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Biomedical subjects

G Levitt

Publications and source records attributed to G Levitt.

17 recordsLinked to original sources

Surveillance for Wilms tumour in at-risk children: pragmatic recommendations for best practice.

BACKGROUND: Most Wilms tumours occur in otherwise healthy children, but a small proportion occur in children with genetic syndromes associated with increased risks of Wilms tumour. Surveillance for Wilms tumour has become widespread, despite a lack of clarity about which children are at increased risk of these tumours and limited evidence of the efficacy of screening or guidance as to how screening should be implemented. METHODS: The available literature was reviewed. RESULTS: The potential risks and benefits of Wilms tumour surveillance are finely balanced and there is no clear evidence that screening reduces mortality or morbidity. Prospective evidence-based data on the efficacy of Wilms tumour screening would be difficult and costly to generate and are unlikely to become available in the foreseeable future. CONCLUSIONS: The following pragmatic recommendations have been formulated for Wilms tumour surveillance in children at risk, based on our review: (1) Surveillance should be offered to children at >5% risk of Wilms tumour. (2) Surveillance should only be offered after review by a clinical geneticist. (3) Surveillance should be carried out by renal ultrasonography every 3-4 months. (4) Surveillance should continue until 5 years of age in all conditions except Beckwith-Wiedemann syndrome, Simpson-Golabi-Behmel syndrome and some familial Wilms tumour pedigrees where it should continue until 7 years. (5) Surveillance can be undertaken at a local centre, but should be carried out by someone with experience in paediatric ultrasonography. (6) Screen-detected lesions should be managed at a specialist centre.

Chromosome Disorders↗

Paediatric rhabdomyosarcoma of the ear and temporal bone.

The objective of the present study was to review the presentation, management, outcome and morbidity of paediatric patients presenting to a single centre with rhabdomyosarcoma of the ear and temporal region. All patients diagnosed with rhabdomyosarcoma of the ear and temporal region between 1980 and 2000 were entered into this retrospective study. Fourteen patients were identified. The median age at presentation was 4.5 years with a mean time of onset of symptoms to diagnosis of 21 weeks. In many patients, the presentation mimicked that of chronic otitis media, delaying diagnosis. Histological subtype was embryonal in 13 patients and alveolar in 1. All patients underwent multimodality treatment. The 5-year disease-free survival rate was 81%. Regional post-treatment morbidity included chronic aural discharge (6/14), facial palsy (8/14), growth disturbance (4/14) and maxillo-facial deformity occurring in four children. From the results, we conclude that these patients should usually present to an ENT surgeon who should keep the diagnosis in mind when dealing with children with chronic otitis media as early diagnosis with referral to a specialist multidisciplinary team will optimize the chance of survival. Discharge, hearing loss and aural polyp, although commonly because of chronic otitis media, should prompt urgent investigation and biopsy, particularly if associated with facial palsy, lymphadenopathy or an obvious mass.

Bone Neoplasms↗

Role of chest computed tomography at diagnosis in the management of Wilms' tumor: a study by the United Kingdom Children's Cancer Study Group.

PURPOSE: This study sought to determine whether the identification of minimal pulmonary metastatic disease by chest computed tomography (CT) performed at diagnosis in patients with Wilms' tumor and normal chest x-rays (CXR) could predict a subgroup of children at increased risk of pulmonary relapse. PATIENTS AND METHODS: A retrospective analysis was carried out of the records of 449 children entered onto the United Kingdom Childrens' Cancer Study Group Second Wilms' Tumor Study between July 1986 and September 1991. The imaging protocol did not stipulate chest CT at diagnosis, but 141 children who had normal frontal and lateral CXRs and a chest CT scan performed at diagnosis were eligible for analysis. After surgery, children with stage I Wilms' tumor received single-agent chemotherapy (vincristine), whereas children with stages II, III, and bilateral Wilms' tumor received combination chemotherapy. Most children with stage III tumors were also treated with abdominal radiotherapy (20 Gy). RESULTS: In 31 patients (22%), pulmonary nodules were visible on chest CT; eight experienced relapse, four (15%) in the lungs. When only stage I patients were analyzed, there was a significant difference between the pulmonary relapse rate of 43% (three of seven) in the CT-positive group and 10% (five of 48) in the CT-negative group (P =.02). Four of eight patients with stage I disease with pulmonary relapse died. CONCLUSION: CT seemed to identify a subgroup of stage I patients who were at increased risk of pulmonary relapse. These children had received only single-agent chemotherapy. A prospective randomized trial is needed to clarify whether these children would benefit from combination chemotherapy.

