David E Gyorki*,1 & Jonathan S Zager2 1Division of Cancer Surgery, Peter MacCallum Cancer Centre & Department of Surgery, University of Melbourne, Melbourne, VIC, 3000 Australia 2Moffitt Cancer Center, Departments of Cutaneous Oncology & Sarcoma, University of South Florida Morsani School of Medicine, Tampa, FL, 33612 USA *Author for correspondence: Tel.: +61 3 8559 7704; David.gyorki@petermac.org
David E Gyorki*，1和Jonathan S Zager2 1墨尔本大学Peter MacCallum癌症中心和外科肿瘤部，墨尔本，维多利亚州，3000澳大利亚2莫菲特癌症中心，皮肤肿瘤和肉瘤部，南佛罗里达大学Morsani医学院，坦帕，佛罗里达州，33612美国*通讯作者:电话:+61 3 8559 7704;David.gyorki@petermac.org
{"title":"Locoregional melanoma: identifying optimal care in a rapidly changing landscape","authors":"D. Gyorki, J. Zager","doi":"10.2217/mmt-2019-0014","DOIUrl":"https://doi.org/10.2217/mmt-2019-0014","url":null,"abstract":"David E Gyorki*,1 & Jonathan S Zager2 1Division of Cancer Surgery, Peter MacCallum Cancer Centre & Department of Surgery, University of Melbourne, Melbourne, VIC, 3000 Australia 2Moffitt Cancer Center, Departments of Cutaneous Oncology & Sarcoma, University of South Florida Morsani School of Medicine, Tampa, FL, 33612 USA *Author for correspondence: Tel.: +61 3 8559 7704; David.gyorki@petermac.org","PeriodicalId":44562,"journal":{"name":"Melanoma Management","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/mmt-2019-0014","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48780377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
E. Samuel, M. Moore, M. Voskoboynik, M. Shackleton, A. Haydon
There is a global increase in the incidence of melanoma, with approximately 300,000 new cases in 2018 worldwide, according to statistics from the International Agency for Research on Cancer. With this rising incidence, it is important to optimize treatment strategies in all stages of the disease to provide better patient outcomes. The role of adjuvant therapy in patients with resected stage 3 melanoma is a rapidly evolving field. Interferon was the first agent shown to have any utility in this space, however, recent advances in both targeted therapies and immunotherapies have led to a number of practice changing adjuvant trials in resected stage 3 disease.
{"title":"An update on adjuvant systemic therapies in melanoma","authors":"E. Samuel, M. Moore, M. Voskoboynik, M. Shackleton, A. Haydon","doi":"10.2217/mmt-2019-0009","DOIUrl":"https://doi.org/10.2217/mmt-2019-0009","url":null,"abstract":"There is a global increase in the incidence of melanoma, with approximately 300,000 new cases in 2018 worldwide, according to statistics from the International Agency for Research on Cancer. With this rising incidence, it is important to optimize treatment strategies in all stages of the disease to provide better patient outcomes. The role of adjuvant therapy in patients with resected stage 3 melanoma is a rapidly evolving field. Interferon was the first agent shown to have any utility in this space, however, recent advances in both targeted therapies and immunotherapies have led to a number of practice changing adjuvant trials in resected stage 3 disease.","PeriodicalId":44562,"journal":{"name":"Melanoma Management","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/mmt-2019-0009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41283898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Management of later stage melanoma has undergone significant changes. Sentinel node biopsy has long been an accepted method of staging, but two recent randomized-controlled trials have provided an evidence base for decision making about completion lymphadenectomy. They showed no survival advantage in further surgery for patients with positive sentinel node biopsies. There is now no evidence to support completion lymphadenectomy in the majority of patients, and this is reflected in international practice guidelines.
