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There are no agreed upon measures to comprehensively determine the quality of radiation oncology (RO) care delivered for prostate cancer. Consequently, it is difficult to assess the implementation of scientific advances and adherence to best practices in routine clinical practice. To address this need, the US Department of Veterans Affairs (VA) National Radiation Oncology Program established the VA Radiation Oncology Quality Surveillance (VA ROQS) Program to develop clinical quality measures to assess the quality of RO care delivered to Veterans with cancer. This article reports the prostate cancer consensus measures.The VA ROQS Program contracted with the American Society for Radiation Oncology to commission a Blue Ribbon Panel of prostate cancer experts to develop a set of evidence-based measures and performance expectations. From February to June 2021, the panel developed quality, aspirational, and surveillance measures for (1) initial consultation and workup, (2) simulation, treatment planning, and delivery, and (3) follow-up. Dose-volume histogram (DVH) constraints to be used as quality measures for definitive and post-prostatectomy radiation therapy were selected. The panel also identified the optimal Common Terminology Criteria for Adverse Events, version 5.0 (CTCAE V5.0), toxicity terms to assess in follow-up.Eighteen prostate-specific measures were developed (13 quality, 2 aspirational, and 3 surveillance). DVH metrics tailored to conventional, moderately hypofractionated, and ultrahypofractionated regimens were identified. Decision trees to determine performance for each measure were developed. Eighteen CTCAE V5.0 terms were selected in the sexual, urinary, and gastrointestinal domains as highest priority for assessment during follow-up.This set of measures and DVH constraints serves as a tool for assessing the comprehensive quality of RO care for prostate cancer. These measures will be used for ongoing quality surveillance and improvement among veterans receiving care across VA and community sites. These measures can also be applied to clinical settings outside of those serving veterans.

Patients with advanced head and neck squamous cell carcinoma (HNSCC) associated with human papillomavirus (HPV) demonstrate favorable clinical outcomes compared to patients bearing HPV-negative HNSCC. We sought to characterize the association between HPV status and mutational profiles among patients served by the Veterans Health Administration (VHA).We performed a retrospective analysis of all Veterans with primary HNSCC tumors who underwent next-generation sequencing (NGS) through the VHA's National Precision Oncology Program between July 2016 and February 2019. HPV status was determined by clinical pathology reports of p16 immunohistochemical staining; gene variant pathogenicity was classified using OncoKB, an online precision oncology knowledge database, and mutation frequencies were compared using Fisher's exact test.A total of 79 patients met inclusion criteria, of which 48 (60.8%) had p16-positive tumors. Patients with p16-negative HNSCC were more likely to have mutations in TP53 (p0.0001), and a trend towards increased mutation frequency was observed within NOTCH1 (p = 0.032) and within the composite CDK/Rb pathway (p = 0.065). Mutations in KRAS, NRAS, HRAS, and FBXW7 were exclusively identified within p16-positive tumors, and a trend towards increased frequency was observed within the PI3K pathway (p = 0.051). No difference in overall mutational burden was observed between the two groups.In accordance with the previous studies, no clear molecular basis for improved prognosis among patients harboring HPV-positive disease has been elucidated. Though no targeted therapies are approved based upon HPV-status, current efforts to trial PI3K inhibitors and mTOR inhibitors across patients with HPV-positive disease bear genomic rationale based upon the current findings.

Background Personalized genomic classifiers have transformed the management of prostate cancer (PCa) by identifying the most aggressive subsets of PCa. Nevertheless, the performance of genomic classifiers to risk classify African American men is thus far lacking in a prospective setting. Methods This is a prospective study of the Decipher genomic classifier for National Comprehensive Cancer Network low- and intermediate-risk PCa. Study-eligible non–African American men were matched to African American men. Diagnostic biopsy specimens were processed to estimate Decipher scores. Samples accrued in NCT02723734, a prospective study, were interrogated to determine the genomic risk of reclassification (GrR) between conventional clinical risk classifiers and the Decipher score. Results The final analysis included a clinically balanced cohort of 226 patients with complete genomic information (113 African American men and 113 non–African American men). A higher proportion of African American men with National Comprehensive Cancer Network–classified low-risk (18.2%) and favorable intermediate-risk (37.8%) PCa had a higher Decipher score than non–African American men. Self-identified African American men were twice more likely than non–African American men to experience GrR (relative risk [RR] = 2.23, 95% confidence interval [CI] = 1.02 to 4.90; P = .04). In an ancestry-determined race model, we consistently validated a higher risk of reclassification in African American men (RR = 5.26, 95% CI = 1.66 to 16.63; P = .004). Race-stratified analysis of GrR vs non-GrR tumors also revealed molecular differences in these tumor subtypes. Conclusions Integration of genomic classifiers with clinically based risk classification can help identify the subset of African American men with localized PCa who harbor high genomic risk of early metastatic disease. It is vital to identify and appropriately risk stratify the subset of African American men with aggressive disease who may benefit from more targeted interventions.

Safeguarding high-quality care using evidence-based radiation therapy for patients with head and neck cancer is crucial to improving oncologic outcomes, including survival and quality of life.The Veterans Administration (VA) National Radiation Oncology Program established the VA Radiation Oncology Quality Surveillance Program (VAROQS) to develop clinical quality measures (QM) in head and neck cancer. As part of the development of QM, the VA commissioned, along with the American Society for Radiation Oncology, a blue-ribbon panel comprising experts in head and neck cancer, to develop QM.We describe the methods used to develop QM and the final consensus QM, as well as aspirational and surveillance QM, which capture all aspects of the continuum of patient care from initial patient work-up, radiation treatment planning and delivery, and follow-up care, as well as dose volume constraints.These QM are intended for use as part of ongoing quality surveillance for veterans receiving radiation therapy throughout the VA as well as outside the VA. They may also be used by the non-VA community as a basic measure of quality care for head and neck cancer patients receiving radiation.

Ensuring high quality, evidence-based radiation therapy for patients with cancer is of the upmost importance. To address this need, the Veterans Affairs (VA) Radiation Oncology Program partnered with the American Society for Radiation Oncology and established the VA Radiation Oncology Quality Surveillance program. As part of this ongoing effort to provide the highest quality of care for patients with rectal cancer, a blue-ribbon panel comprised of rectal cancer experts was formed to develop clinical quality measures.The Rectal Cancer Blue Ribbon panel developed quality, surveillance, and aspirational measures for (a) initial consultation and workup, (b) simulation, treatment planning, and treatment, and (c) follow-up. Twenty-two rectal cancer specific measures were developed (19 quality, 1 aspirational, and 2 surveillance). In addition, dose-volume histogram constraints for conventional and hypofractionated radiation therapy were created.The quality measures and dose-volume histogram for rectal cancer serves as a guideline to assess the quality of care for patients with rectal cancer receiving radiation therapy. These quality measures will be used for quality surveillance for veterans receiving care both inside and outside the VA system to improve the quality of care for these patients.

Background: Clinical data collection related to prostate cancer (PCa) care is often unstructured or heterogeneous among providers, resulting in a high risk for ambiguity in its meaning when sharing or analyzing data. Ontologies, which are shareable formal (i.e., computable) representations of knowledge, can address these challenges by enabling machine-readable semantic interoperability. The purpose of this study was to identify PCa-specific key data elements (KDEs) for standardization in clinic and research. Methods: A modified Delphi method using iterative online surveys was performed to report a consensus agreement on KDEs by a multidisciplinary panel of 39 PCa specialists. Data elements were divided into three themes in PCa and included (1) treatment-related toxicities (TRT), (2) patient-reported outcome measures (PROM), and (3) disease control metrics (DCM). Results: The panel reached consensus on a thirty-item, two-tiered list of KDEs focusing mainly on urinary and rectal symptoms. The Expanded Prostate Cancer Index Composite (EPIC-26) questionnaire was considered most robust for PROM multi-domain monitoring, and granular KDEs were defined for DCM. Conclusions: This expert consensus on PCa-specific KDEs has served as a foundation for a professional society-endorsed, publicly available operational ontology developed by the American Association of Physicists in Medicine (AAPM) Big Data Sub Committee (BDSC).

