Outcomes of Black men with prostate cancer treated with radiation therapy in the Veterans Health Administration.

BACKGROUND: Population-based studies demonstrate that Black men in the United States have an increased risk of death from prostate cancer. Determinants of racial disparities are multifactorial, including socioeconomic and biologic factors. METHODS: The authors conducted a pooled analysis of patients derived from 152 centers within the Veterans Health Administration. The cohort included men who had nonmetastatic prostate diagnosed between 2001 and 2015 and received definitive radiation therapy. The primary endpoint was prostate cancer-specific mortality (PCSM). Secondary endpoints included all-cause mortality (ACM) and the time from a prostate-specific antigen level ≥4 ng/mL to biopsy and radiation therapy. A Cox regression model was performed to adjust for differences between clinical parameters. RESULTS: Among the 31,131 patients included in the cohort, 9584 (30.8%) were Black. The 10-year cumulative incidence of death from prostate cancer was lower in Black men compared with White men (4.0% vs 4.8%; P = .004). In a competing risk model, Black race was associated with a decreased risk of PCSM (subdistribution hazard ratio, 0.79; 95% CI, 0.69-0.92; P = .002). Similarly, the 10-year cumulative incidence of death from any cause was lower in Black men (27.6% vs 31.8%; P < .001). In multivariable analysis, Black men had a 10% decreased risk of ACM (hazard ratio, 0.90; 95% CI, 0.85-0.95; P < .001). CONCLUSIONS: The current results indicate relatively lower PCSM and ACM among Black men who were included in a large Veterans Health Administration cohort and received radiation therapy as primary treatment for nonmetastatic prostate cancer. There is an ongoing need to continue to understand and mitigate the factors associated with disparities in health care outcomes.

Quality of care at safety-net hospitals and the impact on pay-for-performance reimbursement.

BACKGROUND: Pay-for-performance reimbursement ties hospital payments to standardized quality-of-care metrics. To the authors' knowledge, the impact of pay-for-performance reimbursement models on hospitals caring primarily for uninsured or underinsured patients remains poorly defined. The objective of the current study was to evaluate how standardized quality-of-care metrics vary by a hospital's propensity to care for uninsured or underinsured patients and demonstrate the potential impact that pay-for-performance reimbursement could have on hospitals caring for the underserved. METHODS: The authors identified 1,703,865 patients with cancer who were diagnosed between 2004 and 2015 and treated at 1344 hospitals. Hospital safety-net burden was defined as the percentage of uninsured or Medicaid patients cared for by that hospital, categorizing hospitals into low-burden, medium-burden, and high-burden hospitals. The authors evaluated the impact of safety-net burden on concordance with 20 standardized quality-of-care measures, adjusting for differences in patient age, sex, stage of disease at diagnosis, and comorbidity. RESULTS: Patients who were treated at high-burden hospitals were more likely to be young, male, Black and/or Hispanic, and to reside in a low-income and low-educated region. High-burden hospitals had lower adherence to 13 of 20 quality measures compared with low-burden hospitals (all P < .05). Among the 350 high-burden hospitals, concordance with quality measures was found to be lowest for those caring for the highest percentage of uninsured or Medicaid patients, minority patients, and less educated patients (all P < .001). CONCLUSIONS: Hospitals caring for uninsured or underinsured individuals have decreased quality-of-care measures. Under pay-for-performance reimbursement models, these lower quality-of-care scores could decrease hospital payments, potentially increasing health disparities for at-risk patients with cancer.

Survival of African American and non-Hispanic white men with prostate cancer in an equal-access health care system.

