Targeting DOT1L and EZH2 synergizes in breaking the germinal center identity of Diffuse Large B-cell Lymphoma.

Differentiation of antigen-activated B cells into pro-proliferative germinal center (GC) B cells depends on the activity of the transcription factors MYC and BCL6, and the epigenetic writers DOT1L and EZH2. GCB-like Diffuse Large B Cell Lymphomas (GCB-DLBCLs) arise from GCB cells and closely resemble their cell of origin. Given the dependency of GCB cells on DOT1L and EZH2, we investigated the role of these epigenetic regulators in GCB-DLBCLs and observed that GCB-DLBCLs synergistically depend on the combined activity of DOT1L and EZH2.

Personalized, autologous neoantigen-specific T cell therapy in metastatic melanoma: a phase 1 trial.

New treatment approaches are warranted for patients with advanced melanoma refractory to immune checkpoint blockade (ICB) or BRAF-targeted therapy. We designed BNT221, a personalized, neoantigen-specific autologous T cell product derived from peripheral blood, and tested this in a 3 + 3 dose-finding study with two dose levels (DLs) in patients with locally advanced or metastatic melanoma, disease progression after ICB, measurable disease (Response Evaluation Criteria in Solid Tumors version 1.1) and, where appropriate, BRAF-targeted therapy.

Parameter map guided explainable segmentation framework for breast cancer using amide proton transfer weighted imaging.

Background: Amide proton transfer weighted (APTw) imaging has demonstrated extensive clinical applications in diagnosing, treating evaluating, and prognosis prediction of breast cancer. There is a pressing need to automatically segment breast lesions on APTw original images to facilitate downstream quantification, which is however challenging.

Purpose: To build a segmentation model on the original images of APTw imaging sequence by leveraging the varying contrasts between breast lesions and their surrounding glandular and fat tissues displayed on the original images of APTw imaging at different frequency offsets.

Is Frequent Imaging Necessary? Impact of Computed Tomography During Follow-up After Surgical Treatment for Nonmetastatic Renal Cell Carcinoma: A Systematic Review.

Background And Objective: Current guidelines on radiological follow-up (FU) for patients after treatment for nonmetastatic renal cell carcinoma (RCC) are not based on robust evidence. This review aims to evaluate whether the 2022 European Association of Urology (EAU) guidelines are noninferior, in terms of recurrence and (overall) survival, to a higher imaging frequency of computed tomography (CT) of the chest and abdomen.

Methods: A literature search of relevant search machines (PubMed/Medline and EMBASE) was performed up to May 29, 2024.

Longitudinal analysis of the gut microbiota during anti-PD-1 therapy reveals stable microbial features of response in melanoma patients.

Immune checkpoint inhibitors (ICIs) improve outcomes in advanced melanoma, but many patients are refractory or experience relapse. The gut microbiota modulates antitumor responses. However, inconsistent baseline predictors point to heterogeneity in responses and inadequacy of cross-sectional data.

The effect of PSMA PET/CT on clinical decision-making of radical prostatectomy and pelvic lymph node dissection.

Objective: To evaluate the effect of prostate-specific membrane antigen (PSMA) PET/computed tomography (CT) on clinical decision-making of radical prostatectomy (RP) and pelvic lymph node dissection (PLND) after its utilization in daily clinical practice at an European high-volume cancer center.

Materials And Methods: Patients who had unfavorable intermediate- and high-risk prostate cancer between 2017 and 2021 were included retrospectively and divided into two groups; those who staged using PSMA PET/CT (group 1) and those who staged using conventional modalities (group 2). Clinical decision-making of RP over nonsurgical treatments and f PLND were primary endpoints and evaluated using regression models.

A National Study of the Rate of Benign Pathology After Partial Nephrectomy for T1 Renal Cell Carcinoma: Should We Be Satisfied?

: To determine the rate of benign pathology in cT1 tumors following partial nephrectomy in the Netherlands, thereby evaluating the rate of overtreatment. Data were collected from a nationwide database containing histopathology of resected renal tissue from 2014 to 2022. Patients who underwent partial nephrectomy for suspected RCC staged T1a-b were extracted for analysis.

Nature and management of melanoma recurrences following adjuvant anti-PD-1 based therapy.

Introduction: Approximately 50 % of resected stage II-IV melanoma patients develop recurrent disease by 5 years despite adjuvant anti-PD-1 therapy. Data to define best management of recurrences is lacking.

Methods: This was a multicentre, international, retrospective cohort study.

Quantifying and visualising uncertainty in deep learning-based segmentation for radiation therapy treatment planning: What do radiation oncologists and therapists want?

Background And Purpose: During the ESTRO 2023 physics workshop on "AI for the fully automated radiotherapy treatment chain", the topic of deep learning (DL) segmentation was discussed. Despite its widespread use in radiotherapy, the time needed to evaluate and correct DL segmentations remains burdensome. While segmentation uncertainty could be beneficial for clinicians, there is a lack of understanding on what information should be presented to ease their task.

Intra-prostatic recurrences after radiotherapy with focal boost: Location and dose mapping in the FLAME trial.

Introduction: The FLAME trial demonstrated that the dose to the gross tumor volume (GTV) is associated with tumour control in prostate cancer patients. This raises the question if dose de-escalation to the remaining prostate gland can be considered. Therefore, we investigated if intraprostatic recurrences occur at the location of the GTV and which dose was delivered at that location.

