Early-stage Glottic Squamous Cell Carcinoma Research Articles

The association between initiation weekday of radiotherapy and local control in stage 1 glottic carcinoma: a retrospective analysis.

Radiotherapy is one of the definitive treatments for head and neck squamous cell carcinoma, especially early-stage glottic squamous cell carcinoma. Although there are several studies on the initiation weekday of cancer treatment, there are very few studies in the radiotherapy field. Thus, the present study investigated whether the initiation weekday of radiotherapy affects the local control rate for stage 1 glottic squamous cell carcinoma. A total of 105 patients with stage 1 glottic squamous cell carcinoma underwent definitive radiotherapy alone between 2007 and 2021. The group in which radiotherapy was started between Monday and Wednesday was compared with the group in which radiotherapy was started on Thursday or Friday. Sixty-seven patients started radiotherapy between Monday and Wednesday and 38 on Thursday or Friday. The 5-year local control rate was 98% (95% confidence interval: 94-100%) in the Monday-Wednesday group and 83% (95% confidence interval: 71-96%) in the Thursday-Friday group, with a significant difference (P = 0.005). On multivariate analysis including age, overall administration time (days), fractionation, irradiation field size and initiation weekday of radiotherapy, no factors other than initiation weekday affecting local control were identified. Radiotherapy toxicity did not differ between the two groups. For stage 1 glottic squamous cell carcinoma, starting radiotherapy on Thursday or Friday is associated with a lower local control rate; therefore, radiotherapy should be started by Wednesday.

Early-stage vocal cord cancer treated with hypofractionated radiotherapy to the larynx with or without concurrent chemotherapy.

We report outcomes among patients with T2 and select T3 glottic squamous cell carcinoma (SCC) treated with radiotherapy. We reviewed T2 and T3 (only paraglottic space invasion) N0 M0 glottic SCC patients treated with curative-intent hypofractionated larynx radiotherapy, with or without concurrent systemic therapy. Of 71 patients, those who received concurrent chemotherapy (23/71; 32%) had worse prognostic factors, including impaired cord mobility (70% vs. 40%, p=0.02) and larger median gross tumor volume (3.0 vs. 1.6cm3 , p=0.003). Over a median follow-up of 3.8 years, 2-year local controlamong patients with impaired cord mobility appeared higher for those who received chemotherapy (88% vs. 61%, p=0.12), but the difference was not statistically significant. Acute and late toxicity rates were not higher among patients who received chemotherapy. The addition of concurrent platinum-based chemotherapy to hypofractionated larynx radiotherapy among patients with early-stage glottic SCC with impaired cord mobility appears safe and worthy of additional investigation.

Have We Made Progress in Early Stage Vocal Cord Cancer with Impaired Cord Mobility?

<h3>Purpose/Objective(s)</h3> The probability of cure after hypofractionated larynx radiotherapy (RT) decreases among patients with T2 glottic cancers with impaired cord mobility. The role of concurrent chemotherapy in this setting is unclear. We report outcomes of patients with T2 (and T3 based on paraglottic space invasion alone) N0 glottic squamous cell carcinoma (SCC) treated with curative-intent hypofractionated larynx RT with or without chemotherapy. <h3>Materials/Methods</h3> We retrospectively reviewed the medical records of all patients with AJCC 8^th edition stage T2-T3 N0 M0 SCC of the glottic larynx treated with curative intent at a single institution between 2000 and 2020. T3 patients were included if they were upstaged by paraglottic space invasion alone. All patients received hypofractionated RT (2.25 Gy/fraction) to the larynx to 63 - 65.25 Gy, with or without concurrent systemic therapy, and had at least 6 months of follow-up. Disease control and survival outcomes were calculated by the Kaplan-Meier method, and we used descriptive analysis to compare prognostic factors since more robust statistics were limited by sample size. <h3>Results</h3> The study population included 71 patients with a median follow-up time of 3.8 (range, 0.1 – 17.2) years. Major 2-year outcomes (95% CI) were as follows: local control, 74% (62% - 83%); regional control, 92% (83% - 97%); laryngectomy-free survival, 70% (58% - 80%); and overall survival, 82% (71% - 90%). Among the 23 patients who received systemic therapy (92% received weekly cisplatin or carboplatin), a greater proportion had impaired mobility (70% vs. 40%, p=0.02), larger median gross tumor volume (3.0 vs 1.6 cc, p=0.003), and subglottic extension (61% vs. 25%, p=0.008). Despite their worse prognostic factors, patients with impaired cord mobility who received chemotherapy experienced better local control and avoided total laryngectomy, without increased toxicity (see Table). One patient (4%) treated with chemotherapy required gastrostomy tube and tracheostomy during RT (both removed within 1 year). All but 6 late grade 3+ adverse events occurred after salvage laryngectomy for local recurrence. There were only 2 isolated regional relapses despite limited use of elective nodal RT (n=2). <h3>Conclusion</h3> The addition of concurrent platinum-based chemotherapy to hypofractionated larynx RT among patients with early-stage glottic SCC with impaired cord mobility appears safe, effective, and worthy of additional investigation.

