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Young patients, including pediatric, adolescent, and young adult (YA) patients, are most likely to benefit from the reduced integral dose of proton beam radiation therapy (PBT) resulting in fewer late toxicities and secondary malignancies. This study sought to examine insurance approval and appeal outcomes for PBT among YA patients compared with pediatric patients at a large-volume proton therapy center.We performed a cross-sectional cohort study of 284 consecutive patients aged 0 to 39 years for whom PBT was recommended in 2018 through 2019. Pediatric patients were defined as aged 0 to 18 years and YA patients 19 to 39 years. Rates of approval, denials, and decision timelines were calculated. Tumor type and location were also evaluated as factors that may influence insurance decisions.A total of 207 patients (73%) were approved for PBT at initial request. YA patients (n = 68/143, 48%) were significantly less likely to receive initial approval compared with pediatric patients (n = 139/141; 99%) (P.001). Even after 47% (n = 35 of 75) of the PBT denials for YA patients were overturned, YAs had a significantly lower final PBT approval (72% vs pediatric 99%; P.001). The median wait time was also significantly longer for YA patients (median, 8 days; interquartile range [IQR] 3-17 vs median, 2 days; IQR, 0-6; P.001). In those patients requiring an appeal, the median wait time was 16 days (IQR, 9-25).Given the decades of survivorship of YA patients, PBT is an important tool to reduce late toxicities and secondary malignancies. Compared with pediatric patients, YA patients are significantly less likely to receive insurance approval for PBT. Insurance denials and subsequent appeal requests result in significant delays for YA patients. Insurers need to re-examine their policies to include expedited decisions and appeals and removal of arbitrary age cutoffs so that YA patients can gain easier access to PBT. Furthermore, consensus guidelines encouraging greater PBT access for YA may be warranted from both medical societies and/or AYA experts.

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

BACKGROUND AND PURPOSE: Sarcopenia is associated with decreased survival in head and neck cancer patients treated with radiotherapy. This study sought to determine whether in-clinic multifrequency bioelectrical impedance analysis (BIA) can identify survival-associated sarcopenia in patients with head and neck cancer. MATERIALS AND METHODS: This prospective observational study enrolled 50 patients with head and neck cancer undergoing radiation therapy. Baseline BIA measures of skeletal muscle (SM) mass, fat-free mass (FFM), and fat mass (FM) were compared to CT-based estimates using linear regression. Sex-specific BIA-derived thresholds for sarcopenia were defined by the maximum Youden Index on receiver operator characteristic (ROC) curves. Patients were stratified by sarcopenia status and OS was compared using the Kaplan-Meier method and log-rank test. RESULTS: Among 48 evaluable patients, BIA measures of body composition were strongly correlated with CT measures: SM mass (r = 0.97; R(2) = 0.94; p < 0.0001), FFM (r = 0.97; R(2) = 0.94; p < 0.0001) and FM (r = 0.95; R(2) = 0.90; p < 0.0001). SM mass index < 9.19 kg/m(2) identified sarcopenia men with high sensitivity (91.7%) and specificity (92.9%), whereas in women SM mass index < 6.53 kg/m(2) was sensitive for sarcopenia (100%), but not specific. Patients with sarcopenia, defined by either CT or BIA, exhibited decreased OS (HR=not estimable; CT p = 0.009; BIA p = 0.03). CONCLUSION: BIA provides accurate estimates of body composition in head and neck cancer patients. Implementation of BIA in clinical practice may identify patients with sarcopenia at risk for poor survival.

Purpose To report clinical outcomes in terms of disease control and toxicity in patients with major salivary gland cancers (SGCs) treated with proton beam therapy. Materials and Methods Clinical and dosimetric characteristics of patients with SGCs treated from August 2011 to February 2020 on an observational, prospective, single-institution protocol were abstracted. Local control and overall survival were calculated by the Kaplan-Meier method. During radiation, weekly assessments of toxicity were obtained, and for patients with ≥ 90 days of follow-up, late toxicity was assessed. Results Seventy-two patients were identified. Median age was 54 years (range, 23-87 years). Sixty-three patients (88%) received postoperative therapy, and nine patients (12%) were treated definitively. Twenty-six patients (36%) received concurrent chemotherapy. Nine patients (12%) had received prior radiation. All (99%) but one patient received unilateral treatment with a median dose of 64 GyRBE (relative biological effectiveness) (interquartile range [IQR], 60-66), and 53 patients (74%) received intensity-modulated proton therapy with either single-field or multifield optimization. The median follow-up time was 30 months. Two-year local control and overall survival rates were 96% (95% confidence interval [CI] 85%-99%) and 89% (95% CI 76%-95%], respectively. Radiation dermatitis was the predominant grade-3 toxicity (seen in 21% [n = 15] of the patients), and grade ≥ 2 mucositis was rare (14%; n = 10 patients). No late-grade ≥ 3 toxicities were reported. Conclusion Proton beam therapy for treatment of major SGCs manifests in low rates of acute mucosal toxicity. In addition, the current data suggest a high rate of local control and minimal late toxicity.

In most childhood head and neck cancers, radiotherapy is an essential component of treatment; however, it can be associated with problematic long-term complications. Proton beam therapy is accepted as a preferred radiation modality in pediatric cancers to minimize the late radiation side effects. Given that childhood cancers are a rare and heterogeneous disease, the support for proton therapy comes from risk modeling and a limited number of cohort series. Here, we discuss the role of proton radiotherapy in pediatric head and neck cancers with a focus on reducing radiation toxicities. First, we compare the efficacy and expected toxicities in proton and photon radiotherapy for childhood cancers. Second, we review the benefit of proton radiotherapy in reducing acute and late radiation toxicities, including risks for secondary cancers, craniofacial development, vision, and cognition. Finally, we review the cost effectiveness for proton radiotherapy in pediatric head and neck cancers. This review highlights the benefits of particle radiotherapy for pediatric head and neck cancers to improve the quality of life in cancer survivors, to reduce radiation morbidities, and to maximize efficient health care use.

Purpose In value-based health care delivery, radiation oncologists need to compare empiric costs of care delivery with advanced technologies, such as intensity-modulated proton therapy (IMPT) and intensity-modulated radiation therapy (IMRT). We used time-driven activity-based costing (TDABC) to compare the costs of delivering IMPT and IMRT in a case-matched pilot study of patients with newly diagnosed oropharyngeal (OPC) cancer. Materials and Methods We used clinicopathologic factors to match 25 patients with OPC who received IMPT in 2011-12 with 25 patients with OPC treated with IMRT in 2000-09. Process maps were created for each multidisciplinary clinical activity (including chemotherapy and ancillary services) from initial consultation through 1 month of follow-up. Resource costs and times were determined for each activity. Each patient-specific activity was linked with a process map and TDABC over the full cycle of care. All calculated costs were normalized to the lowest-cost IMRT patient. Results TDABC costs for IMRT were 1.00 to 3.33 times that of the lowest-cost IMRT patient (mean ± SD: 1.65 ± 0.56), while costs for IMPT were 1.88 to 4.32 times that of the lowest-cost IMRT patient (2.58 ± 0.39) (P Conclusions In this matched sample, although IMPT was on average more costly than IMRT primarily owing to higher equipment costs, a subset of IMRT patients had similar costs to IMPT patients, owing to greater use of supportive care resources. Multidimensional patient outcomes and TDABC provide vital methodology for defining the value of radiation therapy modalities.

Introduction Tongue-deviating oral stents (TDOS) are commonly used during unilateral neck radiation therapy to reduce unnecessary dose to nontarget oral structures. Their benefit in the setting of highly conformal treatment techniques, however, is not defined. The goal of this study was to investigate the potential benefit of TDOS use on dosimetric parameters in unilateral intensity modulated radiation therapy (IMRT) and intensity modulated proton therapy (IMPT). Methods A total of 16 patients with T1-2 tonsil cancer treated at a single institution were selected, of which 8 were simulated/treated with a TDOS and 8 without a TDOS. All received definitive unilateral IMRT to a dose of 66 Gy in 30 fx. IMPT plans were generated for each patient for study purposes and optimized according to standard institutional practice. Results For IMRT plans, the presence of a TDOS (vs without) was associated with a significantly lower oral mucosa mean dose (31.4 vs 35.3 Gy; P = .020) and V30 (42.7% vs 57.1%; P = .025). For IMPT plans, the presence of TDOS (vs without) was not associated with any improvement in oral mucosa mean dose (18.3 vs 19.9 Gy; P = .274) or V30 (25.0% vs 26.2%; P = .655). IMPT plans without TDOS compared with IMRT plans with TDOS demonstrated reduced oral mucosa mean dose (P < .001) and V30 (P < .001). Conclusion The use of a TDOS for the unilateral treatment of well-lateralized tonsil cancers was associated with oral mucosa sparing for IMRT, but not for IMPT. Moreover, mucosa sparing was improved for IMPT plans without a TDOS compared to IMRT plans with a TDOS.

