Search

Purpose: The aim of this work was to detail the interdisciplinary awake craniotomy program model at The University of Texas MD Anderson Cancer Center integrating speech-language pathology and neuropsychology in the pre-, intra-, and postoperative settings to monitor and maximize expressive and receptive language skills among patients undergoing brain tumor resection. Conclusions: This report outlines the MD Anderson clinical protocols and procedures, with focus on the clinical methods of the speech-language pathologist in pre-, intra-, and postoperative interventions. Case examples are summarized to illustrate dynamic features of implementing this protocol. An intradisciplinary team approach to treatment of patients with brain tumor and specifically those undergoing awake craniotomy may improve care and quality of life.

This study investigated the association of hearing loss and tinnitus with overall health-related quality of life (HRQoL) among long-term oropharyngeal cancer (OPC) survivors.This study included OPC survivors treated between 2000 and 2013 and surveyed from September 2015 to July 2016. Hearing loss and tinnitus were measured by asking survivors to rate their "difficulty with hearing loss and/or ringing in the ears" from 0 (not present) to 10 (as bad as you can imagine). Hearing loss and tinnitus scores were categorized as follows: 0 for none, 1-4 for mild, and 5-10 for moderate to severe. The primary outcome was the mean score of MD nderson Symptom Inventory HeadNeck module interference component as a HRQoL surrogate dichotomized as follows: 0 to 4 for none to mild and 5 to 10 for moderate to severe interference.Among 880 OPC survivors, 35.6% (314), reported none, 39.3% (347) reported mild, and 25.1% (221) reported moderate to severe hearing loss and tinnitus. On multivariable analysis, mild (OR, 5.83; 95% CI; 1.48-22.88; p = 0.012) and moderate (OR, 30.01; 95% CI; 7.96-113.10; p 0.001) hearing loss and tinnitus were associated with higher odds of reporting moderate to severe symptom interference scores in comparison to no hearing loss and tinnitus. This association of hearing dysfunction was consistent with all domains of HRQoL.Our findings provide preliminary evidence to support the need for continued audiological evaluations and surveillance to detect hearing dysfunction, to allow for early management and to alleviate the long-term impact on QoL.

Purpose:In oropharyngeal squamous cell carcinoma (OPC), high CD8+ tumor-infiltrating lymphocyte (CD8+TIL) density confers improved prognosis. We compared neoadjuvant durvalumab (PD-L1 inhibitor) with durvalumab + tremelimumab (CTLA-4 inhibitor) in terms of impact on CD8+TIL density, safety, and efficacy in patients with OPC.Patients and Methods:Patients with newly diagnosed stage II–IVA OPC or locoregionally recurrent OPC amenable to resection were included. Patients were randomized to two cycles of durvalumab or durvalumab + tremelimumab before surgery. The primary endpoint was change between baseline and resection specimen in CD8+TIL density between arms. Secondary endpoints included safety, response rate per RECIST, major pathologic response (MPR; ≤10% viable tumor cells) rate, and patient-reported outcomes.Results:Of 28 eligible patients (14/arm), 20 (71%) had newly diagnosed OPC, and 24 (86%) were p16-positive. The posttreatment to pretreatment median CD8+TIL density ratio was 1.31 for durvalumab and 1.15 for combination treatment (P = 0.97; 95% CI: −1.07–2.28). In each group, 6 patients (43%, 95% CI: 17.66–71.14) had a response. Eight patients (29%) had a MPR at the primary tumor and/or nodal metastases. Neither baseline CD8+TIL density nor PD-L1 expression level correlated with overall response, but a trend toward greater CD8+TIL change in patients with a MPR was seen (P = 0.059; 95% CI: −0.33–3.46). Four patients (14%) had grade ≥3 adverse events. At median follow-up time of 15.79 months, all patients were alive, and one had an additional recurrence.Conclusions:Durvalumab + tremelimumab did not increase CD8+TIL density more than durvalumab alone did. The observed safety and activity support further investigation of neoadjuvant checkpoint inhibitor for OPC.

Supplementary Tables

BackgroundPost-treatment symptoms are a focal point of follow-up visits for head and neck cancer patients. While symptoms such as dysphagia and shortness-of-breath early after treatment may motivate additional work up, their precise association with disease control and survival outcomes is not well established.MethodsThis prospective data cohort study of 470 oropharyngeal cancer patients analyzed patient-reported swallowing, choking and shortness-of-breath symptoms at 3-to-6 months following radiotherapy to evaluate their association with overall survival and disease control. Associations between the presence of moderate-to-severe swallowing, choking and mild-to-severe shortness-of-breath and treatment outcomes were analyzed via Cox regression and Kaplan-Meier. The main outcome was overall survival (OS), and the secondary outcomes were local, regional, and distant disease control.ResultsThe majority of patients (91.3%) were HPV-positive. Median follow-up time was 31.7 months (IQR: 21.9-42.1). Univariable analysis showed significant associations between OS and all three symptoms of swallowing, choking, and shortness-of-breath. A composite variable integrating scores of all three symptoms was significantly associated with OS on multivariable Cox regression (p=0.0018). Additionally, this composite symptom score showed the best predictive value for OS (c-index=0.75). Multivariable analysis also revealed that the composite score was significantly associated with local recurrence/progression (p=0.025). Notably, the same significant associations with OS were seen for HPV-positive only subset analysis (pConclusionsQuantitative patient-reported measures of dysphagia and shortness-of-breath 3-to-6 months post-treatment are significant predictors of OS and disease recurrence/progression in OPC patients and in HPV-positive OPC only.

