Evaluation of 177Lu-PSMA-617 SPECT/CT Quantitation as a Response Biomarker Within a Prospective 177Lu-PSMA-617 and NOX66 Combination Trial (LuPIN)
Evaluation of 177Lu-PSMA-617 SPECT/CT Quantitation as a Response Biomarker Within a Prospective 177Lu-PSMA-617 and NOX66 Combination Trial (LuPIN)
复制标题
DOI：
10.2967/jnumed.122.264398
复制
发表时间：
2023-02-01
影响因子：
9.3
通讯作者：
Emmett, Louise
中科院分区：
文献类型：
--
作者：
Pathmanandavel, Sarennya;Crumbaker, Megan;Emmett, Louise
177Lu-PSMA-617是一种有效的治疗转移性前列腺癌（mCRPC）的新方法。使用预测工具，我们评估反应率和疗效的能力可能会得到提高。本研究探讨了系列177Lu- psma -617 SPECT/CT （177Lu SPECT）成像在监测治疗反应中的预测价值。方法：56名既往接受化疗和新型雄激素信号抑制剂治疗的进展性mCRPC患者被纳入LuPIN试验，接受最多6剂量的177lu - psm -617和一种辐射增敏剂（3-（4-羟基苯基）- 2h -1-苯并吡喃-7-醇[NOX66]）。在研究开始和结束时进行68Ga-PSMA-11和18F-FDG PET/CT检查，并在每次治疗后24 h进行177Lu SPECT检查，从大腿顶点到大腿中部。在治疗第1周期（基线）和第3周期（第12周）进行SPECT定量分析。结果：56名男性中有32人在第1周期和第3周期均有可分析的连续177Lu SPECT成像。在该亚组中，中位前列腺特异性抗原（PSA）无进展生存期（PFS）为6.3个月（95% CI， 5-10个月），中位总生存期为12.3个月（95% CI， 12-24个月）。PSA 50%有效率为63%（20/32）。177Lu SPECT总肿瘤体积（SPECT TTV）减少68%(22/32；中位数，-0.20 m3 [95% CI, -1.4 ~ -0.001])，增加31%（10/32；中位数，0.36 [95% CI, 0.1 ~ 1.4]）。SPECT TTV升高与PSA PFS缩短相关（风险比为4.1 [95% CI, 1.5-11.2]; P = 0.006）。SPECT TTV增加30%或更多也与PSA PFS缩短相关（风险比为3.3 [95% CI, 1.3-8.6]; P =0.02）。肿瘤SUVmax降低91% (29/32)，SUVmean降低84% (27/32)；两者都与PSA、PFS或总生存结果相关。第12周时PSA进展也与PSA PFS缩短相关（风险比为26.5 [95% CI, 5.4-131]）。在第12周SPECT TTV进展的患者中，50%（5/10）没有并发PSA进展（中位PSA PFS， 4.5个月[95% CI， 2.8-5.6个月]），10名男性中有5名在第12周同时出现PSA和SPECT TTV进展（中位PSA PFS， 2.8个月[95% CI， 1.8-3.7个月]）。结论：增加定量177Lu SPECT的SPECT TTV预测PFS较短，可能在未来发挥成像反应生物标志物的作用。
177Lu-PSMA-617 is an effective and novel treatment in metastatic cas-tration-resistant prostate cancer (mCRPC). Our ability to assess response rates and therefore efficacy may be improved using predic-tive tools. This study investigated the predictive value of serial 177Lu-PSMA-617 SPECT/CT (177Lu SPECT) imaging in monitoring treatment response. Methods: Fifty-six men with progressive mCRPC previ-ously treated with chemotherapy and novel androgen signaling inhibi-tor were enrolled into the LuPIN trial and received up to 6 doses of 177Lu-PSMA-617 and a radiation sensitizer (3-(4-hydroxyphenyl)-2H-1-benzopyran-7-ol [NOX66]). 68Ga-PSMA-11 and 18F-FDG PET/CT were performed at study entry and exit, and 177Lu SPECT from vertex to mid thighs was performed 24 h after each treatment. SPECT quanti-tative analysis was undertaken at cycles 1 (baseline) and 3 (week 12) of treatment. Results: Thirty-two of the 56 men had analyzable serial 177Lu SPECT imaging at both cycle 1 and cycle 3. In this subgroup, median prostate-specific antigen (PSA) progression-free survival (PFS) was 6.3 mo (95% CI, 5-10 mo) and median overall survival was 12.3 mo (95% CI, 12-24 mo). The PSA 50% response rate was 63% (20/32). 177Lu SPECT total tumor volume (SPECT TTV) was reduced in 68% (22/32; median, -0.20 m3 [95% CI, -1.4 to -0.001]) and increased in 31% (10/32; median, 0.36 [95% CI, 0.1-1.4]). Any increase in SPECT TTV was associated with shorter PSA PFS (hazard ratio, 4.1 [95% CI, 1.5-11.2]; P = 0.006). An increase of 30% or more in SPECT TTV was also associated with a shorter PSA PFS (hazard ratio, 3.3 [95% CI, 1.3-8.6]; P =0.02). Tumoral SUVmax was reduced in 91% (29/32) and SUVmean in 84% (27/32); neither was associated with PSA PFS or overall survival outcomes. PSA progres-sion by week 12 was also associated with a shorter PSA PFS (hazard ratio, 26.5 [95% CI, 5.4-131]). In the patients with SPECT TTV pro-gression at week 12, 50% (5/10) had no concurrent PSA progression (median PSA PFS, 4.5 mo [95% CI, 2.8-5.6 mo]), and 5 of 10 men had both PSA and SPECT TTV progression at week 12 (median PSA PFS, 2.8 mo [95% CI, 1.8-3.7 mo]). Conclusion: Increasing SPECT TTV on quantitative 177Lu SPECT predicts a short PFS and may play a future role as an imaging response biomarker.