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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. [ABSTRACT FROM AUTHOR]

Purpose: The addition of androgen deprivation therapy (ADT) to radiation therapy (RT) is the standard of care for men with intermediate- and high-risk prostate cancer (PC). However, whether competing mortality (CM) affects the ability of ADT to improve, survival remains unanswered.Methods and Materials: We calculated a CM risk score using a Fine-Gray semiparametric model that included age and cardiometabolic comorbidities from a cohort of 17,669 men treated with high-dose RT with or without supplemental ADT for nonmetastatic PC. Fine and Gray competing risk regression analysis was used to assess whether ADT reduced the risk of PC-specific mortality for men with a low versus a high risk of CM among the 4550 patients within the intermediate- and high-risk cohort after adjustment for established PC prognostic factors, year of treatment, site, and ADT propensity score.Results: After a median follow-up of 8.4 years, 1065 men had died, 89 (8.36%) of PC. Among the men with a low CM score, ADT use was associated with a significant reduction in the risk of PC-specific mortality (adjusted hazard ratio 0.35, 95% confidence interval 0.14-0.87, P=.02) but was not for men with high CM (adjusted hazard ratio 1.33, 95% confidence interval 0.77-2.30, P=.30).Conclusions: Adding ADT to high-dose RT appears to be associated with decreased PC-specific mortality risk in men with a low but not a high CM score. These data should serve to heighten awareness about the importance of considering competing risks when determining whether to add ADT to RT for older men with intermediate- or high-risk PC. [ABSTRACT FROM AUTHOR]

Objective: To determine whether the distance between a prostate cancer patient's home and treatment facility was related to the choice of treatment received among those opting for surgery or radiation.Methods and Materials: We identified 222,804 patients diagnosed with National Comprehensive Cancer Network low-, intermediate-, or high-risk N0M0 prostate cancer and treated with local therapy (surgery or radiation alone, with or without hormone therapy) using the National Cancer Database. We used multivariable logistic regression to determine whether the choice of radiation therapy vs radical prostatectomy varied by distance among patients living in rural and urban areas. Analyses were adjusted for geographic location within the United States, age, race, Charlson/Deyo comorbidity score, year of diagnosis, income quartile, education quartile, Gleason score, prostate-specific antigen level, and T stage.Results: Patients living in urban or rural areas were less likely to receive radiation compared with surgery if they lived farther from the treatment facility. Among urban patients living ≤5 miles from the treatment facility, 53.3% received radiation, compared with 47.0%, 43.6%, and 33.8% of those living 5 to 10, 10 to 15, or >15 miles away, respectively (P<.001 in all cases). Similarly, rural patients were less likely to receive radiation the farther they lived from the treatment facility (≤25 miles: 62.3%; 25-50 miles: 55.5%; 50-75 miles: 38.4%; >75 miles: 23.8%; P<.05 in all cases). These trends were also present when each risk group was analyzed separately.Conclusion: Patients with prostate cancer in both urban and rural settings were less likely to receive radiation therapy rather than surgery the farther away they lived from a treatment center. These findings raise the possibility that the geographic availability of radiation treatment centers may be an important determinant of whether patients are able to choose radiation rather than surgery for localized prostate cancer. [ABSTRACT FROM AUTHOR]

Purpose: Irradiation of pelvic bone marrow (BM) has been correlated with hematologic toxicity (HT) in patients undergoing chemoradiation for anal cancer. We hypothesized that irradiation of hematologically active bone marrow (ABM) subregions defined by fluorodeoxyglucose (FDG) positron emission tomography (PET) is a principal cause of radiation-associated HT.Methods and Materials: The cohort included 45 patients with nonmetastatic anal cancer who underwent FDG-PET imaging prior to definitive chemoradiation with mitomycin-C and 5-fluorouracil. Total bone marrow (TBM) was defined as the external contour of the pelvic bones from the top of lumbar 5 (L5) to the bottom of the ischial tuberosity. Standardized uptake values (SUV) for all voxels within the TBM were quantified and normalized by comparison to normal liver SUV. Subvolumes of the TBM that exhibited the highest and lowest 50% of the SUVs were designated ABM50 and IBM50, respectively. The primary endpoint was the absolute neutrophil count (ANC) nadir during or within 2 weeks of completion of treatment. Multivariate linear modeling was used to analyze the correlation between the equivalent uniform doses (EUD) with an a value of 0.5, 1 (equivalent to mean dose), 3, 7, and 12 to the BM structures and the ANC.Results: Mean ± SD ANC nadir was 0.77 × 10(9)/L (±0.66 × 10(9)/L). Grades 3 and 4 ANC toxicity occurred in 26.7% and 44.4% of patients, respectively. The EUD a parameter of 0.5 was optimal for all BM models indicating high radiation sensitivity. EUD of TBM and ABM50 and IBM50 were all significantly associated with ANC nadir. However, model performance for ABM50 was not superior to that of the TBM and IBM50 models.Conclusions: Irradiation of pelvic BM was associated with HT. However, FDG-PET-defined ABM models failed to improve model performance compared to the TBM model. [ABSTRACT FROM AUTHOR]

Background Clinical trial costs may be reduced by identifying enriched subpopulations of patients with favorable risk profiles for the events of interest. However, increased selectivity affects accrual rates, with uncertain impact on clinical trial cost. Methods We conducted a secondary analysis of Southwest Oncology Group (SWOG) 8794 randomized trial of adjuvant radiotherapy for high-risk prostate cancer. The primary endpoint was metastasis-free survival (MFS), defined as time to metastasis or death from any cause (competing mortality). We used competing risks regression models to identify an enriched subgroup at high risk for metastasis and low risk for competing mortality. We applied a cost model to estimate the impact of enrichment on trial cost and duration. Results The treatment effect on metastasis was similar in the enriched subgroup (HR, 0.42; 95% CI, 0.23–0.76) compared to the whole cohort (HR, 0.50; 95% CI, 0.30–0.81) while the effect on competing mortality was not significant in the subgroup or the whole cohort (HR 0.70; 95% CI 0.39–1.23, vs. HR 0.94; 95% CI, 0.68–1.31). Due to the higher incidence of metastasis relative to competing mortality in the enriched subgroup, the treatment effect on MFS was greater in the subgroup compared to the whole cohort (HR 0.55; 95% CI 0.36–0.82, vs. HR 0.77; 95% CI, 0.58–1.01). Trial cost was 75% less in the subgroup compared to the whole cohort ($1.7 million vs. $6.8 million), and the trial duration was 30% shorter (8.4 vs. 12.0 years). Conclusion Competing event enrichment can reduce clinical trial cost and duration, without sacrificing generalizability. [ABSTRACT FROM AUTHOR]

Abstract: Background: Composite endpoints can be problematic in the presence of competing risks when a treatment does not affect events comprising the endpoint equally. Methods: We conducted secondary analysis of SWOG 8794 trial of adjuvant radiation therapy (RT) for high-risk post-operative prostate cancer. The primary outcome was metastasis-free survival (MFS), defined as time to first occurrence of metastasis or death from any cause (competing mortality (CM)). We developed separate risk scores for time to metastasis and CM using competing risks regression. We estimated treatment effects using Cox models adjusted for risk scores and identified an enriched subgroup of 75 patients at high risk of metastasis and low risk of CM. Results: The mean CM risk score was significantly lower in the RT arm vs. control arm (p=0.001). The effect of RT on MFS (HR 0.70; 95% CI, 0.53–0.92; p=0.010) was attenuated when controlling for metastasis and CM risk (HR 0.76; 95% CI, 0.58–1.00; p=0.049), and the effect of RT on overall survival (HR 0.73; 95% CI, 0.55–0.96; p=0.02) was no longer significant when controlling for metastasis and CM risk (HR 0.80; 95% CI, 0.60–1.06; p=0.12). Compared to the whole sample, the enriched subgroup had the same 10-year incidence of MFS (40%; 95% CI, 22–57%), but a higher incidence of metastasis (30% (95% CI, 15–47%) vs. 20% (95% CI, 15–26%)). A randomized trial in the subgroup would have achieved 80% power with 56% less patients (313 vs. 709, respectively). Conclusion: Stratification on competing event risk may improve the efficiency of clinical trials. [Copyright &y& Elsevier]

