Hypofractionated radiotherapy versus conventional radiotherapy in early glottic cancer T1-2N0M0: A randomized study.

OBJECTIVE: Glottic cancer has an excellent probability of cure. The early glottic cancer is usually treated by radiotherapy with different fractionation schedules. The aim of this study was to compare conventional versus hypofractionated radiotherapy with respect to overall survival and disease-free survival. MATERIALS AND METHODS: A total of fifty patients with T1-2N0M0 glottic cancer with no previous treatment history were prospectively randomized into two arms. In Arm A (Study), patients received a total of 55 Gy in 20# at 2.75 Gy/#, 5 days a week. In Arm B (Control), patients received a total of 66 Gy in 33# at 2 Gy/#, 5 days a week. Disease response was evaluated by the WHO criteria at the end of treatment, then at 1, 2, and 3 months to complete their 6-month follow-up. Overall survival and disease-free survival were evaluated at 1, 2, and 3 years. RESULTS: Overall, 100% of patients in the study arm and 96% of patients in the control arm had complete response after 6 months. Overall survival rates at 1, 2, and 3 years were 96%, 96%, and 88%, respectively, in the study arm, while in the control arm, these values were 92%, 84%, and 80%, respectively, and the difference was not statistically significant (P > 0.05). Disease-free survival at 3 years was 88% in the study arm and 80% in the control arm. CONCLUSION: The study suggests that hypofractionated regimen may be better in local control and symptomatic relief with the added advantage of shorter treatment time, which offers better patient compliance and advantageous in busy setups where there is heavy patient load.

Laser Microsurgery Versus Radiotherapy Versus Open Partial Laryngectomy for T2 Laryngeal Carcinoma: A Systematic Review of Oncological Outcomes.

INTRODUCTION: The aim of the current systematic review is to update the pooled survival outcome of patients with T2 glottic carcinoma treated with either laser surgery (CO2 transoral laser microsurgery [CO2 TOLMS]), radiotherapy (RT), or open partial laryngectomy (OPL). METHODS: A systematic search was performed using the MEDLINE database, Scopus, and Google scholar. The inclusion criteria were studies of patients with T2N0 glottic tumor, treated with either primary CO2 TOLMS, definitive curative RT, or primary OPL, and with reported oncological outcome at 5 years calculated with a Kaplan-Meier or Cox regression method. RESULTS: The results of the current review show that local control (LC) is higher with OPL 94.4%, while there are no differences in LC at 5-year posttreatment for patients treated with RT, compared to those treated with CO2 TOLMS (respectively, 75.6% and 75.4%). Primary treatment with OPL and CO2 TOLMS results in higher laryngeal preservation than primary treatment with RT (respectively 95.8%, 86.9%, and 82.4%). CONCLUSION: First-line treatment with OPL and CO2 TOLMS should be encouraged in selected T2 patients, because it results in higher laryngeal preservation and similar LC compared to primary treatment with RT. The involvement of the anterior commissure in the craniocaudal plane and T2b impaired vocal cord mobility have a poorer prognosis and LC compared to patients with T2a tumors for both CO2 TOLMS and RT.

Evaluating different radiotherapy treatment plans, in terms of critical organ scoring index, conformity index, tumor control probability, and normal tissue complication probability calculations in early glottic larynx carcinoma.

