Pub Date : 2024-12-01Epub Date: 2024-05-30DOI: 10.1007/s12094-024-03494-5
Xiangkai Wei, Guoliang Zhang, Qian Liu, Zhiyuan Niu, Chunhong Chu, Chenxue Liu, Ke Wang, Lanxin Li, Rui Wang, Wenrui Cui, Huixia Xu, Chenyang Liu, Ying Wang, Lei An
Purpose: EGFR classical mutations respond well to EGFR tyrosine kinase inhibitors. However, it is uncertain whether currently available EGFR-TKIs are effective against rare EGFR mutations and compound mutations. Herein, the effectiveness of almonertinib and alflutinib, the third-generation tyrosine kinase inhibitors developed in China, on rare EGFR S768I mutations and compound mutations is identified.
Methods: In this study, using CRISPR method, four EGFR S768I mutation cell lines were constructed, and the sensitivity of EGFR to almonertinib and alflutinib was tested, with positive controls being the 1st (gefitinib), 2nd (afatinib), and 3rd (osimertinib) generation drugs.
Results: The present results indicate that almonertinib and alflutinib can effectively inhibit cell viability and proliferation in rare EGFR S768I mutations through the ERK or AKT pathways in a time-dependent manner, by blocking the cell cycle and inhibiting apoptosis.
Conclusions: These findings suggest that almonertinib and alflutinib may be potential therapeutic options for non-small cell lung cancer patients with the EGFR S768I mutation.
{"title":"Almonertinib and alflutinib show novel inhibition on rare EGFR S768I mutant cells.","authors":"Xiangkai Wei, Guoliang Zhang, Qian Liu, Zhiyuan Niu, Chunhong Chu, Chenxue Liu, Ke Wang, Lanxin Li, Rui Wang, Wenrui Cui, Huixia Xu, Chenyang Liu, Ying Wang, Lei An","doi":"10.1007/s12094-024-03494-5","DOIUrl":"10.1007/s12094-024-03494-5","url":null,"abstract":"<p><strong>Purpose: </strong>EGFR classical mutations respond well to EGFR tyrosine kinase inhibitors. However, it is uncertain whether currently available EGFR-TKIs are effective against rare EGFR mutations and compound mutations. Herein, the effectiveness of almonertinib and alflutinib, the third-generation tyrosine kinase inhibitors developed in China, on rare EGFR S768I mutations and compound mutations is identified.</p><p><strong>Methods: </strong>In this study, using CRISPR method, four EGFR S768I mutation cell lines were constructed, and the sensitivity of EGFR to almonertinib and alflutinib was tested, with positive controls being the 1st (gefitinib), 2nd (afatinib), and 3rd (osimertinib) generation drugs.</p><p><strong>Results: </strong>The present results indicate that almonertinib and alflutinib can effectively inhibit cell viability and proliferation in rare EGFR S768I mutations through the ERK or AKT pathways in a time-dependent manner, by blocking the cell cycle and inhibiting apoptosis.</p><p><strong>Conclusions: </strong>These findings suggest that almonertinib and alflutinib may be potential therapeutic options for non-small cell lung cancer patients with the EGFR S768I mutation.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"3100-3115"},"PeriodicalIF":2.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141176823","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}
Pub Date : 2024-12-01Epub Date: 2024-05-24DOI: 10.1007/s12094-024-03525-1
Qi Yan, Rong Li, Jiayang Yang, Xueqi Bai, Xiudong Guo, Xin Yang, Jianbo Song
Background: Whole-brain radiotherapy (WBRT) is a standard and effective approach for brain metastases, but it is linked to neurocognitive complications, specifically issues related to the hippocampus. Innovative strategies are being explored to enhance outcomes. However, a consensus is yet to be reached in this field. Our aim is to investigate the efficacy and safety of WBRT combined with simultaneous integrated boost (SIB), memantine, and hippocampal avoidance (HA) techniques in treatment of brain metastases.
Methods: In this systematic review and meta-analysis, we comprehensively searched PubMed, MEDLINE, Embase, and Cochrane for studies reporting the efficacy and toxicity of WBRT-based combination therapies from inception to September 19, 2023. Data were pooled using random-effects models. Results were reported as risk ratios (RRs) and risk differences (RDs) for dichotomous outcomes, along with their 95% confidence intervals (CIs). Heterogeneity was evaluated using the I2 statistic.
Results: Among 2175 articles, 29 studies involving 3460 patients were included. The meta-analysis revealed that compared to WBRT alone, combination therapies significantly mitigated neurocognitive function decline (RD = -0.09, 95% CI [-0.18-0.01]; P = 0.03) and intracranial control failure (RR = 0.86, 95% CI [0.52-1.44]; P = 0.02), without increasing the risk of hippocampal recurrence or high-grade toxicities. Notably, HA-WBRT + SIB/memantine demonstrated improved neurocognitive outcomes and survival benefits.
Conclusion: WBRT-based combination therapies demonstrate improved efficacy and comparable safety to WBRT alone, with specific emphasis on the effectiveness of HA-WBRT + Memantine and HA-WBRT + SIB in optimizing therapeutic outcomes for brain metastases.
