What matters most to people with metastatic uveal melanoma? A qualitative study to inform future measurement of health-related quality of life.

Metastatic uveal melanoma (mUM) is a rare cancer with poor prognosis, but novel treatments are emerging. Currently, there are no mUM-specific health-related quality of life (HRQL) questionnaires available for clinical research. We aimed to explore how mUM and its treatment affect HRQL and assess the content validity of existing questionnaires. Participants were patients with mUM and healthcare professionals involved in their care. Qualitative data were collected using semi-structured interviews and focus groups. Data collection and analysis used an integrative approach involving inductive questions/coding to elicit new concepts and deductive questions/coding based on domains of existing HRQL questionnaires. Initial interviews/focus groups focussed on HRQL questionnaires designed for patients with uveal melanoma or liver metastases. As new concepts were elicited, domains and items from other questionnaires were subsequently added. Seventeen patients and 16 clinicians participated. HRQL concerns assessed by uveal melanoma-specific questionnaires were largely resolved by the time of metastasis. The Functional Assessment of Cancer Therapy - Immunotherapy Module (FACT-ICM) adequately captured most immunotherapy-related side effects during initial treatment cycles. However, most patients emphasised emotional impacts over physical ones, focussing on the existential threat posed by disease amidst uncertainty about treatment accessibility and effectiveness. Patients were also concerned with treatment burden, including time commitment, travel, need for hospitalisation, and expenses. The relative importance of HRQL issues varied over time and across treatment modalities, with no single questionnaire being sufficient. Pending further development and psychometric testing, clinical researchers may need to take a modular approach to measuring the HRQL impacts of mUM.

Real-world health-related quality of life outcomes for patients with resected stage III/IV melanoma treated with adjuvant anti-PD1 therapy.

BACKGROUND: While adjuvant therapy with anti-programmed cell death protein-1 (anti-PD1) for patients with resected stage III/IV melanoma has been shown to improve recurrence-free survival, the overall survival benefit remains uncertain. This study aims to evaluate the impact of adjuvant anti-PD1 therapy on the health-related quality of life (HRQOL) of patients with resected stage III/IV melanoma METHODS: Data was used from two melanoma registries in Australia and the Netherlands. Patients with resected stage III/IV melanoma treated with adjuvant anti-PD1 who completed a baseline and at least one post-baseline HRQOL assessment were included. HRQOL was assessed using the EORTC QLQ-C30 at baseline, 3, 6, and 12 months. Established thresholds were used for interpreting changes in QLQ-C30 scores. RESULTS: 92 patients were included. Mean symptom and functioning scores improved or remained stable at 12 months compared to baseline. However, a substantial proportion of patients experienced a clinically significant decline in role (39%, µ = -50.8), social (41%, µ = -32.7), or emotional (50%, µ = -25.1) functioning at 12 months compared to baseline. Younger patients were more likely to experience clinically significant deteriorations in role (OR=1.07, 95% CI: 1.02-1.13, p < 0.01) and social (OR=1.06, 95% CI: 1.01-1.11, p = 0.013) functioning. CONCLUSION: A significant proportion of patients with resected stage III/IV melanoma who received adjuvant anti-PD1 experienced clinically significant declines in role, social and emotional functioning at 12 months compared to baseline. This highlights the HRQOL issues that may arise during adjuvant anti-PD1 therapy which may require supportive care intervention.

Using Implementation Science Frameworks to Guide the Use of Electronic Patient-Reported Outcome Symptom Monitoring in Routine Cancer Care.

