Glottic Larynx Research Articles

Role of CSE1L expression in determining recurrence and survival of laryngeal tumors.

The correlation of CSE1L (human chromosomal segregation 1-like) staining intensity with disease-free survival, disease recurrence and development of distant metastases in Advanced Laryngeal Tumors. Specimens of patients with advanced glottic larynx cancer (T3, T4) were evaluated for nuclear CSE1L staining intensity. According to mild, moderate and severe CSE1L staining, patients were compared in terms of disease-free survival, disease recurrence and development of distant metastases. 17 of the 57 patients died within 5years, distant metastases developed in 5 patients, and recurrence in 5 patients. Of the 17 patients who died within 5years, 10(%59) showed severe staining with CSE1L, 6 (%35) showed moderate staining, and only 1 (%6) patient showed mild staining. 4 (%80) out of 5 patients who developed distant metastases were those with moderate staining with CSE1L. Metastases did not develop in any patient who stained poorly with CSE1L. 2 (%40) of the 5 patients who developed relapse were patients with severe staining with CSE1L, while 3 (%60) were patients with moderate staining with CSE1L. No recurrence was observed in any patient with mild staining with CSE1L. CSE1L will help in demonstrating the increased risk of distant metastasis, increased recurrence probability and shortened life expectancy of advanced laryngeal carcinoma.

Investigation of the Effect of Radiotherapy Dose on Chewing and Swallowing Structures in Head and Neck Cancer Patients Treated with Concomitant Chemoradiotherapy.

Intensity-modulated radiotherapy (IMRT) is a treatment method that is used in the treatment of head and neck cancers. Impairment of chewing and swallowing functions in the early and late periods of radiotherapy is frequent. Therefore, revealing the dose-effect relationship is important. The main purpose of this study is to investigate the dose-effect relationship between chewing and swallowing structures objectively via a standardized videofluoroscopy protocol. The study included 35 participants treated with chemo-IMRT. A videofluoroscopic swallowing study (VFSS) was performed before IMRT, and 3 and 6months after IMRT. VFSS results were scored according to the Modified Barium Swallow Impairment Profile (MBSImP) and the Penetration-Aspiration Scale (PAS). Maximum interincisor mouth opening, body mass index (BMI), and Functional Oral Intake Scale levels were determined in these cases. The quality of life of participants was evaluated. There was a significant increase in PAS and MBSImP scores and a significant decrease in BMI scores of the patients after treatment. Xerotomy and sticky saliva complaints increased after treatment. The dose to the mastication muscles (> 40Gy) and the temporomandibular joint (> 46Gy) were found to be associated with a decrease in BMI; the dose to the superior pharyngeal constructor muscle (> 58Gy) was found to be associated with pharyngeal stripping wave. The presence of aspiration was associated with the inferior pharyngeal constructor muscle, glottic larynx, supraglottic larynx, and upper esophageal sphincter. Important findings to emerge from this study include detected toxic dose limits. These findings may guide physicians to minimize the side effects of IMRT.

Recurrence and Quality-of-Life Following Involved Node Radiotherapy for Head and Neck Squamous Cell Carcinoma: Initial Results From the Phase II INRT-Air Trial

