An Imaging Biomarker of Tumor-Infiltrating Lymphocytes to Risk-Stratify Patients With HPV-Associated Oropharyngeal Cancer.
An Imaging Biomarker of Tumor-Infiltrating Lymphocytes to Risk-Stratify Patients With HPV-Associated Oropharyngeal Cancer.
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DOI：
10.1093/jnci/djab215
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发表时间：
2022-04-11
期刊：
影响因子：
--
通讯作者：
Madabhushi A
中科院分区：
文献类型：
--
作者：
Corredor G;Toro P;Koyuncu C;Lu C;Buzzy C;Bera K;Fu P;Mehrad M;Ely KA;Mokhtari M;Yang K;Chute D;Adelstein DJ;Thompson LDR;Bishop JA;Faraji F;Thorstad W;Castro P;Sandulache V;Koyfman SA;Lewis JS;Madabhushi A
与非病毒相关的口咽鳞状细胞癌相比，人乳头瘤病毒（HPV）相关的口咽鳞状细胞癌（OPSCC）具有优异的控制率。多项试验正在积极测试这些患者的治疗强度降级是否可以在减少治疗相关毒性的同时保持肿瘤平衡。我们已经开发了OP-TIL，一种生物标志物，其表征组织学图像中肿瘤浸润淋巴细胞（TIL）与周围细胞之间的空间相互作用。在此，我们试图测试OP-TIL是否可以将I期HPV相关OPSCC患者分为低风险和高风险组，并帮助选择患者进行降级临床试验。在6个机构队列的439例I期HPV相关OPSCC患者的全载玻片苏木精和伊红图像上探索了OP-TIL与患者结局之间的相关性。一个机构队列（n = 94）用于识别最具预后的特征，并训练考克斯回归模型来预测复发和死亡的风险。生存分析用于验证算法作为剩余5个队列（n = 345）中复发或死亡的生物标志物。所有统计检验均为双侧检验。OP-TIL将具有30包年或更少吸烟史的I期HPV相关OPSCC患者分为低风险（2年无病生存率[DFS] = 94.2%; 5年DFS = 88.4%）和高风险（2年DFS = 82.5%; 5年DFS = 74.2%）组（风险比= 2.56，95%置信区间= 1.52至4.32; P < .001），即使在对DFS的多变量分析中调整了年龄、吸烟状况、T和N分类以及治疗方式后，（风险比= 2.27，95%置信区间= 1.32至3.94; P = 0.003）。OP-TIL可以识别I期HPV相关OPSCC患者，这些患者可能是治疗降级的不良候选人。在对先前完成的多机构临床试验进行验证后，OP-TIL有可能成为超越临床分期和HPV状态的生物标志物，可在临床上用于优化降级患者的选择。
Human papillomavirus (HPV)–associated oropharyngeal squamous cell carcinoma (OPSCC) has excellent control rates compared to nonvirally associated OPSCC. Multiple trials are actively testing whether de-escalation of treatment intensity for these patients can maintain oncologic equipoise while reducing treatment-related toxicity. We have developed OP-TIL, a biomarker that characterizes the spatial interplay between tumor-infiltrating lymphocytes (TILs) and surrounding cells in histology images. Herein, we sought to test whether OP-TIL can segregate stage I HPV-associated OPSCC patients into low-risk and high-risk groups and aid in patient selection for de-escalation clinical trials. Association between OP-TIL and patient outcome was explored on whole slide hematoxylin and eosin images from 439 stage I HPV-associated OPSCC patients across 6 institutional cohorts. One institutional cohort (n = 94) was used to identify the most prognostic features and train a Cox regression model to predict risk of recurrence and death. Survival analysis was used to validate the algorithm as a biomarker of recurrence or death in the remaining 5 cohorts (n = 345). All statistical tests were 2-sided. OP-TIL separated stage I HPV-associated OPSCC patients with 30 or less pack-year smoking history into low-risk (2-year disease-free survival [DFS] = 94.2%; 5-year DFS = 88.4%) and high-risk (2-year DFS = 82.5%; 5-year DFS = 74.2%) groups (hazard ratio = 2.56, 95% confidence interval = 1.52 to 4.32; P < .001), even after adjusting for age, smoking status, T and N classification, and treatment modality on multivariate analysis for DFS (hazard ratio = 2.27, 95% confidence interval = 1.32 to 3.94; P = .003). OP-TIL can identify stage I HPV-associated OPSCC patients likely to be poor candidates for treatment de-escalation. Following validation on previously completed multi-institutional clinical trials, OP-TIL has the potential to be a biomarker, beyond clinical stage and HPV status, that can be used clinically to optimize patient selection for de-escalation.
