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Application of Survival Quilts for prognosis prediction of gastrectomy patients based on the Surveillance, Epidemiology, and End Results database and China National Cancer Center Gastric Cancer database 基于监测、流行病学和终末结果(SEER)数据库和中国国家癌症中心胃癌(NCCGC)数据库的生存被子在胃切除术患者预后预测中的应用
IF 7.6 Q1 ONCOLOGY Pub Date : 2024-06-01 DOI: 10.1016/j.jncc.2024.01.007
Lulu Zhao , Penghui Niu , Wanqing Wang , Xue Han , Xiaoyi Luan , Huang Huang , Yawei Zhang , Dongbing Zhao , Jidong Gao , Yingtai Chen
<div><h3>Objective</h3><p>Accurate prognosis prediction is critical for individualized-therapy making of gastric cancer patients. We aimed to develop and test 6-month, 1-, 2-, 3-, 5-, and 10-year overall survival (OS) and cancer-specific survival (CSS) prediction models for gastric cancer patients following gastrectomy.</p></div><div><h3>Methods</h3><p>We derived and tested Survival Quilts, a machine learning-based model, to develop 6-month, 1-, 2-, 3-, 5-, and 10-year OS and CSS prediction models. Gastrectomy patients in the development set (<em>n</em> = 20,583) and the internal validation set (<em>n</em> = 5,106) were recruited from the Surveillance, Epidemiology, and End Results (SEER) database, while those in the external validation set (<em>n</em> = 6,352) were recruited from the China National Cancer Center Gastric Cancer (NCCGC) database. Furthermore, we selected gastrectomy patients without neoadjuvant therapy as a subgroup to train and test the prognostic models in order to keep the accuracy of tumor-node-metastasis (TNM) stage. Prognostic performances of these OS and CSS models were assessed using the Concordance Index (C-index) and area under the curve (AUC) values.</p></div><div><h3>Results</h3><p>The machine learning model had a consistently high accuracy in predicting 6-month, 1-, 2-, 3-, 5-, and 10-year OS in the SEER development set (C-index = 0.861, 0.832, 0.789, 0.766, 0.740, and 0.709; AUC = 0.784, 0.828, 0.840, 0.849, 0.869, and 0.902, respectively), SEER validation set (C-index = 0.782, 0.739, 0.712, 0.698, 0.681, and 0.660; AUC = 0.751, 0.772, 0.767, 0.762, 0.766, and 0.787, respectively), and NCCGC set (C-index = 0.691, 0.756, 0.751, 0.737, 0.722, and 0.701; AUC = 0.769, 0.788, 0.790, 0.790, 0.787, and 0.788, respectively). The model was able to predict 6-month, 1-, 2-, 3-, 5-, and 10-year CSS in the SEER development set (C-index = 0.879, 0.858, 0.820, 0.802, 0.784, and 0.774; AUC = 0.756, 0.827, 0.852, 0.863, 0.874, and 0.884, respectively) and SEER validation set (C-index = 0.790, 0.763, 0.741, 0.729, 0.718, and 0.708; AUC = 0.706, 0.758, 0.767, 0.766, 0.766, and 0.764, respectively). In multivariate analysis, the high-risk group with risk score output by 5-year OS model was proved to be a strong survival predictor both in the SEER development set (hazard ratio [HR] = 14.59, 95% confidence interval [CI]: 1.872–2.774, <em>P</em> < 0.001), SEER validation set (HR = 2.28, 95% CI: 13.089–16.293, <em>P</em> < 0.001), and NCCGC set (HR = 1.98, 95% CI: 1.617–2.437, <em>P</em> <em><</em> 0.001). We further explored the prognostic value of risk score resulted 5-year CSS model of gastrectomy patients, and found that high-risk group remained as an independent CSS factor in the SEER development set (HR = 12.81, 95% CI: 11.568–14.194, <em>P</em> < 0.001) and SEER validation set (HR = 1.61, 95% CI: 1.338–1.935, <em>P</em> < 0.001).</p></div><div><h3>Conclusion</h3><p>Survival Quilts could allow accurate prediction of 6-m
目的准确的预后预测对胃癌患者的个体化治疗至关重要。我们旨在开发并测试胃癌患者胃切除术后 6 个月、1 年、2 年、3 年、5 年和 10 年总生存期(OS)和癌症特异性生存期(CSS)预测模型。方法我们开发并测试了基于机器学习的 Survival Quilts 模型,以开发 6 个月、1 年、2 年、3 年、5 年和 10 年 OS 和 CSS 预测模型。开发集(n = 20,583)和内部验证集(n = 5,106)中的胃切除术患者来自监测、流行病学和最终结果(SEER)数据库,而外部验证集(n = 6,352)中的胃切除术患者来自中国国家癌症中心胃癌(NCCGC)数据库。此外,为了保证肿瘤-结节-转移(TNM)分期的准确性,我们选择了未接受新辅助治疗的胃切除术患者作为亚组来训练和测试预后模型。结果在SEER开发集中,机器学习模型对6个月、1年、2年、3年、5年和10年OS的预测准确率一直很高(C-index = 0.861, 0.832, 0.789, 0.766, 0.740, and 0.709; AUC = 0.784, 0.828, 0.840, 0.849, 0.869, and 0.902, respectively)、SEER 验证集(C-index = 0.782, 0.739, 0.712, 0.698, 0.681, and 0.660; AUC = 0.751, 0.772, 0.767, 0.762、0.766 和 0.787),以及 NCCGC 集(C-index = 0.691、0.756、0.751、0.737、0.722 和 0.701;AUC = 0.769、0.788、0.790、0.790、0.787 和 0.788)。在 SEER 开发集中,该模型能够预测 6 个月、1 年、2 年、3 年、5 年和 10 年 CSS(C 指数 = 0.879、0.858、0.820、0.802、0.784 和 0.774;AUC = 0.756、0.827、0.852、0.863、0.874 和 0.884)和 SEER 验证集(C-index = 0.790、0.763、0.741、0.729、0.718 和 0.708;AUC = 0.706、0.758、0.767、0.766、0.766 和 0.764)。在多变量分析中,5 年 OS 模型输出风险评分的高危组被证明是 SEER 开发集中一个强有力的生存预测因子(危险比 [HR] = 14.59,95% 置信区间 [CI]:1.872-2.774):1.872-2.774, P < 0.001)、SEER 验证集(HR = 2.28, 95% CI: 13.089-16.293, P < 0.001)和 NCCGC 集(HR = 1.98, 95% CI: 1.617-2.437, P < 0.001)。我们进一步探讨了风险评分导致胃切除术患者5年CSS模型的预后价值,发现在SEER开发集中,高风险组仍然是一个独立的CSS因素(HR = 12.81, 95% CI: 11.568-14.结论 "生存被单 "可准确预测胃癌患者胃切除术后 6 个月、1-、2-、3-、5-和 10 年的 OS 和 CSS。
{"title":"Application of Survival Quilts for prognosis prediction of gastrectomy patients based on the Surveillance, Epidemiology, and End Results database and China National Cancer Center Gastric Cancer database","authors":"Lulu Zhao ,&nbsp;Penghui Niu ,&nbsp;Wanqing Wang ,&nbsp;Xue Han ,&nbsp;Xiaoyi Luan ,&nbsp;Huang Huang ,&nbsp;Yawei Zhang ,&nbsp;Dongbing Zhao ,&nbsp;Jidong Gao ,&nbsp;Yingtai Chen","doi":"10.1016/j.jncc.2024.01.007","DOIUrl":"10.1016/j.jncc.2024.01.007","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;p&gt;Accurate prognosis prediction is critical for individualized-therapy making of gastric cancer patients. We aimed to develop and test 6-month, 1-, 2-, 3-, 5-, and 10-year overall survival (OS) and cancer-specific survival (CSS) prediction models for gastric cancer patients following gastrectomy.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;p&gt;We derived and tested Survival Quilts, a machine learning-based model, to develop 6-month, 1-, 2-, 3-, 5-, and 10-year OS and CSS prediction models. Gastrectomy patients in the development set (&lt;em&gt;n&lt;/em&gt; = 20,583) and the internal validation set (&lt;em&gt;n&lt;/em&gt; = 5,106) were recruited from the Surveillance, Epidemiology, and End Results (SEER) database, while those in the external validation set (&lt;em&gt;n&lt;/em&gt; = 6,352) were recruited from the China National Cancer Center Gastric Cancer (NCCGC) database. Furthermore, we selected gastrectomy patients without neoadjuvant therapy as a subgroup to train and test the prognostic models in order to keep the accuracy of tumor-node-metastasis (TNM) stage. Prognostic performances of these OS and CSS models were assessed using the Concordance Index (C-index) and area under the curve (AUC) values.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;p&gt;The machine learning model had a consistently high accuracy in predicting 6-month, 1-, 2-, 3-, 5-, and 10-year OS in the SEER development set (C-index = 0.861, 0.832, 0.789, 0.766, 0.740, and 0.709; AUC = 0.784, 0.828, 0.840, 0.849, 0.869, and 0.902, respectively), SEER validation set (C-index = 0.782, 0.739, 0.712, 0.698, 0.681, and 0.660; AUC = 0.751, 0.772, 0.767, 0.762, 0.766, and 0.787, respectively), and NCCGC set (C-index = 0.691, 0.756, 0.751, 0.737, 0.722, and 0.701; AUC = 0.769, 0.788, 0.790, 0.790, 0.787, and 0.788, respectively). The model was able to predict 6-month, 1-, 2-, 3-, 5-, and 10-year CSS in the SEER development set (C-index = 0.879, 0.858, 0.820, 0.802, 0.784, and 0.774; AUC = 0.756, 0.827, 0.852, 0.863, 0.874, and 0.884, respectively) and SEER validation set (C-index = 0.790, 0.763, 0.741, 0.729, 0.718, and 0.708; AUC = 0.706, 0.758, 0.767, 0.766, 0.766, and 0.764, respectively). In multivariate analysis, the high-risk group with risk score output by 5-year OS model was proved to be a strong survival predictor both in the SEER development set (hazard ratio [HR] = 14.59, 95% confidence interval [CI]: 1.872–2.774, &lt;em&gt;P&lt;/em&gt; &lt; 0.001), SEER validation set (HR = 2.28, 95% CI: 13.089–16.293, &lt;em&gt;P&lt;/em&gt; &lt; 0.001), and NCCGC set (HR = 1.98, 95% CI: 1.617–2.437, &lt;em&gt;P&lt;/em&gt; &lt;em&gt;&lt;&lt;/em&gt; 0.001). We further explored the prognostic value of risk score resulted 5-year CSS model of gastrectomy patients, and found that high-risk group remained as an independent CSS factor in the SEER development set (HR = 12.81, 95% CI: 11.568–14.194, &lt;em&gt;P&lt;/em&gt; &lt; 0.001) and SEER validation set (HR = 1.61, 95% CI: 1.338–1.935, &lt;em&gt;P&lt;/em&gt; &lt; 0.001).&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;p&gt;Survival Quilts could allow accurate prediction of 6-m","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"4 2","pages":"Pages 142-152"},"PeriodicalIF":7.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S266700542400019X/pdfft?md5=03ed90ba842276e402ae3a9c6f81bd5f&pid=1-s2.0-S266700542400019X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140270218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The prognostic role of circulating tumor DNA across breast cancer molecular subtypes: A systematic review and meta-analysis 乳腺癌分子亚型中循环肿瘤 DNA 的预后作用:系统回顾和荟萃分析
IF 7.6 Q1 ONCOLOGY Pub Date : 2024-06-01 DOI: 10.1016/j.jncc.2024.04.005
Nana Guo , Qingxin Zhou , Meng Zhang , Xiaowei Chen , Baoqi Zeng , Shanshan Wu , Hongmei Zeng , Mopei Wang , Fei Ma , Feng Sun

