Description of supportive care and feasibility of physical exercise program to improve quality of life in advanced melanoma patients.

Physical activity is the first-line treatment of cancer-related fatigue. It has shown benefits on patient's quality of life (QoL) when practiced during and after treatment. New treatments have drastically changed the prognosis of melanoma. Still, few data are available about research program of supportive care in advanced melanoma. The primary outcome was to assess the feasibility of setting up a prospective study evaluating the benefits of Adapted Physical Activity (APA) on the QoL of patients with advanced melanoma. Feasibility was defined with a combination of five criteria including completion of questionnaire, recruitment, participant retention, patient adhesion to supportive care, and absence of adverse event. Between September 2019 and March 2021, 271 melanoma patients were questioned. Around 60% of stage IV melanoma patients were interested in support care. Patient retention at 3 months was sufficient. Only one patient could not be evaluated after 3 months of enrolment because of deterioration of the general state. Adhesion to exercise and sessions was good. Supervised APA program appeared to be safe and well tolerated as no adverse events or discontinuations were reported. Setting up a prospective research program evaluating the benefits of physical activity in advanced melanoma patients seems feasible. With melanoma becoming a chronic disease, supportive care may reduce fatigue, improve QoL and help maintain a healthy lifestyle. Data supporting its benefits on this survivor population are needed.

Outcome of early stage Merkel carcinoma treated by exclusive radiation: a study of 53 patients.

PURPOSE: Early stage Merkel cell carcinoma (MCC) is a rare and aggressive primary skin cancer. The standard of care for MCC is broad excision and adjuvant external beam radiation therapy (EBRT). However, for some patients, anesthesia is contraindicated, while others run the risk of serious aesthetic sequelae. In such cases, exclusive radiotherapy is an interesting alternative to surgery. Though limited data is available, this study evaluates exclusive radiotherapy for MCC, using data from the largest retrospective study to date. METHODS: All patients who were followed in our center between 1989 and 2019 for histologically proven early stage MCC were included in the study. They were treated either by surgery with a 2-cm clear margin followed by adjuvant radiotherapy (RT) or by exclusive RT. Survival rates with adjuvant and exclusive EBRT were analyzed using Cox model and Fine and Gray model depending on the type of survival. p value < 0.05 was considered significant. RESULTS: Eighty-four patients treated for MCC were included. Fifty-three of them (63.1%) were treated by exclusive RT, and 31 (36.9%) had surgical excision followed by adjuvant RT. Local relapse rate was 13.7% (95% CI 8.0-43.7) in the RT monotherapy group (group A) and 25.8% (95% CI 10.3-56.2) in the surgery + RT group (group B) (p = 0.42). No statistical difference was found for nodal relapse (p = 0.81), metastatic relapse (p = 0.10), disease free survival (p = 0.83) or overall survival (p = 0.98). CONCLUSION: Our study suggests that exclusive radiotherapy for early Merkel cell carcinoma leads to a similar oncological outcome as combined treatment, with fewer aesthetic sequelae. The approach is interesting for elderly patients with comorbidities or patients for whom surgery would cause significant functional or aesthetic sequelae.

Vismodegib in neoadjuvant treatment of locally advanced basal cell carcinoma: First results of a multicenter, open-label, phase 2 trial (VISMONEO study): Neoadjuvant Vismodegib in Locally Advanced Basal Cell Carcinoma.

BACKGROUND: Surgery is the primary treatment for basal cell carcinoma (BCC). In locally advanced basal cell carcinoma (laBCC), surgery may cause functional or aesthetic damage. In laBCC, neoadjuvant administration of vismodegib, an inhibitor of the Hedgehog signaling pathway, may reduce tumor size, facilitate resection, and reduce functional and aesthetic consequences of surgery. The VISMONEO study assessed efficacy and safety of vismodegib in neoadjuvant treatment of laBCC. METHODS: VISMONEO (NCT02667574) is an open-label, noncomparative, multicenter, phase 2 study. Patients with ≥1 histologically confirmed facial BCC, inoperable or operable with functional or major aesthetic sequelae risk, were included. Oral vismodegib 150 mg was administered once daily for 4 to 10 months before planned surgery, which was performed once the best response under vismodegib was observed. Primary endpoint was percentage of patients with BCC with tumor downstaging following surgical resection after neoadjuvant vismodegib. Downstaging was defined according to a 6-stage surgical classification related to the aesthetic and functional consequences of surgery. FINDINGS: 55 patients (median age: 73 years) with laBCC were included from November 2014 to June 2015. At inclusion, 4 patients were inoperable, 15 were operable with a major functional risk, and 36 were operable with a minor functional risk or a major aesthetic risk. Mean size of target lesion was 47.3 mm (SD: 27.2 mm). 44 patients presented with downstaging after vismodegib treatment (80%; 95% confidence interval [CI], 67 to 90). Of these 44 patients, 27 had a complete response (25 proved by biopsy). Mean treatment duration was 6.0 months. Overall Response Rate according to RECIST 1.1 criteria was 71% (95% CI, 59 to 88). At 3-years of follow-up, 16/44 patients had known recurrence (36%; 95%CI, 22 to 51). INTERPRETATION: Neoadjuvant vismodegib allows for a downstaging of the surgical procedure for laBCCs in functionally sensitive locations. FUNDING: VISMONEO was funded by F. Hoffmann-La Roche Ltd.

