Effects of rosiglitazone on quality of life and prognosis of patients with early stage glottic laryngeal carcinoma.

Early-stage glottic laryngeal carcinoma refers to Tis-T2 lesions without cervical lymph nodes involvement and distant metastasis. Rosiglitazone facilitates expression of anti-inflammatory substances in the body, protecting immune system and improving patient's treatment efficacy and prognosis. We aimed to clarify the influence of rosiglitazone on prognosis of early-stage glottic laryngeal carcinoma. The control group received low-temperature plasma radiofrequency ablation and the observation group additionally received rosiglitazone; 4 mg, 2 times/day for 6 months. After treatment, the observation group showed reduction in the fundamental frequency perturbation and amplitude perturbation and increase in the harmonic-to-noise ratio relative to the control group. Total effective rate was 80.31% and 77.14% for observation and control groups, respectively (P > 0.05). Peripheral blood immune makers were higher in the observation group. The incidence rates of adverse reactions were lower in the observation group. The median survival time was 33 months in control group and 47 months in observation group (P < 0.05). The five-year survival rate was 77.14% in the observation group and 54.29% in the control group (P < 0.05). Rosiglitazone can prolong the survival of early-stage glottic laryngeal carcinoma patients, improving immune function and reducing adverse reactions during treatment.

Transoral laser microsurgery for T1 glottic cancer with anterior commissure: Identifying clinical and radiological variables that predict oncological outcome.

PURPOSE: The involvement of the anterior commissure (AC) is regarded to be a risk factor for poor results after transoral laser microsurgery (TLM) for early glottic cancer. The objective of this study was to determine how AC-related clinical and radiological factors affected oncological outcomes in a cohort of patients with T1 stage early glottic carcinoma involving the anterior commissure who were treated with TLM with negative surgical margins. METHODS: Retrospective analysis was performed on clinical, radiological, and follow-up data of patients consecutively treated with TLM at a tertiary academic center between November 2011 and August 2021 for T1 glottic squamous cell carcinoma involving the anterior commissure. Recurrence-free survival (RFS), local control with laser alone (LCL), laryngeal preservation (LP), and overall survival (OS) rates (Kaplan-Meier) were the primary outcome metrics. RESULTS: In our series, 5-year OS probability was 75.1%, RFS was 64.8%, LCL was 73.8%, and LP was 83.4%. OS and RFS were higher in patients with early stages of AC pattern than in patients with advanced stage (p = 0.004, p = 0.034, respectively). Vertical extension ratio was found to be associated with OS and RFS (p = 0.023, p = 0.001, respectively), and thyroid cartilage interlaminar angle with LCL by multiple Cox regression analysis (p = 0.041). CONCLUSION: TLM remains a valuable treatment option for AC involvement. AC3 type involvement and elevated vertical extension ratio were associated with negative prognosis. There have been signs that thyroid cartilage with a narrow angle increases recurrence. Alternative modalities should be kept in mind in the treatment decision of these cases.

Minimal invasive LASER-resection vs. radiotherapy as primary treatment of early glottic cancer. A population-based study with, up to 16 years follow up of survival, rate of laryngectomy and voice function.

BACKGROUND: Early glottic cancer can be treated with laser resection or radiotherapy. In an earlier study, we found that voice function after laser resection was inferior to that after radiotherapy. OBJECTIVES: This study was designed to determine if reduced margins at laser resection improved voice function without impairing oncologic results. METHOD: A total of 268 patients with previously untreated T1-T2 glottic carcinoma were studied. They were primarily treated with either radiotherapy (n = 119) or laser resection (n = 149). Survival, need for additional treatment (radiotherapy and/or total layngectomi) and voice function was compared. RESULT: Median follow up time was 7 years with range 0.5-16.6. There was no difference in the overall survival (p = .065) or disease-specific survival. (p = .126). After radiotherapy 32/119 patients and after laser resection 57/149 patients had recurrence. Total rate of laryngectomy was 24% in the radiotherapy group, and 8% in the laser resection group (p = .001). Voice analysis (T1A) showed more roughness in the radiotherapy group, otherwise no difference. CONCLUSIONS: By reducing the surgical margins, we have achieved a better voice function (T1A) but more patients have needed repeated laser excisions and some have also needed supplementary radiotherapy. The risk of laryngectomy and survival were apparently not affected.