Antineoplastic Agents, Phytogenic↗

Growth hormone and segmental growth in survivors of head and neck embryonal rhabdomyosarcoma.

AIMS: To assess the impact of treatment for embryonal rhabdomyosarcoma on spinal growth and limb length and examine the response of these parameters to growth hormone (GH) treatment. METHODS: We conducted a retrospective case note review of 17 survivors of head and neck rhabdomyosarcoma followed up at a single institution. All children had been treated with chemotherapy and local radiotherapy. Growth velocity, height, sitting height, and subischial limb length SDS scores were analysed. RESULTS: Growth failure secondary to isolated GH deficiency (GHD) developed in 7/17 patients. GHD occurred at a median (range) of 3.4 (1.3-9.9) years after radiotherapy tumour doses of 46 (40-50) Gy. Growth velocity, height, and subischial limb length SDS were significantly reduced in the GHD group and improved with GH therapy. CONCLUSIONS: GH treatment resulted in a significant improvement in sitting height SDS. We discuss the unexpected improvement in spinal growth in survivors with GHD.

Body Height↗

Cardioprotection.

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Anthracyclines↗

Radiotherapy omitted in the treatment of selected children under 3 years of age with stage III favorable histology Wilms tumor.

BACKGROUND: Current treatment of stage III favorable histology (FH) Wilms tumor is surgery, radiotherapy to residual disease, and "triple" chemotherapy (vincristine, dactinomycin, and doxorubicin) for 12 months. This study tests the hypothesis that some stage III patients, especially very young children with minimal residual abdominal disease, might be successfully treated without radiotherapy, thereby avoiding the adverse late effects associated with radiotherapy. PROCEDURE: From 1984, radiotherapy was omitted from the treatment of 8 carefully selected children who were younger than 3 years of age at diagnosis with stage III Wilms tumor by virtue of microscopic residual disease after surgery and whose lymph nodes were not involved by tumors. They were followed with bimonthly abdominal ultrasound examinations to assess local control. RESULTS: Follow-up is now from 2 to 12 years (median 6 years) and 7 of the 8 children are alive and well with no abdominal recurrence. One child relapsed in the lungs and despite further treatment died of progressive disease. The disease-free survival (DFS) and overall survival (OS) are therefore both 87.5%. CONCLUSIONS: The DFS and OS in this admittedly small sample are consistent with the survival rates for stage III FH Wilms tumor in the first United Kingdom Children's Cancer Study Group (UKCCSG), North American (NWTS), and European (SIOP) Wilms Tumor studies, Larger numbers of patients are needed to determine whether or not this treatment approach is generally applicable, but we conclude that some children in this stage III "substage" may be treated successfully without radiotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

Anthracycline dose in childhood acute lymphoblastic leukemia: issues of early survival versus late cardiotoxicity.

