PubMed Health⌕ Search

Biomedical subjects

H B Marsden

Publications and source records attributed to H B Marsden.

At least 19 recordsLinked to original sources
PubMed2004

Long-term population-based risks of second malignant neoplasms after childhood cancer in Britain.

In a population-based, retrospective cohort study of 16 541 3-year survivors of childhood cancer treated in Britain up to the end of 1987, 278 second malignant neoplasms (SMNs) were identified against 39.4 expected giving a standardised incidence ratio (SIR) of 6.2. The overall cumulative risk of an SMN by 25 years from 3-year survival from childhood cancer was 4.2%. Analysis of the cohort of nonretinoblastoma childhood cancers combined revealed a significant decline in SIR of SMN with increasing duration of follow-up. There was a greater risk of developing a SMN, particularly secondary acute myeloid leukaemia, in those diagnosed with childhood cancer from 1980 onwards. However, on multivariate modeling, this was not an independent risk factor. There was significant heterogeneity (P<0.001) in SIR of SMN across different treatment groups, the greatest risk observed in the group exposed to both radiotherapy and chemotherapy. The risks of SMN observed were comparable with those in other population-based studies. While the decline in SIR with duration of follow-up and the small excess numbers of cancers observed over later decades after diagnosis are reassuring, the high excess risk, particularly of leukaemia, associated with recent more intense therapy is of concern.

Acute Disease↗
PubMed2004

Outcome of patients with stage III or inoperable WT treated on the second United Kingdom WT protocol (UKWT2); a United Kingdom Children's Cancer Study Group (UKCCSG) study.

BACKGROUND: The aims of UKWT2 included consolidating the results for stage III patients obtained in UKWT1 and improving the outcome for patients with inoperable tumours by giving vincristine, actinomycin-D and doxorubicin in an intensive schedule (Intensive AVA). PROCEDURE: The second UK WT trial (UKWT2) ran between July 1986 and September 1991 accruing 448 patients. One hundred and six patients were diagnosed and treated for stage III disease. Six had clear cell sarcoma of the kidney (CCSK) and seven had rhabdoid tumours of the kidney (RTK) and are analysed separately. One other patient was excluded from overall analysis. Ninety-two patients were followed for a median of 115 months. Seventy-five received standard chemotherapy and abdominal radiotherapy according to protocol. Seventeen had stage III disease at immediate nephrectomy, but radiotherapy was omitted by physician choice. Thirty-three patients had inoperable disease at diagnosis and received pre-nephrectomy chemotherapy. RESULTS: Overall survival (OS) at 4 years for stage III favourable histology (FH) patients receiving abdominal RT was 83% (CI: 73-89). For children with stage III disease in whom RT was omitted the OS was 82% (CI: 59-97) and for inoperable disease 94% (CI: 78-98). The overall and event-free survival (EFS) of children with stage III CCSK was 100% and was achieved with the majority of patients not receiving radiotherapy (CI: 48-100). Three of seven children with RTK are alive EFS and OS 43% (CI: 10-73). For patients treated by abdominal radiotherapy the overall local control rate was 94.4% (CI: 86.4-98.5*%), 96.7% (CI: 88.5-99.6%) for flank RT and 83.3% (51.6-98.0%) for whole abdominal radiotherapy (WRT). CONCLUSIONS: The outcome for stage III FH disease was similar to that reported for UKWT1 and NWTS-3. The combination of abdominal RT together with 3-drug chemotherapy achieves a high abdominal tumour control rate. Flank RT is probably sufficient for localised tumour rupture. The high cure rates for children in this trial with 'inoperable disease' suggests that treatment should be modified according to their post-chemotherapy stage in order to avoid over-treatment. The high OS for stage III CCSK on this protocol suggests that treatment duration could be curtailed and the role of RT reviewed, though the numbers are small. The prognosis for older children with RTK seems to be better than for younger children although larger studies are required to confirm this.

Adolescent↗
PubMed1997

The need for specialist review of pathology in paediatric cancer.

