Introduction: Cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL6), interferon-gamma (IFN-γ), interleukin 17-alpha (IL17-α), and interleukin 33 (IL33) play critical roles in immune responses and may impact cancer prognosis in future. However, few studies have simultaneously explored the prognostic impact of these cytokines for cancer. In this study, we aim to apply the unsupervised clustering analysis to approach the correlation between the expression of these cytokines and the subsequent prognosis of patients with esophageal squamous cell carcinoma (ESCC).
Methods: A robust clustering algorithm was used, the Gaussian mixture method (GMM), through the mclust R package to group patients based on the expression of their cytokines in plasma or tumors. The 324 NTU patients were grouped into 4 clusters, and the 179 GSE53625 patients were grouped into 3 clusters based on expression in plasma and tumors, respectively. Five- and 3-year overall survival (OS) and progression-free survival (PFS) curves of each cluster were compared. Univariate and multivariate Cox regression analyses were also performed.
Results: We successfully distinguished the multimodal distribution of cytokines through GMM clustering and discovered the relationship between cytokines and clinical outcomes. We observed that NTU-G3 and NTU-G4 subgroups showed most variation in 5-, 3-year OS and 5-, 3-year PFS with NTU-G3 being associated with poorer prognosis compared to NTU-G4 (p = 0.016, 0.0052, 0.0575, and 0.0168, respectively). NTU-G3 was characterized with higher TNF-α (median = 3.855, N = 78) and lower IL33 (median = 0.000, N = 78), while NTU-G4 showed lower TNF-α (median = 1.76, N = 51) and higher IL33 (median = 1.070, N = 51). The difference was statistically significant for TNF-α and IL33, with p = 0.0002 and p < 0.0001, respectively. A multivariate Cox-regression analysis revealed that GMM clustering and T/N stage were independent factors for prognosis, suggesting that the prognosis might be dependent on these cytokines.
Conclusions: Our data suggest that expression patterns of IL33 and TNF-α in plasma might serve as a convenient marker to predict the prognosis of ESCC in the future.
{"title":"Plasma Cytokines Pattern as a Prognostic Marker for Esophageal Squamous Cell Carcinoma via Unsupervised Clustering Analyses.","authors":"Cheng-Hsun Chuang, Pei-Ming Huang, Sung-Tzu Liang, Ke-Cheng Chen, Mong-Wei Lin, Shuenn-Wen Kuo, Hsien-Chi Liao, Jang-Ming Lee","doi":"10.1159/000541371","DOIUrl":"10.1159/000541371","url":null,"abstract":"<p><strong>Introduction: </strong>Cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL6), interferon-gamma (IFN-γ), interleukin 17-alpha (IL17-α), and interleukin 33 (IL33) play critical roles in immune responses and may impact cancer prognosis in future. However, few studies have simultaneously explored the prognostic impact of these cytokines for cancer. In this study, we aim to apply the unsupervised clustering analysis to approach the correlation between the expression of these cytokines and the subsequent prognosis of patients with esophageal squamous cell carcinoma (ESCC).</p><p><strong>Methods: </strong>A robust clustering algorithm was used, the Gaussian mixture method (GMM), through the mclust R package to group patients based on the expression of their cytokines in plasma or tumors. The 324 NTU patients were grouped into 4 clusters, and the 179 GSE53625 patients were grouped into 3 clusters based on expression in plasma and tumors, respectively. Five- and 3-year overall survival (OS) and progression-free survival (PFS) curves of each cluster were compared. Univariate and multivariate Cox regression analyses were also performed.</p><p><strong>Results: </strong>We successfully distinguished the multimodal distribution of cytokines through GMM clustering and discovered the relationship between cytokines and clinical outcomes. We observed that NTU-G3 and NTU-G4 subgroups showed most variation in 5-, 3-year OS and 5-, 3-year PFS with NTU-G3 being associated with poorer prognosis compared to NTU-G4 (p = 0.016, 0.0052, 0.0575, and 0.0168, respectively). NTU-G3 was characterized with higher TNF-α (median = 3.855, N = 78) and lower IL33 (median = 0.000, N = 78), while NTU-G4 showed lower TNF-α (median = 1.76, N = 51) and higher IL33 (median = 1.070, N = 51). The difference was statistically significant for TNF-α and IL33, with p = 0.0002 and p < 0.0001, respectively. A multivariate Cox-regression analysis revealed that GMM clustering and T/N stage were independent factors for prognosis, suggesting that the prognosis might be dependent on these cytokines.</p><p><strong>Conclusions: </strong>Our data suggest that expression patterns of IL33 and TNF-α in plasma might serve as a convenient marker to predict the prognosis of ESCC in the future.</p>","PeriodicalId":19497,"journal":{"name":"Oncology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142292673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wei Fang, Shan Chen, Di Wan, Yanhui Peng, Xiaoqin Yang
Introduction: Tongue squamous cell carcinoma (TSCC) is a common malignant tumour type with aggressive invasion and a poor prognosis. To date, invasion-related gene expression signatures for the prognostic stratification of TSCC patients are unavailable in clinical practice. This study aimed to assess the impact of invasion-related genes on the prognosis of TSCC patients.
Methods: We obtained mRNA profiles and clinical data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases (TCGA-TSCC and GSE41116, respectively). The TSCC samples from the TCGA-TSCC cohort were randomly divided into TCGA training and TCGA test datasets at a 7:3 ratio. Next, a disease-free survival (DFS) prognostic risk model was established on the basis of univariate and stepwise multivariate Cox regression analyses of the TCGA training cohort. Moreover, prognostic genes were screened. The model was subsequently evaluated and validated using the TCGA test and GSE41116 datasets. In addition, the prognostic genes were validated in the human TSCC cell line UM1 and the human oral keratinocyte (HOK) cell line using quantitative real-time polymerase chain reaction (qRT-PCR) analysis.
