SEOM-GEICO clinical guideline on epithelial ovarian cancer (2023).

In recent years, the incorporation of new strategies to the therapeutic armamentarium has completely changed the outcomes of epithelial ovarian cancer (EOC). The identification of new predictive and prognostic biomarkers has also enabled the selection of those patients more likely to respond to targeted agents. Nevertheless, EOC is still a highly lethal disease and resistance to many of these new agents is common. The objective of this guideline is to summarize the most relevant strategies to manage EOC, to help the clinician throughout the challenging diagnostic and therapeutic processes and to provide evidence-based recommendations.

Defining a Standard Set of Patient-Reported Outcomes for Patients With Advanced Ovarian Cancer.

Purpose: Advanced ovarian cancer (AOC) and its treatment cause several symptoms and impact on patients' health-related quality of life (HRQoL). We aim to reach a consensus on the most relevant patient-reported outcome (PROs), the corresponding measures (PROMs), and measurement frequency during AOC patients' follow-up from patients' and healthcare professionals' (HCP) perspective. Methods: The project comprised five steps: 1) a literature review, 2) a focus group with patients, 3) a nominal group with HCP, 4) two round-Delphi consultations with patients and HCP, and 5) a final meeting with HCP. Delphi questionnaire was elaborated based on literature review, focus group (n=5 patients), and nominal group (n=16 HCP). The relevance of each PRO and the appropriateness (A) and feasibility (F) of the proposed PROM were assessed (Likert scale 1=strongly agree; 9=strongly disagree). The consensus was reached when at least 75% of the panelists rated it as 'relevant', 'appropriate', or 'feasible' (score 7-9). Results: A total of 56 HCP [51.8% Hospital Pharmacy; 41.1% Oncology; 3.6% Nursing; and 3.6% Psycho-oncology; mean time in specialty 12.5 (8.0) years] and 10 AOC patients [mean time diagnosis 5.4 (3.0) years] participated in the 1st round. All PROs achieved consensus regarding their relevance, except dry skin (58.0%). Agreement was reached for PRO-CTCAE to be used to assess fatigue (A:84.9%; F:75.8%), neuropathy (A:92.4%; F:77.3%), diarrhea (A:87.9%; F:88.7%), constipation (A:86.4%; F:75.8%), nausea (A:89.4%; F:75.8%), insomnia (A:81.8%; F:88.7%), abdominal bloating (A:82.2%; F:82.2%) and sexuality (A:78.8%; F:88.6%); EQ-5D to determine patients' HRQoL (A:87.9%; F:80.3%), pain (A:87.9%; F:75.8%) and mood (A:77.7%; F:85.5%); to assess treatment adherence the Morisky-Green (A:90.9%; F:84.9%) and the dispensing register (A:80.3%; F:80.3%) were chosen. It was agreed to note in the medical record whether the patient's treatment preferences had been considered during decision-making (A:78.8%; F:78.8%) and to use a 5-point Likert scale to assess treatment satisfaction (A:86.4%; F:86.4%). Panelists agreed (A:92.4%; F: 77.3%) to collect these PROs (1) at the time of diagnosis/relapse; (2) one month after starting treatment/change therapeutic strategy; (3) every three months during the 1st-year of treatment; and later (4) every six months until treatment completion/change. Conclusions: The consensus reached represents the first step towards including the patient's perspective in AOC follow-up. The standardized collection of PROs in clinical practice may contribute to optimizing the follow-up of these patients and thus improving the quality of care.

An olaparib window-of-opportunity trial in patients with early-stage endometrial carcinoma: POLEN study.

OBJECTIVE: Olaparib is a potent inhibitor of poly(ADP-ribose) polymerase (PARP)-1, 2, and 3 with potential activity in endometrial cancer (EC). METHODS: In this window-of-opportunity trial, women with operable type 1 EC received olaparib oral tablets (300mg) twice daily for 28days before surgery. The primary objective was to evaluate the effects of olaparib on EC in tissue samples taken at baseline and at treatment completion. Signal of activity was defined as significant changes in the expression of the cell cycle-related proteins cyclin D1, Ki67, and cleaved caspase-3. RESULTS: A total of 31 patients were included in the biomarker analysis. The median time of olaparib exposure was 24 days (1-39). Significant inhibition was found for cyclin D1 (p < 0.01), but not for Ki67 and active caspase 3 immunostaining. PARP-1 levels positively correlated with cyclin D1 levels (rho = 0.661, p = 0.0001). Both PARP-1 and cyclin D1 levels were significantly lower (p = 0.022 and p = 0.004, respectively) in patients with ARID1A[-] tumors than ARID1A[+] tumors. A significant relationship between plasma olaparib concentrations and decreased GLUT1 activity was observed (r = -0.5885; p < 0.05). Drug-related toxicity consisted mostly of gastrointestinal and grade 1 or 2 adverse events. CONCLUSIONS: Olaparib reduced expression of cyclin D1, which positively correlated with PARP-1 levels. This effect was more evident in ARID1A-deficient tumors. Olaparib further induced inhibition of GLUT1 plasma activity. Our findings could have noteworthy implications in predicting which patients with EC would benefit from olaparib-based strategies.