{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T07:00:00Z","timestamp":1792566000516,"version":"4.5.0"},"reference-count":39,"publisher":"American Medical Association (AMA)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n Vascular malformations (VMs) are rare disorders of vasculogenesis associated with substantial morbidity. Improved understanding of their genetic basis is increasingly guiding management, but logistical barriers to obtaining genetic testing in patients with VM may constrain treatment options.<\/jats:p>\n <\/jats:sec>\n \n Objectives<\/jats:title>\n To examine the institutional mechanisms for and obstacles to obtaining genetic testing for VM.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This survey study invited members of the Pediatric Hematology-Oncology Vascular Anomalies Interest Group, representing 81 vascular anomaly centers (VACs) serving individuals up to 18 years of age, to complete an electronic survey. Respondents were mostly pediatric hematologists-oncologists (PHOs) but included geneticists, genetic counselors, clinic administrators, and nurse practitioners. Responses that were received between March 1 and September 30, 2022, were analyzed with descriptive methods. Requirements for genetic testing by several genetics laboratories were also reviewed. Results were stratified by size of the VAC.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n Vascular anomaly center and associated clinician characteristics and practice patterns for ordering and obtaining insurance approval for genetic testing for VMs were collected.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Responses were received from 55 of 81 clinicians, for a response rate of 67.9%. Most respondents were PHOs (50 [90.9%]). Most respondents (32 of 55 respondents [58.2%]) replied that they order genetic testing on 5 to 50 patients per year and reported a genetic testing volume increase of 2- to 10-fold over the past 3 years (38 of 53 respondents [71.7%]). Most testing was ordered by PHOs (35 of 53 respondents [66.0%]), followed by geneticists (28 [52.8%]) and genetic counselors (24 [45.3%]). In-house clinical testing was more common at large and medium-sized VACs. Small VACs were more likely to use oncology-based platforms, which potentially miss low-frequency allelic variants in VM. Logistics and barriers varied by size of the VAC. Obtaining prior authorization was the duty shared among PHOs, nurses, and administrative staff, but the burden of insurance denials and appeals were on PHOs (35 of 53 respondents [66.0%]). Lack of administrative support; unclear institutional, insurance, and laboratory requirements; and lack of clinician education were barriers to genetic testing at VACs of all sizes. The effort to obtain genetic testing for patients with VM, compared with patients with cancer, was perceived as excessive, despite genetic testing being considered standard of care for this population.<\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n Results of this survey study showed the barriers to genetic testing for VM across VACs, described differences between VACs based on size, and proposed multiple interventions to support clinicians ordering genetic testing for VM. The results and recommendations should have broader application to clinicians caring for patients for whom molecular diagnosis is important to medical management.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2023.14829","type":"journal-article","created":{"date-parts":[[2023,5,23]],"date-time":"2023-05-23T11:04:09Z","timestamp":1684839849000},"page":"e2314829","source":"Crossref","is-referenced-by-count":11,"title":["Barriers to Genetic Testing in Vascular Malformations"],"prefix":"10.1001","volume":"6","author":[{"given":"Alexandra J.","family":"Borst","sequence":"first","affiliation":[{"name":"Division of Hematology, The Children\u2019s Hospital of Philadelphia, Philadelphia, Pennsylvania"},{"name":"Division of Oncology, The Children\u2019s Hospital of Philadelphia, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrienne M.","family":"Hammill","sequence":"additional","affiliation":[{"name":"Division of Hematology, Cancer and Blood Diseases Institute, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio"},{"name":"Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shelley