Smoking in adult survivors of childhood acute lymphoblastic leukemia.

BACKGROUND: Health-related behaviors are of particular concern in survivors of childhood cancer as they are at increased risk for second cancers and long-term organ dysfunction. The purpose of this study was to compare the smoking behavior and associated factors in young-adult survivors of childhood acute lymphoblastic leukemia (ALL) with those in sibling controls. METHODS: A telephone interview that surveyed smoking behavior was conducted with 592 young-adult survivors, treated before age 20 years on Children's Cancer Group ALL protocols, and 409 sibling controls. Using stratified chi-squared analyses and Cox proportional hazards models, we compared the rates of smoking initiation and smoking cessation between survivors and control subjects. Demographic characteristics (age, sex, race, and education) and psychological factors (mood and self-concept) were examined as predictors interacting with survivorship in logistic regression analyses to try to distinguish a subgroup of survivors who may be at greater risk for smoking. RESULTS: Survivors were significantly less likely to have ever smoked (23.0% versus 35.7%; P<.0001) and thus were less likely to ever be regular, daily smokers than sibling controls (19.1% versus 31.3%; P<.0001). Survivors were less likely to quit smoking than sibling controls (26.6% versus 35.2%), although this result was not statistically significant. There were no interactions between survivor status and either demographic or psychological features on smoking behavior. CONCLUSIONS: Young-adult survivors of childhood ALL are less likely to experiment with smoking but, once having started, are at similar risk for becoming habitual, persistent smokers as sibling controls.

Patient preferences for axillary dissection in the management of early-stage breast cancer.

BACKGROUND: Recent data on the value of adjuvant therapy in lymph node-negative breast cancer and promising early data on less invasive strategies for managing the axilla have raised questions about the appropriate role of axillary lymph node dissection (ALND) in the management of early-stage breast cancer. We sought to evaluate how women weigh potential benefits of ALND-prognostic information, enhanced local control, and tailored therapy-against the risks of long-term morbidity that are associated with the procedure. METHODS: We used hypothetical scenarios to survey 82 randomly selected women with invasive breast cancer who had been treated with ALND and 62 women at risk for invasive breast cancer by virtue of a history of ductal carcinoma in situ (DCIS) who had not undergone ALND. RESULTS: Women in both the invasive cancer and the DCIS groups required substantial improvements in local control of the cancer (5% and 15%, respectively) and overall survival (3% and 10%, respectively) before they would opt for this procedure. Women with invasive cancer would choose ALND if it had only a 1% chance of altering treatment recommendations, whereas DCIS subjects required a 25% chance. Sixty-eight percent and 29% of women in the invasive cancer and DCIS groups, respectively, would accepted a 40% risk of arm dysfunction to gain prognostic information that would not change treatment. CONCLUSIONS: For most subjects treated previously for invasive breast cancer and almost half those at risk of the disease, the potential benefits of ALND, particularly the value of prognostic information, were sufficient to outweigh the risks of morbidity. However, women varied considerably in their preferences, highlighting the need to tailor decisions regarding management of the axilla to individual patients' values.

A comparison of two methods for estimating the technical costs of external beam radiation therapy.

PURPOSE: To accurately assess the cost-effectiveness of treatment with external beam radiation, it is necessary to have accurate estimates of its cost. One of the most common methods for estimating technical costs has been to convert Medicare charges into costs using Medicare Cost-to-Charge Ratios (CCR). More recently, health care organizations have begun to invest in sophisticated cost-accounting systems (CAS) that are capable of providing procedure-specific cost estimates. The purpose of this study was to examine whether these competing approaches result in similar cost estimates for four typical courses of external beam radiation therapy (EBRT). METHODS AND MATERIALS: Technical costs were estimated for the following treatment courses: 1) a palliative "simple" course of 10 fractions using a single field without blocks; 2) a palliative "complex" course of 10 fractions using two opposed fields with custom blocks; 3) a curative course of 30 fractions for breast cancer using tangent fields followed by an electron beam boost; and 4) a curative course of 35 fractions for prostate cancer using CT-planning and a 4-field technique. Costs were estimated using the CCR approach by multiplying the number of units of each procedure billed by its Medicare charge and CCR and then summing these costs. Procedure-specific cost estimates were obtained from a cost-accounting system, and overall costs were then estimated for the CAS approach by multiplying the number of units billed by the appropriate unit cost estimate and then summing these costs. All costs were estimated using data from 1997. The analysis was also repeated using data from another academic institution to estimate their costs using the CCR and CAS methods, as well as the appropriate relative value units (RVUs) and conversion factor from the 1997 Medicare Fee Schedule to estimate Medicare reimbursement for the four treatment courses. RESULTS: The estimated technical costs for the CCR vs. CAS approaches for the four treatment courses were as follows: palliative "simple" $1,285 vs. $1,195; palliative "complex" $2,345 vs. $1,769; curative breast $6,757 vs. $4,850; and curative prostate $9,453 vs. $7,498. Accordingly, the CCR estimates were 8%, 33%, 39%, and 26% higher than the CAS cost estimates, respectively. The primary cause of the difference between the estimates was the daily cost of delivering a "complex" treatment. In fact, if corrected the difference between the estimates fell to 0%, 1%, 4%, and 0%, respectively. Similar results were observed for both methods when the analysis was repeated using data from another academic institution. Medicare reimbursement was also slightly lower than, but remarkably close to, the costs estimated by the CAS approach. CONCLUSIONS: For "complex" treatment courses, which represent the vast majority of external beam treatments, technical costs estimated using the CCR approach appear to be significantly higher than those estimated using procedure-specific cost estimates. Because cost-effectiveness analyses of radiation therapy tend to be sensitive to the cost of treatment, the use of higher costs will result in radiation therapy appearing less cost-effective.