Purpose: To test the hypothesis that radiation dose to 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET)-defined active bone marrow (BMACT) subregions is correlated with hematologic toxicity in cervical cancer patients treated with chemoradiotherapy. Methods and Materials: The conditions of 26 women with cervical cancer who underwent 18F-FDG-PET before treatment with concurrent cisplatin and intensity-modulated radiation therapy were analyzed. BMACT was defined as the subregion of total bone marrow (BMTOT) with a standardized uptake value (SUV) equal to or above the mean for that individual. Inactive bone marrow (BMINACT) was defined as BMTOT − BMACT. Generalized linear modeling was used to test the correlation between BMACT and BMINACT dose–volume metrics and hematologic nadirs, particularly white blood cell count (WBC) and absolute neutrophil count (ANC). Results: Increased BMACT mean dose was significantly associated with decreased log(WBC) nadir (β = −0.04; 95% CI, −0.07to −0.01; p = 0.009), decreased log(ANC) nadir (β = −0.05; 95% CI, −0.08 to −0.02; p = 0.006), decreased hemoglobin nadir (β = −0.16; 95% CI, −0.27 to −0.05; p = 0.010), and decreased platelet nadir (β = −6.16; 95% CI, −9.37 to −2.96; p < 0.001). By contrast, there was no association between BMINACT mean dose and log(WBC) nadir (β = −0.01; 95% CI, −0.06 to 0.05; p = 0.84), log(ANC) nadir (β = −0.03; 95% CI, −0.10 to 0.04; p = 0.40), hemoglobin nadir (β = −0.09; 95% CI, −0.31 to 0.14; p = 0.452), or platelet nadir (β = −3.47; 95% CI, −10.44 to 3.50; p = 0.339). Conclusions: Irradiation of BM subregions with higher 18F-FDG-PET activity was associated with hematologic toxicity, supporting the hypothesis that reducing dose to BMACT subregions could mitigate hematologic toxicity. Future investigation should seek to confirm these findings and to identify optimal SUV thresholds to define BMACT. [Copyright &y& Elsevier]

Purpose: To evaluate disease outcomes and toxicity in cervical cancer patients treated with pelvic intensity-modulated radiation therapy (IMRT). Methods and Materials: We included all patients with Stage I–IVA cervical carcinoma treated with IMRT at three different institutions from 2000–2007. Patients treated with extended field or conventional techniques were excluded. Intensity-modulated radiation therapy plans were designed to deliver 45 Gy in 1.8-Gy daily fractions to the planning target volume while minimizing dose to the bowel, bladder, and rectum. Toxicity was graded according to the Radiation Therapy Oncology Group system. Overall survival and disease-free survival were estimated by use of the Kaplan-Meier method. Pelvic failure, distant failure, and late toxicity were estimated by use of cumulative incidence functions. Results: The study included 111 patients. Of these, 22 were treated with postoperative IMRT, 8 with IMRT followed by intracavitary brachytherapy and adjuvant hysterectomy, and 81 with IMRT followed by planned intracavitary brachytherapy. Of the patients, 63 had Stage I–IIA disease and 48 had Stage IIB–IVA disease. The median follow-up time was 27 months. The 3-year overall survival rate and the disease-free survival rate were 78% (95% confidence interval [CI], 68–88%) and 69% (95% CI, 59–81%), respectively. The 3-year pelvic failure rate and the distant failure rate were 14% (95% CI, 6–22%) and 17% (95% CI, 8–25%), respectively. Estimates of acute and late Grade 3 toxicity or higher were 2% (95% CI, 0–7%) and 7% (95% CI, 2–13%), respectively. Conclusions: Intensity-modulated radiation therapy is associated with low toxicity and favorable outcomes, supporting its safety and efficacy for cervical cancer. Prospective clinical trials are needed to evaluate the comparative efficacy of IMRT vs. conventional techniques. [ABSTRACT FROM AUTHOR]

Purpose: To test the hypothesis that increased pelvic bone marrow (BM) irradiation is associated with increased hematologic toxicity (HT) in cervical cancer patients undergoing chemoradiotherapy and to develop a normal tissue complication probability (NTCP) model for HT. Methods and Materials: We tested associations between hematologic nadirs during chemoradiotherapy and the volume of BM receiving ≥10 and 20 Gy (V10 and V20) using a previously developed linear regression model. The validation cohort consisted of 44 cervical cancer patients treated with concurrent cisplatin and pelvic radiotherapy. Subsequently, these data were pooled with data from 37 identically treated patients from a previous study, forming a cohort of 81 patients for normal tissue complication probability analysis. Generalized linear modeling was used to test associations between hematologic nadirs and dosimetric parameters, adjusting for body mass index. Receiver operating characteristic curves were used to derive optimal dosimetric planning constraints. Results: In the validation cohort, significant negative correlations were observed between white blood cell count nadir and V10 (regression coefficient (β) = −0.060, p = 0.009) and V20 (β = −0.044, p = 0.010). In the combined cohort, the (adjusted) β estimates for log (white blood cell) vs. V10 and V20 were as follows: −0.022 (p = 0.025) and −0.021 (p = 0.002), respectively. Patients with V10 ≥ 95% were more likely to experience Grade ≥3 leukopenia (68.8% vs. 24.6%, p < 0.001) than were patients with V20 > 76% (57.7% vs. 21.8%, p = 0.001). Conclusions: These findings support the hypothesis that HT increases with increasing pelvic BM volume irradiated. Efforts to maintain V10 < 95% and V20 < 76% may reduce HT. [ABSTRACT FROM AUTHOR]

Simple Summary: This review explores the significant differences in the diagnosis, treatment, and outcomes of urologic cancers, including prostate, bladder, kidney, and testicular cancers, among different population groups. By examining factors like race, socioeconomic status, and access to specialized care, we aim to highlight the disparities that exist in urologic oncology and suggest strategies to ensure that all patients, regardless of their background, receive equitable treatment. The findings from this study are crucial for clinicians, policymakers, and researchers to understand the barriers faced by underserved populations and to develop interventions that can improve cancer care for everyone. Health disparities in urologic oncology, particularly in prostate, bladder, kidney, and testicular cancers, significantly impact patient outcomes across different demographic groups. This narrative review aims to investigate the extent and drivers of these disparities, focusing on the influence of race, socioeconomic status, and geographic location on diagnosis, treatment, and survival outcomes. We conducted a comprehensive review of the existing literature and analyzed data from national cancer databases to identify patterns of inequity. Our findings reveal that minority populations, individuals with lower socioeconomic status, and those residing in underserved areas are less likely to receive timely and guideline-based care, leading to worse outcomes. This review underscores the urgent need for targeted interventions, including policy reforms, health system restructuring, enhanced community outreach, and increased funding for disparity-focused research, to ensure equitable access to high-quality oncologic care. Addressing these disparities is crucial for improving cancer outcomes and achieving health equity in urologic oncology. [ABSTRACT FROM AUTHOR]

Background: This study aims to assess the impact of healthy lifestyle on prostate cancer (PCa) risk in a diverse population. Methods: Data for 281,923 men from the Million Veteran Program (MVP), a nationwide, health system–based cohort study, were analyzed. Self‐reported information at enrollment included smoking status, exercise, diet, family history of PCa, and race/ethnicity. Body mass index (BMI) was obtained from clinical records. Genetic risk was assessed via a validated polygenic score. Cox proportional hazards models were used to assess associations with PCa outcomes. Results: After accounting for ancestry, family history, and genetic risk, smoking was associated with an increased risk of metastatic PCa (hazard ratio [HR], 1.83; 95% confidence interval [CI], 1.64–2.02; p < 10−16) and fatal PCa (HR, 2.73; 95% CI, 2.36–3.25; p < 10−16). Exercise was associated with a reduced risk of fatal PCa (HR, 0.86; 95% CI, 0.76–0.98; p =.03). Higher BMI was associated with a slightly reduced risk of fatal PCa, and diet score was not independently associated with any end point. Association with exercise was strongest among those who had nonmetastatic PCa at MVP enrollment. Absolute reductions in the risk of fatal PCa via lifestyle factors were greatest among men of African ancestry (1.7% for nonsmokers vs. 6.1% for smokers) or high genetic risk (1.4% for nonsmokers vs. 4.3% for smokers). Conclusions: Healthy lifestyle is minimally related to the overall risk of developing PCa but is associated with a substantially reduced risk of dying from PCa. In multivariable analyses, both exercise and not smoking remain independently associated with reduced metastatic and fatal PCa. In this Million Veteran Program study, exercise and not smoking are shown to be minimally related to the overall risk of developing prostate cancer but are associated with a substantially reduced risk of dying from prostate cancer. [ABSTRACT FROM AUTHOR]

The article offers information on the use of postoperative radiation therapy (RT) and hormonal therapy to treat node-positive (pN+) prostate cancer in men. Topics discussed include the radical prostatectomy (RP) performed on men with pN+ prostate cancer; the use of androgen-deprivation therapy (ADT) for treatment; and the side-effects that unnecessary RT can cause for men.

