Targeting the tumor microenvironment of Ewing sarcoma.

Ewing sarcoma is an aggressive tumor type with an age peak in adolescence. Despite the use of dose-intensified chemotherapy as well as radiation and surgery for local control, patients with upfront metastatic disease or relapsed disease have a dismal prognosis, highlighting the need for additional therapeutic options. Different types of immunotherapies have been investigated with only very limited clinical success, which may be due to the presence of immunosuppressive factors in the tumor microenvironment.

Neoadjuvant talimogene laherparepvec plus surgery versus surgery alone for resectable stage IIIB-IVM1a melanoma: a randomized, open-label, phase 2 trial.

Talimogene laherparepvec (T-VEC) is a herpes simplex virus type 1-based intralesional oncolytic immunotherapy approved for the treatment of unresectable melanoma. The present, ongoing study aimed to estimate the treatment effect of neoadjuvant T-VEC on recurrence-free survival (RFS) of patients with advanced resectable melanoma. An open-label, phase 2 trial (NCT02211131) was conducted in 150 patients with resectable stage IIIB-IVM1a melanoma who were randomized to receive T-VEC followed by surgery (arm 1, n = 76) or surgery alone (arm 2, n = 74).

Single-route CNS prophylaxis for aggressive non-Hodgkin lymphomas: real-world outcomes from 21 US academic institutions.

Prophylaxis is commonly used to prevent central nervous sy stem (CNS) relapse in diffuse large B-cell lymphoma (DLBCL), with no clear standard of care. We retrospectively evaluated 1162 adult patients across 21 US academic centers with DLBCL or similar histologies who received single-route CNS prophylaxis as part of frontline therapy between 2013 and 2019. Prophylaxis was administered intrathecally(IT) in 894 (77%) and using systemic high-dose methotrexate (HD-MTX) in 236 (20%); 32 patients (3%) switched route due to toxicity and were assessed separately.

Identification and prioritization of myeloid malignancy germline variants in a large cohort of adult patients with AML.

Inherited predisposition to myeloid malignancies is more common than previously appreciated. We analyzed the whole-exome sequencing data of paired leukemia and skin biopsy samples from 391 adult patients from the Beat AML 1.0 consortium.

FDG positron emission tomography mining for metabolic imaging biomarkers of radiation-induced xerostomia in patients with oropharyngeal cancer.

Purpose: Head and neck cancers radiotherapy (RT) is associated with inevitable injury to parotid glands and subsequent xerostomia. We investigated the utility of SUV derived from FDG-PET to develop metabolic imaging biomarkers (MIBs) of RT-related parotid injury.

Methods: Data for oropharyngeal cancer (OPC) patients treated with RT at our institution between 2005 and 2015 with available planning computed tomography (CT), dose grid, pre- & first post-RT FDG-PET-CT scans, and physician-reported xerostomia assessment at 3-6 months post-RT (Xero 3-6 ms) per CTCAE, was retrieved, following an IRB approval.

An Improved Detection of Circulating Tumor DNA in Extracellular Vesicles-Depleted Plasma.

Circulating tumor DNA (ctDNA) in plasma has been used as a biomarker for cancer detection and outcome prediction. In this study, we collected the five precipitates (fractions 1-5) and leftover supernatant plasma component (fraction 6) by a sequential centrifugation in plasma samples from nine small cell lung cancer (SCLC) patients. The fractions 3, 5 and 6 were large vesicles, exosomes and extracellular vesicles (EVs)-depleted plasma, respectively.

Avelumab first-line maintenance in locally advanced or metastatic urothelial carcinoma: Applying clinical trial findings to clinical practice.

Although urothelial carcinoma (UC) is considered a chemotherapy-sensitive tumor, progression-free survival and overall survival (OS) are typically short following standard first-line (1L) platinum-containing chemotherapy in patients with locally advanced or metastatic disease. Immune checkpoint inhibitors (ICIs) have antitumor activity in UC and favorable safety profiles compared with chemotherapy; however, trials of 1L ICI monotherapy or chemotherapy + ICI combinations have not yet shown improved OS vs chemotherapy alone. In addition to direct cytotoxicity, chemotherapy has potential immunogenic effects, providing a rationale for assessing ICIs as switch-maintenance therapy.

Radiation Oncologists' Views on Breast Radiation Therapy Guidelines: Utilizing an Online Q&A Platform to Assess Current Views on Whole-Breast Irradiation Therapy.

Introduction: Poor adherence to the 2011 American Society for Radiation Oncology (ASTRO) evidence-based guideline on whole-breast irradiation (WBI) has been reported. We utilized theMednet to assess the views of the updated 2018 guideline among radiation oncologists (ROs).

Methods: We identified 11 questions asked by community ROs on theMednet, a web-based platform, between October 27, 2014 and May 2, 2017 that were updated in the 2018 guideline.

Acalabrutinib in treatment-naive chronic lymphocytic leukemia.

