Qualitative evaluation of a multidisciplinary master of cancer sciences: impacts on graduates and influencing curricular factors.

BACKGROUND: Evaluations of continuing professional development programs typically focus on short-term knowledge and skill acquisition. There is a need for more comprehensive program evaluation methods that assess a broader range of impacts and can elicit how and why these outcomes occurred. We conducted a qualitative study to investigate the impacts of a multidisciplinary, online health professional postgraduate degree and to gain insights into the factors that led to these impacts. METHODS: Participants were graduates of the University of Melbourne's Master of Cancer Sciences who could participate in an online interview. Semi-structured, qualitative interviews were conducted exploring a broad range of impacts, including changes in professional practice and career trajectory since graduation, and how the degree influenced these impacts. Data were analysed inductively. RESULTS: Fifteen participants (female: 80%, 31-50 years old: 67%) from a range of professions were interviewed. A number of major themes were uncovered. Impacts on career trajectory included expanded career horizons (e.g. increased role diversity and complexity), and increased confidence in their professional identity. Impacts on professional practice included individual improvements in patient care and research, as well as changes in organisational practice. Factors identified as leading to these impacts were: (i) active, interactive and interprofessional learning; (ii) networking, informal mentoring, and role-modelling; and (iii) support at multiple levels. CONCLUSION: This study provides preliminary evidence of the positive impact of a Master of Cancer Sciences on graduate career trajectory and professional practice. In addition, the inductive methodology enabled identification of the curricular features (both planned and emergent) that influenced these impacts, facilitating potential transferability of learnings to other teaching programs.

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.

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.

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.

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.

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.

Patient-reported outcomes in melanoma survivors at 1, 3 and 5 years post-diagnosis: a population-based cross-sectional study.

PURPOSE: There is a lack of population-based data describing patient reported outcomes (PROs) in melanoma survivors which could guide the development of interventions and resources. This study assessed overall quality of life (QoL), self-reported symptoms and unmet information needs in melanoma survivors 1, 3 or 5 years post-diagnosis. METHODS: A cross-sectional postal survey was conducted in Victoria, Australia, with eligible melanoma survivors identified from a population-based cancer registry. Patient-reported outcome measures included the EuroQoL 5-Dimension 5-Level (EQ-5D-5L), and self-reported symptoms, difficulties and information needs. Associations between demographic, disease and care-related factors and QoL were also assessed. RESULTS: A total of 476 melanoma survivors participated in the study (response rate 46.5%). Anxiety and depressive symptoms were more prevalent in survivors compared to the general population (30.7% vs 21.6%; p < 0.01). Fear of cancer recurrence (48.3%) and fear of cancer spreading (37.8%) were the most commonly reported symptom items, and approximately one in five melanoma survivors had unmet information needs related to psychological aspects of living with melanoma. Recurrent melanoma, living in a nursing home, chronic comorbidities, and melanoma diagnosed at > 2 mm thickness were associated with lower QoL. CONCLUSION: A large proportion of melanoma survivors reported ongoing quality of life deficits, fear of cancer recurrence, as well as unmet information needs up to 5 years after diagnosis. Patients may benefit from tailored informational resources and interventions that address the psychological aspects of living with and beyond melanoma.

Unsuspected allergic contact dermatitis to alcohol swabs following neurosurgery.

We report a case of a 12-year-old girl with severe allergic contact dermatitis following neurosurgery secondary to topical use of isopropyl alcohol swabs. Alcohol swabs should not be overlooked as potential allergens. In our case, it was initially assumed that the cause of her reaction was either tapes or topical local anaesthetic.

Which patients with dermatological conditions are admitted via the emergency department?

BACKGROUND AND OBJECTIVES: Most dermatology admissions to tertiary hospitals in Australia are initially assessed in the emergency department (ED). This 3-year retrospective study examined the types of dermatological conditions that necessitated admission, the factors that predicted admission and the implications for dermatological resource allocation. METHODS: The ED database was searched using the International Statistical Classification of Diseases, 10(th) revision (ICD-10) diagnosis codes and keywords in the presenting complaint and triage notes fields. The two lists were then merged and duplicates removed. All admissions were analysed and the medical records of admissions to the dermatology unit were reviewed to determine their final diagnosis. RESULTS: In total, 4817 patients with dermatological conditions presented over the 3-year period. Of these, 937 (20%) required admission, of whom 108 (12%) were admitted under the dermatology unit. The most common conditions requiring admission were cellulitis (n = 534, 56%), boils, furuncles and pilonidal sinuses (n = 183, 19%), and non-specific skin infections (n = 32, 3%). The most common conditions admitted under dermatology were psoriasis (n = 27, 25%), eczema (n = 25, 23%), and cellulitis (n = 16, 15%). Key predictors of admission were Australasian triage code, referral by a health-care professional or corrections officer and arrival by ambulance. CONCLUSION: Approximately one-fifth of dermatological presentations required admission, mostly for infective processes that did not require specific dermatological care. The predictors of admission reflect the severity of the condition and patients demonstrating these predictors should be referred to the Dermatology unit for admission.

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.

Integrating Patient-Reported Outcomes Into the Care of People With Advanced Cancer-A Practical Guide.

Patient-reported outcomes (PROs) are being increasingly integrated into routine clinical practice to enhance individual patient care. This has been driven by recognition of the benefits of PROs in enhancing symptom management, patient satisfaction, quality of life, and overall survival, and reductions in acute health care utilization. These benefits are reflected in the emergence of value-based health care initiatives incorporating PRO symptom monitoring such as the Enhancing Oncology Model in the United States. However, implementing PROs can be challenging and it can be difficult to know where to begin to select appropriate PROs, and effectively display and appropriately interpret PRO data. This manuscript summarizes an educational session at the 2024 ASCO Annual Meeting, which provided practical guidance to clinicians seeking to incorporate PROs into the care of people with advanced cancer. We focus on why it is important to collect PROs in routine care from a patient's perspective, how to select PROs for symptom monitoring (including using static patient-reported outcome measures and newer item libraries), and highlight key pearls and pitfalls in the display and interpretation of PROs. We highlight the breadth of existing resources available to guide clinicians in PRO implementation.

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.

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.

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.

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.

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.

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.

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.