Multi-component behavioral intervention to promote health protective behaviors in childhood cancer survivors: the protect study.

BACKGROUND: Improved cure rates for childhood cancer have produced a growing population of survivors at risk for late toxicities of chemotherapy and radiation therapy. Healthy behaviors can modify these risks. We initiated a controlled prospective trial to determine if a multi-component behavioral intervention could induce change in childhood cancer survivors' health knowledge, health perceptions, and practice of health-protective behaviors. PROCEDURE: Adolescent cancer survivors attending a long-term follow-up clinic were randomized to receive standard follow-up care or standard care plus the educational intervention. Baseline measures were obtained at randomization (T(0)) and repeated 1 year (T(1)) later during the survivors' annual check-up. RESULTS: Of 272 patients enrolled and randomized, 251 are evaluable at both time points. Treatment and control groups were similar in regards to diagnosis, gender, race, and age. The change in outcome measures over the year (T(1)-T(0)) was not significantly different between the two groups as assessed by a two-sample pooled t test. However, additional exploratory analyses indicated a significant gender difference in knowledge with female survivors in the intervention group having higher scores. In addition, patients who choose certain individual health goals, such as breast/testicular self-examination, showed improved practice of the health behavior. In addition, in a very exploratory analysis, a gender difference in response to the intervention was noted, with females exhibiting a greater improvement in knowledge scores than did males. CONCLUSIONS: Although the multi-behavioral educational intervention did not induce change in health knowledge, perceptions, and behaviors of childhood cancer survivors for the treatment group as a whole, gender differences and specific health goal differences were found. These findings suggest that future interventions should be tailored to reflect gender differences and the nature of the health goal under assessment.

Health status and health-related quality of life in long-term adult survivors of pediatric solid tumors.

We have examined the influence of selected factors (gender, marital status, socio-economic status, co-morbid conditions, access to medical care, age at diagnosis, intensity of therapy and time since diagnosis) on subsequent health status and health-related quality of life (HRQL) of long-term survivors of pediatric solid tumors. Two hundred and twenty individuals who had survived a pediatric solid tumor 15 years or longer completed telephone and written assessments of their current status. Health status was assessed using the Late Effects of Normal Tissues toxicity scale. HRQL was investigated using the Ferrans and Powers Quality of Life Index-Cancer (QLIC) and the EORTC Quality of Life Questionnaire C30 (QLQ-C30). Results indicated that health status and HRQL were better in survivors treated with low-intensity therapy. One hundred and thirty respondents (59.1%) reported at least 1 serious toxicity. Dyspnea and fatigue were commonly reported in survivors of Hodgkin's disease. Correlational analyses showed that predictors of health status included socio-economic status, marital status and the presence of co-morbid factors. Mean HRQL scores for the 4 domains of the Ferrans and Powers QLIC and the functional scales of the EORTC QLQ-C30 indicated that most of the survivors were experiencing moderately good to excellent HRQL. One-third of survivors reported that their history of cancer had an adverse impact on their current financial status. Prediction models constructed for 3 of the domains from the 2 HRQL instruments are presented (health and functioning, global HRQL and financial impact). Within these 3 models, consistent predictors of HRQL outcomes included health status, presence of dyspnea or pain, marital status and socio-economic status.

Feasibility of implementing health promotion interventions to improve health-related quality of life.

Survivors of childhood cancer are a growing and vulnerable population. Cure rates for pediatric cancers now exceed 60% and, by the year 2000, an estimated 1 of every 1,000 young adults will be a cancer survivor. Because this population is at increased risk for late medical and neoplastic complications that impact adversely on health-related quality of life, it is important to investigate methods to promote risk reduction by motivating survivors to practice health-promoting behaviors. With this background, we initiated a prospective, randomized, controlled feasibility study in which survivors attending a long-term follow-up clinic were randomized to receive standard care or standard care plus an educational intervention. Our objectives were to determine if the intervention would improve the survivors' knowledge about their cancer treatment and risks of late effects and increase their practice of health-protective behaviors. Since July 1995, 272 of 318 families (86%) approached about the study agreed to participate. Of these, 266 are evaluable for assessment of baseline knowledge and health behaviors. Demographic features, baseline knowledge, health perceptions and health behaviors did not differ among randomized groups. Assessment of the intervention's efficacy at changing health behaviors of survivors randomized to the intervention group will be available when the 1-year follow-up evaluations are completed for the study cohort. Our preliminary experience with this pilot study supports the feasibility of educational intervention research in a specialty clinic dedicated to monitoring long-term childhood cancer survivors. Int. J. Cancer Suppl. 12:138-142, 1999.

Patient satisfaction after limb-sparing surgery and amputation for pediatric malignant bone tumors.

