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J O'Fallon

Publications and source records attributed to J O'Fallon.

10 recordsLinked to original sources
PubMed2002

Prospective randomized trial of low- versus high-dose radiation therapy in adults with supratentorial low-grade glioma: initial report of a North Central Cancer Treatment Group/Radiation Therapy Oncology Group/Eastern Cooperative Oncology Group study.

PURPOSE: To compare survival and toxicity in adult patients treated with low-dose (50.4 Gy/28 fractions) versus high-dose (64.8 Gy/36 fractions) localized radiation therapy (RT) for supratentorial low-grade astrocytoma, oligodendroglioma, and mixed oligoastrocytoma. PATIENTS AND METHODS: From 1986 to 1994, 203 eligible/analyzable patients were randomized: 101 to low-dose RT, 102 to high-dose RT. Almost half were younger than 40 years, and 95% had grade 2 tumors. Histologic subtype was astrocytoma (or mixed oligo-astrocytoma with astrocytoma dominant) in 32% of patients and oligodendroglioma (or oligoastrocytoma with oligodendroglioma dominant) in 68%. Tumor diameter was less than 5 cm in 35% of patients, and 41% of tumors showed some degree of contrast enhancement. Extent of resection was gross total in 14% of patients, subtotal in 35%, and biopsy only in 51%. RESULTS: At the time of the present analysis, 83 patients (41%) are dead, and median follow-up is 6.43 years in the 120 who are still alive. Survival at 2 and 5 years is nonsignificantly better with low-dose RT; survival at 2 and 5 years was 94% and 72%, respectively, with low-dose RT and 85% and 64%, respectively, with high-dose RT (log rank P =.48). Multivariate analysis identified histologic subtype, tumor size, and age as the most significant prognostic factors. Survival is significantly better in patients who are younger than 40 years and in patients who have oligodendroglioma or oligo-dominant histology. Grade 3 to 5 radiation neurotoxicity (necrosis) was observed in seven patients, with one fatality in each treatment arm. The 2-year actuarial incidence of grade 3 to 5 radiation necrosis was 2.5% with low-dose RT and 5% with high-dose RT. CONCLUSION: This phase III prospective randomized trial of low- versus high-dose radiation therapy for adults with supratentorial low-grade astrocytoma, oligodendroglioma, and oligoastrocytoma found somewhat lower survival and slightly higher incidence of radiation necrosis in the high-dose RT arm. The most important prognostic factors for survival are histologic subtype, tumor size, and age. The study design of the ongoing intergroup trial in this population will be discussed.

Adult↗
PubMed2000

Alterations of chromosome arms 1p and 19q as predictors of survival in oligodendrogliomas, astrocytomas, and mixed oligoastrocytomas.

PURPOSE: A recent report suggests that alterations of chromosome arms 1p and 19q are associated with chemotherapeutic response and overall survival in anaplastic oligodendroglioma patients treated with procarbazine, lomustine, and vincristine chemotherapy. We set out to further clarify the diagnostic and prognostic implications of these alterations in a broader set of diffuse gliomas, including astrocytic neoplasms and low-grade oligodendrogliomas. PATIENTS AND METHODS: Fluorescence in situ hybridization (FISH) signals from DNA probes mapping to 1p and 19q common deletion regions were enumerated in 162 diffuse gliomas (79 astrocytomas, 52 oligodendrogliomas, and 31 mixed oligoastrocytomas), collected as part of an ongoing prospective investigation of CNS tumors. RESULTS: The oligodendroglial phenotype was highly associated with loss of 1p (P =.0002), loss of 19q (P <.0001), and combined loss of 1p and 19q (P <.0001). Combined loss of 1p and 19q was identified as a univariate predictor of prolonged overall survival among patients with pure oligodendroglioma (log-rank, P =.03) and remained a significant predictor after adjusting for the effects of patient age and tumor grade (P <.01). This favorable association was not evident in patients with astrocytoma or mixed oligoastrocytoma. CONCLUSION: Combined loss of 1p and 19q is a statistically significant predictor of prolonged survival in patients with pure oligodendroglioma, independent of tumor grade. Given the lack of this association in patients with astrocytic neoplasms and the previously demonstrated chemosensitivity of oligodendrogliomas, a combined approach of histologic and genotypic assessment could potentially improve existing strategies for patient stratification and management.

Adolescent↗
PubMed1999

Localization of common deletion regions on 1p and 19q in human gliomas and their association with histological subtype.

