PubMed Health⌕ Search

Biomedical subjects

E I Thompson

Publications and source records attributed to E I Thompson.

At least 19 recordsLinked to original sources

Increased mortality after successful treatment for Hodgkin's disease.

PURPOSE: To determine the impact of treatment toxicity on long-term survival in pediatric Hodgkin's disease. PATIENTS AND METHODS: We studied late events in 387 patients treated for pediatric Hodgkin's disease on four consecutive clinical trials at St Jude Children's Research Hospital from 1968 to 1990. Relative risks, actuarial risks, and absolute excess risks for cause-specific deaths were calculated. RESULTS: As of April 1997, 316 (82%) of patients were alive, with a median follow-up of 15.1 (range, 2.9 to 28.6) years. In this cohort, which represented 5,623 person-years of follow-up, 71 fatal events resulted from Hodgkin's disease (n=36), second malignancies (n=14), infections (n=7), accidents (n=7), cardiac disease (n=6), and asphyxiation (n=1). The 5-year estimated event-free survival (EFS) for the entire cohort was 79.6%+/-2.1 %, which declined to 63.1%+/-4.4% by 20 years. Cumulative incidences of cause-specific deaths at 25 years were 9.8%+/-1.6% for Hodgkin's disease, 8.1%+/-2.6% for second malignancy, 4.0%+/-1.8% for cardiac disease, 3.9%+/-1.5% for infection, and 2.1%+/-0.8% for accidents. Standardized incidence ratios showed excess risk for all second malignancies (12; 95% confidence interval [CI], 8 to 17), acute myeloid leukemia (81; 95% CI, 16 to 237), solid tumors (11; 95% CI, 7 to 16), and breast cancer (33; 95% CI, 12 to 72). Standardized mortality ratios also showed excess mortality from cardiac disease (22; 95% CI, 8 to 48) and infection (18; 95% CI, 7 to 38). CONCLUSION: Compared with age- and sex-matched control populations, survivors of pediatric Hodgkin's disease who were treated before 1990 face an increased risk of early mortality related to second cancers, cardiac disease, and infection.

Adolescent↗

Serial pulmonary function studies in children treated for newly diagnosed Hodgkin's disease with mantle radiotherapy plus cycles of cyclophosphamide, vincristine, and procarbazine alternating with cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine.

BACKGROUND: The pulmonary toxicity of bleomycin-containing chemotherapy combined with mantle radiotherapy in children treated for Hodgkin's disease was longitudinally assessed. METHODS: The results of serial pulmonary function studies in 37 children, newly diagnosed and treated at St. Jude Children's Research Hospital between September 23, 1983, and June 30, 1988, with cyclophosphamide, vincristine, and procarbazine (COP) alternating with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) plus low dose mantle radiotherapy are analyzed. All patients had pulmonary function studies at least before the first bleomycin dose, after completion of radiotherapy, and serially upon discontinuation of therapy. Bleomycin therapy was withheld whenever measured carbon monoxide diffusing capacity was less than 50% of the predicted value. RESULTS: Vital capacity, diffusing capacity, and diffusing capacity per unit of alveolar volume declined during the first 6 months of therapy but improved there after. At 2 years postdiagnosis, diffusing capacity per unit of alveolar volume remained significantly reduced. Only one patient was symptomatic at the 2-year point. The survival rate of these patients was 95% at a median follow up of 93 months. CONCLUSION: If bleomycin is with held when diffusing capacity is diminished to 50% predicted, clinical compromise of pulmonary function appears to be minimal in pediatric patients receiving alternating cycles of COP/ ABVD in combination with low-dose mantle radiotherapy. Survival was excellent, even with reduction of the total bleomycin dose.

Adolescent↗

Vincristine neuropathy in type I and type II Charcot-Marie-Tooth disease (hereditary motor sensory neuropathy).

