Electronic malignant bowel obstruction symptom monitoring smartphone application for patients with gynecologic cancers.

OBJECTIVES: Implementation of an interprofessional program at Princess Margaret Cancer Centre, including nurse-led proactive calls to support patients with gynecologic cancers with malignant bowel obstruction, demonstrated improved outcomes compared with historical controls. The aim of the study was to convert the proactive calls into an electronic monitoring program to assess it's feasibility and scalability in patients with gynecologic cancers with or at risk of malignant bowel obstruction. METHODS: 'My Bowels on Track' smartphone application included weekly/biweekly electronic patient-reported outcomes (PROs), educational materials, and a secure messaging system. Based on PRO answers, an alerting system flagged patients with symptoms or uncompleted PROs. Nurses tracked and called patients on receiving clinical or compliance alerts. The primary objective was to assess adherence (≥70% PRO completion per patient considered an adherent patient) in the first 2 months on the program. A secondary objective was to assess the positive predictive value (PPV) of the alerts to trigger recommendations. RESULTS: Forty patients were enrolled between August 2021 and September 2022. Median age was 64.5 years (range 29-79 years). Primary diagnosis was ovarian (75%), endometrial (17.5%), or cervical (7.5%) cancer, and 92.5% of patients were receiving systemic therapy. Median duration on the program was 55 days (range 8-121 days). The 2-month adherence was 65% (95% CI 50% to 80%) and the overall adherence was 60% (95% CI 43% to 75%). Sixty-five symptom-related alerts (75% severe, 25% moderate) were reported in 60% (24/40) of patients. There were 59 recommendations triggered by the alerts. The PPV of the alerts to trigger actions was 72% (95% CI 58% to 82%). CONCLUSIONS: This pilot electronic malignant bowel obstruction monitoring program with real-time PRO assessment was feasible, and 65% of participants were adherent during the first 2 months on the program. The PRO response-based alerting system flagged concerning symptoms in 60% of participants, with a PPV of 72% to trigger nurse-led actions and/or management recommendations. TRIAL REGISTRATION NUMBER: NCT03260647.

Emerging peptide therapeutics for the treatment of ovarian cancer.

INTRODUCTION: The discovery of therapeutic proteomic targets has resulted in remarkable advances in oncology. Identification of functional and hallmark peptides in ovarian cancer can be leveraged for diagnostic and therapeutic targeting. These targets are expressed in different tumor cell locations, making them excellent candidates for theranostic imaging, precision therapeutics, and immunotherapy. The ideal target is homogeneously overexpressed in malignant cells with no expression in healthy cells, thereby avoiding off-tumor bystander toxicity. Several peptides are currently undergoing extensive evaluation for the development of vaccines, antibody-drug conjugates, monoclonal antibodies, radioimmunoconjugates, and cell therapy. AREAS COVERED: This review focuses on the significance of peptides as promising targets in ovarian cancer. English peer-reviewed articles and abstracts were searched in MEDLINE, PubMed, Embase, and major conference databases. EXPERT OPINION: Peptides and proteins expressed in tumor cells are an exciting area of research with great potential and may significantly influence precision therapeutics and immunotherapeutic strategies. Accurate utilization of peptide expression as a predictive biomarker has the potential to greatly enhance treatment precision. The ability to measure receptor expression paves the way for its use as a predictive biomarker for therapeutic targeting and requires critical validation of sensitivity and specificity for each indication to guide therapy.

Antibody-Drug Conjugates: Advancing from Magic Bullet to Biological Missile.

Precision drug development is focusing on targeting tumor cell surface proteins for therapeutic delivery, maximizing biomarker identified on-target damage to the tumor while minimizing toxicity. A recent article demonstrated high expression of B7-H4 antigen on resistant ovarian cancer cells and described preclinical activity of B7-H4-directed antibody-drug conjugate. See related article by Gitto et al., p. 1567.

Mirvetuximab Soravtansine in Platinum-Resistant Ovarian Cancer.

Ovarian cancer is the second leading cause of death from gynecologic malignancies worldwide. Management of platinum-resistant disease is challenging and clinical outcomes with standard chemotherapy are poor. Over the past decades, significant efforts have been made to understand drug resistance and develop strategies to overcome treatment failure. Antibody drug conjugates (ADCs) are a rapidly growing class of oncologic therapeutics, which combine the ability to target tumor-specific antigens with the cytotoxic effects of chemotherapy. Mirvetuximab soravtansine is an ADC comprising an IgG1 monoclonal antibody against the folate receptor alpha (FRα) conjugated to the cytotoxic maytansinoid effector molecule DM4 that has shown promising clinical activity in patients with FR-α-positive ovarian cancer. This review summarizes current evidence of mirvetuximab soravtansine in platinum-resistant ovarian cancer, focusing on clinical activity, toxicity, and future directions.

Fighting resistance: post-PARP inhibitor treatment strategies in ovarian cancer.

Poly (ADP-ribose) polymerase inhibitors (PARPis) represent a therapeutic milestone in the management of epithelial ovarian cancer. The concept of 'synthetic lethality' is exploited by PARPi in tumors with defects in DNA repair pathways, particularly homologous recombination deficiency. The use of PARPis has been increasing since its approval as maintenance therapy, particularly in the first-line setting. Therefore, resistance to PARPi is an emerging issue in clinical practice. It brings an urgent need to elucidate and identify the mechanisms of PARPi resistance. Ongoing studies address this challenge and investigate potential therapeutic strategies to prevent, overcome, or re-sensitize tumor cells to PARPi. This review aims to summarize the mechanisms of resistance to PARPi, discuss emerging strategies to treat patients post-PARPi progression, and discuss potential biomarkers of resistance.

