Journal of the National Cancer Center最新文献

{"title":"Dynamic bTMB combined with residual ctDNA improves survival prediction in locally advanced NSCLC patients with chemoradiotherapy and consolidation immunotherapy","authors":"Yu Wang , Wenqing Wang , Tao Zhang , Yin Yang , Jianyang Wang , Canjun Li , Xin Xu , Yuqi Wu , Ying Jiang , Jinghao Duan , Luhua Wang , Nan Bi","doi":"10.1016/j.jncc.2024.01.008","DOIUrl":"10.1016/j.jncc.2024.01.008","url":null,"abstract":"<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","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}

{"title":"Guidelines for diagnosis and treatment of advanced breast cancer in China (2022 edition)","authors":"Breast Cancer Expert Committee of National Quality Control Center for Cancer;,&nbsp;Breast Cancer Expert Committee of China Anti-Cancer Association;,&nbsp;Cancer Drug Clinical Research Committee of China Anti-Cancer Association","doi":"10.1016/j.jncc.2023.12.001","DOIUrl":"10.1016/j.jncc.2023.12.001","url":null,"abstract":"<div><p>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.</p></div>","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"4 2","pages":"Pages 107-127"},"PeriodicalIF":7.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667005423000832/pdfft?md5=93a405cc18585713cb1f485c4d294200&pid=1-s2.0-S2667005423000832-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139014771","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}

{"title":"Concordance between four PD-L1 immunohistochemical assays and 22C3 pharmDx assay in esophageal squamous cell carcinoma in a multicenter study","authors":"Liyan Xue ,&nbsp;Yuan Li ,&nbsp;Lili Jiang ,&nbsp;Chao Liu ,&nbsp;Na Cheng ,&nbsp;Changyuan Guo ,&nbsp;Yan Jin ,&nbsp;Ping Zhou ,&nbsp;Xuemin Xue ,&nbsp;Yue Wang ,&nbsp;Weiya Wang ,&nbsp;Yanhui Liu ,&nbsp;Jianming Ying","doi":"10.1016/j.jncc.2023.11.003","DOIUrl":"10.1016/j.jncc.2023.11.003","url":null,"abstract":"<div><h3>Background</h3><p>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.</p></div><div><h3>Methods</h3><p>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).</p></div><div><h3>Results</h3><p>Regarding analytical performance, the four testing assays demonstrated good correlations with the 22C3 pharmDx assay when evaluated by the TPS or CPS (ρ &gt; 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 &gt; 0.7 for all four assays). The overall percent agreements between each testing assay and the 22C3 pharmDx assay was at least 87.2 %.</p></div><div><h3>Conclusion</h3><p>This study provides insight into the potential interchangeability of the four PD-L1 assays with the 22C3 pharmDx assay.</p></div>","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"4 2","pages":"Pages 162-168"},"PeriodicalIF":7.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667005423000819/pdfft?md5=416d70d5f83e420162a9782dbf74c963&pid=1-s2.0-S2667005423000819-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139299827","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}

{"title":"Resolving tumor evolution: a phylogenetic approach","authors":"Lin Li ,&nbsp;Wenqin Xie ,&nbsp;Li Zhan ,&nbsp;Shaodi Wen ,&nbsp;Xiao Luo ,&nbsp;Shuangbin Xu ,&nbsp;Yantong Cai ,&nbsp;Wenli Tang ,&nbsp;Qianwen Wang ,&nbsp;Ming Li ,&nbsp;Zijing Xie ,&nbsp;Lin Deng ,&nbsp;Hongyuan Zhu ,&nbsp;Guangchuang Yu","doi":"10.1016/j.jncc.2024.03.001","DOIUrl":"10.1016/j.jncc.2024.03.001","url":null,"abstract":"<div><p>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.</p></div>","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"4 2","pages":"Pages 97-106"},"PeriodicalIF":7.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667005424000206/pdfft?md5=30935fad53e6d15809f0011986581edf&pid=1-s2.0-S2667005424000206-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140280676","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}