{"title":"An evidence-based approach to positive sentinel node disease: should we ever do a completion node dissection?","authors":"J. Downs, D. Gyorki","doi":"10.2217/mmt-2019-0011","DOIUrl":"https://doi.org/10.2217/mmt-2019-0011","url":null,"abstract":"Management of later stage melanoma has undergone significant changes. Sentinel node biopsy has long been an accepted method of staging, but two recent randomized-controlled trials have provided an evidence base for decision making about completion lymphadenectomy. They showed no survival advantage in further surgery for patients with positive sentinel node biopsies. There is now no evidence to support completion lymphadenectomy in the majority of patients, and this is reflected in international practice guidelines.","PeriodicalId":44562,"journal":{"name":"Melanoma Management","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2019-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/mmt-2019-0011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41369145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
James X. Sun, Dennis Kirichenko, J. Zager, Z. Eroglu
The discovery of immunotherapy and targeted therapy has introduced new and effective treatment options for advanced melanoma, providing therapeutic options where none existed before. The natural extension of these novel therapies is to identify their role in the neoadjuvant setting. Neoadjuvant therapy for advanced melanoma is still in its infancy, with a wealth of clinical trials underway. Early results are promising, allowing for management of a disease that previously had few options. We review the current literature and interim results from several ongoing investigations to understand the current state of neoadjuvant treatment options and what is to come. These studies pave the way for further advancements in melanoma therapy.
{"title":"The emergence of neoadjuvant therapy in advanced melanoma","authors":"James X. Sun, Dennis Kirichenko, J. Zager, Z. Eroglu","doi":"10.2217/mmt-2019-0007","DOIUrl":"https://doi.org/10.2217/mmt-2019-0007","url":null,"abstract":"The discovery of immunotherapy and targeted therapy has introduced new and effective treatment options for advanced melanoma, providing therapeutic options where none existed before. The natural extension of these novel therapies is to identify their role in the neoadjuvant setting. Neoadjuvant therapy for advanced melanoma is still in its infancy, with a wealth of clinical trials underway. Early results are promising, allowing for management of a disease that previously had few options. We review the current literature and interim results from several ongoing investigations to understand the current state of neoadjuvant treatment options and what is to come. These studies pave the way for further advancements in melanoma therapy.","PeriodicalId":44562,"journal":{"name":"Melanoma Management","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2019-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/mmt-2019-0007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44332584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Peter Mohr, Felix Kiecker, Virtudes Soriano, Olivier Dereure, Karmele Mujika, Philippe Saiag, Jochen Utikal, Rama Koneru, Caroline Robert, Florencia Cuadros, Matias Chacón, Rodrigo U Villarroel, Yana G Najjar, Lisa Kottschade, Eva M Couselo, Roy Koruth, Annie Guérin, Rebecca Burne, Raluca Ionescu-Ittu, Maurice Perrinjaquet, Jonathan S Zager
Aim: To describe treatment patterns among patients with stage III melanoma who underwent surgical excision in years 2011-2016, and assess outcomes among patients who subsequently received systemic adjuvant therapy versus watch-and-wait.
Methods: Chart review of 380 patients from 17 melanoma centers in North America, South America and Europe.
Results: Of 129 (34%) patients treated with adjuvant therapy, 85% received interferon α-2b and 56% discontinued treatment (mostly due to adverse events). Relapse-free survival was significantly longer for patients treated with adjuvant therapy versus watch-and-wait (hazard ratio = 0.63; p < 0.05). There was considerable heterogeneity in adjuvant treatment schedules and doses. Similar results were found in patients who received interferon-based adjuvant therapy.
Conclusion: Adjuvant therapies with better safety/efficacy profiles will improve clinical outcomes in patients with stage III melanoma.
