An interdisciplinary consensus on the management of brain metastases in patients with renal cell carcinoma.

Brain metastases are a challenging manifestation of renal cell carcinoma. We have a limited understanding of brain metastasis tumor and immune biology, drivers of resistance to systemic treatment, and their overall poor prognosis. Current data support a multimodal treatment strategy with radiation treatment and/or surgery. Nonetheless, the optimal approach for the management of brain metastases from renal cell carcinoma remains unclear. To improve patient care, the authors sought to standardize practical management strategies. They performed an unstructured literature review and elaborated on the current management strategies through an international group of experts from different disciplines assembled via the network of the International Kidney Cancer Coalition. Experts from different disciplines were administered a survey to answer questions related to current challenges and unmet patient needs. On the basis of the integrated approach of literature review and survey study results, the authors built algorithms for the management of single and multiple brain metastases in patients with renal cell carcinoma. The literature review, consensus statements, and algorithms presented in this report can serve as a framework guiding treatment decisions for patients. CA Cancer J Clin. 2022;72:454-489.

Prognosis and risk of suicide after cancer diagnosis.

INTRODUCTION: Suicide rates are elevated after cancer diagnosis. Existential distress caused by awareness of one's impending death is well-described in patients with cancer. The authors hypothesized that suicide risk is associated with cancer prognosis, and the impact of prognosis on suicide risk is greatest for populations with higher baseline suicide risk. METHODS: The authors identified patients (≥16 years old) with newly diagnosed cancers from 2000 to 2019 in the Surveillance, Epidemiology, and End Results database, representing 27% of US cancers. Multiple primary-standardized mortality ratios (SMR) were used to estimate the relative risk of suicide within 6 months of diagnosis compared to the general US population, adjusted for age, sex, race, and year of follow-up. Suicide rates by 20 most common cancer sites were compared with respective 2-year overall survival rates (i.e., prognosis) using a weighted linear regression model. RESULTS: Among 6,754,704 persons diagnosed with cancer, there were 1610 suicide deaths within 6 months of diagnosis, three times higher than the general population (SMR = 3.1; 95% confidence interval, 3.0-3.3). Suicide risk by cancer site was closely associated with overall prognosis (9.5%/percent survival deficit, R2  = 0.88, p < .0001). The association of prognosis with suicide risk became attenuated over time. For men, the risk of suicide increased by 2.8 suicide deaths per 100,000 person-years (p < .0001) versus 0.3 in women (p < .0001). The risk was also higher for persons ≥60 old and for the White (vs. Black) race. CONCLUSIONS: Poorer prognosis was closely associated with suicide risk early after cancer diagnosis and had a greater effect on populations with higher baseline risks of suicide. This model highlights the need for enhanced psychiatric surveillance and continued research in this patient population.

MGMT promoter methylation in 1p19q-intact gliomas.

OBJECTIVE: Standard-of-care for 1p19q-intact anaplastic gliomas is defined by the international randomized phase III CATNON trial, which found an overall survival (OS) benefit for adjuvant temozolomide (TMZ) when added to radiotherapy. Paradoxically, TMZ did not appear to benefit patients with IDH-wildtype gliomas, regardless of MGMT promoter status. The authors concluded that well-powered prospective study on the clinical efficacy of TMZ for patients with IDH-wildtype anaplastic gliomas (meeting criteria for glioblastoma) is warranted. Given that the prognostic and predictive role of MGMT status for grade 2-3 gliomas is unresolved, we determined the effect of MGMT status on OS in patients with 1p19q-intact gliomas in the National Cancer Database (NCDB). METHODS: We queried the NCDB from 2018 to 2019 for patients with diffuse (grade 2) and anaplastic (grade 3) IDH-wildtype or -mutant astrocytomas who received chemotherapy with follow-up through 2022. The Kaplan-Meier method and Cox proportional hazards regressions models were used to determine the association of MGMT with OS. RESULTS: We identified 1514 patients who were newly diagnosed with IDH-wildtype (n = 802, 33% methylated) or -mutant astrocytomas (n = 712, 48% methylated) and received chemotherapy during initial management. An unmethylated promoter was associated with poorer survival in patients with IDH-wildtype (3-year OS 34% [95%CI 29-39%] vs. 46% [95%CI 39-54%], p < .001, adjusted HR 1.53 [95%CI 1.24-1.89]) but not IDH-mutant astrocytomas (3-year OS 79% [95%CI 74-84%] vs. 80% [95%CI 75-86%], p =0 .81, HR 1.04 [95%CI 0.73-1.50]). CONCLUSIONS: This ancillary analysis supports conclusions from the CATNON trial for adjuvant TMZ as standard-of-care for anaplastic astrocytomas (IDH-mutant and 1p19q-intact), irrespective of MGMT status. Determining the optimal strategy for diffuse gliomas that are IDH-wildtype will be particularly important. MGMT promoter methylation should be considered as a stratification factor in future clinical trials for these patients.

