We conducted a randomized controlled trial to determine whether intensive multi-agent adjuvant chemotherapy improves the chances of relapse-free survival in patients with nonmetastatic high-grade osteosarcoma of the extremity, as compared with concurrent controls. After undergoing definitive surgery, 36 patients were randomly assigned to adjuvant chemotherapy or to observation without adjuvant treatment. At two years the actuarial relapse-free survival was 17 percent in the control group, similar to that found in studies before 1970, and 66 percent in the adjuvant-chemotherapy group (P less than 0.001). Similar results were observed among 77 additional patients who declined to undergo randomization but who elected observation or chemotherapy. We conclude that the natural history of osteosarcoma of the extremity has remained stable over the past two decades, that adjuvant chemotherapy increases the chances of relapse-free survival of patients with high-grade osteosarcoma, and that it should be given to all such patients.

In the year 1976, 9614 outpatient throat cultures were received in the Babies Hospital Bacteriology Laboratory. Cultures were plated on sheep blood a ar with bacitracin disc f applied and incubated overnight at 35 C. in a GASPAK anaerobic jar. 60% had no beta hemolytic colonies. Of the 40% with beta hemolytic colonies, 16% requircd further identification. 7% by replate, 9% by fluorescent antibody (PA). 21% of all cultures and 52% of all cultures with beta hemolytic colonies were presumptive Group A Strep (group 3). The incidence of PCP at the University of Florida during the 12 months period 10175 to 10176 was 6.8%(10/147 children treated with intensive chemotherapy). Primary diagnoses included: 7 leukemia and 3 solid tumor patients. 417 ALL patients were in remission(median duration 91.5 days); 3 leukemia and 2 solid tumor patients were in relapse.Presenting symptoms: fever-10110; cough-9/10; tachypnea-6/10 and dyspnea-3/10. In 9/10 cases an interstitial pneumonitis was revealed on x-ray and a lung biopsy was performed within 24 hours following this finding. In one child, first in our series, an abnormal x-ray was present 4 weeks before biopsy.The method of diagnosis, thoracoscopy, was performed under intram! ~cular anesthesia, without endotracheal tube. It allowed for direct observation and intrathoracic biopsy. Equipment utilized for this procedure was the Karl Stolls peritoneoscope set employing the Hopkins fibroscope and biopsy forceps. The method proved safe even in seriously ill patients and complications were minimal. 1 case of pneumothorax was resolved by reposition of tubing and there was 1 case of mild subcutaneous emphysema.All patients were treated with TPM 20mglkgld and SMX 100mglkgId 7 patients recovered, symptoms improved within 4 days after therapy was begun. 3 patients died, 2 patients had progressive tumors. 1 was complicated by sepsis. The cure rate in this incidence was 70%. Analysis of the data demonstrated a small false positive (F.P.) but a marked false negative (F.N.) rate for Bac-U-Dip (BUD). The false negative rate for Bacturcult (B/C) was zero and the false positive rate, when compared to a no-growth culture (NG) was also low (1170).The combination of Bacturcult and Bac-U-Dip provides both low false positive and false negative rates. Previous studies have shown that latex particles coated with glucose oxidaae (GO) would partially correct the metabolic defects in CGD polymorphonuclear leukocytes (Pm). UTILIZATION OF LIPOSOIBS FOR CORRECTION OF THE W T A - BOLIC DEFICIENCIES IN CHRONIC GRANULOMATOUS DISEASE (CCDIn order to develop a technique with better therapeutic advantage, we studied the efficacy of preparing liposomes (LP) containing the hydrogen peroxide (11202) generating ?a. The activity of GO incorporated within the LP could only be demonstrated after treatment of the LP with Triton X-100. LP were coated with heataggregated human IgC, thereby increasing their cs ability to be phagocytized hp PMN. CCD PMN oxidized glucose-l-f4C upon phagocytosis of GO-containing LP at levels 4-f...

BACKGROUNDHigh‐dose methotrexate (HDMTX)‐induced renal dysfunction can be life threatening, because it delays methotrexate (MTX) excretion, thereby exacerbating the other toxicities of MTX. HDMTX‐induced nephrotoxicity has been managed with high‐dose leucovorin, dialysis‐based methods of MTX removal, thymidine, and with the recombinant enzyme, carboxypeptidase‐G2 (CPDG2), which cleaves MTX to inactive metabolites. The objectives of the current study were to estimate the current incidence of HDMTX‐induced renal dysfunction in patients with osteosarcoma and to compare the efficacy and recovery of renal function for dialysis‐based methods of MTX removal with treatment using CPDG2.METHODSThe literature was reviewed for osteosarcoma trials, use of dialysis‐based methods for MTX removal, and reports of MTX‐induced nephrotoxicity, including information regarding recovery of renal function. Clinical trial databases of select osteosarcoma studies were reviewed. The efficacy of CPDG2 and renal recovery after CPDG2 rescue was obtained from the database of a compassionate‐release trial.RESULTSApproximately 1.8% of patients with osteosarcoma (68 of 3887 patients) who received HDMTX developed nephrotoxicity Grade ≥ 2. The mortality rate among those patients was 4.4% (3 of 68 patients). Dialysis‐based methods of MTX removal were used frequently but had limited effectiveness in removing MTX compared with the rapid reductions > 98% in plasma MTX concentrations achieved with CPDG2. CPDG2 did not appear to increase the time to recovery of renal function compared with supportive treatment that included dialysis‐based methods.CONCLUSIONSHDMTX‐induced renal dysfunction continues to occur in approximately 1.8% of patients with osteosarcoma who are treated on clinical protocols with optimal supportive care. For patients with delayed MTX excretion and high plasma MTX concentrations, CPDG2 should be considered over hemodialysis to lower plasma MTX concentrations rapidly and efficiently. Cancer 2004. © 2004 American Cancer Society.

This single-institution study, with a high rate of long-term data capture, demonstrated that brain tumors are a rare, late complication of therapy for ALL. We report many more low-grade tumors than others probably because of exhaustive long-term follow-up evaluation. The importance of limiting cranial radiation is underscored by the dose-dependent tumorigenic effect of radiation therapy seen in this study.

The overall risk of second malignancies after Ewing's sarcomas is similar to that associated with treatment for other childhood cancers. The radiation dose-dependency of secondary sarcomas justifies modification in therapy to reduce radiation doses.

This protracted schedule is well tolerated in children. The absence of significant myelosuppression and encouraging clinical responses suggest compellingly that irinotecan be further evaluated in children using the (qd x 5) x 2 schedule, beginning at a dose of 20 mg/m(2). These results imply that data obtained from xenograft models can be effectively integrated into the design of clinical trials.

Initial signs and symptoms of CRC are similar in pediatric and adult patients. The strikingly higher frequency of mucinous histology suggests that the biology of CRC differs in pediatric and adult patients and may contribute to poor outcomes. Children should be included in prospective clinical trials for CRC.

In this largest single-institution analysis of pediatric patients with surgically resected NRSTS, we identified clinicopathologic features predictive of poor outcome. These variables should be prospectively evaluated as risk-adapted therapies are developed.