{"title":"Adjuvant therapy versus watch-and-wait post surgery for stage III melanoma: a multicountry retrospective chart review.","authors":"Peter Mohr, Felix Kiecker, Virtudes Soriano, Olivier Dereure, Karmele Mujika, Philippe Saiag, Jochen Utikal, Rama Koneru, Caroline Robert, Florencia Cuadros, Matias Chacón, Rodrigo U Villarroel, Yana G Najjar, Lisa Kottschade, Eva M Couselo, Roy Koruth, Annie Guérin, Rebecca Burne, Raluca Ionescu-Ittu, Maurice Perrinjaquet, Jonathan S Zager","doi":"10.2217/mmt-2019-0015","DOIUrl":"10.2217/mmt-2019-0015","url":null,"abstract":"<p><strong>Aim: </strong>To describe treatment patterns among patients with stage III melanoma who underwent surgical excision in years 2011-2016, and assess outcomes among patients who subsequently received systemic adjuvant therapy versus watch-and-wait.</p><p><strong>Methods: </strong>Chart review of 380 patients from 17 melanoma centers in North America, South America and Europe.</p><p><strong>Results: </strong>Of 129 (34%) patients treated with adjuvant therapy, 85% received interferon α-2b and 56% discontinued treatment (mostly due to adverse events). Relapse-free survival was significantly longer for patients treated with adjuvant therapy versus watch-and-wait (hazard ratio = 0.63; p < 0.05). There was considerable heterogeneity in adjuvant treatment schedules and doses. Similar results were found in patients who received interferon-based adjuvant therapy.</p><p><strong>Conclusion: </strong>Adjuvant therapies with better safety/efficacy profiles will improve clinical outcomes in patients with stage III melanoma.</p>","PeriodicalId":44562,"journal":{"name":"Melanoma Management","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2019-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/mmt-2019-0015","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37486814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This report surveys the role of topical and intralesional agents in the management of in-transit melanoma. The extent and progression of in-transit disease is highly variable and many patients can have a protracted period of locoregional control. These agents are useful in the management of patients who have progressed beyond local surgical excision in whom more aggressive therapies, such as isolated limb infusion or use of talimogene laherparepvec, are not appropriate or have failed. In general, these agents are modestly effective and associated with frequent but only minor toxicity. As the mechanism of action of many of these agents includes initiation of a local immune response, combinations with immune checkpoint inhibitors are currently being explored.
{"title":"Topical and intralesional therapies for in-transitmelanoma","authors":"M. Henderson","doi":"10.2217/mmt-2019-0008","DOIUrl":"https://doi.org/10.2217/mmt-2019-0008","url":null,"abstract":"This report surveys the role of topical and intralesional agents in the management of in-transit melanoma. The extent and progression of in-transit disease is highly variable and many patients can have a protracted period of locoregional control. These agents are useful in the management of patients who have progressed beyond local surgical excision in whom more aggressive therapies, such as isolated limb infusion or use of talimogene laherparepvec, are not appropriate or have failed. In general, these agents are modestly effective and associated with frequent but only minor toxicity. As the mechanism of action of many of these agents includes initiation of a local immune response, combinations with immune checkpoint inhibitors are currently being explored.","PeriodicalId":44562,"journal":{"name":"Melanoma Management","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2019-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/mmt-2019-0008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46961049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Immune checkpoint inhibitors and BRAF-MEK inhibitors have revolutionized the management and prognosis of patients with metastatic melanoma. However, there is minimal evidence to guide their incorporation into current treatment paradigms for unresectable stage III disease. The era of effective systemic therapies has prompted a discussion about what constitutes unresectable disease. Patients with unresectable stage III disease can experience significant morbidity from their disease and locoregional therapies, and may progress with distant metastases. Despite increasing use of systemic therapies in unresectable stage III disease, further evidence is needed to establish their degree of benefit in this population.