Circulating tumour DNA dynamics predict recurrence in stage III melanoma patients receiving neoadjuvant immunotherapy.

Background: Neoadjuvant therapy improves recurrence-free survival (RFS) in resectable stage III cutaneous melanoma. However, accurately predicting individual recurrence risk remains a significant challenge. We investigated circulating tumour DNA (ctDNA) as a biomarker for recurrence in measurable stage IIIB/C melanoma patients undergoing neoadjuvant immunotherapy.

An Evidence-Based Rationale for Dose De-escalation of Subcutaneous Atezolizumab.

Background: Atezolizumab is a programmed death-ligand 1 (PD-L1) checkpoint inhibitor for the treatment of different forms of cancer. The subcutaneous formulation of atezolizumab has recently received approval. However, treatment with atezolizumab continues to be expensive, and the number of patients needing treatment with this drug continues to increase.

Efficacy of TIL therapy in advanced cutaneous melanoma in the current immuno-oncology era: updated systematic review and meta-analysis.

Background: Adoptive cell therapy with tumor-infiltrating lymphocytes (TIL-ACT) has consistently shown efficacy in advanced melanoma. New results in the field provide now the opportunity to assess overall survival (OS) after TIL-ACT and to examine the effect of prior anti-programmed cell death protein 1/programmed death-ligand 1 [anti-PD-(L)1] therapy on its efficacy.

Methods: A comprehensive search was conducted in PubMed up to 29 February 2024.

Target Volume Optimization for Localized Prostate Cancer.

Purpose: To provide a comprehensive review of the means by which to optimize target volume definition for the purposes of treatment planning for patients with intact prostate cancer with a specific emphasis on focal boost volume definition.

Methods: Here we conduct a narrative review of the available literature summarizing the current state of knowledge on optimizing target volume definition for the treatment of localized prostate cancer.

Results: Historically, the treatment of prostate cancer included a uniform prescription dose administered to the entire prostate with or without coverage of all or part of the seminal vesicles.

Clinical Impact of Contouring Variability for Prostate Cancer Tumor Boost.

Purpose: The focal radiation therapy (RT) boost technique was shown in a phase III randomized controlled trial (RCT) to improve prostate cancer outcomes without increasing toxicity. This technique relies on the accurate delineation of prostate tumors on MRI. A recent prospective study evaluated radiation oncologists' accuracy when asked to delineate prostate tumors on MRI and demonstrated high variability in tumor contours.

Impact of hormone receptor status and tumor subtypes of breast cancer in young BRCA carriers.

Background: Hormone receptor expression is a known positive prognostic and predictive factor in breast cancer; however, limited evidence exists on its prognostic impact on prognosis of young patients harboring a pathogenic variant (PV) in the BRCA1 and/or BRCA2 genes.

Patients And Methods: This international, multicenter, retrospective cohort study included young patients (aged ≤40 years) diagnosed with invasive breast cancer and harboring germline PVs in BRCA genes. We investigated the impact of hormone receptor status on clinical behavior and outcomes of breast cancer.

Model-Informed Development of a Cost-Saving Dosing Regimen for Sacituzumab Govitecan.

Background: The antibody-drug conjugate sacituzumab govitecan is approved for metastatic triple-negative breast cancer and has shown promising results in various other types of cancer. Its costs may limit patient access to this novel effective treatment modality.

Objective: The purpose of this study was to develop an evidence-based rational dosing regimen that results in targeted drug exposure within the therapeutic range while minimizing financial toxicity, to improve treatment access.

Is neoadjuvant chemotherapy followed by surgery the appropriate treatment for esophagogastric signet ring cell carcinomas? A systematic review and meta-analysis.

Background: The impact of neoadjuvant chemotherapy (nCTX) on survival and tumor response in patients with esophagogastric signet ring cell carcinoma (SRCC) is still controversial.

Methods: Two independent reviewers performed a systematic literature search in Medline, CENTRAL, and Web of Science including prospective and retrospective two-arm non-randomized and randomized controlled studies (RCTs). Data was extracted on overall survival (OS) and tumor regression in resected esophagogastric SRCC patients with or without nCTX.

Reinvestigating the performance of artificial intelligence classification algorithms on COVID-19 X-Ray and CT images.

There are concerns that artificial intelligence (AI) algorithms may create underdiagnosis bias by mislabeling patient individuals with certain attributes (e.g., female and young) as healthy.

The Impact of a Multidisciplinary Tumor Board (MTB) on Treatment Decision Making for Patients With Renal Cell Carcinoma (RCC): 5-Year Data Analysis.

Objective: To describe the impact of a multidisciplinary tumor board (MTB) for renal cell carcinoma (RCC) patients in a locoregional renal cancer network by evaluating shared decision making (SDM) and adherence to MTB recommendations.

Design, Setting And Participants: This prospective cohort study included all cases from a Dutch renal cancer network with suspicion of or histologically confirmed RCC discussed in MTBs between 2017-2022. Main endpoints were distribution of cases presented, proportion of recommendations with multiple treatment options enabling shared decision making (SDM), definite treatment after SDM and adherence to MTB recommendations.