A retrospective histopathological review of 2104 cases of solid tumour was carried out to assess the variability in diagnosis of childhood cancer. Cases were subject to three independent, concurrent opinions from a national panel of specialist pathologists. The conformity between them was analysed using the percentage of agreement and the kappa statistic (kappa), a measure of the level of agreement beyond that which could occur by chance alone, and weighted kappa (w kappa), which demonstrates the degree of variation between opinions. The major groupings of the Birch-Marsden classification were used within which tumours were assigned for kappa analysis according to the clinical significance of the differential diagnoses. The mean agreement for all tumours together was 90%; kappa = 0.82, w kappa = 0.82. Retinoblastoma achieved the highest kappa value (1.0) and lymphoma the lowest (0.66). Of the cases, 16.5% had their original diagnoses amended and the panel confirmed the original diagnosis of paediatric pathologists in 89% of cases compared with 78% for general pathologists. The varying levels of agreement between experts confirm the difficulty of diagnosis in some tumour types, suggesting justification for specialist review in most diagnoses. Specialist training in paediatric pathology is also recommended.

Child↗
PubMed1996

Radiotherapy, alkylating agents, and risk of bone cancer after childhood cancer.

BACKGROUND: Individuals who had cancer in childhood are at higher risk of developing bone cancer than any other type of second primary cancer. PURPOSE: Using the population-based National Registry of Childhood Tumours in Britain, we investigated the incidence and etiology of second primary bone cancer after childhood cancer in a cohort study and in a case-control study. METHODS: A cohort study of 13,175 3-year survivors of childhood cancer diagnosed in Britain between 1940 and 1983 revealed 55 subsequent bone cancers. A largely nested case-control study comprised 59 case subjects developing second primary bone cancer, and 220 control subjects were selected and matched for sex, type of first cancer, age at first cancer, and interval between diagnosis of first cancer and subsequent bone cancer. Outcome measures were the incidence of bone cancer after childhood cancer, the cumulative dose of radiation received at the site of the second cancer in the case subject and at the corresponding anatomic site in the matched control subjects, and the cumulative dose of alkylating agents and vinca alkaloids received by case and control subjects. RESULTS: The percentage of 3-year survivors developing bone cancer within 20 years did not exceed 0.9%, except following heritable retinoblastoma (7.2%), Ewing's sarcoma (5.4%), and other malignant bone tumors (2.4%). The risk of bone cancer increased substantially with increased cumulative dose of radiation to the bone (P< .001, linear trend). At the highest levels of exposure, however, the risk appeared to decline somewhat (P=.065, nonlinearity). Exposure to less than 10 Gy was at worst, associated with only a small increased relative risk (RR) of bone cancer (RR= 0.7; 95% confidence interval = 0.2-2.2). The risk of bone cancer increased linearly (P= .04, one-tailed test) with increased cumulative dose of alkylating agents. IMPLICATIONS: This population-based study provides grounds for reassurance of the majority of survivors in that their risk of developing bone cancer within 20 years of 3-year survival did not exceed 0.9%. The higher risks found for bone cancer following the other specific rare types of childhood cancer provide a rational basis for surveillance. The RRs reported for bone cancer after specified levels of exposure to radiation should help in making decisions concerning future treatment protocols.

Adolescent↗
PubMed1995

Classification of rhabdomyosarcomas and related sarcomas. Pathologic aspects and proposal for a new classification--an Intergroup Rhabdomyosarcoma Study.

BACKGROUND: There is a need to develop a single prognostically significant classification of rhabdomyosarcomas (RMS) and other related tumors of children, adolescents, and young adults which would be a current guide for their diagnosis, allow valid comparison of outcomes between protocols carried out anywhere in the world, and should enhance recognition of prognostic subsets. METHOD: Sixteen pathologists from eight pathology groups, representing six countries and several cooperative groups, classified by four histopathologic classification schemes 800 representative tumors of the 999 eligible cases treated on Intergroup Rhabdomyosarcoma Study II. Each tumor was classified according to each of the four systems by each of the pathologists. In addition, two independent subsamples of 200 of the 800 patients were reviewed according to the new system, so that 343 distinct patients were reviewed once, and 57 of these twice. RESULTS: A study of the survival rates of all subtypes in the sample of 800 patients led to the formation of a new system. This was tested on two independent subsets of 200 of the original cases and found to be reproducible and predictive of outcome by univariate analysis. A multivariate analysis of the 343 patients classified according to the new system indicated that a survival model including pathologic classification and known prognostic factors of primary site, clinical group, and tumor size was significantly better at predicting survival than a model with only the known prognostic factors. CONCLUSION: This new classification, termed International Classification of Rhabdomyosarcoma (ICR) by the authors, was reproducible and predictive of outcome among patients with differing histologies treated uniformly on the Intergroup Rhabdomyosarcoma II protocols. We believe it should be utilized by all pathologists and cooperative groups to classify rhabdomyosarcomas in order to provide comparability among and within multi-institutional studies.

