Publications by authors named "Mary S Huang"

17 Publications

  • Page 1 of 1

Clinical outcomes in a large pediatric cohort of patients with ependymoma treated with proton radiotherapy.

Neuro Oncol 2021 01;23(1):156-166

Department of Radiation Oncology, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts.

Background: Treatment for pediatric ependymoma includes surgical resection followed by local radiotherapy (RT). Proton RT (PRT) enables superior sparing of critical structures compared with photons, with potential to reduce late effects. We report mature outcomes, patterns of failure, and predictors of outcomes in patients treated with PRT.

Methods: One hundred fifty patients (<22 y) with World Health Organization grades II/III ependymoma were treated with PRT between January 2001 and January 2019 at Massachusetts General Hospital. Demographic, tumor, and treatment-related characteristics were analyzed. Event-free survival (EFS), overall survival (OS), and local control (LC) were assessed.

Results: Median follow-up was 6.5 years. EFS, OS, and LC for the intracranial cohort (n = 145) at 7 years were 63.4%, 82.6%, and 76.1%. Fifty-one patients recurred: 26 (51.0%) local failures, 19 (37.3%) distant failures, and 6 (11.8%) synchronous failures. One hundred sixteen patients (77.3%) underwent gross total resection (GTR), 5 (3.3%) underwent near total resection (NTR), and 29 (19.3%) underwent subtotal resection (STR). EFS for the intracranial cohort at 7 years for GTR/NTR and STR was 70.3% and 35.2%. With multivariate analysis, the effect of tumor excision persisted after controlling for tumor location. There was no adverse effect on disease control if surgery to RT interval was within 9 weeks of GTR/NTR.

Conclusion: PRT is effective and safe in pediatric ependymoma. Similar to previous studies, GTR/NTR was the most important prognostic factor. Intervals up to 9 weeks from surgery to PRT did not compromise disease outcomes. There was no LC benefit between patients treated with >54 Gray relative biological effectiveness (GyRBE) versus ≤54 GyRBE.
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http://dx.doi.org/10.1093/neuonc/noaa139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7849993PMC
January 2021

Case 37-2019: A 20-Month-Old Boy with Severe Anemia.

N Engl J Med 2019 Nov;381(22):2158-2167

From the Departments of Pediatrics (B.M.C., A.M.R., M.S.H.), Radiology (R.S.), and Pathology (V.N.), Massachusetts General Hospital, and the Departments of Pediatrics (B.M.C., A.M.R., M.S.H.), Radiology (R.S.), and Pathology (V.N.), Harvard Medical School - both in Boston.

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http://dx.doi.org/10.1056/NEJMcpc1904048DOI Listing
November 2019

Endocrine Deficiency As a Function of Radiation Dose to the Hypothalamus and Pituitary in Pediatric and Young Adult Patients With Brain Tumors.

J Clin Oncol 2018 10 17;36(28):2854-2862. Epub 2018 Aug 17.

Ralph E. Vatner, Andrzej Niemierko, Madhusmita Misra, Elizabeth A. Weyman, Claire P. Goebel, David H. Ebb, Robin M. Jones, Mary S. Huang, Takara Stanley, Shannon M. MacDonald, Nancy J. Tarbell, and Torunn I. Yock, Massachusetts General Hospital, Boston, MA; Ralph E. Vatner, University of Cincinnati College of Medicine and Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Anita Mahajan, Mayo Clinic, Rochester, MN; and David R. Grosshans and Arnold C. Paulino, MD Anderson Cancer Center, Houston, TX.

Purpose: There are sparse data defining the dose response of radiation therapy (RT) to the hypothalamus and pituitary in pediatric and young adult patients with brain tumors. We examined the correlation between RT dose to these structures and development of endocrine dysfunction in this population.

Materials And Methods: Dosimetric and clinical data were collected from children and young adults (< 26 years of age) with brain tumors treated with proton RT on three prospective studies (2003 to 2016). Deficiencies of growth hormone (GH), thyroid hormone, adrenocorticotropic hormone, and gonadotropins were determined clinically and serologically. Incidence of deficiency was estimated using the Kaplan-Meier method. Multivariate models were constructed accounting for radiation dose and age.

