Bouffet E.,University of Toronto |
Jakacki R.,Childrens Hospital of Pittsburgh |
Goldman S.,Childrens Memorial Medical Center |
Hargrave D.,Royal Marsden Hospital |
And 13 more authors.
Journal of Clinical Oncology | Year: 2012
Purpose: To evaluate the efficacy of single-agent vinblastine in pediatric patients with recurrent or refractory low-grade glioma. Patients and Methods: Patients were eligible if they had experienced previous treatment failure (chemotherapy and/or radiation) for incompletely resected or unresectable low-grade glioma (LGG). Vinblastine (6 mg/m 2) was administered weekly for 1 year unless unacceptable toxicity or progression (confirmed on two consecutive imaging studies) occurred. Results: Fifty-one patients (age range, 1.4 to 18.2 years; median age, 7.2 years) were prospectively enrolled onto this phase II study. Fifty patients had previously received at least one prior regimen of chemotherapy, and 10 patients had previously received radiation treatment. Fifty patients were evaluable for response; 18 patients (36%) had a complete, partial, or minor response, and 31 patients completed 1 year of treatment. At a median follow-up of 67 months, 23 patients had not experienced progression; three patients have died. Five-year overall survival was 93.2% ± 3.8%, and 5-year progression-free survival was 42.3% ± 7.2%. Toxicity was manageable and mostly hematologic, although a few patients needed transfusions. Conclusion: Weekly vinblastine seems to be a reasonable alternative to radiation for pediatric patients with LGG who have experienced treatment failure with first-line chemotherapy. The 5-year progressionfree survival observed in this phase II trial is comparable to results observed with first-line chemotherapy in chemotherapy-naive patients. The role of single-agent vinblastine and other vinca alkaloid in the management of pediatric LGGs deserves further investigation. © 2012 by American Society of Clinical Oncology.
Safety, Pharmacokinetics, and Efficacy of Palifermin in Children and Adolescents with Acute Leukemias Undergoing Myeloablative Therapy and Allogeneic Hematopoietic Stem Cell Transplantation: A Pediatric Blood and Marrow Transplant Consortium Trial
Morris J.,Loma Linda University |
Rudebeck M.,Biovitrum |
Neudorf S.,Childrens Hospital of Orange County |
Moore T.,Mattel Childrens Hospital UCLA |
And 6 more authors.
Biology of Blood and Marrow Transplantation | Year: 2016
Currently, effective pharmacologic treatment to reduce severe oral mucositis (OM) resulting from high-dose myeloablative cytotoxic therapy in the pediatric population is not available. Palifermin has been proven to decrease the incidence and duration of severe OM in adults with hematologic malignancies undergoing hematopoietic stem cell transplantation (HSCT). In the pediatric population, however, data on palifermin treatment are limited. A phase I dose-escalation study of palifermin in pediatric patients with acute leukemias undergoing myeloablative HSCT with total body irradiation, etoposide, and cyclophosphamide was performed to determine a safe and tolerable dose and to characterize the pharmacokinetic (PK) profile and efficacy of palifermin. Twenty-seven patients in 3 age groups (1 to 2, 3 to 11, and 12 to 16 years) and 3 dose levels (40, 60, and 80 μg/kg/day) were studied. There were no deaths, dose-limiting toxicities, or treatment-related serious adverse events. Long-term safety outcomes did not differ from what would be expected in this population. PK data showed no differences between the 3 age groups. Exposure did not increase with increase in dose. The maximum severity of OM (WHO grade 4) occurred in 6 patients (22%), none of whom was in the 80-μg/kg/day dosing group. This study showed that all doses were well tolerated and a good safety profile in all 3 pediatric age groups was seen. © 2016 American Society for Blood and Marrow Transplantation.
Results of the Intergroup Rhabdomyosarcoma Study Group D9602 protocol, using vincristine and dactinomycin with or without cyclophosphamide and radiation therapy, for newly diagnosed patients with low-risk embryonal rhabdomyosarcoma: A report from the soft tissue sarcoma committee of the childrens oncology group
Raney R.B.,University of Houston |
Raney R.B.,Dell |
Raney R.B.,Childrens Memorial Medical Center |
Raney R.B.,University of Nebraska Medical Center |
And 66 more authors.
