To compare clinical features and outcomes of adults and children reported to have rhabdomyosarcoma.
We analyzed data from 1,071 adults (age > 19 years) and 1,529 children (age < or = 19 years) ...reported in the public-access Surveillance, Epidemiology and End Results database as having rhabdomyosarcoma, diagnosed from 1973 to 2005. Survival estimates were determined using survival time with the end point being death from any cause.
Adults with rhabdomyosarcoma had significantly worse outcome than children (5-year overall survival rates, 27% +/- 1.4% and 61% +/- 1.4%, respectively; P < .0001). Tumors in adults were more likely to be at an unfavorable site (65% v 55%; P < .0001) and to have histologies that are unusual during childhood, particularly the pleomorphic subtype (19%) and not otherwise specified (43%). Regional and distant spread was not more frequent in adults. Adults had significantly worse outcome than children with similar tumors. The most significant difference was in localized disease; 5-year survival estimates were 82% +/- 2.0% for children and 47% +/- 2.9% for adults (P < .0001). Multivariate analysis showed that age, histologic subtype, primary site location, stage, and local control with surgery and/or radiation were significant predictors of survival. However, alveolar subtype and unfavorable primary site lost significance when analysis was restricted to adults.
Adults reported to have rhabdomyosarcoma had worse survival than children with similar tumors. Predictors of poor outcome in children were valid in adults except for alveolar histology and unfavorable tumor site.
Summary Access to quality cancer care is often unavailable in low-income and middle-income countries, and also in rural or remote areas of high-income countries. Teleoncology—oncology applications of ...medical telecommunications, including pathology, radiology, and other related disciplines—has the potential to enhance access to and quality of clinical cancer care, and to improve education and training. Implementation of teleoncology in the developing world requires an approach tailored to priorities, resources, and needs. Teleoncology can best achieve its proposed goals through consistent and long-term application. We review teleoncology initiatives that have the potential to decrease cancer-care inequality between resource-poor and resource-rich institutions and offer guidelines for the development of teleoncology programmes in low-income and middle-income countries.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Two phase II studies assessed the efficacy of vismodegib, a sonic hedgehog (SHH) pathway inhibitor that binds smoothened (SMO), in pediatric and adult recurrent medulloblastoma (MB).
Adult patients ...enrolled onto PBTC-025B and pediatric patients enrolled onto PBTC-032 were treated with vismodegib (150 to 300 mg/d). Protocol-defined response, which had to be sustained for 8 weeks, was confirmed by central neuroimaging review. Molecular tests to identify patterns of response and insensitivity were performed when tissue was available.
A total of 31 patients were enrolled onto PBTC-025B, and 12 were enrolled onto PBTC-032. Three patients in PBTC-025B and one in PBTC-032, all with SHH-subgroup MB (SHH-MB), exhibited protocol-defined responses. Progression-free survival (PFS) was longer in those with SHH-MB than in those with non-SHH-MB, and prolonged disease stabilization occurred in 41% of patient cases of SHH-MB. Among those with SHH-MB, loss of heterozygosity of PTCH1 was associated with prolonged PFS, and diffuse staining of P53 was associated with reduced PFS. Whole-exome sequencing identified mutations in SHH genes downstream from SMO in four of four tissue samples from nonresponders and upstream of SMO in two of four patients with favorable responses.
Vismodegib exhibits activity against adult recurrent SHH-MB but not against recurrent non-SHH-MB. Inadequate accrual of pediatric patients precluded conclusions in this population. Molecular analyses support the hypothesis that SMO inhibitor activity depends on the genomic aberrations within the tumor. Such inhibitors should be advanced in SHH-MB studies; however, molecular and genomic work remains imperative to identify target populations that will truly benefit.
Challenging issues in pediatric oncology Pui, Ching-Hon; Gajjar, Amar J; Kane, Javier R ...
Nature reviews. Clinical oncology,
09/2011, Volume:
8, Issue:
9
Journal Article
Peer reviewed
Open access
Improvements in protocol-driven clinical trials and supportive care for children and adolescents with cancer have reduced mortality rates by more than 50% over the past three decades. Overall, the ...5-year survival rate for patients with pediatric cancer has increased to approximately 80%. Recognition of the biological heterogeneity within specific subtypes of cancer, the discovery of genetic lesions that drive malignant transformation and cancer progression, and improved understanding of the basis of drug resistance will undoubtedly catalyze further advances in risk-directed treatments and the development of targeted therapies, boosting the cure rates further. Emerging new treatments include novel formulations of existing chemotherapeutic agents, monoclonal antibodies against cancer-associated antigens, and molecular therapies that target genetic lesions and their associated signaling pathways. Recent findings that link pharmacogenomic variations with drug exposure, adverse effects, and efficacy should accelerate efforts to develop personalized therapy for individual patients. Finally, palliative care should be included as an essential part of cancer management to prevent and relieve the suffering and to improve the quality of life of patients and their families.
This report documents the clinical characteristics, molecular grouping, and outcome of young children with ependymoma treated prospectively on a clinical trial.
Fifty-four children (aged ≤3 y) with ...newly diagnosed ependymoma were treated on the St Jude Young Children 07 (SJYC07) trial with maximal safe surgical resection, 4 cycles of systemic chemotherapy, consolidation therapy using focal conformal radiation therapy (RT) (5-mm clinical target volume), and 6 months of oral maintenance chemotherapy. Molecular groups were determined by tumor DNA methylation using Infinium Methylation EPIC BeadChip and profiled on the German Cancer Research Center/Molecular Neuropathology 2.0 classifier.