PURPOSE Increasing utilization of comprehensive genomic profiling (CGP) and a growing number of targeted agents (TAs) have led to substantial improvements in outcomes among patients with cancer with actionable mutations. We sought to evaluate real-world experience with off-label TAs among Veterans who underwent CGP. METHODS The National Precision Oncology Program database and VA Corporate Data Warehouse were queried to identify patients who underwent CGP between February 2019 and December 2021 and were prescribed 1 of 73 TAs for malignancy. OncoKB annotations were used to select patients who received off-label TAs based upon CGP results. Chart abstraction was performed to review response, toxicities, and time to progression. RESULTS Of 18,686 patients who underwent CGP, 2,107 (11%) were prescribed a TA and 169 (0.9%) were prescribed a total of 183 regimens containing off-label TAs for variants in 31 genes. Median age was 68 years and 83% had prior systemic therapy, with 28% receiving three or more lines. Frequency of off-label TA prescriptions was highest for patients undergoing CGP for thyroid (8.6%) and breast (7.6%) cancers. Most patients harbored alterations in BRCA1/BRCA2/ATM (22.5%), ERBB2 (19.5%), and BRAF (19.5%). Among the 160 regimens prescribed > 4 weeks, 43 (27%) led to response. Median progression-free survival and overall survival were 5.3 (4.2-6.5) and 9.7 (7.5-11.9) months, respectively. Patients with OncoKB level 2/3A/3B annotations had longer median progression-free survival (5.8 [4.5-7] months v 3.7 [1.6-7.7] months; hazard ratio, 0.45; 95% CI, 0.24 to 0.82; P = .01) compared with those receiving level 4 treatments. CONCLUSION Although administration of off-label TAs is infrequent after CGP, more than one quarter of treatment regimens led to response. TAs associated with level 4 annotations lead to worse outcomes than TAs bearing higher levels of evidence.

BACKGROUND: Approximately 50% of cancer patients eventually develop a syndrome of prolonged weight loss (cachexia), which may contribute to primary resistance to immune checkpoint inhibitors (ICI). This study utilised radiomics analysis of (18)F-FDG-PET/CT images to predict risk of cachexia that can be subsequently associated with clinical outcomes among advanced non-small cell lung cancer (NSCLC) patients treated with ICI. METHODS: Baseline (pre-therapy) PET/CT images and clinical data were retrospectively curated from 210 ICI-treated NSCLC patients from two institutions. A radiomics signature was developed to predict the cachexia with PET/CT images, which was further used to predict durable clinical benefit (DCB), progression-free survival (PFS) and overall survival (OS) following ICI. RESULTS: The radiomics signature predicted risk of cachexia with areas under receiver operating characteristics curves (AUCs) ≥ 0.74 in the training, test, and external test cohorts. Further, the radiomics signature could identify patients with DCB from ICI with AUCs≥0.66 in these three cohorts. PFS and OS were significantly shorter among patients with higher radiomics-based cachexia probability in all three cohorts, especially among those potentially immunotherapy sensitive patients with PD-L1-positive status (p

Ensuring high quality, evidence-based radiation therapy for patients is of the upmost importance. As a part of the largest integrated health system in America, the Department of Veterans Affairs National Radiation Oncology Program (VA-NROP) established a quality surveillance initiative to address the challenge and necessity of providing the highest quality of care for veterans treated for cancer.As part of this initiative, the VA-NROP contracted with the American Society for Radiation Oncology to commission 5 Blue Ribbon Panels for lung, prostate, rectal, breast, and head and neck cancers experts. This group worked collaboratively with the VA-NROP to develop consensus quality measures. In addition to the site-specific measures, an additional Blue Ribbon Panel comprised of the chairs and other members of the disease sites was formed to create 18 harmonized quality measures for all 5 sites (13 quality, 4 surveillance, and 1 aspirational).The VA-NROP and American Society for Radiation Oncology collaboration have created quality measures spanning 5 disease sites to help improve patient outcomes. These will be used for the ongoing quality surveillance of veterans receiving radiation therapy through the VA and its community partners.

Using evidence-based radiation therapy to direct care for patients with breast cancer is critical to standardizing practice, improving safety, and optimizing outcomes. To address this need, the Veterans Affairs (VA) National Radiation Oncology Program (NROP) established the VA Radiation Oncology Quality Surveillance Program (VAROQS) to develop clinical quality measures (QM). The VA NROP contracted with the American Society for Radiation Oncology (ASTRO) to commission five Blue-Ribbon Panels for breast, lung, prostate, rectal, and headneck cancers.The Breast Cancer Blue-Ribbon Panel experts worked collaboratively with NROP to develop consensus QM for use throughout the VA system. establishing a set of quality measures for patients in several areas including: 1) consultation and work up, 2) simulation, treatment planning and treatment, and 3) follow up care. As part of this initiative, consensus dose volume histogram (DVH) constraints were outlined.In total, 36 quality measures were established. Herein we review the process utilized to develop QM and final consensus QM pertaining to all aspects of radiation patient care as well as DVH constraints.The QM and expert consensus DVH constraints are intended for ongoing quality surveillance within the VA system, centers providing community care for Veterans, and also available for use by the greater non-VA community measures of quality care for breast cancer patients receiving radiation.

PURPOSE Next-generation sequencing (NGS) multigene panel testing has become widespread, including the Veterans Affairs (VA), through the VA National Precision Oncology Program (NPOP). The interpretation of genomic alterations remains a bottleneck for realizing precision medicine. We sought to examine the concordance for pathogenicity determination and clinical actionability of annotation services in NPOP. METHODS Unique gene variants were generated from NGS gene panel results using two sequencing services. For each unique gene variant, annotations were provided through N-of-One (NoO), IBM Watson for Genomics (WfG), and OncoKB. Annotations for pathogenicity (all three sources) and actionability (WfG and OncoKB) were examined for concordance. Cohen’s kappa statistic was calculated to measure agreement between annotation services. RESULTS Among 1,227 NGS results obtained between 2015 and 2017, 1,388 unique variants were identified in 117 genes. The genes with the largest number of variants included TP53 (270), STK11 (92), and CDKN2A (81). The most common cancer type was lung adenocarcinoma (440), followed by colon adenocarcinoma (113). For pathogenic and likely pathogenic variants, there was 30% agreement between WfG and NoO (kappa, −0.26), 76% agreement between WfG and OncoKB (kappa, 0.22), and 42% agreement between NoO and OncoKB (kappa, −0.07). For level 1 drug actionability of gene variant–diagnosis combinations, there was moderate agreement between WfG and OncoKB (96.9%; kappa, 0.44), with 27 combinations identified as level 1 by both services, 58 by WfG alone, and 6 variants by OncoKB alone. CONCLUSION There is substantial variability in pathogenicity assessment of NGS variants in solid tumors by annotation services. In addition, there was only moderate agreement in level 1 therapeutic actionability recommendations between WfG and OncoKB. Improvement in the precision of NGS multigene panel annotation is needed.

