Ranade Rohit, Basu Sandip
Radiation Medicine Centre, Bhabha Atomic Research Centre, Tata Memorial Hospital Annexe, Parel, Mumbai, India.
Radiation Medicine Centre, Bhabha Atomic Research Centre, Tata Memorial Hospital Annexe, Parel, Mumbai, India
J Nucl Med Technol. 2016 Jun;44(2):65-9. doi: 10.2967/jnmt.115.168146. Epub 2016 Feb 4.
Our objective was to assess the renal toxicity profile of (177)Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) in patients with a metastatic neuroendocrine tumor (NET) and a single functioning kidney.
This was a retrospective analysis of NET patients who had undergone (177)Lu-DOTATATE PRRT at a large tertiary-care center. All patients selected for the study had somatostatin receptor-positive NETs, had received at least 3 cycles of (177)Lu-DOTATATE PRRT, and had a documented single functioning kidney. The analyzed parameters included patient characteristics, metastatic burden, renal characteristics at diagnosis and during therapy, and nephrotoxic factors. For the renal assessment, the following characteristics were studied before each PRRT cycle: glomerular filtration rate (GFR) as estimated by (99m)Tc-diethylenetriamine pentaacetic acid renography, effective renal plasma flow (ERPF) as measured by (99m)Tc-ethylenedicysteine renography, and blood urea and serum creatinine levels. Renal toxicity was evaluated using version 4.0 of the Common Terminology Criteria for Adverse Events (NCI-CTCAE score). The percentage reduction in GFR and ERPF was also assessed. Filtration fraction was calculated to clarify whether there was a relatively greater reduction in one index of renal function than in the other.
At the time of analysis, 6 patients met the inclusion criteria, having received between 3 and 5 cycles of therapy with a cumulative activity of 16.6-36.2 GBq. The duration of follow-up ranged from 12 to 56 mo. The overall toxicity profile (as per the NCI-CTCAE score) showed no acute renal toxicity in any patient. Regarding overall chronic renal toxicity, 3 patients had none, 1 patient had grade II, and 2 patients had grade I. All patients with overall chronic renal toxicity showed compromised renal function at the outset (baseline). The 2 patients with grade I chronic renal toxicity after PRRT had grade II at baseline and gradual improvement over the subsequent cycles. One patient with grade II at baseline showed transient worsening to grade III after the first cycle followed by gradual improvement and a return to baseline after the second cycle. Only 2 patients showed a reduction in GFR (5.3% in one and 13.84% in the other). Four patients showed a reduction in ERPF (31.4% in the patient with the greatest reduction), and all had a rise in filtration fraction signifying that tubular parameters were more affected than glomerular parameters.
With proper renal protection and dose fractionation, it is feasible to use (177)Lu-DOTATATE PRRT in patients with NET and a single functioning kidney. Further studies are required to assess the long-term renal consequences of changes in ERPF and filtration fraction in these patients.
我们的目的是评估（177）镥 - 奥曲肽肽受体放射性核素治疗（PRRT）对转移性神经内分泌肿瘤（NET）且仅有一个功能肾的患者的肾毒性情况。
这是一项对在一家大型三级医疗中心接受（177）镥 - 奥曲肽PRRT治疗的NET患者的回顾性分析。所有入选研究的患者均为生长抑素受体阳性的NET患者，接受了至少3个周期的（177）镥 - 奥曲肽PRRT治疗，且有记录显示仅有一个功能肾。分析的参数包括患者特征、转移负担、诊断时及治疗期间的肾脏特征以及肾毒性因素。对于肾脏评估，在每个PRRT周期前研究以下特征：通过（99m）锝 - 二乙三胺五乙酸肾图估计的肾小球滤过率（GFR）、通过（99m）锝 - 乙二巯基半胱氨酸肾图测量的有效肾血浆流量（ERPF）以及血尿素和血清肌酐水平。使用不良事件通用术语标准第4.0版（NCI - CTCAE评分）评估肾毒性。还评估了GFR和ERPF的降低百分比。计算滤过分数以明确肾功能的一个指标是否比另一个指标有相对更大的降低。
在分析时，6例患者符合纳入标准，接受了3至5个周期的治疗，累积活度为16.6 - 36.2 GBq。随访时间为12至56个月。总体毒性情况（根据NCI - CTCAE评分）显示，所有患者均无急性肾毒性。关于总体慢性肾毒性，3例患者无慢性肾毒性，1例患者为II级，2例患者为I级。所有有总体慢性肾毒性的患者在开始时（基线）肾功能均受损。PRRT后有I级慢性肾毒性的2例患者在基线时为II级，在随后的周期中逐渐改善。1例基线时为II级的患者在第一个周期后短暂恶化至III级，随后逐渐改善并在第二个周期后恢复至基线。仅2例患者的GFR降低（1例降低5.3%，另1例降低13.84%）。4例患者的ERPF降低（降低最多的患者降低了31.4%），且所有患者的滤过分数升高，表明肾小管参数比肾小球参数受影响更大。
通过适当的肾脏保护和剂量分割，对NET且仅有一个功能肾的患者使用（177）镥 - 奥曲肽PRRT是可行的。需要进一步研究来评估这些患者中ERPF和滤过分数变化的长期肾脏后果。