BACKGROUND: African American (AA) men in the general US population are more than twice as likely to die of prostate cancer (PC) compared with non-Hispanic white (NHW) men. The authors hypothesized that receiving care through the Veterans Affairs (VA) health system, an equal-access medical system, would attenuate this disparity. METHODS: A longitudinal, centralized database of >20 million veterans was used to assemble a cohort of 60,035 men (18,201 AA men [30.3%] and 41,834 NHW men [69.7%]) who were diagnosed with PC between 2000 and 2015. RESULTS: AA men were more likely to live in regions with a lower median income ($40,871 for AA men vs $48,125 for NHW men; P < .001) and lower high school graduation rates (83% for AA men vs 88% for NHW men; P < .001). At the time of diagnosis, AA men were younger (median age, 63.0 years vs 66.0 years; P < .001) and had a higher prostate-specific antigen level (median, 6.7 ng/mL vs 6.2 ng/mL; P < .001), but were less likely to have Gleason score 8 to 10 disease (18.8% among AA men vs 19.7% among NHW men; P < .001), a clinical T classification ≥3 (2.2% vs 2.9%; P < .001), or distant metastatic disease (2.7% vs 3.1%; P = 0.01). The 10-year PC-specific mortality rate was slightly lower for AA men (4.4% vs 5.1%; P = .005), which was confirmed in multivariable competing-risk analysis (subdistribution hazard ratio, 0.85; 95% CI, 0.78-0.93; P < .001). CONCLUSIONS: AA men diagnosed with PC in the VA health system do not appear to present with more advanced disease or experience worse outcomes compared with NHW men, in contrast to national trends, suggesting that access to care is an important determinant of racial equity.

Palliative Radiotherapy Versus Esophageal Stent Placement in the Management of Patients With Metastatic Esophageal Cancer.

BACKGROUND: Patients with advanced esophageal cancer often experience pain and dysphagia, yet the optimal palliative management remains unclear. This retrospective study evaluated outcomes and adverse effects of palliative radiotherapy (RT) compared with esophageal stenting among a cohort of U.S. veterans with metastatic esophageal cancer. PATIENTS AND METHODS: We identified 1,957 veterans in the United States with metastatic esophageal cancer who received palliative RT to the esophagus or esophageal stenting, and assessed the risks of severe adverse effects, including esophageal fistula formation, perforation, obstruction, hemorrhage, and esophagitis. We determined palliative efficacy by evaluating pain and dysphagia scores before and after intervention. Multivariable analyses were used to control for potential confounding factors. RESULTS: In our cohort, 1,593 patients underwent RT and 364 underwent esophageal stenting. The cumulative incidence of any severe adverse effect at 6 months was higher among patients who received stents compared with those who received RT (21.7% vs 12.4%; P<.0010). In multivariable analysis, patients who received stents had an increased risk of any severe adverse effect, including fistula, perforation, and hemorrhage (all P<.0500). Multivariable analysis also showed that, compared with stenting, RT was associated with more rapid and durable pain relief (P<.0010) with no difference in relief of dysphagia over time when accounting for pretreatment dysphagia scores (P=.1029). CONCLUSIONS: Compared with esophageal stenting, RT was associated with a decreased risk of adverse effects, greater pain relief, and equivalent relief of moderate to severe dysphagia over time. Unmeasured patient- or tumor-related factors could have influenced the choice of intervention, thereby impacting our study outcomes. To our knowledge, this is the largest study to date analyzing the comparative risks and benefits of palliative RT and esophageal stenting among patients with metastatic esophageal cancer.

Androgen deprivation therapy and depression in men with prostate cancer treated with definitive radiation therapy.

BACKGROUND: There is no consensus on the association between the use of androgen deprivation therapy (ADT) and the risk of developing depression. This study investigated the association between ADT use and the development of depression, outpatient psychiatric services, inpatient psychiatric services, and suicide in a homogeneous group of men with prostate cancer (PC) treated with definitive radiation therapy (RT) after controlling for multiple sources of selection bias. METHODS: This was a retrospective, observational cohort study of 39,965 veterans with PC who were treated with definitive RT and were diagnosed by the US Department of Veterans Affairs health care system between January 1, 2001, and October 31, 2015. Exposure was ADT initiation within 1 year of the PC diagnosis. The primary outcome was new development of depression. Secondary outcomes were outpatient psychiatric use, inpatient psychiatric use, and suicide. RESULTS: During follow-up, 934 patients were newly diagnosed with depression, 7825 patients used outpatient psychiatric services, 358 patients used inpatient psychiatric services, and 54 patients committed suicide. In the multivariable competing risks regression model, ADT was associated with the development of depression (subdistribution hazard ratio [SHR], 1.50; 95% confidence interval [CI], 1.32-1.71; P < .001). ADT was also associated with outpatient psychiatric utilization (SHR, 1.21; 95% CI, 1.16-1.27; P < .001). Finally, ADT was not associated with inpatient psychiatric utilization or suicide. CONCLUSIONS: An increase in the risk of depression and the use of outpatient psychiatric services was observed in a large cohort of men with PC who received ADT with definitive RT. These results may provide further evidence for the long-term risks of ADT for psychiatric health in the treatment of PC.