{"title":"Efficacy and safety evaluation of combined therapies incorporating whole-brain radiotherapy in patients with brain metastases: a systematic review and meta-analysis.","authors":"Qi Yan, Rong Li, Jiayang Yang, Xueqi Bai, Xiudong Guo, Xin Yang, Jianbo Song","doi":"10.1007/s12094-024-03525-1","DOIUrl":"10.1007/s12094-024-03525-1","url":null,"abstract":"<p><strong>Background: </strong>Whole-brain radiotherapy (WBRT) is a standard and effective approach for brain metastases, but it is linked to neurocognitive complications, specifically issues related to the hippocampus. Innovative strategies are being explored to enhance outcomes. However, a consensus is yet to be reached in this field. Our aim is to investigate the efficacy and safety of WBRT combined with simultaneous integrated boost (SIB), memantine, and hippocampal avoidance (HA) techniques in treatment of brain metastases.</p><p><strong>Methods: </strong>In this systematic review and meta-analysis, we comprehensively searched PubMed, MEDLINE, Embase, and Cochrane for studies reporting the efficacy and toxicity of WBRT-based combination therapies from inception to September 19, 2023. Data were pooled using random-effects models. Results were reported as risk ratios (RRs) and risk differences (RDs) for dichotomous outcomes, along with their 95% confidence intervals (CIs). Heterogeneity was evaluated using the I<sup>2</sup> statistic.</p><p><strong>Results: </strong>Among 2175 articles, 29 studies involving 3460 patients were included. The meta-analysis revealed that compared to WBRT alone, combination therapies significantly mitigated neurocognitive function decline (RD = -0.09, 95% CI [-0.18-0.01]; P = 0.03) and intracranial control failure (RR = 0.86, 95% CI [0.52-1.44]; P = 0.02), without increasing the risk of hippocampal recurrence or high-grade toxicities. Notably, HA-WBRT + SIB/memantine demonstrated improved neurocognitive outcomes and survival benefits.</p><p><strong>Conclusion: </strong>WBRT-based combination therapies demonstrate improved efficacy and comparable safety to WBRT alone, with specific emphasis on the effectiveness of HA-WBRT + Memantine and HA-WBRT + SIB in optimizing therapeutic outcomes for brain metastases.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"3020-3036"},"PeriodicalIF":2.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141094405","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}
Pub Date : 2024-12-01Epub Date: 2024-06-13DOI: 10.1007/s12094-024-03533-1
Bing Bai, Xia An, Qinghui Qu, Xin Liu, Yuanyuan Liu, Li Wei
Background: TP53 is a frequently mutated oncogene within non-small cell lung cancer (NSCLC). However, the clinical and prognostic significance of co-mutations in TP53 in patients with advanced NSCLC has not been fully elucidated.
Methods: A total of 174 patients with advanced NSCLC were enrolled in this study. All patients were subjected to sequencing analysis of tumor-related genes and information such as PD-L1 expression, TMB, and co-mutation changes were collected. Patients were categorized into TP53 mutant and TP53 wild-type groups according to their TP53 mutation status and then statistically analyzed.
Results: TP53 mutations were the most common among all patients, accounting for 56.32%, followed by epidermal growth factor receptor mutations at 48.27%. The most common mutation sites in the TP53 mutation group were exons 5-8.TP53 mutations were significantly associated with PD-L1 and TMB levels. Univariate Cox analysis showed that gender and EGFR mutation affected the prognosis of TP53-mutated NSCLC patients, and multivariate Cox regression analysis identified EGFR mutation as an independent risk factor. The OS of NSCLC patients in the TP53 mutation group was significantly shorter than that of the TP53wt group. Survival curves in the TP53/EGFR combined mutation group showed that patients with combined EGFR mutation had a lower survival rate.
Discussion: TP53 mutations are associated with different clinical indicators and have important implications in clinical treatment. TP53 is a poor prognostic factor for NSCLC patients, and TP53/EGFR co-mutation will affect the survival time of patients. TP53/EGFR co-mutation may be a new prognostic marker for NSCLC.
{"title":"The clinical features and prognostic implications of the co-mutated TP53 gene in advanced non-small cell lung cancer.","authors":"Bing Bai, Xia An, Qinghui Qu, Xin Liu, Yuanyuan Liu, Li Wei","doi":"10.1007/s12094-024-03533-1","DOIUrl":"10.1007/s12094-024-03533-1","url":null,"abstract":"<p><strong>Background: </strong>TP53 is a frequently mutated oncogene within non-small cell lung cancer (NSCLC). However, the clinical and prognostic significance of co-mutations in TP53 in patients with advanced NSCLC has not been fully elucidated.</p><p><strong>Methods: </strong>A total of 174 patients with advanced NSCLC were enrolled in this study. All patients were subjected to sequencing analysis of tumor-related genes and information such as PD-L1 expression, TMB, and co-mutation changes were collected. Patients were categorized into TP53 mutant and TP53 wild-type groups according to their TP53 mutation status and then statistically analyzed.</p><p><strong>Results: </strong>TP53 mutations were the most common among all patients, accounting for 56.32%, followed by epidermal growth factor receptor mutations at 48.27%. The most common mutation sites in the TP53 mutation group were exons 5-8.TP53 mutations were significantly associated with PD-L1 and TMB levels. Univariate Cox analysis showed that gender and EGFR mutation affected the prognosis of TP53-mutated NSCLC patients, and multivariate Cox regression analysis identified EGFR mutation as an independent risk factor. The OS of NSCLC patients in the TP53 mutation group was significantly shorter than that of the TP53wt group. Survival curves in the TP53/EGFR combined mutation group showed that patients with combined EGFR mutation had a lower survival rate.</p><p><strong>Discussion: </strong>TP53 mutations are associated with different clinical indicators and have important implications in clinical treatment. TP53 is a poor prognostic factor for NSCLC patients, and TP53/EGFR co-mutation will affect the survival time of patients. TP53/EGFR co-mutation may be a new prognostic marker for NSCLC.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"3236-3245"},"PeriodicalIF":2.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141318912","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}
Pub Date : 2024-12-01Epub Date: 2024-06-06DOI: 10.1007/s12094-024-03542-0
Ying Chen, Xianghua Ye, Xinke Li, Fang Wang, Jinsong Yang, Xiaoli Sun, Senxiang Yan
Purpose: Radiotherapy is the major therapy for head and neck squamous cell carcinoma (HNSCC). However, whether gut microbiota changes in HNSCC patients who received concurrent chemoradiotherapy remains unclear. This study aimed to investigate the dynamic change of gut microbiota composition, construct the first radiotherapy-related gut microbiota database in these patients and identify the potential value of the gut microbiota changing in the prediction of acute oral mucositis grade as well as patients' life quality.