PURPOSE Prostate cancer (PCa) is among the leading causes of cancer deaths. While localized PCa has a 5-year survival rate approaching 100%, this rate drops to 31% for metastatic prostate cancer (mPCa). Thus, timely identification of mPCa is a crucial step toward measuring and improving access to innovations that reduce PCa mortality. Yet, methods to identify patients diagnosed with mPCa remain elusive. Cancer registries provide detailed data at diagnosis but are not updated throughout treatment. This study reports on the development and validation of a natural language processing (NLP) algorithm deployed on oncology, urology, and radiology clinical notes to identify patients with a diagnosis or history of mPCa in the Department of Veterans Affairs. PATIENTS AND METHODS Using a broad set of diagnosis and histology codes, the Veterans Affairs Corporate Data Warehouse was queried to identify all Veterans with PCa. An NLP algorithm was developed to identify patients with any history or progression of mPCa. The NLP algorithm was prototyped and developed iteratively using patient notes, grouped into development, training, and validation subsets. RESULTS A total of 1,144,610 Veterans were diagnosed with PCa between January 2000 and October 2020, among which 76,082 (6.6%) were identified by NLP as having mPCa at some point during their care. The NLP system performed with a specificity of 0.979 and sensitivity of 0.919. CONCLUSION Clinical documentation of mPCa is highly reliable. NLP can be leveraged to improve PCa data. When compared to other methods, NLP identified a significantly greater number of patients. NLP can be used to augment cancer registry data, facilitate research inquiries, and identify patients who may benefit from innovations in mPCa treatment.

Background Immunotherapy yields survival benefit for some advanced stage non-small cell lung cancer (NSCLC) patients. Because highly predictive biomarkers of immunotherapy response are an unmet clinical need, we used pretreatment radiomics and clinical data to train and validate a parsimonious model associated with survival outcomes among NSCLC patients treated with immunotherapy. Methods Three cohorts of NSCLC patients treated with immunotherapy were analyzed: training (n = 180), validation 1 (n = 90), and validation 2 (n = 62). The most informative clinical and radiomic features were subjected to decision tree analysis, which stratified patients into risk groups of low, moderate, high, and very high risk of death after initiation of immunotherapy. All statistical tests were 2-sided. Results The very high-risk group was associated with extremely poor overall survival (OS) in validation cohorts 1 (hazard ratio [HR] = 5.35, 95% confidence interval [CI] = 2.14 to 13.36; 1-year OS = 11.1%, 95% CI = 1.9% to 29.8%; 3-year OS = 0%) and 2 (HR = 13.81, 95% CI = 2.58 to 73.93; 1-year OS = 47.6%, 95% CI = 18.2% to 72.4%; 3-year OS = 0%) when compared with the low-risk group (HR = 1.00) in validation cohorts 1 (1-year OS = 85.0%, 95% CI = 60.4% to 94.9%; 3-year OS = 38.9%, 95% CI = 17.1% to 60.3%) and 2 (1-year OS = 80.2%, 95% CI = 40.3% to 94.8%; 3-year OS = 40.1%, 95% CI = 1.3% to 83.5%). The most informative radiomic feature, gray-level co-occurrence matrix (GLCM) inverse difference, was positively associated with hypoxia-related carbonic anhydrase 9 using gene-expression profiling and immunohistochemistry. Conclusion Utilizing standard-of-care imaging and clinical data, we identified and validated a novel parsimonious model associated with survival outcomes among NSCLC patients treated with immunotherapy. Based on this model, clinicians can identify patients who are unlikely to respond to immunotherapy.

Purpose/Objective(s) Prostate cancer (PCa) is a complex disease, with risk factors and outcomes influenced by a combination of socioeconomic and biological factors. African American men (AAM) in the U.S. have higher incidence and mortality rates of PCa than European American men (EAM). Nonetheless, emerging studies have shown comparable outcomes across racial groups when treated in equal access settings. The Veterans Affairs (VA) healthcare system provides a unique environment to thoroughly investigate PCa disparities between AAM and EAM across the disease continuum, within relatively equal access-to-care settings. Materials/Methods This retrospective analysis consists of 7.8 million veterans undergoing routine care within VA hospitals nation-wide from 2005 to 2019. We compared PCa incidence, clinical presentation, treatment, and PCa specific outcomes among AAM and EAM veterans. Methods of categorical analysis were used to investigate the differences between race groups. We then assessed the likelihood of adverse clinical characteristics by race using logistic regression. In survival analysis, time-to-metastasis was used as a primary end point. Finally, we estimated the risk of distant metastasis in conjunction with treatment and baseline clinical characteristics using a multivariable cox proportional hazard model. Results Consistent with population-level data, AAM had an almost 2-fold greater risk of developing PCa than EAM within the relatively equal access-to-care VA network, with age-adjusted incidence rates of 96.7 and 40.1 per 100,000, respectively. Despite similar screening patterns, AAM also had a higher age-adjusted rate of metastasis at diagnosis compared with EAM - 5.66 and 2.37 per 100,000, respectively. AAM were more likely to have higher baseline PSA (aOR = 1.86, 95% CI, 1.77-1.95, P Conclusion This comprehensive analysis reveals a national-level PCa incidence disparity in a relatively equal access-to-care network. AAM display a higher burden of both localized and metastatic PCa, placing them at a higher risk of adverse outcomes across the PCa continuum. Consequently, timely diagnosis and equitable treatment delivery are likely critical factors for reducing disparities in disease outcomes.

Purpose: The goal of this study is to develop innovative methods for identifying radiomic features that are reproducible over varying image acquisition settings. Approach: We propose a regularized partial correlation network to identify reliable and reproducible radiomic features. This approach was tested on two radiomic feature sets generated using two different reconstruction methods on computed tomography (CT) scans from a cohort of 47 lung cancer patients. The largest common network component between the two networks was tested on phantom data consisting of five cancer samples. To further investigate whether radiomic features found can identify phenotypes, we propose a k-means clustering algorithm coupled with the optimal mass transport theory. This approach following the regularized partial correlation network analysis was tested on CT scans from 77 head and neck squamous cell carcinoma (HNSCC) patients in the Cancer Imaging Archive (TCIA) and validated using an independent dataset. Results: A set of common radiomic features was found in relatively large network components between the resultant two partial correlation networks resulting from a cohort of lung cancer patients. The reliability and reproducibility of those radiomic features were further validated on phantom data using the Wasserstein distance. Further analysis using the network-based Wasserstein k-means algorithm on the TCIA HNSCC data showed that the resulting clusters separate tumor subsites as well as HPV status, and this was validated on an independent dataset. Conclusion: We showed that a network-based analysis enables identifying reproducible radiomic features and use of the selected set of features can enhance clustering results.

