was higher in T3/T4 patients who received pretreatment tracheostomy (p = .034). Patients with advanced laryngeal or hypopharyngeal cancer who require tracheostomy before treatment have low rates of decannulation and higher short-term mortality than those who do not require tracheostomy before organ-preservation therapy.

Functional organ preservation in larynx cancer: Correlation with baseline clinical and pathological features.

e16037 Background: Functional organ preservation in larynx cancer has become a treatment quality aim. The goal of our study was to evaluate the potential association between clinical and pathological features and functional larynx preservation (FLP). Methods: Clinical and pathological features were registered from 43 consecutive patients who were diagnosed of squamous cell larynx cancer between Feb 2008 and Sep 2011 and were candidates to organ preservation approaches: surgery (1), radiotherapy (10), chemo/bioradiotherapy (26) or chemo/bioradiotherapy following induction chemotherapy (6). Kaplan Meier procedure was used to estimate FLP and OS. Log-rank test and Cox proportional hazards regression were performed to assess prognostic factors for FLP. Results: Median age was 62 years (23% &gt;70 years). Former smokers 28% and alcohol consumers 70%. Most of the tumors were supraglottic (63% supraglottic/35% glottic/2% subglottic), T3 (T4 9%/T3 67%/T2 19%/T1 5%), N0 (N0 74%/N+ 26%), well/moderated differentiated histologic grade (HG) (I 23%/II 49%/III 14%) and stage III or IV (I 2%/II 16%/III 58%/IVA 23%). 33% required pretreatment tracheostomy. At the time of the analysis, with a median follow-up of 21 months, 7(16%) deaths and 18(42%) recurrences had occurred. The cumulative proportion of patients with larynx preservation at 2 years was 48%, and the median FLP survival was 21 months (CI 95%: 10.5-31.5). The most common cause of FLP failure was recurrence, that required salvage laryngectomy in 77% of cases. The following features were found to have a significant negative impact on FLP: T4 (HR: 9.04), former smoker (HR: 2.45), N+ (HR 1.36) and stage IV (HR: 2.44). Other factors such as tumor location, age, alcohol consumption, HG and pretreatment tracheostomy were not significant. Conclusions: The most relevant risk factors for FLP in our analysis were T4 stage, lymph node status, former smoker status and stage IVA. Therefore, patients presenting these features would not be optimal candidates for organ preservation approaches. Correlation of these prognostic factors with predictive biomarkers for specific treatments is warranted.

Examination of laryngoesophageal dysfunction‐free survival as an endpoint in nonsurgical treatment of squamous cell carcinomas of the larynx and hypopharynx

A recently published consensus guideline suggested a new endpoint for clinical trials involving cancer of the larynx and hypopharynx: laryngoesophageal dysfunction-free survival (LEDFS). The authors of this report examined LEDFS in the context of definitive radiotherapy alone (RT) or with concurrent chemoradiotherapy (CRT). Patients with a stage III to IVB squamous cell carcinomas of the larynx or hypopharynx who received definitive radiotherapy were included. Consensus guidelines also suggested analysis of the following: tumor classification, lymph node status, pretreatment tracheotomy, pretreatment swallowing dysfunction, and subsite. LEDFS was assessed using Kaplan-Meier survival analyses. Eighty-five patients (73.9%) received CRT, and 30 patients (26.1%) received RT. For the entire cohort, the 3-year LEDFS rate was 28.9%. CRT was associated with an improved LEDFS at 3 years (32.2% vs 20%; P = .02). Pretreatment dysphagia (P = .06) and N2 or N3 lymph node status (P = .09) demonstrated a trend toward poorer LEDFS, but patients who had T4 tumors had an LEDFS similar to that of patients who had T2 and T3 tumors. LEDFS was superior in patients who received CRT compared with patients who received RT alone. T4 status was not associated with a worse LEDFS.

