Time tO last ChemotherApy and death in ovaRian cancEr patients: TO CARE/MITO 42 study, a retrospective analysis of italian MITO centers.

Introduction: The European Society for Medical Oncology (ESMO) 2021 Guidelines contraindicate the administration of chemotherapy in the last month of patients' life. The main objective of this multicenter observational retrospective study was to calculate the time elapsed between the date of the last chemotherapy and the date of death of patients with ovarian cancer. The secondary objectives were to identify any factors associated with a greater probability of receiving chemotherapy in the end of life.

Pseudoprogression and improvement of quality of life in a patient with advanced endometrial cancer treated with immunotherapy: a case report.

Until recently, treatment options for patients with recurrent or metastatic endometrial cancer (EC) were limited. First-line treatment is usually based on carboplatin and paclitaxel and there was no standard second-line therapy following platinum failure. However, the introduction of immunotherapy has expanded both first-line and later-line options for EC and made determination of mismatch repair status essential.

Trabectedin maintenance therapy after liposomal doxorubicin plus trabectedin combination in patients with relapsed ovarian cancer: the randomized, phase II TRAMANT study.

Objective: TRAMANT was a multicenter, randomized phase II study assessing the non-inferiority of trabectedin (TRB) as maintenance therapy in patients with relapsed ovarian cancer who responded to initial treatment with pegylated liposomal doxorubicin (PLD) + TRB.

Methods: Patients with partially platinum-sensitive recurrent ovarian cancer, defined by a platinum-free interval of 6-12 months, were randomly assigned to receive either TRB alone or continued combination therapy. The primary endpoint was progression-free survival, with secondary endpoints including overall survival, objective response rate, and quality of life assessments.

PD-1 and PD-L1 Expression in Endometrial Cancer: A Systematic Review of the Literature.

Cancer immunotherapy through the use of PD-1/PD-L1 inhibitors have shown significant promise in endometrial carcinoma (EC), particularly in tumors with microsatellite instability (MSI) or mismatch repair deficiency (dMMR), present in approximately 30% of cases. This review evaluated PD-L1 and PD-1 expression as potential biomarkers for immunotherapy response in EC, focusing on their relationship with MSI status. A systematic review, adhering to PRISMA guidelines, analyzed studies from MEDLINE and Embase until February 2023 on PD-1/PD-L1 expression in EC stratified by MSI status, including diverse study designs but excluding conference abstracts, with independent screening, data extraction, and additional reference checks to ensure comprehensive coverage.

Treatment Strategies for Advanced Endometrial Cancer According to Molecular Classification.

The management of advanced endometrial cancer (EC) has changed in the last few years due to the introduction of a new molecular classification and the approval of immunotherapy. For a long time, carboplatin plus paclitaxel was considered the standard treatment for first-line advanced EC, since the approval of the combination of chemotherapy plus immunotherapy. For patients with recurrent EC, with previous platinum-based chemotherapy, single-agent immunotherapy or in combination with tyrosine-kinase inhibitor (TKI) has been approved according to mismatch repair status.

The Impact of Neoadjuvant Chemotherapy on Ovarian Cancer Tumor Microenvironment: A Systematic Review of the Literature.

Immunotherapy, particularly the use of immune checkpoint inhibitors (ICIs), has shown limited efficacy in treating ovarian cancer (OC), possibly due to diverse T cell infiltration patterns in the tumor microenvironment. This review explores how neoadjuvant chemotherapy (NACT) impacts the immune landscape of OC, focusing on tumor-infiltrating lymphocytes (TILs), PD-1/PD-L1 expression, and their clinical implications. A comprehensive literature search across four databases yielded nine relevant studies.

Management of metastatic endometrial cancer: physicians' choices beyond the first line after approval of checkpoint inhibitors.

Introduction: Endometrial cancer (EC) represents 3.4% of all newly diagnosed cancer cases and is responsible for 2.1% of all cancer-related deaths.

