Radiotherapy In Pediatric Patients Research Articles

The safety of ovarian and testicular cryopreservation in children

While the use of chemotherapy and radiotherapy in pediatric patients has achieved widespread clinical success and increased lifespan, such gonadotoxic treatments may result in infertility and altered quality-of-life. Currently, ovarian and testicular tissue cryopreservation is the only option for fertility preservation (FP) in children. Because of the experimental nature of these procedures, it is important to determine their safety.

Pulmonary function after whole lung irradiation in pediatric patients with solid malignancies

Although whole lung irradiation is used to treat pulmonary metastases of pediatric solid malignancies, few studies have addressed its long-term pulmonary consequences. The authors conducted a retrospective study of longitudinal changes in 171 pulmonary function tests (PFTs) and their relation with clinical features in 48 survivors of pediatric malignant solid tumors treated with whole lung irradiation. Although active respiratory symptoms were seen in only 9 patients (18.8%), abnormalities in forced vital capacity (FVC; 58.3%), forced expiratory volume in 1 second (FEV(1) ; 64.6%), total lung capacity (TLC; 72.9%), and diffusion capacity of the lung for carbon monoxide corrected for hemoglobin (DLCO(corr) ; 70.8%) were common. At a median follow-up of 9.7 years after whole lung irradiation, FVC, FEV(1) , and TLC significantly declined longitudinally (P = .04, .03, and .02, respectively). Focal pulmonary boost irradiation was significantly associated with abnormal FEV(1) /FVC (P = .03), forced expiratory flow between 25% and 75% forced vital capacity (P = .005), residual volume (RV; P = .005), and RV/TLC (P = .002). Ten patients had baseline PFTs, and FVC, FEV(1) , TLC, and DLCO(corr) worsened immediately after radiation, followed by transient improvement but subsequent decline. Thirteen of 32 (40.6%) patients aged >18 years were smokers. Pulmonary dysfunction was prevalent after whole lung irradiation and worsened over time, although most patients were asymptomatic. Boost irradiation impaired pulmonary function, and a significant proportion of patients were smokers. Further studies are planned to assess the predictors and clinical consequences of progressive PFT abnormalities and to evaluate educational interventions.

On the Benefits and Risks of Proton Therapy in Pediatric Craniopharyngioma

Craniopharyngioma is a pediatric brain tumor whose volume is prone to change during radiation therapy. We compared photon- and proton-based irradiation methods to determine the effect of tumor volume change on target coverage and normal tissue irradiation in these patients. For this retrospective study, we acquired imaging and treatment-planning data from 14 children with craniopharyngioma (mean age, 5.1 years) irradiated with photons (54 Gy) and monitored by weekly magnetic resonance imaging (MRI) examinations during radiation therapy. Photon intensity-modulated radiation therapy (IMRT), double-scatter proton (DSP) therapy, and intensity-modulated proton therapy (IMPT) plans were created for each patient based on his or her pre-irradiation MRI. Target volumes were contoured on each weekly MRI scan for adaptive modeling. The measured differences in conformity index (CI) and normal tissue doses, including functional sub-volumes of the brain, were compared across the planning methods, as was target coverage based on changes in target volumes during treatment. CI and normal tissue dose values of IMPT plans were significantly better than those of the IMRT and DSP plans (p < 0.01). Although IMRT plans had a higher CI and lower optic nerve doses (p < 0.01) than did DSP plans, DSP plans had lower cochlear, optic chiasm, brain, and scanned body doses (p < 0.01). The mean planning target volume (PTV) at baseline was 54.8 cm(3), and the mean increase in PTV was 11.3% over the course of treatment. The dose to 95% of the PTV was correlated with a change in the PTV; the R(2) values for all models, 0.73 (IMRT), 0.38 (DSP), and 0.62 (IMPT), were significant (p < 0.01). Compared with photon IMRT, proton therapy has the potential to significantly reduce whole-brain and -body irradiation in pediatric patients with craniopharyngioma. IMPT is the most conformal method and spares the most normal tissue; however, it is highly sensitive to target volume changes, whereas the DSP method is not.