Outcome of radiotherapy for the treatment of laryngeal squamous cell carcinoma in the very elderly population.

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.

Value and role of surgical margins in transoral laser microsurgery of the larynx, literature review and clinical considerations.

PURPOSE: There is no agreement on the most appropriate post-operative pathway for the management of positive margins after laser cordectomy for early stage glottic tumours (T1-2N0M0). This literature review and meta-analysis aim to evaluate the post-operative treatment with the best oncological results among follow-up, radiotherapy (RT) and surgical second look. The parameters utilized were incidence of recurrence, overall (OS), disease-specific (DSS) and disease-free (DFS) survival and larynx preservation (LP). METHODS: The articles were found through a string typed into PubMed from 2007 to 2022. The studies with detailed oncological results were selected according to inclusion criteria, and then the meta-analysis was carried out. RESULTS: Sixteen studies met the inclusion criteria for 2808 patients. The positive margin was found in 748 patients (26.6%), of which 416 were referred to follow-up, 89 to RT and 242 to a surgical second look. A false positive margin was found in 58/104 patients (56%). The recurrence rate in patients with positive margins was significantly higher (p = 0.003). In OS, DSS, DFS and LP, the odds ratio (OR) value was always greater than 1, assessing the role of the positive margin as a risk factor. CONCLUSIONS: Prospective studies will be necessary to establish the role of positive margin as a prognostic factor. A surgical second look in case of positive margin seems to be the best option for the patient in terms of lower risk of recurrence and better oncological results. Better collaboration between surgeon and pathologist would be desirable to limit the real and false positive margins.

Oncological outcomes and failure patterns of laser cordectomy in recurrent glottic cancer.

PURPOSE: Laser cordectomy is a widely accepted treatment modality for selected cases of early glottic cancers, but its role as a salvage treatment remains unclear. We aimed to investigate the oncological outcomes and failure patterns of salvage cordectomy. MATERIALS AND METHODS: This was a retrospective cohort study of patients who underwent cordectomy for early glottic cancer between 2013 and 2022 at a tertiary referral center. The main outcome measures were overall survival, larynx-preservation rate, tracheostomy dependency rate, and disease-free survival. RESULTS: A total of 142 patients (mean age: 63 years, interquartile range [IQR]: 45-72, 123[86.9 %] males) were analyzed. There were 38 (26.8 %) recurrences after a mean of 22 months (IQR: 17-26). Among them, 25 (17.6 %) underwent salvage cordectomy, while 13 (9.1 %) received other salvage treatments (11[7.7 %] (chemo)radiotherapy and 2[1.4 %] total laryngectomy). In comparison to the other salvage treatments, salvage cordectomy demonstrated lower tracheostomy rates (0 vs. 31 %, p = 0.05), comparable 5-year disease-free survival (62 % vs. 54 %, p = 0.4), higher 5-year larynx preservation rate (92 % vs. 54 %, p = 0.02), and improved 5-year overall survival rate (84 % vs. 62 %, p = 0.01). Factors associated with salvage cordectomy failure were age >60 years (odds ratio [OR]: 1.3, 95 % confidence interval [CI]: 1.15-1.53), smoking continuation (OR: 3.73, 95 % CI: 3.5-4.4), heavy smoking (OR: 1.24, 95 % CI:1.07-2.15), and pT1b + (OR: 2.26, 95 % CI: 2.1-2.9). CONCLUSIONS: Salvage cordectomy offers favorable larynx preservation rates and oncological outcomes for recurrent disease amenable to conservative surgery. Smoking, advanced age, and advanced tumor stages are associated with salvage cordectomy failure.

Prognostic analysis of surgical treatment for T3 glottic laryngeal cancer based on different tumor extension patterns.