Objective The primary course of treatment for patients with low- to intermediate-risk tonsil cancer has evolved with a shift toward primary transoral robotic surgery (TORS) or radiation therapy (RT). While favorable outcomes have been reported after deintensification via unilateral TORS or RT (uniRT), comparisons of functional outcomes between these treatments are lacking. We compared clinical outcomes (Dynamic Imaging Grade of Swallowing Toxicity [DIGEST] and feeding tube [FT]) and patient-reported swallowing outcomes (MD Anderson Dysphagia Inventory [MDADI]) based on primary treatment strategy: TORS, uniRT, or bilateral RT (biRT). Study design Secondary analysis of prospective cohort. Setting Single institution. Methods The study sample comprised 135 patients with HPV/p16+ T1-T3, N0-2b (American Joint Committee on Cancer, seventh edition), N0-1 (eighth edition) squamous cell carcinoma of the tonsil were sampled from a prospective registry. Modified barium swallow studies graded per DIGEST, FT placement and duration, and MDADI were collected. Results Baseline DIGEST grade significantly differed among treatment groups, with higher dysphagia prevalence in the TORS group (34%) vs the biRT group (12%, P = .04). No significant group differences were found in DIGEST grade or dysphagia prevalence at subacute and longitudinal time points (P = .41). Mean MDADI scores were similar among groups at baseline (TORS, 92; uniRT, 93; biRT, 93; P = .90), subacute (TORS, 83; uniRT, 88; biRT, 82; P = .38) and late time points (TORS, 86; uniRT, 86; biRT, 87; P = .99). FT placement and duration significantly differed among primary treatment groups (FT [median days]: TORS, 89% [3]; uniRT, 8% [82]; biRT, 37% [104]; P Conclusion While TORS and uniRT offer optimal functional outcomes related to dysphagia, results suggest that no measurable clinician-graded or patient-reported differences in swallow outcomes exist among these primary treatment strategies and biRT. Aside from baseline differences that drive treatment selection, differences in FT rate and duration by primary treatment strategy likely reflect diverse toxicities beyond dysphagia.

Background and Purpose: Conventional magnetic resonance imaging (MRI) poses challenges in quantitative analysis because voxel intensity values lack physical meaning. While intensity standardization methods exist, their effects on head and neck MRI have not been investigated. We developed a workflow based on healthy tissue region of interest (ROI) analysis to determine intensity consistency within a patient cohort. Through this workflow, we systematically evaluated intensity standardization methods for MRI of head and neck cancer (HNC) patients. Materials and Methods: Two HNC cohorts (30 patients total) were retrospectively analyzed. One cohort was imaged with heterogenous acquisition parameters (HET cohort), whereas the other was imaged with homogenous acquisition parameters (HOM cohort). The standard deviation of cohort-level normalized mean intensity (SD NMIc), a metric of intensity consistency, was calculated across ROIs to determine the effect of five intensity standardization methods on T2-weighted images. For each cohort, a Friedman test followed by a post-hoc Bonferroni-corrected Wilcoxon signed-rank test was conducted to compare SD NMIc among methods. Results: Consistency (SD NMIc across ROIs) between unstandardized images was substantially more impaired in the HET cohort (0.29 ± 0.08) than in the HOM cohort (0.15 ± 0.03). Consequently, corrected p-values for intensity standardization methods with lower SD NMIc compared to unstandardized images were significant in the HET cohort (p 0.05). In both cohorts, differences between methods were often minimal and nonsignificant. Conclusions: Our findings stress the importance of intensity standardization, either through the utilization of uniform acquisition parameters or specific intensity standardization methods, and the need for testing intensity consistency before performing quantitative analysis of HNC MRI.

Purpose: Osteoradionecrosis (ORN) of the mandible represents a severe, debilitating complication of radiation therapy (RT) for head and neck cancer (HNC). At present, no normal tissue complication probability (NTCP) models for risk of ORN exist. The aim of this study was to develop a multivariable clinical/dose-based NTCP model for the prediction of ORN any grade (ORNI-IV) and grade IV (ORNIV) after RT (+/- chemotherapy) in patients with HNC.Methods and Materials: Included patients with HNC were treated with (chemo-)RT between 2005 and 2015. Mandible bone radiation dose-volume parameters and clinical variables (ie, age, sex, tumor site, pre-RT dental extractions, chemotherapy history, postoperative RT, and smoking status) were considered as potential predictors. The patient cohort was randomly divided into a training (70%) and independent test (30%) cohort. Bootstrapped forward variable selection was performed in the training cohort to select the predictors for the NTCP models. Final NTCP model(s) were validated on the holdback test subset.Results: Of 1259 included patients with HNC, 13.7% (n = 173 patients) developed any grade ORN (ORNI-IV primary endpoint) and 5% (n = 65) ORNIV (secondary endpoint). All dose and volume parameters of the mandible bone were significantly associated with the development of ORN in univariable models. Multivariable analyses identified D30% and pre-RT dental extraction as independent predictors for both ORNI-IV and ORNIV best-performing NTCP models with an area under the curve (AUC) of 0.78 (AUCvalidation = 0.75 [0.69-0.82]) and 0.81 (AUCvalidation = 0.82 [0.74-0.89]), respectively.Conclusions: This study presented NTCP models based on mandible bone D30% and pre-RT dental extraction that predict ORNI-IV and ORNIV (ie, needing invasive surgical intervention) after HNC RT. Our results suggest that less than 30% of the mandible should receive a dose of 35 Gy or more for an ORNI-IV risk lower than 5%. These NTCP models can improve ORN prevention and management by identifying patients at risk of ORN. (C) 2021 The Author(s). Published by Elsevier Inc.

Highlights • Head and neck cancers radiotherapy (RT) leads to inevitable injury to parotid glands. • We sought to quantify delta-changes of 18FDG-PET metrics in these parotid glands. • Parotid PET delta-changes and clinical variables could predict xerostomia severity., Purpose Head and neck cancers radiotherapy (RT) is associated with inevitable injury to parotid glands and subsequent xerostomia. We investigated the utility of SUV derived from 18FDG-PET to develop metabolic imaging biomarkers (MIBs) of RT-related parotid injury. Methods Data for oropharyngeal cancer (OPC) patients treated with RT at our institution between 2005 and 2015 with available planning computed tomography (CT), dose grid, pre- & first post-RT 18FDG-PET-CT scans, and physician-reported xerostomia assessment at 3–6 months post-RT (Xero 3–6 ms) per CTCAE, was retrieved, following an IRB approval. A CT-CT deformable image co-registration followed by voxel-by-voxel resampling of pre & post-RT 18FDG activity and dose grid were performed. Ipsilateral (Ipsi) and contralateral (contra) parotid glands were sub-segmented based on the received dose in 5 Gy increments, i.e. 0–5 Gy, 5–10 Gy sub-volumes, etc. Median and dose-weighted SUV were extracted from whole parotid volumes and sub-volumes on pre- & post-RT PET scans, using in-house code that runs on MATLAB. Wilcoxon signed-rank and Kruskal-Wallis tests were used to test differences pre- and post-RT. Results 432 parotid glands, belonging to 108 OPC patients treated with RT, were sub-segmented & analyzed. Xero 3–6 ms was reported as: non-severe (78.7%) and severe (21.3%). SUV- median values were significantly reduced post-RT, irrespective of laterality (p = 0.02). A similar pattern was observed in parotid sub-volumes, especially ipsi parotid gland sub-volumes receiving doses 10–50 Gy (p

