Choriocarcinoma Syndrome: A Rare Complication's Impact on Metastatic Germ Cell Tumor Outcomes.

Choriocarcinoma syndrome is a rare form of tumor lysis syndrome that predominantly occurs in patients with metastatic germ cell tumors, particularly those presenting with extensive lung metastases. We report a case of a previously healthy 37-year-old male who presented with a painless left-sided neck lump and nipples with an increased sensitivity to light touch. Workup revealed a significantly elevated beta-human chorionic gonadotropin, a testicular mass, and innumerable pulmonary metastases, suggesting metastatic non-seminomatous germ cell tumor.

Quality of life for men with metastatic castrate-resistant prostate cancer participating in an aerobic and resistance exercise pilot intervention.

Background: Following a prostate cancer diagnosis, disease and treatment-related symptoms may result in diminished quality of life (QoL). Whether exercise improves QoL in men with metastatic castrate-resistant prostate cancer (mCRPC) is not fully understood.

Methods: We conducted a 3-arm pilot randomized controlled trial to assess the feasibility, acceptability, safety, and efficacy of a 12-week remotely monitored exercise program among men with mCRPC.

Emergence of BRCA Reversion Mutations in Patients with Metastatic Castration-resistant Prostate Cancer After Treatment with Rucaparib.

Background: Poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors are approved in the USA for the treatment of patients with BRCA1 or BRCA2 (BRCA) mutated (BRCA+) metastatic castration-resistant prostate cancer (mCRPC). BRCA reversion mutations are a known mechanism of acquired resistance to PARP inhibitors in multiple cancer types, although their impact and prevalence in mCRPC remain unknown.

Objective: To examine the prevalence of BRCA reversion mutations in the plasma of patients with BRCA+ mCRPC after progression on rucaparib.

Orteronel for Metastatic Hormone-Sensitive Prostate Cancer: A Multicenter, Randomized, Open-Label Phase III Trial (SWOG-1216).

Purpose: Orteronel (TAK-700) is a nonsteroidal 17,20-lyase inhibitor suppressing androgen synthesis. We evaluated the clinical benefit of orteronel when added to androgen deprivation therapy (ADT) in patients with newly diagnosed metastatic hormone-sensitive prostate cancer.

Methods: In this open-label randomized phase III study, patients with metastatic hormone-sensitive prostate cancer were randomly assigned 1:1 to ADT with orteronel (300 mg oral twice daily; experimental arm) or ADT with bicalutamide (50 mg oral once daily; control arm).

Feasibility, safety, and acceptability of a remotely monitored exercise pilot CHAMP: A Clinical trial of High-intensity Aerobic and resistance exercise for Metastatic castrate-resistant Prostate cancer.

Background: Exercise may improve clinical and quality of life outcomes for men with prostate cancer. No randomized controlled trials (RCTs) have examined the feasibility, safety, and acceptability of remote exercise training in men with metastatic castrate-resistant prostate cancer (mCRPC).

Methods: We conducted a pilot RCT (1:1:1 aerobic or resistance exercise 3x/week or usual care) to determine the feasibility, safety, and acceptability of remotely monitored exercise over 12 weeks in 25 men with mCRPC.

Implementation of a Multidisciplinary Expert Testicular Cancer Tumor Board Across a Large Integrated Healthcare Delivery System Via Early Case Ascertainment.

Purpose: In 2016, Kaiser Permanente Northern California began regionalizing testicular cancer care using population-based tumor board review. This mixed methods evaluation describes implementation outcomes and learnings.

Methods: We conducted in-depth interviews with key stakeholders, administered surveys to local oncologists and urologists, and used clinical data to evaluate changes in care delivery during 2015-2018.

Baseline Circulating Tumor Cell Count as a Prognostic Marker of PSA Response and Disease Progression in Metastatic Castrate-Sensitive Prostate Cancer (SWOG S1216).

Purpose: In metastatic castrate-sensitive prostate cancer (mCSPC), combined androgen axis inhibition is a standard of care. Noninvasive biomarkers that guide initial therapy decisions are needed. We hypothesized that CellSearch circulating tumor cell (CTC) count, an FDA-cleared assay in metastatic castrate-resistant prostate cancer (mCRPC), is a relevant biomarker in mCSPC.

SARS-CoV-2 Clinical Outcomes in Patients with Cancer in a Large Integrated Health Care System in Northern California.

The SARS-CoV-2 (COVID-19) pandemic continues to affect many lives globally. Patients with cancer undergoing potentially immunosuppressive therapies appear to be at particular risk for the disease and its complications. Here, we describe the experience of patients with cancer within Kaiser Permanente, a large, integrated health system in Northern California.