Results: Of 222 patients in the study, 189 were evaluable by actuarial analysis, with a median follow-up of 4.4 years (range, 0.1 to 13.3 years), with 31 patients (14%) excluded from actuarial analysis for having baseline hormone deficiency and two patients (0.9%) because of lack of follow-up. One hundred thirty patients (68.8%) with medulloblastoma were treated with craniospinal irradiation (CSI) and boost; most of the remaining patients (n = 56) received involved field RT, most commonly for ependymoma (13.8%; n = 26) and low-grade glioma (7.4%; n = 14). The 4-year actuarial rate of any hormone deficiency, growth hormone, thyroid hormone, adrenocorticotropic hormone, and gonadotropin deficiencies were 48.8%, 37.4%, 20.5%, 6.9%, and 4.1%, respectively. Age at start of RT, time interval since treatment, and median dose to the combined hypothalamus and pituitary were correlated with increased incidence of deficiency.

Conclusion: Median hypothalamic and pituitary radiation dose, younger age, and longer follow-up time were associated with increased rates of endocrinopathy in children and young adults treated with radiotherapy for brain tumors.
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http://dx.doi.org/10.1200/JCO.2018.78.1492DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6161835PMC
October 2018

Quality of life in patients with proton-treated pediatric medulloblastoma: Results of a prospective assessment with 5-year follow-up.

Cancer 2018 08 15;124(16):3390-3400. Epub 2018 Jun 15.

Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.

Background: To the authors' knowledge, health-related quality of life (HRQOL) outcomes are not well described in patients with medulloblastoma. The use of proton radiotherapy (RT) may translate into an improved HRQOL. In the current study, the authors report long-term HRQOL in patients with proton-treated pediatric medulloblastoma.

Methods: The current study was a prospective cohort HRQOL study of patients with medulloblastoma who were treated with proton RT and enrolled between August 5, 2002, and October 8, 2015. Both child report and parent-proxy report Pediatric Quality of Life Inventory (PedsQL) surveys were collected at baseline during RT and annually thereafter (score range on surveys of 0-100, with higher scores indicating better HRQOL). Patients were dichotomized by clinical/treatment variables and subgroups were compared. Mixed-model analysis was performed to determine the longitudinal trajectory of PedsQL scores. The Student t test was used to compare long-term HRQOL measures with published means from a healthy child population.

Results: Survey data were evaluable for 116 patients with a median follow-up of 5 years (range, 1-10.6 years); the median age at the time of diagnosis was 7.6 years (range, 2.1-18.1 years). At baseline, children reported a total core score (TCS) of 65.9, which increased by 1.8 points annually (P<.001); parents reported a TCS of 59.1, which increased by 2.0 points annually. Posterior fossa syndrome adversely affected baseline scores, but these scores significantly improved with time. At the time of last follow-up, children reported a TCS of 76.3, which was 3.3 points lower than that of healthy children (P = .09); parents reported a TCS of 69, which was 11.9 points lower than that of parents of healthy children (P<.001). Increased follow-up time from diagnosis correlated with improved HRQOL scores.

Conclusions: HRQOL scores appear to increase over time after treatment in children treated with proton RT for medulloblastoma but remain lower compared with those of parent-proxy reports as well as published means from a healthy normative sample of children. Additional follow-up may translate into continued improvements in HRQOL. Cancer 2018. © 2018 American Cancer Society.
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http://dx.doi.org/10.1002/cncr.31575DOI Listing
August 2018

A 12-Month-Old Healthy Girl with a New Oral Ulcer and Chronic Diaper Rash.

Dermatopathology (Basel) 2017 Jan-Dec;4(1-4):24-30. Epub 2017 Nov 16.

Department of Dermatology, Brigham and Women's Hospital, Boston, MA, USA.

