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Background: Treatment selection for squamous cell carcinoma patients aged over 84 years is controversial. This retrospective chart review examined and compared characteristics of laryngeal squamous cell carcinoma in very elderly (over 84 years) and younger patients (approximately 65 years). The secondary objective was to further evaluate the outcome of radiotherapy as a treatment modality in this patient population. Methods: Of all 23 very elderly patients with laryngeal squamous cell carcinoma treated with radiotherapy, with or without surgery, in the Davidoff Cancer Center, from 1992 to 2012, 19 had sufficient data for analysis, and comprised the study group. Results: Median age at diagnosis was 86 years. Disease stage at diagnosis was I, II, III and IVA in 53 per cent, 21 per cent, 21 per cent and 5 per cent, respectively. Median radiotherapy dose was 60 Gy given in 25 fractions. Three patients had recurrence. No patient discontinued treatment because of toxicity. Median overall survival was 3.6 years (range, 0–10 years). Conclusion: Very elderly laryngeal squamous cell carcinoma patients may derive a similar survival advantage as younger counterparts. Modern radiotherapy is effective and safe for treating laryngeal squamous cell carcinoma in this study population. Further, large-scale studies are needed. [ABSTRACT FROM AUTHOR]

Background: Cancer is a leading health problem in India with approximately 1.1 million cases occurring each year. Cancer of the Larynx represents about 1% of the total cancer burden and accounts for 0.3% of all cancer deaths. Glottic tumors typically metastasize after they have directly invaded adjacent structures with better drainage. Glottic cancer has a high rate of cure and regardless of the modality used. Radiotherapy is generally the favoured treatment in most centers despite comparable cure rates for selected T1 and T2 glottis tumors. The present study was conducted to compare radiation induced acute and late treatment related toxicities of hypo-fractionated radiotherapy and conventional radiotherapy in early glottic cancer T1-2N0M0". Material and Methods: The study was conducted in Acharya Tulsi Regional Cancer Treatment and Research Institute, Sardar Patel Medical College, Bikaner. It was done on 50 histologically proven new cases of early glottic cancer with age <70 years. Patients were treated by radiotherapy and randomized into either of the two arms Arm A (Study) and Arm B (Control). On ARM A Hypo-fractionated radiotherapy 55Gy/20# in 2.75Gy/# in 4 weeks and on ARM B Conventional radiotherapy 66Gy/33# in 2Gy/#6.5 weeks was given. Voice quality and toxicities were graded at the end of treatment, after 1, 2, 3 and 6 months. Data was analyzed using percentage, mean, chi square test and p-value. Results: Majority of the patients were in their 6th decade of life and all patients were male. Majority of the population had ECOG Performance Score of 1. 46 (92%) of patients presented with hoarseness alone while 4 (8%) of them presented with hoarseness and dysphagia, which were comparable in both the groups. Histologically, patients had Squamous Cell carcinoma (SCC). In study vs control arm where 11 (44%) vs 5 (20%) patients were T1A, 9 (36%) vs 5 (20%) in T1B, 4 (20%) vs 10 (40%) in T2A and 1 (4%) vs 5 (20%) in T2B respectively. In the study arm 25 (100%) patients received 58.4 Gy (2GyEq) whereas in control population 15 (60%) received 66 Gy and the rest 10 (40%) received 64 Gy. All 25 (100%) patients in both arms completed treatment. At the end of treatment, only 3 (12%) patients in study arm and 5 (20%) in control arm had normal voice. At 1st month of follow up, 7 (28%) vs 9 (36%) patients, at 3rd month of follow up, 13 (52%) vs 15 (60%) patients and at 6th month follow up, 21 (84%) vs 22 (88%) patients in study and control arm respectively had normal voice. (X² = 1.026, p value = 0.599). As compared, at the end of the treatment, at 1st, 3rd and 6th months follow up, grades of skin reactions, mucositis and dysphagia reduced from 2 to 1 and later 1 to 0. Conclusions: Hypo-fractionated radiotherapy is a safe modality of treatment with high local control rates, acceptable long term toxicities, favorable voice outcomes and symptomatic relief with added advantage of shorter treatment time which offers better patient compliance. [ABSTRACT FROM AUTHOR]

Background: Head and neck cancers (HNCs) patterns vary worldwide in relation to demographic and environmental factors. Objective: The aim of our study was to investigate the pattern of HNCs in Karbala province of Iraq, compare and identify possible changes with other populations. Methods: A retrospective descriptive study was carried out at Al-Hussein Cancer Center in Karbala, Iraq, on 302 patients diagnosed with HNCs between January 2012 and December 2021 with evaluation of age, gender distribution and sites of cancers. Results: Among total 302 patients, median age was 58 years. Males accounted for a higher proportion of patients, (67.55%) were males and (32.45%) were females, with an M:F ratio of 2.08:1. Larynx was the most affected site among our patients contributing (28.48%) followed by nasopharynx (28.14%), lip & oral cavity (14.57%), salivary glands (11.59%), oropharynx (8.28%), paranasal sinuses (5.30%) and hypopharynx (3.64%). The most frequent site of HNCs in males was larynx, while the most frequent site in females was nasopharynx. Conclusion: This is the first statistical study of HNCs in Karbala province of Iraq. It can be used as basic information to investigate epidemiological characteristics, to evaluate progress in recent years and to develop treatment strategies. [ABSTRACT FROM AUTHOR]

Background: The molecular makeup of a head and neck squamous cell carcinoma (HNSCC) could vary as per the geography and corresponding variability in prevalent etiopathological factors. The objective of this study was to analyze the expression pattern of E-cadherin (E-cad), a transmembrane glycoprotein with tumour suppressor function, in a cohort of HNSCC treated at a tertiary care medical centre in the southern part of India. Material and methods: After obtaining the institutional ethics committee's permission, the expression of E-cad in HNSCC was assessed by using immunohistochemistry on retrospectively collected tumour specimens, obtained by a surgical cohort of cases operated between September 2018 and July 2019. The E-cad expression was then correlated with various clinical and pathological characteristics of HNSCC, retrieved via the medical records of corresponding patients. Results: A total of 60 patients of HNSCC were included, most of whom had lesion in the oral cavity, in an advanced stage. The majority had a strong or moderate expression of E-cad on the surface. On analyzing further, oral cavity tumours had significantly less expression of E-cad compared to laryngeal and hypopharyngeal tumours taken together, and primary tumours had less E-cad expression than recurrent cases. Multivariate analysis with proportional odds regression showed the significant associations of low expression of E-cad expression with the moderate/poor differentiation of tumours and with the extranodal extension. Conclusions: Among the HNSCC, the loss of E-cad expression was mostly associated with primary tumours of the oral cavity, moderate/poorly differentiated tumours, and in those HNSCCs that had an extranodal extension. [ABSTRACT FROM AUTHOR]