Adolescent↗
PubMed1995

Results of the United Kingdom Children's Cancer Study Group first Wilms' Tumor Study.

PURPOSE: The first United Kingdom Children's Cancer Study Group (UKCCSG) Wilms' Tumor Trial (UKW1) applied treatment regimens stratified by stage and histology in accordance with National Wilms' Tumor Study (NWTS) criteria, seeking to reduce treatment of low-stage, favorable-histology (FH) tumors without impairing survival and to improve prognosis of stage III and IV (FH) and unfavorable-histology (UH) tumors with more intensive chemotherapy. PATIENTS AND METHODS: Three hundred eighty-four consecutively diagnosed patients with Wilms' tumor were recruited from the 20 UKCCSG centers and Oslo, Norway, between January 1980 and June 1986. The regimen for stage I patients was vincristine (Vcr) only, while stage II patients received Vcr and dactinomycin (Act-D). Stage III patients received three-drug therapy and stage IV and UH patients four-drug regimens. Act-D was given as pulsed doses of 1.5 mg/m2 every 3 or every 6 weeks. No lung irradiation was used in stage IV patients. No randomized comparisons were attempted. End points were survival and event-free survival (EFS). RESULTS: Survival at 6 years in FH patients was 96% for stage I, 93% for stage II, 83% for stage III, 65% for stage IV, and 50% for UH patients of all stages. CONCLUSION: Vcr alone is as effective for stage I FH tumors as the two-drug regimen used in the NWTS and International Society of Pediatric Oncology (SIOP) studies. Fractionation of Act-D is unnecessary. The poorer results for stage IV FH and UH patients compared with the NWTS may be due to treatment differences, such as the use of lung irradiation for stage IV FH patients in NWTS3, and/or to case selection bias.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Agreement among and within groups of pathologists in the classification of rhabdomyosarcoma and related childhood sarcomas. Report of an international study of four pathology classifications.

BACKGROUND: An International Pathology study was conducted to measure the agreement demonstrated among and within groups of pathologists involved in the categorization of childhood rhabdomyosarcoma according to four pathology classifications. Data concerning agreement and survival experience according to patho-new subtypes were used as a basis for selection of a proposed new pathologic classification. METHODS: A random sample of 800 eligible patients was chosen from the Intergroup Rhabdomyosarcoma Study II (IRS-II) and was reviewed by pathologists representing eight institutions. A 20% sample of the 800 patients was then reviewed by the pathologists to determine the level of agreement with their original classification. In each instance the patients were classified according to four pathology systems: the conventional system, the International Society for Pediatric Oncology system (SIOP), the National Cancer Institute (NCI) system, and the cytohistologic system. RESULTS: Among the groups of pathologists, the highest measure of agreement was a Kappa value of K = 0.451 for the conventional system, followed by K = 0.406 for the SIOP system, K = 0.384 for the NCI system, and K = 0.328 for the cytohistologic system. For reproducibility within the groups of pathologists, the highest measure of agreement was K = 0.605 for the conventional system, followed by K = 0.579 for the NCI system, K = 0.573 for the SIOP system, and K = 0.508 for the cytohistologic system. CONCLUSIONS: There was a general similarity between the agreement reached within the modified conventional, STOP, and NCI systems, with the modified conventional system having the highest Kappa values, and thus the highest measure of agreement, both among and within the groups of pathologists. Also, the subtypes of the conventional system demonstrated a highly significant relationship to survival time. Hence, based on criteria of reproducibilty and prognostic significance, the proposed classification will essentially be a modification of the conventional system with elements of the SIOP and NCI systems.

Adolescent↗
PubMed1993

Thirty-year population-based review of childhood renal tumours with an assessment of prognostic features including tumour DNA characteristics.

