Radiomics predicts risk of cachexia in advanced NSCLC patients treated with immune checkpoint inhibitors.

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 18F-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 < 0.05). CONCLUSIONS: PET/CT radiomics analysis has the potential to predict the probability of developing cachexia before the start of ICI, triggering aggressive monitoring to improve potential to achieve more clinical benefit.

Temporary Organ Displacement to Escalate Radiation Dose to Retroperitoneal Tumors and Decrease Toxicity to Organs at Risk.

PURPOSE: To demonstrate that temporary organ displacement (TOD) by drainage catheter placement and hydrodissection is feasible and reproducible for simulation (SIM) and stereotactic body radiation treatment (SBRT). MATERIALS AND METHODS: Between February 2010 and December 2018, 31 consecutive patients (20 men and 11 women; median age, 59 years; range 20-80 years) received both SIM and SBRT with TOD. The minimum required displacement was 10 mm between the gross tumor volume (GTV) and the organ at risk (OAR). Complete displacement was defined as the ability to displace the OAR from the GTV a minimum of 10 mm across the entire boundary. SIM was performed with hydrodissection on the same day. On the day of SBRT, displacement was reproduced by hydrodissection. Displacement was measured on computed tomography images of TOD, SIM, and SBRT. The drain was removed after SBRT. RESULTS: TOD (hydrodissection) was significantly associated with successful displacement of the OAR from a GTV greater than 10 mm (median, 20 mm vs 4.1 mm, P < .001) and maintained displacement at SIM and SBRT (SIM: 29.4 mm vs 4.1 mm, P < .001; SBRT: 32.4 mm vs 4.1 mm, P < .001). The OAR-GTV boundary showed a median reduction of 35 mm (95% confidence interval, 27.5-37.5 mm) after TOD. TOD achieved complete displacement in 22 of 31 (71%) patients, and 25 of 31 (81%) patients were able to undergo single-fraction ablative SBRT. No patients developed procedure-related complications within 30 days. SIM and SBRT were successful without OAR toxicities within a median of 33 months (range, 3-92 months). CONCLUSIONS: TOD with placement of drain and hydrodissection is technically feasible and safe and maintains displacement for SIM and SBRT.

Pathological characteristics of spine metastases treated with high-dose single-fraction stereotactic radiosurgery.

OBJECTIVE Spine radiosurgery is increasingly being used to treat spinal metastases. As patients are living longer because of the increasing efficacy of systemic agents, appropriate follow-up and posttreatment management for these patients is critical. Tumor progression after spine radiosurgery is rare; however, vertebral compression fractures are recognized as a more common posttreatment effect. The use of radiographic imaging alone posttreatment may makeit difficult to distinguish tumor progression from postradiation changes such as fibrosis. This is the largest series from a prospective database in which the authors examine histopathology of samples obtained from patients who underwent surgical intervention for presumed tumor progression or mechanical pain secondary to compression fracture. The majority of patients had tumor ablation and resulting fibrosis rather than tumor progression. The aim of this study was to evaluate tumor histopathology and characteristics of patients who underwent pathological sampling because of radiographic tumor progression, fibrosis, or collapsed vertebrae after receiving high-dose single-fraction stereotactic radiosurgery. METHODS Between January 2005 and January 2014, a total of 582 patients were treated with linear accelerator-based single-fraction (18-24 Gy) stereotactic radiosurgery. The authors retrospectively identified 30 patients (5.1%) who underwent surgical intervention for 32 lesions with vertebral cement augmentation for either mechanical pain or instability secondary to vertebral compression fracture (n = 17) or instrumentation (n = 15) for radiographic tumor progression. Radiation and surgical treatment, histopathology, and long-term outcomes were reviewed. Survival and time to recurrence were calculated using the Kaplan-Meier method. RESULTS The mean age at the time of radiosurgery was 59 years (range 36-80 years). The initial pathological diagnoses were obtained for all patients and primarily included radioresistant tumor types, including renal cell carcinoma in 7 (22%), melanoma in 6 (19%), lung carcinoma in 4 (12%), and sarcoma in 3 (9%). The median time to surgical intervention was 24.7 months (range 1.6-50.8 months). The median follow-up and overall survival for all patients were 42.5 months and 41 months (overall survival range 7-86 months), respectively. The majority of assessed lesions showed no evidence of tumor on pathological review (25 of 32, 78%), while a minority of lesions revealed residual tumor (7 of 32, 22%). The median survival for patients after tumor recurrence was 5 months (range 2-70 months). CONCLUSIONS High-dose single-fraction radiosurgery is tumor ablative in the majority of instances. In a minority of cases, tumor persists and salvage treatments should be considered.

