Publications by authors named "Junne Kamihara"

21 Publications

  • Page 1 of 1

Belzutifan, a Potent HIF2α Inhibitor, in the Pacak-Zhuang Syndrome.

N Engl J Med 2021 11;385(22):2059-2065

From the Departments of Pediatric Oncology (J.K., K.V.H., J.A.P., C.M.C., A.I., C.B.W., K.A.J., S.G.D.) and Medical Oncology (W.G.K.), Dana-Farber Cancer Institute, Harvard Medical School, the Divisions of Hematology and Oncology (J.K., J.A.P., M.M.H., K.A.J., S.G.D.) and Endocrinology (A.J.W.) and the Departments of Surgery (B.R.W.), Pathology (S.O.V.), and Radiology (S.D.V.), Boston Children's Hospital, Harvard Medical School, and the Manton Center for Orphan Disease Research and the Division of Genetics and Genomics, Boston Children's Hospital (J.A.M., J.L.) - all in Boston; Howard Hughes Medical Institute, Chevy Chase, MD (W.G.K.); and Merck, Kenilworth, NJ (R.F.P., N.J.Z.).

The integration of genomic testing into clinical care enables the use of individualized approaches to the management of rare diseases. We describe the use of belzutifan, a potent and selective small-molecule inhibitor of the protein hypoxia-inducible factor 2α (HIF2α), in a patient with polycythemia and multiple paragangliomas (the Pacak-Zhuang syndrome). The syndrome was caused in this patient by somatic mosaicism for an activating mutation in . Treatment with belzutifan led to a rapid and sustained tumor response along with resolution of hypertension, headaches, and long-standing polycythemia. This case shows the application of a targeted therapy for the treatment of a patient with a rare tumor-predisposition syndrome. (Funded by the Morin Family Fund for Pediatric Cancer and Alex's Lemonade Stand Foundation.).
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http://dx.doi.org/10.1056/NEJMoa2110051DOI Listing
November 2021

Performance of the McGill Interactive Pediatric OncoGenetic Guidelines for Identifying Cancer Predisposition Syndromes.

JAMA Oncol 2021 Oct 7. Epub 2021 Oct 7.

Department of Pediatrics, Centre mère-enfant Soleil du CHU de Québec-Université Laval, Québec City, Quebec, Canada.

Importance: Prompt recognition of a child with a cancer predisposition syndrome (CPS) has implications for cancer management, surveillance, genetic counseling, and cascade testing of relatives. Diagnosis of CPS requires practitioner expertise, access to genetic testing, and test result interpretation. This diagnostic process is not accessible in all institutions worldwide, leading to missed CPS diagnoses. Advances in electronic health technology can facilitate CPS risk assessment.

Objective: To evaluate the diagnostic accuracy of a CPS prediction tool (McGill Interactive Pediatric OncoGenetic Guidelines [MIPOGG]) in identifying children with cancer who have a low or high likelihood of having a CPS.

Design, Setting, And Participants: In this international, multicenter diagnostic accuracy study, 1071 pediatric (<19 years of age) oncology patients who had a confirmed CPS (12 oncology referral centers) or who underwent germline DNA sequencing through precision medicine programs (6 centers) from January 1, 2000, to July 31, 2020, were studied.

Exposures: Exposures were MIPOGG application in patients with cancer and a confirmed CPS (diagnosed through routine clinical care; n = 413) in phase 1 and MIPOGG application in patients with cancer who underwent germline DNA sequencing (n = 658) in phase 2. Study phases did not overlap. Data analysts were blinded to genetic test results.

Main Outcomes And Measures: The performance of MIPOGG in CPS recognition was compared with that of routine clinical care, including identifying a CPS earlier than practitioners. The tool's test characteristics were calculated using next-generation germline DNA sequencing as the comparator.

