The use of neoadjuvant larotrectinib in the management of children with locally advanced TRK fusion sarcomas

Background The highly selective oral tropomyosin receptor kinase (TRK) inhibitor larotrectinib has demonstrated significant activity in adult and pediatric TRK fusion cancers. In the current study, the authors describe the clinical course of children with locally advanced TRK fusion sarcoma who were...

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Published in:	Cancer Vol. 124; no. 21; pp. 4241 - 4247
Main Authors:	DuBois, Steven G., Laetsch, Theodore W., Federman, Noah, Turpin, Brian K., Albert, Catherine M., Nagasubramanian, Ramamoorthy, Anderson, Megan E., Davis, Jessica L., Qamoos, Hope E., Reynolds, Mark E., Cruickshank, Scott, Cox, Michael C., Hawkins, Douglas S., Mascarenhas, Leo, Pappo, Alberto S.
Format:	Journal Article
Language:	English
Published:	United States Wiley Subscription Services, Inc 01.11.2018 John Wiley and Sons Inc
Subjects:	Children Complications Enzyme inhibitors Evaluation Fibrosarcoma infantile fibrosarcoma Inhibitors larotrectinib local control Morbidity neurotrophic receptor tyrosine kinase (NTRK) Oncology Original Patients pediatric Pediatrics Sarcoma Solid tumors Surgery Therapy Tropomyosin tropomyosin receptor kinase (TRK) fusion Tumors Wound healing larotrectinib sarcoma tropomyosin receptor kinase (TRK) fusion local control neurotrophic receptor tyrosine kinase (NTRK) infantile fibrosarcoma pediatric surgery
ISSN:	0008-543X, 1097-0142, 1097-0142
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Abstract	Background The highly selective oral tropomyosin receptor kinase (TRK) inhibitor larotrectinib has demonstrated significant activity in adult and pediatric TRK fusion cancers. In the current study, the authors describe the clinical course of children with locally advanced TRK fusion sarcoma who were treated preoperatively with larotrectinib and underwent subsequent surgical resection. Methods A total of 24 children were treated on a pediatric phase 1 trial of larotrectinib (ClinicalTrials.gov identifier NCT02637687). Five children who had a documented TRK fusion sarcoma and underwent surgical resection were included in the current analysis. Tumor response (Response Evaluation Criteria In Solid Tumors [RECIST] version 1.1) and surgical outcomes were collected prospectively. Results A total of 5 patients (median age, 2 years; range, 0.4‐12 years) had locally advanced infantile fibrosarcoma (3 patients) or soft‐tissue sarcoma (2 patients). Four patients had disease that was refractory to standard therapy. All 5 patients achieved a partial response to larotrectinib by version 1.1 of RECIST and underwent surgical resection after a median of 6 cycles (range, 4‐9 cycles) of treatment. Surgical resections were R0 (negative resection margins with no tumor at the inked resection margin) in 3 patients, R1 (microscopic residual tumor at the resection margin) in 1 patient, and R2 (macroscopic residual tumor at the resection margin) in 1 patient. Three patients achieved complete (2 patients) or near‐complete (>98% treatment effect; 1 patient) pathologic responses. These patients remained in follow‐up and were no longer receiving larotrectinib for a minimum of 7 to 15 months postoperatively. Two patients had viable tumor at the time of surgical resection and positive resection margins and continued to receive adjuvant larotrectinib. No patients experienced postoperative complications or wound healing issues. Conclusions Children with locally advanced TRK fusion sarcomas may proceed to surgical resection after treatment with the selective TRK inhibitor larotrectinib, thereby sparing them the potentially significant morbidity noted with current approaches. These results support the evaluation of larotrectinib as presurgical therapy in children with newly diagnosed TRK fusion sarcomas. Children with locally advanced tropomyosin receptor kinase (TRK) fusion sarcomas may proceed to surgical resection after neoadjuvant treatment with the selective oral TRK inhibitor larotrectinib, sparing them the potentially significant morbidity noted with current approaches. The results of the current study support the further evaluation of larotrectinib as neoadjuvant therapy in children with newly diagnosed TRK fusion sarcomas.