Objective

Circulating tumor DNA (ctDNA) is increasingly being used as a potential prognostic biomarker in cancer patients. We aimed to assess the prognostic value of ctDNA in different subtypes of breast cancer patients throughout the whole treatment cycle.

Materials and methods

PubMed, Web of Science, Embase, Cochrane Library, Scopus, and clinical trials.gov databases were searched from January 2016 to May 2022. The following search terms were used: ctDNA OR circulating tumor DNA AND breast cancer OR breast carcinoma. Only studies written in English were included. The following pre-specified criteria should be met for inclusion: (i) original articles, conference abstracts, etc.; (ii) patients with breast cancer; (iii) ctDNA measurement; and (iv) clinical outcome data such as recurrence-free survival (RFS) and overall survival (OS). The random-effects model was preferred considering the potential heterogeneity across studies. The main outcomes are ctDNA detection rate and postoperative long-term outcomes (RFS and OS).

Results

A total of 24 studies were screened. At every measurement time, the ctDNA detection rate of the HR+ subgroup was similar to that of the HR- subgroup (P = 0.075; P = 0.458; P = 0.744; and P = 0.578), and the ctDNA detection rate of the HER2+ subgroup was similar to that of the HER2- subgroup (P = 0.805; P = 0.271; P = 0.807; and P = 0.703). In the HR+ subgroup, RFS and OS of ctDNA positive patients were similar to those of ctDNA negative patients (P = 0.589 and P = 0.110), while RFS and OS of the ctDNA positive group was significantly shorter than those of the ctDNA negative patients in the HR- subgroup (HR = 4.03, P < 0.001; HR = 3.21, P < 0.001). According to HER grouping, the results were the same as above. In the triple negative breast cancer (TNBC) subgroup, the RFS and OS of ctDNA-positive patients was significantly shorter than of the ctDNA negative patients before and after surgery.

Conclusions

ctDNA was more predictive of recurrence-free survival and overall survival in the HR- subgroup than in the HR+ subgroup, and the same result was showed in the HER2- subgroup vs. HER2+ subgroup. The prognosis of the TNBC subtype is closely related to ctDNA before and after surgery.

