Efficacy of radiotherapy and radiotherapy with hyperthermia to delay change of systemic therapy in patients with metastatic melanoma.

Background: The use of radiotherapy (RT) and RT with hyperthermia (HT) as a local treatment for oligoprogression in many tumors is becoming increasingly prevalent. However, there is currently limited data regarding RT efficacy in prolonging systemic therapy in melanoma. To address this lack of evidence, we conducted a single-institution study to establish the role of RT and RT + HT in delaying the time to systemic treatment switch in metastatic melanoma (MM).

Phase II study of retifanlimab in patients with recurrent locally advanced or metastatic Merkel cell carcinoma (POD1UM-201).

Background: POD1UM-201, an open-label, single-arm, phase II multiregional study, evaluated efficacy and tolerability of retifanlimab, a humanized monoclonal antibody targeting programmed cell death protein-1 (PD-1) in chemotherapy-naive patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC).

Methods: Patients were enrolled across 34 sites in the USA, Canada, and Europe. Eligible patients were ≥18 years with confirmed recurrent advanced locoregional or metastatic MCC not amenable to surgery or radiation therapy, had not received previous systemic treatment, had measurable disease, and Eastern Cooperative Oncology Group performance status 0-1.

How to foster new treatment development in ultra-rare tumours? Joint EMA-EORTC multi-stakeholder workshops on ultra-rare sarcomas as a model for rare cancers.

Ultra-rare sarcomas (URS) and ultra-rare cancers (URC) represent a unique challenge in oncology due to their rarity, heterogeneity, and the severe unmet clinical needs of affected patients. In 2024, the European Medicines Agency (EMA) and the European Organisation for Research and Treatment of Cancer (EORTC) convened two multi-stakeholder workshops, bringing together regulators, clinicians, researchers, and patient advocates. These workshops aimed to explore innovative strategies for treatment development and establish a framework for future collaboration.

Real-life data on tebentafusp in metastatic uveal melanoma patients from four EURACAN Expert Centres.

Background: Tebentafusp is the first approved systemic therapy with overall survival (OS) benefit in HLA-A*02:01-positive patients with metastatic uveal melanoma (mUM). We present the largest real-life study on safety and efficacy.

Methods: Retrospective multicenter study, patients started tebentafusp Early Access between May 2021 and May 2023 in 4 EURACAN centres (European Reference Network for Rare Adult Solid Cancers); Institut Curie Paris, Leiden University Medical Center, Maria Skłodowska-Curie National Research Institute of Oncology, and Cliniques universitaires Saint-Luc UCLouvain Bruxelles.

DNA Methylation Profiling Separates SDH-Deficient GISTs From KIT-PDGFRA-Driven GISTs and Identifies Predictive Biomarkers for Targeted Therapy.

Succinate dehydrogenase (SDH), a critical enzyme in the citric acid cycle and respiratory electron transport chain, consists of 4 subunits: SDHA, SDHB, SDHC, and SDHD. Deficiency of a single subunit leads to the loss of SDH activity which is implicated in the development of a subset of gastrointestinal stromal tumors (GISTs): SDH-deficient GISTs. These GISTs arise almost exclusively in the stomach, have a female predilection, and primarily affect children and young adults.

Chemotherapy efficacy in advanced melanoma patients after failure of immune checkpoint and BRAF/MEK inhibitors.

Introduction: Despite the introduction of new therapies for the treatment of advanced melanoma, treatment is ineffective for a certain number of patients. The efficacy of chemotherapy after failure of anti-programmed death receptor (PD-1) immunotherapy alone or combined with anti-cytotoxic T-lymphocyte-associated antigen (CTLA) is not fully understood. It is believed that due to the immunomodulatory effect of cytostatic agents, its efficacy may be greater when applied after the failure of immunotherapy.

Unraveling Relatlimab-Specific Biology Using Biomarker Analyses in Patients with Advanced Melanoma in RELATIVITY-047.

Purpose: Administration of the lymphocyte activation gene 3 (LAG-3) inhibitor relatlimab (RELA) and the PD-1 inhibitor nivolumab (NIVO) significantly prolonged progression-free survival (PFS) versus NIVO alone in patients with advanced melanoma treated in RELATIVITY-047. This report describes correlative analyses of biospecimens collected within that trial to better understand the mechanisms of action and identify patients who could benefit from treatment with NIVO + RELA.

Patients And Methods: Pre- and on-treatment peripheral blood samples from 563 patients were analyzed using flow cytometry for changes in 77 prespecified immune cell populations and using immunoassay for peripheral IFNγ.

Discontinuation of Immune Checkpoint Inhibition in Patients with Advanced Unresectable Melanoma Achieving CR, PR, or SD.

