Guadagni Stefano, Zoras Odysseas, Fiorentini Giammaria, Masedu Francesco, Lasithiotakis Konstantinos, Sarti Donatella, Farina Antonietta Rosella, Mackay Andrew Reay, Clementi Marco
Department of Applied Clinical Sciences and Biotechnology, University of L'Aquila, L'Aquila, Italy.
Department of Surgical Oncology, University of Crete, Heraklion, Greece.
J Surg Res. 2021 Dec;268:737-747. doi: 10.1016/j.jss.2021.05.054. Epub 2021 Jul 10.
Treatment strategies for advanced cutaneous melanoma (CM) patients, resistant or not treatable with novel target and immunotherapeutic drugs, remain a significant challenge, particularly for patients with unresectable stage IIIC/D disease localized to inferior limbs and pelvis, for whom specific outcomes are rarely considered.
This is a prospective study of multidisciplinary treatments, including locoregional melphalan chemotherapy, in 62 BRAF wild-type CM patients with locoregional metastases in the inferior limbs and pelvis, including inguinal regions. Patients were either in progression following or ineligible for, or not treatable with novel immunotherapy. For exclusively inferior limb-localised disease, patients received locoregional melphalan chemotherapy performed by hyperthermic isolated limb perfusion (n = 19) or isolated limb infusion (n = 19), and for synchronous lesions localised to inferior limbs and pelvis, received hypoxic pelvic and limb perfusion (n = 24). Additional multidisciplinary therapy included local, locoregional and systemic treatments and the primary endpoint was tumour response.
The objective response rate following first cycle of locoregional chemotherapy was 37.1% at 3 mo and median progression-free survival was 4-mo, with 12.9% procedure-related complications, 30.6% low-grade haematological toxicity and 11.3% severe limb toxic tissue reactions. Multivariate logistic regression showed that the odds of response were significantly higher for patients ≤ 75 y of age and for patients with locoregional metastases exclusively located in the inferior limbs.
In this subgroup of CM patients with BRAF wild-type status, locoregional metastases localized to inferior limbs and pelvis, in progression following or ineligible for immunotherapy, melphalan locoregional chemotherapy demonstrated a safe and effective profile.
ClinicalTrials.gov Identifier NCT01920516; date of trial registration: August 6, 2013.
对于晚期皮肤黑色素瘤（CM）患者，新型靶向和免疫治疗药物耐药或无法治疗的情况下，治疗策略仍然是一项重大挑战，特别是对于下肢和骨盆出现不可切除的IIIC/D期疾病的患者，其特定结局很少被考虑。
这是一项对62例BRAF野生型CM患者进行多学科治疗的前瞻性研究，这些患者下肢和骨盆包括腹股沟区域出现局部区域转移。患者处于新型免疫治疗进展期、不符合条件或无法接受治疗。对于仅局限于下肢的疾病，患者接受通过热灌注隔离肢体灌注（n = 19）或隔离肢体输注（n = 19）进行的局部区域美法仑化疗，对于同时累及下肢和骨盆的病变，接受低氧盆腔和肢体灌注（n = 24）。额外的多学科治疗包括局部、局部区域和全身治疗，主要终点是肿瘤反应。
局部区域化疗第一周期后的客观缓解率在3个月时为37.1%，无进展生存期的中位数为4个月，有12.9%的手术相关并发症、30.6%的轻度血液学毒性和11.3%的严重肢体毒性组织反应。多变量逻辑回归显示，年龄≤75岁的患者以及局部区域转移仅位于下肢的患者的缓解几率显著更高。
在这一BRAF野生型状态、下肢和骨盆出现局部区域转移、处于免疫治疗进展期或不符合免疫治疗条件的CM患者亚组中，美法仑局部区域化疗显示出安全有效的特征。
ClinicalTrials.gov标识符NCT01920516；试验注册日期：2013年8月6日。