AbstractList	Children with locally advanced tropomyosin receptor kinase (TRK) fusion sarcomas may proceed to surgical resection after neoadjuvant treatment with the selective oral TRK inhibitor larotrectinib, sparing them the potentially significant morbidity noted with current approaches. The results of the current study support the further evaluation of larotrectinib as neoadjuvant therapy in children with newly diagnosed TRK fusion sarcomas. Background The highly selective oral tropomyosin receptor kinase (TRK) inhibitor larotrectinib has demonstrated significant activity in adult and pediatric TRK fusion cancers. In the current study, the authors describe the clinical course of children with locally advanced TRK fusion sarcoma who were treated preoperatively with larotrectinib and underwent subsequent surgical resection. Methods A total of 24 children were treated on a pediatric phase 1 trial of larotrectinib (ClinicalTrials.gov identifier NCT02637687). Five children who had a documented TRK fusion sarcoma and underwent surgical resection were included in the current analysis. Tumor response (Response Evaluation Criteria In Solid Tumors [RECIST] version 1.1) and surgical outcomes were collected prospectively. Results A total of 5 patients (median age, 2 years; range, 0.4‐12 years) had locally advanced infantile fibrosarcoma (3 patients) or soft‐tissue sarcoma (2 patients). Four patients had disease that was refractory to standard therapy. All 5 patients achieved a partial response to larotrectinib by version 1.1 of RECIST and underwent surgical resection after a median of 6 cycles (range, 4‐9 cycles) of treatment. Surgical resections were R0 (negative resection margins with no tumor at the inked resection margin) in 3 patients, R1 (microscopic residual tumor at the resection margin) in 1 patient, and R2 (macroscopic residual tumor at the resection margin) in 1 patient. Three patients achieved complete (2 patients) or near‐complete (>98% treatment effect; 1 patient) pathologic responses. These patients remained in follow‐up and were no longer receiving larotrectinib for a minimum of 7 to 15 months postoperatively. Two patients had viable tumor at the time of surgical resection and positive resection margins and continued to receive adjuvant larotrectinib. No patients experienced postoperative complications or wound healing issues. Conclusions Children with locally advanced TRK fusion sarcomas may proceed to surgical resection after treatment with the selective TRK inhibitor larotrectinib, thereby sparing them the potentially significant morbidity noted with current approaches. These results support the evaluation of larotrectinib as presurgical therapy in children with newly diagnosed TRK fusion sarcomas. Children with locally advanced tropomyosin receptor kinase (TRK) fusion sarcomas may proceed to surgical resection after neoadjuvant treatment with the selective oral TRK inhibitor larotrectinib, sparing them the potentially significant morbidity noted with current approaches. The results of the current study support the further evaluation of larotrectinib as neoadjuvant therapy in children with newly diagnosed TRK fusion sarcomas. The highly selective oral tropomyosin receptor kinase (TRK) inhibitor larotrectinib has demonstrated significant activity in adult and pediatric TRK fusion cancers. In the current study, the authors describe the clinical course of children with locally advanced TRK fusion sarcoma who were treated preoperatively with larotrectinib and underwent subsequent surgical resection.BACKGROUNDThe highly selective oral tropomyosin receptor kinase (TRK) inhibitor larotrectinib has demonstrated significant activity in adult and pediatric TRK fusion cancers. In the current study, the authors describe the clinical course of children with locally advanced TRK fusion sarcoma who were treated preoperatively with larotrectinib and underwent subsequent surgical resection.A total of 24 children were treated on a pediatric phase 1 trial of larotrectinib (ClinicalTrials.gov identifier NCT02637687). Five children who had a documented TRK fusion sarcoma and underwent surgical resection were included in the current analysis. Tumor response (Response Evaluation Criteria In Solid Tumors [RECIST] version 1.1) and surgical outcomes were collected prospectively.METHODSA total of 24 children were treated on a pediatric phase 1 trial of larotrectinib (ClinicalTrials.gov identifier NCT02637687). Five children who had a documented TRK fusion sarcoma