A patient with Ewing's sarcoma and demyelinating type Charcot-Marie-Tooth disease (CMT) developed severe neuropathy after receiving a total vincristine dose of 6 mg. Recovery was slow and incomplete. A second patient with axonal type CMT developed moderate neuropathy but tolerated extended vincristine administration and recovered quickly. Possible underlying neuropathy should be excluded before vincristine treatment is begun by careful examination including inspection of the feet, followed by electrophysiologic studies as indicated. In demyelinating CMT, vincristine should be avoided; in axonal form cautious use may be considered.

Adolescent↗

Health-related behaviors of survivors of childhood cancer.

The health-related beliefs and behaviors of long-term survivors of childhood cancer are important because of vulnerability to adverse late effects from their primary malignancy and its therapy. A health behavior survey was completed by 110 parents of long-term survivors ranging in age from 11-17 years, and by 40 adult long-term survivors of childhood cancer ranging in age from 18-29 years. The survey included questions on the former patient's frequency of alcohol and tobacco use, as well as diet, exercise, sleep, dental, and seatbelt habits. The reported prevalence of tobacco and alcohol use was less than 10% among those less than 18 years old. Among the adults, tobacco (17.5%) and alcohol (72.5%) use was greater, but problem drinking was infrequently reported. In order to assess their perceived vulnerability, we asked the parents and the young adult patients to rate the strength of their belief that it is more important for the patient to keep healthy compared to most other children or young adults. Contrary to our expectation, demographic factors such as the patient's gender, socioeconomic level, or time elapsed since completion of therapy exerted minimal influence on their responses. Over 80% of parents and 60% of young adult survivors believed that it was more important for the former patient to remain healthy compared to most other people. However, this shared belief in increased vulnerability was inconsistently expressed in the patient's health behaviors. These results suggest that specific changes are needed in the health assessment and education of long-term survivors of childhood cancer.

Adolescent↗

Chest wall resection for Ewing's sarcoma of the rib: an unnecessary procedure. 1988. Updated in 1995.

Approximately 10% of all cases of Ewing's sarcoma arise from a rib. Conventional management has included chest wall resection (3 or more ribs) and radiation therapy. These forms of therapy have led to complications such as scoliosis and local deformity. The addition of radiation therapy can result in damage to the lung and adjacent viscera and also potentiate pulmonary restrictive disease. Between 1971 and 1978, 9 patients were treated with surgery, radiation therapy, and combination chemotherapy (three- or four-drug regimen). Only 2 patients (22%) survive. Since 1979, 14 patients were entered into a new protocol consisting of sequential induction chemotherapy, followed by delayed surgical resection whenever feasible. Three patients had complete resection of their primary lesion at onset. Initially, 7 patients had either biopsy (N = 4) or incomplete chest wall resection N = 3). All 4 patients with biopsy only at diagnosis had excellent responses to induction chemotherapy, allowing delayed resection of the involved rib without chest wall resection. Overall, 12 of 14 patients (86%) treated since 1979 survive, with only 2 receiving radiation therapy for residual disease in the primary rib site.

Bone Neoplasms↗

Subsequent malignancies in children and adolescents after treatment for Hodgkin's disease.

PURPOSE: We assessed the cumulative risk of malignancies following treatment for Hodgkin's disease in childhood and adolescence and investigated related patient and treatment characteristics. PATIENTS AND METHODS: Medical records of 499 Hodgkin's disease patients treated between 1962 and 1993 were reviewed. There were 385 adolescents (> or = 10 years of age at diagnosis) and 114 preadolescents (< 10 years). Most patients (n = 346) were treated with radiation plus multiagent chemotherapy, while 30 received only chemotherapy and 123 only radiation therapy. Radiation doses ranged from 20 to 42 Gy. RESULTS: At a median follow-up duration of 9 years (range, 0.1 to 27.4), 25 patients have had second malignancies: 19 solid tumors, four acute nonlymphoblastic leukemias (ANLLs), 1 non-Hodgkin's lymphoma (NHL), and one chronic myeloid leukemia (CML). Three patients have had a third malignancy. The estimated cumulative risk of second malignancies increased from 1.5% at 5 years to 7.7% at 15 years. All but two of the patients with second malignancies were > or = 10 years of age at initial diagnosis, which reflects the higher risk among patients treated for Hodgkin's disease as adolescents (P = .01). Second malignancies were more common among female patients (P = .0002), even when those breast cancer were excluded (P = .007), and in those treated for recurrent Hodgkin's disease (P = .02). Patients with ANLL/NHL were older at diagnosis of Hodgkin's disease than those with solid tumors, (median age, 18.3 v 13.8 years; P = .04). There was no difference between groups treated with radiation therapy alone, chemotherapy alone, or radiation plus multiagent chemotherapy. CONCLUSION: Adolescents treated for Hodgkin's disease are at greater at risk of second malignancies than younger patients. Overall, adolescent females treated for recurrent Hodgkin's disease appear to be at greatest risk, while preadolescents appear to be protected from this late complication.