Simple Summary: Treatment recommendations for head and neck cancer need to be disseminated worldwide becoming available through societies/authors scientific reports and websites with warning updates. This scoping review identifies and compares the worldwide clinical practice guidelines for treating oral, oropharynx, and larynx cancer. We verified the absence of guidelines in Latin American and Oceanian countries, as well as the inequalities between countries/continents, with a similar pattern of recommendations among low-income countries and in developed ones. Recommendations for surgery, radiotherapy, and chemotherapy may differ according to country/institution access and resources Head and neck cancer (HNC) treatments have been based on single or multimodal therapies with surgery, radiotherapy (RT), chemotherapy, and immunotherapy. However, treatment recommendations among countries may differ due to technological/human resources and usual local practices. This scoping review aims to identify, compare, and map the clinical practice guidelines (CPGs) for treating squamous cell carcinoma (SCC) of the oral cavity, oropharynx, and larynx worldwide. A search strategy on global CPGs for HNC was performed by using five electronic databases and grey literature. CPGs were selected for inclusion using EndNote-20 and Rayyan online software. No language or publication date restrictions were applied. The results were analyzed descriptively considering the most updated CPG version. In total, 25 CPGs covering the head and neck region (10), the larynx (7), the oral cavity (5), and the oropharynx (3), were found in 13 geographical regions, and 19 were developed by medical societies from 1996 to 2023. Surgery and RT remain the main modalities for early-stage HNC, with surgery preferred in low-resource countries, and RT in selected cases, especially in the larynx/oropharynx aiming to achieve a cure with organ preservation. Human papillomavirus infection for oropharyngeal SCC is not tested in some Asian countries and there is still no consensus to treat p16-positive cases differently from p16-negative. Recommendations for larynx preservation vary according to facilities in each country, however, individualized choice is emphasized. Inequality across countries/continents is evident, with a similar pattern of recommendations among developed as well as developing ones. No CPGs were found in Latin America as well as Oceania countries, where the incidence of HNC is high and limitations of access to treatment may be encountered. [ABSTRACT FROM AUTHOR]

Squamous cell carcinoma (SCC) of the vocal cord in stages I or II can be treated with radiotherapy (RT) or transoral CO2 laser microsurgery (TLM), with good oncological results. To study the survival of patients with SCC of the vocal cord in early stages, treated with RT or TLM, in a tertiary hospital. Disease-free survival (DFS), specific survival (SS), and overall survival (OS) were studied in patients diagnosed with stage I and II SCC of the vocal cord, for a span of 10 years of follow-up, based on sociodemographic characteristics of the patient and the primary treatment (TLM or RT). Both treatments achieved good survival rates. However, long-term SS was greater in patients treated with TLM compared to those treated with RT (91.7% vs. 50%, respectively, p =.001). In addition, patients treated with TLM presented a higher OS in the short term than those treated with RT (99.0% vs. 89.1%, respectively. p =.004). Primary treatment with TLM obtained better results than RT in the survival of patients with SCC of the vocal cord in the early stages. [ABSTRACT FROM AUTHOR]

Introduction: For patients with locally advanced laryngeal cancer, two main treatment options are either up-front surgery [total laryngectomy (TL)] followed by postoperative adjuvant radiation therapy (RT) or definitive concurrent chemoradiation (CCRT) with surgery retained as salvage. The objectives were to study the feasibility of CCRT using intensity-modulated radiation therapy (IMRT) in locally advanced laryngeal cancer with respect to response, toxicities, and quality of life (QoL) and comparison with other modality—TL with post-operative RT. Material and Methods: The records of 48 patients with locally advanced laryngeal cancer (T3/T4aN0-2), registered between years 2014 and 2017, treated with IMRT (definitive or adjuvant postoperative IMRT) were analysed from the hospital database. The patients received RT either as definitive CCRT or as adjuvant treatment after TL. RT in all patients was delivered with IMRT-SIB(simultaneous integrated boost) technique and concurrent chemotherapy with weekly cisplatin. The response was assessed at 12 weeks. Toxicities and QoL were assessed and compared between patients receiving definitive CCRT and adjuvant RT. Results: 92·3% patients who received definitive CCRT achieved complete response. Toxicities were of low grade in patients receiving both definitive and adjuvant treatments. All the patients (except two partial responders of CCRT) remained disease-free at the last follow-up. At 2 years of follow-up of each patient—Global QoL, emotional and social functioning were better in definitive CCRT patients. Laryngectomy patients had more dyspnoea, insomnia and financial difficulties. Although the problems of dry mouth, sticky saliva and swallowing were comparable, laryngectomy patients faced more problems with speech, senses, social eating, social contact and cough. Conclusions: Definitive CCRT using IMRT-SIB with weekly cisplatin is a feasible option for patients of locally advanced laryngeal cancer with acceptable response rate. IMRT yields better toxicity outcomes with sparing of organs at risk. CCRT patients have better QoL than laryngectomy patients in several parameters. [ABSTRACT FROM AUTHOR]

The article informs about a study on subglottic squamous cell carcinoma. Topics discussed include the clinical course of a complete national cohort of consecutive patients diagnosed with subglottic; laryngectomy-free survival (LFS), an event was defined as death or laryngectomy regardless of cause; and the effect of modern-RT compared to old-RT was adjusted for age, disease stage and differentiation.

Primary laryngeal carcinosarcoma is a rare type of malignancies, and the standard therapeutic protocol for its treatment has yet to be established. This retrospective study analyzed the clinical and pathological characteristics, risk factors, treatment options, and prognosis of 13 patients with primary laryngeal carcinosarcomas. This case series included 11 males and 2 females with an age range from 32 to 78 years at diagnosis. The initial clinical symptoms included hoarseness, dyspnea, and foreign body sensation in the throat. The primary tumor sites were at the glottis, supraglottis, and larynx. All these patients were active or passive smokers, and more than half of them were alcohol addictive. The surgical treatment for laryngeal carcinosarcomas included CO2 laser surgery in seven cases, partial laryngectomy and neck dissection in three cases, and total laryngectomy and neck dissection in three cases. Among them, seven cases received postoperative radiotherapy. After follow-up with a mean of 31.15-month, four cases died. Primary laryngeal carcinosarcoma is a rare but more aggressive malignancy. Contralateral lymph node metastasis can occur at the early stage of this disease. A treatment combining surgery and postoperative radiotherapy is strongly recommended. [ABSTRACT FROM AUTHOR]

The aim of study was to investigate the expression of the proliferation factor Ki-67 and its relationship with histological grade, cancer stage, and treatment outcome in squamous cell carcinoma of the larynx. Samples from 78 patients with laryngeal cancer were analysed retrospectively. Paraffin sections of tumors were immunohistochemically stained for Ki-67 expression. The patients were divided in two groups according to the proliferative factor values (a low Ki-67 index group - Ki-67≤34 and high Ki-67 index group-Ki-67 >34). Statistical analysis of the data shows significant correlation among histological tumor grade and the value of the Ki-67 proliferative index. There was no correlation between tumoral Ki-67 expression and diagnosis, stage of the disease, or treatment outcome. In conclusion, Ki-67 expression in laryngeal cancer is not the most reliable marker for making precise diagnosis and predicting the clinical course. [ABSTRACT FROM AUTHOR]

Background: Laryngeal squamous cell carcinoma (LSCC) is rare in the young. Objectives: We characterized the clinical behavior of LSCC and assessed the presentation of second primary tumors (SPCs) in this patient population. Materials and methods: Data from the Finnish Cancer Registry (FCR) were used to identify an epidemiological series of LSCC patients diagnosed at the age of 40 years or under, during 1953-2012 in Finland. Data regarding primary treatment, survival, and SPCs were available. To further characterize the comorbidity and lifestyle factors of young patients with LSCC, institutional data were collected of patients treated at the Helsinki University Hospital during 1967-2012. Results: We identified 151 patients, with a mean follow-up of 252 months. The 10-year overall survival (OS) was 75% and the disease-specific survival was 84%. SPCs were diagnosed in 26% (n = 39), with a median delay of 28 years. Of the 35 patients in the institutional series from Helsinki, 22 (63%) were current or former smokers. LSCC recurred in 28% of patients. Conclusions and Significance: The delay to SPCs in young patients was significantly longer compared with the general LSCC population. As factors underlying this phenomenon cannot be identified by this retrospective study, further studies are warranted. [ABSTRACT FROM AUTHOR]

Head and neck cancers are the 6th most common cancer type in human malignant tumors and treated with chemoradiotherapy and surgery. Chemotherapy during these treatment modalities leads to damage of intestinal epithelial barriers and results in translocation of intestinal bacteria in bloodstream through invasion in these damaged regions. In this report, we report two cases of hypopharyngeal cancer patients, both of whom received chemotherapy before surgery. The patients demonstrated repeated sepsis before and after surgery, supporting translocation of intestinal bacteria. Proper continuous probiotic use prevented proliferation and intestinal bacterial translocation. Hypothesis of bacterial translocation and prevention by probiotics are discussed. [ABSTRACT FROM AUTHOR]

