Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina, USA.
Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, California, USA.
Cancer. 2022 Aug 15;128(16):3027-3040. doi: 10.1002/cncr.34332. Epub 2022 Jun 7.
Desmoid tumors (DTs) are rare soft tissue mesenchymal neoplasms that may be associated with impairments, disfigurement, morbidity, and (rarely) mortality. DT disease course can be unpredictable. Most DTs are sporadic, harboring somatic mutations in the gene that encodes for β-catenin, whereas DTs occurring in patients with familial adenomatous polyposis have germline mutations in the APC gene, which encodes for a protein regulator of β-catenin. Pathology review by an expert soft tissue pathologist is critical in making a diagnosis. Magnetic resonance imaging is preferred for most anatomic locations. Surgery, once the standard of care for initial treatment of DT, is associated with a significant risk of recurrence as well as avoidable morbidity because spontaneous regressions are known to occur without treatment. Consequently, active surveillance in conjunction with pain management is now recommended for most patients. Systemic medical treatment of DT has evolved beyond the use of hormone therapy, which is no longer routinely recommended. Current options for medical management include tyrosine kinase inhibitors as well as more conventional cytotoxic chemotherapy (e.g., anthracycline-based or methotrexate-based regimens). A newer class of agents, γ-secretase inhibitors, appears promising, including in patients who fail other therapies, but confirmation in Phase 3 trials is needed. In summary, DTs present challenges to physicians in diagnosis and prognosis, as well as in determining treatment initiation, type, duration, and sequence. Accordingly, evaluation by a multidisciplinary team with expertise in DT and patient-tailored management are essential. As management strategies continue to evolve, further studies will help clarify these issues and optimize outcomes for patients.
硬纤维瘤（DTs）是一种罕见的软组织间叶性肿瘤，可能导致功能障碍、畸形、发病率（罕见情况下导致死亡率）升高。DT 的病程可能不可预测。大多数 DTs 是散发性的，存在编码β-连环蛋白的基因突变，而发生于家族性腺瘤性息肉病患者的 DTs 则存在 APC 基因突变，该基因编码β-连环蛋白的蛋白调节因子。由软组织病理专家进行病理审查对于做出诊断至关重要。磁共振成像（MRI）是大多数解剖部位的首选检查方法。手术曾是 DT 初始治疗的标准治疗方法，但与高复发风险和可避免的发病率相关，因为已知 DT 会自发消退而无需治疗。因此，目前建议大多数患者进行积极监测并结合疼痛管理。DT 的系统治疗已超出激素治疗的范围，目前不再常规推荐。目前用于医学治疗的选择包括酪氨酸激酶抑制剂以及更传统的细胞毒性化疗（例如，基于蒽环类药物或甲氨蝶呤的方案）。一类新型药物γ-分泌酶抑制剂似乎很有前景，包括在其他治疗失败的患者中，但仍需要 III 期临床试验的证实。总之，DT 给医生在诊断和预后方面以及在确定治疗的起始、类型、持续时间和顺序方面带来了挑战。因此，需要由在 DTs 方面具有专业知识的多学科团队进行评估并制定个体化的管理方案。随着管理策略的不断发展，进一步的研究将有助于阐明这些问题并优化患者的结局。
