Pub Date : 2024-01-01Epub Date: 2024-03-11DOI: 10.1080/02656736.2024.2320852
Sergio Mingo Barba, Adela Ademaj, Dietmar Marder, Oliver Riesterer, Marco Lattuada, Rudolf M Füchslin, Alke Petri-Fink, Stephan Scheidegger
Introduction: Hyperthermia (HT) induces various cellular biological processes, such as repair impairment and direct HT cell killing. In this context, in-silico biophysical models that translate deviations in the treatment conditions into clinical outcome variations may be used to study the extent of such processes and their influence on combined hyperthermia plus radiotherapy (HT + RT) treatments under varying conditions.
Methods: An extended linear-quadratic model calibrated for SiHa and HeLa cell lines (cervical cancer) was used to theoretically study the impact of varying HT treatment conditions on radiosensitization and direct HT cell killing effect. Simulated patients were generated to compute the Tumor Control Probability (TCP) under different HT conditions (number of HT sessions, temperature and time interval), which were randomly selected within margins based on reported patient data.
Results: Under the studied conditions, model-based simulations suggested a treatment improvement with a total CEM43 thermal dose of approximately 10 min. Additionally, for a given thermal dose, TCP increased with the number of HT sessions. Furthermore, in the simulations, we showed that the TCP dependence on the temperature/time interval is more correlated with the mean value than with the minimum/maximum value and that comparing the treatment outcome with the mean temperature can be an excellent strategy for studying the time interval effect.
Conclusion: The use of thermoradiobiological models allows us to theoretically study the impact of varying thermal conditions on HT + RT treatment outcomes. This approach can be used to optimize HT treatments, design clinical trials, and interpret patient data.
{"title":"Theoretical evaluation of the impact of diverse treatment conditions by calculation of the tumor control probability (TCP) of simulated cervical cancer Hyperthermia-Radiotherapy (HT-RT) treatments in-silico.","authors":"Sergio Mingo Barba, Adela Ademaj, Dietmar Marder, Oliver Riesterer, Marco Lattuada, Rudolf M Füchslin, Alke Petri-Fink, Stephan Scheidegger","doi":"10.1080/02656736.2024.2320852","DOIUrl":"10.1080/02656736.2024.2320852","url":null,"abstract":"<p><strong>Introduction: </strong>Hyperthermia (HT) induces various cellular biological processes, such as repair impairment and direct HT cell killing. In this context, <i>in-silico</i> biophysical models that translate deviations in the treatment conditions into clinical outcome variations may be used to study the extent of such processes and their influence on combined hyperthermia plus radiotherapy (HT + RT) treatments under varying conditions.</p><p><strong>Methods: </strong>An extended linear-quadratic model calibrated for SiHa and HeLa cell lines (cervical cancer) was used to theoretically study the impact of varying HT treatment conditions on radiosensitization and direct HT cell killing effect. Simulated patients were generated to compute the Tumor Control Probability (TCP) under different HT conditions (number of HT sessions, temperature and time interval), which were randomly selected within margins based on reported patient data.</p><p><strong>Results: </strong>Under the studied conditions, model-based simulations suggested a treatment improvement with a total CEM43 thermal dose of approximately 10 min. Additionally, for a given thermal dose, TCP increased with the number of HT sessions. Furthermore, in the simulations, we showed that the TCP dependence on the temperature/time interval is more correlated with the mean value than with the minimum/maximum value and that comparing the treatment outcome with the mean temperature can be an excellent strategy for studying the time interval effect.</p><p><strong>Conclusion: </strong>The use of thermoradiobiological models allows us to theoretically study the impact of varying thermal conditions on HT + RT treatment outcomes. This approach can be used to optimize HT treatments, design clinical trials, and interpret patient data.</p>","PeriodicalId":14137,"journal":{"name":"International Journal of Hyperthermia","volume":"41 1","pages":"2320852"},"PeriodicalIF":3.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140093900","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 : 2024-01-01Epub Date: 2024-02-25DOI: 10.1080/02656736.2024.2306818
Qitao Hu, Zhou Tian, Yongji Sun, Bo Zhang, Zhe Tang
Purpose: To evaluate the safety and efficacy of indocyanine green fluorescence imaging for real-time guidance of laparoscopic thermal ablation in patients with liver cancer.
Materials and methods: A total of 27 patients with 40 liver lesions underwent fluorescence-assisted laparoscopic ablation between January 2020 to March 2023. The sensitivity of indocyanine green (ICG)-fluorescence imaging, technique effectiveness rate and complications of fluorescence-assisted laparoscopic thermal ablation were evaluated.
Results: In total, 33 out of the 40 lesions were identified by ICG-fluorescence imaging technique, with the sensitivity of 82.5%. The sensitivity of ICG-fluorescence imaging of tumor detection in liver surface of parenchyma was significantly higher than that in the deeply located hepatic parenchyma (96.8% vs 33.3%, p = 0.002). ICG-fluorescence imaging procedures detected 4 lesions that cannot be seen on intraoperative ultrasound. It provides clear demarcation lines on the hepatic surface. Technical success is achieved if the necrotic zone had at least a 5 mm ablative margin around the outer edge of the ICG-fluorescence image. Technical success of fluorescence laparoscopic radiofrequency ablation (FLRFA) and fluorescence laparoscopic microwave ablation (FLMWA) was 100% (27/27). Technical effectiveness is defined by the complete necrotic lesions of the local tumor tissue during follow-up. According to the CT/MRI one month after FLRFA or FLMWA, the technical efficacy rate was 92.5% (37/40) and local tumor progression occurred in 7.5% (3/40) of the enrolled lesions. During the follow-up period, no major complications were observed.