目的循环肿瘤 DNA(ctDNA)越来越多地被用作癌症患者潜在的预后生物标志物。我们旨在评估ctDNA在不同亚型乳腺癌患者整个治疗周期中的预后价值。材料和方法检索了2016年1月至2022年5月期间的PubMed、Web of Science、Embase、Cochrane Library、Scopus和clinical trials.gov数据库。使用的检索词如下:ctDNA OR 循环肿瘤 DNA AND 乳腺癌 OR 乳腺癌。仅纳入以英语撰写的研究。纳入研究应符合以下预设标准:(i) 原创文章、会议摘要等;(ii) 乳腺癌患者;(iii) ctDNA 测量;(iv) 无复发生存期(RFS)和总生存期(OS)等临床结果数据。考虑到各研究之间可能存在异质性,因此首选随机效应模型。主要结果为ctDNA检出率和术后长期结果(RFS和OS)。在每个测量时间,HR+亚组的ctDNA检出率与HR-亚组相似(P = 0.075;P = 0.458;P = 0.744;P = 0.578),HER2+亚组的ctDNA检出率与HER2-亚组相似(P = 0.805;P = 0.271;P = 0.807;P = 0.703)。在HR+亚组中,ctDNA阳性患者的RFS和OS与ctDNA阴性患者相似(P = 0.589和P = 0.110),而在HR-亚组中,ctDNA阳性组的RFS和OS明显短于ctDNA阴性患者(HR = 4.03,P <0.001;HR = 3.21,P <0.001)。根据 HER 分组,结果与上述相同。在三阴性乳腺癌(TNBC)亚组中,ctDNA阳性患者手术前后的RFS和OS明显短于ctDNA阴性患者。TNBC亚型的预后与手术前后的ctDNA密切相关。
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引用次数: 0
Dynamic bTMB combined with residual ctDNA improves survival prediction in locally advanced NSCLC patients with chemoradiotherapy and consolidation immunotherapy 动态bTMB与残留ctDNA相结合可提高化放疗和巩固免疫疗法局部晚期NSCLC患者的生存预测能力
IF 7.6 Q1 ONCOLOGY Pub Date : 2024-06-01 DOI: 10.1016/j.jncc.2024.01.008
Yu Wang , Wenqing Wang , Tao Zhang , Yin Yang , Jianyang Wang , Canjun Li , Xin Xu , Yuqi Wu , Ying Jiang , Jinghao Duan , Luhua Wang , Nan Bi
<div><h3>Background</h3><p>Liquid biopsy-based biomarkers, including circulating tumor DNA (ctDNA) and blood tumor mutational burden (bTMB), are recognized as promising predictors of prognoses and responses to immune checkpoint inhibitors (ICIs), despite insufficient sensitivity of single biomarker detection. This research aims to determine whether the combinatorial utility of longitudinal ctDNA with bTMB analysis could improve the prognostic and predictive effects.</p></div><div><h3>Methods</h3><p>This prospective two-center cohort trial, consisting of discovery and validation datasets, enrolled unresectable locally advanced non-small-cell lung cancer (LA-NSCLC) patients and assigned them to chemoradiotherapy (CRT) or CRT + consolidation ICI cohorts from 2018 to 2022. Blood specimens were collected pretreatment, 4 weeks post-CRT, and at progression to assess bTMB and ctDNA using 486-gene next-generation sequencing. Dynamic ∆bTMB was calculated as post-CRT bTMB minus baseline bTMB levels. Decision curve analyses were performed to calculate Concordance index (C-index).</p></div><div><h3>Results</h3><p>One hundred twenty-eight patients were enrolled. In the discovery dataset (<em>n</em> = 73), patients treated with CRT and consolidation ICI had significantly longer overall survival (OS; median not reached [NR] vs 20.2 months; <em>P</em> < 0.001) and progression-free survival (PFS; median 25.2 vs 11.4 months; <em>P</em> = 0.011) than those without ICI. Longitudinal analysis demonstrated a significant decrease in ctDNA abundance post-CRT (<em>P</em> < 0.001) but a relative increase with disease progression. Post-CRT detectable residual ctDNA correlated with significantly shorter OS (median 18.3 months vs NR; <em>P</em> = 0.001) and PFS (median 7.3 vs 25.2 months; <em>P</em> < 0.001). For patients with residual ctDNA, consolidation ICI brought significantly greater OS (median NR vs 14.8 months; <em>P</em> = 0.005) and PFS (median 13.8 vs 6.2 months; <em>P</em> = 0.028) benefit, but no significant difference for patients with ctDNA clearance. Dynamic ∆bTMB was predictive of prognosis. Patients with residual ctDNA and increased ∆bTMB (∆bTMB > 0) had significantly worse OS (median 9.0 vs 23.0 months vs NR; <em>P</em> < 0.001) and PFS (median 3.4 vs 7.3 vs 25.2 months; <em>P</em> < 0.001). The combinatorial model integrating post-CRT ctDNA with ∆bTMB had optimal predictive effects on OS (C-index = 0.723) and PFS (C-index = 0.693), outperforming individual features. In the independent validation set, we confirmed residual ctDNA predicted poorer PFS (median 50.8 vs 14.3 months; <em>P</em> = 0.026) but identified more consolidation ICI benefit (median NR vs 8.3 months; <em>P</em> = 0.039). The combined model exhibited a stable predictive advantage (C-index = 0.742 for PFS).</p></div><div><h3>Conclusions</h3><p>The multiparameter assay integrating qualitative residual ctDNA testing with quantitative ∆bTMB dynamics improves patient prognostic
背景基于液体活检的生物标记物,包括循环肿瘤DNA(ctDNA)和血液肿瘤突变负荷(bTMB),被认为是预测预后和对免疫检查点抑制剂(ICIs)反应的有前途的指标,尽管单一生物标记物检测的灵敏度不足。这项研究旨在确定纵向ctDNA与bTMB分析的组合效用是否能改善预后和预测效果。方法这项前瞻性双中心队列试验由发现数据集和验证数据集组成,从2018年至2022年招募了不可切除的局部晚期非小细胞肺癌(LA-NSCLC)患者,并将他们分配到化疗放疗(CRT)或CRT+巩固ICI队列中。采集治疗前、CRT 后 4 周和进展期的血液标本,使用 486 基因新一代测序技术评估 bTMB 和 ctDNA。动态ΔbTMB的计算方法为CRT后bTMB减去基线bTMB水平。进行决策曲线分析以计算一致性指数(C-index)。在发现数据集中(n = 73),接受 CRT 和巩固 ICI 治疗的患者的总生存期(OS;中位数未达到 [NR] vs 20.2 个月;P < 0.001)和无进展生存期(PFS;中位数 25.2 vs 11.4 个月;P = 0.011)明显长于未接受 ICI 治疗的患者。纵向分析表明,CRT 后 ctDNA 丰度显著下降(P = 0.001),但随着疾病的进展会相对增加。CRT后可检测到的残留ctDNA与明显缩短的OS(中位18.3个月 vs NR;P = 0.001)和PFS(中位7.3个月 vs 25.2个月;P <;0.001)相关。对于有残留ctDNA的患者,巩固ICI可显著提高OS(中位NR vs 14.8个月;P = 0.005)和PFS(中位13.8 vs 6.2个月;P = 0.028),但对于ctDNA清除的患者则无明显差异。动态ΔbTMB可预测预后。残留ctDNA和∆bTMB增加(∆bTMB > 0)的患者的OS(中位9.0个月 vs 23.0个月 vs NR;P <;0.001)和PFS(中位3.4个月 vs 7.3个月 vs 25.2个月;P <;0.001)明显较差。将 CT 后 ctDNA 与 ∆bTMB 整合在一起的组合模型对 OS(C 指数 = 0.723)和 PFS(C 指数 = 0.693)具有最佳预测效果,优于单个特征。在独立验证集中,我们证实残留 ctDNA 预测的 PFS 较差(中位 50.8 个月 vs 14.3 个月;P = 0.026),但识别出了更巩固的 ICI 益处(中位 NR vs 8.3 个月;P = 0.039)。结论将定性残留ctDNA检测与定量ΔbTMB动态分析相结合的多参数检测方法改善了患者预后风险分层和疗效预测,可用于LA-NSCLC的个性化巩固治疗。