PURPOSE: In this study, it is aimed to compare three different radiotherapy treatment planning techniques in terms of critical organ scoring index (COSI), two different conformity index (CI), tumor control probability (TCP), and normal tissue complication probability (NTCP) calculations in early (T1) glottic larynx carcinoma (T1GL). Furthermore, it is aimed to investigate these parameters compliance with dose-volume histograms (DVH) parameters. MATERIALS AND METHODS: Ten T1GL patients were immobilized in a supine position with a head and neck thermoplastic mask. Treatment plans were created with opposed lateral fields (OLAFs) and intensity-modulated radiation therapy (IMRT) techniques with a total dose of 66 Gy in 33 fraction with 2 Gy/day. IMRT fields were selected as five fields (5IMRT) and seven fields (7IMRT). Dosimetric evaluation of three different treatment plans for T1GL carcinoma was performed in two consequential steps. First step was the assessment of planning target volume (PTV), all organs at risks (OARs), and normal tissue (NT) dose calculations according to given dose constraint directions and comparing the plans via DVH. In the second step, for PTV, the compatibility of DVH data with CIs-TCP was investigated where COSI-NTCP was compared with DVH for OARs. The DVH data were considered as reference in all evaluations. RESULTS: The CIRTOG mean values were significantly closer to 1 with IMRT plans when compared to OLAF plans (P = 0.005). The CIPADDICK mean values revealed that OLAF plans were significantly worse than IMRT plans (P = 0.005). No statistically significant difference was found between all three plans in terms of homogeneity index mean values (P = 0.076). The calculated mean TCP values were significantly better for 7IMRT plans when compared to OLAF and 5IMRT plans (P = 0.007 and P = 0.017, respectively). Both NTCP and COSI evaluations, which is compatible with DVH, significantly favored OLAF plan for spinal cord and 7IMRT for thyroid gland. The COSI evaluations, which are compatible with DVH, significantly favored 7IMRT plan for carotid arteries and 5IMRT plan for NT. CONCLUSION: Our results demonstrated that CIPADDICK-TCP calculations for PTV and COSI-NTCP calculations for OARs were compatible with DVH in T1 GL plans. Therefore, we suggest such parameters as valuable tools for choosing the feasible one among multiple plans and even with different treatment machines.

Hypofractionation vs. conventional radiotherapy fractionation in the conservative treatment of T1 glottic cancer: a prospective cohort study.

BACKGROUND: Definitive radiotherapy is an effective single-modality in T1 glottic cancer. Hypofractionated schemes could offer excellent results in a shorter treatment period. We aimed to evaluate the clinical outcomes and toxicity comparing conventional vs. hypofractionated radiotherapy treatment in T1N0M0-glottic cancer. PATIENTS AND METHODS: Between Jan-1st, 2005 and August-1st, 2017, in a prospective cohort study, with 10-year follow-up, 138 patients were treated with conventional schedule 2 Gy/day, total dose 70 Gy/7 weeks (N = 71) or hypofractionated schedule 2, 2-2, 25 Gy/day, total dose 63, 8-63 Gy/5, 5 weeks (N = 67). Endpoints were clinical-response rate, local relapse-free survival (LRFS), laryngectomy-free survival (LFS), toxicity rates, relapse-free survival (RFS), metastasis-free survival (MFS), second tumour-free survival (2TFS), and overall survival (OS). RESULTS: All patients showed a complete clinical response. No differences were found for LRFS (p = 0.869), LFS (p = 0.975), RFS (p = 0.767), MFS (p = 0.601), 2TFS (p = 0.293), or OS (p = 0.685). Acute toxicity for skin and mucosae was similar (p = 0.550 and p = 0.698). Acute laryngeal toxicity was higher in the hypofractionation group (p = 0.004), due to an increase in slight moderate grade. No differences in late laryngeal edema were found (p = 0.989). CONCLUSION: Radiotherapy offers high rate survival, local control, and larynx preservation after 5-10-year follow-up. A hypofractionation could be preferable, since it offers the same results as conventional with fewer treatment sessions.

Factors affecting voice quality in early glottic cancer before and after radiotherapy.