Objective(s): A subset of laryngeal squamous cell carcinoma (LSCC) patients undergoing larynx preserving treatment ultimately require total laryngectomy (TL) for oncologic or functional reasons. This study aims to identify TL risk factors in these patients. Methods: Retrospective cohort study using Veterans Affairs (VA) database. T1–T4 LSCC cases treated with primary radiotherapy (XRT) or chemoradiotherapy (CRT) were assessed for TL and recurrence. Binary logistic and Cox regression and Kaplan–Meier analyses were implemented. Results: Of 5390 cases, 863 (16.0%) underwent TL. On multivariable analysis, age (adjusted odds ratio: 0.97 [0.96–0.98]; p <.001) and N3 disease (0.42 [0.18–1.00]; p =.050) were associated with reduced risk of TL, whereas current alcohol use (1.22 [1.04–1.43]; p =.015) and >T1 disease (T2, 1.76 [1.44–2.17]; p <.001; T3, 2.06 [1.58–2.68]; p <.001; T4, 1.79 [1.26–2.53]; p =.001) were associated with increased risk of TL. However, N2 (adjusted hazard ratio: 1.30 [1.10–1.55]; p =.003) and N3 (2.02 [1.25–3.26]; p =.004) disease were associated with an increased risk for local recurrence. Compared to XRT, treatment with CRT was associated with reduced risk for local recurrence after adjusting for other factors (0.84 [0.70–0.99]; p =.044). Those who do not receive TL following local recurrence have poorer disease‐specific survival (log‐rank, p <.001). In patients without local recurrence, N2 disease was associated with a fourfold increase in risk of TL (4.24 [1.83–9.82]; p <.001). Conclusion: Advanced nodal stage was associated with reduced rates of salvage TL in the setting of local recurrence, and subsequent worse prognosis after recurrence. Conversely, advanced nodal stage may increase the risk for functional salvage TL in patients without recurrence. Level of Evidence: Level 3. [ABSTRACT FROM AUTHOR]

Background: Existing data on the impact of Hispanic ethnicity on outcomes for patients with renal cell carcinoma (RCC) is mixed. The authors investigated outcomes of Hispanic and non‐Hispanic White (NHW) patients with advanced RCC receiving systemic therapy at large academic cancer centers using the International Metastatic Renal Cell Carcinoma Database (IMDC). Methods: Eligible patients included non‐Black Hispanic and NHW patients with locally advanced or metastatic RCC initiating systemic therapy. Overall survival (OS) and time to first‐line treatment failure (TTF) were calculated using the Kaplan–Meier method. The effect of ethnicity on OS and TTF were estimated by Cox regression hazard ratios (HRs). Results: A total of 1563 patients (181 Hispanic and 1382 NHW) (mostly males [73.8%] with clear cell RCC [81.5%] treated with tyrosine kinase inhibitor [TKI] monotherapy [69.9%]) were included. IMDC risk groups were similar between groups. Hispanic patients were younger at initial diagnosis (median 57 vs. 59 years, p =.015) and less likely to have greater than one metastatic site (60.8% vs. 76.8%, p <.001) or bone metastases (23.8% vs. 33.4%, p =.009). Median OS and TTF was 38.0 months (95% confidence interval [CI], 28.1–59.2) versus 35.7 months (95% CI, 31.9–39.2) and 7.8 months (95% CI, 6.2–9.0) versus 7.5 months (95% CI, 6.9–8.1), respectively, in Hispanic versus NHW patients. In multivariable Cox regression analysis, no statistically significant differences were observed in OS (adjusted hazard ratio [HR], 1.07; 95% CI, 0.86–1.31, p =.56) or TTF (adjusted HR, 1.06; 95% CI, 0.89–1.26, p =.50). Conclusions: The authors did not observe statistically significant differences in OS or TTF between Hispanic and NHW patients with advanced RCC. Receiving treatment at tertiary cancer centers may mitigate observed disparities in cancer outcomes. The authors demonstrate that there were no statistically significant differences in overall survival or time to first‐line treatment failure between non‐Black Hispanic and non‐Hispanic White patients with advanced renal cell carcinoma (RCC) treated at these large academic cancer centers. Our findings suggest that receiving treatment at a tertiary cancer center may mitigate previously observed disparities in cancer outcomes for non‐Black Hispanic patients with advanced RCC. [ABSTRACT FROM AUTHOR]

Despite differences in prostate cancer risk across ancestry groups, relative performance of prostate cancer genetic risks scores (GRS) for positive biopsy prediction in different ancestry groups is unknown. This cross-sectional retrospective analysis examines the association between a polygenic hazard score (PHS290) and risk of prostate cancer diagnosis upon first biopsy in male veterans using 2-sided tests. Our analysis included 36 717 veterans (10 297 of African ancestry). Unadjusted rates of positive first prostate biopsy increased with higher genetic risk (low risk: 34%, high risk: 58%; P  < .001). Among men of African ancestry, higher genetic risk was associated with increased prostate cancer detection on first biopsy (odds ratio = 2.18, 95% confidence interval = 1.93 to 2.47), but the effect was stronger among men of European descent (odds ratio = 3.89, 95% confidence interval = 3.62 to 4.18). These findings suggest that incorporating genetic risk into prediction models could better personalize biopsy decisions, although further study is needed to achieve equitable genetic risk stratification among ancestry groups. [ABSTRACT FROM AUTHOR]

Background Opioid tapering in the general population is linked to increases in hospitalizations or emergency department visits related to psychiatric or drug-related diagnoses. Cancer survivors represent a unique population with different opioid indications, prescription patterns, and more frequent follow-up care. This study sought to describe patterns of opioid tapering among older cancer survivors and to test the hypothesis of whether older cancer survivors face increased risks of adverse events with opioid tapering. Methods Using the Surveillance, Epidemiology and End Results Medicare–linked database, we identified 15 002 Medicare-beneficiary cancer survivors diagnosed between 2010 and 2017 prescribed opioids consistently for at least 6 months after their cancer diagnosis. Tapering was defined as a binary time-varying event occurring with any monthly oral morphine equivalent reduction of 15% or more from the previous month. Primary diagnostic billing codes associated with emergency room or hospital admissions were used for the composite endpoint of psychiatric- or drug-related event(s). Results There were 3.86 events per 100 patient-months, with 97.8% events being mental health emergencies, 1.91% events being overdose emergencies, and 0.25% involving both. Using a generalized estimating equation for repeated measure time-based analysis, opioid tapering was not statistically associated with acute events in the 3-month posttaper period (odds ratio [OR] = 1.02; P  = .62) or at any point in the future (OR = 0.96; P  = .46). Conclusions Opioid tapering in older cancer survivors does not appear to be linked to a higher risk of acute psychiatric- or drug-related events, in contrast to prior research in the general population. [ABSTRACT FROM AUTHOR]

We used a novel method (omega score) to analyse the effects of short-term androgen deprivation therapy (ADT) for prostate cancer according to the relative risk of competing events. Among patients with low-risk or favourable intermediate-risk disease, those with higher omega scores selectively benefitted from ADT. Previous studies indicate that the benefit of short-term androgen deprivation therapy (ADT) with radiotherapy (RT) for prostate cancer depends on competing risks. To determine whether a quantitative method to stratify patients by risk for competing events (omega score) could identify subgroups that selectively benefit from ADT. An ancillary analysis of NRG/RTOG 9408 phase 3 trial (NCT00002597) involving 1945 prostate cancer patients was conducted. Short-term ADT. We applied generalised competing event regression models incorporating age, performance status, comorbidity, T category, Gleason score (GS), and prostate-specific antigen (PSA), to stratify patients according to relative hazards for primary cancer-related events (distant metastasis or prostate cancer death) versus competing noncancer mortality. We tested interactions between ADT and subgroups defined by standard risk criteria versus relative risk (RR) using the omega score. T2b, higher GS, and higher PSA were associated with an increased RR for cancer-related versus competing mortality events (a higher omega score); increased age and comorbidity were associated with a decreased omega score. Of 996 patients with low-risk/favourable intermediate-risk (FIR) disease, 286 (28.7%) had a high omega score (≥0.314). Of 768 patients with unfavourable intermediate-risk disease, 175 (22.8%) had a low omega score. The overall discordance in risk classification was 26.1%. Both standard criteria and omega score identified significant interactions for the effect of ADT on cancer-related events and late mortality in low- versus high-risk subgroups. Within the low-risk/FIR subgroup, a higher omega score identified patients in whom ADT significantly reduced cancer events and improved event-free survival. Limitations are the need for external/prospective validation and lower RT doses than contemporary standards. Stratification based on competing event risk is useful for identifying prostate cancer patients who selectively benefit from ADT. We analysed the effectiveness of androgen deprivation therapy (ADT) for localised prostate cancer among patients, defined by the relative risk (RR) for cancer versus noncancer events. Among patients with traditional low-risk/favourable intermediate-risk disease, those with a higher RR benefitted from short-term ADT. [ABSTRACT FROM AUTHOR]

