MyPART promises to share new research and data with the entire rare tumor community and the world. MyPART doctors and researchers publish their findings from laboratory experiments and clinical studies and write about their perspectives on rare tumor research. Read the publication summaries below to learn more about the MyPART team’s research projects and thoughts on rare tumors.
Ioakeim-Ioannidou M, Niemierko A, Kim DW, Tejada A, Urell T, Leahy S, Adams J, Fullerton B, Nielsen GP, Hung YP, Shih AR, Patino M, Buch K, Rincon S, Kelly H, Cunnane MB, Tolia M, Widemann BC, Wedekind MF, John L, Ebb D, Shin JH, Cote G, Curry W, MacDonald SM. Surgery and proton radiation therapy for pediatric base of skull chordomas: Long-term clinical outcomes for 204 patients. Neuro Oncol, 2023. DOI: 10.1093/neuonc/noad068.
Keywords: Chordoma, surgery, proton radiotherapy (PRT), base of skull (BOS) chordomas
Summary: Clinical data on the outcomes of pediatric patients with base of skull (BOS) chordomas are lacking. This paper reports on the findings from 204 pediatric patients with BOS chordomas who were treated with proton radiotherapy (PRT) or a combined proton/photon radiotherapy approach. Overall, the authors found that treating BOS chordoma patients with high dose PRT after surgery was effective and had low rates of late toxicity. This paper represents the largest cohort of BOS chordomas currently available in the literature.
Wedekind MF, Reilly KM, Del Rivero J, Lockridge R, Allen T, Raygada M, Bernstein D, Thomas BJ, Vivelo C, Levine J, Shonkoev N, Aldape K, Glod J, Sandler AB, Widemann BC. NCI intramural program approach to rare tumors: Natural history study of rare solid tumors in children and adults: A longitudinal, comprehensive data and biospecimen collection protocol. Pediatr Blood Cancer, 2023. DOI: 10.1002/pbc.30495.
Keywords: Natural history study, rare tumors, data collection, biospecimen collection
Summary: This paper outlines the National Cancer Institute’s MyPART program to study rare tumors, which are lacking in knowledge, resources, and community. A natural history study protocol, known as the Natural History Study of Rare Solid Tumors, was developed to collect comprehensive longitudinal clinical data, biospecimens, family history data, and patient-reported-outcomes data. This protocol was developed with a focus on collaboration with patients, families, advocacy organizations, researchers, and clinicians, and aims to share the data that is collected and analyzed with the rare tumor community. The ultimate goal of this program is to design clinical trials to improve the outcomes of people with rare cancers. This paper outlines the goals, methods, progress, challenges, and future directions of the MyPART program and the Natural History Study of Rare Solid Tumors.
John, L, Smith H, Ilanchezhian M, Lockridge R, Reilly KM, Raygada M, Dombi E, Sandler A, Thomas BJ, Glod J, Miettinen M, Allen T, Sommer J, Levy J, Lozinsky S, Dix D, Bouffet E, MacDonald S, Mukherjee D, Snyderman CH, Rowan NR, Malyapa R, Park DM, Heery C, Gardner PA, Cote GM, Fuller S, Butman JA, Jackson S, Gulley JL, Widemann BC, Wedekind MF. The NIH pediatric/young adult chordoma clinic and natural history study: Making advances in a very rare tumor. Pediatr Blood Cancer, 2023. DOI: 10.1002/pbc.30358.
Keywords: Chordoma, Natural History Study, rare tumor clinic
Summary: This paper provides an in-depth account of the NIH Pediatric and Young Adult Chordoma Clinic held at the NIH Clinical Center in Bethesda, MD. This clinic invited experts in the field of chordoma to visit the NIH Clinical Center and meet with a small group of patients and families. The paper presents an overview of the data collected at the clinic and outlines the treatment recommendations provided to patients and families. The paper also provides a literature review of a total of 45 pediatric cases of chordoma and summarizes the findings from these cases. The authors conclude that this type of multidisciplinary clinic is feasible and helps improve the understanding of chordoma, and that collaboration is necessary to advance understanding of this rare tumor.
Blakely AM, Glod JW, Wedekind Malone MF. Taming the Wild-Type Gastrointestinal Stromal Tumor: Improved Tissue Culture. Clin Cancer Res, 2022. 28(1): 3-4. doi: 10.1158/1078-0432.CCR-21-3409.
