Glottic Squamous Cell Carcinoma Research Articles

Pneumatosis Intestinalis Following Surgical Gastrostomy Tube Placement in a Patient With Glottic Squamous Cell Carcinoma: A Case Report

Pneumatosis Intestinalis Following Surgical Gastrostomy Tube Placement in a Patient With Glottic Squamous Cell Carcinoma: A Case Report

Targeting Anterior Commissure Involvement with Hyperfractionated Radiotherapy for T1-T2 Squamous Cell Carcinoma of the Glottic Larynx.

Anterior commissure is involved in about 20% of early-stage glottic squamous cell carcinomas (EGSCCs). Treatment outcomes and prognostic factors for EGSCC with anterior commissure involvement (ACI) were evaluated by focusing on hyperfractionated radiotherapy (74.4 Gy in 62 fractions). One-hundred and fifty-three patients with T1-T2 EGSCC were included in this study. The median total doses for T1a, T1b, and T2 were 66, 74.4, and 74.4 Gy, respectively. Overall, 49 (32%) patients had T1a, 38 (25%) had T1b, and 66 (43%) had T2 disease. The median treatment duration was 46 days. The median follow-up duration was 5.1 years. The 10-year overall and cause-specific survival rates were 72% and 97%, respectively. The 10-year local control rates were 94% for T1a, 88% for T1b, and 81% for T2 disease. Local control rates in patients with ACI were slightly better than those in patients without ACI with T1a and T1b diseases; however, the difference was not significant. The 10-year laryngeal preservation rate was 96%. Six patients experienced grade 3 mucositis, and four patients had grade 3 dermatitis. Hyperfractionated radiotherapy was effective for T1 disease with ACI, but insufficient for T2 disease with ACI. Our treatment strategy resulted in excellent laryngeal preservation.

Oncological outcomes of surgical management for T2N0M0 glottic laryngeal squamous cell carcinoma

AbstractObjectivesThe research aimed to evaluate the clinical treatment outcomes of T2N0M0 glottic laryngeal squamous cell carcinoma (LSCC) patients who underwent laryngectomy.MethodsRetrospective review of 533 T2N0M0 glottic LSCC patients.ResultsFive‐year cancer‐specific survival (CSS) rate was 90.0%, and the overall survival (OS) rate was 89.1%. No statistically difference was found between the patients who have undergone total laryngectomy (5‐year disease‐free survival[DFS] = 80.7%, and the CSS = 86.7%) and those who have had partial laryngectomy (the 5‐year DFS = 85.3%, and CSS = 91.1%). There was no difference in the CSS and DFS rates between patients with negative margins and those with positive margins following postoperative radiotherapy (PORT) ± chemotherapy (the CSS: 90.8% vs. 81.8%, p = 0.458 and 5‐year DFS: 84.6% vs. 79.5%, p = 0.371). Patients who underwent vertical partial laryngectomy (VPL) had better survival (5‐year OS was 91.9%, and the CSS was 92.8%) than those who underwent cricohyoidoepiglottopexy (CHEP) or cricohyoidopexy (CHP) (the 5‐year OS = 83.8%, p = 0.022 and CSS = 84.9%, p = 0.038).ConclusionsSurgery remains the gold standard for treating T2N0M0 glottic LSCC patients because it can achieve satisfactory oncological outcomes. Regarding the systemic conditions, the effect of partial laryngectomy is similar to that of total laryngectomy. Moreover, partial laryngectomy preserves the function of the larynx. VPL may be superior to CHP/CHEP, depending upon the invasiveness of the tumor.

Isoprognostic functional CT map for open partial horizontal laryngectomy.