A 12-month-old healthy girl presented with a chronic diaper rash. Physical examination demonstrated crusting of the scalp, erythematous papules with surrounding petechiae on the lower abdomen, and an intraoral palatal ulcer. Further imaging demonstrated bone involvement. Histopathologic examination of involved skin and the intraoral ulcer demonstrated epithelioid histiocytes with "coffee bean-shaped" nuclei, staining positive for CD1a and langerin by immunohistochemistry, consistent with Langerhans cell histiocytosis (LCH). LCH is a disease entity of unknown etiology characterized by histiocytic proliferation that most commonly presents in young children. The cutaneous findings of LCH include a seborrheic dermatitis-like and/or red-brown papular eruption. Intraoral examination is crucial as oral mucosal and maxillofacial skeletal disease can also be seen in LCH. When a child presents with a recalcitrant seborrheic dermatitis-like eruption or chronic diaper rash, the clinician should be alerted to the possibility of LCH. Timely recognition and diagnosis of LCH is important for oncologic referral, evaluation, and treatment.
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http://dx.doi.org/10.1159/000481308DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5803736PMC
November 2017

Adolescent and Young Adult Oncology, Version 2.2018, NCCN Clinical Practice Guidelines in Oncology.

J Natl Compr Canc Netw 2018 Jan;16(1):66-97

This selection from the NCCN Guidelines for Adolescent and Young Adult (AYA) Oncology focuses on treatment and management considerations for AYA patients with cancer. Compared with older adults with cancer, AYA patients have unique needs regarding treatment, fertility counseling, psychosocial and behavioral issues, and supportive care services. The complete version of the NCCN Guidelines for AYA Oncology addresses additional aspects of caring for AYA patients, including risk factors, screening, diagnosis, and survivorship.
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http://dx.doi.org/10.6004/jnccn.2018.0001DOI Listing
January 2018

Facial manifestations of Epstein-Barr virus-related lymphoproliferative disease in childhood acute lymphoblastic leukemia in remission: Two atypical presentations.

Pediatr Blood Cancer 2016 11 8;63(11):2042-5. Epub 2016 Jul 8.

Division of Pediatric Hematology & Oncology, Massachusetts General Hospital for Children, Harvard Medical School, Boston, Massachusetts.

Epstein-Barr virus-related lymphoproliferative disease (EBV-LPD) rarely occurs in patients with acute lymphoblastic leukemia (ALL), who have not received hematopoietic transplantation. We describe EBV-LPD manifesting as facial lesions in two children with ALL in remission. One patient was a 16-year-old male with T-cell ALL with an EBV-positive angiocentric polymorphous lip lesion presenting as right-sided facial swelling. The other patient was a 12-year-old male with B-cell ALL with an EBV-positive polymorphous lymphoplasmacytic infiltrate presenting as bilateral dacryoadenitis. Neither patient had known primary immunodeficiencies. Both cases improved with immunosuppressant de-escalation. These cases suggest that immunosuppression induced by maintenance chemotherapy is sufficient to promote EBV-LPD.
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http://dx.doi.org/10.1002/pbc.26102DOI Listing
November 2016

Long-term toxic effects of proton radiotherapy for paediatric medulloblastoma: a phase 2 single-arm study.

Lancet Oncol 2016 Mar 30;17(3):287-298. Epub 2016 Jan 30.

Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, USA.

Background: Compared with traditional photon radiotherapy, proton radiotherapy irradiates less normal tissue and might improve health outcomes associated with photon radiotherapy by reducing toxic effects to normal tissue. We did a trial to assess late complications, acute side-effects, and survival associated with proton radiotherapy in children with medulloblastoma.

Methods: In this non-randomised, open-label, single-centre, phase 2 trial, we enrolled patients aged 3-21 years who had medulloblastoma. Patients had craniospinal irradiation of 18-36 Gy radiobiological equivalents (GyRBE) delivered at 1·8 GyRBE per fraction followed by a boost dose. The primary outcome was cumulative incidence of ototoxicity at 3 years, graded with the Pediatric Oncology Group ototoxicity scale (0-4), in the intention-to-treat population. Secondary outcomes were neuroendocrine toxic effects and neurocognitive toxic effects, assessed by intention-to-treat. This study is registered at ClinicalTrials.gov, number NCT00105560.

