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The goal of this study was to evaluate disease, survival, and toxic effects after unilateral radiation therapy treatment for tonsillar cancer.A retrospective study was performed of patients treated at our institution within the period from 2000 to 2018. Summary statistics were used to assess the cohort by patient characteristics and treatments delivered. The Kaplan-Meier method was used to determine survival outcomes.The cohort comprised 403 patients, including 343 (85%) with clinical and/or radiographic evidence of ipsilateral cervical nodal disease and 181 (45%) with multiple involved nodes. Human papillomavirus was detected in 294 (73%) tumors. Median follow-up time was 5.8 years. Disease relapse was infrequent with local recurrence in 9 (2%) patients, neck recurrence in 13 (3%) patients, and recurrence in the unirradiated contralateral neck in 9 (2%) patients. Five- and 10-year overall survival rates were 94% and 89%, respectively. Gastrostomy tubes were needed in 32 (9%) patients, and no patient had a feeding tube 6 months after therapy.For patients with well-lateralized tonsillar tumors and no clinically evident adenopathy of the contralateral neck, unilateral radiation therapy offers favorable rates of disease outcomes and a relatively low toxicity profile.

Highlights • The PIRATES protocol is a novel tumor radiation dose-escalation approach. • PIRATES integrates proton therapy, image guided RT and hybrid hyper-fractionation. • It targets only head and neck cancer patients at high risk of treatment failure. • This Phase I trial aims to test the feasibility and safety of PIRATES., Introduction Radiation dose-escalation for head and neck cancer (HNC) patients aiming to improve cure rates is challenging due to the increased risk of unacceptable treatment-induced toxicities. With “Proton Image-guided Radiation Assignment for Therapeutic Escalation via Selection of locally advanced head and neck cancer patients” (PIRATES), we present a novel treatment approach that is designed to facilitate dose-escalation while minimizing the risk of dose-limiting toxicities for locally advanced HPV-negative HNC patients. The aim of this Phase I trial is to assess the safety & feasibility of PIRATES approach. Methods The PIRATES protocol employs a multi-faceted dose-escalation approach to minimize the risk of dose-limiting toxicities (DLTs): 1) sparing surrounding normal tissue from extraneous dose with intensity-modulated proton therapy, 2) mid-treatment hybrid hyper-fractionation for radiobiologic normal tissue sparing; 3) Magnetic Resonance Imaging (MRI) guided mid-treatment boost volume adaptation, and 4) iso-effective restricted organ-at-risk dosing to mucosa and bone tissues. The time-to-event Bayesian optimal interval (TITE-BOIN) design is employed to address the challenge of the long DLT window of 6 months and find the maximum tolerated dose. The primary endpoint is unacceptable radiation-induced toxicities (Grade 4, mucositis, dermatitis, or Grade 3 myelopathy, osteoradionecrosis) occurring within 6 months following radiotherapy. The second endpoint is any grade 3 toxicity occurring in 3–6 months after radiation. Discussion The PIRATES dose-escalation approach is designed to provide a safe avenue to intensify local treatment for HNC patients for whom therapy with conventional radiation dose levels is likely to fail. PIRATES aims to minimize the radiation damage to the tissue surrounding the tumor volume with the combination of proton therapy and adaptive radiotherapy and within the high dose tumor volume with hybrid hyper-fractionation and not boosting mucosal and bone tissues. Ultimately, if successful, PIRATES has the potential to safety increase local control rates in HNC patients with high loco-regional failure risk. Trial registration: ClinicalTrials.gov ID: NCT04870840; Registration date: May 4, 2021. Netherlands Trial Register ID: NL9603; Registration date: July 15, 2021.

