Sebastian Berg

Characterizing trends in treatment modalities for localized muscle-invasive bladder cancer in the pre-immunotherapy era

IntroductionMuscle-invasive bladder cancer (MIBC) is an aggressive disease for which treatment strategies are continuously evolving. We characterized trends in treatment modalities for MIBC from 2004 to 2013 (the “pre-immunotherapy era”) and identified predictors of receiving the current standard of care treatment: neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC).MethodsWe used the National Cancer Database to identify individuals diagnosed with clinically localized MIBC from 2004 to 2013. We calculated the yearly prevalence of NAC followed by RC, RC as first treatment, trimodal therapy, chemotherapy and/or radiation alone, and no treatment. We then identified factors associated with receiving NAC prior to RC.ResultsThere was a notable increase in the use of NAC followed by RC over the study period, from 3.68% in 2004 to 14.83% in 2013 (P < 0.001). Factors associated with decreased odds of receiving this regimen included being older, Black, uninsured, less educated, and more burdened by comorbidities. Rates of trimodal therapy and chemotherapy and/or radiation alone remained relatively constant (approximately 5 and 17%, respectively). There was a consistent decline in the proportion of patients who did not receive any treatment, down to 34.20% in 2013.ConclusionTrends in localized MIBC treatment have evolved substantially since the early 2000s, and certain patient characteristics are associated with lower odds of receiving the current standard of care. This serves as a foundation from which to judge the impact of the upcoming immunotherapy era on the treatment landscape for this disease.

Rho-associated protein kinase 2 (ROCK2): a new target of autoimmunity in paraneoplastic encephalitis

Onconeural antibodies are associated with cancer and paraneoplastic encephalitis. While their pathogenic role is still largely unknown, their high diagnostic value is undisputed. In this study we describe the discovery of a novel target of autoimmunity in an index case of paraneoplastic encephalitis associated with urogenital cancer.A 75-year-old man with a history of invasive bladder carcinoma 6 years ago with multiple recurrences and a newly discovered renal cell carcinoma presented with seizures and progressive cognitive decline followed by super-refractory status epilepticus. Clinical and ancillary findings including brain biopsy suggested paraneoplastic encephalitis. Immunohistochemistry of the brain biopsy was used to characterize the inflammatory response. Indirect immunofluorescence assay (IFA) was used for autoantibody screening. The autoantigen was identified by histo-immunoprecipitation and mass spectrometry and was validated by expressing the recombinant antigen in HEK293 cells and neutralization tests. Sera from 125 control patients were screened using IFA to test for the novel autoantibodies.IFA analysis of serum revealed a novel autoantibody against brain tissue. An intracellular enzyme, Rho-associated protein kinase 2 (ROCK2), was identified as target-antigen. ROCK2 was expressed in affected brain tissue and archival bladder tumor samples of this patient. Brain histopathology revealed appositions of cytotoxic CD8+ T cells on ROCK2-positive neurons. ROCK2 antibodies were not found in the sera of 20 patients with bladder cancer and 17 with renal cancer, both without neurological symptoms, 49 healthy controls, and 39 patients with other antineuronal autoantibodies. In conclusion, novel onconeural antibodies targeting ROCK2 are associated with paraneoplastic encephalitis and should be screened for when paraneoplastic neurological syndromes, especially in patients with urogenital cancers, occur.

Investigating the effect of treatment at high-volume hospitals on overall survival following cytoreductive nephrectomy

PURPOSE Data revealed the benefit of high-volume care in many complex disease processes. Among patients undergoing nephrectomy, those receiving cytoreductive nephrectomy (CN) for metastatic renal cell cancer (mRCC) constitute a unique subset. They often have a greater medical and surgical complexity. Against this backdrop, we sought to investigate the effect of hospital volume on overall survival among patients undergoing CN for mRCC. MATERIAL AND METHODS We identified 11,089 patients who received CN for mRCC in the National Cancer Database from 1998 to 2012. We ranked hospitals based on annual CN volume. Patients who received surgery in hospitals in the top vs. bottom deciles were compared. Inverse Probability of Treatment Weighting (IPTW)-adjusted Kaplan-Meier and Cox regression analyses were used to compare the primary endpoint of overall survival between balanced cohorts of patients. Secondary endpoints were 30-day mortality, 30-day readmissions, and receipt of subsequent systemic therapy. RESULTS Median follow-up was 60.39 months (interquartile range [IQR] 35.09-95.95). Median overall survival was 17.61 months (IQR 7.16-44.58). Following propensity score weighting, surgery at a high-volume hospital was associated with a decreased risk of mortality (IPTW-adjusted Cox proportional Hazard Ratio = 0.91; 95% confidence interval: 0.86-0.96). On our IPTW-adjusted Kaplan-Meier analysis, the median survival was 19.94 months (IQR 7.98-50.27) at high-volume hospitals vs. 15.97 months (IQR 6.6-41.56) at low-volume hospitals. With regard to secondary endpoints, the data did not reveal a significant advantage for treatment at a high-volume hospital. CONCLUSION We found a significant association between receipt of CN at high-volume hospitals and prolonged overall survival, demonstrated by a nearly 4 month survival benefit.