Role of adaptive radiation therapy for pediatric patients with diffuse pontine glioma

We investigate the role of adaptive radiation therapy in pediatric patients with diffuse pontine glioma and the impact of steroid‐related weight gain on treatment parameters utilizing cone‐beam CT. Fifteen patients with diffuse pontine glioma were treated with three‐dimensional conformal radiation therapy and enrolled on a daily localization protocol. The median age was 6 years (range: 2–13 years). Patient charts were examined to obtain the prescribed daily dose of dexamethasone and weight. The original treatment plan was recalculated based on the data obtained from the daily cone‐beam CT. The changes in target and critical structure doses were calculated using gEUD. Correlations between prescribed dexamethasone, weight gain, source‐to‐skin distance (SSD) changes and dosimetric changes were investigated. Eleven of the 15 patients gained weight during radiation therapy, with an average gain of 2.2 kg (8.0%). The mean gEUD decreased was 0.57 Gy (range: 0.24–1.4 Gy) for the PTV, and the mean gEUD increase for critical structures was 1.14%. No strong correlations between prescribed dexamethasone doses, weight gain and dosimetric changes were found. Change in SSD vs. dose to PTV was correlated (R2=0.51). Weight gain and changes to the external surface are apparent in these patients; however, the dosimetric changes to the target and critical structures were small and in most cases did not warrant an adaptive plan. The potential exists for a decrease in target dose in these patients; therefore, they should be monitored to assess for replanning when necessary.PACS number: 87.53Jw

Dosimetric Comparison of Three-Dimensional Conformal Proton Radiotherapy, Intensity-Modulated Proton Therapy, and Intensity-Modulated Radiotherapy for Treatment of Pediatric Craniopharyngiomas

Cranial irradiation in pediatric patients is associated with serious long-term adverse effects. We sought to determine whether both three-dimensional conformal proton radiotherapy (3D-PRT) and intensity-modulated proton therapy (IMPT) compared with intensity-modulated radiotherapy (IMRT) decrease integral dose to brain areas known to harbor neuronal stem cells, major blood vessels, and other normal brain structures for pediatric patients with craniopharyngiomas. IMRT, forward planned, passive scattering proton, and IMPT plans were generated and optimized for 10 pediatric patients. The dose was 50.4 Gy (or cobalt Gy equivalent) delivered in 28 fractions with the requirement for planning target volume (PTV) coverage of 95% or better. Integral dose data were calculated from differential dose-volume histograms. The PTV target coverage was adequate for all modalities. IMRT and IMPT yielded the most conformal plans in comparison to 3D-PRT. Compared with IMRT, 3D-PRT and IMPT plans had a relative reduction of integral dose to the hippocampus (3D-PRT, 20.4; IMPT, 51.3%*), dentate gyrus (27.3, 75.0%*), and subventricular zone (4.5, 57.8%*). Vascular organs at risk also had reduced integral dose with the use of proton therapy (anterior cerebral arteries, 33.3*, 100.0%*; middle cerebral arteries, 25.9%*, 100%*; anterior communicating arteries, 30.8*, 41.7%*; and carotid arteries, 51.5*, 77.6*). Relative reduction of integral dose to the infratentorial brain (190.7*, 109.7%*), supratentorial brain without PTV (9.6, 26.8%*), brainstem (45.6, 22.4%*), and whole brain without PTV (19.4*, 34.4%*) were recorded with the use of proton therapy. (*Differences were significant based on Friedman's test with Bonferroni-Dunn correction, α = 0.05) The current study found that proton therapy was able to avoid excess integral radiation dose to a variety of normal structures at all dose levels while maintaining equal target coverage. Future studies will examine the clinical benefits of these dosimetric advantages.

