A phase 2 study of AZD4635 in combination with durvalumab or oleclumab in patients with metastatic castration-resistant prostate cancer.

Background: Inhibition of the adenosine 2A receptor (AR) diminishes the immunosuppressive effects of adenosine and may complement immune-targeting drugs. This phase 2 study evaluated the AR antagonist AZD4635 in combination with durvalumab or oleclumab in patients with metastatic castration-resistant prostate cancer.

Methods: Patients with histologically/cytologically confirmed disease progressing within 6 months on ≥ 2 therapy lines were randomly assigned to either Module 1 (AZD4635 + durvalumab) or Module 2 (AZD4635 + oleclumab).

Anti-PD-1 immunotherapy with androgen deprivation therapy induces robust immune infiltration in metastatic castration-sensitive prostate cancer.

When compared to other malignancies, the tumor microenvironment (TME) of primary and castration-resistant prostate cancer (CRPC) is relatively devoid of immune infiltrates. While androgen deprivation therapy (ADT) induces a complex immune infiltrate in localized prostate cancer, the composition of the TME in metastatic castration-sensitive prostate cancer (mCSPC), and the effects of ADT and other treatments in this context are poorly understood. Here, we perform a comprehensive single-cell RNA sequencing (scRNA-seq) profiling of metastatic sites from patients participating in a phase 2 clinical trial (NCT03951831) that evaluated standard-of-care chemo-hormonal therapy combined with anti-PD-1 immunotherapy.

A Transcriptome-Based Precision Oncology Platform for Patient-Therapy Alignment in a Diverse Set of Treatment-Resistant Malignancies.

Unlabelled: Predicting in vivo response to antineoplastics remains an elusive challenge. We performed a first-of-kind evaluation of two transcriptome-based precision cancer medicine methodologies to predict tumor sensitivity to a comprehensive repertoire of clinically relevant oncology drugs, whose mechanism of action we experimentally assessed in cognate cell lines. We enrolled patients with histologically distinct, poor-prognosis malignancies who had progressed on multiple therapies, and developed low-passage, patient-derived xenograft models that were used to validate 35 patient-specific drug predictions.

Phase 1 Study of Safety and Preliminary Clinical Activity of JNJ-63898081, a PSMA and CD3 Bispecific Antibody, for Metastatic Castration-Resistant Prostate Cancer.

Introduction: Cancer immunotherapies have limited efficacy in prostate cancer due to the immunosuppressive prostate microenvironment. Prostate specific membrane antigen (PSMA) expression is prevalent in prostate cancer, preserved during malignant transformation, and increases in response to anti-androgen therapies, making it a commonly targeted tumor associated antigen for prostate cancer. JNJ-63898081 (JNJ-081) is a bispecific antibody targeting PSMA-expressing tumor cells and CD3-expressing T cells, aiming to overcome immunosuppression and promoting antitumor activity.

Phase Ia/b, Open-Label, Multicenter Study of AZD4635 (an Adenosine A2A Receptor Antagonist) as Monotherapy or Combined with Durvalumab, in Patients with Solid Tumors.

Purpose: To evaluate AZD4635, an adenosine A2A receptor antagonist, as monotherapy or in combination with durvalumab in patients with advanced solid tumors.

Patients And Methods: In phase Ia (dose escalation), patients had relapsed/refractory solid tumors; in phase Ib (dose expansion), patients had checkpoint inhibitor-naïve metastatic castration-resistant prostate cancer (mCRPC) or colorectal carcinoma, non-small cell lung cancer with prior anti-PD-1/PD-L1 exposure, or other solid tumors (checkpoint-naïve or prior anti-PD-1/PD-L1 exposure). Patients received AZD4635 monotherapy (75-200 mg once daily or 125 mg twice daily) or in combination with durvalumab (AZD4635 75 or 100 mg once daily).

First-in-Human Dose-Escalation Study of Cyclin-Dependent Kinase 9 Inhibitor VIP152 in Patients with Advanced Malignancies Shows Early Signs of Clinical Efficacy.

Purpose: To report on the first-in-human phase I study of VIP152 (NCT02635672), a potent and highly selective cyclin-dependent kinase 9 (CDK9) inhibitor.

Patients And Methods: Adults with solid tumors or aggressive non-Hodgkin lymphoma who were refractory to or had exhausted all available therapies received VIP152 monotherapy as a 30-minute intravenous, once-weekly infusion, as escalating doses (5, 10, 15, 22.5, or 30 mg in 21-day cycles) until the MTD was determined.

