使用（177）Lu-奥曲肽进行肽受体放射性核素治疗后的亚急性血液毒性：预后因素、发生率及病程
Subacute haematotoxicity after PRRT with (177)Lu-DOTA-octreotate: prognostic factors, incidence and course.
作者信息
Bergsma Hendrik, Konijnenberg Mark W, Kam Boen L R, Teunissen Jaap J M, Kooij Peter P, de Herder Wouter W, Franssen Gaston J H, van Eijck Casper H J, Krenning Eric P, Kwekkeboom Dik J
机构信息
Department of Nuclear Medicine, Erasmus University Medical Center, 's-Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands.
Department of Internal Medicine, Erasmus Medical Center, 's-Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands.
出版信息
Eur J Nucl Med Mol Imaging. 2016 Mar;43(3):453-63. doi: 10.1007/s00259-015-3193-4. Epub 2015 Sep 30.
PURPOSE
In peptide receptor radionuclide therapy (PRRT), the bone marrow (BM) is one of the dose-limiting organs. The accepted dose limit for BM is 2 Gy, adopted from (131)I treatment. We investigated the incidence and duration of haematological toxicity and its risk factors in patients treated with PRRT with (177)Lu-DOTA(0)-Tyr(3)-octreotate ((177)Lu-DOTATATE). Also, absorbed BM dose estimates were evaluated and compared with the accepted 2 Gy dose limit.
METHODS
The incidence and duration of grade 3 or 4 haematological toxicity (according to CTCAE v3.0) and risk factors were analysed. Mean BM dose per unit (gigabecquerels) of administered radioactivity was calculated and the correlations between doses to the BM and haematological risk factors were determined.
RESULTS
Haematological toxicity (grade 3/4) occurred in 34 (11 %) of 320 patients. In 15 of the 34 patients, this lasted more than 6 months or blood transfusions were required. Risk factors significantly associated with haematological toxicity were: poor renal function, white blood cell (WBC) count <4.0 × 10(9)/l, age over 70 years, extensive tumour mass and high tumour uptake on the OctreoScan. Previous chemotherapy was not associated. The mean BM dose per administered activity in 23 evaluable patients was 67 ± 7 mGy/GBq, resulting in a mean BM dose of 2 Gy in patients who received four cycles of 7.4 GBq (177)Lu-DOTATATE. Significant correlations between (cumulative) BM dose and platelet and WBC counts were found in a selected group of patients.
CONCLUSION
The incidence of subacute haematological toxicity after PRRT with (177)Lu-DOTATATE is acceptable (11 %). Patients with impaired renal function, low WBC count, extensive tumour mass, high tumour uptake on the OctreoScan and/or advanced age are more likely to develop grade 3/4 haematological toxicity. The BM dose limit of 2 Gy, adopted from (131)I, seems not to be valid for PRRT with (177)Lu-DOTATATE.
目的
在肽受体放射性核素治疗（PRRT）中，骨髓（BM）是剂量限制器官之一。骨髓的公认剂量限值为2 Gy，这是从碘-131治疗中沿用而来。我们调查了用177Lu-DOTA(0)-Tyr(3)-奥曲肽（177Lu-DOTATATE）进行PRRT治疗的患者血液学毒性的发生率、持续时间及其危险因素。此外，还评估了骨髓吸收剂量估计值，并与公认的2 Gy剂量限值进行比较。
方法
分析3级或4级血液学毒性（根据CTCAE v3.0）的发生率、持续时间及危险因素。计算每单位给予放射性活度的平均骨髓剂量（吉贝可勒尔），并确定骨髓剂量与血液学危险因素之间的相关性。
结果
320例患者中有34例（11%）发生血液学毒性（3/4级）。34例患者中有15例持续时间超过6个月或需要输血。与血液学毒性显著相关的危险因素为：肾功能差、白细胞（WBC）计数<4.0×10⁹/L、年龄超过70岁、肿瘤体积大及奥曲肽扫描时肿瘤摄取高。既往化疗与之无关。23例可评估患者每给予一次活度的平均骨髓剂量为67±7 mGy/GBq，接受4个周期7.4 GBq 177Lu-DOTATATE治疗的患者平均骨髓剂量为2 Gy。在一组选定患者中发现（累积）骨髓剂量与血小板及白细胞计数之间存在显著相关性。
结论
用177Lu-DOTATATE进行PRRT后亚急性血液学毒性的发生率是可接受的（11%）。肾功能受损、白细胞计数低、肿瘤体积大、奥曲肽扫描时肿瘤摄取高和/或年龄较大的患者更有可能发生3/4级血液学毒性。从碘-131沿用而来的2 Gy骨髓剂量限值似乎不适用于177Lu-DOTATATE的PRRT。
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