Clinical Outcomes for Metastatic Renal Cell Carcinoma (mRCC) Patients Ineligible for Front-line Clinical Trials

Clinical trials for immunotherapy-based regimens in metastatic renal cell carcinoma (mRCC) have extensive inclusion and exclusion criteria. We investigated the clinical outcomes in a real-world cohort of patients who would not have met the criteria for inclusion in front-line mRCC trials. Patients treated with ipilimumab/nivolumab and axitinib/pembrolizumab for front-line mRCC were identified and divided into clinical trial eligible (CTE) and clinical trial ineligible (CTI) cohorts based on key inclusion or exclusion criteria from their respective Phase-3 registration trials. Clinical outcomes were compared in CTE and CTI cohorts. A total of 62 patients treated with axitinib/pembrolizumab and 103 treated with ipilimumab/nivolumab were identified. The International Metastatic RCC Database Consortium (IMDC) criteria were similar across CTE and CTI patients in axitinib/pembrolizumab and ipilimumab/nivolumab cohorts. In the axitinib/pembrolizumab cohort (n = 62), 24 (39%) patients were CTI. The major reasons for the ineligibility were lab abnormalities (n = 11), histology (n = 9), and brain metastases (n = 3). There was no significant difference in response rates (P = 0.08). The median progression-free survival (PFS) was numerically longer in CTE patients (28 vs 12 months; P = 0.09). The overall survival (OS) was higher in the CTE patients (P = 0.02). In the ipilimumab/nivolumab cohort (n = 103), 59 (57%) were CTI. The most common reasons for ineligibility were brain metastases (n = 18), lab abnormalities (n = 16), and histology (n = 16). There was no significant difference in response rates (P = 0.22). However, PFS (P = 0.003) and OS (P < 0.0001) were higher in the CTE patients. In conclusion, many real-world patients are ineligible for RCC clinical trials and had worse outcomes when compared to trial-eligible patients. Additional treatment options are needed for these patients, as well as strategies to include them in prospective trials

Mode of Effective Connectivity within a Putative Neural Network Differentiates Moral Cognitions Related to Care and Justice Ethics

BACKGROUND: Moral sensitivity refers to the interpretive awareness of moral conflict and can be justice or care oriented. Justice ethics is associated primarily with human rights and the application of moral rules, whereas care ethics is related to human needs and a situational approach involving social emotions. Among the core brain regions involved in moral issue processing are: medial prefrontal cortex, anterior (ACC) and posterior (PCC) cingulate cortex, posterior superior temporal sulcus (pSTS), insula and amygdala. This study sought to inform the long standing debate of whether care and justice moral ethics represent one or two different forms of cognition. METHODOLOGY/PRINCIPAL FINDINGS: Model-free and model-based connectivity analysis were used to identify functional neural networks underlying care and justice ethics for a moral sensitivity task. In addition to modest differences in patterns of associated neural activity, distinct modes of functional and effective connectivity were observed for moral sensitivity for care and justice issues that were modulated by individual variation in moral ability. CONCLUSIONS/SIGNIFICANCE: These results support a neurobiological differentiation between care and justice ethics and suggest that human moral behavior reflects the outcome of integrating opposing rule-based, self-other perspectives, and emotional responses

Management of poor-prognosis testicular germ cell tumors

Currently, the outcome of patients with intermediate- and poor-risk germ cell tumors at diagnosis is optimized by the use of risk-appropriate chemotherapy and post-chemotherapy surgical resection of residual masses. Currently, there is no role for high-dose chemotherapy in the first-line setting. Patients who progress on first-line chemotherapy or who relapse after an initial complete response also have a poor prognosis. In the setting of early relapse, the standard approach at most centers is conventional-dose, ifosfamide-based regimens and post-chemotherapy resection of residual masses. The treatment of patients with late relapse is complete surgical resection whenever feasible. Salvage chemotherapy for late relapse may be used prior to surgery in patients where a complete resection is not feasible. A complete surgical resection of all residual sites of disease after chemotherapy is critical for the prevention of relapse and the long-term survival of patients with advanced germ cell tumors

Guideline Summary ASCO Clinical Practice Guideline on Uses of Serum Tumor Markers in Adult Males With Germ Cell Tumors

ASCO convened an Expert Panel to consider evidence and craft recommendations on serum tumor markers (STMs) for germ cell tumors (GCTs) in adult males. The recommendations were recently published in Journal of Clinical Oncology.1 In males, most GCTs originate in the testes, accounting for approxi-mately 95 % of testicular cancers; however, GCTs occasionally originate extragonadally in the mediastinum or retroperito-neum. Well-established STMs for guiding management of patients with GCTs include human chorionic gonadotropin (hCG), -fetoprotein (AFP), and lactate dehydrogenase (LDH). Poten-tial uses of STMs for GCTs may include screening, diagnosis, monitoring during treatment, and post-therapy surveillance. The guideline1 examines STMs for monitoring or surveillance separately for each histologic GCT subtype: seminoma and nonseminomatous (NS) (including GCTs of mixed histology). No studies directly compared outcomes of patient manage-ment with versus without marker assays. A literature search of MEDLINE and EMBASE identified few prospective studies and no randomized controlled trials; most were retrospective series. For most uses, few studies reported primary outcomes. Thus, Panel recommendations are based primarily on surrogate outcomes, such as rates of relapse in patient subsets with versus without a marker elevation and/or time to detection of relapse

African-American men's perceptions about prostate cancer: Implications for designing educational interventions

This qualitative study explores African-American men's perceptions about prostate cancer (CaP) screening and assesses the acceptability of various strategies and settings for interventions to promote informed decision-making. We conducted four focus groups among healthy men (n=37) and two groups among CaP survivors (n=14) aged 35-70 in the greater Boston area, USA. Also, we conducted 14 in-depth interviews with key community informants. The audio-taped focus groups and interviews were transcribed, coded, and analyzed for emergent themes. Except for survivors, men had insufficient information about the prostate, the elevated cancer risk among African-Americans, and the controversy concerning screening. Key informants and focus group participants cited inadequate access to services, mistrust of the health system, poor relationships with medical providers, and perceived threats to male sexuality as major barriers to receiving prostate care. They recommended that interventions be embedded in community settings, address men's overall health, and be administered by culturally competent providers, and repeatedly emphasized trust building and a sustained presence in the community. Efforts to present balanced information about CaP screening may be hindered by lingering mistrust of the medical system, poor relationships between patients and providers, and enthusiastic support for screening on the part of CaP survivors. Implications for interventions are discussed.Prostate cancer screening Informed decision-making African-American men USA