Marcio H. Malogolowkin

Predictive power of pretreatment prognostic factors in children with hepatoblastoma: A report from the Children's Oncology Group

PRETEXT is used to stratify risk in children with hepatoblastoma by the Liver Tumor Strategy Group (SIOPEL) of the International Society of Pediatric Oncology (SIOP). A recent analysis excluding patients that did not survive neoadjuvant chemotherapy, concluded that PRETEXT was superior to Childrens Oncology Group (COG) stage for predicting survival. Puzzled by this result, we made a similar comparison of PRETEXT and COG stage. This time, however, we include all patients, and we compare predictive value at diagnosis, instead of after neoadjuvant chemotherapy.

Treatment of Wilms tumor relapsing after initial treatment with vincristine, actinomycin D, and doxorubicin. A report from the national Wilms tumor study group

We evaluated the use of alternating cycles of cyclophosphamide/etoposide and carboplatin/etoposide in children entered on National Wilms Tumor Study (NWTS)‐5 who were diagnosed between August 1, 1995 and May 31, 2002 and who relapsed after chemotherapy with vincristine, actinomycin D, and doxorubicin (VAD) and radiation therapy (DD‐4A).

Results of treatment of malignant germ cell tumors in 93 children: a report from the Childrens Cancer Study Group.

We report treatment results in 93 children entered on study from 1978 to 1984 with malignant germ cell tumors (MGCTs), excluding dysgerminoma and tumors of the testis or brain. The estimated 4-year survival and event-free survival (EFS) for all 93 patients were 54% and 49%, respectively. For 30 children with ovarian tumors, the estimated 4-year survival was 67% and EFS was 63%. For 63 children with nongonadal tumors, survival and EFS were 48% and 42%, respectively. The comparison of EFS between ovarian and nongonadal tumors was significant at P = .03. The treatment plan included a second-look surgical procedure after 18 weeks of chemotherapy. Over half of 36 patients evaluated as having a residual mass present immediately before second-look surgery had no malignant tumor after review of surgical specimens. Age greater than 11 years at diagnosis, incomplete removal of tumor at first surgery, and more than one structure or organ involved at diagnosis increased the risk for adverse event. The histologic subtype of the primary tumor was not related to outcome. Diagnosis was verified by independent pathologic review, and treatment was uniform. Seventeen percent of all registered patients (21 of 127) were excluded because of ineligible pathologic diagnoses; sixty percent (13 of 21) were immature teratomas.

Treatment of Wilms tumor relapsing after initial treatment with vincristine and actinomycin D: A report from the National Wilms Tumor Study Group

NWTS‐5 was a multi‐institutional clinical trial for patients less than 16 years of age at diagnosis with specific renal neoplasms who were diagnosed between August 1, 1995 and May 31, 2002. A uniform approach to the treatment of patients with relapse was employed.

Predictors of outcome in children with Langerhans cell histiocytosis.

Our goal was to examine the clinical course of patients with Langerhans cell histiocytosis (LCH), with a special emphasis on bone disease and to attempt to identify and examine the factors that may predict reactivation and overall prognosis.

Risk factors for early infection of central venous catheters in pediatric patients

BACKGROUND In an effort to avoid infections that can lead to the premature removal of indwelling central venous catheters (CVCs), the surgical technique and host factors present in pediatric recipients of permanent CVCs were reviewed. STUDY DESIGN All patients receiving CVCs over a 17-month period were identified. Those patients with fever and positive blood cultures drawn through the CVC within 45 days of line placement were labeled as having early infection. A case-control design was used to select two control patients for each infected patient. Charts from both the infection and control groups were reviewed for several factors present at the time of CVC placement, including fever, neutropenia (absolute neutrophil count [ANC] < 500 and ANC < 1,000), use of perioperative antibiotics, diagnosis, CVC site, and type of CVC. Chi-square test with Yates correction was used to compare the groups. Odds ratios (ORs) and 95% confidence intervals were derived. RESULTS Among the 473 CVCs placed, early infections developed in 53 patients (12%). The control group consisted of 106 patients. Neutropenia was present in 16 of 53 infected patients versus 8 of 106 controls (p = 0.004, OR = 5.30). Perioperative antibiotics were given to 25 of 53 infected patients versus 72 of 106 controls (p = 0.02, OR = 0.42). Fever was present in 12 of 53 infected patients versus 14 of 106 controls (p = 0.19, OR = 1.92). Factors that were equally prevalent between the groups and that did not appear to influence the CVC infection rate included a diagnosis of malignancy, CVC type, and site of placement. Of the 53 infected catheters, 16 (30%) could not be cleared of infection and were removed. CONCLUSIONS This study documents that neutropenia and failure to administer prophylactic antibiotics are risk factors for the development of early CVC infection in pediatric patients. To avoid early infection and possible premature CVC removal, we recommend that placement of permanent CVCs be postponed until the ANC is > 1,000. Perioperative antibiotics should be given. A trend toward higher infection rates was seen in patients with preoperative fever.