Elective neck irradiation (ENI) has long been considered mandatory when treating head and neck squamous cell carcinoma (HNSCC) with definitive radiotherapy (RT). However, ENI is often responsible for the majority of the dose to the salivary glands and swallowing organs-at-risk (OAR), and recent prospective studies have supported reduced elective neck volume and dose. Moreover, with sensitive staging studies and artificial intelligence (AI), our ability to identify occult lymphadenopathy is greatly improving. In this prospective phase II study, we investigated the efficacy and tolerability of eliminating ENI and strictly treating involved and suspicious lymph nodes (LN) with intensity modulated radiation therapy.Patients with newly-diagnosed squamous cell carcinoma of the oropharynx, larynx and hypopharynx were eligible for enrollment, excluding stage I-II glottic larynx. Each LN was characterized as involved or suspicious based on CT (e.g., cross-sectional size, enhancement pattern) and PET criteria and an in-house AI-based classification model. Gross disease and the primary clinical target volume were irradiated to 70 and 63 Gy in 35 fractions, respectively, and suspicious LN were treated to 66.5 Gy. Concurrent chemotherapy was required for stage T3N0-1 and IVA/B patients. The primary endpoint of the study was risk of solitary elective volume LN recurrence (i.e., LN recurrence in a classic ENI field without synchronous in-field or distant failure), with secondary endpoints including patterns-of-failure and patient reported outcomes.Sixty-seven patients were enrolled, with 18 larynx/hypopharynx and 49 oropharynx cancer (88% p16+). In total, 10% and 90% of patients were treated with accelerated RT and chemoRT, respectively. Average contralateral/ipsilateral mean parotid and contralateral submandibular doses were 11.9/18.4 Gy and 34.1 Gy, respectively, and average mean larynx/inferior constrictor/esophagus doses for oropharynx patients were 18.9/12.2/6.7 Gy. With a median follow-up of 12.8 months for surviving patients, there have been no solitary elective volume LN recurrences. Four patients have died from unrelated causes, and one died from in-field local progression. Gastrostomy was placed in 14 (21%), with median removal after 2.8 months for disease-free patients; only one patient is still dependent. Grade 1/2 dermatitis was seen in 90%/10% patients. There was no significant difference in MDADI score between baseline and months 3 and 6 post-RT; for patients with baseline MDADI score > 75, the scores at 3/6 months were 84/83.Preliminary results suggest that eliminating ENI is oncologically sound for HNSCC, with highly favorable OAR dosimetry and promising quality-of-life outcomes. Longer follow-up is needed to confirm these results.

Trends in Cancer Treatment for Oral Cavity, Oropharynx, and Larynx in 2016 Versus 2009: SEER Patterns of Care Studies.

To determine if there was a higher percentage of patients treated surgically and with advanced radiotherapy in 2016 (N = 897) versus 2009 (N = 1136), the patient and tumor characteristics associated with surgical care and advanced radiotherapy, and if chemotherapy or targeted agent use varied over time for squamous cell carcinoma of the head and neck. We utilized Surveillance Epidemiology and End Results Patterns of Care datasets. Rao-Scott Chi-square tests and logistic regressions were applied to determine differences in surgery, advanced radiotherapy (RT), and chemotherapy by year. There was a lower prevalence of surgery only treatment in 2016 versus 2009 with exception of oral cavity stages IVB/IVC and unknown, and larynx stage unknown. Advanced RT was more common in 2016 for patients receiving definitive RT among all sites, excluding stages I/II glottic larynx. Among each site (oral cavity, oropharynx, and larynx) lower stage was associated with increased odds of surgery. Among each site, advanced RT was more common in patients receiving definitive versus postoperative RT. For the larynx site, 2016 versus 2009 was associated with greater odds of advanced RT. Systemic treatment with fluorouracil, taxanes, or cetuximab was less prevalent in 2016. In 2016 versus 2009, there was largely not a higher percentage of patients treated surgically. There was a higher prevalence of advanced RT for definitive care. Further investigations of these patterns are needed, including trend analysis.

Association of tumor volume and outcomes in T3 larynx cancer with organ preservation approach.

e18044 Background: Organ preservation approaches to treatment of locally advanced larynx cancers are widely used and consist of radiotherapy (RT) with or without concurrent systemic therapy (CRT). Analyses of the National Cancer Database point to decreasing survival as CRT became widely adopted in place of total laryngectomy (TL). Tumor volume in T3 laryngeal tumors has been postulated as one variable to explain this finding, with higher volume associated with lower local control based on small sample size studies largely in pre-intensity modulated radiotherapy (IMRT) era, and low volume T3 tumors being associated with improved local control with CRT. We sought to validate these findings in a contemporary cohort of T3 larynx patients treated with IMRT. Methods: This was a national, multicentre retrospective cohort study of patients diagnosed with American Joint Committee on Cancer (AJCC) T3 N0-3 M0 glottic and supraglottic cancers who underwent curative intent IMRT with or without systemic treatment from 2002-2018. Tumor volumes were calculated using a validated standardized approach by a Neuroradiologist. Primary predictor was tumor volume, primary outcome was local control (LC), and secondary outcomes included overall survival (OS), as well as late grade 3+ toxicities. Kaplan Meier estimates and log-rank tests were used for survival analyses, with Cox proportional hazards used for univariable analyses. Results: 246 patients met inclusion criteria, 147 glottic and 99 supraglottic cancers. At baseline, glottic patients were more likely to be male (p < 0.01), have a fixed vocal cord (p < 0.01), not have pre-epiglottic space invasion ( < 0.01), be cN0 (p < 0.01), and have lower grade tumors (p < 0.01). Mean tumor volumes for glottic and supraglottic tumors were 5.0 (4.2-5.8) cc and 13.0 (10.3–15.6) cc respectively. Univariable analysis showed systemic therapy was associated with improved local failure (HR 0.49, 95%CI 0.24 – 0.99, p = 0.05). Within the glottic cohort, tumor volume was not associated with local failure (HR 1.09, 95%CI 0.71 – 1.67, p = 0.38), however having a local failure event was associated with increased feeding tube dependence (HR 2.52, 95%CI 1.05 – 6.02, p = 0.04). Median local failure free survival in the overall cohort was 28.5 months, with median OS 23.2 months. There was a trend towards improved local control in the supraglottic cohort compared to glottic patients (log-rank p = 0.08), but the supraglottic cohort had significantly worse overall survival (log-rank p = 0.02). Conclusions: In this retrospective cohort study, there were baseline and outcome differences between patients with T3 glottic and supraglottic larynx cancer, with worse overall survival in supraglottic patients. Tumor volume was not associated with local control in the glottic cohort. These findings are pending further validation in a larger cohort and will be analyzed separately for supraglottic tumors.