Background: Although Black men are more likely than non‐Hispanic White men to develop and die from prostate cancer, limited data exist to guide prostate‐specific antigen (PSA) screening protocols in Black men. This study investigated whether the risk for prostate cancer was higher than expected among self‐identified Black than White veterans based on prebiopsy PSA level. Methods: Multivariable logistic regression models were estimated to predict the likelihood of prostate cancer diagnosis on first biopsy for 75,295 Black and 207,658 White male veterans. Self‐identified race, age at first PSA test, prebiopsy PSA, age at first biopsy, smoking status, statin use, and socioeconomic factors were used as predictors. The adjusted predicted probabilities of cancer detection on first prostate biopsy from the logistic models at different PSA levels were calculated. Results: After controlling for PSA and other covariates, Black veterans were 50% more likely to receive a prostate cancer diagnosis on their first prostate biopsy than White veterans (odds ratio [OR], 1.50; 95% CI, 1.47‐1.53; p <.001). At a PSA level of 4.0 ng/mL, the probability of prostate cancer for a Black man was 49% compared with 39% for a White man. This model indicated that Black veterans with a PSA of 4.0 ng/mL have an equivalent risk of prostate cancer as White veterans with a PSA of 13.4 ng/mL. Conclusions: The findings indicate that, at any given PSA level, Black men are more likely to harbor prostate cancer than White men. Prospective studies are needed to better evaluate risks and benefits of PSA screening in Black men and other high‐risk populations. At any given prostate‐specific antigen level, Black men have substantially higher risk of prostate cancer detection on their first biopsy compared with White men after accounting for socioeconomic factors, age, and prebiopsy prostate‐specific antigen. This difference was more pronounced among younger men. [ABSTRACT FROM AUTHOR]

Studies have suggested that intraductal carcinoma of the prostate is an aggressive disease entity. We assessed outcomes for patients in the Veterans Health Administration with intraductal carcinoma. Patients with intraductal carcinoma were at higher risk of worse disease and increased risk of biochemical recurrence and metastasis development. Intraductal status is an important prognostic indicator for patients with prostate carcinoma. Purpose: Intraductal carcinoma of the prostate (IDC-P) is a relatively unstudied feature present in some prostate cancer (PC) diagnoses with several studies suggesting associations with higher Gleason scores (GS) and earlier time to biochemical recurrence (BCR) after definitive treatment. We looked to identify cases of IDC-P in the Veterans Health Administration (VHA) database and measure associations between IDC-P and pathological stage, BCR, and metastases. Methods: Patients in the VHA database diagnosed with PC from 2000 to 2017, treated with radical prostatectomy (RP) at the VHA were included in the cohort. BCR was defined as post-RP PSA > 0.2 or administration of androgen deprivation therapy (ADT). Time to event was defined as time from RP to event or censor. Differences in cumulative incidences were assessed through Gray's test. Associations with IDC-P and pathologic features at RP, BCR and metastases were assessed through multivariable logistic and Cox regression models. Results: Of 13,913 patients meeting inclusion cr iter ia, 45 patients had IDC-P. Median follow up was 8.8 years from RP. Multivariable logistic regressions showed patients with IDC-P were more likely to have GS =8 (Odds Ratio (OR) 1.14, P = .009) and higher T stages (T3 or 4 vs. T1 or 2 OR 1.14, P < .001). In total, 4,318 patients experienced a BCR, and 1,252 patients developed metastases of whom 26 and 12, respectively, had IDC-P. On multivariable regression IDC-P was associated with higher risk of BCR (IDC-P Hazard Ratio (HR) 1.71, P = .006) and metastases (HR 2.84, P < .001). Cumulative incidence of metastases at 4 years for IDC-P and non-IDC-P were 15.9% and 5.5% (P < .001) respectively. Conclusions: In this analysis, IDC-P was associated with higher Gleason score at RP, shorter time to BCR, and higher rates of metastases. Further studies are warranted to investigate the molecular underpinnings of IDC-P to better guide treatment strategies for this aggressive disease entity. [ABSTRACT FROM AUTHOR]

Background Genetic scores may provide an objective measure of prostate cancer risk and thus inform screening decisions. We evaluated whether a polygenic hazard score based on 290 genetic variants (PHS290) is associated with prostate cancer risk in a diverse population, including Black men, who have higher average risk of prostate cancer death but are often treated as a homogeneously high-risk group. Methods This was a retrospective analysis of the Million Veteran Program, a national, population-based cohort study of US military veterans conducted 2011-2021. Cox proportional hazards analyses tested for association of genetic and other risk factors (including self-reported race and ethnicity and family history) with age at death from prostate cancer, age at diagnosis of metastatic (nodal or distant) prostate cancer, and age at diagnosis of any prostate cancer. Results A total of 590 750 male participants were included. Median age at last follow-up was 69 years. PHS290 was associated with fatal prostate cancer in the full cohort and for each racial and ethnic group (P  <  .001). Comparing men in the highest 20% of PHS290 with those in the lowest 20% (based on percentiles from an independent training cohort), the hazard ratio for fatal prostate cancer was 4.42 (95% confidence interval = 3.91 to 5.02). When accounting for guideline-recommended risk factors (family history, race, and ethnicity), PHS290 remained a strong independent predictor of any, metastatic, and fatal prostate cancer. Conclusions PHS290 stratified US veterans of diverse ancestry for lifetime risk of prostate cancer, including metastatic and fatal cancer. Predicting genetic risk of lethal prostate cancer with PHS290 might inform individualized decisions about prostate cancer screening. [ABSTRACT FROM AUTHOR]

The COVID‐19 pandemic disrupted prostate‐specific antigen (PSA) screening and prostate biopsy procedures. We sought to determine whether delayed screening and diagnostic workup of prostate cancer (PCa) was associated with increased subsequent rates of incident PCa and advanced PCa and whether the rates differed by race. We analyzed data from the Veterans Health Administration to assess the changes in the rates of PSA screening, prostate biopsy procedure, incident PCa, PCa with high‐grade Gleason score, and incident metastatic prostate cancer (mPCa) before and after January 2020. While the late pandemic mPCa rate among White Veterans was comparable to the pre‐pandemic rate (5.4 pre‐pandemic vs 5.2 late‐pandemic, p = 0.67), we observed a significant increase in incident mPCa cases among Black Veterans in the late pandemic period (8.1 pre‐pandemic vs 11.3 late‐pandemic, p < 0.001). Further investigation is warranted to fully understand the impact of the COVID‐19 pandemic on the diagnosis of advanced prostate cancer. [ABSTRACT FROM AUTHOR]

Background: The 2018 US Preventive Services Task Force guidelines recommend individualizing prostate cancer screening in 55‐ to 69‐year‐old men. Given the higher incidence of prostate cancer in African American (AA) compared to non‐Hispanic White (NHW) men, this study compared reported rates of prostate‐specific antigen (PSA) screening hypothesizing that it would not be commensurate with the relative risk between these two groups. Methods: Using the 2020 Behavioral Risk Factor Surveillance System, we identified 43,685 men (40,301 NHW and 3384 AA) interviewed about PSA screening. Results: AA men had an odds ratio (OR) of 0.80 (95% confidence interval [CI], 0.69–0.93; p =.004) of reporting PSA screening; sequentially correcting for access to care, smoking, and age had minimal effect on this finding, but when correcting for income significantly attenuated this difference (OR, 0.95; 95% CI, 0.81–1.12). Further adding education level eliminated the effect size of AA race entirely with OR, 0.99 (95% CI, 0.84–1.17; p =.91). Further analysis found significant interaction between education and race, with college‐educated AA men having 1.42 OR of receiving screening compared to college‐educated NHW men. Conclusions: Despite prostate cancer being more common and having higher population‐level mortality in AA than NHW men, PSA screening and education patterns do not reflect this increased risk even when adjusting for health access disparities. The authors' findings of significant effect from both income and education suggest that systemic racism is an important factor in the observed difference in PSA screening between AA men and NHW men. Lay summary: In the United States, prostate cancer is more common in African American menNew guidelines from 2018 encourage physicians to consider risk factors in deciding whether or not to recommend screening, but overall African American men continue to be screened at a lower rate than non‐Hispanic White menThis effect disappears when correcting for income and education level, suggesting that several factors including systemic racism, medical mistrust, and self‐advocacy may impact this observed difference African American men continue to report lower rates of PSA screening compared to non‐Hispanic White men in a nationwide survey. This effect appears to be mediated by income and education, suggesting that systemic racism as well as self‐advocacy and medical mistrust may be responsible for this observed difference. [ABSTRACT FROM AUTHOR]

