Functional Assessment Of Cancer Therapy-Melanoma Research Articles

The Symptom Experience of Patients with Advanced Melanoma Undergoing Immune Checkpoint Inhibitor (ICI) Therapy

ObjectivesThe advent of immune checkpoint inhibitor (ICI) therapy has vastly improved outcomes for patients with advanced melanoma. However, the symptom burden and intensity with their impact on quality-of-life (HRQoL) and functionality are heterogeneous and unpredictable. We used descriptive exploratory content analysis from interviews to capture the patient experience after they had completed quantitative data collection of their symptom burden and interference with the use of two patient-reported outcome (PRO) instruments. Data SourcesParticipants from a single center with advanced melanoma (n = 19) who are undergoing ICI therapy completed the Modified MD Anderson Symptom Inventory and Functional Assessment of Cancer Therapy-Melanoma and recorded semistructured interviews. Interpretive description informed the inductive and iterative analysis approach. ConclusionParticipants had a heterogenous experience of ICI and melanoma-related symptoms: distress (84%), fatigue (68%), rash or skin changes (53%), pain (30%), diarrhea (30%), itching (26%), and shortness of breath (21%), with varying interference within HRQoL domains, mood (47%), relations with other people (26%), and activity (21%). Some noted a lack of physical interference (79%). Uncertainty was a pervasive theme in the interviews (68%) despite the majority having positive thoughts about ICI therapy (58%) and expectations of the success of therapy (53%). The physical and emotional burden of a melanoma diagnosis, undergoing therapy, and the uncertainty of the outcomes are pervasive for patients. Implications for Nursing PracticeCommunication surrounding the diagnosis, prognosis, treatment options, and outcomes need to be clear and acknowledge there are unknowns. Nurses may benefit from using a validated PRO instrument to help document and understand the patient's symptom experience while undergoing ICI therapy.

Real-World Effectiveness, Safety, and Health-Related Quality of Life in Patients Receiving Adjuvant Nivolumab for Melanoma in Belgium and Luxembourg: Results of PRESERV MEL.

Nivolumab, an anti-programmed cell death 1 immuno-oncology therapy, is approved as an adjuvant treatment for patients with completely resected stage III or stage IV melanoma. PRESERV MEL (Prospective and REtrospective Study of nivolumab thERapy in adjuVant MELanoma) is a real-world observational study evaluating the effectiveness and safety of adjuvant nivolumab in patients with completely resected stage III or stage IV melanoma in clinical practice in Belgium and Luxembourg. Patients were enrolled prospectively and retrospectively during a 2-year period (January 2019-January 2021), and will be followed for 5 years. The results reported here are for the second interim analysis (cutoff date 31 December 2021). The index date was the date of first administration of adjuvant nivolumab. Patients received nivolumab for up to 12 months per label. Outcomes included relapse-free survival (RFS), adverse events (AEs)/treatment-related AEs (TRAEs), and health-related quality of life (HRQoL; assessed in prospectively enrolled patients using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30), Functional Assessment of Cancer Therapy-Melanoma (FACT-M), and EQ-5D-3L instruments). HRQoL was evaluated at group level (mean change in scores from baseline based on minimally important differences) and individual patient level (percentage of patients with clinically important scores based on threshold of clinical importance). Outcomes were analyzed descriptively. The study enrolled 152 patients (125 prospective, 27 retrospective) at 15 hospitals in Belgium and Luxembourg. Minimum potential follow-up at time of analysis was 11.4 months. Median age was 60 years (range 29-85), and 53% of patients were male. At 12 and 18 months, the RFS rates were 74.7% (95% confidence interval (CI): 66.9-80.9) and 68.4% (95% CI: 60.0-75.5), respectively. Median RFS was not reached. Grade 3 or 4 TRAEs were reported in 14% of patients. AEs led to treatment discontinuation in 23% of patients. Deaths occurred in 3% of patients and were not related to treatment. Questionnaire completion rates for HRQoL were high at baseline (90-94%) and at 24 months (78-81%). In the group-level analysis for HRQoL, mean changes in scores from baseline remained stable and did not exceed prespecified thresholds for minimally important differences during and after treatment, except for a clinically meaningful improvement in FACT-M surgery subscale scores. In the individual patient-level analysis for EORTC QLQ-C30 subscales, the percentages of patients who reported clinically relevant scores for fatigue and cognitive impairment increased during treatment (at 9 months) compared with baseline. After treatment cessation (at 18 months), the percentage of patients who reported clinically relevant scores for fatigue decreased. However, the percentages of patients who reported clinically relevant scores for emotional, cognitive, and social impairment increased at 18 months compared with during treatment. Most patients with emotional impairment at 9 and 18 months did not experience disease recurrence (91% and 89%, respectively). These results confirm the real-world effectiveness and safety of nivolumab as an adjuvant treatment for patients with completely resected stage III or stage IV melanoma. Cancer-specific, disease-specific, and generic HRQoL were maintained during and after treatment. The percentage of patients reporting emotional and cognitive impairment increased after treatment cessation, emphasizing the need for further investigation and tailored supportive care in these patients.

