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BACKGROUND AND PROCEDURE: Eighteen years of experience with Burkitt lymphoma (BL), the most common form of childhood cancer in the Ivory Coast, has been reviewed and the epidemiology analyzed. RESULTS: BL is more commonly found in wooded areas than savannahs by a factor of 5:1. Despite good responses to cyclophosphamide-based chemotherapy, chances for survival are often dictated by socioeconomic factors that limit optimal care. CONCLUSIONS: Better public health measures and improved education and socioeconomic conditions are needed if the fruits of earlier and more aggressive therapies are to be gathered.
Mutations in a large number of retinal and retinal pigment epithelium (RPE) expressed genes can lead to the degeneration of photoreceptors and consequently the loss of vision. The genetic and phenotypic heterogeneity of retinal dystrophies poses a complex problem with respect to rational development of therapeutic strategies. Delineation of physiological functions of disease genes and identification of pathways that lead to disease pathogenesis represent essential goals towards developing a systematic and global approach to gene-based treatments. We are interested in identifying cellular pathways that are involved in photoreceptor differentiation, function and degeneration. We are, therefore, generating comprehensive gene expression profiles of retina and RPE of humans and mice using both cDNA- and oligonucleotide-based (Affymetrix) microarrays. Because of the under-representation of retinal/RPE genes in the public databases, we have constructed several unamplified cDNA libraries and produced almost twenty thousand expressed sequence tags (ESTs) that are being printed onto glass slides ('I-Gene' microarrays). In this presentation, we will report the microarray analysis of the rodless (and cone-enhanced) retina from the Nrl-knockout mouse as a paradigm to initiate the identification of cellular pathways involved in photoreceptor differentiation and function.
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In an Easter Cooperative Oncology Group trial, Cytoxan-prednisone (CP) Induction was compared to BCNU-prednisone (BP) in 273 patients with lymphocytic lymphoma. Response rates were comparable, with 21% achieving complete response and 40%, partial response. Patients with a nodular pattern responded better. Maintenance phase comparing cyclic intensive therapy (BCVP) with intermittent chlorambucil revealed the superiority of BCVP as demonstrated by improvement of the quality of response and somewhat longer remissions. The value of the Rappaport classification in the evaluation of lymphoma chemotherapy results is discussed. It is suggested tha NHL be separated into "favorable" and "unfavorable" groups, based on the presence or absence of nodularity and treatment schedules devised accordingly.
This report is a follow-up of the initial group of 39 children with non-Hodgkin's lymphoma treated with the LSA2-L2 protocol as previously reported in Cancer (37:123--134, 1976). The disease-free actuarial survival is 73%. All surviving patients are off therapy and have shown no evidence of recurrence with a median observation time of 70+ months. Their survival times range from 56+ to 88+ months from diagnosis. An analysis of successes and failures is discussed and modifications in the role of radiation therapy and surgery in the multidisciplinary management of children with non-Hodgkin's lymphoma are advocated. The results in the present series indicate that the LSA2-L2 protocol has substantially improved the prognosis for children with non-Hodgkin's lymphoma. We have concluded that age, sex, primary site (perhaps with the exception of primary skeletal), and histology are not of prognostic significance. The amount of bulky widespread disease at initial presentation, early and aggressive therapy, and the achievement of a complete remission status within 1--2 months from onset of therapy are the most important prognostic factors.
Two hundred and fifty-two patients with advanced stages of favorable non-Hodgkin's lymphoma (NHL) subtypes (nodular histiocytic (NH), and diffuse well-differentiated lymphocytic (DLWD)) were analyzed for response and survival to moderate (cyclophosphamide-prednisone (CP)) vs. intensive (BCVP or COPP) chemotherapy regimens. The overall complete response (CR) rate was 57%. The median duration of remission for the entire group was 88 weeks and 65% of complete responders were in remission at one year. Survival rates at one year were 87% for BCVP, 86% for COPP, and 91% for CP. The response rate, response duration, and survival rate differences between the groups were not significant. Severe and life threatening hematologic toxicity rates were significantly higher with BCVP and COPP as compared to CP (P less than 0.001). The highest CR rate was obtained in NM (74%) and CP gave the highest CR rate in DLWD (60%). Survival rates at one year for NM (97%) and NLPD (90%) were comparable whereas the one-year survival rate for DLWD was significantly lower (75%) than that for NLPD (P less than 0.005) or NM (P less than 0.001). We conclude that in favorable NHL subtypes, cyclophosphamide-prednisone combination is an effective regimen with minimal toxicity.
