Consensus on drivers of maintenance treatment choice and patterns of care in advanced ovarian cancer.

OBJECTIVES: Maintenance therapies, including poly (ADP-ribose) polymerase (PARP) inhibitors and/or bevacizumab, have substantially improved the prognosis of patients with advanced ovarian cancer. Owing to the variability in treatment strategies across Europe, a Delphi study was conducted among European experts to understand the heterogeneity of clinical practice and identify key factors driving maintenance treatment decisions for advanced ovarian cancer. METHODS: A pragmatic literature review was conducted to identify key questions regarding maintenance treatment strategies in patients with advanced ovarian cancer. Utilizing a Delphi methodology, consensus was assessed among a panel of 16 experts using a questionnaire based on results of the pragmatic literature review. RESULTS: Panelists agreed that BRCA mutation and homologous recombination status should be assessed in parallel at diagnosis, and that first-line platinum chemotherapy may be initiated concurrently. There was a consensus that alternative homologous recombination deficiency tests are acceptable provided they are clinically validated. Panelists agreed that Response Evaluation Criteria in Solid Tumors (RECIST) and CA-125 elimination rate constant K (KELIM) scores can help assess tumor chemosensitivity and guide treatment-related decisions. Panelists defined high-risk disease as International Federation of Gynecology and Obstetrics (FIGO) stage IV disease or stage III with residual disease after initial/interval cytoreduction. Risk of disease progression was a key determinant of choice between PARP inhibitor, bevacizumab, or both in combination, as maintenance therapy in advanced ovarian cancer. CONCLUSIONS: Key drivers for selecting advanced ovarian cancer maintenance treatments include tumor mutational status as a key biomarker and clinician perception of the risk for early disease progression.

Room to Improve: An Audit of In-Hospital End-of-Life Care for Oncology Patients in a Tertiary Cancer Centre in Ireland During the COVID-19 Pandemic.

The COVID-19 pandemic compounded isolation for patients through social distancing measures and staff shortages. We were concerned about the impact of COVID-19 on the quality of care provided at end-of-life in 2021 in a national cancer centre, and instigated the first ever review of the care of the dying. Quality of care was assessed retrospectively using a validated instrument developed by the United Kingdom's National Quality Board. Sixty-six patient deaths occurred in our cancer centre in 2021. The 'risk of dying' was documented in 65.2% of records. Palliative care services were involved in 77%, and pastoral care in 10.6%. What was important to the patient was documented in 24.2%. The 'quality-of-death' score was satisfactory for most but poor in 21.2%. Our study prompted change, including appointment of an end-of-life coordinator, development of a checklist to ensure comprehensive communication, expansion of the end-of-life committee to include junior doctors, and regular audit.

Assessing the Quality of Care Delivered to Transgender and Gender Diverse Patients with Cancer in Ireland: A Case Series.

INTRODUCTION: "Transgender" and "gender diverse" are umbrella terms encompassing those whose gender identities or expressions differ from those typically associated with the sex they were assigned at birth. There is scant global information on cancer incidence, outcome, and mortality for this cohort. This group may present with advanced cancer, have mistrust in health care services and report anxiety and depression at higher frequencies, a finding often seen in marginalized groups because of minority stress. MATERIALS AND METHODS: Medical oncologists were contacted by secure email to identify patients who self-identify as transgender and gender diverse in three Irish hospitals. Five patients were identified. A retrospective chart review was conducted and a pseudonymized patient survey was distributed. RESULTS: All patients included in our chart review (n = 5) were diagnosed with advanced disease on initial diagnosis. Two patients identified as men, two as women, and one as a transwoman. Two of five patients' health record charts reflected a name or gender change. Three patients had gender transitioning treatment postponed. Assessing comorbidities, it was seen that four patients required psychiatry input. Predominant issues noted in our patient survey by the two respondents (n = 2) were "mis-gendering," lack of a gender-neutral hospital environment, lack of inclusion in cancer groups, and barriers in changing name and/or sex on hospital records. CONCLUSION: Components of care requiring revision include patient accessible pathways to change names and gender on health records, earlier access to psychological support and targeted screening and support groups. Resources for hospital staff to improve awareness of correct terminology and to provide gender neutral facilities are worthwhile. IMPLICATIONS FOR PRACTICE: The implications for practice on an international level include patient-friendly pathways for changing hospital name and gender so that patients may feel comfortable using wristbands. The need for international screening guidelines for transgender patients and national transgender cancer support groups is highlighted. On a day-to-day level for providers, the correct use of pronouns makes a big difference to patients. Asking about preferred pronoun on first visit and noting on patient's file is worthwhile. It is important for providers to know that increased psychological support should be offered early on first clinic visit and engaged with as necessary when patient has a history of anxiety or depression. Providers should discuss openly that some gender transitioning treatment will be postponed because of cancer care and refer to both the physical and psychological sequelae of this. Asking transgender patients which room or bathroom they would prefer when rooms are gendered is essential.

