Division of Hematology/Oncology, Department of Pediatrics, Arkansas Children's Hospital, University of Arkansas for Medical Sciences, 1 Children's Way, Slot 512-10, Little Rock, AR, 72202-3591, USA.
Division of Hematology and Oncology, Department of Pediatrics, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90027, USA.
Paediatr Drugs. 2022 Sep;24(5):433-445. doi: 10.1007/s40272-022-00526-x. Epub 2022 Jul 29.
Desmoid tumors (DT) are rare fibroblastic, soft-tissue tumors that do not metastasize but can aggressively infiltrate tissues causing significant chronic discomfort and/or functional impairment. In the pediatric population, the incidence of DT is greatest during infancy and adolescence but can occur at any age. Dysregulated β-catenin, most commonly resulting from mutations in either CTNNB1 or germline APC (adenomatous polyposis coli) drives DT. Most cases are sporadic but some are associated with predisposition syndromes such as familial adenomatous polyposis (FAP). Historically, treatment has been surgery. However, the recurrence rate after surgery can be high. Various systemic cytotoxic chemotherapy regimens used in other soft-tissue sarcomas have been applied to DT with differing results. Given the chronic and rarely life-threatening nature of this disease and the potential short- and long-term toxicity of these regimens, especially in children, alternative non-cytotoxic interventions have been investigated. Molecularly targeted agents such as tyrosine kinase and gamma secretase inhibitors have shown activity against DT. Innovative local control therapies are being employed as alternatives to surgery and radiation. Periods of prolonged stability and spontaneous regression in the absence of therapy in some patients has prompted wider adoption of an upfront active surveillance approach in the appropriate setting. This review will briefly summarize the epidemiology, pathophysiology, and clinical presentation of DT in children, then focus on historical, current, and future pharmacotherapeutic management and finally, propose areas for future study.
韧带样纤维瘤（DT）是一种罕见的纤维母细胞性软组织肿瘤，不会转移，但会侵袭性地浸润组织，导致严重的慢性不适和/或功能障碍。在儿科人群中，DT 的发病率在婴儿和青少年期最高，但也可发生于任何年龄。β-连环蛋白的失调，最常见的原因是 CTNNB1 或种系 APC（结肠腺瘤性息肉病）突变，驱动 DT 的发生。大多数病例为散发性，但有些与易感性综合征有关，如家族性腺瘤性息肉病（FAP）。历史上，治疗方法是手术。然而，手术后的复发率可能很高。其他软组织肉瘤中使用的各种全身细胞毒性化疗方案已应用于 DT，但结果不同。鉴于这种疾病的慢性和罕见的致命性质，以及这些方案的短期和长期毒性，特别是在儿童中，已经研究了替代的非细胞毒性干预措施。针对 DT，酪氨酸激酶和γ分泌酶抑制剂等分子靶向药物已显示出活性。创新性的局部控制疗法正被用作手术和放疗的替代方法。一些患者在没有治疗的情况下出现长时间的稳定和自发消退，这促使在适当的情况下更广泛地采用主动监测方法。这篇综述将简要总结儿童 DT 的流行病学、病理生理学和临床表现，然后重点介绍历史、当前和未来的药物治疗管理，最后提出未来研究的领域。
