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Background: This review aimed to investigate the surgical, functional, and oncological outcomes of transoral laser microsurgery supraglottic laryngectomy (TOLM-SGL) for cT1-T3 laryngeal cancers., Methods: PubMed, Scopus, and Cochrane Library were searched by two independent investigators for studies investigating the surgical, functional, and oncological outcomes of TOLM-SGL using the PRISMA statements. A bias analysis was carried out with MINORS., Results: Twenty-four studies were included (937 patients), including 206 (25.9 %) cT1, 467 (58.7 %) cT2, and 123 (15.4 %) cT3 cases. Most patients were cN0 (63.9 %). The mean hospital stay of TOLM was 10.1 days. Aspiration (5.5 %), and bleeding (5.3 %) were the most prevalent complications. The laryngeal preservation rate was 93.7 %. Temporary tracheotomy was performed in 18.0 % of patients, with a mean time of decannulation of 6.8 days. A feeding tube was placed in 59.9 % of patients. The oral diet restarted after 6.4 days. Definitive gastrostomy was necessary in 2.4 % of cases. The 5-year OS and DFS were 70.1 % and 82.0 %, respectively. Distant metastasis, local, and regional recurrence occurred in 4.6 %, 11.6 %, and 5.1 % of patients. There was an important heterogeneity between studies for inclusion criteria, patient profiles, TOLM indications, and details of surgical, functional, and oncological outcomes., Conclusion: TOLM supraglottic laryngectomy is a safe, and effective procedure associated with adequate functional, surgical, and oncological outcomes. Future studies are needed to define the place of TOLM in advanced LSCC; the role and timing of concomitant bilateral neck dissection, the indications of tracheotomy and feeding tube., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objectives: Clinical extranodal extension (cENE) is a cN modifier in TNM-8 for laryngo-hypopharygeal carcinoma (LHC). We hypothesize that image-detected ENE (iENE) can provide additional prognostic value over cENE in LHC., Methods: Baseline CTs/MRIs of cN+ LHC patients treated with definitive (chemo-)radiotherapy between 2010-2019 were re-reviewed by a neuroradiologist using internationally accepted criteria for iENE-positive/negative (iENE+/iENE-). Overall survival (OS) was compared by iENE status. Multivariable analysis (MVA) was performed to confirm the prognostic value of iENE, adjusted for known potential confounders., Results: A total of 232 LHC patients were identified, including 154 iENE-/cENE-, 60 iENE+/cENE-, and 18 iENE+/cENE+. A higher proportion of iENE+ (vs iENE-) patients had lymph node (LN) size > 3 cm [53 (67 %) vs 4 (3 %)], >=5 LNs [51 (65 %) vs 33 (21 %)], and retropharyngeal LN [12 (15 %) vs 6 (4 %)] (all p < 0.01). Median follow-up was 4.8 years. iENE+/cENE- and iENE+/cENE+patients had similarly low 5-year OS [28 % (18-44) and 29 % (13-63)] vs iENE-/cENE- [53 % (45-62)] (p < 0.001). On MVA, mortality risk was higher with iENE+vs iENE- [hazard ratio (HR) 2.22 (95 % CI 1.47-3.36)]. The prognostic value of iENE remained with MVA in larynx (n = 124) (HR 2.51 [1.35-4.68], p = 0.004] or hypopharynx (n = 108) (HR 1.87 [1.02-3.43], p = 0.04) patients, separately., Conclusions: Our study confirms the independent prognostic importance of iENE for LHC following definitive (chemo-)radiotherapy beyond TNM-8 cN status that already contains the cENE parameter. Further research is needed to explore whether iENE could replace cENE for future cN classification., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: T2N0 glottic squamous cell carcinoma (SCC) typically responds well to radiotherapy (RT); however, achieving local control remains challenging. In cases of RT failure, total laryngectomy may be necessary. Improved local control and preservation of the larynx directly enhances patients' quality of life. Our retrospective analysis using the Japan Head and Neck Cancer Registry (JHNCR) aimed to compare the clinical benefits of RT and chemoradiotherapy (CRT) in patients with T2N0 glottic SCC., Methods: Using data from the JHNCR (2011-2015), we included 1,231 patients with T2N0 glottic SCC. Among them, 346 received curative RT and 425 underwent curative CRT. The CRT group was further divided into the oral CRT (Oral CRT, N=120) and intravenous CRT (DIV CRT, N=305) groups. This study assessed local control rate (LCR), progression-free survival (PFS), and overall survival (OS). A 1:1 propensity score-matching analysis was used to adjust for patient characteristics., Results: After matching, 105 pairs compared RT with Oral CRT, and 224 pairs compared RT with DIV CRT. The variables were well-balanced in the matched populations. In the matched populations, the Oral CRT group had significantly better 5-year LCR and PFS than the RT group (LCR, 89.4 % vs. 80.6 %, P=0.043; and PFS, 85.5 % vs. 72.3 %, P=0.025, respectively), while the DIV RT group had significantly better 5-year PFS than the RT group (80.1 % vs. 68.6 %, P=0.026)., Conclusions: The clinical benefits of better local and disease controls were observed when oral chemotherapy was added to RT in patients with T2N0 glottic SCC. Thus, the significance of adding oral chemotherapeutic agents to RT in the treatment of T2N0 glottic SCC requires further prospective investigation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Neoadjuvant chemotherapy for induction selection of definitive treatment (IS) protocols have shown excellent outcomes for organ preservation and survival in patients with T3 laryngeal squamous cell carcinoma (LSCC). We seek to evaluate survival and organ preservation outcomes in T4 LSCC patients treated with IS protocols., Methods: Retrospective cohort of advanced T3 and T4 LSCC patients who underwent IS protocols based upon potential for preserving a functional larynx. Patients received one neoadjuvant cycle of platinum-based chemotherapy with either 5-fluorouracil or docetaxel or with two cycles of platinum-based chemotherapy with docetaxel and a Bcl-2 inhibitor. Patients who achieved ≥ 50 % response as determined by radiographic review and/or endoscopic evaluation received definitive chemoradiation. Patients who had < 50 % response after IS underwent total laryngectomy (TL) followed by post-operative radiation +/- chemotherapy., Results: Amongst T4 patients, 114 met inclusion criteria including 89 who underwent IS protocols and 25 who received an upfront TL. In total, 76.0 % of T3 patients and 71.9 % of T4 patients responded to IS and underwent definitive chemoradiation. There was no significant difference in hazard of death between T4 IS and T4 TL patients (HR: 0.9, p = 0.86). Among responders, there was no significant difference in 5-year laryngectomy-free survival (T3 - 59.6 %, T4 44.3 %, p = 0.15) or laryngeal preservation by T stage (T3 - 72.8 %, T4 - 73.0 %, p = 0.84)., Conclusions: Select T4 patients may benefit from organ preservation using IS protocols with similar response rates to patients with T3 tumors, without compromising survival when compared to upfront TL., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objectives: The systemic inflammatory response is strongly involved in the progression of malignant tumors, and it is useful for predicting survival time and determining therapeutic effects. The inflammatory biomarkers, neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR) are used to assess post-treatment survival and recurrence in various malignant tumors.(Walsh et al., 2005; Burt et al., 2011; Smith et al., 2009) 1 , 2 , 3 These indicators may be effective as predictive markers for head and neck malignancies., Methods: The participants were 125 glottic laryngeal and supraglottic cancer cases who received primary treatment in our department from 2010 to 2016. The NLR, LMR, and PLR for each patient were calculated in addition to the association with overall survival (OS) rate, disease-specific survival (DSS) rate, and laryngeal preservation rate for tumor location, T and N classification, TNM stage classification, treatment, and smoking. We investigated whether inflammatory biomarkers are useful for predicting prognosis., Results: The cutoff values for NLR, LMR, and PLR on the ROC curve were 1.88, 5.57, and 108, respectively. Multivariate analysis with LMR 5.57 as the cutoff value showed significant differences in OS, DSS, and laryngeal preservation. However, setting the cutoff values for NLR 1.88 and PLR 108 showed significant differences only in OS and laryngeal preservation., Conclusion: LMR may be a total survival predictor of laryngeal cancer, including OS, DSS, and laryngeal preservation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Asian Surgical Association and Taiwan Society of Coloproctology. Published by Elsevier B.V. All rights reserved.)