Keywords: Gastrointestinal stromal tumor (GIST), Succinate dehydrogenase (SDH), SDH-deficient GIST
Summary: Wild-type gastrointestinal stromal tumor (GIST) is a rare type of digestive system tumor that does not have mutations in either KIT or PDGFRA found in most GISTs but instead is often characterized by a lack of the protein succinate dehydrogenase, or SDH. Wild-type GIST is also called SDH-deficient GIST. Scientists have tried to create models of this tumor by taking samples of wild-type GIST tumor cells from patients and growing them in the lab, called ex-vivo models, but they have been difficult to develop. This paper describes recent efforts to create ex-vivo models of wild-type GIST. Developing these models is important for testing therapies that may be effective in treating wild-type GIST.
Keywords: Adrenocortical carcinoma (ACC), adrenal tumor, pediatric adrenocortical carcinoma
Summary: This paper presents an overview of what is currently known about pediatric adrenocortical carcinoma (ACC), which is rare and often associated with the genetic conditions Li-Fraumeni syndrome and Beckwith-Wiedemann Syndrome. The paper outlines the current treatment protocols for pediatric patients with ACC, which are modeled after adult protocols, and typically include surgery and/or chemotherapy. The paper also reports on less common treatment options with limited research available, including mitotane, pembrolizumab, cabozantinib, and chimeric antigen receptor autologous cell (CAR-T) therapy, and discusses potential future therapeutic options.
Lockridge R, Bedoya S, Allen T, Widemann BC, Akshintala S, Glod J, Wiener L. Psychosocial Characteristics and Experiences in Patients with Multiple Endocrine Neoplasia Type 2 (MEN2) and Medullary Thyroid Carcinoma (MTC). Children (Basel), 2022. DOI: 10.3390/children9060774.
Keywords: MEN2, Medullary thyroid carcinoma (MTC)
Summary: Multiple endocrine neoplasia type 2 (MEN2) is a genetic cancer predisposition syndrome that leads to the development of medullary thyroid carcinoma (MTC). Little is known about the psychological experiences of people with MEN2. This study surveyed over 60 patients with MEN2 and MTC and their caregivers to learn about issues affecting their life. Almost half of the patients reported that pain interferes with their daily life. Pediatric patients reported trouble concentrating and parents reported that mood changes and becoming easily upset were concerns for their children. This study suggests that ongoing educational resources and symptom management are important to improve the quality of life for people living with MEN2 and MTC.
Raygada M., Raffeld M, Bernstein A, Miettinen M, Glod J, Hughes MS, Reilly K, Widemann B, Del Rivero J. Case report of adrenocortical carcinoma associated with double germline mutations in MSH2 and RET. Am J Med Genet, 2021. 185(4): 1282-1287. doi: 10.1002/ajmg.a.62099.
Keywords: Adrenocortical carcinoma (ACC), MEN2A, Lynch syndrome (LS)
Summary: Adrenocortical carcinoma (ACC) is a rare cancer of the adrenal gland with an incidence of 0.7–1.5 per 1 million people per year. In 5% of ACC cases, the patient also has a hereditary cancer syndrome, such as Lynch syndrome (LS), Li-Fraumeni syndrome (LFS), or familial adenomatous polyposis (FAP). This paper presents the case of an adult female with ACC and two hereditary cancer predisposition syndromes: Lynch syndrome and MEN2A. While the patient knew she had LS, she did not know she also had MEN2A, which was found after genetic testing. The patient received genetic counseling about having two hereditary cancer syndromes and her case will be followed over time through the MyPART Natural History Study of Rare Solid Tumors to help scientists learn more about ACC and hereditary cancer predisposition syndromes.
Fuller SN, Shafiei A, Venzon DJ, Liewehr DJ, Mauda Havanuk M, Ilanchezhian MG, Edgerly M, Anderson VL, Levy EB, Hoang CD, Jones EC, Reilly KM, Widemann BC, Wood BJ, Bagheri H, Del Rivero J. Tumor Doubling Time Using CT Volumetric Segmentation in Metastatic Adrenocortical Carcinoma. Curr Oncol, 2021. 28(6): 4357–4366. doi: 10.3390/curroncol28060370.
Keywords: Adrenocortical carcinoma (ACC), metastasis
Summary: Adrenocortical carcinoma (ACC) is a type of rare, aggressive endocrine tumor that grows in the adrenal glands and has a poor prognosis. In 25-30% of patients diagnosed with ACC, the cancer has already spread to other parts of the body (metastasized), most commonly to the liver, lung, and bone. The growth rate of metastasized tumors can be used to inform treatment and predict outcomes. This study used a method of volumetric segmentation, a more accurate way to determine the size of tumors compared to standard imaging analysis techniques, to measure the growth rate of metastatic ACC tumors in the liver, lung, and lymph nodes of 12 patients. This study found that tumors in the liver grew faster than tumors in the lung or lymph nodes, suggesting that metastases to the liver should be monitored to help guide treatment for patients with metastatic ACC.