2023 Radiation oncology highlights.

Radiation oncology plays an important role in the local treatment of cancers. Understanding recent advances in the application of radiation therapy to solid tumors is important for all disciplines. The radiation oncology section editors for this journal have selected the following articles for their overall significance, relevance to surgical oncologists, and to illustrate important concepts within the practice of radiation oncology.

Emergency department visits for radiation cystitis among patients with a prostate cancer history.

OBJECTIVES: To elucidate the national burden of emergency department (ED) visits for radiation cystitis (RC), a known complication of radiation therapy (RT) to the pelvic area, among patients with a prostate cancer history, and identify those who are at increased risk of requiring invasive measures. PATIENTS AND METHODS: This study queried the Nationwide Emergency Department Sample for all ED visits from January 2006 to December 2015 with a primary diagnosis of RC and secondary diagnosis of prostate cancer. ED visits were characterised by demographic factors, socioeconomic factors, and hospital characteristics. Weighted frequencies were used to create national estimates for all data analysis. RESULTS: A weighted total of 17 382 ED visits occurred for RC among patients with a prostate cancer history, of which 9655 (55.5%) were treated with an invasive procedure. Notable factors associated with undergoing an invasive procedure included having a prior prostatectomy (odds ratio [OR] 5.48, 95% confidence interval [CI] 2.62-11.46), urinary retention (OR 1.35, 95% CI 1.12-1.64), haematuria (OR 1.20, 95% CI 1.01-1.42), and undergoing a blood transfusion (OR 2.12, 95% CI 1.72-2.62). ED visits that were associated with invasive procedures had a higher median total charge ($34 707.53 vs $15 632.53) and an increased median length of stay (5 vs 3 days) compared to visits without an invasive procedure. CONCLUSIONS: Among ED visits for RC in prostate cancer, approximately one half required an invasive procedure for treatment. While RT remains an effective modality for patients with prostate cancer, providers should be mindful of RC as a potential complication.

National Quality Measure Compliance for Palliative Bone Radiation Among Patients With Metastatic Non-Small Cell Lung Cancer.

BACKGROUND: There exists wide practice variability in palliative treatment schedules for bone metastases. In an effort to reduce variation and promote high-quality, cost-conscious care, the National Quality Forum (NQF) endorsed measure 1822 in 2012. This measure recommends the use of 30 Gy in 10 fractions, 24 Gy in 6 fractions, 20 Gy in 5 fractions, or 8 Gy in a single fraction for palliative radiation for bone metastases. We report on longitudinal compliance with this measure. METHODS: Using the National Cancer Database, patients with metastatic thoracic non-small cell lung cancer diagnosed between 2004 and 2016 who received radiation therapy for bony sites of metastatic disease were identified. Treatment courses fitting 1 of the 4 recommended schedules under NQF 1822 were coded as compliant. Rates of compliance by patient, tumor, and treatment characteristics were analyzed. RESULTS: A total of 42,685 patients met the criteria for inclusion. Among all patients, 60.2% of treatment courses were compliant according to NQF 1822. Compliance increased over time and was highest for treatments to the extremity (69.8%), lowest for treatments to the skull or head (48.8%), and higher for academic practice (67.1%) compared with community (56.0%) or integrated network facilities (61.2%). On multivariable analysis, predictors of NQF 1822 compliance included year of diagnosis after 2011, treatment to an extremity, or treatment at an academic facility. Of noncompliant treatment courses, extended fractionation (≥11 fractions) occurred in 62.6% and was more common before 2012, in community practice, and for treatments of the skull or head. CONCLUSIONS: Among patients treated for metastatic non-small cell lung cancer, compliance with NQF 1822 increased over time. Although extended fractionation constituted a majority of noncompliant treatment courses, a substantial proportion also involved shorter courses.