Background Radiotherapy (RT) is a successful mode of treatment for early glottic cancer. The aim of the study was to assess voice quality both before and 3 months after successful RT using multimodal methods while also identifying the factors affecting it. Patients and methods In 50 patients with T1 glottic carcinoma, the subjective (patients' assessment of voice quality [VAS], Voice Handicap Index [VHI] questionnaire, phoniatricians' assessment using the grade/roughness/ breathiness [GRB] scale), and objective assessments (fundamental laryngeal frequency [F0], jitter, shimmer, maximum phonation time [MPT]) of voice quality were performed before RT and 3 months post-RT. The data on gender, age, extent of the tumors, biopsy types, smoking, local findings, and RT were obtained from the medical documentation. Results Three months after the treatment, VAS, VHI, G and R scores, F0, and MPT significantly improved in comparison with their assessment prior to treatment. Before the treatment, the involvement of the anterior commissure significantly deteriorated jitter (p = 0.044) and the involvement of both vocal folds deteriorated jitter (p = 0.003) and shimmer (p = 0.007). After the RT, F0 was significantly higher in the patients with repeated biopsy than in the others (p = 0.047). In patients with post-RT changes, the B score was significantly higher than in those without post-RT changes (p = 0.029). Conclusions Voice quality already significantly improved three months after the treatment of glottic cancer. The main reason for the decreased voice quality prior to treatment is the tumor's extent. Post-RT laryngeal changes and repeated biopsies caused more scarring on vocal folds adversely influencing voice quality after the treatment.

Prognostic factors in patients with T1 glottic cancer treated with radiotherapy.

PURPOSE: Presentation of long-term results of radiation treatment in patients with T1 glottic cancer and evaluation of prognostic factors. METHODS: We performed a retrospective analysis in a group of 569 patients with T1 squamous cell glottic carcinoma treated with radiotherapy at the Center of Oncology in Cracow between 1977 and 2007. In all, 503 (88%) patients presented with T1a stage disease and 66 (12%) with T1b. Anterior commissure infiltration was present in 179 (31%) patients. Average hemoglobin level prior to therapy was 13.9 g/dl. Using the body mass index (BMI), 114 (20%) patients were underweight, and 91 (16%) were overweight. Median time between collecting tumor specimen and beginning of radiotherapy was 56 days (range 14-145 days). Treatment regimen was normofractionated with single fraction ≤2 Gy in 102 (18%) and hypofractionated in 467 (82%) patients. RESULTS: The 5­ and 10-year overall survival (OS), disease-specific survival (DSS) and local control (LC) rates were 85 and 68%, 88 and 86%, 89 and 87%, respectively. Multivariate analysis showed that tobacco smoking, low hemoglobin level (<13 g/dl), anterior commissure infiltration, fraction dose ≤2 Gy and time from collecting specimen to beginning of therapy longer than 30 days had negative impact on LC and DSS. Patients' age over 60 years, worse performance status and malnutrition (BMI <18.5) had negative impacts on OS. CONCLUSIONS: Radiotherapy is a highly effective treatment method in patients with T1N0M0 glottic cancer. LC and DSS may be improved following hypofractionation, smoking cessation, and shortening of waiting-time until start of treatment. OS was mainly influenced by nutritional and performance status.

Volumetric modulated arc therapy with robust optimization for larynx cancer.

PURPOSE: The aim of this study was to perform a comparison between robust optimization and planning target volume (PTV)-based optimization plans using volumetric modulated arc-therapy (VMAT) by evaluating perturbed doses induced by localization offsets for setup uncertainties in larynx cancer radiation therapy. METHODS: Ten patients with early-stage (T1-2N0) glottis carcinoma were selected. The clinical target volume (CTV), carotid arteries, and spinal cord were contoured by a radiation oncologist. PTV-based and robust optimization plans were normalized at D50% to the PTV and D98% to the CTV, respectively. Both optimization plans were evaluated using perturbed doses by specifying user defined shifted values from the isocenter. CTV dose (D98%, D50%, and D2%), homogeneity index (HI) and conformity index (CI95%, CI80%, and CI50%), as well as doses to the carotid arteries and spinal cord were compared between PTV-based and robust optimization plans. RESULTS: The robust optimization plans exhibited superior CTV coverage and a reduced dose to the carotid arteries compared to the PTV-based optimization plans (p < 0.05). HI, CI95% and the dose to the spinal cord did not significantly differ between the PTV-based and robust optimization plans (p > 0.05). The robust optimization plans showed better CI80% and CI50% compared to the PTV-based optimization plans (p < 0.05). Plan perturbed evaluations showed that the robust optimization plan has small variations in the doses to the CTV, carotid arteries, and spinal cord compared to the PTV-based optimization plan. CONCLUSIONS: The robust optimization plan may be a suitable treatment method in radiotherapy for larynx cancer patient.