Results: A total of 70 candidate genes related to invasion were identified in the TCGA-TSCC cohort. DFS data were subsequently constructed, and 6 prognostic genes, HMGN2, MYL12B, ACTB, PPP1CA, PSMB9, and IFITM3, were identified. The TSCC samples were divided into high- and low-risk groups in the TCGA training, TCGA test, and GSE41116 cohorts, respectively. In particular, patients with TSCC in the low-risk group had longer DFS than those in the high-risk group. Furthermore, qRT-PCR analysis confirmed that the expression levels of the 6 prognostic genes were significantly greater in the TSCC cell line UM1 than in the HOK cell line.
Conclusion: This study identified new invasion-related target genes related to poor prognosis in TSCC patients, providing new insights into the underlying mechanisms of TSCC invasion.
{"title":"Identification and Validation of an Invasion-Related Disease-Free Survival Prognostic Model for Tongue Squamous Cell Carcinoma.","authors":"Wei Fang, Shan Chen, Di Wan, Yanhui Peng, Xiaoqin Yang","doi":"10.1159/000540977","DOIUrl":"https://doi.org/10.1159/000540977","url":null,"abstract":"<p><strong>Introduction: </strong>Tongue squamous cell carcinoma (TSCC) <underline>is</underline> a common malignant tumour type with aggressive invasion and a poor prognosis. To date, invasion-related gene expression signatures for the prognostic stratification of TSCC patients are unavailable in clinical practice. This study aimed to assess the impact of invasion-related genes on the prognosis of TSCC patients.</p><p><strong>Methods: </strong>We obtained mRNA profiles and clinical data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases (TCGA-TSCC and GSE41116, respectively). The TSCC samples from the TCGA-TSCC cohort were randomly divided into TCGA training and TCGA test datasets at a 7:3 ratio. Next, a disease-free survival (DFS) prognostic risk model was established on the basis of univariate and stepwise multivariate Cox regression analyses of the TCGA training cohort. Moreover, prognostic genes were screened. The model was subsequently evaluated and validated using the TCGA test and GSE41116 datasets. In addition, the prognostic genes were validated in the human TSCC cell line UM1 and the human oral keratinocyte (HOK) cell line using quantitative real-time polymerase chain reaction (qRT-PCR) analysis.</p><p><strong>Results: </strong>A total of 70 candidate genes related to invasion were identified in the TCGA-TSCC cohort. DFS data were subsequently constructed, and 6 prognostic genes, HMGN2, MYL12B, ACTB, PPP1CA, PSMB9, and IFITM3, were identified. The TSCC samples were divided into high- and low-risk groups in the TCGA training, TCGA test, and GSE41116 cohorts, respectively. In particular, patients with TSCC in the low-risk group had longer DFS than those in the high-risk group. Furthermore, qRT-PCR analysis confirmed that the expression levels of the 6 prognostic genes were significantly greater in the TSCC cell line UM1 than in the HOK cell line.</p><p><strong>Conclusion: </strong>This study identified new invasion-related target genes related to poor prognosis in TSCC patients, providing new insights into the underlying mechanisms of TSCC invasion.</p>","PeriodicalId":19497,"journal":{"name":"Oncology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142292671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jinmiao Wang, Jie Hao, Ying Gao, Shoujun Wang, Duowei Wang, Weijie Tao, Ran Duan, Zhendong Zhang, Ming Gao
Introduction: This study aimed to evaluate the clinical value of iodine-131 combined with levothyroxine sodium in the treatment of patients with differentiated thyroid cancer (DTC) after surgery.
Methods: Prospective randomized controlled studies were conducted. A total of 374 DTC patients who underwent total or near-total thyroidectomy in the Department of Thyroid Surgery, Tianjin Union Medical Center and Tianjin Medical University General Hospital, from January 2019 to February 2022 were selected and divided into control group (187 cases) and observation group (187 cases) according to random number table method. The control group was treated with levothyroxine sodium after surgery, and the observation group was treated with iodine-131 on the basis of the control group. Gender, age, course of disease, tumor diameter, pathological type, TNM classification, treatment effect, thyroglobulin (Tg) levels before and after treatment, SF-36 health status questionnaires (SF-36), occurrence of adverse reactions after treatment, and recurrence rate of 1-year follow-up were compared and analyzed between the two groups.
Results: There was no significant difference in baseline data between the two groups. After treatment, the effective rate of the observation group increased by 11.23% compared to the control group, with a statistically significant difference (91.98% vs. 80.75%, p < 0.05). There was no significant difference in Tg level and scores of SF-36 evaluation including physical functioning, physical problems, vitality, pain, mental health, emotional problems, social functioning, and general health perception between the two groups before surgery (p > 0.05), Tg levels and scores of SF-36 evaluation in all dimensions were significantly improved in both groups after treatment (p < 0.05), and the levels of Tg and scores of SF-36 in all dimensions in observation group were significantly better than those in control group after treatment (p < 0.001). There was no significant difference in the incidence of adverse reactions between the two groups (p > 0.05). The recurrence rate in the observation group was 5.89% lower than that in the control group 1 year after treatment, with a statistically significant difference (2.67% vs. 8.56%, p < 0.05).