The impact of histology and delivered dose on local control of spinal metastases treated with stereotactic radiosurgery.

OBJECTIVE An analysis of factors contributing to durable radiographic control of spinal metastases was undertaken, drawing from a large single-institution database in an attempt to elucidate indications and dose requirements for successful treatment. METHODS All patients treated at a single institution with stereotactic radiosurgery (SRS) of the spine as first-line therapy were assessed for local progression of the treated site, defined as radiographic enlargement of the treated tumor and/or biopsy-proven evidence of active tumor cells. All patients were followed with CT, PET, or MR imaging every 3-6 months until death. Treatment decisions were made by a multidisciplinary team of radiation oncologists, neurosurgeons, and neuroradiologists. Target volumes were defined according to the international consensus guidelines and were reviewed in a multidisciplinary conference. Image-guided techniques and intensity modulation were used for every case. The tumor's histological type, gross tumor volume (GTV), dose that covers 95% of the GTV (GTV D95), percentage of GTV covered by 95% of the prescribed dose (GTV V95), planning target volume (PTV), dose that covers 95% of the PTV (PTV D95), and percentage of PTV covered by 95% of the prescribed dose (PTV V95) were analyzed for significance in relation to local control, based on time to local progression. RESULTS A total of 811 lesions were treated in 657 patients between 2003 and 2015 at a single institution. The mean follow-up and overall survival for the entire cohort was 26.9 months (range 2-141 months). A total of 28 lesions progressed and the mean time to failure was 26 months (range 9.7-57 months). The median prescribed dose was 2400 cGy (range 1600-2600 cGy). Both GTV D95 and PTV D95 were highly significantly associated with local failure in univariate analysis, but GTV and PTV and histological type did not reach statistical significance. The median GTV D95 for the cohort equal to or above the GTV D95 1830 cGy cut point (high dose) was 2356 cGy, and it was 1709 cGy for the cohort of patients who received less than 1830 cGy (low dose). In terms of PTV D95, the median dose for those equal to or above the cut point of 1740 cGy (high dose) was 2233 cGy, versus 1644 cGy for those lesions below the PTV D95 cut point of 1740 cGy (low dose). CONCLUSIONS High-dose single-session SRS provides durable long-term control, regardless of the histological findings or tumor size. In this analysis, the only significant factors predictive of local control were related to the actual dose of radiation given. Although the target volumes were well treated with the intended dose, those lesions irradiated to higher doses (median GTV D95 2356 cGy, minimum 1830 cGy) had a significantly higher probability of durable local control than those treated with lower doses (median PTV D95 2232 cGy, minimum of 1740 cGy) (p < 0.001). Patients in the high-dose cohort had a 2% cumulative rate of local failure. Histological findings were not associated with local failure, suggesting that radioresistant histological types benefit in particular from radiosurgery. For patients with a favorable prognosis, a higher dose of SRS is important for long-term outcomes.

Results of photon radiotherapy for unresectable salivary gland tumors: is neutron radiotherapy's local control superior?