and underwent surgical resection were included in the current analysis. Tumor response (Response Evaluation Criteria In Solid Tumors [RECIST] version 1.1) and surgical outcomes were collected prospectively.A total of 5 patients (median age, 2 years; range, 0.4-12 years) had locally advanced infantile fibrosarcoma (3 patients) or soft-tissue sarcoma (2 patients). Four patients had disease that was refractory to standard therapy. All 5 patients achieved a partial response to larotrectinib by version 1.1 of RECIST and underwent surgical resection after a median of 6 cycles (range, 4-9 cycles) of treatment. Surgical resections were R0 (negative resection margins with no tumor at the inked resection margin) in 3 patients, R1 (microscopic residual tumor at the resection margin) in 1 patient, and R2 (macroscopic residual tumor at the resection margin) in 1 patient. Three patients achieved complete (2 patients) or near-complete (>98% treatment effect; 1 patient) pathologic responses. These patients remained in follow-up and were no longer receiving larotrectinib for a minimum of 7 to 15 months postoperatively. Two patients had viable tumor at the time of surgical resection and positive resection margins and continued to receive adjuvant larotrectinib. No patients experienced postoperative complications or wound healing issues.RESULTSA total of 5 patients (median age, 2 years; range, 0.4-12 years) had locally advanced infantile fibrosarcoma (3 patients) or soft-tissue sarcoma (2 patients). Four patients had disease that was refractory to standard therapy. All 5 patients achieved a partial response to larotrectinib by version 1.1 of RECIST and underwent surgical resection after a median of 6 cycles (range, 4-9 cycles) of treatment. Surgical resections were R0 (negative resection margins with no tumor at the inked resection margin) in 3 patients, R1 (microscopic residual tumor at the resection margin) in 1 patient, and R2 (macroscopic residual tumor at the resection margin) in 1 patient. Three patients achieved complete (2 patients) or near-complete (>98% treatment effect; 1 patient) pathologic responses. These patients remained in follow-up and were no longer receiving larotrectinib for a minimum of 7 to 15 months postoperatively. Two patients had viable tumor at the time of surgical resection and positive resection margins and continued to receive adjuvant larotrectinib. No patients experienced postoperative complications or wound healing issues.Children with locally advanced TRK fusion sarcomas may proceed to surgical resection after treatment with the selective TRK inhibitor larotrectinib, thereby sparing them the potentially significant morbidity noted with current approaches. These results support the evaluation of larotrectinib as presurgical therapy in children with newly diagnosed TRK fusion sarcomas.CONCLUSIONSChildren with locally advanced TRK fusion sarcomas may proceed to surgical resection after treatment with the selective TRK inhibitor larotrectinib, thereby sparing them the potentially significant morbidity noted with current approaches. These results support the evaluation of larotrectinib as presurgical therapy in children with newly diagnosed TRK fusion sarcomas. BackgroundThe highly selective oral tropomyosin receptor kinase (TRK) inhibitor larotrectinib has demonstrated significant activity in adult and pediatric TRK fusion cancers. In the current study, the authors describe the clinical course of children with locally advanced TRK fusion sarcoma who were treated preoperatively with larotrectinib and underwent subsequent surgical resection.MethodsA total of 24 children were treated on a pediatric phase 1 trial of larotrectinib (ClinicalTrials.gov identifier NCT02637687). Five children who had a documented TRK fusion sarcoma and underwent surgical resection were included in the current analysis. Tumor response (Response Evaluation Criteria In Solid Tumors [RECIST] version 1.1) and surgical outcomes were collected prospectively.ResultsA total of 5 patients (median age, 2 years; range, 0.4‐12 years) had locally advanced infantile fibrosarcoma (3 patients) or soft‐tissue sarcoma (2 patients). Four patients had disease that was refractory to standard therapy. All 5 patients achieved a partial response to larotrectinib by version 1.1 of RECIST and underwent surgical resection after a median of 6 cycles (range, 4‐9 cycles) of treatment. Surgical resections were R0 (negative resection margins with no tumor at the inked resection margin) in 