Prognostic factors in children with extragonadal malignant germ cell tumors : A pediatric intergroup study

PURPOSE To investigate prognostic factors for pediatric extragonadal malignant germ cell tumors (PEMGCT). MATERIALS AND METHODS Between 1990 and 1996, patients with stage I through IV PEMGCT were eligible for a trial of cisplatin dose intensity. We retrospectively investigated prognostic factors for PEMGCT, including age, stage, primary site, treatment, and elevated alfa fetoprotein by univariate and multivariate analysis. RESULTS The 165 patients had a median age of 1.9 years (range, 3 days to 18.5 years); 109 were female; and 99 had alfa fetoprotein > or = 10,000. There were 30 stage I/II, 61 stage III, and 74 stage IV tumors; primary sites included 88 sacrococcygeal, 39 thoracic, and 38 others. The 5-year overall survival (OS) and event-free survival (EFS) rates with standard deviations were 83.4% +/- 3.7% and 79.0% +/- 4.1%, respectively. Univariate analysis identified age > or = 12 years as a highly significant prognostic factor for EFS (5-year EFS, 48.9% +/- 15.6% v 84.1% +/- 3.9%; P < .0001) and for OS (5-year OS, 53.7% +/- 14.9% v 88.5% +/- 3.4%; P < .0001), whereas treatment was of borderline significance (P = .0777). Multivariate Cox proportional hazards regression identified only age > or = 12 years as a significant prognostic factor for EFS (P = .0002). In multivariate Cox regression for OS, the combination of age and primary site was highly significant (P < .0001). Patients > or = 12 years of age with thoracic tumors had six times the risk of death compared with patients younger than 12 years with other primaries. CONCLUSION Age is the most predictive factor of EFS in PEMGCT. There is a significant interaction between age and primary site, suggesting that patients > or = 12 years of age with thoracic tumors are a biologically distinct group.

Intensified Platinum Therapy Is an Ineffective Strategy for Improving Outcome in Pediatric Patients With Advanced Hepatoblastoma

PURPOSE The INT-0098 Intergroup Liver Tumor Study demonstrated no statistically significant differences in event-free and overall survival between patients randomized to treatment with either cisplatin + fluorouracil + vincristine (C5V) or cisplatin + doxorubicin. Results from this and other therapeutic trials suggested that cisplatin was the most active agent against hepatoblastoma. To increase the platinum dose-intensity, a novel regimen was developed alternating carboplatin and cisplatin (CC) every 2 weeks. The P9645 study was designed to compare the risk of treatment failure for patients with stage III/IV hepatoblastoma randomized to either C5V or CC. METHODS C5V was given according to INT-0098 and CC consisted of carboplatin at 700 mg/m2 on day 0 (560 mg/m2 after two cycles) followed by cisplatin 100 mg/m2 on day 14. Granulocyte colony-stimulating factor was used after each CC cycle. All patients received four to six cycles of chemotherapy. RESULTS From the time the study was opened until the time that random assignment was halted, 56 patients received CC and 53 patients received C5V. The 1-year event-free survival was 37% for patients receiving CC and 57% for those receiving C5V (P = .017). Patients randomly assigned to CC required more blood product support. As a result of a semiannual review by the Childrens Oncology Group Data and Safety Monitoring Committee, random assignment was discontinued after 3 years of enrollment because the projected improvement in long-term outcome associated with CC was statistically excluded as a possible outcome of this trial. CONCLUSION Intensification of therapy by alternating platinum analogs increased the risk of adverse outcome in children with unresectable or metastatic hepatoblastoma.

Amifostine does not prevent platinum-induced hearing loss associated with the treatment of children with hepatoblastoma. A report of the Intergroup Hepatoblastoma Study P9645 as a part of the Children's Oncology Group

The current study was conducted to determine whether amifostine is effective in reducing the toxicities associated with the administration of platinum‐containing regimens in children with hepatoblastoma (HB).

Long-term outcomes for infants with very low risk wilms tumor treated with surgery alone in national wilms tumor study-5

Objective:To determine the event-free survival (EFS) and overall survival (OS) of children with very low risk Wilms tumor (VLRWT) treated with surgery only. Background:Previous studies suggested that postoperative chemotherapy had not improved the prognosis of children with VLRWT. A total of 77 children <24 months of age with small (<550 g) Stage I favorable histology Wilms tumors were treated with surgery only. This study was closed based on stopping rules to ensure that the 2-year EFS was ≥90%. Methods:A total of 77 children were assessed for EFS and OS. Of these patients, 21 enrolled at the time of closure were recalled, treated with dactinomycin and vincristine (regimen EE4A), and censored for analysis thereafter. About 111 children subsequently treated with EE4A were available for comparison. Results:Median follow-up of surviving patients was 8.2 years for surgery only (range, 1.9–11.8 years) and 5.2 years for the EE4A group (range, 1.6–8.9 years). The estimated 5-year EFS for surgery only was 84% (95% confidence interval [CI]: 73%, 91%); for the EE4A patients it was 97% (95% CI: 92%, 99%, P = 0.002). One death was observed in each treatment group. The estimated 5-year OS was 98% (95% CI: 87%, 99%) for surgery only and 99% (95% CI: 94%, 99%) for EE4A (P = 0.70). Conclusion:The surgery-only EFS was lower than anticipated but, coupled with a much higher than anticipated salvage rate of the chemotherapy naive patients whose disease recurred, led to an observed long-term OS equivalent to that seen with 2-drug chemotherapy. This approach to the treatment of patients with VLRWT eliminates the toxic side-effects of chemotherapy for a large majority of patients. A follow-up study is underway to confirm these findings.