Our purpose was to investigate the effect of physicist-patient consults on patient anxiety and patient satisfaction with a randomized prospective phase III clinical trial. Sixty-six patients were randomly assigned to the physics direct patient care (PDPC) arm or the control arm of the trial. Patients assigned to the PDPC arm received 2 physicist-patient consults to educate them on the technical aspects of their radiation therapy, while patients assigned to the control arm received the standard of care (ie, standard radiation therapy workflow without any additional physicist-patient consults). Questionnaires were administered to all patients at 4 time points (after enrollment, after the simulation, after the first treatment, and after the last treatment) to assess anxiety and satisfaction. The decrease in anxiety for the PDPC arm, compared with the control arm, was statistically significant at the first treatment (P =.027) time point. The increase in technical satisfaction for the PDPC arm, compared with the control arm, was statistically significant at the simulation (P =.005), first treatment (P <.001), and last treatment (P =.002) time points. The increase in overall satisfaction for the PDPC arm, compared with the control arm, was statistically significant at the first treatment (P =.014) and last treatment (P =.001) time points. Physicist-patient consults improved the patient experience by decreasing anxiety and increasing satisfaction. Future work is needed to modify current radiation oncology workflows and medical physics responsibilities to allow all patients to benefit from this advancement in patient care. [ABSTRACT FROM AUTHOR]

Background: Despite higher risks associated with prostate cancer, young African American men are poorly represented in prostate-specific antigen (PSA) trials, which limits proper evidence-based guidance. We evaluated the impact of PSA screening, alongside primary care provider utilization, on prostate cancer outcomes for these patients.Methods: We identified African American men aged 40-55 years, diagnosed with prostate cancer between 2004 and 2017 within the Veterans Health Administration. Inverse probability of treatment-weighted propensity scores were used in multivariable models to assess PSA screening on PSA levels higher than 20, Gleason score of 8 or higher, and metastatic disease at diagnosis. Lead-time adjusted Fine-Gray regression evaluated PSA screening on prostate cancer-specific mortality (PCSM), with noncancer death as competing events. All statistical tests were 2-sided.Results: The cohort included 4726 patients. Mean age was 51.8 years, with 84-month median follow-up. There were 1057 (22.4%) with no PSA screening prior to diagnosis. Compared with no screening, PSA screening was associated with statistically significantly reduced odds of PSA levels higher than 20 (odds ratio [OR] = 0.56, 95% confidence interval [CI] = 0.49 to 0.63; P < .001), Gleason score of 8 or higher (OR = 0.78, 95% CI = 0.69 to 0.88; P < .001), and metastatic disease at diagnosis (OR = 0.50, 95% CI = 0.39 to 0.64; P < .001), and decreased PCSM (subdistribution hazard ratio = 0.52, 95% CI = 0.36 to 0.76; P  < .001). Primary care provider visits displayed similar effects.Conclusions: Among young African American men diagnosed with prostate cancer, PSA screening was associated with statistically significantly lower risk of PSA levels higher than 20, Gleason score of 8 or higher, and metastatic disease at diagnosis and statistically significantly reduced risk of PCSM. However, the retrospective design limits precise estimation of screening effects. Prospective studies are needed to validate these findings. [ABSTRACT FROM AUTHOR]

Background African American patients with bladder cancer have inferior outcomes compared with non-Hispanic White (White) patients. We hypothesize that access to health care is a primary determinant of this disparity. We compared outcomes by race for patients with bladder cancer receiving care within the predominant hybrid-payer health-care model of the United States captured in the Surveillance, Epidemiology, and End Results (SEER) database with those receiving care within the equal-access model of the Veterans' Health Administration (VHA). Methods African American and White patients diagnosed with bladder cancer were identified in SEER and VHA. Stage at presentation, bladder cancer–specific mortality (BCM), and overall survival (OS) were compared by race within each health-care system. Results The SEER cohort included 122 449 patients (93.7% White, 6.3% African American). The VHA cohort included 36 322 patients (91.0% White, 9.0% African American). In both cohorts, African American patients were more likely to present with muscle-invasive disease and metastases, but the differences between races were statistically significantly smaller in VHA. In SEER multivariable models, African American patients had worse BCM (hazard ratio [HR] = 1.22, 95% confidence interval [CI] = 1.15 to 1.29) and OS (HR = 1.26, 95% CI = 1.20 to 1.31). In contrast within the VHA, African American patients had similar BCM (HR = 0.97, 95% CI = 0.88 to 1.07) and OS (HR = 0.99, 95% CI = 0.93 to 1.05). Conclusions In this study of contrasting health-care models, receiving medical care in an equal-access system was associated with reduced differences in stage at presentation and eliminated disparities in survival outcomes for African American patients with bladder cancer. Our findings highlight the importance of reducing financial barriers to care to notably improve health equity and oncologic outcomes for African American patients. [ABSTRACT FROM AUTHOR]

Abstract: Background: Separate analysis of cause-specific treatment effects is important for interpreting results of randomized trials. We sought to determine the extent to which cause-specific effects on primary events are reported in contemporary randomized controlled trials in oncology. Methods: We screened 833 randomized trials published in eight leading medical journals between January 2006 and December 2009. We excluded prevention studies (n =52), secondary reports (n =100), and one retracted study. Analysis was further restricted to 116 trials in non-metastatic/recurrent cancer that used an event-free survival primary endpoint. For each study included in the analysis, we evaluated whether treatment effects on both cancer and non-cancer events comprising the primary endpoint were reported separately and whether statistical analysis was provided. Results: Of the 116 randomized trials, 47 (40%; 95% confidence interval (CI), 32–50%) reported effects on both cancer and non-cancer events comprising the primary endpoint, with statistical analysis provided in 13 (11%; 95% CI, 7–19%). Twenty-six trials (22%; 95% CI, 15–31%) reported effects on cancer but not non-cancer events, with statistical analysis provided in 11 (9%; 95% CI, 5–17%). In 43 studies (37%; 95% CI, 28–47%), no effects on cancer-specific components of the primary endpoint were given. Of these, 33 studies (28%; 95% CI, 21–38%) did report effects on some cancer-specific event, while ten (9%; 95% CI, 4-16%) did not report effects of treatment on any cancer event. Discussion: Many randomized trials in oncology do not report cause-specific effects on primary events. Increased specificity is needed in the design and reporting of cancer clinical trials. [Copyright &y& Elsevier]

Purpose: This study seeks to characterize magnetic resonance imaging (MRI) changes following stereotactic radiosurgery (SRS) of pediatric brain malignancies. Methods: Serial MRI evaluations were performed on 21 lesions treated with SRS for either medulloblastoma ( n = 12), juvenile pilocytic astrocytoma ( n = 4), ependymoma ( n = 2), atypical rhabdoid teratoid tumor ( n = 2), or pineocytoma ( n = 1). Prescription doses ranged from 14 to 30 Gy in one to five fractions. Tumor response was qualified as complete (CR), partial (PR), stable disease (SD), or progressive disease (PD) according to the RECIST v1.1. Median radiographic follow-up after SRS was 17 months. Results: A total of 80 follow-up MRI scans were reviewed with a median of eight per patient. During serial MRI evaluation, eight lesions met criteria for PD at a median of 6 months. However, of these, three (37%) represented transient tumor edema with two lesions later developing a CR at a median of 15 months and one persisting as SD at 12 months. The remaining five lesions were true local failures. Of the 13 lesions that did not show evidence of PD, a CR was obtained in 11 lesions at a median of 3 months (range, 2-6), and SD was seen in the remaining two tumors at last follow-up. Conclusion: Lesion enlargement following SRS for pediatric intracranial tumors is common, and a proportion of patients meeting requirements for PD at early radiographic follow-up may later develop complete resolution of their lesions. Physicians should be aware of these radiographic changes to avoid unwarranted medical and surgical interventions. [ABSTRACT FROM AUTHOR]