The impact of expanded access programs for systemic anticancer therapy in an Irish cancer centre.

BACKGROUND: Expanded access programs (EAPs) allow cancer patients with unmet clinical need to obtain access to pre-authorisation treatments. There is no standardised process for implementing these programs nationally, and real-world data on their impact is lacking. AIMS: This study aimed to evaluate the prevalence of such EAPs and their impact in a cancer centre. METHODS: Data relating to adult cancer patients treated via EAPs from 2011 to 2021 in three Cork university hospitals was collated. Descriptive statistics were employed to get an overview of the impact these programs currently have on cancer care provision. RESULTS: We identified 193 patients who accessed EAPs during the study period, availing of 33 separate drugs for a total of 50 different cancer indications. The prevalence of EAP usage was shown to have been trending upwards in recent years with a total of 189 programs being accessed throughout the period. Drugs provided were from a number of different anti-cancer drug classes, particularly targeted therapies (n = 18) and immune checkpoint inhibitors (n = 17). Cancers from a wide range of both solid and liquid tumour types were treated with EAP drugs, and patients treated were from across a broad spectrum of ages (26-82, SD 11.99). CONCLUSIONS: EAPs have an increasing role in accessing novel cancer therapies in our community and by extension nationally. Equity of EAP access would be facilitated by a national registry of available agents which we have established. Assessment of their benefits and toxicities would be enhanced by the requirement for a real-world database as a condition of EAP approval.

Current Irish medicolegal landscape: an unsustainable trajectory.

A number of outstanding clinical claims that are yet to be resolved as well as their associated estimated costs are at a record high in Ireland. By the end of 2022, the Irish government face 3875 active clinical claims which are expected to cost €3.85 billion in total. This does not account for future claims yet to be brought. The financial burden will be borne by the Irish healthcare system which is already facing unprecedented pressures on its services and staff. If current trends continue, the opportunity costs of the current medicolegal landscape will impact the future provision of healthcare. Aside from the financial consequences, clinical claims have numerous negative impacts on all parties involved. Gaining an understanding as to why claims and costs continue to increase relies on access to, and analysis of high-quality patient safety data, including learning from previous litigation. Addressing the causal and perpetuating factors requires efficient implementation of evidence-based recommendations through engagement with stakeholders, including the public. It is necessary to continuously assess the implementation of recommendations as well as measure their impact. This is to ensure that novel efforts from this point onwards do not suffer the same fate as many previous recommendations that, because of a lack of follow-on research, appear to go no further than the page of the report they are written. Action is required now to change the course of the currently unsustainable trajectory of the Irish medicolegal landscape.

A pilot project investigating the use of ONCOpatient®-An electronic patient-reported outcomes app for oncology patients.

Purpose: To investigate the feasibility of implementing a remote patient monitoring system using an electronic patient-reported outcomes (ePROs) platform in a tertiary cancer center in the Republic of Ireland. Methods: Patients receiving oral chemotherapy and oncology clinicians were invited to participate in the study. Patients were asked to submit weekly symptom questionnaires through an ePRO mobile phone application (app)-ONCOpatient®. Clinical staff were invited to use the ONCOpatient® clinician interface. After 8 weeks all participants submitted evaluation questionnaires. Results: Thirteen patients and five staff were enrolled in the study. The majority of patients were female (85%) with a median age of 48 years (range 22-73). Most (92%) were enrolled over telephone requiring on average 16 minutes. Compliance with the weekly assessments was 91%. Alerts were triggered by 40% of patients who then required phone calls to aid with symptom management. At the end of study, 87% of patients reported they would use the app frequently, 75% reported that the platform met their expectations, and 25% that it exceeded their expectations. Similarly, 100% of staff reported they would use the app frequently, 60% reported that it met their expectations, and 40% that it exceeded their expectations. Conclusions: Our pilot study showed that it is feasible to implement ePRO platforms in the Irish clinical setting. Small sample bias was recognized as a limitation, and we plan to confirm our findings on a larger cohort of patients. In the next phase we will integrate wearables including remote blood pressure monitoring.