Why to start the concomitant boost in accelerated radiotherapy for advanced laryngeal cancer in week 3

We analyzed toxicity and the local control rates for advanced laryngeal cancer, treated with two accelerated fractionation schedules. The main difference between the schedules was the onset of the concomitant boost, in Week 3 or Week 4. Overall treatment time and total dose were equivalent. In a prospective, nonrandomized study of T3, T4, and advanced T2 laryngeal cancer, concomitant boost schedules were used in 100 patients. Thirty patients received a schedule of twice daily 1.2 Gy in Weeks 1-3, followed by twice daily 1.7 Gy in Weeks 4 and 5; total dose was 70 Gy (the hyperfractionated accelerated schedule [HAS] regimen). Seventy patients were treated with 5 times 2 Gy in Weeks 1 and 2, followed by daily 1.8 Gy and 1.5 Gy (boost) in Weeks 3-5; total dose 69.5 Gy (the accelerated schedule only [ASO] regimen). Distribution of T stage was 47%, 40%, and 12% for T2, T3, and T4, respectively. In 24% of the patients, lymph nodes were positive. Pretreatment tracheotomy or stridor or both occurred in 8 patients. The distribution of prognostic factors was not significantly different between the two fractionation schedules. Acute and late toxicity was assessed. Results were estimated by the use of actuarial methods. For late toxicity and local control univariate and multivariate analyses were performed. Tumor control probability analysis was used to model cure rate differences. Overall acute mucositis score was equal for both schedules. Acute mucositis started and decreased significantly earlier in the HAS regimen. In all patients acute mucositis healed completely. The treatment was completed within 38 days in all patients. The regional control rate was 100% for clinical N0, and 75% for the clinical N+ patients. The 3-year local control rate was 59% and 78% for the HAS and ASO regimens, respectively (p = 0.05); the ultimate local control was 80% and 94%, respectively. In multivariate analysis, besides the fractionation schedule (relative risk [RR], 2.6 for HAS vs. ASO), pretreatment tracheotomy/stridor (RR 4.3, yes vs. no), and local tumor response 3-6 weeks after radiotherapy (RR 5.1, no vs. yes) were independent factors for local control. Tumor control probability analysis indicated that the onset of repopulation may be about 4-6 days earlier for the HAS regimen. The onset of repopulation in the HAS regimen is probably at the end of the second week or at the beginning of the third week. Severe late toxicity was observed in the HAS group and ASO group in, respectively, 11% and 16%. In multivariate analysis this toxicity related significantly to the field size and pretreatment tracheotomy/stridor. In our study the timing of the boost in accelerated radiotherapy for advanced laryngeal cancer was an independent factor for local control, favoring the use of a concomitant boost in Week 3. This finding may indicate that accelerated repopulation of tumor cells starts early in the treatment phase.

Prognostic factors in the management outcome of carcinoma of the larynx in Lagos

This is a retrospective analysis on the prognostic factors in the management outcome of clinically and histologically diagnosed carcinoma of larynx seen in Lagos University Teaching Hospital between 1996-1999. Various prognostic factors have been documented as determinants on the probable outcome of carcinoma of the larynx, such as duration of symptoms, smoking, medical status of the patient, degree of differentiation, size and site of tumour and presence of cervical lymph node. Thirty-six patients between 1996-1999 were reviewed, with a male to female ratio of 11:1, and peak age group of occurrence in 50-59 years, majority (86.12%) of which were non-smokers who presented in varied degrees of airway obstruction necessitating pre-treatment tracheostomy in 70% of the patients with more than 50% presenting within 3-6 months of onset of initial symptom. The tumours were staged clinically and histology revealed well differentiated T3 glottic tumour without any clinically palpable neck node in more than 50% of the patients which should predict a better outcome. But the interplay of many prognostic variables like pre-treatment tracheostomy and its attendant complications, supposed biological aggressive tumour in a non-smoker, coupled with treatment biased by patients, high costs of treatment, logistics and poor follow up compliance, resulted in poor outcome of our management.

Hypopharyngeal carcinoma.

