Proposal for an annual skin examination by a general practitioner for patients at high risk for melanoma: a French cohort study

International audienceOBJECTIVE: To evaluate the efficacy of a targeted screening for melanoma in high-risk patients following the receipt of a mailed invitation to an annual skin examination by a general practitioner (GP).METHODS: A prospective cohort study was conducted in a primary care setting in western France. A total of 3897 patients at elevated risk of melanoma (identified using the Self-Assessment of Melanoma Risk Score) consented to participate in a targeted melanoma screening project in 2011. One year later, the participants were invited by mail to consult their GP for an annual skin examination. Efficacy of the procedure was evaluated according to patient participation and the number of melanomas detected. The consultation dates and results were collected during the 12 months postreminder and were analysed using SAS. Analyses of whether participation decreased compared with that during the year of inclusion and whether populations at risk for thick melanoma showed reduced participation in the screening were performed.RESULTS: Of the 3745 patients who received the mailed invitation, 61% underwent a skin examination. The participation of patients at risk for thick melanoma (any patient over 60 years of age and men over 50 years of age) was significantly greater than that of the patients in the other subgroups (72.4% vs 49.6%, p<0.001; and 66% vs 52.4%, p<0.001, respectively). The patients referred to the dermatologist after 1 year were more compliant compared with those referred during the first year (68.8% vs 59.1%, p=0.003). Six melanomas were detected within 1 year postreminder; therefore, the incidence of melanoma in the study population was 160/100 000.CONCLUSIONS: This study confirms the benefits of developing a targeted screening strategy in primary care. In particular, after the annual reminder, patient participation and the diagnosis of melanoma remained high in the patients at elevated risk of thick melanomas

Anxiety, locus of control and sociodemographic factors associated with adherence to an annual clinical skin monitoring: a cross-sectional survey among 1000 high-risk French patients involved in a pilot-targeted screening programme for melanoma

International audienceOBJECTIVE:The aim of the study was to assess whether adherence to annual clinical skin monitoring is dependent on patient sociodemographic characteristics or personality traits.DESIGN:The study was a questionnaire survey.SETTING AND PARTICIPANTS:Data were collected between February and April 2013 in a sample of 1000 patients at high risk of melanoma who participated in a pilot-targeted screening programme in western France.OUTCOME MEASURES:Sociodemographic data, overall anxiety level (State-Trait Anxiety Inventory questionnaire), locus of control (Multidimensional Health Locus of Control scale) and levels of anxiety specifically associated with screening and melanoma were collected. Actual participation in the skin monitoring examination was reported by 78 general practitioner investigators.STATISTICAL ANALYSIS:Statistical analysis was performed using R statistical software. Factors associated with non-adherence were identified by multivariate analysis.RESULTS:Our analysis included 687 responses (526 adherent patients and 161 non-adherent patients). Non-adherence was higher in younger patients and in men (OR=0.63 (0.41-0.99)). Viewing health status as dependent on external persons (OR=0.90, 95% CI 0.83 to 0.97) or determined by chance (OR=0.89, 95% CI 0.80 to 0.98) and overall anxiety (OR=0.98, 95% CI 0.97 to 0.99) were also factors associated with non-adherence. In contrast, there was no link between anxiety specifically associated with the screening performed or melanoma and patient adherence to monitoring. Adherence was higher in married patients (OR=1.68 95% CI 1.08 to 2.60).CONCLUSIONS:The results of this study suggest that sociodemographic and psychological characteristics should be considered when including patients at elevated risk of melanoma in a targeted screening programme

General practitioner management related to skin cancer prevention and screening during standard medical encounters: a French cross-sectional study based on the International Classification of Primary Care