E.","family":"Crary","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology-Oncology, University of Arkansas for Medical Sciences and Arkansas Children\u2019s Hospital, Little Rock"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas W.","family":"McLean","sequence":"additional","affiliation":[{"name":"Section of Pediatric Hematology-Oncology, Atrium Health Wake Forest Baptist, Winston-Salem, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Felton","sequence":"additional","affiliation":[{"name":"McLendon Clinical Laboratories, UNC Health, The University of North Carolina, Chapel Hill"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Blatt","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology-Oncology, The University of North Carolina, Chapel Hill"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","published-online":{"date-parts":[[2023,5,23]]},"reference":[{"issue":"1","key":"zoi230456r1","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1161\/CIRCRESAHA.121.318145","article-title":"Genetic basis and therapies for vascular anomalies.","volume":"129","author":"Queisser","year":"2021","journal-title":"Circ Res"},{"key":"zoi230456r2","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2020.579591","article-title":"A primer on a comprehensive genetic approach to vascular anomalies.","volume":"8","author":"Borst","year":"2020","journal-title":"Front Pediatr"},{"issue":"5","key":"zoi230456r4","doi-asserted-by":"publisher","first-page":"709e","DOI":"10.1097\/PRS.0000000000004294","article-title":"Vascular anomalies: from a clinicohistologic to a genetic framework.","volume":"141","author":"Greene","year":"2018","journal-title":"Plast Reconstr Surg"},{"issue":"4","key":"zoi230456r5","doi-asserted-by":"publisher","DOI":"10.1016\/j.tvir.2019.100629","article-title":"Practical genetic and biologic therapeutic considerations in vascular anomalies.","volume":"22","author":"Adams","year":"2019","journal-title":"Tech Vasc Interv Radiol"},{"issue":"2","key":"zoi230456r7","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2015-3257","article-title":"Efficacy and safety of sirolimus in the treatment of complicated vascular anomalies.","volume":"137","author":"Adams","year":"2016","journal-title":"Pediatrics"},{"issue":"6","key":"zoi230456r8","doi-asserted-by":"publisher","first-page":"1018","DOI":"10.1002\/pbc.v57.6","article-title":"Sirolimus for the treatment of complicated vascular anomalies in children.","volume":"57","author":"Hammill","year":"2011","journal-title":"Pediatr Blood Cancer"},{"issue":"5","key":"zoi230456r9","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1007\/s40257-020-00528-w","article-title":"New and emerging targeted therapies for vascular malformations.","volume":"21","author":"Van Damme","year":"2020","journal-title":"Am J Clin Dermatol"},{"issue":"3","key":"zoi230456r10","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1016\/j.hoc.2019.01.011","article-title":"Vascular anomalies: diagnosis of complicated anomalies and new medical treatment options.","volume":"33","author":"Adams","year":"2019","journal-title":"Hematol Oncol Clin North Am"},{"issue":"4","key":"zoi230456r11","doi-asserted-by":"publisher","first-page":"957","DOI":"10.1016\/j.jid.2017.10.033","article-title":"Analyzing the genetic spectrum of vascular anomalies with overgrowth via cancer genomics.","volume":"138","author":"Siegel","year":"2018","journal-title":"J Invest Dermatol"},{"issue":"8","key":"zoi230456r12","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1002\/gcc.v58.8","article-title":"Comprehensive molecular and clinicopathological analysis of vascular malformations: a study of 319 cases.","volume":"58","author":"Ten Broek","year":"2019","journal-title":"Genes Chromosomes Cancer"},{"issue":"8","key":"zoi230456r13","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1001\/jamasurg.2021.0543","article-title":"AAPOR reporting guidelines for survey studies.","volume":"156","author":"Pitt","year":"2021","journal-title":"JAMA Surg"},{"key":"zoi230456r15","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.v69.S3","article-title":"How we established a multidisciplinary program for vascular anomalies.","volume":"69","author":"Borst","year":"2022","journal-title":"Pediatr Blood