Journal of Clinical Oncology | Year: 2011
Purpose: Patients with localized, grossly resected, or gross residual (orbital only) embryonal rhabdomyosarcoma (ERMS) had 5-year failure-free survival (FFS) rates of 83% and overall survival rates of 95% on Intergroup Rhabdomyosarcoma Study Group (IRSG) protocols III/IV. IRSG D9602 protocol (1997 to 2004) objectives were to decrease toxicity in similar patients by reducing radiotherapy (RT) doses and eliminating cyclophosphamide for the lowest-risk patients. Patients and Methods: Subgroup A patients (lowest risk, with ERMS, stage 1 group I/IIA, stage 1 group III orbit, stage 2 group I) received vincristine plus dactinomycin (VA). Subgroup B patients (ERMS, stage 1 group IIB/C, stage group III nonorbit, stage 2 group II, stage 3 group I/II) received VA plus cyclophosphamide. Patients in group II/III received RT. Compared with IRS-IV, doses were reduced from 41.4 to 36 Gy for stage 1 group IIA patients and from 50 or 59 to 45 Gy for group III orbit patients. Results: Estimated 5-year FFS rates were 89% (95% CI, 84% to 92%) for subgroup A patients (n = 264) and 85% (95% CI, 74%, 91%) for subgroup B patients (n = 78); median follow-up: 5.1 years. Estimated 5-year FFS rates were 81% (95% CI, 68% to 90%) for patients with stage 1 group IIA tumors (n = 62) and 86% (95% CI, 76% to 92%) for patients with group III orbit tumors (n = 77). Conclusion: Five-year FFS and OS rates were similarto those observed in comparable IRS-III patients, including patients receiving reduced RT doses, but were lower than in comparable IRS-IV patients receiving VA plus cyclophosphamide. Five-year FFS rates were similar among subgroups A and B patients. © 2011 by American Society of Clinical Oncology.
Breneman J.,University of Cincinnati |
Meza J.,University of Nebraska Medical Center |
Donaldson S.S.,Stanford University |
Raney R.B.,University of Houston |
And 8 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2012
Purpose: To analyze the effect of reduced-dose radiotherapy on local control in children with low-risk rhabdomyosarcoma (RMS) treated in the Children's Oncology Group D9602 study. Methods and Materials: Patients with low-risk RMS were nonrandomly assigned to receive radiotherapy doses dependent on the completeness of surgical resection of the primary tumor (clinical group) and the presence of involved regional lymph nodes. After resection, most patients with microscopic residual and uninvolved nodes received 36 Gy, those with involved nodes received 41.4 to 50.4 Gy, and those with orbital primary tumors received 45 Gy. All patients received vincristine and dactinomycin, with cyclophosphamide added for patient subsets with a higher risk of relapse in Intergroup Rhabdomyosarcoma Study Group III and IV studies. Results: Three hundred forty-two patients were eligible for analysis; 172 received radiotherapy as part of their treatment. The cumulative incidence of local/regional failure was 15% in patients with microscopic involved margins when cyclophosphamide was not part of the treatment regimen and 0% when cyclophosphamide was included. The cumulative incidence of local/regional failure was 14% in patients with orbital tumors. Protocol-specified omission of radiotherapy in girls with Group IIA vaginal tumors (n = 5) resulted in three failures for this group. Conclusions: In comparison with Intergroup Rhabdomyosarcoma Study Group III and IV results, reduced-dose radiotherapy does not compromise local control for patients with microscopic tumor after surgical resection or with orbital primary tumors when cyclophosphamide is added to the treatment program. Girls with unresected nonbladder genitourinary tumors require radiotherapy for postsurgical residual tumor for optimal local control to be achieved. © 2012 Elsevier Inc. All rights reserved.
Khanna G.,University of Washington |
Naranjo A.,University of Florida |
Hoffer F.,Review Centre |
Mullen E.,Dana-Farber Cancer Institute |
And 7 more authors.