Background This study aimed to evaluate the prognostic value of pre-treatment NLR in patients with oropharyngeal cancer. Methods Patients who completed definitive radiotherapy (RT) for oropharyngeal cancer and had blood counts taken pre-RT from 2002 to 2013 were included. NLR was calculated as total neutrophil/lymphocytes. Survival rates were estimated using the Kaplan–Meier method. Univariable and multivariable analyses were conducted with linear and Cox regression methods. NLR was analysed posteriori and dichotomised on the discovered median. Results Eight hundred and forty-eight patients were analysed. The median pre-RT NLR was 3. Patients with NLR of p p = 0.011; HPV-negative p = 0.003). Freedom from any recurrence (FFR), locoregional control (LRC) and freedom of distant recurrence (FDR) were better in those with NLR p = 0.001), FFR (HR = 1.6, p = 0.006) and LRC (HR = 1.8, p = 0.005) remained significant on multivariable analysis. Conclusions Pre-RT NLR is an independent prognostic factor in patients with oropharyngeal cancer regardless of HPV status. Patients with lower NLR had more favourable OS and disease control.

Purpose Here we provide an analysis of the set-up and positioning accuracy of SABR for skull base malignancies to evaluate the use of site- or axis-specific margins to reduce field size. Methods and Materials Data were prospectively collected on 63 patients who received 304 fractions of SABR for recurrent/previously irradiated skull base tumors. Using our custom cushion-mask-bite-block immobilization system combined with ExacTrac x-ray and cone beam computed tomography (CBCT), set-up, residual, CBCT-positioning agreement, and intrafractional errors were measured. The resulting planning target volume (PTV) margins were estimated across 4 skull base subsites: anterior (group 1), central (group 2), posterolateral (group 3), and skull base–associated sites (eg, nasopharynx/retropharyngeal, cervical vertebrae 1-2, occiput) (group 4). Results On initial set-up, 66% of treatment courses required shifts of >2 mm or >2°, necessitating 4.9 mm PTV margins without image guidance. After correction, only 6 of 304 treatment sessions had residual errors >1 mm. CBCT-ExacTrac agreement was ≤1 mm in 89.1% of treatments and ≤1.5 mm in all but 1 session. Group 4 showed a higher rate of >1 mm or >1° CBCT-positioning differences compared with other groups (24.5% vs 7.8%; P = .0001), and the greatest variations occurred in the craniocaudal translational and the pitch rotational axes. Overall calculated PTV margins (based on intrafractional error) were 1.5 mm across subsites except for group 4, which required 2.0 mm margins. Conclusions The use of 2.0 mm PTV margins for skull base SABR appears feasible using ExacTrac x-ray as the sole imaging modality for most subsites. However, PTVs were not uniformly equal, and the use of a site-specific nonuniform margin reduction to optimize critical-organ dose sparing may be feasible for select cases. These findings warrant clinical investigation.

Background The incidence of oropharyngeal squamous cell carcinoma (OPSCC) in the US is rapidly increasing, driven largely by the epidemic of human papillomavirus (HPV)-mediated OPSCC. Although survival for patients with HPV mediated OPSCC (HPV+ OPSCC) is generally better than that of patients with non-virally mediated OPSCC, this effect is not uniform. We hypothesized that tobacco exposure remains a critical modifier of survival for HPV+ OPSCC patients. Methods We conducted a retrospective analysis of 611 OPSCC patients with concordant p16 and HPV testing treated at a single institute (2002–2013). Survival analysis was performed using Kaplan-Meier analysis and Cox regression. Recursive partitioning analysis (RPA) was used to define tobacco exposure associated with survival (p Results Tobacco exposure impacted overall survival (OS) for HPV+ patients on univariate and multivariate analysis (p = 0.002, p = 0.003 respectively). RPA identified 30 pack-years (PY) as a threshold at which survival became significantly worse in HPV+ patients. OS and disease-free survival (DFS) for HPV+ > 30 PY patients didn’t differ significantly from HPV- patients (p = 0.72, p = 0.27, respectively). HPV+ > 30 PY patients had substantially lower 5-year OS when compared to their ≤30 PYs counterparts: 78.4% vs 91.6%; p = 0.03, 76% vs 88.3%; p = 0.07, and 52.3% vs 74%; p = 0.05, for stages I, II, and III (AJCC 8th Edition Manual), respectively. Conclusions Tobacco exposure can eliminate the survival benefit associated with HPV+ status in OPSCC patients. Until this effect can be clearly quantified using prospective datasets, de-escalation of treatment for HPV + OPSCC smokers should be avoided.

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.

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.

Background and purpose To report physician-assessed toxicities (PATs) and patient-reported outcomes (PROs) in a prospective cohort of patients treated using proton beam therapy (PBT). Methods and materials From 2011 to 2019, PBT-treated patients with a sinonasal malignancy were enrolled with a primary endpoint of toxicity assessment. PATs and PROs were assessed at baseline, acute (during PBT), subacute (within 90 days after PBT), and chronic time points. PATs were graded with the Common Terminology Criteria for Adverse Events V4.0. PROs were assessed with the Xerostomia-Related Quality-of-Life Scale (XeQoLS), MD Anderson Dysphagia Inventory (MDADI), and Functional Assessment of Cancer Therapy (FACT). PRO changes from baseline to follow-up were defined as significantly different based on a paired t-test plus a minimal clinically important difference. Results Sixty-four patients had a median follow-up time of 33 months (interquartile range: 10–52 months). The most common histology was olfactory neuroblastoma (28%) and most patients had T4 disease (46%). One acute G3 neurologic PAT (blurred vision) resolved, and no late G3–4 neurologic PATs were observed. Feeding tube placement occurred in 6% of patients. No significant changes were noted in PROs from baseline to the chronic period. Significant worsening from baseline was noted in the XeQoLS acute-subacute physical functioning, pain, personal/psychological distress, and social function; acute-subacute MDADI physical function; and acute-subacute FACT head/neck subscale. The 3-year local control, disease-free survival, and overall survival rates were 88%, 76%, and 82%, respectively. Conclusions We demonstrate low grade ≥3 toxicity and encouraging disease outcomes with PBT. PROs suggest significant changes in the acute-subacute period but no chronic sequelae.

During the coronavirus disease 2019 pandemic, minimizing exposure risk for patients with cancer and health care personnel was of utmost importance. Here, we present steps taken to date to flatten the curve at the radiation oncology division of a tertiary cancer center with the goal of mitigating risk of exposure among patients and staff, and optimizing resource utilization. Response to the coronavirus disease 2019 pandemic in this large tertiary referral center included volume reduction, personal protective equipment recommendations, flexible clinic visit interaction types dictated by need and risk reduction, and numerous social distancing strategies. We hope these outlined considerations can assist the wider radiation oncology community as we collectively face this ongoing challenge.

BACKGROUND We report outcomes for patients with T2N0M0 glottic squamous cell carcinoma (SCC) treated with radiation therapy (RT). METHODS Patients who received definitive RT for T2 glottic SCC from 2000 through 2013 were retrospectively reviewed. RESULTS One hundred and thirteen patients were analyzed (median follow-up time 91 months; 85 patients received three-dimensional conformal radiotherapy [3D-CRT] and 28 received intensity-modulated radiation therapy [IMRT]). Fractionation was conventional (58%) or altered (42%); 20 patients (18%) received concurrent chemotherapy. Five-year local control was 83% for the 3D-CRT vs 81% for the IMRT group (P = .76). The ultimate locoregional control at 5 years was 100% for IMRT vs 91% for 3D-CRT (P = .1). The 5-year overall survival (OS) was 78% for 3D-CRT vs 81% for IMRT (P = .83). On multivariate analysis, younger age was the only independent predictor of improved OS (P = .0002). CONCLUSIONS Oncologic and survival outcomes were excellent for patients with T2N0 glottic cancer. Patients treated with IMRT and 3D-CRT had no statistically significant differences in all investigated endpoints.

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.

Highlights • GTVs on the 60 kV and 140 kV from DECT, and the T1c and T2 from MRI were compared. • Delineation was the most consistent using T1c (no interobserver difference in DSC). • T1c MRI provided higher interobserver agreement for skull base tumors. • 60 kV DECT provided higher interobserver agreement for non-skull base tumors., In treatment planning, multiple imaging modalities can be employed to improve the accuracy of tumor delineation but this can be costly. This study aimed to compare the interobserver consistency of using dual energy computed tomography (DECT) versus magnetic resonance imaging (MRI) for delineating tumors in the head and neck cancer (HNC) re-irradiation scenario. Twenty-three patients with recurrent HNC and had planning DECT and MRI were identified. Contoured tumor volumes by seven radiation oncologists were compared. Overall, T1c MRI performed the best with median DSC of 0.58 (0–0.91) for T1c. T1c MRI provided higher interobserver agreement for skull base sites and 60 kV DECT provided higher interobserver agreement for non-skull base sites.