Results: In phase 1, a total of 413 patients with cancer (median age, 3.0 years; range, 0-18 years) and a confirmed CPS were identified. MIPOGG correctly recognized 410 of 412 patients (99.5%) as requiring referral for CPS evaluation at the time of primary cancer diagnosis. Nine patients diagnosed with a CPS by a practitioner after their second malignant tumor were detected by MIPOGG using information available at the time of the first cancer. In phase 2, of 658 children with cancer (median age, 6.6 years; range, 0-18.8 years) who underwent comprehensive germline DNA sequencing, 636 had sufficient information for MIPOGG application. When compared with germline DNA sequencing for CPS detection, the MIPOGG test characteristics for pediatric-onset CPSs were as follows: sensitivity, 90.7%; specificity, 60.5%; positive predictive value, 17.6%; and negative predictive value, 98.6%. Tumor DNA sequencing data confirmed the MIPOGG recommendation for CPS evaluation in 20 of 22 patients with established cancer-CPS associations.

Conclusions And Relevance: In this diagnostic study, MIPOGG exhibited a favorable accuracy profile for CPS screening and reduced time to CPS recognition. These findings suggest that MIPOGG implementation could standardize and rationalize recommendations for CPS evaluation in children with cancer.
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http://dx.doi.org/10.1001/jamaoncol.2021.4536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8498936PMC
October 2021

Survival Benefit for Individuals With Constitutional Mismatch Repair Deficiency Undergoing Surveillance.

J Clin Oncol 2021 09 4;39(25):2779-2790. Epub 2021 May 4.

Lebanese American University Medical Center-Rizk, Beirut, Lebanon.

Purpose: Constitutional mismatch repair deficiency syndrome (CMMRD) is a lethal cancer predisposition syndrome characterized by early-onset synchronous and metachronous multiorgan tumors. We designed a surveillance protocol for early tumor detection in these individuals.

Patients And Methods: Data were collected from patients with confirmed CMMRD who were registered in the International Replication Repair Deficiency Consortium. Tumor spectrum, efficacy of the surveillance protocol, and malignant transformation of low-grade lesions were examined for the entire cohort. Survival outcomes were analyzed for patients followed prospectively from the time of surveillance implementation.

Results: A total of 193 malignant tumors in 110 patients were identified. Median age of first cancer diagnosis was 9.2 years (range: 1.7-39.5 years). For patients undergoing surveillance, all GI and other solid tumors, and 75% of brain cancers were detected asymptomatically. By contrast, only 16% of hematologic malignancies were detected asymptomatically ( < .001). Eighty-nine patients were followed prospectively and used for survival analysis. Five-year overall survival (OS) was 90% (95% CI, 78.6 to 100) and 50% (95% CI, 39.2 to 63.7) when cancer was detected asymptomatically and symptomatically, respectively ( = .001). Patient outcome measured by adherence to the surveillance protocol revealed 4-year OS of 79% (95% CI, 54.8 to 90.9) for patients undergoing full surveillance, 55% (95% CI, 28.5 to 74.5) for partial surveillance, and 15% (95% CI, 5.2 to 28.8) for those not under surveillance ( < .0001). Of the 64 low-grade tumors detected, the cumulative likelihood of transformation from low-to high-grade was 81% for GI cancers within 8 years and 100% for gliomas in 6 years.

Conclusion: Surveillance and early cancer detection are associated with improved OS for individuals with CMMRD.
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http://dx.doi.org/10.1200/JCO.20.02636DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8407605PMC
September 2021

Natural History of Thyroid Disease in Children with PTEN Hamartoma Tumor Syndrome.

J Clin Endocrinol Metab 2021 03;106(3):e1121-e1130

Thyroid Center, Boston Children's Hospital, Boston, MA, USA.

Context: Thyroid ultrasound screening is recommended in children with PTEN hamartoma tumor syndrome (PHTS) due to increased risk of thyroid neoplasia, but the natural history of thyroid disease in children with PHTS is unclear.

Objective: Determine the prevalence and natural history of thyroid disease in children with PHTS.

Methods: Retrospective cohort study (1998-2019) in an academic pediatric hospital of individuals with genetically confirmed PHTS diagnosed before age 19 years. Clinical, thyroid ultrasound, and laboratory characteristics are described. Primary outcomes were the prevalence of thyroid nodules ≥10 mm diameter and time course and risk factors for nodule development assessed by Cox regression analysis. Secondary outcomes included thyroid nodule requiring biopsy, other ultrasound findings, and prevalence of autoimmune thyroid disease.