To identify a radiological map of laryngeal subsites whose involvement by the tumor could predict patients' functional outcomes after open partial horizontal laryngectomy (OPHL). The present retrospective analysis concerned 96 patients with glottic squamous cell carcinoma, who were radiologically staged with contrast-enhanced neck CT scans before undergoing supracricoid or supratracheal laryngectomy. A radiological map of patients' functional risk was developed by considering the distribution of functional outcomes in relation to the laryngeal subsites involved. The functional outcomes considered were: (i) decannulation at discharge; (ii) time to removal of the nasogastric feeding tube (NFT); (iii) postoperative complication rate; and (iv) length of hospital stay. Involvement of the anterior supraglottis was related to a longer need for NFT, and a longer hospital stay (p = 0.003, and p = 0.003, respectively). Involvement of the posterior glottis negatively affected the time to decannulation, and the likelihood of postoperative complications (p = 0.000, and p = 0.002, respectively). Anterior glottic small tumors (without significant subglottic and/or supraglottic extension) are related to the best functional outcomes after OPHL, since the suprahyoid epiglottis and both the arytenoids are likely to be spared.

Measurement and Incorporation of Laryngeal Motion Using cine-MRI on an MR-Linear Accelerator to Generate Radiation Therapy Plans for Early-stage Squamous Cell Cancers of the Glottis

IntroductionSwallow-related motion of the larynx is most significant in the cranio-caudal directions and of short duration. Conventional target definition for radical radiotherapy includes coverage of the whole larynx. This study longitudinally examined respiration- and swallow-related laryngeal motions using cine-MRI. We further analysed the dosimetry to organs at risk by comparing 3D-conformal radiotherapy (3D-CRT), Volumetric-Modulated Arc Therapy (VMAT) and Intensity-Modulated Radiotherapy (IMRT) techniques. MethodsFifteen patients with T1-2 N0 glottic squamous cell carcinomas were prospectively recruited for up to three cine-MRI scans on the Elekta Unity MR-Linear accelerator, at the beginning, middle and end of a course of radical radiotherapy. Swallow frequency and motion of the hyoid bone, cricoid and thyroid cartilages and vocal cords were recorded during swallow and rest. Adapted treatment volumes consisted of GTV + 0.5-1 cm to a CTV with an additional ITV for personalised resting-motion. Swallow-related motion was deemed infrequent and was not accounted for in the ITV. We compared radiotherapy plans for 3D-CRT (whole larynx), VMAT (whole larynx), VMAT and IMRT (ITV for resting motion). ResultsResting- and swallow- motions were most prominent in the craniocaudal plane. There were no significant changes in the magnitudes of motions over the course of radiotherapy. There was a trend for a progressive reduction in the frequency of swallow. Treatment of partial-larynx volumes with intensity-modulated methods significantly reduced the dose to carotid arteries compared to whole-larynx. Robustness analysis demonstrated that when accounting for intra-fraction swallow, the total dose delivered to the ITV/PTV was maintained above 95%. ConclusionsSwallow-related motions are infrequent and accounting for resting motion in an ITV is sufficient. VMAT/IMRT techniques that treat more conformal targets can significantly spare critical organs at risk such as the carotid arteries and thyroid gland, potentially reducing the risk of carotid artery stenosis related and other complications long-term.

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

PurposeThe 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.MethodsRetrospective 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.ResultsIn 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).ConclusionTLM 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.

Patterns of Care for T1 Glottic Squamous Cell Carcinomas from 2004-2020.

Describe recent national trends in overall treatment modalities for T1 glottic squamous cell carcinomas (SCC), and identify factors associated with treatment regimens. National Cancer Database from 2004-2020 was queried for all patients with glottic cT1N0M0 SCC. Treatment patterns over time were analyzed using the Cochran-Armitage test for trend. Multivariable logistic regressions were used to determine the factors associated with treatment regimens. Of the 22,414 patients identified, most patients received RT only (57%), 21% received surgery only, and 22% received dual-modality treatment ("over-treatment"). Over the time period, there was a decreasing trend in rates of over-treatment for T1 glottic SCC (p < 0.001) and an increasing trend in surgery only (p < 0.001). Treatment in 2016-2018 (OR: 1.168 [1.004 to 1.359]), 2013-2015 (OR: 1.419 [1.221 to 1.648]), 2010-2012 (OR: 1.611 [1.388 to 1.871]), 2007-2009 (OR: 1.682 [1.450 to 1.951]), or 2004-2006 (OR: 1.795 [1.548 to 2.081]) versus 2019-2020 was associated with greater likelihood of over-treatment. T1b tumors were less likely to be over-treated (OR: 0.795 [0.707 to 0.894]) versus T1a tumors, and less likely to receive surgery first (OR: 0.536 [0.485 to 0.592]) versus T1a tumors. Over-treatment for T1 glottic SCC has been declining, with increasing rates of surgery only. Year of treatment was significantly associated with the receipt of dual-modality treatment. Finally, patients with T1b disease were more likely to receive RT as the first and only treatment. 3 Laryngoscope, 2024.