Adolescent↗

A phase I study of ifosfamide with Mesna given daily for 3 consecutive days to children with malignant solid tumors.

BACKGROUND: The authors conducted a Phase I dose escalation trial of ifosfamide given daily for 3 consecutive days to 29 children with malignant solid tumors. Twenty-eight of these children had received prior chemotherapy. METHODS: Patients were assigned to dosage cohorts separately on the basis of prior exposure to the platinum alkylating agents cisplatin or carboplatin (n = 20) or the absence of such exposure (n = 9). At least three patients in each category were treated at a starting dosage of 2133 mg/m2/d for 3 days. This dosage represented 80% of the total dose delivered in the prior study of ifosfamide given daily over 5 days with dosage escalation of 20% in subsequent cohorts. RESULTS: Myelosuppression was dose-limiting at the second dosage level (2560 mg/m2/d) for patients previously treated with platinum and at the third dosage level (3072 mg/m2/d) for those not previously treated with platinum. Dose-limiting neurotoxicity was seen at 2560 mg/m2/d for the former group, but was not encountered in the latter group. CONCLUSIONS: Delivery of ifosfamide daily for 3 days is feasible and safe at recommended dosages of 2133 mg/m2/d for children with prior exposure to platinum and 3000 mg/m2/d for those without prior exposure.

Adolescent↗

Treatment of childhood germ cell tumors. Review of the St. Jude experience from 1979 to 1988.

BACKGROUND: The outlook for patients with germ cell tumors was poor before the advent of effective chemotherapy. The authors assessed the outcome of treatment with multiagent chemotherapy (with or without radiation therapy) in children treated for germ cell tumors at St. Jude Children's Research Hospital (SJCRH). METHODS: Sixty children with germ cell tumors were treated between January 1979 and June 1988. Postsurgical treatment was based on tumor site, stage, and histology. Most patients received chemotherapy with vincristine, actinomycin-D, and cyclophosphamide (VAC), or a modified Einhorn regimen (cisplatin, bleomycin, and vinblastine [PVB]); in the absence of response to initial therapy, patients received alternating courses of VAC and PVB (VAC/PVB regimen). Exceptions were patients with Stage I testicular tumors (observation only) and ovarian germinomas (Stage I tumors measuring less than 10 cm, observation only; tumors larger than 10 cm or Stage II-III disease, radiation only; and Stage IV disease, VAC plus radiation). RESULTS: The estimated 5-year survival is 100% for patients with Stage I disease (n = 18), 87% for patients with Stage II (n = 8), 72% for Stage III (n = 25), and 56% for Stage IV (n = 9). Patients with testicular tumors of any stage or with Stage I-II ovarian tumors had 100% 5-year survival. Extragonadal tumors responded poorly to VAC alone with recurrent or progressive disease in eight of nine patients. Treatment for those tumors was changed to alternating courses of VAC and PVB, which failed in only one of seven patients. Nine of 19 patients with advanced ovarian tumors had disease recurrence with VAC; these patients then received PVB, which was effective in four cases. CONCLUSIONS: For patients with advanced germ cell cancers, intensification of therapy or the development of new approaches is necessary. In contrast, future trials in children with limited stage should focus on reducing acute and long-term toxicities.