P50 Exploring unmet needs and attitudes to skin self-examination in melanoma survivors: EUNASS study

Abstract A melanoma diagnosis can have significant emotional and psychosocial impact, yet little guidance exists on how best to support individuals following initial diagnosis. This multicentre UK study aimed to evaluate the baseline needs of melanoma survivors and assess attitudes towards practising skin self-examination (SSE) to inform the development of intervention(s) that best support patients with melanoma beyond diagnosis. A prospective multicentre questionnaire study was conducted across four UK sites, including adults diagnosed with American Joint Cancer Committee (AJCC version 8) stage I–III primary cutaneous melanoma. Participants were invited within 3–12 months of their initial diagnosis to self-complete an electronic questionnaire (using Qualtrics software) evaluating unmet needs, which included the Functional Assessment of Cancer Therapy—Melanoma (FACT-M), Fear of Cancer Recurrence Inventory-Short Form (FCRI-SF), Melanoma specific unmet needs (SF-36), Sun Protection Behaviour Scale (SPBS), Skin Self-Examination (SSE) benefits and barriers scale, and European Quality of Life 5 Dimensions (EQ-5D). STATA 17 was used for the data analysis. Overall, 252 participants were recruited and 55 excluded for failure to provide any responses. The sample was predominantly male (56.3%) and White (100%), with high educational qualifications (52.1%) and not in paid/self-employment (53.2%). Sites of primary melanoma included the trunk (n = 61; 31.0%), head/neck (n = 45; 22.8%), arm (n = 44; 22.3%), leg (n = 33; 16.8%), hands/feet (n = 10; 5.1%) and genitals (n < 5; < 2.5%). SSE barrier and benefit scales had median scores of 29 [interquartile range (IQR) 27–32] and 27 (IQR 22–32), respectively, indicating positive attitudes towards SSE; however, several barriers exist, including identifying abnormal moles and associated anxiety. The majority of participants (56.4%) were identified as having at least one unmet care need, most commonly with regard to information on recurrence risk (37.1%) and SSE (33.0%). The FACT-M, FACT-M trial outcome index and FACT-G (general) had median scores of 26 (IQR 12–38; n = 180), 16 (IQR 6–22, n = 183) and 21 (IQR 8–29; n = 180), respectively. Participants had a median EQ-5D score of 0.92 [IQR 0.86–1.0; full health = 1.0 (n = 189)] and 59.9% were identified as having less than full health. This multicentre UK study indicates that melanoma survivors experience low quality of life within the first year of their diagnosis. Routine collection of melanoma-specific patient-reported outcome measures could improve the patient experience by stratifying patients to receive appropriate supportive care. Focused educational tools guiding sun protection habits and SSE are needed to reduce the risk of further melanomas. Future qualitative data will support an evidence base to develop supportive tools, enabling patients to take an active role in self-management.

DS09 (P50) Exploring Unmet Needs and Attitudes to Skin ­Self-examination in melanoma survivors: EUNASS study

Abstract A melanoma diagnosis can have significant emotional and psychosocial impact, yet little guidance exists on how best to support individuals following initial diagnosis. This multicentre UK study aimed to evaluate the baseline needs of melanoma survivors and assess attitudes towards practising skin self-examination (SSE) to inform the development of intervention(s) that best support patients with melanoma beyond diagnosis. A prospective multicentre questionnaire study was conducted across four UK sites, including adults diagnosed with American Joint Cancer Committee (AJCC version 8) stage I–III primary cutaneous melanoma. Participants were invited within 3–12 months of their initial diagnosis to self-complete an electronic questionnaire (using Qualtrics software) evaluating unmet needs, which included the Functional Assessment of Cancer Therapy—Melanoma (FACT-M), Fear of Cancer Recurrence Inventory—Short Form (FCRI-SF), Melanoma-specific unmet needs (SF-36), Sun Protection Behaviour Scale (SPBS), Skin Self-Examination (SSE) benefits and barriers scale and European Quality of Life 5 Dimensions (EQ-5D). STATA 17 was used for the data analysis. Overall, 252 participants were recruited and 55 excluded for failure to provide any responses. The sample was predominantly male (56.3%) and White (100%), with high educational qualifications (52.1%) and not in paid/self-employment (53.2%). Sites of primary melanoma included the trunk (n = 61; 31.0%), head/neck (n = 45; 22.8%), arm (n = 44; 22.3%), leg (n = 33; 16.8%), hands/feet (n = 10; 5.1%) and genitals (n < 5; < 2.5%). Skin self-examination barriers and benefits scales had median scores of 29 [interquartile range (IQR) 27–32] and 27 (IQR 22–32), respectively, indicating positive attitudes towards SSE; however, several barriers exist, including identifying abnormal moles and associated anxiety. The majority of participants (56.4%) identified as having at least one unmet care need, most commonly with regard to information on recurrence risk (37.1%) and SSE (33.0%). The FACT-M, FACT-M trial outcome index and FACT-G (general) had median scores of 26 (IQR 12–38; n = 180), 16 (IQR 6–22, n = 183) and 21 (IQR 8–29; n = 180), respectively. Participants had a median EQ-5D score of 0.92 [IQR 0.86–1.0; full health = 1.0 (n = 189)], and 59.9% were identified as having less than full health. This multicentre UK study indicates that melanoma survivors experience low quality of life within the first year of their diagnosis. Routine collection of melanoma-specific patient-reported outcome measures could improve the patient experience by stratifying patients to receive appropriate supportive care. Focused educational tools guiding sun protection habits and SSE are needed to reduce the risk of further melanomas. Future qualitative data will support an evidence base to develop supportive tools, enabling patients to take an active role in self-management.