Exploring the Interplay Between Radiotherapy Dose and Physiological Changes in the Swallowing Mechanism in Patients Undergoing (Chemo)radiotherapy for Oropharynx Cancer

This study explored associative relationships between radiotherapy dose volumes delivered to the dysphagia aspiration risk structures (DARS) and swallowing physiological disturbance at 3 months post treatment in a homogenous cohort of patients who received (chemo)radiotherapy ((C)RT) for oropharyngeal head and neck cancer (HNC). Participants(n = 53) were a subgroup of patients previously recruited as part of a prospective randomised trial, and had undergone physiological swallowing assessment using videofluroscopic swallowing study (VFSS) at 3 months post (C)RT. The extended oral cavity (EOC), supraglottic larynx (SGL), glottic larynx (GL), cricopharyngeal inlet (CI), and pharyngeal constrictor muscles (PCM) were contoured as per international consensus guidelines and dose volume histograms (DVHs) were generated for each structure. Each DVH was analysed to reveal mean, maximum and partial radiotherapy doses of V40, V50 and V60 for each structure. Physiological swallowing function on VFSS was rated using the Modified Barium Swallow Impairment Profile (MBSImP). A binary logistic regression model was used to establish associative relationships between radiotherapy dose to the DARS and physiological changes within the swallowing mechanism. Structures that received the largest volumes of radiotherapy dose were the PCM and SGL. Significant relationships were found between the proportion of the EOC, SGL, GL and PCMs that received radiotherapy doses > 40 Gy, > 50 Gy and > 60 Gy and the likelihood of a moderate-severe physiological swallowing impairment (on the MBSImP). Whilst the current study was exploratory in nature, these preliminary findings provide novel evidence to suggest structure-specific associative relationships between radiotherapy dose and impacts to corresponding swallow physiology in patients with oropharyngeal HNC.

The Relationships Between Radiation Dosage and Long-term Swallowing Kinematics and Timing in Nasopharyngeal Carcinoma Survivors.

This study aimed to investigate the relationship between intensity-modulated radiation therapy (IMRT) dosimetry and swallowing kinematic and timing measures. Thirteen kinematic and timing measures of swallowing from videofluoroscopic analysis were used as outcome measures to reflect swallowing function. IMRT dosimetry was accessed for thirteen swallowing-related structures. A cohort of 44 nasopharyngeal carcinoma (NPC) survivors at least 3 years post-IMRT were recruited. The cohort had a mean age of 53.2 ± 11.9 years, 77.3% of whom were male. There was an average of 68.24 ± 14.15 months since end of IMRT; 41 (93.2%) had undergone concurrent chemotherapy. For displacement measures, female sex and higher doses to the cricopharyngeus, glottic larynx, and base of tongue were associated with reduced hyolaryngeal excursion and pharyngeal constriction, and more residue. For timing measures, higher dose to the genioglossus was associated with reduced processing time at all stages of the swallow. The inferior pharyngeal constrictor emerged with a distinctly different pattern of association with mean radiation dosage compared to other structures. Greater changes to swallowing kinematics and timing were observed for pudding thick consistency than thin liquid. Increasing radiation dosage to swallowing-related structures is associated with reduced swallowing kinematics. However, not all structures are affected the same way, therefore organ sparing during treatment planning for IMRT needs to consider function rather than focusing on select muscles. Dose-response relationships should be investigated with a comprehensive set of swallowing structures to capture the holistic process of swallowing.

