Clinical Study Adoptive TIL Transfer in the Adjuvant Setting for Melanoma: Long-Term Patient Survival

Two first analyses of our clinical trial on TIL as adjuvant therapy for melanoma were published in 2002 and 2007. We present here an update of the clinical results after a 17-year median followup. In this trial, disease-free patients were randomly assigned to receive either TIL/IL-2 or IL-2. The relapse-free survival (RFS) was the primary objective. Eighty-eight patients were enrolled. A new analysis performed in May 2013 did not show significant changes in RFS or OS duration. However, our first finding on the association between the number of invaded lymph nodes and TIL effectiveness was strengthened. The Cox model adjusted on this interaction showed for the first time a significant treatment effect when considering the overall population, both on the RFS and OS. Patients treated with TIL had a longer RFS ( = 0.023) or OS ( = 0.020). This study being with a very long followup (17 years), confirmed the association between TIL effectiveness and the number of invaded lymph nodes, indicating that a low tumor burden could be a crucial factor enhancing the curative effect of TIL in possible microscopic residual disease. Moreover, we confirmed that a prolonged survival was associated with the presence of specific TIL and a decrease in Foxp3 expression

Coping Strategies at the Time of Diagnosis and Quality of Life 2 Years Later: A Study in Primary Cutaneous Melanoma Patients

International audienceBACKGROUND: While coping has been found to have time-lagged effects on psychological adjustment in cancer patients, studies addressing this issue are missing in melanoma patients. OBJECTIVE: The aim of this study was to provide more insight into the links between coping strategies at the time of diagnosis and quality of life (QOL) 2 years later in patients with primary cutaneous melanoma. METHODS: Patients who received diagnosis of melanoma (n = 78) were assessed regarding coping strategies within 1 month of diagnosis (T1); their anxiety, depression, control, QOL, and life satisfaction were evaluated 24 months later (T2). Relevant medical and sociodemographic data were collected at T1 and T2. Hierarchical regression analyses were performed. RESULTS: Consistent with the literature, we found that higher positive reframing was associated with greater life satisfaction and that increased behavioral disengagement was related to decreased cognitive functioning. Surprisingly, our results highlighted that higher active coping predicted lower emotional functioning and that greater religious coping was associated with more reports of nausea symptoms. We also noticed that depression was strongly related to QOL beyond the end of interferon α therapy. CONCLUSION: The findings of the present study suggest that specific coping strategies may have time-lagged effects on QOL when the treatment is completed. IMPLICATIONS FOR PRACTICE: These findings provide new insights into the coping strategies that could be promoted in coping skills interventions in dermatology units and reveal the significant role of preventive care concerning the posttreatment period

Chemotherapy efficacy after first-line immunotherapy in 18 advanced melanoma patients

International audienceIn BRAF wild type advanced melanoma, immune checkpoint blockers such as anti-PD1 (anti-programmed cell death 1) are usually continued beyond progression for a hypothetical rare further response. Chemotherapy as a second-line option is considered ineffective by many practitioners based on historical data. Continuing anti-PD1 beyond progression has a high health-economic impact and is not recommended by the FDA. This study aimed to describe the efficacy and survival of advanced melanoma patients who received second-line (or more) chemotherapy after immunotherapy failure. This was a retrospective single center study conducted in a French University Hospital during an 11-month period. All advanced melanoma patients treated with chemotherapy after immunotherapy failure were included. Eighteen patients were analyzed. Therapeutic response to chemotherapy was evaluable in 16 patients: partial response was achieved in 3/16 (19%), stable disease in 1/16 (6%) and progressive disease in 12/16 (75%). Median overall survival from chemotherapy start was 12 months. Median progression-free survival was 5.4 months. The 6-month overall survival rate was 81% and the 6-month progression-free survival rate was 40%. Although the disease control rate with chemotherapy was low (25%), survival data in our study are far superior to those previously published. This could be linked to a high proportion of patients treated with anti-PD1 just prior to chemotherapy, which may suggest a potential synergy between immunotherapy and chemotherapy