Conclusion: ICG-fluorescence imaging guided laparoscopic thermal ablation was feasible, safe and effective.
{"title":"Safety and efficacy of indocyanine green fluorescence imaging for real-time guidance of laparoscopic thermal ablation in patients with liver cancer.","authors":"Qitao Hu, Zhou Tian, Yongji Sun, Bo Zhang, Zhe Tang","doi":"10.1080/02656736.2024.2306818","DOIUrl":"https://doi.org/10.1080/02656736.2024.2306818","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate the safety and efficacy of indocyanine green fluorescence imaging for real-time guidance of laparoscopic thermal ablation in patients with liver cancer.</p><p><strong>Materials and methods: </strong>A total of 27 patients with 40 liver lesions underwent fluorescence-assisted laparoscopic ablation between January 2020 to March 2023. The sensitivity of indocyanine green (ICG)-fluorescence imaging, technique effectiveness rate and complications of fluorescence-assisted laparoscopic thermal ablation were evaluated.</p><p><strong>Results: </strong>In total, 33 out of the 40 lesions were identified by ICG-fluorescence imaging technique, with the sensitivity of 82.5%. The sensitivity of ICG-fluorescence imaging of tumor detection in liver surface of parenchyma was significantly higher than that in the deeply located hepatic parenchyma (96.8% vs 33.3%, <i>p</i> = 0.002). ICG-fluorescence imaging procedures detected 4 lesions that cannot be seen on intraoperative ultrasound. It provides clear demarcation lines on the hepatic surface. Technical success is achieved if the necrotic zone had at least a 5 mm ablative margin around the outer edge of the ICG-fluorescence image. Technical success of fluorescence laparoscopic radiofrequency ablation (FLRFA) and fluorescence laparoscopic microwave ablation (FLMWA) was 100% (27/27). Technical effectiveness is defined by the complete necrotic lesions of the local tumor tissue during follow-up. According to the CT/MRI one month after FLRFA or FLMWA, the technical efficacy rate was 92.5% (37/40) and local tumor progression occurred in 7.5% (3/40) of the enrolled lesions. During the follow-up period, no major complications were observed.</p><p><strong>Conclusion: </strong>ICG-fluorescence imaging guided laparoscopic thermal ablation was feasible, safe and effective.</p>","PeriodicalId":14137,"journal":{"name":"International Journal of Hyperthermia","volume":"41 1","pages":"2306818"},"PeriodicalIF":3.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139971801","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 : 2024-01-01Epub Date: 2024-09-26DOI: 10.1080/02656736.2024.2408374
Shi-Liang Cao, Wan-Ying Shi, Zhen-Long Zhao, Ying Wei, Na Yu, Jie Wu, Li-Li Peng, Yan Li, Ming-An Yu
Objective: Thermal ablation (TA) is a safe and effective treatment for benign thyroid nodules (BTNs). However, there has been no consensus on the optimal maximum diameter (MD) of BTNs for TA. This study aimed to identify the optimal MD of BTNs for TA based on complete disappearance rate after TA.
Materials and methods: This retrospective study included 639 BTNs treated with TA from June 2014 to January 2022. The complete disappearance rate of BTNs after TA was summarized, related influencing factors were explored, and the optimal MD of BTNs for TA was identified.
Results: At the final follow-up (median: 40 months, range: 24-95 months), the overall volume reduction rate was 95.4 ± 9.0%, and 50.5% of the BTNs (323/639) completely disappeared. The MD was significantly negatively correlated with complete disappearance (odds ratio 0.89, 95% confidence interval 0.87-0.92; p < 0.001). Calcification, comet-tail artifacts, multilocular cysts, and composition of BTNs, as well as diabetes were negatively correlated with complete disappearance. Restricted cubic spline indicated that an MD of 25.0 mm was the optimal threshold of BTNs for TA, which was confirmed by subgroup logistic regression analysis. Compared with BTNs with MD ≤ 25.0 mm, those with MD > 25.0 mm had a greater complication rate (6.5% vs. 2.4%, p = 0.012).
Conclusions: The MD of BTNs was negatively correlated with complete disappearance after TA; an MD > 25.0 mm indicated a reduced likelihood of complete disappearance compared with an MD ≤ 25.0 mm. An MD of 25.0 mm is an appropriate threshold of BTNs for TA on the basis of complete disappearance rate.