Incidence and characteristics of metastatic intracranial lesions in stage III and IV melanoma: a single institute retrospective analysis.

INTRODUCTION: The study aimed to describe the brain metastases (BM) incidence, at diagnosis and follow-up, in patients initially presenting with stage III or IV melanoma and characterize their metastatic brain lesions. We also sought to describe the association of common genetic mutations and immunotherapy with BM development in advanced melanoma. METHODS: Using our institution's tumor registry, we identified patients with initial diagnoses of stage III and stage IV melanoma. In this cohort, we obtained BM incidence at diagnosis and follow-up, characterized the metastatic brain lesions and primary tumor's genetic profile. RESULTS: During the follow-up period, 22.9% of patients with an initial diagnosis of stage III developed BM. In this cohort, the median time for BM occurrence was 20 months; [95% CI (14-29)]. Likewise, 37.7% of patients with Stage IV melanoma presented with BM at the time of diagnosis, and 22.7% of remaining patients developed BM at follow-up over a median duration of 6 months [95% CI (4-11)]. Therefore, suggesting an overall incidence of 51.9% in stage IV melanoma. Next, we observed that the incidence of BM development during the follow-up period significantly decreased from 2012 to 2017 (p < 0.001). Lastly, we found a significantly higher frequency of mutational BRAF in the primary tumor of patients with BM (68.7% vs. 31.2%; p = 0.02). CONCLUSIONS: While the overall incidence of BM remains high, the decreasing incidence of BM over the follow-up period is promising. Similar BM incidence in patients with an initial diagnosis of stage III or stage IV warrants appropriate imaging surveillance regimen for stage III patients.

National trends in the management of patients with positive surgical margins at radical prostatectomy.

PURPOSE: To evaluate practice patterns of planned post-operative radiation therapy (RT) among men with positive surgical margins (PSM) at radical prostatectomy. METHODS: We identified 43,806 men within the National Cancer Database with pathologic node-negative prostate cancer diagnosed in 2010 through 2014 with PSM. The primary endpoint was receipt of planned (RT) within a patient's initial course of treatment. We examined post-RP androgen deprivation therapy (ADT) with RT as a secondary endpoint. We evaluated patterns of post-operative management and characteristics associated with planned post-prostatectomy RT. RESULTS: Within 12 months of RP, 87.0% received no planned RT, 8.5% RT alone, 1.3% ADT alone, and 3.1% RT with ADT. In a multivariable logistic regression model, planned RT use was associated with clinical and pathologic characteristics as estimated by surgical Cancer of the Prostate Risk Assessment (CAPRA-S) category (intermediate versus low, OR = 2.87, 95% CI 2.19-3.75, P < 0.001; high versus low, OR = 10.23, 95% CI 7.79-13.43, P < 0.001), treatment at community versus academic centers (OR = 1.24, 95% CI 1.15-1.34, P < 0.001), shorter distance to a treatment facility (OR = 0.97 for each 10-mile, 95% CI 0.96-0.98, P < 0.001), and uninsured status (OR = 1.39, 95% CI 1.10-1.77, P = 0.005). The odds of receiving planned RT were lower in 2014 versus 2010 (OR = 0.76, 95% CI 0.68-0.85, P < 0.001). There was no significant change in the use of ADT with RT. High versus low CAPRA-S category was associated with the use of ADT in addition to RT (OR = 5.13, 95% CI 1.57-16.80, P = 0.007). CONCLUSION: The use of planned post-prostatectomy RT remained stable among patients with PSM and appears driven primarily by the presence of other adverse pathologic features.