Methods: We enrolled 47 HNSCC patients who scheduled with concurrent chemoradiotherapy. The field was irradiated with a total dose of 66-70 Gy in 33-35 fractions. All the patients received 2-3 cycles of platinum-based chemotherapy. After feces specimens collected, bacterial genomic DNA was isolated using magnetic beads and then analyzed by the Illumina MiSeq Sequencing System based on the V3-V4 hypervariable regions of the 16S rRNA gene.
Results: 194 genera which belonged to 27 phyla were found in 141 samples. Increased abundance of microbiota in diversity and richness was observed in mid-radiotherapy group. Bacteroides, Blautia, Phascolarctobacterium were three main genera in all three groups and the mid-radiotherapy group had the highest relative abundance of Phascolarctobacterium. What is more, most significantly altered bacteria shared the same variation pattern which was increased in mid-radiotherapy while decreased to the almost same level of as pre-radiotherapy in post-radiotherapy group. Further analysis indicated that Bacteroidetes showing an upward trend while Proteobacteria declining in higher grade of acute mucositis. Moreover, relatively low abundant Proteobacteria was significantly correlated with high-grade acute oral mucositis. As for the quality of life, Lactobacillales and Actinomycetales were specifically found in better life quality group. However, Clostridia_UCG_014, Eubacteriaceae, UCG_010 and Moraxellaceae were unique abundantly present in worse life quality group.
Conclusion: Chemoradiotherapy can affect the composition of the gut microbiota in HNSCC patients during the mid-term of treatment. Yet self-stabilized ability maintained the gut microbiota homeostasis. Dynamic change of specific species could help predict acute oral mucositis grade and characterize different quality of life group in these patients.
{"title":"Dynamic change of gut microbiota in head and neck concurrent chemoradiotherapy patients and its potential value in the prediction of acute oral mucositis grade as well as quality of life.","authors":"Ying Chen, Xianghua Ye, Xinke Li, Fang Wang, Jinsong Yang, Xiaoli Sun, Senxiang Yan","doi":"10.1007/s12094-024-03542-0","DOIUrl":"10.1007/s12094-024-03542-0","url":null,"abstract":"<p><strong>Purpose: </strong>Radiotherapy is the major therapy for head and neck squamous cell carcinoma (HNSCC). However, whether gut microbiota changes in HNSCC patients who received concurrent chemoradiotherapy remains unclear. This study aimed to investigate the dynamic change of gut microbiota composition, construct the first radiotherapy-related gut microbiota database in these patients and identify the potential value of the gut microbiota changing in the prediction of acute oral mucositis grade as well as patients' life quality.</p><p><strong>Methods: </strong>We enrolled 47 HNSCC patients who scheduled with concurrent chemoradiotherapy. The field was irradiated with a total dose of 66-70 Gy in 33-35 fractions. All the patients received 2-3 cycles of platinum-based chemotherapy. After feces specimens collected, bacterial genomic DNA was isolated using magnetic beads and then analyzed by the Illumina MiSeq Sequencing System based on the V3-V4 hypervariable regions of the 16S rRNA gene.</p><p><strong>Results: </strong>194 genera which belonged to 27 phyla were found in 141 samples. Increased abundance of microbiota in diversity and richness was observed in mid-radiotherapy group. Bacteroides, Blautia, Phascolarctobacterium were three main genera in all three groups and the mid-radiotherapy group had the highest relative abundance of Phascolarctobacterium. What is more, most significantly altered bacteria shared the same variation pattern which was increased in mid-radiotherapy while decreased to the almost same level of as pre-radiotherapy in post-radiotherapy group. Further analysis indicated that Bacteroidetes showing an upward trend while Proteobacteria declining in higher grade of acute mucositis. Moreover, relatively low abundant Proteobacteria was significantly correlated with high-grade acute oral mucositis. As for the quality of life, Lactobacillales and Actinomycetales were specifically found in better life quality group. However, Clostridia_UCG_014, Eubacteriaceae, UCG_010 and Moraxellaceae were unique abundantly present in worse life quality group.</p><p><strong>Conclusion: </strong>Chemoradiotherapy can affect the composition of the gut microbiota in HNSCC patients during the mid-term of treatment. Yet self-stabilized ability maintained the gut microbiota homeostasis. Dynamic change of specific species could help predict acute oral mucositis grade and characterize different quality of life group in these patients.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"3191-3201"},"PeriodicalIF":2.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141285211","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}
Pub Date : 2024-12-01Epub Date: 2024-05-27DOI: 10.1007/s12094-024-03498-1
Qu Xie, Yanzhen Yang, Weiyuan Hao, Cong Luo
Background: The purpose of this study is to compare the efficacy and safety of transarterial chemoembolization (TACE) alone with transarterial chemoembolization combined with the arterial infusion of bevacizumab (TACE + Bev) in patients with unresectable hepatocellular carcinoma (uHCC).