Purpose: To study the effects of increasing pelvic bone marrow (BM) radiation dose on acute hematologic toxicity in patients undergoing chemoradiotherapy, using a novel modeling approach to preserve the local spatial dose information. Methods and Materials: The study included 37 cervical cancer patients treated with concurrent weekly cisplatin and pelvic radiation therapy. The white blood cell count nadir during treatment was used as the indicator for acute hematologic toxicity. Pelvic BM radiation dose distributions were standardized across patients by registering the pelvic BM volumes to a common template, followed by dose remapping using deformable image registration, resulting in a dose array. Principal component (PC) analysis was applied to the dose array, and the significant eigenvectors were identified by linear regression on the PCs. The coefficients for PC regression and significant eigenvectors were represented in three dimensions to identify critical BM subregions where dose accumulation is associated with hematologic toxicity. Results: We identified five PCs associated with acute hematologic toxicity. PC analysis regression modeling explained a high proportion of the variation in acute hematologicity (adjusted R 2, 0.49). Three-dimensional rendering of a linear combination of the significant eigenvectors revealed patterns consistent with anatomical distributions of hematopoietically active BM. Conclusions: We have developed a novel approach that preserves spatial dose information to model effects of radiation dose on toxicity, which may be useful in optimizing radiation techniques to avoid critical subregions of normal tissues. Further validation of this approach in a large cohort is ongoing. [ABSTRACT FROM AUTHOR]

Purpose: To report on the acute and late gastrointestinal (GI) and genitourinary (GU) toxicity associated with a unique technique of image-guided radiotherapy (IGRT) in patients undergoing postprostatectomy irradiation. Methods and Materials: Fifty patients were treated with intensity-modulated radiation therapy (IMRT) after radical prostatectomy. Daily image guidance was performed to localize the prostate bed using kilovoltage imaging or cone-beam computed tomography. The median prescription dose was 68 Gy (range, 62–68 Gy). Toxicity was graded every 3 to 6 months according to the Common Terminology Criteria for Adverse Events version 3.0. Results: The median follow-up was 24 months (range, 13–38 months). Grade 2 acute GI and GU events occurred in 4 patients (8%) and 7 patients (14%), respectively. No Grade 3 or higher acute GI or GU toxicities were observed. Late Grade 2 GI and GU events occurred in 1 patient (2%) and 8 patients (16%), respectively. Only a single (2%) Grade 3 or higher late toxicity was observed. Conclusions: Image-guided IMRT in the postprostatectomy setting is associated with a low frequency of acute and late GI/GU toxicity. These results compare more favorably to radiotherapy techniques that do not use in-room image-guidance, suggesting that daily prostate bed localization may reduce the incidence of adverse events in patients undergoing postprostatectomy irradiation. [Copyright &y& Elsevier]

Radiotherapy has a well-established role in the management of head and neck cancers. Over the past decade, a variety of new imaging modalities have been incorporated into the radiotherapy planning and delivery process. These technologies are collectively referred to as image-guided radiotherapy and may lead to significant gains in tumor control and radiation side effect profiles. In the following review, these techniques as they are applied to head and neck cancer patients are described, and clinical studies analyzing their use in target delineation, patient positioning, and adaptive radiotherapy are highlighted. Finally, we conclude with a brief discussion of potential areas of further radiotherapy advancement. [ABSTRACT FROM AUTHOR]

Background: This study was done to determine the representation of minorities, women, and the elderly in National Cancer Institute (NCI) clinical trials. Methods: This is an analysis in the NCI Clinical Data Update System. Patients were evaluated in breast, colorectal, lung, and prostate cancer trials from 2000 to 2019. Representation in a trial was determined by race/ethnicity, sex, and age. Secondarily, the change in trial participation by multivariable analysis by comparing years 2000 through 2004 to 2015 through 2019 was evaluated. Results: The cohort included 242,720 participants: 197,320 Non‐Hispanic White (81.3%), 21,190 Black (8.7%), 11,587 Hispanic (4.8%), and 6880 Asian/Pacific Islander (2.8%). Black and Hispanic patients were underrepresented for colorectal (odds ratio [OR], 0.58; 95% confidence interval [CI], 0.50‐0.67; P <.001 and OR, 0.74; 95% CI, 0.64‐0.87; P <.001, respectively), lung (OR, 0.83; 95% CI, 0.76‐0.91; P <.001 and 0.66; 95% CI, 0.57‐0.77; P <.001, respectively), and prostate cancer trials (OR, 0.85; 95% CI, 0.79‐0.92; P <.001 and OR, 0.58; 95% CI, 0.51‐0.66; P <.001) between 2015 and 2019. The odds of participation in 2015 to 2019 increased among Black patients in breast (OR, 2.19; 95% CI, 2.07‐%2.32; P <.001), lung (OR, 1.54; 95% CI, 1.38‐1.73; P <.001), and prostate cancer trials (OR, 1.14; 95% CI, 1.04‐1.26; P <.001). The odds of participation in a trial among Hispanic patients increased for breast (OR, 3.32; 95% CI, 3.09‐3.56; P <.001), colorectal (OR, 2.46; 95% CI, 2.04‐2.96; P <.001), lung (OR, 3.88; 95% CI, 3.20‐4.69; P <.001), and prostate cancer (OR, 1.70; 95% CI, 1.42‐2.04; P =.005). Conclusions: This study identified that Black and Hispanic patients remain underrepresented in trials, but in recent years, participation has increased. These findings indicate that minority participation has increased over time, but further efforts are needed. Minorities, women, and the elderly have remained underrepresented in clinical trials in recent years. However, some minority participation has increased in recent years. [ABSTRACT FROM AUTHOR]

Background: The safety of active surveillance (AS) for African American men compared with non‐Hispanic White (White) men with intermediate‐risk prostate cancer is unclear. Methods: The authors identified patients with modified National Comprehensive Cancer Network favorable ("low‐intermediate") and unfavorable ("high‐intermediate") intermediate‐risk prostate cancer diagnosed between 2001 and 2015 and initially managed with AS in the Veterans Health Administration database. They analyzed definitive treatment, disease progression, metastases, prostate cancer–specific mortality (PCSM), and all‐cause mortality by using cumulative incidences and multivariable competing‐risks (disease progression, metastasis, and PCSM) or Cox (all‐cause mortality) regression. Results: The cohort included 1007 men (African Americans, 330 [32.8%]; Whites, 677 [67.2%]) followed for a median of 7.7 years; 773 (76.8%) had low‐intermediate‐risk disease, and 234 (23.2%) had high‐intermediate‐risk disease. The 10‐year cumulative incidences of definitive treatment were not significantly different (African Americans, 83.5%; 95% confidence interval [CI], 78.5%‐88.7%; Whites, 80.6%; 95% CI, 76.6%‐84.4%; P =.17). Among those with low‐intermediate‐risk disease, there were no significant differences in the 10‐year cumulative incidences of disease progression (African Americans, 46.8%; 95% CI, 40.0%‐53.3%; Whites, 46.9%; 95% CI, 42.1%‐51.5%; P =.91), metastasis (African Americans, 7.1%; 95% CI, 3.7%‐11.8%; Whites, 10.8%; 95% CI, 7.6%‐14.6%; P =.17), or PCSM (African Americans, 3.8%; 95% CI, 1.6%‐7.5%; Whites, 3.8%; 95% CI, 2.0%‐6.3%; P =.69). In a multivariable regression including the entire cohort, African American race was not associated with increased risks of definitive treatment, disease progression, metastasis, PCSM, or all‐cause mortality (all P >.30). Conclusions: Outcomes in the Veterans Affairs Health System were similar for African American and White men treated for low‐intermediate‐risk prostate cancer with AS. The safety of active surveillance for African American men with intermediate‐risk prostate cancer is unclear. This study has measured similar clinical outcomes for African American men and non‐Hispanic White men treated for either modified National Comprehensive Cancer Network (NCCN) favorable ("low‐intermediate") or unfavorable ("high‐intermediate") intermediate‐risk prostate cancer with active surveillance, and it suggests that active surveillance may be an appropriate option for both African American men and non‐Hispanic White men with modified NCCN favorable ("low‐intermediate") intermediate‐risk prostate cancer. [ABSTRACT FROM AUTHOR]