{"title":"Dynamic bTMB combined with residual ctDNA improves survival prediction in locally advanced NSCLC patients with chemoradiotherapy and consolidation immunotherapy","authors":"Yu Wang ,&nbsp;Wenqing Wang ,&nbsp;Tao Zhang ,&nbsp;Yin Yang ,&nbsp;Jianyang Wang ,&nbsp;Canjun Li ,&nbsp;Xin Xu ,&nbsp;Yuqi Wu ,&nbsp;Ying Jiang ,&nbsp;Jinghao Duan ,&nbsp;Luhua Wang ,&nbsp;Nan Bi","doi":"10.1016/j.jncc.2024.01.008","DOIUrl":"10.1016/j.jncc.2024.01.008","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;p&gt;Liquid biopsy-based biomarkers, including circulating tumor DNA (ctDNA) and blood tumor mutational burden (bTMB), are recognized as promising predictors of prognoses and responses to immune checkpoint inhibitors (ICIs), despite insufficient sensitivity of single biomarker detection. This research aims to determine whether the combinatorial utility of longitudinal ctDNA with bTMB analysis could improve the prognostic and predictive effects.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;p&gt;This prospective two-center cohort trial, consisting of discovery and validation datasets, enrolled unresectable locally advanced non-small-cell lung cancer (LA-NSCLC) patients and assigned them to chemoradiotherapy (CRT) or CRT + consolidation ICI cohorts from 2018 to 2022. Blood specimens were collected pretreatment, 4 weeks post-CRT, and at progression to assess bTMB and ctDNA using 486-gene next-generation sequencing. Dynamic ∆bTMB was calculated as post-CRT bTMB minus baseline bTMB levels. Decision curve analyses were performed to calculate Concordance index (C-index).&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;p&gt;One hundred twenty-eight patients were enrolled. In the discovery dataset (&lt;em&gt;n&lt;/em&gt; = 73), patients treated with CRT and consolidation ICI had significantly longer overall survival (OS; median not reached [NR] vs 20.2 months; &lt;em&gt;P&lt;/em&gt; &lt; 0.001) and progression-free survival (PFS; median 25.2 vs 11.4 months; &lt;em&gt;P&lt;/em&gt; = 0.011) than those without ICI. Longitudinal analysis demonstrated a significant decrease in ctDNA abundance post-CRT (&lt;em&gt;P&lt;/em&gt; &lt; 0.001) but a relative increase with disease progression. Post-CRT detectable residual ctDNA correlated with significantly shorter OS (median 18.3 months vs NR; &lt;em&gt;P&lt;/em&gt; = 0.001) and PFS (median 7.3 vs 25.2 months; &lt;em&gt;P&lt;/em&gt; &lt; 0.001). For patients with residual ctDNA, consolidation ICI brought significantly greater OS (median NR vs 14.8 months; &lt;em&gt;P&lt;/em&gt; = 0.005) and PFS (median 13.8 vs 6.2 months; &lt;em&gt;P&lt;/em&gt; = 0.028) benefit, but no significant difference for patients with ctDNA clearance. Dynamic ∆bTMB was predictive of prognosis. Patients with residual ctDNA and increased ∆bTMB (∆bTMB &gt; 0) had significantly worse OS (median 9.0 vs 23.0 months vs NR; &lt;em&gt;P&lt;/em&gt; &lt; 0.001) and PFS (median 3.4 vs 7.3 vs 25.2 months; &lt;em&gt;P&lt;/em&gt; &lt; 0.001). The combinatorial model integrating post-CRT ctDNA with ∆bTMB had optimal predictive effects on OS (C-index = 0.723) and PFS (C-index = 0.693), outperforming individual features. In the independent validation set, we confirmed residual ctDNA predicted poorer PFS (median 50.8 vs 14.3 months; &lt;em&gt;P&lt;/em&gt; = 0.026) but identified more consolidation ICI benefit (median NR vs 8.3 months; &lt;em&gt;P&lt;/em&gt; = 0.039). The combined model exhibited a stable predictive advantage (C-index = 0.742 for PFS).&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;p&gt;The multiparameter assay integrating qualitative residual ctDNA testing with quantitative ∆bTMB dynamics improves patient prognostic","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"4 2","pages":"Pages 177-187"},"PeriodicalIF":7.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667005424000218/pdfft?md5=949feb9359945cd4e35bb2c25ed9dbe8&pid=1-s2.0-S2667005424000218-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140771120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Guidelines for diagnosis and treatment of advanced breast cancer in China (2022 edition) 中国晚期乳腺癌诊治指南(2022 年版)✰
IF 7.6 Q1 ONCOLOGY Pub Date : 2024-06-01 DOI: 10.1016/j.jncc.2023.12.001
Breast Cancer Expert Committee of National Quality Control Center for Cancer;, Breast Cancer Expert Committee of China Anti-Cancer Association;, Cancer Drug Clinical Research Committee of China Anti-Cancer Association