We surveyed 65 patients age 13 years or older who had been treated for malignant bone tumors and were in remission at least 1 year after limb-sparing surgery (LS) or amputation (AMP) to assess general satisfaction with the surgical outcome and its impact on various areas of functioning. Of 130 eligible patients, 65 responded (61 treated for osteosarcoma, 3 for Ewing's sarcoma, and 1 for mesenchymoma). The median current age of the cohort was 25.8 years (range, 14.2 to 47.5 years). The median time from surgery was 14.2 years (range, 4.0 to 30.4 years) for the AMP group, and 5.5 years (range, 2.0 to 13.8 years) for the LS patients. Questionnaire responses of patients treated with AMP compared to those who had LS surgery showed no significant differences in the impact of the surgical procedure on educational and occupational status, functional limitations, pain intensity and degree of pain interference, emotional distress, interpersonal/social interactions and self-image, rehabilitation experience, and overall satisfaction with the surgical procedure. Functional limitation was significantly related to pain interference, as well as emotional distress, self-image, and interpersonal difficulties for the entire cohort. Our findings highlight procedure-related advantages and difficulties that may potentially enhance decision making regarding the selection of the surgical procedure for individual patients with malignant bone tumors of an extremity.

Orbital development in long-term survivors of retinoblastoma.

PURPOSE: To determine the effects of enucleation, irradiation, and age at diagnosis on bony orbital growth in long-term survivors of retinoblastoma using measurements based on computed tomographic (CT) imaging. PATIENTS AND METHODS: We used CT obtained at a median age of 13 years to measure orbital volume and configuration in 54 patients who had been treated for retinoblastoma a minimum of 5 years previously. RESULTS: Enucleation and high-dose orbital irradiation (> 35 Gy) both independently adversely affected orbital development (P = .014 and P = .022, respectively). Orbital volume differences for children treated when < or = 1 year old were no greater than those for children treated when older than 1 year of age. In children treated for bilateral retinoblastoma, the impact of enucleation on orbital development was not statistically different from that of irradiation (P = .13). Small implants (12 to 14 mm in diameter) were more commonly associated with smaller orbital volumes. Migration of orbital implants was associated with the smaller orbital sphere size in children < or = 1 year of age (P < .035). CONCLUSION: Treatment for retinoblastoma compromises orbital development. Resulting orbital asymmetry seems to be at least partially related to the size of the implant. Detailed imaging-based measurements of orbital volume and configuration may aid the planning for cosmetic and reconstructive surgery in those who develop orbital asymmetry.

Ultrasonography for thyroid screening after head and neck irradiation in childhood cancer survivors.

We prospectively used ultrasonography to detect thyroid abnormalities in 96 long-term survivors of childhood cancer, who received head and neck radiation therapy at a median age of 8.9 years. The median time interval since irradiation was 10.8 years (range 5.6-22.8 years). Most survivors of leukemia received 24 Gy cranial irradiation for central nervous system prophylaxis; patients with solid tumors received between 20 and 66 Gy (median 37.5 Gy). The total evaluation included clinical history, physical examination, thyroid function tests, and thyroid ultrasonography; radionuclide scans were performed in patients whose abnormalities persisted on subsequent ultrasound exams. Clinical history and physical examination revealed thyroid abnormalities in 14 patients (15%), but ultrasound detected abnormalities in 42 patients (44%). These findings included inhomogeneity (n = 29), cysts (n = 15), and nodules (n = 22) and occurred in nearly half of patients treated with 15 Gy or more directly to the thyroid gland. Radionuclide scans confirmed the presence of thyroid nodules in 13 of 15 patients with ultrasonographic evidence of nodules. Six patients had thyroid neoplasia, including one case of papillary carcinoma. All patients with neoplasia had nodules demonstrated on ultrasonography. Our experience suggests that in childhood cancer survivors, ultrasonography is a sensitive, affordable, and noninvasive means of detecting subtle parenchymal abnormalities. We recommend thyroid ultrasonography for childhood cancer survivors who received head and neck irradiation. A baseline study should be obtained within 1 year of completion of therapy. The frequency of subsequent examinations should be based on the radiation dose and the patient's age at the time of irradiation.

The experience of South American mothers who have a child being treated for malignancy in the United States.

This phenomenological study examined the experience of South American mothers who brought their children to the United States for cancer treatment. Five mothers were interviewed twice about their subjective experiences. Data were analyzed using Colaizzi's method of phenomenology. Thirty-two significant statements were grouped into eight themes. The South American mothers brought their children to the United States in hopes of finding effective treatment, illustrating the major theme of our findings that no effort or sacrifice was too great to save their children's lives. The diagnosis of cancer had an overwhelming impact on the child and the family. This was made worse by the uncertainty of treatment outcome. Although the decision to come disrupted family life and caused economic and cultural hardship, it was uniformly believed to have been the right decision. The greatest challenges experienced by the mothers were language difficulties and the constant preoccupation with the child's illness. Through faith and a variety of coping strategies, these South American mothers succeeded in adapting. They transcended life disruption and focused on the critical goal of restoring their child's health. Central to their experience is that everything humanly possible be done to preserve the life of their child.

