PDF(Pubmed)
Abstract：
BACKGROUND: Cancers of the Vater ampulla (ampullary cancers, ACs) account for less than 1% of all gastrointestinal tumors. ACs are usually diagnosed at advanced stage, with poor prognosis and limited therapeutic options. BRCA2 mutations are identified in up to 14% of ACs and, differently from other tumor types, therapeutic implications remain to be defined. Here, we report a clinical case of a metastatic AC patient in which the identification of a BRCA2 germline mutation drove a personalized multimodal approach with curative-intent.
METHODS: A 42-year-old woman diagnosed with stage IV BRCA2 germline mutant AC underwent platinum-based first line treatment achieving major tumor response but also life-threatening toxicity. Based on this, as well as on molecular findings and expected low impact of available systemic treatment options, the patient underwent radical complete surgical resection of both primary tumor and metastatic lesions. Following an isolated retroperitoneal nodal recurrence, given the expected enhanced sensitivity to radiotherapy in BRCA2 mutant cancers, the patient underwent imaging-guided radiotherapy leading to long-lasting complete tumor remission. After more than 2 years, the disease remains radiologically and biochemically undetectable. The patient accessed a dedicated screening program for BRCA2 germline mutation carriers and underwent prophylactic bilateral oophorectomy.
CONCLUSIONS: Even considering the intrinsic limitations of a single clinical report, we suggest that the finding of BRCA germline mutations in ACs should be taken into consideration, together with other clinical variables, given their potential association with remarkable response to cytotoxic chemotherapy that might be burdened with enhanced toxicity. Accordingly, BRCA1/2 mutations might offer the opportunity of personalizing treatment beyond PARP inhibitors up to the choice of a multimodal approach with curative-intent.
METHODS: A 42-year-old woman diagnosed with stage IV BRCA2 germline mutant AC underwent platinum-based first line treatment achieving major tumor response but also life-threatening toxicity. Based on this, as well as on molecular findings and expected low impact of available systemic treatment options, the patient underwent radical complete surgical resection of both primary tumor and metastatic lesions. Following an isolated retroperitoneal nodal recurrence, given the expected enhanced sensitivity to radiotherapy in BRCA2 mutant cancers, the patient underwent imaging-guided radiotherapy leading to long-lasting complete tumor remission. After more than 2 years, the disease remains radiologically and biochemically undetectable. The patient accessed a dedicated screening program for BRCA2 germline mutation carriers and underwent prophylactic bilateral oophorectomy.
CONCLUSIONS: Even considering the intrinsic limitations of a single clinical report, we suggest that the finding of BRCA germline mutations in ACs should be taken into consideration, together with other clinical variables, given their potential association with remarkable response to cytotoxic chemotherapy that might be burdened with enhanced toxicity. Accordingly, BRCA1/2 mutations might offer the opportunity of personalizing treatment beyond PARP inhibitors up to the choice of a multimodal approach with curative-intent.
摘要：
背景：Vater壶腹癌（壶腹癌，AC）占所有胃肠道肿瘤的不到1％。ACs通常在晚期诊断，预后差，治疗选择有限。BRCA2突变在高达14%的ACs中被鉴定，不同于其他类型的肿瘤，治疗意义仍有待定义。这里,我们报告了一例转移性AC患者的临床病例,其中BRCA2种系突变的鉴定驱动了具有治愈意向的个性化多模式方法.
方法：一名42岁女性被诊断为IV期BRCA2种系突变型AC，接受以铂为基础的一线治疗，获得了主要的肿瘤反应，但也有危及生命的毒性。基于此,以及分子研究结果和可用的系统治疗方案的预期低影响，患者接受了原发肿瘤和转移病灶的根治性完整手术切除.在孤立的腹膜后淋巴结复发后，考虑到BRCA2突变型癌症对放疗的敏感性预期增强，患者接受影像引导放疗,导致肿瘤长期完全缓解.两年多之后,该疾病在放射学和生物化学上仍然无法检测到。患者接受了针对BRCA2种系突变携带者的专门筛查程序，并接受了预防性双侧卵巢切除术。
结论：即使考虑到单一临床报告的内在局限性，我们建议应考虑到ACs中BRCA种系突变的发现，连同其他临床变量，考虑到它们可能与细胞毒性化疗的显着反应相关，而细胞毒性化疗可能会增加毒性。因此，BRCA1/2突变可能提供超越PARP抑制剂的个性化治疗的机会，直至选择具有治愈意图的多模式方法。
方法：一名42岁女性被诊断为IV期BRCA2种系突变型AC，接受以铂为基础的一线治疗，获得了主要的肿瘤反应，但也有危及生命的毒性。基于此,以及分子研究结果和可用的系统治疗方案的预期低影响，患者接受了原发肿瘤和转移病灶的根治性完整手术切除.在孤立的腹膜后淋巴结复发后，考虑到BRCA2突变型癌症对放疗的敏感性预期增强，患者接受影像引导放疗,导致肿瘤长期完全缓解.两年多之后,该疾病在放射学和生物化学上仍然无法检测到。患者接受了针对BRCA2种系突变携带者的专门筛查程序，并接受了预防性双侧卵巢切除术。
结论：即使考虑到单一临床报告的内在局限性，我们建议应考虑到ACs中BRCA种系突变的发现，连同其他临床变量，考虑到它们可能与细胞毒性化疗的显着反应相关，而细胞毒性化疗可能会增加毒性。因此，BRCA1/2突变可能提供超越PARP抑制剂的个性化治疗的机会，直至选择具有治愈意图的多模式方法。