Allelic alterations of chromosomes 1 and 19 are frequent events in human diffuse gliomas and have recently proven to be strong predictors of chemotherapeutic response and prolonged survival in oligodendrogliomas (Cairncross et al., 1998; Smith et al., submitted). Using 115 human diffuse gliomas, we localized regions of common allelic loss on chromosomes 1 and 19 and assessed the association of these deletion intervals with glioma histological subtypes. Further, we evaluated the capacity of multiple modalities to detect these alterations, including loss of heterozygosity (LOH), fluorescence in situ hybridization (FISH), and comparative genomic hybridization (CGH). The correlation coefficients for detection of 1p and 19q alterations, respectively, between modalities were: 0.98 and 0.87 for LOH and FISH, 0.79 and 0.60 for LOH and CGH, and 0.79 and 0.53 for FISH and CGH. Minimal deletion regions were defined on 19q13.3 (D19S412-D19S596) and 1p (D1S468-D1S1612). Loss of the 1p36 region was found in 18% of astrocytomas (10/55) and in 73% (24/33) of oligodendrogliomas (P < 0.0001), and loss of the 19q13.3 region was found in 38% (21/55) of astrocytomas and 73% (24/33) of oligodendrogliomas (P = 0.0017). Loss of both regions was found in 11% (6/55) of astrocytomas and in 64% (21/33) of oligodendrogliomas (P < 0.0001). All gliomas with LOH on either 1p or 19q demonstrated loss of the corresponding FISH probe, 1p36 or 19q13.3, suggesting not only locations of putative tumor suppressor genes, but also a simple assay for assessment of 1p and 19q alterations as diagnostic and prognostic markers.

Astrocytoma↗
PubMed1998

Gene amplification as a prognostic factor in primary and secondary high-grade malignant gliomas.

The purpose of this study was to examine the incidence of gene amplification in patients with primary (de novo) and secondary high-grade gliomas (gliomas evolving from lower grade malignancies) and to assess its prognostic significance. A total of 186 prospectively collected frozen surgical specimens were analyzed. Extracted DNA was examined by Southern blot using probes corresponding to the EGFR, CDK4, MDM2, n-MYC, CYCD1, PDGFR-alpha, MET, c-MYC oncogenes. Complete clinical data regarding age, sex, tumor size, extent of surgical resection, postoperative therapy and patient survival were collected. We showed that EGFR followed by CDK4 were the most frequent oncogene amplifications. Oncogene amplification events were significantly more frequent in grade 4 than in grade 3 astrocytomas, mixed gliomas or oligodendrogliomas (P<0.001). With respect to EGFR, there was a significant difference in the frequency of amplification between primary and secondary gliomas (P=0.001); however, no difference in the amplification frequency of the other oncogenes was observed. There was no apparent correlation between the occurrence of gene amplification and patient survival, possibly because the genes amplified in human gliomas are part of larger signaling pathways.

Adolescent↗
PubMed1995

The data and safety monitoring board and acquired immune deficiency syndrome (AIDS) clinical trials.

The urgency of the Acquired immune deficiency syndrome (AIDS) epidemic has mandated that multiple therapeutic approaches be developed and that these approaches be evaluated through clinical trials. To oversee these trials, the National Institute of Allergy and Infectious Diseases (NIAID) has created three large clinical trial programs monitored by a Data and Safety Monitoring Board (DSMB). For each clinical trial, this Board uses a standardized approach employing contemporary biostatistical, medical, and ethical principles. The DSMB is responsible for reviewing interim data on clinical trial performance, treatment safety and efficacy, and overall study progress. If interim results provide convincing evidence of either excessive adverse effects or significant treatment benefit, the DSMB may recommend early termination of the trial to the NIAID and the study investigators. The responsibility, organization, and operating procedures of this DSMB are presented and illustrated through three clinical trials sponsored by NIAID and monitored by the Board. The rationale and operational model for the DSMB may be a useful example for the development of similar review processes in other HIV clinical trial settings.

Advisory Committees↗
PubMed1994

Regular use of a verbal pain scale improves the understanding of oncology inpatient pain intensity.

PURPOSE: This study was undertaken to determine if the daily use of a verbal pain scale could improve the correlation of pain perception between hospitalized oncology patients and their caregivers. PATIENTS AND METHODS: Hospitalized oncology patients were asked to rate verbally their average pain over the past 24 hours on a scale ranging from 0 to 10. The patients' primary-care physicians and nurses were asked the same question on the same morning after they had evaluated their patients. RESULTS: During a baseline study, only 64% of caregivers' pain scores were within two points of the respective patient's score. Caregivers tended to underestimate patients' pain scores. Caregivers were alerted to these poor results and then requested to ask each patient daily for the average pain score and record this score on the patient's medical record. Nonetheless, correlation between patients' and caregivers' pain scores remained poor (68% within two points of each other) during a second study. The major reason for the poor results appeared to be because caregivers did not routinely ask patients for pain scores. Subsequently, a renewed, more intensive educational effort was undertaken and a third study was conducted. During the third study, 85% of caregivers' and patients' pain scores were within two points of each other (P = .001 when compared with baseline). CONCLUSION: The enforced use of a simple verbal pain assessment tool appears to improve caregiver's understanding of the pain status of hospitalized oncology patients.