3534 Background: Clinical trials have demonstrated improvements in survival with immune checkpoint inhibitors (ICIs) for advanced colorectal cancer patients with MSI-H/dMMR detected using PCR-based assays (PCR) or immunohistochemistry (IHC), respectively. MSI-H can also be assessed by next-generation sequencing (NGS). Evaluation of real-world outcomes among MSI-H patients by NGS treated with ICIs are warranted, particularly when results are discordant between these tests. Methods: The VA National Precision Oncology Program Database was accessed to select veterans with colorectal cancer and an MSI-H biomarker by NGS. Baseline patient variables, disease characteristics, and duration of ICI treatment were obtained from the VA’s Corporate Data Warehouse. Concordance between NGS and IHC or PCR testing was computed, and the response rate and duration of ICI treatment in patients with discordant test results were recorded from chart review. Results: Among 1,276 colorectal cancer patients, 71 (5.6%) were found to have MSI-H by NGS. Of these, 22 (30.1%) received ICI. Among 49 patients who did not receive ICI, 36 had stage I-III disease, 5 had limited performance status, 5 were actively being treated with chemotherapy and 3 had completely resected stage IV disease. Of the 71 patients, 29 had dMMR IHC testing, 8 had MSI-H PCR testing, 1 had both IHC and PCR testing, and 34 patients had only NGS testing. No PCR tests were discordant with NGS but 8 of 29 IHC tests were discordant. Among these 8 patients with discordant IHC MMR and MSI-H by NGS, 5 received pembrolizumab. There were 3 partial responses, 1 stable disease and 1 progressive disease. Durable responses were seen with 3 of 5 patients remaining on therapy without progression at the time of this analysis at a median follow up of 8.5 months. Conclusions: In a cohort of NGS MSI-H colorectal cancer patients, there was a high rate of discordant IHC results. Clinical benefit is seen in patients treated with ICI with discordant testing results, suggesting that NGS testing identifies patients with false negative dMMR IHC testing in the real-world clinical setting.

e18676 Background: The increasing availability of comprehensive genomic profiling (CGP) and a growing number of targeted agents (TAs) has led to substantial improvements in outcomes among cancer pts with actionable mutations. CGP has led to identification of both on-label (level 1) variants, for which TAs have known efficacy, and off-label variants with lesser strength of supporting data. We sought to evaluate real-world prescription patterns and outcomes of off-label TA prescriptions among pts who underwent CGP. Methods: The NPOP database and VA Corporate Data Warehouse were queried to identify pts who had underwent CGP between February 2019 and December 2021 and were prescribed at least 1 of 73 TAs before January 2022. TAs prescribed for FDA-approved indications not relying on CGP as a companion diagnostic were excluded. OncoKB was used to annotate gene variants and evaluated against prescriptions to select pts who received off-label TAs. The frequency of off-label TA use, and for those treated > 4 weeks, rate of pts treated for 6 months or longer, median treatment duration and overall survival (OS) were computed. Results: Of the 18686 patients who underwent CGP, 2107 (11%) were prescribed any TA, and 191 (1%) were prescribed off-label TAs, with 31 receiving multiple concurrent or sequential off-label TAs. Mean age was 65.5 years, and 88% were male. TAs were most often prescribed for cancers of unknown primary (CUP, 29), NSCLC (24), and colorectal cancer (22). Frequency of off-label prescriptions was highest for pts who completed CGP for thyroid cancer (9%), breast cancer (8%), and CUP (2%). Most common variants involved BRAF (21%), ERBB2 (18%), BRCA1/BRCA2/ATM (9%), and PIK3CA (6%). Among all 164 pts treated > 4 weeks, 40% received TAs for 6 months or longer, including 50%, 47%, and 46% of pts bearing BRAF-, ERBB2-, and PIK3CA-mutant disease, respectively. Median therapy duration and OS was 141 [78.5 – 317, IQR] days and 181 [96.5 – 304.5, IQR] days, respectively. Conclusions: Though overall use of off-label TAs following CGP is low, nearly 10% of advanced thyroid and breast cancer patients are prescribed TAs for off-label indications. Forty percent of all pts receiving off-label TAs continue for at least 6 months, with higher rates for pts bearing BRAF-, ERBB2-, and PIK3CA-mutant disease. CGP-guided off-label treatment approaches offer unique options for advanced stage cancer with amenable molecular profiles.

BackgroundCachexia is present in up to 50% of patients with cancer and may contribute to primary resistance to immunotherapy. Biomarkers to predict cachexia are urgently required for early intervention. Herein, we test the hypothesis that pre-treatment 18F-FDG-PET/CT-based radiomics can be used to predict cachexia and subsequently associated with clinical outcomes among patients with advanced non-small cell lung cancer (NSCLC) who are treated with immunotherapy.MethodsThis retrospective multi-institution study included 210 patients with histologically confirmed stage IIIB-IV NSCLC who were treated with immune checkpoint blockade between June 2011 and August 2019. Baseline (pre-immunotherapy) PET/CT images of 175 patients from Moffitt Cancer Center were used to train (N=123) and test (N=52) a radiomics signature to predict cachexia, which was also used to predict durable clinical benefit (DCB), progression-free survival (PFS) and overall survival (OS) subsequently. An external cohort that enrolled 35 patients from James A. Haley Veterans’ Hospital (VA) was used to further validate the predictive and prognostic value of this signature.ResultsA radiomics signature demonstrated cachexia prediction ability with areas under receiver operating characteristics curves (AUC) of 0.77 (95%CI:0.68-0.85), 0.75 (95%CI:0.60-0.86) and of 0.73 (95%CI:0.53-0.92) in the training, test and external VA cohorts, respectively. For the further investigation of prognostic value, this signature could identify the patients with DCB with AUC of 0.67 (95%CI:0.57-0.77), 0.66 (95%CI:0.51-0.81), and 0.72 (95%CI:0.54-0.89) in these three cohorts. Additionally, the PFS and OS were significantly shorter among patients with higher radiomics signature in all the three cohorts (pConclusionUsing PET/CT radiomics analysis, cachexia could be predicted before the start of the immunotherapy, making it possible to monitor the patients with a higher risk of cachexia and identify patients most likely to benefit from immunotherapy.

Currently only a fraction of patients with non-small cell lung cancer (NSCLC) experience durable clinical benefit (DCB) from immunotherapy, robust biomarkers to predict response prior to initiation of therapy are an emerging clinical need. PD-L1 expression status from immunohistochemistry is the only clinically approved biomarker, but a non-invasive complimentary approach that could be used when tissues are not available or when the IHC fails and can be assessed longitudinally would have important implications for clinical decision support. In this study, 18F-FDG-PET/CT images and clinical data were curated from 697 NSCLC patients from three institutions. Utilizing PET/CT images, a deeply-learned-score (DLS) was developed by training a small-residual-convolutional-network model to predict the PD-L1 expression status, which was further used to predict DCB, progression-free survival (PFS), and overall survival (OS) in both retrospective and prospective test cohorts of immunotherapy-treated patients with advanced stage NSCLC. This PD-L1 DLS significantly discriminated PD-L1 positive and negative patients (AUC≥0.82 in all cohorts). Further, higher PD-L1 DLS was significantly associated with higher probability of DCB, longer PFS, and longer OS. The DLS combined with clinical characteristics achieved C-indices of 0.86, 0.83 and 0.81 for DCB prediction, 0.73, 0.72 and 0.70 for PFS prediction, and 0.78, 0.72 and 0.75 for OS prediction in the retrospective, prospective and external cohorts, respectively. The DLS provides a non-invasive and promising approach to predict PD-L1 expression and to infer clinical outcomes for immunotherapy-treated NSCLC patients. Additionally, the multivariable models have the potential to guide individual pre-therapy decisions pending in larger prospective trials.Statement of SignificancePD-L1 expression status by immunohistochemistry (IHC) is the only clinically-approved biomarker to trigger immunotherapy treatment decisions, but a non-invasive complimentary approach that could be used when tissues are not available or when the IHC fails and can be assessed longitudinally would have important implications for clinical decision support. Utilizing PET/CT images, we developed and tested a convolutional neural network model to predict PD-L1 expression status with high accuracy in cohorts from different institutions. And the generated signature may serve as a prognostic biomarker for immunotherapy response in patients with NSCLC, and outperforms the clinical characteristics.