The 100 ml water swallow test (WST) is a validated swallow assessment used in head and neck cancer (HNC). We aimed to determine the level of agreement when completing the 100 ml WST via clinician-graded video-testing or patient self-testing compared to standard face-to-face assessment (FTF).Convenience sampling from four UK centers.patients with HNC treated with any modality prior to, or within 5 years of treatment. Participants were recruited to complete the 100 ml WST by video-testing or self-testing and compared with FTF.Sixty-three patients were recruited; 1 was unable to perform the task; 30 in video-testing; and 32 in self-testing. There was no difference in swallow capacity (p = 0.424) and volume (p = 0.363) for the video-testing or the self-testing swallow capacity (p = 0.777) and volume (p = 0.445).This study demonstrates that video-testing and self-testing are reliable methods of completing the 100 ml WST for this sample of patients with HNC.

Purpose While flexible endoscopic evaluation of swallowing (FEES) is a common clinical procedure used in the head and neck cancer (HNC) population, extant outcome measures for FEES such as bolus-level penetration–aspiration and residue scores are not well suited as global patient-level endpoint measures of dysphagia severity in cooperative group trials or clinical outcomes research. The Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) was initially developed and validated for use during videofluoroscopic evaluations as a way to grade safety, efficiency, and overall pharyngeal swallowing impairment. The purpose of this study was to adapt and validate DIGEST for use with FEES. Method A modified Delphi exercise was conducted for content validation, expert consensus, adaptation, and operationalization of DIGEST-FEES. Three blinded, expert raters then evaluated 100 de-identified post-HNC treatment FEES examinations. Intra- and interrater reliability were tested with quadratic weighted kappa. Criterion validity against the MD Anderson Dysphagia Inventory, Functional Oral Intake Scale, Secretion Severity Scale, and Yale Residue Rating Scale was assessed with Spearman correlation coefficients. Results Interrater reliability was almost perfect for overall DIGEST-FEES grade (κ w = 0.83) and safety grade (κ w = 0.86) and substantial for efficiency grade (κ w = 0.74). Intrarater reliability was excellent for all raters (0.9–0.91). Overall DIGEST-FEES grade correlated with MD Anderson Dysphagia Inventory ( r = −.43, p < .0001), Functional Oral Intake Scale ( r = −.43, p < .0001), Secretion Severity Scale ( r = .47, p < .0001), Yale Vallecular Residue ( r = .73, p < .0001), and Yale Pyriform Sinus Residue ( r = .65, p < .0001). Conclusion DIGEST-FEES is a valid and reliable scale to describe the severity of pharyngeal dysphagia in patients with HNC. Supplemental Material https://doi.org/10.23641/asha.14642787

OBJECTIVE: To describe the physiologic swallowing impairments (MBSImP™©) associated with safety/efficiency impairments (DIGEST(safety)/DIGEST(efficiency) grades) at 3–6 months after transoral robotic surgery (TORS) or radiation therapy (RT). STUDY DESIGN: Secondary analysis of registry data. SETTING: Single, academic institution. METHODS: Two hundred and fifty-seven patients with HPV+ oropharynx cancer were stratified by primary treatment (75 TORS, 182 RT). Modified barium swallow studies were analyzed at baseline and 3–6 months using MBSImP scores and DIGEST(safety)/DIGEST(efficiency) grades. DIGEST(safety)/DIGEST(efficiency) grades and MBSImP were compared groupwise and associations between DIGEST(safety)/DIGEST(efficiency) grades and MBSImP were explored by ordinal logistic regression. Exploratory analyses were stratified by multimodality treatment. RESULTS: Neither DIGEST(safety)/DIGEST(efficiency) differed significantly between groups at baseline or 3–6 months. Laryngeal vestibule closure was impaired more frequently in the RT group (RT: 41% vs. TORS: 27%; p = 0.02) while the TORS group had significantly more pharyngeal contraction impairment (63%; p < 0.001) compared to RT at 3–6 months. CONCLUSION: The results suggest a focal injury associated with DIGEST(safety)/DIGEST(efficiency) post-TORS in contrast to a low-level diffuse physiologic impairment associated with post-RT dysphagia.

Purpose To report patient-reported outcomes (PROs) derived from the Functional Assessment of Cancer Therapy-Head and Neck (FACT-HN) tool, in patients with oropharynx cancer (OPC) treated with intensity-modulated proton therapy (IMPT) in the context of first-course irradiation. Materials and Methods Patients with locally advanced OPC treated with radical IMPT between 2011 and 2018 were included in a prospective registry. FACT-HN scores were measured serially during and 24 months following IMPT. PRO changes in the FACT-HN scores over time were assessed with mixed-model analysis. Results Fifty-seven patients met inclusion criteria. Median age was 60 years (range, 41-84), and 91% had human papillomavirus-associated disease. In total, 28% received induction chemotherapy and 68% had concurrent chemotherapy. Compliance to FACT-HN questionnaire completion was 59%, 48%, and 42% at 6, 12, and 24 months after treatment, respectively. The mean FACT-General (G), FACT-Total, and FACT-Trial Outcome Index (TOI) score changes were statistically and clinically significant relative to baseline from week 3 of treatment up to week 2 after treatment. Nadir was reached at week 6 of treatment for all scores, with maximum scores dropping by 15%, 20%, and 39% compared to baseline for FACT-G, FACT-Total, and FACT-TOI, respectively. Subdomain scores of physical well-being, functional well-being, and head and neck additional concerns decreased from baseline during treatment and returned to baseline at week 4 after treatment. Conclusions IMPT was associated with a favorable PRO trajectory, characterized by an acute decline followed by rapid recovery to baseline. This study establishes the expected acute, subacute, and chronic trajectory of PROs for patients undergoing IMPT for OPC.