Gross AM. Using real world data to support regulatory approval of drugs in rare diseases: A review of opportunities, limitations & a case example. Curr Probl Cancer, 2021. 45(4):100769. doi: 10.1016/j.currproblcancer.2021.100769.
Keywords: Rare diseases, clinical trial design, external control data
Summary: Clinical trials for rare diseases, including rare cancers, are difficult to conduct for several reasons, with one of the most prominent reasons being the small number of patients available to participate in trials. This paper explains why the traditional randomized controlled clinical trial design does not work for rare disease populations where there are few patients who are usually geographically spread far apart, making it difficult to conduct a trial at a single institution or a trial with a control or “placebo” arm. This article discusses how real-world data, such as data collected through observational studies like natural history studies, patient registries, or other trials, can be used as external control data to help accelerate the approval of treatments. This article also discusses the US Food and Drug Administration (FDA) draft guidance published in 2019, “Submitting Documents Using Real-World Data and Real-World Evidence to FDA for Drugs and Biologics,” which supports using external control data to accelerate clinical trials in rare disease populations. The case study of the successful use of external controls in the approval of selumetinib, the first drug approved to treat children 2 years and older with Neurofibromatosis type 1 and inoperable nerve tumors, is also presented.
Okafor C, Hogan J, Raygada M, Thomas BJ, Akshintala S, Glod JW, Del Rivero J. Update on Targeted Therapy in Medullary Thyroid Cancer. Front Endocrinol (Lausanne), 2021. doi: 10.3389/fendo.2021.708949.
Keywords: Medullary thyroid cancer (MTC), tyrosine kinase inhibitors (TKIs)
Summary: Medullary thyroid cancer (MTC) is a type of rare neuroendocrine tumor that accounts for about 2-4% of thyroid cancer cases. Tyrosine kinase inhibitors (TKIs) provide treatment options for patients with MTC caused by mutations in the RET gene, but patients with tumors resistant to TKIs or tumors driven by mutations other than RET have fewer treatment options. This paper describes the different types of TKIs and how they target MTC tumors caused by mutations in RET. This paper also outlines potential strategies for treating MTC caused by mutations in the RAS gene. Other treatment options for MTC described in this paper include peptide receptor radionuclide therapy and immunotherapy. The paper discusses opportunities for future studies of pathways leading to MTC resistance that may inform clinical trial design and lead to potential new treatments.
Wedekind MF, Widemann B, Cote G. Chordoma: Current status, problems, and future directions. Curr Probl Cancer, 2021. 45(4): 100771. doi: 10.1016/j.currproblcancer.2021.100771.
Summary: Chordoma is a rare type of bone tumor occurring in about 1 per 1,000,000 people per year in the US and Europe. There are three subtypes of chordoma: conventional or chondroid chordomas (which make up the majority of cases), poorly differentiated chordomas (which occur more often in adolescents and young adults), and dedifferentiated chordomas (the rarest subtype of chordoma). Symptoms of chordoma can vary depending on where the tumor is growing in the spine. Understanding the natural history of each subtype is important for the treatment and management of patients with chordoma. This article outlines what is currently known about each subtype of chordoma and describes what the standard of care should be for each subtype depending on what has been shown effective in clinical studies.
Torres MB, Diggs LP, Wei JS, Khan J, Miettinen M, Fasaye G, Gillespie A, Widemann BC, Kaplan RN, Davis JL, Hernandez JM, Del Rivero J. Ataxia telangiectasia mutated germline pathogenic variant in adrenocortical carcinoma. Cancer Genet, 2021. DOI: 10.1016/j.cancergen.2021.03.003.
Keywords: Adrenocortical carcinoma (ACC)
Summary: Adrenocortical carcinoma (ACC) is a rare tumor that grows in the adrenal gland. Previous studies have found genetic mutations that may lead to ACC. This paper reports a case study of a 56-year-old woman with ACC. Researchers sequenced her tumor and found a mutation in the gene Ataxia Telangiectasia Mutated (ATM), suggesting this gene may play a role in some cases of ACC.
Reilly KM. Sharing data for the benefit of children with cancer. In: Buckley A (ed). On Medicine. BMC, 2019.
Keywords: Childhood cancer, data sharing, childhood cancer data initiative (CCDI)
Summary: Cancer is rarer in children than adults, generally, yet children with cancer are 20 times more likely to participate in clinical trials. Because all childhood cancers are rare, it is important that all available data from clinical trials be used to find new treatments. But, taking advantage of data from different studies can be hard because of barriers to finding, sharing, and combining data. To help solve these problems, the NCI is working on several new projects to make childhood cancer research easier. These projects include MyPART, the Childhood Cancer Data Initiative, and improving biobanking for childhood cancers. The entire pediatric cancer research community must do their part to help lower the barriers to data sharing and finding cures.