ALCAM is a biomarker of tumor aggressiveness and worse prognosis in glottic laryngeal squamous cell carcinoma.

Laryngeal squamous cell carcinoma (LSCC) is the second most frequent head and neck tumor. Prognosis of patients with LSCC has not improved in recent decades, showing a need for the identification of prognostic biomarkers and new therapeutic targets. Recently, we showed that ALCAM overexpression was associated with glottic LSCC prognosis. Aiming to validate the prognostic value of ALCAM, we evaluate the ALCAM protein levels by immunohistochemistry in 263 glottic LSCC surgically treated with neck dissection. ALCAM was expressed in 48.7% and overexpressed in 36.5% of glottic LSCC samples. ALCAM overexpression was associated with lymph node metastasis (p = 0.030), lymphovascular involvement (p = 0.0002), high-grade tumors (p = 0.025), and tumor relapse (p = 0.043). Multivariate survival analyses showed an overfitting between ALCAM overexpression and lymph node metastasis as a prognostic variable. High ALCAM expression was associated with an aggressive glottic LSCC profile.

Prognostic value of preoperative inflammatory ratios in early glottic cancer treated with transoral laser surgery.

There is growing evidence regarding the prognostic utility of ratios such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammatory index (SIII) in head and neck squamous cell carcinoma (HNSCC). However, most studies to date include heterogeneous series with different treatments or tumor subsites. We collected data from 201 patients with stage I-II glottic squamous cell carcinoma treated with transoral laser surgery. NLR, PLR, and SIII were calculated from preoperative cell blood count, cut-off points were obtained by ROC curve analysis, and survival rates were calculated. High NLR (p = 0.012) and SIII (p = 0.037), but not PLR (p = 0.48), were associated with worse disease-specific survival (DSS). A similar trend was observed with overall survival (OS), although it did not reach statistical significance. On multivariable analyses, both high NLR (HR = 3.8, 95% CI = 1.5-9.9, p = 0.006) and high SIII (HR = 2.77, 95% CI = 1.1-6.9, p = 0.03) were significantly associated with shortened DSS. Preoperative NLR and SIII emerge as independent prognostic biomarkers for early-stage surgically treated glottic tumors and could guide individualized follow-up.

A Rare Occurrence of Acute Carotid Blowout Syndrome in Saudi Arabia

Abstract An unfortunate and feared complication of oncologic head-and-neck surgery is acute carotid blowout syndrome (ACBS). We present a rare case of ACBS in a patient who underwent salvage total laryngectomy after treatment with organ-sparing radiochemotherapy. A 62-year-old male with a history of glottic squamous cell carcinoma presented with massive transoral and transnasal bleeding 5 weeks following total salvage laryngectomy. Computed tomography angiography showed aneurysmal bleeding from the right common carotid artery. The active oral and nasal bleeding presentations were not provided with external warning signs of its forthcoming existence. The patient underwent emergent right carotid stenting by an interventional radiologist. Hemostasis was achieved without any neurological deficits. Carotid blowout syndrome prevention by early identification of the risk factors is necessary to prevent fatal hemorrhage or grave neurological morbidity. Early intervention to control bleeding results in significantly lower morbidity and mortality rates.

Management of positive resection margins following transoral laser microsurgery for glottic cancer.