Methods: A retrospective analysis was conducted on 446 uHCC patients treated with TACE or TACE + Bev between January 2021 and March 2023. The study evaluated objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events in both treatment groups.
Results: Finally, the TACE group comprised 295 patients, and the TACE + Bev group comprised 151 patients. Patients in the TACE + Bev group exhibited significantly prolonged median PFS (7.9 months vs. 10.3 months, P = 0.013) and median OS (16.1 months vs. 21.4 months, P = 0.041), improved ORR (26.8% vs. 37.7%, P = 0.017) and DCR (71.5% vs. 80.8%, P = 0.033) compared to the TACE group. Multifactorial Cox analysis identified alpha-fetoprotein (AFP) > 400 ng/ml as an independent prognostic factor for PFS and OS. Meanwhile, portal vein cancer thrombosis and distant metastasis are poor prognostic factors for OS. The overall incidence of adverse events was similar between the two groups.
Conclusion: In comparison with the TACE group, the TACE + Bev group demonstrated efficacy in improving outcomes for patients with uHCC with a manageable safety profile.
{"title":"Unleashing the potential: transarterial chemoembolization combined with intra-arterial infusion of bevacizumab for unresectable hepatocellular carcinoma.","authors":"Qu Xie, Yanzhen Yang, Weiyuan Hao, Cong Luo","doi":"10.1007/s12094-024-03498-1","DOIUrl":"10.1007/s12094-024-03498-1","url":null,"abstract":"<p><strong>Background: </strong>The purpose of this study is to compare the efficacy and safety of transarterial chemoembolization (TACE) alone with transarterial chemoembolization combined with the arterial infusion of bevacizumab (TACE + Bev) in patients with unresectable hepatocellular carcinoma (uHCC).</p><p><strong>Methods: </strong>A retrospective analysis was conducted on 446 uHCC patients treated with TACE or TACE + Bev between January 2021 and March 2023. The study evaluated objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events in both treatment groups.</p><p><strong>Results: </strong>Finally, the TACE group comprised 295 patients, and the TACE + Bev group comprised 151 patients. Patients in the TACE + Bev group exhibited significantly prolonged median PFS (7.9 months vs. 10.3 months, P = 0.013) and median OS (16.1 months vs. 21.4 months, P = 0.041), improved ORR (26.8% vs. 37.7%, P = 0.017) and DCR (71.5% vs. 80.8%, P = 0.033) compared to the TACE group. Multifactorial Cox analysis identified alpha-fetoprotein (AFP) > 400 ng/ml as an independent prognostic factor for PFS and OS. Meanwhile, portal vein cancer thrombosis and distant metastasis are poor prognostic factors for OS. The overall incidence of adverse events was similar between the two groups.</p><p><strong>Conclusion: </strong>In comparison with the TACE group, the TACE + Bev group demonstrated efficacy in improving outcomes for patients with uHCC with a manageable safety profile.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"3075-3084"},"PeriodicalIF":2.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141154994","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}
Objective: The purpose of this article was to investigate the value of combined MRI, enhanced CT and 18F-FDG PET/CT in the diagnosis of recurrence and metastasis after surgery for ovarian cancer.
Methods: Ninety-five ovarian cancer patients were selected as the study subjects, all of them underwent surgical treatment, and MRI, enhanced CT and 18F-FDG PET/CT were performed on all of them in the postoperative follow-up, and the pathological results after the second operation were used as the diagnostic "gold standard". The diagnostic value (sensitivity, specificity, accuracy, negative predictive value and positive predictive value) of the three examination methods alone or in combination for the diagnosis of postoperative recurrence and metastasis of ovarian cancer was compared, and the detection rate was calculated when the lesion was the unit of study, so as to compare the efficacy of the three methods in the diagnosis of postoperative recurrent metastatic lesions of ovarian cancer.
Results: The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of the combined group were higher than those of MRI and enhanced CT for recurrence and metastasis of ovarian cancer after surgery, and the specificity, accuracy and positive predictive value of the combined group were higher than those of the 18F-FDG PET/CT group, and those of the 18F-FDG PET/CT group were higher than those of the enhanced CT group (all P < 0.05). When the postoperative recurrent metastatic lesions of ovarian cancer were used as the study unit, the detection rate of lesions in the combined group was higher than that of the three examinations detected individually, and the detection rate of lesions in 18F-FDG PET/CT was higher than that of enhanced CT and MRI (P < 0.05).
