Gandhi D, Chepeha D B, Miller T, Carlos R C, Bradford C R, Karamchandani R, Worden F, Eisbruch A, Teknos T N, Wolf G T, Mukherji S K
Department of Radiology, University of Michigan Health System, Ann Arbor, MI 48109, USA.
AJNR Am J Neuroradiol. 2006 Jan;27(1):101-6.
Current organ-preservation regimens for upper aerodigestive tract squamous cell carcinoma (SCCA) require endoscopic procedures under general anesthesia to evaluate the tumor response. The purpose of our study was to determine whether CT perfusion (CTP) parameters correlate with response to induction chemotherapy as assessed by endoscopy under general anesthesia.
Nine patients with advanced (stage 3 or 4) SCCA of the oropharynx were enrolled in a nested phase 2 prospective trial in which induction chemotherapy was used to assess the tumor response. Patients underwent direct laryngoscopy and CTP before and 3 weeks after one cycle of induction chemotherapy. The outcome variables were the surgeon's estimate of tumor volume during endoscopy with biopsy under anesthesia and CTP parameters (capillary permeability (CP), blood volume (BV), blood flow (BF), and mean transit time (MTT)). Wilcoxon rank sum analysis was used to correlate the baseline values of BF and BV with response to induction chemotherapy. Comparison of agreement between the reduction in tumor volume and change in CTP parameters was performed by using kappa estimates.
Seven of 9 patients demonstrated > or =50% tumor volume reduction, representing positive response to induction chemotherapy. In the responder group, the following changes in mean pre- and postinduction chemotherapy values were noted: mean BF, 114.2 mL/100 g /min (preinduction) to 45.1 mL/100 g/min (postinduction); mean BV, 5.11 mL/100 g to 3.1 mL/100 g; mean CP, 25.6 mL/100 g /min (preinduction) to 18.3 mL/100 g / min (postinduction); mean MTT, 4.9 seconds (preinduction) to 8.0 seconds (postinduction). In the nonresponder group, the following changes were noted: mean BF, 56.9 mL/100 g/min to 75.9 mL/100 g/min; mean, BV 2.7 mL/100 g to 4.71 mL/100 g; mean CP, 24.1 mL/100 g/min to 23.7 mL/100 g/min; mean MTT, 4.3 seconds to 5.34 seconds. Higher baseline (pretherapy) values of BV showed significant correlation with endoscopic tumor response (P < .05). Reduction in the BV (by >/=20%) on follow-up studies also showed substantial agreement with clinical response as assessed with endoscopy (kappa = 0.73). The agreement between decreased BF, decreased CP, and increased MTT and clinical response was fair (kappa = 0.37).
These preliminary results show that deconvolution-based CTP technique offers potential for noninvasive monitoring of response to induction chemotherapy in patients with oropharyngeal cancers. Percentage reduction of BV is significantly correlated to endoscopic response to induction chemotherapy, though we acknowledge that the data correspond to short-term outcomes and long-term durability of response cannot be established. Nevertheless, validation of the use of deconvolution CTP parameters as predictors of tumor response may permit replacement of an invasive diagnostic procedure conducted under anesthesia currently used to assess response with noninvasive perfusion CT imaging.
目前上消化道鳞状细胞癌(SCCA)的器官保存方案需要在全身麻醉下进行内镜检查以评估肿瘤反应。我们研究的目的是确定CT灌注(CTP)参数是否与全身麻醉下经内镜评估的诱导化疗反应相关。
9例晚期(3或4期)口咽SCCA患者参加了一项嵌套的2期前瞻性试验,该试验采用诱导化疗来评估肿瘤反应。患者在诱导化疗一个周期前和3周后接受直接喉镜检查和CTP检查。结局变量为麻醉下活检时内镜检查期间外科医生对肿瘤体积的估计以及CTP参数(毛细血管通透性(CP)、血容量(BV)、血流(BF)和平均通过时间(MTT))。采用Wilcoxon秩和分析将BF和BV的基线值与诱导化疗反应相关联。通过kappa估计对肿瘤体积减少与CTP参数变化之间的一致性进行比较。
9例患者中有7例肿瘤体积减少≥50%,代表对诱导化疗有阳性反应。在有反应组中,诱导化疗前后的平均数值有以下变化:平均BF,从诱导前的114.2 mL/100 g/min降至诱导后的45.1 mL/100 g/min;平均BV,从5.11 mL/100 g降至3.1 mL/100 g;平均CP,从诱导前的25.6 mL/100 g/min降至诱导后的18.3 mL/100 g/min;平均MTT,从诱导前的4.9秒增至诱导后的8.0秒。在无反应组中,有以下变化:平均BF,从56.9 mL/100 g/min增至75.9 mL/100 g/min;平均BV,从2.7 mL/100 g增至4.71 mL/100 g;平均CP,从24.1 mL/100 g/min降至23.7 mL/100 g/min;平均MTT,从4.3秒增至5.34秒。较高的基线(治疗前)BV值与内镜肿瘤反应显著相关(P<0.05)。随访研究中BV降低(≥20%)也与内镜评估的临床反应有高度一致性(kappa = 0.73)。BF降低、CP降低和MTT增加与临床反应之间的一致性一般(kappa = 0.37)。
这些初步结果表明,基于去卷积的CTP技术为无创监测口咽癌患者诱导化疗反应提供了可能。BV降低百分比与诱导化疗的内镜反应显著相关,尽管我们承认这些数据对应短期结果,且无法确定反应的长期持久性。然而,验证将去卷积CTP参数用作肿瘤反应预测指标可能允许用无创灌注CT成像替代目前用于评估反应的麻醉下侵入性诊断程序。