Treatment of rectal carcinomas with endocavitary irradiation is now an established method in the United States and is an important advance in the curative management of patients with selected cancers of the rectum that should be available to all such patients. Excellent palliation can also be achieved in many cases with advanced local disease. The total experience at Highland Hospital, Rochester, New York, is over 70 cases. Now that there are more centers using this method of treatment, an awareness of some of the problems and pitfalls encountered at Highland Hospital becomes relevant.
To assess the results of therapeutic advances in the treatment of small cell carcinoma of the lung (SCCL) achieved during the past 15-year period at a single large institution, 508 patients treated between 1968 and 1982 were divided into two groups: 157 patients (66 in the category of limited-stage disease and 91 in the extensive-stage disease category) treated with low-dose small-volume radiotherapy (RT) (time dose fractionation [TDF] 49-66) and with cyclophosphamide alone or a COPP program during the first period of 7 years (1968-1974); 351 patients (180 in limited and 171 in extensive stage) treated with multidrug chemotherapy (CT) and high-dose large-volume RT (TDF 73-89) during the second period of 8 years (1975-1982). For patients with limited-stage cancer, 5-year actuarial survivals were 3% versus 7% for the periods 1968-1974 versus 1975-1982, respectively, P less than 0.01. For patients with extensive-stage cancer, the median survival time (MST) and 2-year actuarial survivals were 5 months and 2% versus 7 months and 4% for the periods 1968-1974 versus 1975-1982, respectively. To evaluate the outcome of a contemporary approach, i.e., CT alone, with RT reserved for locoregional failure, 180 patients with limited-stage cancer who were treated (1975-1982) were further analyzed for MST, 2- and 5-year actuarial survival figures, and local-tumor control rates according to the therapeutic approaches employed: CT + RT (112); CT alone (36); RT alone (17); and surgery (S) +/- CT +/- RT (15). Although the 36 patients in CT alone seems a small number, 17 of the 36 patients were enrolled in this approach in 1981-1982, reflecting a shift of emphasis from RT to CT. The MST and 2-year actuarial survival figures were 11 months and 0% versus 13 months and 21% for CT alone versus CT + RT respectively, P less than 0.05. CT + RT achieved a 5-year cure rate of 8%. S +/- CT +/- RT or RT alone also achieved 5-year cure rates of 8% and 10.5%, respectively, in selected subsets of patients. Local relapse rates were 80% (29/36) versus 25% (28/112) for CT alone versus CT + RT. These data emphasize the importance of thoracic RT given at the early phase of treatment to improve long-term survival for patients with limited-stage SCCL.