20-year experience in childhood craniopharyngioma.

PURPOSE: The management of craniopharyngioma is controversial, and surgery alone is frequently advocated. The purpose of this study was to assess the long-term impact of various treatments in childhood craniopharyngioma. METHODS AND MATERIALS: Sixty-one children < or = 21 years of age at diagnosis were treated for craniopharyngioma at Children's Hospital and the Joint Center for Radiation Therapy in Boston from 1970 to 1990. The median age was 7.5 years (range 10 months-21 years). There were 33 females and 28 males. The median follow-up was 10 years (range 2-20.5 years). Neuroimaging was available for detailed review in 53. Nine children were treated with radiotherapy alone, 15 were treated with surgery alone, and 37 were treated with both surgery and radiotherapy. All patients in the radiotherapy and surgery plus radiotherapy groups were treated with megavoltage radiation with a median dose of 5464 cGy. RESULTS: All nine of the children treated with radiation therapy alone are alive; none have recurred. Nine of the 15 children treated with surgery alone have recurred (p = 0.007 Fisher exact test). Two are alive with disease, and seven are alive without disease after treatment at relapse with radiation therapy, surgery, or both. Seven of the 37 patients treated with surgery plus radiotherapy have recurred. Three of the seven patients are dead of disease, three patients are alive with disease, and one patient is alive without disease after further treatment. The 10-year actuarial overall survival was 91% for all patients. The 10-year actuarial freedom from progression for the surgery group was 31% compared with 100% for patients treated with radiation therapy only (log rank p = 0.01), and 86% for patients treated with surgery plus radiotherapy at diagnosis (p = 0.001). There were two treatment related deaths, both in the surgery plus radiotherapy group. A higher incidence of visual loss and diabetes insipidus was associated with the use of aggressive surgery. The size of the tumor at presentation correlated with an increased risk of recurrence; 5 of 6 patients with tumors > or = 5 cm experienced recurrences while only 6 of 30 recurred when the tumor was < 5 cm. CONCLUSIONS: Overall survival in childhood craniopharyngioma is excellent. However, patients treated with surgery alone have a significantly worse freedom from progression when compared to patients treated with surgery and radiation therapy or radiation therapy alone.

Childhood optic chiasm gliomas: radiographic response following radiotherapy and long-term clinical outcome.

PURPOSE: In children with chiasmal gliomas, radiation therapy can arrest progressive visual and neurologic impairment. We examined the radiographic response and clinical outcomes after irradiation. METHODS AND MATERIALS: Forty-two children (median age at diagnosis, 6.6 years) with chiasmal gliomas were managed as follows: 11 asymptomatic patients with neurofibromatosis-1 (NF-1) were observed only; 2 patients, less than 3 years old, underwent surgery and chemotherapy to delay irradiation; and 29 patients with progressive disease received radiation with or without prior surgery or chemotherapy. Time to radiographic response, long-term tumor control and late sequelae were reviewed for the 29 irradiated patients. RESULTS: The probability of at least 50% radiographic response at 24 months after irradiation was 18.1% and increased to 38.2% by 48 months and 45.9% by 60 months. By actuarial analysis, the median time for such radiographic response was 62 months. For the 29 irradiated patients, the 10-year freedom from progression and overall survival rates were 100% and 89%, respectively (median follow-up for surviving patients, 108 months). Stabilization or improvement in vision occurred in 81% of 26 evaluable irradiated patients. CONCLUSIONS: Notable radiographic response may be observed years after irradiation. Radiation therapy provides excellent long-term tumor control and vision preservation or improvement in the majority of patients with progressive chiasmal gliomas.

Duplication of the escape-response neural pathway by mutation of the bithorax-complex.

Each Drosophila segment exhibits specific patterns of epidermal cells, muscles, and neurons. Mutations in the homeotic genes of the bithorax-complex cause transformations of these patterns. Whereas abundant information exists concerning homeotic transformation of epidermis, transformations of muscles and motor neurons have been largely unexplored. An important indication of neuromuscular transformation in a segment is the expression of novel behavioral and physiological functions within that segment. We have resolved some of the segmental identities of neuromuscular elements in the transformed metathorax of the bithorax-complex mutant, abx bx3 pbx/Df(3R) P2, and have established the presence of a duplicated neural pathway for the escape-jump response within that segment. Although we observed frequent homeotic transformation of neural elements and the tergotrochanteral ("jump") muscle in mutants, corresponding transformation of flight muscles was infrequent, indicating that the presence of a motor neuron was not always sufficient to induce or determine the development of its target muscle.