Conclusion: The combination of MRI, enhanced CT and 18F-FDG PET/CT can accurately diagnose recurrence and metastasis of ovarian cancer after surgery, detect recurrent metastatic lesions as early as possible, and improve patients' prognosis.
{"title":"The value of combined MRI, enhanced CT and <sup>18</sup>F-FDG PET/CT in the diagnosis of recurrence and metastasis after surgery for ovarian cancer.","authors":"Yong Hong, Jianfeng Peng, Yanni Zeng, Xuewen Deng, Wanjun Xu, Juanting Wang","doi":"10.1007/s12094-024-03499-0","DOIUrl":"10.1007/s12094-024-03499-0","url":null,"abstract":"<p><strong>Objective: </strong>The purpose of this article was to investigate the value of combined MRI, enhanced CT and <sup>18</sup>F-FDG PET/CT in the diagnosis of recurrence and metastasis after surgery for ovarian cancer.</p><p><strong>Methods: </strong>Ninety-five ovarian cancer patients were selected as the study subjects, all of them underwent surgical treatment, and MRI, enhanced CT and <sup>18</sup>F-FDG PET/CT were performed on all of them in the postoperative follow-up, and the pathological results after the second operation were used as the diagnostic \"gold standard\". The diagnostic value (sensitivity, specificity, accuracy, negative predictive value and positive predictive value) of the three examination methods alone or in combination for the diagnosis of postoperative recurrence and metastasis of ovarian cancer was compared, and the detection rate was calculated when the lesion was the unit of study, so as to compare the efficacy of the three methods in the diagnosis of postoperative recurrent metastatic lesions of ovarian cancer.</p><p><strong>Results: </strong>The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of the combined group were higher than those of MRI and enhanced CT for recurrence and metastasis of ovarian cancer after surgery, and the specificity, accuracy and positive predictive value of the combined group were higher than those of the <sup>18</sup>F-FDG PET/CT group, and those of the <sup>18</sup>F-FDG PET/CT group were higher than those of the enhanced CT group (all P < 0.05). When the postoperative recurrent metastatic lesions of ovarian cancer were used as the study unit, the detection rate of lesions in the combined group was higher than that of the three examinations detected individually, and the detection rate of lesions in <sup>18</sup>F-FDG PET/CT was higher than that of enhanced CT and MRI (P < 0.05).</p><p><strong>Conclusion: </strong>The combination of MRI, enhanced CT and <sup>18</sup>F-FDG PET/CT can accurately diagnose recurrence and metastasis of ovarian cancer after surgery, detect recurrent metastatic lesions as early as possible, and improve patients' prognosis.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"3013-3019"},"PeriodicalIF":2.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141080374","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}
Pub Date : 2024-12-01Epub Date: 2024-06-01DOI: 10.1007/s12094-024-03519-z
Jieqiong Fan, Tao Zhang
Objective: This research conducted multi-index comprehensive evaluations of the immunotherapeutic efficacy and response in non-small cell lung cancer (NSCLC).
Methods: Forty-five patients with epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK) wild-type advanced NSCLC who received immunotherapy were included. Immunohistochemistry was adopted to detect the expression levels of programmed death ligand 1 (PD-L1) with X-ray cross-complementing protein 1 (XRCC1) and excision repair cross-complementing group 1 (ERCC1) proteins in tumor tissues. Flow cytometry was utilized to measure the levels of T-cell subsets in peripheral blood before and after treatment. PCR-RELP method was employed to evaluate XRCC1 and ERCC1 gene polymorphisms in peripheral blood. According to the treatment effect, patients evaluated as complete response (CR), partial response (PR), and stable disease (SD) were categorized into the immune response group, and patients evaluated as progressive disease (PD) were categorized into the immune unresponsive group. The correlation between PD-L1 protein expression, XRCC1 and ERCC1 protein expression, gene polymorphisms, T-cell subpopulation levels, and treatment efficacy was analyzed.
Results: The therapeutic efficacy of patients with positive PD-L1 expression was better than that of patients with negative PD-L1 expression (P < 0.05). After treatment, peripheral blood CD3+ and CD4+ cell levels and Thl/Th2 cell levels were higher and CD8+ T cells were lower in the immune response group than in the immune unresponsive group (P < 0.05). Among the patients in the immune response group, peripheral blood CD3+ and CD4+ cell levels were higher and CD8+ T cells were lower in patients with positive PD-L1 expression than in patients with negative PD-L1 expression (P < 0.05). In the XRCC1 gene, the proportion of patients in the immune response group carrying the Arg/Trp + Trp/Trp genotype was higher than that of patients in the immune unresponsive group (P < 0.05). In the ERCC1 gene, the proportion of patients in the immune response group carrying the C/T + T/T genotype was higher than that of patients in the immune unresponsive group (P < 0.05). The positive expression rates of XRCC1 and ERCC1 in patients in the immune unresponsive group were higher than those in the immune response group (P < 0.05).
Conclusion: PD-L1 protein expression, XRCC1 and ERCC1 protein expression, and gene polymorphisms are associated with immunotherapy outcome in EGFR/ALK wild-type advanced NSCLC patients, and may be biological indicators for predicting immunotherapy outcome in EGFR/ALK wild-type advanced NSCLC patients.