BACKGROUND AND OBJECTIVES: To investigate the prognostic impact of different tumor invasion patterns in the surgical treatment of T3 glottic laryngeal cancer. METHODS: We conducted a retrospective analysis of clinical data of 91 patients with T3 glottic laryngeal cancer. RESULTS: We found that the posterior invasion being significantly associated with involvement of the lamina of cricoid cartilage (P < 0.001), arytenoid cartilage (P = 0.001), and subglottic (P = 0.001). There was no statistical difference in survival outcomes between the total laryngectomy (TL) group and the partial laryngectomy (PL) group, but in the PL group, tumors with anterior invasion were associated with a better 5-year DFS than tumors with posterior invasion (HR: 4.681, 95% CI: 1.337-16.393, P = 0.016), and subglottic involvement was associated with worse LRRFS (HR: 3.931, 95% CI: 1.054-14.658, P = 0.041). At the same time, we found that involvement of the lamina of cricoid cartilage was an independent risk factor for postoperative laryngeal stenosis in PL patients (HR: 11.67, 95% CI: 1.89-71.98, P = 0.008). CONCLUSION: Selectively performed PL can also achieve favorable oncological outcomes comparable to those of TL. Posterior invasion and subglottic involvement are independent prognostic factors for recurrence after PL in T3 glottic laryngeal cancer, and involvement of the lamina of cricoid cartilage is associated with postoperative laryngeal stenosis. The tumor invasion pattern of patients with laryngeal cancer should be further subdivided to allow for selection of a more individualized treatment plan.

Horizontal middle partial laryngectomy with cricothyroidopexy: an effective treatment for stage T1b glottic carcinoma.

BACKGROUND: The current treatment options for T1b glottic carcinoma often lead to poor treatment outcomes or voice quality. OBJECTIVES: This study evaluates the therapeutic efficacy of horizontal middle partial laryngectomy with cricothyroidopexy (HMPL-CTP) for stage T1b glottic carcinoma. MATERIAL AND METHODS: A retrospective analysis was conducted on 73 patients with T1b glottic carcinoma. The patients were categorized into three groups: Group A (n = 22) underwent transoral laser microsurgery (TLMS), Group B (n = 21) received frontolateral vertical partial laryngectomy (FVPL), and Group C (n = 30) underwent HMPL-CTP. The study analyzed the 5-year overall survival rate (OS), recurrence rate, phonatory status, and incidence of laryngeal stenosis. RESULTS: Voice quality scores varied significantly in the three groups, while the 5-year OS were similar. The local recurrence rate is higher in Group A than in the other two groups. The laryngeal stenosis rate in Group B is higher than in Groups A and C. Adhesions in the anterior commissure were observed in 18 cases in Group A and nine cases in Group C. CONCLUSIONS AND SIGNIFICANCE: HMPL-CTP demonstrates efficacy as a treatment for stage T1b glottic carcinoma, offering favorable preservation of laryngeal function and minimal complications.

Is CO2 laser microsurgery better than radiotherapy in early glottic cancer: a meta-analysis.

The choice between radiotherapy (RT) and CO2 laser surgery (CO2-LS) for early glottic cancer remains controversial. We systematically examined electronic databases in order to identify prospective trials comparing patients who had undergone CO2-LS or RT to treat early glottic cancer. Eleven studies involving 1053 patients were included. In the selected literature, the parameter setting of CO2 laser equipment can be summarized as wavelength 10.6 µm, superpulsed mode, continuous setting, power tailored on target structures (1-3 W for subtle resections and 4-15 W for cutting a larger tumor), and approximately 2080-3900 W/cm2 of laser energy. Using RevMan 5.3, we estimated pooled odds ratios (ORs) for dichotomous variables and pooled mean differences (MDs) for continuous variables, along with associated 95% confidence intervals (CIs). The heterogeneity in the treatment variables was measured using Higgins' inconsistency test and expressed as I2 values. The continuous variables were then depicted as histograms developed using PlotDigitizer 2.6.8. Compared to patients treated with CO2-LS, those treated with RT had better jitter (MD 1.27%, 95% CI 1.21 ~ 1.32, P < 0.001), and high scores on the "Grade (MD 6.54, 95% CI 5.31 ~ 7.76, P < 0.001), Breathiness (MD 9.08, 95% CI 4.02 ~ 14.13, P < 0.001), Asthenia (MD 2.13, 95% CI 0.29 ~ 3.98, P = 0.02), and Strain (MD 3.32, 95% CI 0.57 ~ 6.07, P = 0.02)" scale. Patients treated with CO2-LS had worse local control rates (OR 3.14, 95% CI 1.52 ~ 6.48, P = 0.002) while lower incidence of second primary tumor (OR 0.30, 95% CI 0.15 ~ 0.61, P < 0.001). It is hoped that retrospective analysis can provide suggestions for early glottis patients to choose personalized treatment.

