Introduction There is growing concern about the aggressiveness of cancer care at the end of life (ACCEoL), defined as overly aggressive treatments that compromise the quality of life at its end. Recognising the most affected patients is a cornerstone to improve oncology care. Our aim is to identify factors associated with ACCEoL for patients with cancer dying in hospitals. Methods All adult patients with cancer who died in public hospitals in mainland Portugal (January 2010 to December 2015), identified from the hospital morbidity database. This database provided individual clinical and demographic data. We obtained hospital and region-level variables from a survey and National Statistics. The primary outcome is a composite ACCEoL measure of 16 indicators. We used multilevel random effects logistic regression modelling (p14 days in the hospital (43%, 42–43) and surgery (28%, 28–28) in the last 30 days. Older age (p<0·001), breast cancer (OR 0·83; 95% CI 0·76 to 0·91), and metastatic disease (0·54; 95% CI 0·50 to 0·58) were negatively associated with ACCEoL. In contrast, higher Deyo-Charlson Comorbidity Index (p<0·001), gastrointestinal and haematological malignancies (p<0·001), and death at cancer centre (1·31; 95% CI 1·01 to 1·72) or hospital with medical oncology department (1·29; 95% CI 1·02 to 1·63) were positively associated with ACCEoL. There was no association between hospital palliative care services at the hospital of death and ACCEoL. Conclusion Clinical factors related to a better understanding of disease course are associated with ACCEoL reduction. Patients with more comorbidities and gastrointestinal malignancies might represent groups with complex needs, and haematological patients may be at increased risk because of unpredictable prognosis. Improvement of hospital palliative care services could help reduce ACCEoL, particularly in cancer centres and hospitals with medical oncology department, as those services are usually under-resourced, thus reaching few.

(1) Background: Current scientific evidence suggests that most cancers, including breast cancer, can be treated during pregnancy without compromising maternal and fetal outcomes. This, however, raises questions regarding the ethical implications of clinical care. (2) Methods: Using a systematic literature search, 32 clinical practice guidelines for cancer treatment during pregnancy published between 2002 and 2021 were selected for analysis and 25 of them mentioned or made references to medical ethics when offering clinical management guidance for clinicians. (3) Results: Four bioethical themes were identified: respect for patient’s autonomy, balanced approach to maternal and fetal beneficence, protection of the vulnerable and justice in resource allocation. Most guidelines recommended informing the pregnant patient about available evidence-based treatment options, offering counselling and support in the process of decision making. The relational aspect of a pregnant patient’s autonomy was also recognized and endorsed in a significant number of available guidelines. (4) Conclusions: Recognition and support of a patient’s autonomy and its relational aspects should remain an integral part of future clinical practice guidelines. Nevertheless, a more structured approach is needed when addressing existing and potential ethical issues in clinical practice guidelines for cancer treatment during pregnancy.

(1) Background: Caring for pregnant cancer patients is clinically and ethically complex. There is no structured ethical guidance for healthcare professionals caring for these patients. (2) Objective: This concept paper proposes a theoretically grounded framework to support ethical and patient-centred care of pregnant cancer patients. (3) Methodological approach: The framework development was based on ethical models applicable to cancer care during pregnancy—namely principle-based approaches (biomedical ethics principles developed by Beauchamp and Childress and the European principles in bioethics and biolaw) and relational, patient-focused approaches (relational ethics, ethics of care and medical maternalism)—and informed by a systematic review of clinical practice guidelines. (4) Results: Five foundational discussion themes, summarising the key ethical considerations that should be taken into account by healthcare professionals while discussing treatment and care options with these patients, were identified. This was further developed into a comprehensive ethics checklist that can be used during clinical appointments and highlights the need for a holistic view to patient treatment, care and counselling while providing ethical, patient-centric care. (5) Conclusion: The proposed framework was further operationalised into an ethics checklist for healthcare professionals that aims to help them anticipate and address ethical concerns that may arise when attending to pregnant cancer patients. Further studies exploring clinicians’ attitudes towards cancer treatment in the course of pregnancy and patient experiences when diagnosed with cancer while pregnant and wider stakeholder engagement are needed to inform the development of further ethical, patient-centred guidance.