Adolescent↗

Escalating sequential high-dose carboplatin and etoposide with autologous marrow support in children with relapsed solid tumors.

Thirty patients with relapsed pediatric solid tumors received high-dose carboplatin and etoposide with autologous marrow support in a dose-escalation trial. These patients had received extensive prior treatment, which included both cisplatin and etoposide in 25 cases. Six patient cohorts received carboplatin in doses of 1200-2100 mg/m2 and etoposide in doses of 960-1500 mg/m2. All courses were associated with severe neutropenia and thrombocytopenia. The median times from bone marrow infusion to granulocyte recovery (> 0.5 x 10(9)/l) and platelet recovery (> 50 x 10(9)/l) were 33 and 28 days, respectively, with similar findings for all dosage levels. The frequency of non-hematologic toxicities was generally low, although hyponatremia (Na+ < 129 mEq/l) was seen in one-third of the courses. Hepatoxicity was dose-limiting and was significantly associated with the cumulative prior cisplatin dose (p = 0.006). There were four toxic deaths (CNS hemorrhage, alfa-streptococcal sepsis, Candida sepsis, and enterocolitis). Eleven patients received a second course of therapy; toxicity profiles and times to hematologic recovery were similar for the two courses. Clinical responses were observed at all dosage levels. Eleven of 26 evaluable patients achieved a clinical response (one complete, 10 partial). The majority of responses were in patients with neuroblastoma (six of 16) or Hodgkin's disease (two of three). For phase II clinical trials, we recommend dosages of 2100 mg/m2 of carboplatin and 1500 mg/m2 of etoposide for children with prior cumulative cisplatin exposure < 960 mg/m2. This carboplatin dose represents a three- to four-fold increase over pediatric doses tolerated without bone marrow support.

Adolescent↗

The role of second-look surgery in the management of advanced germ cell malignancies.

The need for second-look surgery after chemotherapy in children with advanced germ cell tumors is controversial, particularly when levels of the tumor markers alpha-fetoprotein (AFP) or beta-human chorionic gonadotropin (beta HCG) are elevated at diagnosis. The authors evaluated the outcome of second-look surgery in relationship to tumor marker status in 27 patients with Stage III to IV disease who had completed four courses of chemotherapy. Markers were elevated at diagnosis in 19 patients. After chemotherapy, markers normalized in 12 of these patients. Second-look surgery confirmed complete response (CR) in these 12 patients, two of whom had residual masses on computed tomography (CT) scan (mature teratoma and necrotic tumor). The AFP decreased but did not normalize in seven patients; five had residual disease at second look and the other two later developed measurable disease. Of the eight patients with normal AFP at diagnosis, second look confirmed clinical CR in four. The other four patients had CT evidence of residual masses: surgery showed necrotic tissue in two cases, mature glial elements in one, and mature teratoma with glial elements in one. Thus second-look surgery added no information for treatment planning in children with elevated tumor markers at diagnosis and might best be reserved for patients without tumor markers at diagnosis and residual masses on CT scan, and those with persistent elevation of tumor markers and potentially resectable residual disease. Because of the possibility of small amount of residual tumor, second-look surgery may also be useful in patients whose markers normalize but who have residual masses on CT scans.

Adolescent↗

The survivors of childhood solid tumors.

With the improvement in cancer therapy in recent years, the number of cancer survivors is rapidly increasing. Potential late medical and psychosocial sequelae of cancer therapy are reviewed. A practical guide for the primary health care giver is provided.

Central Nervous System↗

Primary Ewing sarcoma: follow-up with Ga-67 scintigraphy.

While avid accumulation of gallium-67 citrate and technetium-99m methylene diphosphonate (MDP) occurs initially in most cases of primary Ewing sarcoma, uptake after therapy is less well defined. Thirty patients with Ewing sarcoma who underwent Ga-67 and bone scintigraphy at diagnosis, at completion of therapy, and at relapse from 1978 to 1988 were evaluated. All 30 patients showed less primary site Ga-67 activity following therapy. Twenty-three of 28 patients who underwent corresponding bone scintigraphy showed less uptake, but residual activity was usually more intense than with Ga-67. Avid reaccumulation of Ga-67 occurred in four of five patients with primary site relapse, while patients who underwent bone scintigraphy showed less change. It was concluded that a greater decrease in Ga-67 than in Tc-99m MDP uptake often occurs in patients successfully treated for primary Ewing sarcoma. Information obtained at Ga-67 scintigraphy is most likely to be helpful if results of bone scintigraphy remain abnormal or if occult relapse is suspected.