Tumor Burden and Health-Related Quality of Life in Patients with Melanoma In-Transit Metastases.

Few studies have investigated the health-related quality of life (HRQOL) in patients with melanoma in-transit metastases (ITM). The aim was to investigate the association between tumor burden and HRQOL, including disparities pertaining to sex and age, in treatment-naïve patients with ITM. Functional Assessment of Cancer Therapy-Melanoma (FACT-M) questionnaire was used to assess HRQOL Pairwise comparisons using t-tests between clinical cutoffs are presented and multiple linear regression analysis showing the unique associations of gender, age, number of tumors, tumor size, presence of lymph node metastases, and tumor localization. A total of 95 patients, 47% females and 53% males (median age 72 years) were included between 2012 and 2021. Women scored significantly lower on emotional well-being (p = 0.038) and lower on FACT-M (p = 0.058). Patients who had ≥10 tumors scored significantly lower on FACT-M (p = 0.015), emotional- and functional well-being (p = 0.04, p = 0.004, respectively), melanoma scale (p = 0.005), and FACT-G (p = 0.027). There was no significant difference in HRQOL depending on age, size of tumors, localization, or presence of lymph node metastases. For patients with melanoma ITMs, the female sex and higher tumor burden (i.e., number of tumors) were significantly correlated with lower HRQOL. However, these findings do not fully explain HRQOL for this patient population, and future research should consider the possibility that there are specific questions for patients with ITM where current instruments might fail to measure their discomfort to the full extent.

803P Patient-reported outcomes in patients with resected, stage III BRAF V600+ melanoma treated with adjuvant dabrafenib + trametinib: COMBI-APlus study

COMBI-APlus, an open-label, phase 3b study, met its primary endpoint of significant reduction in composite pyrexia events compared with a historical control from COMBI-AD. Here, we report the patient-reported outcomes (PROs) during the 12-month adjuvant dabrafenib plus trametinib (D + T) treatment in patients (pts) with stage III BRAF V600+ melanoma after complete resection. Eligible pts aged ≥18 years with resected stage III BRAF V600E/K–mutant melanoma received oral adjuvant D (150 mg twice daily) + T (2 mg once daily) for up to 12 months (mo). A 16-item melanoma subscale of the Functional Assessment of Cancer Therapy-Melanoma (FACT-M) tool was used to assess the quality of life (QOL). Respondents were asked to score the statements related to their QoL with melanoma, based on a four-point response scale, with 4 being the best response. The FACT-M scores were assessed at baseline and at every month up to month 12. Time to first deterioration, which was defined as the time from inclusion in the study to the first decrease in QoL scores according to baseline score, and effect of age, stage, baseline score, visit, and status visit on PRO using a mixed-effect model were also evaluated. A total of 552 pts were enrolled and included in this analysis. The mean (SD) FACT-M score at baseline for all pts was 57.44 (5.203), which changed to 55.31 (7.392) at 6 months, and 56.02 (7.324) at 12 months. Overall, data of individual questions showed that pts were at their best state at most of the visits, with non-relapsed pts showing better change in scores than relapsed pts. The minimal point of worsening was observed at point 5, and the median time for minimal worsening of melanoma-related symptoms was 5.55 mo. The mixed-effect model showed that the disease stage at baseline had a significant effect on the change in PRO score. PRO data from COMBI-APlus study showed no clear worsening of QOL during the treatment unless there was a relapse. This implies that disease evolution but not treatment affects the QOL, supporting use of D + T as adjuvant treatment in pts with stage III BRAF V600+ melanoma after complete resection.

Real-world outcomes with immuno-oncology (IO) therapies: A prospective, observational cohort study in patients (pts) with advanced melanoma (OPTIMIzE).

