Dept. of Dermatology, University Hospital Essen, University of Duisburg-Essen, Hufelandstr. 55, 45122, Essen, Germany; German Cancer Consortium (DKTK), Heidelberg, Germany.
Dept. of Dermatology, University Hospital Essen, University of Duisburg-Essen, Hufelandstr. 55, 45122, Essen, Germany; German Cancer Consortium (DKTK), Heidelberg, Germany.
Eur J Cancer. 2021 Jul;152:139-154. doi: 10.1016/j.ejca.2021.04.032. Epub 2021 Jun 5.
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.
皮肤黑色素瘤以发生转移（ITM）而臭名昭著。由于未知的生物学原因，一些患者的 ITM 仍然是主要的肿瘤表现，而没有向远处转移。
对 16 个皮肤癌中心的 191 例最初不可切除的 III 期 ITM 和卫星转移患者进行回顾性评估，以评估其肿瘤特征、生存和治疗反应。根据疾病动力学（无远处进展、缓慢（>6 个月）和快速（<6 个月）远处进展）将三组分别进行分析。
从不可切除的 ITM 开始，中位随访时间为 30.5 个月（范围 0.8-154.0）。56.5%的病例进展为 IV 期。无远处转移的患者更多为女性，年龄较大（>70 岁），初次诊断时表现为 III 期，伴有淋巴结或 ITM 的占 45.7%。与非腿部原发性黑色素瘤相比，腿部黑色素瘤的总生存期（OS）从初始诊断时间开始明显更好（风险比 [HR] 0.61，95%置信区间 [CI] 0.40-0.91；p=0.017），但从不可切除的 III 期诊断时间开始（HR 0.67，95%CI 0.45-1.02；p=0.06）没有更好。40%的患者接受了卫星和 ITM 的局部治疗。所有局部一线治疗的总缓解率（ORR）为 38%；疾病控制率（DCR）为 49%。共有 72.3%的患者接受了不可切除的 IIIB-D 期的全身治疗。靶向治疗（n=19）的 ORR 最高，为 63.2%，DCR 为 84.2%，而 PD-1 治疗患者（n=70）的 ORR 为 31.4%，DCR 为 54.3%。接受 PD-1 和局部注射替莫唑胺拉帕替尼（n=12）的患者的 ORR 为 41.7%，DCR 为 75%。
不可切除的 ITM 且无远处进展的患者更多为女性，年龄较大，且原发性肿瘤位于腿部。该队列中 PD-1 抑制剂的反应低于预期，但需要进一步研究来阐明 ITM 发展的生物学机制及其与免疫系统的相互作用。