Pembrolizumab for management of patients with NSCLC and brain metastases: long-term results and biomarker analysis from a non-randomised, open-label, phase 2 trial.

BACKGROUND: We did a phase 2 trial of pembrolizumab in patients with non-small-cell lung cancer (NSCLC) or melanoma with untreated brain metastases to determine the activity of PD-1 blockade in the CNS. Interim results were previously published, and we now report an updated analysis of the full NSCLC cohort. METHODS: This was an open-label, phase 2 study of patients from the Yale Cancer Center (CT, USA). Eligible patients were at least 18 years of age with stage IV NSCLC with at least one brain metastasis 5-20 mm in size, not previously treated or progressing after previous radiotherapy, no neurological symptoms or corticosteroid requirement, and Eastern Cooperative Oncology Group performance status less than two. Modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria was used to evaluate CNS disease; systemic disease was not required for participation. Patients were treated with pembrolizumab 10 mg/kg intravenously every 2 weeks. Patients were in two cohorts: cohort 1 was for those with PD-L1 expression of at least 1% and cohort 2 was patients with PD-L1 less than 1% or unevaluable. The primary endpoint was the proportion of patients achieving a brain metastasis response (partial response or complete response, according to mRECIST). All treated patients were analysed for response and safety endpoints. This study is closed to accrual and is registered with ClinicalTrials.gov, NCT02085070. FINDINGS: Between March 31, 2014, and May 21, 2018, 42 patients were treated. Median follow-up was 8·3 months (IQR 4·5-26·2). 11 (29·7% [95% CI 15·9-47·0]) of 37 patients in cohort 1 had a brain metastasis response. There were no responses in cohort 2. Grade 3-4 adverse events related to treatment included two patients with pneumonitis, and one each with constitutional symptoms, colitis, adrenal insufficiency, hyperglycaemia, and hypokalaemia. Treatment-related serious adverse events occurred in six (14%) of 42 patients and were pneumonitis (n=2), acute kidney injury, colitis, hypokalaemia, and adrenal insufficiency (n=1 each). There were no treatment-related deaths. INTERPRETATION: Pembrolizumab has activity in brain metastases from NSCLC with PD-L1 expression at least 1% and is safe in selected patients with untreated brain metastases. Further investigation of immunotherapy in patients with CNS disease from NSCLC is warranted. FUNDING: Merck and the Yale Cancer Center.

Geographic-Level Association of Contemporary Changes in Localized and Metastatic Prostate Cancer Incidence in the Era of Decreasing PSA Screening.

Decreased prostate-specific antigen screening since 2008 has generated much concern, including report of recent increase in metastatic prostate cancer incidence among older men. Although increased metastatic disease was temporally proceeded by decreased screening and decreased localized prostate cancer at diagnosis, it is unclear whether the 2 trends are geographically connected. We therefore used the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) database to assess geographic-specific associations between changes in localized (2008-2011) and later changes in metastatic prostate cancer incidence (2012-2015). We examined trends from 200 health-care service areas (HSAs) within SEER 18 registries. While on average for each HSA, localized incidence decreased by 27.4 and metastatic incidence increased by 2.3 per 100 000 men per year, individual HSA-level changes in localized incidence did not correlate with later changes in metastatic disease. Decreased detection of localized disease may not fully explain the recent increase in metastatic disease at diagnosis.

Resident attitudes and benefits of mock oral board examinations in radiation oncology.