Conclusions: The combination of iodine-131 and levothyroxine sodium in the postoperative treatment of DTC can improve the therapeutic effect and reduce the postoperative recurrence rate without increasing adverse reactions, which is worthy of clinical reference and promotion.
简介本研究旨在评估碘 131 联合左甲状腺素钠治疗术后分化型甲状腺癌(DTC)患者的临床价值:方法:进行前瞻性随机对照研究。选取2019年1月至2022年2月在天津协和医院、天津医科大学总医院甲状腺外科行甲状腺全切或近全切术的DTC患者共374例,按随机数字表法分为对照组(187例)和观察组(187例)。对照组术后使用左甲状腺素钠治疗,观察组在对照组基础上使用碘-131治疗。比较分析两组患者的性别、年龄、病程、肿瘤直径、病理类型、TNM分型、治疗效果、治疗前后甲状腺球蛋白(Tg)水平、SF-36健康状况问卷(SF-36)、治疗后不良反应发生情况以及随访一年的复发率:结果:两组基线数据无明显差异。治疗后,观察组有效率比对照组提高了 11.23%,差异有统计学意义(91.98% vs. 80.75%,P<0.05)。两组患者术前Tg水平及SF-36评价包括身体功能、身体问题、活力、疼痛、心理健康、情绪问题、社会功能、一般健康知觉的评分无明显差异(P>0.05),治疗后两组患者Tg水平及SF-36评价各维度评分均有明显改善(P<0.05),且治疗后观察组Tg水平及SF-36各维度评分均明显优于对照组(P<0.001)。两组不良反应发生率无明显差异(P>0.05)。治疗一年后,观察组的复发率比对照组低 5.89%,差异有统计学意义(2.67% vs. 8.56%,P<0.05):碘131与左甲状腺素钠联合应用于分化型甲状腺癌术后治疗,可提高疗效,降低术后复发率,且不增加不良反应,值得临床借鉴与推广。
{"title":"Application Value of Iodine-131 Combined with Levothyroxine Sodium in Patients with Differentiated Thyroid Cancer after Surgery.","authors":"Jinmiao Wang, Jie Hao, Ying Gao, Shoujun Wang, Duowei Wang, Weijie Tao, Ran Duan, Zhendong Zhang, Ming Gao","doi":"10.1159/000541546","DOIUrl":"10.1159/000541546","url":null,"abstract":"<p><strong>Introduction: </strong>This study aimed to evaluate the clinical value of iodine-131 combined with levothyroxine sodium in the treatment of patients with differentiated thyroid cancer (DTC) after surgery.</p><p><strong>Methods: </strong>Prospective randomized controlled studies were conducted. A total of 374 DTC patients who underwent total or near-total thyroidectomy in the Department of Thyroid Surgery, Tianjin Union Medical Center and Tianjin Medical University General Hospital, from January 2019 to February 2022 were selected and divided into control group (187 cases) and observation group (187 cases) according to random number table method. The control group was treated with levothyroxine sodium after surgery, and the observation group was treated with iodine-131 on the basis of the control group. Gender, age, course of disease, tumor diameter, pathological type, TNM classification, treatment effect, thyroglobulin (Tg) levels before and after treatment, SF-36 health status questionnaires (SF-36), occurrence of adverse reactions after treatment, and recurrence rate of 1-year follow-up were compared and analyzed between the two groups.</p><p><strong>Results: </strong>There was no significant difference in baseline data between the two groups. After treatment, the effective rate of the observation group increased by 11.23% compared to the control group, with a statistically significant difference (91.98% vs. 80.75%, p < 0.05). There was no significant difference in Tg level and scores of SF-36 evaluation including physical functioning, physical problems, vitality, pain, mental health, emotional problems, social functioning, and general health perception between the two groups before surgery (p > 0.05), Tg levels and scores of SF-36 evaluation in all dimensions were significantly improved in both groups after treatment (p < 0.05), and the levels of Tg and scores of SF-36 in all dimensions in observation group were significantly better than those in control group after treatment (p < 0.001). There was no significant difference in the incidence of adverse reactions between the two groups (p > 0.05). The recurrence rate in the observation group was 5.89% lower than that in the control group 1 year after treatment, with a statistically significant difference (2.67% vs. 8.56%, p < 0.05).</p><p><strong>Conclusions: </strong>The combination of iodine-131 and levothyroxine sodium in the postoperative treatment of DTC can improve the therapeutic effect and reduce the postoperative recurrence rate without increasing adverse reactions, which is worthy of clinical reference and promotion.</p>","PeriodicalId":19497,"journal":{"name":"Oncology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142292658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Diluka Pinto, Mallika Dhanda, Amit Agarwal, George Hsy He, Jolene Li Ling Chia, Rajeev Parameswaran
Background: Preoperative diagnosis of parathyroid cancer (PC) where possible allows for en-bloc resection of the tumour, which is associated with excellent prognosis. The rule of >3 (size of tumour larger than 3 cm; corrected calcium more than 3 mmol/L) as proposed by Schulte and Talat has a specificity of 95% in predicting malignancy in parathyroid neoplasms. We looked at the impact of rule of 3 in predicting malignancy and outcomes on intervention in a South Asian cohort.
Methods: Patients who underwent parathyroid surgery between 2010 and 2023 at two tertiary referral centres were assessed. Patients with PC were selected and their clinicopathological parameters, treatment modalities, and outcomes were analysed.