Objectives: To assess the feasibility and efficacy of intensity-modulated radiation implemented with helical tomotherapy image-guided with daily megavoltage computed tomography for head and neck cancer. Methods: Between May 2010 and May 2013, 72 patients were treated with curative intent. The median age was 64 years, with 57% undergoing definitive and 43% postoperative radiotherapy. Primary tumour sites were oral cavity (21%), oropharynx (26%), hypopharynx (20%), larynx (22%), and others (11%). Staging included 4% stage I, 15% II, 26% III, 48% IVa, and 7% IVb. Radiotherapy was combined with chemotherapy in 64%. Primary endpoint was locoregional control, and secondary endpoints survival and toxicity. Results: Median follow-up was 20 months, with 11 locoregional recurrences. Three-year disease-free survival was 58% and overall survival 57%. In the multivariate analysis, age under 64 years, no extracapsular extension, postoperative radiotherapy, induction chemotherapy, and non-oral cavity tumour were significant favourable prognostic factors for disease-free-survival. The overall incidence of acute grade ≥3 toxicities were mucositis 32%, pain 11%, xerostomia 7%, dysphagia 53%, radiodermatitis 44%, and osteonecrosis 1%. Late grade ≥3 toxicities were fibrosis 6%, dysphagia 21%, fistula 1%, and skin necrosis 1%. Conclusions: Intensity-modulated radiation with helical tomotherapy achieved respectable locoregional control and overall survival, with acceptable toxicity, in head and neck cancer patients. [ABSTRACT FROM AUTHOR]

Objectives: To assess five-year local control and ultimate local control rates of patients treated for locally advanced T3–4 glottic carcinoma with surgery only, radiotherapy only, or surgery plus radiotherapy. Cancer-specific survival, overall survival and rates of malignancy development were also assessed. Methods: A retrospective review was conducted on patients from 1967 to 2015, with analysis of local control, ultimate local control, overall survival and cancer-specific survival performed using Kaplan–Meier and Cox regression. Results: Of 169 eligible patients, the majority (59 per cent) were treated with surgery plus radiotherapy, with laryngectomy being the most common surgical procedure. Local control and ultimate local control rates were higher with surgery only (94.1 per cent) and surgery plus radiotherapy (87.9 and 86.8 per cent respectively), compared to radiotherapy only (46.8 and 52.4 per cent) (both p < 0.001). Cancer-specific survival, overall survival and malignancy development did not differ between groups. Conclusion: Surgery, with or without radiotherapy, offers significantly higher five-year local control and ultimate local control for patients with advanced glottic carcinoma, compared to radiotherapy only. [ABSTRACT FROM AUTHOR]

Objectives: Unlike glottic cancer, supraglottic cancer often presents with neck metastases. This different might be attributable to the location of the primary lesion. This study aimed to clarify the relationships between the sublocation of T1-2 supraglottic cancer, human papillomavirus (HPV) infection, neck metastasis, and prognosis of supraglottic cancer.Methods: This retrospective clinical study investigated 55 Japanese patients with T1-2 supraglottic cancer treated between 1994 and 2015.Results: Of 55 patients with T1-2 supraglottic cancer, neck metastasis was present at initial diagnosis in 14 patients (25.5%). Presence of neck metastasis was the only factor associated with worse prognosis of T1-2 supraglottic cancer (p=0.004). In multivariate analysis, age <70years (p=0.033) and sublocation of the primary lesion in the superior epilaryngeal portion (p=0.017) were significantly associated with presence of neck metastasis in multivariate analysis. Twelve (27.9%) of 43 patients showed positive results for human papillomavirus infection. However, human papillomavirus infection was not associated with prognosis, presence of neck metastasis, or primary lesion sublocation in T1-2 supraglottic cancer.Conclusion: Relatively young patients with supraglottic cancer at the superior epilaryngeal portion are more likely to show neck metastasis. Human papillomavirus infection was not associated with frequency of neck metastasis. [ABSTRACT FROM AUTHOR]

Introduction: The concept of neck dissection (ND) in the management armamentarium of head and neck squamous cell carcinoma has evolved throughout the years. Nowadays, ND becomes more functional.Methodology: A retrospective study of 865 patients was performed at Netherlands Cancer Institute-Antoni Van Leeuwenhoek Hospital to investigate the feasibility of selective ND (SND). All patients with squamous cell carcinoma of the pharynx and larynx who received primary radiation and underwent salvage ND were included in the study.Result: A total of 29 NDs were analyzed. In 17 neck sides, viable metastases were found (58%), whereas in the other 12 specimens there were no viable metastases. In 16 of the 17 necks (94%), the metastases were located either in level II, III, or IV or in a combination of these 3 levels. Level V was involved in only 1 case (6%).Conclusion: It is well justified to perform a salvage SND (levels II, III, and IV) for pharyngeal and laryngeal carcinoma after primary radiation. In carefully selected cases of supraglottic and oropharyngeal carcinoma, a superselective ND also appears as an efficient option. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study is to investigate the associations between patient activation and total costs in cancer patients treated with total laryngectomy (TL).Methods: All members of the Dutch Patients' Association for Laryngectomees were asked to participate in this cross-sectional study. TL patients who wanted to participate were asked to complete a survey. Costs were measured using the medical consumption and productivity cost questionnaire and patient activation using the Patient Activation Measure (PAM). Sociodemographic and clinical characteristics were self-reported, and health status measured using the EQ-5D. The difference in total costs from a healthcare and societal perspective among four groups with different PAM levels were compared using (multiple) regression analyses (5000 bootstrap replications).Results: In total, 248 TL patients participated. Patients with a higher (better) PAM (levels 2, 3, and 4) had a probability of 70, 80, and 93% that total costs from a healthcare perspective were lower than in patients with the lowest PAM level (difference €-375 to €-936). From a societal perspective, this was 73, 87, and 82% (difference €-468 to €-719). After adjustment for time since TL, education, and sex, the probability that total costs were lower in patients with a higher PAM level compared to patients with the lowest PAM level changed to 62-91% (healthcare) and 63-92% (societal). After additional adjustment for health status, the probability to be less costly changed to 35-71% (healthcare) and 31-48% (societal).Conclusions: A better patient activation is likely to be associated with lower total costs from a healthcare and societal perspective. [ABSTRACT FROM AUTHOR]

Background: The optimal treatment for T3 glottic cancers continues to be debated. Organ preservation has become the standard of care, but not all tumors respond equally. The purpose of this was to investigate the long-term survival outcomes of organ preservation protocols based on tumor volume.Methods: A retrospective review of prospectively collected data from 1966 to 2016 was performed. Patients with T3 vocal cord cancer treated with radiation therapy (RT) at the University of Florida were included. Local control rates as well as survival rates were determined with a Kaplan Meier and Cox regression analysis. Survival was analyzed as a function of tumor volume and an optimal cut point was determined.Results: 107/234 patients were included. 79% received RT and 21% chemo-RT. 5-year local control was 61.5% and 5-year disease specific survival was 79.3%. Tumor volume was a significant predictor of survival (p = 0.007). An optimal cut point for tumor volume was 2.5 cc. Patients with tumor volumes ≥2.5 cc had significantly worse (p < 0.05) tumor control rates (100% vs. 70.4%).Conclusion: Tumor volume is a significant predictor of survival outcomes in T3 vocal cord cancers, but will need external validation. Tumors <2.5 cc have favorable outcomes. Those with higher volume tumors should be counselled appropriately and be considered for primary surgical management. [ABSTRACT FROM AUTHOR]

The article discusses the surgical treatment of head and neck cancers which requires an ever increasing resources for in-patients in hospitals. It states that surgery followed by radiotherapy and chemotherapy in various combinations offers optimal prospects of survival and whenever possible, to preserve organs even in advanced cases.