{"title":"Comparative study of cancer profiles between 2020 and 2022 using global cancer statistics (GLOBOCAN)","authors":"Wei Cao ,&nbsp;Kang Qin ,&nbsp;Feng Li ,&nbsp;Wanqing Chen","doi":"10.1016/j.jncc.2024.05.001","DOIUrl":"10.1016/j.jncc.2024.05.001","url":null,"abstract":"<div><h3>Background</h3><p>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).</p></div><div><h3>Methods</h3><p>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.</p></div><div><h3>Results</h3><p>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.</p></div><div><h3>Conclusions</h3><p>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.</p></div>","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"4 2","pages":"Pages 128-134"},"PeriodicalIF":7.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667005424000279/pdfft?md5=0d8a64b119e52b175e636d1d62424f14&pid=1-s2.0-S2667005424000279-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141049352","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}

{"title":"Clinical, pathological, and adjuvant chemotherapy use differences among microsatellite unstable and microsatellite stable colon cancers","authors":"Baqir Hasan Jafry ,&nbsp;Munir Hassan Buhaya ,&nbsp;Allante Milsap ,&nbsp;Amy Little Jones ,&nbsp;Suleyman Yasin Goksu ,&nbsp;Nilesh Verma ,&nbsp;Timothy J. Brown ,&nbsp;Amy Hughes ,&nbsp;Rasmi Nair ,&nbsp;Nina Sanford ,&nbsp;Joseph Su ,&nbsp;Emina Huang ,&nbsp;Syed Mohammad Ali Kazmi","doi":"10.1016/j.jncc.2024.04.003","DOIUrl":"10.1016/j.jncc.2024.04.003","url":null,"abstract":"<div><h3>Background</h3><p>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.</p></div><div><h3>Methods</h3><p>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.</p></div><div><h3>Results</h3><p>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 (&lt;40 years = 22%; ≥75 years = 26%) and was frequent among females (22%) and non-Hispanic Whites (20%). Among those &lt; 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 &lt;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.</p></div><div><h3>Conclusions</h3><p>MSI-H colon cancer had bimodal age distribution. Among stage 2 MSI-H patients &lt;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.</p></div>","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"4 2","pages":"Pages 169-175"},"PeriodicalIF":7.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667005424000243/pdfft?md5=0bdda20c47cf519b6436fa6d84f43bf2&pid=1-s2.0-S2667005424000243-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140778719","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}

{"title":"A glimpse into the future: mapping global research trends in immunotherapy for rare tumors","authors":"Guo Zhao ,&nbsp;Yuning Wang ,&nbsp;Shuhang Wang,&nbsp;Ning Li","doi":"10.1016/j.jncc.2023.11.002","DOIUrl":"10.1016/j.jncc.2023.11.002","url":null,"abstract":"","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"4 2","pages":"Pages 93-96"},"PeriodicalIF":7.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667005423000807/pdfft?md5=82513e1387b2b76160ab8cd06ba334c0&pid=1-s2.0-S2667005423000807-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139298080","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}

{"title":"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","authors":"Rong Li ,&nbsp;Hongping Zhang ,&nbsp;Qingshui Li ,&nbsp;Guangwen Yuan ,&nbsp;Yanjie Zhou ,&nbsp;Rutie Yin ,&nbsp;He Wang ,&nbsp;Chunyan Wang ,&nbsp;Yi Huang ,&nbsp;Wei Wang ,&nbsp;Xiaojian Yan ,&nbsp;Lingying Wu ,&nbsp;Qi Zhou","doi":"10.1016/j.jncc.2024.04.004","DOIUrl":"https://doi.org/10.1016/j.jncc.2024.04.004","url":null,"abstract":"<div><h3>Background</h3><p>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.</p></div><div><h3>Methods</h3><p>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.</p></div><div><h3>Results</h3><p>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.</p></div><div><h3>Conclusion</h3><p>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.</p></div>","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"4 2","pages":"Pages 135-141"},"PeriodicalIF":7.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667005424000255/pdfft?md5=0f5183a94b95cd5275373c3ffc4d2fc7&pid=1-s2.0-S2667005424000255-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141482249","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}