Transcriptional subtypes of glottic cancer characterized by differential activation of canonical oncogenic programming.

BACKGROUND: There is a paucity of data concerning molecular heterogeneity among glottic squamous cell carcinoma, and the clinical implications thereof. METHODS: Data corresponding to glottic squamous cell carcinoma were derived from The Cancer Genome Atlas. The Onco-GPS computational methodology was levied to derive four patterns of transcriptional activity and three functional subtypes of glottic cancer. RESULTS: Thirty glottic cancer samples stratified to three distinct oncogenic states (S0-S2) based on a Onco-GPS model containing four transcriptional components (F0-F3). Membership in S2 and association with transcriptional component F0 conveyed an invasive phenotype, with transcriptional activity strongly reflecting EMT programming (including TGF-B and NF-KB signaling). S2 membership also correlated with inferior disease-specific survival (HR 9.027, 95% CI 1.021-79.767), and higher incidences of extracapsular spread and perineural invasion. CONCLUSIONS: We present a functional taxonomy of glottic cancer, with subtypes demonstrating differential upregulation of canonical oncogenic networks and survival implications.

Real-world evidence for oncological outcomes after radiotherapy or surgery for T1a-T1b glottic squamous cell carcinoma: A population-based cohort study.

BACKGROUND: Compare outcomes after surgery (S) or radiotherapy (RT) for T1a-T1b glottic squamous cell carcinoma (T1GSCC) in a population-based cohort study. METHODS: Patients diagnosed with T1GSCC from 1999 to 2020 were identified from a public database. Clinical, demographic, and social data were extracted. Treatment and patient groups and subgroups were compared with log-rank test, Cox proportional test, and propensity-score matched (PSM). RESULTS: Eight hundred and eighty-eight patients with T1GSCC were included in the study, with a median follow-up of 61 months. The 5- and 10-year overall survival (OS) S versus RT were 76% versus 71% and 60% versus 52% (p = 0.02), respectively. In the subgroup analysis, S was associated with better OS for T1b, male, and public service patients (p < 0.05). In the PSM cohort of S versus RT with 110 patients each, there was no significant difference in the OS, CSS, and LC. CONCLUSIONS: T1GSCC has favorable outcomes with S or RT.

Overview of glottic laryngeal cancer treatment recommendation changes in the NCCN guidelines from 2011 to 2022.