Results: Thirteen of 336 (3.8%) patients with a mean age of 61.8 (±17.5) years were diagnosed with PC during the study period. The highest mean preoperative values were PTH (92.4 ± 66.27 pmol/L), highest corrected calcium (3.21 ± 0.28 mmol/L), and alkaline phosphatase (419 IU/mL). Nine patients underwent en-bloc excision while the other had focussed parathyroidectomy. Recurrences were recorded in 2 (28.5%) patients over a mean follow-up period of 69 (±48.6) months. One patient with lung metastasis underwent video-assisted thoracic surgery. There was no disease specific mortality in this cohort during the study period.
Conclusions: In our experience, the predictive rule of 3 has low sensitivity to suspect PC preoperatively, resulting in limited usefulness in clinical practice. Outcomes appear to be less favourable with higher recurrence rates in cases where less than en-bloc resection is performed.
{"title":"Predictive Ability of Rule of 3 in Parathyroid Cancer: Outcomes from a South Asian Cohort.","authors":"Diluka Pinto, Mallika Dhanda, Amit Agarwal, George Hsy He, Jolene Li Ling Chia, Rajeev Parameswaran","doi":"10.1159/000541543","DOIUrl":"10.1159/000541543","url":null,"abstract":"<p><strong>Background: </strong>Preoperative diagnosis of parathyroid cancer (PC) where possible allows for en-bloc resection of the tumour, which is associated with excellent prognosis. The rule of >3 (size of tumour larger than 3 cm; corrected calcium more than 3 mmol/L) as proposed by Schulte and Talat has a specificity of 95% in predicting malignancy in parathyroid neoplasms. We looked at the impact of rule of 3 in predicting malignancy and outcomes on intervention in a South Asian cohort.</p><p><strong>Methods: </strong>Patients who underwent parathyroid surgery between 2010 and 2023 at two tertiary referral centres were assessed. Patients with PC were selected and their clinicopathological parameters, treatment modalities, and outcomes were analysed.</p><p><strong>Results: </strong>Thirteen of 336 (3.8%) patients with a mean age of 61.8 (±17.5) years were diagnosed with PC during the study period. The highest mean preoperative values were PTH (92.4 ± 66.27 pmol/L), highest corrected calcium (3.21 ± 0.28 mmol/L), and alkaline phosphatase (419 IU/mL). Nine patients underwent en-bloc excision while the other had focussed parathyroidectomy. Recurrences were recorded in 2 (28.5%) patients over a mean follow-up period of 69 (±48.6) months. One patient with lung metastasis underwent video-assisted thoracic surgery. There was no disease specific mortality in this cohort during the study period.</p><p><strong>Conclusions: </strong>In our experience, the predictive rule of 3 has low sensitivity to suspect PC preoperatively, resulting in limited usefulness in clinical practice. Outcomes appear to be less favourable with higher recurrence rates in cases where less than en-bloc resection is performed.</p>","PeriodicalId":19497,"journal":{"name":"Oncology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142292674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: Evidence of biliary invasion as a prognostic factor in patients with hepatocellular carcinoma (HCC) is unclear. We aimed to verify the significance of clinically diagnosed biliary involvement in patients with Barcelona Clinic Liver Cancer stage B-C (BCLC B-C) HCC.
Methods: The Korean Liver Cancer Study Group randomly extracted data of patients with HCC enrolled in the Korean Central Cancer Registry between 2011 and 2016 from approximately 50 hospitals nationwide. After excluding records without information regarding serum bilirubin level, alpha-fetoprotein (AFP) level, and Child-Pugh class, a pre-propensity score matching cohort comprising 4,077 patients was included. Considering age, sex, body mass index, viral cause, serum bilirubin level, AFP, Child-Pugh class, tumor size, multiplicity, portal invasion, and extrahepatic metastasis, patients with and without bile duct invasion at initial imaging diagnosis were matched at a ratio of 1:2 from the pre-propensity score matching cohort to form a matched cohort (propensity score matching cohort).
Results: The pre-propensity score matching cohort included 4,077 patients with BCLC B-C and 165 (4.0%) with biliary invasion at diagnosis. Regarding biliary invasion at diagnosis, 1- and 2-year overall survival (OS) rates were 41.2% and 29.1% (with invasion) and 54% and 40.9% (without invasion), respectively (p < 0.0001). Corresponding cancer-specific survival (CSS) rates at 1 and 2 years were 43.4% and 30.7% (with invasion) and 56.6% and 44% (without invasion), respectively (p < 0.0001). Although biliary invasion was a significant factor affecting overall and CSS rates in a univariate analysis, it was not statistically significant in multivariate analyses for overall (p = 0.153) and cancer-specific (p = 0.198) survival rates. The propensity score matching cohort included 165 patients with biliary invasion at diagnosis and 330 without biliary invasion. In the propensity score matching cohort, biliary invasion at diagnosis was not a significant factor affecting overall (p = 0.603) or cancer-specific (p = 0.960) survival rates in the univariate analyses. One- and 2-year OS were 41.2% and 29.1% (with invasion) and 36.1% and 28.2% (without invasion), respectively. The corresponding CSS at one and 2 years were 43.4% and 30.7% (with invasion) and 39.8% and 31.4% (without invasion), respectively. Multivariate analyses revealed that AFP levels, Child-Pugh class, tumor singularity, tumor size, portal invasion, lymph node metastases, and distant metastases significantly affected both overall and CSS rates.
Conclusion: Biliary invasion at diagnosis in patients with BCLC B-C does not affect overall or CSS rates; however, other prognostic factors associated with biliary invasion could have a greater impact.