PURPOSE: Electronic patient-reported outcomes (ePROs) are an evidence-based means of detecting symptoms earlier and improving patient outcomes. However, there are few examples of successful implementation in routine cancer care. We conducted a qualitative study to identify barriers and facilitators to implementing ePRO symptom monitoring in routine cancer care using the Consolidated Framework for Implementation Research (CFIR). METHODS: Participants were adult patients with cancer, their caregivers, or health care professionals involved in ePRO monitoring or processes. Focus groups or individual interviews were conducted using a semistructured approach informed by the CFIR. Data were analyzed deductively using the CFIR. Barriers were matched to theory-informed implementation strategies using the CFIR-Expert Recommendations for Implementing Change (ERIC) matching tool. RESULTS: Thirty participants were interviewed: 22 females (73%), aged 31-70 years (28, 94%), comprising patients (n = 8), caregivers (n = 2), medical oncologists (n = 4), nurses (n = 4), hospital leaders (n = 6), clinic administrators (n = 2), pharmacists (n = 2), and information technology specialists (n = 2). Barriers pertaining to four CFIR domains were identified and several were novel, including the challenge of adapting ePROs for different anticancer treatments. Facilitators pertaining to all CFIR domains were identified, such as leveraging acceptability of remote care post-COVID-19 to drive implementation. Conducting consensus discussions with stakeholders to tailor ePROs to the local setting, identifying/preparing individual and group-level champions, and assessing readiness for change (including leveraging technological advances and increased confidence in using remote monitoring post-COVID-19) were the most frequently recommended implementation strategies. CONCLUSION: The CFIR facilitated identification of known and novel barriers and facilitators to implementing ePRO symptom monitoring in routine cancer care. Implementation strategies summarized in a conceptual framework will be used to codesign an ePRO symptom monitoring system for immunotherapy side effects.

Designing a wholly online, multidisciplinary Master of Cancer Sciences degree.

BACKGROUND: Improving oncology-specific knowledge and skills of healthcare professionals is critical for improving the outcomes of people with cancer. Many current postgraduate education offerings may be inaccessible to busy professionals, contain minimal consumer input or do not focus on the multidisciplinary nature of cancer care. In response to these needs, a Master of Cancer Sciences degree was developed. Our aim is to describe the development of the Master of Cancer Sciences. METHODS: We describe the development of the Master of Cancer Sciences, including its theoretical and its pedagogical underpinnings. RESULTS: Our approach to curriculum design was guided by Kern's Six-Step Approach to Medical Curriculum and underpinned by the Seven Principles of Online Learning. These approaches were further underpinned by the Cognitive Theory of Multimedia Learning which informed our approach to audio and visual information design. The pedagogy is interactive, experiential, interprofessional and importantly, includes consumers as educators. In practice, learning activities include peer feedback, multidisciplinary team meeting simulations, group work and clinical role plays. The online environment was visually shaped through infographics, high-quality educational videos and gamification. CONCLUSION: We have designed a Master of Cancer Sciences that is one of the first wholly online, cancer-specific Masters' programs. Its industry-led curriculum using evidence-based pedagogical choices utilises a range of novel digital formats and integrates the consumer perspective to provide a holistic overview of the field. Quantitative and qualitative evaluation of learning outcomes is ongoing.

Evaluation of Managing Cancer and Living Meaningfully (CALM) in people with advanced non-small cell lung cancer treated with immunotherapies or targeted therapies: protocol for a single-arm, mixed-methods pilot study.

INTRODUCTION: People with advanced non-small cell lung cancer (NSCLC) treated with immunotherapies (IT) or targeted therapies (TT) may have improved outcomes in a subset of people who respond, raising unique psychological concerns requiring specific attention. These include the need for people with prolonged survival to reframe their life plans and tolerate uncertainty related to treatment duration and prognosis. A brief intervention for people with advanced cancer, Managing Cancer and Living Meaningfully (CALM), could help people treated with IT or TT address these concerns. However, CALM has not been specifically evaluated in this population. This study aims to evaluate the acceptability and feasibility of CALM in people with advanced NSCLC treated with IT or TT and obtain preliminary evidence regarding its effectiveness in this population. METHODS AND ANALYSIS: Twenty people with advanced NSCLC treated with IT or TT will be recruited from Peter MacCallum Cancer Centre, Melbourne, Australia. Participants will complete three to six sessions of CALM delivered over 3-6 months. A prospective, single-arm, mixed-methods pilot study will be conducted. Participants will complete outcome measures at baseline, post-intervention, 3 months and 6 months, including Patient Health Questionnaire, Death and Dying Distress Scale, Functional Assessment of Cancer Therapy General and Clinician Evaluation Questionnaire. The acceptability of CALM will be assessed using patient experiences surveys and qualitative interviews. Feasibility will be assessed by analysis of recruitment rates, treatment adherence and intervention delivery time. ETHICS AND DISSEMINATION: Ethics approval has been granted by the Peter MacCallum Cancer Centre Human Research Ethics Committee (HREC/82047/PMCC). Participants with cancer will complete a signed consent form prior to participation, and carers and therapists will complete verbal consent. Results will be made available to funders, broader clinicians and researchers through conference presentations and publications. If CALM is found to be acceptable in this cohort, this will inform a potential phase 3 trial.