BACKGROUND: The results of RTOG-MRC randomized trial of photon (n=15) versus neutron (n=17) therapy in the 1980's reported an improved local control (LC) with neutron radiotherapy for unresectable salivary gland tumors. Due to increased severe toxicity with neutron radiotherapy and the paucity of neutron-therapy centers, we analyzed our institution's results of photon radiotherapy for unresectable salivary gland tumors. PATIENTS AND METHODS: From 1990 to 2009, 27 patients with unresectable salivary gland cancer underwent definitive photon radiotherapy at our institution. Nodal involvement on presentation was found in 9 patients. Median dose of radiotherapy was 70 Gy. Chemotherapy was given to 18 patients, most being platinum-based regimens. Local control (LC), locoregional control (LRC), distant metastasis-free survival (DMFS), overall survival (OS), and toxicity outcomes were assessed. RESULTS: With a median follow-up of 52.4 months, the 2/5-year actuarial LC was 69% (95%CI ± 21.0%)/55% (± 24.2%), LRC was 65% (± 21.4%)/47% (± 21.6%), and DMFS was 71% (± 21.8%)/51% (± 22.8%), respectively using competing risk analysis. The median OS was 25.7 months, and the 2/5-year OS rates were 50% (± 19.0%)/29% (± 16.6%), respectively. Higher histologic grade was significant for an increased rate of DM (intermediate grade vs. low grade, p=0.04, HR 7.93; high grade vs. low grade, p=0.01, HR 13.50). Thirteen (48%) patient's experienced acute grade 3 toxicity. Late grade 3 toxicity occurred in three (11%) patients. CONCLUSIONS: Our data compares favorably to neutron radiotherapy with fewer late complications. Photon radiotherapy is an acceptable alternative to neutron radiotherapy in patients who present with unresectable salivary gland tumors.

Risk, prevention, screening and management of carotid artery stenosis in head & neck cancer patients-An evidence based review.

Our review aims to clarify the incidence of carotid artery stenosis, risks of development, screening, management, and primary prevention strategies documented in the literature after radiation therapy for head and neck cancers. The high prevalence of carotid stenosis after radiation therapy for head and neck cancers has made surveillance and risk stratification critical. In addition to general cardiovascular risk factors such as smoking, diabetes, and dyslipidemia, risk factors for carotid artery stenosis after head and neck radiation included total plaque score, radiotherapy use and dosage, length of time after radiotherapy, and age greater than 50. Cancer subtype, namely nasopharyngeal cancer, may be correlated with increased risk as well, though contrasting results have been found. Interestingly, however, no significant relationship has been found between radiotherapy dose and stroke risk. Surgical management of post-radiation carotid stenosis is similar to that of stenosis unrelated to radiation, with carotid endarterectomy considered to be the gold standard treatment and carotid artery stenting being an acceptable, less-invasive alternative. Medical management of these patients has not been well-studied, but antiplatelet therapy, statins, and blood pressure control may be beneficial. The mainstay of screening for radiation-induced stenosis has been Doppler ultrasound, with measurement of changes in the intima-media thickness being a primary marker of disease development. A literature review was carried out using the MeSH terms "Carotid Artery Stenosis," "Head and Neck Neoplasms," and "Radiotherapy."

Digital twins for health: a scoping review.

The use of digital twins (DTs) has proliferated across various fields and industries, with a recent surge in the healthcare sector. The concept of digital twin for health (DT4H) holds great promise to revolutionize the entire healthcare system, including management and delivery, disease treatment and prevention, and health well-being maintenance, ultimately improving human life. The rapid growth of big data and continuous advancement in data science (DS) and artificial intelligence (AI) have the potential to significantly expedite DT research and development by providing scientific expertise, essential data, and robust cybertechnology infrastructure. Although various DT initiatives have been underway in the industry, government, and military, DT4H is still in its early stages. This paper presents an overview of the current applications of DTs in healthcare, examines consortium research centers and their limitations, and surveys the current landscape of emerging research and development opportunities in healthcare. We envision the emergence of a collaborative global effort among stakeholders to enhance healthcare and improve the quality of life for millions of individuals worldwide through pioneering research and development in the realm of DT technology.

Molecular-Guided Off-Label Targeted Therapy in a Large-Scale Precision Oncology Program.

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.

Mutational profiles of head and neck squamous cell carcinomas based upon human papillomavirus status in the Veterans Affairs National Precision Oncology Program.

BACKGROUND: 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). METHODS: 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. RESULTS: 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 (p < 0.0001), 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. CONCLUSIONS: 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.

Identification of Key Elements in Prostate Cancer for Ontology Building via a Multidisciplinary Consensus Agreement.

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).