Acalabrutinib has demonstrated significant efficacy and safety in relapsed chronic lymphocytic leukemia (CLL). Efficacy and safety of acalabrutinib monotherapy were evaluated in a treatment-naive CLL cohort of a single-arm phase 1/2 trial (ACE-CL-001). Adults were eligible for enrollment if chemotherapy was declined or deemed inappropriate due to comorbidities (N = 99).

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.

Role of immunotherapy in Ewing sarcoma.

Ewing sarcoma (ES) is thought to arise from mesenchymal stem cells and is the second most common bone sarcoma in pediatric patients and young adults. Given the dismal overall outcomes and very intensive therapies used, there is an urgent need to explore and develop alternative treatment modalities including immunotherapies. In this article, we provide an overview of ES biology, features of ES tumor microenvironment (TME) and review various tumor-associated antigens that can be targeted with immune-based approaches including cancer vaccines, monoclonal antibodies, T cell receptor-transduced T cells, and chimeric antigen receptor T cells.

RON signalling promotes therapeutic resistance in ESR1 mutant breast cancer.

Background: Oestrogen Receptor 1 (ESR1) mutations are frequently acquired in oestrogen receptor (ER)-positive metastatic breast cancer (MBC) patients who were treated with aromatase inhibitors (AI) in the metastatic setting. Acquired ESR1 mutations are associated with poor prognosis and there is a lack of effective therapies that selectively target these cancers.

Methods: We performed a proteomic kinome analysis in ESR1 Y537S mutant cells to identify hyperactivated kinases in ESR1 mutant cells.

Radiation therapy and secondary malignancy in Li-Fraumeni syndrome: A hereditary cancer registry study.

Background: Li-Fraumeni Syndrome (LFS) is a rare cancer-predisposing condition caused by germline mutations in TP53. Conventional wisdom and prior work has implied an increased risk of secondary malignancy in LFS patients treated with radiation therapy (RT); however, this risk is not well-characterized. Here we describe the risk of subsequent malignancy and cancer-related death in LFS patients after undergoing RT for a first or second primary cancer.

Naproxen chemoprevention promotes immune activation in Lynch syndrome colorectal mucosa.

Objective: Patients with Lynch syndrome (LS) are at markedly increased risk for colorectal cancer. It is being increasingly recognised that the immune system plays an essential role in LS tumour development, thus making an ideal target for cancer prevention. Our objective was to evaluate the safety, assess the activity and discover novel molecular pathways involved in the activity of naproxen as primary and secondary chemoprevention in patients with LS.

COVID-19 and androgen-targeted therapy for prostate cancer patients.

The current pandemic (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global health challenge with active development of antiviral drugs and vaccines seeking to reduce its significant disease burden. Early reports have confirmed that transmembrane serine protease 2 (TMPRSS2) and angiotensin converting enzyme 2 (ACE2) are critical targets of SARS-CoV-2 that facilitate viral entry into host cells. TMPRSS2 and ACE2 are expressed in multiple human tissues beyond the lung including the testes where predisposition to SARS-CoV-2 infection may exist.

Safety and efficacy of CDX-014, an antibody-drug conjugate directed against T cell immunoglobulin mucin-1 in advanced renal cell carcinoma.

CDX-014 is an antibody-drug conjugate directed against TIM-1, a surface marker highly expressed in renal cell carcinoma (RCC) and ovarian carcinoma. This phase I, first-in-human trial was conducted to evaluate the safety and preliminary activity of CDX-014 in patients with advanced refractory RCC, following a dose-escalation and dose expansion design. CDX-014 was administered intravenously at doses ranging from 0.

Locally Advanced, Unresectable Non-Small Cell Lung Cancer.

Purpose Of Review: Treatment of locally advanced, unresectable non-small cell lung cancer (NSCLC) has recently been revolutionized by the incorporation of immunotherapy to standard platinum-based concurrent chemoradiation. This review examines the current standard practices and ongoing studies on the management of locally advanced, unresectable NSCLC.

Recent Findings: Concurrent chemoradiation is the cornerstone of treatment of unresectable, locally advanced NSCLC.

The promise of adoptive cellular immunotherapies in hepatocellular carcinoma.

Hepatocellular Carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. Current systemic therapies result only in modest benefits and new therapeutic options are critically needed. Some patients show promising clinical responses to immune checkpoint inhibitors, however, additional immunotherapeutic approaches, such as adoptive cell therapies (ACT), need to be developed.

B cell maturation antigen-specific chimeric antigen receptor T cells for relapsed or refractory multiple myeloma: A meta-analysis.

Introduction: Chimeric antigen receptor (CAR) T cells targeting B cell maturation antigen (BCMA) have shown impressive results in clinical studies for relapsed/refractory multiple myeloma (RRMM). We performed a systematic literature review to summarize the current body of evidence on the role of anti-BCMA CAR T cells for RRMM.

Objectives And Methods: Fifteen studies comprising a total of 285 patients with heavily pretreated RRMM were included using a conventional meta-analysis.