Multinational retrospective analysis of bridging therapy prior to chimeric antigen receptor t cells for relapsed/refractory acute lymphoblastic leukemia in children and young adults.

Anti-CD19 chimeric antigen receptor T cells (CAR) are a well-established treatment option for children and young adults suffering from relapsed/refractory B-lineage acute lymphoblastic leukemia. Bridging therapy is used to control disease prior to start of lymphodepletion before CAR infusion and thereby improve efficacy of CAR therapy. However, the effect of different bridging strategies on outcome, side effects and response to CAR therapy is still poorly understood.

Evaluation of circulating tumor DNA as a prognostic and predictive biomarker in BRAF V600E mutated colorectal cancer-results from the FIRE-4.5 study.

The randomized FIRE-4.5 (AIO KRK0116) trial compared first-line therapy with FOLFOXIRI (folinic acid, fluorouracil, oxaliplatin, and irinotecan) plus either cetuximab or bevacizumab in B-Raf proto-oncogene, serine/threonine kinase (BRAF) V600E-mutant metastatic colorectal cancer (mCRC) patients. This study was accompanied by a prospective translational project analyzing cell-free circulating tumor DNA (ctDNA) in plasma to test whether ctDNA analysis may help to guide clinical treatment decision making.

Radical cystectomy in patients aged < 80 years versus ≥ 80 years: analysis of preoperative geriatric assessment scores in predicting postoperative morbidity and mortality.

Purpose: Pre-operative assessment of surgical risk is essential for patient counselling in the elderly patient population. Our purpose was to compare validated geriatric assessment scores (GAS) in predicting postoperative morbidity and mortality in patients ≥ 80 years.

Methods: Overall, eight preoperative GAS were assessed for each patient who received RC from 2016 to 2021.

Translating efficacy of liver transplantation in liver-limited metastatic colorectal cancer into clinical practice: the TransMet trial.

Pioneer studies suggested that liver transplantation (LT) has the potential to provide long-term survival in patients with liver-limited metastatic colorectal cancer (mCRC) not amenable for surgery of metastases. Evidence, however, was limited to single-arm studies with few patients enrolled and suboptimal selection criteria, with concerns over access to organ availability overcoming the potential efficacy of LT in this setting. Recently, 5-year survival rates with chemotherapy followed by LT (73%) compared with chemotherapy alone (9%) have been demonstrated by the randomized TransMet trial, enrolling 94 definitively unresectable strictly selected liver-limited mCRC patients.

Overcoming Resistance to Immune Checkpoint Blockade in Liver Cancer with Combination Therapy: Stronger Together?

Primary liver cancer, represented mainly by hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (CCA), is one of the most common and deadliest tumors worldwide. While surgical resection or liver transplantation are the best option in early disease stages, these tumors often present in advanced stages and systemic treatment is required to improve survival time. The emergence of immune checkpoint inhibitor (ICI) therapy has had a positive impact especially on the treatment of advanced cancers, thereby establishing immunotherapy as part of first-line treatment in HCC and CCA.

A meta-analysis of efficacy and safety data from head-to-head first-line trials of epidermal growth factor receptor inhibitors versus bevacizumab in adult patients with RAS wild-type metastatic colorectal cancer by sidedness.

The first-line treatment choice of EGFRIs plus doublet chemotherapy vs. bevacizumab plus doublet chemotherapy remains a topic of interest for patients with left-sided RAS WT mCRC. We conducted a systematic literature review and meta-analysis of clinical trial data published between 2015 and 2024.

Negative Hyperselection of Resistance Mutations for Panitumumab Maintenance in RAS Wild-Type Metastatic Colorectal Cancer (PanaMa Phase II Trial, AIO KRK 0212).

Purpose: We evaluated additional mutations in RAS wild-type (WT) metastatic colorectal cancer (mCRC) as prognostic and predictive biomarkers for the efficacy of added panitumumab to a 5-fluorouracil plus folinic acid (FU/FA) maintenance as pre-specified analysis of the randomized PanaMa trial.

Patients And Methods: Mutations (MUT) were identified using targeted next-generation sequencing (NGS; Illumina Cancer Hotspot Panel v2) and IHC. RAS/BRAF V600E/PIK3CA/AKT1/ALK1/ERBB2/PTEN MUT and HER2/neu overexpressions were negatively hyperselected and correlated with median progression-free survival (PFS) and overall survival (OS) since start of maintenance treatment, and objective response rates (ORR).