{"title":"Multi-index comprehensive evaluation of the efficacy and response mechanism of immunotherapy in non-small cell lung cancer.","authors":"Jieqiong Fan, Tao Zhang","doi":"10.1007/s12094-024-03519-z","DOIUrl":"10.1007/s12094-024-03519-z","url":null,"abstract":"<p><strong>Objective: </strong>This research conducted multi-index comprehensive evaluations of the immunotherapeutic efficacy and response in non-small cell lung cancer (NSCLC).</p><p><strong>Methods: </strong>Forty-five patients with epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK) wild-type advanced NSCLC who received immunotherapy were included. Immunohistochemistry was adopted to detect the expression levels of programmed death ligand 1 (PD-L1) with X-ray cross-complementing protein 1 (XRCC1) and excision repair cross-complementing group 1 (ERCC1) proteins in tumor tissues. Flow cytometry was utilized to measure the levels of T-cell subsets in peripheral blood before and after treatment. PCR-RELP method was employed to evaluate XRCC1 and ERCC1 gene polymorphisms in peripheral blood. According to the treatment effect, patients evaluated as complete response (CR), partial response (PR), and stable disease (SD) were categorized into the immune response group, and patients evaluated as progressive disease (PD) were categorized into the immune unresponsive group. The correlation between PD-L1 protein expression, XRCC1 and ERCC1 protein expression, gene polymorphisms, T-cell subpopulation levels, and treatment efficacy was analyzed.</p><p><strong>Results: </strong>The therapeutic efficacy of patients with positive PD-L1 expression was better than that of patients with negative PD-L1 expression (P < 0.05). After treatment, peripheral blood CD3<sup>+</sup> and CD4<sup>+</sup> cell levels and Thl/Th2 cell levels were higher and CD8<sup>+</sup> T cells were lower in the immune response group than in the immune unresponsive group (P < 0.05). Among the patients in the immune response group, peripheral blood CD3<sup>+</sup> and CD4<sup>+</sup> cell levels were higher and CD8<sup>+</sup> T cells were lower in patients with positive PD-L1 expression than in patients with negative PD-L1 expression (P < 0.05). In the XRCC1 gene, the proportion of patients in the immune response group carrying the Arg/Trp + Trp/Trp genotype was higher than that of patients in the immune unresponsive group (P < 0.05). In the ERCC1 gene, the proportion of patients in the immune response group carrying the C/T + T/T genotype was higher than that of patients in the immune unresponsive group (P < 0.05). The positive expression rates of XRCC1 and ERCC1 in patients in the immune unresponsive group were higher than those in the immune response group (P < 0.05).</p><p><strong>Conclusion: </strong>PD-L1 protein expression, XRCC1 and ERCC1 protein expression, and gene polymorphisms are associated with immunotherapy outcome in EGFR/ALK wild-type advanced NSCLC patients, and may be biological indicators for predicting immunotherapy outcome in EGFR/ALK wild-type advanced NSCLC patients.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"3124-3130"},"PeriodicalIF":2.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141187128","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}
<p><strong>Background: </strong>The combination of preoperative chemotherapy and surgical treatment has been shown to significantly enhance the prognosis of colorectal cancer with liver metastases (CRLM) patients. Nevertheless, as a result of variations in clinicopathological parameters, the prognosis of this particular group of patients differs considerably. This study aimed to develop and evaluate Cox proportional risk regression model and competing risk regression model using two patient cohorts. The goal was to provide a more precise and personalized prognostic evaluation system.</p><p><strong>Methods: </strong>We collected information on individuals who had a pathological diagnosis of colorectal cancer between 2000 and 2019 from the Surveillance, Epidemiology, and End Results (SEER) Database. We obtained data from patients who underwent pathological diagnosis of colorectal cancer and got comprehensive therapy at the hospital between January 1, 2010, and June 1, 2022. The SEER data collected after screening according to the inclusion and exclusion criteria were separated into two cohorts: a training cohort (training cohort) and an internal validation cohort (internal validation cohort), using a random 1:1 split. Subgroup Kaplan-Meier (K-M) survival analyses were conducted on each of the three groups. The data that received following screening from the hospital were designated as the external validation cohort. The subsequent variables were chosen for additional examination: age, gender, marital status, race, tumor site, pretreatment carcinoembryonic antigen level, tumor size, T stage, N stage, pathological grade, number of tumor deposits, perineural invasion, number of regional lymph nodes examined, and number of positive regional lymph nodes. The primary endpoint was median overall survival (mOS). In the training cohort, we conducted univariate Cox regression analysis and utilized a stepwise regression approach, employing the Akaike information criterion (AIC) to select variables and create Cox proportional risk regression models. We evaluated the accuracy of the model using calibration curve, receiver operating characteristic curve (ROC), and area under curve (AUC). The effectiveness of the models was assessed using decision curve analysis (DCA). To evaluate the non-cancer-related outcomes, we analyzed variables that had significant impacts using subgroup cumulative incidence function (CIF) and Gray's test. These analyses were used to create competing risk regression models. Nomograms of the two models were constructed separately and prognostic predictions were made for the same patients in SEER database.</p><p><strong>Results: </strong>This study comprised a total of 735 individuals. The mOS of the training cohort, internal validation cohort, and QDU cohort was 55.00 months (95%CI 46.97-63.03), 48.00 months (95%CI 40.65-55.35), and 68.00 months (95%CI 54.91-81.08), respectively. The multivariate Cox regression analysis revealed that age, N
