Advanced Stage Laryngeal Cancer Research Articles

Abstract 4812: Evaluating racial and ethnic differences in advanced-stage laryngeal cancer treatment and outcomes in Florida: Unmasking the inequities

Abstract Purpose: To evaluate the association between race/ethnicity, treatment, and mortality among individuals with advanced-stage laryngeal cancer in Florida. Methods: We obtained data from the Florida Cancer Data System (FCDS) on non-Hispanic (NH)-White (the reference group), Hispanic, and NH-Black patients with advanced-stage (regional and distant) laryngeal cancer from 2009 to 2020. Sociodemographic factors were obtained from FCDS (age, marital status, and insurance) and the United States Census at the county level (education, household income, and rurality). Treatment strategies included chemoradiation, surgery followed by chemoradiation, chemotherapy, radiation, surgery, and surgery followed by chemotherapy. The primary outcome was overall mortality. Multivariable Cox proportional hazard models were used to calculate hazard ratios (HR) and 95% confidence intervals (95% CI) and to examine the association of race/ethnicity with treatment and survival, while adjusting for sociodemographic factors. Results: There were 4,522 participants with advanced-stage laryngeal cancer (57.9% <65 years, 79.5% male, 75.4% NH-White, 13.1% Hispanic, and 11.5% NH-Black) included in the analysis. Compared to NH-White patients, NH-Black patients were less likely to be married, have private insurance, and live in an urban county. Moreover, NH-Black individuals were less likely to receive chemoradiation alone and were more likely to receive surgery followed by chemoradiation. Government insurance was highly associated with chemoradiation receipt. In age-adjusted models, NH-Black patients with advanced-stage laryngeal cancer had a higher risk of death compared to NH-White patients (HR: 1.19; 95% CI: 1.06, 1.32), while Hispanic patients had a lower risk of death compared to NH-White patients (HR: 0.80; 95% CI: 0.71, 0.89). After adjusting for sociodemographic factors, there was no statistically significant difference in overall mortality in NH-Black patients compared to NH-White patients (HR: 1.07; 95% CI: 0.96, 1.20). However, among individuals who received chemoradiation, NH-Black patients had a higher risk of mortality, even after adjusting for sociodemographic factors, compared to NH-White patients (HR: 1.27; 95% CI: 1.04, 1.55). Conclusions: Among patients with advanced-stage laryngeal cancer in Florida, NH-Black patients experienced a higher risk of overall mortality compared to other racial and ethnic groups, but this discrepancy was primarily among those who received chemoradiation, even after accounting for sociodemographic factors. This study emphasizes the urgency of expanding laryngeal cancer care access for NH-Black individuals and investigating possible biological variations in their response to chemoradiation and subsequent survival outcomes. Citation Format: Caretia J. Washington, Chayil Lattimore, Dejana Braithwaite, Kristianna Fredenburg, Shama Karanth. Evaluating racial and ethnic differences in advanced-stage laryngeal cancer treatment and outcomes in Florida: Unmasking the inequities [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4812.

The Role of Surveillance Imaging in Patients with Advanced Laryngeal Cancer

Background: While almost one-third of patients treated for laryngeal cancer will experience disease recurrence, the current National Comprehensive Cancer Network guidelines do not recommend routine post-treatment imaging follow-up. We aimed to examine the yield of post-treatment imaging surveillance among patients with primary advanced laryngeal cancer. Methods: Patients treated for advanced-stage laryngeal carcinoma between 2000 and 2020 in a tertiary care medical center were retrospectively reviewed. Data collected included demographics, clinical and pathological features, treatment modalities, tumor recurrence data including the diagnostic modality (patient’s symptoms, physical examination, or imaging), and outcome. Results: The cohort included 123 patients with advanced-stage laryngeal cancer. Thirty-five (28.7%) patients experienced disease recurrence with fourteen recurrences (40%) diagnosed by imaging. Patients diagnosed by imaging had a shorter time to recurrence diagnosis (23.8 vs. 45.9 months, p-value = 0.016), with similar 5-year overall and disease-specific survival (20.6% vs. 26.6%, log-rank p-value = 0.53 and 62.1% vs. 59.7%, log-rank p-value = 0.87, respectively). Conclusions: Performance of routine post-treatment imaging follow-up in patients with advanced laryngeal cancer was associated with a shorter time to diagnosis of recurrence and similar survival rates. Imaging follow-up should be considered in cases where clinical follow-up is limited and according to the judgment of the treating physician.