Findings: We enrolled 59 patients from May 20, 2003, to Dec 10, 2009: 39 with standard-risk disease, six with intermediate-risk disease, and 14 with high-risk disease. 59 patients received chemotherapy. Median follow-up of survivors was 7·0 years (IQR 5·2-8·6). All patients received the intended doses of proton radiotherapy. The median craniospinal irradiation dose was 23·4 GyRBE (IQR 23·4-27·0) and median boost dose was 54·0 GyRBE (IQR 54·0-54·0). Four (9%) of 45 evaluable patients had grade 3-4 ototoxicity according to Pediatric Oncology Group ototoxicity scale in both ears at follow-up, and three (7%) of 45 patients developed grade 3-4 ototoxicity in one ear, although one later reverted to grade 2. The cumulative incidence of grade 3-4 hearing loss at 3 years was 12% (95% CI 4-25). At 5 years, it was 16% (95% CI 6-29). Pediatric Oncology Group hearing ototoxicity score at a follow-up of 5·0 years (IQR 2·9-6·4) was the same as at baseline or improved by 1 point in 34 (35%) of 98 ears, worsened by 1 point in 21 (21%), worsened by 2 points in 35 (36%), worsened by 3 points in six (6%), and worsened by 4 points in two (2%). Full Scale Intelligence Quotient decreased by 1·5 points (95% CI 0·9-2·1) per year after median follow-up up of 5·2 years (IQR 2·6-6·4), driven by decrements in processing speed and verbal comprehension index. Perceptual reasoning index and working memory did not change significantly. Cumulative incidence of any neuroendocrine deficit at 5 years was 55% (95% CI 41-67), with growth hormone deficit being most common. We recorded no cardiac, pulmonary, or gastrointestinal late toxic effects. 3-year progression-free survival was 83% (95% CI 71-90) for all patients. In post-hoc analyses, 5-year progression-free survival was 80% (95% CI 67-88) and 5-year overall survival was 83% (95% CI 70-90).

Interpretation: Proton radiotherapy resulted in acceptable toxicity and had similar survival outcomes to those noted with conventional radiotherapy, suggesting that the use of the treatment may be an alternative to photon-based treatments.

Funding: US National Cancer Institute and Massachusetts General Hospital.
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http://dx.doi.org/10.1016/S1470-2045(15)00167-9DOI Listing
March 2016

Clinical outcomes and late endocrine, neurocognitive, and visual profiles of proton radiation for pediatric low-grade gliomas.

Int J Radiat Oncol Biol Phys 2014 Aug 8;89(5):1060-1068. Epub 2014 Jul 8.

Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts. Electronic address:

Purpose/objective(s): Primary low-grade gliomas are common brain tumors of childhood, many of which require radiation therapy (RT) as definitive treatment. Increased conformality of RT could decrease the incidence and severity of late effects. We report our experience with 32 pediatric patients treated with proton RT.

Methods And Materials: Thirty-two pediatric patients with low-grade gliomas of the brain or spinal cord were treated with proton RT from 1995 to 2007. Sixteen patients received at least 1 regimen of chemotherapy before definitive RT. The median radiation dose was 52.2 GyRBE (48.6-54 GyRBE).

Results: The median age at treatment was 11.0 years (range, 2.7-21.5 years), with a median follow-up time of 7.6 years (range, 3.2-18.2 years). The 6-year and 8-year rates of progression-free survival were 89.7% and 82.8%, respectively, with an 8-year overall survival of 100%. For the subset of patients who received serial neurocognitive testing, there were no significant declines in Full-Scale Intelligence Quotient (P=.80), with a median neurocognitive testing interval of 4.5 years (range, 1.2-8.1 years) from baseline to follow-up, but subgroup analysis indicated some significant decline in neurocognitive outcomes for young children (<7 years) and those with significant dose to the left temporal lobe/hippocampus. The incidence of endocrinopathy correlated with a mean dose of ≥40 GyRBE to the hypothalamus, pituitary, or optic chiasm. Stabilization or improvement of visual acuity was achieved in 83.3% of patients at risk for radiation-induced injury to the optic pathways.