e14144 Background: There is little real-world evidence evaluating treatment patterns and outcomes with IO therapies for pts with advanced melanoma (aMEL). We present results from the OPTIMIzE (NCT02780089) study in pts with aMEL receiving IO therapies. Methods: OPTIMIzE is a US-based multisite (150 sites), community-based study of adult pts with aMEL. Pts receiving first-line (1L) nivolumab (NIVO)+ipilimumab (IPI), anti-PD-1 (NIVO/pembrolizumab), or IPI between 2011-2018 with a minimum 1 y of follow-up were included. Baseline characteristics, objective response rate (ORR), overall survival (OS), treatment-related adverse events (TRAEs), and quality of life (QoL) were analyzed. QoL assessments included the Functional Assessment of Cancer Therapy–Melanoma (FACT-M), EQ-5D index, and visual analog scale (VAS). Results: Cohort size: 81 NIVO+IPI, 147 anti-PD-1, and 16 IPI (IPI arm not included in the analysis). Overall, mean age was 64.5 y; 42% had BRAF mutation. Mean follow-up was 14.1 mo. Pts in the NIVO+IPI group were younger, had better ECOG performance status, and a higher likelihood of M1c disease and elevated LDH vs the anti-PD-1 group. ORR was higher for pts treated with NIVO+IPI vs anti-PD-1 (48% vs 33%, P= 0.08). Unadjusted 1-y OS was 78.4% for NIVO+IPI and 73.1% for anti-PD-1. In multivariate Cox model analysis, the hazard ratio for OS for NIVO+IPI vs anti-PD-1 was 0.78 (95% CI, 0.46–1.33; P= 0.36). Grade 3/4 TRAEs occurred in 53% and 22% of pts in the NIVO+IPI and anti-PD-1 groups, respectively ( P˂0.001). QoL changes from baseline were clinically meaningful for EQ-5D VAS and FACT-M in the NIVO+IPI group at 12 mo (Table). After adjusting for baseline covariates, the difference at 12 mo between NIVO+IPI vs anti-PD-1 was 6.7 ( P= 0.04) for EQ-5D VAS and 8.8 ( P= 0.02) for FACT-M. Conclusions: Safety and efficacy outcomes from this prospective real-world study are consistent with those reported in prior clinical trials in treatment-naive aMEL pts. No clinically meaningful deterioration in QoL measures was observed in either group. Clinical trial information: NCT02780089. [Table: see text]

Quality of life measurement in skin cancer patients: literature review and position paper of the European Academy of Dermatology and Venereology Task Forces on Quality of Life and Patient Oriented Outcomes, Melanoma and Non-Melanoma Skin Cancer.

The European Academy of Dermatology and Venereology (EADV) Task Forces (TFs) on Quality of Life (QoL) and Patient Oriented Outcomes, Melanoma and Non-Melanoma Skin Cancer (NMSC) present a review of the literature and position statement on health-related (HR) QoL assessment in skin cancer patients. A literature search was carried out to identify publications since 1980 that included information about the impact of SC on QoL. Generic, dermatology-specific, cancer-specific, SC-specific, facial SC-specific, NMSC-specific, basal cell carcinoma-specific and melanoma-specific QoL questionnaires have been used to assess HRQoL in SC patients. HRQoL was assessed in the context of creation and validation of the HRQoL instruments, clinical trials, comparison of QoL in SC and other cancers, other diseases or controls, HRQoL assessment after treatment, comorbidities, behaviour modification, predictors of QoL and survival, supportive care needs, coping strategies and fear of cancer recurrence. The most widely used instruments for HRQoL assessment in SC patients are the European Organisation for Research and Treatment of Cancer Core Questionnaire (EORTC QLQ-C30), the Functional Assessment of Cancer Therapy-Melanoma (FACT-M), Skin Cancer Index (SCI), Short Form 36 Item Health Survey (SF-36) and the Dermatology Life Quality Index (DLQI). The TFs recommend the use of the cancer-specific EORTC QLQ-C30, especially in late stages of disease, and the melanoma-specific FACT-M and SC-specificSCI questionnaires. These instruments have been well validated and used in several studies. Other HRQoL instruments, also with good basic validation, are not currently recommended because the experience of their use is too limited. Dermatology-specific HRQoL instruments can be used to assess the impact of skin-related problems in SC. The TFs encourage further studies to validate HRQoL instruments for use in different stages of SC, in order to allow more detailed practical recommendations on HRQoL assessment in SC.

Health-related quality of life in patients with malignant melanoma by stage and treatment status

Health-related quality of life in patients with malignant melanoma by stage and treatment status

Sensitivity of Preference-Based Quality-of-Life Measures for Economic Evaluations in Early-Stage Melanoma

The diagnosis of a life-threatening disease like melanoma can affect all aspects of a person's life, including health-related quality of life (HRQOL) and psychological aspects of melanoma such as fear of cancer recurrence (FCR). Economic evaluations of psychological interventions require preference-based (utility) instruments that are sensitive to changes in well-being and HRQOL; however, very few studies have evaluated the sensitivity of these instruments when used for people with melanoma. To compare utility scores from the multiple-attribute instrument Assessment of Quality of Life-8-Dimension Scale (AQoL-8D) with the mapped utility scores of the Functional Assessment of Cancer Therapy-Melanoma (FACT-M) and to investigate the sensitivity of both instruments in identifying the influence of FCR on HRQOL. This assessment of data from a randomized clinical trial of a psychoeducational intervention to reduce FCR, conducted at 3 high-risk melanoma clinics in Australia, evaluated 164 patients with early-stage melanoma and a high risk of developing a second primary melanoma. The FACT-M and AQoL-8D were used to assess HRQOL and FCR among the study participants. Concurrent validity was assessed by comparing the total and subdomain scores of the 2 instruments, and the strength of associations was assessed using Pearson correlation coefficient. Convergent validity was assessed by comparing participants' HRQOL, demographic, and clinical characteristics using the χ2 test and F statistic. Both the FACT-M and AQoL-8D utilities were regressed on FCR Inventory (FCRI) severity scores to estimate the effect of elevated FCR on HRQOL. A total of 164 participants completed the baseline questionnaires, but only 163 met all inclusion criteria and underwent the full analysis: 72 were women; 91 were men; and mean (SD) age was 58.2 (12.1) years. Both the AQoL-8D and FACT-M instruments showed good concurrent validity and could differentiate between relevant subgroups including level of FCRI severity. The AQoL-8D and FACT-M utilities were strongly correlated (r2 = 0.57). Respondents had a mean (SD) AQoL-8D utility of 0.77 (0.2), and a mean (SD) FACT-M utility score of 0.76 (0.07). High levels of FCRI severity were associated with a decrease in utility of 0.12 (95% CI, -0.19 to -0.05) as measured by AQoL-8D, and a decrease of 0.03 (95% CI, -0.05 to -0.01) as measured by the FACT-M. For economic evaluations of psychological interventions in melanoma, the AQoL-8D and FACT-M are valid measures of utility; however, the AQoL-8D demonstrates greater sensitivity to FCRI severity. Our results suggest a significant association between FCR and HRQOL.