A Phase 1/2A trial of idroxioleic acid: first-in-class sphingolipid regulator and glioma cell autophagy inducer with antitumor activity in refractory glioma.

BACKGROUND: The first-in-class brain-penetrating synthetic hydroxylated lipid idroxioleic acid (2-OHOA; sodium 2-hydroxyoleate), activates sphingomyelin synthase expression and regulates membrane-lipid composition and mitochondrial energy production, inducing cancer cell autophagy. We report the findings of a multicentric first-in-human Phase 1/2A trial (NCT01792310) of 2-OHOA, identifying the maximum tolerated dose (MTD) and assessing safety and preliminary efficacy. METHODS: We performed an open-label, non-randomised trial to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and anti-tumour activity of daily oral treatment with 2-OHOA monotherapy (BID/TID) in 54 patients with glioma and other advanced solid tumours. A dose-escalation phase using a standard 3 + 3 design was performed to determine safety and tolerability. This was followed by two expansion cohorts at the MTD to determine the recommended Phase-2 dose (RP2D). RESULTS: In total, 32 recurrent patients were enrolled in the dose-escalation phase (500-16,000 mg/daily). 2-OHOA was rapidly absorbed with dose-proportional exposure. Treatment was well-tolerated overall, with reversible grade 1-2 nausea, vomiting, and diarrhoea as the most common treatment-related adverse events (AEs). Four patients had gastrointestinal dose-limiting toxicities (DLTs) of nausea, vomiting, diarrhoea (three patients at 16,000 mg and one patient at 12,000 mg), establishing an RP2D at 12,000 mg/daily. Potential activity was seen in patients with recurrent high-grade gliomas (HGG). Of the 21 patients with HGG treated across the dose escalation and expansion, 5 (24%) had the clinical benefit (RANO CR, PR and SD >6 cycles) with one exceptional response lasting >2.5 years. CONCLUSIONS: 2-OHOA demonstrated a good safety profile and encouraging activity in this difficult-to-treat malignant brain-tumour patient population, placing it as an ideal potential candidate for the treatment of glioma and other solid tumour malignancies. CLINICAL TRIAL REGISTRATION: EudraCT registration number: 2012-001527-13; Clinicaltrials.gov registration number: NCT01792310.

Health-related quality of life in patients with melanoma brain metastases treated with immunotherapy.

Aims: To describe the health-related quality of life (HRQoL) of melanoma brain metastasis (MBM) patients throughout the first 18 weeks of ipilimumab-nivolumab or nivolumab treatment. Materials & methods: HRQoL data (European Organisation for Research and Treatment of Cancer's Core Quality of Life Questionnaire, additional Brain Neoplasm Module, and EuroQol 5-Dimension 5-Level Questionnaire) were collected as a secondary outcome of the Anti-PD1 Brain Collaboration phase II trial. Mixed linear modeling assessed changes over time, whereas the Kaplan-Meier method was used to determine median time to first deterioration. Results: Asymptomatic MBM patients treated with ipilimumab-nivolumab (n = 33) or nivolumab (n = 24) maintained baseline HRQoL. MBM patients with symptoms or leptomeningeal/progressive disease treated with nivolumab (n = 14) reported a statistically significant trend toward improvement. Conclusion: MBM patients treated with either ipilimumab-nivolumab or nivolumab did not report a significant deterioration in HRQoL within 18 weeks of treatment initiation. Clinical trial registration: NCT02374242 (ClinicalTrials.gov).