Telemedicine in management of genitourinary malignancies: Patient and physician perspectives.

Purpose: The rapid expansion of telemedicine has presented a challenge for the care of patients with genitourinary malignancies. We sought to assess patient and physician perspectives on the use of telemedicine for genitourinary cancer care.

Methods: We conducted a prospective cross-sectional study of patients who had telemedicine visits with urology, medical oncology, or radiation oncology for management of genitourinary malignancies from July-August 2020.

Use of Bisphosphonates in Elderly Patients With Newly Diagnosed Multiple Myeloma.

Bisphosphonates reduce skeletal-related events (SREs) in patients with multiple myeloma (MM) and, in some studies, improved survival. Since 2011, bisphosphonate use has been recommended by NCCN for all patients with newly diagnosed MM receiving antineoplastic therapy independent of the presence of bone disease. This study investigated their use after these guidelines were established.

Dynamic Diffuse Optical Tomography for Monitoring Neoadjuvant Chemotherapy in Patients with Breast Cancer.

Purpose To identify dynamic optical imaging features that associate with the degree of pathologic response in patients with breast cancer during neoadjuvant chemotherapy (NAC). Materials and Methods Of 40 patients with breast cancer who participated in a longitudinal study between June 2011 and March 2016, 34 completed the study. There were 13 patients who obtained a pathologic complete response (pCR) and 21 patients who did not obtain a pCR.

Use of Adjuvant Chemotherapy in Patients with Advanced Bladder Cancer after Neoadjuvant Chemotherapy.

Objectives: To compare the outcomes of adjuvant chemotherapy (AC) versus observation in patients with non-organ confined disease after neoadjuvant chemotherapy and radical cystectomy (RC).

Materials And Methods: Using the National Cancer Database, we identified patients who received NAC prior to RC and had advanced stage (pT3/4) or pathologically involved nodes (pN+) at the time of surgery from 2004-2013. We determined whether patients then received AC or were managed with observation only and used multivariable proportional hazards regression to estimate the impact of AC on overall survival.

Diffuse optical tomography changes correlate with residual cancer burden after neoadjuvant chemotherapy in breast cancer patients.

Purpose: Breast cancer (BC) patients who achieve a favorable residual cancer burden (RCB) after neoadjuvant chemotherapy (NACT) have an improved recurrence-free survival. Those who have an unfavorable RCB will have gone through months of ineffective chemotherapy. No ideal method exists to predict a favorable RCB early during NACT.

Long-term Diet and Biomarker Changes after a Short-term Intervention among Hispanic Breast Cancer Survivors: The ¡Cocinar Para Su Salud! Randomized Controlled Trial.

Background: Among Hispanic breast cancer survivors, we examined the long-term effects of a short-term culturally based dietary intervention on increasing fruits/vegetables (F/V), decreasing fat, and changing biomarkers associated with breast cancer recurrence risk.

Methods: Spanish-speaking women (n = 70) with a history of stage 0-III breast cancer who completed treatment were randomized to ¡Cocinar Para Su Salud! (n = 34), a culturally based 9-session program (24 hours over 12 weeks, including nutrition education, cooking classes, and food-shopping field trips), or a control group (n = 36, written dietary recommendations for breast cancer survivors). Diet recalls, fasting blood, and anthropometric measures were collected at baseline, 6, and 12 months.

Identifying Severe Adverse Event Clusters Using the National Cancer Institute's Common Terminology Criteria for Adverse Events.

Purpose: Exploring the relationships among adverse events is important because those that arise from a common mechanism are amenable to a common intervention, which can improve symptom management, quality of life, and treatment adherence. To date, symptom cluster studies have used patient-reported data, which are not always available in clinical trials. In this study, we proposed using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) to identify adverse event clusters because the CTCAE data are collected as standard practice and can therefore be used when patient-reported outcomes are unavailable.

Phase 1b Study of Abiraterone Acetate Plus Prednisone and Docetaxel in Patients with Metastatic Castration-resistant Prostate Cancer.

Unlabelled: Coadministration of docetaxel and abiraterone acetate plus prednisone (AA + P) may benefit patients with metastatic castration-resistant prostate cancer (mCRPC) because of complementary mechanisms of action. COU-AA-206 was a phase 1b study to determine the safe dose combination of docetaxel and AA + P in three cohorts of chemotherapy-naïve mCRPC patients. Twenty-two patients received escalating doses of docetaxel plus AA + P.