Introduction: Life expectancy is rising and consequently also the number of older patients with head and neck cancer. Different treatment regimens are often applied for older patients. The aim of this study is to investigate how treatment patterns and survival rates have changed over the past 20 years in older patients with head and neck squamous cell carcinoma (HNSCC)., Materials: Patient and tumour characteristics, treatment and 5-year survival data from the Netherlands Cancer Registry of patients aged ≥60 years diagnosed with HNSCC in 1990-1995 and 2010-2015 were compared using chi-square test and relative survival analysis., Results: Data of 14,114 patients were analyzed. Oral cavity cancer treatment did not change over time, while survival improved from 54% to 58% (p = 0.03). Oropharyngeal and hypopharyngeal cancer treatment shifted towards non-surgical, with survival improving from 31% to 51% (p < 0.01) and 26% to 34% (p < 0.01), respectively. Laryngeal cancer treatment changed towards surgery in stage I and non-surgical treatment in stage III and IV disease. Survival in laryngeal cancer stage I remained stable and favorable at a relative survival rate of around 90%. Survival non-significantly changed from 54% to 49% for stage III disease and from 37% to 33% for disease., Conclusion: Relative survival increased for all head and neck cancer sites in older patients, except for laryngeal cancer. For oropharyngeal, hypopharyngeal and advanced laryngeal cancer, a shift towards non-surgical treatment modalities was observed., Competing Interests: Declarations of competing interest None., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Gender and race disparities in head and neck squamous cell carcinoma (HSNCC) survival are independently well documented, but no prior studies have examined the joint effect of these factors on HSNCC outcomes. We aim to comprehensively estimate the effect of gender and race on overall survival in HNSCC. We constructed a retrospective cohort from the National Cancer Database for primary HNSCC of the larynx, hypopharynx, oral cavity, and oropharynx from 2010 to 2015. We used Kaplan-Meier curves and Cox proportional hazards regressions to calculate hazard ratios adjusting for treatment type, age, insurance, staging classifications, and comorbidities. Oral cavity cancer was significantly more common among Hispanic and White females compared to other sites. Female non-oropharyngeal HNSCC cases had better five-year overall survival than males (56.3% versus 54.4%, respectively), though Black females (52.8%) had poorer survival than both White (56.2%) and Hispanic (57.9%) males. There were significant differences in oropharyngeal cancer by HPV status. Notably, Black females with HPV-positive oropharyngeal OPSCC had far worse survival than any other race and gender group. These results persisted even when adjusting for potential mediating factors. Clearly gender is a significant prognosticator for HNSCC and has meaningful interactions with race. The distinct site distributions across gender and race reveal important insights into HNSCC among females. Taking into account these gender disparities while considering race is essential to providing appropriate care to head and neck patients and accurately counselling these individuals on prognosis and outcomes., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: To examine the impact of treatment sequences of Immune checkpoint inhibitor (ICI) and cetuximab on clinical outcomes in patients with recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC)., Materials and Methods: Clinicopathologic data were retrospectively collected on patients with R/M HNSCC who received ICI treatment. Association between treatment sequence and clinical outcomes were assessed., Results: A total of 113 patients with R/M HNSCC were analyzed. Patients who had cetuximab prior to ICI had worse overall (HR, 1.83) and progression-free survival (HR, 1.76) compare to those without prior cetuximab. Among patients who had subsequent therapy after ICI, cetuximab-based therapy was associated with a trend toward higher response rate and longer survival than non-cetuximab regimen., Conclusion: Our single institution analysis showed that treatment sequence of cetuximab and ICI in R/M HNSCC may affect clinical outcomes. Cetuximab prior to ICI was associated with worse outcomes while the efficacy of cetuximab may be enhanced after ICI therapy., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Expression of the mu-opioid receptor (MOR) is associated with poor long-term outcomes in various types of cancer. The association between MOR expression and clinical outcomes in laryngeal squamous cell carcinoma (LSCC) is not clear., Methods: This retrospective study included patients who underwent laryngectomy for LSCC. The expression pattern of the MOR protein and OPRM1 gene in tumours and corresponding adjacent non-carcinoma specimens was measured. Propensity score matching was used to minimise bias. The primary endpoints were overall survival (OS) and disease-free survival (DFS). The secondary endpoints were intraoperative sufentanil consumption, grade of surgical complications according to the Clavien-Dindo classification, and hospital length of stay., Results: A total of 207 LSCC patients were enrolled. After propensity score matching, there was a significant difference in DFS between groups at 1, 3, and 5 yr (60.2% vs 81.2%, P=0.019; 39.4% vs 50.2%, P=0.026; 37.5% vs 42.5%, P=0.023, respectively) in patients with high MOR expression. The OS rates at 1, 3, and 5 yr were significantly lower in the high MOR expression group (81.2% vs 93.2%, P=0.027; 57.7% vs 78.3%, P<0.001; 42.5% vs 60.3%, P<0.001, respectively). The multivariate analysis indicated that high MOR expression was associated with worse DFS and OS (hazard ratio: 1.52, 95% confidence interval: 1.07, 2.25, P=0.034; hazard ratio: 1.42, 95% confidence interval: 1.17, 2.34, P=0.032)., Conclusion: High MOR expression may be associated with poor prognosis in patients with LSCC, suggesting that MOR could be used as a valuable molecular biomarker to predict prognosis of LSCC patients., (Copyright © 2020 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Objectives: This multicenter retrospective cohort study aimed to evaluate the significance of adding S-1 to radiotherapy (RT) for the treatment of T2N0 glottic cancer using a propensity score matched analysis in Japan., Materials and Methods: This study was conducted on 287 patients with T2N0 glottic cancer who were treated with definitive RT or chemoradiotherapy with S-1 (S-1 RT) between April 2007 and March 2017. Propensity score matched analysis was performed to ensure the well-balanced characteristics of the groups of patients who received RT alone and S-1 RT. Overall, progression-free and laryngectomy-free survivals and local control and laryngeal preservation rates were compared., Results: Fifty-four pairs of patients were selected after performing propensity score matched analysis. Clinical characteristics were well-balanced between the two groups. The overall survival of patients in the S-1 RT group was significantly better than those in the RT alone group (P = 0.008). The progression-free and laryngectomy-free survivals of patients in the S-1 RT group were also better than those in the RT alone group; however, the differences were not significant. In contrast, patients in the S-1 RT group had slightly lower local control and laryngeal preservation rates compared with those in the RT alone group. The incidence of dermatitis in the S-1 RT group was significantly higher than that in the RT alone group in the matched population (P = 0.013)., Conclusions: The addition of S-1 to RT for the treatment of T2N0 glottic cancer was not associated with better local control and laryngeal preservation rates in this study., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Introduction: The aim of this study was to assess the validity of a treatment strategy for T1N0 glottic squamous cell carcinoma., Methods: One hundred and seventeen patients were prospectively treated according to institutional guidelines. using 1) laser microsurgery (L) for exophytic tumor, limited to one vocal cord, without extension to the anterior commissure or the vocal process of the arytenoid cartilage, 2) radiotherapy (RT) for large or infiltrative tumor reaching the anterior commissure or the vocal process of the arytenoid cartilage, poor endoscopic exposure and cT1b or 3) partial laryngectomy (PL) for tumor infiltrating the anterior commissure. Ninety-five patients were treated with RT and 22 with surgery alone (S) [L:19; PL:3]., Results: The 5-year overall survival (OS) and disease-specific survival (DSS) were 81.5% and 97.1% (median follow-up: 73 months), respectively. There was no statistically significant difference in OS or DSS between patients treated with RT or S (logrank test: p = 0.974 and 0.978). The 5-year ultimate local control rate reached 98.3%. The local control rate with larynx preservation was 94.9% with no difference between RT (94.7%) and S (95.5%) (χ 2 : p = 0.891). Continued smoking after RT was significantly associated with a lower 5-year OS (77.9% versus 87%), [HR 3.458; p = 0.043 (95%CI 1.010-11.837)]., Conclusions: For patients with T1 glottic carcinoma, and based on our previous studies, these data prospectively confirm the oncologic validity of an institutional treatment strategy. Continued smoking after RT correlated with poor OS., (Copyright © 2019 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Objectives: The prognostic value of metabolic tumor volume (MTV) in locally advanced laryngeal or hypopharyngeal cancer is established in the setting of chemoradiotherapy, while it remains unknown in the setting of upfront total laryngectomy., Materials and Methods: We retrospectively analyzed 88 patients receiving total laryngectomy and neck dissection, using Cox regression models., Results and Conclusion: Variables related to metastatic lymph node were associated with overall survival, whereas those related to primary tumor were not. In multivariable models, MTV of metastatic lymph nodes (N-MTV) as a continuous variable (Akaike's information criterion (AIC), 277.5) was equivalent to pathological nodal status (AIC, 278.2; P = 0.40), and superior to pathological nodal classification as an ordinal variable (AIC, 281.4; P < 0.05) in ability of predicting death. The risk of death was increased by 1.2-fold (95% confidence interval (CI), 1.0-1.4; P = 0.03) every 10-ml increment of N-MTV, while patients with pN+ disease were at a higher risk of death by 2.9-fold (95% CI, 1.0-12.2; P < 0.05) compared with patients with pN0 disease. Using recursive partitioning analysis (RPA), we classified the patients as having a low, intermediate, or high risk of death on the basis of N-MTV and extranodal extension (ENE). This RPA classification system exhibited greater concordance with overall survival than the classification considering pathological nodal status and ENE (AIC, 275.8 versus 281.4; P = 0.02). In the setting of upfront total laryngectomy, N-MTV is a critical predictor of mortality. A staging system in which N-MTV is incorporated may better inform adjuvant treatment decisions., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Salvage total laryngectomy is often indicated in patients with recurrent or persistent laryngeal cancer after radiation or chemoradiation treatment. This article reviews and discusses key considerations regarding salvage laryngectomy. Within this article, a review of the salvage laryngectomy incidence in the major organ preservation trials, survival rates, predictors of outcomes, complication rates, and the roles of elective neck dissection and free tissue transfer for reconstruction in patients undergoing salvage laryngectomy is provided., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Over the course of the last several decades, the treatment options for early laryngeal cancers (T1 and T2) have evolved; however, simultaneously the mortality rate has increased. As larynx preservation approaches have become the standard of care, the selection of the proper treatment modality has become paramount. Radiation therapy or transoral laser microsurgery are the most common options for treatment of these early lesions. Oncologic and functional outcomes are considered equivalent between the two modalities for early glottic cancers; however, no direct comparisons exist for robust analysis. In terms of larynx preservation, there also is not compelling data favoring one treatment option or another. For early stage lesions, the goal for any larynx-sparing technique, either radiation or surgery, should be the intent to cure with single modality treatment and minimal short- and long-term toxicity. This article is designed to create a frame of reference for managing early stage disease with respect to lesions of the glottis and supraglottis while weighing treatment implications from an oncologic, functional, and cost perspective., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Organ preservation protocols utilizing induction chemotherapy as a selection agent have played a critical role in the treatment of advanced laryngeal squamous cell carcinoma (LSCC). The selection of patients who will have a good response to chemoradiation allows for organ preservation in a significant group of patients and minimizes the rate of surgical salvage. While there remains debate regarding its utility when compared to surgery or other organ preservation regimens, the data does suggest an important role for induction chemotherapy in LSCC. In addition, there are continued opportunities to identify pretreatment biomarkers for induction chemotherapy, whether genetic, epigenetic or cellular, that could predict response to treatment and select patients to therapy (whether organ preservation or surgery). As our understanding of the biology of larynx cancer advances, induction paradigms have utility for the development and adoption of novel agents and therapeutics. The background of induction chemotherapy as a selection agent and future directions of this approach are discussed., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Organ preservation versus total laryngectomy for advanced laryngeal cancer continues to be hotly debated. This review presents evidence-based decision making points for these patents., (Published by Elsevier Ltd.)