Background: Despite guideline recommendations, utilization of low‐dose computed tomography (LDCT) for lung cancer screening remains low. The driving factors behind these low rates and the real‐world effect of LDCT utilization on lung cancer outcomes remain limited. Methods: We identified patients diagnosed with non‐small cell lung cancer (NSCLC) from 2015 to 2017 within the Veterans Health Administration. Multivariable logistic regression assessed the influence of LDCT screening on stage at diagnosis. Lead time correction using published LDCT lead times was performed. Cancer‐specific mortality (CSM) was evaluated using Fine–Gray regression with non‐cancer death as a competing risk. A lasso machine learning model identified important predictors for receiving LDCT screening. Results: Among 4664 patients, mean age was 67.8 with 58‐month median follow‐up, 95% CI = [7–71], and 118 patients received ≥1 screening LDCT before NSCLC diagnosis. From 2015 to 2017, LDCT screening increased (0.1%–6.6%, mean = 1.3%). Compared with no screening, patients with ≥1 LDCT were more than twice as likely to present with stage I disease at diagnosis (odds ratio [OR] 2.16 [95% CI 1.46–3.20]) and less than half as likely to present with stage IV (OR 0.38 [CI 0.21–0.70]). Screened patients had lower risk of CSM even after adjusting for LDCT lead time (subdistribution hazard ratio 0.60 [CI 0.42–0.85]). The machine learning model achieved an area under curve of 0.87 and identified diagnosis year and region as the most important predictors for receiving LDCT. White, non‐Hispanic patients were more likely to receive LDCT screening, whereas minority, older, female, and unemployed patients were less likely. Conclusions: Utilization of LDCT screening is increasing, although remains low. Consistent with randomized data, LDCT‐screened patients were diagnosed at earlier stages and had lower CSM. LDCT availability appeared to be the main predictor of utilization. Providing access to more patients, including those in diverse racial and socioeconomic groups, should be a priority. [ABSTRACT FROM AUTHOR]

Purpose: Neutrophil-lymphocyte ratio has been explored as a prognosticator in several cancer types, but its association with larynx cancer outcomes is not well known. We aimed to identify an optimal NLR cutoff point and examine the prognostic utility of this biomarker in patients with locoregionally advanced larynx cancer treated with curative intent. Methods: In the Veterans Affairs' (VA) national database, we identified patients with locoregionally advanced (T3-4N0-3M0) laryngeal squamous cell carcinoma diagnosed between 2000 and 2017 and treated with curative intent. NLR cutoff points were calculated using Contal/O'Quigley's method. Outcomes of larynx cancer-specific survival (CSS), overall survival (OS), and non-larynx cancer survival (NCS) were evaluated in multivariable Cox and Fine-Gray models. Results: In 1047 patients, the optimal pretreatment NLR cutoff was identified as 4.17 - 722 patients with NLR ⩽ 4.17, 325 patients with NLR > 4.17. The elevated NLR cohort had a higher proportion of T4 disease (39.4% vs 28.4%), node positive disease (52.3% vs 43.1%), and surgical treatment (43.7% vs 35.2%). In multivariable analysis, NLR > 4.17 was independently associated with worse OS (HR 1.31, 95% CI 1.12-1.54, P =.001) and worse CSS (HR 1.46, 95% CI 1.17-1.83, P <.001), but not with NCS (HR 0.94, 95% CI 0.75-1.18, P =.58). Conclusion: In locoregionally advanced larynx cancer treated with curative intent, we identified elevated NLR to be associated with inferior OS and CSS. Further prospective studies are needed to investigate pretreatment NLR and our identified 4.17 cutoff as a potential larynx cancer-specific marker for this high risk population. [ABSTRACT FROM AUTHOR]

Background: Disparities in prostate cancer-specific mortality (PCSM) between African American and non-Hispanic White (White) patients have been attributed to biological and systemic factors. We evaluated drivers of these disparities in the Surveillance, Epidemiology, and End Results (SEER) national registry and an equal-access system, the Veterans Health Administration (VHA).Methods: We identified African American and White patients diagnosed with prostate cancer between 2004 and 2015 in SEER (n = 311 691) and the VHA (n = 90 749). We analyzed the association between race and metastatic disease at presentation using multivariable logistic regression adjusting for sociodemographic factors and PCSM using sequential competing-risks regression adjusting for disease and sociodemographic factors.Results: The median follow-up was 5.3 years in SEER and 4.7 years in the VHA. African American men were more likely than White men to present with metastatic disease in SEER (adjusted odds ratio = 1.23, 95% confidence interval [CI] = 1.17 to 1.30) but not in the VHA (adjusted odds ratio = 1.07, 95% CI = 0.98 to 1.17). African American vs White race was associated with an increased risk of PCSM in SEER (subdistribution hazard ratio [SHR] = 1.32, 95% CI = 1.10 to 1.60) but not in the VHA (SHR = 1.00, 95% CI = 0.93 to 1.08). Adjusting for disease extent, prostate-specific antigen, and Gleason score eliminated the association between race and PCSM in SEER (aSHR = 1.04, 95% CI = 0.93 to 1.16).Conclusions: Racial disparities in PCSM were present in a nationally representative registry but not in an equal-access health-care system, because of differences in advanced disease at presentation. Strategies to increase health-care access may bridge the racial disparity in outcomes. Longer follow-up is needed to fully assess mortality outcomes. [ABSTRACT FROM AUTHOR]

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. NLP identifies more patients with mPCa than cancer registries and other structured methods combined. [ABSTRACT FROM AUTHOR]

Background: Black patients with laryngeal squamous cell carcinoma (LSCC) historically have inferior outcomes in comparison with White patients. The authors investigated these racial disparities within the Veterans Health Administration (VHA), an equal‐access system, and within the Surveillance, Epidemiology, and End Results (SEER) program, which is representative of the US hybrid‐payer system. Methods: Patients with invasive (T1 or greater) LSCC were included from SEER (2004‐2015) and the VHA (2000‐2017). The primary outcomes of overall survival (OS) and larynx cancer–specific survival (LCS) were evaluated in Cox and Fine‐Gray models. Results: In the SEER cohort (7122 patients: 82.6% White and 17.4% Black), Black patients were more likely to present with advanced disease and had inferior OS (hazard ratio [HR], 1.37; 95% CI, 1.26‐1.50; P <.0001) in a multivariable analysis. Black LCS was worse in a univariable analysis (HR, 1.42; 95% CI, 1.27‐1.58; P <.0001), but this effect was attenuated by 83% when the authors controlled for the TNM category and was found to be insignificant in a multivariable analysis (HR, 1.05; 95% CI, 0.93‐1.18; P =.42). In the VHA cohort (9248 patients: 79.7% White and 20.3% Black), the 2 racial cohorts presented with similar tumor characteristics and similar OS (HR, 0.95; 95% CI, 0.89‐1.02; P =.14). Black LCS was similar in univariable (HR, 1.10; 95% CI, 1.00‐1.22; P =.05) and multivariable analyses (HR, 1.02; 95% CI, 0.92‐1.14; P =.67). Conclusions: Black patients with LSCC had a tumor burden at diagnosis and survival outcomes comparable to those of White patients within the VHA; this was counter to what was observed in the SEER analysis and prior national trends. This study's findings point toward the notable role of health care access in contributing to racial health disparities in the realm of larynx cancer. Within the "equal‐access" veterans' health system, Black and White patients with larynx cancer have similar disease burdens at diagnosis and similar larynx cancer survival outcomes. These observations, in contrast to Surveillance, Epidemiology, and End Results data, suggest that health care access may be a significant mediator of race‐based larynx cancer survival disparities. [ABSTRACT FROM AUTHOR]