Fuller S, Del Rivero J, Venzon D, Ilanchezhian M, Allen D, Folio L, Ling A, Widemann B, Fontana JR, Glod J. Pulmonary Function in Patients With Multiple Endocrine Neoplasia 2B. J Clin Endocrinol Metab, 2020. 105(9): 2919-2928. doi: 10.1210/clinem/dgaa296.
Keywords: Multiple endocrine neoplasia 2B (MEN2B), Medullary thyroid cancer (MTC)
Summary: Multiple Endocrine Neoplasia 2B (MEN2B) is a rare cancer predisposition syndrome that causes visible changes in the body (like bumps on the lips, eyelids and tongue and having long arms, legs, and fingers) and can lead to the development of medullary thyroid cancer. This study is the first to look at how the lungs function in people with MEN2B. Researchers looked at pulmonary function tests (a type of test that looks at how well the lungs are working) and imaging scans in a small group of young people with MEN2B and found changes in the lungs, called abnormalities. Most people in the study showed changes in the ability of their lung tissue to move gasses across the tissue and into blood vessels, called diffusion abnormalities. Some people showed small structures called cysts in the lungs. The researchers need to do more studies to find out why these changes are happening.
Ilanchezhian M, Jha A, Pacak K, Del Rivero J. Emerging Treatments for Advanced/Metastatic Pheochromocytoma and Paraganglioma. Curr Treat Options Oncol, 2020. 21(11):85. doi: 10.1007/s11864-020-00787-z.
Keywords: Pheochromocytoma, paraganglioma, endocrine tumors
Summary: Pheochromocytomas and paragangliomas are rare endocrine tumors that affect about 1 in 300,000 people and can spread to other parts of the body (called metastatic disease) in about 35% of people with these tumors. The tumors cause the overproduction of certain hormones in the body, which can cause a variety of different symptoms. There is currently no cure for metastatic pheochromocytomas or paragangliomas. These tumors can be divided into three groups depending on the types of gene mutations in the tumor: pseudohypoxia, kinase signaling, and Wnt signaling. Depending on which group the tumor falls into, certain therapies may be more effective at treating the tumor. This paper describes the different types of potential treatment options, which include inhibitors, immunotherapies, and radiotherapies, for each of the three groups of tumors. Some of these treatments are already approved for other types of rare solid tumors. Clinical trials are testing some of these treatments in people with pheochromocytomas and paragangliomas. New treatments are necessary to improve the quality of life and overall survival of people with pheochromocytomas and paragangliomas.
Ilanchezhian M, Khan S, Okafor C, Glod J, Del Rivero J. Update on the Treatment of Medullary Thyroid Carcinoma in Patients with Multiple Endocrine Neoplasia Type 2. Horm Metab Res, 2020. 52(8):588-597. doi: 10.1055/a-1145-8479.
Keywords: Medullary thyroid carcinoma (MTC), multiple endocrine neoplasia type 2 (MEN2)
Summary: Medullary thyroid carcinoma (MTC) is a type of rare endocrine tumor making up about 2% of thyroid cancers in the US. About 25% of MTC cases are the result of the genetic tumor predisposition syndrome, multiple endocrine neoplasia type 2A (MEN2A) or 2B (MEN2B), which can be hereditary (passed down from parent to child). This article discusses the potential treatment options for people with MTC and MEN2. The first line of treatment is usually the removal of the thyroid (thyroidectomy) or the use of tyrosine kinase inhibitors. Several other treatments are being studied, including peptide receptor radionucleotide therapy (PRRT) and immunotherapy.
Shetty I, Fuller S, Raygada M, Merino MJ, Thomas BJ, Widemann BC, Reilly KM, Pacak K, Del Rivero J. Adrenocortical carcinoma masquerading as pheochromocytoma: a histopathologic dilemma. Endocrinol Diabetes Metab Case Rep, 2020. doi: 10.1530/EDM-19-0147.
Keywords: Adrenocortical carcinoma (ACC), pheochromocytoma
Summary: Adrenocortical carcinoma (ACC) is a rare, aggressive tumor that forms in the adrenal gland. Diagnosing ACC is difficult and requires specific pathology tests to determine the correct diagnosis. This paper discusses the case of a 57-year-old woman who was originally diagnosed as having a pheochromocytoma, another type of rare endocrine tumor, at age 51. Several years later, her tumor returned and was studied by imaging and biopsy tests. One institution diagnosed her with metastatic pheochromocytoma while another institution diagnosed her with ACC. When she came to the NIH, her diagnosis of ACC was confirmed after undergoing multiple tests. This case demonstrated the importance of using a multi-disciplinary approach, including genetic testing and pathology studies, for correctly diagnosing ACC, which can inform treatment options for the patient.