We have reviewed all paediatric kidney tumours seen in the West Midlands Health Authority Region over a 30-year period. There were 205 cases confirmed after a review of the pathology by three paediatric pathologists. Seven were cases of bone metastasising renal tumour (clear cell sarcoma), 5 were rhabdoid tumours, 2 were renal cell carcinomas, and 13 were mesoblastic nephromas. In 3 cases, it was not possible to define further the histological diagnosis. The remaining 175 cases were considered to be Wilms' tumour (86%), which is equivalent to an incidence of 5.7/10(6)/year. In the cases of Wilms' tumour, there were 91 boys and 84 girls (1.1:1). The majority of patients were Caucasian with only 7% of non-Caucasian origin. At presentation, 78% of the patients were less than 5 years old. All of these patients except 9 had surgery as part of their treatment, 154 children had total nephrectomy, 3 had partial nephrectomy, and 9 had other surgical procedures. The majority also received chemotherapy and radiotherapy. Sex, chemotherapy, and stage all had prognostic significance in univariate analysis. The actuarial survival at 10 years increased from 17% for patients treated in the first decade of the study to 78% for patients treated in the third. DNA characteristics were investigated using flow cytometry in paraffin-embedded material and adequate information was obtained in 73 cases of Wilms' tumour. Only 7 had aneuploid tumours. Univariate survival analysis of these 73 results showed that stage, sex, the percentage of cells in the synthetic phase and the proliferative index from the DNA investigations had predictive value.

Actuarial Analysis↗
PubMed1993

Primitive malignant nonepithelial hepatic tumors in children.

Primary intrahepatic malignant nonepithelial tumors are very rare in children and account for 2% of all malignant mesenchymatous tumors under the age of 15 years. Clinical presentation, radiologic features, and histologic types are not unequivocal. The predominant role of surgery takes place either initially in small localized tumors or later, after initial reductive chemotherapy. In all cases, complete resection is the necessary but not sufficient condition for cure. Additional radiotherapy seems ineffective. High-dose chemotherapy and/or liver transplantation can be proposed for resistant cases. The disease-free survival rate is 37% at 2 years for the whole series.

Adolescent↗
PubMed1992

Epipodophyllotoxins, alkylating agents, and radiation and risk of secondary leukaemia after childhood cancer.

OBJECTIVE: To investigate the incidence and aetiology of secondary leukaemia after childhood cancer in Britain. DESIGN: Cohort study and a case-control study. SETTING: Britain and population based National Register of Childhood Tumours. SUBJECTS: Cohort of 16,422 one year survivors of childhood cancer diagnosed in Britain between 1962 and 1983, among whom 22 secondary leukaemias were observed. A case-control study of 26 secondary leukaemias observed among survivors of childhood cancer diagnosed in Britain between 1940 and 1983; 96 controls were selected matched for sex, type of first cancer, age at first cancer, and interval to diagnosis of secondary leukaemia. MAIN OUTCOME MEASURES: Dose of radiation averaged over patients' active bone marrow and total accumulated dose of epipodophyllotoxins, alkylating agents, vinca alkaloids, antimetabolites, and antibiotics (mg/m2) given for the original cancer. RESULTS: Cumulative risk of secondary leukaemia within the cohort did not exceed 0.5% over the initial five years beyond one year survival, except that after non-Hodgkin's lymphomas 1.4% of patients developed secondary leukaemia. Corresponding figure for patients treated for non-Hodgkin's lymphomas in the early 1980s was 4%. The relative risk of secondary leukaemia increased significantly with exposure to epipodophyllotoxins and dose of radiation averaged over patients' active bone marrow. Ten patients developed leukaemia after having an epipodophyllotoxin-teniposide in nine cases, etoposide in one. Chromosomal translocations involving 11q23 were observed relating to two secondary leukaemias from a total of six for which there were successful cytogenetic studies after administration of an epipodophyllotoxin. CONCLUSIONS: Epipodophyllotoxins acting alone or together with alkylating agents or radiation seem to be involved in secondary leukaemia after childhood cancer.

Alkylating Agents↗
PubMed1991

Congenital mesoblastic nephroma: possible prognostic and management value of assessing DNA content.

