Phase II randomized study of dostarlimab alone or with bevacizumab versus non-platinum chemotherapy in recurrent gynecological clear cell carcinoma (DOVE/APGOT-OV7/ENGOT-ov80).

Background: Recurrent gynecological clear cell carcinoma (rGCCC) has a low objective response rate (ORR) to chemotherapy. Previous preclinical and clinical data suggest a potential synergy between immune checkpoint inhibitors and bevacizumab in rGCCC. Dostarlimab, a humanized monoclonal antibody targeting programmed cell death protein 1 (PD-1), combined with the anti-angiogenic bevacizumab, presents a novel therapeutic approach.

The IMRiS Trial: A Phase 2 Study of Intensity Modulated Radiation Therapy in Extremity Soft Tissue Sarcoma.

Purpose: Primary soft tissue sarcoma (STS) is rare, with many tumors occurring in extremities. Local management is limb-sparing surgery and preoperative/postoperative radiation therapy (RT) for patients at high risk of local recurrence. We prospectively investigated late normal tissue toxicity and limb function observed after intensity modulated RT (IMRT) in extremity STS.

A novel predictive algorithm to personalize autologous T-cell harvest for chimeric antigen receptor T-cell manufacture.

Background Aims: The most widely accepted starting materials for chimeric antigen receptor T-cell manufacture are autologous CD3+ T cells obtained via the process of leukapheresis, also known as T-cell harvest. As this treatment modality gains momentum and apheresis units struggle to meet demand for harvest slots, strategies to streamline this critical step are warranted.

Methods: This retrospective review of 262 T-cell harvests, with a control cohort of healthy donors, analyzed the parameters impacting CD3+ T-cell yield in adults with B-cell malignancies.

The mSteps pilot study: Analysis of the distance walked using a novel smartphone application in multiple sclerosis.

Background: Clinical studies in multiple sclerosis (MS) often require accurate measurement of walking distance. Utilisation of electronic devices could theoretically improve this. Mobile devices have the potential to continuously monitor health by collecting movement data.

A local human Vδ1 T cell population is associated with survival in nonsmall-cell lung cancer.

Murine tissues harbor signature γδ T cell compartments with profound yet differential impacts on carcinogenesis. Conversely, human tissue-resident γδ cells are less well defined. In the present study, we show that human lung tissues harbor a resident Vδ1 γδ T cell population.

New genomic technologies for multi-cancer early detection: Rethinking the scope of cancer screening.

Cancers other than breast, colorectal, cervical, and lung do not have guideline-recommended screening. New multi-cancer early detection (MCED) tests-using a single blood sample-have been developed based on circulating cell-free DNA (cfDNA) or other analytes. In this commentary, we review the current evidence on these tests, provide several major considerations for new MCED tests, and outline how their evaluation will need to differ from that established for traditional single-cancer screening tests.

Neoadjuvant Chemotherapy in Locally Advanced Cervical Carcinoma - a Role in Patients with Para-aortic Lymph Node Involvement? A 10-year Institutional Experience.

Aims: Overall survival and progression-free survival with concomitant chemoradiotherapy for locally advanced cervical carcinoma have been described as 66% and 58%, respectively, at 5 years. Para-aortic lymph node involvement significantly increases the risk of relapse and death. The role of additional chemotherapy in these patients is as yet undefined.

Prevention of early complications following total hip replacement.

Total hip arthroplasty (THA) has been quoted as "the operation of the century", owing to its efficacy and the substantial improvements evidenced with respect to functional patient outcomes and quality of life. However, early postoperative complications are often inevitable, hence it is imperative to take every step to prevent them and minimise morbidity and mortality. This manuscript focuses on the most common early complications following THA, namely venous thromboembolism (VTE), prosthetic joint infection, periprosthetic fracture, instability, and leg length inequality.

Associations between cardiac irradiation and survival in patients with non-small cell lung cancer: Validation and new discoveries in an independent dataset.

Introduction: In 'IDEAL-6' patients (N = 78) treated for locally-advanced non-small-cell lung cancer using isotoxically dose-escalated radiotherapy, overall survival (OS) was associated more strongly with V, the left atrial (LA) wall volume receiving 64-73 Gy equivalent dose in 2 Gy fractions (EQD2), than with whole-heart irradiation measures. Here we test this in an independent cohort 'OX-RT' (N = 64) treated routinely.

Methods: Using Cox regression analysis we assessed how strongly OS was associated with V, with whole-heart volumes receiving 64-73 Gy EQD2 or doses above 10-to-70 Gy thresholds, and with principal components of whole-heart dose-distributions.