Breast cancer is the most common cancer among women worldwide. It has been estimated that about 416 000 new cases and over 117 000 deaths of breast cancer occurred in China in 2020. Among the new cases of breast cancer diagnosed each year, 3–10% have distant metastasis at the time of initial diagnosis. In addition, approximately 30% of patients with early-stage breast cancer may eventually experience recurrence or metastases. The 5-year survival rate of patients with advanced breast cancer is only 20% with a median overall survival of 2–3 years. Although advanced breast cancer remains incurable at present, new therapeutic options and multidisciplinary treatment could be utilized to alleviate symptoms, improve quality of life, and prolong patients’ survival. The choice of treatment regimens for patients with advanced breast cancer is very important, and the optimal treatment strategy beyond the first- and second-line therapy is often lacking. Herein, the China Advanced Breast Cancer Guideline Panel discussed and summarized recent clinical evidence, updated the guidelines for the diagnosis and treatment of advanced breast cancer based on the 2020 edition, and formulated the “Guidelines for diagnosis and treatment of advanced breast cancer in China (2022 edition)” for clinicians' reference.

乳腺癌是全球妇女最常见的癌症。据估计,2020 年中国乳腺癌新发病例约为 416 000 例,死亡病例超过 117 000 例。在每年新确诊的乳腺癌病例中,3%-10%的患者在初诊时已出现远处转移。此外,约 30% 的早期乳腺癌患者最终会出现复发或转移。晚期乳腺癌患者的 5 年生存率仅为 20%,中位总生存期为 2-3 年。虽然晚期乳腺癌目前仍无法治愈,但可以利用新的治疗方案和多学科治疗来缓解症状,改善生活质量,延长患者的生存期。晚期乳腺癌患者治疗方案的选择非常重要,但往往缺乏一线和二线治疗之外的最佳治疗策略。在此,中国晚期乳腺癌指南专家组讨论并总结了最新的临床证据,在2020年版的基础上更新了晚期乳腺癌诊治指南,并制定了《中国晚期乳腺癌诊治指南(2022年版)》,供临床医生参考。
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引用次数: 0
Concordance between four PD-L1 immunohistochemical assays and 22C3 pharmDx assay in esophageal squamous cell carcinoma in a multicenter study 在一项多中心研究中,食管鳞状细胞癌中四种 PD-L1 免疫组化测定与 22C3 pharmDx 测定之间的一致性
IF 7.6 Q1 ONCOLOGY Pub Date : 2024-06-01 DOI: 10.1016/j.jncc.2023.11.003
Liyan Xue , Yuan Li , Lili Jiang , Chao Liu , Na Cheng , Changyuan Guo , Yan Jin , Ping Zhou , Xuemin Xue , Yue Wang , Weiya Wang , Yanhui Liu , Jianming Ying

Background

The prediction of response to immunotherapy mostly depends on the programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) status, and the 22C3 pharmDx assay has been approved in esophageal squamous cell carcinoma (ESCC). However, the widespread use of the 22C3 pharmDx assay is limited due to its availability. Thus, alternative PD-L1 assays are needed. We aimed to investigate the analytical and clinical diagnostic performances of four PD-L1 assays and to compare their concordances with the 22C3 pharmDx assay.