Conclusions: This report of late effects in children with low-grade gliomas after proton RT is encouraging. Proton RT appears to be associated with good clinical outcome, especially when the tumor location allows for increased sparing of the left temporal lobe, hippocampus, and hypothalamic-pituitary axis.
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http://dx.doi.org/10.1016/j.ijrobp.2014.04.053DOI Listing
August 2014

Adolescent and young adult oncology, version 2.2014.

J Natl Compr Canc Netw 2014 Jan;12(1):21-32; quiz 32

From 1Fred & Pamela Buffett Cancer Center at The Nebraska Medical Center; 2St. Jude Children's Research Hospital/The University of Tennessee Health Science Center; 3Robert H. Lurie Comprehensive Cancer Center of Northwestern University; 4City of Hope Comprehensive Cancer Center; 5Vanderbilt-Ingram Cancer Center; 6The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute; 7Dana-Farber/Brigham and Women's Cancer Center; 8UCSF Helen Diller Family Comprehensive Cancer Center; 9Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine; 10Massachusetts General Hospital Cancer Center; 11Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance; 12Roswell Park Cancer Institute; 13Stanford Cancer Institute; 14Memorial Sloan-Kettering Cancer Center; 15The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; 16Moffitt Cancer Center; 17Huntsman Cancer Institute at the University of Utah; 18The University of Texas MD Anderson Cancer Center; 19Fox Chase Cancer Center; 20Duke Cancer Institute; 21University of Alabama at Birmingham Comprehensive Cancer Center; 22University of Michigan Comprehensive Cancer Center; and 23National Comprehensive Cancer Network.

The NCCN Guidelines Insights on Adolescent and Young Adult (AYA) Oncology discuss the fertility and endocrine issues that are relevant to the management of AYA patients with cancer. Fertility preservation should be an essential part in the treatment of AYA patients with cancer. The NCCN Guidelines recommend discussion of fertility preservation and contraception before the start of treatment. Oophoropexy and embryo cryopreservation are the 2 established options for fertility preservation in women. Semen cryopreservation before the start of treatment is the most reliable and well-established method of preserving fertility in men. AYA women with cancer also have unique contraception needs, depending on the type of cancer, its treatment, and treatment-related complications. Management of cancer during pregnancy poses significant diagnostic and therapeutic challenges for both the patient and the physician. AYA women diagnosed with cancer during pregnancy require individualized treatment from a multidisciplinary team involving medical, surgical, radiation, and gynecologic oncologists; obstetricians; and perinatologists.
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http://dx.doi.org/10.6004/jnccn.2014.0004DOI Listing
January 2014

The use of an intrathecal pump to manage intractable cancer pain in a pediatric patient: a case report.

J Pediatr Hematol Oncol 2014 Apr;36(3):e162-4

*Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital †Department of Pediatric Hematology & Oncology, Massachusetts General Hospital for Children, Boston, MA.

A 15-year-old girl with combined immune deficiency syndrome, diagnosed with metastatic squamous cell cancer of the anus, had significant pain secondary to vulvar-perianal condyloma. Conventional treatment with oral and intravenous analgesics was limited by significant side effects of mental status changes and urinary retention leading to clinical deterioration that precluded attempts at chemotherapy. An intrathecal pump was implanted in the challenging setting of neutropenia. There was a drastic improvement in her quality of life and the ability to tolerate further chemotherapy. The option of an intrathecal pump for pain control extended our patient's ability to enjoy important quality time with family by several months.
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http://dx.doi.org/10.1097/MPH.0b013e31828e5dcaDOI Listing
April 2014

The use of an intrathecal pump to manage intractable cancer pain in a pediatric patient: a case report.

J Pediatr Hematol Oncol 2014 Apr;36(3):e162-4

*Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital †Department of Pediatric Hematology & Oncology, Massachusetts General Hospital for Children, Boston, MA.