Superior loco-regional control after primary surgery compared to chemo-radiotherapy for advanced stage laryngeal cancer.

The optimal strategy to treat loco-regionally advanced squamous cell carcinoma of the larynx (LSCC) remains to be defined. The goal of this single institution retrospective study was to report on oncologic outcome of advanced LSCC treated with curative intent. Patients diagnosed and treated for stage T3-T4a LSCC between 2001 and 2014 were retrospectively analyzed. Time-to-event endpoints were calculated beginning from the date of histologic diagnosis, which were analyzed with log-rank test and Cox proportional hazard models. The cohort was divided into two subgroups: primary radiotherapy with concomitant cisplatin (CRT) (n=30, 38%) and primary surgery (n=48, 62%). Median follow-up was 56 months. Locoregional control (LRC) for the primary surgery and CRT were 95% and 50% in 5 years, respectively (p<0.01). Progression free survival (PFS) for the primary surgery and CRT were 61% and 38% in 5 years, respectively (p=0.23). The overall survival (OS) after primary surgery and CRT in 5 years were 63% vs. 65%, respectively (p=0.93). The 5-years LRC was significantly superior after surgery compared to RT for cT3 primaries (100% vs 50%, p= 0.0022). No significant differences were observed in the remaining subgroups regarding cT stage and PFS or OS. Our series demonstrated superior LRC after primary surgery followed by risk-adapted adjuvant (C)RT compared to primary CRT in cT3 LSCC, but no significant difference in PFS or OS in locally-advanced LSCC. The optimal patient selection criteria for the ideal treatment for loco-regionally advanced LSCC still needs to be defined.

The value of preoperative inflammatory markers in patients through total laryngectomy for advanced stage larynx carcinoma

The aim of this study is to evaluate the difference between neutrophil, lymphocyte, platelet and RDW (red cell distribution width) counts and NLR (neutrophil/lymphocyte ratio) and PLR (platelet/lymphocyte ratio) between patients who underwent total laryngectomy for advanced stage laryngeal squamous cell carcinoma and healthy control group. The study group consisted of 37 patients (36 male, 1 female) who underwent total laryngectomy and bilateral neck dissection for advanced stage laryngeal squamous cell carcinoma between January 2017 and December 2019. As a control group, complete blood count records of 35 healthy individuals who were routinely examined in 2019 within the scope of occupational health and safety were compiled. Blood was collected preoperatively from the patient in the study group. The data obtained from the whole blood counts of the two groups were analyzed statistically by comparing neutrophil, lymphocyte, platelet, RDW, NLR and PLR values. The age difference between the study and control groups was not significant (p&gt;0.05). Neutrophil, platelet and RDW counts were higher in the study group compared to the control group and this difference was statistically significant (p=0.001, p=0.035, p=0.001, respectively). Although the lymphocyte count was high in the study group, the difference was not significant (p=0.061). The difference between NLR and PLR between the two groups was high in the study group and this difference was statistically significant (p=0.001, p=0.007, respectively). Neutrophil, platelet, RDW, NLR, PLR values were significantly higher in patients with advanced stage laryngeal cancer than in the control group. NLR, PLR and RDW values, which can be obtained cheap, simple and rapidly at the diagnosis stage of laryngeal cancers, may be biomarkers in determining prognosis. For this, multicenter, prospective studies are needed.

Advanced stage laryngeal cancer in Egypt: Quality of life in the scope

Advanced stage laryngeal cancer in Egypt: Quality of life in the scope

Primary radiation therapy for advanced-stage laryngeal cancer: A laryngo-esophageal dysfunction disease-free survival.