Retrospective Analysis of the Correlation of MSI-h/dMMR Status and Response to Therapy for Endometrial Cancer: RAME Study, a Multicenter Experience.

Background: There is poor evidence regarding sensitivity to chemotherapy in endometrial cancer (EC) based on microsatellite instability (MSI)/mismatch repair (MMR) status.

Methodology: The RAME study is a retrospective analysis aiming to assess response to chemotherapy in MSI-high (h)/deficient (d) MMR and MSI-low (l)/proficient (p) MMR EC patients. Primary endpoints were recurrence-free survival (RFS) for patients with localized disease and progression-free survival (PFS) and overall survival (OS) in patients with advanced/recurrent disease.

Analysis of the adequacy of control arms in oncology randomised clinical trials published between 2017 and 2021: a meta-research study.

Introduction: Randomised controlled trials (RCTs) are usually considered the highest level of evidence for clinical practice. Patients assigned to control arm in RCTs should always receive the best available treatments to protect participants while also allowing for proper interpretation and applicability of study results. Here we analysed RCTs published in oncology between 2017 and 2021 to describe the frequency of suboptimal control arms.

Effect of bevacizumab in advanced low grade serous ovarian cancer: Data from the MITO 22 trial.

Objective: The aim of the present analysis was to explore the efficacy of Bevacizumab (Bev) on survival outcome in advanced low grade serous ovarian cancer (LGSOC) both in first line and in recurrent setting.

Methods: In retrospective observational multicenter study, we described the outcome of LGSOC patients enrolled in the MITO 22 study and treated with chemotherapy (CT) with or without Bev. Patients receiving Bev in first-line or in recurrence were considered and compared with patients receiving CT alone (stage III and IV in first line; platinum based-CT in second line).

Time trends in health-related quality of life assessment and reporting within publications of oncology randomised phase III trials: a meta-research study.

Objective: To assess time trends in the inclusion of health-related quality of life (QoL) among study endpoints and in the reporting of QoL results in study publications, randomised phase III oncology trials published between 2017 and 2021 were compared with the trials published in the previous 5 years.

Methods And Analysis: All issues published between 2012 and 2021 by 11 major journals were handsearched for primary publications of phase III trials in adult patients with solid tumours. Trials published in 2017-2021 were compared with trials published in 2012-2016 for three endpoints: (1) proportion of publications including QoL among endpoints out of all the eligible publications; (2) proportion of publications presenting QoL results out of those including QoL among endpoints and (3) proportion of publications presenting QoL data out of all the eligible publications.

Ki67 as a Predictor of Response to PARP Inhibitors in Platinum Sensitive BRCA Wild Type Ovarian Cancer: The MITO 37 Retrospective Study.

Background: There is compelling need for novel biomarkers to predict response to PARP inhibitors (PARPi) in BRCA wild-type (WT) ovarian cancer (OC).

Methods: MITO 37 is a multicenter retrospective study aiming at correlating Ki67 expression at diagnosis with a clinical outcome following platinum treatment and PARPi maintenance. Clinical data were collected from high grade serous or endometroid BRCAWT OC treated with niraparib or rucaparib maintenance between 2010-2021 in 15 centers.

Prescribing pattern of anticoagulants in patients with cancer associated thrombosis: Results of a survey among MITO group and AIOM society.

Introduction: Low molecular weight heparin (LMWH) has been the backbone of the treatment of cancer associated thrombosis (CAT). Direct-acting oral anticoagulants (DOACs) have shown efficacy and safety not inferior to LMWH and guidelines included DOACs as an option for CAT treatment. Nevertheless, DOACs are still poorly prescribed in patients with cancer.

MEK inhibitor as single agent in low grade serous ovarian and peritoneal cancer: a systematic review and meta-analysis.

Background: Low grade serous carcinoma of the ovary and peritoneum (LGSC) is characterized by low response rates to chemotherapy and by MAPK pathway alterations. Phase II/III clinical trials tested different MEK inhibitors (MEKis) in this complex malignancy, with heterogenous results. Purpose of this systematic review and meta-analysis is to define activity and efficacy of these agents and explore differences in clinical outcomes related to RAS/RAF mutational status.