Real-world outcomes and toxicity of adjuvant chemotherapy in NSCLC: a single-center experience.

Aim: Adjuvant chemotherapy in NSCLC is associated with modest benefits and significant toxicity. We sought to evaluate the toxicity of adjuvant chemotherapy and disease-specific outcomes in a real-world population. Methods: We performed a retrospective analysis of patients undergoing adjuvant chemotherapy for NSCLC in an Irish center over a 7-year period. We described treatment-associated toxicity, recurrence-free survival and overall survival. Results: 62 patients underwent adjuvant chemotherapy. Treatment-associated hospitalisation occurred in 29% of patients. Relapse was recorded in 56% of patients and median recurrence-free survival was 27 months. Conclusion: High rates of disease recurrence and treatment-associated morbidity were observed in patients receiving adjuvant chemotherapy for NSCLC. Novel therapeutic strategies are required to improve outcomes in this population.

Early NSCLC is primarily managed with lung cancer surgery. Chemotherapy is offered to some patients with early NSCLC after surgery depending on the size of the tumor and lymph node involvement. The benefit of post-surgery (adjuvant) chemotherapy in reducing the chance of cancer recurrence has been shown to be relatively small in previous studies. Large studies of post-surgery chemotherapy in NSCLC have included limited numbers of older patients, and patients with significant medical issues. This study looked to evaluate the safety and treatment-associated side effects of adjuvant chemotherapy in a group of patients more reflective of everyday clinical practice, and to assess the rates of cancer recurrence in these patients. In our study of 62 patients who underwent adjuvant chemotherapy for NSCLC, nearly 1 in 3 patients required hospital admission due to treatment-associated side effects. Almost 40% of patients experienced significant blood test abnormalities (including anaemia, reduced platelets, and reduced white blood cells). Approximately 1 in 4 patients required a reduction in the doses of their treatment due to treatment-associated side effects. More than half of the patients in our study experienced a recurrence of their cancer. Our study demonstrates the significant side effects associated with adjuvant chemotherapy in NSCLC and highlights the need for better-tolerated treatment strategies to reduce cancer recurrence in early NSCLC.

Tisotumab Vedotin in Combination With Carboplatin, Pembrolizumab, or Bevacizumab in Recurrent or Metastatic Cervical Cancer: Results From the innovaTV 205/GOG-3024/ENGOT-cx8 Study.

PURPOSE: Tissue factor is highly expressed in cervical carcinoma and can be targeted by tisotumab vedotin (TV), an antibody-drug conjugate. This phase Ib/II study evaluated TV in combination with bevacizumab, pembrolizumab, or carboplatin for recurrent or metastatic cervical cancer (r/mCC). METHODS: This open-label, multicenter study (ClinicalTrials.gov identifier: NCT03786081) included dose-escalation arms that assessed dose-limiting toxicities (DLTs) and identified the recommended phase II dose (RP2D) of TV in combination with bevacizumab (arm A), pembrolizumab (arm B), or carboplatin (arm C). The dose-expansion arms evaluated TV antitumor activity and safety at RP2D in combination with carboplatin as first-line (1L) treatment (arm D) or with pembrolizumab as 1L (arm E) or second-/third-line (2L/3L) treatment (arm F). The primary end point of dose expansion was objective response rate (ORR). RESULTS: A total of 142 patients were enrolled. In dose escalation (n = 41), no DLTs were observed; the RP2D was TV 2 mg/kg plus bevacizumab 15 mg/kg on day 1 once every 3 weeks, pembrolizumab 200 mg on day 1 once every 3 weeks, or carboplatin AUC 5 on day 1 once every 3 weeks. In dose expansion (n = 101), the ORR was 54.5% (n/N, 18/33; 95% CI, 36.4 to 71.9) with 1L TV + carboplatin (arm D), 40.6% (n/N, 13/32; 95% CI, 23.7 to 59.4) with 1L TV + pembrolizumab (arm E), and 35.3% (12/34; 19.7 to 53.5) with 2L/3L TV + pembrolizumab (arm F). The median duration of response was 8.6 months, not reached, and 14.1 months, in arms D, E, and F, respectively. Grade ≥3 adverse events (≥15%) were anemia, diarrhea, nausea, and thrombocytopenia in arm D and anemia in arm F (none ≥15%, arm E). CONCLUSION: TV in combination with bevacizumab, carboplatin, or pembrolizumab demonstrated manageable safety and encouraging antitumor activity in treatment-naive and previously treated r/mCC.