{"title":"Investigating the optimal maximum diameter of benign thyroid nodules for thermal ablation on the basis of complete disappearance rate.","authors":"Shi-Liang Cao, Wan-Ying Shi, Zhen-Long Zhao, Ying Wei, Na Yu, Jie Wu, Li-Li Peng, Yan Li, Ming-An Yu","doi":"10.1080/02656736.2024.2408374","DOIUrl":"https://doi.org/10.1080/02656736.2024.2408374","url":null,"abstract":"<p><strong>Objective: </strong>Thermal ablation (TA) is a safe and effective treatment for benign thyroid nodules (BTNs). However, there has been no consensus on the optimal maximum diameter (MD) of BTNs for TA. This study aimed to identify the optimal MD of BTNs for TA based on complete disappearance rate after TA.</p><p><strong>Materials and methods: </strong>This retrospective study included 639 BTNs treated with TA from June 2014 to January 2022. The complete disappearance rate of BTNs after TA was summarized, related influencing factors were explored, and the optimal MD of BTNs for TA was identified.</p><p><strong>Results: </strong>At the final follow-up (median: 40 months, range: 24-95 months), the overall volume reduction rate was 95.4 ± 9.0%, and 50.5% of the BTNs (323/639) completely disappeared. The MD was significantly negatively correlated with complete disappearance (odds ratio 0.89, 95% confidence interval 0.87-0.92; <i>p</i> < 0.001). Calcification, comet-tail artifacts, multilocular cysts, and composition of BTNs, as well as diabetes were negatively correlated with complete disappearance. Restricted cubic spline indicated that an MD of 25.0 mm was the optimal threshold of BTNs for TA, which was confirmed by subgroup logistic regression analysis. Compared with BTNs with MD ≤ 25.0 mm, those with MD > 25.0 mm had a greater complication rate (6.5% vs. 2.4%, <i>p</i> = 0.012).</p><p><strong>Conclusions: </strong>The MD of BTNs was negatively correlated with complete disappearance after TA; an MD > 25.0 mm indicated a reduced likelihood of complete disappearance compared with an MD ≤ 25.0 mm. An MD of 25.0 mm is an appropriate threshold of BTNs for TA on the basis of complete disappearance rate.</p>","PeriodicalId":14137,"journal":{"name":"International Journal of Hyperthermia","volume":"41 1","pages":"2408374"},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142346204","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 : 2024-01-01Epub Date: 2024-09-24DOI: 10.1080/02656736.2024.2406889
Qian Zhang, Guangfei Yang, Ruijiao Chang, Fuxia Wang, Tao Han, Jin Tian, Wen Wang
Objective: This study aimed to explore marker genes and their potential molecular mechanisms involved in US-guided MWA for glioma in mice.
Method: The differentially expressed genes (DEGs1 and DEGs2) and lncRNAs (DELs1 and DELs2) were obtained between Non (glioma tissues without MWA) and T0 groups (0h after MWA), as well as between Non and T24 groups (24h after MWA). The down-regulation cluster genes (CONDOWNDEGs) and upregulation cluster genes (CONUPDEGs) were identified by time series analysis. Candidate genes were obtained by overlapping CONDOWNDEGs with downregulation DEGs (DOWNDEGs)1 and DOWNDEGs2, as well as CONUPDEGs with up-regulation DEGs (UPDEGs)1 and UPDEGs2. The expressions of immune checkpoints and inflammatory factors, gene set enrichment analysis (GSEA), and protein subcellular localization were performed. The eXpression2Kinases (X2K), GeneMANIA, transcription factor (TF), and competing endogenous (ce) RNA regulatory networks were conducted. The expression of marker genes was validated by quantitative real-time polymerase chain reaction (qRT-PCR).
Results: Five marker genes (IL32, VCAM1, IL34, NFKB1 and CXCL13) were identified, which were connected with immune-related functions. Two immune checkpoints (CD96 and TIGIT) and six inflammatory factors played key roles in US-guided MWA for glioma. ceRNA regulatory networks revealed that miR-625-5p, miR-625-3p, miR-31-5p and miR-671-5p were associated with target genes. qRT-PCR indicated both IL32, VCAM1, and NFKB1 were potential markers under US-guided MWA-related time series analysis.
Conclusion: The use of US-guided MWA might be a practical method for influencing the function of target genes, regulating time frames to decrease inflammation, and stimulating immune responses in glioma therapy.
{"title":"Time series analysis combined with transcriptome sequencing to explore characteristic genes and potential molecular mechanisms associated with ultrasound-guided microwave ablation of glioma.","authors":"Qian Zhang, Guangfei Yang, Ruijiao Chang, Fuxia Wang, Tao Han, Jin Tian, Wen Wang","doi":"10.1080/02656736.2024.2406889","DOIUrl":"https://doi.org/10.1080/02656736.2024.2406889","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to explore marker genes and their potential molecular mechanisms involved in US-guided MWA for glioma in mice.</p><p><strong>Method: </strong>The differentially expressed genes (DEGs1 and DEGs2) and lncRNAs (DELs1 and DELs2) were obtained between Non (glioma tissues without MWA) and T0 groups (0h after MWA), as well as between Non and T24 groups (24h after MWA). The down-regulation cluster genes (CONDOWNDEGs) and upregulation cluster genes (CONUPDEGs) were identified by time series analysis. Candidate genes were obtained by overlapping CONDOWNDEGs with downregulation DEGs (DOWNDEGs)1 and DOWNDEGs2, as well as CONUPDEGs with up-regulation DEGs (UPDEGs)1 and UPDEGs2. The expressions of immune checkpoints and inflammatory factors, gene set enrichment analysis (GSEA), and protein subcellular localization were performed. The eXpression2Kinases (X2K), GeneMANIA, transcription factor (TF), and competing endogenous (ce) RNA regulatory networks were conducted. The expression of marker genes was validated by quantitative real-time polymerase chain reaction (qRT-PCR).</p><p><strong>Results: </strong>Five marker genes (<i>IL32, VCAM1</i>, <i>IL34</i>, <i>NFKB1</i> and <i>CXCL13</i>) were identified, which were connected with immune-related functions. Two immune checkpoints (CD96 and TIGIT) and six inflammatory factors played key roles in US-guided MWA for glioma. ceRNA regulatory networks revealed that miR-625-5p, miR-625-3p, miR-31-5p and miR-671-5p were associated with target genes. qRT-PCR indicated both <i>IL32</i>, <i>VCAM1</i>, and <i>NFKB1</i> were potential markers under US-guided MWA-related time series analysis.</p><p><strong>Conclusion: </strong>The use of US-guided MWA might be a practical method for influencing the function of target genes, regulating time frames to decrease inflammation, and stimulating immune responses in glioma therapy.</p>","PeriodicalId":14137,"journal":{"name":"International Journal of Hyperthermia","volume":"41 1","pages":"2406889"},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142346205","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 : 2024-01-01Epub Date: 2024-07-31DOI: 10.1080/02656736.2024.2385600
Qian Wang, Zhenjiang Lin, Xiaogang Zhu, Yangyang Wang, Ying Zhang, Min He, Lian Zhang
Objective: To develop a diagnostic model for predicting occult uterine sarcoma in patients with presumed uterine fibroids.