Efficacy of laser surgery versus radiotherapy for treatment of glottic carcinoma: a systematic review and meta-analysis.

Laser surgery and radiotherapy are the two most common ways to treat glottic carcinomas, which is more efficacious and remains controversial. PubMed, Embase, and Cochrane Library were searched to identify relevant studies of laser surgery versus radiotherapy in patients with glottic carcinomas through April 2017. Sensitivity analysis and subgroup analysis were performed to evaluate heterogeneity. Eighteen studies were selected, which included 2480 patients. Patients who had laser surgery had higher rates of laryngeal preservation (OR 3.852; 95% CI 1.922-7.721) and overall survival (OR 1.388; 95% CI 1.063-1.811) versus who had radiotherapy. No significant differences were observed between laser surgery and radiotherapy on local control (OR 1.186; 95% CI 0.759-1.854), recurrence (OR 0.758; 95% CI 0.445-1.289), or disease-specific survival (OR 1.597; 95% CI 0.887-2.876). There were clinical benefits for patients with glottic carcinoma after laser surgery compared with radiotherapy with respect to survival and laryngeal preservation.

Long-term Voice Outcome Following Radiation Versus Laser Microsurgery in Early Glottic Cancer.

OBJECTIVES: Long-term voice outcome (LTVO) after radiation (XRT) or trans-oral laser microsurgery (TLM) is unclear. This study is a multi-modality analysis of LTVO following XRT or TLM in patients with early glottic cancer. We hypothesize that as compared with TLM, LTVO is worse in the XRT group because of progressive fibrosis in the glottic tissue MATERIAL AND METHODS: One hundred and two patients with early glottic carcinoma (carcinoma in situ, T1, T2) were included. Multi-modality voice analyses were performed with self-perception using Voice Handicap Index-10, objective analysis using Analysis of Dysphonia in Speech and Voice Software (Cepstral Spectral Index of Dysphonia score for Consensus Auditory-Perceptual Evaluation of Voice sentences), and perceptual rating by two blinded speech language pathologists (GRBAS scale). RESULTS: Fifty-five patients received TLM (mean follow-up = 52 months) and 47 patients had XRT (mean follow-up = 65 months). There is no difference between the two groups in sex, age, stage, and follow-up time. Intraclass correlation coefficient between raters was high at 0.94. Controlling for age and stage, XRT increases total GRBAS score by 1.38 points (P = 0.006) and increases Cepstral Spectral Index of Dysphonia score by 13.7 points (P < 0.001) when compared with the TLM group. No significant differences were found in the Voice Handicap Index score between the XRT and the TLM groups. CONCLUSIONS: This is the first multi-modality voice analysis to suggest TLM results in better LTVO than XRT in GRBAS score and objective voice analysis but not in self-perception. These differences may reflect the progressive effects of XRT on glottic tissue. A randomized controlled study is required to confirm our findings.

Treatment of early-stage laryngeal cancer: A comparison of treatment options.

Over the course of the last several decades, the treatment options for early laryngeal cancers (T1 and T2) have evolved; however, simultaneously the mortality rate has increased. As larynx preservation approaches have become the standard of care, the selection of the proper treatment modality has become paramount. Radiation therapy or transoral laser microsurgery are the most common options for treatment of these early lesions. Oncologic and functional outcomes are considered equivalent between the two modalities for early glottic cancers; however, no direct comparisons exist for robust analysis. In terms of larynx preservation, there also is not compelling data favoring one treatment option or another. For early stage lesions, the goal for any larynx-sparing technique, either radiation or surgery, should be the intent to cure with single modality treatment and minimal short- and long-term toxicity. This article is designed to create a frame of reference for managing early stage disease with respect to lesions of the glottis and supraglottis while weighing treatment implications from an oncologic, functional, and cost perspective.