To evaluate the outcomes of advanced-stage laryngeal squamous cell carcinoma (SCC) patients treated with functional-preservation strategy with a specific focus on laryngo-esophageal dysfunction disease-free survival (LEDDFS). A retrospective review was conducted of stage III-IVB laryngeal SCC patients who were treated with curative-intent radiotherapy (RT) (2007-2018). Patients were preferentially managed with upfront chemoradiation (CCRT); except for those with cN2-3, cT4, or large volume cT3 (induction chemotherapy followed by RT or CCRT is an option), and those who were unfit or declined chemotherapy (received altered RT). The primary endpoint was 3-year LEDDFS, and secondary endpoints were 3-year local failure (LF), regional failure (RF), distant metastasis (DM), overall survival (OS), disease-free survival (DFS), and acute and late toxicities. Cox proportional hazard tests were used for multivariable analysis (MVA). A total of 213 cases were included. With a median follow-up of 37 months, the 3-year LEDDFS was 50%, while the 3-year OS, DFS, LF, RF, and DM were 81%, 74%, 9%, 5%, and 7%, respectively. On MVA, cT4-category was the only predictor of inferior LEDDFS (HR: 0.47, [95% CI: 0.29-0.74], p < .01). The most common grade ≥ 3 acute and late radiation therapy oncology group (RTOG) toxicity were esophageal toxicity: 16.7% and 29.6%, respectively. Primary RT resulted in favorable oncologic and functional outcomes in only half of the advanced-stage laryngeal cancer patients. Future clinical trials are required to investigate further treatment options aiming to improve the oncologic and maintain functional outcomes with utilization of LEDDFS as the primary endpoint. 4.

Intensified Radiation Therapy for Laryngeal Cancer: Oncologic and Functional Outcomes

<h3>Purpose/Objective(s)</h3> To evaluate the outcomes of advanced-stage laryngeal squamous cell carcinoma (SCC) patients (pts) treated with functional-preservation strategy at a tertiary cancer center with a specific focus on laryngo-esophageal dysfunction disease free survival (LDDFS). <h3>Materials/Methods</h3> Retrospective review was conducted of stage III-IVB laryngeal SCC pts who were treated with curative-intent radiotherapy (RT) (2007-2018). Pts were preferentially managed with upfront chemoradiation (CRT); except for those with cN2-3, cT4, or large volume cT3 (induction chemotherapy followed by RT or CRT is an option), and those who were unfit or declined chemotherapy (received accelerated RT). The primary endpoint was 3-yr LDDFS, and secondary endpoints were 3-yr local failure (LF), regional failure (RF), distant metastasis (DM), overall survival (OS), disease-free survival (DFS) and acute and late toxicities. Events for LDDFS included death, tumor relapse (i.e., LF, RF, DM), and late laryngo-esophageal dysfunction (defined by feeding tube dependence, tracheostomy or aspiration pneumonia >6 months post-RT), whichever occurred first. Cox proportional hazard test were used for multivariable analysis (MVA). <h3>Results</h3> A total of 213 cases were included (table 1). With a median follow-up of 37 months, the 3-yr LDDFS was 50%, while the 3-yr OS, DFS, LF, RF, and DM were 81%, 74%, 9%, 5% and 7%, respectively. On MVA, cT4- category was the only predictor of inferior LDDFS (HR: 0.47, [95%CI: 0.29-0.74], p<0.01). The most common grade ≥ 3 acute and late RTOG toxicity were esophageal toxicity: 16.7% and 29.6%, respectively. <h3>Conclusion</h3> Intensified RT resulted in favorable oncologic and functional outcome in only half of the advanced stage laryngeal cancer pts. Future clinical trials are required to investigate further treatment intensification particularly in T4-primary tumors aiming to improve the oncologic and maintain functional outcomes with utilization of LDDFS as the primary endpoint.

Upfront surgical organ-preservation strategy in advanced-stage laryngeal cancer

PurposeAdvanced-stage laryngeal cancer is a challenging disease that needs multimodal treatment. Medical and surgical organ-preservation strategies have been developing in the last decades to spare these functions while granting cancer cure. The current work presents the experience of a tertiary-care center in conservative surgery for advanced-stage laryngeal cancer. Materials and methodsWe collected clinical data of patients submitted to open partial horizontal laryngectomies (OPHLs) and any possible adjuvant treatment from 2005 to 2018. Outcomes were also compared to the most recent studies reporting on both medical and surgical organ-preservation strategies. ResultsOne hundred ten patients were included in the analysis. Adjuvant therapy was employed in 51% of cases. The local control rate was 96.4%, while overall survival (OS) was 67%, and laryngo-esophageal dysfunction free survival (LEDFS) was 66%. Stage IV and vascular invasion were associated with a statistically-significant worse survival. ConclusionsOPHLs are valid as upfront treatment in fit patients affected by advanced-stage laryngeal cancer. Disease control and function preservation are granted in a significant percentage of cases, even when followed by adjuvant therapy.