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/objectivePain is the most common acute toxicity following radiation therapy (RT) for head and neck cancer (HNC). The multifactorial origin of radiotherapy-induced pain makes it highly challenging to manage in HNC patients. Multiple studies have been conducted to identify different germline genetic variants associated with cancer pain, however few of them focused on RT-induced acute pain. In this systematic review, we summarize potential mechanisms of acute pain after radiotherapy in HNC focusing on oral cavity/oropharyngeal cancer and identify genetic variants associated with radiotherapy-induced acute pain and other relevant acute toxicities.MethodsA comprehensive search of Ovid Medline, EMBASE and Web of Science databases using concepts and terms including “Variants”, “Polymorphisms”, “Radiotherapy”, “Acute pain”, “Acute toxicity” published up to February 28, 2022 was performed by two reviewers. Review articles and citations were reviewed manually. The reported SNPs associated with RT-induced acute pain and toxicities were reported, and the molecular function of the associated genes and pathways were described based on genetic annotation using The Human Gene Database; GeneCards.ResultsA total of 386 articles were identified electronically and an additional 8 articles were included after manual search. 39 articles were finally included. 51 variants were associated with 40 genes, of which 30 % had function in DNA damage response and repair, 25% in inflammatory and immune response, 17.5 % in cell death or cell cycle, and were associated with RT-inflammatory pain and acute mucositis or dermatitis. 4 variants in 4 genes were associated with neuropathy and neuropathic pain. 13 variants in 10 genes and were associated with RT-induced mixed types of post-RT-pain.ConclusionDifferent types of pain develop after RT, including inflammatory pain (acute mucositis and acute skin reaction); neuropathic pain; nociceptive pain; and mixed oral pain. Genetic variants involved in DNA damage response and repair, cell death, inflammation and neuropathic pathways may affect pain presentation post-RT. These variants could be used for acute pain prediction and personalized pain management in HNC patients receiving RT.

OBJECTIVES/HYPOTHESIS To report the largest single-institution review of temporal bone osteoradionecrosis (TBORN), and characterize the disease's natural history, prognostic factors, management, and outcomes. STUDY DESIGN Retrospective chart review. METHODS Retrospective review was conducted to identify patients with TBORN. Pertinent data were extracted. Descriptive statistics were used to summarize patient, tumor, and treatment characteristics. Multivariable analyses were conducted to explore associations between these characteristics and time to TBORN diagnosis and risk of developing diffuse disease. RESULTS TBORN was identified in 145 temporal bones from 128 patients. Mean age at diagnosis was 62 years, and mean time to diagnosis after radiotherapy was 10 years. Age greater than 50 years was associated with earlier diagnosis. According to the Ramsden criteria, 76% of TBs had localized and 24% had diffuse disease at initial diagnosis; 37% had diffuse disease at last follow-up. On multivariable analysis, diabetes, three-dimensional conformal radiotherapy (3D-CRT), and periauricular skin malignancy were significant risk factors for developing diffuse disease. Localized disease was successfully managed with conservative measures, whereas surgery was often necessary for diffuse disease. When TBORN spread outside the mastoid or infratemporal fossa, conservative measures were always unsuccessful. CONCLUSIONS TBORN occurs earlier in older patients. While diffuse disease is less common than localized disease, it occurs more frequently in patients with diabetes, history of 3D-CRT, and periauricular skin malignancies. Conservative management is appropriate for localized disease, while surgery is often necessary for diffuse disease. The prognostic factors identified helped propose a TBORN staging system and treatment guidelines which may improve patient risk stratification and disease management. LEVEL OF EVIDENCE 4 Laryngoscope, 131:2578-2585, 2021.

Background Recurrent head and neck cancer has poor prognosis. Stereotactic body radiotherapy (SBRT) may improve outcomes by delivering ablative radiation doses. Methods We reviewed patients who received definitive-intent SBRT reirradiation at our institution from 2013 to 2020. Patterns of failure, overall survival (OS), and toxicities were analyzed. Results One hundred and thirty-seven patients were evaluated. The median OS was 44.3 months. The median SBRT dose was 45 Gy and median target volume 16.9 cc. The 1-year local, regional, and distant control was 78%, 66%, and 83%, respectively. Systemic therapy improved regional (p = 0.004) and distant control (p = 0.04) in nonmetastatic patients. Grade 3+ toxicities were more common at mucosal sites (p = 0.001) and with concurrent systemic therapy (p = 0.02). Conclusions In a large cohort of SBRT reirradiation for recurrent, small volume head and neck cancers, a median OS of 44.3 months was observed. Systemic therapy improved regional and distant control. Toxicities were modulated by anatomic site and systemic therapy.

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.