Stereotactic radiosurgery for pediatric recurrent intracranial ependymomas

To evaluate the role of stereotactic radiosurgery (SRS) in patients with recurrent or residual intracranial ependymomas after resection and fractionated radiation therapy (RT), the authors assessed overall survival, distant tumor relapse, progression-free survival (PFS), and complications. The authors retrospectively reviewed the records of 21 children with ependymomas who underwent SRS for 32 tumors. There were 17 boys and 4 girls with a median age of 6.9 years (range 2.9-17.2 years) in the patient population. All patients underwent resection of an ependymoma followed by cranial or neuraxis (if spinal metastases was confirmed) RT. Eleven patients had adjuvant chemotherapy. Twelve patients had low-grade ependymomas (17 tumors), and 9 patients had anaplastic ependymomas (15 tumors). The median radiosurgical target volume was 2.2 cm(3) (range 0.1-21.4 cm(3)), and the median dose to the tumor margin was 15 Gy (range 9-22 Gy). Follow-up imaging demonstrated therapeutic control in 23 (72%) of 32 tumors at a mean follow-up period of 27.6 months (range 6.1-72.8 months). Progression-free survival after the initial SRS was 78.4%, 55.5%, and 41.6% at 1, 2, and 3 years, respectively. Factors associated with a longer PFS included patients without spinal metastases (p = 0.033) and tumor volumes < 2.2 cm(3) (median tumor volume 2.2 cm(3), p = 0.029). An interval ≥ 18 months between RT and SRS was also associated with longer survival (p = 0.035). The distant tumor relapse rate despite RT and SRS was 33.6%, 41.0%, and 80.3% at 1, 2, and 3 years, respectively. Factors associated with a higher rate of distant tumor relapse included patients who had spinal metastases before RT (p = 0.037), a fourth ventricle tumor location (p = 0.002), and an RT to SRS interval < 18 months (p = 0.015). The median survival after SRS was 27.6 months (95% CI 19.33-35.87 months). Overall survival after SRS was 85.2%, 53.2%, and 23.0% at 1, 2, and 3 years, respectively. Adverse radiation effects developed in 2 patients (9.5%). Stereotactic radiosurgery offers an additional option beyond repeat surgery or RT in pediatric patients with residual or recurrent ependymomas after initial management. Patients with smaller-volume tumors and a later recurrence responded best to radiosurgery.

Whole Lung Irradiation in Pediatric Patients using Tomotherapy to Minimize Cardiac, Breast and Thyroid Irradiation

Whole Lung Irradiation in Pediatric Patients using Tomotherapy to Minimize Cardiac, Breast and Thyroid Irradiation

Growth Hormone Secretion after Conformal Irradiation in Pediatric Patients with Localized Brain Tumors

Growth Hormone Secretion after Conformal Irradiation in Pediatric Patients with Localized Brain Tumors

The Effects of Anemia and Red Blood Cell Transfusions during Radiotherapy in Pediatric Patients with Extracranial Solid Tumors

The Effects of Anemia and Red Blood Cell Transfusions during Radiotherapy in Pediatric Patients with Extracranial Solid Tumors

Early Results of a Prospective Study Delivering Limited Margin Radiotherapy for Pediatric Patients with Ewing's Sarcoma Family of Tumors

Results: Actuarial 10-year local control is 100%; 10-year event-free (EFS) and overall survival (OS) are 62% and 63%, respectively. Poor prognostic factors for recurrence include group III disease (p = 0.01) and lymph node involvement (p = 0.05). More patients in the RT group had alveolar histology, group III disease, and nodal involvement, as compared to the surgery group. There is no difference in 10-year EFS (57% vs. 66%)or OS (63% vs. 63%) between patients who underwentsurgery or local RT. Surgery was more often performed on tumors of the feet as compared to tumors of the hands (71% vs. 29%; p = 0.01). Complete surgical resection without amputation was achieved in only 4 patients (8%) in the surgical group and 6 patients overall (13%). Regional lymph node biopsy or dissection was performed in 35 patients (73%); of these, 16 (46%) had lymph node involvement. Among relapsing patients, there are no long-term survivors. No second cancers or deaths from non-RMS causes were seen in patients who were long-term disease-free. Long-term functional outcome is excellent in all patients who did not have amputation. Conclusions: Despite having high-risk features, patients treated with local RT achieved excellent local control, although overall diseasecontrolremainssuboptimal.Thesmallnumberofpatientswhounderwentacompletesurgicalresectionwithoutamputation highlights the difficulty of achieving a complete resection in the hand or foot. Therefore, we recommend either definitive radiation therapy or surgical resection which maintains form and function as primary local therapy rather than amputation in children with rhabdomyosarcoma of the hand and foot.

Late Effects of Conformal Radiation Therapy for Pediatric Patients With Low-Grade Glioma: Prospective Evaluation of Cognitive, Endocrine, and Hearing Deficits