Recurrent or previously irradiated head and neck cancers (HNC) are therapeutically challenging and may benefit from high-dose, highly accurate radiation techniques, such as stereotactic ablative radiation therapy (SABR). Here, we compare set-up and positioning accuracy across HNC subsites to further optimize the treatment process and planning target volume (PTV) margin recommendations for head and neck SABR.We prospectively collected data on 405 treatment fractions across 79 patients treated with SABR for recurrent/previously irradiated HNC. First, interfractional error was determined by comparing ExacTrac x-ray to the treatment plan. Patients were then shifted and residual error was measured with repeat x-ray. Next, cone beam computed tomography (CBCT) was compared with ExacTrac for positioning agreement, and final shifts were applied. Lastly, intrafractional error was measured with x-ray before each arc. Results were stratified by treatment site into skull base, neck/parotid, and mucosal.Most patients (66.7%) were treated to 45 Gy in 5 fractions (range, 21-47.5 Gy in 3-5 fractions). The initial mean ± standard deviation interfractional errors were -0.2 ± 1.4 mm (anteroposterior), 0.2 ± 1.8 mm (craniocaudal), and -0.1 ± 1.7 mm (left-right). Interfractional 3-dimensional vector error was 2.48 ± 1.44, with skull base significantly lower than other sites (2.22 vs 2.77; P = .0016). All interfractional errors were corrected to within 1.3 mm and 1.8°. CBCT agreed with ExacTrac to within 3.6 mm and 3.4°. CBCT disagreements and intrafractional errors of1 mm or1° occurred at significantly lower rates in skull base sites (CBCT: 16.4% vs 50.0% neck, 52.0% mucosal, P.0001; intrafractional: 22.0% vs 48.7% all others, P.0001). Final PTVs were 1.5 mm (skull base), 2.0 mm (neck/parotid), and 1.8 mm (mucosal).Head and neck SABR PTV margins should be optimized by target site. PTV margins of 1.5 to 2 mm may be sufficient in the skull base, whereas 2 to 2.5 mm may be necessary for neck and mucosal targets. When using ExacTrac, skull base sites show significantly fewer uncertainties throughout the treatment process, but neck/mucosal targets may require the addition of CBCT to account for positioning errors and internal organ motion.

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

Background and purpose: Computed tomography (CT) scanning is the basis for radiation treatment planning, but the 50-cm standard scanning field of view (sFOV) may be too small for imaging larger patients. We evaluated the 65-cm high-definition (HD) FOV of a large-bore CT scanner for CT number accuracy, geometric distortion, image quality degradation, and dosimetric accuracy of photon treatment plans. Materials and methods: CT number accuracy was tested by placing two 16-cm acrylic phantoms on either side of a 40-cm phantom to simulate a large patient extending beyond the 50-cm-diameter standard scanning FOV. Dosimetric accuracy was tested using anthropomorphic pelvis and thorax phantoms, with additional acrylic body parts on either side of the phantoms. Two volumetric modulated arc therapy beams (a 15-MV and a 6-MV) were used to cover the planning target volumes. Two-dimensional dose distributions were evaluated with GAFChromic film and point dose accuracy was checked with multiple thermoluminescent dosimeter (TLD) capsules placed in the phantoms. Image quality was tested by placing an American College of Radiology accreditation phantom inside the 40-cm phantom. Results: The HD FOV showed substantial changes in CT numbers, with differences of 314 HU–725 HU at different density levels. The volume of the body parts extending into the HD FOV was distorted. However, TLD-reported doses for all PTVs agreed within ±3%. Dose agreement in organs at risk were within the passing criteria, and the gamma index pass rate was >97%. Image quality was degraded. Conclusions: The HD FOV option is adequate for RT simulation and met accreditation standards, although care should be taken during contouring because of reduced image quality. Keywords: CT extended field of view, CT number accuracy, Large bore CT scanner, Dose uncertainty

Patient-reported outcome measures (PROMs) are increasingly incorporated as endpoints in oncology clinical trials but are often only validated in English. ClinicalTrials.gov was queried for cancer-specific randomized control trials (RCTs) addressing a therapeutic intervention and enrolling primarily in the USA. Peer-reviewed validation of Spanish and Chinese versions of each PROM was assessed. Of 103 eligible trials, a PROM was used as a primary endpoint in 25 RCTs (24.3%) and as a secondary endpoint in 78 RCTs (75.7%). A total of 61 of the 103 eligible trials (59.2%) and 17 of the 25 trials with a PROM primary endpoint (68.0%) used a PROM with either no Spanish or Chinese validation. The absence of validated PROM translations may diminish the voices of non-English language speaking trial participants. With an increasingly diverse US population, validation of non-English PROM translations may decrease disparities in trial participation and improve generalizability of study results.

Second primary malignancy (SPM) may occur after index head and neck cancer (HNC) treatment. This study evaluated the prevalence and outcome of SPM in patients with HNC treated with definitive radiotherapy. Eligible patients include those with index mucosal HNC treated with definitive radiotherapy between 2000 and 2010. SPM was defined as an invasive cancer at a noncontiguous site diagnosed at least 6 months after completion of radiotherapy. Clinical data were collected, and the Kaplan–Meier method was used to estimate overall survival. In total, 1512 patients were studied. The majority of patients had index oropharyngeal cancer (86%). In all, 130 (9%) patients developed a SPM. The risk of SPM increased exponentially with time with 5-, 10-, and 15-year rates of 4, 10, and 25%. Half of SPMs were within the head and neck or thoracic regions. SPM rates were significantly higher (p

Purpose Proton therapy is increasingly prescribed for cancer treatment, given its potential for improvements in clinical outcomes and toxicity reduction; however, insurance coverage continues to be a barrier to patient access. This study examined insurance approval and appeal outcomes at a large-volume proton therapy center to clarify the process and identify areas for improvement. Methods and Materials In 2013 to 2016, 1753 patients with thoracic or head and neck cancer were considered for proton therapy; 903 (553 thoracic, 350 head and neck) entered the insurance process. Rates of and times to approval and successful appeal after initial denial were calculated. Clinical factors were evaluated for association with insurance outcomes via logistic regression. Results Approval rates by Medicare (n = 538) and private insurance (n = 365) were 91% and 30% on initial request, at a median 3 days and 14 days from inquiry to determination. Of the 306 patients initially denied coverage, 276 appealed the decision, and denial was overturned for 189 patients (68%; median time, 21 days from initial inquiry). On multivariable analysis, Medicare (odds ratio [OR], 14.20; P Conclusions Despite an 87% ultimate approval rate for proton therapy, the insurance process is a resource-intensive barrier to patient access associated with significant time delays to cancer treatment. These findings, plus the lack of clinical correlates with insurance outcomes, highlight a need for increased efficiency, transparency, and collaboration among stakeholders to promote timely patient care and research.

Background The optimal treatment for regional lymphatic recurrences from head and neck cancer has not been fully established. In order to explore the therapeutic benefit of surgical resection and adjuvant brachytherapy, the authors reviewed their experience utilizing interstitial brachytherapy (IBT) at the M. D. Anderson Cancer Center. Methods A retrospective chart review of the 51 patients who received salvage surgical resection of lymphatic recurrences and adjuvant IBT between 1993 and 2012 at the M. D. Anderson Cancer Center was undertaken. All patients underwent neck dissection with complete resection and intraoperative placement of afterloading brachytherapy catheters. Soft tissue reconstruction was performed as necessary. The technical aspects of IBT were reviewed, and the overall and disease free survival rates and the recurrence rates were determined. Results All patients had received external beam radiation (EBRT) as part of their initial treatment to a median dose of 66 Gy; 40 and 68% of the patients also had a neck dissection or chemotherapy, respectively. The cumulative regional recurrence probability is 28 and 38% at 5 years and 10 years. All of the patients underwent salvage neck dissection and IBT, with 81% also undergoing soft tissue reconstruction. The median dose delivered to the tumor bed was 60 Gy over a median duration of 4.5 days. There were 21 early adverse events, 8 of which were severe, and 19 late adverse events, 6 of which were severe. The most common early and late adverse events due to surgery and brachytherapy were dysphagia (7.1%) and true vocal cord paralysis (17.9%), respectively. There were no perioperative deaths or carotid hemorrhages. Nineteen patients developed recurrence including regional recurrence and distinct metastasis. The median time to recurrence is 130 months using Kaplan-Meier product limit method. The 2-year disease-free survival rate was 58%. The 2-year, 5-year, and 10-year overall survival rates were 69, 56, and 46%, respectively. Conclusions Regional recurrences in previously irradiated tissues after the definitive treatment of primary head and neck cancers represent a challenging problem. We demonstrated that salvage neck dissection with IBT provided encouraging regional control and survival rates, while maintaining relatively low acute and long-term toxicity rates.