Clinical characteristics and molecular aspects of low-grade serous ovarian and peritoneal cancer: a multicenter, observational, retrospective analysis of MITO Group (MITO 22).

Background: Low-grade serous ovarian and peritoneal cancer (LGSC) is a rare disease and few data on the clinical and genomic landscape have been published.

Methods: A retrospective analysis of patients diagnosed with LGSC between 1996 and 2019 was conducted in MITO centers. Objective Response Rate (ORR) to treatments, progression-free survival (PFS) and overall survival (OS) were assessed.

Management of Metastatic Endometrial Cancer: Physicians' Choices Beyond the First Line. A MITO Survey.

Background: Endometrial cancer (EC) therapeutic and diagnostic approaches have been changed by the development of a new prognostic molecular classification, the introduction of dostarlimab in microsatellite instability (MSI) high pre-treated advanced EC patients with further expected innovation deriving from lenvatinib plus pembrolizumab regardless MSI status. How this is and will be translated and embedded in the clinical setting in Italy is not known; this is why we developed Multicentre Italian Trials in Ovarian cancer and gynaecologic malignancies (MITO) survey on the current practice and expected future changes in EC.

Methods: We designed a self-administered, multiple-choice online questionnaire available only for MITO members for one month, starting in April 2021.

Immunotherapy for Cervical Cancer: Are We Ready for Prime Time?

The prognosis of invasive cervical cancer (CC) remains poor, with a treatment approach that has remained the same for several decades. Lately, a better understanding of the interactions between the disease and the host immune system has allowed researchers to focus on the employment of immune therapy in various clinical settings. The most advanced strategy is immune checkpoint inhibitors (ICIs) with numerous phase II and III trials recently concluded with very encouraging results, assessing single agent therapy, combinations with chemotherapy and radiotherapy.

Biological Role of Tumor/Stromal CXCR4-CXCL12-CXCR7 in MITO16A/MaNGO-OV2 Advanced Ovarian Cancer Patients.

This study investigated the prognostic role of the CXCR4-CXCL12-CXCR7 axis in advanced epithelial ovarian cancer (EOC) patients receiving first-line treatment within the MITO16A/MaNGO-OV2 phase-IV trial. CXCR4-CXCL12-CXCR7 expression was evaluated in the epithelial and stromal component of 308 EOC IHC-stained tumor samples. The statistical analysis focused on biomarkers' expression, their association with other variables and prognostic value.

Biomarkers of Central Nervous System Involvement from Epithelial Ovarian Cancer.

Epithelial ovarian cancer (EOC) is the leading cause of death among women affected by gynaecological malignancies. Most patients show advanced disease at diagnosis (FIGO stage III-IV) and, despite the introduction of new therapeutic options, most women experience relapses. In most cases, recurrence is abdominal-pelvic; however, EOC can occasionally metastasize to distant organs, including the central nervous system.

The Role of PARP Inhibitors in the Ovarian Cancer Microenvironment: Moving Forward From Synthetic Lethality.

PARP inhibitors (PARPi) have shown promising clinical results and have revolutionized the landscape of ovarian cancer management in the last few years. While the core mechanism of action of these drugs has been largely analyzed, the interaction between PARP inhibitors and the microenvironment has been scarcely researched so far. Recent data shows a variety of mechanism through which PARPi might influence the tumor microenvironment and especially the immune system response, that might even partly be the reason behind PARPi efficacy.

Differences in PARP Inhibitors for the Treatment of Ovarian Cancer: Mechanisms of Action, Pharmacology, Safety, and Efficacy.

Poly(ADP-ribose) polymerases (PARP) are proteins responsible for DNA damage detection and signal transduction. PARP inhibitors (PARPi) are able to interact with the binding site for PARP cofactor (NAD+) and trapping PARP on the DNA. In this way, they inhibit single-strand DNA damage repair.