Safety outcomes and immunological correlates in a prospective clinical trial of immune checkpoint therapy plus debulking surgery for patients with metastatic renal cell carcinoma.

Surgical removal of primary tumors was shown to reverse tumor-mediated immune suppression in pre-clinical models with metastatic disease. However, how cytoreductive surgery in the metastatic setting modulates the immune responses in patients, especially in the context of immune checkpoint therapy (ICT)-containing treatments is not understood. Here, we report the first prospective, non-comparative clinical trial to evaluate the feasibility, clinical benefits, and immunologic changes of combining three different ICT-containing strategies with cytoreductive surgery or biopsy for patients with metastatic clear cell renal cell carcinoma (mccRCC).

Body composition in recurrent prostate cancer and the role of steroidogenic genotype.

Hormone therapy (HT) to treat prostate cancer is reported to cause adverse changes in body composition. Clinically, interpatient body composition changes are heterogeneous, but the biological and clinical determinants of body composition toxicity are unknown. Herein, we test the hypothesis that inherited polymorphisms in steroidogenic genes are associated with differential changes in body composition after HT.

Body composition as a determinant of the therapeutic index with androgen signaling inhibition.

Background: Androgen signaling is central to prostate cancer and men's health. Prior data indicates that increasing body fat is unfavorable in the localized setting yet associated with favorable outcomes in men with metastatic disease. Understanding the biological links between adiposity and prostate cancer may optimize the therapeutic index with ASI.

A Modular Trial of Androgen Signaling Inhibitor Combinations Testing a Risk-Adapted Strategy in Patients with Metastatic Castration-Resistant Prostate Cancer.

Purpose: To determine the efficacy and safety of risk-adapted combinations of androgen signaling inhibitors and inform disease classifiers for metastatic castration-resistant prostate cancers.

Patients And Methods: In a modular, randomized phase II trial, 192 men were treated with 8 weeks of abiraterone acetate, prednisone, and apalutamide (AAPA; module 1) and then allocated to modules 2 or 3 based on satisfactory (≥50% PSA decline from baseline and <5 circulating tumor cell/7.5 mL) versus unsatisfactory status.

Efficacy of Systemic Chemotherapy in Patients With Low-grade Mucinous Appendiceal Adenocarcinoma: A Randomized Crossover Trial.

Importance: Appendiceal adenocarcinoma is a rare tumor, and given the inherent difficulties in performing prospective trials in such a rare disease, there are currently minimal high-quality data to guide treatment decisions, highlighting the need for more preclinical and clinical investigation for this disease.

Objective: To prospectively evaluate the effectiveness of fluoropyrimidine-based systemic chemotherapy in patients with inoperable low-grade mucinous appendiceal adenocarcinoma.

Design, Setting, And Participants: This open-label randomized crossover trial recruited patients at a single tertiary care comprehensive cancer center from September 2013 to January 2021.

A Phase Ib/II Study of Ivosidenib with Venetoclax ± Azacitidine in IDH1-Mutated Myeloid Malignancies.

Unlabelled: The safety and efficacy of combining the isocitrate dehydrogenase-1 (IDH1) inhibitor ivosidenib (IVO) with the BCL2 inhibitor venetoclax (VEN; IVO + VEN) ± azacitidine (AZA; IVO + VEN + AZA) were evaluated in four cohorts of patients with IDH1-mutated myeloid malignancies (n = 31). Most (91%) adverse events were grade 1 or 2. The maximal tolerated dose was not reached.

Prognosis Associated With CA19-9 Response Dynamics and Normalization During Neoadjuvant Therapy in Resected Pancreatic Adenocarcinoma.

Objective: To characterize associations between carbohydrate antigen 19-9 (CA19-9) dynamics during neoadjuvant therapy (NT) and survival for patients with pancreatic ductal adenocarcinoma (PDAC).

Background: Although normalization of CA19-9 during NT is associated with improved outcomes following PDAC resection, we hypothesize that CA19-9 dynamics during NT can improve prognostication.

Methods: Characteristics for patients with PDAC undergoing NT (July 2011-October 2018) with ≥3 CA19-9 results (bilirubin<2mg/dL) were collected and grouped by CA19-9 dynamics.

Predictive capacity of a miRNA panel in identifying teratoma in post-chemotherapy consolidation surgeries.

Objectives: To investigate the utility of a novel serum miRNA biomarker panel to distinguish teratoma from nonmalignant necrotic/fibrotic tissues or nonviable tumours in patients with NSGCT undergoing post-chemotherapy consolidation surgery.