A multicenter phase I study of cabazitaxel, mitoxantrone, and prednisone for chemotherapy-naïve patients with metastatic castration-resistant prostate cancer: A department of defense prostate cancer clinical trials consortium study.

Background: Cabazitaxel plus prednisone has significant activity in patients with chemotherapy-naïve and pretreated metastatic castration-resistant prostate cancer (mCRPC). Mitoxantrone has antitumor activity in mCRPC and nonoverlapping mechanism of action and toxicity profile.

Objective: To establish the maximally tolerated dose of the combination of cabazitaxel, mitoxantrone, and prednisone.

Preexisting Levels of CD4 T Cells Expressing PD-1 Are Related to Overall Survival in Prostate Cancer Patients Treated with Ipilimumab.

Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) blockade can induce tumor regression and improved survival in cancer patients. This treatment can enhance adaptive immune responses without an exogenous vaccine, but the immunologic biomarkers associated with improved clinical outcome in cancer patients are not fully established. A phase Ib trial in patients with metastatic, castration-resistant prostate cancer was performed combining ipilimumab with sargramostim (GM-CSF).

Sequential use of the androgen synthesis inhibitors ketoconazole and abiraterone acetate in castration-resistant prostate cancer and the predictive value of circulating androgens.

Purpose: Patients previously treated with ketoconazole were excluded from phase III trials of abiraterone acetate due to potential overlapping mechanism of action. The purpose of this study was to determine the clinical utility of abiraterone and its impact on circulating androgens following ketoconazole.

Experimental Design: Chemotherapy-naïve patients with progressive metastatic castration-resistant prostate cancer (mCRPC) and prior ketoconazole therapy ≥28 days received abiraterone acetate 1,000 mg daily and prednisone 5 mg twice daily.

Cabozantinib in chemotherapy-pretreated metastatic castration-resistant prostate cancer: results of a phase II nonrandomized expansion study.

Purpose: Cabozantinib (XL184), an oral inhibitor of multiple receptor tyrosine kinases such as MET and VEGFR2, was evaluated in a phase II nonrandomized expansion study in castration-resistant prostate cancer (CRPC).

Patients And Methods: Patients received open-label cabozantinib at daily starting doses of 100 mg or 40 mg until disease progression or unacceptable toxicity. The primary end point was bone scan response, defined as ≥ 30% reduction in bone scan lesion area.

Phase II results of Dovitinib (TKI258) in patients with metastatic renal cell cancer.

Purpose: Fibroblast growth factor (FGF) signaling regulates tumor growth and vascularization and partly mediates antiangiogenic escape from VEGF receptor (VEGFR) inhibitors. Dovitinib (TKI258) is a tyrosine kinase inhibitor (TKI) that inhibits FGF receptor (FGFR), VEGFR, and platelet-derived growth factor receptor, which are known drivers of antiangiogenic escape, angiogenesis, and tumor growth in renal cell carcinoma (RCC).

Experimental Design: Patients with advanced or metastatic RCC were treated with oral dovitinib 500 mg/day (5-days-on/2-days-off schedule).

Effects of cabozantinib on pain and narcotic use in patients with castration-resistant prostate cancer: results from a phase 2 nonrandomized expansion cohort.

Background: Pain negatively affects quality of life for cancer patients. Preliminary data in metastatic castration-resistant prostate cancer (mCRPC) suggested a benefit of the oral tyrosine kinase inhibitor cabozantinib to pain palliation.

Objective: Prospective evaluation of cabozantinib's benefits on pain and narcotic use in mCRPC.

A phase II trial of AS1411 (a novel nucleolin-targeted DNA aptamer) in metastatic renal cell carcinoma.

Background: DNA aptamers represent a novel strategy in anti-cancer medicine. AS1411, a DNA aptamer targeting nucleolin (a protein which is overexpressed in many tumor types), was evaluated in patients with metastatic, clear-cell, renal cell carcinoma (RCC) who had failed treatment with ≥1 prior tyrosine kinase inhibitor.

Methods: In this phase II, single-arm study, AS1411 was administered at 40 mg/kg/day by continuous intravenous infusion on days 1-4 of a 28-day cycle, for two cycles.

Metabolic imaging of patients with prostate cancer using hyperpolarized [1-¹³C]pyruvate.

This first-in-man imaging study evaluated the safety and feasibility of hyperpolarized [1-¹³C]pyruvate as an agent for noninvasively characterizing alterations in tumor metabolism for patients with prostate cancer. Imaging living systems with hyperpolarized agents can result in more than 10,000-fold enhancement in signal relative to conventional magnetic resonance (MR) imaging. When combined with the rapid acquisition of in vivo ¹³C MR data, it is possible to evaluate the distribution of agents such as [1-¹³C]pyruvate and its metabolic products lactate, alanine, and bicarbonate in a matter of seconds.

Platinum-based chemotherapy for variant castrate-resistant prostate cancer.