Objective: The aim of this study was to investigate the effect of the Akt inhibitor Src-homology 5 (SH-5) on the proliferation and apoptosis of laryngeal squamous cell carcinoma cells (LSCC; Hep-2 cells) and to elucidate the possible mechanisms of such effects.Materials and Methods: Hep-2 cells were treated with different concentrations of the Akt inhibitor SH-5. The inhibitory effect of SH-5 on cell proliferation was examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, whereas apoptosis was detected by flow cytometric based on Annexin V/propidium iodide (PI) staining. In addition, the expression level of Akt protein was evaluated by Western blot analysis.Results: MTT assay results revealed that SH-5 inhibited the proliferation of Hep-2 cells, with its greatest effect being observed at 2 μM. Apoptosis of Hep-2 cells increased following treatment with SH-5. Treatment of Hep-2 cells with SH-5 decreased the expression of Akt, and this effect was statistically significantly when compared with that in controls (P < 0.05).Conclusion: SH-5 inhibited proliferation and induced apoptosis in the LSCC cell line Hep-2. These effects may be caused by inhibition of the phosphoinositide 3-kinase-Akt signaling pathway. We believe that our data will provide useful insights into LSCC target treatment and future researchn. [ABSTRACT FROM AUTHOR]

Objectives: To examine the ability of comorbidity indices to predict the prognosis of laryngopharyngeal cancer and their association with treatment modalities. Methods: This retrospective study included 198 patients with laryngeal, hypopharyngeal, and oropharyngeal cancers. The effect of comorbidity indices on overall survival between surgery and (chemo)- radiation therapy ((C)RT) groups was analyzed. The cumulative incidence rates for cancer mortality and other mortalities according to the age-adjusted Charlson Comorbidity Index (ACCI) and Charlson Comorbidity Index (CCI) were compared. Results: Univariate survival analyses showed a significant association between the ACCI and overall survival in the (C)RT group, but not in the surgery group. The association between the CCI and overall survival was not significant in either group. In multivariate analyses, a high ACCI score was an independent prognostic factor in the (C)RT group (HR 2.89, 95% confidence interval (CI) 1.28-6.49), but not in the surgery group (HR 1.39, 95%CI 0.27-5.43). The higher ACCI group had increased mortality from other causes compared with the lower ACCI group (5-year cumulative incidence, 8.5% and 17.8%, respectively, p=.003). Conclusion: The ACCI was a better prognostic factor than the CCI. Surgery may be more beneficial than radiation for patients with a high ACCI. [ABSTRACT FROM AUTHOR]

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Background: In patients with head and neck cancer, the management of second primary cancer (SPC) is particularly important for improving survival because of its high incidence and associated mortality. We evaluated the impact of combination chemotherapy on survival and SPC.Method: We retrospectively analyzed data from 49 patients treated with definitive radiation therapy (RT) for T2N0M0 laryngeal squamous cell carcinoma between 2003 and 2011. Among them, 22 patients received combined modality treatment with radiotherapy and S-1 (RT+CT group).Results: The median follow-up period was 71months (32-111months). A significant difference in overall survival (OS, P<0.01) was observed between the RT+CT group (n=22) and the RT alone group (n=27) though no significant differences were observed in local control and disease specific survival. Univariate analyses showed that an older age (P<0.05) and a higher grade (P<0.05) were associated with OS. Multivariate analysis identified chemotherapy as the most significant predictor of survival (OR, 0.056; 95% CI, 0.008-0.353, P<0.01). A significantly lower incidence of distant metastasis (DM)+SPC (5-year incidence: 5% vs. 19%, P<0.05) and fewer deaths from these causes (1 vs. 8: P<0.05) were observed in the RT+CT group. Multivariate analysis showed that chemotherapy was the most significant factor for the incidence of DM+SPC (OR, 0.074; 95% CI, 0.0065-0.84; P<0.05).Conclusion: The findings of this study suggest the possibility that combined modality treatment with radiotherapy and S-1 improve survival by preventing distant metastasis and second primary cancer. [ABSTRACT FROM AUTHOR]

Introduction: It is estimated that around 10% of all head and neck cancer patients in India are aged over 70 years. Elderly patients are often subjected to palliative or inadequate treatment for head and neck cancers in spite of being candidates for curative intent therapy. In this study we evaluated our use of radical radiotherapy in carcinoma larynx for patients over seventy years of age to determine morbidity, likelihood of completing therapy, functional and oncological outcomes.Materials and Methods: 132 patients of squamous cell carcinoma of the larynx treated between 2005-2015 at Amrita Institute of Medical Sciences, Kochi who were seventy years of age or older were included. The endpoint for analysis was overall survival. Survival curves were generated using Kaplan Meier method and univariable analysis was performed using log rank test.Results: The median age of patients was 77 years (range 70-102). All patients (100%) completed radiotherapy with 6 (5%) requiring treatment breaks. All patients had at least minor (grade I/II) toxicities. Grade III toxicities were seen in 10 (8%) of patients. No grade IV reactions or treatment related deaths occurred. When a univariate analysis was performed for determinants of major toxicities with age range, performance status, smoking, number of co-morbidities or TNM stage, no determinants were statistically significant. 2-year disease free survival for stage I, II, III and IV was 100%, 98%, 80% and 64% respectively, and the 2-year overall survival for all four stages was 100%.Conclusion: Patients over seventy years tolerate radical radiotherapy for treatment of laryngeal cancer. In spite of minor toxicities, all patients completed treatment and had good oncological outcomes. Patients with stage III/IV unfit for concomitant chemotherapy administration treated with radiotherapy alone had a good disease free survival. Curative intent therapy should not be withheld from elderly patients on the basis of age. [ABSTRACT FROM AUTHOR]

Objective: Thrombocytosis is commonly observed in patients with solid tumors. This study aimed to evaluate the prognostic role of circulating pretreatment platelet count in a large series of patients with head and neck squamous cell carcinoma (HNSCC).Methods: We retrospectively studied 824 patients with HNSCC treated at a single institution from 2000 to 2012. Disease-specific survival and local, regional, and distant recurrence-free survival were analyzed according to the distribution of the platelet count.Results: By defining the platelet count 250.05×109/L as a cut-off point with the best predictive capacity, we classified the patients into two groups: those with a high platelet count (n=378, 45.9%), and those with a low platelet count (n=446, 54.1%). On univariate analysis, there were significant differences in disease-specific survival depending on pretreatment platelet count (P=0.001). The 5-year specific survival rates were 74.1% (CI 95%: 69.8-78.4%) and 61.6% (CI 95%: 56.4-66.8%) for patients with a low and high platelet count, respectively. According to the results of a multivariate analysis, patients with a high count of platelets had a tendency to a lower disease-specific survival, but the hazard ratio did not reach statistically significant differences (HR 1.24, CI 95%: 0.97-1.61, P=0.085).Conclusion: Platelet count was significantly associated with survival in univariate analysis. However, in a multivariate analysis it lost its prognostic capacity, limiting its utility as a prognostic marker in patients with HNSCC. Considering separately each primary tumor location, patients with hypopharyngeal cancer and a high platelet count had a significant decrease of disease-specific survival. [ABSTRACT FROM AUTHOR]

