Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
Curr Treat Options Oncol. 2020 Aug 29;21(11):85. doi: 10.1007/s11864-020-00787-z.
The incidence of metastatic pheochromocytoma (PHEO) and paraganglioma (PGL) may occur in as many as 35% of patients particularly with PGL and even more frequently in those with specific mutations. Biochemical, morphological, and molecular markers have been investigated for use in the distinction of benign from malignant PHEO/PGL. PHEO/PGL metastasizes via hematogenous or lymphatic routes and shows differences based on mutational status. The most common sites of involvement in patients that have an SDHB mutation are the bone (78%), lungs (45%), lymph nodes (36%), and liver (35%). In patients with sporadic PHEO/PGL, the most common sites of metastasis are the bones (64%), lungs (47%), lymph nodes (36%), and liver (32%). Metastases may be present at presentation or may occur later. Metastases to the liver and lungs are associated with a shorter survival. Overall, the estimated 5-year survival rates are between 34 and 74%. Currently, treatments for metastatic PHEO/PGL are essentially palliative. Surgery is potentially curative; however, tumor dissemination limits the chance for a curative resection. When surgical intervention is not amenable, the therapeutic options include radiolabeled MIBG (Azedra®-iobenguane 131 was recently FDA-approved for patients > 12 years and older with iobenguane scan positive) or systemic chemotherapy with cyclophosphamide, vincristine, and dacarbazine (CVD) with an overall objective response rate (ORR) of less than 40%; however, it is not clear if the administration of CVD impacts overall survival, as nearly all patients develop progressive and ultimately fatal disease. Other treatment modalities under investigation include cytoreductive techniques, novel radiopharmaceuticals, chemotherapy, radiotherapy, immunotherapy, and experimental therapies. Here we are discussing emerging treatment for advanced/metastatic PHEO/PGL.
转移性嗜铬细胞瘤 (PHEO) 和副神经节瘤 (PGL) 的发病率在多达 35%的患者中可能发生，特别是在 PGL 患者中，甚至在具有特定突变的患者中更为常见。已经研究了生化、形态和分子标志物，用于区分良性和恶性 PHEO/PGL。PHEO/PGL 通过血行或淋巴途径转移，并根据突变状态显示出差异。具有 SDHB 突变的患者中最常见的受累部位是骨骼 (78%)、肺部 (45%)、淋巴结 (36%) 和肝脏 (35%)。在散发性 PHEO/PGL 患者中，最常见的转移部位是骨骼 (64%)、肺部 (47%)、淋巴结 (36%) 和肝脏 (32%)。转移可能在出现时存在，也可能在以后出现。肝和肺转移与生存时间较短相关。总体而言，估计的 5 年生存率在 34%至 74%之间。目前，转移性 PHEO/PGL 的治疗基本上是姑息性的。手术有治愈的潜力；然而，肿瘤播散限制了治愈性切除的机会。当手术干预不可行时，治疗选择包括放射性标记的 MIBG（Azedra®-碘苯胍 131 最近获得 FDA 批准，用于 12 岁及以上碘苯胍扫描阳性的患者）或全身性化疗联合环磷酰胺、长春新碱和达卡巴嗪 (CVD)，总客观缓解率 (ORR) 低于 40%；然而，尚不清楚 CVD 的给药是否会影响总体生存，因为几乎所有患者都会出现进行性和最终致命的疾病。正在研究的其他治疗方式包括细胞减灭术、新型放射性药物、化疗、放疗、免疫疗法和实验疗法。在这里，我们正在讨论用于晚期/转移性 PHEO/PGL 的新兴治疗方法。