We conducted a prospective trial to evaluate late effects in pediatric patients with low-grade glioma (LGG) treated with conformal radiation therapy (CRT). Between August 1997 and August 2006, 78 pediatric patients with LGG (mean age, 9.7 years; standard deviation, +/-4.4 years) received 54 Gy of CRT with a 10-mm clinical target volume margin. Tumor locations were diencephalon (n = 58), cerebral hemisphere (n = 3), and cerebellum (n = 17). Baseline and serial evaluations were performed to identify deficits in cognition, endocrine function, and hearing. Deficits were correlated with clinical factors and radiation dose within specific normal tissue volumes. Cognitive effects of CRT through 5 years after CRT correlated with patient age, neurofibromatosis type 1 status, tumor location and volume, extent of resection, and radiation dose. The effect of age exceeded that of radiation dose; patients younger than 5 years experienced the greatest decline in cognition. Before CRT, growth hormone (GH) secretion abnormality was diagnosed in 24% of tested patients, and 12% had precocious puberty. The 10-year cumulative incidence of GH replacement was 48.9%; of thyroid hormone replacement, 64.0%; of glucocorticoid replacement, 19.2%; and of gonadotropin-releasing hormone analog therapy, 34.2%. The mean +/- standard errors of the cumulative incidence of hearing loss at 10 years did not exceed 5.7% +/- 3.3% at any frequency. To our knowledge, this is the largest series of prospectively followed children with LGG to undergo irradiation. Adverse effects are limited and predictable for most patients; however, this study provides additional evidence that CRT should be delayed for young patients and identifies the potential benefits of reducing radiation dose to normal brain.

Pulmonary function after whole lung radiation in pediatric patients with malignant solid tumors

10025 Background: Pediatric malignant solid tumors are increasingly curable; whole lung irradiation (WLI) may be used to treat pulmonary tumor involvement. Few studies have addressed long-term pulmonary function after WLI during childhood. Methods: We conducted a retrospective review of pulmonary function tests (PFTs) in 1 year survivors of pediatric malignant solid tumors treated with WLI. We assessed PFT changes over time and the relationship of abnormal values to clinical parameters (diagnosis, radiation dose, and presence or absence of boost lung irradiation or surgical resection). Results: We evaluated 164 PFTs performed on 49 patients with the diagnoses of Wilms tumor (38), rhabdomyosarcoma (5), Ewing sarcoma (3), synovial sarcoma (2), and thymoma (1). Median age at radiation was 6.3 years (range, 0.5–20.2 years); median WLI dose was 12 Gy (range, 10.5–18 Gy). Seventeen (34.7%) had focal pulmonary boost irradiation and 21 (42.9%) had partial lung resection. Across the entire population, forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) declined after irradiation with a median follow-up of 9.3 years. The odds of having a normal FEV1 and FVC decreased by a factor of 0.90 (p = 0.0387) and 0.91 (p = 0.0445), respectively, every year, indicating that the proportion of patients with normal values of FEV1 and FVC decreases over time. FEV1/FVC ratio and forced expiratory flow (FEF25%-75%) remained stable. Abnormal FEV1/FVC and FEF25%-75% were more likely in patients who received boost irradiation than in patients who did not (p = 0.0034 and 0.0233, respectively). Conclusions: Pulmonary function worsened over time in this cohort of childhood cancer survivors treated with WLI. Boost irradiation further impaired pulmonary function. Further studies are planned to assess the clinical consequences of these progressive PFT abnormalities and to identify risk factors associated with clinically significant pulmonary dysfunction after WLI. No significant financial relationships to disclose.

A simple technique for cranio-spinal irradiation in pediatric patients

Field matching poses challenges in craniospinal irradiation (CSI) as it leads either to underdosage or overdosage in the junctional area. A simple technique for CSI in pediatric patients is proposed. Computed tomography scans were performed in the prone position. Two lateral cranial fields and a direct posterior spinal field were planned with a common central axis. Half-beam-blocked cranial fields with zero collimator rotation were used for treating the cranium. A half-beam-blocked field defined with jaws was used to treat the spinal column at an extended source-to-surface distance. Before treating the patient, matching of the cranial and spinal field junction along the central axis was verified with an extended dose range film. The technique described is simple and easy to implement and can be applied to pediatric patients undergoing CSI. This method has the potential to reduce daily setup time and setup errors. This technique is ideally suitable for patients with spinal fields less than 30 cm.