Background: To clarify the effect of induction chemotherapy (ICT) in patients with advanced pharyngeal and laryngeal squamous cell carcinoma (PLSCC) treated with concurrent chemoradiotherapy (CCRT)., Methods: Patients with treatment-naïve nonmetastatic advanced PLSCC were stratified according to disease stage (III or IV) and resectability before being randomized to either a ICT/CCRT or CCRT arm. A cisplatin/tegafur-uracil/leucovorin regimen was administered during ICT and CCRT. The primary end point was overall survival (OS)., Results: We enrolled 151 patients during December 2006 to February 2011. The median follow-up of surviving patients was 54.5 months. The ICT/CCRT arm included more patients with hypopharynx cancer (57.1% vs 40.5%, p = 0.09) and N2 or N3 diseases (85.7% vs 74.4%, p = 0.02). In the ICT/CCRT and CCRT arms, the 5-year OS was 48.1% and 53.2% (p = 0.45); progression-free survival (PFS) was 31.8% and 55.6% (p = 0.015); and locoregional control (LRC) was 37.7% and 56.2% (p = 0.026), respectively. The adverse events and compliance to radiotherapy were similar. However, the proportion of patients receiving a total dose of cisplatin during CCRT <150 mg/m 2 was higher in the ICT/CCRT arm (46.8% vs 16.2%; p = 0.000) and independently predicted poorer PFS and LRC in multivariate analysis., Conclusion: OS did not vary between the ICT/CCRT and CCRT arms. However, poorer compliance to CCRT and inferior LRC and PFS were observed in the ICT/CCRT arm. Optimizing the therapeutic ratio in both ICT and CCRT settings are necessary for developing a sequential strategy for patients with advanced-stage PLSCC., (Copyright © 2018 Chang Gung University. Published by Elsevier B.V. All rights reserved.)