¡Cocinar Para Su Salud!: Randomized Controlled Trial of a Culturally Based Dietary Intervention among Hispanic Breast Cancer Survivors.

Background: There is a need for culturally relevant nutrition programs targeted to underserved cancer survivors.

Objective: Our aim was to examine the effect of a culturally based approach to dietary change on increasing fruit/vegetable (F/V) intake and decreasing fat intake among Hispanic breast cancer survivors.

Design: Participants were randomized to Intervention and Control groups.

¡Cocinar Para Su Salud!: Randomized Controlled Trial of a Culturally Based Dietary Intervention among Hispanic Breast Cancer Survivors.

Background: There is a need for culturally relevant nutrition programs targeted to underserved cancer survivors.

Objective: Our aim was to examine the effect of a culturally based approach to dietary change on increasing fruit/vegetable (F/V) intake and decreasing fat intake among Hispanic breast cancer survivors.

Design: Participants were randomized to Intervention and Control groups.

Increased expression of tumor proliferation genes in Hispanic women with early-stage breast cancer.

Hispanic women have higher breast cancer mortality compared to non-Hispanic whites. We evaluated for Proliferation Axis Score differences, as determined by Oncotype Dx, in Hispanic and non-Hispanic white women with newly diagnosed breast cancer. We matched 219 women, based upon age, stage, and nodal status.

Metastatic epidural spinal cord compression among elderly patients with advanced prostate cancer.

Background: A recent randomized trial demonstrated that for metastatic epidural spinal cord compression (MESCC), a complication of advanced prostate cancer, surgical decompression may be more effective than external beam radiation therapy (RT). We investigated predictors of MESCC, its treatment, and its impact on hospital length of stay for patients with advanced prostate cancer.

Methods: We used the SEER-Medicare database to identify patients >65 years with stage IV (n = 14,800) prostate cancer.

Optical biomarkers for breast cancer derived from dynamic diffuse optical tomography.

Diffuse optical tomography (DOT) is a noninvasive, nonionizing imaging modality that uses near-infrared light to visualize optically relevant chromophores. A recently developed dynamic DOT imaging system enables the study of hemodynamic effects in the breast during a breath-hold. Dynamic DOT imaging was performed in a total of 21 subjects (age 54±10  years) including 3 healthy subjects and 18 subjects with benign (n=8) and malignant (n=14) masses.

Contraindicated use of bevacizumab and toxicity in elderly patients with cancer.

Purpose: Drugs are approved on the basis of randomized trials conducted in selected populations. However, once approved, these treatments are usually expanded to patients ineligible for the trial.

Patients And Methods: We used the SEER-Medicare database to identify subjects older than 65 years with metastatic breast, lung, and colon cancer, diagnosed between 2004 and 2007 and undergoing follow-up to 2009, who received bevacizumab.

Renal cell cancer treated with a single-edged sword.

Preclinical and early clinical data suggest that antiangiogenic treatments may lead to more aggressive tumors. In this issue of Cell Reports, Blagoev et al. (2013) show that sunitinib, a multikinase inhibitor with antiangiogenic effects, does not worsen the survival of patients with metastatic kidney cancer.

Diabetes, body mass index, and outcomes in hepatocellular carcinoma patients undergoing liver transplantation.

Unlabelled: For many cancers, features of the metabolic syndrome, such as diabetes and obesity, have been associated with both increased risk of cancer development and poor outcomes.

Methods: We examined a large retrospective cohort of 342 consecutive patients who underwent liver transplantation for hepatocellular carcinoma between January 1999 and July 2010 at our institution. We evaluated the relationship between diabetes, obesity, hepatocellular carcinoma (HCC) recurrence, and overall survival.

Obesity and microvascular invasion in hepatocellular carcinoma.

Background: We hypothesized that hepatocellular carcinoma (HCC) patients with higher Body Mass Index (BMI) might have more microvascular invasion (MVI) in their tumors.

Methods: Records from 138 consecutive patients who underwent surgery at Columbia University Medical Center from January 1, 2002 to January 9, 2008 were evaluated.

Results: 40 patients (29%) had MVI, including 14% with BMI <25, 31% with BMI = 25-30, and 40% with BMI >30 (p = .