{"title":"Establishing the homologous recombination score threshold in metastatic prostate cancer patients to predict the efficacy of PARP inhibitors","authors":"Diwei Zhao ,&nbsp;Anqi Wang ,&nbsp;Yuanwei Li ,&nbsp;Xinyang Cai ,&nbsp;Junliang Zhao ,&nbsp;Tianyou Zhang ,&nbsp;Yi Zhao ,&nbsp;Yu Dong ,&nbsp;Fangjian Zhou ,&nbsp;Yonghong Li ,&nbsp;Jun Wang","doi":"10.1016/j.jncc.2024.05.005","DOIUrl":"10.1016/j.jncc.2024.05.005","url":null,"abstract":"<div><h3>Background</h3><p>The homologous recombination deficiency (HRD) score serves as a promising biomarker to identify patients who are eligible for treatment with PARP inhibitors (PARPi). Previous studies have suggested a 3-biomarker Genomic Instability Score (GIS) threshold of ≥ 42 as a valid biomarker to predict response to PARPi in patients with ovarian cancer and breast cancer. However, the GIS threshold for prostate cancer (PCa) is still lacking. Here, we conducted an exploratory analysis to investigate an appropriate HRD score threshold and to evaluate its ability to predict response to PARPi in PCa patients.</p></div><div><h3>Methods</h3><p>A total of 181 patients with metastatic castration-resistant PCa were included in this study. Tumor tissue specimens were collected for targeted next-generation sequencing for homologous recombination repair (HRR) genes and copy number variation (CNV) analysis. The HRD score was calculated based on over 50,000 single-nucleotide polymorphisms (SNP) distributed across the human genome, incorporating three SNP-based assays: loss of heterozygosity, telomeric allelic imbalance, and large-scale state transition. The HRD score threshold was set at the last 5th percentile of the HRD scores in our cohort of known HRR-deficient tumors. The relationship between the HRD score and the efficacy in 16 patients of our cohort who received PARPi treatment were retrospectively analyzed.</p></div><div><h3>Results</h3><p>Genomic testing was succeeded in 162 patients. In our cohort, 61 patients (37.7%) had HRR mutations (HRRm). <em>BRCA</em> mutations occurred in 15 patients (9.3%). The median HRD score was 4 (ranged from 0 to 57) in the total cohort, which is much lower than that in breast and ovarian cancers. Patients who harbored HRRm and <em>BRCA</em> or <em>TP53</em> mutations had higher HRD scores. CNV occured more frequently in patients with HRRm. The last 5th percentile of HRD scores was 43 in the HRR-mutant cohort and consequently HRD high was defined as HRD scores <span><math><mrow><mo>≥</mo><mspace></mspace></mrow></math></span>43. In the 16 patients who received PARPi in our cohort, 4 patients with a high HRD score achieved an objective response rate (ORR) of 100% while 12 patients with a low HRD score achieved an ORR of 8.3%. Progression-free survival (PFS) in HRD high patients was longer compared to HRD low patients, regardless of HRRm.</p></div><div><h3>Conclusions</h3><p>A HRD score threshold of 43 was established and preliminarily validated to predict the efficacy of PARPi in this study. Future studies are needed to further verify this threshold.</p></div>","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"4 3","pages":"Pages 280-287"},"PeriodicalIF":7.6,"publicationDate":"2024-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667005424000437/pdfft?md5=71938580a84e1e26f7364a42bb5c0ec5&pid=1-s2.0-S2667005424000437-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142048652","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}

{"title":"Precision radiation therapy in the modern era of multidisciplinary care in oncology: What matters to our patients and beyond?","authors":"","doi":"10.1016/j.jncc.2024.05.004","DOIUrl":"10.1016/j.jncc.2024.05.004","url":null,"abstract":"","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"4 3","pages":"Pages 260-262"},"PeriodicalIF":7.6,"publicationDate":"2024-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667005424000309/pdfft?md5=a6de2dde265b559dcbf419bd036231a4&pid=1-s2.0-S2667005424000309-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141031323","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}