PURPOSE: Local/systemic symptoms during cancer therapy may be exacerbated by dysregulated inflammation and its downstream toxic effects. Minocycline can suppress proinflammatory cytokine release; therefore, we investigated its potential to reduce patient-reported symptom severity during radiotherapy (RT) for head and neck cancer (HNC). METHODS: Eligible patients for this blinded, placebo–controlled trial were adults with T0–3, N-any, and M0 HNC receiving single-modality RT. Participants were randomized 1:1 to either minocycline (200 mg/day) or placebo during RT. The primary endpoint was the area under the curve (AUC) of 5 prespecified symptoms (pain, fatigue, disturbed sleep, poor appetite, difficulty swallowing/chewing) during RT, assessed with the MD Anderson Symptom Inventory for HNC (MDASI-HN). RESULTS: We analyzed data from 20 evaluable patients per arm. Overall, 75% had oropharyngeal cancer and 78% were male. No grade 3+ adverse events potentially related to study medication were observed. Two minocycline patients required a feeding tube during RT vs 5 placebo patients (P = 0.21). The average daily AUC during RT for the 5 MDASI-HN symptoms was 3.1 (SD =1.0) for minocycline and 3.7 (SD = 1.7) for placebo (P = 0.16); the 0.37 effect size was less than our 0.70 target. AUC comparisons for several individual symptoms and symptom interference favored minocycline but were not statistically significant. The greatest numerical differences occurred for systemic symptoms, larger toward treatment end, and in early post-RT recovery. CONCLUSIONS: Minocycline was feasible, well tolerated, and achieved a positive signal toward reducing patient-reported symptom severity during RT for HNC, particularly for systemic symptoms. This justifies additional study and informs future trial design.

OBJECTIVEThe objective of this study was to assess outcomes after Gamma Knife radiosurgery (GKRS) re-irradiation for palliation of patients with trigeminal pain secondary to recurrent malignant skull base tumors.METHODSFrom 2009 to 2016, 26 patients who had previously undergone radiation treatment to the head and neck received GKRS for palliation of trigeminal neuropathic pain secondary to recurrence of malignant skull base tumors. Twenty-two patients received single-fraction GKRS to a median dose of 17 Gy (range 15–20 Gy) prescribed to the 50% isodose line (range 43%–55%). Four patients received fractionated Gamma Knife Extend therapy to a median dose of 24 Gy in 3 fractions (range 21–27 Gy) prescribed to the 50% isodose line (range 45%–50%). Those with at least a 3-month follow-up were assessed for symptom palliation. Self-reported pain was evaluated by the numeric rating scale (NRS) and MD Anderson Symptom Inventory–Head and Neck (MDASI-HN) pain score. Frequency of as-needed (PRN) analgesic use and opioid requirement were also assessed. Baseline opioid dose was reported as a fentanyl-equivalent dose (FED) and PRN for breakthrough pain use as oral morphine-equivalent dose (OMED). The chi-square and Student t-tests were used to determine differences before and after GKRS.RESULTSSeven patients (29%) were excluded due to local disease progression. Two experienced progression at the first follow-up, and 5 had local recurrence from disease outside the GKRS volume. Nineteen patients were assessed for symptom palliation with a median follow-up duration of 10.4 months (range 3.0–34.4 months). At 3 months after GKRS, the NRS scores (n = 19) decreased from 4.65 ± 3.45 to 1.47 ± 2.11 (p < 0.001); MDASI-HN pain scores (n = 13) decreased from 5.02 ± 1.68 to 2.02 ± 1.54 (p < 0.01); scheduled FED (n = 19) decreased from 62.4 ± 102.1 to 27.9 ± 45.5 mcg/hr (p < 0.01); PRN OMED (n = 19) decreased from 43.9 ± 77.5 to 10.9 ± 20.8 mg/day (p = 0.02); and frequency of any PRN analgesic use (n = 19) decreased from 0.49 ± 0.55 to 1.33 ± 0.90 per day (p = 0.08). At 6 months after GKRS, 9 (56%) of 16 patients reported being pain free (NRS score 0), with 6 (67%) of the 9 being both pain free and not requiring analgesic medications. One patient treated early in our experience developed a temporary increase in trigeminal pain 3–4 days after GKRS requiring hospitalization. All subsequently treated patients were given a single dose of intravenous steroids immediately after GKRS followed by a 2–3-week oral steroid taper. No further cases of increased or new pain after treatment were observed after this intervention.CONCLUSIONSGKRS for palliation of trigeminal pain secondary to recurrent malignant skull base tumors demonstrated a significant decrease in patient-reported pain and opioid requirement. Additional patients and a longer follow-up duration are needed to assess durability of symptom relief and local control.

Background The current study was performed to assess the efficacy of surveillance imaging in patients with head and neck cancer (HNC) who are treated definitively with radiotherapy. Methods Eligible patients included those with a demonstrable disease-free interval (≥1 follow-up imaging procedure without evidence of disease and a subsequent visit/imaging procedure) who underwent treatment of HNC from 2000 through 2010. Results A total of 1508 patients were included. The median overall survival was 99 months, with a median imaging follow-up period of 59 months. Of the 1508 patients, 190 patients (12.6%) experienced disease recurrence (107 patients had locoregional and 83 had distant disease recurrence). A total of 119 patients (62.6%) in the group with disease recurrence were symptomatic and/or had an adverse clinical finding associated with the recurrence. Approximately 80% of patients with locoregional disease recurrences presented with a clinical finding, whereas 60% of distant disease recurrences were detected by imaging in asymptomatic patients. Despite the earlier detection of disease recurrence via imaging, those patients in the group of patients with clinically detected disease recurrence were significantly more likely to undergo salvage therapy compared with those whose recurrence was detected on imaging (odds ratio, 0.35). There was no difference in overall survival noted between those patients with disease recurrences that were detected clinically or with imaging alone. Approximately 70% of disease recurrences occurred within the first 2 years. In those patients who developed disease recurrence after 2 years, the median time to recurrence was 51 months. After 2 years, the average number of imaging procedures per patient for the detection of a salvageable recurrence for the imaging-detected group was 1539. Conclusions Surveillance imaging in asymptomatic patients with HNC who are treated definitively with radiotherapy without clinically suspicious findings beyond 2 years has a low yield and a high cost. Physicians ordering these studies must use judicious consideration and discretion.

BACKGROUND: The objective of the current study was to characterize the incidence, pattern, and impact on oncologic outcomes of retropharyngeal lymph node (RPLN) involvement in HPV-associated oropharyngeal cancer (OPC). METHODS: Data regarding patients with HPV-associated OPC who were treated at The University of Texas MD Anderson Cancer Center with intensity-modulated radiotherapy from 2004 through 2013 were analyzed retrospectively. RPLN status was determined by reviewing pretreatment imaging and/or reports. Outcomes analysis was restricted to patients with lymph node-positive (+) disease. Kaplan-Meier survival estimates were generated and survival curves were compared using the log-rank test. Bayesian information criterion assessed model performance changes with the addition of RPLN status to current American Joint Committee on Cancer staging. Competing risk analysis compared modes of disease recurrence. RESULTS: The incidence of radiographic RPLN involvement was 9% (73 of 796 patients) and was found to vary by primary tumor site. The 5-year rates of freedom from distant metastases (FDM) and overall survival were lower in patients with RPLN(+) status compared with those with RPLN-negative (−) status (84% vs 93% [P = .0327] and 74% vs 87% [P = .0078], respectively). RPLN(+) status was not found to be associated with outcomes on multivariate analysis. Bayesian information criterion analysis demonstrated that current American Joint Committee on Cancer staging was not improved with the inclusion of RPLN. Locoregional and distant disease recurrence probabilities for those patients with RPLN(+) status were 8% and 13%, respectively, compared with 10% and 6%, respectively, for those with RPLN(−) status. RPLN(+) status portended worse 5-year FDM in the low-risk subgroup (smoking history of

Background: Anaplastic thyroid carcinoma (ATC) is an aggressive thyroid cancer that requires a rapid diagnosis and treatment to achieve disease control. Gene mutation profiling of circulating cell-free DNA (cfDNA) in peripheral blood may help to facilitate early diagnosis and treatment selection. The relatively rapid turnaround time compared with conventional tumor mutation testing is a major advantage. The objectives of this study were to examine the concordance of ATC-related mutations detected in cfDNA with those detected in the corresponding tumor tissue, and to determine the prognostic significance of cfDNA mutations in ATC patients. Methods: The ATC patients who were diagnosed and treated at The University of Texas MD Anderson Cancer Center between January 2015 and February 2018 and who had cfDNA testing were included in this study. cfDNA was collected by blood draw and was analyzed by next-generation sequencing (NGS) using the Guardant360-73 gene platform. Results: A total of 87 patients were included in the study. The most frequently mutated genes detected in cfDNA were TP53, BRAF, and PIK3CA. In 28 treatment naive ATC patients, the concordance rate of detected mutations in TP53, BRAF(V600E), and PIK3CA between cfDNA and matched tissue NGS was 82.1%, 92.9%, and 92.9%, respectively. Patients with a PIK3CA mutation detected on cfDNA had worse overall survival (OS) (p = 0.03). This association was observed across various treatment modalities, including surgery, cytotoxic chemotherapy, radiation, and BRAF inhibitor (BRAFi) therapy. With regard to treatment, BRAFi therapy significantly improved ATC OS (p = 0.003). Conclusions: cfDNA is a valuable tool to evaluate a tumor's molecular profile in ATC patients. We identified high concordance rates between the gene mutations identified via cfDNA analysis and those identified from the NGS of the corresponding tumor tissue sequencing. Identified mutations in cfDNA can potentially provide timely information to guide treatment selection and evaluate the prognosis in patients with ATC.