Role of FDG-PET in Definition of Involved-field Radiation Therapy for Pediatric Patients with Hodgkin's Lymphoma

Role of FDG-PET in Definition of Involved-field Radiation Therapy for Pediatric Patients with Hodgkin's Lymphoma

Early Results of a Prospective Study Delivering Limited Margin Radiotherapy for Pediatric Patients With Rhabdomyosarcoma

Early Results of a Prospective Study Delivering Limited Margin Radiotherapy for Pediatric Patients With Rhabdomyosarcoma

Analysis of the Incidence of Oral Complications from Cancer Chemo- and/or Radiation Therapy in Pediatric Patients

Analysis of the Incidence of Oral Complications from Cancer Chemo- and/or Radiation Therapy in Pediatric Patients

Concurrent carbogen and radiation therapy in children with high‐risk brainstem gliomas

In an attempt to improve local control, we assessed the feasibility of the addition of 4 min of carbogen inhalation (as a radiosensitizer) to daily fractionated radiotherapy in pediatric patients with high grade and/or diffuse brainstem gliomas. Ten patients inhaled carbogen for >90% of the radiation treatments. Median survival time from start of therapy was 0.80 years. Carbogen inhalation did not appear to improve the dismal prognosis.

Effects of Radiation Therapy on Chondrocytes In Vitro

The negative irradiation complications of growth loss leading to limb length asymmetry and pathological fracture incurred following radiation therapy in pediatric patients has led to a renewed interest in understanding the specific effects of irradiation on the growth plate and the surrounding bone. In the present report, we examined the radiation therapy effects on primary rat growth cartilage chondrocytes in order to determine the chondrocyte radiosensitivity relative to other bone cell constituents and tumor cells, the postirradiation temporal progression of radiation-induced alterations in chondrocyte function, and the time course for the functional restoration of chondrocyte pathways that drive the eventual recovery in growth function. We employed an in vitro primary rat costochondral growth cartilage cell culture model system to evaluate the radiation therapy effects on proliferative chondrocytes using serial radiation doses (0-20 Gy) that are well within the clinically relevant range. Following irradiation, all of the following occurred in a dose-dependent manner: proliferation decreased, cytotoxicity increased, several markers of apoptosis increased, markers of radiation-induced cellular differentiation increased, and cell synthetic activity was disturbed. Alterations in proliferation, cell death, and induction of apoptosis are likely due to a transient radiation-induced derangement of the parathyroid hormone-related protein-Indian hedgehog proliferation-maturation pathway. Alterations in cellular differentiation and cell synthetic activity are novel observations for chondrocytes. Further, these results correspond very well to our previous work in an in vivo Sprague-Dawley rat model, making this model particularly relevant to researching the radiation therapy effects on longitudinal growth.

Phase II trial of conformal radiation therapy for pediatric patients with craniopharyngioma and correlation of surgical factors and radiation dosimetry with change in cognitive function

A Phase II trial of conformal radiation therapy (CRT) for craniopharyngioma was conducted to determine whether the irradiated volume could be safely reduced to decrease effects on cognitive function. Between July 1997 and January 2003, 28 pediatric patients (median age 7.3 +/- 4.12 years) received CRT in whom doses (54-55.8 Gy) were administered to the gross tumor volume (solid and cystic components) surrounded by a 1-cm clinical target volume margin. Patients were evaluated serially with neuropsychometric testing. Statistical analyses were performed to determine the effect of clinical factors and radiation dosimetry on intelligence quotient (IQ). The median follow-up period was 36.6 months (range 24.4-80 months). The estimated 3-year progression-free survival rate was 90.3 +/- 7.3%. Three patients experienced local disease progression. Cognitive outcome for patients was adversely affected by the following factors: age younger than 7.4 years (p = 0.001), an interval between symptoms and diagnosis of more than 73 days (p = 0.06), more extensive surgery (p = 0.014), multiple surgical procedures (p = 0.002), diabetes insipidus (p = 0.02), hydrocephalus at diagnosis (p = 0.009), a cerebrospinal fluid shunt (p = 0.005), shunt revisions (p = 0.01), Ommaya reservoir laterality (p = 0.005), and cyst aspirations (p = 0.02). The percentage of total brain, supratentorial brain, or left temporal lobe volumes receiving a dose in excess of 45 Gy had a significant impact on longitudinal IQ. The use of CRT with a 1-cm margin for clinical target volume results in tumor control equivalent to that achieved using conventionally planned radiation therapy. Surgical morbidity and a volume-receiving dose more than 45 Gy are factors affecting longitudinal IQ after CRT in patients treated for craniopharyngioma.

Phase II trial of conformal radiation therapy for pediatric patients with craniopharyngioma and correlation of surgical factors and radiation dosimetry with change in cognitive function

Phase II trial of conformal radiation therapy for pediatric patients with craniopharyngioma and correlation of surgical factors and radiation dosimetry with change in cognitive function