Methods

The PD-L1 22C3 pharmDx assay was performed on the Dako Autostainer Link 48 platform, three testing assays (PD-L1 E1L3N XP antibody [Ab], PD-L1 BP6099 Ab and PD-L1 CST E1L3N Ab) on the Leica BOND-MAX/III platform, and one testing assay (PD-L1 MXR006 Ab) on the Roche VENTANA Benchmark Ultra platform. A total of 218 ESCC cases from four centers were included in this retrospective study. Professionals from each center stained and read the IHC slides independently and determined the combined positive score (CPS) and the tumor proportion score (TPS).

Results

Regarding analytical performance, the four testing assays demonstrated good correlations with the 22C3 pharmDx assay when evaluated by the TPS or CPS (ρ > 0.8 for all four assays). Regarding diagnostic performance (CPS ≥ 10 was used as the cutoff), the four testing assays showed moderate concordances with the 22C3 pharmDx assay (kappa > 0.7 for all four assays). The overall percent agreements between each testing assay and the 22C3 pharmDx assay was at least 87.2 %.

Conclusion

This study provides insight into the potential interchangeability of the four PD-L1 assays with the 22C3 pharmDx assay.

背景预测对免疫疗法的反应主要取决于程序性死亡配体 1(PD-L1)的免疫组化(IHC)状态,22C3 pharmDx 检测法已被批准用于食管鳞状细胞癌(ESCC)。然而,22C3 pharmDx 检测法的广泛使用因其可用性而受到限制。因此,我们需要其他的 PD-L1 检测方法。我们旨在研究四种 PD-L1 检测方法的分析和临床诊断性能,并比较它们与 22C3 pharmDx 检测方法的一致性。方法PD-L1 22C3 pharmDx测定在Dako Autostainer Link 48平台上进行,三种检测测定(PD-L1 E1L3N XP抗体[Ab]、PD-L1 BP6099抗体和PD-L1 CST E1L3N抗体)在Leica BOND-MAX/III平台上进行,一种检测测定(PD-L1 MXR006抗体)在Roche VENTANA Benchmark Ultra平台上进行。这项回顾性研究共纳入了来自四个中心的 218 例 ESCC 病例。结果在分析性能方面,四种检测试剂与 22C3 pharmDx 检测试剂在 TPS 或 CPS 评估中表现出良好的相关性(所有四种检测试剂的相关性均为ρ > 0.8)。在诊断性能方面(以 CPS ≥ 10 为临界值),四种检测方法与 22C3 pharmDx 检测方法显示出中等程度的一致性(四种检测方法的 kappa 均为 0.7)。结论:本研究深入探讨了四种 PD-L1 检测方法与 22C3 pharmDx 检测方法的潜在互换性。
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引用次数: 0
Resolving tumor evolution: a phylogenetic approach 解决肿瘤进化问题:系统发生学方法
IF 7.6 Q1 ONCOLOGY Pub Date : 2024-06-01 DOI: 10.1016/j.jncc.2024.03.001
Lin Li , Wenqin Xie , Li Zhan , Shaodi Wen , Xiao Luo , Shuangbin Xu , Yantong Cai , Wenli Tang , Qianwen Wang , Ming Li , Zijing Xie , Lin Deng , Hongyuan Zhu , Guangchuang Yu

The evolutionary dynamics of cancer, characterized by its profound heterogeneity, demand sophisticated tools for a holistic understanding. This review delves into tumor phylogenetics, an essential approach bridging evolutionary biology with oncology, offering unparalleled insights into cancer's evolutionary trajectory. We provide an overview of the workflow, encompassing study design, data acquisition, and phylogeny reconstruction. Notably, the integration of diverse data sets emerges as a transformative step, enhancing the depth and breadth of evolutionary insights. With this integrated perspective, tumor phylogenetics stands poised to redefine our understanding of cancer evolution and influence therapeutic strategies.

癌症的进化动态以其深刻的异质性为特征,需要复杂的工具来全面了解。本综述深入探讨了肿瘤系统发育学,这是一种连接进化生物学与肿瘤学的重要方法,能为癌症的进化轨迹提供无与伦比的洞察力。我们概述了包括研究设计、数据采集和系统发育重建在内的工作流程。值得注意的是,整合不同的数据集是一个变革性的步骤,它提高了进化洞察的深度和广度。有了这种综合视角,肿瘤系统发生学将重新定义我们对癌症进化的理解,并影响治疗策略。
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引用次数: 0
Comparative study of cancer profiles between 2020 and 2022 using global cancer statistics (GLOBOCAN) 利用全球癌症统计数据(GLOBOCAN)对 2020 年和 2022 年癌症概况进行比较研究
IF 7.6 Q1 ONCOLOGY Pub Date : 2024-06-01 DOI: 10.1016/j.jncc.2024.05.001
Wei Cao , Kang Qin , Feng Li , Wanqing Chen

Background

The International Agency for Research on Cancer (IARC) released the latest estimates of the global burden of cancer. We present a comparison of cancer profiles between 2020 and 2022, leveraging data from the Global Cancer Statistics (GLOBOCAN).