Caregivers↗
PubMed1988

Grading of astrocytomas. A simple and reproducible method.

This study determines the effectiveness and reproducibility of a previously published method of grading gliomas. The method under study is for use on "ordinary astrocytoma" cell types, i.e., fibrillary, protoplasmic, gemistocytic, anaplastic astrocytomas and glioblastomas, and is based upon the recognition of the presence or absence of four morphologic criteria: nuclear atypia, mitoses, endothelial proliferation, and necrosis. The method results in a summary score which is translated into a grade as follows: 0 criteria = grade 1, 1 criterion = grade 2, 2 criteria = grade 3, 3 or 4 criteria = grade 4. The histologic material and clinical data were derived from a previously reported series of patients with astrocytomas, radiotherapeutically treated at Mayo Clinic between the years 1960 and 1969. From this series, initially graded 1 to 4, according to the Kernohan system, 287 "ordinary astrocytomas" were entered into the study; 51 pilocytic astrocytomas and microcystic cerebellar-type astrocytomas also were included for comparison. Among ordinary astrocytomas, the grading method under study distinguished 0.7% of grade 1, 17% of grade 2, 18% of grade 3, and 65.3% of grade 4. A 15-year period of follow-up was available on all surviving patients. Statistical analysis showed that in ordinary astrocytomas, each of the four histologic criteria, as well as the resultant grade, were strongly correlated to survival (P less than 0.0001). Median survival was 4 years in grade 2, 1.6 years in grade 3, and 0.7 years in grade 4 tumors. Of the two patients with grade 1 ordinary astrocytomas, 1 had 11 years of survival, and the other was alive at 15 years. Furthermore, based upon the Cox Model, grade was found to be the major prognostic factor, superceding the effects of age, sex, and location. Among ordinary astrocytomas, the grading system under consideration clearly distinguished four distinct grades of malignancy, whereas, the Kernohan grading system accurately distinguished only two major groups of patients. Survival curve of patients with our grade 2 tumors coincided with the grade 1 and 2 Kernohan survival curves. Similarly, our grade 4 survival curve coincided with the Kernohan grade 3 and 4 survival curves. As a result, our proposed grading method generated an individualized curve corresponding to grade 3 tumors. Double-blind grading between two independent observers was concordant in 94% of ordinary astrocytomas; reproducibility was 81% in low-grade (grades 1 and 2) and 96% in high-grade (grades 3 and 4) astrocytomas of ordinary type.(ABSTRACT TRUNCATED AT 400 WORDS)

Astrocytoma↗
PubMed1978

Development of a computerised cancer data management system at the Mayo Clinic.

A multidisciplinary team was assembled to design a cancer data management system that would meet the storage, retrieval and analysis NEEDS OF Mayo's clinical trials of anti-tumour drugs. To fulfill these requirements, a computerised data entry and retrieval system was developed, the primary patient health record used by the oncologists was redesigned and the clerical procedures and work flow within the Cancer Center Statistics Office were reorganised. The end result of this project is a system that has: (1) enabled Mayo to meet its reporting requirements as a Comprehensive Cancer Center; (2) provided the statisticians and the physicians with the capacity to perform more detailed and accurate analyses of clinical trials; (3) reduced the clerical effort needed for preparing reports and analyses; (4) provided the potential for expansion to meet the growing requirements of the future and (5) attained that often elusive goal of computer systems--user satisfaction.

Antineoplastic Agents↗
PubMed1978

Evaluation of a fixed alternating treatment in patients with advanced breast cancer.

A total of 128 patients were randomly assigned to two induction treatment programs: Adriamycin and L-PAM versus Cytoxan, 5-Fluorouracil, and Prednisone in an effort to assess their primary capacity for objective response. The two regimens appeared quite comparable in this respect. The 100 patients who had achieved clinical benefit following initial treatment were subsequently randomly allocated to reveive either a fixed alternate treatment program involving the two drug regimens or were continued on the treatment program responsible for their initial improvement. Although those patients who received the fixed alternate treatment shcedule had a somewhat longer progression-free interval compared to the two single-treatment programs (median duration of 16 months versus 12 months, respectively), the three treatment programs including the fixed alternate treatment schedules had comparable median survivals of 21-24 months with little difference noted in survival curves at any point thus far in the analysis. There were no differences noted in survival for the fixed alternating treatment group of patients, with respect to which induction regimen had been utilized to achieve initial response. The toxicity for these treatment programs was tolerable and compatible with outpatient administration. Myelosuppression occurred in the vast majority of patients on either regimen but in both regimens was relatively platelet sparing.

Antineoplastic Agents↗