{"title":"Systemic therapies for unresectable locoregional melanoma: a significant area of need","authors":"E. Nan Tie, J. Lai-Kwon, D. Gyorki","doi":"10.2217/mmt-2019-0010","DOIUrl":"https://doi.org/10.2217/mmt-2019-0010","url":null,"abstract":"Immune checkpoint inhibitors and BRAF-MEK inhibitors have revolutionized the management and prognosis of patients with metastatic melanoma. However, there is minimal evidence to guide their incorporation into current treatment paradigms for unresectable stage III disease. The era of effective systemic therapies has prompted a discussion about what constitutes unresectable disease. Patients with unresectable stage III disease can experience significant morbidity from their disease and locoregional therapies, and may progress with distant metastases. Despite increasing use of systemic therapies in unresectable stage III disease, further evidence is needed to establish their degree of benefit in this population.","PeriodicalId":44562,"journal":{"name":"Melanoma Management","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2019-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/mmt-2019-0010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41836644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Locoregional disease remains a challenging problem in cutaneous melanoma and uveal melanoma. Arterial-based chemoperfusion strategies enable regional therapy delivery with minimal systemic toxicity. Herein we discuss intra-arterial therapies for in-transit cutaneous melanoma of the extremity including hyperthermic-isolated limb perfusion and isolated limb infusion. We also discuss open (isolated hepatic perfusion) and percutaneous hepatic perfusion techniques for isolated liver metastases from uveal melanoma. We review the current state of knowledge with respect to indications, procedural techniques, outcomes and expected toxicities for intra-arterial chemoperfusion for locoregional melanoma metastases.
{"title":"Intra-arterial perfusion-based therapies for regionally metastatic cutaneous and uveal melanoma.","authors":"Kristy K Broman, Jonathan S Zager","doi":"10.2217/mmt-2019-0006","DOIUrl":"10.2217/mmt-2019-0006","url":null,"abstract":"<p><p>Locoregional disease remains a challenging problem in cutaneous melanoma and uveal melanoma. Arterial-based chemoperfusion strategies enable regional therapy delivery with minimal systemic toxicity. Herein we discuss intra-arterial therapies for in-transit cutaneous melanoma of the extremity including hyperthermic-isolated limb perfusion and isolated limb infusion. We also discuss open (isolated hepatic perfusion) and percutaneous hepatic perfusion techniques for isolated liver metastases from uveal melanoma. We review the current state of knowledge with respect to indications, procedural techniques, outcomes and expected toxicities for intra-arterial chemoperfusion for locoregional melanoma metastases.</p>","PeriodicalId":44562,"journal":{"name":"Melanoma Management","volume":null,"pages":null},"PeriodicalIF":1.0,"publicationDate":"2019-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6891941/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45267786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Robert V Rawson, Teresa Bailey, Andrew J Colebatch, Peter Ferguson
Hauschild A, Dummer R, Schadendorf D et al. Longer follow-up confirms relapse-free survival benefit with adjuvant dabrafenib plus trametinib in patients with resected BRAF V600-mutant Stage III melanoma. J. Clin. Oncol. 36(35), 3441–3449 (2018) This publication, an update of the COMBI-AD trial, provides the most mature data with extended follow-up in Stage III metastatic melanoma patients treated with immune checkpoint or targeted therapies in the adjuvant setting. The results of this study of Stage III BRAF V600 mutant metastatic melanoma continue to show relapse-free survival (RFS) benefit at 40 months of dabrafenib plus trametinib therapy over placebo with an absolute difference of almost 20% between the arms. The RFS benefit was also confirmed regardless of stage, clinical and pathological subgroups. For the first time, the somewhat controversial, Weibull mixture cure-rate analysis has been used in metastatic melanoma patients and showed estimated cure rates of 54% (treatment arm) versus 37% (placebo arm). Moving forward it will be interesting to compare these results with the results of immunotherapy and combinations therapy trials in the adjuvant and neoadjuvant setting to ascertain the optimal treatment protocol for BRAF-mutant metastatic melanoma patients. – Written by Robert V Rawson