A Comparison of Posttraumatic Growth Changes in Breast Cancer and Melanoma

International audienceOBJECTIVE: This article presents a comparison of the changes of Posttraumatic Growth (PTG) in breast cancer and melanoma patients over a 2-year follow-up period and investigates the associations between coping strategies, anxiety, depression, emotional functioning, and PTG over time. METHOD: Seventy-eight early stage melanoma patients from Nantes University Hospital and 215 breast cancer patients from Nantes Cancerology Institute completed self-administered questionnaires collecting sociodemographic and medical information and assessing health-related quality of life, coping strategies, anxiety and depression within 1 month of diagnosis and 6, 12, and 24 months after the diagnosis. PTG was assessed at 6, 12, and 24 months postdiagnosis. RESULTS: We found that PTG increased over time for both cancers, but that breast cancer and melanoma patients did not experience the same magnitude of changes in PTG depending on time and on depression. While we did not find any relationship between anxiety, emotional functioning, negative coping and PTG; positive and emotional coping were positively associated with PTG changes for both cancers. Substance use was negatively related to PTG at 2 years postdiagnosis for melanoma and breast cancer. CONCLUSIONS: Our findings reveal that PTG increases over time for both cancers. In addition, it provides relevant information about the coping strategies that are associated with the experience of positive changes. (PsycINFO Database Record (c) 2019 APA, all rights reserved)

Sexual well-being in patients with vulvar disease: Results from a preliminary prospective matched case-control study

International audienceIntroduction Only a few studies have focused on the description of sexual well-being in patients with vulvar disease (VD). The aim of this study was to test the hypothesis that VD patients have an overall impaired sexual well-being that varies depending on the type of VD. Study design An observational, prospective, single center and 1:1 matched case-control study was conducted in Nantes University Hospital (France). All new patients attending the specific consultation for VD between June 2011 and January 2013 were included. A control group was randomly selected from women who had a scheduled consultation for gynecologic follow-up. A validated French version of the Female Sexual Function Index (FSFI) was used. This self-administered questionnaire was distributed to all case and control women. VD was classified into 4 groups: inflammatory, (pre)malignant, infectious, and other VD. Descriptive statistics and multivariate mixed analyses were performed. Results Seventy-two VD patients and seventy-two control women completed the FSFI questionnaire. The median FSFI score was 21.1 in the VD patients versus 28.1 in the control patients. In the multivariate analysis, the FSFI score was significantly decreased by an average of 4.5 points (p = 0.003) in the VD patients. On the FSFI subscores, VD had significant impacts on items related to "arousal", "pain", "lubrication", "satisfaction", and "desire". When comparing the VD groups, the total FSFI score seemed lower for (pre)malignant VD. Conclusion This preliminary study showed that VD patients had an impaired sexual well-being

Pyoderma Gangrenosum Under Dabrafenib and Trametinib for Metastatic Melanoma

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Circulating Tumor DNA Early Kinetics Predict Response of Metastatic Melanoma to Anti-PD1 Immunotherapy: Validation Study

International audienceThe ability of early (first weeks of treatment) ctDNA kinetics to identify primary resistance to anti-PD1 immunotherapies was evaluated with a validation cohort of 49 patients treated with anti-PD1 for metastatic BRAF or NRAS-mutated melanoma, alone and pooled with the 53 patients from a previously described derivation cohort. BRAF or NRAS mutations were quantified on plasma DNA by digital PCR at baseline and after two or four weeks of treatment. ctDNA kinetics were interpreted according to pre-established biological response criteria. A biological progression (bP, i.e., a significant increase in ctDNA levels) at week two or week four was associated with a lack of benefit from anti-PD1 (4-month PFS = 0%; 1-year OS = 13%; n = 12/102). Patients without initial bP had significantly better PFS and OS (4-month PFS = 78%; 1-year OS = 73%; n = 26/102), as did patients whose ctDNA kinetics were not evaluable, due to low/undetectable baseline ctDNA (4-month PFS = 80%; 1-year OS = 81%; n = 64/102). ctDNA detection at first-line anti-PD1 initiation was an independent prognostic factor for OS and PFS in multivariate analysis. Overall, early ctDNA quantitative monitoring may allow the detection of primary resistances of metastatic melanoma to anti-PD1 immunotherapies