Materials and methods: We retrospectively reviewed 41631 patients with presumed uterine fibroids who presented for HIFU treatment in 13 hospitals between November 2008 and October 2023. Of these patients, 27 with occult uterine sarcoma and 54 with uterine fibroids were enrolled. Univariate analysis and multivariate logistics regression analysis were used to determine the independent risk factors for the diagnosis of occult uterine sarcoma. A prediction model was constructed based on the coefficients of the risk factors.
Results: The multivariate analysis revealed abnormal vaginal bleeding, ill-defined boundary of tumor, hyperintensity on T2WI, and central unenhanced areas as independent risk factors. A scoring system was created to assess for occult uterine sarcoma risk. The score for abnormal vaginal bleeding was 56. The score for ill-defined lesion boundary was 90. The scores for lesions with hypointensity, isointensity signal/heterogeneous signal intensity, and hyperintensity on T2WI were 0, 42, and 93, respectively. The scores for lesions without enhancement on the mass margin, uniform enhancement of tumor, and no enhancement in the center of tumor were 0, 20, and 100, respectively. Patients with a higher total score implied a higher likelihood of a diagnosis of occult uterine sarcoma than that of patients with a lower score. The established model showed good predictive efficacy.
Conclusions: Our results demonstrated that the diagnostic prediction model can be used to evaluate the risk of uterine sarcoma in patients with presumed uterine fibroids.
{"title":"Risk assessment and prediction of occult uterine sarcoma in patients with presumed uterine fibroids before high-intensity focused ultrasound treatment.","authors":"Qian Wang, Zhenjiang Lin, Xiaogang Zhu, Yangyang Wang, Ying Zhang, Min He, Lian Zhang","doi":"10.1080/02656736.2024.2385600","DOIUrl":"https://doi.org/10.1080/02656736.2024.2385600","url":null,"abstract":"<p><strong>Objective: </strong>To develop a diagnostic model for predicting occult uterine sarcoma in patients with presumed uterine fibroids.</p><p><strong>Materials and methods: </strong>We retrospectively reviewed 41631 patients with presumed uterine fibroids who presented for HIFU treatment in 13 hospitals between November 2008 and October 2023. Of these patients, 27 with occult uterine sarcoma and 54 with uterine fibroids were enrolled. Univariate analysis and multivariate logistics regression analysis were used to determine the independent risk factors for the diagnosis of occult uterine sarcoma. A prediction model was constructed based on the coefficients of the risk factors.</p><p><strong>Results: </strong>The multivariate analysis revealed abnormal vaginal bleeding, ill-defined boundary of tumor, hyperintensity on T2WI, and central unenhanced areas as independent risk factors. A scoring system was created to assess for occult uterine sarcoma risk. The score for abnormal vaginal bleeding was 56. The score for ill-defined lesion boundary was 90. The scores for lesions with hypointensity, isointensity signal/heterogeneous signal intensity, and hyperintensity on T2WI were 0, 42, and 93, respectively. The scores for lesions without enhancement on the mass margin, uniform enhancement of tumor, and no enhancement in the center of tumor were 0, 20, and 100, respectively. Patients with a higher total score implied a higher likelihood of a diagnosis of occult uterine sarcoma than that of patients with a lower score. The established model showed good predictive efficacy.</p><p><strong>Conclusions: </strong>Our results demonstrated that the diagnostic prediction model can be used to evaluate the risk of uterine sarcoma in patients with presumed uterine fibroids.</p>","PeriodicalId":14137,"journal":{"name":"International Journal of Hyperthermia","volume":"41 1","pages":"2385600"},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141859733","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 : 2024-01-01Epub Date: 2024-04-23DOI: 10.1080/02656736.2024.2342348
Siyer Roohani, Felix Ehret, Marcus Beck, Danai P Veltsista, Jacek Nadobny, Sebastian Zschaeck, Sultan Abdel-Rahman, Franziska Eckert, Anne Flörcken, Rolf D Issels, Stephan Klöck, Robert Krempien, Lars H Lindner, Markus Notter, Oliver J Ott, Daniel Pink, Vlatko Potkrajcic, Peter Reichardt, Oliver Riesterer, Mateusz Jacek Spałek, Emanuel Stutz, Rüdiger Wessalowski, Thomas Zilli, Daniel Zips, Pirus Ghadjar, David Kaul
Purpose: To analyze the current practice of regional hyperthermia (RHT) for soft tissue sarcoma (STS) at 12 European centers to provide an overview, find consensuses and identify controversies necessary for future guidelines and clinical trials.
Methods: In this cross-sectional survey study, a 27-item questionnaire assessing clinical subjects and procedural details on RHT for STS was distributed to 12 European cancer centers for RHT.
Results: We have identified seven controversies and five consensus points. Of 12 centers, 6 offer both, RHT with chemotherapy (CTX) or with radiotherapy (RT). Two centers only offer RHT with CTX and four centers only offer RHT with RT. All 12 centers apply RHT for localized, high-risk STS of the extremities, trunk wall and retroperitoneum. However, eight centers also use RHT in metastatic STS, five in palliative STS, eight for superficial STS and six for low-grade STS. Pretherapeutic imaging for RHT treatment planning is used by 10 centers, 9 centers set 40-43 °C as the intratumoral target temperature, and all centers use skin detectors or probes in body orifices for thermometry.