Background: The optimal duration of immunotherapy (ITH) remains undefined for patients with metastatic melanoma, and debates on de-escalation strategies are ongoing. Patients in the pivotal KEYNOTE and CheckMate trials who experienced a complete response (CR) on ITH had long-term responses, even after treatment was terminated early because of toxicity or at the physician's discretion.

Objective: Our study explores the duration of planned ITH drug holidays-intentional ITH suspension until disease progression off treatment-in patients with unresectable and metastatic melanoma treated for at least 6 months with ITH.

Defining benchmark values for outcomes of comprehensive resection of primary retroperitoneal liposarcoma: a retrospective multicenter study.

Background: Comprehensive resection represents the standard of care for patients affected by retroperitoneal well- or dedifferentiated liposarcoma (WDLPS/DDLPS). However, reference values to indicate the best achievable results are currently lacking. As such, the study aimed to define clinically relevant benchmark values for intra- and postoperative outcomes of patients undergoing comprehensive resection for primary retroperitoneal WDLPS/DDLPS.

Global Variations in Patterns of Care for Retroperitoneal Sarcoma.

Objective: To examine variations in patterns of care for retroperitoneal sarcoma (RPS) among sarcoma centres globally, including diagnostic work-up, surgical strategies and (neo)adjuvant therapies.

Methods: Retrospective analysis for primary RPS, from 19 RPS referral centres worldwide, prospectively collected within the RESAR repository (NCT03838718) between Feb 2017 - July 2022. Centres were categorised high volume (HVC) or low volume (LVC).

Diagnostic work-up of lipomatous tumors: a decision-making analysis among European sarcoma centers.

Objectives: Lipomatous soft-tissue tumors present a diagnostic burden. The aim of this work was to compare standard operating procedures (SOPs) for the diagnostic management of lipomatous soft-tissue tumors among European academic centers.

Methods: Experts of the Soft Tissue and Bone Sarcoma Group of the European Organization for Research and Treatment of Cancer were asked for their SOPs in the diagnosis of adipocytic soft-tissue tumors in an otherwise healthy patient.

Nivolumab plus relatlimab in advanced melanoma: RELATIVITY-047 4-year update.

Background: In phase 2/3 randomized RELATIVITY-047, nivolumab plus relatlimab demonstrated a statistically significant improvement in progression-free survival (PFS), a clinically meaningful but not statistically significant improvement in overall survival (OS), and a numerically higher objective response rate (ORR) versus nivolumab alone in patients with previously untreated advanced melanoma.

Methods: Descriptive 4-year updated analyses in patients treated with nivolumab 480 mg plus relatlimab 160 mg fixed-dose combination versus nivolumab 480 mg intravenously every 4 weeks are presented. Primary endpoint was PFS by blinded independent central review (BICR).

Combined immunotherapy with nivolumab and ipilimumab with and without sequential or concomitant stereotactic radiotherapy in patients with melanoma brain metastasis: An international retrospective study.

Background: Ipilimumab plus nivolumab (COMBO) is the standard treatment in patients with asymptomatic melanoma brain metastases (MBM). We report a retrospective study aiming to assess the outcome of patients with MBM treated with COMBO with or without sequential/concomitant stereotactic radiotherapy (SRT).

Methods: MBM patients treated with COMBO with or without SRT have been retrieved: demographics, steroid treatment, Central Nervous System [CNS]-related symptoms, BRAF status, radiotherapy (yes/no and timing) or surgery, number of MBM, maximum diameter of metastasis, overall response rate (ORR), progression-free (PFS) and overall survival (OS) have been analyzed.

Avelumab plus axitinib in patients with advanced gastrointestinal stromal tumor.

Background: Treatment options for patients with advanced gastrointestinal stromal tumor (GIST) after failure of standard therapies with tyrosine kinase inhibitor (TKI) remain very limited. As vascular endothelial growth factor (VEGF) inhibitors are considered to have immunomodulatory effects, we hypothesized that the combination of VEGF and PD-L1 inhibitors may have a synergistic effect and enhance the efficacy of both therapies.

Methods: AXAGIST was a phase II trial evaluating the efficacy and safety of avelumab 10 mg/kg iv Q2W in combination with axitinib 5 mg po BID in patients with unresectable/metastatic GIST after failure of standard therapy.

Adjuvant Cemiplimab or Placebo in High-Risk Cutaneous Squamous-Cell Carcinoma.

Background: Patients who have cutaneous squamous-cell carcinoma with high-risk features are at risk for recurrence after definitive local therapy. The benefit of systemic adjuvant therapy options has not been well established in clinical trials.