FOLFOXIRI Plus Cetuximab or Bevacizumab as First-Line Treatment of -Mutant Metastatic Colorectal Cancer: The Randomized Phase II FIRE-4.5 (AIO KRK0116) Study.

Purpose: mutation is associated with a poor outcome in metastatic colorectal cancer (mCRC). This clinical trial investigated the efficacy of triplet chemotherapy (fluorouracil, folinic acid, oxaliplatin, and irinotecan) combined with either cetuximab or bevacizumab in patients with previously untreated -mutant mCRC.

Patients And Methods: In this controlled, randomized, open-label phase II trial, 109 patients were randomly assigned, 107 of whom were included into the full analysis set (FAS).

Effectiveness of mogamulizumab in patients with Mycosis Fungoides or Sézary syndrome: A multicentre, retrospective, real-world French study.

Background: Efficacy and safety of mogamulizumab, a monoclonal antibody directed against C-C chemokine receptor 4, were demonstrated in a previous multinational clinical trial conducted in patients with previously treated cutaneous T-cell lymphoma (CTCL): Sézary syndrome (SS) or Mycosis Fungoides (MF).

Objectives: The real-world French OMEGA study aimed to describe effectiveness and tolerability of mogamulizumab in adult patients with CTCL, overall and according to the disease (SS or MF).

Methods: In this retrospective study, patients treated with mogamulizumab for SS or MF were included from 14 French expert centres.

Consensus Molecular Subtypes as Biomarkers of Fluorouracil and Folinic Acid Maintenance Therapy With or Without Panitumumab in Wild-Type Metastatic Colorectal Cancer (PanaMa, AIO KRK 0212).

Purpose: Consensus molecular subtypes (CMSs) were evaluated as prognostic and predictive biomarkers of patients with wild-type metastatic colorectal cancer (mCRC) receiving fluorouracil and folinic acid (FU/FA) with or without panitumumab (Pmab) after Pmab + mFOLFOX6 induction within the randomized phase II PanaMa trial.

Methods: CMSs were determined in the safety set (ie, patients that received induction) and full analysis set (FAS; ie, randomly assigned patients who received maintenance) and correlated with median progression-free survival (PFS) and overall survival (OS) since the start of induction or maintenance treatment and objective response rates (ORRs). Hazard ratios (HRs) and 95% CI were calculated by univariate/multivariate Cox regression analyses.

European expert panel consensus on the clinical management of BRAF-mutant metastatic colorectal cancer.

Metastatic colorectal cancer (mCRC) is a heterogenous disease caused by various genetic alterations. The BRAF mutation occurs in approximately 8-12% of patients and is characterised by an aggressive clinical course and poor prognosis. Here we review the current knowledge on BRAF-mutant mCRC and provide a series of consensus statements on its clinical management.

Anti-GD2 Antibody Dinutuximab Beta and Low-Dose Interleukin 2 After Haploidentical Stem-Cell Transplantation in Patients With Relapsed Neuroblastoma: A Multicenter, Phase I/II Trial.

Purpose: Patients with relapsed high-risk neuroblastoma (rHR-NB) have a poor prognosis. We hypothesized that graft-versus-neuroblastoma effects could be elicited by transplantation of haploidentical stem cells (haplo-SCT) exploiting cytotoxic functions of natural killer cells and their activation by the anti-GD2 antibody dinutuximab beta (DB). This phase I/II trial assessed safety, feasibility, and outcomes of immunotherapy with DB plus subcutaneous interleukin-2 (scIL2) after haplo-SCT in patients with rHR-NB.

Geriatric assessment and the variance of treatment recommendations in geriatric patients with gastrointestinal cancer-a study in AIO oncologists.

Background: Geriatric assessment (GA) is recommended to detect vulnerabilities for elderly cancer patients. To assess whether results of GA actually influence the treatment recommendations, we conducted a case vignette-based study in medical oncologists.

Materials And Methods: Seventy oncologists gave their medical treatment recommendations for a maximum of 4 out of 10 gastrointestinal cancer patients in three steps: (i) based on tumor findings alone to simulate the guideline recommendation for a '50-year-old standard patient without comorbidities'; (ii) for the same situation in elderly patients (median age 77.

Treatment strategies in patients with gynecological sarcoma: Results of the prospective intergroup real-world registry for gynecological sarcoma in Germany (REGSA-NOGGO RU1).