Consensus Quality Measures and Dose Constraints for Prostate Cancer From the Veterans Affairs Radiation Oncology Quality Surveillance Program and American Society for Radiation Oncology Expert Panel.

PURPOSE: 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. METHODS AND MATERIALS: 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. RESULTS: 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. CONCLUSIONS: 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.

Identifying and overcoming barriers to participation of minority populations in clinical trials: Lessons learned from the VanDAAM study.

Participation in cancer research trials by minority populations is imperative in reducing disparities in clinical outcomes. Even with increased awareness of the importance of minority patient inclusion in clinical research to improve cancer care and survival, significant barriers persist in accruing and retaining minority patients into clinical trials. This study sought to identify and address barriers to minority accrual to a minimal risk clinical research study in real-time.

Consensus Quality Measures and Dose Constraints for Breast Cancer From the Veterans Affairs Radiation Oncology Quality Surveillance Program and American Society for Radiation Oncology Expert Panel.

PURPOSE: Using evidence-based radiation therapy to direct care for patients with breast cancer is critical to standardize practice, improve safety, and optimize outcomes. To address this need, the Veterans Affairs (VA) National Radiation Oncology Program (NROP) established the VA Radiation Oncology Quality Surveillance Program to develop clinical quality measures (QMs). The VA NROP contracted with the American Society for Radiation Oncology to commission 5 Blue Ribbon Panels for breast, lung, prostate, rectal, and head and neck cancers. METHODS AND MATERIALS: The Breast Cancer Blue Ribbon Panel experts worked collaboratively with the NROP to develop consensus QMs for use throughout the VA system, establishing a set of QMs for patients in several areas, including consultation and work-up; simulation, treatment planning, and treatment; and follow-up care. As part of this initiative, consensus dose-volume histogram (DVH) constraints were outlined. RESULTS: In total, 36 QMs were established. Herein, we review the process used to develop QMs and final consensus QMs pertaining to all aspects of radiation patient care, as well as DVH constraints. CONCLUSIONS: The QMs and expert consensus DVH constraints are intended for ongoing quality surveillance within the VA system and centers providing community care for Veterans. They are also available for use by greater non-VA community measures of quality care for patients with breast cancer receiving radiation.

Consensus Quality Measures and Dose Constraints for Lung Cancer From the Veterans Affairs Radiation Oncology Quality Surveillance Program and ASTRO Expert Panel.

PURPOSE: For patients with lung cancer, it is critical to provide evidence-based radiation therapy to ensure high-quality care. The US Department of Veterans Affairs (VA) National Radiation Oncology Program partnered with the American Society for Radiation Oncology (ASTRO) as part of the VA Radiation Oncology Quality Surveillance to develop lung cancer quality metrics and assess quality of care as a pilot program in 2016. This article presents recently updated consensus quality measures and dose-volume histogram (DVH) constraints. METHODS AND MATERIALS: A series of measures and performance standards were reviewed and developed by a Blue-Ribbon Panel of lung cancer experts in conjunction with ASTRO in 2022. As part of this initiative, quality, surveillance, and aspirational metrics were developed for (1) initial consultation and workup; (2) simulation, treatment planning, and treatment delivery; and (3) follow-up. The DVH metrics for target and organ-at-risk treatment planning dose constraints were also reviewed and defined. RESULTS: Altogether, a total of 19 lung cancer quality metrics were developed. There were 121 DVH constraints developed for various fractionation regimens, including ultrahypofractionated (1, 3, 4, or 5 fractions), hypofractionated (10 and 15 fractionations), and conventional fractionation (30-35 fractions). CONCLUSIONS: The devised measures will be implemented for quality surveillance for veterans both inside and outside of the VA system and will provide a resource for lung cancer-specific quality metrics. The recommended DVH constraints serve as a unique, comprehensive resource for evidence- and expert consensus-based constraints across multiple fractionation schemas.

Consensus Quality Measures and Dose Constraints for Head and Neck Cancer with an emphasis on Oropharyngeal and Laryngeal Cancer from the Veterans Affairs Radiation Oncology Quality Surveillance Program and American Society for Radiation Oncology Expert Panel.

PURPOSE: 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. METHODS AND MATERIALS: 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. RESULTS: 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. CONCLUSION: 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.