BACKGROUND Induction chemotherapy (IC) has been associated with a decreased risk of distant metastasis in locally advanced head and neck squamous cell carcinoma. However, its role in the treatment of oropharyngeal squamous cell carcinoma (OPSCC) is not well established. METHODS The outcomes of patients with OPSCC treated with IC followed by concurrent chemoradiation (CRT) were compared with the outcomes of those treated with CRT alone. The primary outcome was overall survival (OS), and the secondary end points were the times to locoregional and distant recurrence. RESULTS In an existing database, 585 patients met the inclusion criteria: 137 received IC plus CRT, and 448 received CRT. Most patients were positive for human papillomavirus (HPV; 90.9%). Patients receiving IC were more likely to present with a higher T stage, a higher N stage, and low neck disease. The 3-year OS rate was significantly lower in patients receiving IC (75.7%) versus CRT alone (92.9%). In a multicovariate analysis, receipt of IC (adjusted hazard ratio [aHR], 3.4; P < .001), HPV tumor status (aHR, 0.36; P = .002), and receipt of concurrent cetuximab (aHR, 2.7; P = .002) were independently associated with OS. The risk of distant metastasis was also significantly higher in IC patients (aHR, 2.8; P = .001), whereas an HPV-positive tumor status (aHR, 0.44; P = .032) and completion of therapy (aHR, 0.51; P = .034) were associated with a lower risk of distant metastasis. In HPV-positive patients, IC remained associated with distant metastatic progression (aHR, 2.6; P = .004) but not OS. CONCLUSIONS In contrast to prior studies, IC was independently associated with worse OS and a higher risk of distant metastasis in patients with OPSCC. Future studies are needed to validate these findings.

Background The last revision of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual included a specific system for cutaneous squamous cell carcinoma (CSCC) of the head and neck. Here, we assessed the prognostic performance of six candidate modified T-classification models in head and neck CSCC patients. Methods Analysis of 916 patients with head and neck CSCC given treatment with curative intent at The University of Texas MD Anderson Cancer Center between 1995 and 2019 was performed. The main outcome was disease-specific survival (DSS), and the impact of depth of invasion (DOI) was analyzed using multivariable regression models. Candidate models were developed using the optimal DOI cut points for each AJCC T classification based on goodness of fit of the model and the simplicity of the model. Staging systems were compared using Harrell's concordance index. Results Median age was 70 years (range, 19–97years) and median follow-up time of 22 months (range, 1–250months). The median DOI was 6.0 mm (range, 0.1–70.0 mm). The five-year DSS rate was 80.7% (95%CI, 77.4–83.7%). We found significant association between DOI (hazard ratio, 1.21 [95%CI: 1.01–1.43]) and DSS on multivariable analysis. Based on a low Akaike information criterion score, improvement in the concordance index, and Kaplan–Meier curves, model 6 surpassed the AJCC staging system. Conclusions Incorporation of DOI in the current AJCC staging system improves discrimination of T classifications in head and neck CSCC patients. Lay summary The current staging system for head and neck cutaneous squamous cell carcinoma demonstrates wide prognostic variability and provides suboptimal risk stratification. Incorporation of depth of invasion in the T-classification system improves risk prediction and patient counseling. Precis We propose improved head and neck cutaneous squamous cell carcinoma T staging that will include depth of invasion and should be considered in future versions of the American Joint Committee on Cancer after external validation.

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.

Background The prognostic performance of the recently updated American Joint Committee on Cancer lymph node classification of cutaneous head and neck squamous cell carcinoma (HNSCC) has not been validated. The objective of this study was to assess the prognostic role of extranodal extension (ENE) in cutaneous HNSCC. Methods This was a retrospective analysis of 1258 patients with cutaneous HNSCC who underwent surgery with or without adjuvant therapy between 1995 and 2019 at The University of Texas MD Anderson Cancer Center. The primary outcome was disease-specific survival (DSS). Local, regional, and distant metastases-free survival were secondary outcomes. Recursive partitioning analysis (RPA) and a Cox proportional hazards regression model were used to assess the fitness of staging models. Results No significant differences in 5-year DSS were observed between patients with pathologic lymph node-negative (pN0) disease (67.4%) and those with pN-positive/ENE-negative disease (68.2%; hazard ratio, 1.02; 95% CI, 0.61-1.79) or between patients with pN-positive/ENE-negative disease and those with pN-positive/ENE-positive disease (52.7%; hazard ratio, 0.57; 95% CI, 0.31-1.01). The RPA-derived model achieved better stratification between high-risk patients (category III, ENE-positive with >2 positive lymph nodes) and low-risk patients (category I, pN0; category II, ENE-positive/pN1 and ENE-negative with >2 positive lymph nodes). The performance of the RPA-derived model was better than that of the pathologic TNM classification (Akaike information criterion score, 1167 compared with 1176; Bayesian information criterion score, 1175 compared with 1195). Conclusions The number of metastatic lymph nodes and the presence of ENE are independent prognostic factors for DSS in cutaneous HNSCC, and incorporation of these factors in staging systems improves the performance of the American Joint Committee on Cancer lymph node classification.