BACKGROUND: The feasibility of screening and early detection of prostate cancer are controversial issues at this time. To conduct a randomized screening study with prostate cancer mortality as the major endpoint is one possible solution to the present controversy. METHODS: Eight pilot studies have been conducted in the Netherlands (Rotterdam) and Belgium (Antwerp) to evaluate the feasibility of a large scale European randomized study of screening for prostate cancer. Randomization and all other administrative steps necessary to conduct a large scale screening study were evaluated in the two centers. Participation rates were from 30%-42%. Essential adjustments in pilot protocols were made during the study and led to significant changes. RESULTS: Administrative procedures necessary to run a large scale randomized study were successfully established at the two centers. The experience can be used to establish similar procedures in other European countries. Follow-up in the no screening arm and information with relation to the major endpoint, prostate cancer mortality, are not yet available. In the screening arm, detection rates varied from 3.2% to 3.6%. Major changes in the application of the screening tests made during the course of the pilot studies were the use of random biopsies for prostate specific antigen (PSA) values between 4 and 10 ng/ml as well as the biopsy indication for all suspicious lesions in those men with a PSA below 4.0 ng/ml. One-third of all cancer cases were detected in this latter group. The application of the screening tests to men with low PSA values is still under evaluation. CONCLUSIONS: The pilot studies led to a common, agreed set of minimal requirements for participation in the European study. These features include randomization, PC mortality as major endpoint, age 55-70 years, biopsy policy, rescreening interval, treatment policies, and follow-up. A randomized screening study seems to be feasible in Europe.
Scrapie agent contains a proteinaceous component as well as an 'informational' molecule (suggested by the existence of distinct strains of scrapie). These operationally defined entities may be the same molecule, an infectious protein, or distinct, in which case a nucleic acid might encode the genetic information. Purification of scrapie agent enriched a protein, PrPSc, by virtue of its relative protease resistance. There is only a single PrP gene and the primary translation product of PrP mRNA is the same in normal and scrapie-infected brain; therefore the normal PrPC and the protease-resistant isoform, PrPSc, found in scrapie, probably result from different post-translational events. To search for scrapie-specific nucleic acid, globin RNA made in vitro was added to highly purified infectious preparations at a ratio of 10(3) molecules per infectious unit, nucleic acids were isolated and denatured, and cDNA synthesized using random oligonucleotide primers. Clones containing globin-related sequences were identified by in situ hybridization. 150 plaques not hybridizing to the globin probe were isolated. Inserts larger than 50 base pairs were analysed. By hybridization to a globin probe at reduced stringency all but four clones were found to contain small globin related inserts; two of these hybridized to hamster repetitive sequences as shown by Southern blot analysis. The other clones not related to hamster nucleic acids may be derived from unknown sources of contamination or from scrapie-specific nucleic acids.
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New York State has established a program to screen post-pubertal mentally retarded males for the fragile X [fra(X)] syndrome. The goal of the program is to identify affected males and inform their families of the diagnosis. Females in these families who are at risk for inheriting the mutation will then be able to determine their carrier status and consider that information in making reproductive decisions. Males were evaluated for 10 features of the syndrome by physicians and nurses throughout the state; cytogenetic analysis was carried out on a subset of this population. A total of 1332 males has been screened and chromosome studies have been completed for 489. Forty-three (9%) were positive for fra(X), and an additional 11 other chromosome abnormalities were identified. The 43 patients belonged to 38 families. Of the 24 families who were informed of the diagnosis, 12 consulted genetic counseling centers for follow-up studies and 12 did not.
A prospective study of the fragile X syndrome [fra(X)] was initiated one year ago to refine the estimates of recurrence risks based on the phenotype of the mother and the family history of the syndrome. The basic unit of data consists of the description of the conceptus of women known to carry the fra(X) gene or of mothers of an isolated case. To date, information on 261 women and their conceptuses was ascertained primarily through prenatal diagnosis; these data are summarized here. Although tests of significance were limited due to small sample sizes in subgroups, the following trends were observed: 1) the penetrance of fra(X) site expression was 80% in both male and female conceptuses suggesting that fra(X) site expression is equally penetrant early in development; 2) the sex ratio at the time of prenatal diagnosis did not differ from one, indicating that selection against fra(X) fetuses, if any, does not differ among sexes; 3) the recurrence risk among offspring of borderline/mildly retarded mothers was higher than that among offspring of intellectually normal mothers; 4) the recurrence risk in offspring did not differ based on the mother's fra(X) site expression; and 5) the recurrence risk in offspring of mothers with isolated cases was slightly less (34%) than that of obligate carrier mothers (41%) although this was not significant. The potential use of these prospective data on the fra(X) syndrome is emphasized.
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