3 patients, R1 (microscopic residual tumor at the resection margin) in 1 patient, and R2 (macroscopic residual tumor at the resection margin) in 1 patient. Three patients achieved complete (2 patients) or near‐complete (>98% treatment effect; 1 patient) pathologic responses. These patients remained in follow‐up and were no longer receiving larotrectinib for a minimum of 7 to 15 months postoperatively. Two patients had viable tumor at the time of surgical resection and positive resection margins and continued to receive adjuvant larotrectinib. No patients experienced postoperative complications or wound healing issues.ConclusionsChildren with locally advanced TRK fusion sarcomas may proceed to surgical resection after treatment with the selective TRK inhibitor larotrectinib, thereby sparing them the potentially significant morbidity noted with current approaches. These results support the evaluation of larotrectinib as presurgical therapy in children with newly diagnosed TRK fusion sarcomas. The highly selective oral tropomyosin receptor kinase (TRK) inhibitor larotrectinib has demonstrated significant activity in adult and pediatric TRK fusion cancers. In the current study, the authors describe the clinical course of children with locally advanced TRK fusion sarcoma who were treated preoperatively with larotrectinib and underwent subsequent surgical resection. A total of 24 children were treated on a pediatric phase 1 trial of larotrectinib (ClinicalTrials.gov identifier NCT02637687). Five children who had a documented TRK fusion sarcoma and underwent surgical resection were included in the current analysis. Tumor response (Response Evaluation Criteria In Solid Tumors [RECIST] version 1.1) and surgical outcomes were collected prospectively. A total of 5 patients (median age, 2 years; range, 0.4-12 years) had locally advanced infantile fibrosarcoma (3 patients) or soft-tissue sarcoma (2 patients). Four patients had disease that was refractory to standard therapy. All 5 patients achieved a partial response to larotrectinib by version 1.1 of RECIST and underwent surgical resection after a median of 6 cycles (range, 4-9 cycles) of treatment. Surgical resections were R0 (negative resection margins with no tumor at the inked resection margin) in 3 patients, R1 (microscopic residual tumor at the resection margin) in 1 patient, and R2 (macroscopic residual tumor at the resection margin) in 1 patient. Three patients achieved complete (2 patients) or near-complete (>98% treatment effect; 1 patient) pathologic responses. These patients remained in follow-up and were no longer receiving larotrectinib for a minimum of 7 to 15 months postoperatively. Two patients had viable tumor at the time of surgical resection and positive resection margins and continued to receive adjuvant larotrectinib. No patients experienced postoperative complications or wound healing issues. Children with locally advanced TRK fusion sarcomas may proceed to surgical resection after treatment with the selective TRK inhibitor larotrectinib, thereby sparing them the potentially significant morbidity noted with current approaches. These results support the evaluation of larotrectinib as presurgical therapy in children with newly diagnosed TRK fusion sarcomas. Children with locally advanced tropomyosin receptor kinase (TRK) fusion sarcomas may proceed to surgical resection after neoadjuvant treatment with the selective oral TRK inhibitor larotrectinib, sparing them the potentially significant morbidity noted with current approaches. The results of the current study support the further evaluation of larotrectinib as neoadjuvant therapy in children with newly diagnosed TRK fusion sarcomas.
Author	Turpin, Brian K. Reynolds, Mark E. Anderson, Megan E. DuBois, Steven G. Cox, Michael C. Cruickshank, Scott Federman, Noah Mascarenhas, Leo Albert, Catherine M. Nagasubramanian, Ramamoorthy Pappo, Alberto S. Laetsch, Theodore W. Davis, Jessica L. Hawkins, Douglas S. Qamoos, Hope E.
AuthorAffiliation	6 Department of Pediatrics Nemours Children’s Hospital Orlando Florida 5 Department of Pediatrics, Seattle Children’s Hospital, Fred Hutchinson Cancer Research Center University of Washington Seattle Washington 9 Loxo Oncology Inc South San Francisco California 10 Department of Pediatrics, Children’s Hospital Los Angeles, Keck School of Medicine University of Southern California Los Angeles California 4 Cancer and Blood Diseases Institute Cincinnati Children’s Hospital Medical Center Cincinnati Ohio 11 Department of Oncology St Jude Children’s Research Hospital Memphis Tennessee 3 Department of Pediatrics University of California at Los Angeles Los Angeles California 1 Pediatric Hematology/Oncology, Dana‐Farber/Boston Children’s Cancer and Blood Disorders Center Harvard Medical School Boston Massachusetts 7 Department of Orthopedic Surgery Boston Children’s Hospital, Harvard Medical School Boston Massachusetts 8 Department of Pathology Oregon Health and Science University Portland Oregon 2 Depar