Cost-effectiveness of Intraoperative MRI for Treatment of High-Grade Gliomas.

Background Intraoperative MRI has been shown to improve gross-total resection of high-grade glioma. However, to the knowledge of the authors, the cost-effectiveness of intraoperative MRI has not been established. Purpose To construct a clinical decision analysis model for assessing intraoperative MRI in the treatment of high-grade glioma. Materials and Methods An integrated five-state microsimulation model was constructed to follow patients with high-grade glioma. One-hundred-thousand patients treated with intraoperative MRI were compared with 100 000 patients who were treated without intraoperative MRI from initial resection and debulking until death (median age at initial resection, 55 years). After the operation and treatment of complications, patients existed in one of three health states: progression-free survival (PFS), progressive disease, or dead. Patients with recurrence were offered up to two repeated resections. PFS, valuation of health states (utility values), probabilities, and costs were obtained from randomized controlled trials whenever possible. Otherwise, national databases, registries, and nonrandomized trials were used. Uncertainty in model inputs was assessed by using deterministic and probabilistic sensitivity analyses. A health care perspective was used for this analysis. A willingness-to-pay threshold of $100 000 per quality-adjusted life year (QALY) gained was used to determine cost efficacy. Results Intraoperative MRI yielded an incremental benefit of 0.18 QALYs (1.34 QALYs with intraoperative MRI vs 1.16 QALYs without) at an incremental cost of $13 447 ($176 460 with intraoperative MRI vs $163 013 without) in microsimulation modeling, resulting in an incremental cost-effectiveness ratio of $76 442 per QALY. Because of parameter distributions, probabilistic sensitivity analysis demonstrated that intraoperative MRI had a 99.5% chance of cost-effectiveness at a willingness-to-pay threshold of $100 000 per QALY. Conclusion Intraoperative MRI is likely to be a cost-effective modality in the treatment of high-grade glioma. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Bettmann in this issue.

Combined Androgen Blockade in Localized Prostate Cancer Treated With Definitive Radiation Therapy.

BACKGROUND: The addition of androgen deprivation therapy to radiation therapy (RT) improves survival in patients with intermediate- and high-risk prostate cancer (PCa), but it is not known whether combined androgen blockade (CAB) with a gonadotropin-releasing hormone agonist (GnRH-A) and a nonsteroidal antiandrogen improves survival over GnRH-A monotherapy. METHODS: This study evaluated patients with intermediate- and high-risk PCa diagnosed in 2001 through 2015 who underwent RT with either GnRH-A alone or CAB using the Veterans Affairs Informatics and Computing Infrastructure. Associations between CAB and prostate cancer-specific mortality (PCSM) and overall survival (OS) were determined using multivariable regression with Fine-Gray and multivariable Cox proportional hazards models, respectively. For a positive control, the effect of long-term versus short-term GnRH-A therapy was tested. RESULTS: The cohort included 8,423 men (GnRH-A, 4,529; CAB, 3,894) with a median follow-up of 5.9 years. There were 1,861 deaths, including 349 resulting from PCa. The unadjusted cumulative incidences of PCSM at 10 years were 5.9% and 6.9% for those receiving GnRH-A and CAB, respectively (P=.16). Compared with GnRH-A alone, CAB was not associated with a significant difference in covariate-adjusted PCSM (subdistribution hazard ratio [SHR], 1.05; 95% CI, 0.85-1.30) or OS (hazard ratio, 1.02; 95% CI, 0.93-1.12). For high-risk patients, long-term versus short-term GnRH-A therapy was associated with improved PCSM (SHR, 0.74; 95% CI, 0.57-0.95) and OS (SHR, 0.82; 95% CI, 0.73-0.93). CONCLUSIONS: In men receiving definitive RT for intermediate- or high-risk PCa, CAB was not associated with improved PCSM or OS compared with GnRH alone.

A Population-Based Study of Morbidity After Pancreatic Cancer Diagnosis.