Humanistic burden of disease in earlier stage metastatic (stage IIIb/c-IVM1a) versus late stage metastatic (IVM1b/c) melanoma patients in a real-world setting in the U.S.

9561 Background: To assess melanoma specific health-related quality of life (HRQoL) and health states in patients with earlier stage metastatic (IIIb/c-IVM1a) versus late stage metastatic (IVM1b/c) melanoma. Methods: Data were collected from the Adelphi Real World Advanced Melanoma Disease-Specific Programme, a cross-sectional survey of 112 physicians and their patients (N = 666). Data were collected between March and July 2016 in the US. A subset of 183 patients completed the Functional Assessment of Cancer Therapy Melanoma (FACT-M) and EuroQol-5D (EQ-5D) one time. Patients were classified by stage of melanoma at time of consultation. Descriptive analyses of HRQoL scores between earlier and late stage metastatic melanoma were assessed using Mann-Whitney U tests. Results: The mean age of the earlier stage and late stage metastatic patients was 62 and 64 respectively. More earlier stage metastatic patients had an ECOG status of 0 or 1 versus late stage metastatic patients (85%, 75% respectively). A total of 31% of late stage metastatic patients required caregiver support and had a median time since primary diagnosis of 5.0 months whereas earlier stage metastatic patients reported 14% and 5.2 months respectively. Patients with earlier stage metastatic melanoma had better mean EQ-5D index scores versus late stage metastatic melanoma patients (0.81 (n = 84), 0.76 (n = 93); p = 0.0103). Higher scores indicating better HRQoL were observed between earlier stage metastatic versus late stage metastatic melanoma patients for the FACT-M (120.7 (n = 81), 107.4 (n = 91); p = 0.0017) and subscales (except Social Well Being). Clinically meaningful differences between groups using published minimal important differences (MIDs) were observed in in 6/7 FACT-M subscales and EQ-5D VAS. Conclusions: Differences in HRQoL and health states were observed between earlier stage metastatic and late stage metastatic melanoma populations, highlighting the detrimental effect of developing metastatic disease. These results suggest that treatments that delay progression of the disease are important to conserve patients HRQoL

Topical immunotherapy with diphencyprone (DPCP) for in-transit and unresectable cutaneous melanoma lesions: an inaugural Canadian series

ABSTRACTBackground: Diphencycprone (DPCP) is an immune contact sensitizer applied to melanoma lesions. Early studies show favorable efficacy. We present the first North-American series of patients treated with DPCP.Methods: A single center retrospective study of patients with in-transit or unresectable melanoma lesions treated with DPCP from December 1,2014 to December 31,2015 was completed. Primary objectives were response rate and toxicity. Secondary objective was health-related quality of life assessment with the Functional Assessment of Cancer Therapy-Melanoma (FACT-M) questionnaire.Results: Fifteen consecutive patients were identified with median age of 78 (range 43–92). 73% of patients had prior treatment. Two patients (13%) had a complete response after 25 and 32 weeks, respectively. Four patients (27%) had a partial response with a mean treatment time of 30 weeks (range 6–51 weeks). Six (40%) had stable disease. Six patients stopped DPCP – three from systemic progression and three from toxicity. The most common toxicity was blisters; one patient had significant skin ulceration that resolved on stopping DPCP. Median FACT-M score was 142.95 (possible total 172). Mean overall follow-up time was 22.7 weeks.Conclusion: DPCP is a feasible option for in-transit and other melanoma cutaneous lesions ineligible/refractory to surgery and may delay need for systemic therapy.

Health-Related Quality of Life for Patients Who have In-Transit Melanoma Metastases Treated with Isolated Limb Perfusion.