BACKGROUND: Presently, educational programming is not standardized across radiation oncology (RO) training programs. Specifically, there are limited materials through national organizations or structured practice exams for residents preparing for the American Board of Radiology (ABR) oral board examination. We present our 2019 experience implementing a formalized program of early mock oral board examinations (MOBE) for residents in post-graduate years (PGY) 3-5. METHODS: A mixed-methods survey regarding MOBE perception and self-reported comfort across five clinical domains were administered to PGY2-5 residents. MOBEs and a post-intervention survey were implemented for the PGY3-5. The pre and post-intervention score across clinical domains were compared using t-tests. Faculty and residents were asked for post-intervention comments. RESULTS: A total of 14 PGY2-5 residents completed the pre-intervention survey; 9 residents participated in the MOBE (5/14 residents were PGY2s) and post-intervention survey. This was the first mock oral radiation oncology examination experience for 65% of residents. 100% of residents felt the MOBE increased their clinical knowledge and comfort with clinical reasoning. Overall, there was a trend towards improved resident confidence giving planning dose parameters and (p = 0.08). There was also unanimous request for more MOBE experiences from residents and faculty, but time was identified as a significant barrier. CONCLUSIONS: Future directions for this MOBE program are inclusion of more disease sites, better emulation of the exam, the creation of a more rigorous consolidated format testing all sites at once, and consideration for grading of these sessions for future correlation with certifying oral board examination (OBE) performance.

Conservative management of low-risk prostate cancer among young versus older men in the United States: Trends and outcomes from a novel national database.

BACKGROUND: Management for men aged ≤55 years with low-risk prostate cancer (LRPC) is debated given quality-of-life implications with definitive treatment versus the potential missed opportunity for cure with conservative management. The objective of this study was to define rates of conservative management for LRPC and associated short-term outcomes in young versus older men in the United States. METHODS: The nonpublic Surveillance, Epidemiology, and End Results Prostate with Active Surveillance/Watchful Waiting (AS/WW) Database identified 50,302 men who were diagnosed with LRPC from 2010 through 2015. AS/WW rates in the United States were stratified by age (≤55 vs ≥56 years). Prostate cancer-specific mortality and overall mortality were defined by initial management type (AS/WW vs definitive treatment [referent]) and age. RESULTS: AS/WW utilization increased from 8.61% (2010) to 34.56% (2015) among men aged ≤55 years (P for trend <0.001) and from 15.99% to 43.81% among men aged ≥56 years (P for trend <.001). Among patients who had ≤2 positive biopsy cores, AS/WW rates increased from 12.90% to 48.78% for men aged ≤55 years and from 21.85% to 58.01% for men aged ≥56 years. Among patients who had ≥3 positive biopsy cores, AS/WW rates increased from 3.89% to 22.45% for men aged ≤55 years and from 10.05% to 28.49% for men aged ≥56 years (all P for trend <.001). Five-year prostate cancer-specific mortality rates were <0.30% across age and initial management type subgroups. CONCLUSIONS: AS/WW rates quadrupled for patients aged ≤55 years from 2010 to 2015, with favorable short-term outcomes. These findings demonstrate the short-term safety and increasing acceptance of AS/WW for both younger and older patients. However, there are still higher absolute rates of AS/WW in older patients (P < .001), suggesting some national ambivalence toward AS/WW in younger patients.

Association between prolonged metastatic free interval and recurrent metastatic breast cancer survival: findings from the SEER database.

PURPOSE: The prevalence of patients living with prolonged interval between initial breast cancer diagnosis and development of subsequent metastatic disease may be increasing with improved treatment. In order to counsel these patients as to their prognosis, we investigated the association between metastatic free interval (MFI) and subsequent survival from newly diagnosed metastatic breast cancer (MBC) in a population-level U.S. cohort. METHODS: The Surveillance, Epidemiology and End Results database was used to identify patients with both an initial stage 1-3 breast cancer diagnosis and subsequent MBC diagnosis recorded from 1988 to 2014. Patients were stratified by MFI (< 5 years, 5-10 years, > 10 years). The association between MFI and metastatic breast cancer-specific mortality (MBCSM) was analyzed with Fine-Gray competing risks regression. RESULTS: Five-year recurrent metastatic breast cancer-specific survival rate was 23%, 26%, and 35% for patients with MFI < 5, 5-10, and > 10 years, respectively. Patients with > 10 year MFI were less likely to die of breast cancer when compared with a referent group with < 5 years MFI (standard hazard ratio (SHR) 0.77 [95% CI 0.65-0.90] P < 0.001). There was no significant difference for patients with MFI of 5-10 years (SHR 0.92 [95% CI 0.81-1.04, P 0.191]) compared to < 5 years. Other prognostic factors like White race, lower tumor grade, and ER/PR-positive receptors were also associated with improved cancer-specific survival after diagnosis of MBC. CONCLUSION: Prolonged MFI greater than 10 years between initial breast cancer diagnosis and subsequent metastatic disease was found to be associated with improved recurrent MBC 5-year survival and decreased risk of breast cancer-specific mortality. This has potential implications for counseling patients as to prognosis, choice of treatment, as well as the stratification of patients considered for MBC clinical trials.