Comparison between transoral laser surgery and radiotherapy in the treatment of early glottic cancer: A systematic review and meta-analysis.

A therapeutic decision in the treatment of Tis/T1a glottic carcinoma with radiotherapy (RT) or transoral laser surgery (TOS) is still an open issue. Oncologic outcome and voice quality may support the choice for the latter To conduct a systematic review and meta-analysis to compare oncologic and functional outcomes of TOS and RT as treatment options for Tis/T1a glottic cancer. Literature research on online databases was carried out. Potentially eligible articles were reviewed. Relevant articles were selected and evaluated. There was statistical significance favoring patients initially treated with TOS when it comes to overall survival, disease-specific survival and larynx preservation. No difference in local control was found. TMF, Jitter and Shimmmer measurements presented statistically significant results in favor of RT. Self-assessment of voice quality (VHI) and f0 showed no statistically significant differences. Maximum Phonation Time (MPT) had a better response to RT. There is a trend in favor of RT. Tis/T1a glottic cancer patients submitted to TOS had significant overall and disease specific survival and had fewer risks of having a total laryngectomy, when compared to the radiotherapy group. The self-assessment of voice quality and f0 did not show any difference; however, Jitter, Shimmer and MPT measurements favored radiotherapy.

Treatment of early stage Supraglottic squamous cell carcinoma: meta-analysis comparing primary surgery versus primary radiotherapy.

OBJECTIVES: For early stage supraglottic squamous cell carcinoma (SCC), single modality treatment either in the form of primary organ preservation surgery alone or radiation alone is recommended. Thus, a definite treatment strategy for early stage supraglottic SCC remains undefined. The primary objective of this study was to conduct a systematic review and meta-analysis comparing the oncologic outcomes of surgery and radiotherapy in early stage (Stage I and II) T1 N0 and T2 N0 supraglottic SCC. METHODS: Systematic methods were used to identify published and unpublished data. Two reviewers independently screened all titles, abstracts and articles for relevance using predefined criteria. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. RESULTS: Five studies met the inclusion criteria for disease specific mortality with a total of 2864 pooled patients. 5-year disease specific mortality was lower in the surgery group (ORs 0.43, 95% CI 0.31-0.60). Four studies met the inclusion criteria for 5-year overall mortality with a total of 2790 pooled patients. Five-year overall mortality was lower in surgery group (ORs 0.40, 95% CI 0.29-0.55). CONCLUSIONS: This is the first study to examine the management of early stage supraglottic SCC using meta-analytic methodology. Our results suggest that primary surgery may result in decreased disease specific and overall mortality compared to primary radiotherapy.

Oncologic and functional outcomes of patients treated with transoral CO2 laser microsurgery or radiotherapy for T2 glottic carcinoma: a systematic review of the literature.

PURPOSE OF REVIEW: To give an overview of the laryngeal preservation and functional outcomes of patients treated with transoral CO2 laser microsurgery (TLM) or radiotherapy for T2 glottic carcinoma. This information supports physicians and patients in treatment counselling and choices. RECENT FINDINGS: A recent systematic review showed that local control rates at 5-year did not differ between radiotherapy and TLM for T2 glottic tumours. However, there is a lack of comparative data on laryngeal preservation as well as functional outcomes in T2 glottic carcinoma. SUMMARY: Laryngeal preservation for T2 tumours in this review is higher for patients treated primarily with TLM (88.8 vs. 79.0%). It is important to differentiate between tumours with normal and impaired mobility (T2a and T2b) because the latter showed poorer prognosis for both TLM and radiotherapy. Involvement of the anterior commissure does not result in significantly lower oncological results, if adequately staged and treated. More studies are needed to support these data and to compare the functional outcomes between TLM and radiotherapy for T2 glottic carcinoma.