The incidence of malignant melanoma is increasing, and up to 5% of patients will experience in-transit metastases. Normally, the initial treatment is surgical excision, but when not possible, locoregional treatment options such as isolated limb perfusion (ILP) are an alternative. This study aimed to assess health-related quality of life (HRQoL) prospectively for patients whose in-transit metastases is treated with ILP. More specifically, the study aimed to describe HRQoL for patients with in-transit extremity melanoma metastases, to describe changes in HRQoL after ILP, and to correlate HRQoL with local toxicity and clinical response after ILP. The Functional Assessment of Cancer Therapy-Melanoma (FACT-M) consists of 51 items comprising the Functional Assessment of Cancer Therapy-General (FACT-G), the melanoma subscale , and the melanoma surgery scale. Forty-five patients answered the FACT-M questionnaire before ILP (52 procedures) and at 3, 6 and 12 months after ILP. Response and toxicity were analyzed and correlated with the changes in the HRQoL of the patients. Patients with in-transit metastasis have an HRQoL mainly influenced by tumor burden, defined as more or <10 tumors (FACT-M: 142.5 vs. 128.4 points; p=0.02). After ILP, there was a trend toward a decrease in FACT-G (+0.1 vs. -7.3 points; p=0.05) and FACT-M (+1.6 vs. -8.9 points; p=0.08) when Wieberdink classifications 1-2 and 3-4 were compared at 3months. A significant difference in FACT-G (+1.0 vs. -13.0 points; p=0.04) was observed 12months after ILP as well as a trend for FACT-M (+1.7 vs. -14.6 points; p=0.08) when the patients who had a complete response were compared with those who did not. This study found that patients with in-transit metastases have an HRQoL mainly influenced by tumor burden. After ILP, there is an initial decrease in HRQoL due to local toxicity. After 12months, the patients with a complete response maintained an HRQoL at baseline level, strengthening the use of ILP as a palliative treatment.

Comparison of dabrafenib and trametinib combination therapy with vemurafenib monotherapy on health-related quality of life in patients with unresectable or metastatic cutaneous BRAF Val600-mutation-positive melanoma (COMBI-v): results of a phase 3, open-label, randomised trial

In the COMBI-v trial, patients with previously untreated BRAF Val600Glu or Val600Lys mutant unresectable or metastatic melanoma who were treated with the combination of dabrafenib and trametinib had significantly longer overall and progression-free survival than those treated with vemurafenib alone. Here, we present the effects of treatments on health-related quality of life (HRQoL), an exploratory endpoint in the COMBI-v study. COMBI-v was an open-label, randomised phase 3 study in which 704 patients with metastatic melanoma with a BRAF Val600 mutation were randomly assigned (1:1) by an interactive voice response system to receive either a combination of dabrafenib (150 mg twice-daily) and trametinib (2 mg once-daily) or vemurafenib monotherapy (960 mg twice-daily) orally as first-line therapy. The primary endpoint was overall survival. In this pre-specified exploratory analysis, we prospectively assessed HRQoL in the intention-to-treat population with the European Organisation for Research and Treatment of Cancer quality of life (EORTC QLQ-C30), EuroQoL-5D (EQ-5D), and Melanoma Subscale of the Functional Assessment of Cancer Therapy-Melanoma (FACT-M), completed at baseline, during study treatment, at disease progression, and after progression. We used a mixed-model, repeated measures ANCOVA to assess differences in mean scores between groups with baseline score as covariate; all p-values are descriptive. The COMBI-v trial is registered with ClinicalTrials.gov, number NCT01597908, and is ongoing for the primary endpoint, but is not recruiting patients. From June 4, 2012, to Oct 7, 2013, 1645 patients at 193 centres worldwide were screened for eligibility, and 704 patients were randomly assigned to dabrafenib plus trametinib (n=352) or vemurafenib (n=352). Questionnaire completion rates for both groups were high (>95% at baseline, >80% at follow-up assessments, and >70% at disease progression) with similar HRQoL and symptom scores reported at baseline in both treatment groups for all questionnaires. Differences in mean scores between treatment groups were significant and clinically meaningful in favour of the combination compared with vemurafenib monotherapy for most domains across all three questionnaires during study treatment and at disease progression, including EORTC QLQ-C30 global health (7·92, 7·62, 6·86, 7·47, 5·16, 7·56, and 7·57 at weeks 8, 16, 24, 32, 40, 48, and disease progression, respectively; p<0·001 for all assessments except p=0·005 at week 40), EORTC QLQ-C30 pain (-13·20, -8·05, -8·82, -12·69, -12·46, -11·41, and -10·57 at weeks 8, 16, 24, 32, 40, 48, and disease progression, respectively; all p<0·001), EQ-5D thermometer scores (7·96, 8·05, 6·83, 11·53, 7·41, 9·08, and 10·51 at weeks 8, 16, 24, 32, 40, 48, and disease progression, respectively; p<0·001 for all assessments except p=0·006 at week 32), and FACT-M Melanoma Subscale score (3·62, 2·93, 2·45, 3·39, 2·85, 3·00, and 3·68 at weeks 8, 16, 24, 32, 40, 48, and disease progression, respectively; all p<0·001). From the patient's perspective, which integrates not only survival advantage but also disease-associated and adverse-event-associated symptoms, treatment with the combination of a BRAF inhibitor plus a MEK inhibitor (dabrafenib plus trametinib) adds a clear benefit over monotherapy with the BRAF inhibitor vemurafenib and supports the combination therapy as standard of care in this population.