Professional and personal opinions of doctors in training during the first wave of the COVID19 pandemic.

BACKGROUND: The COVID19 pandemic is one of the greatest modern global healthcare crises. The resultant morbidity and mortality of public and healthcare professionals has led to psychological impacts and economic repercussions. We set out to assess the concerns of doctors in training during this crisis. METHODS: A questionnaire was developed and delivered via Survey Monkey to doctors in training from 27 March to 6 April 2020, 2 weeks prior to the expected surge in Ireland and UK. The Perceived Stress Scale (PSS) was incorporated to gauge respondent stress as they prepared for the COVID19 impact. RESULTS: A total of 285 participants engaged with 197 (69%) completing all questions. Almost 86% of respondents had been trained in donning and doffing personal protective equipment (PPE), and nearly 85% felt confident in the process. Overall, most respondents felt somewhat prepared (60%) or well prepared (20%) to treat COVID19 patients. However, 42% worried that their hospital would struggle, or not cope at all; in particular, 91% highlighted the risk of running out of PPE. Family health (86%), personal health (72%), and social life (47%) topped the list of junior doctor concerns. According to the PSS, the majority of respondents (62%) had moderate stress. CONCLUSIONS: This survey is the first to measure the concerns of doctors in training in Ireland as regards the COVID19 pandemic. Worries included PPE exhaustion and personal and family health. A significant majority had moderate stress. Additional supports for doctors in training are essential to aid stress and manage concerns better.

The Women's Health Initiative cancer survivorship clinic incorporating electronic patient-reported outcomes: a study protocol for the Linking You to Support and Advice (LYSA) randomized controlled trial.

BACKGROUND: The improved survival rate for many cancers in high-income countries demands a coordinated multidisciplinary approach to survivorship care and service provision to ensure optimal patient outcomes and quality of life. This study assesses the feasibility of introducing a Women's Health Initiative cancer survivorship clinic in Ireland. METHODS: The trial https://spcare.bmj.com/content/9/2/209.short comprises an intervention and control arm. Two hundred participants will be recruited. Key eligibility (1) women with early-stage hormone receptor-positive breast or gynecologic cancer (cervix or endometrial), within 12 months of completion of primary curative therapy, and (2) access to the Internet. The complex intervention comprises a nurse-led clinic targeting symptom management through a trigger alert system, utilizing electronic patient-reported outcome (ePRO) assessments at baseline, and 2, 4, 6, 8, 10, and 12 months. It also includes input from a dietitian monitoring diet and nutritional status. The control group will receive their usual care pathway standard of care and attend the cancer survivorship clinic and complete ePRO assessments at the start and end of the study. The primary endpoint (feasibility) includes the proportion of enrolled participants who complete baseline and follow-up ePRO surveys and partake in health professional consultations after ePRO data triggers. Secondary endpoints include changes in cancer-related symptom scores assessed by ePROs, health-related Quality of Life Questionnaire (QLQ) scores, Appraisal Self-Care Agency-R scores, and adjuvant endocrine therapy medication adherence. A process evaluation will capture the experiences of participation in the study, and the healthcare costs will be examined as part of the economic analysis. Ethical approval was granted in December 2020, with accrual commencing in March 2021. DISCUSSION: This protocol describes the implementation of a parallel arm randomized controlled trial (RCT) which examines the feasibility of delivering a Cancer Survivorship Clinic. The ePRO is an innovative symptom monitoring system which detects the treatment-related effects and provides individualized support for cancer survivors. The findings will provide direction for the implementation of future survivorship care. TRIAL REGISTRATION: ClinicalTrials.gov , NCT05035173 . Retrospectively registered on September 5, 2021.

