Improved survival in primary nonmetastatic pediatric osteosarcoma of the extremity.

UNLABELLED: A prospective study using a dose-intensified neoadjuvant intra-arterial chemotherapy regimen was designed to improve survival rates of young patients with primary, nonmetastatic osteosarcoma of the extremity. Arteriography was implemented to individualize duration of therapy by serially assessing change in tumor neovascularity. Intravenous doxorubicin and intra-arterial cisplatin were administered repetitively at 3-week intervals until > or = 90% reduction in tumor neovascularity was achieved. Surgery was delayed until this good arteriographic response was documented. After resection, prediction of tumor neovascularity was compared with tumor necrosis. Since 1987, 62 eligible patients younger than 22 years old were treated with an average of four neoadjuvant courses. Toxicities were manageable. Fifty-four (87%) patients had a good histologic response. The rate of limb preservation surgery was 93.5% (58/62). Accuracy and sensitivity of serial arteriography in predicting histologic response were 92% and 98% respectively, and greatly assisted surgical planning. With an average followup of 91 months, estimated Kaplan-Meier survival at 10 years was 93% and event-free survival was 86%. Osteosarcoma survival rates were significantly improved by the use of this regimen compared with previously reported results. Serial arteriography succeeded in individualizing duration of neoadjuvant therapy and led to a higher rate of good histologic response. LEVEL OF EVIDENCE: Therapeutic study, level II-1 (prospective cohort study). See the Guidelines for Authors for a complete description of levels of evidence.

Blasts in CSF with a normal cell count do not justify alteration of therapy for acute lymphoblastic leukemia in remission: a Childrens Cancer Group study.

PURPOSE: The Childrens Cancer Group (CCG) requires both a CSF WBC count of more than five cells per microliter and demonstration of blast cells in the cytocentrifuge specimen to support a diagnosis of CNS relapse. We reviewed the CSF examinations of patients with intermediate-risk acute lymphoblastic leukemia (ALL) to determine the clinical significance of blast cells reported in the cytocentrifuge when the total CSF cell count was normal. PATIENTS AND METHODS: Children treated on CCG-105 for ALL had CSF examinations every 12 weeks during maintenance therapy. The outcome of children who had a positive CSF cytocentrifuge examination without an elevated CSF WBC count was compared with that of children who did not have any CSF blast cells observed. RESULTS: Sixty-four patients had 81 CSF examinations with blast cells and a normal cell count. By Cox life-table regression analysis, patients with blasts had a different disease-free survival (DFS) distribution, with relapses tending to occur earlier (P = .008). However, the DFS for these patients was 63% +/- 9.6% at 5 years from the time of the abnormal cytocentrifuge result as compared with 69% +/- 1.5% for 1,490 children who did not have blasts in their CSF. This difference is not significant. CONCLUSION: Blast cells were infrequently identified in cytocentrifuge preparations of CSF when the cell count was normal. The majority of patients in whom such an event was observed have not experienced a subsequent relapse as measured by life-table analysis at 5 years. The data do not justify changing or augmenting therapy based on cytocentrifuge results alone.

Peripheral neuroepithelioma of the soft tissues. A retrospective analysis of fifteen pediatric patients.

PURPOSE: The purpose of this study was to determine the clinical outcome for pediatric patients with peripheral neuroepithelioma treated with combined modality therapy and followed long enough to account for late relapses. PATIENTS AND METHODS: Fifteen patients, ages 3 3/12 to 19 10/12 years, with peripheral neuroepithelioma (median follow-up 91 months) were diagnosed at The Children's Hospital, Denver, Colorado over the period 1980-1989. All of these malignancies originated in the soft tissues. A critical review of these cases was performed with particular consideration given to the site and stage of the tumor and to the radiographic findings at presentation. Thirteen patients had bulk (> 5 cm in the greatest dimension) or metastatic disease. Four patients had primary tumors involving the chest wall. All patients received chemotherapy, which included at least doxorubicin, vincristine, and cyclophosphamide. Definitive surgical resections were performed on 13 of 15 patients. RESULTS: Five patients relapsed. Three were late relapses 24-44 months after diagnosis. Three of the five patients who relapsed had chest wall primaries. There were three deaths in this series due to peripheral neuroepithelioma and one due to sepsis. The overall survival was 68.5%, and the recurrence-free, survival 55.2%. Two patients with pulmonary relapses were treated with surgery and intensive chemotherapy and remain free of disease > 51 months following recurrence. CONCLUSIONS: Combined treatment modalities appear to be important for optimal outcome. This series represents the first report of favorable outcome of peripheral neuroepithelioma using a series with follow-up that is long enough to account for late relapses.

Second malignant neoplasms in survivors of childhood cancer.

As the treatment of childhood cancer continues to improve, the number of survivors at risk for late effects rises. One such late effect is the risk of second malignant neoplasms. Large multicenter registries have been established to accumulate data on the incidence of second cancers. Relative risks and cumulative risks can now be calculated for retinoblastoma, Wilm's tumor and Hodgkin's disease. Early data are now available for leukemia, sarcomas and central nervous system tumors. Genetic cancer syndromes, radiation therapy and treatment with chemotherapeutic agents are known risk factors for second malignant neoplasms in survivors of childhood cancer.