Discussion: There is disagreement regarding the integration of RHT in contemporary interdisciplinary care of STS patients. Many clinical controversies exist that require a standardized consensus guideline and innovative study ideas. At the same time, our data has shown that existing guidelines and decades of experience with the technique of RHT have mostly standardized procedural aspects.
Conclusions: The provided results may serve as a basis for future guidelines and inform future clinical trials for RHT in STS patients.
{"title":"Regional hyperthermia for soft tissue sarcoma - a survey on current practice, controversies and consensus among 12 European centers.","authors":"Siyer Roohani, Felix Ehret, Marcus Beck, Danai P Veltsista, Jacek Nadobny, Sebastian Zschaeck, Sultan Abdel-Rahman, Franziska Eckert, Anne Flörcken, Rolf D Issels, Stephan Klöck, Robert Krempien, Lars H Lindner, Markus Notter, Oliver J Ott, Daniel Pink, Vlatko Potkrajcic, Peter Reichardt, Oliver Riesterer, Mateusz Jacek Spałek, Emanuel Stutz, Rüdiger Wessalowski, Thomas Zilli, Daniel Zips, Pirus Ghadjar, David Kaul","doi":"10.1080/02656736.2024.2342348","DOIUrl":"10.1080/02656736.2024.2342348","url":null,"abstract":"<p><strong>Purpose: </strong>To analyze the current practice of regional hyperthermia (RHT) for soft tissue sarcoma (STS) at 12 European centers to provide an overview, find consensuses and identify controversies necessary for future guidelines and clinical trials.</p><p><strong>Methods: </strong>In this cross-sectional survey study, a 27-item questionnaire assessing clinical subjects and procedural details on RHT for STS was distributed to 12 European cancer centers for RHT.</p><p><strong>Results: </strong>We have identified seven controversies and five consensus points. Of 12 centers, 6 offer both, RHT with chemotherapy (CTX) or with radiotherapy (RT). Two centers only offer RHT with CTX and four centers only offer RHT with RT. All 12 centers apply RHT for localized, high-risk STS of the extremities, trunk wall and retroperitoneum. However, eight centers also use RHT in metastatic STS, five in palliative STS, eight for superficial STS and six for low-grade STS. Pretherapeutic imaging for RHT treatment planning is used by 10 centers, 9 centers set 40-43 °C as the intratumoral target temperature, and all centers use skin detectors or probes in body orifices for thermometry.</p><p><strong>Discussion: </strong>There is disagreement regarding the integration of RHT in contemporary interdisciplinary care of STS patients. Many clinical controversies exist that require a standardized consensus guideline and innovative study ideas. At the same time, our data has shown that existing guidelines and decades of experience with the technique of RHT have mostly standardized procedural aspects.</p><p><strong>Conclusions: </strong>The provided results may serve as a basis for future guidelines and inform future clinical trials for RHT in STS patients.</p>","PeriodicalId":14137,"journal":{"name":"International Journal of Hyperthermia","volume":"41 1","pages":"2342348"},"PeriodicalIF":3.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140858911","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 : 2024-01-01Epub Date: 2024-08-19DOI: 10.1080/02656736.2024.2390124
Rong Ma, Diego Armando Burgos Briones, Min Zou, Yu Xiong, Jin Bai, Lian Zhang
Objectives: To investigate all pregnancies and analyze the factors influencing pregnancy outcomes in patients with adenomyosis after high intensity focused ultrasound (HIFU).
Materials and methods: A total of 231 patients with adenomyosis who completed HIFU and wished to conceive were enrolled. The symptom improvement and information of pregnancy were recorded during the follow-up period. Factors influencing pregnancy outcomes were analyzed using multivariate regression analysis and survival analysis.
Results: After HIFU, 100 of 231 (43.3%) patients became pregnant within 96 months, including 77 (77/194, 39.7%) in natural and 23 (23/37, 62.2%) in vitro fertilization and embryo transfer (IVF-ET) pregnancies following gonadotropin-releasing hormone agonist (GnRHa). Among the 108 (46.8%, 108/231) infertile patients (defined as the failure to achieve pregnancy after 12 months of regular unprotected sexual intercourse, 40 primary infertility and 68 secondary infertility), 31 (28.7%) became pregnant. At the end of the follow-up, 70 successfully delivered 71 healthy babies. No uterine rupture occurred during pregnancy and delivery. Patients with pelvic adhesion and infertility history had a lower pregnancy chance than that of patients without pelvic adhesion and infertility history (OR < 1, p < 0.05). Patients with small adenomyotic lesion volume had a greater pregnancy chance than that of patients with large lesion volume (OR < 1, p < 0.05). IVF-ET following GnRHa had a better pregnancy chance (p < 0.05).
Conclusions: HIFU seems to have a beneficial effect on fertility of patients with adenomyosis. Pelvic adhesion, infertility history, and large adenomyotic lesion volume have adverse effects on pregnancy, but IVF-ET following GnRHa after HIFU could increase the pregnancy chance.