Checkpoint blockade immunotherapy provides improved long-term survival in a subset of advanced stage non-small cell lung cancer (NSCLC) patients. However, highly predictive biomarkers of immunotherapy response are unmet clinical need. In this study, we utilized pre-treatment clinical factors and quantitative image-based biomarkers (radiomics) to identify a parsimonious model that predicts survival outcomes among NSCLC patients treated with immunotherapy. The NSCLC patients treated with single or double agent immunotherapy were included in three different cohorts: Training (N = 180), test (N = 90) and validation (N = 62) cohorts. The models were created based on overall survival (OS) and were additionally assessed for progression-free survival (PFS). Including most predictive radiomic features and clinical covariates, Classification and Regression Tree analysis was applied to stratify patients into survival risk-groups in the training cohort. The risk groups were later generated in the test and validation cohorts. Four independent NSCLC cohorts (total N = 446) were utilized for further validation of the radiomic signature. The biological underpinnings of the most informative radiomics were assessed using gene expression data from a radiogenomics dataset and validated by immunohistochemistry data (IHC). A parsimonious clinical-radiomics model was found to be significantly associated with OS and PFS after stratifying patients into groups of low-, moderate-, high-, and very-high risk of death and progression. This trained model was further tested and validated in two independent cohorts. When the extreme phenotypes were compared, the very-high risk group was found to be associated with extremely poor OS in both the test (hazard ratio [HR] = 5.35, 95% confidence interval [CI]: 2.14 – 13.36; 1-year OS = 11.1%) and validation (HR = 13.81, 95% CI: 2.58 – 73.93; 1-year OS = %47.6) cohorts when compared to the low risk group (HRs = 1.00; 1-year OS = 85.0% & 80.2%). Similar findings were observed for PFS. The final radiomic feature (GLCM inverse difference) was associated with OS in four independent NSCLC cohorts and was found to be positively associated with the hypoxia-related carbonic anhydrase, CAIX, by gene expression profiling and immunohistochemistry. We validated a novel clinical-radiomics model that is associated with OS and PFS among NSCLC patients treated with immunotherapy and identified a highly vulnerable subset of patients that are unlikely to respond to immunotherapy. The most informative radiomic feature was associated with CAIX, a marker of tumor hypoxia, tumor acidosis, and treatment resistance.

BACKGROUND Postoperative chemoradiotherapy (CRT) is considered standard of care in patients with locally advanced head and neck cancer with positive margins and/or extracapsular extension (ECE). METHODS The National Cancer Data Base (NCDB) was queried to identify patients with squamous cell carcinoma of the head and neck with stages III to IVB disease or with positive margins and/or ECE diagnosed between 2004 and 2012 receiving postoperative radiotherapy (RT). Using univariable and multivariable logistic and Cox regression, we assessed for predictors of CRT use and covariables impacting overall survival (OS), including in a propensity-matched subset. RESULTS Of 12 224 patients, 67.1% with positive margins and/or ECE received CRT as well as 54.0% without positive margins and/or ECE. The 5-year OS was 61.6% for RT alone versus 67.4% for CRT. In the propensity-matched cohort, OS benefit persisted with CRT, including in a subset with positive margins and/or ECE but not without. CONCLUSION Postoperative CRT seems underutilized with positive margins and/or ECE and overutilized without positive margins and/or ECE. The CRT was associated with improved OS but the benefit persisted only in the subset with positive margins and/or ECE.

Key Points Question Are there racial and ethnic disparities associated with the incidence, clinical stage, and outcomes of prostate cancer among men treated in the Veterans Affairs health care system? Findings In this cohort study of 7.8 million patients, compared with White veterans, African American (or Black) veterans displayed increased risk of developing localized and de novo metastatic prostate cancer across nationwide Veterans Affairs centers. Despite equitable treatment response, a persistent residual metastatic burden of nearly 2-fold was observed for African American veterans across National Comprehensive Cancer Network risk groups, when factoring in the higher incidence rate. Meaning Treatment in an equal-access setting may partially address institution-specific disparities, but overall racial disparity gaps remain., Importance Prostate cancer (PCa) disproportionately affects African American men, but research evaluating the extent of racial and ethnic disparities across the PCa continuum in equal-access settings remains limited at the national level. The US Department of Veterans Affairs (VA) Veterans Hospital Administration health care system offers a setting of relatively equal access to care in which to assess racial and ethnic disparities in self-identified African American (or Black) veterans and White veterans. Objective To determine the extent of racial and ethnic disparities in the incidence of PCa, clinical stage, and outcomes between African American patients and White patients who received a diagnosis or were treated at a VA hospital. Design, Setting, and Participants This retrospective cohort study included 7 889 984 veterans undergoing routine care in VA hospitals nationwide from 2005 through 2019 (incidence cohort). The age-adjusted incidence of localized and de novo metastatic PCa was estimated. Treatment response was evaluated, and PCa-specific outcomes were compared between African American veterans and White veterans. Residual disparity in PCa outcome, defined as the leftover racial and ethnic disparity in the outcomes despite equal response to treatment, was estimated. Exposures Self-identified African American (or Black) and White race and ethnicity. Main Outcomes and Measures Time to distant metastasis following PCa diagnosis was the primary outcome. Descriptive analyses were used to compare baseline demographics and clinic characteristics. Multivariable logistic regression was used to evaluate race and ethnicity association with pretreatment clinical variables. Multivariable Cox regression was used to estimate the risk of metastasis. Results Data from 7 889 984 veterans from the incidence cohort were used to estimate incidence, whereas data from 92 269 veterans with localized PCa were used to assess treatment response. Among 92 269 veterans, African American men (n = 28 802 [31%]) were younger (median [IQR], 63 [58-68] vs 65 [62-71] years) and had higher prostate-specific antigen levels (>20 ng/mL) at the time of diagnosis compared with White men (n = 63 467; [69%]). Consistent with US population-level data, African American veterans displayed a nearly 2-fold greater incidence of localized and de novo metastatic PCa compared with White men across VA centers nationwide. Among veterans screened for PCa, African American men had a 29% increased risk of PCa detection on a diagnostic prostate biopsy compared with White (hazard ratio, 1.29; 95% CI, 1.27-1.31; P, This cohort study assesses the extent of racial and ethnic disparities in the incidence, clinical stage, and outcomes of prostate cancer among African American and White men treated in the Veterans Affairs health care system.

Dose-volume tolerance of the spinal cord (SC) in spinal stereotactic radiosurgery (SRS) is difficult to define because radiation myelitis rates are low, and published reports document cases of myelopathy but do not account for the total number of patients treated at given dose-volume combinations who do not have myelitis. This study reports SC toxicity from single-fraction spinal SRS and presents a comprehensive atlas of the incidence of adverse events to examine dose-volume predictors.A prospective database of all patients undergoing single-fraction spinal SRS at our institution between 2004 and 2011 was reviewed. SC toxicity was defined by clinical myelitis with accompanying magnetic resonance imaging (MRI) signal changes that were not attributable to tumor progression. Dose-volume histogram (DVH) atlases were created for these endpoints. Rates of adverse events with 95% confidence limits and probabilities that rates of adverse events were2% and5% for myelitis were determined as functions of dose and absolute volume.Information about DVH and myelitis was available for 228 patients treated at 259 sites. The median follow-up time was 14.6 months (range, 0.1-138.3 months). The median prescribed dose to the planning treatment volume was 24 Gy (range, 18-24 Gy). There were 2 cases of radiation myelitis (rate r=0.7%) with accompanying MRI signal changes. Myelitis occurred in 2 patients, with Dmax13.33 Gy, and minimum doses to the hottest 0.1, 0.2, 0.5, and 1 cc were10.66, 10.9, and 8 Gy, respectively; however, both myelitis cases occurred below the 34th percentile for Dmax and there were 194 DVHs in total with Dmax13.33 Gy.A median SC Dmax of 13.85 Gy is safe and supports that a Dmax limit of 14 Gy carries a low1% rate of myelopathy. No dose-volume thresholds or relationships between SC dose and myelitis were apparent. This is the largest study examining dosimetric data and radiation-induced myelitis in de novo spine SRS.

