Persistent Hematologic Dysfunction after Peptide Receptor Radionuclide Therapy with 177Lu-DOTATATE: Incidence, Course, and Predicting Factors in Patients with Gastroenteropancreatic Neuroendocrine Tumors
Persistent Hematologic Dysfunction after Peptide Receptor Radionuclide Therapy with 177Lu-DOTATATE: Incidence, Course, and Predicting Factors in Patients with Gastroenteropancreatic Neuroendocrine Tumors
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DOI：
10.2967/jnumed.117.189712
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发表时间：
2018-03-01
影响因子：
9.3
通讯作者：
Kwekkeboom, Dik J.
中科院分区：
文献类型：
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作者：
Bergsma, Hendrik;van Lom, Kirsten;Kwekkeboom, Dik J.
肽受体放射性核素治疗（PRRT）可能会引起骨髓（BM）的长期毒性。本研究的目的是分析胃肠胰神经内分泌肿瘤 (GEP NETs) 患者接受 Lu-177-DOTATATE PRRT 后持续性血液功能障碍 (PHD)。方法：对 367 名生长抑素受体阳性肿瘤患者中的 274 名 GEP NET 患者的 PHD 发生率和病程进行了分析。 PHD 被定义为骨髓增生异常综合征 (MDS)、急性髓系白血病 (AML)、骨髓增生性肿瘤 (MPN)、MDS/MPN 或其他原因不明的血细胞减少症（>6 个月）的诊断。使用荷兰癌症登记处的数据，计算了预期的造血系统肿瘤（MDS、AML、MPN 和 MDS/MPN）数量，并根据性别、年龄和随访期进行了调整。评估以下危险因素：性别、年龄超过 70 岁、骨转移、既往化疗、既往外照射放疗、[In-111-DTPA(0)]奥曲肽扫描摄取、肿瘤负荷、治疗期间 3-4 级血液学毒性、估计吸收 BM 剂量、升高的血浆嗜铬粒蛋白 A 水平、基线血细胞计数和肾功能。结果：274 名患者中有 11 名 (4%) 在 Lu-177-DOTATATE 治疗后出现 PHD：8 名患者 (2.9%) 出现造血系统肿瘤（4 名 MDS、1 名 AML、1 名 MPN 和 2 名 MDS/MPN），3 名患者 (1.1%) 出现以血细胞减少和 BM 再生障碍为特征的 BM 衰竭。诊断（或首次怀疑 PHD）的中位潜伏期为 41 个月（范围：15-84 个月）。根据荷兰癌症登记数据，造血系统肿瘤的预期数量为 3.0，相对风险为 2.7（95% 置信区间，0.7-10.0）。对于 GEP NET 患者，无法确定 PHD 的危险因素，甚至无法确定骨转移或估计的 BM 剂量。七名 PHD 患者出现贫血并伴有平均红细胞体积增加。结论：在我们的患者群体中，Lu-177-DOTATATE PRRT 后 PHD 的患病率为 4%。发生 PHD 的中位时间为第一个 PRRT 周期后 41 个月。发生造血系统肿瘤的相对风险为 2.7。未发现 GEP NET 患者发生 PHD 的危险因素。
Peptide receptor radionuclide therapy (PRRT) may induce long-term toxicity to the bone marrow (BM). The aim of this study was to analyze persistent hematologic dysfunction (PHD) after PRRT with Lu-177-DOTATATE in patients with gastroenteropancreatic neuroendocrine tumors (GEP NETs). Methods: The incidence and course of PHD were analyzed in 274 GEP NET patients from a group of 367 patients with somatostatin receptor-positive tumors. PHD was defined as diagnosis of myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), myeloproliferative neoplasm (MPN), MDS/ MPN, or otherwise unexplained cytopenia (for >6 mo). Using data from The Netherlands Cancer Registry, the expected number of hematopoietic neoplasms (MDS, AML, MPN, and MDS/ MPN) was calculated and adjusted for sex, age, and follow-up period. The following risk factors were assessed: sex, age over 70 y, bone metastasis, prior chemotherapy, prior external-beam radiotherapy, uptake on the [In-111-DTPA(0)] octreotide scan, tumor load, grade 3-4 hematologic toxicity during treatment, estimated absorbed BM dose, elevated plasma chromogranin A level, baseline blood counts, and renal function. Results: Eleven (4%) of the 274 patients had PHD after treatment with Lu-177-DOTATATE: 8 patients (2.9%) developed a hematopoietic neoplasm (4 MDS, 1 AML, 1 MPN, and 2 MDS/ MPN) and 3 patients (1.1%) developed BM failure characterized by cytopenia and BM aplasia. The median latency period at diagnosis (or first suspicion of a PHD) was 41 mo (range, 15-84 mo). The expected number of hematopoietic neoplasms based on The Netherlands Cancer Registry data was 3.0, resulting in a relative risk of 2.7 (95% confidence interval, 0.7-10.0). No risk factors for PHD could be identified for the GEP NET patients, not even bone metastasis or estimated BM dose. Seven patients with PHD developed anemia in combination with a rise in mean corpuscular volume. Conclusion: The prevalence of PHD after PRRT with Lu-177-DOTATATE was 4% in our patient population. The median time at which PHD developed was 41 mo after the first PRRT cycle. The relative risk for developing a hematopoietic neoplasm was 2.7. No risk factors were found for the development of PHD in GEP NET patients.