PURPOSE: Late abnormalities of left ventricular (LV) performance occur in most survivors of childhood acute lymphoblastic leukemia (ALL) treated with moderate anthracycline doses. We studied the prevalence of late cardiotoxicity in patients treated with lower anthracycline doses and related this to survival. PATIENTS AND METHODS: Echocardiograms were performed in 50 normal children and 120 relapse-free ALL survivors 6.2 +/- 2.0 years after the end of cumulative daunorubicin doses of 90 mg/m2 (n = 40), 180 mg/m2 (n = 40), or 270 mg/m2 (n = 40) on UKALL X pilot (1982 to 1984) or UKALL X (1985 to 1989) protocols. Age at treatment onset was 4.7 +/- 2.8 years. Cardiac abnormalities were reviewed in light of the UKALL X 5-year disease-free survival rates of 57% (95% confidence interval [CI], 51% to 63%), 61% to 62% (95% CI, 56% to 68%), and 71% (95% CI, 66% to 76%) for the groups that received 90, 180, and 270 mg/m2 of daunorubicin, respectively. RESULTS: ALL survivors had reduced LV fractional shortening (FS) compared with normal (32.3% +/- 4.4% v 35.9% +/- 4.2%, P < .005), which was accounted for by increased LV end-systolic stress (49.4 +/- 13.5 v 42.2 +/- 9.1 g/cm2, P < .001), whereas LV contractility independent of loading conditions was normal for the group as a whole. Of 27 patients (23%) with cardiac abnormalities, 25 (21%) had increased end-systolic stress, whereas only two (2%) had reduced contractility. The proportion with cardiac abnormality was similar in the three dose groups. Anthracycline dose, age at treatment, sex, follow-up duration, growth hormone, pubertal status, hemoglobin level, and total WBC count at presentation were not predictive of increased LV end-systolic stress. CONCLUSION: There was a reduced incidence and severity of cardiac abnormalities with the lower anthracycline dose protocols (90 to 270 mg/m2) studied compared with previous reports in which subjects had received moderate anthracycline doses (approximately 300 to 550 mg/m2). Cumulative anthracycline dose within the range 90 to 270 mg/m2 did not relate to cardiac abnormalities. This suggests that there may be no safe anthracycline dose to avoid late cardiotoxicity, but reinforces the use of the protocol that affords best survival within the dose range studied.

Adolescent↗

Cardiac transplantation in childhood cancer survivors in Great Britain.

The aim of this study was to identify patients treated in Great Britain for childhood cancer and subsequently referred for cardiopulmonary transplantation in order to assess diagnosis, cancer treatment, management and outcome. Computerised record linkage between the National Registry of Childhood Tumours and the national transplant database held and maintained by the United Kingdom Transplant Support Service Authority (UKTSSA) was used to identify patients. Verification and clinical details were then obtained from the oncology and transplant centres. 16 patients were identified from the 31992 cases of childhood malignancy diagnosed in Britain since 1970. These comprised 13 heart transplants, 2 heart/lung transplants and 1 patient who died while on the heart transplantation waiting list. All 14 potential heart transplant patients had cardiomyopathy presumed secondary to anthracycline therapy. The original diagnoses were acute myeloblastic leukaemia (3), Wilms' tumour (4), rhabdomyosarcoma (2) and one each of five different solid tumours. Median age at diagnosis was 44 months (range 4-165 months). Median anthracycline dose was 413 mg/m2 (range 240-680 mg/m2). 13 of the 14 potential cardiac transplantation patients were more than 2 years from end of their cancer treatment before requiring transplantation and the transplantation was performed 2-126 months after onset of cardiac failure at a median age of 163 months. Five year actuarial survival from transplantation was 74%. There was no recurrence of the original malignancy in any of these patients. Both heart/lung patients died, 3 and 11 months after the transplant. These heart transplantation data suggest that, in Britain, survival compares favourably with that of patients whose heart transplant was required for other causes of cardiomyopathy. This indicates that patients successfully treated for childhood cancer should not be excluded from transplant programmes.

Adolescent↗

Clinic audit for long-term survivors of childhood cancer.

Follow up for survivors of childhood cancer is considered essential in order to document any continuing impact on growth, fertility and other systems, as well as provide appropriate care and information to individuals themselves. Appropriate follow up needs to take into account the survivors' own views about reasons for attendance and perceived satisfaction with the services provided. Information was sought from 93 survivors (more than five years from diagnosis) and 68 of their parents regarding current attendance, understanding of the purpose of the clinic and satisfaction, and future preferences. Patients' main reasons for attending were to gain reassurance that they were well and information about the disease. There were some discrepancies between the types of information patients would like from clinic attendance and what they remembered being given. Parents were more positive than patients. Our data suggest that (i) knowledge in survivors is poor and (ii) it may be possible to define a subgroup for whom less frequent follow up is appropriate. A key component of care must involve education of patients, both about their past and the implications for future health.