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

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.

CT-guided treatment delivery can improve target localization in mediastinal lymphoma patients treated with "butterfly" intensity-modulated radiotherapy and deep-inspiration breath hold. Although daily CT imaging adds additional radiation exposure, its use may be justified given the greater normal tissue sparing enabled by PTV margin reduction.

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 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.

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.

Purpose: Metaplastic breast cancer (BC) is an uncommon yet aggressive histologic subtype of BC. We sought to identify factors associated with its diagnosis and compare the management and outcomes of metaplastic BC with those of other BCs and triple negative invasive ductal carcinoma in particular given how often it has a triple negative phenotype. Patients and Methods: We identified women diagnosed with invasive BC in 2010-2014 in the National Cancer Data Base, and used univariate analysis to compare baseline patient and tumor characteristics by BC subtype. Overall survival (OS) was estimated with the Kaplan-Meier method, and multivariate Cox proportional hazards models were used to identify independent predictors of OS. Results: Of 247,355 cases, 2,084 (0.8%) were metaplastic BC, 55,998 (23%) triple negative BC, and 77% other BC. Relative to non-metaplastic BC, women with metaplastic BC were more likely to be older at diagnosis (median age, 62 vs. 59 years), have ≥1 comorbid conditions (22% vs. 18%), and be on Medicare (41% vs. 33%; P

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.

Introduction Stereotactic body radiotherapy (SBRT) results in excellent local control of stage I NSCLC. Radiobiology models predict greater tumor response when higher biologically effective doses (BED10) are given. Prior studies support a BED10 greater than or equal to 100 Gy with SBRT; however, data are limited comparing outcomes after various SBRT regimens. We therefore sought to evaluate national trends and the effect of using “low” versus “high” BED10 SBRT courses on overall survival (OS). Methods This retrospective study used the National Cancer Data Base to identify patients diagnosed with clinical stage I (cT1-2aN0M0) NSCLC from 2004 to 2014 treated with SBRT. Patients were categorized into LowBED (100-129 Gy) or HighBED (≥130 Gy) groups. A 1:1 matched analysis based on patient and tumor characteristics was used to compare OS by BED10 group. Tumor centrality was not assessed. Results O 25,039 patients treated with LowBED (n = 14,756; 59%) or HighBED (n = 10,283; 41%) SBRT, 20,542 were matched. Shifts in HighBED to LowBED SBRT regimen use correlated with key publications in the literature. In the matched cohort, 5-year OS rates were 26% for LowBED and 34% for HighBED groups (p = 0.039). On multivariate analysis, receipt of LowBED was associated with significantly worse survival (hazard ratio = 1.046, 95% confidence interval: 1.004–1.090, p = 0.032). Conclusions LowBED SBRT for treating stage I NSCLC is becoming more common. However, our findings suggest SBRT regimens with BED10 greater than or equal to 130 Gy may confer an additional survival benefit. Additional studies are required to evaluate the dose-response relationship and toxicities associated with modern HighBED SBRT.

Highlights • Early stage tonsillar cancers may be treated with unilateral neck radiotherapy (RT). • We performed a dosimetric study comparing three common radiotherapy modalities. • No significant differences in target coverage existed between all plans. • Laryngeal doses were reduced using whole-field intensity modulated RT and VMAT. • Shorter treatment times and required monitor units were also associated with VMAT., Background and purpose Minimizing radiation dose exposure to nearby organs is key to limiting clinical toxicities associated with radiotherapy. Several treatment modalities such as split- or whole-field intensity-modulated radiotherapy (SF-IMRT, WF-IMRT) and volumetric modulated arc therapy (VMAT) are being used to treat tonsillar cancer patients with unilateral neck radiotherapy. Herein, we provide a modern dosimetric comparison of all three techniques. Materials and methods Forty patients with tonsillar cancer treated with definitive, ipsilateral neck SF-IMRT were evaluated. Each patient was re-planned with WF-IMRT and VMAT techniques, and doses to selected organs-at-risk (OARs) including the larynx, esophagus, and brainstem were compared. Results No significant differences in target coverage existed between plans; however, the heterogeneity index improved using WF-IMRT and VMAT relative to SF-IMRT. Compared to SF-IMRT, WF-IMRT and VMAT plans had significantly lower mean doses to the supraglottic larynx (31 Gy, 18.5 Gy, 17 Gy; p