Perceptions of Barriers Towards Active Surveillance for Low-Risk Prostate Cancer: Results From a National Survey of Radiation Oncologists and Urologists.

PURPOSE: The reasons for low clinical adoption of active surveillance (AS) for low-risk prostate cancer (PCa) remain poorly understood. Thus, we conducted a national survey of radiation oncologists (ROs) and urologists (UROs) to elucidate perceived barriers to AS for low-risk PCa. METHODS: In 2017, we undertook a four-wave mail survey of 1855 ROs and UROs. The survey instrument assessed attitudes about possible barriers towards AS for low-risk PCa. We used Pearson Chi square and multivariable logistic regression analyses to identify physician characteristics associated with attitudes about AS. RESULTS: We received 691 completed surveys for an overall response rate of 37.3%. A majority of respondents indicated that they felt comfortable recommending AS (90.0%), agreed that high-level evidence supports it (82.3%), and considered AS equally effective for survival compared with surgery and radiation therapy (84.4%). UROs were less likely to agree that patients were not interested in AS for low-risk PCa compared with ROs (16.5 vs. 48.9%; adjusted odds ratio [OR] 0.18, p < 0.001). Similarly, UROs were less likely to concur patients avoid AS because of repeat prostate biopsies than ROs (36.3 vs. 55.4%; adjusted OR 0.41, p < 0.001). ROs and UROs were more likely to agree that patients preferred treatments delivered by the respondent's specialty. CONCLUSIONS: Physician perceptions of patient lack of interest in AS, need for repeat prostate biopsies, and biases of patient treatment preferences in favor of their own specialty treatments represent key barriers to AS. Shared decision making may be a meaningful approach to engaging patients in conversations about treatment decisions.

The case for radiotherapy in a Value based environment.

AIM: Describe the Value proposition for radiotherapy (RT) in the United States. BACKGROUND: In the United States since 2005, two forces have worked to decrease RT cost per patient: Federal changes in reimbursement and hypofractionation of treatment courses. We theorize that these have driven stable reimbursement in the context of increasing technology of intensity modulation (IMRT) and image guidance (IGRT). This phenomenon provides increasing Value of the discipline to patients and systems. MATERIALS AND METHODS: We searched the Medicare Physician/Supplier data for Program Payments per Person with Utilization for 2000 through 2016. This involves two databases: Enrollment Database (EDB) for 2000-2012 and Common Medicare Enrollment (CME) since 2013. RT payments to individual patients accessing services were retrieved. RESULTS: Taking into account the change of calculation algorithm used by CMS in 2013, costs per patient were similar in 2012 and 2003, and 2016 and 2013. CONCLUSIONS: In the United States, stabilizing costs in the face of increasing work, better outcomes, and decreased toxicity contributes to increasing RT value over the past 10 years.

Prostate cancer outcomes for men aged younger than 65 years with Medicaid versus private insurance.