Results: Among 64 subjects with PHTS, 50 underwent thyroid ultrasound. A thyroid nodule ≥10 mm was diagnosed in 22/50 (44%) subjects at median (range) age 13.3 (7.0-22.9) years. Nodules were diagnosed earlier in females than in males (10.8 [7.0-17.9] vs 14.2 [9.9-22.9] years, P = .009). In multivariate analysis, risk of thyroid nodules was significantly associated with female sex (hazard ratio 2.90, 95% CI 1.16-7.27, P = .02) and inversely associated with the presence of neurologic findings of PHTS (HR 0.27, 95% CI 0.10-0.69, P = .007). Abnormal-appearing lymph nodes with echogenic foci were observed by ultrasound in 20% of subjects, but these were not associated with malignancy. Autoimmune thyroid disease was present in 10/33 (30.3%) of subjects in whom it was assessed.

Conclusion: Thyroid disease is common in children with PHTS. This study supports current consensus recommendations for ultrasound screening.
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http://dx.doi.org/10.1210/clinem/dgaa944DOI Listing
March 2021

DICER1-associated central nervous system sarcoma in children: comprehensive clinicopathologic and genetic analysis of a newly described rare tumor.

Mod Pathol 2020 10 14;33(10):1910-1921. Epub 2020 Apr 14.

Department of Pathology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.

The spectrum of neoplasms associated with DICER1 variants continues to expand, with the recent addition of primary "DICER1-associated central nervous system sarcoma" (DCS). DCS is a high-grade malignancy predominantly affecting pediatric patients. Six pediatric DCS were identified through a combination of clinical diagnostic studies, archival inquiry, and interinstitutional collaboration. Clinical, histologic, immunohistologic, and molecular features were examined. Genomic findings in the 6 DCS were compared with those in 14 additional DICER1-associated tumors sequenced with the same assay. The six patients presented at ages 3-15 years with CNS tumors located in the temporal (n = 2), parietal (n = 1), fronto-parietal (n = 1), and frontal (n = 2) lobes. All underwent surgical resection. Histologic examination demonstrated high-grade malignant spindle cell tumors with pleuropulmonary blastoma-like embryonic "organoid" features and focal rhabdomyoblastic differentiation; immature cartilage was seen in one case. Immunohistochemically, there was patchy desmin and myogenin staining, and patchy loss of H3K27me3, and within eosinophilic cytoplasmic globules, alfa-fetoprotein staining. Biallelic DICER1 variants were identified in all cases, with germline variants in two of five patients tested. DCS demonstrated genomic alterations enriched for Ras pathway activation and TP53 inactivation. Tumor mutational burden was significantly higher in the 6 DCS tumors than in 14 other DICER1-associated tumors examined (mean 12.9 vs. 6.8 mutations/Mb, p = 0.035). Postoperative care included radiation (n = 5) and chemotherapy (n = 3); at the last follow-up, three patients were alive without DCS, and three had died of disease. Our analysis expands the clinical, histologic, immunohistological, and molecular spectrum of DCS, identifying distinctive features that can aid in the diagnosis, multidisciplinary evaluation, and treatment of DCS.
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http://dx.doi.org/10.1038/s41379-020-0516-1DOI Listing
October 2020

It's ALL in the Family: IKZF1 and Hereditary Leukemia.

Cancer Cell 2018 05;33(5):798-800

Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Boston, MA, USA. Electronic address:

IKZF1 plays an essential role in lymphopoiesis, and somatic IKZF1 variants in acute lymphoblastic leukemia (ALL) are associated with poor prognosis. In this issue of Cancer Cell, Churchman et al. add to the list of leukemia predisposition genes with the identification and characterization of germline IKZF1 variants in childhood ALL.
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http://dx.doi.org/10.1016/j.ccell.2018.04.008DOI Listing
May 2018

and Associated Conditions: Identification of At-risk Individuals and Recommended Surveillance Strategies.

Clin Cancer Res 2018 05 17;24(10):2251-2261. Epub 2018 Jan 17.

Department of Pathology, Center for Cancer and Immunology Research, Children's National Medical Center, Washington D.C.