Purpose To introduce a contouring guideline for the taste bud bearing tongue mucosa for head and neck cancer patients receiving radiotherapy. Methods and Materials CT simulation images of oropharyngeal cancer patients were used to delineate both the whole tongue (extrinsic/intrinsic tongue muscles, floor of mouth) and the taste bud bearing tongue mucosa (method A: adaptation of the whole tongue structure; method B: axial adaptation of a mid-sagittal contour). Volumetric and dosimetric parameters of the whole tongue and the two methods of mucosal delineation, spatial overlap between methods A and B, and inter-observer variability for method B were calculated. Results The study cohort was comprised of 70 patients with T1–4 N0–1 tonsillar (83%) and base of tongue (17%) cancers. Most of the comparative parameters between the whole tongue and mucosa (method A) significantly differed (mean, minimum, and maximum dose, V5–V70, D40–D90). The mean dose calculated for the whole tongue deviated on average 3.77 Gy compared to method A. No significant differences were found between methods A and B of the taste bud bearing tongue mucosa structure, and none of the dosimetric parameters differed more than 1.03 Gy on average. The mean Dice similarity coefficient for both mucosal structures was 0.79 ± 0.05, and 0.63 ± 0.12 for the inter-observer analysis of method B. Conclusions We defined two methods for delineating the taste bud bearing mucosa and both are equally satisfactory procedures. Either method is preferable over delineation of the whole tongue as organ at risk for taste impairment.

Opinion statementThe rise in the incidence of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPC), the relatively young age at which it is diagnosed, and its favorable prognosis necessitate the use of treatment techniques that reduce the likelihood of side effects during and after curative treatment. Intensity-modulated proton therapy (IMPT) is a form of radiotherapy that de-intensifies treatment through dose de-escalation to normal tissues without compromising dose to the primary tumor and involved, regional lymph nodes. Preclinical studies have demonstrated that HPV-positive squamous cell carcinoma is more sensitive to proton radiation than is HPV-negative squamous cell carcinoma. Retrospective studies comparing intensity-modulated photon (X-ray) radiotherapy to IMPT for OPC suggest comparable rates of disease control and lower rates of pain, xerostomia, dysphagia, dysgeusia, gastrostomy tube dependence, and osteoradionecrosis with IMPT—all of which meaningfully affect the quality of life of patients treated for HPV-associated OPC. Two phase III trials currently underway—the “Randomized Trial of IMPT versus IMRT for the Treatment of Oropharyngeal Cancer of the Head and Neck” and the “TOxicity Reduction using Proton bEam therapy for Oropharyngeal cancer (TORPEdO)” trial—are expected to provide prospective, level I evidence regarding the effectiveness of IMPT for such patients.

Background Patients with locoregionally advanced oral cavity squamous cell carcinoma (OCSCC) have a poor survival outcome. Treatment involves extensive surgery, adjuvant radiation, or chemoradiation and results in high morbidity. In this study, the authors' objective was to evaluate their experience with induction chemotherapy (IC) in the treatment of locoregionally advanced OCSCC. Methods A retrospective review of the medical records of all patients with locoregionally advanced (stage III and IV) OCSCC who received IC followed by definitive local therapy was conducted. Outcomes included response to IC and survival. Results In total, 120 patients were included in the study. The overall stage was stage IV in 79.2% of patients. After 2 cycles of IC, 76 patients (63.3%) achieved at least a partial response, including 13 who had a complete response. Stable disease was observed in 30 patients (25%), and 14 patients (11.7%) had progressive disease. Among responders, 16 patients received definitive chemoradiation or radiation therapy, and 60 underwent surgical resection, of whom 15 had less extensive surgery than was originally planned. Overall, organ preservation was achieved in 40.8% of patients who had a favorable response to IC. The 5-year overall and disease-specific survival rates were 51.4% and 66.9%, respectively. Patients who had at least a partial response had better 5-year overall survival (60.1%) and disease-specific survival (78.5%) compared with nonresponders (33.8% and 46.4%, respectively). Conclusions The results demonstrate a response rate to IC in patients with advanced OCSCC similar to what has been observed in patients with cancer in other head and neck subsites. Patients who achieved at least a partial response to IC had a more favorable outcome, with ensuing organ preservation. Further studies are warranted.

Background Risk of recurrence among patients with oropharyngeal cancer (OPC) who survive 5 years is low. The goal of this study was to assess long-term survival of patients with OPC alive without recurrence 5 years after diagnosis. Methods This study included newly diagnosed patients with OPC, who had been treated with radiation and were alive without recurrence 5 years after diagnosis. Overall survival (OS) probabilities beyond 5 years were estimated using the Kaplan-Meier method. Factors associated with OS were determined using Bayesian piecewise exponential survival regression. Standardized mortality ratios for all-cause death were estimated controlling for study year, age, and sex in the US general population. Results Among 1699 patients, the additional 2-year, 5-year, and 10-year OS probabilities were 94%, 83%, and 63%, respectively, and were lower than those in the general population. Patients who were older, were current or former smokers, had other than tonsil or base of tongue tumors, or had T4 tumors had a higher risk of death. Patients who had base of tongue tumors and had received intensity-modulated radiation therapy (IMRT) or lower-radiation doses had a lower risk of death. Standardized mortality ratios were higher among current and heavy smokers and lower among recipients of IMRT and lower radiation doses. Conclusions In this large cohort, long-term survival among patients with OPC was good but lower than predicted for the general population. Patients treated with IMRT and those with less tobacco exposure had better outcomes.

IMPORTANCE: Anaplastic thyroid carcinoma (ATC) historically has a 4-month median overall survival (OS) from time of diagnosis, with disease-specific mortality approaching 100%. The association between recent major advancements in treatment and OS has yet to be evaluated. OBJECTIVE: To evaluate rates of OS in patients with ATC over the last 2 decades. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study in a single tertiary care institution. Patients with histopathological confirmation of ATC from January 2000 to October 2019 were included and divided into 3 groups according to date of presentation: 2000-2013, 2014-2016, and 2017-2019. MAIN OUTCOMES AND MEASURES: Overall survival compared among different treatment eras and differing therapies, including targeted therapy, immunotherapy, and surgery. RESULTS: Of 479 patients (246 men [51%]; median age, 65.0 [range, 21.1-92.6] years) with ATC evaluated, 52 (11%) were stage IVA, 172 (36%) stage IVB, and 255 (53%) stage IVC at presentation. The median OS of the entire cohort was 0.79 years (9.5 months), ranging from 0.01 to 16.63. The OS at 1 and 2 years was 35% (95% CI, 29%-42%) and 18% (95% CI, 13%-23%) in the 2000-2013 group (n = 227), 47% (95% CI, 36%-56%) and 25% (95% CI, 17%-34%) in the 2014-2016 group (n = 100), and 59% (95% CI, 49%-67%) and 42% (95% CI, 30%-53%) in the 2017-2019 group (n = 152), respectively (P

PURPOSE: Prior authorization (PA) can be a resource-intensive barrier to oncologic care. To improve patient access and reduce delays at our large, academic proton therapy center, we implemented a novel payor-focused strategy to efficiently navigate the PA process while eliminating physician burden and reducing inappropriate denials. METHODS: In 2017, business operations were redesigned to better reflect the insurance process: (1) certified medical dosimetrists (CMDs), with their unique treatment expertise, replaced our historical PA team to function as an effective interface among physicians, patients, and payors; (2) a structured, tiered timeline was implemented to hold payors accountable to PA deadlines; and (3) our PA team provided administrative leadership with requisite insurance knowledge. PA outcomes were compared 6 months before and after the intervention. RESULTS: After implementation of this multifaceted strategy, the median time to successful appeal (after initial denial of coverage) decreased from 30 to 18 days ( P < .001), and the total number of overturned denials increased by 56%. Because of the efficiency of the CMDs, full-time equivalents on the PA team actually decreased by 44%, translating to a 34% reduction in team personnel expenses. Internal referrals increased by 29%, attributable to optimized communication and diminished administrative burden for providers. New treatment starts also increased, resulting in a 37% larger patient census on treatment. CONCLUSION: Incorporating payor-focused strategies can improve patient access in a cost-effective manner while decreasing time and administrative burden associated with the PA process. These operational concepts can be adapted for other oncologic practice settings facing analogous PA-related obstacles.