Background: Single-modality radiotherapy is considered a standard-of-care option for certain stage III, T1-2N1 head and neck squamous cell carcinomas (HNSCCs). The role of concomitant chemoradiation is not well established because there have been no studies comparing chemoradiation with radiation alone in this population.Methods: This study analyzed patients in the National Cancer Data Base with cT1-2N1M0 invasive squamous cell carcinomas of the oropharynx, larynx, and hypopharynx who were diagnosed between 2004 and 2012 and were undergoing definitive radiation. Patients who were undergoing surgery before radiation with unknown follow-up or for whom either the receipt or timing of chemotherapy was unknown were excluded.Results: In all, 5030 patients with T1-2N1 oropharyngeal, laryngeal, or hypopharyngeal cancer were included. The median follow-up was 56.8 months (95% confidence interval [CI], 55.7-58.6 months). Overall, 68% of the patients received concomitant chemoradiation (CCRT). The use of CCRT significantly increased during the time period of this study from 53% in 2004 to 78% in 2012 (P < .001). CCRT was associated with improved overall survival (OS) in comparison with radiation alone in a multivariate analysis (hazard ratio [HR], 0.80; 95% CI, 0.72-0.88; P < .001). In propensity score-adjusted analyses, CCRT remained significantly associated with improved OS, with 5-year OS rates of 63.5% (95% CI, 60.7%-66.2%) and 55.6% (95% CI, 52.7%-58.4%; P < .001) with CCRT and radiation alone, respectively. Subgroup analyses showed a benefit across the majority of subgroups, including patients with oropharyngeal cancer (HR, 0.74; 95% CI, 0.65-0.85; P < .001).Conclusions: Concomitant chemoradiation is associated with improved survival for patients with T1-2N1 HNSCC. Prospective trials in this population should be pursued. Cancer 2017;123:1555-1565. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the efficacy and safety of induction chemotherapy (IC) followed by bioradiotherapy (BRT) to achieve functional larynx preservation in the setting of locally advanced head and neck tumors.Methods and Materials: This was a phase 2, open-label, multicenter study of patients with stage III and IVA laryngeal carcinoma who were candidates for total laryngectomy. The primary endpoint was the rate of survival with functional larynx (SFL) at 3 years, with a critical value to consider the study positive of SFL >59%. Patients received 3 cycles of IC with TPF (docetaxel, cisplatin, and 5-fluorouracil), and those who responded received conventional BRT with cetuximab. In patients with residual nodal disease after BRT, neck dissection was planned 2 months after BRT. Patients who did not respond to IC underwent total laryngectomy plus neck dissection and radiation therapy.Results: A total of 93 patients started TPF. Responses to IC on larynx target lesion were as follows: 37 patients (40%) showed a complete response; 38 patients (41%) showed a partial response; 8 patients (9%) showed stabilization; 2 patients (2%) showed progressive disease, and 8 patients (9%) were not evaluated (2 deaths, 5 adverse events, and 1 lost to follow-up). Seventy-three patients (78%) received BRT: 72 as per protocol, but 1 with only stable disease. Median follow-up was 53.7 months. Three-year actuarial rates were as follows: SFL: 70% (95% confidence interval [CI] 60%-79%); laryngectomy-free survival: 72% (95% CI 61%-81%); overall survival: 78% (95% CI: 63%-82%). The acute toxicity observed during both IC and BRT was as expected, with only 1 toxicity-related death (local bleeding) during BRT.Conclusions: According to this protocol, the SFL rate was clearly higher than the critical value, with acceptable levels of toxicity. The use of cetuximab added to radiation therapy in patients with stage III and IVA laryngeal cancer who respond to TPF could improve functional larynx preservation. A phase 3 trial is warranted. [ABSTRACT FROM AUTHOR]

Background: To assess the efficacy of concurrent chemoradiotherapy (CCRT) with daily low-dose cisplatin (CDDP) plus weekly docetaxel (DTX) for patients with T2N0 glottic cancer.Methods: Between January 2004 and December 2013, 62 treatment-naive patients with histologically proven T2N0 glottic cancer were treated with concurrent chemoradiotherapy. Radiation therapy (RT; 2 Gy daily fractions up to a total dose of 66 Gy) was administered in combination with daily low-dose CDDP (6 mg/m2, five times a week), plus weekly DTX (10 mg/m2) for up to 4 weeks from the commencement of RT.Results: Median duration of follow-up was 70 months. The actuarial 3-year and 5-year overall survival rates were 95% and 93%. The 3-year and 5-year cause-specific survival rates were both 100%. The actuarial 3-year and 5-year local control rates were 94% and 94%, respectively. Hematologic toxicity (neutoropenia of severity ≥ Grade 3) was observed in 8% of the patients, and non-hematologic toxicity (radiation mucositis of severity ≥ Grade 3) developed in one patient (2%). Radiation dermatitis of severity ≥ Grade 3 and laryngeal necrosis developed in one patient.Conclusion: CCRT with weekly DTX and low-dose CDDP appears to be a practical and safe modality and is expected to improve local control.Trial Registration: UMIN000025046 . Registered 1 October 2015, retrospectively registered. [ABSTRACT FROM AUTHOR]

Previous studies have found that miR-375 and miR-205 were significantly dysregulated in laryngeal squamous cell carcinoma, which contributed to the invasion and migration of LSCC. However, the mechanisms of miR-375 and miR-205 regulating the invasion and migration of LSCC remain unknown. qRT-PCR was performed in 40 pairs of tissue samples to investigate the expression of miR-375 and miR-205 in LSCC and paracarcinoma tissues. To investigate whether or not miR-375 and miR-205 regulated the invasion and migration of LSCC synergistically via AKT-mediated epithelial-mesenchymal transition, miR-375 mimic and miR-205 inhibitor were transfected into SNU899 cells and miR-375 inhibitor and miR-205 mimic were transfected into SNU899 cells, respectively, with or without AKT inhibitor. Then the expressions of miR-375 and miR-205 were validated by qRT-PCR, cell migration and invasion were determined by wound healing assay and transwell invasive assay, and western blot analysis was performed to detect the expression of related proteins. Our results showed that miR-375 and miR-205 regulated the invasion and migration of LSCC via AKT-mediated EMT synergistically. In conclusion, our findings provided not only new information about the molecular mechanism of miRNAs regulating invasion and migration of LSCC, but also a theoretical principle for potential targeting therapy of laryngeal squamous carcinoma. [ABSTRACT FROM AUTHOR]

Purpose: We assessed the presence of salivary cytokines, their modulation during chemoradiation therapy (CTRT), and their association with oral mucositis severity in patients with head and neck cancer (HNC).Methods and Materials: The present prospective observational study enrolled 55 patients with locally advanced HNC requiring CTRT. We also studied 10 healthy volunteers and 10 patients with other cancers. The salivary levels of 13 cytokines were analyzed. We constructed a cytokine predictive score of oral mucositis severity.Results: The baseline salivary cytokine levels were not associated with the severity of treatment-induced oral mucositis. The cytokine levels overall increased during treatment, especially in patients with worse mucositis. In particular, on univariable analysis, an increase of interleukin (IL)-1β (area under the curve [AUC] 0.733; P=.009), IL-6 (AUC 0.746; P=.005), and tumor necrosis factor-α (AUC 0.710; P=.005) at the third week of treatment was significantly associated with the development of severe oral mucositis. On multivariable analysis, the predictive score based on the IL-1β and IL-6 changes from baseline to week 3 was an early strong predictor of higher grade oral mucositis.Conclusions: The treatment of HNC patients with concurrent CTRT induces a significant increase in the salivary levels of IL-1β, IL-6, and tumor necrosis factor-α, all positively associated with the severity of mucosal toxicity. A greater increase of IL-1β and IL-6 3 weeks after treatment initiation is predictive of worse oral mucositis, representing a potential tool for the early identification of patients at risk. [ABSTRACT FROM AUTHOR]