One of the 54 study patients had metastases (cerebrospinal fluid positive) at diagnosis. Gross or near-total resection was achieved in 48 (89%) patients prior to RT. At a median follow-up of 4.4 years (range, 0.2-10.3 y), 4-year progression-free survival (PFS) was 75.1% ± 7.2%, and overall survival was 92.6% ± 4.4%. The molecular groups showed no significant difference in PFS (4-year estimates: posterior fossa ependymoma group A PF-EPN-A; 42/54, 71.2% ± 8.3%; supratentorial ependymoma positive for v-rel avian reticuloendotheliosis viral oncogene homolog A ST-EPN-RELA; 8/54, 83.3% ± 17.0%; and supratentorial ependymoma positive for Yes-associated protein 4/54, 100%, P = 0.22). Subtotal resection prior to RT was associated with an inferior PFS compared with gross or near-total resection (4-year PFS: 41.7% ± 22.5% vs 79.0% ± 7.1%, P = 0.024), as was PF-EPN-A group with 1q gain (P = 0.05). Histopathologic grading was not associated with outcomes (classic vs anaplastic; P = 0.89).
In this prospectively treated cohort of young children with ependymoma, ST-EPN-RELA tumors had a more favorable outcome than reported from retrospective data. Histologic grade did not impact outcome. PF-EPN-A with 1q gain and subtotal resection were associated with inferior outcomes.
The diencephalon is a complex midline structure consisting of the hypothalamus, neurohypophysis, subthalamus, thalamus, epithalamus, and pineal body. Tumors arising from each of these diencephalic ...components differ significantly in terms of biology and prognosis. The aim of this comprehensive review is to describe the epidemiology, clinical symptoms, imaging, histology, and molecular markers in the context of the
. We will also discuss the current management of each of these tumors.
Carboplatin-induced ototoxicity remains poorly defined but is of potential great consequence in children with retinoblastoma. We retrospectively assessed the incidence of ototoxicity and its risk ...factors in children with retinoblastoma who were treated with carboplatin.
We reviewed the audiologic test results of 60 patients with retinoblastoma who received front-line treatment with systemic carboplatin and vincristine according to the St Jude RET-3 protocol (n = 23) or best clinical management (n = 37). Ototoxicity was evaluated by three different grading systems.
Twelve patients (20%) developed ototoxicity at some time after treatment initiation; however, ototoxicity resolved in two patients, and thus,10 patients (17%) had sustained hearing loss as documented at their most recent audiologic evaluation. Nine of these 10 patients had grade 3 or 4 ototoxicity, and nine patients were less than 6 months of age at the start of chemotherapy. Age at the start of chemotherapy was the only risk factor identified as a significant predictor of sustained hearing loss. Younger age was associated with an increased incidence of hearing loss. The different ototoxicity grading systems showed good overall agreement in the identification of patients with ototoxicity. Agreement was greatest between the Brock and Children's Cancer Group systems.
We found that young patients with retinoblastoma who were treated with systemic carboplatin had a higher incidence of ototoxicity than previously reported. Younger patients (< 6 months of age at the start of treatment) were more likely to have ototoxicity than were older patients. Children treated with carboplatin should routinely undergo thorough, long-term audiologic monitoring.
Abstract
Pediatric high-grade glioma (pHGG) is a major contributor to cancer-related death in children. In vitro and in vivo disease models reflecting the intimate connection between developmental ...context and pathogenesis of pHGG are essential to advance understanding and identify therapeutic vulnerabilities. Here we report establishment of 21 patient-derived pHGG orthotopic xenograft (PDOX) models and eight matched cell lines from diverse groups of pHGG. These models recapitulate histopathology, DNA methylation signatures, mutations and gene expression patterns of the patient tumors from which they were derived, and include rare subgroups not well-represented by existing models. We deploy 16 new and existing cell lines for high-throughput screening (HTS). In vitro HTS results predict variable in vivo response to PI3K/mTOR and MEK pathway inhibitors. These unique new models and an online interactive data portal for exploration of associated detailed molecular characterization and HTS chemical sensitivity data provide a rich resource for pediatric brain tumor research.
Introduction
Retinoblastoma (RB) is the most common primary intraocular cancer of childhood. Over the last few decades, a variety of techniques and treatment modalities emerged that improved the ...survival and ocular salvage rate of patients with RB. We investigated the relative survival trends of patients with RB from 2000 to 2018 by using the Surveillance, Epidemiology, and End Results (SEER) database.
Design
Retrospective database review.
Methods
We extracted data from SEER 18 from 2000 to 2018. All patients with clinically diagnosed RB during the study period were included. We utilized SEER*Stat 8.3.9 and JPSurv software to estimate relative 5‐ and 10‐year survival rates and trends and generated descriptive analyses with IBM SPSS.
Main Outcome Measures
Patient survival rates at 5‐ and 10‐year after RB diagnosis.
Results
RB was diagnosed in 1479 patients within the SEER 18 Program during our study period. The cohort comprised 776 (52.5%) males, 615 (41.6%) non‐Hispanic whites, 487(32.9%) Hispanics, 1030 (69.6%) patients with unilateral disease, and 1087 (73.5%) patients with localized disease. Relative survival trends at 5‐ and 10‐year significantly declined over the study periods (−0.42%, and −0.50% annually, respectively) but the decline was not significant in unilateral and bilateral RB cases separately.
Conclusions
Five‐ and ten‐year relative survival trends declined from 2000 to 2018 and were significantly decreasing. Further studies that include more patients are needed to identify the factors contributing to reduced survival of patients with RB over time.
Retinoblastoma was one of the success stories in pediatric oncology, with survival exceeding 98%. However, here we show a decline in the survival of retinoblastoma at the population level. This can be attributed to the new therapies practices in smaller centers with decentralization of services.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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