BACKGROUND: In the current national debate regarding private insurance versus Medicaid expansion, understanding how insurance is associated with racial disparities in prostate cancer (CaP) outcomes has broad policy implications. In the current study, the authors examined the association between insurance status, race, and CaP outcomes. METHODS: The Surveillance, Epidemiology, and End Results program identified 155,524 men aged < 65 years who were diagnosed with CaP from 2007 through 2014. The association between insurance and stage of disease at the time of presentation was examined. Among men with localized CaP, the associations between insurance and receipt of therapy and prostate cancer-specific mortality (PCSM) were determined. RESULTS: Compared with private insurance, men with Medicaid were more likely to present with metastatic disease (adjusted odds ratio [AOR], 4.27; 95% confidence interval [95% CI], 4.01-4.55), were less likely to receive definitive treatment (AOR, 0.67; 95% CI, 0.62-0.71), and had increased PCSM (adjusted hazard ratio, 1.83; 95% CI, 1.50-2.24), regardless of race. Significant interactions between race and insurance status indicated that insurance had more than an additive association with race. Among privately insured patients, disparities in PCSM (AOR, 1.2; 95% CI, 1.03-1.40 [P = .019]) and presentation with metastatic disease (AOR, 1.13; 95% CI, 1.06-1.21 [P<.001]) were observed. No disparities were observed among patients with Medicaid insurance with regard to PCSM (AOR, 0.79; 95% CI, 0.52-1.20 [P = .272]) and metastatic disease (AOR, 0.91; 95% CI, 0.80-1.03 [P = .139]). CONCLUSIONS: Racial disparities in the outcomes of patients with CaP were observed in privately insured cohorts, whereas these disparities appeared to be reduced among patients with Medicaid insurance. However, outcomes need to be improved overall. Whether the equality in outcomes for Medicaid is due to white and African American patients doing "equally poorly" or "equally well" is unclear. Cancer 2018;124:752-9. © 2017 American Cancer Society.

Travel distance and stereotactic body radiotherapy for localized prostate cancer.

BACKGROUND: Definitive stereotactic body radiotherapy (SBRT) represents an emerging and debated treatment option for patients with prostate cancer, with potential economic savings and reports of short-term efficacy since 2006. The current study sought to define national trends in definitive prostate SBRT use and determine whether patterns vary by travel distance for treatment. METHODS: The National Cancer Data Base identified 181,544 men with localized prostate cancer who were treated with definitive external beam radiotherapy from 2004 through 2012. Joinpoint regression analyzed definitive prostate SBRT trends over time, whereas multivariable logistic regression defined the odds for its receipt by travel distance for treatment. RESULTS: Definitive prostate SBRT use increased from 1.8% in 2004 to 5.9% in 2012 (P for trend <.0001), with a joinpoint for increased use noted in 2006 (P<.0001). Higher SBRT use was found to be associated with longer travel distance for treatment, younger age, white race, more affluent zip code of residence, academic treatment center, favorable disease characteristics, and fewer comorbidities (all P<.0001). Compared with travel distances <25 miles for treatment, travel distances of 25 to 50 miles and >50 miles were associated with increasing adjusted odds of receipt of definitive prostate SBRT (1.63 [95% confidence interval, 1.51-1.76] and 2.35 [95% confidence interval, 2.14-2.57], respectively; both P < .0001). CONCLUSIONS: Definitive prostate SBRT use increased more than 3-fold since 2004, with a significant increase in use coinciding with early reports of short-term efficacy. Long-distance travel for treatment was associated with greater than twice the odds of receipt of definitive prostate SBRT compared with short-distance travel, suggesting that treatment decisions with unknown long-term clinical implications may be strongly driven by sociodemographic factors. Cancer 2018;124:1141-9. © 2017 American Cancer Society.

Angiotensin receptor blockade: a novel approach for symptomatic radiation necrosis after stereotactic radiosurgery.