BackgroundPain is a common, debilitating symptom experienced by patients with oral cavity and oropharyngeal cancer (OC/OPC) treated with radiotherapy (RT). Managing acute pain (AP) over 6 - 7 weeks of RT remains a significant challenge, warranting further investigation. Using a modern prospective registry, the objective of this study was to characterize longitudinal AP profiles and temporal changes in vital signs (VS), radiation toxicities, and analgesic prescribing patterns during RT.MethodsA total of 351 patients with OC (n=120) and OPC (n=228) treated with curative RT from 2013-2021 were included. Baseline cohort characteristics, weekly patient-reported pain descriptors, physician-graded toxicities (CTCAE v5), and analgesic orders during RT were extracted. Temporal changes in AP scores and VS were analyzed using linear mixed effect models. AP trajectories were reduced to single metric area under the curve calculations (AUCpain). Correlations were assessed using Spearman correlation coefficients.ResultsMedian age was 60 years, and 70% and 42% received chemotherapy and surgery, respectively. A significant increase in pain, mucositis, dermatitis, and overall treatment toxicity severity were observed by the end of RT. AUCpain was significantly different based on gender, primary tumor site, surgery, drug use history and pre-RT pain. There was a temporal mean weight loss of 7.1% bodyweight (95%CI, 10-8.2; PPPP.001) while weight and MAP were negatively associated over time (PConclusionThis study characterizes longitudinal treatment-related toxicity kinetics using a prospective OC/OPC registry and demonstrates an ongoing need for optimized, timely pain control. Pain AUC metrics preserve temporal information and may be useful for developing algorithmic pain prediction and management models.

Purpose To determine the optimal dose‐volume constraint for laryngeal sparing using three commonly employed intensity modulated radiation therapy (IMRT) approaches in patients with oropharyngeal cancer treated to the bilateral neck. Materials and methods Thirty patients with stage II‐IVA oropharynx cancers received definitive radiotherapy with split‐field IMRT (SF‐IMRT) to the bilateral neck between 2008 and 2013. Each case was re‐planned using whole‐field IMRT (WF‐IMRT) and volumetric modulated arc therapy (VMAT) and plan quality metrics and dose to laryngeal structures was evaluated. Two larynx volumes were defined and compared on the current study: the Radiation Therapy Oncology Group (RTOG) larynx as defined per the RTOG 1016 protocol and the MDACC larynx defined as the components of the larynx bounded by the superior and inferior extent of the thyroid cartilage. Results Target coverage, conformity, and heterogeneity indices were similar in all techniques. The RTOG larynx mean dose was lower with WF‐IMRT than SF‐IMRT (22.1 vs 25.8 Gy; P

Objectives Evaluate the use of induction chemotherapy (IC) in oropharyngeal cancer (OPC) and its impact on subjective functional outcomes using a validated MD Anderson Symptom Inventory‐Head and Neck (MDASI‐HN) survey tool. Methods A single institution retrospective review of OPC patients who received IC, including reasons given for using IC, regimens employed, responses, and patient‐reported outcomes (PRO). The latter included pain, distress, dysphagia, xerostomia, and feeding tube placement and dependency. PRO's were assessed using the validated MD Anderson Symptom Inventory‐Head and Neck (MDASI‐HN) conducted at baseline, during treatment, and at six‐month follow up. Results One hundred and twenty‐five patients were evaluable. They were more likely to have large primary and/or bulky or low neck nodal disease as a reason for IC. A taxane‐containing regimen was most common. Primary tumor response was seen in 83.2% and the nodal response in 81.6%. Pain and xerostomia improved with IC, dysphagia was not adversely affected with IC. These symptoms all increased with consolidation chemoradiotherapy (CRT) but returned to baseline by 6 months post treatment. Feeding tube placement did not increase with IC but did with CRT, most patients were no longer feeding tube dependent at 6 months. Conclusion This retrospective review of subjective functional outcomes, especially swallowing and feeding tube dependency, using the MDASI survey tool in 125 oropharyngeal cancer patients with large primary tumors and/or bulky adenopathy treated predominantly with platinum‐taxane based induction chemotherapy showed that such outcomes were not adversely impacted. While not standard, such approach may be beneficial in such patients. Level of Evidence 2., HPV‐positive oropharyngeal cancer typically has a good survival prognosis. Standard treatment with radiation and chemotherapy, while curative, can produce long term dysfunctional outcomes. Induction chemotherapy has not been shown to improve overall survival but is occasionally used in patients with high stage and/or aggressive disease. we looked at the impact of induction chemotherapy on subjective functional outcomes.

OBJECTIVE: The purpose of this study was to estimate prevalence/severity of self-reported trismus, determine association with quality of life (QOL), and examine clinical risk factors in a large population of patients treated for oropharyngeal cancer. MATERIALS AND METHODS: A cross-sectional survivorship survey was conducted among patients who completed definitive treatment for oropharyngeal carcinoma, disease-free ≥ 1-year post-treatment (median survival, 7 years among 892 survivors). Associations between trismus and QOL were also analyzed using MDASI-HN, EQ-5D, and MDADI. Dietary and feeding tube status were also correlated to trismus status. RESULTS: Trismus was self-reported in 31%. Severity of trismus positively correlated (r = 0.29) with higher mean interference scores reflecting a moderate association with quality of life (p < 0.0001). There was a negative correlation for MDADI composite scores (r = − 0.33) indicating increased perceived dysphagia related to trismus severity (p < 0.0001). EQ-5D VAS scores were also negatively correlated with trismus severity (r = − 0.26, p < 0.0001). Larger T-stage (p ≤ 0.001), larger nodal stage (p = 0.03), tumor sub-site (p = 0.05), and concurrent chemoradiation (p = 0.01) associated with increased prevalence of trismus. Diet negatively correlated (r = − 0.27) with trismus severity (p = < 0.0001), and survivors with severe trismus were also more likely to be feeding tube-dependent. CONCLUSION: Severity of trismus appears to negatively impact quality of life and associate with various adverse functional outcomes in long-term oropharyngeal cancer survivorship. Trismus remains associated with advanced disease stages, tumor sub-site (tonsil), and addition of chemotherapy. Further investigation is merited for the dose-effect relationship to the muscles of mastication.

