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Pamela Soberanis Pina, Stephanie Lheureux Department of Medical Oncology, Princess Margaret Cancer Centre, Toronto, ON, CanadaCorrespondence: Stephanie Lheureux, Princess Margaret Cancer Centre, 700 University Avenue, Toronto, M5G 1Z5, Ontario, Canada, Email Stephanie.Lheureux@uhn.caAbstract: Endometrial cancer (EC) has a high epidemiological impact with incidence and mortality rising worldwide. In recent years, the integration of the pathologic and molecular classification has provided relevant information to understand the heterogeneity in the biology of EC, which led to the evolution in the management of patients. Currently, therapeutic breakthroughs have been made in advanced EC to improve oncologic outcomes, with efforts to include patient reported outcomes. Precision and personalized medicine are under way in EC exploring different combination approaches to target cross-talk pathways, cancer cell microenvironment, and metabolic vulnerabilities and improve drug delivery. Yet, collaborative efforts are needed to face the challenges in practice by refining patient selection, ideal biomarker identification, and de-escalation of therapies according to emerging molecular and genomic features of EC.Keywords: endometrial cancer, targeted therapy, molecular targets, precision medicine

Purpose: ctDNA is a novel technique extensively studied in solid tumors, although not currently well defined in endometrial cancer., Experimental Design: A de-identified retrospective analysis of 1,988 patients with advanced/recurrent endometrial cancer was performed. In addition, an analysis of a real-world evidence cohort was completed (n = 1,266). Patients underwent ctDNA testing using Guardant360 during routine clinical care. The objective was to describe and assess molecular landscape using ctDNA., Results: Among 1,988 ctDNA samples, at least one somatic alteration was detected in 91.6% (n = 1,821). Most frequently altered genes were TP53 (64%), PIK3CA (29%), PTEN (25%), ARID1A (20%), and KRAS (14%). Overall, 18.5% had amplifications, with the majority identified in CCNE1 (40.9%), PIK3CA (22%), and EGFR (19.3%). From the real-world evidence cohort, those with TP53 mutations had a worse overall survival (OS) versus those without TP53 mutations (P = 0.02) and those with TP53 comutations had an inferior OS in comparison with TP53-mutated only (P = 0.016). Amongst these, patients with a PIK3CA comutation (P = 0.012) and CCNE1 amplification (P = 0.01) had an inferior OS compared with those with only TP53 mutations. Fifty-seven patients with newly diagnosed endometrial cancer had at least two serial ctDNA samples showing evolution in detected variants compared with baseline samples, with TP53 being the most frequent change., Conclusions: This study is one of the largest cohorts of ctDNA currently reported in endometrial cancer. The presence of TP53 mutation and other comutations detected by ctDNA have a negative effect on outcomes. This report suggests that ctDNA analysis is feasible and could become a useful biomarker for endometrial cancer., (©2024 The Authors; Published by the American Association for Cancer Research.)