Patients with unresectable cT4b esophageal cancer (EC) are rare and largely excluded from prospective trials. As a result, current treatment recommendations are based on limited evidence. This study sought to evaluate national practice patterns and outcomes for this population and evaluated 3 primary cohorts: patients receiving chemotherapy (CT) with or without subtherapeutic radiotherapy (RT), definitive chemoradiotherapy (CRT), or CT with or without RT followed by definitive surgery.The National Cancer Data Base was queried for cT4b Nany M0 EC. Exclusion criteria were patients with unspecified staging, palliative treatment, improper, or no histologic confirmation, or lack of CT. Multivariable logistic regression determined factors predictive of receiving surgical therapy. Kaplan-Meier analysis evaluated overall survival (OS), and Cox proportional hazards modeling determined variables associated with OS.Altogether, 519 patients met inclusion criteria; 195 (38%) underwent CT, 291 (56%) underwent definitive CRT, and 33 (6%) underwent surgical-based therapy. Surgery was more likely performed in patients residing in rural areas, living farther from the treating facility, and N1 status (P0.05 for all). Median OS in the respective cohorts were 6.0, 12.7, and 43.9 months (P0.001). On multivariate Cox proportional hazards modeling, among others, nonsurgical treatment was associated with poorer OS (P0.05 for both).In the largest study to date evaluating patterns of care for cT4b EC, as compared with CT alone, addition of definitive RT was associated with higher OS. Although causation is clearly not implied, well-selected responders to CT and/or RT may be able to undergo resection and numerically prolonged survival, but patient selection remains paramount.

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.

PurposeTo develop a decision-making tool to choose the optimal treatment for oropharyngeal squamous cell cancer (OPSCC) patients who are eligible for primary transoral robotic surgery (TORS) and primary (chemo)radiation therapy with comparable locoregional control and survival.MethodsDecision tree models were constructed to study two decision-making scenarios, 1) TORS vs. definitive radiation therapy (RT), and 2) TORS vs. definitive chemo(radiation) therapy (CRT) based on well-established objective and subjective swallowing-function instruments, MD Anderson Dysphagia Inventory (MDADI), MD Anderson Symptom Inventory–Head and Neck Module (MDASI-HN), and clinician-rated Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) that measure swallowing-related toxicity pre-therapy, 3-6 months (short-term), and 18-24 months (long-term) after therapy for five treatment cohorts (RT, CRT, TORS, TORS with adjuvant RT, and TORS with adjuvant CRT). The optimal treatment was sought as a function of postoperative extranodal extension (ENE) and/or positive margin (PM) that can trigger the adjuvant therapy. 2D heatmaps were constructed indicating the thresholds of postoperative events likelihoods required for TORS or definitive therapy to become the optimal treatment. Additionally, a risk calculation model was developed to quantify the risk associated with TORS in the settings that estimation of postoperative complications likelihoods may not be available.ResultsUnder the first scenario and for short-term measures, MDADI and MDASI instruments indicate the superiority of definitive therapy to TORS at all times, while DIGEST required a maximum of 40% likelihood for both ENE and PM events to indicate TORS as the optimal treatment. For 18-24 months measures, MDASI indicated TORS as the optimal treatment; however, MDADI- and DIGEST-based long-term measures indicated threshold likelihoods of 90% and 25%, respectively, for TORS to remain the optimal treatment. For short-term outcomes, TORS resulted in higher toxicity even when the likelihood associated with postoperative tumor resection margin (TM) are extremely low. For higher probability of postoperative TM, all instruments indicated high risk associated with TORS (>83%). For long-term swallowing-related toxicity, TORS remained the optimal therapy independent from the probability of postoperative TM based on MDASI instrument. However, MDADI-based measure assigned a high risk to TORS (>86%) when postoperative TM is extremely likely. DIGEST-based measures indicated a very high risk associated with TORS independent from the postoperative TM likelihood (>91%).Under the second scenario (TORS vs. definitive CRT), Both MDASI- and MDADI-based short-term measures indicated TORS as the optimal therapy independent from postoperative ENE/PM events. However, according to the DIGEST-based measure, definitive RT remained the optimal therapy when the probability of postoperative ENE and PM events exceed 80%. In this case, TORS was the optimal therapy if both events were not relatively likely (90%), DIGEST-based measures demonstrated the superiority of definitive CRT once the likelihood of postoperative ENE or PM is, at least, 60%. Long-term measures indicated higher sensitivity to postoperative TM likelihood with both MDADI- and DIGEST-based measures indicating a moderately high risk (> 60%) with TORS causing higher clinician-rated swallowing toxicity compared to definitive CRT when postoperative TM is extremely likely.ConclusionThe current study using decision modeling shows proof of concept that in the absence of reliable estimation of postoperative ENE/PM events concurrent with significant postoperative positive margins (i.e., more than 2mm) that can trigger adjuvant therapy, the overall toxicity level incurred by OPSCC patients undergoing TORS may become more severe compared to patients receiving non-surgical treatments thus advocating definitive (C)RT protocols. The results further demonstrated that, when available, the likelihoods of postoperative events triggering postoperative adjuvant therapy must be incorporated when choosing the optimal treatment plan for eligible patients.