Historically, people whose melanoma had spread to the brain (known as brain metastases) lived only 4­6 months after diagnosis, with less than 15% alive at 12 months. However, the development of immunotherapies such as nivolumab and ipilimumab to treat advanced melanoma has resulted in more than 50% of patients being alive 5 years after diagnosis. With the effectiveness of these immunotherapies demonstrated in clinical trials, we wanted to examine the impact of these treatments on the health-related quality of life of people with melanoma brain metastases. Using data from a clinical trial evaluating the effectiveness of immunotherapies in people diagnosed with melanoma brain metastases, this study investigated the impact of nivolumab and nivolumab combined with ipilimumab on quality of life. We found that neither nivolumab alone nor nivolumab combined with ipilimumab had a negative effect on quality of life. In summary, this study provides further support for the use of these immunotherapies as first-line treatment for melanoma brain metastases.

The Feasibility, Acceptability, and Effectiveness of Electronic Patient-Reported Outcome Symptom Monitoring for Immune Checkpoint Inhibitor Toxicities: A Systematic Review.

PURPOSE: Increasing use of immune checkpoint inhibitors (ICIs) in routine cancer care will increase the incidence of immune-related adverse events (irAEs). Systems are needed to support remote monitoring for irAEs. Electronic patient-reported outcome (ePRO) symptom monitoring systems can help monitor and manage symptoms and side effects. We assessed the content and features of ePRO symptom monitoring systems for irAEs, and their feasibility, acceptability, and impact on patient outcomes and health care utilization. METHODS: A systematic literature search was conducted in May 2022 on MEDLINE, Embase, PsycINFO, and Cochrane Central Register of Controlled Trials. Quantitative and qualitative data relevant to the review questions were extracted and synthesized in tables. RESULTS: Seven papers describing five ePRO systems were included. All systems collected PROs between clinic visits. Two of five used validated symptom questionnaires, 3/5 provided prompts to complete questionnaires, 4/5 provided reminders to self-report, and 3/5 provided clinician alerts for severe/worsening side effects. Four of five provided coverage of ≥26/30 irAEs in the ASCO irAE guideline. Feasibility and acceptability were demonstrated with consent rates of 54%-100%, 17%-27% of questionnaires generating alerts, and adherence rates of 74%-75%. One paper showed a reduction in grade 3-4 irAEs, treatment discontinuation, clinic visit duration, and emergency department presentations, while another showed no difference in these outcomes or the rate of steroid use. CONCLUSION: There is preliminary evidence of the feasibility and acceptability of ePRO symptom monitoring for irAEs. However, further studies are needed to confirm the impact on ICI-specific outcomes, such as the frequency of grade 3-4 irAEs and duration of immunosuppression. Suggestions for the content and features of future ePRO systems for irAEs are provided.

Efficacy of ipilimumab 3 mg/kg following progression on low-dose ipilimumab in metastatic melanoma.

BACKGROUND: Differing doses of ipilimumab (IPI) are used in combination with an anti-PD1 antibody in advanced melanoma. There is no data on the outcomes of patients who progress following low-dose IPI (< 3 mg/kg) and are subsequently treated with IPI 3 mg/kg (IPI3). We conducted a multicentre retrospective survey to assess the efficacy of this strategy. METHODS: Patients with resected stage III, unresectable stage III or IV melanoma who received low dose IPI (< 3 mg/kg) with an anti-PD1 antibody with recurrence (neo/adjuvant) or progressive disease (metastatic), who then received IPI3± anti-PD1 antibody were eligible. Best investigator-determined Response Evaluation Criteria in Solid Tumours response, progression-free survival (PFS) and overall survival (OS) were analysed. RESULTS: Total 36 patients received low-dose IPI with an anti-PD1 antibody, 18 (50%) in the neo/adjuvant and 18 (50%) in the metastatic setting. Of which, 20 (56%) had primary resistance and 16 (44%) had acquired resistance. All patients received IPI3 for unresectable stage III or IV melanoma; median age 60 (29-78), 18 (50%) M1d disease, 32 (89%) Eastern Cooperative Oncology Group performance status 0-1. Around 35 (97%) received IPI3 with nivolumab and 1 received IPI3 alone. The response rate to IPI3 was 9/36 (25%). In patients with primary resistance, the response rate was 6/20 (30%). After a median follow-up of 22 months (95% CI: 15-27 months), the median PFS and OS were not reached in patients who responded; 1-year PFS and OS were 73% and 100%, respectively. CONCLUSIONS: IPI3 following recurrence/progression on low dose IPI has clinical activity, including in primary resistance. IPI dosing is therefore critical in a subset of patients.