Early-Stage Glottic Squamous Cell Carcinoma in the Era of Image-Guided Radiotherapy.

Early-stage squamous cell cancer (SCC) of the glottis has a good prognosis. Therefore, patients have long survival outcomes and may potentially suffer from late toxicities of radiotherapy. Radiotherapy with a conventional parallel-opposed-pair or anterior-oblique beam arrangements for stage 1 and 2 glottic SCC have field borders that traditionally cover the entire larynx, exposing organs-at-risk (e.g. carotid arteries, contralateral vocal cord, contralateral arytenoid and inferior pharyngeal constrictor muscles) to high radiation doses. The potential long-term risk of cerebrovascular events has attracted much attention to the dose that carotid arteries receive. Swallow and respiratory motion of laryngeal structures has been an important factor that previously limited reduction of the radiation treatment volume. Motion has been evaluated using multiple imaging modalities and this information has been used to calculate PTV margins for generation of more limited target volumes. This review discusses the current literature surrounding dose-effect relationships for various organs-at-risk and the late toxicities that are associated with them. This article also reviews the currently available data and effects of laryngeal motions on dosimetry to the primary target. We also review the current limitations and benefits of a more targeted approach of radiotherapy for early-stage glottic SCCs and the evolution of CT-based IGRT and MR-guided radiotherapy techniques that may facilitate a shift away from a conventional 3D-conformal radiotherapy approach.

Predictors of Postoperative Radiation Following Laser Resection in Early-Stage Glottic Cancer.

Guideline recommendations for the treatment of early-stage glottic cancer are limited to single-modality therapy with surgery or radiation alone. We sought to investigate the clinicopathologic and treatment factors associated with the use of postoperative radiation therapy (PORT) following laser excision for patients with T1-T2N0 glottic squamous cell carcinoma (SCC). Retrospective observational study of the National Cancer Database. National Cancer Database review from 2004 to 2014. A total of 1338 patients with primary cT1-T2N0M0 glottic SCC undergoing primary laser excision were included. Hospitals were divided into quartiles based on yearly volume of laryngeal laser cases performed. Multivariate logistic regression was performed to identify independent predictors of PORT. The overall rate of PORT was 30.0%. Predictors of PORT included treatment at lower-volume hospitals (adjusted odds ratio [aOR] for quartiles 2-4, 1.32-4.84), positive margins (aOR, 3.83 [95% CI, 2.54-5.78]), and T2 tumors (aOR, 3.58 [95% CI, 2.24-5.74]). PORT utilization demonstrated a strong inverse correlation with hospital volume. Among top-quartile hospitals, the rate of PORT was 11.2%, while rates of PORT at second-, third-, and fourth-quartile institutions were 19.2%, 32.2%, and 37.4%, respectively. Predictors of PORT in multivariable analysis included treatment at lower-volume facilities, positive margins, and T2 disease. This study highlights the importance of treating early-stage glottic carcinoma at high-volume institutions. In addition, there is a need to reevaluate the use of PORT and reduce the rate of dual-modality therapy for patients with early-stage glottic SCC.

