Pediatr Blood Cancer

Descriptive epidemiology of Kaposi sarcoma in Europe. Report from the RARECARE project

The soft-tissue sarcomas (STS) of childhood are a relatively rare and heterogeneous group of tumors that may occur anywhere in the body and respond quite differently to therapy. STSs account for 7.4% of all cancers in children younger than 20 years [1]. These soft tissue sarcomas are divided almost equally between rhabdomyosarcomas originating from striated muscle and nonrhabdomyosarcoma soft tissue sarcomas (NRSTS). Sarcomas are malignant tumors of mesenchymal cell origin. They are named according to the normal tissue they resemble — for example, rhabdomyosarcoma (skeletal muscle), leiomyosarcoma (smooth muscle), and fibrosarcoma and malignant fibrous histiocytoma (connective tissue), neurofibrosarcoma or malignant peripheral nerve sheath tumor (neurofibrosarcomas, as seen in patients with neurofibromatosis), liposarcoma (adipose), synovial sarcoma (synovium), peripheral nerve sheath tumors (peripheral nerve), and angiosarcoma (blood and/or lymphatic vessels). Other sarcomas include rare entities such as alveolar softpart sarcoma, extraosseous Ewing’s sarcoma, peripheral neuroectodermal tumors, epitheloid sarcoma, and hemangiopericytoma.

Soft Tissue Sarcoma

Summary 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.

https://www.thelancet.com/pdfs/journals/lanonc/PIIS1470-2045(15)00167-9.pdf

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

In the US, approximately 850-900 children are diagnosed each year with soft tissue sarcomas (STS). Key findings from recent Children's Oncology Group (COG) clinical trials include safe reduction in therapy for low risk rhabdomyosarcoma (RMS), validation of FOXO1 fusion as a prognostic factor, a modest improvement in outcome for high-risk RMS, and a biologically designed non-cytotoxic therapy for pediatric desmoid tumor. Planned Phase 2 trials include targeted agents for VEGF/PDGF, mTOR, and IGF-1R for children with RMS and VEGF for children with non-RMS STS (NRSTS). For RMS, COG Phase 3 trials potentially will explore VEGF/mTOR inhibition or chemotherapy interval compression. For NRSTS, a COG Phase 3 trial will explore VEGF inhibition.

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Children's Oncology Group's 2013 blueprint for research: Soft tissue sarcomas.

Background
Soft tissue sarcomas (STS) are a heterogeneous group of mesenchymal malignancies that occur throughout the lifespan. The impact of age on disease features and outcome is unclear.

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Soft tissue sarcoma across the age spectrum: A population-based study from the surveillance epidemiology and end results database†

NIH Public Access Author Manuscript Pediatr Blood Cancer. Author manuscript; available in PMC 2015 February 01. NIH-PA Author Manuscript Published in final edited form as: Pediatr Blood Cancer. 2014 February ; 61(2): 319–325. doi:10.1002/pbc.24819. Pulmonary Outcomes in Survivors of Childhood Central Nervous System Malignancies: A Report from the Childhood Cancer Survivor Study Tseng Tien Huang, PT, PhD 1 , Yan Chen, MSc 2 , Andrew C. Dietz, MD, MS 3 , Yutaka Yasui, PhD 2 , Sarah S. Donaldson, MD 4 , Dennis C. Stokes, MD 5 , Marilyn Stovall, PhD 6 , Wendy M. Leisenring, ScD 7 , Charles A. Sklar, MD 8 , Lisa R. Diller, MD 9 , Ann C. Mertens, PhD 10 , Gregory T. Armstrong, MD, MSCE 1 , Daniel M. Green, MD 1 , Leslie L. Robison, PhD 1 , and Kirsten K. Ness, PT, PhD 1 1 Department of Epidemiology and Cancer Control, St Jude Children’s Research Hospital, Memphis, TN NIH-PA Author Manuscript 2 School of Public Health, University of Alberta, Edmonton, Alberta, AB 3 Division of Hematology/Oncology/BMT, Department of Pediatrics, University of California San Diego & Rady Children’s Hospital 4 Department of Radiation Oncology, Stanford University Medical Center, Stanford, CA 5 Department of Pediatric Pulmonary Medicine, St Jude Children’s Research Hospital, Memphis, TN 6 Department of Radiation Physics, University of Texas, M.D. Anderson Cancer Center, Houston, Texas 7 Department of Clinical Statistics and Cancer Prevention, Fred Hutchinson Cancer Research Center, Seattle, WA NIH-PA Author Manuscript 8 Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY 9 Department of Pediatric Oncology, Dana-Farber Cancer Institute and Children’s Hospital, Boston, MA 10 Department of Pediatrics, Emory University, Atlanta, GA 10 Department of Oncology, St Jude Children’s Research Hospital, Memphis, TN CORRESPONDING AUTHOR: Kirsten K. Ness, PT, PhD, Department of Epidemiology and Cancer Control, St Jude Children’s Research Hospital, 262 Danny Thomas Place, Mail Stop 735, Memphis, TN 38105, kiri.ness@stjude.org, Telephone (901) 595-5157; Fax (901) 595-5845. Author contributions Drs. Huang, Stovall, Leisenring, Mertens, Green, Robison, and Ness conceived of the project and designed the study. Drs. Robison, Mertens, Armstrong, and Stovall acquired the data. Drs. Chen, Yasui, Leisenring, and Ness designed and conducted the analysis. Drs. Huang, Chen, Dietz, Yasui, Donaldson, Stokes, Stovall, Leisenring, Sklar, Diller, Mertens, Armstrong, Green, Robison, Ness interpreted the data. Drs. Huang, Chen, Yasui, and Ness drafted the manuscript. Drs. Huang, Chen, Dietz,, Yasui, Donaldson, Stokes, Stovall, Leisenring, Sklar, Diller, Mertens, Armstrong, Green, Robison, and Ness made revisions for important intellectual content. All authors provided final approval of the submitted version. SUMMARY CONFLICT OF INTERESTS: The authors have no conflicts of interest to disclose.

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Tseng Tien Huang

Papers

Soft tissue sarcoma across the age spectrum: A population-based study from the surveillance epidemiology and end results database†

Pulmonary outcomes in survivors of childhood central nervous system malignancies: A report from the childhood cancer survivor study