Cryotherapy With in Situ Immunotherapy in Melanoma Metastasis

Cryotherapy With in Situ Immunotherapy in Melanoma Metastasis

Publication date: May 14, 2019

Melanoma is the deadliest form of skin cancer and its incidence has doubled every 20 years in France, where this cancer is responsible of more than 1600 deaths each year. Patients with early diagnosis have good prognosis and can be generally cured by surgery only. Advanced melanoma however has a very bad prognosis. Loco-regional lymph nodes are usually the first distant localization in metastatic melanoma. Lymph node dissection is then the recommended treatment, although it’s impact on survival has never been proven. In the same way, the benefit risk profile of interferon as adjuvant treatment after lymph node dissection is still much debated. Recently, new treatments either with immunotherapy (ipilimumab, nivolumab) or by the targeted therapy dabrafenib/trametinib in patients with BRAF mutation have shown an impact on survival in the adjuvant setting after lymph node dissection. But, it has not yet been established if this strategy has a benefit gain compared to starting those treatments only in the metastatic setting after watchful follow-up. Moreover, if these novel therapies (targeted therapies: TT, immunotherapies : IT) demonstrated for the first time a real benefit in terms of survival or of responses rates in melanoma, physicians and patients had to address new problems, such as the management of unusual adverse events. Partial and dissociated responses can also be seen with those new treatments. Some patients will have complete response in some lesions, stabilization in others and progression in a few. It is to be expected that one of the real key points of this therapy is to be found here, as this situation is commonly seen, and it would probably be a poor choice to stop a treatment that is globally effective for progression of only 1 or 2 lesions, in a patient otherwise stabilized. That is the context in which interventional radiology (IR) should be considered as an extremely efficient option. IR is a real medical revolution in the last 2 decades. It provides not only the opportunity to determine the characteristics of residual lesion (fibrosis, necrosis, metastasis, or sarcoidosis,?) by biopsy, but allows also their targeted destruction through different technics (cryotherapy, radiofrequency, laser,?). The investigators are fortunate to have in their institution one of the best IR department of the world (headed by Prof. Afshin GANGI), with a technical platform unique in Europe that allows IR through ultrasound, scan, petscan and MRI. To the best of their knowledge, Immunotherapy associated with IR has not been performed so far. This association could in theory: 1. Combine immunotherapy with tumoral necrosis, which inherently increases the effects of immunotherapy by massive tumoral leakage of danger signals and tumoral antigens; 2. Allow direct injection in targeted zones, where the beneficial effect is desired, and thus increase the expected immune response; 3. Reduce side effects related to immunotherapy, by reducing quantities injected; which seems particularly important in the (neo)-adjuvant setting. That’s why the investigators are willing to conduct this pilot project, the objectives of which are: 1. Providing a proof of the feasibility of this association, 2. Obtaining preliminary insights on the effects on non-targeted lesions, 3. Adding a translational research to establish the effect on tumor antigenic expression and the immune response.

Concepts Keywords
Adjuvant Cryotherapy
Afshin Immunotherapy
Antigens Surgery
Bilirubin Immunotherapy tumoral necrosis
Biopsy Rates melanoma
BRAF Tumor
Condom Ipilimumab
Contraception Immunotherapy
Cryotherapy Cancer treatments
Diaphragm RTT
Direct Injection Melanoma
Dissection Cancer
Europe Clinical medicine
Fibrosis Medicine
France Contraception
Haemoglobin Immunotherapies
Immune Response MRI
Immunotherapies Laser
Immunotherapy Ultrasound
Incidence Breast cancer management
Infusion Metastasis
Interferon Adjuvant therapy
Interventional Radiology Targeted therapy
Ipilimumab
Laser
Lesion
Leukocytes
Lymph Node
Lymph Node Dissection
Lymph Nodes
Melanoma
Metastases
Metastasis
Metastatic
MRI
Mutation
Necrosis
Neutrophils
Platelets
Prognosis
Radiofrequency
Real Revolution
Sarcoidosis
Strasbourg
Targeted Therapies
Targeted Therapy
Tumor
Ultrasound Scan

Semantics

Type Source Name
gene UNIPROT ELL
disease MESH men
gene UNIPROT EGR3
gene UNIPROT ITPRIP
gene UNIPROT CYREN
gene UNIPROT WDFY2
gene UNIPROT BEST1
disease DOID sarcoidosis
disease MESH sarcoidosis
disease MESH fibrosis
gene UNIPROT MAP6
gene UNIPROT BRAF
drug DRUGBANK Trametinib
drug DRUGBANK Dabrafenib
drug DRUGBANK Nivolumab
drug DRUGBANK Ipilimumab
gene UNIPROT IMPACT
gene UNIPROT BAD
disease MESH diagnosis
disease DOID cancer
disease MESH cancer
disease DOID skin cancer
disease MESH skin cancer
disease MESH Metastasis
pathway BSID Melanoma
disease DOID Melanoma
disease MESH Melanoma

Original Article

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