Adoptive TIL Transfer in the Adjuvant Setting for Melanoma: Long-Term Patient Survival

Two first analyses of our clinical trial on TIL as adjuvant therapy for melanoma were published in 2002 and 2007. We present here an update of the clinical results after a 17-year median followup. In this trial, disease-free patients were randomly assigned to receive either TIL/IL-2 or IL-2. The relapse-free survival (RFS) was the primary objective. Eighty-eight patients were enrolled. A new analysis performed in May 2013 did not show significant changes in RFS or OS duration. However, our first finding on the association between the number of invaded lymph nodes and TIL effectiveness was strengthened. The Cox model adjusted on this interaction showed for the first time a significant treatment effect when considering the overall population, both on the RFS and OS. Patients treated with TIL had a longer RFS (P=0.023) or OS (P=0.020). This study being with a very long followup (17 years), confirmed the association between TIL effectiveness and the number of invaded lymph nodes, indicating that a low tumor burden could be a crucial factor enhancing the curative effect of TIL in possible microscopic residual disease. Moreover, we confirmed that a prolonged survival was associated with the presence of specific TIL and a decrease in Foxp3 expression

Blood Predictive Biomarkers for Nivolumab in Advanced Melanoma

Nivolumab response rate is 40% in metastatic melanoma. Few studies have evaluated pre-treatment biomarkers predictive of response. The aim of this study was to identify potential peripheral blood biomarkers associated with survival in patients with advanced melanoma treated with nivolumab. All advanced melanoma cases treated with anti-programmed cell death protein 1 (anti-PD1) over a 3-year period in the Dermato-Oncology Department, Nantes, France were identified. For each case, 9 potential blood biomarkers were identified. Bivariate and multivariate analyses, adjusted for the American Joint Committee on Cancer (AJCC) classification stage, Eastern Cooperative Oncology Group (ECOG) performance status, lactate dehydrogenase (LDH) level and failure to respond to first-line therapy, were used to test the association between biomarkers and overall survival (primary outcome) or progression-free survival (secondary outcome). Increased monocyte count, leukocyte/lymphocyte ratio and neutrophil/lymphocyte ratio were significantly associated with decreased overall survival after bivariate and multivariate analyses. Increased monocyte count was also significantly associated with decreased progression-free survival. These blood variables are easily measured and could help to predict patient response before the introduction of anti-PD1 therapy

Tissue biomarkers in melanoma patients treated with TIL.

While treating stage III melanoma patients with autologous therapeutic TIL in an adjuvant setting, we previously reported a significant benefit of treatment on both progression-free survival and overall survival in patients with only one invaded lymph node (early stage III) compared to patients with more than one invaded lymph nodes (advanced stage III). In this context, in order to understand the difference of activity of TIL therapy according to the progression of the illness at stage III, the first objective of the present study was to determine potential differences in the characteristics of TIL populations obtained from an early stage III and a more advanced stage III when tumor burden is more important. The second objective was to determine possible differences in tissue expression level of several molecules involved in interactions between tumor cells and T cells between early and advanced stage III considering that the tumor microenvironment of invaded lymph nodes could become more tolerant with the progression of the disease. A total of 47 samples of melanoma invaded LN from stage IIIb (AJCC 2007) melanoma patients treated with TIL plus IL-2 were included in this study. We confirmed that both PFS and OS were significantly associated to the presence of tumor-reactive T-cells among TIL injected to the patients and that these tumor reactive T cells were more frequently observed at the early stage III. Moreover, while analyzing the expression of 17 markers on 34/47 tumor specimens using immunohistochemistry, we identified that 3 tissue markers involved in interactions between melanoma cells and T cells have a significant difference of expression between early and advanced stage III: MHC class I, adhesion molecule ICAM-1 and the co-stimulation molecule LFA-3 had a significantly weaker expression in melanoma tissue specimens from advanced stage III. In addition, the expression of the alpha chain of the IL-2 receptor (CD25) and the nuclear transcription factor Foxp3 was significantly increased in the melanoma tissue specimens from advanced stage III. Our results suggest differences in the immunological status of the tumor microenvironment between early and advanced stage III, which could explain the difference in clinical response to TIL infusion in an adjuvant setting between early and advanced stage III