PURPOSE: To ascertain the dose-toxicity relationship for the prevalence of self-reported trismus in long-term survivors after intensity-modulated radiotherapy (IMRT) for oropharyngeal carcinoma (OPC). MATERIALS AND METHODS: Self-reported mouth opening was ascertained prospectively via a cross-sectional survey of OPC survivors using the intraoral finger-test. RT dose-volume histograms (DVHs) were generated for the following masticatory regions of interest: medial pterygoid, lateral pterygoid, and masseter muscles which were designated as ipsilateral or contralateral to the primary tumor. Trismus was defined as self-reported mouth opening of

Purpose: In oropharyngeal squamous cell carcinoma (OPC), high CD8+ tumor-infiltrating lymphocyte (CD8+TIL) density confers improved prognosis. We compared neoadjuvant durvalumab (PD-L1 inhibitor) with durvalumab + tremelimumab (CTLA-4 inhibitor) in terms of impact on CD8+TIL density, safety, and efficacy in patients with OPC. Patients and Methods: Patients with newly diagnosed stage II–IVA OPC or locoregionally recurrent OPC amenable to resection were included. Patients were randomized to two cycles of durvalumab or durvalumab + tremelimumab before surgery. The primary endpoint was change between baseline and resection specimen in CD8+TIL density between arms. Secondary endpoints included safety, response rate per RECIST, major pathologic response (MPR; ≤10% viable tumor cells) rate, and patient-reported outcomes. Results: Of 28 eligible patients (14/arm), 20 (71%) had newly diagnosed OPC, and 24 (86%) were p16-positive. The posttreatment to pretreatment median CD8+TIL density ratio was 1.31 for durvalumab and 1.15 for combination treatment (P = 0.97; 95% CI: −1.07–2.28). In each group, 6 patients (43%, 95% CI: 17.66–71.14) had a response. Eight patients (29%) had a MPR at the primary tumor and/or nodal metastases. Neither baseline CD8+TIL density nor PD-L1 expression level correlated with overall response, but a trend toward greater CD8+TIL change in patients with a MPR was seen (P = 0.059; 95% CI: −0.33–3.46). Four patients (14%) had grade ≥3 adverse events. At median follow-up time of 15.79 months, all patients were alive, and one had an additional recurrence. Conclusions: Durvalumab + tremelimumab did not increase CD8+TIL density more than durvalumab alone did. The observed safety and activity support further investigation of neoadjuvant checkpoint inhibitor for OPC.

Background and purpose With an enlarging population of long-term oropharyngeal cancer survivors, dysphagia is an increasingly important toxicity following oropharynx cancer treatment. While lower doses to normal surrounding structures may be achieved with intensity modulated proton therapy (IMPT) compared to photon-based radiation, the clinical benefit is uncertain. Methods and materials Seventy-one patients with stage III/IV oropharyngeal cancer (AJCC 7th edition) undergoing definitive IMPT on a longitudinal prospective cohort study who had completed the MD Anderson Dysphagia Inventory (MDADI) at pre-specified time points were included. Results The majority of patients had HPV-positive tumors (85.9%) and received bilateral neck radiation (81.4%) with concurrent systemic therapy (61.8%). Mean composite MDADI scores decreased from 88.2 at baseline to 59.6 at treatment week 6, and then increased to 74.4 by follow up week 10, 77.0 by 6 months follow up, 80.5 by 12 months follow up, and 80.1 by 24 months follow up. At baseline, only 5.6% of patients recording a poor composite score (lower than 60), compared to 61.2% at treatment week 6, 19.1% at follow up week 10, 13.0% at 6 months follow up, 13.5% at 1 year follow up, and 11.1% at 2 years follow up. Conclusions Patient reported outcomes following IMPT for oropharyngeal cancer demonstrates decreased swallowing function at completion of treatment with relatively rapid recovery by 10 weeks follow up and steady improvement through 2 years. The results are comparable to similar longitudinal studies of photon-based radiotherapy for oropharynx cancer, and suggest that IMPT confers no additional excess toxicity related to swallowing.

Author(s): MD Anderson Head and Neck Surgery Treatment Guidelines Consortium; Consortium members; Maniakas, Anastasios; Jozaghi, Yelda; Zafereo, Mark E; Sturgis, Erich M; Su, Shirley Y; Gillenwater, Ann M; Gidley, Paul W; Lewis, Carol M; Diaz, Eduardo; Goepfert, Ryan P; Kupferman, Michael E; Gross, Neil D; Hessel, Amy C; Pytynia, Kristen B; Nader, Marc-Elie; Wang, Jennifer R; Lango, Miriam N; Kiong, Kimberley L; Guo, Theresa; Zhao, Xiao; Yao, Christopher MKL; Appelbaum, Eric; Alpard, Jennifer; Garcia, Jose A; Terry, Shawn; Flynn, Jill E; Bauer, Sarah; Fournier, Danielle; Burgess, Courtlyn G; Wideman, Cayla; Johnston, Matthew; You, Chenxi; De Luna, Rolando; Joseph, Liza; Diersing, Julia; Prescott, Kaitlin; Heiberger, Katherine; Mugartegui, Lilian; Rodriguez, Jessica; Zendehdel, Sara; Sellers, Justin; Friddell, Rebekah A; Thomas, Ajay; Khanjae, Sonam J; Schwarzlose, Katherine B; Chambers, Mark S; Hofstede, Theresa M; Cardoso, Richard C; Wesson, Ruth Aponte; Won, Alex; Otun, Adegbenga O; Gombos, Dan S; Al-Zubidi, Nagham; Hutcheson, Katherine A; Gunn, G Brandon; Rosenthal, David I; Gillison, Maura L; Ferrarotto, Renata; Weber, Randal S; Hanna, Ehab Y; Myers, Jeffrey N; Lai, Stephen Y | Abstract: BackgroundCOVID-19 pandemic has strained human and material resources around the world. Practices in surgical oncology had to change in response to these resource limitations, triaging based on acuity, expected oncologic outcomes, availability of supportive resources, and safety of health care personnel.MethodsThe MD Anderson Head and Neck Surgery Treatment Guidelines Consortium devised the following to provide guidance on triaging head and neck cancer (HNC) surgeries based on multidisciplinary consensus. HNC subsites considered included aerodigestive tract mucosa, sinonasal, salivary, endocrine, cutaneous, and ocular.RecommendationsEach subsite is presented separately with disease-specific recommendations. Options for alternative treatment modalities are provided if surgical treatment needs to be deferred.ConclusionThese guidelines are intended to help clinicians caring for patients with HNC appropriately allocate resources during a health care crisis, such as the COVID-19 pandemic. We continue to advocate for individual consideration of cases in a multidisciplinary fashion based on individual patient circumstances and resource availability.