A Randomized, Phase III Trial to Evaluate Rucaparib Monotherapy as Maintenance Treatment in Patients With Newly Diagnosed Ovarian Cancer (ATHENA-MONO/GOG-3020/ENGOT-ov45).

PURPOSE: ATHENA (ClinicalTrials.gov identifier: NCT03522246) was designed to evaluate rucaparib first-line maintenance treatment in a broad patient population, including those without BRCA1 or BRCA2 (BRCA) mutations or other evidence of homologous recombination deficiency (HRD), or high-risk clinical characteristics such as residual disease. We report the results from the ATHENA-MONO comparison of rucaparib versus placebo. METHODS: Patients with stage III-IV high-grade ovarian cancer undergoing surgical cytoreduction (R0/complete resection permitted) and responding to first-line platinum-doublet chemotherapy were randomly assigned 4:1 to oral rucaparib 600 mg twice a day or placebo. Stratification factors were HRD test status, residual disease after chemotherapy, and timing of surgery. The primary end point of investigator-assessed progression-free survival was assessed in a step-down procedure, first in the HRD population (BRCA-mutant or BRCA wild-type/loss of heterozygosity high tumor), and then in the intent-to-treat population. RESULTS: As of March 23, 2022 (data cutoff), 427 and 111 patients were randomly assigned to rucaparib or placebo, respectively (HRD population: 185 v 49). Median progression-free survival (95% CI) was 28.7 months (23.0 to not reached) with rucaparib versus 11.3 months (9.1 to 22.1) with placebo in the HRD population (log-rank P = .0004; hazard ratio [HR], 0.47; 95% CI, 0.31 to 0.72); 20.2 months (15.2 to 24.7) versus 9.2 months (8.3 to 12.2) in the intent-to-treat population (log-rank P < .0001; HR, 0.52; 95% CI, 0.40 to 0.68); and 12.1 months (11.1 to 17.7) versus 9.1 months (4.0 to 12.2) in the HRD-negative population (HR, 0.65; 95% CI, 0.45 to 0.95). The most common grade ≥ 3 treatment-emergent adverse events were anemia (rucaparib, 28.7% v placebo, 0%) and neutropenia (14.6% v 0.9%). CONCLUSION: Rucaparib monotherapy is effective as first-line maintenance, conferring significant benefit versus placebo in patients with advanced ovarian cancer with and without HRD.

Lack of familiarity with genetic testing among patients in Ireland with Cancer.

BACKGROUND: Cancer gene panel testing is available in Ireland. The need for a clear strategy to deal with patient information generated from tumour genomic testing is recognised as a challenge in the National Cancer Strategy. However, the public's attitude and opinions regarding these results is not known in Ireland. AIMS: This prospective questionnaire study assessed the knowledge and opinions of patients in a national oncology centre, surrounding cancer gene panel testing. METHODS: An anonymised modified validated questionnaire was completed by volunteering patients in the medical oncology department. It comprised 14 questions which assessed patient's familiarity, intention, benefits and concerns associated with tumour genetic testing using a four-point Likert scale. Patients recorded their primary cancer diagnosis and family cancer history. RESULTS: Eighty-four patients completed the questionnaire with 77 (92%) patients declaring their primary cancer diagnosis. The median age was 56 (range 26 to 83) years. Overall, 42% (n = 35) of oncology patients were familiar/somewhat familiar with testing and 90% (n = 76) stated they would avail of genetic testing if available. Patients with breast cancer were no more likely to avail of genetic testing when compared with the non-breast cancer cohort (n = 21 vs. 56, p = 0.58) though they identified concerns with potential discrimination. CONCLUSION: This is the first prospective Irish study to assess opinions surrounding cancer gene results. Addressing patient's lack of information as regards genetic testing is the first step in establishing a national cancer genetics testing programme in Ireland.

The PI3K Pathway at the Crossroads of Cancer and the Immune System: Strategies for Next Generation Immunotherapy Combinations.

