Tumor fraction-based prognostic tool for cancer patients referred to early phase clinical trials.

Selecting patients for phase I cancer trials is crucial to ensure a sufficient life expectancy. Frail patients, better suited for palliative care, should not be exposed to new drugs with minimal benefit. Enrolling patients at high risk of early death can jeopardize the study.

Identification of microenvironment features associated with primary resistance to anti-PD-1/PD-L1 + antiangiogenesis in gastric cancer through spatial transcriptomics and plasma proteomics.

Anti-angiogenic agents elicit considerable immune modulatory effects within the tumor microenvironment, underscoring the rationale for synergistic clinical development of VEGF and immune checkpoint inhibitors in advanced gastric cancer (AGC). Early phase studies involving Asian patients demonstrated encouraging anti-tumor efficacies. We report the results of the REGOMUNE phase II study, in which Caucasian patients were administered regorafenib, a multi-tyrosine kinase inhibitor, in combination with avelumab, a PD-L1-targeting monoclonal antibody.

Sample Size Estimation Using a Partially Clustered Frailty Model for Biomarker-Strategy Designs With Multiple Treatments.

Biomarker-guided therapy is a growing area of research in medicine. To optimize the use of biomarkers, several study designs including the biomarker-strategy design (BSD) have been proposed. Unlike traditional designs, the emphasis here is on comparing treatment strategies and not on treatment molecules as such.

An update on the novel methods for the discovery of antiseizure and antiepileptogenic medications: where are we in 2024?

Introduction: Despite the availability of around 30 antiseizure medications, 1/3 of patients with epilepsy fail to become seizure-free upon pharmacological treatment. Available medications provide adequate symptomatic control in two-thirds of patients, but disease-modifying drugs are still scarce. Recently, though, new paradigms have been explored.

Short-term Darolutamide (ODM-201) Concomitant to Radiation Therapy for Patients with Unfavorable Intermediate-risk Prostate Cancer: The Darius (AFU-GETUG P15) Phase 2 Trial Protocol.

Background: Combination of androgen deprivation therapy (ADT) with external beam radiation therapy (EBRT) is a standard of care for patients with intermediate-risk prostate cancer (PCa). However, 6 months of ADT generates multiple side effects impacting quality of life (QoL). Darolutamide (an androgen receptor targeting agent [ARTA]) is associated with low blood-brain barrier penetrance and less drug-drug interaction.

Reshaping the tumor microenvironment of cold soft-tissue sarcomas with oncolytic viral therapy: a phase 2 trial of intratumoral JX-594 combined with avelumab and low-dose cyclophosphamide.

Most soft-tissue sarcomas (STS) exhibit an immunosuppressive tumor microenvironment (TME), leading to resistance against immune checkpoint inhibitors (ICIs) and limited therapeutic response. Preclinical data suggest that oncolytic viral therapy can remodel the TME, facilitating T cell accumulation and enhancing the immunogenicity of these tumors.We conducted the METROMAJX, a phase II clinical trial, to investigate the combination of JX-594, an oncolytic vaccinia virus engineered for selective tumor cell replication, with metronomic cyclophosphamide and the PD-L1 inhibitor avelumab in patients with advanced, 'cold' STS, characterized by an absence of tertiary lymphoid structures.

Sample size estimation for recurrent event data using multifrailty and multilevel survival models.

In epidemiology and clinical research, recurrent events refer to individuals who are likely to experience transient clinical events repeatedly over an observation period. Examples include hospitalizations in patients with heart failure, fractures in osteoporosis studies and the occurrence of new lesions in oncology. We provided an in-depth analysis of the sample size required for the analysis of recurrent time-to-event data using multifrailty or multilevel survival models.

Handling missing covariates in observational studies: an illustration with the assessment of prognostic factors of survival outcomes in soft-tissue or visceral sarcomas in irradiated fields (SIF).

Background: Missing covariates are common in observational research and can lead to bias and loss of statistical power. Limited data regarding prognostic factors of survival outcomes of sarcomas in irradiated fields (SIF) are available. Because of the long lag time between irradiation of first cancer and scarcity of SIF, missing data are a critical issue when analyzing long-term outcomes.

Real-World Treatment Patterns and Effectiveness of Patients With Advanced Renal Cell Carcinoma: A Nationwide Observational Study.

Background: Treatment landscape for advanced renal cell carcinoma (aRCC) has evolved quickly and few data about the real-world treatment patterns are available. This study aimed at describing the real-world treatment patterns and effectiveness of all systemic treatments available for aRCC in first and second-line treatment.

Materials And Methods: A cohort of patients initiating a first-line systemic treatment for aRCC in 2016 was extracted from the French nationwide healthcare insurance system database (SNDS).

Anastomotic leakage and functional outcomes following total mesorectal excision with delayed and immediate colo-anal anastomosis for rectal cancer: Two single-arm phase II trials.

Background: Anastomotic leakage (AL) remains a major cause of morbidity following total mesorectal excision (TME). A diverting ileostomy reduces the risk of AL but impairs quality of life (QoL). Delayed colo-anal anastomosis (DCAA) may be an alternative to immediate colo-anal anastomosis (ICAA) without creation of a diverting ileostomy.