Health-related quality of life in patients with melanoma expressed as utilities and disability weights

Few studies about health-related quality of life (HRQoL) in patients with melanoma have expressed their results in terms of utilities or disability weights (DWs). Utilities are required for calculating quality-adjusted life years and therefore for cost-effectiveness analyses. DWs are useful to assess the burden of diseases through disability-adjusted life years. To provide utilities and DWs regarding patients with melanoma. The patients were classified into eight groups using four stages based on the 2009 American Joint Committee on Cancer stages, with each stage subdivided into treatment and remission phases. The EuroQoL Five Dimensions Five Levels (EQ-5D-5L) questionnaire was completed by the patients with melanoma to provide a mean utility for each group. In addition to this, the EuroQoL visual analogue scale (VAS) and a validated quality-of-life questionnaire dedicated to patients with melanoma [Functional Assessment of Cancer Therapy Melanoma (FACT-M)] were completed by the same patients in order to compare their results with the obtained utilities. DWs were obtained by calculating, for each patient, the difference between his/her utility and the corresponding sex- and age-specific population norm. A total of 395 questionnaire sets were completed. Utilities and DWs showed significant differences between follow-up groups. Treatment groups had similar utilities and DWs but these results were obtained during different treatment durations and therefore have different weights. The VAS and the FACT-M were found to be less sensitive. Nevertheless, the FACT-M identified some problems not found by the EQ-5D-5L questionnaire. The EQ-5D-5L questionnaire seems adequate to provide utilities and DWs in patients with melanoma. Lower HRQoL in female patients with melanoma is probably linked to lower HRQoL in the general population.

Supportive care needs, anxiety, depression and quality of life amongst newly diagnosed patients with localised invasive cutaneous melanoma in Queensland, Australia.

The aim of this paper is to determine levels of supportive care needs, anxiety, depression and symptoms amongst patients newly diagnosed with localised invasive primary melanoma and if these varied amongst patients who had a sentinel lymph node biopsy (SLNB). We also considered quality of life compared with general population norms. Patients newly diagnosed with clinical stage IB-II invasive melanoma were ascertained through Queensland hospitals, specialist clinics and pathology laboratories. Validated surveys measured 46 need items (Supportive Care Needs Survey-Short Form + melanoma subscale), anxiety and depression (Hospital Anxiety and Depression Scale) and quality of life and symptoms (Functional Assessment of Cancer Therapy-Melanoma). Regression models compared outcomes according to whether or not participants had a SLNB. We surveyed 386 patients, 155 before and 231 after wide local excision, of whom 46% reported ≥1 moderate-level or high-level unmet need. The three highest needs were for help with fears about cancer spreading (17%), information about risk of recurrence (17%) and outcomes when spread occurred (16%). Those who had a SLNB were more likely to report a moderate or high unmet need for help with uncertainty about the future or with lymphoedema (p < 0.05). Overall, 32% of participants had anxiety and 15% had depression regardless of performance of SLNB. Melanoma-specific symptoms were worse in SLNB patients (p = 0.03). Compared with the general population, emotional well-being was lower amongst melanoma patients. A substantial proportion of newly diagnosed patients with localised invasive melanoma need further melanoma-specific information and support with psychological concerns. Patients who have a SLNB clear of disease may need help with symptoms after surgery.

Prevalence and correlates of unmet supportive care needs in patients with resected invasive cutaneous melanoma

Knowledge about supportive care needs in patients with cutaneous invasive melanoma is scarce. We examined the unmet needs of melanoma patients treated with surgery and factors associated with these needs to assist health professionals identify areas needing clinical attention. Cross-sectional multisite survey of UK patients ascertained 3 months to 5 years after complete resection of stage I-III cutaneous melanoma. Participants completed the following validated questionnaires: Supportive Care Needs Survey (SCNS-SF34 with melanoma module), Hospital Anxiety and Depression Scale and 51-item Functional Assessment of Cancer Therapy-Melanoma quality-of-life scale. A total of 472 participants were recruited [319 (67%) clinical stage I-II). Mean age was 60 years (standard deviation = 14) and 255 (54%) were female. One hundred and twenty-three (27%) participants reported at least one unmet need (mostly 'low' level). The most frequently reported unmet needs were fears of cancer returning (n = 138, 29%), uncertainty about the future (n = 119, 25%), lack of information about risk of recurrence (n = 112, 24%) and about possible outcomes if melanoma were to spread (n = 91, 20%). One hundred and thirty-eight (29%) participants reported anxiety and 51 (11%) depression at clinical or subclinical levels. Patients with nodal disease had a significantly higher level of unmet supportive care needs (P < 0.001) as did patients with anxiety or depression (P < 0.001). Key correlates of the total SCNS-SF34 score for unmet supportive care needs were younger age (odds ratio, OR = 2.23, P < 0.001) and leaving school early (OR = 4.85, P < 0.001), while better emotional (OR = 0.89, P < 0.001) and social well-being (OR = 0.91, P < 0.001) were linked with fewer unmet needs. Neither patients' sex nor tumour thickness was associated with unmet needs. Around a quarter of melanoma patients may have unmet support needs in the mid to long term after primary treatment. In particular, patients who are younger, less educated, distressed or socially isolated could benefit from more support.