Characteristics of speech production in patients with T1 glottic cancer who underwent laser cordectomy or radiotherapy.

PURPOSE: Laser cordectomy (LC) or radiotherapy (RT) is often recommended in the early stage of laryngeal cancer. We conducted perceptual and acoustic analysis to compare sustained vowel and stop consonants since there is no article evaluating both the sustained vowel and stop consonants. Eventually, we might determine which management is superior in terms of speech production. SUBJECTS AND METHODS: A total of 28 patients who underwent LC and RT for early T1 glottic cancer were selected. The sustained vowel /a/ and bilabial stop consonants were used to assess the perceptual scores. The fundamental frequency (Fo), jitter, shimmer and noise-to-harmonic ratio (NHR) levels for sustained vowels were evaluated. Voice onset time (VOT), vowel duration (VD) and closure duration of the bilabial plosives were analyzed. A receiver operating characteristic curve analysis was used to evaluate significant results statistically. RESULTS: The GRBAS and discrimination scores were not significantly different between two groups. Fo and jitter were significantly higher in the LC than RT. The cut-off value was statistically higher in the LC group and statistically lower in the RT group. The VOT was significantly longer in the LC than RT. The cut-off value of the /pipida/ VOT was statistically longer in the LC group and statistically shorter in the RT group. CONCLUSIONS: The differences may have been due to muscular fibrosis after RT. Movements of vocal cords with fibrosis were sluggish, when impulsion developed to pronounce the initial /p/ sound, so the VOT was shortened and the VD was longer after RT.

Voice Outcomes after Radiotherapy Treatment for Early Glottic Cancer: Long-Term Follow-Up.

OBJECTIVES: The aim of this study was to investigate long-term voice outcomes and voice-related quality of life (QOL) for early glottic cancer treated with radiotherapy. STUDY DESIGN: Long-term exploratory follow-up study of a prospective patient cohort comparing outcomes at a mean of 11 years postradiotherapy with the original 1-year posttreatment results. METHOD: Eight patients completed voice tasks for auditory perception and acoustic and aerodynamic measures. Patient-reported voice-related QOL (VR-QOL) and voice quality were measured. Changes in outcomes over time were analysed using repeated-measures linear mixed models. RESULTS: Acoustic and aerodynamic outcomes remained stable from 1 year postradiotherapy to long-term follow-up, with only jitter mildly increasing from 1.9% at 1 year posttreatment to 2.8% (difference = 1.0%, 95% confidence interval [CI] = 0.1-1.9). Perceptually, voice remained relatively stable with only phonation breaks slightly increasing within the normal range, from 1.1 to 1.7 (difference = 0.6, 95% CI = 0.3-0.9) and breathy quality increasing from normal to slight impairment, with scores increasing from 1.8 to 2.4 (difference = 0.6, 95% CI = 0.3-1.1). QOL scores indicate a good level of VR-QOL that were unchanged at long-term follow-up when compared with 1 year posttreatment. CONCLUSIONS: Improvement in voice outcomes found at 1 year postradiotherapy were largely maintained long term, with only minor changes observed. QOL scores indicate that a high level of VR-QOL was maintained many years after curative radiotherapy.

Conventional fractionation should not be the standard of care for T2 glottic cancer.