Cancer"},{"issue":"1","key":"zoi230456r16","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.26716","article-title":"Vascular anomaly cases for the pediatric hematologist oncologists\u2014an interdisciplinary review.","volume":"65","author":"Adams","year":"2018","journal-title":"Pediatr Blood Cancer"},{"issue":"3","key":"zoi230456r17","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1055\/s-0037-1604297","article-title":"Advances in the medical management of vascular anomalies.","volume":"34","author":"Ricci","year":"2017","journal-title":"Semin Intervent Radiol"},{"issue":"5","key":"zoi230456r18","doi-asserted-by":"publisher","first-page":"1189","DOI":"10.1038\/s41436-018-0297-9","article-title":"Safety and efficacy of low-dose sirolimus in the PIK3CA-related overgrowth spectrum.","volume":"21","author":"Parker","year":"2019","journal-title":"Genet Med"},{"key":"zoi230456r19","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2022.857436","article-title":"Indications and limitations of sirolimus in the treatment of vascular anomaliess\u2014insights from a retrospective case series.","volume":"10","author":"Karastaneva","year":"2022","journal-title":"Front Pediatr"},{"issue":"1","key":"zoi230456r20","doi-asserted-by":"publisher","DOI":"10.1097\/JOVA.0000000000000038","article-title":"Clinical response to PI3K-a inhibition in a cohort of children and adults with PIK3CA-related overgrowth spectrum disorders.","volume":"3","author":"Raghavendran","year":"2022","journal-title":"J Vasc Anom (Phila)"},{"issue":"3","key":"zoi230456r21","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20212148","article-title":"Treatment of two infants with PIK3CA-related overgrowth spectrum by alpelisib.","volume":"219","author":"Morin","year":"2022","journal-title":"J Exp Med"},{"issue":"15","key":"zoi230456r22","doi-asserted-by":"publisher","first-page":"TPS3160","DOI":"10.1200\/JCO.2021.39.15_suppl.TPS3160","article-title":"EPIK-P2: a prospective phase 2, double-blind, randomized, placebo-controlled study of alpelisib in pediatric and adult patients (Pts) with PIK3CA-related overgrowth spectrum (PROS).","volume":"39","author":"Canaud","year":"2021","journal-title":"J Clin Oncol"},{"issue":"7711","key":"zoi230456r23","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1038\/s41586-018-0217-9","article-title":"Targeted therapy in patients with PIK3CA-related overgrowth syndrome.","volume":"558","author":"Venot","year":"2018","journal-title":"Nature"},{"key":"zoi230456r24","doi-asserted-by":"publisher","first-page":"S755","DOI":"10.1016\/j.annonc.2022.07.597","article-title":"468P Clinical benefit of alpelisib in pediatric patients with PIK3CA-related overgrowth spectrum (PROS): an EPIK-P1 analysis.","volume":"33","author":"Canaud","year":"2022","journal-title":"Ann Oncol"},{"issue":"3","key":"zoi230456r25","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2019-3206","article-title":"Monitoring arteriovenous malformation response to genotype-targeted therapy.","volume":"146","author":"Edwards","year":"2020","journal-title":"Pediatrics"},{"issue":"2","key":"zoi230456r26","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1093\/hmg\/ddac169","article-title":"Trametinib as a promising therapeutic option in alleviating vascular defects in an endothelial KRAS-induced mouse model.","volume":"32","author":"Nguyen","year":"2023","journal-title":"Hum Mol Genet"},{"issue":"2","key":"zoi230456r27","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1001\/jamadermatol.2018.4653","article-title":"Genotype-guided medical treatment of an arteriovenous malformation in a child.","volume":"155","author":"Lekwuttikarn","year":"2019","journal-title":"JAMA Dermatol"},{"issue":"10","key":"zoi230456r28","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.202012324","article-title":"Kaposiform lymphangiomatosis effectively treated with MEK inhibition.","volume":"12","author":"Foster","year":"2020","journal-title":"EMBO Mol Med"},{"issue":"6","key":"zoi230456r29","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2020-0167","article-title":"Severe lymphatic disorder resolved with MEK inhibition in a patient with Noonan syndrome and SOS1 mutation.","volume":"146","author":"Dori","year":"2020","journal-title":"Pediatrics"},{"issue":"6","key":"zoi230456r30","doi-asserted-by":"publisher","DOI":"10.1101\/mcs.a006134","article-title":"Case