Background: Clinical guidelines recommend that providers risk-stratify patients with cancer before prescribing opioids. Prior research has demonstrated that a simple cancer opioid risk score might help identify to patients with cancer at the time of diagnosis with a high likelihood of long-term posttreatment opioid use. This current project validates this cancer opioid risk score in a generalizable, population-based cohort of elderly cancer survivors.Methods: This study identified 44,932 Medicare beneficiaries with cancer who had received local therapy. Longitudinal opioid use was ascertained from Medicare Part D data. A risk score was calculated for each patient, and patients were categorized into low-, moderate-, and high-risk groups on the basis of the predicted probability of persistent opioid use. Model discrimination was assessed with receiver operating characteristic curves.Results: In the study cohort, 5.2% of the patients were chronic opioid users 1 to 2 years after the initiation of cancer treatment. The majority of the patients (64%) were at low risk and had a 1.2% probability of long-term opioid use. Moderate-risk patients (33% of the cohort) had a 5.6% probability of long-term opioid use. High-risk patients (3.5% of the cohort) had a 75% probability of long-term opioid use. The opioid risk score had an area under the receiver operating characteristic curve of 0.869.Conclusions: This study found that a cancer opioid risk score could accurately identify individuals with a high likelihood of long-term opioid use in a large, generalizable cohort of cancer survivors. Future research should focus on the implementation of these scores into clinical practice and how this could affect prescriber behavior and patient outcomes.Lay Summary: A novel 5-question clinical decision tool allows physicians treating patients with cancer to accurately predict which patients will persistently be using opioid medications after completing therapy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: Neutrophil-lymphocyte ratio has been explored as a prognosticator in several cancer types, but its association with larynx cancer outcomes is not well known. We aimed to identify an optimal NLR cutoff point and examine the prognostic utility of this biomarker in patients with locoregionally advanced larynx cancer treated with curative intent. Methods: In the Veterans Affairs' (VA) national database, we identified patients with locoregionally advanced (T3-4N0-3M0) laryngeal squamous cell carcinoma diagnosed between 2000 and 2017 and treated with curative intent. NLR cutoff points were calculated using Contal/O'Quigley's method. Outcomes of larynx cancer-specific survival (CSS), overall survival (OS), and non-larynx cancer survival (NCS) were evaluated in multivariable Cox and Fine-Gray models. Results: In 1047 patients, the optimal pretreatment NLR cutoff was identified as 4.17 - 722 patients with NLR ⩽ 4.17, 325 patients with NLR > 4.17. The elevated NLR cohort had a higher proportion of T4 disease (39.4% vs 28.4%), node positive disease (52.3% vs 43.1%), and surgical treatment (43.7% vs 35.2%). In multivariable analysis, NLR > 4.17 was independently associated with worse OS (HR 1.31, 95% CI 1.12-1.54, P =.001) and worse CSS (HR 1.46, 95% CI 1.17-1.83, P <.001), but not with NCS (HR 0.94, 95% CI 0.75-1.18, P =.58). Conclusion: In locoregionally advanced larynx cancer treated with curative intent, we identified elevated NLR to be associated with inferior OS and CSS. Further prospective studies are needed to investigate pretreatment NLR and our identified 4.17 cutoff as a potential larynx cancer-specific marker for this high risk population. [ABSTRACT FROM AUTHOR]

Importance: There is concern that African American men with low-risk prostate cancer may harbor more aggressive disease than non-Hispanic White men. Therefore, it is unclear whether active surveillance is a safe option for African American men.Objective: To compare clinical outcomes of African American and non-Hispanic White men with low-risk prostate cancer managed with active surveillance.Design, Setting, and Participants: Retrospective cohort study in the US Veterans Health Administration Health Care System of African American and non-Hispanic White men diagnosed with low-risk prostate cancer between January 1, 2001, and December 31, 2015, and managed with active surveillance. The date of final follow-up was March 31, 2020.Exposures: Active surveillance was defined as no definitive treatment within the first year of diagnosis and at least 1 additional surveillance biopsy.Main Outcomes and Measures: Progression to at least intermediate-risk, definitive treatment, metastasis, prostate cancer-specific mortality, and all-cause mortality.Results: The cohort included 8726 men, including 2280 African American men (26.1%) (median age, 63.2 years) and 6446 non-Hispanic White men (73.9%) (median age, 65.5 years), and the median follow-up was 7.6 years (interquartile range, 5.7-9.9; range, 0.2-19.2). Among African American men and non-Hispanic White men, respectively, the 10-year cumulative incidence of disease progression was 59.9% vs 48.3% (difference, 11.6% [95% CI, 9.2% to 13.9%); P < .001); of receipt of definitive treatment, 54.8% vs 41.4% (difference, 13.4% [95% CI, 11.0% to 15.7%]; P < .001); of metastasis, 1.5% vs 1.4% (difference, 0.1% [95% CI, -0.4% to 0.6%]; P = .49); of prostate cancer-specific mortality, 1.1% vs 1.0% (difference, 0.1% [95% CI, -0.4% to 0.6%]; P = .82); and of all-cause mortality, 22.4% vs 23.5% (difference, 1.1% [95% CI, -0.9% to 3.1%]; P = 0.09).Conclusions and Relevance: In this retrospective cohort study of men with low-risk prostate cancer followed up for a median of 7.6 years, African American men, compared with non-Hispanic White men, had a statistically significant increased 10-year cumulative incidence of disease progression and definitive treatment, but not metastasis or prostate cancer-specific mortality. Longer-term follow-up is needed to better assess the mortality risk. [ABSTRACT FROM AUTHOR]

Background: Ultrahypofractionation using stereotactic body radiotherapy (SBRT) is an increasingly utilized technique for men with prostate cancer (PC). The comparative efficacy of SBRT plus androgen deprivation therapy (ADT) compared to fractionated radiotherapy (EBRT) plus ADT in higher-risk prostate cancer is unknown.Methods: Men > 40 years old with localized PC treated with external beam radiation and concomitant ADT for curative intent between 2004 and 2016 were analyzed from the National Cancer Database. Patients who lacked ADT or risk stratification data were excluded. 558 men treated with SBRT versus 40,797 men treated with conventional or moderately hypofractionated EBRT were included. Patients were stratified by unfavorable intermediate (UIR) and high (HR) risk using NCCN criteria. Kaplan Meier and Cox proportional hazards were used to compare overall survival (OS) between RT modality, adjusting for age, race, and comorbidity index.Results: With a median follow up of 74 months, there was no difference in estimated 6-year OS between men treated with SBRT versus EBRT regardless of risk group. On multivariable analysis, there was no difference in risk of death for men treated with SBRT compared to EBRT (UIR: adjusted HR 1.09, 95% CI 0.68-1.74, p = .72; HR: adjusted HR 0.93, 95% CI 0.76-1.14, p = .51). On sensitivity analyses, when confining the cohort to men treated with NCCN-preferred dose fractionations, with no comorbidities, or < 65 years old, there remained no survival difference between treatment groups for both UIR and HR.Conclusion: Within study limitations, we found no difference in survival between SBRT+ADT and standard of care EBRT+ADT for UIR or HR PC. These results support recent NCCN guideline updates, which include SBRT as a non-preferred option for higher risk men. Prospective validation would further strengthen the evidence basis behind these recommendations. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: Inflammatory bowel disease (IBD) is a known risk factor for rectal cancer, and RT is often an important part of therapy for these patients. Previously published studies have raised concerns for increased rates of RT toxicity in patients with IBD. We performed a matched case-control analysis to assess RT-related toxicity in a large sample of U.S. veterans afflicted with IBD and rectal cancer.Methods and Materials: We identified 186 veterans with rectal cancer (71 Patients with IBD treated with RT, 71 matched controls without IBD treated with RT, and 44 nonmatched controls with IBD treated without RT) diagnosed between 2000 and 2015. We analyzed short- and long-term toxicity and mortality in multivariable logistic regression, Fine-Gray, and frailty models, adjusting for potential confounders.Results: When comparing patients with and without IBD treated with RT there were no differences in RT breaks (adjusted odds ratio [aOR], 1.70; 95% confidence interval [CI], 0.38-4.76; P = .49) or the need for antidiarrheal medication during RT (aOR, 1.53; 95% CI, 0.70-3.35; P = .29). There was a trend toward higher risk of hospital admission during RT for RT + patients with IBD (aOR, 2.69; 95% CI, 0.88-8.22; P = .08). There were higher rates of small bowel obstruction (OR, 15; 95% CI, 1.9-115; P = .009) and a trend toward higher rates of abdominopelvic adhesions (OR, 3.6; 95% CI, 0.98-13; P = .05) in the RT + IBD cohort. However, compared with a nonmatched cohort of patients with IBD treated without RT there were no differences in long-term complications. No differences were found in other acute or long-term toxicities. Rectal cancer-specific mortality appeared similar across all cohorts.Conclusions: RT does not appear to increase the rates of acute or long-term toxicity in patients with IBD and should be considered a standard part of therapy when otherwise indicated. [ABSTRACT FROM AUTHOR]

Survival analyses appropriately account for these possibilities, permitting inclusion of early PCa diagnoses in analyses of critical endpoints that early detection strategies intend to avoid (metastatic or fatal PCa). We thank the writers for their interest in our work and for their important contributions to prostate cancer (PCa) genetics. We included 3 endpoints: PCa incidence, metastatic PCa, and fatal PCa. [Extracted from the article]