Immunotherapy has led to a paradigm shift in the treatment of some malignancies, providing long-term, durable responses for a subset of patients with advanced cancers. Increasingly, research has identified links between the immune system and critical oncogenic growth factor pathways. The phosphoinositide 3-kinase (PI3K)-AKT-mTOR cascade is frequently hyperactivated in cancer, and plays an integral role in many cellular processes including tumour growth and survival and can underlie resistance to therapies. In this review, we first summarize two key learnings from the initial studies of inhibitors of this pathway, including the profile of immune-related adverse events such as colitis, transaminitis and pneumonitis and the increased incidence of infections with the majority of agents that target the PI3K-AKT-mTOR pathway. We then discuss recent advances in our understanding of the role of this pathway in the tumour micro-environment, and in the regulation of innate and adaptive immune responses, and propose synergistic combination strategies with PI3K-network inhibitors and cancer immunotherapy.

Towards Precision Medicine in the Clinic: From Biomarker Discovery to Novel Therapeutics.

Precision medicine continues to be the benchmark to which we strive in cancer research. Seeking out actionable aberrations that can be selectively targeted by drug compounds promises to optimize treatment efficacy and minimize toxicity. Utilizing these different targeted agents in combination or in sequence may further delay resistance to treatments and prolong antitumor responses. Remarkable progress in the field of immunotherapy adds another layer of complexity to the management of cancer patients. Corresponding advances in companion biomarker development, novel methods of serial tumor assessments, and innovative trial designs act synergistically to further precision medicine. Ongoing hurdles such as clonal evolution, intra- and intertumor heterogeneity, and varied mechanisms of drug resistance continue to be challenges to overcome. Large-scale data-sharing and collaborative networks using next-generation sequencing (NGS) platforms promise to take us further into the cancer 'ome' than ever before, with the goal of achieving successful precision medicine.

Advances in the Development of Molecularly Targeted Agents in Non-Small-Cell Lung Cancer.

Non-small-cell lung cancer (NSCLC) remains a significant global health challenge and the leading cause of cancer-related mortality. The traditional 'one-size-fits-all' treatment approach has now evolved into one that involves personalized strategies based on histological and molecular subtypes. The molecular era has revolutionized the treatment of patients harboring epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK) and ROS1 gene aberrations. In the appropriately selected population, anti-tumor agents against these molecular targets can significantly improve progression-free survival. However, the emergence of acquired resistance is inevitable. Novel potent compounds with much improved and rational selectivity profiles, such as third-generation EGFR T790M resistance mutation-specific inhibitors, have been developed and added to the NSCLC armamentarium. To date, attempts to overcome resistance bypass pathways through downstream signaling blockade has had limited success. Furthermore, the majority of patients still do not harbor known driver genetic or epigenetic alterations and/or have no new available treatment options, with chemotherapy remaining their standard of care. Several potentially actionable driver aberrations have recently been identified, with the early clinical development of multiple inhibitors against these promising targets currently in progress. The advent of immune checkpoint inhibitors has led to significant benefit for advanced NSCLC patients with durable responses observed. Further interrogation of the underlying biology of NSCLC, coupled with modern clinical trial designs, is now required to develop novel targeted therapeutics rationally matched with predictive biomarkers of response, so as to further advance NSCLC therapeutics through the next decade.

National Incidence, Management and Survival of Urachal Carcinoma.

Urachal carcinoma is an uncommon cancer whose rarity has precluded its study and evidence-based management strategies are lacking. This study assessed all urachal carcinomas in Ireland and clinical parameters in order to improve understanding. Urachal carcinomas diagnosed from 1994 to 2011 were identified from the National Cancer Registry in Ireland. Data obtained included patient age, gender, diagnostic year, pathology, tumor stage, patient treatment strategies and survival. Twenty-six urachal carcinomas were identified, the majority being adenocarcinoma. This comprised 0.3% of all invasive bladder tumors. Patients were predominantly male (62%) and over 50 years of age (58%). Twenty-two patients (85%) underwent surgery, with only six (23%) undergoing chemotherapy. On average, median overall survival was 2.6 years (range 0-15.2 yrs). Survival was longer in women (5 vs. 1.9 yrs), patients under 50 years of age (3.6 vs. 1.9 yrs), those without confirmed metastasis (4.1 vs. 0.7 yrs) and those who received chemotherapy (3.6 vs. 2.6 yrs). The overall survival of urachal carcinoma in Ireland is less than expected from published literature. This study highlights the need for centralization of rare tumors with international collaboration to identify the optimal treatment strategy and improve outcome.