Aim The aim is to evaluate the impact of cisplatin dose modification on outcomes of human papillomavirus (HPV)-related (HPV+) and HPV-unrelated (HPV−) locally advanced head and neck cancer (LAHNC) treated with chemoradiotherapy (CRT). Patients and methods A pooled analysis was conducted of stage III/IV oropharyngeal cancer (OPC), carcinoma of unknown primary (CUP) and laryngo-hypopharyngeal cancer (LHC) patients treated with single-agent cisplatin CRT in 2000–2012 from two tertiary academic cancer centres. HPV status was determined by p16 staining and/or in situ hybridisation. LHC was assumed to be HPV−. Unknown HPV status OPC/CUPs were excluded. Overall survival (OS) was calculated. Multivariable analysis (MVA) evaluated the impact of cisplatin dose intensity on survival for HPV+ and HPV− cohorts separately. Results A total of 404 HPV+ and 255 HPV− LAHNC (481 OPC, 18 CUP, 160 LHC) patients were included. Median follow-up was 4.3 (0.5–11.9) years. Three-year OS for cisplatin <200, =200, and >200 mg/m 2 subgroups were 52%, 60%, and 72% ( P = 0.001) for the HPV− and 91%, 90%, and 91% ( P = 0.30) for the HPV+ patients. MVA confirmed a survival benefit with cisplatin >200 mg/m 2 for the HPV− (hazard ratio [HR] 0.5, 95% confidence interval [CI]: 0.3–0.7, P < 0.001) but not for HPV+ (HR 0.6, 95% CI: 0.4–1.1, P = 0.104). There was a superior OS trend in the HPV+ T4 or N3 high-risk subset ( N = 107) with cisplatin >200 mg/m 2 (HR 0.5, 95% CI: 0.2–1.1, P = 0.07). Conclusions A survival benefit of cisplatin dose >200 mg/m 2 is evident for HPV− LAHNC patients, but not for HPV+ cohort overall, although the T4 or N3 subset may benefit from a higher cumulative cisplatin dose. [ABSTRACT FROM AUTHOR]

Background: The treatment of patients with advanced stage laryngeal cancer includes surgery or concurrent chemoradiation (CRT). Although CRT has become more common in recent years, to the authors' knowledge, the effectiveness of complete CRT in improving survival over surgery has not been studied.Methods: The authors examined patients in the Surveillance, Epidemiology, and End Results (SEER)-Medicare claims-linked data set with locoregional laryngeal cancer who were diagnosed between 1997 and 2007. Multivariate Cox proportional hazard analyses were conducted to compare overall and cause-specific 5-year survival rates between treatment modalities, adjusting for patient sociodemographic and clinical characteristics. A propensity score-matched subcohort also was used to compare survival.Results: Of the 3212 patients in the study cohort, 42% underwent surgery and 18% underwent CRT. Only approximately one-quarter of patients who were treated with CRT completed the courses. In adjusted analyses, the authors were unable to reject the null hypothesis of no difference in 5-year all-cause or cause-specific mortality risk between patients treated with surgery and patients undergoing complete CRT (hazards ratio, 1.25 [95% confidence interval, 0.91-1.71; P = .16] and hazard ratio, 1.41 [95% confidence interval, 0.9-2.2; P = .14], respectively). Older age, not currently married, Medicaid eligibility, and prior cancer history were found to be associated with a higher risk of mortality (P<.05).Conclusions: Patients with advanced laryngeal cancer who underwent complete CRT were found to have overall and cause-specific survival rates similar to those of patients undergoing surgery. However, a substantial percentage of patients who initiated CRT did not complete the course. Although CRT provides organ preservation, the benefits and trade-offs of CRT and total laryngectomy should be discussed fully with patients. The importance of completing the full course of CRT should be emphasized. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2845-2856. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to evaluate the functional and oncological outcomes of patients treated for T3 laryngeal squamous cell carcinoma. Specifically comparing transoral laser microsurgery and radiotherapy/ chemoradiotherapy treatment modalities. Method: A retrospective review of patients treated for T3 laryngeal SCC between 2002 and 2010 was undertaken. Results: Forty-nine patients were included. 15 cases were glottic, (9 treated with TLM, 6 with RT/CRT), 33 supraglottic (6 treated with TLM, 27 with RT/CRT) and 1 subglottic subsite (treated with RT/CRT). There was no statistical difference between treatment groups for 24 month locoregional control (72.3 %), overall survival (glottis 86.7 %, supraglottic 70. 4 %) and disease specific survival (glottic 93.3 % and supraglottic 74.1 %). Overall laryngeal preservation (84.9 %) was also similar in both groups. Conclusion: Our institution is expanding the application of TLM to selected patients with T3 laryngeal carcinoma. Oncological outcomes have not been jeopardized by this approach and the treatment is well tolerated by patients with few complications. [ABSTRACT FROM AUTHOR]

Conclusion The melanoma-associated antigens A1, -A9, -A11 (MAGE-A1, -A9, -A11) are relatively tumor-specific in laryngeal squamous cell carcinoma (LSCC), and could be ideal antigens for LSCC immunotherapy. In addition, MAGE-A9 probably is a poor prognostic marker for LSCC patients. Objective The MAGE-A family belongs to Cancer/testis antigens (CTA). However, the expression pattern of MAGE-A1, MAGE-A9, and MAGE-A11 in LSCC is still unclear. This study aims to evaluate the expression and possible prognostic role of MAGE-A1, MAGE-A9, and MAGE-A11 in LSCC patients. Methods The expression of MAGE-A1, MAGE-A9, and MAGE-A11 in LSCC specimens was investigated by immunohistochemistry, and the association of their expression and the clinical parameters and the survival of LSCC patients were analyzed by chi-square test, Kaplan-Meier survival and Cox regression analysis. Results The expression rates of MAGE-A1, MAGE-A9, and MAGE-A11 in LSCC were 54.7%, 46.2%, and 51.9%, respectively. The expression of MAGE-A1, MAGE-A9, and MAGE-A11 in LSCC was correlated with clinical stage, lymph node metastasis, and tumor size. The overall survival of LSCC patients with positive MAGE-A1, MAGE-A9, or MAGE-A11 expression was lower than the patients without MAGE-A1, MAGE-A9, or MAGE-A11 expression. Cox's multivariable analysis showed that MAGE-A9 expression was an independently poor prognostic factor for LSCC patients. [ABSTRACT FROM AUTHOR]

Background and Aim: Stapling devices are used for pharyngeal closure after laryngectomy for the past few decades although it has not gained wide acceptance. This study is aimed at evaluating the role of stapler in pharyngeal closure after laryngectomy.Methods: Thirty consecutive patients who underwent stapled laryngectomy at our institution from October 2004 to February 2008 were evaluated retrospectively. Linear stapler (Proximate TX 60; Ethicon Inc.) was used for closure of neopharynx.Results: There were 28 males and 2 females with mean age of 54.5 years (54.5 ± 11.2). Nineteen of these patients (63.3%) had salvage laryngectomy and two patients (6.7%) had laryngectomy for a second primary tumor. Twenty-eight patients had total laryngectomy (TL), whereas two had extended TL. Eight patients had salivary leak (26.7%). Of these, 6 (75%) had prior radiation. All salivary leaks except one were managed conservatively. Follow-up ranged from 7 to 54 months (median: 21 months). Seven patients (23.3%) developed recurrence, six at the stoma, of which 5 (83.3%) had initial extension of disease to the subglottis. Four-year disease-free survival was 54.4%.Conclusion: Pharyngeal closure by linear stapler is an efficient and safe method of fashioning the neopharynx after laryngectomy with no added risk of occurrence of pharyngocutaneous fistula in primary and salvage laryngectomies. [ABSTRACT FROM AUTHOR]