Radiation-induced bone abnormalities after bone marrow transplantation for childhood leukemia.

PURPOSE: To identify bone abnormalities related to total-body irradiation (TBI) in long-term survivors of bone marrow transplantation (BMT) for childhood leukemia. MATERIALS AND METHODS: The authors obtained skeletal surveys of 10 survivors of childhood leukemia, ages 5-27 years, who had undergone BMT 7-9 years previously. Pretransplantation "conditioning" regimens were composed of chemotherapy and TBI in doses of 12 or 14.4 Gy. RESULTS: Of the six survivors who received TBI before age 8 years, five had osteochondromas and three had metaphyseal growth abnormalities. One also had slipped femoral capital epiphysis. Findings in the four remaining patients, who received TBI at ages 12-19 years, were less severe and less clearly related to TBI (mild scoliosis in two cases, avascular necrosis of the femoral condyles in one, and a femoral enchondroma in one). CONCLUSIONS: Skeletal abnormalities, previously recognized as sequelae of local external-beam irradiation in children, may occur in long-term survivors of BMT who have received TBI. Younger patients appear to be at the greatest risk.

Skeletal scintigraphy in patients with bilateral retinoblastoma.

One hundred-seventeen radionuclide bone scans were performed on 46 patients with bilateral retinoblastoma between diagnosis and 19 years from diagnosis for the purpose of detecting skeletal metastases or other malignant neoplasms of bone that might develop in this group of patients at high risk for a second malignancy. Only one child, who had been symptomatic for 1.5 years, had a scan positive for metastasis at diagnosis. Scans in three additional children became positive (in one after the development of metastatic disease involving bone and soft tissue but not bone marrow 2 years after the diagnosis of retinoblastoma, and in two others after the development of osteosarcoma at 10.5 and 16 years from the diagnosis of retinoblastoma). Our data indicate that bone scans should not remain as part of the initial staging of patients with bilateral retinoblastoma unless there is clinical or pathologic evidence of extraocular disease at diagnosis. The performance of skeletal scintigraphy also is not warranted, with the expectation of diagnosing a second malignant neoplasm (namely osteosarcoma).

The use of bone marrow aspirations and lumbar punctures at the time of diagnosis of retinoblastoma.

Lumbar punctures (n = 115) and bone marrow aspirations (n = 114) were performed as part of the routine initial diagnostic evaluation of 115 children with retinoblastoma. Three spinal fluid examinations were positive for tumor cells, and bone marrow smears of three children demonstrated clumps of tumor cells. Five of the six positive studies were in patients with stage IV (extraglobar) disease. These results show that demonstrable CSF or bone marrow involvement is so infrequent an event at diagnosis in patients without symptoms, signs, or histologic evidence of tumor dissemination (stages I-II) as to support a recommendation that these studies need not be performed routinely in such patients. If, after enucleation, there is evidence of extraglobar extension, or if patients have symptoms or signs of CNS or systemic spread (stages III or IV), both procedures should be performed to accurately stage disease and provide baseline measurements of tumor involvement for monitoring of response to chemotherapy and/or irradiation. These results have importance in terms of justification of invasive work-up of most (greater than 85%) affected children, and cost containment.

Malignancy in the neonate.

From January 1962 to July 1988, 34 infants less than 29 days of age who had cancer were seen at St. Jude Children's Research Hospital (SJCRH). The malignancies in this group consisted of 19 neuroblastomas, 6 leukemias, 3 retinoblastomas, 2 Wilms' tumors, 2 melanomas, and 2 teratomas. Twenty-three patients (68%) are alive and free of disease 2 months to 24 years after diagnosis. We reviewed the presentation and initial symptoms, pathology reports, patient population, associated anomalies, potential genetic influences, and possible perinatal factors. The most common initial symptom was an enlarging abdomen or abdominal mass. Pathological findings were occasionally difficult to interpret; five additional infants who were referred to us did not have malignancies. There was no increased incidence of associated anomalies or perinatal insults. The only genetic factor was retinoblastoma in one parent of each infant diagnosed as having retinoblastoma. The possible etiology of neonatal tumors is discussed.

Phase I clinical and pharmacokinetic study of bisantrene in refractory pediatric solid tumors.