Veterans Affairs Radiation Oncology Quality Surveillance Program and American Society for Radiation Oncology Quality Measures Initiative.

PURPOSE: 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. METHODS AND MATERIALS: 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). CONCLUSIONS: 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.

Racial and Ethnic Disparities in Prostate Cancer Outcomes in the Veterans Affairs Health Care System.

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 < .001). African American men who received definitive primary treatment of PCa experienced a lower risk of metastasis (hazard ratio, 0.89; 95% CI, 0.83-0.95; P < .001). However, African American men who received nondefinitive treatment classified as "other" were more likely to develop metastasis (adjusted hazard ratio, 1.29; 95% CI, 1.17-1.42; P < .001). Using the actual rate of metastasis from veterans who received definitive primary treatment, a persistent residual metastatic burden for African American men was observed across all National Comprehensive Cancer Network risk groups (low risk, 4 vs 2 per 100 000; intermediate risk, 13 vs 6 per 100 000; high risk, 19 vs 9 per 100 000). Conclusions and Relevance: This cohort analysis found significant disparities in the incidence of localized and metastatic PCa between African American veterans and White veterans. This increased incidence is a major factor associated with the residual disparity in PCa metastasis observed in African American veterans compared with White veterans despite their nearly equal response to treatment.

Consensus Quality Measures and Dose Constraints for Rectal Cancer From the Veterans Affairs Radiation Oncology Quality Surveillance Program and American Society for Radiation Oncology (ASTRO) Expert Panel.

PURPOSE: 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. METHODS AND MATERIALS: 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. CONCLUSIONS: 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.

Genomic Testing in Localized Prostate Cancer Can Identify Subsets of African Americans With Aggressive Disease.

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.

Hydronephrosis as a prognostic indicator of survival in advanced cervix cancer.

OBJECTIVE: To determine whether hydronephrosis is an independent prognostic indicator of survival among patients with advanced cervical carcinoma. Moreover, we wanted to demonstrate the relationship between unilateral and bilateral hydronephrosis and overall survival. METHODS: Retrospective analysis of 197 patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIIB cervical carcinoma or higher treated between 1990 and 2007 was conducted. Inclusion criteria were clinical staging according to FIGO criteria, standardized radiation treatment and cisplatin-based chemosensitization regimens. Associations between hydronephrosis and covariates-age, race, histopathologic diagnosis, pelvic sidewall involvement, stage, nodal involvement, and Gynecologic Oncology Group/Eastern Cooperative Oncology Group performance status (PS)-were determined. Statistical analysis including Kaplan-Meier, log-rank test, proportional hazards regression, Fisher exact test, and Mann-Whitney test were used where appropriate, with P < 0.05 considered significant. RESULTS: Of 143 included patients, 73 patients had no hydronephrosis (HN), 39 patients had unilateral HN, and 31 patients had bilateral HN. Twenty-nine patients (40%) with no HN died compared to 24 patients (61.5%) with unilateral HN and 21 patients (67.7%) with bilateral HN. Median time to death was significantly shorter for patients with unilateral HN (27 months; 95% confidence interval [CI], 10-48) and bilateral HN (12 months; 95% CI, 6-23) versus patients without HN (68 months; 95% CI, 39-∞; P < 0.001). Unadjusted hazard ratio (HR) for HN (both unilateral and bilateral) was 2.4 (95% CI, 1.5-3.8); P < 0.001. Of potential covariates evaluated, PS and sidewall involvement were significantly associated with HN (P = 0.021 and P = 0.014, respectively). Proportional hazards regression revealed that controlling for use of radiation, chemotherapy, and for PS, HN was still significantly associated with poor prognosis (HR unilateral HN = 2.0, 95% CI, 1.2-3.5; HR bilateral HN = 3.2, 95% CI, 1.7-6.0); P ≤ 0.001. CONCLUSION: Hydronephrosis is an independent poor prognostic indicator of survival in patients with advanced cervical cancer. Bilateral hydronephrosis compared to unilateral involvement confers a worse overall prognosis. Additional studies are needed to determine if FIGO staging should be amended.