Purpose: The main objective of this study was to evaluate the 5-year efficacy of exclusive laryngeal radiotherapy without node prophylactic irradiation for localized cancers of the vocal cords., Patients and Methods: We retrospectively reviewed charts from 258 patients with T1-T2N0 glottic carcinoma irradiated from April 1987 to March 2015 in four France western centers, including pretreated patients. Toxicity was analyzed according to CTCAE v4.0 classification., Results: The median follow-up was 50 months. The median age was 67 years with 87% men and 85.5% had T1 tumor. Five years overall survival was 77.5% (95% confidence interval [95% CI]: 71.4-83.5), 5 years local control was 86.8% (95% CI: 82.3-91.3), specific survival rate was 95% (95% CI: 92.2-97.9) and final laryngectomy-free survival was 87.5% (95% CI: 82.2-92.9). Most toxicities were grade 1 and 2. Grade 3 acute toxicity was 15.5% for the radiation laryngitis, 3.5% for radiodermatitis and 7.7% for dysphonia. Grade 3 chronic toxicity was 3.5% for dysphonia and there were two cases of tracheal stenosis treated by tracheotomy., Conclusion: Radiotherapy provides good results in local control of stage I and II vocal cords cancers as well as the toxicity level., (Copyright © 2017 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Objective: Analysis of laryngeal cancer mortality trends in Brazil and its geographic regions for the period 1996-2010 and calculation of mortality predictions for the period 2011-2030., Study Design: An epidemiologic, ecologic, demographic-based study, which utilized information from the Mortality Information System on all cancer-related deaths in Brazil, is presented here. Mortality trends were analyzed by Joinpoint regression, and Nordpred was utilized for the calculation of predictions., Results: When comparing the last observed period and the last predicted period for men, an increase of 10,588 deaths is expected, representing an increase of 69%. For women, the expected increase in the number of deaths will be 2217, representing an increase of 104%. Laryngeal cancer mortality rates will increase in the North and Northeast regions for men and in the Northeast and Southeast regions for women., Conclusions: Despite the current high mortality for laryngeal cancer, rates will continue to increase until 2030 in Brazil., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To investigate the therapeutic effect of surgery, radiotherapy and photodynamic therapy on early glottic carcinoma and prognostic factors., Methods: Retrospective analysis of 202 cases with early glottic carcinoma (Tis-T2N0M0) underwent surgery (n=152), radiotherapy (n=20) and PDT (n=30) from 2000 to 2013 The KPS score, the disease-free survival (DFS), overall survival (OS), local control (LC), larynx preservation rate, laryngeal function were evaluated. The methods of χ (2)test or Fisher's exact probability method, Kaplan Meier method, log-rank test of Kaplan-Meier method, Cox proportional hazards model were used to analyze the data., Results: There was no statistical significance in OS, DFS and LC among the three groups. The laryngeal function preservation rate of RT group, PDT group and Surgery group were 90%, 86.7% and 65.1% respectively, with the former two groups significantly superior to Surgery group. While there is no statistical significance between RT group and PDT group. Single factor analysis showed that KPS score before treatment, vocal fold mobility limitation and differentiation degree could have an effect on prognosis. Multivariate regression analyses indicated that anterior commissure invasion, T stage and KPS score before treatment were independent adverse prognostic factors for OS. T stage and differentiation degree were adverse prognostic factors for DFS. T stage was also an adverse factor of LC. Thirty-three cases experienced local recurrence or cervical lymph node metastasis. Three groups showed no statistical difference in local recurrence or lymph node metastasis, with twenty-two cases in Surgery group, four in RT group and seven in PDT group., Conclusions: The therapeutic effect was approximate in surgery group, radiotherapy group and photodynamic group, and all three treatment regimens achieved good clinical effect. Radiotherapy and photodynamic therapy may be the first or very important treatment on early stage glottic squamous cell cancer (Tis∼T2N0M0). However only 6 patients underwent PDT for T2 disease, making definitive treatment conclusions for this subgroup unclear., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Purpose: The long-term results of RTOG 91-11 suggested increased deaths not attributed to larynx cancer after concomitant chemoradiotherapy (CRT) despite no apparent increase in late effects. Because the timing of events was not reported by RTOG 91-11, one possibility is that severe late dysphagia (SLD) develops beyond five years and leads to unreported treatment-related deaths. Here we explore the timing of SLD after CRT., Methods: Patients who would have met eligibility criteria for RTOG 91-11 and were treated with CRT between 1993 and 2013 were identified. Events occurring beyond 3months after treatment and suggestive of SLD were recorded including esophageal stricture dilations, hospital admissions for aspiration pneumonia or feeding-tube insertion. Feeding-tube dependence beyond one year was also considered SLD. The cumulative incidence of SLD and its components was quantified using Gray's competing risk analysis with recurrence or death considered competing risks., Results: Eighty-four patients were included with a median follow-up of 43months. The 5-year overall survival was 70% (95% CI 58-80%). No death was directly a result of treatment-induced late dysphagia. The 5-year incidence of SLD was 26.5%. While 15 of 18 (83%) first stricture dilations occurred within 5years after CRT, 3 of 5 (60%) aspiration admissions and 5 of 8 late feeding tube insertions occurred beyond five years from CRT., Conclusions: SLD is common after CRT for larynx cancer and can occur beyond 5years from the end of treatment, emphasizing the importance of survivorship follow-up. Despite the incidence of SLD, death related to dysphagia is uncommon., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objectives: Long term outcomes of patients with head and neck cancer (HNC) are rarely reported, but of potential benefit to clinicians and researchers. Squamous cell carcinomas (SCC) of the head and neck represent a heterogeneous group of cancers. The purpose of this population based study is to describe primary site specific, long term outcomes of HNC., Methods: All patients from a Canadian province diagnosed between 1986 and 1990 with SCC of the oral cavity, pharynx, and larynx were identified. Chart review and patient data were abstracted through the provincial cancer registry database. Survival analysis was performed with Kaplan Meier methods, while differences in survival between groups were assessed with log-rank tests. Multivariable analysis was performed using Cox-regression., Results: 1657 patients were analyzed during the study period. Almost half (50.9%) of the cases were advanced stage (stage III IV) at presentation. Two, 5, 15 & 25year overall survival (OS) and HNC specific survival for all the patients were 64%, 46%, 21%, 11% and 74%, 63%, 53% & 49%, respectively. OS and HNC-specific mortality were statistically inferior among men, older age at diagnosis, advanced stages of disease, and was primary cancer site specific, with worse survival in oropharyngeal & hypopharyngeal sites, p<0.001., Conclusions: Survival rates vary by primary HNC site, and the overall survival & HNC specific survival differ over this long follow up assessment. Head and neck cancer specific death is most common in the first five years, and is subsequently dominated by competing causes of mortality. These results are useful as a reference tool for clinicians, researchers, and trainees., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Angiogenesis is active in localised laryngeal squamous cell carcinoma. We assessed relative messenger RNA (mRNA) and immunohistochemical (IHC) expression of Vascular Endothelial Growth Factors (VEGF) A, B, C, their receptors VEGFR1, 2, 3, Neuropilins 1, 2 (NRP1, 2) and Hypoxia-Inducible Factor 1A (HIF1A) in paraffin-embedded localised laryngeal carcinomas. In 289 patients with T3-4 (77.8%), node-negative (84.1%) tumours of the larynx, high VEGFA and VEGFR1 mRNA correlated with advanced T stage, while low VEGFB and VEGFC mRNA with alcohol abuse and supraglottic primary, respectively (p<0.05). Age <55 was associated with high IHC expression of VEGFA, C and poor tumour differentiation with high IHC VEGFA. At a median follow-up of 74.5months, patients with VEGFR1-high tumours had significantly poorer disease-free survival (Hazard Ratio [HR] 1.93, p=0.008) and shorter overall survival (OS, HR 1.71, p=0.041). An association with dismal OS was seen for high VEGFR3 tumoural mRNA expression (HR 1.76, p=0.02). IHC expression of VEGF family proteins in the tumour was not prognostic and had poor concordance with mRNA expression (kappa<0.1, p=NS). In multivariate analysis, node-positive status, non-supraglottic localization, high VEGFR1 mRNA and high IHC VEGFA expression were significantly associated with relapse, while node-positive status, high VEGFR1 and VEGFC mRNA expression in the tumour with risk of death. In laryngeal cancer, upregulated mRNA expression of VEGFR1 and VEGFC is associated with poor patient outcome., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Different modalities of treatment in early laryngeal cancer lead to equivalent oncological outcomes. Hence this systematic review was undertaken to synthesise the key oncological outcomes following primary open partial laryngectomy for laryngeal cancer., Methods: A systematic review of the English literature with statistical pooling of outcomes, the main outcome measure being local control at 24 months., Results: A total of 53 articles satisfied inclusion criteria and were included in the review. The pooled local control rate at 24 months from 5061 patients was 89.8% (95% CI 88.3-91.2), pooled overall survival was 79.7% (n = 3967; 95% CI 76.5-782.8) and pooled mean disease free survival was 84.8% (n = 2344; 95% CI 80.6-88.7). The pooled mean operative mortality, laryngectomy for function, tracheostomy decannulation and permanent gastrostomy rates were 0.7%, 1.7%, 96.3%, and 2.0%, respectively., Conclusions: Open conservation laryngectomy is a good option in selected primary laryngeal cancers with excellent oncological outcomes., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Laryngeal cancer in men is a relatively common malignancy, with a marked socioeconomic gradient in survival between affluent and deprived patients. Cancer of the larynx in women is rare. Survival tends to lower than for men, and little is known about the association between deprivation and survival in women with laryngeal cancer. This paper explores the trends and socio-economic inequalities in laryngeal cancer survival in women, with comparison to men. We examined relative survival among men and women diagnosed with laryngeal cancer in England and Wales during 1991-2006, followed up to 31 December 2007. We estimated the difference in survival between the most deprived and most affluent groups (the 'deprivation gap') at one and five years after diagnosis, for each sex, anatomical subsite and calendar period. Five year survival for all laryngeal cancers combined was up to 8% lower in women than in men. This difference is only partially explained by the differential distribution of anatomical subsites in men and women. Disparities in survival between men and women were also present within specific subsites. In contrast to men, there was little evidence of a consistent deprivation gap in survival for women at any of the anatomical subsites. The stark socioeconomic inequalities in laryngeal cancer survival in men do not appear to be replicated in women. The origins of the socio-economic inequalities in survival among men, and the disparities in survival between men and women at specific tumour subsites remains unclear., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Survival in patients with laryngeal cancer has not increased remarkably within the last years. It is presumed that a variety of factors act jointly in predicting survival after diagnosis: tumour stage, tumour site, treatment approaches, age and comorbidities. The aim of this German clinical multi-centre study is to present results from multivariate analysis. A retrospective cohort study was conducted in four hospitals in South-West Germany. Incident cases with laryngeal squamous cell carcinoma were included for the years 1998 to 2004, resulting in a population sample of 594 patients. Multivariate regression analysis was performed using the Cox proportional hazards model. Patients were followed up for 64.1months on average. Overall 5-year survival was 66% (95% confidence interval (CI): 62-70%). The strongest risk factors in multivariate analysis were age at first diagnosis (hazard ratio (HR): 1.5; 95% CI: 1.5-1.7 per each additional 10years), tumour stage, and the development of recurrences (HR 3.1; 95% CI: 2.3-4.2) or second primary carcinomas (HR 2.1; 95% CI: 1.4-3.1). A somewhat weaker effect was shown for patients with comorbidities (using Charlson's comorbidity index). The choice of treatment did not strongly affect survival when adjusting for other factors, possibly because the optimal treatment approach was applied for the specific constitution and requirements of each patient. For future research it would be desirable to study the effect of treatment on quality of life in multivariate analysis as well as other modifiable risk factors as smoking and drinking reduction or cessation after diagnosis., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Ataxia telangiectasia mutated (ATM) kinase is a critical regulator in initiating DNA damage response and activating DNA repair. However, the correlation between ATM expression and the outcome of laryngopharyngeal cancer patients is unknown. We hypothesize that ATM expression is correlated with a worse outcome in laryngopharyngeal cancer patients., Patients and Methods: The ATM messenger RNA (mRNA) expression of 80 tumors of laryngeal and pharyngeal cancer was examined by real-time quantitative RT-PCR. Overall survival rates were measured using Kaplan-Meier estimates and the log-rank tests. The adjusted hazard rate ratios (HRRs) were computed by multivariate Cox regressions., Results: Reduced ATM mRNA was found in 65 of 80 studied cases. Lower ATM expression [tumor/normal <0.3, HRR = 2.49; 95% confidence interval (CI) 1.27-4.88], younger age (<55 years, HRR = 2.71; 95% CI 1.16-6.32), and larger tumor (T(3)/T(4), HRR = 2.21; 95% CI 1.10-4.44) were independent risk factors for survival. Patients with lower ATM and younger age (HRR = 6.51; 95% CI 2.05-20.66) or with lower ATM and T(3)/T(4) tumor (HRR = 5.23; 95% CI 2.04-13.40) exhibited the poorest outcome., Conclusion: The expression of ATM mRNA, which is frequently downregulated in laryngeal and pharyngeal cancers, could be a valuable prognostic marker.