Purpose/Objective(s) The investigators’ 2013 use it or lose it study suggested functional benefit of two pharyngeal activities during head and neck radiotherapy (RT) – maintenance of oral intake (EAT) and swallowing exercise. EAT and EXERCISE independently associated with better odds of resuming a regular diet in long term survivorship and shorter duration of gastrostomy (FT) dependence. The prior work is limited by the retrospective nature of the dataset and historically far higher FT utilization. Our aim was to validate the previous work in a contemporary cohort of oropharyngeal cancer (OPC) survivors treated with RT using prospectively acquired validated outcome measures. Materials/Methods Endpoints included subacute diet after RT per the performance status scale for head and neck cancer (PSS-HN; solid food diet coded as ≥60 and no FT) and length of FT-dependence in days. Primary independent variables included oral intake (PO) at the end of RT (nothing per oral/NPO; partial PO; full PO) and swallow exercise adherence. Multiple linear regression and logistic regression models were analyzed adjusting for tumor location, baseline diet, chemotherapy and N and T stage. Results Analysis included 595 patients treated with primary radiotherapy (RT; 19% 111) /chemoradiation (CRT; 73% 434) or primary TORS + CRT (8% 50) for OPC (base of tongue/glossopharyngeal sulcus [46% 276]; tonsil [44% 263]; other [9% 56]). At the end of RT 9% of patients were NPO (55), 19% partial PO (115), 71% full PO (425). Statistically significant (P Conclusion These prospective registry data validate prior work that indicate independent benefit of EAT and swallowing EXERCISE adherence during RT on subacute functional outcomes. Patients who maintained full PO and/or exercise were more likely to eat solid foods by 3-6 months after treatment, while patients who EAT during treatment expectedly have the shortest feeding tube dependence.

Purpose/Objective(s) Stereotactic body radiotherapy (SBRT) is an emerging modality for the reirradiation of head and neck cancers (HNC). The need to use smaller reirradiation volumes to limit severe toxicity concerns represents a challenge in determining optimal target coverage. Herein, we investigate the associated patterns of failure after SBRT using previously defined spatial and dosimetric analysis (Mohamed et al, Radiat Oncol. 2017). Materials/Methods SBRT reirradiation HNC cases treated between 2014-2019 and surveilled by CT, PET/CT, and/or MRI were reviewed retrospectively in this IRB approved study. Patients with radiographic evidence of recurrence within the head and neck region after SBRT were identified. Multifocal disease was defined as any non-contiguous FDG-avid or biopsy positive disease seen on imaging. Diagnostic scans were co-registered with planning CT scans (pCT) for manual segmentation of recurrent gross volumes (rGTV). rGTVs were then deformed to co-registered pCTs for failure classification. The classification followed a granular typology of 5 failure categories: central high-dose (type A or “in-field”), peripheral high-dose (type B), central low-dose (type C), peripheral low-dose (type D or “marginal”), and extraneous-dose (type E or “out of field”). Each type was determined based on the centroid location of rGTV relative to the planning target volumes plus the dose received by 95% of rGTV volume. Results A total of 106 SBRT cases were reviewed out of which 34 patients (32%) recurred after SBRT; 27 (79%) patients had squamous cell carcinomas, 7 (21%) received postoperative SBRT, and 24 (71%) received concurrent systemic therapy. Twenty-three (68%) patients received 42.5-45 Gy in 5 fractions (Fx) and 7 (21%) patients received 36 Gy in 6 Fx. Median time to failure was 5.5 months (range, 1-22 months). Twenty-two recurrences (65%) were out-of-field type E failures, 6 (18%) type A, 3 (9%) type C, and 3 (9%) type D. Fourteen of 16 (88%) multifocal SBRT reirradiation cases had Type E failures compared to 8 of 18 (44%) unifocal SBRT cases. Among the 6 in-field failures, 3 received 36 Gy in 6 Fx and 3 received 42.5-45 Gy in 5 Fx. Conclusion Post SBRT reirradiation recurrences were seen in one-third of cases with the majority of failures being Type E (outside the treatment field), particularly in patients who were treated for multifocal disease. The use of 42.5-45 Gy in 5 Fx appears to be an effective biological dose for local tumor control. Marginal (Type C and D) failures may be reduced with larger margins, but limit feasibility of SBRT. Therefore, future reirradiation strategies should aim to improve patient selection, multimodal therapy, and margin definition in the HNC SBRT reirradiation setting.