Patients with metastatic disease including polymetastatic, oligometastatic, and oligorecurrent spinal lesions have extended life expectancy secondary to improvements in systemic agents, and thus require durable local control of spine metastases. Stereotactic body radiotherapy (SBRT), which uses highly conformal treatment planning techniques coupled with image-guided technology, has enabled the safe delivery of tumor-ablative doses of radiotherapy. The NOMS decision framework has been developed as a tool to aid in the determination of the optimal treatment of spinal metastases, incorporating radiosurgery, separation surgery, stabilization techniques, and conventional radiation. Tumor radiosensitivity is critical in determining appropriateness of radiosurgery. In general, higher radiation doses provide significant, more durable tumor control, whether single-fraction or hypofractionated regimens are used. Spine SBRT can provide a high likelihood of durable tumor control with very low rates of serious toxicity, and careful attention should be given to dose constraints of organs at risk. Here, we review the indications for spine SBRT via the NOMS decision framework and provide practical information to the radiation oncologist regarding spine radiosurgery.

PurposeTo construct robust and validated radiomic predictive models, the development of a reliable method that can identify reproducible radiomic features robust to varying image acquisition methods and other scanner parameters should be preceded with rigorous validation. Due to the property of high correlation present between radiomic features, we hypothesize that reproducible radiomic features across different datasets that are obtained from different image acquisition settings preserve some level of connectivity between features in the form of a network.MethodsWe propose a regularized partial correlation network to identify robust and reproducible radiomic features. This approach was tested on two radiomic feature sets generated with two different reconstruction methods from a cohort of 47 lung cancer patients. The commonality of the resulting two networks was assessed. A largest common network component from the two networks was tested on phantom data consisting of 5 cancer samples. We further propose a novel K-means algorithm coupled with the optimal mass transport (OMT) theory to cluster samples. This approach following the regularized partial correlation analysis was tested on computed tomography (CT) scans from 77 head and neck cancer patients that were downloaded from The Cancer Imaging Archive (TCIA) and validated on CT scans from 83 head and neck cancer patients treated at our institution.ResultsCommon radiomic features were found in relatively large network components between the resulting two partial correlation networks from a cohort of 47 lung cancer patients. The similarity of network components in terms of the common number of radiomic features was statistically significant. For phantom data, the Wasserstein distance on a largest common network component from the lung cancer data was much smaller than the Wasserstein distance on the same network using random radiomic features, implying the reliability of those radiomic features present in the network. Further analysis using the proposed Wasserstein K-means algorithm on TCIA head and neck cancer data showed that the resulting clusters separate tumor subsites and this was validated on our institution data.ConclusionsWe showed that a network-based analysis enables identifying reproducible radiomic features. This was validated using phantom data and external data via the Wasserstein distance metric and the proposed Wasserstein K-means method.

Background: Standard of care treatment for anal squamous cell carcinoma (SCC) is concurrent chemoradiation (CRT). However, the necessity of CRT over radiation alone for T1-2N0 disease is less certain. Methods: The National Cancer Database (NCDB) was queried to identify patients who received CRT, defined as initiation of chemo and RT within 14 days of each other, or RT alone (without any chemo during initial treatment phase) for cT1-2N0M0 SCC of the anus. The cohort was limited to patients less than 70 years old with Charlson-Deyo Comorbidity Index of 0, receiving a radiation dose range of 4,500–5,940 cGy. Univariable and multivariable logistic regression were performed to assess for predictors of CRT usage. Five-year overall survival (OS) was analyzed using the Kaplan-Meier method with the log rank test both for the full cohort and then on the subsets of T1 and T2 patients. Results: We identified 4,564 patients, of whom 4,371 (95.8%) received CRT and 193 (4.2%) received RT alone. Median follow up was 49.8 months. About 33.5% of patients had cT1N0 disease, while 66.5% of patients had cT2N0 disease. On multivariable logistic regression, patients were more likely to receive CRT if they had T2 disease [OR 2.318 (1.732–3.102), P

5005 Background: Risk stratification of prostate cancer (PC) using routine clinical variables remains suboptimal as they do not account for underlying tumor biology. The genomic classifier provides information on underlying biology and independently predicts an individual patient’s risk of metastasis. Although the performance of the genomic classifier has been tested across different cohorts primarily comprised of White men, its validation as an optimal genomic risk classifier for African American men (AAM) is thus far lacking in a prospective trial. We report the initial results on the prospective validation of the genomic classifier in a matched cohort of AAM and non-AAM (NAAM). Methods: This was a multisite, prospective validation trial of the genomic classifier i.e. Decipher score in AAM. Participants were recruited on a 1:1 enrollment ratio of AAM to NAAM diagnosed with low-intermediate risk PC. Patient on active surveillance were ineligible. NAAM were matched to AAM on PSA, age, biopsy Gleason score, clinical stage, and percent positive biopsy cores. Diagnostic biopsy specimens were processed at a CLIA certified laboratory and Decipher score was assessed using whole transcriptome profiling platform. Total target accrual was 250 men treated for low-intermediate PC over three years. Statistical analyses include categorical comparison of race dependent risk group migration between NCCN risk group and genomic classifier. Relative risk of metastasis was estimated using negative binomial model. Results: Final analytical cohort included 207 evaluable cases (AAM = 102 and NAAM = 107) with comprehensive genomic information. Risk of metastasis was determined based on pretreatment biopsy Decipher score, and patients were classified as low, favorable-, and unfavorable intermediate risk. Despite achieving a robustly matched clinical cohort, we observed significant genomic heterogeneity between AAM and NAAM across NCCN risk groups. In a comparative analysis, 49% of low-favorable intermediate risk AAM harbored high genomic risk tumors as compared to only 10% NAAM, p = 0.02. Similarly, using the modified clinico-genomic risk classifier (cGC), comprised of both Decipher score and clinical variables, AAM experienced an extreme deviation of risk status (difference [δ] between cGC and NCCN ≥ 2) as compared to NAAM (26.8% vs 8.1%, p = 0.03). In a binomial model, low-favorable NCCN risk AAM were 3.9 times more likely to be reclassified as high genomic risk for distant metastasis compared to NAAM (RR = 3.99, 95% CI, 1.15 – 13.86, p = 0.02). Conclusions: Clinical NCCN risk classification is an inadequate surrogate of tumor biology and offers suboptimal risk stratification for AAM with PC. Integration of patient specific genomic classifier into standard of care will improve accuracy in disease risk classification and treatment recommendations for AAM. Clinical trial information: NCT02723734.

Aim To examine the value of proton therapy in relation to other treatment modalities in head and neck cancer. Review Proton therapy has evolved into more sophisticated and costly intensity-modulated proton therapy and has resulted in even greater dose reduction to normal critical structures at risk as compared with photon therapy. Early clinical studies in head and neck cancers, especially for tumors of the skull base and paranasal sinuses, suggest that proton therapy is excellent in terms of local control and is comparable to intensity-modulated radiation therapy photons but with lower rates of morbidity. Results There are many potential advantages to radiation therapy with protons. While there are many single institution studies examining the added value of protons to photon therapy, the value of proton therapy must be examined in prospective randomized clinical studies and across many subsites of head and neck cancer. Additional evidence is necessary to guide efficient clinical practice, patient selection, and tumors that are most likely to benefit from this treatment modality and justify proton therapy use given its significant cost. How to cite this article Katsoulakis E, Chernichenko N, Schreiber D. Proton Therapy in the Treatment of Head and Neck Cancer. Int J Head Neck Surg 2017;8(2):45-48.