Methods

Cancer incidence and mortality data were sourced from two different years, 2020 and 2022, in the GLOBOCAN database. We tracked changes in age-standardized incidence and mortality rates, as well as estimated numbers of new cancer cases and deaths of the 15 most common cancer types globally and in China between 2020 and 2022. Additionally, we conducted comparisons to assess alterations in the cancer burden and variations in mortality-to-incidence ratio (MIR) across different regions and countries for both 2020 and 2022.

Results

Lung cancer remained the most common cancer and the leading cause of cancer death worldwide. The new cases of thyroid cancer witnessed a sharp increase in 2022. Conversely, the numbers of new cancer cases and deaths from stomach and esophageal cancer decreased significantly in 2022. The geographic distribution of cancer incidence and mortality across six continents in 2022 largely mirrored that of 2020. Higher Human Development Index (HDI) levels in countries corresponded with elevated rates of cancer incidence and mortality, consistent with the previous year. Among 185 countries or territories, China's age-standardized incidence rate (ASIR) ranked 64th and its age-standardized mortality rate (ASMR) ranked 68th, aligning with global averages. Lung cancer continued to impose the greatest burden of incidence and mortality. Stomach, breast, and esophageal cancers showed declines in both case counts and ASIR. Noteworthy reductions in both ASMR and absolute mortality numbers were observed in liver, stomach, and esophageal cancers. The global MIR decreased from 0.516 in 2020 to 0.488 in 2022. MIR trends indicated an upward trajectory with decreasing HDI levels in both 2022 and 2020. While Canada, Germany, India, Italy, Japan, and the United Kingdom demonstrated increasing MIRs, China exhibited the most significant decrease, followed by Russia and the United States.

Conclusions

The global landscape of cancer incidence and mortality in 2022 reflects ongoing trends observed in 2020. Cancer burdens vary notably across countries with differing socioeconomic statuses. Decreases in stomach, liver, and esophageal cancer cases and deaths signify progress in cancer control efforts. The decrease in the global MIRs highlights potential improvements in cancer management.

背景国际癌症研究机构(IARC)发布了对全球癌症负担的最新估计。我们利用全球癌症统计数据(GLOBOCAN)中的数据,对 2020 年和 2022 年的癌症概况进行了比较。方法癌症发病率和死亡率数据来自 GLOBOCAN 数据库中的 2020 年和 2022 年两个不同年份。我们追踪了 2020 年至 2022 年期间全球和中国 15 种最常见癌症的年龄标准化发病率和死亡率的变化,以及新发癌症病例和死亡人数的估计值。此外,我们还进行了比较,以评估 2020 年和 2022 年不同地区和国家癌症负担的变化以及死亡率与发病率之比(MIR)的变化。2022 年,甲状腺癌新发病例急剧增加。相反,2022 年胃癌和食道癌的新发病例和死亡人数大幅下降。2022 年六大洲癌症发病率和死亡率的地理分布与 2020 年基本一致。人类发展指数(HDI)水平较高的国家癌症发病率和死亡率也相应升高,这与上一年的情况一致。在185个国家或地区中,中国的年龄标准化发病率(ASIR)排名第64位,年龄标准化死亡率(ASMR)排名第68位,与全球平均水平持平。肺癌仍然是发病率和死亡率最高的癌症。胃癌、乳腺癌和食道癌的病例数和年龄标准化死亡率均有所下降。值得注意的是,肝癌、胃癌和食道癌的 ASMR 和绝对死亡率都有所下降。全球死亡率中位数从 2020 年的 0.516 降至 2022 年的 0.488。随着 2022 年和 2020 年人类发展指数水平的下降,中位数趋势呈上升趋势。加拿大、德国、印度、意大利、日本和英国的癌症发病率与死亡率中位数呈上升趋势,而中国的癌症发病率与死亡率中位数下降幅度最大,其次是俄罗斯和美国。癌症负担在社会经济地位不同的国家之间存在明显差异。胃癌、肝癌和食道癌发病率和死亡率的下降标志着癌症控制工作取得了进展。全球癌症中位数的下降凸显了癌症管理方面的潜在改进。
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引用次数: 0
Clinical, pathological, and adjuvant chemotherapy use differences among microsatellite unstable and microsatellite stable colon cancers 微卫星不稳定和微卫星稳定结肠癌在临床、病理和辅助化疗使用方面的差异
IF 7.6 Q1 ONCOLOGY Pub Date : 2024-06-01 DOI: 10.1016/j.jncc.2024.04.003
Baqir Hasan Jafry , Munir Hassan Buhaya , Allante Milsap , Amy Little Jones , Suleyman Yasin Goksu , Nilesh Verma , Timothy J. Brown , Amy Hughes , Rasmi Nair , Nina Sanford , Joseph Su , Emina Huang , Syed Mohammad Ali Kazmi

Background

Colon cancers are categorized into mismatch repair deficient/microsatellite unstable (MSI-H) and mismatch repair proficient/microsatellite stable (MSS) cancers. This study aims to compare the disease characteristics and trends in the utilization of cancer therapies across different age groups and stages in these two groups.

Methods

MSI-H and MSS colon adenocarcinomas from 2010 to 2016 were identified using the National Cancer Database. We compared patient and disease characteristics between the two groups and evaluated the use of adjuvant chemotherapy across age groups and cancer stages. Within MSI-H and MSS groups, we conducted a landmark analysis after propensity score matching for adjuvant chemotherapy versus no chemotherapy to determine its effect on survival.

Results

Of the 542,368 patients that met inclusion criteria, 120,751 (22%) had mismatch repair results available—out of these 96,928 (80%) had MSS colon cancers while 23,823 (19.7%) had MSI-H cancers. MSI-H disease had a bimodal age distribution (<40 years = 22%; ≥75 years = 26%) and was frequent among females (22%) and non-Hispanic Whites (20%). Among those < 65 years, 15% of low-risk stage 2 MSI-H patients and 40% of high-risk stage 2 MSI-H patients received adjuvant chemotherapy. More than two-thirds of stage 3 patients <65 years received adjuvant chemotherapy in both groups. After conducting propensity-score matching for age, gender, and co-morbidities, we found that adjuvant chemotherapy use had a trend towards lower overall survival (OS) in low-risk stage 2 MSI-H (HR = 1.8 [95% CI, 0.8–4.02]) and high-risk stage 2 MSI-H (HR = 1.42 [95% CI, 0.96–2.12]) groups. Adjuvant chemotherapy significantly improved OS in stage 3 colon cancer patients irrespective of microsatellite status or risk category of disease.