Impact of immune checkpoint inhibitors and targeted therapy on health-related quality of life of people with stage III and IV melanoma: a mixed-methods systematic review.

BACKGROUND: Immune checkpoint inhibitors (ICI) and targeted therapies (TT) have significantly improved disease control and survival in people with stage III and IV cutaneous melanoma. Understanding the impact of therapy on health-related quality of life (HRQL) is vital for treatment decision-making and determining targets for supportive care intervention. We conducted a mixed-methods systematic review to synthesise the impact of ICIs and TT on all domains of HRQL in these populations. METHODS: A systematic literature search was conducted in April 2022 on MEDLINE, PsycINFO, Embase and the Cochrane Central Register of Controlled Trials. Quantitative and qualitative data relevant to the review question were extracted and synthesised in tables according to setting (adjuvant versus metastatic), treatment type (ICI versus TT) and HRQL issue. RESULTS: Twenty-eight papers describing 27 studies were included: 15 randomised controlled trials (RCTs), four cohort studies, four single arm cross-sectional studies, two qualitative studies, one case control study and one mixed-methods study. In four studies of people with resected stage III melanoma, adjuvant pembrolizumab and dabrafenib-trametinib did not clinically or statistically change HRQL compared to baseline. In 17 studies of people with unresectable stage III/IV melanoma, inconsistencies in the impact of ICI on symptoms, functioning and overall HRQL were noted across different study designs. TT was associated with improvements in symptoms, functioning and HRQL across six studies. CONCLUSION: This review highlights the key physical, psychological and social issues experienced by people with stage III and IV melanoma treated with ICI and TT. Inconsistencies in the impact of ICI on HRQL were observed in different study designs. This highlights the need for treatment-specific patient-reported outcome measures for determining the impact of these therapies on HRQL and real-world data to inform treatment decision-making and appropriate supportive care interventions.

Common toxicities associated with immune checkpoint inhibitors and targeted therapy in the treatment of melanoma: A systematic scoping review.

INTRODUCTION: This systematic scoping review compares the toxicities experienced by patients receiving immune checkpoint inhibitors (ICIs) or targeted therapy (TT) for stage III (resected and unresectable) and stage IV melanoma. METHODS: OVID Medline, Embase, and PsycInfo were searched to identify Phase III trials reporting toxicities of FDA-approved ICIs and TT for advanced melanoma. AEs that were reported by ≥ 10% of patients in the evaluated trials were included. RESULTS: Toxicity profiles of 11208 patients from 24 studies were reviewed. The rate of AEs was lower with ICIs compared to TT. However, ICIs were associated with higher rates of long-term or permanent AEs compared to TT, where toxicities generally were shortterm and reversible with treatment discontinuation. CONCLUSION: The toxicity profiles of ICIs and TT vary substantially. Whilst the rate of AEs was lower with ICIs than during TT, it was also associated with higher rates of potentially chronic AEs.

International Validation of the EORTC QLQ-ANL27, a Field Study to Test the Anal Cancer-Specific Health-Related Quality-of-Life Questionnaire.

