Department of Radiation Oncology, University of Utah- Huntsman Cancer Institute, Salt Lake City, UT, USA.
Department of Pediatric Hematology and Oncology, University of Utah- Huntsman Cancer Institute, Salt Lake City, UT, USA.
Cancer Med. 2020 Nov;9(21):7954-7963. doi: 10.1002/cam4.3427. Epub 2020 Sep 15.
Li-Fraumeni Syndrome (LFS) is a rare cancer-predisposing condition caused by germline mutations in TP53. Conventional wisdom and prior work has implied an increased risk of secondary malignancy in LFS patients treated with radiation therapy (RT); however, this risk is not well-characterized. Here we describe the risk of subsequent malignancy and cancer-related death in LFS patients after undergoing RT for a first or second primary cancer.
We reviewed a multi-institutional hereditary cancer registry of patients with germline TP53 mutations who were treated from 2004 to 2017. We assessed the rate of subsequent malignancy and death in the patients who received RT (RT group) as part of their cancer treatment compared to those who did not (non-RT group).
Forty patients with LFS were identified and 14 received RT with curative intent as part of their cancer treatment. The median time to follow-up after RT was 4.5 years. Fifty percent (7/14) of patients in the curative-intent group developed a subsequent malignancy (median time 3.5 years) compared to 46% of patients in the non-RT group (median time 5.0 years). Four of seven subsequent malignancies occurred within a prior radiation field and all shared histology with the primary cancer suggesting recurrence rather than new malignancy.
We found that four of14 patients treated with RT developed in-field malignancies. All had the same histology as the primary suggesting local recurrences rather than RT-induced malignancies. We recommend that RT should be considered as part of the treatment algorithm when clinically indicated and after multidisciplinary discussion.
李-佛美尼综合征（Li-Fraumeni Syndrome，LFS）是一种罕见的癌症易感症，由 TP53 种系突变引起。传统观念和先前的研究表明，接受放射治疗（Radiation Therapy，RT）的 LFS 患者发生继发性恶性肿瘤的风险增加；然而，这种风险尚未得到很好的描述。在这里，我们描述了 LFS 患者在接受首次或第二次原发性癌症的 RT 治疗后发生后续恶性肿瘤和癌症相关死亡的风险。
我们回顾了一个多机构遗传性癌症登记处的患者，这些患者具有种系 TP53 突变，并于 2004 年至 2017 年接受治疗。我们评估了在癌症治疗中接受 RT（RT 组）的患者与未接受 RT（非 RT 组）的患者的后续恶性肿瘤和死亡发生率。
确定了 40 例 LFS 患者，其中 14 例患者接受了根治性 RT 作为其癌症治疗的一部分。RT 后中位随访时间为 4.5 年。根治性 RT 组中 50%（7/14）的患者发生了继发性恶性肿瘤（中位时间 3.5 年），而非 RT 组中 46%（中位时间 5.0 年）的患者发生了继发性恶性肿瘤。在根治性 RT 组的 7 例后续恶性肿瘤中，有 4 例发生在既往放疗野内，且所有肿瘤的组织学与原发性癌症相同，提示为局部复发而不是新的恶性肿瘤。
我们发现，在接受 RT 治疗的 14 例患者中，有 4 例发生了放疗野内的恶性肿瘤。所有患者的组织学均与原发性癌症相同，提示为局部复发而非 RT 诱导的恶性肿瘤。我们建议，在临床上需要且经过多学科讨论后，应将 RT 视为治疗方案的一部分。