Radiology | Year: 2013
Purpose: To retrospectively determine the diagnostic performance of computed tomography (CT) in identifying the presence or absence of preoperative Wilms tumor rupture. Materials and The cohort was derived from the AREN03B2 study of the Methods: Children's Oncology Group. The study was approved by the institutional review board and was compliant with HIPAA. Written informed consent was obtained before enrollment. The diagnosis of Wilms tumor rupture was established by central review of notes from surgery and/or pathologic examination. Seventy Wilms tumor cases with rupture were matched to 70 Wilms tumor controls without rupture according to age and tumor weight (within 6 months and 50 g, respectively). CT scans were independently reviewed by two radiologists, and the following CT fndings were assessed: poorly circumscribed mass, perinephric fat stranding, peritumoral fat planes obscured, retroperitoneal fluid (subcapsular vs extracapsular), ascites beyond the cul-de-sac, peritoneal implants, ipsilateral pleural effusion, and intratumoral hemorrhage. All fluids were classified as hemorrhagic or nonhemorrhagic by using a cutoff of 30 HU. The relationship between CT fndings and rupture was assessed with logistic regression models. Results: The sensitivity and specificity for detecting Wilms tumor rupture were 54% (36 of 67 cases) and 88% (61 of 69 cases), respectively, for reviewer 1 and 70% (47 of 67 cases) and 88% (61 of 69 cases), respectively, for reviewer 2. Interobserver agreement was substantial (κ = 0.76). All imaging signs tested, except peritoneal implants, intratumoral hemorrhage, and subcapsular fluid, showed a significant association with rupture (P <.02). The attenuation of ascitic fluid did not have a significant correlation with rupture (P =.9990). Ascites beyond the cul-de-sac was the single best indicator of rupture for both reviewers, followed by perinephric fat stranding and retroperitoneal fluid for reviewers 1 and 2, respectively (P <.01). Conclusion: CT has moderate specificity but relatively low sensitivity in the detection of preoperative Wilms tumor rupture. Ascites beyond the cul-de-sac, irrespective of attenuation, is most predictive of rupture. © RSNA, 2012.
Walterhouse D.O.,Childrens Memorial Medical Center |
Meza J.L.,University of Nebraska Medical Center |
Breneman J.C.,Childrens Hospital Medical Center |
Donaldson S.S.,Stanford University |
And 6 more authors.
Pediatric Blood and Cancer | Year: 2011
Background: The local control approach for girls with non-resected vaginal rhabdomyosarcoma (RMS) enrolled onto Intergroup RMS Study Group (IRSG)/Children's Oncology Group (COG) studies has differed from that used at other primary sites by delaying or eliminating radiotherapy (RT) based on response achieved with chemotherapy and delayed primary resection. Procedures: We reviewed locoregional treatment and outcome for patients with localized RMS of the vagina on the two most recent COG low-risk RMS studies. Results: Forty-one patients with localized vaginal RMS were enrolled: 25 onto D9602 and 16 onto Subset 2 of ARST0331. Only four of the 39 with non-resected tumors received RT. The 5-year cumulative incidence of local recurrence was 26% on D9602, and the 2-year cumulative incidence of local recurrence was 43% on ARST0331. Increased local failure rates appeared to correlate with chemotherapy regimens that incorporated lower cumulative doses of cyclophosphamide. Estimated 5-year and 2-year failure free survival rates were 70% (95% CI: 46%, 84%) on D9602 and 42% (95% CI: 11%, 70%) on ARST0331, respectively. Conclusions: To prevent local recurrence, we recommend a local control approach for patients with non-resected RMS of the vagina that is similar to that used for other primary sites and includes RT. We recognize that potential long-term effects of RT are sometimes unacceptable, especially for children less than 24 months of age. However, when making the decision to eliminate RT, the risk of local recurrence must be considered especially when using a chemotherapy regimen with a total cumulative cyclophosphamide dose of ≤4.8g/m2. © 2011 Wiley-Liss, Inc.