BACKGROUND: Pancreatic cancer is an aggressive disease characterized by early and relentless tumor spread, thus leading healthcare providers to consider it a "distant disease." However, local pancreatic tumor progression can lead to substantial morbidity. This study defines the long-term morbidity from local and nonlocal disease progression in a large population-based cohort. METHODS: A total of 21,500 Medicare beneficiaries diagnosed with pancreatic cancer in 2000 through 2011 were identified. Hospitalizations were attributed to complications of either local disease (eg, biliary disorder, upper gastrointestinal ulcer/bleed, pain, pancreas-related, radiation toxicity) or nonlocal/distant disease (eg, thromboembolic events, cytopenia, dehydration, nausea/vomiting/motility problem, malnutrition and cachexia, ascites, pathologic fracture, and chemotherapy-related toxicity). Competing risk analyses were used to identify predictors of hospitalization. RESULTS: Of the total cohort, 9,347 patients (43.5%) were hospitalized for a local complication and 13,101 patients (60.9%) for a nonlocal complication. After adjusting for the competing risk of death, the 12-month cumulative incidence of hospitalization from local complications was highest in patients with unresectable disease (53.1%), followed by resectable (39.5%) and metastatic disease (33.7%) at diagnosis. For nonlocal complications, the 12-month cumulative incidence was highest in patients with metastatic disease (57.0%), followed by unresectable (56.8%) and resectable disease (42.8%) at diagnosis. Multivariable analysis demonstrated several predictors of hospitalization for local and nonlocal complications, including age, race/ethnicity, location of residence, disease stage, tumor size, and diagnosis year. Radiation and chemotherapy had minimal impact on the risk of hospitalization. CONCLUSIONS: Despite the widely known predilection of nonlocal/distant disease spread in pancreatic cancer, local tumor progression also leads to substantial morbidity and frequent hospitalization.

The impact of traveling distance and hospital volume on post-surgical outcomes for patients with glioblastoma.

BACKGROUND: High-volume hospitals are associated with improved outcomes in glioblastoma (GBM). However, the impact of travel burden to high-volume centers is poorly understood. We examined post-operative outcomes between GBM patients that underwent treatment at local, low-volume hospitals with those that traveled long distances to high-volume hospitals. METHODS: The National Cancer Database was queried for GBM patients that underwent surgery (2010-2014). We established two cohorts: patients in the lowest quartile of travel distance and volume (Short-travel/Low-Volume: STLV) and patients in the highest quartile of travel and volume (Long-travel/High-Volume: LTHV). Outcomes analyzed were 30-day, 90-day mortality, overall survival, 30-day readmission, and hospital length of stay. RESULTS: Of 35,529 cases, STLV patients (n = 3414) traveled a median of 3 miles (Interquartile range [IQR] 1.8-4.2) to low-volume centers (5 [3-7] annual cases) and LTHV patients (n = 3808) traveled a median of 62 miles [44.1-111.3] to high-volume centers (48 [42-71]). LTHV patients were younger, had lower Charlson scores, largely received care at academic centers (84.4% vs 11.9%), were less likely to be minorities (8.1% vs 17.1%) or underinsured (6.9% vs 12.1), and were more likely to receive trimodality therapy (75.6% vs 69.2%; all p < 0.001). On adjusted analysis, LTHV predicted improved overall survival (HR 0.87, p = 0.002), decreased 90-day mortality (OR 0.72, p = 0.019), lower 30-day readmission (OR 0.42, p < 0.001), and shorter hospitalizations (RR 0.79, p < 0.001). CONCLUSIONS: Glioblastoma patients who travel farther to high-volume centers have superior post-operative outcomes compared to patients who receive treatment locally at low-volume centers. Strategies that facilitate patient travel to high-volume hospitals may improve outcomes.

Clinical Impact of Local Progression in Pancreatic Cancer.

Background: The high prevalence of distant metastatic disease among patients with pancreatic cancer often draws attention away from the local pancreatic tumor. This study aimed to define the complications and hospitalizations from local versus distant disease progression among a retrospective cohort of patients with pancreatic cancer. Methods: Records of 298 cases of pancreatic cancer treated at a single institution from 2004 through 2015 were retrospectively reviewed, and cancer-related symptoms and complications requiring hospitalization were recorded. Hospitalizations related to pancreatic cancer were attributed to either local or distant progression. Cumulative incidence analyses were used to estimate the incidence of hospitalization, and multivariable Fine-Gray regression models were used to identify factors predictive of hospitalizations. Results: The 1-year cumulative incidences of hospitalization due to local versus distant disease progression were 31% and 24%, respectively. Among 509 recorded hospitalizations, leading local etiologies included cholangitis (10%), biliary obstruction (7%), local procedure complication (7%), and gastrointestinal bleeding (7%). On multivariable analysis, significant predictors of hospitalization from local progression included unresectable disease (subdistribution hazard ratio [SDHR], 2.42; P<.01), black race (SDHR, 3.34; P<.01), younger age (SDHR, 1.02 per year; P=.01), tumor in the pancreatic head (SDHR, 2.19; P<.01), and larger tumor size (SDHR, 1.13 per centimeter; P=.02). Most patients who died in the hospital from pancreatic cancer (56%) were admitted for complications of local disease progression. Conclusions: Patients with pancreatic cancer experience significant complications of local tumor progression. Although distant metastatic progression represents a hallmark of pancreatic cancer, future research should also focus on improving local therapies.