International audienceOBJECTIVE:The aim of this study was to assess general practitioner (GP) management practices related to skin cancer prevention and screening during standard medical encounters.SETTING:Data on medical encounters addressing skin cancer issues were obtained from a French database containing information from 17 019 standard primary care consultations.PARTICIPANTS:Data were collected between December 2011 and April 2012 by 54 trainees who reported the regular practice of 128 GPs using the International Classification of Primary Care.OUTCOME MEASURES:Reasons for encounters and the following care processes were recorded: counselling, clinical examinations and referral to a specialist. Medical encounters addressing skin cancer issues were compared with medical encounters that addressed other health problems using a multivariate analysis.RESULTS:Only 0.7% of medical encounters addressed skin cancer issues. When patients did require management of a skin cancer-related issue, this was more likely initiated by the doctor than the patient (70.7% vs 29.3%; p<0.001). Compared with medical encounters addressing other health problems, encounters that addressed skin cancer problems required more tasks (3.7 vs 2.5; p<0.001) and lasted 1 min and 20 s longer (p=0.003). GPs were less involved in clinical examinations (67.5% vs 97.1%; p<0.001), both complete (7.3% vs 22.3%, p<0.001) and partial examinations (60.2% vs 74.9%), and were less involved in counselling (5.7% vs 16.9%; p<0.001). Patients presenting skin cancer issues were referred to a specialist more often than patients consulting for other health problems (39.0% vs 12.1%; p<0.001). GPs performed a biopsy in 6.7% of all skin cancer-related encounters.CONCLUSIONS:This study demonstrates discrepancies between the high prevalence of skin cancer and the low rate of medical encounters addressing these issues in general practice. Our findings should be followed by qualitative interviews to better understand the observed practices in this field

Inclusion of populations at risk of advanced melanoma in an opportunistic targeted screening project involving general practitioners

Objective: The study objective was to measure the rates of inclusion of populations at risk of advanced melanoma in a pilot targeted screening project involving general practitioners. Design: This cross-sectional database study compared the inclusion rates of patients who signed inclusion in a targeted screening project with those of patients who did not, during a period in which both groups of patients consulted investigators. Setting: Data were extracted from the national healthcare insurance records in western France from 11 April to 30 October 2011. Patients: Patients, older than 18, considered for the data extraction had consulted one of the 78 participating GPs during the study period, and were affiliated with the national healthcare insurance. Main outcome measures: Inclusion in the screening was the main outcome measure. Patients at risk of advanced melanoma were characterized by male gender, age over 50, low income, rural residence, farmer, and presence of chronic disease. Results: A total of 57,279 patients consulted GPs during the inclusion period and 2711 (4.73%) were included in the targeted screening. Populations at risk of advanced melanoma were less included: men (OR = 0.67; 95%CI [0.61–0.73]; p < 0.001), older than 50 (OR = 0.67; 95%CI [0.60–0.74]; p < 0.001), low income (OR = 0.65; 95%CI [0.55–0.77]; p < 0.001), farmer (OR = 0.23; 95%CI [0.17–0.30]; p < 0.001) and presence of a chronic disease (OR = 0.87; 95%CI [0.77–0.98]; p < 0.028). Conclusion: This study demonstrated inequalities in the inclusion of patients in a melanoma screening. Patients at risk of advanced cancer were screened less often. Further studies should focus on GPs ability to identify and screen these patients.KEY POINTS Advanced melanoma is more frequently diagnosed in men, older patients and socioeconomically disadvantaged populations, which leads to survival inequalities. • Despite the involvement of general practitioners, the implementation of targeted melanoma screening did not avoid inclusion inequalities. • Men, older patients, patients suffering from chronic diseases, and low-income patients were less likely to benefit from screening. • The display of a conventional or an alarmist poster in the waiting room did not statistically reduce these inclusion inequalities

Treatment of Metastatic Melanoma with Autologous Melan-A/Mart-1-Specific Cytotoxic T Lymphocyte Clones

International audienceImmunotherapy by adoptive T-cell transfer aims at maximizing tumor antigen-specific T-cell responses. We treated 14 patients at the metastatic stage in a phase II study with Melan-A-specific T-cell clones generated from patient blood. During the period required for T-cell clone generation, the patients were treated by dacarbazine. Every patient received a T-cell clone suspension followed by subcutaneous injections of interleukin 2 and interferon alpha. Patients were monitored until disease progression occurred. We succeeded in obtaining autologous Melan-A-specific cytotoxic T lymphocyte clones, which were highly reactive against tumor cells for all the patients. Of the 14 patients treated, six (43%) experienced an objective response (CR þ PR) with long-term complete remission for two patients (1 CR for 5 years and 1 CR for 28 months). Furthermore, we showed that all the clinical responses were significantly associated with in vivo expansion of the Melan-A-specific T-cell repertoire. This phenomenon appeared to be significantly associated with clinical responses. Thus, over the course of an adoptive cell transfer, monitoring this melanoma-specific T-cell expansion in patient blood appears crucial for predicting the clinical efficiency of such an immunological approach