{"title":"Clinical Significance of Biliary Invasion at Diagnosis in Barcelona Clinic Liver Cancer Stage B-C Hepatocellular Carcinoma: A Nationwide Cohort Analysis in South Korea.","authors":"Chai Hong Rim, Won Sup Yoon, Sunmin Park","doi":"10.1159/000541545","DOIUrl":"10.1159/000541545","url":null,"abstract":"<p><strong>Introduction: </strong>Evidence of biliary invasion as a prognostic factor in patients with hepatocellular carcinoma (HCC) is unclear. We aimed to verify the significance of clinically diagnosed biliary involvement in patients with Barcelona Clinic Liver Cancer stage B-C (BCLC B-C) HCC.</p><p><strong>Methods: </strong>The Korean Liver Cancer Study Group randomly extracted data of patients with HCC enrolled in the Korean Central Cancer Registry between 2011 and 2016 from approximately 50 hospitals nationwide. After excluding records without information regarding serum bilirubin level, alpha-fetoprotein (AFP) level, and Child-Pugh class, a pre-propensity score matching cohort comprising 4,077 patients was included. Considering age, sex, body mass index, viral cause, serum bilirubin level, AFP, Child-Pugh class, tumor size, multiplicity, portal invasion, and extrahepatic metastasis, patients with and without bile duct invasion at initial imaging diagnosis were matched at a ratio of 1:2 from the pre-propensity score matching cohort to form a matched cohort (propensity score matching cohort).</p><p><strong>Results: </strong>The pre-propensity score matching cohort included 4,077 patients with BCLC B-C and 165 (4.0%) with biliary invasion at diagnosis. Regarding biliary invasion at diagnosis, 1- and 2-year overall survival (OS) rates were 41.2% and 29.1% (with invasion) and 54% and 40.9% (without invasion), respectively (p < 0.0001). Corresponding cancer-specific survival (CSS) rates at 1 and 2 years were 43.4% and 30.7% (with invasion) and 56.6% and 44% (without invasion), respectively (p < 0.0001). Although biliary invasion was a significant factor affecting overall and CSS rates in a univariate analysis, it was not statistically significant in multivariate analyses for overall (p = 0.153) and cancer-specific (p = 0.198) survival rates. The propensity score matching cohort included 165 patients with biliary invasion at diagnosis and 330 without biliary invasion. In the propensity score matching cohort, biliary invasion at diagnosis was not a significant factor affecting overall (p = 0.603) or cancer-specific (p = 0.960) survival rates in the univariate analyses. One- and 2-year OS were 41.2% and 29.1% (with invasion) and 36.1% and 28.2% (without invasion), respectively. The corresponding CSS at one and 2 years were 43.4% and 30.7% (with invasion) and 39.8% and 31.4% (without invasion), respectively. Multivariate analyses revealed that AFP levels, Child-Pugh class, tumor singularity, tumor size, portal invasion, lymph node metastases, and distant metastases significantly affected both overall and CSS rates.</p><p><strong>Conclusion: </strong>Biliary invasion at diagnosis in patients with BCLC B-C does not affect overall or CSS rates; however, other prognostic factors associated with biliary invasion could have a greater impact.</p>","PeriodicalId":19497,"journal":{"name":"Oncology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142292660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ahmed A Refae, Rafat I Abu Shakra, Ezzeldin M Ibrahim
Introduction: Patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations face poor outcomes after progression on tyrosine kinase inhibitors (TKIs). The efficacy of immune checkpoint inhibitors (ICIs) combined with chemotherapy in these patients remains uncertain.
Methods: We searched for studies published between randomized controlled trials of ICIs in combination therapies in advanced NSCLC patients post-EGFR TKI progression. Data on progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) were extracted and analyzed.
Results: Six studies with a total of 2,225 patients were analyzed. The pooled hazard ratio (HR) for PFS was 0.60 (95% CI, 0.55-0.65; p < 0.0001), indicating a significant improvement in PFS with ICIs. Subgroup analysis suggested that patients with prior exposure to third-generation TKIs showed a more pronounced benefit (HR = 0.61; 95% CI, 0.49-0.76; p < 0.0001). However, no benefit was found in patients without prior exposure. The efficacy of the experimental interventions was also shown on the pooled estimates of OS (HR = 0.87; 95% CI, 0.77-0.0.99; p value = 0.04) and ORR (OR = 1.91; 95% CI, 1.32-2.76; p < 0.0001).
Conclusion: ICIs may significantly benefit PFS among patients with EGFR-mutated NSCLC who have progressed on TKI treatment. Future research should continue stratifying patients based on prior treatment exposure to optimize therapeutic strategies.