Management of glioblastoma at safety-net hospitals.

BACKGROUND: Safety-net hospitals (SNHs) provide disproportionate care for underserved patients. Prior studies have identified poor outcomes, increased costs, and reduced access to certain complex, elective surgeries at SNHs. However, it is unknown whether similar patterns exist for the management of glioblastoma (GBM). We sought to determine if patients treated at HBHs receive equitable care for GBM, and if safety-net burden status impacts post-treatment survival. METHODS: The National Cancer Database was queried for GBM patients diagnosed between 2010 and 2015. Safety-net burden was defined as the proportion of Medicaid and uninsured patients treated at each hospital, and stratified as low (LBH), medium (MBH), and high-burden (HBH) hospitals. The impact of safety-net burden on the receipt of any treatment, trimodality therapy, gross total resection (GTR), radiation, or chemotherapy was investigated. Secondary outcomes included post-treatment 30-day mortality, 90-day mortality, and overall survival. Univariate and multivariate analyses were utilized. RESULTS: Overall, 40,082 GBM patients at 1202 hospitals (352 LBHs, 553 MBHs, and 297 HBHs) were identified. Patients treated at HBHs were significantly less likely to receive trimodality therapy (OR = 0.75, p < 0.001), GTR (OR = 0.84, p < 0.001), radiation (OR = 0.73, p < 0.001), and chemotherapy (OR = 0.78, p < 0.001) than those treated at LBHs. Patients treated at HBHs had significantly increased 30-day (OR = 1.25, p = 0.031) and 90-day mortality (OR = 1.24, p = 0.001), and reduced overall survival (HR = 1.05, p = 0.039). CONCLUSIONS: GBM patients treated at SNHs are less likely to receive standard-of-care therapies and have increased short- and long-term mortality. Additional research is needed to evaluate barriers to providing equitable care for GBM patients at SNHs.

Breast Cancer Presenting With Intravascular Tumor Emboli in Axillary Soft Tissue: Recurrence Risk and Radiation Therapy Outcomes.

Purpose: Intravascular tumor emboli in axillary soft tissue (ITE) is a rare pathologic finding in breast cancer and is associated with higher axillary nodal disease burden. The independent prognostic and predictive value of this entity is unknown, as is the role of radiation therapy for ITE. Methods and Materials: We analyzed a prospectively maintained database of breast cancer patients treated from 1992 to 2020. Patients with ITE were matched to those without (1:2) based on propensity scores to control for potential confounding factors. Locoregional (LRR) and distant recurrence (DR) were evaluated using competing risks methods accounting for death as a competing event. Overall survival (OS) and disease-free survival (DFS) were evaluated by Cox regression models. Among patients with ITE, we also evaluated whether RT improved outcomes. Results: Among 2377 total patients, 129 had ITE, of whom 126 were propensity score matched to 252 without ITE. Median follow-up from time of surgery was 5.5 years (IQR 2.3, 9.7). There were no statistically significant differences in the 5-year incidence of LRR between groups (5.4% [95% CI, 1.6%-13%] with ITE vs 10% [95% CI, 6.7%-15%] without, P = .53) or DR (24% [95% CI, 15% 35%] with ITE vs 21% [95% CI, 16%-27%] without, P = .51). Five-year OS and DFS did not differ between groups (P > .9 for both comparisons, patients with ITE vs without ITE). In analyzing the effect of RT among patients with ITE, receipt of RT was associated with significantly improved DFS (HR, 0.34, 95% CI, 0.12-0.93, P = .04). Conclusions: Patients with ITE do not exhibit significantly worse LRR, DR, DFS, or OS compared with a propensity-score-matched cohort without ITE. However, among patients with ITE, those who received RT demonstrated significantly improved DFS. Larger studies with longer follow-up are needed to evaluate the prognostic and predictive implications of ITE.

