Multi-institutional Analysis of Immune-Oncology Combination Therapy for Metastatic MiT Family Translocation Renal Cell Carcinoma.

Metastatic translocation renal cell carcinomas (mtRCCs) are rare and aggressive tumors with limited treatment options. Recent studies demonstrated promising activity of immune-oncology (IO) combinations in mtRCC. However, the effectiveness of dual IO combinations versus IO plus VEGF-TKI combinations remains unclear.

Testicular Germ Cell Tumors: A Review.

Importance: Testicular cancer is the most common solid malignancy among males aged 15 to 40 years in the US, with approximately 10 000 new cases diagnosed each year. Between 90% and 95% of testicular cancers are germ cell tumors (GCTs).

Observations: The mean age at diagnosis for testicular cancer is 33 years.

Pan-tumor analysis to investigate the obesity paradox in immune checkpoint blockade.

Background: Obesity is a risk factor for developing cancer but is also associated with improved outcomes after treatment with immune checkpoint inhibitors (ICIs), a phenomenon called the obesity paradox. To interrogate mechanisms of divergent immune responses in obese and non-obese patients, we examined the relationship among obesity status, clinical responses, and immune profiles from a diverse, pan-tumor cohort of patients treated with ICI-based therapy.

Methods: From June 2021 to March 2023, we prospectively collected serial peripheral blood samples from patients with advanced or metastatic solid tumors who received ICI as standard of care at Johns Hopkins.

Management of translocation carcinomas of the kidney.

Microphthalmia-associated transcription factor family translocation renal cell carcinoma (MiT-tRCC) stands out as a rare subtype of kidney cancer with distinct biological features compared to other kidney cancer subtypes. It encompasses TFE3-rearranged RCC (also known as Xp11 translocation RCC) and TFE-rearranged translocations RCC, although multiple new fusion partners were identified. Traditionally thought to primarily affect children and young adults, more cases of MiT-tRCC are being identified in adults.

Kidney Cancer Research Highlights from ASCO-GU 2024 Meeting.

The 2024 American Society of Clinical Oncology (GU ASCO 2024) Genitourinary Cancers Symposium brought together leading cancer specialists from around the world to discuss the latest breakthroughs in treating genitourinary cancers, especially kidney cancer. The focus was on immunotherapy and combination treatments, offering promising new options for patients with advanced and high-risk tumors. The symposium also highlighted advancements in patient care, including a new tool to assess quality of life in people with metastatic kidney cancer.

Abscopal effect following checkpoint inhibitor therapy and localized radiotherapy for metastatic clear cell renal cell carcinoma: A case report.

We present the case of a 64-year-old patient with metastatic renal cell carcinoma, who experienced disease progression despite undergoing multiple lines of systemic therapy, including immune checkpoint inhibitors (ICI). Two months after stereotactic radiosurgery to his brain lesions and while the patient was not on any systemic therapy, restaging scans demonstrated a dramatic near complete regression of the primary renal lesion and metastatic sites, which was attributed to the abscopal effect, mediated by the exposure to ICI and radiotherapy. While its mechanisms are not fully understood, it is believed to stem from the tumor immunosuppression and immunogenicity induced by radiation.

Social supports in patients with cancer attending an Irish cancer center: a cross-sectional study.

A positive association has been demonstrated between social supports, quality of life, and survival outcomes in cancer. This study assessed levels of social supports among patients with cancer in an Irish institution, with an age- and gender-specific stratification. The study highlights relatively low levels of perceived socio-emotional support and social connectedness, but good levels of tangible and informational support in our cohort of patients with cancer.

First-in-human Phase I Trial of TPST-1120, an Inhibitor of PPARα, as Monotherapy or in Combination with Nivolumab, in Patients with Advanced Solid Tumors.

Purpose: TPST-1120 is a first-in-class oral inhibitor of peroxisome proliferator-activated receptor α (PPARα), a fatty acid ligand-activated transcription factor that regulates genes involved in fatty acid oxidation, angiogenesis, and inflammation, and is a novel target for cancer therapy. TPST-1120 displayed antitumor activity in xenograft models and synergistic tumor reduction in syngeneic tumor models when combined with anti-PD-1 agents.

Experimental Design: This phase I, open-label, dose-escalation study (NCT03829436) evaluated TPST-1120 as monotherapy in patients with advanced solid tumors and in combination with nivolumab in patients with renal cell carcinoma (RCC), cholangiocarcinoma (CCA), or hepatocellular carcinoma.

High-Grade, Nonsarcomatoid Chromophobe Renal Cell Carcinoma: A Series of 22 Cases With Novel Molecular Features on a Subset.

Chromophobe renal cell carcinoma (ChRCC) is the third most common subtype of renal cell carcinoma and typically exhibits indolent behavior, though a rare subset can exhibit high-grade morphologic features and is associated with a poor prognosis. Although there are limited data on the molecular characteristics of metastatic and sarcomatoid ChRCC, the molecular features of high-grade, nonsarcomatoid ChRCC remain unexplored. Herein, we characterize 22 cases of ChRCC with high-grade, nonsarcomatoid components.

NCCN Guidelines® Insights: Kidney Cancer, Version 2.2024.

