Erika Martinelli, Davide Ciardiello, Giulia Martini, Stefania Napolitano, Sara Del Tufo, Luca D'Ambrosio, Marco De Chiara, Vincenzo Famiglietti, Valeria Nacca, Claudia Cardone, Antonio Avallone, Chiara Cremolini, Filippo Pietrantonio, Evaristo Maiello, Vincenza Granata, Teresa Troiani, Salvatore Cappabianca, Fortunato Ciardiello, Valerio Nardone, Alfonso Reginelli
{"title":"评估转移性结直肠癌肝转移患者治疗反应的放射学参数：CAVE-GOIM mCRC 2 期试验结果。","authors":"Erika Martinelli, Davide Ciardiello, Giulia Martini, Stefania Napolitano, Sara Del Tufo, Luca D'Ambrosio, Marco De Chiara, Vincenzo Famiglietti, Valeria Nacca, Claudia Cardone, Antonio Avallone, Chiara Cremolini, Filippo Pietrantonio, Evaristo Maiello, Vincenza Granata, Teresa Troiani, Salvatore Cappabianca, Fortunato Ciardiello, Valerio Nardone, Alfonso Reginelli","doi":"10.1007/s40261-024-01372-0","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>CAVE is a single arm, Phase 2 trial, that demonstrated anti-tumor activity of cetuximab rechallenge plus avelumab in patients with RAS wild type (wt) metastatic colorectal cancer (mCRC).</p><p><strong>Objective: </strong>We conducted a post hoc analysis to identify potential radiomic biomarkers for patients with CRC liver metastasis (LM).</p><p><strong>Patients and methods: </strong>Patients with LM that could be measured by enhanced contrast phase computed tomography (CT) imaging at baseline and at first response evaluation were included. Multiple texture parameters were extracted with the LifeX Software. Delta-texture (D-TA) variations were calculated by comparing data at baseline and after treatment.</p><p><strong>Results: </strong>Overall, 55/77 patients (71%) had LM; 39 met the inclusion criteria for the current analysis. The D-TA parameters that significantly correlated at univariate analysis with median progression-free survival (mPFS) were Entropy<sup>Histogram</sup> (p = 0.021), Homogeneity<sup>GLCM</sup> (p < 0.001) and Dissimilarity <sup>GLCM</sup> (p = 0.002). At multivariate analysis, only Homogeneity<sup>GLCM</sup> resulted significant for PFS (p = 0.001). Patients (19/39, 48.7%) with reduction of Homogeneity<sup>GLCM</sup> experienced better mPFS (4.6 vs 2.9 months; HR 0.45; 95% CI 0.23-0.88; p = 0.021) and median overall survival (mOS) (17.3 vs 6.8 months; HR 0.40, 95% CI 0.21-0.80; p = 0.010). A trend to better mPFS, was also observed in patients with RAS/BRAF wt circulating tumor DNA and reduction of Homogeneity<sup>GLCM</sup>. Overall survival was significantly better in this subgroup of patients with low Homogeneity<sup>GLCM</sup>: mOS was 17.8 (95% CI 15.5-20.2) versus 6.8 months (95% CI 3.6-10.0) (HR 0.34, 95% CI 0.14-0.81; p = 0.016).</p><p><strong>Conclusion: </strong>Reduction in the D-TA parameter Homogeneity<sup>GLCM</sup> by radiomic analysis correlates with improved outcomes in patients with LM receiving cetuximab rechallenge plus avelumab therapy. Larger prospective studies are needed to validate and confirm these findings.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"541-548"},"PeriodicalIF":2.9000,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Radiomic Parameters for the Evaluation of Response to Treatment in Metastatic Colorectal Cancer Patients with Liver Metastasis: Findings from the CAVE-GOIM mCRC Phase 2 Trial.