The aim of the study was to compare prostate cancer-specific mortality (PCSM) in young men with clinically localized prostate cancer treated by either external beam radiation (EBRT) alone or brachytherapy with or without external beam radiation.Utilizing the Surveillance, Epidemiology and End Results database, 15,505 patients ≤60 years of age diagnosed with prostate cancer between 2004 and 2009 and treated with radiation therapy alone were identified. Incidence of PCSM was determined for both groups and compared using competing risk models.The overall 8-year PCSM for the study population was 1.9% (95% confidence interval [CI]: 1.6-2.2). For patients treated with EBRT or brachytherapy with or without external beam, the 8-year PCSM was found to be 2.8% (CI: 2.2-3.4) and 1.2% (CI: 0.9-1.6), respectively (p 0.001). Univariable analysis demonstrated that brachytherapy was associated with lower PCSM risk (hazard ratio = 0.40; CI: 0.30-0.54; p0.001). High Gleason risk category, black race, higher Tumor (T) stage, and higher grade were all associated with greater mortality risk (p0.01). On multivariable analysis, brachytherapy continued to be associated with a significantly lower mortality risk (hazard ratio = 0.65; CI: 0.47-0.89; p = 0.008). Subgroup analyses found that among those with Gleason score ≥8, younger patients had increased risk of PCSM (p = 0.001).In men ≤60 years of age with prostate cancer, radiation therapy continues to offer excellent outcomes. After adjusting for relevant variables, the use of brachytherapy was associated with reduced PCSM compared to treatment with EBRT alone.

PURPOSE: To identify whether radiomic features from pre-treatment computed tomography (CT) scans can predict molecular differences between head and neck squamous cell carcinoma (HNSCC) using The Cancer Imaging Archive (TCIA) and The Cancer Genome Atlas (TCGA). METHODS: 77 patients from the TCIA with HNSCC had imaging suitable for analysis. Radiomic features were extracted and unsupervised consensus clustering was performed to identify subtypes. Genomic data was extracted from the matched patients in the TCGA database. We explored relationships between radiomic features and molecular profiles of tumors, including the tumor immune microenvironment. A machine learning method was used to build a model predictive of CD8+ T-cells. An independent cohort of 83 HNSCC patients was used to validate the radiomic clusters. RESULTS: We initially extracted 104 two-dimensional radiomic features, and after feature stability tests and removal of volume dependent features, reduced this to 67 features for subsequent analysis. Consensus clustering based on these features resulted in two distinct clusters. The radiomic clusters differed by primary tumor subsite (p=0.0096), HPV status (p=0.0127), methylation-based clustering results (p=0.0025), and tumor immune microenvironment. A random forest model using radiomic features predicted CD8+ T-cells independent of HPV status with R(2)=0.30 (p

OBJECTIVE Early-stage oral cavity squamous cell carcinoma (OCSCC) represents a heterogeneous group of patients, and locoregional recurrence rates are as high as 25% with surgery alone. Radiotherapy (RT) is typically reserved as part of salvage multimodality therapy after salvage surgery because it is generally thought that there is no significant detriment to salvage therapy. Our aim was to examine outcomes for recurrent OCSCC treated with salvage surgery and radiation and compare them to outcomes for patients treated with adjuvant postoperative RT upfront. METHODS We identified 425 patients with OCSCC treated with postoperative RT at our institution. The 5-year rates of local failure, locoregional failure (LRF), survival, and distant metastasis (DM) were the main outcome measures. We performed a landmark analysis and examined the same outcomes in the adjuvant versus salvage cohorts using Cox proportional hazards and Fine-Gray competing risk method. RESULTS The adjuvant cohort had higher tumor (T) (P

Objectives/hypothesis Compare outcomes of hypopharyngeal carcinoma that received conventional radiotherapy versus intensity-modulated radiotherapy (IMRT). Study design Retrospective single-institution trial. Methods Between April 1990 and May 2011, 100 patients with hypopharyngeal cancer underwent curative radiotherapy (RT) at our institution: 50 with IMRT and 50 with conventional RT. The median age was 63 years. There were 12 T1, 22 T2, 37 T3, and 28 T4 patients. The majority of patients (82%) had nodal disease: 54% N2 and 8% N3. The majority of patients (83%) received chemotherapy. Of the patients who received chemotherapy, 84% received a platinum-based regimen. The median RT dose was 7,000 cGy. The majority of patients (62%) had prophylactic percutaneous endoscopic gastrostomy tube placement. Toxicities were reviewed. Local control (LC), locoregional control (LRC), freedom from distant metastasis (FFM) rates, functional larynx preservation (LP), laryngectomy-free survival (LFS), and overall-survival (OS) curves were generated using the Kaplan-Meier method. The log-rank test was used to test prognostic variables. Results With a median follow up of 48.4 months, the 3/5-year LC, LRC, FFM, LP, LFS and OS rates were 74%/69%, 77%/74%, 70%/66%, 51%/29%, 49.6%/31.8%, and 49%/34%, respectively. The median OS was 2.9 years. The 3-year LC rate for IMRT was 77% versus 81% for conventional RT (P = .91); 3-year LRC for IMRT was 85% versus 76% for conventional RT (P = .32). There was no increased local failure with IMRT. There was no difference in the rate of stricture with IMRT (32%) versus conventional RT (25.3%) (P = .86). Conclusions IMRT achieved comparable LC and LRC rates to conventional RT. Level of evidence 4 Laryngoscope, 126:620-626, 2016.

Purpose To characterize local tumor control and toxicity risk in very long-term survivors (>5 years) after high-dose spinal image guided, intensity modulated radiation therapy delivered as single-dose stereotactic radiosurgery (SRS). Previously published spinal SRS outcome analyses have included a heterogeneous population of cancer patients, mostly with short survival. This is the first study reporting the long-term tumor control and toxicity profiles after high-dose single-fraction spinal SRS. Methods and Materials The study population included all patients treated from June 2004 to July 2009 with single-fraction spinal SRS (dose 24 Gy) who had survived at least 5 years after treatment. The endpoints examined included disease progression, surgical or radiation retreatment, in-field fracture development, and radiation-associated toxicity, scored using the Radiation Therapy Oncology Group radiation morbidity scoring criteria and the Common Terminology Criteria for Adverse Events, version 4.0. Local control and fracture development were assessed using Kaplan-Meier analysis. Results Of 278 patients, 31 (11.1%), with 36 segments treated for spinal tumors, survived at least 5 years after treatment and were followed up radiographically and clinically for a median of 6.1 years (maximum 102 months). The histopathologic findings for the 5-year survivors included radiation-resistant metastases in 58%, radiation-sensitive metastases in 22%, and primary bone tumors in 19%. In this selected cohort, 3 treatment failures occurred at a median of 48.6 months, including 2 recurrences in the radiation field and 1 patient with demonstrated progression at the treatment margins. Ten lesions (27.8%) were associated with acute grade 1 cutaneous or gastrointestinal toxicity. Delayed toxicity ≥3 months after treatment included 8 cases (22.2%) of mild neuropathy, 2 (5.6%) of gastrointestinal discomfort, 8 (22.2%) of dermatitides, and 3 (8.3%) of myalgias/myositis. Thirteen treated levels (36.1%) in 12 patients demonstrated progressive vertebral body collapse or endplate fractures at a median of 25.7 months (range 11.6-76.0), of which 5 (14%) became symptomatic and subsequently required percutaneous cement augmentation or surgery. Conclusions In the longest-term series to date, high-dose single-fraction spinal SRS retained an excellent safety profile among long-term survivors (>5 years).