Prospective non interventional Study Evaluating Prognostic and Predictive value of PDL-1 expression and associated T-cell infiltration in Primary Laryngeal Squamous Cell Carcinoma

Abstract Background Immune system plays an important role in cancer evolution. However, cancer cells affect the immune system and use it for its growth and survival. Tumor infiltration lymphocytes and PDL-1 expression proved to play an important prognostic role in different malignancies. We aimed at evaluating this role in laryngeal cancer. Methodology We prospectively analyzed the pre-treatment paraffin blocks for laryngeal cancer patients, whether on the laryngoscopy or operative specimens, to identify the CD8-positive cells in the tumor epithelium or stroma and the PDL-1 expression on the tumor cells. Appropriate tissue was used as positive control; placenta for PDL-1 and tonsil for CD8. A total score formed of the sum of percentage and intensity of PDL-1. A final comprehensive rate was considered as low expression when combined percentage and intensity score from 0 to 4, and high expression when score from 5-7. According to the distribution, the CD8+T cell invasion was divided into strong infiltration (&amp;gt; 10/100 of epithelial cells; &amp;gt;20/100 stromal cell infiltration) and weak infiltration (&amp;lt; 10/100 epithelial cells; &amp;lt; 20/100 stromal cell infiltration). Results 40 patients were included in our study; 12 patients had early stage disease (I or II) and 28 with advanced stage (III or IV). PDL-1 expression was positive in 92.5%. Neither the PDL-1 nor CD-8 were found significantly correlated to OS in the whole population, however patients with advanced stage, median OS was significantly low for negative or low compared to high PDL-1 expression (11.7 vs 25.2 months (p = 0.036)), a trend of better OS in high CD8 Epithelial expression (25.1 versus 15.9, P = 0.514) and again trend of higher OS in high CD8 Stromal expression (25.3 versus 15.6 months, p = 0.375). Also there were significant correlation between the CD8 expression in the tumor epithelium and stroma with the PDL-1 expression with p-value of 0.001 and &amp;lt; 0.0001 respectively. Conclusion there is a positive correlation between tumor infiltration lymphocytes and PDL-1 expression in laryngeal squamous carcinoma and the higher PDL-1 expression in advanced stage laryngeal cancer is associated with better OS.

Role of Clinical-Demographic Data in Survival Rates of Advanced Laryngeal Cancer.

Background and Objectives: Laryngeal cancer is one of the most common cancers in the upper aerodigestive tract, and tobacco and alcohol habits are the most relevant risk factors. The role of these risk factors in the incidence of laryngeal carcinomas is well known, yet only a few studies have been conducted on their role as risk factors of prognosis. The aim of the study was to assess the impact of clinical–demographic data on overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS) in patients with advanced-stage laryngeal cancer (Stage III–IV) who underwent total laryngectomy. Materials and Methods: This retrospective study was carried out on patients with Stage III–IV laryngeal squamous cell carcinoma treated with total laryngectomy between 2004 and 2014. For each patient, clinical and anamnestic data were collected and collated in a database, including alcohol and smoking habits. Results: Considering the variable age, family history, alcohol, grading, subsite, stage, pT stage, pN stage, and adjuvant therapy, no statistical significance was found for five-year OS. Smoking was the only variable that was statistically significant (p = 0.0043). A relevant difference was noted in the five-year DFS between pN-negative and pN-positive tumors (74.3% vs. 55.26%, respectively; p = 0.056), and a statistically significant difference was found between non- and ≤20 cigarettes/day smokers and heavy smokers (77.78% vs. 53.66%, respectively; p = 0.021). The five-year disease-specific survival rate was 68.83%, and a significant difference was detected for the smoking and pN stage variables. Heavy smokers (43.90% died vs. 16.67% of the non- and ≤20 cigarettes/day smokers; p = 0.0057) and pN-positive (42.1% died vs. 20.51% of the pN-negative patients; p = 0.042) patients had a worse prognosis. Conclusion: Smoking in our study was found to be an important independent risk factor for worse OS and DSS in patients with advanced laryngeal cancer.