Estimating the population health impact of a multi-cancer early detection genomic blood test to complement existing screening in the US and UK.

Background: Multi-cancer early detection (MCED) next-generation-sequencing blood tests represent a potential paradigm shift in screening.

Methods: We estimated the impact of screening in the US and UK. We used country-specific parameters for uptake, and test-specific sensitivity and false-positive rates for current screening: breast, colorectal, cervical and lung (US only) cancers.

Deep Learning-Based Conformal Prediction of Toxicity.

Predictive modeling for toxicity can help reduce risks in a range of applications and potentially serve as the basis for regulatory decisions. However, the utility of these predictions can be limited if the associated uncertainty is not adequately quantified. With recent studies showing great promise for deep learning-based models also for toxicity predictions, we investigate the combination of deep learning-based predictors with the conformal prediction framework to generate highly predictive models with well-defined uncertainties.

Incorporating patient centered benefits as endpoints in randomized trials of maintenance therapies in advanced ovarian cancer: A position paper from the GCIG symptom benefit committee.

Background: Quality of life and patient reported outcome measures (PROMs) are important secondary endpoints and incorporated in most contemporary clinical trials. There have been deficiencies in their assessment and reporting in ovarian cancer clinical trials, particularly in trials of maintenance treatment where they are of particular importance. The Gynecologic Cancer InterGroup (GCIG) symptom benefit committee (SBC) recently convened a brainstorming meeting with representation from all collaborative groups to address questions of how to best incorporate PROMs into trials of maintenance therapies to support the primary endpoint which is usually progression free survival (PFS).

Changing the HTS Paradigm: AI-Driven Iterative Screening for Hit Finding.

Iterative screening is a process in which screening is done in batches, with each batch filled by using machine learning to select the most promising compounds from the library based on the previous results. We believe iterative screening is poised to enhance the screening process by improving hit finding while at the same time reducing the number of compounds screened. In addition, we see this process as a key enabler of next-generation high-throughput screening (HTS), which uses more complex assays that better describe the biology but demand more resource per screened compound.

Ganetespib in Combination with Pemetrexed-Platinum Chemotherapy in Patients with Pleural Mesothelioma (MESO-02): A Phase Ib Trial.

Purpose: Ganetespib, a highly potent, small-molecule Heatshock protein 90 inhibitor, has potential efficacy in malignant pleural mesothelioma (MPM) via activity on critical survival pathways and known synergies with antifolates and platinum chemotherapy. We conducted a dose-escalation study to identify the maximum tolerated dose (MTD) of ganetespib in patients with chemotherapy-naïve MPM.

Patients And Methods: MESO-02 (ClinicalTrials.

Adverse outcomes in SAR-CoV-2 (COVID-19) and SARS virus related pregnancies with probable vertical transmission.

The global severe acute respiratory syndrome-related coronavirus SARS-CoV-2 (COVID-19) pandemic has had an unprecedented impact on all aspects of daily life and healthcare. Information on the infection risks for pregnant women and their offspring have so far been limited to small case series, until a large UK report on 427 SARS-CoV-2 infected pregnant women was published. Previous SARS epidemic experiences were drawn upon.

Impact of compliance to chemoradiation on long-term outcomes in squamous cell carcinoma of the anus: results of a post hoc analysis from the randomised phase III ACT II trial.

Background: Concurrent chemoradiation is standard-of-care for patients with squamous cell carcinoma of the anus. Poor compliance to chemotherapy, radiotherapy treatment interruptions and unplanned breaks may impact adversely on long-term outcomes.

Methods: The ACT II trial recruited 940 patients with localised squamous cell carcinoma of the anus, and assigned patients to mitomycin (week 1) or cisplatin (weeks 1 and 5), with fluorouracil (weeks 1 and 5) and radiotherapy (50.

Publisher Correction: A clonal expression biomarker associates with lung cancer mortality.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Geospatial immune variability illuminates differential evolution of lung adenocarcinoma.

Remarkable progress in molecular analyses has improved our understanding of the evolution of cancer cells toward immune escape. However, the spatial configurations of immune and stromal cells, which may shed light on the evolution of immune escape across tumor geographical locations, remain unaddressed. We integrated multiregion exome and RNA-sequencing (RNA-seq) data with spatial histology mapped by deep learning in 100 patients with non-small cell lung cancer from the TRACERx cohort.

Using Predicted Bioactivity Profiles to Improve Predictive Modeling.

Predictive modeling is a cornerstone in early drug development. Using information for multiple domains or across prediction tasks has the potential to improve the performance of predictive modeling. However, aggregating data often leads to incomplete data matrices that might be limiting for modeling.