Stem cell-like T cell depletion in the recurrent head and neck cancer immune microenvironment.

Human papilloma virus (HPV)-related oncogenesis in head and neck cancer establishes a local microenvironment rich with immune cells, however the composition of the microenvironment in recurrent disease following definitive treatment is poorly understood. Here, we investigate the composition and spatial relationships between tumor and immune cells in recurrent head and neck cancer following curative intent chemoradiotherapy. Multiplexed immunofluorescence with 12 unique markers, through two multiplex immunofluorescent panels, was performed to evaluate 27 tumor samples including 18 pre-treatment primary and 9 paired recurrent tumors. Tumor and immune cell populations were phenotyped and quantified using a previously validated semi-automated digital pathology platform for cell segmentation. Spatial analysis was conducted by evaluating immune cells within the tumor, peri-tumoral stroma, and distant stroma. Initial tumors in patients with subsequent recurrence were found to be enriched in tumor associated macrophages and displayed an immune excluded spatial distribution. Recurrent tumors after chemoradiation were hypo-inflamed, with a statistically significant reduction in the recently identified stem-like TCF1+ CD8 T-cells, which normally function to maintain HPV-specific immune responses in the setting of chronic antigen exposure. Our findings indicate that the tumor microenvironment of recurrent HPV-related head and neck cancers displays a reduction in stem-like T cells, consistent with an immune microenvironment with a reduced ability to mount T-cell-driven anti-tumor immune responses.

Impact of endorectal filling on interobserver variability of MRI based rectal primary tumor delineation.

Background: Online adaptive MR-guided radiotherapy allows for the reduction of safety margins in dose escalated treatment of rectal tumors. With the use of smaller margins, precise tumor delineation becomes more critical. In the present study we investigated the impact of rectal ultrasound gel filling on interobserver variability in delineation of primary rectal tumor volumes. Methods: Six patients with locally advanced rectal cancer were scanned on a 1.5 T MRI-Linac without (MRI_e) and with application of 100 cc of ultrasound gel transanally (MRI_f). Eight international radiation oncologists expert in the treatment of gastrointestinal cancers delineated the gross tumor volume (GTV) on both MRI scans. MRI_f scans were provided to the participating centers after MRI_e scans had been returned. Interobserver variability was analyzed by either comparing the observers' delineations with a reference delineation (approach 1) and by building all possible pairs between observers (approach 2). Dice Similarity Index (DICE) and 95 % Hausdorff-Distance (95 %HD) were calculated. Results: Rectal ultrasound gel filling was well tolerated by all patients. Overall, interobserver agreement was superior in MRI_f scans based on median DICE (0.81 vs 0.74, p < 0.005 for approach 1 and 0.76 vs 0.64, p < 0.0001 for approach 2) and 95 %HD (6.9 mm vs 4.2 mm for approach 1, p = 0.04 and 8.9 mm vs 6.1 mm, p = 0.04 for approach 2). Delineated median tumor volumes and inter-quartile ranges were 26.99 cc [18.01-50.34 cc] in MRI_e and 44.20 [19.72-61.59 cc] in MRI_f scans respectively, p = 0.012. Conclusions: Although limited by the small number of patients, in this study the application of rectal ultrasound gel resulted in higher interobserver agreement in rectal GTV delineation. The endorectal gel filling might be a useful tool for future dose escalation strategies.

Clinical-genomic determinants of immune checkpoint blockade response in head and neck squamous cell carcinoma.

BACKGROUNDRecurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) is generally an incurable disease, with patients experiencing median survival of under 10 months and significant morbidity. While immune checkpoint blockade (ICB) drugs are effective in approximately 20% of patients, the remaining experience limited clinical benefit and are exposed to potential adverse effects and financial costs. Clinically approved biomarkers, such as tumor mutational burden (TMB), have a modest predictive value in HNSCC.METHODSWe analyzed clinical and genomic features, generated using whole-exome sequencing, in 133 ICB-treated patients with R/M HNSCC, of whom 69 had virus-associated and 64 had non-virus-associated tumors.RESULTSHierarchical clustering of genomic data revealed 6 molecular subtypes characterized by a wide range of objective response rates and survival after ICB therapy. The prognostic importance of these 6 subtypes was validated in an external cohort. A random forest-based predictive model, using several clinical and genomic features, predicted progression-free survival (PFS), overall survival (OS), and response with greater accuracy than did a model based on TMB alone. Recursive partitioning analysis identified 3 features (systemic inflammatory response index, TMB, and smoking signature) that classified patients into risk groups with accurate discrimination of PFS and OS.CONCLUSIONThese findings shed light on the immunogenomic characteristics of HNSCC tumors that drive differential responses to ICB and identify a clinical-genomic classifier that outperformed the current clinically approved biomarker of TMB. This validated predictive tool may help with clinical risk stratification in patients with R/M HNSCC for whom ICB is being considered.FUNDINGFundación Alfonso Martín Escudero, NIH R01 DE027738, US Department of Defense CA210784, The Geoffrey Beene Cancer Research Center, The MSKCC Population Science Research Program, the Jayme Flowers Fund, the Sebastian Nativo Fund, and the NIH/NCI Cancer Center Support Grant P30 CA008748.

Split course palliative radiotherapy for advanced lung cancer with 3D planning based analysis of outcome: a retrospective review.

BACKGROUND: Durable palliation of advanced lung cancer is a common objective for radiation oncologists. However, there is no consensus on how to deliver the radiation course. Herein we report our experience of using split course radiotherapy and our assessment of outcomes based on planning from three-dimensional (3D) simulation before each treatment course. METHODS: All lung cancer patients from 2006-2020 were identified. Of these, 52 patients received a split course treatment of 50-60 Gy in 18-25 fractions intended to provide durable palliation for disease not amenable to curative therapy. Treatment involved 3D planning with repeat computed tomography (CT) simulation prior to the second course. Survival and symptomatic response were analyzed via chart review. We categorized rapid responders versus non-rapid responders from the initial radiation course based on ≥30% gross tumor volume (GTV) reduction at the second CT simulation. We evaluated the impact of response on overall survival and palliative response. RESULTS: Among our cohort treated with split course palliative radiotherapy, 33 (63%) had a rapid response to initial treatment. There was no difference in survival between groups [hazard ratio (HR) =1.30, P=0.47]. There was no significant difference in palliative response rates between rapid and non-rapid responders. On multivariable analysis, only female sex (HR =0.26, P<0.01) and receipt of systemic therapy following radiotherapy (HR =0.19, P<0.01) were associated with improved survival. CONCLUSIONS: There is currently significant practice pattern variability for palliative lung radiotherapy. Split course palliative radiation of 50-60 Gy in 18-25 fractions represents an option to consider for patients with advanced lung cancer who do not undergo definitive therapy and may benefit from a higher dose regimen. Our retrospective review suggests that rapid tumor response in a split course model does not predict survival or symptomatic response. Prospective studies are needed to further define which lung cancer patients may benefit from higher dose regimens.

Paraspinal Myosistis After Stereotactic Radiation Surgery.

Myositis of the paraspinal muscles can be a clinically significant side effect of spinal radiation surgery. This report describes the typical clinical scenario, relevant radiologic findings, treatment, and management with the best available evidence.

Impact of Radiation on Cardiovascular Outcomes in Older Resectable Esophageal Cancer Patients With Medicare.

OBJECTIVES: Preoperative radiotherapy improves outcomes for operable esophageal cancer patients, though the proximity of the heart to the esophagus puts patients at risk of radiation-induced cardiovascular disease. This study characterizes the impact of radiotherapy and different radiation techniques on cardiovascular morbidity among a cohort of esophageal cancer patients. MATERIALS AND METHODS: We identified 1125 patients aged 65 and older diagnosed between 2000 and 2011 with esophageal cancer who received surgery alone, or surgery preceded by either preoperative chemotherapy or preoperative chemoradiation from the Surveillance Epidemiology and End Results (SEER)-Medicare database. We used Medicare claims to identify severe perioperative and late cardiovascular events. Multivariable logistic regression and Fine-Gray models were used to determine the effect of presurgery treatment on the risk of perioperative and late cardiovascular disease. RESULTS: Preoperative chemotherapy or chemoradiation did not significantly increase the risk of perioperative cardiovascular complications compared with surgery alone. Patients treated with preoperative chemoradiation had a 36% increased risk of having a late cardiovascular event compared with patients treated with surgery alone (subdistribution hazard ratio [SDHR]: 1.36; P=0.035). There was no significant increase in late cardiovascular events among patients treated with preoperative chemotherapy (SDHR: 1.18; P=0.40). Among patients treated with preoperative chemoradiation, those receiving intensity modulated radiotherapy had a 68% decreased risk of having a late cardiovascular event compared with patients receiving conventional radiation (SDHR: 0.32; P=0.007). CONCLUSIONS: This study demonstrates an increased risk of cardiovascular complications among operative esophageal cancer patients treated with preoperative chemoradiation, though these risks might be reduced with more cardioprotective radiation techniques such as intensity modulated radiotherapy.

