Division of Hematology-Oncology, Massachusetts General Hospital (MGH) Cancer Center, Boston, MA, USA.
J Nucl Med. 2012 Nov;53(11):1670-5. doi: 10.2967/jnumed.112.105007. Epub 2012 Sep 14.
One of the central unanswered questions in prostate cancer research is the significance of tyrosine kinase inhibitor (TKI)-induced improvements in (99m)Tc-methylene diphosphonate ((99m)Tc-MDP) bone scans. Multitargeted tyrosine kinase inhibition has recently shown promise in the management of castration-resistant prostate cancer. In some cases, TKI inhibition has produced unprecedented improvements in bone metastases as detected by (99m)Tc-MDP bone scans. The significance of these improvements is not known. In order to gain insight about the effects of TKIs on bone scans in prostate cancer, we systematically evaluated images from a phase II study of sunitinib, a multitargeted TKI.
We analyzed images and data from a previously reported open-label phase II study that enrolled 34 men with advanced castration-resistant prostate cancer. Participants received sunitinib in 6-wk cycles (50 mg daily; 4 wk on, 2 wk off). We examined baseline and 12-wk bone scan images. Partial response was defined as an improvement of at least 50% in previous metastatic lesions subjectively or a change from prior diffuse skeletal metastases (superscan) to recognizable individual metastatic lesions. Our primary objective was to define the incidence of at least partial bone scan response. We also examined concomitant changes in CT and prostate-specific antigen (PSA) evidence of disease.
Analysis at 12 wk revealed 1 partial response by the response evaluation criteria in solid tumors (RECIST) and 2 confirmed PSA responses. There were 25 subjects who underwent bone scans at both time points (baseline and week 12) and who had bone metastases detectable at baseline. Within that group of 25, we found 5 bone scan partial responses and 1 complete response. None of those 6 subjects exhibited a PSA response (≥50% decline from baseline) or RECIST response.
We found a relatively high rate of (99m)Tc-MDP bone scan response to sunitinib among men with metastatic prostate cancer. Further, we found that none of the subjects exhibiting bone scan responses experienced concordant improvements in PSA or CT evidence of disease by accepted criteria. This discordance argues that osteoblastic assessment provides an incomplete assessment of treatment-induced changes. Rational development of multitargeted TKIs for prostate cancer requires improved understanding of treatment-induced bone scan changes. Optimal imaging strategies may include evaluation of perfusion or direct tumor activity.
研究酪氨酸激酶抑制剂（TKI）引起的（99m）Tc-亚甲基二膦酸盐（（99m）Tc-MDP）骨扫描改善的意义是前列腺癌研究中的一个核心未解决问题。多靶点酪氨酸激酶抑制在去势抵抗性前列腺癌的治疗中显示出良好的前景。在某些情况下，TKI 抑制产生了前所未有的骨转移改善，如（99m）Tc-MDP 骨扫描所示。这些改善的意义尚不清楚。为了深入了解 TKI 对前列腺癌骨扫描的影响，我们系统地评估了舒尼替尼的 II 期研究的图像，舒尼替尼是一种多靶点 TKI。
我们分析了先前报道的开放标签 II 期研究的图像和数据，该研究纳入了 34 名患有晚期去势抵抗性前列腺癌的男性。参与者接受舒尼替尼 6 周周期治疗（每日 50mg；4 周用药，2 周停药）。我们检查了基线和 12 周的骨扫描图像。部分缓解定义为以前转移性病变的主观改善至少 50%，或从前弥漫性骨骼转移（超级扫描）转变为可识别的单个转移性病变。我们的主要目标是确定至少部分骨扫描反应的发生率。我们还检查了同时发生的 CT 和前列腺特异性抗原（PSA）疾病证据的变化。
根据实体瘤反应评估标准（RECIST），分析在 12 周时发现 1 例部分缓解和 2 例确认的 PSA 缓解。有 25 名受试者在基线和第 12 周都进行了骨扫描，且基线时可检测到骨转移。在这 25 名受试者中，我们发现 5 例骨扫描部分缓解和 1 例完全缓解。这些受试者中没有 1 例出现 PSA 缓解（与基线相比下降≥50%）或 RECIST 缓解。
我们发现转移性前列腺癌男性中舒尼替尼对（99m）Tc-MDP 骨扫描的反应率相对较高。此外，我们发现，没有一个表现出骨扫描反应的受试者通过公认的标准在 PSA 或 CT 疾病证据方面表现出一致的改善。这种不一致表明，成骨评估提供了对治疗诱导变化的不完整评估。为了开发前列腺癌的多靶点 TKI，需要更好地了解治疗诱导的骨扫描变化。最佳的成像策略可能包括评估灌注或直接肿瘤活性。