A comparison of smoking patterns in the People's Republic of China with the United States. An impending health catastrophe in the middle kingdom.

Half of the global increase in tobacco use from 1976 to 1986 occurred in the People's Republic of China. In 1984, the first national smoking survey was conducted in China, involving over a half-million subjects. Sixty-one percent of Chinese males over age 15 smoke, with higher rates in all occupational groups than for corresponding groups in the United States. Current smoking patterns in China are similar to those in the United States during the 1950s, and these patterns forecast a steadily increasing epidemic of smoking-related deaths. It is estimated that by 2025, two million Chinese men will die annually from smoking. Foreign tobacco companies are mounting massive production and advertising campaigns in China. Government health education programs lack funds to counter these influences with sustained and comprehensive educational and interventional campaigns. To avert an impending national health catastrophe, China must launch a comprehensive smoking-control initiative aimed at public education, cessation, and legislation and policy.

Hepatitis B virus vaccine. Cost-benefit analysis of its use in a children's hospital.

A cost-benefit analysis of routine active immunization against hepatitis B virus (HBV) for 500 nursing personnel at The Children's Mercy Hospital in Kansas City, Missouri, is described. Based on outcomes of HBV infection, local charges for medical care and wages lost from illness, the authors calculate the average cost per case of HBV infection to be $1,990. Including the current system of postexposure prophylaxis and an annual attack rate of 1 percent the current annual cost of HBV infection in The Children's Mercy Hospital is $12,630. The HBV immunization program would have to continue for 15 years before its cumulative costs ($189,133) were exceeded by those of the current system ($189,450). Therefore routine immunization of nurses would not be cost effective in the near future. If, however, a subset of high-risk employees with a 2 percent attack rate is identified, or the cost of the HBV vaccine series fell from the current $103 to $27, then routine immunization would become cost beneficial within 6 years.

Work-related risk factors for hepatitis B virus infection in personnel of a children's hospital.

Seroprevalence of hepatitis B virus markers was examined in employees participating in patient care at The Children's Mercy Hospital in Kansas City, Missouri. Of 377 workers tested in 1985-86, 36 (9.6%) were seropositive for any marker. Among 285 employees who presumably have only work-related hepatitis B exposure, 14 (4.9%) were seropositive. Age 50 years and older, black race, and education no more than 12 years were associated with seropositivity among workers with work-related exposure. Employees in the clinics, laboratories, emergency room, and operating room had an increased prevalence of hepatitis B markers compared to those in other work locations (8 vs. 2%, p less than 0.05). Traditional risk factors for infection were not predictive of seropositivity. Although the risk of acquiring hepatitis B infection from employment in a children's hospital is low, this study does identify work-related risk factors. Possible reasons for this association are discussed.

Passive smoking on commercial airline flights.

In-flight exposure to nicotine, urinary cotinine levels, and symptom self-reports were assessed in a study of nine subjects (five passengers and four attendants) on four routine commercial flights each of approximately four hours' duration. Urine samples were collected for 72 hours following each flight. Exposures to nicotine measured during the flights using personal exposure monitors were found to be variable, with some nonsmoking areas attaining levels comparable to those in smoking sections. Attendants assigned to work in nonsmoking areas were not protected from smoke exposure. The type of aircraft ventilation was important in determining the levels of in-flight nicotine exposure. The environmental tobacco smoke levels that occurred produced measurable levels of cotinine (a major metabolite of nicotine) in the urine of passengers and attendants. Passengers who experienced the greatest smoke exposure had the highest levels of urinary cotinine. Changes in eye and nose symptoms between the beginning and end of the flights were significantly related both to nicotine exposure during the flight and to the subsequent urinary excretion of cotinine. In addition, subjects' perceptions of annoyance and smokiness in the airplane cabin were also related to in-flight nicotine exposure and urinary excretion measures.

The National Cancer Institute's intervention trials.

The National Cancer Institute (NCI) has increased its emphasis in cancer prevention by undertaking a number of human intervention trials. Special emphasis is placed on chemoprevention, diet, and smoking and tobacco use. Some 24 clinical trials are ongoing in chemoprevention to assess the role of specific chemicals (natural and synthetic) in preventing, inhibiting, or reversing carcinogenesis. In diet and nutrition, several macronutrient trials are underway. The most significant of these is examining the relationship between dietary fat and breast cancer. In 1982, the NCI initiated a broad intervention research effort in smoking and tobacco use which has resulted in 46 prevention and clinical trials covering 25 states and more than 200 cities. More recently, a North American community-based intervention trial was begun to test cessation strategies for heavy smokers in 22 different sites. All of these intervention research efforts are testing strategies which later can be applied to large target population thereby supporting NCI's ambitious goal to reduce cancer mortality in this nation 50% by the year 2000.