The purpose of the research was to evaluate postoperative complications, functional outcome and survival after salvage laryngectomy. Second, to evaluate the management of the neck in combination with a laryngectomy in this group of patients. A retrospective analysis of all patients who underwent total laryngectomy for residual or recurrent squamous cell laryngeal carcinoma after (chemo)radiotherapy between November 1990 and June 2007 was performed. Of the 120 patients that were included, the complication rate was 56% (33% major and 23% minor). In univariate analyses, T-stage (p=0.05), bilateral neck dissection (p=0.09) and ASA score (p=0.08) showed a trend for postoperative major complications. Lymph node metastases were found in 26% of the neck dissection specimens, with a trend towards more regional disease at higher initial N-stage (p=0.06) and T-stage (p=0.08). Five-year disease specific survival was 58%. In univariate analyses pre-operative chemoradiation (vs. radiation) (p=0.0001), N3 neck (p=0.001) and positive surgical margins (p=0.02) were significant predictors for a worse disease specific survival, but only positive surgical margins (p<0.001) maintained significance in multivariate analysis. Eighty-seven percent of the patients were able to produce speech using a voice prosthesis, and 84% of the patients were able to have a 'normal' or 'soft' diet. There was an almost significant increase in mean body mass index (BMI) 6-12 months postoperative (p=0.057). Laryngectomy after radiotherapy offers good survival, with a substantial risk of complications and good functional outcome., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Aim: The aim of this paper was to compare demographics, treatment and outcomes from two large prospective audits of head and neck cancer patients in two disparate regions of the UK., Methods: In the Scottish Audit of Head and Neck Cancer (SAHNC) a total of 1910 patients with new head and neck cancers were registered in a two year period from September 1999 to August 2001. The South and West Audit of Head and Neck Cancer (SWAHN) was carried out in three phases between 1996 and 2002 with a total of 2050 cases., Results: There were more men in SAHNC than SWAHN (71% vs 67%, p<0.01) and patients in SAHNC presented at a younger age (76% aged 45-74 compared with 64%, p<0.001). Significantly more patients in Scotland had advanced (stage III/IV) laryngeal cancer (44% vs 30%, p<0.001). The overall disease specific five year survival was 54.5 for SAHNC and 54.2 for SWAHN., Conclusion: This comparison of large head and neck cancer cohorts provides important data to base UK head and neck cancer care and hypotheses regarding pathogenesis and the effects of treatment processes. Given the heterogeneity in disease, patient and healthcare characteristics between the two regions, the similarities in survival and process outcomes are striking.

Comorbidity and diagnostic delay are independent prognostic factors in head and neck cancer, most notably in laryngeal cancer. We investigated their inter-relationship and their relative significance in survival of three different head and neck cancers. A population-based retrospective cohort of 221 patients with cancer of oral tongue, pharynx or larynx diagnosed between 1986 and 1996. Diagnostic delays and data on the onset of symptoms from real-time primary care charts. Comorbidity classified according to Charlson comorbidity index. Survival analyses were performed using Cox multivariate model. Significant association was found between increased comorbidity score and long professional delay in laryngeal cancer. In tongue cancer, longer patient delay and increased comorbidity were associated. In laryngeal cancer, high comorbidity (adjusted hazard ratio HR 5.6), professional delay of 6 months (HR 3.3) and advanced stage (HR 3.8) all were independent determinants of survival. In laryngeal cancer, comorbid illnesses are associated with professional diagnostic delay. However, despite their inter-correlation both comorbidity and professional delay are significant and independent prognostic factors.