AuthorAffiliation_xml	– name: 4 Cancer and Blood Diseases Institute Cincinnati Children’s Hospital Medical Center Cincinnati Ohio – name: 10 Department of Pediatrics, Children’s Hospital Los Angeles, Keck School of Medicine University of Southern California Los Angeles California – name: 5 Department of Pediatrics, Seattle Children’s Hospital, Fred Hutchinson Cancer Research Center University of Washington Seattle Washington – name: 9 Loxo Oncology Inc South San Francisco California – name: 11 Department of Oncology St Jude Children’s Research Hospital Memphis Tennessee – name: 6 Department of Pediatrics Nemours Children’s Hospital Orlando Florida – name: 8 Department of Pathology Oregon Health and Science University Portland Oregon – name: 2 Department of Pediatrics University of Texas Southwestern Medical Center/Children’s Health Dallas Texas – name: 3 Department of Pediatrics University of California at Los Angeles Los Angeles California – name: 1 Pediatric Hematology/Oncology, Dana‐Farber/Boston Children’s Cancer and Blood Disorders Center Harvard Medical School Boston Massachusetts – name: 7 Department of Orthopedic Surgery Boston Children’s Hospital, Harvard Medical School Boston Massachusetts
Author_xml	– sequence: 1 givenname: Steven G. surname: DuBois fullname: DuBois, Steven G. email: steven_dubois@dfci.harvard.edu organization: Harvard Medical School – sequence: 2 givenname: Theodore W. surname: Laetsch fullname: Laetsch, Theodore W. organization: University of Texas Southwestern Medical Center/Children’s Health – sequence: 3 givenname: Noah surname: Federman fullname: Federman, Noah organization: University of California at Los Angeles – sequence: 4 givenname: Brian K. surname: Turpin fullname: Turpin, Brian K. organization: Cincinnati Children’s Hospital Medical Center – sequence: 5 givenname: Catherine M. surname: Albert fullname: Albert, Catherine M. organization: University of Washington – sequence: 6 givenname: Ramamoorthy surname: Nagasubramanian fullname: Nagasubramanian, Ramamoorthy organization: Nemours Children’s Hospital – sequence: 7 givenname: Megan E. surname: Anderson fullname: Anderson, Megan E. organization: Boston Children’s Hospital, Harvard Medical School – sequence: 8 givenname: Jessica L. surname: Davis fullname: Davis, Jessica L. organization: Oregon Health and Science University – sequence: 9 givenname: Hope E. surname: Qamoos fullname: Qamoos, Hope E. organization: Loxo Oncology Inc – sequence: 10 givenname: Mark E. surname: Reynolds fullname: Reynolds, Mark E. organization: Loxo Oncology Inc – sequence: 11 givenname: Scott surname: Cruickshank fullname: Cruickshank, Scott organization: Loxo Oncology Inc – sequence: 12 givenname: Michael C. surname: Cox fullname: Cox, Michael C. organization: Loxo Oncology Inc – sequence: 13 givenname: Douglas S. surname: Hawkins fullname: Hawkins, Douglas S. organization: University of Washington – sequence: 14 givenname: Leo surname: Mascarenhas fullname: Mascarenhas, Leo organization: University of Southern California – sequence: 15 givenname: Alberto S. surname: Pappo fullname: Pappo, Alberto S. organization: St Jude Children’s Research Hospital
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Keywords	larotrectinib sarcoma tropomyosin receptor kinase (TRK) fusion local control neurotrophic receptor tyrosine kinase (NTRK) infantile fibrosarcoma pediatric surgery
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License	Attribution-NonCommercial-NoDerivs 2018 American Cancer Society. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
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Notes	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 We thank the participating patients and their families and contributing clinical staff across all sites. We also thank Alturas Analytics Inc for providing real‐time bioanalytical assessments. Medical writing services were provided by Jim Heighway, PhD, of Cancer Communications and Consultancy Ltd (Knutsford, United Kingdom).