Preclinical evidence suggests angiotensin blockade therapy (ABT) decreases late radiation toxicities. This study aims to investigate the association between ABT and symptomatic radiation necrosis (SRN) following stereotactic radiosurgery (SRS). Resected brain metastases (rBM) and arteriovenous malformation (AVM) patients treated with SRS from 2002 to 2015 were identified. Patients in the ABT cohort were on therapy during SRS and at 1-month follow up. Kaplan Meier method and cumulative incidence model were used to analyze overall survival (OS) and intracranial outcomes. 228 consecutive patients were treated with SRS: 111 with rBM and 117 with AVM. Overall, 51 (22.4%) patients were in the ABT group: 32 (28.8%) in the rBM and 19 (16.2%) in AVM cohorts. Baseline characteristics were similar, except for higher Graded Prognostic Analysis (3-4) in the rBM (ABT: 25.0% vs. non-ABT: 49.0%, p = 0.033) and median age in the AVM (ABT: 51.4 vs. non-ABT: 35.4, p < 0.001) cohorts. In both populations, OS and intracranial efficacy (rBM-local control; AVM-obliteration rates) were statistically similar between the cohorts. ABT was associated with lower 1-year SRN rates in both populations: rBM, 3.1 versus 25.3% (p = 0.003); AVM, 6.7 vs. 14.6% (p = 0.063). On multivariate analysis, ABT was a significant predictive factor for rBM (HR: 0.17; 95% CI 0.03-0.88, p = 0.035), but did not reach statistical significance for AVM (HR: 0.36; 95% CI 0.09-1.52, p = 0.165). ABT use appears to be associated with a reduced risk of SRN following SRS, without detriment to OS or intracranial efficacy. A prospective trial to validate these findings is warranted.

Bladder Preserving Trimodality Therapy for Muscle-Invasive Bladder Cancer.

PURPOSE OF REVIEW: Here, we will review and summarize the current status and emerging data supporting the use of trimodality therapy as an alternative to cystectomy for patients with muscle-invasive bladder cancer. RECENT FINDINGS: There are no randomized-controlled data comparing radical cystectomy with bladder preserving trimodality therapy available for comparison. However, observational data suggests acceptable bladder preservation and functional outcomes in patients receiving bladder preserving trimodality therapy as well as similar oncologic outcomes in select patients compared to radical cystectomy. Future trials are focusing on new techniques and novel therapeutics in patients with bladder cancer. Bladder preserving trimodality therapy results in satisfactory quality of life and comparable disease outcomes for select patients with muscle-invasive urothelial carcinoma of the bladder compared to cystectomy.

Myelodysplastic Syndromes and Acute Myeloid Leukemia After Radiotherapy for Prostate Cancer: A Population-Based Study.

BACKGROUND: To understand the impact of radiotherapy on the development of myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) among elderly prostate cancer patients. METHODS: We performed a retrospective cohort study of elderly prostate cancer patients diagnosed during 1999-2011 by using the National Cancer Institute's Surveillance, Epidemiology and End Results-Medicare linked database. Competing risk analyses adjusting for patient characteristics were conducted to assess the impact of radiotherapy on the development of subsequent MDS/AML, compared with surgery. RESULTS: Of 32,112 prostate cancer patients, 14,672 underwent radiotherapy, and 17,440 received surgery only. The median follow-up was 4.68 years. A total of 157 (0.47%) prostate cancer patients developed subsequent MDS or AML, and the median time to develop MDS/AML was 3.30 (range: 0.16-9.48) years. Compared with prostate cancer patients who received surgery only, patients who underwent radiotherapy had a significantly increased risk of developing MDS/AML (hazard ratio [HR] =1.51, 95% confidence interval [CI]: 1.07-2.13). When radiotherapy was further categorized by modalities (brachytherapy, conventional conformal radiotherapy, and intensity-modulated radiotherapy [IMRT]), increased risk of second MDS/AML was only observed in the IMRT group (HR = 1.66, 95% CI: 1.09-2.54). CONCLUSIONS: Our findings suggest that radiotherapy for prostate cancer increases the risk of MDS/AML, and the impact may differ by modality. Additional studies with longer follow-up are needed to further clarify the role of radiotherapy in the development of subsequent myeloid malignancies. A better understanding may help patients, physicians, and other stakeholders make more informed treatment decisions. Prostate 77:437-445, 2017. © 2016 Wiley Periodicals, Inc.