Heterogeneity and treatment landscape of ovarian carcinoma.

Ovarian carcinoma is characterized by heterogeneity at the molecular, cellular and anatomical levels, both spatially and temporally. This heterogeneity affects response to surgery and/or systemic therapy, and also facilitates inherent and acquired drug resistance. As a consequence, this tumour type is often aggressive and frequently lethal. Ovarian carcinoma is not a single disease entity and comprises various subtypes, each with distinct complex molecular landscapes that change during progression and therapy. The interactions of cancer and stromal cells within the tumour microenvironment further affects disease evolution and response to therapy. In past decades, researchers have characterized the cellular, molecular, microenvironmental and immunological heterogeneity of ovarian carcinoma. Traditional treatment approaches have considered ovarian carcinoma as a single entity. This landscape is slowly changing with the increasing appreciation of heterogeneity and the recognition that delivering ineffective therapies can delay the development of effective personalized approaches as well as potentially change the molecular and cellular characteristics of the tumour, which might lead to additional resistance to subsequent therapy. In this Review we discuss the heterogeneity of ovarian carcinoma, outline the current treatment landscape for this malignancy and highlight potentially effective therapeutic strategies in development.

Discrepancies in breast cancer's oncological outcomes between public and private institutions in the southeast region of Brazil: a retrospective cohort study.

Background: Brazil is a middle-income country with inequalities in its healthcare system. The disparities between public and private services affect the diagnosis and treatment of patients with breast cancer. The aim of this study is to assess whether disease-free survival (DFS) and overall survival (OS) are different in public and private specialized centers. Patient and methods: A retrospective cohort study with 1,545 breast cancer patients diagnosed from 2003 to 2011 at Barretos Cancer Hospital-BCH (public group, N = 1,408) and InORP Oncoclinicas (private group, N = 137) was conducted. A 1:1 propensity score matching (PSM) analysis was used to adjust the differences between the groups' characteristics (n = 137 in each group). Results: The median age at diagnosis was 54.4 years. Estimated DFS rates at 1, 5, and 10 years were 96.0%, 71.8%, and 59.6%, respectively, at BCH and 97.8%, 86.9%, and 78%, respectively, at InORP (HR: 2.09; 95% confidence interval [CI], 1.41-3.10; p < 0.0001). Estimated OS rates at 1, 5, and 10 years were 98.1%, 78.5%, and 65.4%, respectively, at BCH and 99.3%, 94.5%, and 91.9%, respectively, at InORP (HR: 3.84; 95% CI, 2.16-6.82; p < 0.0001). After adjustment by PSM, DFS and OS results in 1, 3, and 5 years remained worse in the public service compared to the private service. Conclusion: Patients treated in a public center have worse DFS and OS after a follow-up period of more than 5 years. These results were corroborated after carrying out the PSM.

Taking the Road Less Traveled: Following Molecular Trail Markers.

Targeted therapy largely remains an unmet therapeutic need for low-grade serous ovarian carcinomas. However, recent advances in molecular characterization are beginning to change the landscape. A recent article highlights the association of genetic alterations with clinical outcomes, widening the scope of novel targeted therapies. See related article by Manning-Geist et al., p. 4456.

Predicting the necessity of adding catheters to intracavitary brachytherapy for women undergoing definitive chemoradiation for locally advanced cervical cancer.

PURPOSE: To identify if baseline patient or magnetic resonance imaging (MRI) features can predict which women are at risk for inadequate tumor coverage with only intracavitary tandem and ovoid (T + O) brachytherapy and to correlate tumor coverage with clinical outcomes. METHODS AND MATERIALS: We performed a retrospective study of 50 women with cervical cancer treated with chemoradiation at a single institution between January 2014 and December 2015. All patients had a 3T-MRI performed at baseline (MRI1) and at the completion of external beam radiation therapy (MRI2). Gross tumor volume initial (GTV-Tinit) was measured on MRI1 and high-risk clinical tissue volume (CTVHR) on MRI2. CTVHR extending beyond point A was classified as too large for adequate coverage with T + O and requiring interstitial needles. Multivariate analysis was performed to determine predictive factors of inadequate coverage. Kaplan-Meier and Cox Regression were performed to correlate inadequate coverage with outcomes. RESULTS: Mean patient age was 49.2 ± 13.2 years, and 84% had Federation of Gynecology and Obstetrics IIB/IIIB disease. Forty-two percent of women were estimated to have inadequate tumor coverage with T + O brachytherapy. The GTV-Tinit volume and dimensions (superior-inferior, left-right, anterior-posterior) on MRI1 were all important predictive factors of inadequate coverage on multivariate analysis. Receiver operating characteristics curves identified optimal thresholds of superior-inferior ≥ 4.5 cm (area under the curve [AUC] = 0.718), left-right ≥ 4.5 cm (AUC = 0.745), anterior-posterior ≥ 5.0 cm (AUC = 0.767), and GTV-Tinit ≥ 85 cm3 (AUC = 0.842). Patients with inadequate coverage had worse clinical outcomes. CONCLUSIONS: Baseline MRI tumor size may predict inadequate CTVHR coverage at the time of brachytherapy (i.e., the need for interstitial needles). This may help identify a subset of women requiring early referral to adequately resourced centers to improve clinical outcomes.