Erken Evre Glottik Larenks Kanserli Hastalarda Radyoterapi Tekniğinin Karotis Arter Dozu Üzerine Etkisi

Objective: The aim of this study was to compare two radiotherapy techniques in early stage glottic laryngeal cancer patients in terms of radiotherapy dose applied to the carotid artery.Material - Methods: In this study, we included 10 early-stage (T1/2) glottic larynx cancer patients. Both intensity-modulated radiotherapy (IMRT) and 3-dimension conformal radiotherapy (3DCRT) treatment plans were prepared for each patient. Treatment volumes (CTV, PTV) were created for all patients. The entire larynx was described as CTV to include both false and true vocal cords, anterior-posterior commissures, arytenoids, aryepiglottic folds, subglottic region. For planning target volüme (PTV), while 5-mm was added to CTV in all directions, 3-mm margin was given to protect the carotid artery and spinal cord in posterolaterally. Spinal cord and carotid artery were contoured as the organ at risk (OAR). The doses of the target volumes, the OAR volumes, the homogeneity index (HI) were compared. Results: PTV parameters (Dmin, Dmean, Dmax, D90, D95) was compared in the 2 different technique. IMRT in comparison to 3DCRT significantly reduced the high-dose volumes (V30, V35, V50) of carotid artery (p < 0.001), but not to the low dose volume (V10). CI was similar (0.9 vs. 0.9, p = 0.3) compared to 3DCRT. However, HI was significantly improved with IMRT (0.1 vs. 0.08, p < 0.001). The maximum dose of the spinal cord was lower in 3DCRT compared to IMRT (18 Gy vs. 44Gy). Conclusion: IMRT is a superior radiotherapy (RT) technique in patients with T1/T2 glottic cancer in terms of protecting carotid artery.

Pill Ingestion and Caustic Laryngeal Injury

To highlight an unusual mechanism of laryngeal injury. Case report and literature review. A 66-year-old male ingested an over-the-counter preparation of bile acids as a dietary supplement. The capsule lodged in the patient's pharynx, and he sustained a caustic injury to the supraglottic and glottic larynx. His injury was managed conservatively, and his symptoms gradually resolved over a period of 8 weeks. A follow-up laryngoscopy at 8 weeks and 6 months showed no signs of injury. A barium swallow at 8 weeks was normal at that time and videostroboscopy results normalized with resolution of the injury as well. Caustic injury to the upper aerodigestive tract from pill ingestion is uncommon, and laryngeal injury even less so. Urgent evaluation should be undertaken, and appropriate therapies instituted promptly. Laryngeal injury can respond to conservative therapy, but there is a lack of clinical information to evaluate optimum treatment of this unusual injury.

Postoperative Radiotherapy Omitting Level Ⅳ for Locally Advanced Supraglottic and Glottic Laryngeal Carcinoma.

Background:Cervical lymph nodes metastases are one of the most significant prognostic factors in patients with laryngeal carcinoma, whether treatment by surgery or by radiotherapy. The current study retrospected the postoperative radiotherapy of locally advanced supraglottic and glottic laryngeal carcinoma (at a greater risk of lymph node metastasis) to determine the effect of radiotherapy excluding cervical level Ⅳ lymph nodes.Methods:Patients of supraglottic type and glottic type were irradiated with level Ⅳ from January 2012 to June 2013, without level Ⅳ from July 2013 to December 2014, according to physicians’ decision. Ninety-three patients were selective neck irradiation (SNI) of levels Ⅱ-Ⅳ (Group A) and 87 patients were SNI of levels Ⅱ and Ⅲ (Group B). The comparison between Group A and Group B was made with observation of clinical risk of recurrence and radiation complications, as well as overall survival (OS), progress-free survival (PFS) and regional nodal recurrence-free survival.Results:No remarkable difference was observed in the distribution of recurrence, levels of relapse, OS, PFS and regional nodal recurrence-free survival between the 2 groups (p > 0.05). Mean radiation dose at level Ⅳ, thyroid and cervical esophagus showed significant difference between the 2 therapeutic groups (p < 0.01). As regard radiation complications, no significant difference was found in radiation dermatitis of any grade between the 2 groups (p > 0.05). However, there was remarkable difference in clinical hypothyroidism and radiation esophagitis between Group A and Group B (p < 0.05).Conclusions:Radiotherapy after surgery omitting level Ⅳ may improve the quality of life in patients with locally advanced supraglottic and glottic laryngeal carcinoma, won’t worsen the prognosis as well.