Severe skin toxicity with organ damage under the combination of targeted therapy following immunotherapy in metastatic melanoma.

Targeted therapy combination (TTC: antiRAF+antiMEK) is known to improve metastatic melanoma survival. Few severe skin toxicities (grade ≥3) are described with first-line TTC (17% for vemurafenib+cobimetinib and none for dabrafenib+trametinib) in a phase III trial. Among our 42 patients treated by TTC between January 2014 and March 2017, 4.8% (2/42) of those treated in the first line presented severe skin rash versus 19% (8/42) of patients treated in the second line after previous immunotherapy. In particular, we observed one case of Stevens-Johnson syndrome and four cases of severe drug reaction with eosinophilia and systemic symptoms syndrome under TTC in patients who had received immunotherapy previously. Thus, previous immunotherapy appears to play an important role in the skin rash onset and severity induced by TTC.

Leptomeningeal metastasis in melanoma: a prospective clinical study of nine patients.

BACKGROUND: Melanoma has the highest rate of spread to the leptomeninges and the incidence of melanoma has been steadily rising. This article describes recent experience at the Lille University Hospital, between 2007 and 2011 and discusses the possibilities for treatment of leptomeningeal metastasis. PATIENTS AND METHODS: Nine patients were diagnosed with leptomeningeal metastasis of melanoma. The standard criteria were used for the diagnosis. The treatment consisted of a combination of intrathecal chemotherapy, systemic chemotherapy and best supportive care. RESULTS: The overall median survival from the time of leptomeningeal metastasis diagnosis was eight weeks (range=1-168 weeks). In two cases, the median overall survival was 104 weeks. For these patients, there was a clear benefit in intrathecal chemotherapy combined with systemic treatment. No complication was observed. CONCLUSION: Despite a poor prognosis, treatment of melanoma leptomeningeal metastasis is needed in order to improve the quality of life, neurological progression-free survival and overall survival of patients.

Radiotherapy alone for Merkel cell carcinoma: a comparative and retrospective study of 25 patients.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare skin cancer. Cumulative data from retrospective series support the notion that benefits are obtained by both wide excision and adjuvant radiation therapy. However, surgery may be difficult to perform with tumors located in the head and neck region and/or in elderly patients with comorbidities incompatible with general anesthesia. OBJECTIVE: We assessed the benefit of treating MCC exclusively with radiation when conventional treatment (surgery followed by radiotherapy) is not possible. METHODS: A total of 25 patients with primary MCC were treated at our institution exclusively with radiotherapy. Because there is no consensus about this specific approach, we compared the recurrence rate of the 25 patients receiving radiotherapy alone with that of 25 patients who received conventional treatment at our institution. RESULTS: The median follow-up periods were 3 years (range: 5 months-11 years) for the group receiving only radiotherapy (group 1) and 9 years (range: 12 months-16 years) for the conventional therapy group (group 2). No local relapses were observed, but two locoregional relapses were observed in group 1, and 4 in group 2. No statistical differences were found in overall and disease-free survival between the two groups of patients. LIMITATIONS: The limitation of this study is its retrospective nature. CONCLUSIONS: This study confirms the results of our previous research demonstrating that it is possible to treat inoperable MCC exclusively with radiotherapy to obtain an outcome similar to that which is achievable with conventional treatment.

Oral metronomic cyclophosphamide in elderly with metastatic melanoma.

INTRODUCTION: In Western countries, the number of frail elderly people with metastatic melanoma (MM) keeps increasing. Conventional chemotherapy frequently induces imbalance in frail physiological cases. We propose to treat these patients with oral metronomic cyclophosphamide. PATIENTS AND METHODS: This retrospective study analyses the data of patients with unresectable MM who received 50 to 100 mg of cyclophosphamide a day, 3 weeks out of 4. Main evaluation criterion was safety. Secondary evaluation criteria were objective response rate and overall survival. RESULTS: Thirteen patients were included (median age: 80, 5 AJCC stage III and 8 AJCC stage IV). Clinical and biological safety were good, leading to long home staying and rare treatment discontinuations. Main toxicity observed was lymphopenia; no opportunist infection occurred. The control rate was 46%: one partial response and five stable diseases (median: 10 months). Survival after beginning of treatment ranged from 4 to 37 months (median: 8 months). DISCUSSION: Literature about MM in frail elderly is limited. Still, specific treatment is necessary. Cyclophosphamide in metronomic schema was well tolerated. The response rate was difficult to assess (small population) but several patients presented with long lasting stabilisation. The mechanisms of action of this treatment are original, associating antiangiogenic action and immunomodulation. CONCLUSION: Cyclophosphamide in metronomic schema showed good safety results for this frail population. Oral treatment enabled patients to stay at home longer and limited hospitalisation time. A larger controlled study will be necessary to confirm these encouraging results in elderly with MM, a classical chemoresistant tumor.