Background The survival benefit of elective neck dissection (END) for patients with cutaneous squamous cell carcinoma (cSCC) of the head and neck and no evidence of regional metastasis (cN0) has never been reported. The aim of this study was to determine the effect of END on patient survival. Methods The authors included patients with head and neck cSCC who had undergone primary surgery from 1995 to 2017. The primary end point was survival, and the secondary end points were the incidence of occult regional disease and regional disease control. To assess the impact of END on survival, the authors used multivariable Cox proportional hazards models with propensity score and matching techniques for internal validation. Results A total of 1111 patients presented with no evidence of nodal disease; 173 had END, and 938 were observed. Adjuvant radiotherapy to the neck was administered to 101 patients (9%). END resulted in a 5-year overall survival rate of 52%, whereas the rate was 63% in the observation group (P = .003 [log-rank]). The 5-year disease-free survival rate for patients undergoing END was similar to that for the observation group (73% vs 75%; P = .429). A multivariate regression model showed that the performance of END was not associated with improved rates of overall, disease-specific, or disease-free survival; similarly, among patients with advanced disease (T3-4), those who underwent END did not have improved survival rates. Conclusions Among patients with cSCC of the head and neck, observation of the neck nodes resulted in noninferior survival rates in comparison with END at the time of primary surgery. Further studies are required to elucidate the role of END in patients with advanced disease.

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 The goal of this study was to comprehensively investigate the association of chemotherapy with trajectories of acute symptom development and late symptom recovery in patients with oropharyngeal cancer (OPC) by comparing symptom burden between induction chemotherapy followed by concurrent chemoradiotherapy (ICRT), concurrent chemo‐radiotherapy (CRT), or radiotherapy (RT) alone. METHODS Among a registry of 717 patients with OPC, the 28‐item patient‐reported MD Anderson Symptom Inventory–Head and Neck Module (MDASI‐HN) symptoms were collected prospectively at baseline, weekly during RT, and 1.5, 3 to 6, 12, and 18 to 24 months after RT. The effect of the treatment regimen (ICRT, CRT, and RT alone) was examined with mixed‐model analyses for the acute and late period. In the CRT cohort, the chemotherapy agent relationship with symptoms was investigated. RESULTS Chemoradiation (ICRT/CRT) compared with RT alone resulted in significantly higher acute symptom scores in the majority of MDASI‐HN symptoms (ie, 21 out of 28). No late symptom differences between treatment with or without chemotherapy were observed that were not attributable to ICRT. Nausea was lower for CRT with carboplatin than for CRT with cisplatin; cetuximab was associated with particularly higher scores for acute and late skin, mucositis, and 6 other symptoms. The addition of ICRT compared with CRT or RT alone was associated with a significant increase in numbness and shortness of breath. CONCLUSION The addition of chemotherapy to definitive RT for OPC patients was associated with significantly worse acute symptom outcomes compared with RT alone, which seems to attenuate in the late posttreatment period. Moreover, induction chemotherapy was specifically associated with worse numbness and shortness of breath during and after treatment. LAY SUMMARY Chemotherapy is frequently used in addition to radiotherapy cancer treatment, yet the (added) effect on treatment‐induced over time is not comprehensively investigatedThis study shows that chemotherapy adds to the symptom severity reported by patients, especially during treatment, Induction/concurrent chemotherapy significantly augments patient‐reported symptom burden of radiotherapy among patients with oropharyngeal cancer, as worse acute symptom outcomes are observed compared with radiotherapy alone. Induction chemotherapy is associated with greater numbness and shortness of breath during and after treatment.