Pathogenic germline variants cause a hereditary cancer predisposition syndrome with a variety of manifestations. In addition to conferring increased cancer risks for pleuropulmonary blastoma (PPB) and ovarian sex cord-stromal tumors, particularly Sertoli-Leydig cell tumor, individuals with pathogenic germline variants may also develop lung cysts, cystic nephroma, renal sarcoma and Wilms tumor, nodular hyperplasia of the thyroid, nasal chondromesenchymal hamartoma, ciliary body medulloepithelioma, genitourinary embryonal rhabdomyosarcoma, and brain tumors including pineoblastoma and pituitary blastoma. In May 2016, the International PPB Registry convened the inaugural International Symposium to develop consensus testing and surveillance and treatment recommendations. Attendees from North America, Europe, and Russia provided expert representation from the disciplines of pediatric oncology, endocrinology, genetics, genetic counseling, radiology, pediatric surgery, pathology, and clinical research. Recommendations are provided for genetic testing; prenatal management; and surveillance for -associated pulmonary, renal, gynecologic, thyroid, ophthalmologic, otolaryngologic, and central nervous system tumors and gastrointestinal polyps. Risk for most -associated neoplasms is highest in early childhood and decreases in adulthood. Individual and caregiver education and judicious imaging-based surveillance are the primary recommended approaches. These testing and surveillance recommendations reflect a consensus of expert opinion and current literature. As research expands, guidelines for screening and treatment will continue to be updated. .
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http://dx.doi.org/10.1158/1078-0432.CCR-17-3089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6260592PMC
May 2018

Screening with whole-body magnetic resonance imaging in pediatric subjects with Li-Fraumeni syndrome: A single institution pilot study.

Pediatr Blood Cancer 2018 Feb 27;65(2). Epub 2017 Oct 27.

Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.

Background: Li-Fraumeni syndrome (LFS) is an autosomal dominant hereditary cancer syndrome associated with germline mutations in the TP53 gene and a high risk of childhood-onset malignancies. Cancer surveillance is challenging in pediatric mutation carriers given the anatomic spectrum of malignancies and young age of onset. Whole-body magnetic resonance imaging (WB-MRI) may provide an acceptable method for early cancer detection.

Procedure: We conducted a prospective feasibility pilot study of pediatric subjects (age < 18 years) with LFS to determine return rates for annual WB-MRI scan. Secondary objectives included characterization of incident cancers (and how they were detected).

Results: Forty-five WB-MRI scans in 20 subjects were performed over 5 years; two patients enrolled without subsequently undergoing scans. Eighty-nine percent of participants scanned (95% confidence interval: 67-99%) returned for second examinations. Fifty-five percent of participants required general anesthesia, which was well tolerated in all cases. Six patients required dedicated follow-up imaging. One participant required biopsy of a detected brain lesion; pathology demonstrated reactive gliosis. Another participant, with prior choroid plexus carcinoma, had a new brain lesion detected on clinical follow-up MRI not seen on WB-MRI 6 months prior. All other participants remain well (median: 3 years, range: 0.08-4 years).

Conclusions: WB-MRI in pediatric subjects is a well-tolerated approach to cancer surveillance despite the need for general anesthesia in some patients. A large multicenter trial would determine true test characteristics and efficacy of this approach for early cancer detection in children at high cancer risk.
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http://dx.doi.org/10.1002/pbc.26822DOI Listing
February 2018

Multiple Endocrine Neoplasia and Hyperparathyroid-Jaw Tumor Syndromes: Clinical Features, Genetics, and Surveillance Recommendations in Childhood.

Clin Cancer Res 2017 07;23(13):e123-e132

Department of Pediatrics and Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah.

Children and adolescents who present with neuroendocrine tumors are at extremely high likelihood of having an underlying germline predisposition for the multiple endocrine neoplasia (MEN) syndromes, including MEN1, MEN2A and MEN2B, MEN4, and hyperparathyroid-jaw tumor (HPT-JT) syndromes. Each of these autosomal dominant syndromes results from a specific germline mutation in unique genes: MEN1 is due to pathogenic variants (11q13), MEN2A and MEN2B are due to pathogenic variants (10q11.21), MEN4 is due to pathogenic variants (12p13.1), and the HPT-JT syndrome is due to pathogenic variants (1q25). Although each of these genetic syndromes share the presence of neuroendocrine tumors, each syndrome has a slightly different tumor spectrum with specific surveillance recommendations based upon tumor penetrance, including the age and location for which specific tumor types most commonly present. Although the recommended surveillance strategies for each syndrome contain similar approaches, important differences do exist among them. Therefore, it is important for caregivers of children and adolescents with these syndromes to become familiar with the unique diagnostic criteria for each syndrome, and also to be aware of the specific tumor screening and prophylactic surgery recommendations for each syndrome. .
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http://dx.doi.org/10.1158/1078-0432.CCR-17-0548DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5547889PMC
July 2017

Retinoblastoma and Neuroblastoma Predisposition and Surveillance.