For more than 20 years, the policy at the University of Florida has been to treat patients with favorable stage T1-T2 pyriform sinus carcinoma by using radiation therapy alone, or with a planned neck dissection if advanced nodal disease is present. This approach usually leaves the patient with nearly normal swallowing and speech, and provides bilateral coverage of the regional neck and retropharyngeal lymphatics. More advanced lesions often are not controlled with radiation alone and are usually considered for partial or total laryngopharyngectomy if the patient is medically operable. Radiation is usually administered postoperatively in this setting, unless the neck disease is thought to be unresectable, in which case preoperative radiation is given. Recent data have shown that adjuvant chemotherapy administered concomitantly with radiotherapy results in improved cure rates for patients with advanced disease compared with irradiation alone. Time-honored established guidelines are still used, although the edges have become blurred. Therefore, patients with larger primary tumors now may be considered for organ preservation treatment with irradiation and chemotherapy, reserving surgery for salvage situations. The subset of patients with advanced T4 pyriform sinus cancers (in whom cure with chemoradiation would likely result in tracheostomy and/or gastrostomy dependence) may be better served with elective surgery and postoperative irradiation. The definition of this subset of patients is unclear but probably includes patients with significant cartilage destruction and those who require pretreatment tracheostomy. The policy at the University of Florida is to treat essentially all pharyngeal wall cancers with external-beam irradiation alone.

The Prognostic Significance of Tracheostomy in Carcinoma of the Larynx Treated With Radiotherapy and Surgery for Salvage

Purpose: To determine retrospectively the prognostic significance of airway compromise necessitating tracheostomy in carcinoma of the larynx managed with radical radiotherapy and surgery for salvage (RRSS). Methods and Materials: The charts of 270 patients managed with RRSS at the Toronto-Sunnybrook Regional Cancer Centre between June 1980 and December 1990 were reviewed. Airway compromise necessitating tracheostomy was documented in 26 patients prior to radiotherapy and 3 patients during radiotherapy. Of 29, 27 had T3T4 primaries. Patients have been followed for a median of 5 years. Results: Patients managed without tracheostomy had a 2-year disease-free survival of 74% compared to 41% for those managed with tracheostomy. The adverse impact of airway compromise was more marked in patients with glottic primaries (78% vs. 32%, p = 0.0001) than those with supraglottic primaries (64% vs. 47%, p = 0.18). Tracheostomy was identified in univariate analysis, but not in multivariate analysis, as having a statistically significant impact on local control and local-regional control. Radiotherapy controlled disease above the clavicles in 185 of 267 (69%) evaluable patients. 83% of isolated local-regional failures underwent salvage surgery. Among those managed without tracheostomy, ultimate local-regional control (LRC) was achieved in 161 (94%) of 172 glottic primaries and 54 (81%) of 67 supraglottic primaries. Among those managed with tracheostomy, ultimate LRC was achieved in 9 (69%) of 13 glottic primaries and 12 (80%) of 15 supraglottic primaries. In a subset analysis of 76 patients with T3T4 primaries, there was no statistically significant difference in larynx preservation, disease-free survival, or cause-specific survival between those managed with and without tracheostomy. Conclusion: Airway compromise necessitating tracheostomy is an adverse prognostic factor in patients with carcinoma of the larynx. However, larynx preservation is possible in over 40% of those undergoing tracheostomy and radiotherapy with no compromise of cause-specific survival. The need for pretreatment tracheostomy should not rule out the possibility of RRSS.

T2‐T3 carcinoma of the supraglottic larynx: A comparison of surgery and radiotherapy