{"title":"Analysis of factors affecting pregnancy outcomes in patients with adenomyosis after high intensity focused ultrasound ablation: a retrospective study.","authors":"Rong Ma, Diego Armando Burgos Briones, Min Zou, Yu Xiong, Jin Bai, Lian Zhang","doi":"10.1080/02656736.2024.2390124","DOIUrl":"https://doi.org/10.1080/02656736.2024.2390124","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate all pregnancies and analyze the factors influencing pregnancy outcomes in patients with adenomyosis after high intensity focused ultrasound (HIFU).</p><p><strong>Materials and methods: </strong>A total of 231 patients with adenomyosis who completed HIFU and wished to conceive were enrolled. The symptom improvement and information of pregnancy were recorded during the follow-up period. Factors influencing pregnancy outcomes were analyzed using multivariate regression analysis and survival analysis.</p><p><strong>Results: </strong>After HIFU, 100 of 231 (43.3%) patients became pregnant within 96 months, including 77 (77/194, 39.7%) in natural and 23 (23/37, 62.2%) <i>in vitro</i> fertilization and embryo transfer (IVF-ET) pregnancies following gonadotropin-releasing hormone agonist (GnRHa). Among the 108 (46.8%, 108/231) infertile patients (defined as the failure to achieve pregnancy after 12 months of regular unprotected sexual intercourse, 40 primary infertility and 68 secondary infertility), 31 (28.7%) became pregnant. At the end of the follow-up, 70 successfully delivered 71 healthy babies. No uterine rupture occurred during pregnancy and delivery. Patients with pelvic adhesion and infertility history had a lower pregnancy chance than that of patients without pelvic adhesion and infertility history (OR < 1, <i>p</i> < 0.05). Patients with small adenomyotic lesion volume had a greater pregnancy chance than that of patients with large lesion volume (OR < 1, <i>p</i> < 0.05). IVF-ET following GnRHa had a better pregnancy chance (<i>p</i> < 0.05).</p><p><strong>Conclusions: </strong>HIFU seems to have a beneficial effect on fertility of patients with adenomyosis. Pelvic adhesion, infertility history, and large adenomyotic lesion volume have adverse effects on pregnancy, but IVF-ET following GnRHa after HIFU could increase the pregnancy chance.</p>","PeriodicalId":14137,"journal":{"name":"International Journal of Hyperthermia","volume":"41 1","pages":"2390124"},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142004194","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 : 2024-01-01Epub Date: 2024-09-01DOI: 10.1080/02656736.2024.2396122
Yitong Guo, Weice Wang, Weichen Li, Junyao Li, Mingxu Zhu, Ruteng Song, Wenjing Zhu, Lei Wang, Zhenyu Ji, Xuetao Shi
Objective: Understansding the changing patterns of in vivo electrical properties for the target tissue is crucial for the accurate temperature monitoring and the treatment efficacy in thermal therapy. Our research aims to investigate the changing patterns and the reversibility of in vivo electrical properties for both healthy livers and liver tumors in a mouse model over a frequency range of 1 Hz to 1 MHz at temperatures between 30 °C to 90 °C.
Methods and materials: The mice were anesthetized and the target organ was exposed. An 808-nm near-infrared laser was employed as the heating source to heat the organ in vivo. The four-needle electrode, connected to an impedance analyzer, was utilized to obtain the impedance at varying temperatures, which were monitored by a thermocouple.
Results: The findings indicated a gradual decline in impedance with an increase in temperature. Furthermore, the impedance was normalized to that at 30 °C, and the real part of the normalized impedance was defined as the k-values, which range from 0 to 1. The results demonstrated a linear correlation between k-values and temperatures (R2 > 0.9 for livers and R2 > 0.8 for tumors). Significant differences were observed between livers and tumors at 1, 10 and 50 kHz (p < 0.05). Additionally, it was demonstrated that the electrical properties could be reversed when the temperature was below or equal to 45 °C.
Conclusion: We believe that these results will contribute to the advancement of radiofrequency ablation systems and the development of techniques for temperature monitoring during liver thermal treatment.
目的:了解目标组织体内电特性的变化规律对于准确监测温度和热疗疗效至关重要。我们的研究旨在研究小鼠模型中健康肝脏和肝脏肿瘤在 30 °C 至 90 °C 温度下,在 1 Hz 至 1 MHz 频率范围内体内电特性的变化规律和可逆性:麻醉小鼠并暴露靶器官。采用波长为 808 纳米的近红外激光作为加热源,对体内器官进行加热。利用连接阻抗分析仪的四针电极获得不同温度下的阻抗,并通过热电偶进行监测:结果:研究结果表明,随着温度的升高,阻抗逐渐下降。此外,阻抗被归一化为 30 °C 时的阻抗,归一化阻抗的实部被定义为 k 值,范围在 0 至 1 之间。结果表明,k 值与温度呈线性相关(肝脏的 R2 > 0.9,肿瘤的 R2 > 0.8)。在 1、10 和 50 kHz 频率下,肝脏和肿瘤之间存在显著差异(p):我们相信,这些结果将有助于射频消融系统的进步和肝脏热处理期间温度监测技术的发展。
{"title":"<i>In vivo</i> electrical properties of the healthy liver and the hepatic tumor in a mouse model between 1 Hz and 1 MHz during a thermal treatment.","authors":"Yitong Guo, Weice Wang, Weichen Li, Junyao Li, Mingxu Zhu, Ruteng Song, Wenjing Zhu, Lei Wang, Zhenyu Ji, Xuetao Shi","doi":"10.1080/02656736.2024.2396122","DOIUrl":"https://doi.org/10.1080/02656736.2024.2396122","url":null,"abstract":"<p><p><b>Objective:</b> Understansding the changing patterns of <i>in vivo</i> electrical properties for the target tissue is crucial for the accurate temperature monitoring and the treatment efficacy in thermal therapy. Our research aims to investigate the changing patterns and the reversibility of <i>in vivo</i> electrical properties for both healthy livers and liver tumors in a mouse model over a frequency range of 1 Hz to 1 MHz at temperatures between 30 °C to 90 °C.</p><p><p><b>Methods and materials:</b> The mice were anesthetized and the target organ was exposed. An 808-nm near-infrared laser was employed as the heating source to heat the organ <i>in vivo</i>. The four-needle electrode, connected to an impedance analyzer, was utilized to obtain the impedance at varying temperatures, which were monitored by a thermocouple.</p><p><p><b>Results:</b> The findings indicated a gradual decline in impedance with an increase in temperature. Furthermore, the impedance was normalized to that at 30 °C, and the real part of the normalized impedance was defined as the k-values, which range from 0 to 1. The results demonstrated a linear correlation between k-values and temperatures (R<sup>2</sup> > 0.9 for livers and R<sup>2</sup> > 0.8 for tumors). Significant differences were observed between livers and tumors at 1, 10 and 50 kHz (<i>p</i> < 0.05). Additionally, it was demonstrated that the electrical properties could be reversed when the temperature was below or equal to 45 °C.</p><p><p><b>Conclusion:</b> We believe that these results will contribute to the advancement of radiofrequency ablation systems and the development of techniques for temperature monitoring during liver thermal treatment.</p>","PeriodicalId":14137,"journal":{"name":"International Journal of Hyperthermia","volume":"41 1","pages":"2396122"},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142107201","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: Cryoablation (Cryo) is a minimally invasive treatment for tumors. Cryo can activate the body's immune response, although it is typically weak. The immune response induced by Cryo in hepatocellular carcinoma (HCC) is poorly understood. PD-1 and CTLA-4 monoclonal antibodies are immune checkpoint inhibitors used in immunotherapy for tumors. The combined use of these antibodies with Cryo may enhance the immune effect.