Long-term follow-up of patients treated by adoptive transfer of melanoma tumor-inWltrating lymphocytes as adjuvant therapy for stage III melanoma

International audienceThe first analysis of our clinical trial on interest of using tumor-infiltrating lymphocytes (TIL) as adjuvant therapy for stage III (regional lymph nodes) melanoma was published in 2002 [5]. The aim of this paper is to update clinical results of 7 years of follow-up after the last treated patient. In the trial conducted between December 1993 and January 1999, patients without any detectable metastases after lymph node excision were randomly assigned to receive either TIL plus interleukin-2 (IL-2) for 2 months, or IL-2 only. The duration of the relapse-free interval was the primary objective. Eighty-eight patients were enrolled in the study. Currently, the last analysis performed in June 2006, after a median follow-up of 114.8 months, did not show change of non-signiWcant extension of the relapse-free interval or overall survival. However, this second analysis strengthens our first hypothesis about the relationship between number of invaded lymph nodes and TIL treatment eVectiveness. In the group with only one invaded lymph node, the estimated relapse rate was signiWcantly lower (P adjusted = 0.0219) and the overall survival was increased (P adjusted = 0.0125) in the TIL+IL-2 arm compared with the IL-2 only arm. No diVerences between the two arms, either with regard to the duration of disease-free survival (P adjusted = 0.38) or overall survival (P adjusted = 0.43), were noted in the group with more than one invaded lymph node, whatever the number of invaded lymph nodes. Treatment was compatible with normal daily activity. This study, with a very long follow up (median of almost 10 years), postulates for the Wrst time relationship between TIL eYciency in stage III melanoma (AJCC) and number of invaded lymph nodes, indicating that tumor burden might be a crucial factor in the production of an eVective in vitro expansion of T cells speciWc for autologous tumor antigen, a finding which could be of value in future vaccine development for the treatment of melanoma

Tumor infiltrating lymphocytes as adjuvant treatment in stage III melanoma patients with only one invaded lymph node after complete resection: results from a multicentre, randomized clinical phase III trial

International audienceBackground: Adoptive tumor-infiltrating lymphocytes (TIL) therapy and interleukin-2 (IL-2) have been investigated in melanoma.Aim: To confirm previously observed preventive effects of TIL + IL2 in a subgroup of patients with relapsing metastatic stage III melanoma.Methodology: Open-label, randomized two-group, multicenter five-year trial in adult stage III melanoma patients with only one invaded lymph node after complete resection. Patients received TIL + IL2 or abstention. TIL + IL2 was administered within 8 weeks after lymph node resection and 4 weeks after. Disease-free survival was assessed every 2 months up to month 18, every 3 months up to month 36 and every 4 months up to 5 years. A once-a-year follow-up was scheduled beyond the five-year follow-up. Safety was assessed throughout the trial.Results: Overall, 49 patients accounted for the modified intent-to-treat and 47 for the PP. Slightly more male than female patients participated; mean age was 57.7 ± 11.4 years in the TIL + IL2 group and 53.5 ± 13.0 years in the abstention group. After 5 years of follow-up, 11/26 patients in the TIL + IL2 group and 13/23 in the abstention group had relapsed. There was no statistical difference between the groups (HR: 0.63 CI 95% [0.28-1.41], p = 0.258), nine patients in the TIL + IL2 and 11 in the abstention group died with no significant difference between the two groups (HR: 0.65 CI95% [0.27 - 1.59], p = 0.34). Safety was good.Conclusion: We did not confirm results of a previous trial. However, ulceration of the primary melanoma may be considered predictive of the efficacy of TIL in melanoma in adjuvant setting, in a manner similar to interferon α