Background: Palliative radiotherapy (RT) is effective, but some patients die during treatment or too soon afterward to experience benefit. This study investigates end-of-life RT patterns to inform shared decision-making and facilitate treatment consistent with palliative goals. Materials and Methods: All patients who died ≤6 months after initiating palliative RT at an academic cancer center between 2015 and 2018 were identified. Associations with time-to-death, early mortality (≤30 days), and midtreatment mortality were analyzed. Results: In total, 1,620 patients died ≤6 months from palliative RT initiation, including 574 (34%) deaths at ≤30 days and 222 (14%) midtreatment. Median survival was 43 days from RT start (95% CI, 41–45) and varied by site (PPPPP=.008), whereas stereotactic technique (HR, 0.77; PP10 fractions (median, 40 vs 47 days; P=.272), although the latter entailed longer courses. The 30-day mortality group included 335 (58%) inpatients, who were 27% more likely to die midtreatment (P=.031). On multivariable analysis, midtreatment mortality among these inpatients was associated with thoracic (odds ratio [OR], 2.95; P=.002) and central nervous system (CNS; OR, 2.44; P=.002) indications, >5-fraction courses (OR, 3.27; PP=.050). Conversely, palliative/supportive care consultation was associated with decreased midtreatment mortality (OR, 0.60; P=.045). Conclusions: Earlier referrals and hypofractionated courses (≤5–10 treatments) should be routinely considered for palliative RT indications, given the short life expectancies of patients at this stage in their disease course. Providers should exercise caution for emergent thoracic and CNS indications among inpatients with poor prognoses due to high midtreatment mortality.

Highlights • Prospective cohort of 121 cancer patients tested for SARS-CoV-2 over 35 days. • Of 7 positive cases, 6 were admitted with 4 warranting intensive care, and 2 died. • RT was delayed in one-third of patients while awaiting RT-PCR test results. • With a dual PPE policy, newly quarantined employees decreased 6-fold per day. • Each patient was an exposure risk to 5 employees, most commonly RTTs (38%), Background and purpose The COVID-19 pandemic warrants operational initiatives to minimize transmission, particularly among cancer patients who are thought to be at high-risk. Within our department, a multidisciplinary tracer team prospectively monitored all patients under investigation, tracking their test status, treatment delays, clinical outcomes, employee exposures and quarantines. Materials and methods Prospective cohort tested for SARS-COV-2 infection over 35 consecutive days of the early pandemic (03/19/2020-04/22/2020). Results A total of 121 Radiation Oncology patients underwent RT-PCR testing during this timeframe. Of the 7 (6%) confirmed-positive cases, 6 patients were admitted (including 4 warranting intensive care), 2 of whom died from acute respiratory distress syndrome. Radiotherapy was deferred or interrupted for 40 patients awaiting testing. As the median turnaround time for RT-PCR testing decreased from 1.5 (IQR: 1-4) to ≤1-day (P

Highlights • The use of oral stents during RT was associated with reduced late morbidity. • OPC patients with bilateral RT and tongue-depressing stents had less dysphagia. • Patients with unilateral RT and tongue-deviating stent had better taste/appetite., Objectives To evaluate whether the use of oral stents during intensity modulated radiation therapy (IMRT) for oropharyngeal cancer (OPC) is associated with long-term patient reported symptoms. Materials and methods Data was obtained from a prospective observational study of disease-free head and neck cancer survivors. Radiation-associated patient reported symptoms were assessed using the MD Anderson Symptom Inventory Head and Neck module (MDASI-HN). Scores of ≥5 (11-point Likert scale, 0-10) were considered moderate/severe. Stratification was performed regarding IMRT volume (uni- versus bilateral neck) and stent utilization, with non-parametric analyses between groups. Results 462 OPC survivors formed the cohort (54% tonsil, 46% base of tongue primaries). A tongue-deviating stent was used in 17%, tongue-depressing stent in 46%, and no stent in 37%. Median prescribed dose to the high dose clinical target volume was 66.0 Gy. Median follow-up from RT to MDASI-HN assessment was 68 months. Twenty percent had received unilateral neck RT (all had tonsil primaries), in whom a significant improvement in the proportion of patients with moderate/severe taste impairment (2% vs. 15%, p = 0.047) and lack of appetite (0% vs. 9%, p = 0.019) was associated with the use of tongue-deviating stents compared to no oral stent. In those who had received bilateral neck RT, a significant improvement in the proportion of patients with moderate/severe difficulty swallowing/chewing was associated with use of a tongue-depressing stent (21% vs. 31% without oral stent, p = 0.013). Conclusion Disease-site specific select use of oral stents during IMRT was associated with reduced long-term patient reported symptoms in OPC survivors.

Node positive head and neck squamous cell carcinomas (HNSCCs) patients exhibit worse outcomes in terms of regional neck control, risk for distant metastases and overall survival. Smaller non-palpable lymph nodes may be inflammatory or may harbor clinically occult metastases, a characterization that can be challenging to make using routine imaging modalities. Ferumoxytol has been previously investigated as an intra-tumoral contrast agent for magnetic resonance imaging (MRI) for intracranial malignancies and lymph node agent in prostate cancer. Hence, our group was motivated to carry out a prospective feasibility study to assess the feasibility of ferumoxytol dynamic contrast enhanced (DCE)-weighted MRI relative to that of gadolinium-based DCE-MRI for nodal and primary tumor imaging in patients with biopsy-proven node-positive HNSCC or melanoma. Although this institutional review board (IRB)-approved study was prematurely terminated because of an FDA black box warning, the investigators sought to curate and publish this unique dataset of matched clinical, and anatomical and DCE MRI data for the enrolled five patients to be available for scientists interested in molecular imaging., Measurement(s)imaging assay • head and neck squamous cell carcinomaTechnology Type(s)magnetic resonance imagingFactor Type(s)contrast agentSample Characteristic - OrganismHomo sapiens Machine-accessible metadata file describing the reported data: 10.6084/m9.figshare.11409516

Purpose/Objective Radiation-induced lymphopenia has been associated with poor survival outcomes in certain solid tumors such as esophageal, lung, cervical and pancreatic cancers. We aim to determine the effect of treatment-related lymphopenia during radiotherapy on outcomes of patients with oropharyngeal cancer. Materials/Methods A retrospective analysis of all patients who completed definitive radiotherapy for oropharyngeal cancer at The University of Texas MD Anderson Cancer Center and had blood counts taken during radiotherapy from 2002 to 2013 were included. Patient, tumor and treatment characteristics, clinical outcomes and lymphocyte counts during radiotherapy were recorded. Lymphopenia was graded according to the CTCAE v4.0. Survival rates were estimated using the Kaplan-Meier method and compared with log-rank tests. Results 850 patients were evaluated. The median age was 57 years. The majority of the cohort had p16/HPV-positive disease (71%), 8% had HPV-negative disease and 21% were unknown. The median radiation total dose was 70 Gy. 45% of patients had induction chemotherapy, and 87% had concurrent chemotherapy. 703 (83%) patients developed ≥grade 3 (G3) lymphopenia and 209 (25%) had grade 4 (G4) lymphopenia during radiotherapy. The median follow-up was 59 months; the 5-year overall survival rate was 81%. There were no significant differences in overall survival rates nor in disease control rates, in those who developed G3/G4 lymphopenia compared with those who did not. No significant effect of lymphopenia on survival was observed when analyzed according to p16/HPV status. Conclusion In this large cohort of patients with oropharyngeal cancer, the development of lymphopenia during radiotherapy did not impact outcomes.

