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首页> 外文期刊>Journal of Surgical Oncology >Neoadjuvant therapy for high-risk bulky regional melanoma.
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Neoadjuvant therapy for high-risk bulky regional melanoma.

机译：高危大块黑色素瘤的新辅助治疗。

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Clinically detectable regional lymph node melanoma metastasis (AJCC stage IIIB-C) carries a risk of relapse and death that approaches 70% at 5 years. Surgical management is the cornerstone of therapy, with postoperative adjuvant therapy utilizing high-dose interferon alfa-2b (HDI). Neoadjuvant chemotherapy or immunotherapy in addition to surgery has been demonstrated to improve outcome in the management of patients with a variety of solid tumors. In patients with melanoma, the characteristics of the host immune response differ between patients with earlier stage and those with more advanced stages of disease (and particularly between those with measurable active disease and those without measurable gross disease) providing rationale for neoadjuvant approaches with immunotherapy. Host immune tolerance is now understood to impede the results of therapy for advanced disease, but appears to be less an issue for patients with microscopic high-risk operable disease, where the host may be more susceptible to immunologic interventions. Phase II studies have shown that neoadjuvant biochemotherapy has limited activity in melanoma patients with local-regional metastases, where chemotherapy may potentially alter the effects of immunotherapeutic agents. Studies of neoadjuvant HDI therapy for high-risk melanoma patients with bulky regional stage IIIB-C lymphadenopathy have shown unexpectedly high clinical and pathologic response rates, without increased morbidity. Through the design of neoadjuvant trials utilizing promising emerging melanoma therapeutics in which it is possible to obtain biopsy samples before and after therapy, a greater understanding of the dynamic interaction between tumors and the immune system is possible. This should lead to the identification of new targets for the treatment of melanoma and aid the development of new immunotherapy that may have greater specificity and less toxicity. This will simplify the evaluation of promising new combinations of agents with HDI to build on the clinical, immunologic, and molecular effect of this therapy for patients with melanoma.
机译：临床上可检测到的区域淋巴结黑色素瘤转移（AJCC IIIB-C期）在5年时复发和死亡的风险接近70％。手术管理是治疗的基石，术后辅助治疗采用大剂量干扰素α-2b（HDI）。除手术外，新辅助化疗或免疫疗法已被证明可以改善各种实体瘤患者的治疗效果。在患有黑素瘤的患者中，宿主免疫应答的特征在疾病的早期阶段和疾病晚期阶段的患者之间有所不同（尤其是在具有可测量的活动性疾病的患者与没有可测量的总体疾病的患者之间），为免疫治疗的新辅助方法提供了依据。现在已经理解，宿主的免疫耐受性会阻碍晚期疾病的治疗结果，但是对于微观高风险可操作疾病的患者而言似乎并不是一个大问题，在宿主中，宿主可能更容易受到免疫干预。 II期研究表明，新辅助生物化学疗法对患有局部转移的黑色素瘤患者的活性有限，其中化学疗法可能会改变免疫治疗剂的作用。对具有大的区域性IIIB-C期淋巴结肿大的高危黑色素瘤患者的新辅助HDI治疗的研究表明，其出乎意料的高临床和病理学反应率，且未增加发病率。通过利用有前途的新兴黑色素瘤疗法设计新辅助试验，可以在治疗前后获得活检样本，从而可以更好地了解肿瘤与免疫系统之间的动态相互作用。这应导致确定用于治疗黑素瘤的新靶标，并有助于开发可能具有更高特异性和更低毒性的新免疫疗法。这将简化对有前途的新型药物与HDI的新组合​​的评估，以建立这种疗法对黑色素瘤患者的临床，免疫和分子作用。

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