Purpose: Clinical features characteristic of small-cell prostate carcinoma (SCPC), "anaplastic," often emerge during the progression of prostate cancer. We sought to determine the efficacy of platinum-based chemotherapy in patients meeting at least one of seven prospectively defined "anaplastic" clinical criteria, including exclusive visceral or predominantly lytic bone metastases, bulky tumor masses, low prostate-specific antigen levels relative to tumor burden, or short response to androgen deprivation therapy.

Experimental Design: A 120-patient phase II trial of first-line carboplatin and docetaxel (CD) and second-line etoposide and cisplatin (EP) was designed to provide reliable clinical response estimates under a Bayesian probability model with early stopping rules in place for futility and toxicity.

Ipilimumab alone or in combination with radiotherapy in metastatic castration-resistant prostate cancer: results from an open-label, multicenter phase I/II study.

Background: This phase I/II study in patients with metastatic castration-resistant prostate cancer (mCRPC) explored ipilimumab as monotherapy and in combination with radiotherapy, based on the preclinical evidence of synergistic antitumor activity between anti-CTLA-4 antibody and radiotherapy.

Patients And Methods: In dose escalation, 33 patients (≥6/cohort) received ipilimumab every 3 weeks × 4 doses at 3, 5, or 10 mg/kg or at 3 or 10 mg/kg + radiotherapy (8 Gy/lesion). The 10-mg/kg cohorts were expanded to 50 patients (ipilimumab monotherapy, 16; ipilimumab + radiotherapy, 34).

Five-year survival in patients with cytokine-refractory metastatic renal cell carcinoma treated with axitinib.

Background: In a phase II study of axitinib for cytokine-refractory metastatic renal cell carcinoma, median overall survival (OS) was 29.9 months (95% CI, 20.3 to not estimable months).

Phase I study of dovitinib (TKI258), an oral FGFR, VEGFR, and PDGFR inhibitor, in advanced or metastatic renal cell carcinoma.

Purpose: Signaling through the fibroblast growth factor (FGF) pathway may account for tumor resistance to antiangiogenic therapies targeting the VEGF pathway. Here, dovitinib (TKI258), a potent oral inhibitor of FGF receptor, VEGF receptor (VEGFR), and platelet-derived growth factor receptor tyrosine kinases, is studied in a dose escalation trial.

Experimental Design: Patients with advanced or metastatic renal cell carcinoma (RCC) with predominant clear cell histology were treated with oral dovitinib 500 or 600 mg/day (5-days-on/2-days-off schedule).

Phase II and biomarker study of the dual MET/VEGFR2 inhibitor foretinib in patients with papillary renal cell carcinoma.

Purpose: Foretinib is an oral multikinase inhibitor targeting MET, VEGF, RON, AXL, and TIE-2 receptors. Activating mutations or amplifications in MET have been described in patients with papillary renal cell carcinoma (PRCC). We aimed to evaluate the efficacy and safety of foretinib in patients with PRCC.

Cabozantinib in patients with advanced prostate cancer: results of a phase II randomized discontinuation trial.

Purpose: Cabozantinib (XL184) is an orally bioavailable tyrosine kinase inhibitor with activity against MET and vascular endothelial growth factor receptor 2. We evaluated the activity of cabozantinib in patients with castration-resistant prostate cancer (CRPC) in a phase II randomized discontinuation trial with an expansion cohort.

Patients And Methods: Patients received 100 mg of cabozantinib daily.

A phase II study of insulin-like growth factor receptor inhibition with nordihydroguaiaretic acid in men with non-metastatic hormone-sensitive prostate cancer.

Insulin-like growth factor (IGF)-mediated signaling is a newly recognized clinical target in prostate cancer, and it is hypothesized that blockade of the IGF receptor (IGF1R) will impair downstream signaling and slow tumor growth. In this study the efficacy of nordihydroguaiaretic acid (NDGA), a small molecule inhibitor of the IGF-1R, was prospectively evaluated in patients with non-metastatic hormone-sensitive prostate cancer (HSPC). Eligible patients had non-metastatic HSPC with a rising prostate-specific antigen (PSA) and a normal testosterone level.

Ixabepilone, mitoxantrone, and prednisone for metastatic castration-resistant prostate cancer after docetaxel-based therapy: a phase 2 study of the Department Of Defense Prostate Cancer Clinical Trials Consortium.

Background: Mitoxantrone plus prednisone and ixabepilone each have modest activity as monotherapy for second-line chemotherapy in patients with docetaxel-refractory castration-resistant prostate cancer. Clinical noncross- resistance was previously observed. Phase 1 testing determined the maximum tolerated dose and dose-limiting toxicities with the combination regimen; a phase 2 study was conducted to evaluate the activity of the combination.