Lysyl Oxidase Like-4 (LOXL4) as a tumor marker and prognosticator in advanced stage laryngeal cancer

IntroductionLysyl oxidase-like 4 is an amine oxidase from the lysyl oxidase family that was previously shown to be overexpressed in head and neck cancer and upregulated in response to hypoxia. The possible role of lysyl oxidase-like 4 as a tumor marker in advanced stage larynx cancer was investigated. ObjectiveTo investigate the expression of lysyl Oxidase-Like 4 protein in advanced stage laryngeal cancer and elucidate its possible role as a tumor marker, predictor of treatment response and prognosticator. MethodsDiagnostic specimens of 72 patients treated for stage III–IV laryngeal squamous cell carcinoma were evaluated for lysyl oxidase-like 4 expression by immunohistochemistry. ResultsLysyl oxidase-like 4 expression was correlated with advanced tumor stage (p = 0.041) and better differentiation (p = 0.025) but was independent of tumor diameter (p = 0.456). Response to induction chemotherapy or the need for salvage laryngectomy were not affected by lysyl oxidase-like 4 expression (p = 0.999, p = 0.070 respectively). Increased lysyl oxidase-like 4 expression was associated with better 2 year overall survival in both univariate (p = 0.036) and multivariate analyses (p = 0.014). ConclusionLysyl oxidase-like 4 expression emerges with advancing stages, is lost with worsening differentiation, and may have tumor suppressive properties in larynx cancer.

Investigation of Pepsin in Laryngeal Squamous Cell Carcinoma Specimens

Objective: Squamous cell carcinoma (SCC) composes 95% of the carcinoma of the larynx. One of the factor recognized in the past two decades as increasing the risk of SCC is laryngopharyngeal reflux (LPR). The role and mechanism of LPR in laryngeal cancer remain unclear. The aim of this study was to assess the presence of pepsin in laryngeal formalin-fixed, paraffin-embedded (FFPE) squamous cell carcinoma (SCC) specimens in order to test the hypothesis that LPR plays a role in the development of laryngeal SCC. Method: A total of 29 pathology specimens of advanced-stage laryngeal cancer patients who had undergone total laryngectomy were evaluated. The specimens were confirmed histopathologically as SCC and maintained in paraffin blocks in the pathology department. The western blot (WB) or the enzyme-linked immunosorbent assay (ELISA) analyses were used to measure pepsin enzyme levels. Results: According to the WB and ELISA analyses, there was no presence of the pepsin enzyme in any of the 29 formalin-fixed, paraffin-embedded (FFPE) laryngeal SCC specimens. However, pepsin was detected with both the WB and the ELISA tests in positive controls and fresh rat stomach specimen. Conclusion: Pepsin was not present in any of the malignant laryngeal squamous cell carcinoma specimens in this study. Relationship between LPR and laryngeal SCC still remains unclear and further studies are needed to verify the role of pepsin and LPR in laryngeal SCC.

Assessment of HPV 16, HPV 18, p16 expression in advanced stage laryngeal cancer patients and prognostic significance

IntroductionHuman papilloma virus is an etiological risk factor for a subset of head and neck squamous cell carcinomas. HPV has been proven to be a powerful prognostic biomarker for oropharyngeal cancer, but its role in the larynx has not been explored in depth. The developmental mechanisms of laryngeal carcinomas are quite complex and controlled by various factors. Smoking and alcohol are most important risk factors. Recent studies indicate that HPV infection also plays an important role in larynx carcinomas. HPV related laryngeal carcinomas especially occur at the supraglottic region of larynx. ObjectiveWe aimed to determine the frequency of HPV/protein16 positivity in patients with laryngeal carcinoma and association of HPV and/or p16 positivity with variables such as age, sex, smoking habits, tumor localization, lymph node metastasis, recurrence and survival in advanced stage laryngeal carcinoma in our study. MethodsThis retrospective study included 90 patients with advanced laryngeal carcinoma. The Control group was 10 normal larynx mucosa specimens. The presence of HPV was investigated polyclonally by polymerase chain reaction, and protein16 with immunohistochemical method. In HPV positive cases, the presence of HPV types 16, 18 were evaluated by polymerase chain reaction. Demographic features of patients were noted. Patient survival and association with HPV/protein16 was determined. ResultsPolyclonal HPV positivity was detected in 11 (12.2%) of 90 cases. Out of these 11 cases, HPV 16 was positive in 6, HPV 18 in 4, and both HPV 16 and 18 were positive in 1. In 18 (20%) of the cases, p16 was positive. Six of the cases (6.6%) had both HPV and protein16 positivity. In cases where protein16 alone or HPV and protein16 were co-positive, alcohol use was less and the tumor was found more likely to be localized in the supraglottic area. These ratios were statistically significant. Supraglottic localization of tumor was determined to be increased in protein16 positive cases. The correlation between protein16 positivity and supraglottic area location was determined to be statistically significant (p = 0.011). 55.6% of protein16 positive cases was located in the supraglottic region, 33.3% was glottic and 11.1% was transglottic. Although life expectancy over 5 years were numerically higher in HPV and protein16 positive cases, this was not found to be statistically significant. There was no statistically significant relationship between HPV positivity and mean age, differentiation, smoking and alcohol use, tumor progression, lymph node metastasis, localization, recurrence, cause of mortality and treatment methods in our study. The mean follow-up period of our patients was 6.7 years. ConclusionThe close relationship between HPV and oropharyngeal squamous cell carcinoma could not be shown in larynx malignancy in many studies, including our study. Our findings support a limited role of HPV in laryngeal carcinogenesis. Protein16 is not a reliable surrogate for HPV status in laryngeal cancers and is not a predictor of laryngeal cancer survival. Supraglottic localization of tumor was determined to be increased in protein16 positive cases. The correlation between protein16 positivity and supraglottic area location was determined to be statistically significant. There is a need for more populated clinical trials, where neoplastic proliferation is better demonstrated and the accuracy of the results obtained is supported by different techniques.