Methods: A Balb/c mouse model of HCC was established and treated with Cryo, immune checkpoint blockade (ICB), or Cryo + ICB (combination therapy). The growth trend of right untreated tumors and survival time of mice were determined. The expression of apoptosis-related proteins was detected by Western blot (WB) assay. The percentages of immune cells and immunosuppressive cells were analyzed by flow cytometry. The numbers of infiltrating T lymphocytes were checked by immunohistochemistry, and the levels of T-cell-associated cytokines were detected by Quantitative real-time Polymerase Chain Reaction (qRT-PCR) assays and Enzyme-Linked Immunosorbent Assays (ELISA) assays.
Results: Cryo + ICB inhibited the growth of right untreated tumors, promoted tumor cell apoptosis, and prolonged the survival time of mice. Local T-cell infiltration in right tumor tissues increased after the combination therapy, while the number of immunosuppressive cells was significantly reduced. In addition, the combination therapy may induce the production of multiple Th1-type cytokines but reduce the production of Th2-type cytokines.
Conclusions: Cryo can activate CD8+ and CD4+ T-cell immune responses. Cryo + ICB can relieve the immunosuppressive tumor microenvironment and shift the Th1/Th2 balance toward Th1 dominance, further enhancing the Cryo-induced T-cell immune response and resulting in a stronger antitumor immune response.
背景:低温消融术(Cryo)是一种微创的肿瘤治疗方法。冷冻可激活机体的免疫反应,但通常较弱。冷冻疗法在肝细胞癌(HCC)中诱导的免疫反应尚不清楚。PD-1 和 CTLA-4 单克隆抗体是用于肿瘤免疫疗法的免疫检查点抑制剂。将这些抗体与冷冻联合使用可能会增强免疫效果:方法:建立 Balb/c 小鼠 HCC 模型,并使用 Cryo、免疫检查点阻断疗法(ICB)或 Cryo + ICB(联合疗法)进行治疗。测定未经治疗的右侧肿瘤的生长趋势和小鼠的存活时间。通过 Western 印迹(WB)检测凋亡相关蛋白的表达。流式细胞术分析了免疫细胞和免疫抑制细胞的百分比。免疫组化法检测浸润的 T 淋巴细胞数量,定量实时聚合酶链式反应(qRT-PCR)和酶联免疫吸附试验(ELISA)检测 T 细胞相关细胞因子的水平:低温+ ICB抑制了未经治疗的右侧肿瘤的生长,促进了肿瘤细胞的凋亡,延长了小鼠的存活时间。联合治疗后,右侧肿瘤组织中的局部 T 细胞浸润增加,而免疫抑制细胞的数量明显减少。此外,联合疗法可诱导产生多种Th1型细胞因子,但减少了Th2型细胞因子的产生:结论:低温疗法可激活 CD8+ 和 CD4+ T 细胞免疫反应。低温+ ICB 可以缓解肿瘤微环境的免疫抑制作用,并使 Th1/Th2 平衡向 Th1 主导方向转变,进一步增强低温诱导的 T 细胞免疫反应,从而产生更强的抗肿瘤免疫反应。
{"title":"Cryoablation combined with dual immune checkpoint blockade enhances antitumor efficacy in hepatocellular carcinoma model mice.","authors":"Jun Gu, Zepeng Yu, Xiangxiang Tang, Wenying Chen, Xuedong Deng, Xiaoli Zhu","doi":"10.1080/02656736.2024.2373319","DOIUrl":"https://doi.org/10.1080/02656736.2024.2373319","url":null,"abstract":"<p><strong>Background: </strong>Cryoablation (Cryo) is a minimally invasive treatment for tumors. Cryo can activate the body's immune response, although it is typically weak. The immune response induced by Cryo in hepatocellular carcinoma (HCC) is poorly understood. PD-1 and CTLA-4 monoclonal antibodies are immune checkpoint inhibitors used in immunotherapy for tumors. The combined use of these antibodies with Cryo may enhance the immune effect.</p><p><strong>Methods: </strong>A Balb/c mouse model of HCC was established and treated with Cryo, immune checkpoint blockade (ICB), or Cryo + ICB (combination therapy). The growth trend of right untreated tumors and survival time of mice were determined. The expression of apoptosis-related proteins was detected by Western blot (WB) assay. The percentages of immune cells and immunosuppressive cells were analyzed by flow cytometry. The numbers of infiltrating T lymphocytes were checked by immunohistochemistry, and the levels of T-cell-associated cytokines were detected by Quantitative real-time Polymerase Chain Reaction (qRT-PCR) assays and Enzyme-Linked Immunosorbent Assays (ELISA) assays.</p><p><strong>Results: </strong>Cryo + ICB inhibited the growth of right untreated tumors, promoted tumor cell apoptosis, and prolonged the survival time of mice. Local T-cell infiltration in right tumor tissues increased after the combination therapy, while the number of immunosuppressive cells was significantly reduced. In addition, the combination therapy may induce the production of multiple Th1-type cytokines but reduce the production of Th2-type cytokines.</p><p><strong>Conclusions: </strong>Cryo can activate CD8<sup>+</sup> and CD4<sup>+</sup> T-cell immune responses. Cryo + ICB can relieve the immunosuppressive tumor microenvironment and shift the Th1/Th2 balance toward Th1 dominance, further enhancing the Cryo-induced T-cell immune response and resulting in a stronger antitumor immune response.</p>","PeriodicalId":14137,"journal":{"name":"International Journal of Hyperthermia","volume":"41 1","pages":"2373319"},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141491891","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 : 2024-01-01Epub Date: 2024-01-08DOI: 10.1080/02656736.2023.2299480