Adolescent↗

Cardiac function in Wilms' tumor survivors.

PURPOSE: To study late cardiac function in a single diagnostic group (children with Wilms' tumor) with good long-term survival; to compare patients treated with anthracyclines (doxorubicin) with patients treated without anthracyclines and with a normal child/adolescent group; and to examine the risk factors involved in late cardiac dysfunction. PATIENTS AND METHODS: Echocardiographic studies were performed on 97 Wilms' tumor patients treated with anthracyclines (mean cumulative dose, 303 mg/m2) with a mean follow-up time of 7.1 years, on 39 Wilms' tumor patients treated without anthracyclines with a mean follow-up time of 8.9 years, and on 50 normal subjects. Left ventricular (LV) dimensions, end systolic wall stress (a measure of afterload), and load-dependent and -independent measures of contractility were compared between groups. Potential risk factors, including age at diagnosis, follow-up duration, sex, pubertal status, cardiac irradiation, dose-intensity, and cumulative dose of anthracyclines, were studied by multivariate analysis. RESULTS: Twenty-five percent of the anthracycline-treated group showed cardiac abnormalities. All but one of these patients had increased LV afterload. Risk factors for increased afterload were anthracycline cumulative dose (P < .05) and anthracycline dose-intensity (P < .02). Wilms' tumor patients treated without anthracyclines had thickened LV walls compared with normal subjects (P < .05). CONCLUSION: Total dose and dose-intensity of anthracycline were risk factors for increased LV afterload in long-term Wilms' tumor survivors treated on standard protocols. The increase in afterload accounted for reduced LV shortening, whereas contractility was rarely abnormal. The new finding that Wilms' tumor survivors who do not receive anthracyclines have mild LV hypertrophy may provide some protection against anthracycline-induced cardiotoxic effects.

Adolescent↗

Etoposide in relapsed or refractory Wilms' tumor: a phase II study by the French Society of Pediatric Oncology and the United Kingdom Children's Cancer Study Group.

PURPOSE: Despite a high cure rate of approximately 85% in Wilms' tumor by multimodality therapy, to date only four drugs are known to be active against such tumors. There is a clear need for new active drugs. PATIENTS AND METHODS: Thirty-one patients with relapsed or refractory Wilms' tumor from three British and 14 French centers were treated with intravenous (IV) etoposide 200 mg/m2 daily for 5 days. Original stage was I (n = 3), II (n = 7), III (n = 9), IV (n = 10), and V (n = 2). Prior chemotherapy, administered initially or at relapse, included vincristine and dactinomycin in all cases, doxorubicin or epirubicin in 30, and ifosfamide in 20. Sites of relapse or resistant disease were lung in 13, abdomen or pelvis in six, liver in one, and multiple in 11. When entered onto the study, 12 patients were in first relapse, 10 in second relapse, and four in third or more relapse. Five had never obtained a complete remission. All but two (progressing) patients received two courses of etoposide, the second course being administered at day 21. RESULTS: A complete response (CR) was documented in two patients, partial response (PR) in 11, stable disease in 10, and progressive disease (PD) in eight. The duration of response could not be evaluated, because all responding patients were subsequently treated with multimodality therapy. The major toxicities observed were neutropenia and thrombocytopenia, but most patients had been heavily pretreated. No toxic death clearly associated with etoposide was noted. CONCLUSION: It is concluded that etoposide in this schedule is an active agent in Wilms' tumor and should be considered for inclusion in regimens for high-risk patients, such as those with metastatic disease at diagnosis and those who relapse after multiagent chemotherapy.

Adolescent↗