Even though 15% to 50% of patients with head and neck squamous cell carcinoma (HNSCC) experience recurrence, relatively little is known regarding patterns of treatment failure and postrecurrence outcomes after chemoradiotherapy using modern radiation techniques (intensity-modulated radiotherapy [IMRT]). Recurrence patterns are significantly affected by variations in the quality of radiotherapy, which may confound findings from multicenter trials.To assess patterns of treatment failure and postrecurrence outcomes for patients with HNSCC treated with contemporary radiotherapy techniques.This large single-institution cohort study reviewed the outcomes of 1000 consecutive patients with stage III to IVB oropharyngeal carcinoma (n = 703), laryngeal carcinoma (n = 126), or hypopharyngeal carcinoma (n = 46) treated with definitive IMRT with or without concurrent chemotherapy, as well as patients with oral cavity carcinoma (n = 125) treated with postoperative IMRT with or without concurrent systemic therapy, from December 1, 2001, to December 31, 2013, with a median follow-up of 65.1 months among surviving patients. Data analysis was performed from January 31, 2016, to February 17, 2017.Patterns of treatment failure and overall survival following locoregional failure or distant metastasis.Among the 1000 patients (186 women and 814 men; mean [SD] age, 59.3 [10.8] years), there were no marginal or isolated out-of-radiation-field failures. Among subsites, the cumulative incidence of local failure was highest among patients with oral cavity carcinoma vs those with oropharyngeal carcinoma (hazard ratio, 5.2; 95% CI, 3.1-8.6; P .001). Furthermore, patients with oral cavity carcinoma experienced significantly shorter survival following distant metastasis (hazard ratio, 3.66; 95% CI, 1.98-6.80; P .001). Patients with oropharyngeal carcinoma positive for human papillomavirus or p16 lived longer after locoregional failure compared with patents with oropharyngeal carcinoma negative for human papillomavirus or p16 (median survival, 36.5 vs 13.6 months; P = .007) but not after distant metastasis. Salvage surgery was associated with improved overall survival following locoregional failure (hazard ratio, 0.51; 95% CI, 0.34-0.77; P = .001); oligometastatic disease (1 vs ≥2 lesions: hazard ratio, 0.32; 95% CI, 0.16-0.63; P = .001) was associated with improved overall survival following distant metastasis.Overall survival after recurrence of HNSCC is influenced by the HNSCC subsite and human papillomavirus or p16 status, as well surgical and systemic interventions. An oligometastatic phenotype characterizes patients with solitary metastasis after chemoradiotherapy. These findings have important implications for clinical trial designs for HNSCC in the recurrent and oligometastatic setting.

Summary Purpose We sought to identify risk factors for distant metastasis (DM) in patients with oropharyngeal cancer (OPC) and perform a recursive partition analysis (RPA) to identify patients both at low and high risk for DM. Methods Our center treated 647 consecutive OPC patients with IMRT between 9/98 and 1/12. The following clinical features were used as prognostic factors: T Stage, N Stage, smoking history, tumor grade, tumor sub-site, the presence of a low lying (level IV or VB) lymph node (LLLN). A Cox model of the risk of DM was used to identify independent prognostic factors. RPA was used to identify patients at low, intermediate, and high risk for DM. Results The median follow-up time in living patients was 42.2 months (range: 2–166). The primary OPC site was the tonsil in 296 patients, base of tongue in 315 patients, and soft palate or pharyngeal wall in 36 patients. For the entire cohort, the Kaplan–Meier estimate for 3 year freedom from distant metastasis was 88.4%. A Cox model identified T Stage ( p p = 0.02), and LLLN ( p = 0.002) as independent predictors of DM. RPA identified patients at low, intermediate, and high risk of DM, with a 3-year freedom-from DM of 98%, 91.1%, and 65.4% respectively. Conclusion The presence of a low lying lymph node is significantly associated with an increased risk of DM in OPC. RPA identified patients both at very low and very high risk for DM with information routinely obtained in clinic.

Objective To determine the incidence of regional lymph node involvement for early-stage endometrial cancer by using the Surveillance, Epidemiology, and End Results (SEER) registry. Methods In a retrospective study, data were analyzed from patients who were diagnosed with stage IA–IIB endometrioid adenocarcinoma and were treated between 1998 and 2003. The incidence of pelvic and para-aortic lymph node involvement was determined. Results Data were analyzed from 4052 patients. Incidences of pelvic and para-aortic lymph node metastases were: 1% and 0% in stage IA, grade 1 disease; 2% and 0% in IA, grade 2; 2% and 1% in IA, grade 3; 2% and 0% in IB, grade 1; 3% and 1% in IB, grade 2; 3% and 2% in IB, grade 3; 7% and 3% in IC, grade 1; 8% and 5% in IC, grade 2; 12% and 8% in IC, grade 3; 7% and 3% in IIA, grade 1; 10% and 4% in IIA, grade 2; 10% and 5% in IIA, grade 3; 8% and 4% in IIB, grade 1; 13% and 8% in IIB, grade 2; and 19% and 12% in IIB, grade 3. Conclusion Incidences of pelvic and para-aortic metastases were lower than previously reported. Patients at higher stages and grades had a 10% or higher risk of lymph node involvement and might benefit from aggressive therapy.

Introduction There are little data on the outcomes and tolerance, as well as the impact on the CD4 counts, of human immunodeficiency virus (HIV)–positive patients with prostate cancer who undergo high-dose external beam radiotherapy. Materials and Methods We identified 15 HIV-positive patients with prostate cancer who were treated with external beam radiation to a dose ≥ 75.6 Gy at the New York Harbor Department of Veterans Affairs between 2003 and 2010. Kaplan-Meier analyses were used to measure biochemical control outcomes. Toxicity and CD4 counts before, after, and during treatments were analyzed. Results A total of 15 patients were identified, with a median follow-up period of 49 months. There were 2 biochemical failures, which occurred at 28 months and 63 months, respectively. In neither of these 2 patients was there evidence of metastatic disease. The overall 5-year biochemical control was 92.3%. There appeared to be a consistent decline in the CD4 counts both during and immediately after the radiation treatments. Most of these patients had a subsequent improvement in their CD4 counts. Toxicity was mild overall, though there was 1 patient who developed rectal bleeding 11 months post treatment, which required argon plasma coagulation. Conclusion Dose-escalated external beam radiation is well tolerated in HIV-positive patients with durable biochemical control and mild toxicity. A substantial decline in CD4 counts is associated with the radiation; therefore, these counts need to be monitored closely, in conjunction with the infectious-disease specialist.

Excellent local–regional control can be achieved for major salivary gland tumors treated with surgery and postoperative radiotherapy. We evaluated the cumulative incidence and predictors of distant metastasis in high-risk major salivary gland tumors. Between 1990 and 2011, 200 patients with major salivary gland tumors received postoperative radiotherapy at our center. The patients’ median age was 60 years. Patients had primary tumors of the parotid gland (84 %), submandibular (16 %), and one sublingual gland. Among the patients, 34 % had T3-T4 tumors, 32 % had nodal involvement. Other high-risk features included close/positive margins and high-grade tumors. The median RT dose was 63 Gy. With a median follow-up of 50 months, the 5-year local control and regional control were 88 and 94 %, respectively. The 5-year freedom from distant metastasis was 73 %. The median overall survival was 14.6 years corresponding to a 5- and 10-year overall survival of 77 and 59 %, respectively. T category and nodal involvement were independent predictors of distant metastasis. Nodal involvement was also an independent predictor of overall survival. Distant relapse was the predominant mode of failure despite excellent local–regional control in high-risk major salivary gland tumors. Both advanced T category and nodal involvement were independent predictors of distant metastasis. More effective systemic therapy is needed to combat distant relapse.