Clin Cancer Res 2017 07;23(13):e98-e106

Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.

Retinoblastoma (RB) is the most common intraocular malignancy in childhood. Approximately 40% of retinoblastomas are hereditary and due to germline mutations in the gene. Children with hereditary RB are also at risk for developing a midline intracranial tumor, most commonly pineoblastoma. We recommend intensive ocular screening for patients with germline mutations for retinoblastoma as well as neuroimaging for pineoblastoma surveillance. There is an approximately 20% risk of developing second primary cancers among individuals with hereditary RB, higher among those who received radiotherapy for their primary RB tumors. However, there is not yet a clear consensus on what, if any, screening protocol would be most appropriate and effective. Neuroblastoma (NB), an embryonal tumor of the sympathetic nervous system, accounts for 15% of pediatric cancer deaths. Prior studies suggest that about 2% of patients with NB have an underlying genetic predisposition that may have contributed to the development of NB. Germline mutations in and account for most familial NB cases. However, other cancer predisposition syndromes, such as Li-Fraumeni syndrome, RASopathies, and others, may be associated with an increased risk for NB. No established protocols for NB surveillance currently exist. Here, we describe consensus recommendations on hereditary RB and NB from the AACR Childhood Cancer Predisposition Workshop. .
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http://dx.doi.org/10.1158/1078-0432.CCR-17-0652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7266051PMC
July 2017

, and Their Associated Tumor Susceptibility Syndromes: Clinical Features, Genetics, and Surveillance Recommendations in Childhood.

Clin Cancer Res 2017 Jun;23(12):e76-e82

Department of Human Genetics and Research Institute, McGill University Health Centre, McGill University, Montreal, Québec, Canada.

hamartoma tumor syndrome (PHTS), syndrome, and hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome are pleiotropic tumor predisposition syndromes that include benign and malignant neoplasms affecting adults and children. PHTS includes several disorders with shared and distinct clinical features. These are associated with elevated lifetime risk of breast, thyroid, endometrial, colorectal, and renal cancers as well as melanoma. Thyroid cancer represents the predominant cancer risk under age 20 years. syndrome includes risk for pleuropulmonary blastoma, cystic nephroma, ovarian sex cord-stromal tumors, and multinodular goiter and thyroid carcinoma as well as brain tumors including pineoblastoma and pituitary blastoma. Individuals with HLRCC may develop multiple cutaneous and uterine leiomyomas, and they have an elevated risk of renal cell carcinoma. For each of these syndromes, a summary of the key syndromic features is provided, the underlying genetic events are discussed, and specific screening is recommended.
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http://dx.doi.org/10.1158/1078-0432.CCR-17-0629DOI Listing
June 2017

Von Hippel-Lindau and Hereditary Pheochromocytoma/Paraganglioma Syndromes: Clinical Features, Genetics, and Surveillance Recommendations in Childhood.

Clin Cancer Res 2017 Jun;23(12):e68-e75

Division of Endocrinology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.