The current literature provides limited guidance on the management of positive margins (PMs) following transoral laser microsurgery (TLM) for glottic squamous cell carcinoma (SCC). Long-term data exploring the treatment of PMs with both initial observation and re-resection are limited. Our objective was to determine the optimal treatment for PM patients following TLM for glottic SCC. Clinical information on glottic SCC patients with PMs following treatment with TLM was prospectively collected at our institution from 2007 to 2018. We use a laryngeal template during the initial TLM where the area of resection is outlined for future reference. Data were compared with univariate analysis and survival plots were generated using the Kaplan-Meier method. A total of 29 patients with PMs were treated with either re-resection (19 patients), close observation (6 patients), or adjuvant radiation alone (4 patients). Re-resection patients had SCC or severe dysplasia on initial margin pathology and 23% with early-stage disease had recurrence (T1-T2). Five (83%) patients who underwent close observation required re-resection based on clinical suspicion of recurrence (confirmed on final pathology), which was significantly different from the re-resection patients (p < .05). Close observation was therefore discontinued as a management of PMs. Four patients (21%) had no residual malignancy on re-resection specimens. Deep margins only accounted for 17% of all PMs. Disease-specific survival for all PM patients at 5 years was 82.4% (SE 9.6%, CI 53.4%-91.6%). Our long-term experience with treating early-stage glottic SCC with TLM supports re-resection as an appropriate management for cases of PMs. 4.

Daily fraction dose-adjusted radiotherapy policy to avoid prolonging the overall treatment time for early glottic squamous cell carcinoma: a single-institutional retrospective study.

The objective of this study was to determine the outcomes of radical radiotherapy for early glottic squamous cell carcinoma (EGSCC) with the policy of increasing the fraction size during radiotherapy when the overall treatment time (OTT) was expected to be prolonged. Patients diagnosed with clinical T1-2N0M0 EGSCC, who were treated with radical radiotherapy between 2008 and 2019 at Hokkaido University Hospital, were included. Patients received 66Gy in 33 fractions for T1 disease and 70Gy in 35 fractions for T2 disease as our standard regimen (usual group [UG]). If the OTT was expected to extend for >1 week, the dose fraction size was increased from 2.0to 2.5Gy from the beginning or during radiotherapy (adjusted group [AG]). At this time, we performed a statistical analysis between UG and AG. In total, 116 patients were identified, and the treatment schedules of 29 patients were adjusted. The median follow-up was 60.9months. In the T1 group, the cumulative 5-year local failure rate was 12.0% in the AG and 15.4% in the UG, and in the T2 group, the rate was 40.7% in the AG and 25.3% in the UG. There were no significant differences between the AG and UG. Similarly, no significant differences were observed for overall survival and progression-free survival rates. Our single-institutional retrospective analysis of EGSCC patients suggested that a method of adjusting the radiotherapy schedule to increase fraction size from the beginning or during the course may be effective in maintaining treatment outcomes.

Contact Endoscopic Surface Vascular and Epithelial Morphology in Leukoplakia and Carcinoma of the Vocal Cords

Purpose Leukoplakia is a macroscopic morphological term for thick white or grey mucosal patches that can represent various histologic diagnostic entities ranging from hyperplasia to malignancy. Aim was the study morphology of the superficial mucosa and microvascular network of the vocal cords in patients with suspected glottic squamous cell carcinoma (SCC) using contact endoscopy (CE). Material and Methods Seventy-nine patients (21 female, 58 male), with a mean age of 57.5 years ± 7.12 (range, 32–73 years), were prospectively enrolled and evaluated. Of these patients, 58 had leukoplakia (Group A/41 males and 17 females, with a mean age of 53.7 years ± 6.65), and 21 (Group B/ 17males and 4 females/ with a mean age of 60.5 years ± 6.04) had malignant lesions (pT1, n = 6; p T2, n = 8; pT3, n = 8; Group B), as proven by the results of the histological examination. Further, 79 non-smokers (control group—group C) were studied. CE imaging findings were classified into five types (I to V) based on the features of the mucosal intra-epithelial capillary loops. CE findings were correlated to the histologic findings. A separate analysis involving smoking status was done. Results The CE-based intraepithelial papillary capillary loop classification score was strongly correlated with the histological findings. Age was strongly associated with both malignancy and bilateral involvement. Smoking habits didn’t significantly differ between patients with unilateral and bilateral SCC. Conclusions CE imaging of the vocal cord mucosal capillaries may be useful for the early detection of glottic SCC and pre-cancerous lesions.