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., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: Currently there is no standard therapy to improve cancer-related anorexia, hampering survival. Mirtazapine has been suggested as a feasible option in this context., Objectives: To assess the effect of mirtazapine on appetite and energy consumption in patients with advanced non-small cell lung cancer (NSCLC)., Design, Setting, and Participants: This randomized, double-blind, placebo-controlled clinical trial including adults was performed in a tertiary cancer care center from August 2018 to May 2022 with a follow-up of 8 weeks. Overall, 134 patients were screened; 114 were assessed for eligibility and 28 were excluded., Interventions: Patients were randomized in a 1:1 ratio to receive mirtazapine, 15 mg, or placebo for 2 weeks followed by a dose escalation to 30 mg until week 8 or placebo. Both groups received nutritional assessment and dietary advice., Main Outcomes and Measures: Appetite was assessed by the Anorexia Cachexia Scale and energy intake. Dietary parameters were evaluated at baseline, 4 weeks, and 8 weeks, with a 24-hour dietary recall, and energy quantification based on the Mexican system of nutritional equivalents., Results: A total of 86 patients met the inclusion criteria and were randomized to the placebo (n = 43) or the mirtazapine group (n = 43). The mean (SD) age was 63.5 (11.2) years, 41 were women (57.7%) and had adenocarcinoma, Eastern Cooperative Oncology Group performance status scale score of 1, stage IV NSCLC, and were receiving first-line treatment. Baseline characteristics were similar between groups. There was no difference in appetite scores in patients who received mirtazapine or placebo after 4 and 8 weeks. After 4 weeks, mirtazapine significantly increased energy intake (379.3 kcal; 95% CI, 1382.6-576.1; P < .001) including proteins (22.5 g; 95% CI, 11.5-33.4; P = .001), carbohydrates (43.4 g; 95% CI, 13.1-73.8; P = .006), and fats (13.2 g; 95% CI, 6.0-20.4; P = .006). Fats intake was significantly higher in patients in the mirtazapine group (14.5 g vs 0.7 g; P = .02) after 8 weeks. The mirtazapine group significantly decreased the proportion of patients with sarcopenia (82.8% vs 57.1%, P = .03) at 8 weeks. Patients on mirtazapine tolerated the treatment well, but reported a higher perception of nightmares at 2 weeks based on a 10 cm VAS score (0 [25th-75th percentile, 0-1] vs 0 [25th-75th percentile, 0-0] in the control group; P = .009) but this finding was nonsignificant after 4 and 8 weeks., Conclusion and Relevance: In this randomized clinical trial of patients with advanced NSCLC, there was no difference in appetite scores in all patients who received mirtazapine or placebo, but the mirtazapine group had a significant increase in energy intake through the 4- and 8-week follow-up, mainly in fat intake, which is a better and crucial source of energy. The addition of mirtazapine in the treatment of patients with advanced NSCLC and anorexia may help these patients achieve their energy requirements and improve health-related quality of life, specifically emotional and cognitive functioning., Trial Registration: ClinicalTrials.gov Identifier: NCT04748523.

The complex interplay between ovarian cancer cells and the tumor microenvironment (TME) modulates progression, with dynamic cellular interactions influenced by external modulators, including neoadjuvant chemotherapy (NACT). A recent article described the alterations within the TME following NACT, either with or without bevacizumab, in ovarian cancer. See related article by Tavira et al., p. 176., (©2023 American Association for Cancer Research.)

The identification of Epidermal Growth Factor Receptor (EGFR) mutations in lung adenocarcinoma has facilitated the development of personalized medicine based on oncogenic drivers. EGFR-Tyrosine Kinase Inhibitors (TKIs) are part of the targeted therapy; they impede the phosphorylation of the intracellular tyrosine kinase component of EGFR and consequently block signal transduction pathways. These drugs inhibit the proliferation and survival of tumor cells, leading to long-term progression-free survival and overall survival. Diarrhea is one of the most frequent adverse events associated with EGFR-TKIs, affecting at least 18% of patients and reaching up to 95% in some cases. Diarrhea should be managed carefully given its association with important complications, treatment interruptions, and dose reductions. Moreover, nutritional status and quality of life (QoL) can deteriorate due to severe diarrhea. Changes in diet, such as increment of fiber, supplementation with glutamine, and use of probiotics, may contribute to a decrease in the incidence of diarrhea. Improving the control of diarrhea can provide a significant benefit to the QoL of patients., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2023.)

Lung cancer (LC) is one of the most common causes of death worldwide. The identification of oncogene-addicted driving mutations suitable for targeted therapy has improved clinical outcomes in advanced diseases. Clinical trials, on the other hand, rarely involve vulnerable groups such as pregnant women. We report a 37-year-old woman with advanced non-small cell lung cancer (NSCLC) harboring an exon 19 deletion of EGFR treated with afatinib. After the initial treatment, the patient achieved a complete response and had an unplanned pregnancy. Targeted therapy was withheld during the first trimester and resumed with osimertinib in the second trimester in which the patient developed oligohydramnios and intrauterine growth restriction (IUGR) of the baby. Osimertinib was delayed at two different times during the third trimester with complete resolution of the oligohydramnios. The baby was born at 37.3 weeks of gestation (WOG) with no signs of congenital disorders. After delivery, the mother restarted osimertinib and maintained a complete response. This case suggests that osimertinib could be an acceptable option for tumor control during pregnancy in EGFR-mutant NSCLC. This information do not replace current recommendations for avoiding pregnancy and promoting contraceptive usage in patients receiving any cancer therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Soberanis Pina, Lara-Mejía, Matias-Cruz, Barrón, Cardona, Raez, Rios-Garcia and Arrieta.)