Correlation between tumour infiltration lymphocyte and PDL-1 expression in laryngeal cancer and its prognostic significance: A prospective, non-interventional trial

Abstract Background Immune system plays an important role in cancer evolution. However, cancer cells affect the immune system and use it for its growth and survival. Tumour infiltration lymphocytes and PDL-1 expression proved to play an important prognostic role in different malignancies. We aimed at evaluating this role in laryngeal cancer. Methods We prospectively analyzed the pre-treatment paraffin blocks for laryngeal cancer patients, whether on the laryngoscopy or operative specimens, to identify the CD8-positive cells in the tumour epithelium or stroma and the PDL-1 expression on the tumour cells. Appropriate tissue was used as positive control; placenta for PDL-1 and tonsil for CD8. A total score formed of the sum of percentage and intensity of PDL-1. A final comprehensive rate was considered as low expression when combined percentage and intensity score from 0 to 4, and high expression when score from 5-7. According to the distribution, the CD8+T cell invasion was divided into strong infiltration (> 10/100 of epithelial cells; >20/100 stromal cell infiltration) and weak infiltration ( Results 40 patients were included in our study; 12 patients had early stage disease (I or II) and 28 with advanced stage (III or IV). PDL-1 expression was positive in 92.5%. Neither the PDL-1 nor CD-8 were found significantly correlated to OS in the whole population, however patients with advanced stage, median OS was significantly low for negative or low compared to high PDL-1 expression (11.7 vs 25.2 months (p = 0.036)), a trend of better OS in high CD8 Epithelial expression (25.1 versus 15.9, P = 0.514) and again trend of higher OS in high CD8 Stromal expression (25.3 versus 15.6 months, p = 0.375). Also there were significant correlation between the CD8 expression in the tumour epithelium and stroma with the PDL-1 expression with p-value of 0.001 and Conclusion There is a positive correlation between tumour infiltration lymphocytes and PDL-1 expression in laryngeal squamous carcinoma and the higher PDL-1 expression in advanced stage laryngeal cancer is associated with better OS. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

A randomized trial of laryngeal organ preservation evaluating two cycles of induction chemotherapy with platinum, docetaxel, and a novel Bcl-xL inhibitor.