Evaluation of the contribution of demographics, access to health care, treatment, and tumor characteristics to racial differences in survival of advanced prostate cancer

BackgroundRacial differences in prostate cancer (PCa) outcomes in the United States may be due to differences in tumor biology and race-based differences in access and treatment. We designed a study to estimate the relative contribution of these factors on Black/White disparities in overall survival (OS) in advanced PCa.MethodsWe identified Black and White men aged ≥ 40 years with metastatic or locally advanced PCa (cN+ cM+ and/or T3/4) between 2004 and 2010 using the National Cancer Database. We employed sequential propensity score weighting procedures to generate simulated cohorts of Black and White patients with equal demographics, access to care, treatment, and tumor characteristics. Adjusted survival analyses were used to compare survival in these simulated cohorts. The changes in relative survival after each weighting procedure were used to infer the contribution of each set of variables on the excess risk of mortality in Blacks.ResultsIn total, 35,611 men met inclusion criteria, 5927 (16.77%) of whom were Black. Survival was significantly worse for Black men after adjusting for demographics and comorbidities (hazard ratio (HR) 1.27, 95%-confidence interval (95%-CI) 1.2–1.34, p < 0.001). After simulating equal access to care, there was no significant difference in survival between races (HR 1.04, 95%-CI 0.97–1.12, p = 0.276), despite worse tumor characteristics in Blacks. After simulating equal treatment and equivalent tumor characteristics, Black men had a better survival than Whites (HR 0.93, 95%-CI 0.86–1.01, p = 0.071 and HR 0.92, 95%-CI 0.84–1.00, p = 0.043, respectively). Overall, access-related variables explained 84.7% of the excess risk of death in Black men.ConclusionOur analysis of men with advanced PCa revealed worse OS among Blacks. However, when access to care, treatment, and cancer characteristics are accounted for, Black race was associated with better OS. These findings suggest that initiatives to improve access to care may represent an effective tool to reduce disparities in PCa outcomes.

Adoption of robotic surgery: driven by market competition or a desire to improve patient care?

Aggarwal, Ajay; Lewis, Daniel; Mason, Malcolm; Purushotham, Arnie; Sullivan, Richard; van der Meulen, Jan; (2018) Adoption of robotic surgery: driven by market competition or a desire to improve patient care? Authors’ reply. The lancet oncology, 19 (2). e67-. ISSN 1470-2045 DOI: https://doi.org/10.1016/S1470-2045(18)30022-6 Downloaded from: http://researchonline.lshtm.ac.uk/id/eprint/4646562/ DOI: https://doi.org/10.1016/S1470-2045(18)30022-6

Evaluation of magnetic resonance imaging and targeted biopsy: The difficulty of finding the right reference standard: Correspondence

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The new frontier of prostate biopsy: determining the role of image-guidance in moving the needle

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Use of Preventive Health Services Among Cancer Survivors in the U.S.

INTRODUCTION With improvements in early detection and treatment, a growing proportion of the population now lives with a personal history of a cancer. Although many cancer survivors are in excellent health, the underlying risk factors and side effects of cancer treatment increase the risk of medical complications and secondary malignancies. METHODS The 2013 National Health Interview Survey was utilized to assess the association between personal history of cancer and receipt of U.S. Preventive Services Task Force-recommended services, comprising three cancer screening tests (mammography, colonoscopy, and Pap smear) and six general medical preventive care services (aspirin for prevention of cardiovascular disease; blood pressure, cholesterol, and diabetes screening; diet/activity counseling; and tobacco use counseling). For each preventive service, patients with a history that would preclude that test were excluded. One to three matching of cancer survivors to controls was performed using propensity scores generated from patient-level demographic variables. Conditional logistic regression models were employed to compare odds of screening between matched cohorts of cancer survivors and controls. The years of analysis were 2015 and 2017. RESULTS A total of 2,639 cancer patients and 31,885 controls were extracted from the merged 2013 National Health Interview Survey. In the propensity score-matched cohorts of eligible adults, only one of the three cancer screening tests, colorectal, was more common in cancer survivors (OR=1.52, 95% CI=1.32, 1.75, p<0.001), whereas breast and cervical cancer screening were not more common in survivors. By contrast, all of the medical screening tests, with the exception of diabetes screening, were more common among cancer survivors. CONCLUSIONS The association between receipt of recommended preventive medical care and personal history of cancer varied, depending on the preventive service in question, but in the majority of preventive services assessed, cancer survivors had more frequent screening compared with non-cancer survivors.