Ovarian cancer (OC) is one of the most lethal tumors in women, mostly diagnosed at advanced stages. Standard of care is based on surgery and platinum-based chemotherapy which provides high rates of response, although most patients will relapse. Poly(ADP-ribose) polymerase inhibitors (PARPi) have recently been incorporated in the treatment strategy for high-grade OC, particularly for those with defects in DNA repair pathways (homologous repair deficiency (HRd)). However, some tumor cells may not respond and some others will develop mechanisms of resistance to adapt. The most known mechanism of PARPi resistance is the reversion of HRd to homologous repair proficiency driven by epigenetic and genetic changes. Ongoing research is exploring different agents that are trying to re-sensitize tumor cells,overcome or bypass resistance to PARPi. Current investigations are focused on agents that target replication stress and DNA repair pathways, improve drug delivery, and target other cross-talk pathways. A crucial challenge in practice will be to identify and select patients for the appropriate therapy or combination strategies. However, efforts are needed to decrease overlapping toxicity and define the correct schedule timing of dosing to maximize the therapeutic index., Competing Interests: Competing interests: SL reports grants or contracts to their institution from Merck, AstraZeneca, Regeneron, Roche, Repare, GSK, Seagen; consulting fees from Novocure, Merck, AstraZeneca, GSK, Roche, Eisai, and Shattuck Labs; payment or honoraria for lectures, presentations, speakers bureaus, or educational events from AstraZeneca, GSK, and Eisai; and participation on a data safety monitoring board or advisory board from AstraZeneca. She has been principal investigator or co-investigator of different trials with PARPi and DDR agents. PSP declares no potential conflicts of interest., (© IGCS and ESGO 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: In Mexico, breast cancer is the leading cause of death by malignant tumors in women aged 20 and older. The World Health Organization estimates that 69% of deaths caused by breast cancer occur in developing countries. Little is known about the prevalence of breast carcinoma in Mexico and its molecular subclassification., Methods: This retrospective cross-sectional study included patients who underwent a mastectomy (single, radical or lumpectomy) or a breast tumor biopsy (core-needle or excisional) from January 2002 to December 2018. The primary purpose of the study was to determine the prevalence and molecular profile of breast in comprehensive cancer center in Mexico and compare our results with those published in the US. This study was approved by our scientific and bioethical committee., Results: The final analysis included 379 patients. The youngest patient was 23 years old and the oldest patient was 89; the mean age at diagnosis was 54.63 years. Patients of 40 years old or younger accounted for 48 of the cases (12.66%) and those older than 40 accounted for 331 of the cases (87.33%). The molecular subclassification showed luminal A subtype in 139 cases (36.67%), luminal B subtype in 143 cases (37.73%), human epidermal growth factor receptor 2-positive carcinomas in 32 cases (8.44%) and triple-negative carcinomas in 65 cases (17.15%). Diabetes mellitus was present in 43 patients (11.34%), hypertension in 78 patients (20.58%), obesity in 82 patients (21.63%) and 66 patients reported being treated with exogenous hormone therapy (17.41%)., Conclusions: Breast carcinoma occurs at an earlier age in Mexican women compared to women in the US. Hormone-positive tumors were found to be more prevalent in older patients, while high-grade tumors were more frequently identified in younger patients., Competing Interests: DMK has provided Principal Investigator of clinical trials, advisory and speaker services to AstraZeneca, Merck Sharp & Dohme, Roche and Bristol-Myers Squibb. JMRM has provided advisory and speaker services to Ipsen, Bristol-Myers Squibb, Merck Sharp & Dohme and Novartis and received sponsorship for travel and expenses from Bayer. RDH has provided advisory services Merck Sharp & Dohme and received sponsorship for travel and expenses from Roche. The rest of authors declare no conflict of interest., (Copyright 2021, Macari et al.)