{"title":"Constructing a prognostic model for colorectal cancer with synchronous liver metastases after preoperative chemotherapy: a study based on SEER and an external validation cohort.","authors":"Yixin Ding, Xiaoxi Han, Shufen Zhao, Shasha Wang, Jing Guo, Chuanyu Leng, Xiangxue Li, Kongjia Wang, Wensheng Qiu, Weiwei Qi","doi":"10.1007/s12094-024-03513-5","DOIUrl":"10.1007/s12094-024-03513-5","url":null,"abstract":"<p><strong>Background: </strong>The combination of preoperative chemotherapy and surgical treatment has been shown to significantly enhance the prognosis of colorectal cancer with liver metastases (CRLM) patients. Nevertheless, as a result of variations in clinicopathological parameters, the prognosis of this particular group of patients differs considerably. This study aimed to develop and evaluate Cox proportional risk regression model and competing risk regression model using two patient cohorts. The goal was to provide a more precise and personalized prognostic evaluation system.</p><p><strong>Methods: </strong>We collected information on individuals who had a pathological diagnosis of colorectal cancer between 2000 and 2019 from the Surveillance, Epidemiology, and End Results (SEER) Database. We obtained data from patients who underwent pathological diagnosis of colorectal cancer and got comprehensive therapy at the hospital between January 1, 2010, and June 1, 2022. The SEER data collected after screening according to the inclusion and exclusion criteria were separated into two cohorts: a training cohort (training cohort) and an internal validation cohort (internal validation cohort), using a random 1:1 split. Subgroup Kaplan-Meier (K-M) survival analyses were conducted on each of the three groups. The data that received following screening from the hospital were designated as the external validation cohort. The subsequent variables were chosen for additional examination: age, gender, marital status, race, tumor site, pretreatment carcinoembryonic antigen level, tumor size, T stage, N stage, pathological grade, number of tumor deposits, perineural invasion, number of regional lymph nodes examined, and number of positive regional lymph nodes. The primary endpoint was median overall survival (mOS). In the training cohort, we conducted univariate Cox regression analysis and utilized a stepwise regression approach, employing the Akaike information criterion (AIC) to select variables and create Cox proportional risk regression models. We evaluated the accuracy of the model using calibration curve, receiver operating characteristic curve (ROC), and area under curve (AUC). The effectiveness of the models was assessed using decision curve analysis (DCA). To evaluate the non-cancer-related outcomes, we analyzed variables that had significant impacts using subgroup cumulative incidence function (CIF) and Gray's test. These analyses were used to create competing risk regression models. Nomograms of the two models were constructed separately and prognostic predictions were made for the same patients in SEER database.</p><p><strong>Results: </strong>This study comprised a total of 735 individuals. The mOS of the training cohort, internal validation cohort, and QDU cohort was 55.00 months (95%CI 46.97-63.03), 48.00 months (95%CI 40.65-55.35), and 68.00 months (95%CI 54.91-81.08), respectively. The multivariate Cox regression analysis revealed that age, N","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"3169-3190"},"PeriodicalIF":2.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11564222/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141248994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-06-03DOI: 10.1007/s12094-024-03539-9
Sergi Benavente, Alexandra Giraldo, Alejandro Seoane, Mónica Ramos, Ramona Vergés
Purpose: The increasing complexity of radiation treatments can hinder its clinical success. This study aimed to better understand evolving risks by re-evaluating a Failure Mode and Effects Analysis (FMEA) in lung SBRT.
Methods: An experienced multidisciplinary team conducted an FMEA and made a reassessment 3 years later. A process map was developed with potential failure modes (FMs) identified. High-risk FMs and their possible causes and corrective actions were determined. The initial FMEA analysis was compared to gain a deeper perspective.
Results: We identified 232 FMs. The high-risk processes were plan approval, target contouring, and patient evaluation. The corrective measures were based on stricter standardization of plan approval, pre-planning peer review, and a supporting pretreatment checklist, which substantially reduced the risk priority number in the revised FMEA. In the FMEA reassessment, we observed that the increased complexity and number of patients receiving lung SBRT conditioned a more substantial presence of human factors and communication errors as causal conditions and a potential wrong dose as a final effect.
Conclusions: Conducting a lung SBRT FMEA analysis has identified high-risk conditions that have been effectively mitigated in an FMEA reanalysis. Plan approval has shown to be a weak link in the process. The increasing complexity of treatments and patient numbers have shifted causal factors toward human failure and communication errors. The potential of a wrong dose as a final effect augments in this scenario. We propose that digital and artificial intelligence options are needed to mitigate potential errors in high-complexity and high-risk RT scenarios.