Background: Locally advanced laryngeal and hypopharyngeal cancers (LHC) represent a group of cancers for which surgery, laryngectomy-free survival (LFS), overall survival (OS), and progression-free survival (PFS) are clinically meaningful end points., Patients and Methods: These outcomes were analyzed in the subgroup of assessable LHC patients enrolled in TAX 324, a phase III trial of sequential therapy comparing docetaxel plus cisplatin and fluorouracil (TPF) against cisplatin and fluorouracil (PF), followed by chemoradiotherapy., Results: Among 501 patients enrolled in TAX 324, 166 had LHC (TPF, n = 90; PF, n = 76). Patient characteristics were similar between subgroups. Median OS for TPF was 59 months [95% confidence interval (CI): 31-not reached] versus 24 months (95% CI: 13-42) for PF [hazard ratio (HR) for death: 0.62; 95% CI: 0.41-0.94; P = 0.024]. Median PFS for TPF was 21 months (95% CI: 12-59) versus 11 months (95% CI: 8-14) for PF (HR: 0.66; 95% CI: 0.45-0.97; P = 0.032). Among operable patients (TPF, n = 67; PF, n = 56), LFS was significantly greater with TPF (HR: 0.59; 95% CI: 0.37-0.95; P = 0.030). Three-year LFS with TPF was 52% versus 32% for PF. Fewer TPF patients had surgery (22% versus 42%; P = 0.030)., Conclusions: In locally advanced LHC, sequential therapy with induction TPF significantly improved survival and PFS versus PF. Among operable patients, TPF also significantly improved LFS and PFS. These results support the use of sequential TPF followed by carboplatin chemoradiotherapy as a treatment option for organ preservation or to improve survival in locally advanced LHC.

Background: Installations that burn fossil fuels to generate power may represent a health problem due to the toxic substances which they release into the environment., Objectives: To investigate whether there might be excess mortality due to tumors of lung, larynx and bladder in the population residing near Spanish combustion installations included in the European Pollutant Emission Register., Methods: Ecologic study designed to model sex-specific standardized mortality ratios for the above three tumors in Spanish towns, over the period 1994-2003. Population exposure to pollution was estimated on the basis of distance from town of residence to pollution source. Using mixed Poisson regression models, we analyzed: risk of dying from cancer in a 5-kilometer zone around installations that commenced operations before 1990; effect of type of fuel used; and risk gradient within a 50-kilometer radius of such installations., Results: Excess mortality (relative risk, 95% confidence interval) was detected in the vicinity of pre-1990 installations for lung cancer (1.066, 1.041-1.091 in the overall population; 1.084, 1.057-1.111 in men), and laryngeal cancer among men (1.067, 0.992-1.148). Lung cancer displayed excess mortality for all types of fuel used, whereas in laryngeal and bladder cancer, the excess was associated with coal-fired industries. There was a risk gradient effect in the proximity of a number of installations., Conclusions: Our results could support the hypothesis of an association between risk of lung, laryngeal and bladder cancer mortality and proximity to Spanish combustion installations.

The goal of this study was to identify host and tumour factors associated with postoperative pneumonia (PP) in a selected population of laryngeal cancer patients, treated by partial laryngectomy in 20 years at our Institution and to assess its potential prognostic impact. Clinical records of 416 consecutive patients were retrospectively reviewed. Tobacco consumption, body mass index (BMI), previous pulmonary disease, age, sex, preoperative blood gas analysis values, tumour stage and type of surgery were tested as potential risk factors for PP. Finally, the prognostic impact of these variables, including PP, in terms of disease-free and actuarial survival by Kaplan-Meier and Cox analyses were evaluated. PP developed in 73 patients (16.8%). We identified two groups of patients: 26 patients experienced an early PP within the first 7-9 days after surgery, whilst 44 experienced an ab ingestis PP following attempts of oral food intake restoration, three patients died for PP related sepsis. At multivariate Cox analysis, age older than 60 years and BMI greater than 30 were statistically associated with early PP; whereas male gender and laryngectomy with neck dissection were statistically related to a higher risk of ab ingestis PP. Interestingly, the occurrence of early PP was a negative independent prognostic factor for 5-years disease-free and actuarial survival (p=0.049 and p=0.001, respectively). The occurrence of early-onset pneumonia in laryngeal cancer patients selected for conservative laryngectomies is predictable and associated with poor clinical outcome.

Background: Randomized trials established chemoradiotherapy as standard treatment for advanced laryngeal cancer. Patients with large-volume T4 disease (LVT4) were excluded from these trials. The purpose of this study was to report T4 laryngeal cancer patient outcome, including those with LVT4 disease, treated with chemoradiotherapy., Patients and Methods: This study is a retrospective subset analysis of 32 patients with T4 laryngeal carcinoma including LVT4 tumors treated on three consecutive protocols investigating paclitaxel (Taxol), 5-fluorouracil, hydroxyurea, and 1.5-Gy twice daily (BID) radiotherapy (TFHX)., Results: Median follow-up is 43 months. Four-year locoregional control (LRC), disease-free survival (DFS), overall survival (OS), and laryngectomy-free survival (LFS) was 71%, 67%, 53%, and 86%, respectively. Four patients required laryngectomy for recurrent or persistent disease. Of disease-free patients with >or=1 year follow-up, 90% demonstrated normal or understandable speech. None required laryngectomy for complications. Among LVT4 patients, 4-year LRC, DFS, OS, and LFS was 71%, 65%, 56%, and 81%, respectively. Induction chemotherapy improved 4-year LRC (90% versus 46%, P = 0.03) and DFS (84% versus 42%, P = 0.03)., Conclusions: Promising control and functional outcomes are achieved with TFHX for T4 laryngeal patients. LVT4 disease had outcomes similar to patients with less advanced disease treated on Radiation Therapy Oncology Group 91-11. Induction chemotherapy improved outcomes, warranting further investigation.

Purpose: A retrospective study to re-assess the indications for postoperative radiation therapy in squamous cell carcinoma of the larynx staged N0 after gross resection., Patients and Methods: Between January 1975 and December 2000, 166 patients with squamous cell carcinoma of the larynx were treated by total laryngectomy with or without neck dissection. Surgery was completed by external radiotherapy delivering 45 to 65 Gy to the tumour bed and 45 to 50 Gy to cervical lymphatic chains. Minimal follow-up was 36 months and median follow-up was 98 months., Results: The rate of nodal recurrence was 6% (median time for relapse was 9 months). The survival rates at 1, 2, 3 and 5 years were 93.5, 84, 80 and 69% respectively, with a 8 year 3 month median survival. The univariate analysis showed 4 parameters, which significantly increased the risk of local recurrence: the medical necessity for immediate tracheotomy, the subglottic involvement, the involvement of the whole larynx and the presence of lymphatic embols in the neck dissection. There was no statistically significant difference between the patients with or without a neck dissection. Fifty-nine secondary cancers were observed, 15 of them occurring in the head and neck area. The late complications consisted of cervical subcutaneous fibrosis (7%), oesophageal stricture (4%), oeso-tracheal fistula (l%), hypothyroidism (3%), bone necrosis (1%)., Conclusion: Prophylactic cervical radiotherapy in laryngeal cancers resulted in 6% cervical node recurrence rate. This value may represent the maximal rate to accept if one would favour new therapeutic strategies based on restricted indications for radiotherapy.