A 15-year-old girl with combined immune deficiency syndrome, diagnosed with metastatic squamous cell cancer of the anus, had significant pain secondary to vulvar-perianal condyloma. Conventional treatment with oral and intravenous analgesics was limited by significant side effects of mental status changes and urinary retention leading to clinical deterioration that precluded attempts at chemotherapy. An intrathecal pump was implanted in the challenging setting of neutropenia. There was a drastic improvement in her quality of life and the ability to tolerate further chemotherapy. The option of an intrathecal pump for pain control extended our patient's ability to enjoy important quality time with family by several months.
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http://dx.doi.org/10.1097/MPH.0b013e31828e5dcaDOI Listing
April 2014

Pediatric-type nodal follicular lymphoma: an indolent clonal proliferation in children and adults with high proliferation index and no BCL2 rearrangement.

Blood 2012 Sep 31;120(12):2395-404. Epub 2012 Jul 31.

James Homer Wright Pathology Laboratories, Massachusetts General Hospital, Boston, MA, USA.

Pediatric follicular lymphoma (PFL) is a variant of follicular lymphoma (FL) presenting as localized lymphadenopathy in children. Unlike conventional adult FL, PFL typically does not recur or progress. Clear diagnostic criteria for PFL are lacking, and it is uncertain whether this indolent lymphoma is defined by age or may occur in adults. We analyzed 27 FL in patients < 40 years of age and found that all 21 cases that lacked a BCL2 gene abnormality (BCL2-N; P < .0001) and had > 30% Ki67 fraction (high proliferation index, HPI; P = .0007) were stage I and did not progress or recur; in comparison, all 6 cases with BCL2 rearrangement and/or PI < 30% were stage III/IV, and 5 of 6 recurred or progressed. In a separate cohort of 58 adult FL (≥ 18 years of age), all 13 BCL2-N/HPI cases were stage I, and none progressed or relapsed, whereas 11 of 15 stage I cases with BCL2 gene abnormality and/or LPI relapsed or progressed (P = .0001). The adult and pediatric BCL2-N/HPI FL cases had similar morphologic features. Our results confirm the highly indolent behavior of PFL and suggest that these are characterized by HPI and absence of BCL2 gene abnormality. PFL-like cases also occur in adults and are associated with indolent behavior in this patient population.
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http://dx.doi.org/10.1182/blood-2012-05-429514DOI Listing
September 2012

Proton radiotherapy for pediatric Ewing's sarcoma: initial clinical outcomes.

Int J Radiat Oncol Biol Phys 2012 Mar 18;82(3):1142-8. Epub 2011 Aug 18.

ATreP (Provincial Agency for Proton Therapy), Trento, Italy.

Purpose: Proton radiotherapy (PT) has been prescribed similarly to photon radiotherapy to achieve comparable disease control rates at comparable doses. The chief advantage of protons in this setting is to reduce acute and late toxicities by decreasing the amount of normal tissue irradiated. We report the preliminary clinical outcomes including late effects on our pediatric Ewing's sarcoma patients treated with PT at the Francis H. Burr Proton Therapy Center at Massachusetts General Hospital (Boston, MA).

Methods And Materials: This was a retrospective review of the medical records of 30 children with Ewing's sarcoma who were treated with PT between April 2003 and April 2009.

Results: A total of 14 male and 16 female patients with tumors in several anatomic sites were treated with PT at a median age of 10 years. The median dose was 54 Gy (relative biological effectiveness) with a median follow-up of 38.4 months. The 3-year actuarial rates of event-free survival, local control, and overall survival were 60%, 86%, and 89%, respectively. PT was acutely well tolerated, with mostly mild-to-moderate skin reactions. At the time of writing, the only serious late effects have been four hematologic malignancies, which are known risks of topoisomerase and anthracyline exposure.

Conclusions: Proton radiotherapy was well tolerated, with few adverse events. Longer follow-up is needed to more fully assess tumor control and late effects, but the preliminary results are encouraging.
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http://dx.doi.org/10.1016/j.ijrobp.2011.03.038DOI Listing
March 2012

Case records of the Massachusetts General Hospital. Case 39-2007. A 5-month-old girl with skin lesions.

N Engl J Med 2007 12;357(25):2616-23

Department of Pediatric Dermatology, Massachusetts General Hospital, Boston, USA.

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http://dx.doi.org/10.1056/NEJMcpc0706920DOI Listing
December 2007