6066 Background: Laryngeal bio-selection with induction chemotherapy (platinum + 5-FU infusion: PF) has been demonstrated to result in impressive rates of survival and organ preservation with moderate toxicities. We sought to reduce the toxicity of PF by substituting docetaxel (T) for 5-FU and improve the tumor response rate with the addition of the Bcl-xL inhibitor AT-101. Methods: Pts with advanced stage laryngeal cancer were treated with 1 cycle of T 75 mg/m2 + platinum (P) (cisplatin 100 mg/m2 or carboplatin AUC 6) and were randomized 2:1 to the addition of AT-101. Patients with a CR proceeded to chemoradiation (CRT) with concurrent weekly P. All pts with PR or NR underwent a second cycle of induction with TP + AT-101. Pts with a &gt; 50% response (CR or PR) after the second cycle of induction chemotherapy underwent CRT. Pts with a ≤ 50% response (NR) underwent laryngectomy. PET-CT was performed 12 weeks after CRT. Pts with residual disease underwent salvage laryngectomy (SL). Results: 54 eligible pts were enrolled; 46 M, 8 F; median age 59; 26 T4; stage III 16, stage IV 38; site: 2 hypopharyngeal, 39 supraglottic, 11 glottic, 2 subglottic. After cycle 1 of induction, 2/54 (4%) died prior to assessment by DL and 2 were removed from protocol due to adverse events (AEs). 29/50 pts (58%) had ≥ 50% response, 3 of which had CR; 2 proceeded to CRT &amp; 1 received a 2nd cycle of IC. 21/50 pts (42%) had &lt; 50% response. A total of 48 pts received cycle 2 of IC. After the 2nd cycle, a total of 39/50 pts (78%) had ≥ 50% response &amp; received CRT. No difference in response was seen with addition of AT-101. 11/50 pts (22%) had &lt; 50% response- 8 had laryngectomy &amp; 3 refused. Following CRT, 10 pts underwent SL, 2 for residual disease &amp; 8 late SL. The organ preservation rate was 31/50 (62%). The most common grade 3/4 toxicities associated with IC were nausea 9%, neutropenia 9%, &amp; infection 7%. 1 pt died of CNS hemorrhage unrelated to therapy &amp; 1 from sepsis. The median follow-up time is 28 months. The 2 yr laryngectomy-free survival is 54% (95% CI:38-68) &amp; 2 yr overall survival is 81% (95% CI: 64-90). Conclusions: AT-101 did not improve responses to P. Treatment with 2 cycles of IC with PT produced similar response rates to our institutional controls, but organ preservation was somewhat less following treatment with weekly P + RT. Toxicities were overall improved with this treatment strategy. Clinical trial information: NCT01633541.

Srednji volumen trombocita kod karcinoma grkljana – uloga u određivanju stadija karcinoma

Aim: This study aimes to investigate alteration of MPV (mean platelet volume) in laryngeal cancer. The hypothesis is that different clinical stages of laryngeal cancer and histological characteristics may be the basis of the pathophysiological changes in size and number of platelets. Materials and methods: Laboratory and clinical data were analysed retrospectively from 76 patients with laryngeal squamous cell carcinoma. Two main groups were formed upon TNM clasification: early stage and advanced stage laryngeal cancer. Furthermore, the patients were subdivided according to cancer degree of differentiation and presence of blood vessel invasion. Results: Statisticly significant difference between early and advanced stage cancer in the demographic and smoking data was not found. The comparison of MPV values showed statistically significant difference (P=0,003) between early and advanced laryngeal cancer. Furthermore, platelet values were significantly higher in the advanced group (P <0,001). The patients with poor differentiated cancer had significantly lower MPV values (P=0,001) compared to the ones with well and moderate differentiated stage. The difference in platelet count in the same groups was not statistically significant (P=0,132). The MPV value was significantly lower (P <0,001) in the group with vascular invasion compared to the group without that cancer characteristic. Conclusion: Our results suggest the possibility of using MPV values to help the clinician in prognosis of laryngeal cancer. Determining MPV values and platelet count is easily accessible and inexpensive method that provides useful information in everyday clinical practice.

Effects of Different Treatment Strategies and Tumor Stage on Survival of Patients with Advanced Laryngeal Carcinoma: A 15-Year Cohort Study.

Background Laryngeal cancer is the second most common cancer in the head and neck. Since laryngeal cancer management is a complex process, there is still no standard strategy to treat this disease in order to increase the survival rate of the patients especially among those with advanced form of the disease. Methods A cohort study was undertaken to analyze factors predicting survival of the patients in advanced stage laryngeal cancer in the Southern Iran among all patients newly diagnosed with laryngeal cancer between 2000 and 2015. Results Data of a total number of 415 patients who have had been diagnosed with advanced laryngeal cancer during this period was used for analysis. The patients' 1-, 3-, 5-, and 10-year survival rates were 81%, 62%, 53%, and 38%, respectively. Multivariable Cox regression analyses indicated a significant relationship between patients' survival and age at diagnosis (P < 0.001), disease stage (P = 0.002), tumor grade (P = 0.008), positive L. node (P = 0.008), and type of treatment (P < 0.001). As expected, treatment strategy was identified as the most effective factor in survival of the patients. According to the results, patients who undergone surgical treatment experienced a longer survival than those who received other treatments. Conclusion This study showed that the survival of patients depends on several factors, among which, treatment strategy is the most important. Combination of total laryngectomy plus chemoradiation provides superior local control and better survival compared to either radiotherapy or chemoradiation in patients with advanced laryngeal cancer.