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

There is a paucity of data concerning molecular heterogeneity among glottic squamous cell carcinoma, and the clinical implications thereof. 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. 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. We present a functional taxonomy of glottic cancer, with subtypes demonstrating differential upregulation of canonical oncogenic networks and survival implications.

Socioeconomic position and the pre-diagnostic interval among patients diagnosed with head and neck squamous cell carcinoma - a population-based study from DAHANCA

Background The socioeconomic differences in survival are pronounced for patients diagnosed with head and neck cancer; disease stage at diagnosis is suggested to be a main driver of this association. This nationwide, population-based study investigates socioeconomic differences in the pre-diagnostic interval and disease stage at diagnosis. Material and Methods Information on patient-reported symptoms, symptom onset and disease-specific factors was obtained from the nationwide population-based Danish Head and Neck Cancer Group (DAHANCA) database for patients diagnosed with head and neck squamous cell carcinoma between 2008 and 2019 in Denmark. Socioeconomic position (SEP) was measured by individual-level education, income and cohabitation status obtained from administrative registers. Socioeconomic differences in the interval from symptom onset to diagnosis were investigated in general linear models with 95% confidence intervals (CIs); overall and by subsite, symptom and comorbidity score. Consultation patterns prior to diagnosis were examined using methods for change-point detection. Associations with advanced-stage disease were estimated in logistic regression models. Results Patients with low, medium and high SEP had a similar interval from patient-reported symptom onset to diagnosis of 10 weeks. Although this interval varied according to primary symptom and anatomical subsite, no apparent socioeconomic differences were observed within these subgroups. Aligned with the patient-reported symptom onset, a distinct increase in consultation rates was observed at 9 weeks (95% CI [7.3; 10.7]) for patients with low SEP and 7 weeks (95% CI [4.8; 9.2]) for patients with high SEP, with overlapping CIs. Patients with low compared to high SEP had increased odds for advanced-stage glottic and oral cavity squamous cell carcinoma. For the remaining subsites the association varied according to SEP-indicator and TNM-edition. Conclusion The interval from symptom onset to diagnosis and consultation patterns were similar across SEP groups. Still, socioeconomic differences in stage at diagnosis were observed for some – but not all – subsites.

Oncologic Outcomes of T1–T2N0 Glottic Cancer Treatment: Single Center Experiences of 417 Patients Over 20 Years

Background and Objectives For T1–T2 early glottic cancer, single modality treatment with radiation therapy (RT) or transoral laser microsurgery is the standard therapeutic option. However, the choice between surgery and RT has been debated for decades. Even though patient selection bias for each modality inherently exists in the retrospective study, this study aimed to compare the oncologic outcomes of the actual treatment of these patients between surgery-based treatment and RT.Materials and Method The medical records of 417 patients with T1–T2N0 glottic squamous cell carcinoma were reviewed who were treated at our institution between 1995 and 2014. The patients were divided into two groups; primarily surgery-based treatment (OP, n=209) or RT (n=208).Results In the T1 stage, local failure, overall survival (OS), and disease-free survival (DFS) rates were not different between the OP and RT groups. However, in the T2 stage, the local failure rate was higher in the RT group (p&lt;0.01). OS and DFS were higher in the OP group (p=0.019 and p=0.004, respectively). Larynx-preservation rate was similar in both groups (97.1% and 96.2%, p=0.576). Multivariate analysis showed that age (&gt;65), presence of multiple primary cancer, and treatment modality were significant variables influencing OS and DFS.Conclusion Surgery-based treatment provided better local control rates, DFS, and OS in patients with T1–T2N0 glottic SCC. In the T1 stage, treatment outcomes were similar between OP and RT groups. In the T2 stage, OP showed better results than RT, suggesting that refined strategies are required to improve the oncologic outcomes of RT for T2 glottic cancer.

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

Compare outcomes after surgery (S) or radiotherapy (RT) for T1a-T1b glottic squamous cell carcinoma (T1GSCC) in a population-based cohort study. 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). 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. T1GSCC has favorable outcomes with S or RT.