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References	2009; 45 1987 2018; 19 2017; 7 2018; 21 2010; 28 2016; 57 2012; 846 2018; 378 e_1_2_8_3_1 e_1_2_8_2_1 e_1_2_8_5_1 e_1_2_8_4_1 e_1_2_8_6_1 Hermanek P (e_1_2_8_7_1) 1987 e_1_2_8_9_1 e_1_2_8_8_1 e_1_2_8_10_1 28683589 - Pediatr Dev Pathol. 2018 Jan-Feb;21(1):68-78 29606586 - Lancet Oncol. 2018 May;19(5):705-714 19917847 - J Clin Oncol. 2010 Jan 10;28(2):318-23 29466156 - N Engl J Med. 2018 Feb 22;378(8):731-739 26849118 - Eur J Cancer. 2016 Apr;57:1-9 28578312 - Cancer Discov. 2017 Sep;7(9):963-972 22367796 - Methods Mol Biol. 2012;846:1-12 19097774 - Eur J Cancer. 2009 Jan;45(2):228-47
References_xml	– volume: 45 start-page: 228 year: 2009 end-page: 247 article-title: New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1) publication-title: Eur J Cancer – volume: 57 start-page: 1 year: 2016 end-page: 9 article-title: Conservative strategy in infantile fibrosarcoma is possible: the European paediatric Soft tissue sarcoma Study Group experience publication-title: Eur J Cancer – volume: 846 start-page: 1 year: 2012 end-page: 12 article-title: The neurotrophin family of neurotrophic factors: an overview publication-title: Methods Mol Biol – volume: 21 start-page: 68 year: 2018 end-page: 78 article-title: Infantile NTRK‐associated mesenchymal tumors publication-title: Pediatr Dev Pathol – volume: 19 start-page: 705 year: 2018 end-page: 714 article-title: Larotrectinib for paediatric solid tumours harbouring NTRK gene fusions: a multicentre, open‐label, phase 1 study publication-title: Lancet Oncol – volume: 28 start-page: 318 year: 2010 end-page: 323 article-title: Infantile fibrosarcoma: management based on the European experience publication-title: J Clin Oncol – year: 1987 – volume: 7 start-page: 963 year: 2017 end-page: 972 article-title: A next‐generation TRK kinase inhibitor overcomes acquired resistance to prior TRK kinase inhibition in patients with TRK fusion–positive solid tumors publication-title: Cancer Discov – volume: 378 start-page: 731 year: 2018 end-page: 739 article-title: Efficacy of larotrectinib in TRK fusion–positive cancers in adults and children publication-title: N Engl J Med – ident: e_1_2_8_4_1 doi: 10.1056/NEJMoa1714448 – ident: e_1_2_8_3_1 doi: 10.1177/1093526617712639 – ident: e_1_2_8_10_1 doi: 10.1158/2159-8290.CD-17-0507 – ident: e_1_2_8_2_1 doi: 10.1007/978-1-61779-536-7_1 – ident: e_1_2_8_6_1 doi: 10.1016/j.ejca.2008.10.026 – volume-title: TNM Classification of Malignant Tumors year: 1987 ident: e_1_2_8_7_1 – ident: e_1_2_8_8_1 doi: 10.1016/j.ejca.2015.12.028 – ident: e_1_2_8_9_1 doi: 10.1200/JCO.2009.21.9972 – ident: e_1_2_8_5_1 doi: 10.1016/S1470-2045(18)30119-0 – reference: 22367796 - Methods Mol Biol. 2012;846:1-12 – reference: 29466156 - N Engl J Med. 2018 Feb 22;378(8):731-739 – reference: 28683589 - Pediatr Dev Pathol. 2018 Jan-Feb;21(1):68-78 – reference: 28578312 - Cancer Discov. 2017 Sep;7(9):963-972 – reference: 19097774 - Eur J Cancer. 2009 Jan;45(2):228-47 – reference: 19917847 - J Clin Oncol. 2010 Jan 10;28(2):318-23 – reference: 29606586 - Lancet Oncol. 2018 May;19(5):705-714 – reference: 26849118 - Eur J Cancer. 2016 Apr;57:1-9
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Snippet	Background The highly selective oral tropomyosin receptor kinase (TRK) inhibitor larotrectinib has demonstrated significant activity in adult and pediatric TRK... Children with locally advanced tropomyosin receptor kinase (TRK) fusion sarcomas may proceed to surgical resection after neoadjuvant treatment with the... The highly selective oral tropomyosin receptor kinase (TRK) inhibitor larotrectinib has demonstrated significant activity in adult and pediatric TRK fusion... BackgroundThe highly selective oral tropomyosin receptor kinase (TRK) inhibitor larotrectinib has demonstrated significant activity in adult and pediatric TRK...
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SubjectTerms	Children Complications Enzyme inhibitors Evaluation Fibrosarcoma infantile fibrosarcoma Inhibitors larotrectinib local control Morbidity neurotrophic receptor tyrosine kinase (NTRK) Oncology Original Patients pediatric Pediatrics Sarcoma Solid tumors Surgery Therapy Tropomyosin tropomyosin receptor kinase (TRK) fusion Tumors Wound healing
Title	The use of neoadjuvant larotrectinib in the management of children with locally advanced TRK fusion sarcomas
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