Von Hippel-Lindau disease (vHL) is a hereditary tumor predisposition syndrome that places affected individuals at risk for multiple tumors, which are predominantly benign and generally occur in the central nervous system or abdomen. Although the majority of tumors occur in adults, children and adolescents with the condition develop a significant proportion of vHL manifestations and are vulnerable to delayed tumor detection and their sequelae. Although multiple tumor screening paradigms are currently being utilized for patients with vHL, surveillance should be reassessed as the available relevant clinical information continues to expand. We propose a new vHL screening paradigm similar to existing approaches, with important modifications for some tumor types, placing an emphasis on risks in childhood. This includes advancement in the timing of surveillance initiation and increased frequency of screening evaluations. Another neuroendocrine-related familial condition is the rapidly expanding hereditary paraganglioma and pheochromocytoma syndrome (HPP). The tumor spectrum for patients with HPP syndrome includes paragangliomas, pheochromocytomas, renal cancer, and gastrointestinal stromal tumors. The majority of patients with HPP syndrome harbor an underlying variant in one of the genes (, and ), although other genes also have been described ( and ). Annual screening for elevated plasma or urine markers along with complete blood count and biennial whole-body MRI accompanied by focal neck MRI is recommended for older children and adults with HPP syndrome to detect tumors early and to decrease morbidity and mortality from HPP-related tumors.
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http://dx.doi.org/10.1158/1078-0432.CCR-17-0547DOI Listing
June 2017

Cancer Surveillance in Gorlin Syndrome and Rhabdoid Tumor Predisposition Syndrome.

Clin Cancer Res 2017 Jun;23(12):e62-e67

Dana-Farber/Boston Children's Cancer and Blood Disorders Center and Harvard Medical School, Boston, Massachusetts.

Gorlin syndrome and rhabdoid tumor predisposition syndrome (RTPS) are autosomal dominant syndromes associated with an increased risk of childhood-onset brain tumors. Individuals with Gorlin syndrome can manifest a wide range of phenotypic abnormalities, with about 5% of family members developing medulloblastoma, usually occurring in the first 3 years of life. Gorlin syndrome is associated with germline mutations in components of the Sonic Hedgehog pathway, including Patched1 ( and Suppressor of fused ( mutation carriers appear to have an especially high risk of early-onset medulloblastoma. Surveillance MRI in the first years of life in mutation carriers is, therefore, recommended. Given the risk of basal cell carcinomas, regular dermatologic examinations and sun protection are also recommended. Rhabdoid tumors (RT) are tumors initially defined by the descriptive "rhabdoid" term, implying a phenotypic similarity with rhabdomyoblasts at the microscopic level. RTs usually present before the age of 3 and can arise within the cranium as atypical teratoid/rhabdoid tumors or extracranially, especially in the kidney, as malignant rhabdoid tumors. However, RTs of both types share germline and somatic mutations in or, more rarely, , each of which encodes a chromatin remodeling family member. mutations are particularly associated with small cell carcinoma of the ovary, hypercalcemic type (SCCOHT). The outcome following a diagnosis of any of these tumors is often poor, and the value of surveillance is unknown. International efforts to determine surveillance protocols are underway, and preliminary recommendations are made for carriers of and mutations.
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http://dx.doi.org/10.1158/1078-0432.CCR-17-0595DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7309678PMC
June 2017

Synchronous occurrence of acute lymphoblastic leukemia and wilms tumor in two patients: underlying etiology and combined treatment plan.

Pediatr Blood Cancer 2017 05 15;64(5). Epub 2016 Nov 15.

Department of Pediatric Oncology, Dana-Farber/Cancer Institute, Harvard Medical School, Boston, Massachusetts.

Synchronous cancers are extraordinarily rare in pediatric patients and present a therapeutic challenge. Patient A presented with synchronous unilateral Wilms tumor (WT) and standard-risk (SR) B-precursor acute lymphoblastic leukemia (ALL). Genetic testing revealed bialleleic BRCA2/FANCD1 mutations. Patient B, after SR B-precursor ALL induction therapy, was noted on fever workup to have a renal mass; pathology demonstrated lesion indeterminate between WT and nephrogenic rest. Therapy was customized for each patient to treat both cancers. Both patients have ongoing remission from their cancers, without excessive toxicity. We report two regimens for treating synchronous WT and ALL and recommend screening such patients for cancer predisposition.
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http://dx.doi.org/10.1002/pbc.26345DOI Listing
May 2017

Socioeconomic status and global variations in the incidence of neuroblastoma: call for support of population-based cancer registries in low-middle-income countries.

Pediatr Blood Cancer 2017 02 13;64(2):321-323. Epub 2016 Oct 13.

Department of Epidemiology and Pediatrics (Division of Oncology), Columbia University, New York, New York.

