From the *Radiation Medicine Centre, Bhabha Atomic Research Centre, and Departments of †Biostatistics, and ‡Medical Oncology, Tata Memorial Hospital, Parel, Mumbai.
Clin Nucl Med. 2017 Jun;42(6):428-435. doi: 10.1097/RLU.0000000000001639.
The aims of this study were to perform multiparametric response assessment of metastatic/advanced pulmonary neuroendocrine tumors (NETs) to Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) (clinical, biochemical, molecular/structural imaging, and survival assessment) and to study the relationship between response, mortality, and overall survival with dual-tracer molecular imaging parameters.
Twenty-two patients (6 women, 16 men; median age, 44 years; range, 16-72 years) of histopathologically proven pulmonary NETs with metastatic/advanced disease were included and analyzed retrospectively. Lu-DOTATATE PRRT was administered using standardized protocol (150 mCi [5.55 GBq] per cycle, cycles repeated at 12-16 weeks' intervals [range, 1-5 cycles; average, 4 cycles]) with amino acid-based renal protection. Assessment with Tc-HYNIC-TOC (in the initial years of PRRT development, n = 11)/Ga-DOTATATE PET/CT (presently, n = 11) and F-FDG PET/CT (n = 22), symptomatic and biochemical parameters (serum CgA and urinary 5-HIAA levels), and anatomical response using contrast-enhanced CT (after 3 cycles) was part of routine pretreatment and response evaluation. The patients were designated as responders and nonresponders based on predefined response assessment criteria. Kaplan-Meier product-limit method was calculated for overall survival (OS) curve after the first PRRT, and corresponding 95% confidence intervals (95% CIs) were estimated for annual survival at 1, 2, 3, and 4 years. The various prognostic variables were also investigated for association with mortality, OS, and treatment response following PRRT.
Of 22 patients, 6 had undergone surgical resection of primary tumors. All patients were symptomatic before start of PRRT. Two patients did not qualify for PRRT, and 1 received single cycle with follow-up less than 3 months, hence excluded from the present analysis. Thus, a total 19 patients were analyzed in our study. Symptomatic response following PRRT was observed in 15 (79%) of 19 patients. Based on predefined 3-scale response evaluation criteria, of 19 patients, 12 patients (63%) were finally characterized as responders, and 7 patients (37%) were overall nonresponder to PRRT. All 7 nonresponders had moderate to intense FDG-avid primary lung lesion (SUVmax >5 in 4 of 7 patients), and 5 had FDG-avid metastatic liver disease (SUVmax >5). Peptide receptor radionuclide therapy was well tolerated in all with no major hematologic and renal toxicity (except for 2 patients showing mild grade I renal and hematologic toxicity in the initial cycles and recovery in subsequent follow-up). Seven (37%) of 19 died at the time of analysis. The observed annual OS rates were as follows: 1 year: 94.7% (95% CI, 68.1%-99.2%), 2 years: 66% (95% CI, 35.5%-84.5%), 3 years: 57.7% (95% CI, 28-78.9%), and 4 years: 38.5% (95% CI, 8.1%-69.5%); median OS was 40 months with 39% (95% CI, 13.1%-64.8%). In conclusion, Lu-DOTATATE PRRT was found safe and well tolerated in receptor-positive pulmonary NET. FDG positivity appeared to forecast aggressive tumor behavior.
本研究旨在对转移性/晚期肺神经内分泌肿瘤（NET）患者进行 Lu-DOTATATE 肽受体放射性核素治疗（PRRT）的多参数反应评估（临床、生化、分子/结构影像学和生存评估），并研究反应、死亡率和总生存与双示踪剂分子成像参数之间的关系。
回顾性纳入并分析了 22 名经组织病理学证实的肺 NET 伴转移性/晚期疾病的患者（6 名女性，16 名男性；中位年龄为 44 岁；年龄范围为 16-72 岁）。Lu-DOTATATE PRRT 使用标准化方案（每个周期 150 mCi[5.55GBq]，周期间隔 12-16 周[范围 1-5 个周期；平均 4 个周期]，并用氨基酸基肾保护剂）进行。采用 Tc-HYNIC-TOC（PRRT 开发初期，n=11）/Ga-DOTATATE PET/CT（目前，n=11）和 F-FDG PET/CT（n=22）评估，评估症状和生化参数（血清 CgA 和尿 5-HIAA 水平），并使用对比增强 CT（在第 3 个周期后）进行解剖学反应评估，这些都是常规预处理和反应评估的一部分。根据预先确定的反应评估标准，将患者指定为反应者和非反应者。在第一次 PRRT 后计算总生存（OS）曲线的 Kaplan-Meier 乘积限法，并估计每年 1、2、3 和 4 年的生存概率。还研究了各种预后变量与 PRRT 后的死亡率、OS 和治疗反应的关系。
22 名患者中，6 名患者接受了原发性肿瘤的手术切除。所有患者在开始 PRRT 前均有症状。2 名患者不符合 PRRT 条件，1 名患者仅接受了 1 个周期的治疗，随访时间少于 3 个月，因此被排除在本分析之外。因此，在我们的研究中分析了总共 19 名患者。19 名患者中有 15 名（79%）在 PRRT 后出现症状缓解。根据预先确定的 3 级反应评估标准，19 名患者中，12 名（63%）最终被确定为反应者，7 名（37%）总体对 PRRT 无反应。7 名无反应者的肺部原发性病变均具有中至高强度 FDG 摄取（7 名患者中有 4 名患者的 SUVmax>5），5 名患者的肝转移病灶也具有 FDG 摄取（SUVmax>5）。所有患者均耐受良好，无明显血液学和肾毒性（除了 2 名患者在最初的几个周期中出现轻微的 1 级肾和血液学毒性，在随后的随访中恢复）。19 名患者中有 7 人（37%）在分析时死亡。观察到的年 OS 率如下：1 年：94.7%（95%CI，68.1%-99.2%），2 年：66%（95%CI，35.5%-84.5%），3 年：57.7%（95%CI，28-78.9%），4 年：38.5%（95%CI，8.1%-69.5%）；中位 OS 为 40 个月，39%（95%CI，13.1%-64.8%）。总之，Lu-DOTATATE PRRT 在受体阳性肺 NET 患者中是安全且耐受良好的。FDG 阳性似乎预示着肿瘤具有侵袭性。