\",\"authors\":\"Erika Martinelli, Davide Ciardiello, Giulia Martini, Stefania Napolitano, Sara Del Tufo, Luca D'Ambrosio, Marco De Chiara, Vincenzo Famiglietti, Valeria Nacca, Claudia Cardone, Antonio Avallone, Chiara Cremolini, Filippo Pietrantonio, Evaristo Maiello, Vincenza Granata, Teresa Troiani, Salvatore Cappabianca, Fortunato Ciardiello, Valerio Nardone, Alfonso Reginelli\",\"doi\":\"10.1007/s40261-024-01372-0\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>CAVE is a single arm, Phase 2 trial, that demonstrated anti-tumor activity of cetuximab rechallenge plus avelumab in patients with RAS wild type (wt) metastatic colorectal cancer (mCRC).</p><p><strong>Objective: </strong>We conducted a post hoc analysis to identify potential radiomic biomarkers for patients with CRC liver metastasis (LM).</p><p><strong>Patients and methods: </strong>Patients with LM that could be measured by enhanced contrast phase computed tomography (CT) imaging at baseline and at first response evaluation were included. Multiple texture parameters were extracted with the LifeX Software. Delta-texture (D-TA) variations were calculated by comparing data at baseline and after treatment.</p><p><strong>Results: </strong>Overall, 55/77 patients (71%) had LM; 39 met the inclusion criteria for the current analysis. The D-TA parameters that significantly correlated at univariate analysis with median progression-free survival (mPFS) were Entropy<sup>Histogram</sup> (p = 0.021), Homogeneity<sup>GLCM</sup> (p < 0.001) and Dissimilarity <sup>GLCM</sup> (p = 0.002). At multivariate analysis, only Homogeneity<sup>GLCM</sup> resulted significant for PFS (p = 0.001). Patients (19/39, 48.7%) with reduction of Homogeneity<sup>GLCM</sup> experienced better mPFS (4.6 vs 2.9 months; HR 0.45; 95% CI 0.23-0.88; p = 0.021) and median overall survival (mOS) (17.3 vs 6.8 months; HR 0.40, 95% CI 0.21-0.80; p = 0.010). A trend to better mPFS, was also observed in patients with RAS/BRAF wt circulating tumor DNA and reduction of Homogeneity<sup>GLCM</sup>. Overall survival was significantly better in this subgroup of patients with low Homogeneity<sup>GLCM</sup>: mOS was 17.8 (95% CI 15.5-20.2) versus 6.8 months (95% CI 3.6-10.0) (HR 0.34, 95% CI 0.14-0.81; p = 0.016).</p><p><strong>Conclusion: </strong>Reduction in the D-TA parameter Homogeneity<sup>GLCM</sup> by radiomic analysis correlates with improved outcomes in patients with LM receiving cetuximab rechallenge plus avelumab therapy. Larger prospective studies are needed to validate and confirm these findings.</p>\",\"PeriodicalId\":10402,\"journal\":{\"name\":\"Clinical Drug Investigation\",\"volume\":\" \",\"pages\":\"541-548\"},\"PeriodicalIF\":2.9000,\"publicationDate\":\"2024-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical Drug Investigation\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s40261-024-01372-0\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/6/17 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Drug Investigation","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s40261-024-01372-0","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/6/17 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
摘要