BACKGROUND: The treatment of glottic cancer remains challenging, especially with regard to morbidity reduction and larynx preservation rates. The National Comprehensive Cancer Network (NCCN) has published guidelines to aid decision-making about this treatment according to the tumor site, clinical stage, and patient medical status. AIM: The present review was conducted to identify changes in the NCCN guidelines for glottic cancer treatment made between 2011 and 2022 and to describe the published evidence concerning glottic cancer treatment and oncological outcomes in the same time period. METHODS AND RESULTS: Clinical practice guidelines for head and neck cancer published from 2011 up to 2022 were obtained from the NCCN website (www.NCCN.org). Data on glottic cancer treatment recommendations were extracted, and descriptive analysis was performed. In addition, a review of literature registered in the PubMed database was performed to obtain data on glottic cancer management protocols and treatment outcomes from randomized controlled trials, systematic reviews, and meta-analyses published from 2011 to 2022. In total, 24 NCCN guidelines and updates and 68 relevant studies included in the PubMed database were identified. The main guideline changes made pertained to surgical and systemic therapies, the consideration of adverse features, and new options for the treatment of metastatic disease at initial presentation. Early-stage glottic cancer received the most research attention, with transoral endoscopic laser surgery and radiotherapy assessed and compared as the main treatment modalities. Reported associations between treatment types and survival rates for this stage of glottic cancer appear to be similar, but functional outcomes can be highly compromised. CONCLUSION: NCCN panel members provide updated recommendations based on currently accepted treatment approaches for glottic cancer, constantly reviewing new surgical and non-surgical techniques. The guidelines support decision-making about glottic cancer treatment that should be individualized and prioritize patients' quality of life, functionality, and preferences.

Intensity-Modulated Radiation Therapy for Early-Stage Squamous Cell Carcinoma of the Glottic Larynx: A Systematic Review and Meta-Analysis.

PURPOSE: Early-stage squamous cell carcinoma of the glottic larynx is commonly treated with 2-dimensional or 3-dimensional conventional radiation therapy (CRT). Despite its use in other head and neck cancers, intensity-modulated radiation therapy (IMRT) remains controversial in this patient population. METHODS AND MATERIALS: A systematic review was performed by querying 3 databases (Pubmed, Embase, Web of Science) for articles published between December 1, 2000 and September 2, 2022. Included studies reported outcomes in at least 10 patients treated with IMRT for early-stage glottic cancer. Data were extracted and reported following PRISMA standards. Pooled outcomes were estimated using random-effects models. Primary outcome was the rate of local failure (LF) following IMRT. Secondary outcomes included rates of regional failure (RF) following IMRT and rates of LF and RF following CRT. RESULTS: A total of 15 studies (14 retrospective, 1 prospective) consisting of 2083 patients were identified. IMRT was used in 873 patients (64% T1, 28% T2). Multiple treatment (partial larynx, single vocal cord carotid sparing) and image-guided radiation therapy techniques were used. The pooled crude rate of LF was 7.6% (95% confidence inverval [CI], 3.6%-11.5%) and actuarial LF rates at 3 and 5 years were 6.3% (95% CI, 2.2%-10.3%) and 9.0% (95% CI, 4.4%-13.5%), respectively. The pooled crude rate of RF after IMRT was 1.5% (95% CI, 0.5%-2.5%). On metaregression analysis, increased rate of LF was significantly associated with T2 disease (P < .001) and grade 2 to 3 histology (P < .001). Treatment with CRT was reported in 738 patients (76% T1, 22% T2). Among the studies reporting outcomes of both modalities, there was no significant difference in LF (log odds ratio; P = .12) or RF (log odds ratio; P = .58) between IMRT or CRT. CONCLUSIONS: In patients with early-stage glottic cancer, retrospective data suggests local and regional control are similar for patients treated with IMRT and CRT. Additional prospective studies with uniform methods of volume delineation and image guidance are needed to confirm the efficacy of IMRT.

Predictive value of pathological carcinoma size in patients with T2 glottic laryngeal squamous cell carcinoma.

BACKGROUND: T2N0M0 glottic laryngeal squamous cell carcinoma (LSCC) is a common type of laryngeal cancer. OBJECTIVES: The objective of this research was to assess the predictive value of tumor size for the rates of overall survival (OS) and disease-free survival (DFS) as determined by postoperative pathological examination in patients with T2 LSCC. METHODS: A retrospective study was conducted on 535 successive patients with T2 glottic LSCC who underwent operation from 2005 to 2010. The effect of tumor size on OS and DFS results was evaluated by the affected area. RESULTS: Of the cohort, 528 (98.7%) were male, and 7 (1.3%) were female, with an average age of 60.1 ± 9.4 years. The 10-year DFS and OS rates were 72.1% and 76.3%, respectively. The tumor diameter and area cut-off values that best discriminated OS and DFS rates were 1.35 cm and 1 cm2, respectively. Patients with glottis carcinoma with a longer tumor diameter and larger tumor area had inferior OS and DFS rates. Tumor diameter and tumor area were independent predictive factors for the rates of OS and DFS in patients with T2 glottic LSCC. CONCLUSION AND SIGNIFICANCE: This research showed that patients with T2 glottic LSCC with a carcinoma diameter >1.35 cm or a tumor area >1 cm2 have worse survival outcomes. These factors independently predict survival outcomes in patients.