Evolution of Patterns of Care and Outcomes in the Real-Life Setting for Patients with Metastatic GIST Treated in Three French Expert Centers over Three Decades.

Gastrointestinal stromal tumors (GIST) are rare mesenchymal tumors characterized by or mutations. Over three decades, significant changes in drug discovery and loco-regional (LR) procedures have impacted treatment strategies. We assessed the evolution of treatment strategies for metastatic GIST patients treated in the three national coordinating centers of NetSarc, the French network of sarcoma referral centers endorsed by the National Institute of Cancers, from 1990 to 2018.

Assessing patient-reported outcomes (PROs) and patient-related outcomes in randomized cancer clinical trials for older adults: Results of DATECAN-ELDERLY initiative.

As older adults with cancer are underrepresented in randomized clinical trials (RCT), there is limited evidence on which to rely for treatment decisions for this population. Commonly used RCT endpoints for the assessment of treatment efficacy are more often tumor-centered (e.g.

Impact of the coronavirus disease 2019 pandemic on sarcoma management in France: a 2019 and 2020 comparison.

Background: The coronavirus disease 2019 (COVID-19) pandemic was an unprecedented shock to the healthcare systems, and its consequences on managing rare cancers are unknown. We investigated COVID-19's impact on the activity of sarcoma-labeled networks by comparing key indicators in 2019-2020 (before and during the pandemic, respectively).

Methods: We compared the incidence of limb and trunk soft tissue sarcomas, surgery rate, surgery center, surgery quality, and surgery delays nationally and in various regions, focusing on the three most severely affected regions.

High dose (54 Gy) pre-operative helical tomotherapy for retroperitoneal liposarcoma: Results of a phase II multicenter study.

Purpose: To evaluate efficacy and feasibility of high-dose intensity-modulated radiotherapy (RT) with pre-operative helical tomotherapy, delivering 54 Gy/30 fractions in patients with retroperitoneal liposarcomas (RPLS).

Materials And Methods: Patients with operable, biopsy-proven, RPLS were included in this phase II multicenter study (ClinicalTrials.gov: NCT01841047).

Survival outcomes of patients with metastatic non-small cell lung cancer receiving chemotherapy or immunotherapy as first-line in a real-life setting.

Treatment of metastatic non-small cell lung cancer (mNSCLC) has been modified due to the development of immunotherapy. We assessed survival outcomes (overall [OS] and progression-free [rwPFS] survivals, time-to-next-treatment [TNT]) in mNSCLC patients after first-line immunotherapy and chemotherapy in real-life settings. Association between rwPFS and TNT, two candidate surrogate endpoints (SE), with OS was assessed.

Association between progression-free survival and overall survival in women receiving first-line treatment for metastatic breast cancer: evidence from the ESME real-world database.

Background: Overall survival (OS) is the gold standard endpoint to assess treatment efficacy in cancer clinical trials. In metastatic breast cancer (mBC), progression-free survival (PFS) is commonly used as an intermediate endpoint. Evidence remains scarce regarding the degree of association between PFS and OS.

Standardized Pathology Screening of Mature Tertiary Lymphoid Structures in Cancers.

Mature tertiary lymphoid structures (mTLSs) are organized lymphoid structures containing B lymphocytes admixed to CD23+ follicular dendritic cells. Their presence has been linked to improved survival and sensitivity to immune checkpoint inhibitors in several cancers, emerging as a promising pancancer biomarker. However, the requirements for any biomarker are clear methodology, proven feasibility, and reliability.

Determination of Interactive States of Immune Checkpoint Regulators in Lung Metastases after Radiofrequency Ablation.

Background: Cases of the spontaneous regression of multiple pulmonary metastases, after radiofrequency ablation (RFA), of a single lung metastasis, have been documented to be mediated by the immune system. The interaction of immune checkpoints, e.g.

Phase 2 trial of intravenous oncolytic virus JX-594 combined with low-dose cyclophosphamide in patients with advanced breast cancer.

Breast cancer is one the most common cause of cancer death in women worldwide. We report here the first phase II study investigating a virus genetically engineered for tumor-selective replication in patients with breast cancer. Ten patients were treated with a combination of low-dose oral cyclophosphamide and intra-venous JX-594, a thymidine kinase gene-inactivated oncolytic vaccinia virus engineered for the expression of transgenes encoding human granulocyte-macrophage colony-stimulating factor (GM-CSF) and β-galactosidase.

A Two-Step Frailty Assessment Strategy in Older Patients With Solid Tumors: A Decision Curve Analysis.

Purpose: The intended clinical value of frailty screening is to identify unfit patients needing geriatric assessment (GA) and to prevent unnecessary GA in fit patients. These hypotheses rely on the sensitivity and specificity of screening tests, but they have not been verified.

Methods: We performed a cross-sectional analysis of outpatients age ≥ 70 years with prostate, breast, colorectal, or lung cancer included in the ELCAPA cohort study (ClinicalTrials.