Tubo-ovarian high-grade serous carcinoma (HGSC) with proficient homologous recombination (HR) DNA repair (HRP) accounts for approximately 50% of cases and is associated with platinum-resistance and poor prognosis. We hypothesize that the acquisition of hybrid phenotypes displaying both epithelial and mesenchymal (E/M) features may be involved in the malignant transformation and tumour dissemination in this subgroup. Therefore, we analysed, by digital pathology, the expression and prognostic significance of 3 classic cadherins (E-cadherin, epithelial marker; N-cadherin, mesenchymal marker; and P-cadherin, candidate marker of hybrid E/M) in 577 formalin-fixed paraffin-embedded human samples representing the putative stepwise serous carcinogenesis in the Fallopian tube epithelium (FTE). We observed a non-canonical N-to-P-cadherin switch along the carcinogenic progression, with a statistically significant overexpression of P-cadherin in pre-malignant and malignant samples, compared to the control FTE. Interestingly, this overexpression was most pronounced in precursor lesions and HGSC cells from malignant ascites. Tumours with high P-cadherin expression were significantly associated with worse overall survival, especially in the subgroup without BRCA1/2 mutations. Transient P-cadherin knock-down resulted in in vitro significant reduction of functional hybrid E/M hallmarks, namely decreased anoikis resistance, reduced collective migration and invasion in a representative platinum-resistant HRP cell line. Taken together, our results suggest that P-cadherin overexpression is an early event in the serous carcinogenesis and may be involved in hybrid E/M activation in HRP-HGSC, further supporting this adhesion molecule as a promising biomarker for this poor prognostic subgroup.

Aim: Granulosa cell tumour (GCT) is a rare ovarian malignancy. There is currently no consensus on the optimal management of advanced/ relapsed disease and evidence is limited. Hormonal therapy (HT) is a potential option as the majority of GCTs express steroid receptors. Granulosa cells are known to have relatively high aromatase activity. The aim of this study was to evaluate the effectiveness of letrozole, a non-steroidal aromatase inhibitor, in the management of recurrent GCTs. Methods: A retrospective analysis of patients with GCT treated at a single centre between 01/01/2002 - 31/12/2012 was performed. Patient clinical details were identified from the hospital electronic database. The primary outcome was response rate (RR); secondary outcomes included clinical benefit rate (CBR) defined as partial response and disease stabilisation ≥6 months rates and progression-free survival (PFS). Results: A total of 47 OGT patients were identified of whom 29 (61.7%) had recurrent disease. 16 patients were treated with letrozole (mean age 49.4 years [28-78], median number of previous treatments 4 [1-8], 31% FIGO stage 1c at diagnosis). Previous treatment for recurrent disease included platinum-based chemotherapy (50%), at least one surgery (75%) and HT (62.5%) with tamoxifen and/or goserelin. 50% of patients received letrozole following 4^th relapse. The median follow-up was 33.5 months at the time of analysis. The RR (radiological) was 56.3% (n = 9); CBR 100%; median PFS 21.3 months (95% CI, 12.9 -29.6). At the time of analysis, the median duration of treatment was 19.45 months [8.17; 76.8]; 43.8% (n = 7) were still on letrozole. Further updated clinical outcomes will be presented. Conclusions: Significant clinical activity was achieved with letrozole in heavily pretreated GCT patients including prior HT. To our knowledge, this is the largest case series to report on the effectiveness of letrozole in recurrent GCTs. Aromatase inhibitors should be considered a valid option for advanced/ recurrent GCTs. Prospective studies will further clarify the role of aromatase inhibitors as standard of care. Disclosure: All authors have declared no conflicts of interest.