Potential benefits of adaptive intensity-modulated proton therapy in nasopharyngeal carcinomas.

PurposeTo investigate potential advantages of adaptive intensity‐modulated proton beam therapy (A‐IMPT) by comparing it to adaptive intensity‐modulated X‐ray therapy (A‐IMXT) for nasopharyngeal carcinomas (NPC).MethodsTen patients with NPC treated with A‐IMXT (step and shoot approach) and concomitant chemotherapy between 2014 and 2016 were selected. In the actual treatment, 46 Gy in 23 fractions (46Gy/23Fx.) was prescribed using the initial plan and 24Gy/12Fx was prescribed using an adapted plan thereafter. New treatment planning of A‐IMPT was made for the same patients using equivalent dose fractionation schedule and dose constraints. The dose volume statistics based on deformable images and dose accumulation was used in the comparison of A‐IMXT with A‐IMPT.ResultsThe means of the Dmean of the right parotid gland (P < 0.001), right TM joint (P < 0.001), left TM joint (P < 0.001), oral cavity (P < 0.001), supraglottic larynx (P = 0.001), glottic larynx (P < 0.001), , middle PCM (P = 0.0371), interior PCM (P < 0.001), cricopharyngeal muscle (P = 0.03643), and thyroid gland (P = 0.00216), in A‐IMPT are lower than those of A‐IMXT, with statistical significance. The means of, D0.03cc, and Dmean of each sub portion of auditory apparatus and D30% for Eustachian tube and D0.5cc for mastoid volume in A‐IMPT are significantly lower than those of A‐IMXT. The mean doses to the oral cavity, supraglottic larynx, and glottic larynx were all reduced by more than 20 Gy (RBE = 1.1).ConclusionsAn adaptive approach is suggested to enhance the potential benefit of IMPT compared to IMXT to reduce adverse effects for patients with NPC.

Second primary tumors in head and neck cancer patients: The importance of a "tailored" surveillance.

Head and neck cancer survivors have increased risk of developing second primary tumors compared to overall population. Because second primary represents a major cause of morbidity and mortality in this population, early detection is fundamental. In this 10-year single-institution study, we investigated the following: incidence, clinical-pathological risk factors, and survival of patients with second primary tumor. We included all patients with diagnosis of squamous cell carcinoma of the head and neck seen at the Modena University Hospital from 2008 to 2018. Among 1,177 patients included, 222 (18.9%) developed second primary tumor; its survival probability at 5years was 40.6%. Alcohol consumption (p=.0055) and index cancer in oropharynx (p=.0029), supraglottic larynx (p=.0000), glottic larynx (p=.0222) were associated with higher risk of second primary. The most common second primary sites were head and neck district and lung (70, 31.5%, and 67, 30.2%, respectively). Head and neck district were more common in oral cavity (18, 43%) and oropharynx index cancer (20, 31%); lung second primary in hypopharynx (4, 40%), supraglottic larynx (17, 43%), and glottic larynx index cancer (23, 35%). Head and neck cancer survivors developing a second primary tumor have dismal prognosis. Tailored surveillance is recommended.

Mass Cytometry for Comprehensive Profiling of Systemic Immune Composition in Head and Neck Squamous Cell Carcinoma Patients Reveals Dynamic Changes Early in Therapy