{"title":"Immunotherapy plus Chemotherapy for Patients with EGFR-Mutated Non-Squamous Cell Lung Cancer for Disease Progression after EGFR Tyrosine-Kinase Inhibitor: A Meta-Analysis of Randomized Controlled Trials.","authors":"Ahmed A Refae, Rafat I Abu Shakra, Ezzeldin M Ibrahim","doi":"10.1159/000541415","DOIUrl":"10.1159/000541415","url":null,"abstract":"<p><strong>Introduction: </strong>Patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations face poor outcomes after progression on tyrosine kinase inhibitors (TKIs). The efficacy of immune checkpoint inhibitors (ICIs) combined with chemotherapy in these patients remains uncertain.</p><p><strong>Methods: </strong>We searched for studies published between randomized controlled trials of ICIs in combination therapies in advanced NSCLC patients post-EGFR TKI progression. Data on progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) were extracted and analyzed.</p><p><strong>Results: </strong>Six studies with a total of 2,225 patients were analyzed. The pooled hazard ratio (HR) for PFS was 0.60 (95% CI, 0.55-0.65; p < 0.0001), indicating a significant improvement in PFS with ICIs. Subgroup analysis suggested that patients with prior exposure to third-generation TKIs showed a more pronounced benefit (HR = 0.61; 95% CI, 0.49-0.76; p < 0.0001). However, no benefit was found in patients without prior exposure. The efficacy of the experimental interventions was also shown on the pooled estimates of OS (HR = 0.87; 95% CI, 0.77-0.0.99; p value = 0.04) and ORR (OR = 1.91; 95% CI, 1.32-2.76; p < 0.0001).</p><p><strong>Conclusion: </strong>ICIs may significantly benefit PFS among patients with EGFR-mutated NSCLC who have progressed on TKI treatment. Future research should continue stratifying patients based on prior treatment exposure to optimize therapeutic strategies.</p>","PeriodicalId":19497,"journal":{"name":"Oncology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142292672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Su Ho Kim, Jung Suk Oh, Chang Ho Jeon, Ho Jong Chun, Byung Gil Choi
Introduction: This study aimed to assess the effectiveness and safety of hepatic arterial infusion chemotherapy (HAIC) in 2 groups of patients: those who receive lipiodol (referred to as the lipiodol group) and those who do not receive lipiodol (referred to as the control group).
Methods: From January 2016 through December 2023, 85 patients with advanced hepatocellular carcinoma were enrolled in this retrospective study. In total, 40 patients received HAIC with lipiodol, while 45 patients were given HAIC without lipiodol. The modified response evaluation criteria for solid tumors were used to evaluate the tumor response, which was assessed through an imaging study. The two groups were compared regarding their overall survival (OS), progression-free survival (PFS), and safety.
Results: The outcomes between the lipiodol group and control group demonstrated no significant difference: the objective response rates (p = 0.066) were 32.5% and 15.6%; the disease control rates (p = 0.556) were 67.5% and 73.3%; the median OS times (p = 0.339) were 224 days and 398 days; the median PFS (p = 0.334) times were 191 days and 286 days in the lipiodol group and the control group, respectively. Adverse events also showed no significant difference between the two groups: elevation of total bilirubin (p = 0.834) rates were 40.0% and 37.8%; elevation of alanine aminotransferase (p = 0.191) percentages were 35.0% and 22.2%; and elevation of aspartate aminotransferase values (p = 0.058) were 65.0% and 44.4% in the lipiodol group and the control group, respectively.
Conclusions: HAIC without lipiodol was non-inferior to HAIC with lipiodol in the clinical outcome.
{"title":"Clinical Effects and Safety of Intra-Arterial Infusion Chemotherapy with Lipiodol versus Intra-Arterial Infusion Chemotherapy Alone for Treatment of Advanced Hepatocellular Carcinoma.","authors":"Su Ho Kim, Jung Suk Oh, Chang Ho Jeon, Ho Jong Chun, Byung Gil Choi","doi":"10.1159/000541114","DOIUrl":"10.1159/000541114","url":null,"abstract":"<p><strong>Introduction: </strong>This study aimed to assess the effectiveness and safety of hepatic arterial infusion chemotherapy (HAIC) in 2 groups of patients: those who receive lipiodol (referred to as the lipiodol group) and those who do not receive lipiodol (referred to as the control group).</p><p><strong>Methods: </strong>From January 2016 through December 2023, 85 patients with advanced hepatocellular carcinoma were enrolled in this retrospective study. In total, 40 patients received HAIC with lipiodol, while 45 patients were given HAIC without lipiodol. The modified response evaluation criteria for solid tumors were used to evaluate the tumor response, which was assessed through an imaging study. The two groups were compared regarding their overall survival (OS), progression-free survival (PFS), and safety.</p><p><strong>Results: </strong>The outcomes between the lipiodol group and control group demonstrated no significant difference: the objective response rates (p = 0.066) were 32.5% and 15.6%; the disease control rates (p = 0.556) were 67.5% and 73.3%; the median OS times (p = 0.339) were 224 days and 398 days; the median PFS (p = 0.334) times were 191 days and 286 days in the lipiodol group and the control group, respectively. Adverse events also showed no significant difference between the two groups: elevation of total bilirubin (p = 0.834) rates were 40.0% and 37.8%; elevation of alanine aminotransferase (p = 0.191) percentages were 35.0% and 22.2%; and elevation of aspartate aminotransferase values (p = 0.058) were 65.0% and 44.4% in the lipiodol group and the control group, respectively.</p><p><strong>Conclusions: </strong>HAIC without lipiodol was non-inferior to HAIC with lipiodol in the clinical outcome.</p>","PeriodicalId":19497,"journal":{"name":"Oncology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142292659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
INTRODUCTIONIn atezolizumab plus bevacizumab (Atezo/Bev) combination treatment, both drugs act on the immune system. Previously we reported that immunological changes after Atezo/Bev administration for unresectable hepatocellular carcinoma (uHCC) revealed significant alterations in interleukin (IL)-6, soluble IL-2 receptor, tumor necrosis factor-alpha, and programmed cell death-1 levels. Among these variable factors, serum levels of IL-6 can be easily measured on a commercial baias. Therefore, this study aimed to investigate the utility of serum IL-6 as a predictor of tumor response to Atezo/Bev treatment for uHCC.METHODSThe study included 44 patients with HCC treated with Atezo/Bev. Blood samples were collected before and 3 weeks after treatment, and tumor response was assessed using contrast-enhanced computed tomography 6 weeks after treatment.RESULTSSignificant changes in serum IL-6 levels were observed in patients treated with Atezo/Bev as first-line therapy but not in those treated with it as second line or later-line therapy. In patients treated with Atezo/Bev as first-line therapy, serum IL-6 levels increased significantly after treatment in patients with a complete or partial response but not in patients with stable or progressive disease. Furthermore, compared to other tumor markers such as alpha-fetoprotein, lens culinaris agglutinin-reactive fraction of alpha-fetoprotein, and des-gamma-carboxyprothrombin, serum IL-6 levels exhibited the highest sensitivity in predicting tumor response during the treatment period.CONCLUSIONIn patients with uHCC treated with Atezo/Bev, serum IL-6 levels could serve as a potential predictor of tumor response. Elevated levels after treatment may indicate a favorable tumor response and prognosis.
