Hellwig Konstantin, Ellmann Stephan, Eckstein Markus, Wiesmueller Marco, Rutzner Sandra, Semrau Sabine, Frey Benjamin, Gaipl Udo S, Gostian Antoniu Oreste, Hartmann Arndt, Iro Heinrich, Fietkau Rainer, Uder Michael, Hecht Markus, Bäuerle Tobias
Institute of Radiology, University Hospital Erlangen, Erlangen, Germany.
Institute of Pathology, University Hospital Erlangen, Erlangen, Germany.
Front Oncol. 2021 Oct 21;11:734872. doi: 10.3389/fonc.2021.734872. eCollection 2021.
To assess the predictive value of multiparametric MRI for treatment response evaluation of induction chemo-immunotherapy in locally advanced head and neck squamous cell carcinoma.
Twenty-two patients with locally advanced, histologically confirmed head and neck squamous cell carcinoma who were enrolled in the prospective multicenter phase II CheckRad-CD8 trial were included in the current analysis. In this unplanned secondary single-center analysis, all patients who received contrast-enhanced MRI at baseline and in week 4 after single-cycle induction therapy with cisplatin/docetaxel combined with the immune checkpoint inhibitors tremelimumab and durvalumab were included. In week 4, endoscopy with representative re-biopsy was performed to assess tumor response. All lesions were segmented in the baseline and restaging multiparametric MRI, including the primary tumor and lymph node metastases. The volume of interest of the respective lesions was volumetrically measured, and time-resolved mean intensities of the golden-angle radial sparse parallel-volume-interpolated gradient-echo perfusion (GRASP-VIBE) sequence were extracted. Additional quantitative parameters including the T1 ratio, short-TI inversion recovery ratio, apparent diffusion coefficient, and dynamic contrast-enhanced (DCE) values were measured. A model based on parallel random forests incorporating the MRI parameters from the baseline MRI was used to predict tumor response to therapy. Receiver operating characteristic (ROC) curves were used to evaluate the prognostic performance.
Fifteen patients (68.2%) showed pathologic complete response in the re-biopsy, while seven patients had a residual tumor (31.8%). In all patients, the MRI-based primary tumor volume was significantly lower after treatment. The baseline DCE parameters of time to peak and wash-out were significantly different between the pathologic complete response group and the residual tumor group (p < 0.05). The developed model, based on parallel random forests and DCE parameters, was able to predict therapy response with a sensitivity of 78.7% (95% CI 71.24-84.93) and a specificity of 78.6% (95% CI 67.13-87.48). The model had an area under the ROC curve of 0.866 (95% CI 0.819-0.914).
DCE parameters indicated treatment response at follow-up, and a random forest machine learning algorithm based on DCE parameters was able to predict treatment response to induction chemo-immunotherapy.
评估多参数磁共振成像(MRI)对局部晚期头颈部鳞状细胞癌诱导化疗免疫治疗反应评估的预测价值。
本分析纳入了22例局部晚期、组织学确诊的头颈部鳞状细胞癌患者,这些患者参与了前瞻性多中心II期CheckRad-CD8试验。在这项非计划的单中心二次分析中,纳入了所有在基线时以及在接受顺铂/多西他赛联合免疫检查点抑制剂曲美木单抗和度伐利尤单抗单周期诱导治疗后第4周接受对比增强MRI检查的患者。在第4周,进行内镜检查并取代表性的再次活检以评估肿瘤反应。在基线和重新分期的多参数MRI中对所有病变进行分割,包括原发肿瘤和淋巴结转移。对各个病变的感兴趣体积进行体积测量,并提取金角径向稀疏平行体积插值梯度回波灌注(GRASP-VIBE)序列的时间分辨平均强度。测量包括T1比率、短TI反转恢复比率、表观扩散系数和动态对比增强(DCE)值等其他定量参数。使用基于并行随机森林并结合基线MRI的MRI参数的模型来预测肿瘤对治疗的反应。采用受试者操作特征(ROC)曲线来评估预后性能。
15例患者(68.2%)在再次活检中显示病理完全缓解,而7例患者有残留肿瘤(31.8%)。在所有患者中,治疗后基于MRI的原发肿瘤体积显著降低。病理完全缓解组和残留肿瘤组之间基线DCE参数的达峰时间和廓清时间存在显著差异(p<0.05)。基于并行随机森林和DCE参数建立的模型能够预测治疗反应,灵敏度为78.7%(95%CI 71.24-84.93),特异性为78.6%(95%CI 67.13-87.48)。该模型的ROC曲线下面积为0.866(95%CI 0.819-0.914)。
DCE参数表明随访时的治疗反应,基于DCE参数的随机森林机器学习算法能够预测诱导化疗免疫治疗的反应。