We hypothesized that peripheral blood from patients undergoing RT would demonstrate quantifiable changes in immune cell composition early during therapy, and that some of these features would ultimately correlate with clinical outcomes. To this end, we leveraged mass cytometry (CyTOF) to comprehensively profile all major immune subpopulations in peripheral blood of head and neck cancer (HNC) patients before and up to two weeks after initiation of RT. As a pilot, we obtained peripheral blood samples from 5 patients with HNC and 5 healthy control patients. For cancer patients, samples were acquired prior to initiation of any therapy, prior to fraction 4 and prior to fraction 9 of RT. Samples were barcoded and stained using a panel of 40 metal-conjugated antibodies prior to data acquisition on Helios mass cytometer (Fluidigm). Debarcoded and normalized data were analyzed by UMAP dimensionality reduction and unsupervised segmentation using CLARA (Clustering Large Applications). Cancer patients had a median age of 60 (range 49-67), HNC squamous cell carcinoma (2 tonsil, 1 base of tongue, 1 glottic larynx, 1 unknown primary), locoregionally advanced disease, and median RT fraction size of 212 cGy. The majority of patients had p16+ HNC (3) and received concurrent platinum-based chemotherapy (4). All patients had primary and nodal disease in situ at time of radiation. Neutrophils predominated in whole blood as expected (71.9% controls, 80.6% patients, p = 0.056). When analysis was limited to non-neutrophils, 16 immune subpopulations were additionally identified via unsupervised clustering. At baseline, there were no differences in proportions of most subsets except for an increase in regulatory T cells (Tregs, p = 0.016) and decreases in naïve CD8 T cells (p = 0.032) and gdT cells (p = 0.016) in cancer patients as compared to healthy controls. However, Post-RT samples displayed dynamic and divergent changes in cell frequencies. 3 patients demonstrated up to a 5.6-fold increase in CD14+ HLA-DR-/lo monocytes (often referred to as monocytic myeloid-derived suppressor cells or M-MDSCs) typically associated with immunosuppression. Type 2 conventional dendritic cells, critical mediators of antigen cross-presentation, were increased in 3 patients, stable in 1 patient and decreased in 1 patient. Interestingly, Treg frequency was dramatically reduced at timepoint 2 before returning to near baseline levels at timepoint 3, a pattern seen in 4 patients. Major immune subpopulations can be robustly quantified in pre- and post-RT whole blood samples using CyTOF and patterns of change were evident even in a small number of patients. Dynamic changes in immune cell composition are notable even within 1-2 weeks of RT initiation. More detailed correlation with treatment regimens and therapeutic outcomes in a larger patient cohort may allow identification of prognostic immunologic biomarkers.

Outcomes of frontolateral vertical partial laryngectomy in T1b glottic carcinomas

Background The treatment of T1b glottic carcinomas with invasion of the anterior commissure (AC) is still a challenge in larynx oncology. The diversity in treatment protocols is due to the difficulty in achieving safety margins of resection, especially in the AC. Objective The treatment success rate of frontolateral vertical partial laryngectomy (FVPL) for the treatment of stage T1b squamous cell carcinoma of the glottic larynx infiltrating the AC. Material and Methods Clinical data of patients, who were diagnosed with stage T1b squamous cell carcinoma of the glottic larynx and who underwent a FVPL from 01/2003 to 12/2016 in our ENT clinic were retrospectively evaluated. Clinical and oncological outcomes were analyzed. Results 39 patients were included in this study. The mean follow-up duration was 79.95 ± 20.59 months. Intraoperative R0 resection was achieved in all patients. In 33.3% patients, documented complications were tissue granulation and synechia formation in the glottic area. The 5-year recurrence-free survival was 82.1%, the 5-year overall survival rate 97.4%, and the 5-year laryngeal preservation rate 94.8%. Conclusion Our clinical data demonstrate that T1b glottic carcinomas with invasion of the AC can be effectively treated with FVPL. The outcome is similar to other methods such as transoral laser microsurgery, supracricoidal partial laryngectomy, and radiotherapy.

Surface guided motion management in glottic larynx stereotactic body radiation therapy