{"title":"The usefulness of serum interleukin-6 as a predictor of response to atezolizumab plus bevacizumab combination treatment in hepatocellular carcinoma.","authors":"Takanori Mukozu,Hidenari Nagai,Hideki Nagumo,Kunihide Mohri,Naoyuki Yoshimine,Kojiro Kobayashi,Yu Ogino,Teppei Matsui,Yasuko Daido,Noritaka Wakui,Koichi Momiyama,Koji Higai,Takahisa Matsuda,Yoshinori Igarashi","doi":"10.1159/000541372","DOIUrl":"https://doi.org/10.1159/000541372","url":null,"abstract":"INTRODUCTIONIn atezolizumab plus bevacizumab (Atezo/Bev) combination treatment, both drugs act on the immune system. Previously we reported that immunological changes after Atezo/Bev administration for unresectable hepatocellular carcinoma (uHCC) revealed significant alterations in interleukin (IL)-6, soluble IL-2 receptor, tumor necrosis factor-alpha, and programmed cell death-1 levels. Among these variable factors, serum levels of IL-6 can be easily measured on a commercial baias. Therefore, this study aimed to investigate the utility of serum IL-6 as a predictor of tumor response to Atezo/Bev treatment for uHCC.METHODSThe study included 44 patients with HCC treated with Atezo/Bev. Blood samples were collected before and 3 weeks after treatment, and tumor response was assessed using contrast-enhanced computed tomography 6 weeks after treatment.RESULTSSignificant changes in serum IL-6 levels were observed in patients treated with Atezo/Bev as first-line therapy but not in those treated with it as second line or later-line therapy. In patients treated with Atezo/Bev as first-line therapy, serum IL-6 levels increased significantly after treatment in patients with a complete or partial response but not in patients with stable or progressive disease. Furthermore, compared to other tumor markers such as alpha-fetoprotein, lens culinaris agglutinin-reactive fraction of alpha-fetoprotein, and des-gamma-carboxyprothrombin, serum IL-6 levels exhibited the highest sensitivity in predicting tumor response during the treatment period.CONCLUSIONIn patients with uHCC treated with Atezo/Bev, serum IL-6 levels could serve as a potential predictor of tumor response. Elevated levels after treatment may indicate a favorable tumor response and prognosis.","PeriodicalId":19497,"journal":{"name":"Oncology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142255258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background This study aimed to evaluate the clinical impact of skeletal muscle mass and nutritional status in gastric cancer patients treated with nivolumab monotherapy as late-line treatment. Methods We conducted a multi-institutional retrospective study of 90 gastric cancer patients who previously received anti-PD-1 therapy (nivolumab). On computed tomography images captured before nivolumab induction, the skeletal muscle index (SMI, cm2/m2) was defined as the erector muscle area (cm2) divided by the height (m) squared. Patients were divided into two groups: those with SMI-high (n = 45) and those with SMI-low (n = 45). Prognostic nutritional index (PNI) was also calculated before nivolumab induction. The associations of SMI and PNI with response rate (RR), progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and safety were analyzed. Results The cutoff values for SMI were determined as 13.45 for males and 10.41 for females. SMI-high was significantly associated with a higher RR (odds ratio = 12.36, p = 0.02) and DCR (odds ratio = 2.97, p = 0.02). Although not significant, PNI-high also tended to be associated with a higher RR. Multivariate analysis showed that SMI-high was independently associated with a higher RR and higher DCR in gastric cancer. Moreover, prognostic analyses revealed that SMI-high (log-rank test p = 0.008) and PNI-high (log-rank test p = 0.0008) were significantly associated with longer OS since nivolumab induction. SMI-high was also associated with longer PFS (log-rank test p = 0.03). There were no significant differences in irAE between SMI-low and SMI-high. Conclusions SMI and PNI were associated with nivolumab efficacy in gastric cancer patients. Management of skeletal muscle loss and nutritional status in gastric cancer patients who will receive nivolumab would be beneficial to enhance survival outcomes.