PURPOSE: The European Organisation for Research and Treatment of Cancer (EORTC) health-related quality of life questionnaire for anal cancer (QLQ-ANL27) supplements the EORTC cancer generic measure (QLQ-C30) to measure concerns specific to people with anal cancer treated with chemoradiotherapy. This study tested the psychometric properties and acceptability of the QLQ-ANL27. METHODS AND MATERIALS: People with anal cancer were recruited from 15 countries to complete the QLQ-C30 and QLQ-ANL27 and provide feedback on the QLQ-ANL27. Item responses, scale structure (multitrait scaling, factor analysis), reliability (internal consistency and reproducibility) and sensitivity (known group comparisons and responsiveness to change) of the QLQ-ANL27 were evaluated. RESULTS: Data from 382 people were included in the analyses. The EORTC QLQ-ANL27 was acceptable, comprehensive, and easy to complete, taking an average 8 minutes to complete. Psychometric analyses supported the EORTC QLQ-ANL27 items and reliability (Cronbach's α ranging from 0.71-0.93 and test-retest coefficients above 0.7) and validity of the scales (particularly nonstoma bowel symptoms and pain/discomfort). Most scales distinguished people according to treatment phase and performance status. Bowel (nonstoma), pain/discomfort, and vaginal symptoms were sensitive to deteriorations over time. The stoma-related scales remained untested because of low numbers of people with a stoma. Revisions to the scoring and question ordering of the sexual items were proposed. CONCLUSIONS: The QLQ-ANL27 has good psychometric properties and is available in 16 languages for people treated with chemoradiotherapy for anal cancer. It is used in clinical trials and has a potential role in clinical practice.

Entanglements and imagined futures: The subject(s) of precision in oncology.

Precision oncology holds an increasingly powerful social function. In the era of precision, how people encounter, live with, and experience cancer, how they imagine their lives, how they navigate treatment regimens, and experience side effects, have been radically transformed. Innovations in oncology - in this case precision-related - are always more-than-clinical; their circulation exceeds the laboratory and the hospital, but what this 'circulation of innovation' produces has been thus far opaque. To begin to comprehend what is emergent at the cancer-precision nexus in people's everyday lives, we draw on qualitative interviews with twenty people diagnosed with metastatic non-small cell lung cancer undergoing immunotherapy and/or targeted therapy and we discuss how precision inflects survivorship, entangles subjects in chronic living, and induces novel temporalities. Through such inflections of survivorship, precision innovation re-shapes expectations and possibilities, and sometimes enacts new, unexpected (or, for some, unwanted) futures. Such illness and survivorship narratives indicate the importance of orientating the social science scholarship toward considerations of temporality and entanglements for comprehending precision innovation in oncology. And in doing so, provide a nuanced account of how innovations unsettle and recast, rather than unravel, the normative scene of cancer.

Feasibility, acceptability, and utility of a nurse-led survivorship program for people with metastatic melanoma (MELCARE).

PURPOSE: Immune checkpoint inhibitors (ICIs) and targeted therapy (TT) have improved the survival of people with metastatic melanoma. We assessed the feasibility, acceptability, and utility of a novel model of nurse-led, telehealth-delivered survivorship care (MELCARE) for this survivor group. METHODS: People ≥ 18 years diagnosed with unresectable stage III or stage IV melanoma who were ≥ 6 months post initiation of ICI/TT with a radiological response suggestive of a long-term response to ICI/TT were recruited from a specialist melanoma centre in Australia. All participants received MELCARE, a nurse-led survivorship program involving two telehealth consultations 3 months apart, needs assessment using the Distress Thermometer (DT) and Problem List, and creation of a survivorship care plan. Feasibility, acceptability, and utility were assessed using rates of consent and study completion, time taken to complete each component of MELCARE, the Acceptability of Intervention Measure (AIM), and a customised utility survey. RESULTS: 31/54 (57%) people consented. Participants were male (21, 68%), with a median age of 67 (range: 46-82). Eleven (35%) were receiving/had received ipilimumab and nivolumab and 27 (87%) had ceased treatment. Feasibility was demonstrated with 97% completing MELCARE. Utility was demonstrated on a customised survey and supported by a reduction in the mean DT score (initial: 5.6, SD: 2.9; follow-up: 1.5, SD: 1.2). Acceptability was demonstrated on 3/4 AIM items. CONCLUSION: MELCARE was feasible and acceptable with high levels of utility. However, the consent rate was 57% indicating some people do not require support. Future studies should consider MELCARE's optimal timing, resourcing, and cost-effectiveness.