Background and purposeInvoluntary motion due to swallowing cause inaccurate dose delivery during larynx radiotherapy, a deviation that may be particularly problematic during stereotactic body radiation therapy (SBRT). The goal of this study was to develop a motion management solution for larynx SBRT using surface imaging. Material and methodsTen patients were recently treated on a phase II study of larynx SBRT on a LINAC equipped with a surface guidance system. A small region of the immobilization mask was manually cut open to allow surface tracking. Pre-treatment and intra-fractional CBCTs were acquired to verify internal anatomy. Patients were verbally instructed not to swallow during treatment. During treatment delivery, beam hold was initiated by the Motion Management Interface if surface motion exceeded a patient-specific threshold. Patient motion was recorded in log files and analyzed. We also performed phantom studies to assess the theoretical impact of gating on dose delivery. ResultsThe frequency (6.5 ± 5.2 times per fraction) and duration (3.9 ± 2.5 seconds per swallow) of swallowing varied both between patients and fractions. The magnitude of each swallow showed mean peak amplitude at 5.8 ± 3.8 mm above baseline, mostly in the longitudinal direction. Beam duty cycle was 95.0% ± 7.0% (absolute range: 76–100%), with inefficiency most prominent in the early fractions. The 95th percentile residual motion was reduced from 3.4 mm to 2.3 mm with both verbal instruction and gating. Phantom studies confirmed dose delivery accuracy represented by gamma pass rate was improved by 5% using this approach. ConclusionsLaryngeal motion management using surface imaging is feasible and efficacious. Uncontrolled movement of the larynx was not uncommon during treatment, with gating reducing potential for unplanned dose deviations. Additional research is needed to determine the clinical benefit with this system.

Squamous Cell Carcinoma of Head and Neck in Vajira Hospital: The Outcomes in a Real-World Practice

Background: Squamous cell carcinoma of the head and neck (SCCHNC) is the fifth most common cancer in Thailand. Even though the multi-modality treatment including surgery, radiotherapy, and chemotherapy is the standard practice, the survival outcomes are not impressive. Objective: The primary objectives were to determine the overall survival (OS) and 3-year OS of all patients with SCCHNC and as analysis according to the primary site of the primary tumor. The secondary objectives were progression-free survival (PFS), outcomes of induction chemotherapy (IC), prevalence of serious toxicities from treatments, and independent factors of survival. Materials and Methods: Retrospective analyses were conducted in patients who had SCCHNC confirmed by histology with complete details of staging and treatment, excluding nasopharyngeal carcinoma, carcinoma of the salivary glands, carcinoma of paranasal sinuses, and cutaneous squamous cell carcinoma. Results: There were 216 eligible patients. OS of all participants was 24.1 months (IQR 14.3 to 50.1). At the median follow-up of 51.49 months, 3-year OS was 52.2% (95% CI 45 to 95). The patients with primary tumor site at the glottic larynx had the longest OS of 45 months (IQR 21.2 to 64.8). The patients with primary sites at the oral cavity (OS 20.1 months, IQR 13.4 to 45.8), oropharynx (OS 20.05 months, IQR 12.4 to 48.5), hypopharynx (OS 23.3 months, IQR 13.3 to 44.6), and supraglottic or transglottic larynx (OS 25.15, IQR 19.55 to 37.8) had nearly equally worst OS. Stratified by primary site of tumor, the investigators found that PFS of patients with glottic larynx was the longest (23.6 months, IQR 17.5 to 53.4). On the other hand, PFS of patients with supraglottic or transglottic laryngeal cancer, oral cavity cancer, oropharynx, hypopharynx was only 11.35 months (IQR 5.8 to 28.65), 12.5 months (IQR 6.2 to 31.3 months), 13.2 months (IQR 6.3 to 27.8), and 15.1 (IQR 8.9 to 29.3), respectively. The IC did not improve the patients’ outcomes. Thirty patients (22.4%) had serious (grade 3 to 4) adverse effects from definitive treatment, mostly from severe mucositis. The primary sites at the oral cavity and hypopharynx, T4 diseases, and failure to primary definitive treatment were the independent predictors of early deaths. Conclusion: Due to the very late stage at presentation, the OS of the participants was only two years. The primary sites at the oral cavity and hypopharynx, T4 diseases rather than the composite TNM staging, and failure to primary definitive treatment were the independent prognostic factors of short survival. Keywords: Squamous cell carcinoma of the head and neck, Multi-modality treatment, Outcomes, Survival

Predictive factors for local control of early glottic squamous cell carcinomas after definitive radiotherapy.