Conclusions

MSI-H colon cancer had bimodal age distribution. Among stage 2 MSI-H patients <65 years, a notable proportion received adjuvant chemotherapy. Among MSI-H stage 2 patients, adjuvant chemotherapy use was associated with lower survival while it significantly improved survival for stage 3 patients, irrespective of MSI status.

背景结肠癌分为错配修复缺陷型/微卫星不稳定型(MSI-H)和错配修复熟练型/微卫星稳定型(MSS)癌症。本研究旨在比较这两类癌症不同年龄段和分期的疾病特征和使用癌症疗法的趋势。方法通过国家癌症数据库确定了2010年至2016年的MSI-H和MSS结肠腺癌。我们比较了两组患者和疾病特征,并评估了不同年龄组和癌症分期的辅助化疗使用情况。在MSI-H组和MSS组中,我们对辅助化疗与不化疗进行倾向得分匹配后进行了地标分析,以确定化疗对生存率的影响。结果在542,368名符合纳入标准的患者中,120,751人(22%)有错配修复结果,其中96,928人(80%)患有MSS结肠癌,23,823人(19.7%)患有MSI-H结肠癌。MSI-H 癌症的年龄分布呈双峰分布(40 岁 = 22%;≥75 岁 = 26%),女性(22%)和非西班牙裔白人(20%)多发。在 65 岁以上的患者中,15% 的低危 2 期 MSI-H 患者和 40% 的高危 2 期 MSI-H 患者接受了辅助化疗。在两组患者中,超过三分之二的 3 期 65 岁患者接受了辅助化疗。在对年龄、性别和合并疾病进行倾向得分匹配后,我们发现辅助化疗在低危2期MSI-H组(HR = 1.8 [95% CI, 0.8-4.02])和高危2期MSI-H组(HR = 1.42 [95% CI, 0.96-2.12])有降低总生存率(OS)的趋势。无论微卫星状态或疾病风险类别如何,辅助化疗都能明显改善3期结肠癌患者的OS。在MSI-H 2期患者中,接受辅助化疗的患者比例明显高于65岁的患者。在MSI-H 2期患者中,辅助化疗与较低的生存率相关,而对于3期患者,无论MSI状态如何,辅助化疗都能显著提高生存率。
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引用次数: 0
A glimpse into the future: mapping global research trends in immunotherapy for rare tumors 未来一瞥:绘制全球罕见肿瘤免疫疗法研究趋势图
IF 7.6 Q1 ONCOLOGY Pub Date : 2024-06-01 DOI: 10.1016/j.jncc.2023.11.002
Guo Zhao , Yuning Wang , Shuhang Wang, Ning Li
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引用次数: 0
Efficacy and safety of paclitaxel liposome versus paclitaxel in combination with carboplatin in the first-line chemotherapy for ovarian cancer: a multicenter, open-label, non-inferiority, randomized controlled trial 紫杉醇脂质体与紫杉醇联合卡铂在卵巢癌一线化疗中的疗效和安全性:一项多中心、开放标签、非劣效随机对照试验
IF 7.6 Q1 ONCOLOGY Pub Date : 2024-06-01 DOI: 10.1016/j.jncc.2024.04.004
Rong Li , Hongping Zhang , Qingshui Li , Guangwen Yuan , Yanjie Zhou , Rutie Yin , He Wang , Chunyan Wang , Yi Huang , Wei Wang , Xiaojian Yan , Lingying Wu , Qi Zhou

Background

The paclitaxel liposome formulation, encapsulating paclitaxel within a phospholipid bilayer, addresses the insolubility of traditional paclitaxel formulations, thereby reducing toxicity without compromising its antitumor efficacy.

Methods

This multicenter, open-label, non-inferiority randomized controlled trial (ChiCTR2000038555) evaluates the efficacy and safety of paclitaxel liposome in comparison to the standard regimen of paclitaxel combined with carboplatin (PLC vs. PC) as first-line therapy in patients with epithelial ovarian cancer.

Results

An analysis of median progression-free survival (PFS) revealed non-inferior outcomes between 263 patients in the PLC group and 260 patients in the PC group (32.3 vs. 29.9 months, hazard ratio [HR], 0.89 [95% CI, 0.64−1.25]), using a non-inferior margin of 1.3. Although the overall incidence of treatment-related adverse events was comparable between groups, the PLC group experienced significantly fewer non-hematologic toxicities than those treated with the PC regimen.

Conclusion

The findings affirm the non-inferiority of paclitaxel liposome compared to the combination of paclitaxel and carboplatin regarding therapeutic efficacy, with an enhanced safety profile marked by reduced non-hematologic toxicities.

背景紫杉醇脂质体制剂将紫杉醇包裹在磷脂双分子层中,解决了传统紫杉醇制剂不溶解的问题,从而在降低毒性的同时不影响其抗肿瘤疗效。方法这项多中心、开放标签、非劣效性随机对照试验(ChiCTR2000038555)评估了紫杉醇脂质体与紫杉醇联合卡铂(PLC vs. PC)标准方案作为一线疗法的疗效和安全性。结果 对中位无进展生存期(PFS)的分析显示,PLC组263例患者的疗效与PC组260例患者的疗效(32.3个月对29.9个月,危险比[HR],0.89[95% CI,0.64-1.25])并无差别,非劣效值为1.3。结论研究结果证实,紫杉醇脂质体与紫杉醇和卡铂联合治疗相比,在疗效方面并无劣势,而且安全性更高,非血液学毒性降低。
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引用次数: 0
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Journal of the National Cancer Center
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