Skeletal Sequelae of Radiation Therapy for Malignant Childhood Tumors

Ms, Butler; Ww, Robertson; Rate, William; Gj, D'Angio; Ds, Drummond

doi:10.1097/00003086-199002000-00039

Cited by 61 publications

(47 citation statements)

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“…Similarly, varied thresholds for radiation dose are reported to increase risk for spinal malalignment including, > 20 Gy (34), > 23 Gy (52), > 24 Gy (28), and > 26 Gy (23). Asymmetric radiation increases the risk of spinal deformity in two ways (27, 34, 47). It is possible that radiation impairs the vertebral growth plate more on one side than the other.…”

Section: Resultsmentioning

confidence: 99%

A Systematic Review of Selected Musculoskeletal Late Effects in Survivors of Childhood Cancer

Gawade¹,

Hudson²,

Kaste³

et al. 2015

CPR

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Survivors of childhood cancer are at risk for treatment-related musculoskeletal late effects. Early detection and orthopedic intervention can help ameliorate musculoskeletal late effects and prevent subsequent complications. This systematic review summarizes the literature describing associations between cancer, its treatment, and musculoskeletal late effects. We searched PubMed and Web of Science for English language articles published between January 1970 and December 2012. The search was limited to investigations with at least 15 participants and conducted at least 2 years after completion of therapy for childhood, adolescent, or young adult cancer. Some late skeletal effects, including low bone mineral density, osteonecrosis, slipped capital femoral epiphyses, oncogenic rickets, and hormone-related growth disturbances have been previously reviewed and were excluded, as were outcomes following amputation and limb-salvage procedures. Of 2347 references identified, 30 met inclusion criteria and were retained. An additional 54 studies that met inclusion criteria were found in reference lists of retained studies. Of 84 studies, 60 focused on associations between radiotherapy, six between chemotherapy, and 18 between surgery and musculoskeletal late effects. We found that younger age, higher radiation dosage, and asymmetric or partial bone radiation volume influences the effects of radiation on the musculoskeletal system. Methotrexate and vincristine are associated with long-term muscular strength and flexibility deficits. Laminectomy and chest wall resection are associated with spinal malalignment, and enucleation is associated with orbital deformities among survivors. Radiotherapy, chemotherapy, and surgery are associated with musculoskeletal late effects independently and additively. Associations are additionally influenced by host and treatment characteristics.

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Section: Resultsmentioning

confidence: 99%

A Systematic Review of Selected Musculoskeletal Late Effects in Survivors of Childhood Cancer

Gawade¹,

Hudson²,

Kaste³

et al. 2015

CPR

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“…The corrosive impact of these radiationinduced side effects can be unrelenting and their complex management is rarely remedial. Radiation therapy changes the biologic environment of bone, resulting in a severe attenuation of cellularity and fibrosis [4,5], decreased vascular density, obliteration of small blood vessels, poor fracture and soft tissue healing [6][7][8][9], impaired growth [10], and the late devastating complication of osteoradionecrosis. The bone subjected to X-ray radiation therapy (XRT) demonstrates increased bone resorption, decreased osteogenesis, and reduced [11,12] mechanical strength [13] that predisposes the patients to the debilitating problem of late pathologic fractures with disastrous functional consequences [14].…”

Section: Introductionmentioning

confidence: 99%

Stem Cell Therapy Remediates Reconstruction of the Craniofacial Skeleton After Radiation Therapy

Deshpande

Gallagher

Donneys

et al. 2013

Stem Cells and Development

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This study utilized transplanted bone marrow stromal cells (BMSCs) as a cellular replacement therapy to remedy radiation-induced injury and restore impaired new bone formation during distraction osteogenesis (DO). BMSC therapy brought about the successful generation of new bone and significantly improved both the rate and quality of a bony union of irradiated, distracted [X-ray radiation therapy (XRT)/DO] murine mandibles to the level of nonirradiated DO animals. The bone mineral density and bone volume fraction were also significantly improved by the BMSC replacement therapy showing no difference when compared to nonirradiated animals. Finally, a biomechanical analysis examining the yield, failure load, and ultimate load also demonstrated a significantly improved structural integrity in BMSC-treated XRT/DO mandibles over XRT/DO alone. These results indicate that administration of BMSCs intraoperatively to a radiated distraction gap can function as an adequate stimulant to rescue the ability for irradiated bone to undergo DO and produce a healed regenerate of a vastly superior quality and strength. We believe that the fundamental information on the optimization of bone regeneration in the irradiated mandible provided by this work has immense potential to be translated from the bench to the bedside to lead to improved therapeutic options for patients suffering from the disastrous sequelae of radiation therapy.

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“…The longitudinal growth of bone is known to be a result of the orderly coordination of chondrocyte proliferation and hypertrophy, calcification of the matrix, vascular invasion, and completion of endochondral bone formation in the growth plate [Butler et al, 1990;Goldwein, 1991;Robertson et al, 1991]. Radiotherapy for bone or soft-tissue sarcomas close to the growth plate can result in the development of growth arrest, angular deformity, and/or limb length discrepancy.…”

Section: Introductionmentioning

confidence: 99%

Microarray Analysis of Irradiated Growth Plate Zones following Laser Microdissection Shows Later Importance of Differentially Expressed Genes during Radiorecovery

Pritchard

Horton²,

Keenawinna³

et al. 2010

Cells Tissues Organs

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Purpose: Potential targets for selective radiorecovery modulation were investigated via the identification of late upregulated genes and pathways during growth plate chondrocyte recovery. Methods and Materials: Three groups of six 5-week-old male Sprague-Dawley rats underwent fractionated irradiation to the right tibiae over 5 days totaling 17.5 Gy and were then killed at 7, 11, and 16 days following the first radiotherapy fraction. The growth plates were collected from the proximal tibiae bilaterally and subsequently underwent laser microdissection to separate reserve, perichondral, proliferative, and hypertrophic zones. Differential gene expression was analyzed between irradiated right and nonirradiated left tibiae using RAE230 2.0 GeneChip microarray, compared between zones and time points, and subjected to functional pathway cluster analysis with real-time polymerase chain reaction (PCR) to confirm selected results. Results: The reserve zone showed the greatest number of differentially expressed genes and enriched pathways: 259 and 134, respectively. Differentially expressed genes included: Timp3, Gpx1, Gas6, Notch2, VEGF, and HIF-1. Enriched pathways included the developmental processes of regeneration, antiapoptosis, developmental growth, tissue regeneration, mesenchymal cell proliferation, negative regulation of immune response, and determination of symmetry. The reserve zone late upregulation of genes was validated using real-time PCR for Mgp, Gas6, and Eef1a1. Conclusions: A significant difference in late upregulated genes between growth plate zones exists. The reserve zone shows the greatest change, containing a 10-fold increase in the total number of genes differentially expressed between days 7 and 16. These findings suggest that reserve zone chondrocytes may play a later role in growth plate recovery response following irradiation.

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Skeletal Sequelae of Radiation Therapy for Malignant Childhood Tumors

Cited by 61 publications

References 0 publications

A Systematic Review of Selected Musculoskeletal Late Effects in Survivors of Childhood Cancer

A Systematic Review of Selected Musculoskeletal Late Effects in Survivors of Childhood Cancer

Stem Cell Therapy Remediates Reconstruction of the Craniofacial Skeleton After Radiation Therapy

Microarray Analysis of Irradiated Growth Plate Zones following Laser Microdissection Shows Later Importance of Differentially Expressed Genes during Radiorecovery

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