Using Patient-Reported Outcomes in Dose-Finding Oncology Trials: Surveys of Key Stakeholders and the National Cancer Research Institute Consumer Forum.

BACKGROUND: Patient-reported adverse events may be a useful adjunct for assessing a drug's tolerability in dose-finding oncology trials (DFOT). We conducted surveys of international stakeholders and the National Cancer Research Institute (NCRI) Consumer Forum to understand attitudes about patient-reported outcome (PRO) use in DFOT. METHODS: A 35-question survey of clinicians, trial managers, statisticians, funders, and regulators of DFOT was distributed via professional bodies examining experience using PROs, benefits/barriers, and their potential role in defining tolerable doses. An 8-question survey of the NCRI Consumer Forum explored similar themes. RESULTS: International survey: 112 responses from 15 September-30 November 2020; 103 trialists [48 clinicians (42.9%), 38 statisticians (34.0%), 17 trial managers (15.2%)], 7 regulators (6.3%), 2 funders (1.8%)]. Most trialists had no experience designing (73, 70.9%), conducting (52, 50.5%), or reporting (88, 85.4%) PROs in DFOT. Most agreed that PROs could identify new toxicities (75, 67.0%) and provide data on the frequency (86, 76.8%) and duration (81, 72.3%) of toxicities. The top 3 barriers were lack of guidance regarding PRO selection (73/103, 70.9%), missing PRO data (71/103, 68.9%), and overburdening staff (68/103, 66.0%). NCRI survey: 57 responses on 21 March 2021. A total of 28 (49.1%) were willing to spend <15 min/day completing PROs. Most (55, 96.5%) preferred to complete PROs online. 61 (54.5%) trialists and 57 (100%) consumers agreed that patient-reported adverse events should be used to inform dose-escalation decisions. CONCLUSION: Stakeholders reported minimal experience using PROs in DFOT but broadly supported their use. Guidelines are needed to standardize PRO selection, analysis, and reporting in DFOT.

Management of common clinical problems experienced by survivors of cancer.

Improvements in early detection and treatment have led to a growing prevalence of survivors of cancer worldwide. Models of care fail to address adequately the breadth of physical, psychosocial, and supportive care needs of those who survive cancer. In this Series paper, we summarise the evidence around the management of common clinical problems experienced by survivors of adult cancers and how to cover these issues in a consultation. Reviewing the patient's history of cancer and treatments highlights potential long-term or late effects to consider, and recommended surveillance for recurrence. Physical consequences of specific treatments to identify include cardiac dysfunction, metabolic syndrome, lymphoedema, peripheral neuropathy, and osteoporosis. Immunotherapies can cause specific immune-related effects most commonly in the gastrointestinal tract, endocrine system, skin, and liver. Pain should be screened for and requires assessment of potential causes and non-pharmacological and pharmacological approaches to management. Common psychosocial issues, for which there are effective psychological therapies, include fear of recurrence, fatigue, altered sleep and cognition, and effects on sex and intimacy, finances, and employment. Review of lifestyle factors including smoking, obesity, and alcohol is necessary to reduce the risk of recurrence and second cancers. Exercise can improve quality of life and might improve cancer survival; it can also contribute to the management of fatigue, pain, metabolic syndrome, osteoporosis, and cognitive impairment. Using a supportive care screening tool, such as the Distress Thermometer, can identify specific areas of concern and help prioritise areas to cover in a consultation.

Embedding electronic patient-reported outcome measures into routine care for patients with stage III MELanoma (ePROMs-MEL): protocol for a prospective, longitudinal, mixed-methods pilot study.