AbstractThis paper compares results for T2‐T3 carcinoma of the supraglottic larynx treated with radiotherapy (RT), supraglottic laryngectomy, or total laryngectomy. Two hundred thirty patients with T2‐T3 carcinoma of the supraglottic larynx were treated at the University of Florida between 1964 and 1989. All had a minimum 2‐year follow‐up. Patients were treated with RT alone (160), supraglottic laryngectomy (25), or total laryngectomy (45). The probabilities of local control, local‐regional control, distant metastasis, and survival were calculated by the Kaplan‐Meier product‐limit method and comparisons were made between the three treatment methods. American Joint Committee on Cancer (AJCC) stage, T stage, anatomic suitability for a supraglottic laryngectomy, treatment group, and presence or absence of a pretreatment tracheostomy were evaluated in multivariate analyses for the various end points. The 2‐year local control rates for patients treated with RT alone, supraglottic laryngectomy, and total laryngectomy for T2 lesions were 87%, 82%, and 100%, respectively, and rates for T3 lesions were 70%, 71%, and 81%. In the multivariate analyses, T stage was of independent prognostic significance for the end point of local control, whereas AJCC stage was a significant prognostic factor for control above the clavicles and cause‐specific survival. The incidence of severe complications was as follows: RT (6%), supraglottic laryngectomy (20%), and total laryngectomy (16%). In this analysis of T2‐T3 supraglottic larynx carcinomas, treatment with RT offered equivalent local control rates, local‐regional control rates, and survival rates with fewer severe complications compared with supraglottic laryngectomy. Although total laryngectomy was associated with a modest improvement in local‐regional control, the differences were not statistically significant, and this procedure would rarely be indicated today for T2 lesions and uncommonly for T3 lesions. © 1995 Wiley‐Liss, Inc.

Uni- und Multivarianzanalyse prognostischer Faktoren bei T3-Kehlkopfkarzinomen*

In 511 patients with T3N0-3M0 laryngeal carcinoma, 24 possible prognostic factors were analysed retrospectively. The factors were age, sex, mode of treatment, duration of several clinical symptoms, the presence of sore throat, otalgia, dyspnoea, and dysphagia, previous tracheotomy, tumour extension, lymph node status (five items), histologic grading, smoking habits, and alcohol intake. For 300 patients in whom surgery was part of the primary treatment, pathologic staging of the primary tumour and of lymph nodes in neck dissection specimens, cartilage invasion, radicality of the operation, differentiation grade, and subglottic extension were also evaluated. Univariate analysis revealed prognostic significance on survival for tumour extension (limited to the glottic region), lymph node status (clinically palpable lymph nodes, cytologically confirmed positive lymph nodes), level of lymph node metastasis (high and midjugular site), histologic grading (poor differentiation grade), and treatment modality (planned combined therapy). In the group that underwent surgery, all factors derived from specimens of the larynx and neck dissections had prognostic significance. Multivariate analysis revealed that the glottic site of the tumour, the presence of cyto- and histopathologically proven metastatic lymph nodes, pretreatment tracheotomy, positive resection margins, and planned combined treatment had a significant influence on corrected actuarial survival.

Prognostic factors for survival in patients with T3 laryngeal carcinoma

In a total of 511 patients with T3,N0-3,M0 laryngeal carcinoma, 24 possible prognostic factors were analyzed retrospectively. The factors were age, sex, mode of treatment, duration of several clinical symptoms, the presence of sore throat, otalgia, dyspnea, and dysphagia, previous tracheotomy, tumor extension, lymph node status (five items), histologic grading, smoking habits, and alcohol intake. For 300 patients in whom surgery was part of the primary treatment, pathologic staging of the primary tumor and of lymph nodes in neck dissection specimens, cartilage invasion, radicality of the operation, differentiation grade, and subglottic extension ware also evaluated. In a univariate analysis for the whole group, tumor extension (limited to the glottic region), lymph node status (clinically palpable lymph nodes, cytologically confirmed positive lymph nodes), level of lymph node metastasis (high and midjugular site), histologic grading (poor differentiation grade), and treatment modality (planned combined therapy) were considered to be prognostic factors of corrected actuarial survival. In the group that underwent surgery, all factors derived from specimens of the larynx and neck dissections had prognostic significance. Multivariate analysis revealed that the glottic site of the tumor, the presence of cyto- and histopathologically proven metastatic lymph nodes, pretreatment tracheotomy, positive resection margins, and planned combined treatment had a significant influence on corrected actuarial survival.