Biomaterial Database

Clinical characteristics and therapy response in unresectable melanoma patients stage IIIB-IIID with in-transit and satellite metastases. 2021

Anne Zaremba, and Manuel Philip, and Jessica C Hassel, and Valerie Glutsch, and Zeno Fiocco, and Carmen Loquai, and David Rafei-Shamsabadi, and Ralf Gutzmer, and Jochen Utikal, and Sebastian Haferkamp, and Lydia Reinhardt, and Katharina C Kähler, and Carsten Weishaupt, and Alvaro Moreira, and Kai-Martin Thoms, and Tabea Wilhelm, and Claudia Pföhler, and Alexander Roesch, and Selma Ugurel, and Lisa Zimmer, and Nadine Stadtler, and Antje Sucker, and Felix Kiecker, and Lucie Heinzerling, and Friedegund Meier, and Frank Meiss, and Max Schlaak, and Bastian Schilling, and Susanne Horn, and Dirk Schadendorf, and Elisabeth Livingstone

Dept. of Dermatology, University Hospital Essen, University of Duisburg-Essen, Hufelandstr. 55, 45122, Essen, Germany; German Cancer Consortium (DKTK), Heidelberg, Germany. Electronic address: anne.zaremba@uk-essen.de.

Cutaneous melanoma is notorious for the development of in-transit metastases (ITM). For unknown biological reasons, ITM remain the leading tumour manifestation without progression to distant sites in some patients. In total, 191 patients with initially unresectable stage III ITM and satellite metastases from 16 skin cancer centres were retrospectively evaluated for their tumour characteristics, survival and therapy response. Three groups according to disease kinetics (no distant progress, slow (>6 months) and fast (<6 months) distant progression) were analysed separately. Median follow-up time was 30.5 (range 0.8-154.0) months from unresectable ITM. Progression to stage IV was observed in 56.5% of cases. Patients without distant metastasis were more often female, older (>70 years) and presented as stage III with lymph node or ITM at initial diagnosis in 45.7% of cases. Melanoma located on the leg had a significantly better overall survival (OS) from time of initial diagnosis compared to non-leg localised primaries (hazard ratio [HR] = 0.61, 95% confidence interval [CI] 0.40-0.91; p = 0.017), but not from diagnosis of unresectable stage III (HR = 0.67, 95% CI 0.45-1.02; p = 0.06). Forty percent of patients received local therapy for satellite and ITM. Overall response rate (ORR) to all local first-line treatments was 38%; disease control rate (DCR) was 49%. In total, 72.3% of patients received systemic therapy for unresectable stage IIIB-D. ORR for targeted therapy (n = 19) was highest with 63.2% and DCR was 84.2% compared to an ORR of 31.4% and a DCR of 54.3% in PD-1 treated patients (n = 70). Patients receiving PD-1 and intralesional talimogene laherparepvec (n = 12) had an ORR of 41.7% and a DCR of 75%. Patients with unresectable ITM and without distant progression are more often female, older, and have a primary on the leg. Response to PD-1 inhibitors in this cohort was lower than expected, but further investigation is required to elucidate the biology of ITM development and the interplay with the immune system.

UI	MeSH Term	Description	Entries
D007167	Immunotherapy	Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection.	Immunotherapies
D008297	Male		Males
D008545	Melanoma	A malignant neoplasm derived from cells that are capable of forming melanin, which may occur in the skin of any part of the body, in the eye, or, rarely, in the mucous membranes of the genitalia, anus, oral cavity, or other sites. It occurs mostly in adults and may originate de novo or from a pigmented nevus or malignant lentigo. Melanomas frequently metastasize widely, and the regional lymph nodes, liver, lungs, and brain are likely to be involved. The incidence of malignant skin melanomas is rising rapidly in all parts of the world. (Stedman, 25th ed; from Rook et al., Textbook of Dermatology, 4th ed, p2445)	Malignant Melanoma,Malignant Melanomas,Melanoma, Malignant,Melanomas,Melanomas, Malignant
D008875	Middle Aged	An adult aged 45 - 64 years.	Middle Age
D009367	Neoplasm Staging	Methods which attempt to express in replicable terms the extent of the neoplasm in the patient.	Cancer Staging,Staging, Neoplasm,Tumor Staging,TNM Classification,TNM Staging,TNM Staging System,Classification, TNM,Classifications, TNM,Staging System, TNM,Staging Systems, TNM,Staging, Cancer,Staging, TNM,Staging, Tumor,System, TNM Staging,Systems, TNM Staging,TNM Classifications,TNM Staging Systems
D005260	Female		Females
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000082082	Immune Checkpoint Inhibitors	Drugs that block negative regulator IMMUNE CHECKPOINT proteins (e.g., PD-1 RECEPTOR and CTLA-4 ANTIGEN) thereby increasing suppressed immune activation in immunotherapies.	CTLA-4 Inhibitor,CTLA-4 Inhibitors,Cytotoxic T-Lymphocyte-Associated Protein 4 Inhibitor,Cytotoxic T-Lymphocyte-Associated Protein 4 Inhibitors,Immune Checkpoint Blockade,Immune Checkpoint Blockers,Immune Checkpoint Inhibition,Immune Checkpoint Inhibitor,PD-1 Inhibitor,PD-1 Inhibitors,PD-1-PD-L1 Blockade,PD-L1 Inhibitor,PD-L1 Inhibitors,Programmed Cell Death Protein 1 Inhibitor,Programmed Cell Death Protein 1 Inhibitors,Programmed Death-Ligand 1 Inhibitors,Blockade, PD-1-PD-L1,CTLA 4 Inhibitor,CTLA 4 Inhibitors,Checkpoint Blockade, Immune,Checkpoint Blockers, Immune,Checkpoint Inhibition, Immune,Checkpoint Inhibitor, Immune,Checkpoint Inhibitors, Immune,Cytotoxic T Lymphocyte Associated Protein 4 Inhibitor,Cytotoxic T Lymphocyte Associated Protein 4 Inhibitors,Inhibitor, PD-1,PD 1 Inhibitor,PD 1 Inhibitors,PD 1 PD L1 Blockade,PD L1 Inhibitor,PD L1 Inhibitors,Programmed Death Ligand 1 Inhibitors
D000328	Adult	A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available.	Adults
D000368	Aged	A person 65 years of age or older. For a person older than 79 years, AGED, 80 AND OVER is available.	Elderly