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影响因子：
10.6
作者：
Mahmood F;Borders D;Chen RJ;Mckay GN;Salimian KJ;Baras A;Durr NJ
通讯作者：
Durr NJ
空间结构和肿瘤浸润淋巴细胞的排列，以预测早期非小细胞肺癌中复发的可能性。
DOI：
10.1158/1078-0432.ccr-18-2013
发表时间：
2019-03-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Corredor G;Wang X;Zhou Y;Lu C;Fu P;Syrigos K;Rimm DL;Yang M;Romero E;Schalper KA;Velcheti V;Madabhushi A
通讯作者：
Madabhushi A
影响因子：
82.9
作者：
AbdulJabbar K;Raza SEA;Rosenthal R;Jamal-Hanjani M;Veeriah S;Akarca A;Lund T;Moore DA;Salgado R;Al Bakir M;Zapata L;Hiley CT;Officer L;Sereno M;Smith CR;Loi S;Hackshaw A;Marafioti T;Quezada SA;McGranahan N;Le Quesne J;TRACERx Consortium;Swanton C;Yuan Y
通讯作者：
Yuan Y
影响因子：
6.7
作者：
Hendry S;Salgado R;Gevaert T;Russell PA;John T;Thapa B;Christie M;van de Vijver K;Estrada MV;Gonzalez-Ericsson PI;Sanders M;Solomon B;Solinas C;Van den Eynden GGGM;Allory Y;Preusser M;Hainfellner J;Pruneri G;Vingiani A;Demaria S;Symmans F;Nuciforo P;Comerma L;Thompson EA;Lakhani S;Kim SR;Schnitt S;Colpaert C;Sotiriou C;Scherer SJ;Ignatiadis M;Badve S;Pierce RH;Viale G;Sirtaine N;Penault-Llorca F;Sugie T;Fineberg S;Paik S;Srinivasan A;Richardson A;Wang Y;Chmielik E;Brock J;Johnson DB;Balko J;Wienert S;Bossuyt V;Michiels S;Ternes N;Burchardi N;Luen SJ;Savas P;Klauschen F;Watson PH;Nelson BH;Criscitiello C;O'Toole S;Larsimont D;de Wind R;Curigliano G;André F;Lacroix-Triki M;van de Vijver M;Rojo F;Floris G;Bedri S;Sparano J;Rimm D;Nielsen T;Kos Z;Hewitt S;Singh B;Farshid G;Loibl S;Allison KH;Tung N;Adams S;Willard-Gallo K;Horlings HM;Gandhi L;Moreira A;Hirsch F;Dieci MV;Urbanowicz M;Brcic I;Korski K;Gaire F;Koeppen H;Lo A;Giltnane J;Rebelatto MC;Steele KE;Zha J;Emancipator K;Juco JW;Denkert C;Reis-Filho J;Loi S;Fox SB
通讯作者：
Fox SB
影响因子：
6.4
作者：
Facompre ND;Rajagopalan P;Sahu V;Pearson AT;Montone KT;James CD;Gleber-Netto FO;Weinstein GS;Jalaly J;Lin A;Rustgi AK;Nakagawa H;Califano JA;Pickering CR;White EA;Windle BE;Morgan IM;Cohen RB;Gimotty PA;Basu D
通讯作者：
Basu D