Efficacy comparison between primary total laryngectomy and nonsurgical organ-preservation strategies in treatment of advanced stage laryngeal cancer: A meta-analysis.

Background:We aimed to provide a pooled analysis of controlled trials comparing long-term survival after primary laryngectomy and primary organ preservation methods in patients with T3-4 laryngeal cancer.Methods:We performed random-effects meta-analyses on overall survival (OS), disease-free survival (DFS), disease-specific survival (DSS), and locoregional control (LRC).Results:Fifteen studies met the selection criteria including 6288 patients (2696 patients who underwent primary laryngectomy and 3592 patients who underwent primary nonsurgical organ preservation therapy). There was a significant difference between the groups with respect to OS (HR 0.71, 95% CI 0.57–0.89, P = .003). However, a subgroup analysis found OS was not significantly worse for patients with T3 laryngeal cancer who received primary organ preservation compared with patients who underwent primary laryngectomy (HR 0.96, 95% CI 0.45–2.03, P = .91). There was no significant difference for DFS (HR 0.63, 95% CI 0.39–1.04, P = .07) in two groups. Patients with laryngeal cancer who underwent primary laryngectomy had a better DSS (HR 0.47, 95% CI 0.25–0.88, P = .02) and LRC (HR 0.56, 95% CI 0.390.80, P = .001) than patients who underwent primary nonsurgical organ preservation therapy.Conclusion:Our results support total laryngectomy for patients with T4 laryngeal cancer and show that primary organ preservation for laryngeal cancer has no advantage and also did not decrease the rate of OS in patients with T3 laryngeal cancer when compared with primary total laryngectomy.

İleri evre larenks kanserinde tedavi öncesi fonksiyonel görüntülemeye dayalı biyobelirteçlerin öngördürücü ve prognostik değeri

Objective: To determine the quantitative values of apparent diffusion coefficient (ADC), standardized uptake values (SUVmax, SUVmean), metabolic tumor volume (MTV), metabolic tumor volume indexes (MTImax, and MTImean) using diffusion weighted-MRI (DW-MRI) and positron emission tomography/computed tomography (PET/CT), and analyze the predictive and prognostic values of these biomarkers in a homogenous group of patients with advanced-stage laryngeal cancer. Methods: Patients with newly diagnosed advanced-stage laryngeal cancer who had both DW-MRI and 18F-FDG PET/CT before treatment, and who had curative cancer treatment (surgery ± adjuvant therapy or radio ± chemotherapy) between 2011 and 2015 were included in this study. All patients were followed up clinically and radiologically, if necessary every 3 months for the first 2 years, every 4-6 months for year 3, and then annually thereafter. Results: Thirty-eight patients were retrospectively analyzed. Our analysis demonstrated statistically significant differences when the pretreatment SUV and MTImean value were compared between patients with stages III and IV. Standardized uptake value was also a predictive factor for N-stage. Moreover, a statistically significant difference was determined when patients with and without perinodal involvement (PNI) were compared. Log rank analysis demonstrated that none of functional imaging-based biomarkers had a prognostic role for oncological outcomes. Conclusion: Our results demonstrated that pretreatment SUV and MTImean values were predictive factors for staging, N-stage and PNI. Indeed, functional imaging-based biomarkers are promising, novel, non-invasive techniques that may provide additional information about tumor characteristics, treatment selection and prognosis in the near future.

Postsurgical Disfigurement Influences Disgust Recognition: A Case-Control Study

Little is known about how emotion recognition may be modified in individuals prone to elicit disgust. We sought to determine if subjects with total laryngectomy would present a modified recognition of facial expressions of disgust. A total of 29 patients presenting with a history of advanced-stage laryngeal cancer were recruited, 17 being surgically treated (total laryngectomy) and 12 treated with chemoradiation therapy only. Based on a validated set of images of facial expressions of fear, disgust, surprise, happiness, sadness and anger displayed by 6 actors, we presented participants with expressions of each emotion at 5 levels of increasing intensity and measured their ability to recognize these emotions. Participants with (vs without) laryngectomy showed a higher threshold for the recognition of disgust (3.2. vs 2.7 images needed before emotion recognition, p = 0.03) and a lower success rate of correct recognition (75.5% vs 88.9%, p = 0.03). Subjects presenting with an aesthetic impairment of the head and neck showed poorer performance in disgust recognition when compared with those without disfigurement. These findings might relate either to some perceptual adaptation, habituation phenomenon, or to some higher-level processes related to emotion regulation strategies.