report: five-year experience of AKT inhibition with miransertib (MK-7075) in an individual with Proteus syndrome.","volume":"7","author":"Ours","year":"2021","journal-title":"Cold Spring Harb Mol Case Stud"},{"issue":"4","key":"zoi230456r31","doi-asserted-by":"publisher","first-page":"1496","DOI":"10.1172\/JCI98589","article-title":"Mosaic RAS\/MAPK variants cause sporadic vascular malformations which respond to targeted therapy.","volume":"128","author":"Al-Olabi","year":"2018","journal-title":"J Clin Invest"},{"issue":"7","key":"zoi230456r32","doi-asserted-by":"publisher","first-page":"1116","DOI":"10.1038\/s41591-019-0479-2","article-title":"ARAF recurrent mutation causes central conducting lymphatic anomaly treatable with a MEK inhibitor.","volume":"25","author":"Li","year":"2019","journal-title":"Nat Med"},{"issue":"18","key":"zoi230456r33","doi-asserted-by":"publisher","first-page":"3233","DOI":"10.1093\/hmg\/ddy218","article-title":"Pathogenic variant in EPHB4 results in central conducting lymphatic anomaly.","volume":"27","author":"Li","year":"2018","journal-title":"Hum Mol Genet"},{"issue":"1","key":"zoi230456r34","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1038\/s41436-020-00943-8","article-title":"Cell-free DNA as a diagnostic analyte for molecular diagnosis of vascular malformations.","volume":"23","author":"Zenner","year":"2021","journal-title":"Genet Med"},{"issue":"6","key":"zoi230456r35","doi-asserted-by":"publisher","first-page":"530","DOI":"10.1093\/ajcp\/aqy021","article-title":"The impact of an electronic expensive test notification.","volume":"149","author":"Riley","year":"2018","journal-title":"Am J Clin Pathol"},{"issue":"2","key":"zoi230456r36","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1038\/s41431-022-01247-y","article-title":"Managing expectations, rights, and duties in large-scale genomics initiatives: a European comparison.","volume":"31","author":"Horn","year":"2023","journal-title":"Eur J Hum Genet"},{"issue":"5","key":"zoi230456r37","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1007\/s12687-020-00503-2","article-title":"Valuing genetic and genomic testing in France: current challenges and latest evidence.","volume":"13","author":"Lejeune","year":"2022","journal-title":"J Community Genet"},{"issue":"1","key":"zoi230456r38","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1038\/s41587-021-01191-0","article-title":"Expanding global access to genetic therapies.","volume":"40","author":"Muigai","year":"2022","journal-title":"Nat Biotechnol"},{"key":"zoi230456r3","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/978-3-030-25624-1_3","volume-title":"Vascular Anomalies: A Guide for the Hematologist\/Oncologist","author":"Nguyen","year":"2020"},{"key":"zoi230456r14","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/978-88-470-0569-3_14","volume-title":"Hemangiomas and Vascular Malformations: An Atlas of Diagnosis and Treatment","author":"Tasn\u00e1di","year":"2009"},{"key":"zoi230456r6","unstructured":"International Society for the Study of Vascular Anomalies. Classification of vascular anomalies. 2018. Accessed April 23, 2020. http:\/\/issva.org\/classification"},{"key":"zoi230456r39","unstructured":"Prater, E. It takes an average of 8 years for a rare disease patient to get diagnosed. Why is it so hard to get life-altering genetic testing in the U.S.? Fortune Well. February 28, 2023. Accessed March 25, 2023. https:\/\/fortune.com\/well\/2023\/02\/28\/rare-disease-patients-diagnostic-odyssey-whole-genome-sequencing-wgs-genetic-testing\/"}],"container-title":["JAMA Network Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/articlepdf\/2805169\/borst_2023_oi_230456_1683899146.81923.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,23]],"date-time":"2023-05-23T11:04:15Z","timestamp":1684839855000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/fullarticle\/2805169"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,23]]},"references-count":39,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2023,5,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamanetworkopen.2023.14829","relation":{},"ISSN":["2574-3805"],"issn-type":[{"value":"2574-3805","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,23]]}}}