研究背景CAVE是一项单臂2期试验，在RAS野生型（wt）转移性结直肠癌（mCRC）患者中证实了西妥昔单抗再挑战加阿维列单抗的抗肿瘤活性：我们进行了一项事后分析，以确定CRC肝转移（LM）患者的潜在放射组学生物标记物：纳入基线和首次反应评估时可通过增强对比相计算机断层扫描（CT）成像测量的肝转移瘤患者。使用 LifeX 软件提取多种纹理参数。通过比较基线和治疗后的数据，计算Δ纹理（D-TA）变化：共有 55/77 例患者（71%）患有 LM，其中 39 例符合本次分析的纳入标准。在单变量分析中，与中位无进展生存期（mPFS）显著相关的 D-TA 参数是熵组图（P = 0.021）、同质性 GLCM（P < 0.001）和异质性 GLCM（P = 0.002）。在多变量分析中，只有同质性 GLCM 对 PFS 有显著影响（p = 0.001）。同质性 GLCM 减少的患者（19/39，48.7%）的 mPFS（4.6 个月 vs 2.9 个月；HR 0.45；95% CI 0.23-0.88；p = 0.021）和中位总生存期（mOS）（17.3 个月 vs 6.8 个月；HR 0.40，95% CI 0.21-0.80；p = 0.010）更好。在RAS/BRAF wt循环肿瘤DNA和HomogeneityGLCM减少的患者中，也观察到中位总生存期改善的趋势。低HomogeneityGLCM亚组患者的总生存期明显更好：mOS为17.8个月（95% CI 15.5-20.2）对6.8个月（95% CI 3.6-10.0）（HR 0.34，95% CI 0.14-0.81；p = 0.016）：结论：通过放射学分析降低D-TA参数HomogeneityGLCM与接受西妥昔单抗再挑战加阿维列单抗治疗的LM患者的预后改善相关。需要更大规模的前瞻性研究来验证和确认这些发现。
Radiomic Parameters for the Evaluation of Response to Treatment in Metastatic Colorectal Cancer Patients with Liver Metastasis: Findings from the CAVE-GOIM mCRC Phase 2 Trial.
Background: CAVE is a single arm, Phase 2 trial, that demonstrated anti-tumor activity of cetuximab rechallenge plus avelumab in patients with RAS wild type (wt) metastatic colorectal cancer (mCRC).
Objective: We conducted a post hoc analysis to identify potential radiomic biomarkers for patients with CRC liver metastasis (LM).
Patients and methods: Patients with LM that could be measured by enhanced contrast phase computed tomography (CT) imaging at baseline and at first response evaluation were included. Multiple texture parameters were extracted with the LifeX Software. Delta-texture (D-TA) variations were calculated by comparing data at baseline and after treatment.
Results: Overall, 55/77 patients (71%) had LM; 39 met the inclusion criteria for the current analysis. The D-TA parameters that significantly correlated at univariate analysis with median progression-free survival (mPFS) were EntropyHistogram (p = 0.021), HomogeneityGLCM (p < 0.001) and Dissimilarity GLCM (p = 0.002). At multivariate analysis, only HomogeneityGLCM resulted significant for PFS (p = 0.001). Patients (19/39, 48.7%) with reduction of HomogeneityGLCM experienced better mPFS (4.6 vs 2.9 months; HR 0.45; 95% CI 0.23-0.88; p = 0.021) and median overall survival (mOS) (17.3 vs 6.8 months; HR 0.40, 95% CI 0.21-0.80; p = 0.010). A trend to better mPFS, was also observed in patients with RAS/BRAF wt circulating tumor DNA and reduction of HomogeneityGLCM. Overall survival was significantly better in this subgroup of patients with low HomogeneityGLCM: mOS was 17.8 (95% CI 15.5-20.2) versus 6.8 months (95% CI 3.6-10.0) (HR 0.34, 95% CI 0.14-0.81; p = 0.016).
Conclusion: Reduction in the D-TA parameter HomogeneityGLCM by radiomic analysis correlates with improved outcomes in patients with LM receiving cetuximab rechallenge plus avelumab therapy. Larger prospective studies are needed to validate and confirm these findings.
期刊介绍：
Clinical Drug Investigation provides rapid publication of original research covering all phases of clinical drug development and therapeutic use of drugs. The Journal includes:
-Clinical trials, outcomes research, clinical pharmacoeconomic studies and pharmacoepidemiology studies with a strong link to optimum prescribing practice for a drug or group of drugs.
-Clinical pharmacodynamic and clinical pharmacokinetic studies with a strong link to clinical practice.
-Pharmacodynamic and pharmacokinetic studies in healthy volunteers in which significant implications for clinical prescribing are discussed.
-Studies focusing on the application of drug delivery technology in healthcare.
-Short communications and case study reports that meet the above criteria will also be considered.
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