Methods: In a phase 3, randomized trial, we enrolled patients with local or regional cutaneous squamous-cell carcinoma, after surgical resection and postoperative radiotherapy, at high risk for recurrence owing to nodal features (extracapsular extension with largest node ≥20 mm in diameter or at least three involved nodes) or nonnodal features (in-transit metastases, T4 lesion [with bone invasion], perineural invasion, or locally recurrent tumor with ≥1 additional risk feature).

Ocelli: an open-source tool for the analysis and visualization of developmental multimodal single-cell data.

The recent expansion of single-cell technologies has enabled simultaneous genome-wide measurements of multiple modalities in the same single cell. The potential to jointly profile such modalities as gene expression, chromatin accessibility, protein epitopes, or multiple histone modifications at single-cell resolution represents a compelling opportunity to study developmental processes at multiple layers of gene regulation. Here, we present Ocelli, a lightweight Python package implemented in Ray for scalable visualization and analysis of developmental multimodal single-cell data.

Radiologic and Pathologic Response Evaluation After Neoadjuvant Chemotherapy for Primary Retroperitoneal Sarcoma: A Transatlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG) Collaboration.

Background: Comsplete resection is the primary treatment for retroperitoneal sarcomas (RPS). The role of neoadjuvant chemotherapy (NACT) in improving oncologic outcomes is currently under investigation in the STRASS 2 trial. This study assessed the association between change in tumor size or pathologic response and oncologic outcomes.

A pattern of local failure after preoperative 5 × 5 Gy in soft tissue sarcomas: A long-term real-world experience.

Introduction: Preoperative radiotherapy (RT) is used to improve local control (LC) and facilitate limb-sparing procedures in patients with localized soft tissue sarcomas (STS). While conventional preoperative RT delivers 50-50.4 Gy in 25-28 fractions, alternative hypofractionated regimens are under investigation.

Pembrolizumab versus placebo as adjuvant therapy in resected stage IIB or IIC melanoma: Long-term follow-up, crossover, and rechallenge with pembrolizumab in the phase III KEYNOTE-716 study.

Background: Adjuvant pembrolizumab prolonged recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) in patients with resected stage IIB/IIC melanoma in KEYNOTE-716. Results of a post hoc 4-year analysis are reported, including progression/recurrence-free survival 2 (PRFS2).

Methods: Patients were randomly assigned 1:1 to pembrolizumab 200 mg or placebo intravenously every 3 weeks (part 1).

Conference on challenges in sarcoma (CCS) 2024: Expert opinions on non-evidence-based management aspects.

Background: Soft tissue sarcomas (STS) and other mesenchymal tumours belong to rare, heterogeneous neoplasms with over 150 subtypes that pose significant challenges in diagnosis and clinical decision making. While guidelines address evidence-based diagnostic and therapeutic procedures, clinical situations and scenarios without evidence remain controversial in daily practice. The 2024 Conference on Challenges in Sarcoma (CCS2024) aimed to narrow these gaps with the support of an international and multidisciplinary panel of sarcoma experts.

Neoadjuvant or Adjuvant Chemotherapy in Soft-Tissue Sarcoma?

Purpose Of Review: The review compares the effectiveness of neoadjuvant(pre-operative, NAC) and adjuvant(post-operative, AC) in Soft Tissue Sarcomas as this topic is controvesial and multiple new studies have been over the years.

Recent Findings: Sarculator and other nomograms assess patients with a predicted 10-year OS below 60% who will benefit from perioperative chemotherapy. Further research supports perioperative chemotherapy's role.

Meeting Highlights The 4th Marie Skłodowska-Curie Symposium on cancer research and care: Mechanisms of support for regional & international collaborations.

The Marie Skłodowska-Curie Symposia on Cancer Research and Care (MSCS-CRC) promote collaborations between cancer researchers and care providers in the United States, Canada and Central and Eastern European Countries (CEEC) to accelerate the development of new cancer therapies, new strategies for early detection and prevention, and improve cancer care and the quality of life for patients and their families. The 4th MSCS-CRC (September 25-27, 2024, Buffalo, New York) brought together 147 participants from the US, Canada, Croatia, Czechia, Lithuania, Poland, Romania and Ukraine, and involved representatives of the US Centers for Disease Control and Prevention (CDC), National Cancer Institute (NCI) and their counterparts from Poland, Ukraine Lithuania and other CEECs. They were accompanied by New York State (NYS) and local representatives of the NYS Empire State Development, and of the Translational Research Consortium of Cancer Centers (TRCCC), involving 13 cancer centers from the Northeastern US and Canada, as well as several Pharma and Biotech companies.