Coventry Brendon J, Baume Dominique, Lilly Carrie
Discipline of Surgery, Royal Adelaide Hospital, University of Adelaide, Adelaide, SA, Australia.
Cancer Manag Res. 2015 Apr 29;7:93-103. doi: 10.2147/CMAR.S76163. eCollection 2015.
Patients with advanced metastatic melanoma are often confronted with little prospect of medium- to longer-term survival by any currently available therapeutic means. However, most clinicians are aware of exceptional cases where survival defies the notion of futility. Prolonged survival from immunotherapies, including interleukin-2, vaccines and antibodies to cytotoxic lymphocyte antigen-4, and programmed death-1 receptor inhibitory monoclonal antibody, implies a role for immune system modulation. We aimed to identify cases where exceptional survival from advanced melanoma occurred prior to recent novel therapies to facilitate better understanding of this phenomenon.
Cases of long-term survival of ≥3 years' duration (from diagnosis of metastatic disease) were identified from the database of one clinician; these cases were treated before the availability of newer immunotherapies, and they were documented and examined. A literature search for reported outcome measures from published studies using older and recent therapies for advanced melanoma was conducted to enable the comparison of data.
Eighteen cases were identified that identified survival of ≥3 years' duration from metastatic disease (12 American Joint Committee on Cancer [AJCC] Stage IV cases; six AJCC III cases) diagnosis. These were assessed and reported to detail the clinical course. Standard clinical prognostication methods predicted high risk of early mortality in those patients. No identifiable differences could be detected between these and other patients with similar patterns of disease. At evaluation, 17 patients (94%) had survived ≥5 years, and eleven patients (61%) had survived ≥10 years (range: 3-15 years). The median survival duration with metastatic disease was 11 years; 15 remained alive and three had died. Published studies of melanoma therapies were tabled for comparison.
The fact that 18 cases of exceptional survival in advanced melanoma were identified is remarkable in itself. Even with recent therapies, the factors for improved survival remain enigmatic; however, one apparent common denominator in most cases was the persistent use of repeated therapies to reduce tumor bulk, induce tumor necrosis, and/or cause immunostimulation. These cases are instructive, suggesting manipulation of an established, endogenous, existing immune response. These observations provide practical evidence that the course for any patient with advanced melanoma at the outset should be considered unpredictable, open to immunomanipulation, and thus not uniformly fatal. The findings were compared and interpreted with reported newer immunotherapeutic approaches.
晚期转移性黑色素瘤患者通过目前任何可用的治疗手段，中期至长期生存的前景往往渺茫。然而，大多数临床医生都知晓一些特殊病例，其生存情况打破了治疗无效的观念。包括白细胞介素-2、疫苗以及细胞毒性淋巴细胞抗原-4抗体和程序性死亡-1受体抑制性单克隆抗体在内的免疫疗法带来的长期生存，意味着免疫系统调节发挥了作用。我们旨在识别在近期新型疗法出现之前晚期黑色素瘤患者出现超长生存的病例，以更好地理解这一现象。
从一位临床医生的数据库中识别出疾病持续生存≥3年（从转移性疾病诊断起）的长期生存病例；这些病例在更新的免疫疗法可用之前接受治疗，并进行了记录和检查。对已发表的关于使用旧疗法和近期疗法治疗晚期黑色素瘤的研究报告的结果指标进行文献检索，以便比较数据。
识别出18例从转移性疾病诊断起生存≥3年的病例（12例美国癌症联合委员会[AJCC]IV期病例；6例AJCC III期病例）。对这些病例进行了评估并详细报告了临床病程。标准临床预后方法预测这些患者早期死亡风险很高。在这些患者与其他疾病模式相似的患者之间未发现可识别的差异。评估时，17例患者（94%）存活≥5年，11例患者（6例）存活≥10年（范围：3至15年）。转移性疾病的中位生存时间为11年；15例仍存活，3例已死亡。列出已发表的黑色素瘤治疗研究以供比较。
识别出18例晚期黑色素瘤超长生存病例这一事实本身就很引人注目。即使采用近期疗法，生存改善的因素仍然不明；然而，大多数病例中一个明显的共同特征是持续使用重复疗法以减少肿瘤体积、诱导肿瘤坏死和/或引起免疫刺激。这些病例具有指导意义，提示对已建立的内源性现有免疫反应进行调控。这些观察结果提供了实际证据，表明任何晚期黑色素瘤患者从一开始其病程就应被视为不可预测的、可进行免疫调控的，因此并非一律致命。将这些发现与报告的更新的免疫治疗方法进行了比较和解读。