Pathologic nodal downstaging in men with clinically involved lymph nodes undergoing radical prostatectomy: Implications for definitive locoregional therapy.

A prostate cancer (CaP) patient with nonmetastatic but clinical positive lymph nodes (cN+) represents a difficult clinical scenario. We compare overall survival (OS) between cN+ men that underwent radical prostatectomy (RP) and were found to have negative node status (pN) with those found to have positive nodal status (pN+), and assess predictors of discordant nodal status. We queried the National Cancer Data Base between 2004 and 2015 for patients that were cT1-3 cN+ cM0 CaP treated with RP. Patients with 0 nodes, cT4, or cM1 disease were excluded. We compared groups based on pathologic nodal status: Discordant (cN+ -> pN) & Concordant (cN+ -> pN+). Kaplan Meier estimations were used to compare OS. Logistic regression was used to determine possible predictors of nodal status. We find that of 6470 cN+ patients, 1,367 (21.1%) underwent RP, 866 (13.4%) had confirmed nodal status. Discordant status was found in 159 (18.4%) and concordant staging in 707 (81.6%). Differences exist in PSA at diagnosis (7.3 vs. 11.2), biopsy group, # of nodes examined (7 vs. 10), race, and Charlson index. Discordant staging had longer OS compared to Concordant staging (P = 0.007) and similar OS to a 3:1 matched cohort of high risk localized CaP patients used as reference (P = 0.46). Lower Gleason Score (GG1-3) was associated with an increased likelihood of discordant staging. Clinical nodal staging is associated with a substantial false positive rate. Discordant status had better OS than Concordant status and similar OS to matched patients with localized CaP. Clinical nodal staging may inappropriately lead to noncurative therapy in a substantial number of men with potentially curable disease.

Impact of positive surgical margins on survival after partial nephrectomy in localized kidney cancer: analysis of the National Cancer Database.

BACKGROUND: The impact of positive surgical margins (PSM) on outcomes in partial nephrectomy (PN) is controversial. We investigated impact of PSM for patients undergoing PN on overall survival (OS) in different stages of renal cell carcinoma (RCC). METHODS: Retrospective analysis of patients from the US National Cancer Database who underwent PN for cT1a-cT2b N0M0 RCC between 2004-13. Patients were stratified by pathological stage (pT1a, pT1b, pT2a, pT2b, and pT3a [upstaged]) and analyzed by margin status. Cox Regression multivariable analysis (MVA) was performed to investigate associations of PSM and covariates on all-cause mortality (ACM). Kaplan-Meier analysis (KMA) of OS was performed for PSM versus negative margin (NSM) by pathological stage. Sub-analysis of Charlson Comorbidity Index 0 (CCI=0) subgroup was conducted to reduce bias from comorbidities. RESULTS: We analyzed 42,113 PN (pT1a: 33,341 [79.2%]; pT1a, pT1b: 6689 [15.9%]; pT2a: 757 [1.8%]; pT2b: 165 [0.4%]; and pT3a: upstaged 1161 [2.8%]). PSM occurred in 6.7% (2823) (pT1a: 6.5%, pT1b: 6.3%, pT2a: 5.9%, pT2b: 6.1%, pT3a: 14.1%, P<0.001). On MVA, PSM was associated with 31% increase in ACM (HR 1.31, P<0.001), which persisted in CCI=0 sub-analysis (HR: 1.25, P<0.001). KMA revealed negative impact of PSM vs. NSM on 5-year OS: pT1 (87.3% vs. 90.9%, P<0.001), pT2 (86.7% vs. 82.5%, P=0.48), and upstaged pT3a (69% vs. 84.2%, P<0.001). CONCLUSIONS: PSM after PN was independently associated with across-the-board decrement in OS, which worsened in pT3a disease and persisted in sub-analysis of patients with CCI=0. PSM should prompt more aggressive surveillance or definitive resection strategies.