The case records and pathology of all children with kidney tumours treated in the West Midlands Health Authority Region (WMHAR) from 1957 to 1986 were reviewed. The histology was reviewed by a panel of three paediatric pathologists. Thirteen (6%) out of 211 cases were considered to have congenital mesoblastic nephroma (CMN). Nine were of the conventional type, three of the atypical cellular type, and one mixed. DNA ploidy was investigated and showed two of the tumours to be aneuploid and nine diploid (tissue was not available in the two other cases). The two aneuploid tumours were of atypical cellular and mixed histology, respectively; the diploid tumours were of the conventional type in eight cases and atypical cellular in one. The atypical cellular type has been reported to behave more aggressively, but the benefit of additional treatment after surgery to prevent recurrence remains unclear. Measurement of DNA content by flow cytometry, together with histological subclassification, may be useful in selecting patients who will benefit from further treatment after surgery.

DNA, Neoplasm↗
PubMed1990

N-myc gene is amplified in alveolar rhabdomyosarcomas (RMS) but not in embryonal RMS.

DNA from 13 (6 alveolar and 7 embryonal) childhood rhabdomyosarcomas (RMS) was examined to determine the incidence and prognostic relevance of N- and c-myc genes. Southern analysis showed 5- to 20-fold amplification of N-myc gene in 4 of 6 alveolar but in none of 7 embryonal RMS (p less than 0.04; Fisher's exact test). The number of children who died with multiple- and single-copy N-myc gene was 4/4 and 5/9 respectively (p greater than 0.05; Chi-squared test). There was no statistically significant correlation between N-myc amplification and age, gender, site, stage or survival time. There was no amplification or gross rearrangement of c-myc in any of the 13 RMS.

Blotting, Southern↗
PubMed1990

Proliferative fascitis in childhood: a case report.

A case of proliferative fascitis in the forearm of a 7-year-old child is presented. The lesion is composed of spindle cells and large bizarre ganglionlike cells in a collagenous matrix with some myxoid areas. The cells contain intracytoplasmic inclusions of collagen. The cytoplasm stains for vimentin, and the cells have ultrastructural features of myofibroblasts. This is the second case reported of proliferative fasciitis occurring in a child, and the importance of distinguishing this lesion from childhood neoplasms with a similar appearance is discussed.

Child↗
PubMed1989

Are germ cell tumors part of the Li-Fraumeni cancer family syndrome?

The occurrence of six cases of germ cell tumors, five testicular and one ovarian, in relatives of children with bone or soft tissue sarcomas is described. It is proposed that germ cell tumors may be an uncommon manifestation of the genetic predisposition to cancer that exists in the Li-Fraumeni cancer family syndrome.

Adult↗
PubMed1989

Histopathological classification of childhood rhabdomyosarcoma: a report from the International Society of Pediatric Oncology pathology panel.

Five hundred thirteen soft tissue tumours of childhood referred to the International Society of Pediatric Oncology (SIOP) Rhabdomyosarcoma study have been reviewed. The period covered was from January 1975 to December 1983. Three hundred thirty-nine neoplasms were regarded as embryonal rhabdomyosarcoma. The histological diagnosis of all referred tumours is given, and a classification of rhabdomyosarcomas developed during the course of the study is described. The relationship between histological subtypes and aspects of clinical behaviour is presented. The classification is thought to be helpful in diagnosis and also in assessment of the likelihood of recurrence and/or metastasis of childhood rhabdomyosarcoma.

Adolescent↗
PubMed1989

Prognostic relevance of DNA content in childhood renal tumours.

The DNA content of paraffin embedded tumour specimens from 100 children with kidney tumours was studied by flow cytometry. Data of adequate quality were obtained from 93 cases comprising 67 Wilms' tumours with a favourable histology (FH), 12 Wilms' tumours with unfavourable histology (UH) (pleomorphic), 8 bone-metastasising renal tumours of childhood (BMRTC) and 6 rhabdoid renal tumours. Only 4.5% FH compared with 75% UH Wilms' were aneuploid (P less than 0.001). Although BMRTC and rhabdoid tumours are associated with poor prognosis, there were no examples of aneuploidy in these tumours. The proliferation index was found to be of no prognostic value. Staging and ploidy were not correlated with each other in any of the various histological types of renal tumours studied.

Child↗