BACKGROUND: The aim of this study was to report outcomes and late toxicity following hypofractionated accelerated radiotherapy for T2 glottic cancers. We highlight the importance of hypofractionated treatments with shorter overall treatment times, in improving outcomes for T2 glottic cancers. We also compare the biologically effective dose of hypofractionated regimes, with conventional fractionation. METHODS: One hundred twelve patients with T2 glottic cancer were treated between January 1999 and December 2005. All patients were prescribed a hypofractionated accelerated radiotherapy dose of 52.5 Gray in 3.28 Gray per fraction, delivered over 22 days. Radiobiological calculations were used to assess the relationship of fraction size and overall treatment time on local control outcomes and late toxicity. RESULTS: The 5-year overall survival was 67%, the 5-year local control was 82%, and the 5-year disease-specific survival was 90%. The respective 5-year local control for T2a and T2b disease was 88.8 and 70.8% (p = 0.032). Severe late toxicity occurred in two patients (1.8%). Radiobiological calculations showed an increase in local control of nearly 12%, with a 10 Gray increase in biologically effective dose. CONCLUSION: This study has demonstrated that accelerated hypofractionated regimes have improved local control and similar late toxicity compared with conventional fractionation schedules. This supports the use of hypofractionated regimes as the standard of care for early glottic laryngeal cancers.

WRAP53ß, survivin and p16INK4a expression as potential predictors of radiotherapy/chemoradiotherapy response in T2N0-T3N0 glottic laryngeal cancer.

The current treatment recommendation for T2-3N0M0 glottic squamous cell carcinoma (SCC) in the Nordic countries comprises of radiotherapy (RT) and chemoradiotherapy (CRT). Tumor radiosensitivity varies and another option is primary surgical treatment, which underlines the need for predictive markers in this patient population. The aim of the present study was to investigate the relation of the proteins WRAP53ß, survivin and p16INK4a to RT/CRT response and ultimate outcome of patients with T2-T3N0 glottic SCC. Protein expression was determined using immunohistochemistry on tumors from 149 patients consecutively treated with RT or CRT at Helsinki University Hospital, Karolinska University Hospital, and Linköping University Hospital during 1999-2010. Our results demonstrate a significantly better 5-year relapse-free survival, disease-free survival (DFS), disease-specific survival and overall survival of patients with T3N0 tumors treated with CRT compared with RT alone. Patients with tumors showing a cytoplasmic staining of WRAP53ß revealed significantly worse DFS compared with those with nuclear staining. For survivin, we observed a trend towards better 5-year DFS in patients with strong nuclear survivin expression compared with those with weak nuclear survivin expression (p=0.091). Eleven (7%) tumors showed p16 positivity, with predilection to younger patients, and this age group of patients with p16-positive SCC had a significantly better DFS compared with patients with p16-negative SCC. Taken together, our results highlight WRAP53ß as a potential biomarker for predicting RT/CRT response in T2-T3N0 glottic SCC. p16 may identify a small but distinct group of glottic SCC with favorable outcome. Furthermore, for T3N0 patients better outcome was observed following CRT compared to RT alone.

Hypofractionated Radiotherapy for Patients with Early-Stage Glottic Cancer: Patterns of Care and Survival.

Background: Radiotherapy alone is often used to treat early-stage glottic cancer (ESGC); however, the optimal radiation treatment schedule remains unknown. The National Comprehensive Cancer Network (NCCN) guidelines recommend both hypofractionated radiotherapy (HFX) and conventionally fractionated radiotherapy (CFX). We compared overall survival (OS) and treatment patterns among patients treated with HFX vs CFX for ESGC using a large national database. Methods: We identified patients diagnosed with stage I-II (cT1-2N0M0) glottic cancer from 2004 to 2013 within the National Cancer Data Base who were treated with either HFX (2.25 Gy/fraction to 63-65.25 Gy) or CFX (2.0 Gy/fraction to 66-70 Gy). The overall survival of patients receiving HFX vs CFX was compared using the log-rank test, multivariable Cox proportional hazards regression, and propensity score matching. All statistical tests were two-sided. Results: Among 10 212 included patients, 4030 patients (39.5%) received HFX and 6182 patients (60.5%) received CFX. Predictors for receipt of HFX included clinical T1 disease, recent year of diagnosis, and treatment at academic and higher-volume centers (all P < .001). Patients treated with HFX increased from 22.1% in 2004 to 58.0% in 2013. HFX was associated with improved OS compared with CFX on univariate (five-year OS = 77.1%, 95% CI = 75.2% to 78.8%, vs 73.5%, 95% CI = 72.1% to 74.8%, respectively, log-rank P < .001) and multivariable analysis (HR = 0.89, 95% CI = 0.81 to 0.98, P = .02), a finding confirmed on propensity score matching. Conclusions: HFX is associated with improved survival compared with CFX among patients treated with definitive radiotherapy for ESGC, particularly among patients with cT2 disease. HFX utilization increased over the study period; however, 40% of patients in our cohort did not receive HFX in the most recent year of our analysis.