Objective: Gynecological sarcomas account for 3% of all gynecological malignancies and are associated with a poor prognosis. Due to the rarity and heterogeneity of gynecological sarcomas there is still no consensus on optimal therapeutic strategies. This study's objective was to describe the treatment strategies used in patients with gynecological sarcomas in the primary course of disease.

BH3 mimetics targeting BCL-XL impact the senescent compartment of pilocytic astrocytoma.

Background: Pilocytic astrocytoma (PA) is the most common pediatric brain tumor and a mitogen-activated protein kinase (MAPK)-driven disease. Oncogenic MAPK-signaling drives the majority of cells into oncogene-induced senescence (OIS). While OIS induces resistance to antiproliferative therapies, it represents a potential vulnerability exploitable by senolytic agents.

Controversial Role of the Immune Checkpoint OX40L Expression on Platelets in Breast Cancer Progression.

In conventional T cells, OX40 has been identified as a major costimulating receptor augmenting survival and clonal expansion of effector and memory T cell populations. In regulatory T cells, (Treg) OX40 signaling suppresses cellular activity and differentiation. However, clinical trials investigating OX40 agonists to enhance anti-tumor immunity, showed only limited success so far.

Genetic variants involved in the cGAS-STING pathway predict outcome in patients with metastatic colorectal cancer: Data from FIRE-3 and TRIBE trials.

Background: The activation of stimulator of interferon genes (STING) was reported to enhance cetuximab-mediated natural killer cell activation and dendritic cell maturation. Polymorphisms in genes in the cyclic GMP-AMP synthase (cGAS)-STING pathway may affect innate immune response. Therefore, we hypothesised that genetic variants in the cGAS-STING pathway may predict the efficacy of cetuximab-based treatment in patients with metastatic colorectal cancer.

Encorafenib in Combination With Cetuximab After Systemic Therapy in Patients With BRAF Mutant Metastatic Colorectal Cancer: German Health Technology Assessment-Driven Analyses From the BEACON CRC Study.

Background: Purpose of this analysis was to report data of the BEACON CRC trial used in the German Health Technology Assessment (HTA) and previously unpublished data focusing on the dual blockade (encorafenib + cetuximab) and appropriate comparative therapy (ACT/control: cetuximab + irinotecan-based chemotherapy) of patients with BRAF-mutant mCRC.

Materials And Methods: Analyses included overall survival (OS) and time-to-event analyses of morbidity and safety.

Results: A total of 220 patients received encorafenib + cetuximab and 221 patients ACT/control.

Pleomorphic xanthoastrocytoma is a heterogeneous entity with pTERT mutations prognosticating shorter survival.

Pleomorphic xanthoastrocytoma (PXA) in its classic manifestation exhibits distinct morphological features and is assigned to CNS WHO grade 2 or grade 3. Distinction from glioblastoma variants and lower grade glial and glioneuronal tumors is a common diagnostic challenge. We compared a morphologically defined set of PXA (histPXA) with an independent set, defined by DNA methylation analysis (mcPXA).

Complete Pathological Response After Neoadjuvant Short-Course Immunotherapy with Ipilimumab and Nivolumab in Locally Advanced MSI-H/dMMR Rectal Cancer.

Background: Patients with colorectal carcinoma and high-grade microsatellite instability (MSI-H) or deficiency in mismatch repair (dMMR) exceptionally respond to immune checkpoint inhibitors (ICIs). ICIs are more active in treatment-naïve patients than in patients with refractory MSI-H/dMMR metastatic colorectal cancer and even more active in patients with locally advanced tumors.

Material And Methods: A 33-year-old male patient with Lynch syndrome was diagnosed with a locally advanced rectal cancer and refused standard neoadjuvant chemoradiation because of the potential harm of sexual dysfunction.

Secondary resistance to anti-EGFR therapy by transcriptional reprogramming in patient-derived colorectal cancer models.

Background: The development of secondary resistance (SR) in metastatic colorectal cancer (mCRC) treated with anti-epidermal growth factor receptor (anti-EGFR) antibodies is not fully understood at the molecular level. Here we tested in vivo selection of anti-EGFR SR tumors in CRC patient-derived xenograft (PDX) models as a strategy for a molecular dissection of SR mechanisms.

Methods: We analyzed 21 KRAS, NRAS, BRAF, and PI3K wildtype CRC patient-derived xenograft (PDX) models for their anti-EGFR sensitivity.