Early-stage glottic cancer of rare squamous cell carcinoma variants: a population-based study.

BACKGROUND: Squamous cell carcinoma (SCC) is the most common histological type of laryngeal cancer. Several variants of SCC have been reported. However, how these variants differ from conventional SCC and how they should be treated remain to be elucidated. OBJECTIVE: To compare the prognosis of early-stage glottic cancer among SCC variants. METHODS: We obtained data from 12471 cases using the Surveillance, Epidemiology, and End Results database. Disease-specific survival (DSS) and overall survival (OS) rates were estimated using the Kaplan-Meier method. A Cox proportional hazard model was used to estimate hazard ratios (HRs) according to the variants. RESULTS: HRs for DSS and OS compared with well-differentiated SCC were 3.83 and 3.48 for adenosquamous, 1.42 and 1.42 for basaloid, 1.14 and 1.17 for papillary, 0.85 and 0.94 for spindle, and 0.81 and 1.00 for verrucous SCC. The difference in DSS among the treatment modalities was significant in conventional and papillary SCC (p < .001 and p = .032, respectively). CONCLUSIONS: The prognosis of SCC variants, except for adenosquamous SCC, is comparable to that of conventional SCC.

Survival outcomes for patients with T3N0M0 squamous cell carcinoma of the glottis treated with definitive radiation alone versus chemoradiation.

BACKGROUND: Given the poor lymphatics of the glottis, we evaluated omission of chemotherapy in patients treated definitely for T3N0M0 squamous cell carcinoma (SCC) of the glottis. METHODS: We performed survival analysis of patients with T3N0M0 SCC of the glottis identified in the National Cancer Database treated with radiation alone versus chemoradiation. RESULTS: A total of 3785 patients were identified. Patients age ≥70 and those with comorbidities were less likely to receive chemotherapy (odds ratio [OR] 0.30, 95% CI [0.25-0.37] and 0.48 [0.31-0.76], respectively). Five-year OS was lower in patients treated with radiation versus chemoradiation (33.8% [30.3%-37.2%] vs. 58.0% [55.8%-60.0%]). In patients <70 with no comorbidities this difference persisted (51.0% [44.5%-57.0%] versus 66.7% [64.0%-69.3%]). CONCLUSION: Overall survival was higher in patients treated with chemoradiation compared to radiation alone, even when controlling for age and comorbidities. Radiotherapy with chemotherapy omission is not appropriate in patients with T3N0M0 SCC of the glottis.

The role of adjuvant therapy in pT4N0 laryngectomized patients: Multicentric observational study.

BACKGROUND: To retrospectively evaluate oncological outcomes in two groups of patients with pT4aN0 glottic SCC treated with total laryngectomy (TL) and neck dissection (ND) who underwent postoperative radiotherapy or exclusive clinical and radiological follow-up. METHODS: It includes patients with pT4N0 glottic SCC who underwent TL and unilateral or bilateral ND with or without PORT. Divided in two comparison groups: the first group underwent adjuvant RT (TL-PORT); the second group referred to clinical and radiological follow-up (TL). RESULTS: PORT was associated with a better OS while no differences were found in terms of DSS. A better local control is achieved when PORT is administered while no differences in terms of regional and distant control rates were found. Bilateral ND positively impacts on the regional control while the PNI negatively impact the regional control. CONCLUSIONS: A tailored PORT protocol might be considered for pT4N0 glottic SCC treated with TL and ND, both considering the ND's extent and presence of PNI.