Patients And Methods: We prospectively collected pre-surgical serum samples from 22 consecutive testicular NSGCT patients with residual NSGCT after chemotherapy undergoing post-chemotherapy consolidation surgery. We measured serum miRNA expression of four microRNAs (miRNA-375, miRNA-200a-3p, miRNA-200a-5p and miRNA-200b-3p) and compared with pathologic findings at time of surgery.

Genotype-to-Phenotype Associations in the Aggressive Variant Prostate Cancer Molecular Profile (AVPC-m) Components.

The aggressive variant prostate cancer molecular profile (AVPC-m), composed of combined defects in TP53, RB1 and PTEN, characterizes a subset of prostate cancers linked to androgen indifference and platinum sensitivity. To contribute to the optimization of the AVPC-m assessment for inclusion in prospective clinical trials, we investigated the status of the AVPC-m components in 28 patient tumor-derived xenografts (PDXs) developed at MDACC. We subjected single formalin-fixed, paraffin-embedded (FFPE) blocks from each PDX to immunohistochemistry (IHC), targeted next-generation genomic sequencing (NGS) and Clariom-S Affymetrix human microarray expression profiling.

MTAP deficiency creates an exploitable target for antifolate therapy in 9p21-loss cancers.

Methylthioadenosine phosphorylase, an essential enzyme for the adenine salvage pathway, is often deficient (MTAP) in tumors with 9p21 loss and hypothetically renders tumors susceptible to synthetic lethality by antifolates targeting de novo purine synthesis. Here we report our single arm phase II trial (NCT02693717) that assesses pemetrexed in MTAP urothelial carcinoma (UC) with the primary endpoint of overall response rate (ORR). Three of 7 enrolled MTAP patients show response to pemetrexed (ORR 43%).

Lessons Learned From Implementing a Novel Bayesian Adaptive Dose-Finding Design in Advanced Pancreatic Cancer.

Purpose: Novel Bayesian adaptive designs provide an effective way to improve clinical trial efficiency. These designs are superior to conventional methods, but implementing them can be challenging. The aim of this article was to describe what we learned while applying a novel Bayesian phase I-II design in a recent trial.

Increasing referral of at-risk women for genetic counseling and BRCA testing using a screening tool in a community breast imaging center.

Background: Genetic evaluation and testing for hereditary breast and ovarian cancer (HBOC) remain suboptimal. The authors evaluated the feasibility of using a screening tool at a breast imaging center to increase HBOC assessment referrals.

Methods: A brief questionnaire based on the National Comprehensive Cancer Network HBOC genetic counseling referral guidelines was developed and added to the standard intake forms of patients undergoing mammography at a community breast imaging center from 2012 through 2015.

Venetoclax plus intensive chemotherapy with cladribine, idarubicin, and cytarabine in patients with newly diagnosed acute myeloid leukaemia or high-risk myelodysplastic syndrome: a cohort from a single-centre, single-arm, phase 2 trial.

Background: Addition of the BCL2 inhibitor venetoclax to lower intensity therapy has been shown to improve overall survival in older (aged 75 years or older) and unfit patients with newly diagnosed acute myeloid leukaemia. The aim of this study was to investigate the activity of venetoclax combined with intensive chemotherapy in patients aged 65 years or younger with acute myeloid leukaemia.

Methods: This cohort study was done at the MD Anderson Cancer Center in the USA, as part of the single-centre, single arm, phase 2, CLIA trial.

Pilot Clinical Trial of Perioperative Durvalumab and Tremelimumab in the Treatment of Resectable Colorectal Cancer Liver Metastases.

Purpose: Despite the prognostic importance of immune infiltrate in colorectal cancer, immunotherapy has demonstrated limited clinical activity in refractory metastatic proficient mismatch-repair (pMMR) colorectal cancer. This study explores combining anti-CTLA-4 and an anti-PD-L1 therapy in the preoperative management of resectable colorectal cancer liver metastases with the intent to improve immune responses in this disease setting.

Patients And Methods: Patients with resectable colorectal cancer liver-only metastases received one dose of tremelimumab and durvalumab preoperatively followed by single-agent durvalumab postoperatively.

Timing of allogeneic hematopoietic cell transplantation (alloHCT) for chronic myeloid leukemia (CML) patients.

While TKI are the preferred first-line treatment for chronic phase (CP) CML, alloHCT remains an important consideration. The aim is to estimate residual life expectancy (RLE) for patients initially diagnosed with CP CML based on timing of alloHCT or continuation of TKI in various settings: CP1 CML, CP2 + [after transformation to accelerated phase (AP) or blast phase (BP)], AP, or BP. Non-transplant cohort included single-institution patients initiating TKI and switched TKI due to failure.