Highlights • The majority of OPC patients are affected from late taste impairment after RT. • Taste markedly improved in the first years from end of RT, but plateaued after year 5. • Treatment site, CTV1 dose and age might have an influence on taste impairment., Background and purpose Taste impairment is a common radiation-induced toxicity in head and neck cancer (HNC) patients acutely. However, data on the potential for recovery and the time dependent course of late taste impairment are limited. Materials and methods As part of an IRB-approved observational prospective study, HNC patients underwent serial surveys including the MD Anderson Symptom Inventory - Head and Neck module (MDASI-HN). For our analysis, we extracted MDASI-HN taste item results from oropharyngeal cancer patients treated with intensity-modulated radiotherapy or volumetric modulated arc therapy and at least two taste assessments after ≥1 year from end of radiotherapy (RT). Results 1214 MDASI taste items from 326 patients between 1 and 13 years post-RT were included. Median prescribed dose to the high-dose clinical target volume (CTV1) was 66.0 Gy, with 180 patients (55%) receiving chemotherapy. Taste markedly improved in the first years from end of RT, but plateaued after year 5. In patients with taste assessment in subsequent years, a significant reduction in taste impairment was found from the second to the third year (p = 0.001) and tended towards significance from the third to the fourth year (p = 0.058). Multivariate analysis revealed treatment site as significant factor in the sixth year from RT and CTV1 dose and age in the seventh year. Conclusion Radiation-induced taste impairment may improve over an extended time interval, but becomes relatively stable from year 5 post-RT. Direct characterization of RT-induced taste impairment and the calculation of normal tissue complication probability should include consideration of the time-dependent course in taste recovery.

Purpose Patients with p16/human papilloma virus (HPV)–associated oropharyngeal squamous cell carcinoma have a favorable outcome after treatment. In this group of patients who could have a long life expectancy, the optimal surveillance strategy and modality is not well established. We aim to determine the ability of a negative postradiation positron emission tomography (PET)/computed tomography scan to predict the risk of subsequent relapse in these patients. Materials and Methods A retrospective analysis of patients with p16/HPV-associated oropharyngeal squamous cell carcinoma who completed definitive (chemo)radiation therapy and had a posttreatment PET/computed tomography scan from 2006 to 2013 was performed. Patient, tumor, and treatment characteristics and clinical outcomes were recorded. Tumors were considered HPV/p16 positive if either HPV (by in situ hybridization) or p16 (by immunohistochemistry) was positive. Disease-free survival and overall survival rates were estimated using the Kaplan-Meier method. Results In our study, 327 patients were evaluated. The median age was 57 years. The most common primary sites were base of tongue (50%) and tonsil (48%). Of the patients evaluated, 291 (89%) had a negative posttreatment PET scan. For these 291 patients who had a complete metabolic response after treatment, the 5-year disease-free survival and overall survival rates were 91% and 89%, respectively. The median time to development of recurrence was 16 months. Of the 291 patients, 24 patients (8%) had disease recurrence; 13 recurrences were locoregional, and 13 were distant. Eleven (4%) patients with recurrence had further surgery or radiation, and 8 patients (3%) were without disease as of the last follow-up. Conclusions Patients who achieve a complete metabolic response on posttreatment PET imaging have an excellent prognosis, and the risk of developing a recurrence in the future is very low. Therefore, a more cost effective surveillance program should be considered for this subgroup of patients.

Purpose Our primary aim was to prospectively validate retrospective dose–response models of chronic radiation-associated dysphagia (RAD) after intensity modulated radiotherapy (IMRT) for oropharyngeal cancer (OPC). The secondary aim was to validate a grade ≥2 cut-point of the published videofluoroscopic dysphagia severity (Dynamic Imaging Grade for Swallowing Toxicity, DIGEST) as radiation dose-dependent. Material and methods Ninety-seven patients enrolled on an IRB-approved prospective registry protocol with stage I–IV OPC underwent pre- and 3–6 month post-RT videofluoroscopy. Dose–volume histograms (DVH) for swallowing regions of interest (ROI) were calculated. Dysphagia severity was graded per DIGEST criteria (dichotomized with grade ≥2 as moderate/severe RAD). Recursive partitioning analysis (RPA) and Bayesian Information Criteria (BIC) were used to identify dose–volume effects associated with moderate/severe RAD. Results 31% developed moderate/severe RAD (i.e. DIGEST grade ≥2) at 3–6 months after RT. RPA found DVH-derived dosimetric parameters of geniohyoid/mylohyoid (GHM), superior pharyngeal constrictor (SPC), and supraglottic region were associated with DIGEST grade ≥2 RAD. V61 ≥ 18.57% of GHM demonstrated optimal model performance for prediction of DIGEST grade ≥2. Conclusion The findings from this prospective longitudinal registry validate prior observations that dose to submental musculature predicts for increased burden of dysphagia after oropharyngeal IMRT. Findings also support dichotomization of DIGEST grade ≥2 as a dose-dependent split for use as an endpoint in trials or predictive dose–response analysis of videofluoroscopy results.

Background Functional outcomes after treatment for oropharyngeal squamous cell carcinoma (SCC) are increasingly prioritized. The purpose of this study was to investigate the incidence of gastrostomy tube placement and weight loss in patients with oropharyngeal SCC who may be eligible for either transoral robotic surgery (TORS) or nonsurgical management. Methods We conducted a retrospective review of previously untreated T1 to T2 and N0 to N2b oropharyngeal SCC to determine the rates of gastrostomy tube placement and weight loss according to Common Terminology Criteria for Adverse Events (CTCAE) criteria. Multivariate regression models were fit to compare these end points between groups. Results Two hundred twenty-three patients were included, comprised of 66 patients who underwent TORS and 157 patients who underwent (chemo)radiation. Thirty-two (48.5%) of the TORS patients received adjuvant radiation. On multivariate analysis, patients treated nonsurgically were 10.6 times and 8.1 times more likely to receive a gastrostomy tube and experience greater than CTCAE grade 1 weight loss, respectively. Conclusion In selected patients with oropharyngeal SCC, TORS may help avoid critical weight loss and gastrostomy tube placement in the acute treatment period.

Highlights • The average dose to 95% of initial PTV volume was 70.7 Gy for standard plans vs. 58.5 Gy for adaptive plans. • MRI-guided adaptive approach resulted in decrease dose to normal tissue compared with standard plans. • NTCP of post-treatment dysphagia, feeding tube, and hypothyroidism were reduced using the adaptive approach., Purpose We aim to determine the feasibility and dosimetric benefits of a novel MRI-guided IMRT dose-adaption strategy for human papillomavirus positive (HPV+) oropharyngeal squamous cell carcinoma (OPC). Materials/methods Patients with locally advanced HPV+ OPC underwent pre-treatment and in-treatment MRIs every two weeks using RT immobilization setup. For each patient, two IMRT plans were created (i.e. standard and adaptive). The prescription dose for the standard plans was 2.12 Gy/fx for 33 fractions to the initial PTV. For adaptive plans, a new PTVadaptive was generated based on serial MRIs in case of detectable tumor shrinkage. Prescription dose to PTVadaptive was 2.12 Gy/fx to allow for maximum dose to the residual disease. Any previously involved volumes received minimally a floor dose of 50.16 Gy. Uninvolved elective nodal volumes were prescribed 50.16 Gy in 1.52 Gy/fx. Dosimetric parameters of organs at risk (OARs) were recorded for standard vs. adaptive plans. Normal tissue complication probability (NTCP) for toxicity endpoints was calculated using literature-derived multivariate logistic regression models. Results Five patients were included in this pilot study, 3 men and 2 women. Median age was 58 years (range 45–69). Three tumors originated at the tonsillar fossa and two at the base of tongue. The average dose to 95% of initial PTV volume was 70.7 Gy (SD,0.3) for standard plans vs. 58.5 Gy (SD,2.0) for adaptive plans. The majority of OARs showed decrease in dosimetric parameters using adaptive plans vs. standard plans, particularly swallowing related structures. The average reduction in the probability of developing dysphagia ≥ grade2, feeding tube persistence at 6-month post-treatment and hypothyroidism at 1-year post-treatment was 11%, 4%, and 5%, respectively. The probability of xerostomia at 6-month was only reduced by 1% for adaptive plans vs. standard IMRT. Conclusion These in silico results showed that the proposed MRI-guided adaptive approach is technically feasible and advantageous in reducing dose to OARs, especially swallowing musculature.

Objectives To investigate the impact of 3-Diminsional (3D) tumor volume (TV) and extent of involvement of primary tumor on treatment outcomes in a large uniform cohort of T3 laryngeal carcinoma patients treated with nonsurgical laryngeal preservation strategies. Materials and Methods The pretreatment contrast-enhanced computed tomography images of 90 patients with T3 laryngeal carcinoma were reviewed. Primary gross tumor volume (GTVp) was delineated to calculate the 3D TV and define the extent of invasion. Cartilage and soft tissue involvement was coded. The extent of invasion was dichotomized into non/limited invasion versus multiple invasion extension (MIE), and was subsequently correlated with survival outcomes. Results The median TV was 6.6 cm3. Sixty-five patients had non/limited invasion, and 25 had MIE. Median follow-up for surviving patients was 52 months. The 5-year local control and overall survival rates for the whole cohort were 88% and 68%, respectively. There was no correlation between TV and survival outcomes. However, patients with non/limited invasion had better 5-year local control (LC) than those with MIE (95% vs 72%, p = .009) but did not have a significantly higher rate of overall survival (OS) (74% vs 67%, p = .327). In multivariate correlates of LC, MIE maintained statistical significance whereas baseline airway status showed a statistically significance trend with poor LC (p = .0087 and 0.06, respectively). Baseline good performance status was an independent predictor of improved OS (p = .03) in multivariate analysis. Conclusion The extent of primary tumor invasion is an independent prognostic factor of LC of the disease after definitive radiotherapy in T3 larynx cancer.