Background This study reports long-term head and neck cancer (HNC) patient-reported symptoms using the MD Anderson Symptom Inventory Head and Neck Cancer Module (MDASI-HN) in a large cohort of HNC survivors. Methods MDASI-HN results were prospectively collected from an institutional survivorship database. Associations with clinicopathologic data were analyzed using χ2 , Mann-Whitney, and univariate regression. Results Nine hundred and twenty-eight patients were included. Forty-six percent had oropharyngeal primary tumors. Eighty-two percent had squamous cell carcinoma. Fifty-six percent of patients had ablative surgery and 81% had radiation therapy as a component of treatment. The most severe symptoms were xerostomia and dysphagia. Symptom scores were worst for hypopharynx and varied by subsite. Patients treated with chemoradiation or surgery followed by radiation ± chemotherapy reported the worst symptoms while patient treated with surgery plus radiation ± chemotherapy reported the worst interference. Conclusion HNC survivors describe their long-term symptom burden and inform efforts to improve care many years into survivorship.

Purpose: To evaluate 2 published normal tissue complication probability models for radiation-induced hypothyroidism (RHT) on a large cohort of oropharyngeal carcinoma (OPC) patients who were treated with intensity-modulated radiation therapy (IMRT). Methods and Materials: OPC patients treated with retrievable IMRT Digital Imaging and Communications in Medicine (DICOMs) data and available baseline and follow-up thyroid function tests were included. Mean dose (Dmean) to the thyroid gland (TG) and its volume were calculated. The study outcome was clinical HT at least 6 months after radiation therapy, which was defined as grade ≥2 HT per Common Terminology Criteria for Adverse Events grading system (symptomatic hypothyroidism that required thyroid replacement therapy). Regression analyses and Wilcoxon rank-sum test were used. Receiver operating characteristic curves and area under the curve for the fitted model were calculated. Results: In the study, 360 OPC patients were included. The median age was 58 years. Most tumors (51%) originated from the base of tongue. IMRT-split field was used in 95%, and median radiation therapy dose was 69.96 Gy. In the study, 233 patients (65%) developed clinical RHT that required thyroid replacement therapy. On multivariate analysis higher Dmean and smaller TG volume maintained the statistically significant association with the risk of clinical RHT (P

PurposeTo quantitatively compare and assess the geometric distortion and apparent diffusion coefficient (ADC) accuracy of conventional single-shot EPI (SSEPI)-DWI, readout segmentation of long variable echo-trains (RESOLVE)-DWI, and BLADE-DWI techniques in both phantom and volunteer imaging studies.MethodsPhantom measurements were obtained using the QIBA DWI phantom at 0° and at ambient temperature (~17°). DW images were acquired using SSEPI-DWI, RESOLVE-DWI, and BLADE-DWI. Image geometric distortion factors (compression and dilation, shear distortion), and image shift factors were measured and compared with computed tomography images. ADC and signal-to-noise ratio (SNR) values were measured for the various DWI techniques. Images were also obtained from three healthy volunteers and three oropharynx cancer patients. Geometric distortion parameters and ADC values were analyzed in the following head and neck regions of interest (ROI): salivary glands, tonsils, and primary tumors (patient only). The metric evaluation included Dice similarity coefficient and Hausdorff distance mean. T2-weighted images were used as a reference to evaluate geometric distortion.ResultsIn the phantom experiment, the vials were prominently distorted on the SSEPI-DWI and RESOLVE-DWI images but were less distorted on the BLADE-DWI image, as determined by the overall effects of Image geometric distortion factors. The paired t-test showed no significant difference (0.15 < p < 0.88) in ADC values among the three DWI techniques; however, BLADE-DWI led to a lower SNR in vials. In the volunteer and patient studies, an ROI-based overlap metrics analysis of the salivary glands and gross tumor volumes were less distorted for BLADE-DWI than for EPI-based DWI, as determined by Wilcoxon paired signed-rank test.ConclusionBLADE-DWI demonstrated excellent geometric accuracy, with similar quantitative ADC values to those of EPI-based DW-MRI, thus potentially making this technique suitable for target volume delineation and functional assessment for head and neck radiation treatment in the future.

IMPORTANCE: Trismus is highly prevalent in head and neck cancer (HNC) survivorship. Current standards for trismus treatment include various stretch-based exercise protocols as a primary and single treatment modality with limited evidence regarding the role of manual therapy (MT) for this indication. OBJECTIVE: To assess the effect size and associations of response to MT to increase oral opening in the setting of radiation-associated trismus. DESIGN, SETTING, AND PARTICIPANTS: This retrospective case series was conducted at the University of Texas MD Anderson Cancer Center between 2016 and March 2020 (before COVID-19 interruption) and included 49 disease-free survivors of HNC who were referred for treatment of radiation-associated trismus. INTERVENTION: Intraoral MT (including or excluding external head and neck) targeting the muscles of mastication. MAIN OUTCOMES AND MEASURES: Maximum interincisal opening (MIO) before and after the initial MT session compared with serial MT sessions. Covariates were examined to determine the association with response to MT for trismus. RESULTS: A total of 49 survivors of HNC (13 women [27%]; 24 [49%] 64 years or younger; 25 [51%] 65 years or older; mean [range] of 6.6 [0-33] years postradiotherapy were included, 9 [18.4%] of whom underwent a single MT session; 40 [81.6%] who underwent multiple sessions [mean, 6; median (range), 3 (2-48)]). The MIO improved after a single session by a mean (SD) of 4.1 (1.9) mm (0.45 effect size) and after serial MT sessions by a mean (SD) of 6.4 (4.8) mm with an effect size of 0.7. No covariates were found to be clinically meaningfully associated with MIO improvement following MT. CONCLUSIONS AND RELEVANCE: The findings of this case series study suggest that MT improved MIO with a medium to large effect size in survivors of HNC with radiation-associated trismus. The results suggest that the largest increase in oral opening was achieved after the initial treatment and although gains were more modest, oral opening continued to improve with serial treatment. Covariates were not associated with MT response, suggesting that patients with clinical features often considered treatment refractory (eg, advanced disease, multiple lines of oncology treatment, ≥5 years posttreatment) may benefit from treatment with MT. Manual therapy may be a beneficial frontline or adjuvant treatment when combined with traditional stretching therapy. A clinically meaningful increase in oral opening has the potential to improve swallow function, speech, pain, and quality of life.

