Cohort study of Gorlin syndrome with emphasis on standardised phenotyping and quality of life assessment.

BACKGROUND: Gorlin syndrome (nevoid basal cell carcinoma syndrome) is a rare genetic predisposition to basal cell carcinomas (BCC), keratocysts of the jaw and calcification of the falx cerebri among other clinical features. With the advent of sonic hedgehog inhibitors for the treatment of BCC, it is timely to establish a cohort of individuals with Gorlin syndrome and collect standardised phenotypic information on these individuals. Moreover, the health-related quality of life (QoL) in individuals with Gorlin syndrome is not well studied. AIM: To establish a Victorian cohort of Gorlin syndrome and study the QoL in these individuals. METHODS: Phenotypic data were obtained by reviewing medical records of individuals attending two major tertiary/quaternary genetic referral centres in Victoria, followed by telephone or face-to-face interviews where possible. QoL information was obtained utilising the AQoL-6D quality of life survey form. RESULTS: The median number of BCC in the 19 individuals studied was 17.5 (interquartile range 3-70). The number of patients with ≥100 BCC in this group was similar to a previously described national cohort (22.2 vs 27% respectively). A total of 58% of referrals to the genetics clinics originated from maxillofacial surgeons and 42% from dermatologists. Individuals with ≥100 BCC had worse median QoL scores compared to those with <100 BCC (36 vs 29, P-value of 0.031). CONCLUSION: The clinical features in our cohort were congruent with those previously described in Australia. The QoL is adversely correlated with increased BCC burden.

Reliability and validity of the Advanced Basal Cell Carcinoma Index (aBCCdex).

BACKGROUND: Patient-reported outcome (PRO) questionnaires were recently developed specifically for use with patients with advanced basal cell carcinoma (aBCC) and basal cell carcinoma naevus syndrome (BCCNS). OBJECTIVES: To evaluate the measurement properties of PRO questionnaires for use in patients with aBCC or BCCNS. METHODS: In total 129 patients from 10 clinical sites in the U.S.A. and the BCCNS Support Network completed the two newly developed questionnaires multiple times over 3 months. Patients also completed the Skindex-16 and the 12-Item Short-Form Health Survey as collateral measures. Psychometric properties of the questionnaires were evaluated, including internal consistency and test-retest reliability, construct and known-groups validity, and responsiveness. RESULTS: Based on the results of exploratory factor analysis and clinical input, the two newly developed questionnaires were combined into a single questionnaire, called the aBCCdex, which is relevant for patients with both aBCC and BCCNS. The internal consistency reliability was acceptable, and all aBCCdex scale scores correlated significantly with conceptually similar scales. When divided into groups that differed based on scores from collateral measures, aBCCdex scale scores differentiated between groups (known-groups validity) and were responsive to change. CONCLUSIONS: The aBCCdex is a brief and comprehensive questionnaire appropriate for use with patients with aBCC and BCCNS. Its reliability and validity have been confirmed. Further research is necessary to estimate the minimally important difference in a larger patient population.

Assessing health-related quality of life for advanced basal cell carcinoma and basal cell carcinoma nevus syndrome: development of the first disease-specific patient-reported outcome questionnaires.

IMPORTANCE Little is known about patients' experiences of advanced basal cell carcinoma (aBCC) and basal cell carcinoma nevus syndrome (BCCNS), a rare genetic disorder that greatly increases the number of BCCs. OBJECTIVE To develop a questionnaire to measure patient-reported outcomes (PROs) in these populations. DESIGN, SETTING, AND PARTICIPANTS Concept elicitation interviews were conducted with patients with aBCC and BCCNS from 5 US clinical sites and the BCCNS Life Support Network and 4 physicians. The PRO questionnaires were drafted based on results from a literature review and findings from these interviews. Questionnaires were finalized after cognitive debriefing interviews were conducted with patients. Concept elicitation interviews were conducted with 30 patients (14 with aBCC, 16 with BCCNS) and 4 physicians (2 dermatologists, 1 Mohs surgeon, and 1 oncologist) in the United States. A subset of 10 of these patients (5 with aBCC, 5 with BCCNS) took part in cognitive debriefing interviews. MAIN OUTCOMES AND MEASURES Development of 2 questionnaires to allow clinicians to assess the emotional, social, and physical impacts of the disease on patients with aBCC and BCCNS. RESULTS Most concept elicitation interview patients were male (63%) and white (93%); their mean age was 57 years. There were impacts on emotional, social, and physical functioning in both conditions. Patients were unable to do many activities and avoided other activities. Seventy-nine percent of patients with aBCC and all patients with BCCNS reported scarring. Physician interviews revealed similar findings. During cognitive debriefing interviews, the questionnaires were found to be relevant, clear, and comprehensive. CONCLUSIONS AND RELEVANCE Advanced BCC and BCCNS affect patients in unique and substantial ways. These PRO questionnaires were developed with patient and clinician input and measure the key areas that have an impact on patients with these conditions.

The impact of inoperable advanced basal cell carcinoma: the economic, physical, and psychological burden of the disease.

The development of vismodegib and its recent approval by the United States Food and Drug Administration for use in patients with locally advanced or metastatic basal cell carcinoma (BCC) carries with it a renewed sense of optimism. Once BCC has progressed to an advanced, or so-called inoperable stage, there has been a paucity of effective therapies, making the new small molecule inhibitors targeting the hedgehog pathway particularly hopeful prospects. In order to better understand the utility of these new treatments, it is important to assess the existing economic, physical, and psychological burden of advanced BCC. This review aims to recognize the impact of inoperable and metastatic BCC, as well as to better characterize the various types of advanced BCC. The use of vismodegib as a prophylactic treatment in patients with basal cell nevus syndrome is also addressed, including possible adverse events, tumor resistance, and new onset malignancies.

Quality of life and depression assessment in nevoid basal cell carcinoma syndrome.

BACKGROUND: Nevoid basal cell carcinoma syndrome (NBCCS) is a rare genetic disease which causes a variety of dermatological lesions, especially basal cell carcinomas (BCCs), often on the face, neck, and head. METHODS: Persons attending a national NBCCS support group meeting were asked to participate in survey-based assessments of quality of life and depressive symptoms. Inclusion criteria required a self-reported NBCCS diagnosis, voluntary agreement to participate, and age over 18 years. Exclusion criteria included cognitive impairment. Skin-related quality of life was assessed with Skindex-29, completed by 32 participants. Depressive symptomatology was determined with the Center for Epidemiological Studies Depression Scale (CES-D), completed by 18 participants. Sociodemographic, medical, and social variables were also analyzed. RESULTS: Median Skindex-29 scores for the emotions, symptoms, and functioning scales were 42.50, 32.14, and 28.13, respectively (means: 41.17, 37.05, and 29.30, respectively). These scores were slightly higher than those observed in patients with neurofibromatosis type 1, a similar genetic disease with skin symptoms. The CES-D scores (median = 15.50, mean = 17.50) suggested that 50% of participants had significant depressive symptomatology. Variables showing moderate associations with the scores included diet, number of affected family members, and treatment type. Interestingly, the number of BCCs had no effect. CONCLUSIONS: Nevoid basal cell carcinoma syndrome impacts the quality of life of its subjects in a similar manner to other genodermatoses. Depressive symptoms are particularly prevalent. Several demographic, medical, and social characteristics affect these outcomes. Thus, the psychological impact of this disorder should be evaluated in the course of considering the care of persons with NBCCS.