Reducing patient burden to the FACT-Melanoma quality-of-life questionnaire

Respondent burden has been defined as the cumulative demand placed on study participants related to the use of questionnaires or measurement instruments. The aim of this study was to reduce respondent burden associated with the Functional Assessment of Cancer Therapy-Melanoma (FACT-M), a melanoma-specific quality-of-life questionnaire, through item reduction using multiple psychometric approaches. Data for this study were pooled from three institutional review board-approved protocols. Poorly performing items were identified through distributional and correlation analyses, confirmatory factor analysis, reliability estimation, and Rasch-based approaches in a developmental dataset, and the reduced scale was assessed in a separate testing cohort. Validity, reliability, goodness of fit, and Rasch-based testing were carried out for both the full and the reduced scales. The clinical characteristics of the development (n=198) and testing (n=204) cohorts were similar. Three items identified through classical psychometric approaches and three items identified by Rasch-based analyses were excluded from the FACT-M subscale. Two additional items were identified for potential reduction but were ultimately maintained due to the adverse consequences to the psychometric integrity of the reduced instrument. The reduced FACT-M module contains 18 items. In addition to psychometric assessment, expert consultation was essential when examining areas of content redundancy and was critical when considering specific items for removal. This methodological approach reduced respondent burden by 25% while maintaining the psychometric integrity of the FACT-M.

Health-related quality of life among patients with metastatic melanoma

Clinical and health-related quality of life (HRQoL) information was analyzed to determine: (a) patient-reported signs, symptoms, and functioning, (b) HRQoL questionnaire psychometrics, and (c) treatment impact on HRQoL. Data from the Melanoma Subscale (MS) of the Functional Assessment of Cancer Therapy-Melanoma and the worst pain question from the Brief Pain Inventory (BPI) were taken from a clinical trial evaluating intetumumab alone or with dacarbazine in Stage IV metastatic melanoma. Descriptive statistics examined patient-reported disease burden at baseline. Correlations explored clinical endpoint and HRQoL associations. Psychometrics included Cronbach's α internal consistency and intraclass correlation coefficient (ICC). Treatment impact on HRQoL was evaluated through HRQoL maintenance and response analyses. Patients (n=127) had a mean age of 62 years, a mean±SD hemoglobin of 13.0±2.6 g/dl, and a mean±SD lactic dehydrogenase of 394±454 IU/l. Ninety-eight percent were Caucasian, 67% were men, and 64% had an Eastern Cooperative Oncology Group status of 0. Baseline BPI worst pain and MS scores (mean±SD) were 1.6±2.2 and 54.5±7.2, respectively. Top three patient-reported health decrements in the MS were appetite, fatigue, and limited physical activity. Observed HRQoL decrements were consistent with the literature. MS and BPI worst pain item demonstrated good psychometrics: Cronbach's α and ICC for the MS were 0.79 and 0.86, respectively; BPI ICC was 0.74. A trend for HRQoL response was observed 3 weeks postbaseline in the dacarbazine + 10 mg/kg intetumumab arm compared with dacarbazine + placebo: 22 versus 10%, respectively, for the MS; 23 versus 5% for the BPI. Further research on the HRQoL benefit of intetumumab in larger studies appears warranted.

Mapping FACT-Melanoma Quality-of-Life Scores to EQ-5D Health Utility Weights

ObjectivesWe sought to develop a mapping function from functional assessment of cancer therapy-melanoma (FACT-M) quality of life scores to the EuroQol-5D (EQ-5D) utility scores. MethodsFACT-M and EQ-5D scores were collected during a prospective study of melanoma-related quality of life at a tertiary cancer care center in the United States. The study sample was divided into development and validation datasets with equal distributions by cancer stage and treatment status. Censored Least Absolute Deviation (CLAD) and Ordinary Least Squares (OLS) regression analyses were performed using the developmental dataset to derive mapping functions, and model performance was examined through comparisons of residuals and measures of fit in the validation dataset. Exploratory analyses examined the predictive ability of clinical factors and individual subscales. ResultsOf 273 patients, 75 were undergoing treatment with 198 in follow-up surveillance. Relatively even distributions were observed by melanoma stage: I/II (n = 102), III (n = 100), and IV (n = 71). OLS regression resulted in a mapping function of EQ-5D = 0.0037*FACT-M+0.2238 with an R2 0.499. CLAD regression resulted in a mapping function of EQ-5D = 0.0042*FACT-M+0.1648 with pseudo R2 0.328. When applied to the validation dataset, correlations between observed and predicted values resulted in identical coefficients (r = 0.824, P < 0.001). Though the mapping functions were similar, residuals were smaller at the 20th, 40th, and 60th percentiles using the OLS model. The CLAD derived mapping function resulted in smaller residuals only for patients whose EQ-5D = 1. ConclusionsThe OLS mapping function demonstrated better predictive ability and will facilitate the derivation of utilities when direct population preference measures are not available.