Squamous cell carcinoma in children and adolescents is extremely rare. Less than 80 case reports have been reported in the literature since it was first reported in 1868. In this article, we intend to report a case where a 16-year-old girl who presented with complaints of change in voice was found to have early-stage vocal cord carcinoma on evaluation. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Conclusion: Photodynamic therapy (PDT) is a viable and safe option for early laryngeal cancer that would be less suitably treated with radiation or trans-oral laser surgery (TLS). The cure rates with PDT appear to be comparable to those of conventional therapy, and the voice outcomes are also comparable. In the case of many sarcomas, PDT appears to be an organ- and function-sparing therapy, although it is more costly than other treatments. Objectives: The aim of this study was to show the results of PDT when it is used as a primary treatment of early laryngeal cancer. Methods: We studied the results of PDT when used as a primary treatment. We looked at survival, effect on tumor, side effects, voice, and costs. Results: The follow-up period was a median of 59 months. Nine of 10 patients were cured of their laryngeal cancer. PDT alone cured seven patients. All four of the sarcomas were cured using temoporfin. Two of three tumors that involved the anterior commissure were cured using only interstitial illumination with PDT. No serious side effects were noted. The patient's voices were improved after treatment in 5 of 10 cases, and none had a worsened voice. [ABSTRACT FROM AUTHOR]

Conclusion: The epidermal growth factor receptor (EGFR) mutation is rare in patients with laryngeal squamous cell carcinoma (LSCC) in China. Objective: To determine the incidence of EGFR mutations in patients with LSCC who underwent surgical resection in mainland China. Methods: xTAG technology was used to detect the EGFR exon 19, exon 20, and exon 21 mutations in 132 patients with LSCC who underwent surgical treatment in our hospital from 2010 to 2013. Results: Of the 132 LSCC specimens examined, only 1 specimen was found to be positive for EGFR exon 20 mutation (0.76%). The mutation was p.T790M in exon 20. Two LSCC specimens were positive for EGFR exon 21 mutation (1.52%). The mutation was p.L858R in exon 21. None of the samples was found to be positive for EGFR exon 19 mutation. [ABSTRACT FROM AUTHOR]

Background Management of advanced laryngeal cancer is complex and ideal strategy is yet to be defined. This study evaluates the experience of a single head and neck oncologic centre in the management of T4 laryngeal cancer. Methods Retrospective assessment of cases primarily treated for T4a squamous cell carcinoma of the larynx, between 1980 and 2007, at a tertiary referral center. Results A total of 384 cases were studied. Five-year disease specific survival was 56.2% and local control 87.4%. Regional and distal control estimates were 90.3% and 88.3% respectively. Prognosis was significantly superior for cases treated with primary surgery compared to cases solely managed with non-surgical modalities. Positive surgical margins and regional disease worsened prognosis. Conclusion This study suggests that primary surgery remains a key element in the treatment of advanced laryngeal cancer. The need for well-designed, prospective, randomised studies in order to further evaluate the remaining role of primary surgery in the modern management of locally advanced laryngeal lesions is emphasized. [ABSTRACT FROM AUTHOR]

Osteoradionecrosis (ORN) is a known entity in patients with head and neck malignancy treated by radiotherapy. Involvement of mandible (0.8-37%) and maxilla (2-11%) is quiet common but upper cervical spine involvement is rare. One needs to have a high index of suspicion for the diagnosis of ORN after radiotherapy in the head and neck region. It may mimic either metastasis or an infection and needs histopathology to make definitive diagnosis. We reported the successful treatment of a patient with ORN involving upper cervical spine by posterior decompression and stabilisation. In addition, a new technique of reaching the odontoid process from posterior aspect for biopsy has been described. [ABSTRACT FROM AUTHOR]

Background. Synovial sarcoma is common in the extremities. Our search revealed only 17 cases of synovial sarcoma of the larynx in the English-language literature. Case report. We report an additional case of a 37-year-old man with primary laryngeal synovial sarcoma who underwent positron emission tomography/computed tomography (PET/CT) following the treatment. Although the patient received comprehensive therapy including surgery, radiotherapy, repeated chemotherapies, and targeted therapies, he had an unfavourable outcome and died of distant metastases. Conclusions. In synovial sarcoma of the larynx, PET/CT can detect recurrence and metastasis. PET/CT can also predict the treatment effect in patients with synovial sarcoma. [ABSTRACT FROM AUTHOR]

Objective:Review of the literature on the role of surgery in the management of head and neck cancer in the era of organ preservation.Method:Literature search based on the essential practice guidelines set out by the US National Comprehensive Cancer Network.Results:Despite the increasing popularity of non-surgical treatment options, the surgeon remains a key figure in the multidisciplinary head and neck cancer team, along with the radiation oncologist, the medical oncologist and the speech and swallowing therapist. Even when organ preservation is successful, early and late toxicity may cause serious complications, including laryngeal dysfunction with a ‘frozen larynx’. When organ preservation fails, salvage surgery is often associated with increased complications and reduced survival.Conclusion:There is a definite need to apply more rigorous standards to the use of organ preservation strategies, and to re-evaluate the role of surgery in head and neck cancer treatment. [ABSTRACT FROM AUTHOR]

Objectives: Radiation Therapy Oncology Group study 91-11 found that in resectable advanced laryngeal cancer, the locoregional control rate achieved with reduced intra-arterial cisplatin and concurrent radiotherapy (RADPLAT) was comparable to that of a concurrent chemoradiotherapy arm, with reduced toxicities. However, distant metastases were more frequent. Our study retrospectively evaluated the efficacy and feasibility of adjuvant chemotherapy with S-1, an oral fluoropyrimidine, for distant metastases following reduced RADPLAT. Methods: We analyzed 61 patients who were treated with reduced RADPLAT and achieved a complete response at the primary site. After the use of reduced RADPLAT, 24 patients were administered S-1 for 2 weeks followed by 1 week of rest, and the cycle was repeated for 6 months (S-1+ group). Thirty-seven patients were not administered S-1 (S-1-group). Results: The hazard ratio for distant metastases in the S-1+ group was 0.114 (95% confidence interval, 0.015 to 0.881; p = 0.0374). There was a significant difference in disease-free survival in favor of the S-1+ group (p = 0.0455). Nineteen patients (79.2%) in the S-1+ group received S-1 according to the planned schedule and dose. Grade 3 toxicities were observed in 2 patients (8.3%), but there was no grade 4 event. Conclusions: In resectable advanced laryngeal cancer, S-1 adjuvant chemotherapy is an effective and feasible treatment option to control distant metastases following reduced RADPLAT. [ABSTRACT FROM AUTHOR]

Angiogenesis is a hallmark of cancer, fundamental to its growth. The 'angiogenic switch' occurs when pro-angiogenic factors are not balanced by anti-angiogenic factors. A correlation between angiogenic properties and oncological prognosis (for laryngeal squamous cell carcinoma (LSCC) too) was first hypothesized in the 1990s. An exhaustive literature review was performed to investigate available data on angiogenesis markers and their biological role and therapeutic potential in LSCC. The prognostic significance of microvascular density in LSCC was investigated with endothelial targets, e.g. CD105, CD34, and CD31. Epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), VEGF receptor 2, angiogenin, hypoxia-inducible factor 1, and other biological markers were also studied. Only anti-EGFR therapy has been approved by the USFood and Drug Administration (FDA) for head and neck carcinoma in recent years, while several agents interfering with VEGF and its receptors are being studied. Experimental findings indicate that anti-CD105 monoclonal antibodies efficiently inhibit tumor angiogenesis. There are two main ways to approach the vascular profile of solid malignancies: by inhibiting new vessel formation (anti-angiogenic therapy) or selectively damaging neoplastic vessels (vascular targeting therapy). In advanced LSCC, both these strategies seem promising and warrant further preclinical and clinical investigation. [ABSTRACT FROM AUTHOR]