Oncological and Surgical Outcomes of Patients Treated by Transoral CO2 Laser Cordectomy for Early-Stage Glottic Squamous Cell Carcinoma: A Retrospective Chart Review

To investigate the feasibility and the outcomes of transoral laser CO2 microsurgery (TLM) for resection of early-stage squamous cell carcinoma (SCC) of the vocal folds through several additional surgical procedures and tips improving the glottic exposure. Retrospective chart review of patients treated by TLM cordectomy in a single European University Hospital for early-stage vocal fold SCCs (Tis, T1a, T1b, and T2). The following TLM outcomes were studied regarding the tumor size (Tis and T1a vs T1b and T2) and the margin status (negative vs positive/suspicious): patient position; type of laryngoscope; requirement to external counter pressure; resection of supraglottic structures (eg, ventricular band, epiglottic petiole, and suprahyoid epiglottis); pre- and postoperative complications; overall survival; disease-specific survival (DSS); and disease-free survival (DFS). A total of 148 patients were included. The TLM was realized in 95.3% of cases. External counter pressure, partial, or total vestibulectomy were necessary in 65.9%, 57.4%, and 4.2% of cases, respectively. A resection of the epiglottic petiole was required in 24.8% of cases. The realization of both epiglottis petiole resection and vestibulectomies were significantly higher in patients with T2 and T1b SCCs compared to those with T1a and Tis SCCs (P = .01). Different procedure tips were described for improving the laryngeal exposition. The 5-year laryngeal preservation rate, DSS, and DFS were significantly better in patients without SCC involvement of the anterior commissure, and did not vary according to the margin status. The laryngeal exposure difficulties did not impact the margin status. The exposure of glottis is possible in 95% of cases of early-stage vocal cord SCC but requires the use of several additional surgical procedures, especially for anterior commissure SCCs. The SCC involvement of the vocal fold anterior commissure is associated with lower DSS, DFS, and laryngeal preservation rate.

Addition of Chemotherapy Is Associated With Decreased Survival in Early-Stage (T1-2N0M0) Glottic Squamous Cell Carcinoma Treated With Definitive Radiotherapy.

The role of chemoradiation (CRT) in treating patients with early-stage glottic squamous cell carcinoma (SCC), especially for T2N0M0 glottic SCC with impaired vocal cord mobility, remains unexplored. We sought to evaluate the impact of CRT on survival in early-stage glottic SCC by using the SEER database. We included patients with localized (T1-4N0M0) glottic SCC (N = 4,743) diagnosed between 2004 and 2014 and treated with definitive radiotherapy (RT) alone, CRT, or laryngectomy alone in the SEER database. Disease-specific mortality (DSM) was evaluated via multivariable regression using a competing risk model that accounts for other-cause mortality as a competing risk event for DSM. One-to-one propensity score matching between CRT and RT cohorts was also performed to facilitate comparison of cumulative DSM and other-cause mortality incidences stratified by T stage. After stratification by T stage, CRT was associated with increased DSM in T1-2N0M0 glottic SCC (adjusted hazard ratios [AHRs], 4.222 and 2.260 for T1 and T2 disease, respectively; P < .001 for both). For T2N0M0 glottic SCC with and without impaired vocal cord mobility, CRT resulted in significantly increased DSM compared with RT alone in both cohorts (AHR, 2.084; P = .046 and AHR, 2.412; P < .001, respectively). After propensity score matching, cumulative incidence plots demonstrated a statistically significant increase in DSM associated with CRT compared with RT alone for both T1 and T2 glottic SCC (P < .001 and P = .003, respectively). CRT for T1-2N0M0 glottic SCC was associated with increased DSM compared with RT alone. This pattern persisted upon further stratification on the basis of vocal cord mobility status for T2N0M0 glottic SCC. This finding warrants careful consideration of chemotherapy in early-stage glottic SCC.

Influencing Factors on Radiotherapy Outcome in Stage I-II Glottic Larynx Cancer-A Multicenter Study.