The NCCN Guidelines for Kidney Cancer provide multidisciplinary recommendations for diagnostic workup, staging, and treatment of patients with renal cell carcinoma (RCC). These NCCN Guidelines Insights focus on the systemic therapy options for patients with advanced RCC and summarize the new clinical data evaluated by the NCCN panel for the recommended therapies in Version 2.2024 of the NCCN Guidelines for Kidney Cancer.

Prognostic significance of pT3a staging subclassifications in renal cell carcinoma: Not all pT3a are equal.

Objective: To examine the prognostic significance of perinephric fat, renal sinus fat, and renal vein invasion in patients with pT3a renal cell carcinoma (RCC) by histologic type.

Methods: A population-based retrospective cohort study of patients with pT3aN0M0 RCC was performed using Surveillance, Epidemiology, and End Results (SEER) data for the years 2010 through 2019. Cox proportional hazards models were used to examine the relationship between pT3a subclassification groups and cancer-specific survival (CSS) by histological subtype (clear cell, papillary, chromophobe, and other).

Kidney Cancer Updates from the 2023 American Society of Clinical Oncology Annual Meeting in Chicago.

This report highlights key research from the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, with a focus on clear cell renal cell carcinoma (ccRCC) and non-clear cell RCC (nccRCC) across clinical trials and translational studies. Essential updates in the metastatic ccRCC clinical space encompass results from the CONTACT-03 study, which evaluated an immunotherapy containing regimen for patients who progressed on an initial immunotherapy containing regimen, alongside updated results from the KEYNOTE-426 and CLEAR trials. In the metastatic nccRCC domain, we review clinical trials of combination immunotherapies and tyrosine kinase inhibitors (TKIs).

Beyond the knife: strategic patient selection for cytoreductive nephrectomy.

Purpose Of Review: To evaluate the current role of cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC) within the context of evolving treatment paradigms, focusing on implications for patient selection.

Recent Findings: Two randomized trials failed to show significant benefits from CN for intermediate and poor-risk patients undergoing targeted therapy. Despite this, subgroup analysis and retrospective data suggest potential benefits for a subset of good and intermediate-risk patients.

Immunomodulatory response to neoadjuvant nivolumab in non-metastatic clear cell renal cell carcinoma.

Novel perioperative strategies are needed to reduce recurrence rates in patients undergoing nephrectomy for high-risk, non-metastatic clear cell renal cell carcinoma (ccRCC). We conducted a prospective, phase I trial of neoadjuvant nivolumab prior to nephrectomy in 15 evaluable patients with non-metastatic ccRCC. We leveraged tissue from that cohort to elucidate the effects of PD-1 inhibition on immune cell populations in ccRCC and correlate the evolving immune milieu with anti-PD-1 response.

Socioeconomic determinants of racial disparities in survival outcomes among patients with renal cell carcinoma.

Purpose: Racially driven outcomes in cancer are challenging to study. Studies evaluating the impact of race in renal cell carcinoma (RCC) outcomes are inconsistent and unable to disentangle socioeconomic disparities from inherent biological differences. We therefore seek to investigate socioeconomic determinants of racial disparities with respect to overall survival (OS) when comparing Black and White patients with RCC.

Vascular Expression of Prostate-specific Membrane Antigen (PSMA) in MiTF Family Translocation Renal Cell Carcinoma and Related Neoplasms.

Multiple studies have demonstrated prostate-specific membrane antigen (PSMA) expression in the neo-vasculature of non-prostate tumors including clear cell renal cell carcinoma (ccRCC). However, PSMA expression in rare renal tumors including MiTF family translocation renal cell carcinoma has not been previously characterized. We examined PSMA expression by immunohistochemistry in a series of MiTF family translocation renal cell carcinomas as well as in several genetically related tumors including alveolar soft part sarcoma and PEComas with TFE3 rearrangements.

Molecular differences in renal cell carcinoma between males and females.

Purpose: The disparity in renal cell carcinoma (RCC) risk and treatment outcome between males and females is well documented, but the underlying molecular mechanisms remain poorly elucidated.

Methods: We performed a narrative review synthesizing contemporary evidence on sex-specific molecular differences in healthy kidney tissue and RCC.

Results: In healthy kidney tissue, gene expression differs significantly between males and females, including autosomal and sex-chromosome-linked genes.

Combinatorial biomarker for predicting outcomes to anti-PD-1 therapy in patients with metastatic clear cell renal cell carcinoma.

With a rapidly developing immunotherapeutic landscape for patients with metastatic clear cell renal cell carcinoma, biomarkers of efficacy are highly desirable to guide treatment strategy. Hematoxylin and eosin (H&E)-stained slides are inexpensive and widely available in pathology laboratories, including in resource-poor settings. Here, H&E scoring of tumor-infiltrating immune cells (TIL) in pre-treatment tumor specimens using light microscopy is associated with improved overall survival (OS) in three independent cohorts of patients receiving immune checkpoint blockade.

Kidney Cancer Research Highlights from ASCO 2022 Annual Meeting.

The 2022 American Society of Clinical Oncology (ASCO) annual meeting was held June 3-7, 2022, in Chicago, Illinois. This hybrid meeting gathered international cancer experts across multidisciplinary specialties and was held both virtually and in-person. Here, we highlight key kidney cancer research updates presented at the meeting.