Fourteen patients with pediatric malignant solid tumors, median age 15 years, received 22 courses of bisantrene in a Phase I study. Dosage escalations ranged from 10 to 120 mg/m2 daily for 5 consecutive days. Toxicity included myelosuppression and phlebitis. A sensitive (detection limit of 2 ng/ml) and specific HPLC method was developed to quantitate bisantrene in patient's plasma and urine. Peak plasma concentrations at the end of 60 minute infusions ranged from 568 ng/ml at 10 mg/m2 to 6800 ng/ml at the 100 mg/m2 dosage. The elimination half life (T 1/2 beta) averaged about 10 hours but increased to 20 hours in a patient with liver disease. Only 2.4 - 10% of the bisantrene dose was eliminated in the urine suggesting that the liver may be the major route of elimination for this antineoplastic anthracene derivative.

Treatment of unresectable or metastatic osteosarcoma with cisplatin or cisplatin-doxorubicin.

Responses and toxicity after treatment with cisplatin and cisplatin-doxorubicin were compared in two groups of patients with unresectable or metastatic osteosarcoma. Complete or partial responses developed in 3 of 18 individuals treated with cisplatin, and in 5 of 19 after the two-drug combination. Hematologic and gastrointestinal complications were more frequent and severe in patients who received both agents. The combined use of cisplatin and doxorubicin is justified for patients with unresectable or metastatic osteosarcoma at diagnosis because of the potential therapeutic benefits for these individuals.

The use of chemotherapy for extraocular retinoblastoma.

Among the 114 children with retinoblastoma seen at St. Jude Children's Research Hospital 1962-1984, 11 have received treatment with chemotherapy for measurable extraocular disease which was present at diagnosis (seven patients) or developed later during the subsequent course of their disease (four patients). Metastatic disease involved the brain and spinal fluid of four persons, the orbit of five, the bone marrow of five, lymph nodes of four, and soft tissues of three individuals at the time of their treatments. Single agents or combinations were used. Two patients with orbital extension of primary retinoblastoma developed complete responses following chemotherapy and subsequently received orbital irradiation, and have had long-term disease-free survival. Additional responses developed in patients who received vincristine, cyclophosphamide, adriamycin, cisplatin, VM-26, and ifosfamide, singly or in combination. With future identification of effective chemotherapy, new studies may be focused upon patients with localized disease to reduce radiation dosage or the need for immediate surgical resection of all involved eyes.

Cisplatin and doxorubicin for locally recurrent and metastatic childhood rhabdomyosarcoma.

Five pediatric subjects, each of whom had been treated with multiple agents including doxorubicin, received cisplatin and doxorubicin following the development of locally recurrent or metastatic rhabdomyosarcoma. Although there was no definite evidence that the tumor of these individuals was resistant to doxorubicin, tumor responses developed in 3 of 5 patients. Additional trials of this combination in similar patients with primary or recurrent metastatic rhabdomyosarcoma are indicated.

The effect of prior cisplatin therapy on the pharmacokinetics of high-dose methotrexate.

The pharmacokinetics of high-dose methotrexate (MTX, 5-15 g/m2) were evaluated in 11 children and adolescents who had previously received two to eight doses of cisplatin (90 mg/m2) in the treatment of malignant solid tumors. The half-life for disappearance of MTX from serum during the first 24 hours after infusion was determined from serum samples obtained at the end of a six-hour infusion and six, 12, and 24 hours after infusion. These values were compared to a mean half-life of 2.83 (+/- 0.34) hours following 489 courses administered to 71 patients who had not received cisplatin. Stepwise multiple linear regression analysis of patient variables revealed cumulative cisplatin dosage and time from last cisplatin dose as the best predictors of MTX half-life (r2 = 65.4%, p less than 0.001). The best predictors of 24-hour serum concentration were cumulative cisplatin dosage and MTX dosage (r2 = 54.2%, p less than 0.001) in the multiple linear regression model. Patients with delayed MTX clearance received additional leucovorin and experienced no severe toxicity. Patients receiving up to 270 mg/m2 of cisplatin appear to have minimal increases in MTX half-life, while the likelihood of delayed clearance increases in patients who have received 360 mg/m2 or more of cisplatin. All patients who have previously received cisplatin should be treated cautiously with high-dose MTX and prospective pharmacokinetic monitoring should be routinely performed.

Fatal congestive heart failure following mitoxantrone treatment in two children previously treated with doxorubicin and cisplatin.

Two children, who had received chemotherapy with doxorubicin and cisplatin for disseminated chondrosarcoma and recurrent rhabdomyosarcoma, developed congestive heart failure following treatment with mitoxantrone (DHAD); the total doses of DHAD were 128 and 90 mg/m2, respectively. The patient with chondrosarcoma had relief of his cardiac symptoms with digitalis and furosemide. The patient with rhabdomyosarcoma, whose tumor responded following treatment with DHAD, died 2 weeks after development of congestive heart failure. For patients who have received prior treatment with potentially cardiotoxic agents, administration of DHAD should be followed by careful monitoring of cardiac function.