{"title":"Journal Watch: our panel of experts highlight the most important research articles across the spectrum of topics relevant to the field of melanoma management.","authors":"Robert V Rawson, Teresa Bailey, Andrew J Colebatch, Peter Ferguson","doi":"10.2217/mmt-2019-0002","DOIUrl":"https://doi.org/10.2217/mmt-2019-0002","url":null,"abstract":"Hauschild A, Dummer R, Schadendorf D et al. Longer follow-up confirms relapse-free survival benefit with adjuvant dabrafenib plus trametinib in patients with resected BRAF V600-mutant Stage III melanoma. J. Clin. Oncol. 36(35), 3441–3449 (2018) This publication, an update of the COMBI-AD trial, provides the most mature data with extended follow-up in Stage III metastatic melanoma patients treated with immune checkpoint or targeted therapies in the adjuvant setting. The results of this study of Stage III BRAF V600 mutant metastatic melanoma continue to show relapse-free survival (RFS) benefit at 40 months of dabrafenib plus trametinib therapy over placebo with an absolute difference of almost 20% between the arms. The RFS benefit was also confirmed regardless of stage, clinical and pathological subgroups. For the first time, the somewhat controversial, Weibull mixture cure-rate analysis has been used in metastatic melanoma patients and showed estimated cure rates of 54% (treatment arm) versus 37% (placebo arm). Moving forward it will be interesting to compare these results with the results of immunotherapy and combinations therapy trials in the adjuvant and neoadjuvant setting to ascertain the optimal treatment protocol for BRAF-mutant metastatic melanoma patients. – Written by Robert V Rawson","PeriodicalId":44562,"journal":{"name":"Melanoma Management","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2019-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/mmt-2019-0002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37358792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Perez, J. Zager, T. Amatruda, R. Conry, C. Ariyan, Anupam M. Desai, J. Kirkwood, S. Treichel, D. Cohan, L. Raskin
Aim: Talimogene laherparepvec (T-VEC) is an intralesional treatment for unresectable cutaneous, subcutaneous and nodal melanoma. COSMUS-1 was conducted to examine how T-VEC is used in US clinical practice. Materials & methods: A chart review was conducted at seven centers, with 78 patients screened and 76 eligible. Results: Patients began treatment with T-VEC between October 2015 and December 2016. Median follow-up was 9.4 months. Twenty percent of patients (n = 15) completed T-VEC treatment with no remaining injectable lesions or pathologic complete response. Flu-like symptoms were the most commonly reported adverse events (n = 8; 10.5%), followed by lesion ulceration (n = 4; 5.3%). No herpetic lesions or infections were reported. Conclusion: T-VEC was well tolerated and showed clinical utility.
{"title":"Observational study of talimogene laherparepvec use for melanoma in clinical practice in the United States (COSMUS-1)","authors":"M. Perez, J. Zager, T. Amatruda, R. Conry, C. Ariyan, Anupam M. Desai, J. Kirkwood, S. Treichel, D. Cohan, L. Raskin","doi":"10.2217/mmt-2019-0012","DOIUrl":"https://doi.org/10.2217/mmt-2019-0012","url":null,"abstract":"Aim: Talimogene laherparepvec (T-VEC) is an intralesional treatment for unresectable cutaneous, subcutaneous and nodal melanoma. COSMUS-1 was conducted to examine how T-VEC is used in US clinical practice. Materials & methods: A chart review was conducted at seven centers, with 78 patients screened and 76 eligible. Results: Patients began treatment with T-VEC between October 2015 and December 2016. Median follow-up was 9.4 months. Twenty percent of patients (n = 15) completed T-VEC treatment with no remaining injectable lesions or pathologic complete response. Flu-like symptoms were the most commonly reported adverse events (n = 8; 10.5%), followed by lesion ulceration (n = 4; 5.3%). No herpetic lesions or infections were reported. Conclusion: T-VEC was well tolerated and showed clinical utility.","PeriodicalId":44562,"journal":{"name":"Melanoma Management","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2019-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/mmt-2019-0012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49513528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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