The question of larynx preservation is central in the management of patients with a carcinoma of the larynx or hypopharynx, especially to preserve the main functions of the larynx. In early stages (T1-earlyT2) Larynx preservation can generally be obtained with partial surgery or radiotherapy. Some other approaches such as exclusive chemotherapy require further investigations. In locally advanced and infiltrating larynx/hypopharynx carcinomas, (advancedT2-T3), several ways have been used to preserve the larynx including exclusive radiotherapy which can be improved by modified fractionation and acceleration. The efficacy of radiotherapy can be also markedly increased by adding concomitant cisplatin based chemotherapy, as reported recently in a large randomized trial. An alternative approach consisted in using induction chemotherapy (cisplatin-5FU) and followed by a local treatment adapted to the response to chemotherapy. The combined analysis of 3 such randomized trials (GETTEC, Veteran et EORTC) showed that this approach has to be used with caution, and could be safer in good responders to induction chemotherapy. Finally, larynx preservation is generally not proposed in patients with deeply infiltrating tumors and or tumor invading the cartilage or soft tissue in the neck (T4).

Background: Early glottic carcinomas can be treated with radiotherapy or surgery with similar local control rates but with better functional results with radiotherapy. The aim of this study was to analyze the results of our experience of exclusive radiotherapy., Patients and Methods: From 1975 to 2001, 155 patients with Tis, T1 and T2 glottic carcinomas were treated with exclusive radiotherapy. Prognostic factors of survival, local control and larynx-preservation rates were analyzed in uni and multivariate analyses., Results: Median prescribed dose was 65 Gy in 44 days. Overall survival was 75% for the whole group, 75% for Tis, 85% for T1a, 72% for T1b, 59% for T2. Specific survival was 88% for the whole group, 75% for Tis, 94% for T1a, 90% for T1b, 69% for T2. Disease-free survival was 68% for the whole group, 75% for Tis, 77% for T1a, 51% for T1b, 58% for T2. Laryngeal preservation rate was 85% (133/155). Twenty-nine (29/155, 18%) patients developed a local relapse within 31 months. Out of the 10/86 (12%) T1a-Tis relapses, 7/10 patients underwent total laryngectomy and 79/86 larynx were preserved (92%). Out of the 8/22 (36%) T1b relapses, 4/8 patients underwent total laryngectomy. Out of the 11/47 (23%) T2 relapses, 8/11 patients underwent total laryngectomy. Increased overall treatment time, tumor stage, sub-glottis extension were associated with poorer local control. Second malignancies remain a major problem in the outcome of this population., Conclusion: Radiotherapy remains an efficient option in the treatment of early glottic carcinomas providing a high local control rate with excellent functional results in laryngectomy-free patients. This strategy should be discussed according to the tumor stage, feasibility of conservative surgery and patient's preferences.

The epidemiology of cancers is known in France through mortality data provided by Inserm and morbidity data obtained by French tumor registries. The purpose of this study was to compare the incidence of laryngeal cancers in 9 French departments and to give an estimate of this incidence for the whole of France, based on this data. Incidence and mortality data were collected over the period 1978-1997. The incidence and mortality rates were estimated for each year from 1978 up to 2000. Observed incidence and mortality data in the population covered by cancer registries were modelled using age-cohort methods. An estimation of the incidence/mortality ratio was obtained from these models and applied to the mortality rates predicted from an age-cohort model for the entire French population. The estimated number of laryngeal cancers was 3,865 in males and 361 in females. There were pronounced contrasts in laryngeal cancer incidence between cancer registries. The incidence rate of laryngeal cancers were especially high in the Somme and Calvados department compared to those observed in Haut-Rhin and Tarn. The ratio incidence/mortality was 2.4 in Doubs and 1.3 in Somme. France is among the countries which have the highest rates of incidence and mortality for laryngeal cancer in Europe.

Purpose: The aim of this paper is to present results of analysis of 102 females with laryngeal cancer., Materials and Methods: Between 1974 and 1995, 102 female patients with cancer of larynx were treated at Radiotherapy Department of Oncology Centre in Kraków. Twenty-six of them had positive familial oncological history. The treatment method depended on stage of disease. Primary radical irradiation was performed in 66 patients, 29 patients received postoperative radiotherapy after surgery (total or partial laryngectomy), seven patients received induction chemotherapy followed by laryngectomy with postoperative radiotherapy or radical irradiation. The median dose applied with radiotherapy was 60 Gy, and dose per fraction was 2 Gy., Results: The actuarial 5-year rates were as follows: 88.9% for overall survival, 84.2% for disease-free survival, and 85.4% for local control. Only tumour stage and nodal involvement were found to be significant factor for all three endpoints. We found that younger patients had more supraglottic primary localisation, and these patients frequently were non-smoker., Conclusions: The tumour stage and nodal involvement were found to be significant prognostic factors in analysed group of female treated with laryngeal cancer.

Aim: Survival in head and neck cancers reflect loco-regional control. With an aim of organ and function preservation the present study was undertaken to compare local failure and survivals., Material and Methods: Between August 1991-December 1995, 72 patients with resectable advanced supraglottic cancers, were randomized to radical surgery followed by post-operative radiation therapy (Sx+PORT) (Arm I) or radical radiation therapy followed by salvage surgery (RRT+/-SSx) (Arm II)., Results: Sixty-four of 72 patients were evaluable, 55 were T3 (86%) and 9 were T4 (14%) tumors. In Arm I (n=35) with a mean follow-up of 24 months (2-86 months), 21 patients were alive without disease. Six patients had recurrence, one each at local and tracheostomy stoma, four had nodal recurrence only, and two developed 2nd primary in soft palate/tonsil and parotid at 15 and 18 months respectively. In Arm II (n=29), with a mean follow-up of 24 months (3-81 months), 14 patients were alive without disease. Thirteen patients had recurrence, eight had local (one patient had persistent disease), two nodal only, three loco-regional and two patients developed distant metastasis (lung). One out of eight local recurrence and 2/2 nodal recurrences were salvaged with Sx. There was a significant difference in disease-free survival between the two treatment arms, DFS (5 years) of 70% in Arm I vs 50% in Arm II (p=0.04), but did not have any impact on overall survival OAS (5 years); 73% vs 77% (p=0.79). Voice/laryngeal preservation was possible in 18/29 patients (62%) treated with RRT+/- Sx, without significantly affecting the OAS. "Pathological upstaging" was another significant finding seen in 64% of clinical T3 after radical surgery., Conclusion: RRT+/-SSx can be a feasible option in low volume, favourable resectable stage III and IV supraglottic lesions for better quality of life.

The survival experience of patients with cancer of the larynx (ICD 10) registered by the Bombay population-based cancer registry India, during the years 1992-1994, is described. The vital status of these subjects were established by matching with death certificates from the Bombay Municipal death register and by active methods such as reply-paid postal enquiries, telephone enquiries, scrutiny of case records and house visits. Of the 675 eligible cases for analysis, 458 (67.9%) were dead and 217 (32.1%) were alive at last follow-up. The 5-year observed and relative survival rates were 29.1 and 38.2%, respectively; these were 52.1 and 58.5% for glottic laryngeal cancer and 24.2 and 31.4% for supraglottic laryngeal cancer, respectively. The 5-year observed survival was 53.1% for those with localised cancer and 17.8% for those with regional extension. Advancing age, regional and metastatic disease and supraglottic cancers were associated with significantly reduced survival. Early detection and prompt treatment should improve overall survival from laryngeal cancer.