{"title":"Clinical effects of re-evaluating a lung SBRT failure mode and effects analysis in a radiotherapy department.","authors":"Sergi Benavente, Alexandra Giraldo, Alejandro Seoane, Mónica Ramos, Ramona Vergés","doi":"10.1007/s12094-024-03539-9","DOIUrl":"10.1007/s12094-024-03539-9","url":null,"abstract":"<p><strong>Purpose: </strong>The increasing complexity of radiation treatments can hinder its clinical success. This study aimed to better understand evolving risks by re-evaluating a Failure Mode and Effects Analysis (FMEA) in lung SBRT.</p><p><strong>Methods: </strong>An experienced multidisciplinary team conducted an FMEA and made a reassessment 3 years later. A process map was developed with potential failure modes (FMs) identified. High-risk FMs and their possible causes and corrective actions were determined. The initial FMEA analysis was compared to gain a deeper perspective.</p><p><strong>Results: </strong>We identified 232 FMs. The high-risk processes were plan approval, target contouring, and patient evaluation. The corrective measures were based on stricter standardization of plan approval, pre-planning peer review, and a supporting pretreatment checklist, which substantially reduced the risk priority number in the revised FMEA. In the FMEA reassessment, we observed that the increased complexity and number of patients receiving lung SBRT conditioned a more substantial presence of human factors and communication errors as causal conditions and a potential wrong dose as a final effect.</p><p><strong>Conclusions: </strong>Conducting a lung SBRT FMEA analysis has identified high-risk conditions that have been effectively mitigated in an FMEA reanalysis. Plan approval has shown to be a weak link in the process. The increasing complexity of treatments and patient numbers have shifted causal factors toward human failure and communication errors. The potential of a wrong dose as a final effect augments in this scenario. We propose that digital and artificial intelligence options are needed to mitigate potential errors in high-complexity and high-risk RT scenarios.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"3142-3149"},"PeriodicalIF":2.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141238794","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}
Pub Date : 2024-12-01Epub Date: 2024-06-13DOI: 10.1007/s12094-024-03557-7
Abraham André Arturo Geng-Cahuayme, Blanca Peregrín-Pastor, Mónica Ramos-Albiac, Enar Recalde-Vizcay, Juan Sebastián Parada-Zuluaga, Jordi Giralt-López de Sagredo, Xavier Maldonado-Pijoan, Alexandra Giraldo-Marín
Purpose: To evaluate clinical outcomes after SABR in a cohort of early-stage non-small cell lung cancer (NSCLC) or pulmonary metastases in chronic obstructive pulmonary disease (COPD) patients with forced expiratory volume in the first second predicted (FEV1) ≤ 50%.
Methods: Retrospective single-center study was performed to analyze clinical outcomes and toxicities in COPD patients with severe lung dysfunction treated with SABR from 1st June 2015 to 31st October 2022.
Results: Thirty four patients (forty locations) were enrolled for analysis. Median follow-up was 2.9 years. Median age was 73.5 years (range, 65.6-80.1). FEV1 was 38% (range, 28.2-50.0) prior to radiotherapy. Median overall survival (OS) was 41.1 months (95% CI 38.9-not reached). OS rates at 2-, 3-, and 5- years were 79%, 71%, and 36%, respectively. Cancer-specific survival rates at 2-, 3-, and 5- years were 96%, 96%, and 68%, respectively. Local control rates at 2-, 3-, and 5- years were 88%, 83%, and 83%, respectively. No grade 4 or 5 toxicity was observed. The most common acute toxicity was pneumonitis (38.2%), of which only 1 patient (2.9%) reported grade 3 acute toxicity.
Conclusions: Lung SABR in patients with poor pulmonary function may be effective with acceptable toxicity.
{"title":"Stereotactic ablative radiotherapy (SABR) for patients with lung tumor and severe pulmonary function impairment.","authors":"Abraham André Arturo Geng-Cahuayme, Blanca Peregrín-Pastor, Mónica Ramos-Albiac, Enar Recalde-Vizcay, Juan Sebastián Parada-Zuluaga, Jordi Giralt-López de Sagredo, Xavier Maldonado-Pijoan, Alexandra Giraldo-Marín","doi":"10.1007/s12094-024-03557-7","DOIUrl":"10.1007/s12094-024-03557-7","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate clinical outcomes after SABR in a cohort of early-stage non-small cell lung cancer (NSCLC) or pulmonary metastases in chronic obstructive pulmonary disease (COPD) patients with forced expiratory volume in the first second predicted (FEV1) ≤ 50%.</p><p><strong>Methods: </strong>Retrospective single-center study was performed to analyze clinical outcomes and toxicities in COPD patients with severe lung dysfunction treated with SABR from 1st June 2015 to 31st October 2022.</p><p><strong>Results: </strong>Thirty four patients (forty locations) were enrolled for analysis. Median follow-up was 2.9 years. Median age was 73.5 years (range, 65.6-80.1). FEV1 was 38% (range, 28.2-50.0) prior to radiotherapy. Median overall survival (OS) was 41.1 months (95% CI 38.9-not reached). OS rates at 2-, 3-, and 5- years were 79%, 71%, and 36%, respectively. Cancer-specific survival rates at 2-, 3-, and 5- years were 96%, 96%, and 68%, respectively. Local control rates at 2-, 3-, and 5- years were 88%, 83%, and 83%, respectively. No grade 4 or 5 toxicity was observed. The most common acute toxicity was pneumonitis (38.2%), of which only 1 patient (2.9%) reported grade 3 acute toxicity.</p><p><strong>Conclusions: </strong>Lung SABR in patients with poor pulmonary function may be effective with acceptable toxicity.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"3246-3251"},"PeriodicalIF":2.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141312242","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}