Prostate low dose rate (LDR) brachytherapy is a well-established standard of care treatment option for men with localized prostate cancer, with long-term follow-up and outcome data available. Image guidance is crucial for high-quality brachytherapy. Ongoing development and research are underway to incorporate more advanced imaging techniques into the procedure to enhance the quality and minimize the side effects of treatment. This chapter will discuss the history, rationale, and anatomy related to prostate brachytherapy. It also covers the various brachytherapy workflow steps involving the traditional computed tomography (CT) and ultrasound (US) imaging-directed brachytherapy and more recent advancements in incorporating magnetic resonance imaging (MRI) into the procedure.

Head and neck squamous cell carcinoma (HNSCC) treatment response relies heavily on macroscopic clinical findings. Blood monitoring of circulating markers during treatment may improve earlier detection of responders versus non-responders during radiotherapy. In this study, patients with intact tumour of HNSCC were enrolled in the prospective PREDICT-HN study. Pre-, after first treatment, weekly, and post-treatment blood samples were collected. CTC was enumerated using the CellSearch system. cfDNA was quantified from cfNA isolated at pre-, mid- and post-treatment timepoints. Blood samples were collected from 45 patients. Of the 339 samples analysed for CTC, 31% had detectable CTCs. Nine patients had detectable CTCs (1-3/7.5ml blood) in pre-treatment samples. After 1 fraction, 16 patients had CTCs detected, with 12 who had no pre-treatment CTC. Sixteen (36%) patients had detectable CTC in final week of treatment. There was no correlation between cancer stage, nodal status and tumour burden with CTC. cfDNA levels increased during treatment, with its highest level in the final week and lowest at post-treatment. Our results showed in HNSCC that CTCs can be detected during radiotherapy, suggesting mobilization into circulation during treatment, with as-yet-unknown viability. cfDNA kinetics during treatment correlated with CTC release, and may indicate apoptotic change.Simple SummaryHead and neck squamous cell carcinoma (HNSCC) treatment response relies heavily on macroscopic clinical findings. Blood monitoring of circulating markers such as circulating tumour cell (CTC) and cell-free DNA (cfDNA) during treatment may improve earlier detection of responders versus non-responders during definitive radiotherapy. Although the detection of CTCs and cfDNA in patients with HNSCC has been described, there is minimal data on the kinetics of CTC counts and cfDNA levels during radiotherapy in patients with HNSCC. Here, our study prospectively describes the changes in CTC and cfDNA enumeration during radiotherapy in patients with HNSCC. Our results showed, for the first time to our knowledge, in HNSCC, that CTCs can be detected during radiotherapy, suggesting mobilization into peripheral circulation during treatment, with as-yet-unknown viability. cfDNA kinetics during treatment correlated with CTC release, may indicate apoptotic change during radiotherapy. Combined cfDNA-CTC as an early marker of treatment response should be investigated further.

Purpose: To examine national care patterns in proton radiation therapy (PBT) use for non–small cell lung cancer (NSCLC) and the effect of facility type on survival. Patients and Methods: Using the National Cancer Database, we identified 506 patients with a diagnosis of NSCLC from 2004-2014 who underwent PBT. Patients were categorized as having received treatment at an academic/research facility (ARF) or a form of community cancer program (CCP). Descriptive analysis was performed, and overall survival was analyzed by Kaplan-Meier methods and Cox proportional hazard models. Results: Treatments at ARFs and CCPs were equally distributed with 253 patients at each facility type. A positive trend in PBT use over time was observed with 2.8% of cases being treated in 2008 compared to 21.5% in 2014 (P = .001). Definitive doses (≥60 Gy) were more commonly given at ARFs than CCPs (72% versus 45%, respectively; P

Following complete resection of pN2 non-small cell lung cancer (NSCLC), national guidelines recommend either sequential (sCRT) or concurrent chemoradiotherapy (cCRT). This is the largest study to date evaluating survival between both approaches. In sCRT patients, sequencing ‘chemotherapy first’ versus ‘radiotherapy first’ was also addressed. The National Cancer Data Base (NCDB) was queried for patients with primary NSCLC undergoing surgery (without neoadjuvant radiotherapy or chemotherapy), pN2 disease with negative surgical margins, and receiving postoperative CRT. Multivariable logistic regression ascertained factors associated with cCRT administration. Kaplan–Meier analysis evaluated overall survival (OS), and Cox proportional hazards modeling determined variables associated with OS. Propensity matching was performed to address group imbalances and indication biases. Of 1924 total patients, 1115 (58%) received sCRT and 809 (42%) underwent cCRT. Median OS in the sCRT and cCRT cohorts was 53 months versus 37 months (p