Aim: This study was designed to examine the prognostic significance of the coexpression of three genes (bax, bcl-2 and p53) which play a critical role in the apoptotic mechanisms in patients with squamous cell laryngeal carcinoma., Materials and Methods: The immunohistochemical expression of bcl-2, bax and p53 genes was retrospectively examined in 38 patients with squamous cell laryngeal carcinoma and in five controls (necrotomic tissue). Tissue specimens were obtained both during the diagnostic biopsy and at the time of surgery. Clinicopathological and survival data were correlated with the staining results., Results: Bcl-2 protein expression (P=0.0472), stage (P=0.0087) and lymph-node involvement (P=0.0488) were found to be independent prognostic factors. Increased bcl-2 protein expression correlated with a better 5-year survival (P=0.0472). Patients who were bcl-2(-)/p53(-) (n=25) or bax(+)/bcl-2(-) (n=13) had a significantly worse overall survival (P=0.0305 and P=0.0482, respectively). Similarly, patients who were bax(+)/bcl-2(-)/p53(-) (n=11) also had a worse 5-year survival compared with the rest of the group (P=0.0088). Changes that were noticed in bax and p53 protein expression from the time of biopsy until the time of surgery did not correlate with a significant increase in the overall survival., Conclusions: The expression of bcl-2 gene appears to be an independent prognostic factor for patients with laryngeal carcinoma. The coexpression of the genes studied can be used to determine aggressive clinical phenotypes., (Copyright 2001 Harcourt Publishers Limited.)

We compared the management and outcome of glottic cancer in Ontario, Canada to that in the Surveillance, Epidemiology and End Results (SEER) Program areas in the United States to determine whether the greater use of primary radiotherapy with surgery reserved for salvage in Ontario was associated with similar survival and better larynx retention rates than the U.S. approach where primary surgery is used more often. Electronic, clinical and hospital data were linked to cancer registry data and supplemented by chart review where necessary. Initial treatment and survival in patients diagnosed in the SEER areas from 1988 through 1994 were compared to patients from Ontario diagnosed from 1982 through 1995. Actuarial laryngectomy rates were compared for patients over 65 at diagnosis in the two regions. Analyses were conducted over all cases and stratified by disease stage. In localized disease (T1 or T2), conservative treatment was the most common initial treatment in both regions, although total laryngectomy was used more often in SEER than Ontario (6.2% vs. 0.2%, respectively, P <.001). In advanced disease (T3 or T4), total laryngectomy was more commonly used as initial treatment in SEER (62.9% vs. 21.0% in Ontario, P < or =.001). Over all cases, the relative survival rate was 80% in Ontario at 5 years compared to 78% in SEER (P =.33). In localized disease, the relative survival rates were 4 to 5% higher in Ontario from the second year on, while in advanced disease 2 to 3% higher rates in SEER did not approach statistical significance. Actuarial laryngectomy rates at 3 years differed between the two regions, with a 4% higher rate in SEER (P =.01). In localized disease, 12.6% of Ontario patients had a laryngectomy by 3 years postdiagnosis compared to 17.9% in SEER (P =.05). In advanced disease, the rates were 63.3% and 79.2%, respectively (P =.07). There are large differences in the management of glottic cancer between the SEER areas of the U.S. and Ontario and no evidence that a policy emphasizing radiotherapy with surgery reserved for salvage is associated with worse survival. Ultimate laryngectomy rates are lower in Ontario for localized disease and may be lower for advanced disease. Conservation treatment should be used for localized disease while the treatment decision in advanced disease may be especially sensitive to patient values for voice retention versus initial cure.

Purpose: To determine overall survival, progression-free survival, rate of voice preservation, and patterns of failure in locoregionally advanced laryngeal cancer treated with induction chemotherapy with or without surgery followed by concomitant chemoradiation., Background: Locoregionally advanced laryngeal cancer has been conventionally treated with either surgery and adjuvant radiotherapy or radiotherapy alone, and clinical and functional outcomes have been poor. Chemoradiotherapy has been demonstrated to improve functional outcome and disease control over conventional treatment in recent randomized head and neck trials., Patients and Methods: Advanced head and neck cancer patients were enrolled onto two consecutive phase II studies. Induction treatment consisted of three cycles of cisplatin, 5-fluorouracil (5-FU), leucovorin, and interferon-alpha 2b (PFL-IFN) followed by surgery for residual disease. Surgical intent was to spare the larynx when possible. All patients then proceeded to concomitant chemoradiation consisting of seven or eight cycles of 5-FU, hydroxyurea, and a planned total radiotherapy dose of 7000 cGy (FHX)., Results: A subset of thirty-two laryngeal cancer patients with predominantly stage IV disease comprises the study group for this report. Clinical CR was observed in 59% of patients following induction therapy. The median follow-up was 63.0 months for surviving patients and 44.5 months for all patients. At five years, overall survival is 47%, progression-free survival is 78%, and locoregional control is 78%. No distant failures were observed. Voice preservation with disease control was 75% at five years. Only two total laryngectomies were performed during the course of treatment and follow-up. Treatment-related toxicity accounted for two deaths., Conclusions: The addition of concomitant chemoradiotherapy to induction chemotherapy for locoregionally advanced laryngeal cancer appears to increase locoregional control and survival rates. PFL-IFN-FHX resulted in high rates of disease cure and voice preservation in a group of patients that has traditionally fared poorly in both clinical and functional outcome.

Background: Despite more than 70 randomised trials, the effect of chemotherapy on non-metastatic head and neck squamous-cell carcinoma remains uncertain. We did three meta-analyses of the impact of survival on chemotherapy added to locoregional treatment., Methods: We updated data on all patients in randomised trials between 1965 and 1993. We included patients with carcinoma of the oropharynx, oral cavity, larynx, or hypopharynx., Findings: The main meta-analysis of 63 trials (10,741 patients) of locoregional treatment with or without chemotherapy yielded a pooled hazard ratio of death of 0.90 (95% CI 0.85-0.94, p<0.0001), corresponding to an absolute survival benefit of 4% at 2 and 5 years in favour of chemotherapy. There was no significant benefit associated with adjuvant or neoadjuvant chemotherapy. Chemotherapy given concomitantly to radiotherapy gave significant benefits, but heterogeneity of the results prohibits firm conclusions. Meta-analysis of six trials (861 patients) comparing neoadjuvant chemotherapy plus radiotherapy with concomitant or alternating radiochemotherapy yielded a hazard ratio of 0.91 (0.79-1.06) in favour of concomitant or alternating radiochemotherapy. Three larynx-preservation trials (602 patients) compared radical surgery plus radiotherapy with neoadjuvant chemotherapy plus radiotherapy in responders or radical surgery and radiotherapy in non-responders. The hazard ratio of death in the chemotherapy arm as compared with the control arm was 1.19 (0.97-1.46)., Interpretation: Because the main meta-analysis showed only a small significant survival benefit in favour of chemotherapy, the routine use of chemotherapy is debatable. For larynx preservation, the non-significant negative effect of chemotherapy in the organ-preservation strategy indicates that this procedure must remain investigational.

The aim of this study is to show the epidemiologic features of upper aerodigestive tract cancers in the department of Somme. This study focused on the 1984-1995 period. For men, the upper aerodigestive tract cancers are the most frequent cancers in the Somme area. The incidence rate of pharynx cancers has shown slightly a decline over the past 10 years. The mortality rate of larynx cancers for males fell from 18.2 in 1984-1987 to 13.8 in 1992-1995 per 100,000. 5-year survival rates are between 20 and 39% for men, and from 23 to 42% for women. France has the highest incidence of these cancers in Europe. Within the country, the Somme area has a high risk for incidences and mortality as well. The results of this study indicate that upper aerodigestive tract cancers represent a serious problem for public health. Further areas need to be researched before such factors can be causally implicated in the aetiology of the disease in order to make up the prevention.