BACKGROUND: DIGEST is a validated method to grade the severity of pharyngeal swallowing impairment as a toxicity of cancer based on degree and patterns of penetration/aspiration and pharyngeal residue over a standardly acquired radiographic modified barium swallow (MBS) study. Since implementation in 2016, areas for refinement of grading mild safety impairment were identified by clinical and research users. The objective was to assess performance and validity of refined DIGEST(safety) grading criteria (per DIGEST(v2)). METHODS: Refined safety criteria were developed and vetted with clinical and research users. DIGEST(v2) includes two changes to safety criteria. All MBS with blinded DIGEST(v1) grading were sampled from a registry database (1,331 patients underwent MBS over the period 12/2005 to 07/2019). New criteria were applied to derive DIGEST(safety) grade version 2. Measures of criterion validity, including MDADI composite score, MBSImP(™)© Pharyngeal Total, MBSImP(™)© hyolaryngeal components (items 8–11), and PSS-HN diet, were correlated with DIGEST(safety) and overall DIGEST grade from v1 and v2, and compared pairwise between re-assigned grades. RESULTS: With application of v2 Safety criteria, 112/1,331 (8.4%) and 79/1,331 (5.9%) of exams changed in DIGEST(safety) and overall grades, respectively. Safety and overall DIGEST grades v1 and v2 significantly correlated with criterion measures including MBSImP pharyngeal total, laryngeal MBSImP parameters of interest, MDADI, and PSS-HN (p

BACKGROUND: The study objective is to identify risk factors associated with fatigue among long-term OPC survivors. METHODS: This cross-sectional study included disease-free OPC survivors treated curatively between 2000 and 2013 who were surveyed from September 2015 to July 2016. The outcome variable was patient-reported fatigue. Multivariable logistic regression was used to identify factors associated with moderate to severe fatigue. RESULTS: Among 863 OPC survivors, 17.4% reported moderate to severe fatigue. Self-reported thyroid problems (OR: 2.01; p = 0.003), current cigarette smoking at time of survey (OR: 3.85; p = 0.001), late lower cranial neuropathy (OR: 3.44; p = 0.002), and female sex (OR: 1.91; p = 0.010) were concurrent risk factors of reporting moderate to severe fatigue. Ipsilateral intensity-modulated radiotherapy (OR: 0.18; p = 0.014) was associated with lower risk of reporting moderate to severe fatigue. CONCLUSIONS: Our study identified thyroid problems, smoking, and late lower cranial neuropathy as associated with moderate to severe fatigue. These findings should be further validated in prospective studies to address fatigue among OPC survivors.

We sought to determine overall survival (OS), prognostic factors, cost, and functional outcomes after surgery for locally recurrent oral cavity squamous cell carcinoma (OCSCC).We retrospectively reviewed 399 cases of locally recurrent OCSCC from 1997 to 2011, of which 259 patients were treated with salvage surgery. Survival and prognostic factors were evaluated using univariable and multivariable Cox regression, the Kaplan-Meier method, and the log-rank test.The 5-year OS for patients undergoing surgical salvage, nonsurgical therapy, or supportive care was 44.2%, 1.5%, and 0%, respectively. For patients who underwent surgical salvage, 133 (51%) patients experienced a second recurrence at a median of 17 months. Factors associated with OS included disease-free interval ≤ 6 months (P =.0001), recurrent stage III-IV disease (P lt;.0001), and prior radiation (P =.0001). Patients with both advanced stage and prior radiation had a 23% 5-year OS, compared with 70% for those with neither risk (P lt;.001). Functionally, 85% of patients had gt; 80% speech intelligibility and 81% were able to eat by mouth following salvage surgery. Of the patients who required tracheostomy, 78% were decannulated. The adjusted median hospital and professional charges for patients were $129,696 (range $9,238-$956,818).Patients with recurrent OCSCC who underwent salvage surgery have favorable functional outcomes with half of alive at 5 years but poorer OS for advanced disease, disease-free interval ≤ 6 months, and prior radiation. Additionally, treatment is associated with high cost, and about half of patients ultimately develop another recurrence.