{"title":"Clinical impact of skeletal muscle mass and nutritional status in patients with recurrent or advanced gastric cancer treated with nivolumab.","authors":"Qingjiang Hu,Kensuke Kudo,Takafumi Yukaya,Hirofumi Hasuda,Ryota Nakanishi,Tomonori Nakanoko,Koji Ando,Mitsuhiko Ota,Yasue Kimura,Tadashi Koga,Tetsuya Kusumoto,Eiji Oki,Tomoharu Yoshizumi","doi":"10.1159/000540840","DOIUrl":"https://doi.org/10.1159/000540840","url":null,"abstract":"Background This study aimed to evaluate the clinical impact of skeletal muscle mass and nutritional status in gastric cancer patients treated with nivolumab monotherapy as late-line treatment. Methods We conducted a multi-institutional retrospective study of 90 gastric cancer patients who previously received anti-PD-1 therapy (nivolumab). On computed tomography images captured before nivolumab induction, the skeletal muscle index (SMI, cm2/m2) was defined as the erector muscle area (cm2) divided by the height (m) squared. Patients were divided into two groups: those with SMI-high (n = 45) and those with SMI-low (n = 45). Prognostic nutritional index (PNI) was also calculated before nivolumab induction. The associations of SMI and PNI with response rate (RR), progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and safety were analyzed. Results The cutoff values for SMI were determined as 13.45 for males and 10.41 for females. SMI-high was significantly associated with a higher RR (odds ratio = 12.36, p = 0.02) and DCR (odds ratio = 2.97, p = 0.02). Although not significant, PNI-high also tended to be associated with a higher RR. Multivariate analysis showed that SMI-high was independently associated with a higher RR and higher DCR in gastric cancer. Moreover, prognostic analyses revealed that SMI-high (log-rank test p = 0.008) and PNI-high (log-rank test p = 0.0008) were significantly associated with longer OS since nivolumab induction. SMI-high was also associated with longer PFS (log-rank test p = 0.03). There were no significant differences in irAE between SMI-low and SMI-high. Conclusions SMI and PNI were associated with nivolumab efficacy in gastric cancer patients. Management of skeletal muscle loss and nutritional status in gastric cancer patients who will receive nivolumab would be beneficial to enhance survival outcomes.","PeriodicalId":19497,"journal":{"name":"Oncology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142269060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
INTRODUCTIONAtezolizumab (ATZ) and bevacizumab (BEV) combination therapy is widely used in patients with unresectable hepatocellular carcinoma (HCC). However, combination therapy is typically interrupted or discontinued owing to BEV-related adverse events. In this study, we examined the effects of BEV dose-reduction on the treatment of unresectable HCC using propensity score matching (PSM).METHODOverall, 119 patients with HCC who were treated with ATZ + BEV between November 2020 and October 2022 were enrolled retrospectively at our institute. The therapeutic effects and safety of BEV dose-reduction and non-dose reduction after PSM were compared. Decision-tree analysis was used to investigate treatment duration in the patients.RESULTSSignificant differences were not observed between the two groups after PSM. The objective response rate (ORR) and disease control rate (DCR) assessed by modified RECIST did not differ significantly between the two groups (BEV non-dose-reduction/dose-reduction: ORR; 46/34%, DCR; 80/91%). Progression-free survival (PFS) and overall survival (OS) also did not differ significantly between the two groups (BEV non-dose-reduction /dose-reduction: PFS; 5.6/8.6 months, OS; 18.6/15.5 months). The median duration of treatment in the BEV dose-reduction group was significantly longer than that in the non-dose-reduction group (BEV non-dose-reduction /dose-reduction: 4.8/9.1 months, P = 0.038). Decision-tree analysis revealed that dose-reduction of BEV was the first distinguishae factor for the extension of treatment duration with ATZ + BEV.CONCLUSIONBEV dose-reduction can be effectively used in maintaining the treatment duration of ATZ + BEV while maintaining therapeutic effects and safety in real-world clinical practice.
{"title":"Dose-reduction of bevacizumab in atezolizumab plus bevacizumab therapy extends treatment duration with disease control in patients with hepatocellular carcinoma.","authors":"Miwa Sakai,Hideki Iwamoto,Shigeo Shimose,Takashi Niizeki,Masahito Nakano,Tomotake Shirono,Yu Noda,Etsuko Moriyama,Hiroyuki Suzuki,Hironori Koga,Ryoko Kuromatsu,Takumi Kawaguchi","doi":"10.1159/000541082","DOIUrl":"https://doi.org/10.1159/000541082","url":null,"abstract":"INTRODUCTIONAtezolizumab (ATZ) and bevacizumab (BEV) combination therapy is widely used in patients with unresectable hepatocellular carcinoma (HCC). However, combination therapy is typically interrupted or discontinued owing to BEV-related adverse events. In this study, we examined the effects of BEV dose-reduction on the treatment of unresectable HCC using propensity score matching (PSM).METHODOverall, 119 patients with HCC who were treated with ATZ + BEV between November 2020 and October 2022 were enrolled retrospectively at our institute. The therapeutic effects and safety of BEV dose-reduction and non-dose reduction after PSM were compared. Decision-tree analysis was used to investigate treatment duration in the patients.RESULTSSignificant differences were not observed between the two groups after PSM. The objective response rate (ORR) and disease control rate (DCR) assessed by modified RECIST did not differ significantly between the two groups (BEV non-dose-reduction/dose-reduction: ORR; 46/34%, DCR; 80/91%). Progression-free survival (PFS) and overall survival (OS) also did not differ significantly between the two groups (BEV non-dose-reduction /dose-reduction: PFS; 5.6/8.6 months, OS; 18.6/15.5 months). The median duration of treatment in the BEV dose-reduction group was significantly longer than that in the non-dose-reduction group (BEV non-dose-reduction /dose-reduction: 4.8/9.1 months, P = 0.038). Decision-tree analysis revealed that dose-reduction of BEV was the first distinguishae factor for the extension of treatment duration with ATZ + BEV.CONCLUSIONBEV dose-reduction can be effectively used in maintaining the treatment duration of ATZ + BEV while maintaining therapeutic effects and safety in real-world clinical practice.","PeriodicalId":19497,"journal":{"name":"Oncology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142255261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}