The aim of the present study was to retrospectively investigate the risk factors of local failure for T1 glottic carcinoma irradiated with a prescription dose of 66 Gy. Between July 2006 and December 2017, 64 patients with T1 glottic squamous cell carcinoma treated with 66 Gy/33 fractions were analyzed for risk factors of local failure. The sex, age, performance status, T stage, overall treatment time, anterior commissure involvement, smoking status during/after treatment, histological tumor grade and pretreatment hemoglobin level were investigated. The maximum, mean and minimum doses, and the homogeneity index for the glottic larynx were calculated for dosimetric risk factors of local failure. The median follow-up duration was 51 months. Local failure was observed in 6 patients (9.5%). Among all risk factors, only the minimum dose to the glottic larynx was found to be significantly associated with local failure (P=0.025). The 5-year local control rates for a minimum dose to the glottic larynx of <65 and ≥65 Gy were 79 and 95%, respectively, with a statistically significant difference (P=0.015). No patients exhibited grade ≥3 late adverse effects. The minimum dose to the glottic larynx was the only factor significantly associated with local failure. Thus, local control of T1 glottic carcinoma may improve with a minimum dose of ≥65 Gy to the glottic larynx. In conclusion, radiotherapy with a minimum prescription dose of ≥65 Gy to the glottic larynx appears to be safe and achieves a high local control rate for T1 glottic carcinoma.

Intensity-modulated radiation therapy in early stage squamous cell carcinoma of the larynx: treatment trends and outcomes.

PurposeDefinitive radiotherapy remains a primary treatment option for early stage glottic cancer. Intensity-modulated radiation therapy (IMRT) has emerged as the standard treatment technique for advanced head and neck cancers, whereas three-dimensional conformal radiotherapy (3D-CRT) has remained standard for early glottic cancers. We used the National Cancer Database (NCDB) to identify predictors of IMRT use and effect on outcome in these patients.Materials and MethodsWe queried the NCDB from 2004–2015 for squamous cell carcinoma of the glottic larynx staged Tis-T2N0 treated with radiation alone. Logistic regression was used to identify predictors of IMRT. Cox regression was used to identify factors predictive of overall survival. Propensity matching was conducted to account for indication bias. ResultsWe identified 15,627 patients, of which 11% received IMRT. IMRT use rose from 2% in 2004 to 16% in 2015. Predictors of IMRT include: increased comorbidity, T2 stage, urban location, chemotherapy, treatment at an academic center, and later treatment year. Predictors of improved survival were female gender, higher income, lower stage, no chemotherapy, academic facility, and more remote year. There was no difference in survival between 3D-CRT and IMRT across all stages. ConclusionsThe rate of IMRT use for early stage glottic laryngeal cancer has increased over time. There was no difference in outcome in patients receiving IMRT versus 3D-CRT across the cohort.

Comparison of Current Surgical and Non-Surgical Treatment Strategies for Early and Locally Advanced Stage Glottic Laryngeal Cancer and Their Outcome.

For the treatment of early and locally advanced glottic laryngeal cancer, multiple strategies are available. These are pursued and supported by different levels of evidence, but also by national and institutional traditions. The purpose of this review article is to compare and discuss the current evidence supporting different loco-regional treatment approaches in early and locally advanced glottic laryngeal cancer. The focus is kept on randomized controlled trials, meta-analyses, and comparative retrospective studies including the treatment period within the last twenty years (≥ 1999) with at least one reported five-year oncologic and/or functional outcome measure. Based on the equipoise in oncologic and functional outcome after transoral laser surgery and radiotherapy, informed and shared decision-making with and not just about the patient poses a paramount importance for T1-2N0M0 glottic laryngeal cancer. For T3-4aN0-3M0 glottic laryngeal cancer, there is an equipoise regarding the partial/total laryngectomy and non-surgical modalities for T3 glottic laryngeal cancer. Patients with extensive and/or poorly functioning T4a laryngeal cancer should not be offered organ-preserving chemoradiotherapy with salvage surgery as a back-up plan, but total laryngectomy and adjuvant (chemo) radiation. The lack of high-level evidence comparing contemporary open or transoral robotic organ-preserving surgical and non-surgical modalities does not allow any concrete conclusions in terms of oncological and functional outcome. Unnecessary tri-modality treatments should be avoided. Instead of offering one-size-fits-all approaches and over-standardized rigid institutional strategies, patient-centered informed and shared decision-making should be favored.

Trends in Intensity Modulated Radiation Therapy for Early Stage Glottic Larynx Cancer and Impact on Outcome

Definitive radiation remains a treatment option for early stage glottic larynx cancer. Intensity modulated radiation therapy (IMRT) has been the standard treatment for more advanced head and neck cancers, while 3D conformal radiotherapy (3D CRT) has remained standard for early glottic cancers. We used the National Cancer Database (NCDB) to identify predictors of IMRT use and effect on outcome in these patients.