Conclusion: A long-term study was carried out on 57 patients treated with radiation alone who had T2N0M0 squamous cell carcinoma of the glottic larynx. The response and survival rates were satisfactory, but the complete response (CR) and the larynx preservation rates showed a need for improvement. Thirty-four patients underwent salvage operations and a safe margin for the partial laryngectomy was evaluated by histopathological examination of serial sections of the surgical specimen. Objective: Although the effectiveness of combined chemoradiation therapy in the treatment of head and neck cancer has been reported, the facts remain unclear. The purpose of this study was to analyze the long-term outcomes of radiation therapy alone for T2N0M0 squamous cell carcinoma of the glottic larynx, i.e. the survival rate, the larynx preservation rate, and the reality of salvage operations. This is expected to contribute to an understanding of the synergistic effects of anticancer drugs used in combined chemoradiation therapy, the use of which will be expanded in the future. The reason for this is that the radiation source, radiation field, and radiation dose are nearly identical for patients with T2N0M0 squamous cell carcinoma of the glottic larynx. Methods: The subjects were 57 patients with untreated T2N0M0 squamous cell carcinoma of the glottic larynx. There were 55 males and 2 females. Their ages ranged from 31 to 86 years. The 4 MV Liniac X-ray external beam radiation therapy was carried out via two-dimensional horizontal opposing ports, 2 Gy per dose, five times a week with a total of 66 Gy. Results: In 57 patients, we observed CR in 33 patients, partial response (PR) in 20 patients, no change (NC) in 4 patients, and progression disease (PD) in none of the patients. The response rate was 93.0% and the CR rate was 57.9%. The survival rates (Kaplan-Meier method) were: 5-year survival rate of 88.5% and 10-year survival rate of 73.5%. The larynx preservation rates (Kaplan-Meier method) were: 5-year larynx preservation rate of 60.4% and 10-year larynx preservation rate of 50.1%. The main side effect of grade 3 or more was only stomatitis in four patients, all of which were reversible changes (CTCAT v3.0 JCOG/JSCO). Salvage operation was required in 34 (59.6%) of 57 patients, 10 patients underwent partial laryngectomy, total laryngectomy was performed in 3 of the 10 patients following the partial laryngectomy, and 27 patients (47.4%) underwent total laryngectomy. The surgical specimens were serially sectioned at a thickness of 4 μm and examined histopathologically and compared to the macroscopic findings at surgery. The safe margin for partial laryngectomy was considered grossly to be 5 mm from the edge of the tumor. [ABSTRACT FROM AUTHOR]

An international consensus panel was convened to develop guidelines for the conduct of phase III clinical trials of larynx preservation in patients with locally advanced laryngeal and hypopharyngeal cancer. According to their recommendations, future trial populations should include patients with T2 or T3 laryngeal or hypopharyngeal squamous cell carcinoma not considered for partial laryngectomy and should exclude those with laryngeal dysfunction or aged >70 years. Baseline and post-treatment functional assessments should include speech and swallowing evaluations. Furthermore, voice should be routinely assessed with a simple, validated instrument. Regarding endpoints, the primary endpoint should capture survival and function. As a result, the panel created a new endpoint of laryngoesophageal dysfunction (LED)-free survival, which includes the events of death, local relapse, total or partial laryngectomy, tracheotomy at ≥2 years, or feeding tube at ≥2 years. Recommended secondary endpoints are freedom from LED, overall survival, progression-free survival, locoregional control, time to tracheotomy, time to laryngectomy, time to discontinuation of feeding tube, and quality of life/patient-reported outcomes. Future exploratory correlative biomarker studies should include epidermal growth factor receptor, excision repair cross-complementation group 1 gene, E-cadherin and β-catenin, epiregulin and amphiregulin, and TP53 mutation. Revised trial designs in several key areas are needed to advance the study of larynx preservation. With consistent methodologies, clinical trials can more effectively evaluate and quantify the therapeutic benefit of novel treatment options for patients with locally advanced laryngeal and hypopharyngeal cancer. [ABSTRACT FROM AUTHOR]

Background: Primary radiotherapy (RT) is a mainstay of treatment for laryngeal squamous cell carcinoma (LSCC). Although the cure rates for early (T1) vocal cord tumours are high, RT proves ineffective in up to a third of T3 carcinomas. Moreover, RT is associated with debilitating early- and late-treatment-related toxicity, thus finding means to de-escalate therapy, while retaining/augmenting therapeutic effectiveness, is highly desirable. p53 is a key mediator of radiation responses; we therefore investigated whether Nutlin-3, a small-molecule inhibitor of MDM2 (mouse double minute 2; an essential negative regulator of p53), might radiosensitise LSCC cells.Methods: We performed clonogenic assays to measure radiosensitivity in a panel of LSCC cell lines (for which we determined p53 mutational status) in the presence and absence of Nutlin-3.Results: LSCC cells harbouring wild-type p53 were significantly radiosensitised by Nutlin-3 (P<0.0001; log-rank scale), and displayed increased cell cycle arrest and significantly increased senescence (P<0.001) in the absence of increased apoptosis; thus, our data suggest that senescence may mediate this increased radiosensitivity.Conclusion: This is the first study showing Nutlin-3 as an effective radiosensitiser in LSCC cells that retain wild-type p53. The clinical application of Nutlin-3 might improve local recurrence rates or allow treatment de-escalation in these patients. [ABSTRACT FROM AUTHOR]

Background: Verrucous carcinoma occurs infrequently in the vocal folds. This tumour has an excellent prognosis with proper treatment. Management strategies include surgery, radiotherapy or both. Aim: To evaluate the long-term results of type I and II laser cordectomy for the treatment of verrucous carcinoma of the vocal folds. Materials and methods:We reviewed the files of 18 patients with verrucous carcinoma of the vocal folds treated by type I or II laser cordectomy in our department from 1989 to 2006, and recorded clinical and outcome data. Results: None of the patients had any major post-operative complications. All had a subjectively satisfactory quality of voice, with no morbidity. Patient follow up ranged from three to 228 months (mean, 48 months). Five patients were treated with post-operative radiotherapy for persistent disease, of whom four underwent repeated surgery due to recurrence. Conclusion: Type I or II laser cordectomy is a safe, feasible, secure method of treating verrucous carcinoma of the vocal folds. There were no major complications in our patient series. Most recurrent disease was manageable locally with repeated surgery. [ABSTRACT FROM AUTHOR]

Background: Primary tumors of the airway with proximity to vocal cords and recurrent laryngeal nerves can be resected with sparing of the larynx. Long-term data on survival and local recurrence after laryngotracheal resection are scarce. Methods: We conducted a retrospective study of laryngotracheal resection and reconstruction for primary tumors of the airway since 1972. Results: Twenty-five patients aged 15 to 77 years presented with adenoid cystic carcinomas (n = 9), squamous cell carcinomas (n = 6), and other airway tumors (n = 10). Subglottic resection consisted of anterior cricoid in 5 patients; posterior cricoid mucosa in 9 patients, with resection of the posterior cricoid plate in 3 patients; lateral resection in 7 patients; and combined anterior and posterior elements in 4 patients. Vascularized trachea was tailored to reconstruct the defect. Seven patients without hoarseness required resection of the recurrent laryngeal nerve, and 4 other patients with hoarseness did not. There were no operative deaths. Two (8.0%) patients who had received prior high-dose cervical radiation had anastomotic separation, one requiring laryngectomy. One patient needed permanent tracheostomy, and temporary (<2 months) airway tubes were used in 5 patients. Sixteen patients received postoperative radiation. Median follow-up was 101 months. Four (16%) patients died of disease. Overall survival at 5 and 10 years was 79% and 64%, respectively. No patient underwent laryngectomy for recurrence. Conclusion: Laryngotracheal resection and immediate reconstruction for subglottic tumors is achieved with good preservation of voice, low morbidity, and no compromise of long-term survival. [ABSTRACT FROM AUTHOR]