Adolescent↗

A second nonrandom translocation, der(16)t(1;16)(q21;q13), in Ewing sarcoma and peripheral neuroectodermal tumor.

The majority of Ewing sarcomas and peripheral neuroectodermal tumors (PNET) that have been karyotyped contain a specific translocation, t(11;22)(q23;q11). We report here a second nonrandom translocation, der(16)t(1;16)(q21;q13), in 2 of 20 cases of Ewing sarcoma (seven previously unreported) and 2 of 7 cases of PNET (all previously unreported). All cases with this translocation also contained the t(11;22). Comparison of C-banding patterns in tumor and peripheral lymphocyte karyotypes in one case indicated that the likely breakpoints were 1q21 and 16q13. The presence of this translocation in cell lines will enable further investigation of the molecular events important in the pathogenesis of Ewing sarcoma and PNET.

Adolescent↗

Phase I study of 4'-deoxydoxorubicin (esorubicin) in children with malignant solid tumors.

4'-Deoxydoxorubicin was given to 15 patients with drug-resistant pediatric malignant solid tumors with the objectives of determining the maximum tolerated dosage and dose-limiting toxicity. Maximum tolerated dosage was 36 mg/m2 given IV once every 3 weeks. Dose limiting toxicity was myelosuppression, which was severe and prolonged. Therapeutic benefits were not observed for these patients.

Adolescent↗

Ifosfamide in pediatric malignant solid tumors.

Ifosfamide/mesna was given to 97 patients who had malignant solid tumors diagnosed before they were 21 years of age. Patients received 1.6 g/m2 ifosfamide daily x 5, given i.v. over 15 min, followed by 400 mg/m2 i.v. mesna at 15 min and 4 and 6 h after ifosfamide. Responses were noted in patients with osteosarcoma, Ewing's sarcoma, rhabdomyosarcoma and other soft-tissue sarcomas, rhabdoid tumor, neuroblastoma, Wilms' tumor, primitive neuroectodermal tumor, retinoblastoma, germ-cell tumors, and B-cell lymphoma. Toxicity included mild to moderate nausea and vomiting, transient, reversible myelosuppression, transient elevations of serum blood urea nitrogen (BUN) and creatinine and liver enzymes, infections, and self-limiting neurotoxicity characterized by changes in mental status, motor dysfunction, cranial nerve palsy, cerebellar dysfunction, and seizures. Neurotoxic symptoms were generally seen in patients who had previously received cisplatin. Ifosfamide is an important alkylating agent that should be combined with other agents in phase II and III trials. Alternate dose schedules should also be investigated.

Adolescent↗

Two decades of experience with testicular tumors in children at St Jude Children's Research Hospital.

From 1968 to 1988, 24 children and adolescents with malignant testicular tumors were treated at St Jude Children's Research Hospital. Pure yolk sac tumors (YST) were present in 13 cases; 11 patients had other types of nonseminomatous malignant germ cell tumors. Children with localized and totally resectable disease (stage I) were treated by orchiectomy alone; all others also received chemotherapy. Five of ten patients treated before the implementation of a multiagent chemotherapy protocol in 1979 have died. By contrast, all of the 14 patients treated on this protocol are alive. The improved survival during the past decade is attributable to better diagnostic imaging techniques, the availability of serum tumor markers to monitor disease activity, and more effective chemotherapy. Orchiectomy alone is sufficient treatment for patients with clinical stage I disease who show appropriate reductions in tumor marker levels after surgery. Modern platinum-based chemotherapy provides disease control in patients with higher stage disease.

Adolescent↗