Rogier van Oossanen, Alexandra Maier, Jérémy Godart, Jean-Philippe Pignol, Antonia G Denkova, Gerard C van Rhoon, Kristina Djanashvili
Objective: To investigate the potential of hybrid Pd/Fe-oxide magnetic nanoparticles designed for thermo-brachytherapy of breast cancer, considering their specific loss power (SLP) and clinical constraints in the applied magnetic field.
Methods: Hybrid nanoparticles consisting of palladium-core and iron oxide shell of increasing thickness, were suspended in water and their SLPs were measured at varying magnetic fields (12-26 mT peak) and frequencies (50-730 kHz) with a commercial alternating magnetic field generator (magneTherm™ Digital, nanoTherics Ltd.).
Results: Validation of the heating device used in this study with commercial HyperMag-C nanoparticles showed a small deviation (±4%) over a period of 1 year, confirming the reliability of the method. The integration of dual thermometers, one in the center and one at the bottom of the sample vial, allowed monitoring of homogeneity of the sample suspensions. SLPs measurements on a series of nanoparticles of increasing sizes showed the highest heating for the diameter of 21 nm (SLP = 225 W/g) at the applied frequencies of 346 and 730 kHz. No heating was observed for the nanoparticles with the size <14 nm, confirming the importance of the size-parameter. The heating ability of the best performing Pd/Fe-oxide-21 was calculated to be sufficient to ablate tumors with a radius ±4 and 12 mm using 10 and 1 mg/mL nanoparticle concentration, respectively.
Conclusions: Nanoparticles consisting of non-magnetic palladium-core and magnetic iron oxide shell are suitable for magnetic hyperthermia/thermal ablation under clinically safe conditions of 346 kHz and 19.1 mT, with minimal eddy current effects in combination with maximum SLP.
{"title":"Magnetic hybrid Pd/Fe-oxide nanoparticles meet the demands for ablative thermo-brachytherapy.","authors":"Rogier van Oossanen, Alexandra Maier, Jérémy Godart, Jean-Philippe Pignol, Antonia G Denkova, Gerard C van Rhoon, Kristina Djanashvili","doi":"10.1080/02656736.2023.2299480","DOIUrl":"10.1080/02656736.2023.2299480","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the potential of hybrid Pd/Fe-oxide magnetic nanoparticles designed for thermo-brachytherapy of breast cancer, considering their specific loss power (<i>SLP</i>) and clinical constraints in the applied magnetic field.</p><p><strong>Methods: </strong>Hybrid nanoparticles consisting of palladium-core and iron oxide shell of increasing thickness, were suspended in water and their <i>SLPs</i> were measured at varying magnetic fields (12-26 mT peak) and frequencies (50-730 kHz) with a commercial alternating magnetic field generator (magneTherm™ Digital, nanoTherics Ltd.).</p><p><strong>Results: </strong>Validation of the heating device used in this study with commercial HyperMag-C nanoparticles showed a small deviation (±4%) over a period of 1 year, confirming the reliability of the method. The integration of dual thermometers, one in the center and one at the bottom of the sample vial, allowed monitoring of homogeneity of the sample suspensions. <i>SLP</i>s measurements on a series of nanoparticles of increasing sizes showed the highest heating for the diameter of 21 nm (<i>SLP</i> = 225 W/g) at the applied frequencies of 346 and 730 kHz. No heating was observed for the nanoparticles with the size <14 nm, confirming the importance of the size-parameter. The heating ability of the best performing Pd/Fe-oxide-21 was calculated to be sufficient to ablate tumors with a radius ±4 and 12 mm using 10 and 1 mg/mL nanoparticle concentration, respectively.</p><p><strong>Conclusions: </strong>Nanoparticles consisting of non-magnetic palladium-core and magnetic iron oxide shell are suitable for magnetic hyperthermia/thermal ablation under clinically safe conditions of 346 kHz and 19.1 mT, with minimal eddy current effects in combination with maximum <i>SLP</i>.</p>","PeriodicalId":14137,"journal":{"name":"International Journal of Hyperthermia","volume":"41 1","pages":"2299480"},"PeriodicalIF":3.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139377562","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}