T1-2 glottic cancer treated with radiotherapy and/or surgery.

BACKGROUND: The optimal treatment strategy for stage I-II glottic squamous cell carcinoma (SCC) is not well-defined. This study analyzed treatment results and prognostic factors. PATIENTS AND METHODS: This is a single-institution retrospective analysis of 244 patients with T1-2 glottic SCC who underwent normofractionated radiotherapy (RT) and/or surgery between 1990 and 2013. The primary endpoint was relapse-free survival (RFS). RESULTS: Median age was 65 years (range: 36-92 years), the majority (82%) having stage I disease. Definitive RT was used in 82% (median dose: 68 Gy, 2 Gy per fraction). Median follow-up was 59 months. The 5­year RFS rates were 83 and 75% (p = 0.05) for stage I and 62 and 50% (p = 0.47) for stage II in the RT and surgery groups, respectively. Multivariate analyses indicate T1 vs. T2 and RT vs. surgery as independent prognostic factors for RFS, with hazard ratios of 0.38 (95% confidence interval, CI: 0.21-0.72) and 0.53 (95% CI: 0.30-0.99), respectively (p < 0.05). The 5­year overall and cause-specific survival rates in the whole cohort were 92 and 96%, respectively, with no significant differences between treatment groups. Anterior commissure involvement was neither a prognostic nor a predictive factor. The incidence of secondary malignancies was not significantly different between patients treated with and without RT (22 vs. 9% at 10 years, respectively, p = 0.18). CONCLUSION: Despite a possible selection bias, our series demonstrates improved RFS with RT over surgery in stage I glottic SCC.

SBRT for early-stage glottic larynx cancer-Initial clinical outcomes from a phase I clinical trial.

PURPOSE: To confirm safety and feasibility of hypofractionated SBRT for early-stage glottic laryngeal cancer. METHODS: Twenty consecutive patients with cTis-T2N0M0 carcinoma of glottic larynx were enrolled. Patients entered dose-fractionation cohorts of incrementally shorter bio-equivalent schedules starting with 50 Gy in 15 fractions (fx), followed by 45 Gy/10 fx and, finally, 42.5 Gy/5 fx. Maximum combined CTV-PTV expansion was limited to 5 mm. Patients were treated on a Model G5 Cyberknife (Accuray, Sunnyvale, CA). RESULTS: Median follow-up is 13.4 months (range: 5.6-24.6 months), with 12 patients followed for at least one year. Maximum acute toxicity consisted of grade 2 hoarseness and dysphagia. Maximum chronic toxicity was seen in one patient treated with 45 Gy/10 fx who continued to smoke >1 pack/day and ultimately required protective tracheostomy. At 1-year follow-up, estimated local disease free survival for the full cohort was 82%. Overall survival is 100% at last follow-up. CONCLUSIONS: We were able to reduce equipotent total fractions of SBRT from 15 to 5 without exceeding protocol-defined acute/subacute toxicity limits. With limited follow-up, disease control appears comparable to standard treatment. We continue to enroll to the 42.5 Gy/5 fx cohort and follow patients for late toxicity. TRIAL REGISTRATION: ClinicalTrials.gov NCT01984502.