ImportancePreviously published work reported independent benefit of maintenance of oral intake (eat) and swallowing exercise adherence (exercise) during radiotherapy (RT) on diet and functional outcomes. The current study seeks to validate the authors’ previously published findings in a large contemporary cohort of patients with oropharynx cancer (OPC) and address limitations of the prior retrospective study using prospective, validated outcome measures.ObjectiveTo examine the longitudinal association of oral intake and swallowing exercise using validated, clinician-graded and patient-reported outcomes.Design, Setting, and ParticipantsSecondary analysis of a prospective OPC registry including patients who underwent primary RT/chemoradiotherapy (CRT) or primary transoral robotic surgery plus RT/CRT for OPC at a single-institution comprehensive cancer center.ExposuresAdherence to speech pathology swallowing intervention during RT coded as (1) eat: oral intake at end of RT (nothing by mouth [NPO]; partial oral intake [PO], with feeding tube [FT] supplement; full PO); and (2) exercise: swallowing exercise adherence (nonadherent vs partial/full adherence).Main Outcomes and MeasuresFeeding tube and diet (Performance Status Scale for Head and Neck Cancer) patient-reported swallowing-related quality of life (MD Anderson Dysphagia Inventory; MDADI) and clinician-graded dysphagia severity grade (videofluoroscopic Dynamic Imaging Grade of Swallowing Toxicity; DIGEST) were collected at baseline, 3 to 6 months, and 18 to 24 months post-RT.ResultsA total of 595 patients (mean [SD] age, 65 [10] years; 532 [89%] male) who underwent primary RT (111 of 595 [19%]), CRT (434 of 595 [73%]), or primary transoral robotic surgery plus RT/CRT (50 of 595 [8%]) were included in this cohort study. At the end of RT, 55 (9%) patients were NPO, 115 (19%) were partial PO, 425 (71%) were full PO, and 340 (57%) reported exercise adherence. After multivariate adjustment, subacute return to solid diet and FT were independently associated with oral intake (odds ratio [OR], 2.0; 95% CI, 1.0-4.1; OR, 0.1; 95% CI, 0.0-0.2, respectively) and exercise (OR, 2.9; 95% CI, 1.9-4.5; OR, 0.3; 95% CI, 0.1-0.5, respectively). Subacute MDADI (β = 6.5; 95% CI, 1.8-11.2), FT duration (days; β = −123.4; 95% CI, −148.5 to −98.4), and less severe dysphagia per DIGEST (OR, 0.6; 95% CI, 0.3-1.0) were independently associated with oral intake, while exercise was independently associated with less severe laryngeal penetration/aspiration per DIGEST-safety (OR, 0.7; 95% CI, 0.4-1.0). DIGEST grade associations with oral intake were not preserved long-term; however, exercise was associated with a higher likelihood of solid diet intake and better swallow safety per DIGEST.Conclusions and RelevanceThe findings of this cohort study extend the authors’ previously published findings that oral intake and swallowing exercise during RT are associated with favorable functional outcomes, now demonstrated with broader domains of function using validated measures. Patterns of benefit differed in this study. Specifically, better subacute recovery of swallow-related quality of life and less severe dysphagia were found among patients who maintained oral intake independent of exercise adherence, and shorter FT utilization and better long-term diet and swallowing safety were found among those who exercised independent of oral intake.

Genetic susceptibility for xerostomia, a common sequela of radiotherapy and chemoradiotherapy for head and neck cancer, is unknown. Therefore, to identify genetic variants associated with moderate to severe xerostomia, we conducted a GWAS of 359 long-term oropharyngeal cancer (OPC) survivors using 579,956 autosomal SNPs. Patient-reported cancer treatment-related xerostomia was assessed using the MD Anderson Symptom Inventory. Patient response was dichotomized as moderate to severe or none to mild symptoms. In our study, 39.2% of OPC survivors reported moderate to severe xerostomia. Our GWAS identified eight SNPs suggestively associated with higher risk of moderate to severe xerostomia in six genomic regions (2p13.3, rs6546481, Minor Allele (MA) = A, ANTXR1, P = 4.3 × 10–7; 5p13.2–p13.1, rs16903936, MA = G, EGFLAM, P = 5.1 × 10–6; 4q21.1, rs10518156, MA = G, SHROOM3, P = 7.1 × 10–6; 19q13.42, rs11882068, MA = G, NLRP9, P = 1.7 × 10–5; 12q24.33, rs4760542, MA = G, GLT1D1, P = 1.8 × 10–5; and 3q27.3, rs11714564, MA = G, RTP1, P = 2.9 × 10–5. Seven SNPs were associated with lower risk of moderate to severe xerostomia, of which only one mapped to specific genomic region (15q21.3, rs4776140, MA = G, LOC105370826, a ncRNA class RNA gene, P = 1.5 × 10–5). Although our small exploratory study did not reach genome-wide statistical significance, our study provides, for the first time, preliminary evidence of genetic susceptibility to xerostomia. Further studies are needed to elucidate the role of genetic susceptibility to xerostomia.

Background This study was conducted to identify clinicodemographic risk factors for xerostomia among long-term oropharyngeal cancer (OPC) survivors. Methods This cross-sectional study included 906 disease-free, adult OPC survivors with a median survival duration at the time of survey of 6 years (range, 1-16 years); self-reported xerostomia scores were available for 877 participants. Study participants had completed curative treatment between January 2000 and December 2013 and responded to a survey administered from September 2015 to July 2016. The primary outcome variable was cancer patient-reported xerostomia measured with the MD Anderson Symptom Inventory Head and Neck Cancer Module. Clinicodemographic risk factors for moderate to severe xerostomia were identified via multivariable logistic regression. Results Moderate to severe xerostomia was reported by 343 of the respondents (39.1%). Female sex (odds ratio [OR], 1.82; 95% CI, 1.22-2.71; P = .003; Bayesian false-discovery probability [BFDP] = 0.568), high school or lower education (OR, 1.73; 95% CI, 1.19-2.52; P = .004; BFDP = 0.636), and current cigarette smoking at the time of survey (OR, 2.56; 95% CI, 1.19-5.47; P = .016; BFDP = 0.800) were risk factors for moderate to severe xerostomia, and bilateral intensity-modulated radiotherapy (IMRT) combined with proton therapy and ipsilateral IMRT were protective. Conclusions In this large xerostomia study, modern radiotherapy was a protective factor, and continued cigarette smoking at the time of survey, female sex, and high school or lower education were identified as other contributing risk factors associated with moderate to severe xerostomia. Importantly, these findings need to be confirmed in prospective studies. These results can inform future research and targeted patient-centered interventions to monitor and manage radiation therapy-associated xerostomia and preserve quality of life among patients with OPC.

BACKGROUND Oropharyngeal cancer survivors experience difficulty returning to work after treatment. To better understand specific barriers to returning to work, we investigated factors associated with discontinuing employment among older and working-age survivors. METHODS The sample included 675 oropharyngeal cancer survivors (median: 6 years posttreatment) diagnosed from 2000 to 2013 and employed at diagnosis. Relative risk models were constructed to examine the independent associations of demographic and health factors, and symptom experiences per the MD Anderson Symptom Inventory - Head and Neck Module (MDASI-HN) with posttreatment employment, overall and by age (