INTRODUCTION: The benefits of patient-reported feedback, using questionnaires that allow patients to report how they feel and function without any interpretation from healthcare professionals, are well established. However, patient-reported outcomes measures (PROMs) are not routinely collected in patients with melanoma in Australia. The aim of this study is to evaluate the feasibility and acceptability of implementing electronic PROMs (ePROMs) into routine care from the perspectives of patients with stage III melanoma and their treating clinical team. METHODS AND ANALYSIS: A minimum of 50 patients and 5 clinicians will be recruited to this prospective, longitudinal pilot study (ePROMs-MELanoma). The study uses a mixed-methods approach (quantitative PROMs questionnaires and end-of-study surveys with qualitative interviews) and commenced in May 2021 in surgical and medical melanoma clinics at two sites in metropolitan Sydney, Australia. The primary outcomes are measures of feasibility and acceptability, comprising descriptive questionnaire completion statistics, and proportion of patients who reported that these PROMs were easy to complete and measured items they considered important. Clinician and clinic staff views will be canvassed on the appropriateness of these PROMs for their patients, change in referral practice and uptake and incorporation into routine practice. Secondary aims include measurement of improvements in patients' emotional and physical health and well-being, and utility of real-time data capture and clinician feedback. All participants will complete the Distress Thermometer and EQ-5D-5L questionnaires in the clinic using a tablet computer at baseline and two to three subsequent follow-up appointments. Participants who report a score of 4 or higher on the Distress Thermometer will be triaged to complete an additional three questionnaires: the QLQ-C30, Depression, Anxiety and Stress Scale and Melanoma Concerns Questionnaire-28. Results will be generated in real time; patients with psychosocial distress or poor quality of life will discuss possible referral to appropriate allied health services with their clinician. Thematic analysis of interviews will be conducted. ETHICS AND DISSEMINATION: Ethics approval obtained from St Vincent's Hospital Human Research Ethics Committee on 19 September 2019 (2019/ETH10558), with amendments approved on 8 June 2022. Patient consent is obtained electronically prior to questionnaire commencement. Dissemination strategies will include publication in peer-reviewed journals and presentation at international conferences, tailored presentations for clinical societies and government bodies, organisational reporting through multidisciplinary meetings and research symposia for local clinicians and clinic staff, and more informal, lay reports and presentations for consumer melanoma representative bodies and patient participants and their families. TRIAL REGISTRATION NUMBER: ACTRN12620001149954.

Trends in patient-reported outcome use in early phase dose-finding oncology trials - an analysis of ClinicalTrials.gov.

BACKGROUND: Patient-reported adverse events (AEs) may be a useful adjunct to clinician-assessed AEs for assessing tolerability in early phase, dose-finding oncology trials (DFOTs). We reviewed DFOTs on ClinicalTrials.gov to describe trends in patient-reported outcome (PRO) use. METHODS: DFOTs commencing 01 January 2007 - 20 January 2020 with 'PROs' or 'quality of life' as an outcome were extracted and inclusion criteria confirmed. Study and PRO characteristics were extracted. Completed trials that reported PRO outcomes and published manuscripts on ClinicalTrials.gov were identified, and PRO reporting details were extracted. RESULTS: 5.3% (548/10 372) DFOTs included PROs as an outcome. 231 (42.2%) were eligible: adult (224, 97%), solid tumour (175, 75.8%), and seamless phase 1/2 (108, 46.8%). PRO endpoints were identified in more trials (2.3 increase/year, 95% CI: 1.6-2.9) from an increasing variety of countries (0.7/year) (95% CI: 0.4-0.9) over time. PROs were typically secondary endpoints (207, 89.6%). 15/77 (19.5%) completed trials reported results on the ClinicalTrials.gov results database, and of those eight included their PRO results. Eighteen trials had published manuscripts available on ClinicalTrials.gov. Three (16.7%) used PROs to confirm the maximum tolerated dose. No trials identified who completed the PROs or how PROs were collected. CONCLUSIONS: PRO use in DFOT has increased but remains limited. Future work should explore the role of PROs in DFOT and determine what guidelines are needed to standardise PRO use.