Background and Purpose: Larynx cancer represents one of the most frequently diagnosed head and neck malignancies, which is most often confined to the glottic area. The aim of this study was to report the oncological outcome and identify prognostic factors in early-stage glottic squamous cell carcinoma treated with radiotherapy.Material and Methods: Patients (n = 761) diagnosed and treated in 10 centers between 1990 and 2015 were retrospectively analyzed. Probabilities of loco-regional control (LRC) and overall survival (OS) were calculated and possible prognostic factors were analyzed using Cox proportional hazards models.Results: The median follow-up was 63 months (range: 2–243). Three hundred and sixty-four, 148 and 249 patients had cT1a, cT1b, and cT2 stage I-II disease, respectively. Five and 10-years LRC/OS rates in the whole cohort were 83/82% and 80/68%, respectively. Three patients developed distant recurrences. In univariate analysis, male sex (HR: 3.49; 95% CI: 1.47–11.37; p < 0.01), T2 vs. T1a (HR: 1.62; 95% CI: 1.08–2.43; p = 0.02) and anterior commissure involvement (ACI) (HR: 1.66; 95% CI: 1.38–2.45; p < 0.01) were associated with impaired LRC. In multivariate analysis, male sex (HR: 3.42; 95% CI: 1.44–11.17; p < 0.01) and ACI (HR: 1.51; 95% CI: 1.01–2.28; p = 0.047) remained poor prognostic factors. No relation of treatment technique and biologically equivalent dose (BED) to oncological outcome was identified except for higher BED10(L = 25; T = 1) yielding better LRC in T1a tumors (p = 0.04) in univariate analyses.Conclusion: Our results highlight the negative impact of ACI on tumor control. A less-expected finding was the impact of sex on tumor control. Further research is needed to validate its prognostic value and investigate any related biologic or behavioral factors, which may be modified to improve oncologic outcome.

Prognostic significance of surgical margins after transoral laser microsurgery for early-stage glottic squamous cell carcinoma

ObjectivesThe impact of positive tumor margin status and other clinicopathological factors on prognosis in early stage glottic squamous cell carcinoma (SCC) treated with transoral laser microsurgery (TLM) remains unclear. This study examined overall survival (OS) rates of patients with positive tumor margin status compared to negative tumor margin status after TLM in clinical T1-2 glottic SCC. Materials and MethodsThe National Cancer Data Base (NCDB) was queried for patients who underwent resection of T1-2 glottic SCC by TLM. Patients were treated from 2004 to 2013. Overall survival was assessed with Kaplan-Meier curve analysis, and univariate and multivariate Cox proportional hazards analysis. Differences in clinicopathologic factors between positive and negative margin groups were compared using Pearson Chi-squared analysis. ResultsOf 747 patients meeting inclusion criteria, 598 (80.1%) had negative margins. Median follow-up time was 48.0 months. Unadjusted 5-year OS for positive margins (80.0%) was lower compared to that of negative tumor margins (82.9%), but this was not statistically significant (P = 0.265). This persisted after multivariate analysis (P = 0.960). When tumors were stratified by T stage (647 T1, 100 T2), unadjusted 5-year OS based on margin status remained statistically insignificant for both T1 (P = 0.933) and T2 tumors (P = 0.350). ConclusionPositive margins did not negatively impact overall survival among patients with TLM-treated early-stage glottic cancer. This finding might be useful clinically in deciding treatment modality for early stage glottic SCC.

Low expression of pRB predicts disease relapse in early glottic cancer treated with transoral laser microsurgery.