Global variations in the incidence of pediatric cancers have been described; however, the causes of such differences are not known. We investigated the relationship between the incidence of embryonal tumors and human development index on a global scale. Increasing incidence of neuroblastoma correlates significantly with an increasing index of human development, with greater incidence among countries with high socioeconomic development, in apparent contrast to the incidence of retinoblastoma. While more data are needed to corroborate this observation, our findings suggest new avenues for etiological research and serve as a call for support of population-based cancer registries in low-middle-income countries.
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http://dx.doi.org/10.1002/pbc.26244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5554414PMC
February 2017

Parental hope for children with advanced cancer.

Pediatrics 2015 May 6;135(5):868-74. Epub 2015 Apr 6.

The Department of Pediatric Oncology and the Center for Population Sciences, Dana-Farber Cancer Institute, Boston, Massachusetts;

Background: Previous work suggests that parents of children with cancer can remain hopeful despite receiving prognostic information, but we know little about what hope means to such parents, or the extent to which parents can feel hopeful even while facing the child's impending death.

Methods: We audiotaped conversations between clinicians and parents of 32 children with relapsed or refractory cancer, and then interviewed parents about their hopes and expectations for their child.

Results: Parent statements about prognosis in interviews mirrored those made by clinicians during discussions about the child's diagnosis with refractory or relapsed cancer. Clinicians used language referring to hope during these conversations but did not ask parents directly about their hopes. Parents expressed a range of hopes for their children, from hopes related to cure or treatment response, to quality of life, normalcy, and love and relationships for the child. For most parents, expectations about prognosis were not aligned with their hopes for the child; for example, many parents hoped for a cure and also reported that they did not believe cure was possible. Many parents were able to acknowledge this incongruence.

Conclusions: Parents accurately conveyed the reality of their child's serious condition in the setting of advanced cancer, and yet maintained hope. Hopes were not limited to hope for cure/treatment response. Clinicians should be encouraged to engage in direct conversations about hope with parents as a means to elicit realistic hopes that can help to focus the most meaningful plans for the child and family.
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http://dx.doi.org/10.1542/peds.2014-2855DOI Listing
May 2015

Neuromyelitis optica in an adolescent after bone marrow transplantation.

Pediatr Neurol 2015 Jan 27;52(1):119-24. Epub 2014 Aug 27.

Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.

Background: Central nervous system complications of bone marrow transplant are a common occurrence and the differential diagnosis is quite broad, including opportunistic infections, medications toxicities, graft versus host disease, and other autoimmune processes.

Patient Description: We summarize previously reported cases of autoimmune myelitis in post-transplant patients and discuss a 17-year-old boy who presented with seronegative neuromyelitis optica after a bone marrow transplant for acute myeloid leukemia. Our patient had a marked improvement in symptoms after plasmapheresis.

Conclusion: Including our patient, there have been at least eight cases of post-transplant autoimmune myelitis presented in the literature, and at least three of these are suspicious for neuromyelitis optica. Several of these patients had poor outcomes with persistent symptoms after the myelitis. Autoimmune processes such as neuromyelitis optica should be carefully considered in patients after transplant as aggressive treatment like early plasmapheresis may improve outcomes.
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http://dx.doi.org/10.1016/j.pediatrneurol.2014.07.007DOI Listing
January 2015

Germline TP53 mutations and the changing landscape of Li-Fraumeni syndrome.

Hum Mutat 2014 Jun;35(6):654-62

Division of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.

Since its description by Li and Fraumeni over 40 years ago, Li-Fraumeni syndrome (LFS) remains one of the most striking familial cancer predisposition syndromes. Children and adults are affected by a wide array of cancers that occur predominantly at younger ages. This review discusses LFS, describes its association with TP53, and examines the classic and evolving definitions of the syndrome. The potential implications of multigene assessments of individuals at increased cancer risk, which have already begun to identify those with very little personal or family cancer history carrying germline TP53 mutations, are considered. Newer options in the management of individuals with LFS are also discussed, highlighting the importance of further clinical trials for cancer detection, prevention, and management. Finally, we observe how the clinical criteria for TP53 mutation screening appear to be evolving as our understanding of the impact of germline TP53 mutations continues to expand.
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http://dx.doi.org/10.1002/humu.22559DOI Listing
June 2014
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