Deficiencies in care for adults with vascular anomalies Open Access

TO THE EDITOR:

Vascular anomalies (VAs) are disorders characterized by abnormal formation of arteries, veins, capillaries, and/or lymphatic vessels.^1-4 Some patients with VAs also have overgrowth of bone, muscle, brain, and fatty tissue.^1-4 The incidence of VAs is 1 case per 1000 live births, with complex VAs affecting 1 in 25 000 live births.⁵ These lesions are generally present at birth and last throughout the lifetime. VAs can be associated with significant morbidity secondary to pain, disfigurement, bleeding, thrombosis, and poor quality of life. In severe cases, VAs can be life-threatening.^1-3 As such, patients with VAs require comprehensive and usually multidisciplinary care over their lifetime. In pediatric care, pediatric hematologists and oncologists play a central role in caring for this patient population, yet there is a paucity of adult hematologists and oncologists involved in VA care. As a result, many adult patients struggle to access and coordinate complex expert care.^1-3,6 We call for concerted efforts to develop a workforce of adult hematologists and oncologists with interest, expertise, and institutional support to care for adults with VAs.

Hematologists and oncologists have critical skills with emerging medical therapeutics for VAs. The past decade has led to the discovery of gain-of-function variants in mechanistic target of rapamycin (mTOR) and Ras pathway genes that drive the growth of most VAs.^7-14 Accordingly, available targeted inhibitors of mTOR and Ras pathways have been repurposed to manage many of these disorders.¹⁵ Growing evidence also suggests a role for anticoagulant therapy in low-flow VAs, especially venous malformations, which can be associated with localized intravascular coagulopathy and high rates of thrombosis.^16,17 Finally, some patients require periprocedural thromboprophylaxis owing to localized intravascular coagulopathy and the inherent risk of thrombosis during or after procedures.^16-18 In pediatric care, these advances in VA therapeutics have led hematologists and oncologists to become central members of multidisciplinary VA teams. They prescribe anticoagulant therapy and targeted inhibitors (eg, sirolimus, trametinib, alpelisib) and often oversee the coordination of specialist care for these patients. For adult hematologists and oncologists, caring for this patient population provides opportunities for advancing research and clinical care while addressing major unmet needs of adults with VAs.

Owing to the paucity of adult hematologists and oncologists involved in VA care, many adult patients lack a medical home or clinicians with expertise to guide and coordinate this complex care.^1-3,6 Owing to these shortages of adult clinicians, many patients with VAs receive care from pediatric hematologists and oncologists well into adulthood. Nearly all comprehensive VA centers are housed within academic children’s hospitals, and 93% of these VA centers treat adults in their VA programs.¹⁹ In a survey of adults with VAs who could no longer receive care from pediatric hematologists/oncologists, 45% were left without a specialist clinician to manage their VA and 34% had abandoned searching for an adult specialist.²⁰ Qualitative and quantitative studies further demonstrate that many adults lack options for expert VA care, with this disparity increasing for patients in rural areas who live far from specialist medical centers.²¹ This stopgap approach of pediatricians treating adults is necessary, but it can result in unsafe or incomplete care and fractured continuity of care when transitioning from childhood to adulthood. Adult patients with VAs would benefit from specialized care by adult providers with dedicated training and expertise in the diagnosis and management of VAs.

Adult hematologists and oncologists are also underrepresented in research efforts involving VA populations, whereas pediatric hematologists and oncologists are key drivers of this research. For example, the Consortium of Investigators of Vascular Anomalies (CaNVAS) is a national consortium of 25 multidisciplinary VA centers that collaborate to develop and coordinate VA clinical trials.²² CaNVAS was founded by pediatric hematologists and oncologists, site principal investigators must be hematologists or oncologists, and all CaNVAS centers are housed in children’s hospitals. Although each CaNVAS center can include 2 coinvestigators from any specialty, only 1 current coinvestigator is an adult hematologist. This underrepresentation by adult hematologists and oncologists is further demonstrated by the sparsity of research on VAs that has been presented at national and international conferences. In collaboration with a medical librarian, we performed a systematic search of all abstracts from 5 preeminent international hematology and oncology conferences held between January 2020 and July 2024. Our results highlight 2 disparities for this patient population. First, of 66 125 conference abstracts, only 108 (0.16%) focused on VAs (Table 1). Second, after excluding preclinical and industry-led research, most research was led by pediatric researchers, with pediatricians representing 73% of senior authors. This lack of research and investigation by adult providers represents a missed opportunity for improving care and understanding outcomes in this aging patient population.

There has been growing interest across federal and private funding agencies in supporting research on VAs. The National Institutes of Health has demonstrated specific interest in this population, with requests for grant applications related to lymphatic anomalies and vascular malformations, as well as a current National Institutes of Health National Commission on Lymphatic Diseases.²³ In recent years, the Department of Defense has included both lymphatic disease and vascular malformations in the list of selected disorders for the Congressionally Directed Medical Research Programs. Other funding agencies offer mechanisms that could also apply to VAs. For example, the Patient-Centered Outcomes Research Institute has a focus on comparative effectiveness trials in rare diseases and engagement with patient advocates, and the Agency for Healthcare Research and Quality has an interest in leveraging primary care to optimize care for patients with rare diseases. Furthermore, multiple pharmaceutical companies have demonstrated interest in developing clinical trials for new and repurposed drug therapies to treat VAs.^24-28 Thus, the time is opportune to engage and involve adult hematologists and oncologists in the rapidly advancing field of research on VAs.

Hematologists and oncologists are well positioned to meet the clinical care and research needs of patients with VAs, but developing this workforce requires concerted efforts by educational programs, academic leaders, and research funders. For example, fellowship leaders and educators could incorporate exposure to and training in VAs as a formalized part of the educational program. This may require engagement with pediatric hematologists and oncologists to build collaborative relationships, encourage the development of VA proficiency, and establish transition pathways from pediatric to adult care. Divisional leaders in hematology and oncology could encourage and prioritize the care of VAs in their programs, especially for early career faculty who are still developing their clinical and/or research agendas. National hematology and oncology societies could also bring attention and interest to VA research and care. For example, the American Society of Hematology incorporated the first educational session dedicated to VAs at the annual meeting in 2025. This can and should prompt additional societies to recognize the importance of VAs in hematology and oncology. Research funders can continue to create funding opportunities to support the development of VA-focused research agendas.

These and other efforts will be necessary to ensure that VA research and care for adult patients do not fall further behind. For example, physicians from other disciplines, such as internal medicine and vascular medicine, could also assume a role in caring for adult patients with VAs. This broader engagement with adult physicians will be especially important given that not every center will have hematologists or oncologists with the interest, capacity, and willingness to care for these patients. Hematologists, oncologists, and other physicians with adult expertise have an opportunity and an imperative to provide expert care for these patients. The entire community of pediatric and adult hematology and oncology must collaborate to ensure that these patients get the care they need and deserve.

Contribution: B.A.S. wrote the initial draft of the manuscript; A.M.K., S.C.-C., and K.S. revised the manuscript; and all authors conceived the study, planned the experiment, and approved the final manuscript.

Conflict-of-interest disclosure: B.A.S. reports consultancy with Novartis Pharmaceuticals, Kaken Pharmaceuticals, Palvella Pharmaceuticals, and Relay Therapeutics. The remaining authors declare no competing financial interests.

Correspondence: Bryan A. Sisk, Washington University School of Medicine, 600 S Euclid Ave, St. Louis, MO 63110; email: siskb@wustl.edu.