Programmed death-ligand 1 and tumor-infiltrating lymphocytes (TILs) - low TIL density may predict poorer long-term prognosis in T1 laryngeal cancer.

We evaluated the prognostic role of programmed death-ligand 1 (PD-L1) and tumor-infiltrating lymphocytes (TILs) in T1 glottic laryngeal squamous cell carcinoma (LSCC). T1 glottic LSCC patients (n = 174) treated at five Finnish university hospitals between 2003 and 2013 were included. Tissue microarray (TMA) blocks were used for PD-L1 immunohistochemistry. TILs were scored from intratumoral and stromal regions in whole tissue sections. Of 174 patients, 92 (53%) had negative, 66 (38%) intermediate, and 16 (9%) high PD-L1 levels. Of 80 patients whose TILs were analyzed, 50 (63%) had low and 30 (38%) high stromal TIL density. Patients with a local recurrence or a new primary tumor of the larynx had lower TIL density than had other patients (p = 0.047). High PD-L1 expression with low stromal TIL density was associated with inferior 5-year disease-specific survival (85% vs. 100%, p = 0.02). In conclusion, in patients treated for T1 glottic LSCC, low stromal TIL density was associated with local recurrences and new primary tumors of the larynx. High PD-L1 expression with low stromal TIL density may be associated with worse survival in T1 glottic LSCC.

Association between locoregional failure and NFE2L2/KEAP1/CUL3 pathway mutations in NRG/RTOG 9512: A randomized trial of hyperfractionation vs. conventional fractionation in T2N0 glottic squamous cell carcinoma (SCC).

6054 Background: Radiotherapy (RT) is the primary treatment for patients with T2N0 glottic SCC. ~30% of these patients experience locoregional relapse despite dose escalation. Mutations in the NFE2L2/KEAP1/CUL3 pathway have been linked to radioresistance preclinically and in small retrospective studies. We tested the hypothesis that patients with T2 glottic SCCs having these mutations would show radioresistance and more local (LF) and locoregional failures (LRF) when treated with RT compared to those without, using samples from a phase III trial. Methods: Of 250 randomized patients with T2N0 glottic SCC receiving definitive RT in RTOG 9512, 119 had available biospecimens that were subjected to amplicon-based next generation sequencing (appropriate to low-input DNA from biopsy specimens) to assess for presence of NFE2L2/KEAP1/CUL3 mutations without regard to outcomes. The association between binary mutation status and LF, LRF, disease-free survival (DFS), and overall survival (OS) was assessed using (cause-specific) Cox models (2-sided alpha of 0.05). LR/LRF rates were estimated by the cumulative incidence method and DFS/OS rates by the Kaplan-Meier method. Results: Nineteen of 119 patients (16.0%; 95% confidence interval [CI] 9.4, 22.6) had mutations in the NFE2L2/KEAP1/CUL3 pathway. Patient and tumor characteristics were similar between those with and without mutation.There were 32 LF, 37 LRF, and 80 DFS events, and 52 deaths. Patients with mutation compared to those without had significantly higher LF and LRF rates (Table). Median DFS was 0.9 years (95% CI 0.4, not reached) for the mutation group compared to 4.2 years (95% CI 3.2, 6.4) for those without. The hazard ratio (HR) for DFS was significantly higher for the mutated compared to the non-mutated group in the first 2 years after randomization but declined thereafter (Table), likely due to limited events after 2 years in the mutation group. There was no significant difference in OS between the two groups (HR = 0.76; 95% CI 0.35, 1.6; p = 0.48). Conclusions: NFE2L2/KEAP1/CUL3 pathway mutations may predict radiation treatment failure in T2N0 glottic cancer. They may also be a prognostic biomarker for DFS, but the current evidence supports the harmful effect of these mutations only during the first 2 years from randomization. Clinical trial information: NCT00002727 . [Table: see text]

Clinical Outcome and Survival Analysis of Rigid Carbon Dioxide Transoral Laser Microsurgery in Glottic Squamous Cell Carcinoma of the Larynx

Clinical Outcome and Survival Analysis of Rigid Carbon Dioxide Transoral Laser Microsurgery in Glottic Squamous Cell Carcinoma of the Larynx