Background There are few published studies to guide the treatment of carcinoma metastatic to the neck from an unknown primary (CUP). In this regard, the objective of the current study was to share the authors' current experience treating patients with CUP using intensity-modulated radiation therapy (IMRT), which principally targeted both sides of the neck, the nasopharynx, and the oropharynx. Methods This was a retrospective study in which an institutional database search was conducted to identify patients with CUP who received IMRT. Data analysis included frequency tabulation, survival analysis, and multivariable analysis. Results Two-hundred sixty patients met inclusion criteria. The most common lymph node category was N2b (54%). IMRT volumes included the entire pharyngolaryngeal mucosa in 78 patients, the nasopharynx and oropharynx in 167 patients, and treatment limited to the involved neck in 11 patients. Eighty-four patients underwent neck dissections. The 5-year overall survival, regional control, and distant metastases-free survival rates were 84%, 91%, and 94%, respectively. Over 40% of patients had gastrostomy tubes during therapy, and 7% patients were diagnosed with chronic radiation-associated dysphagia. Higher lymph node burden was associated with worse disease-related outcomes, and in subgroup analysis, patients with human papillomavirus-associated disease had better outcomes. No therapeutic modality was statistically associated with either disease-related outcomes or toxicity. Conclusions Comprehensive IMRT with treatment to both sides of the neck and to the oropharyngeal and nasopharyngeal mucosa results in high rates of disease control and survival. The investigators were unable to demonstrate that treatment intensification with chemotherapy or surgery added benefit or excessive toxicity. Cancer 2018;124:1415-27. © 2018 American Cancer Society.

To identify a clinically meaningful cut-point for the single item dry mouth question of the MD Anderson Symptom Inventory-Head and Neck module (MDASI-HN).Head and neck cancer survivors who had received radiation therapy (RT) completed the MDASI-HN, the University of Michigan Hospital Xerostomia Questionnaire (XQ), and the health visual analog scale (VAS) of the EuroQol Five Dimension Questionnaire (EQ-5D). The Bayesian information criteria (BIC) were used to test the prediction power of each tool for EQ-5D VAS. The modified Breiman recursive partitioning analysis (RPA) was used to identify a cut point of the MDASI-HN dry mouth score (MDASI-HN-DM) with EQ-5D VAS, using a ROC-based approach; regression analysis was used to confirm the threshold effect size.Two-hundred seven respondents formed the cohort. Median follow-up from the end of RT to questionnaire completion was 88 months. The single item MDASI-HN-DM score showed a linear relationship with the XQ composite score (ρ = 0.80, p 0.001). The MDASI-HN-DM displayed improved model performance for association with EQ-5D VAS as compared to XQ (BIC of 1803.7 vs. 2016.9, respectively). RPA showed that an MDASI-HN-DM score of ≥6 correlated with EQ-5D VAS decline (LogWorth 5.5).The single item MDASI-HN-DM correlated with the multi-item XQ and performed favorably in the prediction of QOL. A MDASI-HN-DM cut point of ≥6 correlated with decline in QOL.

Radiomics is one such “big data” approach that applies advanced image refining/data characterization algorithms to generate imaging features that can quantitatively classify tumor phenotypes in a non-invasive manner. We hypothesize that certain textural features of oropharyngeal cancer (OPC) primary tumors will have statistically significant correlations to patient outcomes such as local control. Patients from an IRB-approved database dispositioned to (chemo)radiotherapy for locally advanced OPC were included in this retrospective series. Pretreatment contrast CT scans were extracted and radiomics-based analysis of gross tumor volume of the primary disease (GTVp) were performed using imaging biomarker explorer (IBEX) software that runs in Matlab platform. Data set was randomly divided into a training dataset and test and tuning holdback dataset. Machine learning methods were applied to yield a radiomic signature consisting of features with minimal overlap and maximum prognostic significance. The radiomic signature was adapted to discriminate patients, in concordance with other key clinical prognosticators. 465 patients were available for analysis. A signature composed of 2 radiomic features from pre-therapy imaging was derived, based on the Intensity Direct and Neighbor Intensity Difference methods. Analysis of resultant groupings showed robust discrimination of recurrence probability and Kaplan-Meier-estimated local control rate (LCR) differences between “favorable” and “unfavorable” clusters were noted.

Key Points Question What factors are associated with moderate to severe voice and speech symptoms among long-term survivors of oropharyngeal cancer (OPC)? Findings In this retrospective cohort study with cross-sectional survivorship survey administration, of 881 survivors of OPC who were included in analysis, 113 (12.8%) reported moderate to severe voice and speech symptoms. Increasing survival time and total radiation dose, Black race, Hispanic ethnicity, current cigarette smoking at the time of the survey, multimodality treatment with induction and concurrent chemotherapy, and late and baseline lower cranial neuropathy were identified as risk factors for moderate to severe voice and speech symptoms, and an intensity-modulated split-field radiotherapy regimen was associated with better voice and speech symptoms. Meaning These findings may have clinical implications for OPC treatment and survivorship, and the preservation of function and quality of life should be considered without compromising oncological outcomes., Importance Voice and speech production are critical physiological functions that affect quality of life and may deteriorate substantially after oropharyngeal cancer (OPC) treatment. There is limited knowledge about risk factors associated with voice and speech outcomes among survivors of OPC. Objective To identify the risk factors of voice and speech symptoms among long-term survivors of OPC. Design, Setting, and Participants This retrospective cohort study with cross-sectional survivorship survey administration includes cancer-free survivors of OPC who were treated curatively between January 2000 and December 2013 at MD Anderson Cancer Center (Houston, Texas) who participated in a survey from September 2015 to July 2016. Of 906 survivors of OPC with a median survival duration at time of survey of 6 years (range, 1-16 years), patient-rated voice and speech outcomes for 881 were available and analyzed. The data were analyzed from June 30, 2020, to February 28, 2021. Main Outcomes and Measures The primary outcome variable was patient-reported voice and speech scores that were measured using the MD Anderson Symptom Inventory–Head and Neck Cancer Module. Voice and speech scores of 0 to 4 were categorized as none to mild symptoms, and scores of 5 to 10 were categorized as moderate to severe symptoms. Risk factors for moderate to severe voice and speech symptoms were identified by multivariable logistic regression. Results Among 881 survivors of OPC (median [range] age, 56 [32-84] years; 140 women [15.5%]; 837 White [92.4%], 17 Black [1.9%], and 35 Hispanic individuals [3.8%]), 113 (12.8%) reported moderate to severe voice and speech scores. Increasing survival time (odds ratio [OR], 1.17; 95% CI, 1.06-1.30) and increasing total radiation dose (OR, 1.16; 95% CI, 1.00-1.34), Black race (OR, 3.90; 95% CI, 1.02-14.89), Hispanic ethnicity (OR, 3.74; 95% CI, 1.50-9.35), current cigarette smoking at the time of survey (OR, 3.98; 95% CI, 1.56-10.18), treatment with induction and concurrent chemotherapy (OR, 1.94; 95% CI, 1.06-3.57), and late (OR, 7.11; 95% CI, 3.08-16.41) and baseline lower cranial neuropathy (OR, 8.70; 95% CI, 3.01-25.13) were risk factors associated with moderate to severe voice and speech symptoms. Intensity-modulated radiotherapy split-field regimen (OR, 0.31; 95% CI, 0.12-0.80; P = .01) was associated with lower likelihood of moderate to severe voice and speech symptoms. Conclusions and Relevance This large OPC survivorship cohort study identified many treatment-related factors, including increasing total radiotherapy dose, multimodality induction and concurrent chemotherapy regimens, and continued smoking, as well as clinical and demographic factors, as risk factors that were associated with moderate to severe voice and speech symptoms. The key findings in this study were the protective associations of split-field radiation and that longer-term survivors, and those who continued to smoke, had worse voice and speech symptoms. These findings may inform research and effective targeted clinical voice and speech preservation interventions and smoking cessation interventions to maximize voice and speech function and address quality of life among patients with OPC., This cross-sectional study examines risk factors of voice and speech symptoms among survivors of long-term oropharyngeal cancer.