To elucidate the associations among the immunohistochemical expression of tumor markers, clinicopathological variables, and disease-free survival (DFS) in patients with early-stage glottic squamous cell carcinoma (SCC) who underwent transoral laser microsurgery (TLM) as the primary treatment. Retrospective chart review. The records of consecutive patients with Tis-T2N0 glottic SCC who underwent TLM between August 1, 2012 and October 31, 2015 were reviewed. Expression of Bcl-2, pRB, p16INK4A , p53, c-Myc, E-cadherin, and EGFR was examined using tissue microarrays containing tumor specimens through immunohistochemistry. Three-year DFS rates were calculated. A total of 65 consecutive patients were identified, of which 28 were excluded due to insufficient tissue (n = 22) and low biomarker quality (n = 6). Therefore, 37 patients with complete records were included. The included patients were significantly older and had a more advanced type of cordectomy than did the excluded patients (P = .015 and .009, respectively). According to the findings of univariate analysis, age, betel quid chewing, type of cordectomy, BCL-2 expression, and pRB expression significantly predicted 3-year DFS. According to the findings of multivariate analysis, age (adjusted hazard ratio: 0.94, 95% CI: 0.88-1.00), betel quid chewing (adjusted hazard ratio: 5.07, 95% CI: 1.32-19.44), and pRB expression (adjusted hazard ratio: 0.02, 95% CI: 0.00-0.28) were independent predictors of 3-year DFS. Low pRB expression is a potential biomarker for predicting disease relapse after primary TLM for early-stage glottic SCC and may help to identify high-risk patients who can subsequently undergo intensive management. 4 Laryngoscope, 129:E220-E226, 2019.

Carotid Artery Sparing With Photon and Proton-Based Radiation Therapy Techniques for Early-Stage Glottic Squamous Cell Carcinoma

Carotid Artery Sparing With Photon and Proton-Based Radiation Therapy Techniques for Early-Stage Glottic Squamous Cell Carcinoma

Early glottic cancer involving the anterior commissure treated by transoral laser cordectomy

Anterior commissure involvement is considered to be a risk factor for poorer outcomes after transoral laser cordectomy (TLC) for early glottic cancer. The objective of this study was to determine the outcomes and relevance of the tumor-node-metastasis (TNM) classification in a large series of patients with early glottic cancer involving the anterior commissure treated by TLC. The clinical and surgical parameters, as well as follow-up results, of the patients treated consecutively for early-stage glottic squamous cell carcinoma involving the anterior commissure (Tis, T1a, T1b, and T2) by transoral CO2 laser cordectomy in an urban academic medical center from January 2001 to March 2013 were analyzed retrospectively. The main outcomes measures were: 5-year disease free survival (DFS), ultimate local control with laser alone, laryngeal preservation, overall-survival (OS) rates, and disease-specific survival (DSS) rates (Kaplan-Meier). Ninety-six patients treated from January 2001 to March 2013 were included. The 5-year DFS and ultimate local control with laser alone rates were 61.7% and 74.4%, respectively. The laryngeal preservation rate was 93.4%; and the OS and DSS rates were 79.2% and 91.5%, respectively. Postoperative T classification (pT) status was not found to be a significant predictor of recurrences, but was predictive of more severe recurrences requiring other treatments than laser. TLC is an effective treatment for early stage glottic cancer involving the anterior commissure. The TNM classification is a relevant prognosis factor for severe recurrences. 4. Laryngoscope, 126:1817-1822, 2016.

FADD Expression as a Prognosticator in Early-Stage Glottic Squamous Cell Carcinoma of the Larynx Treated Primarily With Radiotherapy

We recently reported on the identification of the Fas-associated death domain (FADD) as a possible driver of the chromosome 11q13 amplicon and the association between increased FADD expression and disease-specific survival in advanced-stage laryngeal carcinoma. The aim of this study was to examine whether expression of FADD and its Ser194-phosphorylated isoform (pFADD) predicts local control in patients with early-stage glottic carcinoma primarily treated with radiotherapy only. Immunohistochemical staining for FADD and pFADD was performed on pretreatment biopsy specimens of 92 patients with T1-T2 glottic squamous cell carcinoma primarily treated with radiotherapy between 1996 and 2005. Cox regression analysis was used to correlate expression levels with local control. High levels of pFADD were associated with significantly better local control (hazard ratio, 2.40; 95% confidence interval, 1.04-5.55; p = 0.040). FADD overexpression showed a trend toward better local control (hazard ratio, 3.656; 95% confidence interval, 0.853-15.663; p = 0.081). Multivariate Cox regression analysis showed that high pFADD expression was the best predictor of local control after radiotherapy. This study showed that expression of phosphorylated FADD is a new prognostic biomarker for better local control after radiotherapy in patients with early-stage glottic carcinomas.