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Biomedical subjects

C Scott

Publications and source records attributed to C Scott.

At least 37 records · Page 2Linked to original sources

Phase I/II trial of accelerated fractionation in brain metastases RTOG 85-28.

PURPOSE: Radiation Therapy Oncology Group 85-28 represents a Phase I/II trial of accelerated fractionation in patients with brain metastases. METHODS AND MATERIALS: Patients entered had controlled or absent primary with metastases other than brain which were stable or only brain metastases with the primary uncontrolled. Karnosfky status was required to be greater than 60. Patients received 1.6 Gy twice daily separated by 4-8 hr delivered 5 days a week. The entire brain was treated to 32.0 Gy and the boost dose escalated from 16.0 Gy to 22.40 Gy and subsequently 32.00 Gy and 42.40 Gy. RESULTS: We observed no undue toxicity with escalating dose of irradiation. An incremental, although not statistically significant improvement in survival was noted with escalating doses. Median survival ranged from 4.2 months to 6.4 months with escalating dose of irradiation. Median survival also increased in patients with controlled primary tumors, non-lung primaries and solitary metastasis. CONCLUSION: The incremental improvement in survival in patients with good prognostic factors appeared encouraging. The Radiation Therapy Oncology Group will test the 54.4 Gy study against 30 Gy in 2 weeks in a Phase III trial based on the results of this trial.

Adult

Influence of location and extent of surgical resection on survival of patients with glioblastoma multiforme: results of three consecutive Radiation Therapy Oncology Group (RTOG) clinical trials.

PURPOSE: The influence of tumor site, size, and extent of surgery on the survival of patients with glioblastoma multiforme treated on three consecutive prospectively randomized Radiation Therapy Oncology Group trials employing surgery and irradiation plus or minus chemotherapy was studied. METHODS AND MATERIALS: Six hundred forty-five patients with a diagnosis of glioblastoma multiforme on central pathological review were analyzed for survival with respect to known prognostic factors, that is, age and Karnofsky Performance Status, as well as extent of surgery, site, and size. Surgical treatment consisted of biopsy only in 17%, partial resection in 64%, and total resection in 19%. Tumors were located in frontal lobe in 43%, temporal lobe in 28%, and parietal lobe in 25%. Maximum tumor diameter as determined on computed tomography or magnetic resonance imaging scans was less than 5 cm for 38%, between 5-10 cm for 56% and greater than 10 cm for 6% of patients. The extent of surgical therapy was the same for tumors greater than 5 or greater than 10 cm, whereas total resection was more often performed for tumors less than 5 cm. The extent of surgery did not appear to vary with age or site. RESULTS: Patients undergoing total resection had a median survival of 11.3 months compared to 6.6 months for patients with a biopsy only. A significant difference in median survival was also found for partial resection versus biopsy only treatment (10.4 vs. 6.6 months). There was no difference in survival for the different tumor sizes. Patients with frontal lobe tumors survived longer than those with temporal or parietal lobe lesions (11.4 months, 9.1 months, and 9.6 months, respectively) (p = 0.01). A Cox multivariate model confirmed a significant correlation of age, Karnofsky Performance Status, extent of surgery, and primary site with survival. The best survival rates occurred in patients who had at least three of the following features: < 40 years of age, high Karnofsky Performance Status, frontal tumors, and total resection (17 months median). CONCLUSION: We conclude that biopsy only yields inferior survival to more extensive surgery for patients with glioblastoma multiforme treated with surgery and radiation therapy.

Adult

Hyperfractionated radiation therapy and bis-chlorethyl nitrosourea in the treatment of malignant glioma--possible advantage observed at 72.0 Gy in 1.2 Gy B.I.D. fractions: report of the Radiation Therapy Oncology Group Protocol 8302.

Between January 1983 and November 1987, the Radiation Therapy Oncology Group conducted a prospective, randomized, multi-institutional, dose searching Phase I/II trial to evaluate hyperfractionated radiation therapy in the treatment of supratentorial malignant glioma. Patients with anaplastic astrocytoma, or glioblastoma multiforme, age 18-70 years with a Karnofsky performance status of 40-100 were stratified according to age, Karnofsky performance status, and histology, and were randomized. Initially randomization was to one of three arms: 64.8 Gy, 72.0 Gy, and 76.8 Gy. Fractions of 1.2 Gy were given twice daily, 5 days per week, with intervals of 4 to 8 hr. All patients received bis-chlorethyl nitrosourea (BCNU) 80 mg/m2 on days 3, 4, 5 of radiation therapy and then every 8 weeks for 1 year. After acceptable rates of acute and late effects were found, the randomization was changed to 81.6 Gy and 72.0 Gy with a weighting of 2:1. Out of 466 patients randomized, 435 were analyzed. The distribution of prognostic factors was comparable among the 76.8 Gy arm, 81.6 Gy arm, and the final randomization of the 72 Gy arm. The 64.8 Gy arm and the initial randomization of the 72 Gy arm had somewhat worse prognostic variables. Late radiation toxicity occurred in 1.3-6.8% of the patients, with a modest increase with increasing radiation dose. The best survival occurred in those patients treated with 72 Gy (median survival of 12.8 months overall, and 14 months for the final 72 Gy randomization). The Cox proportional hazards model confirmed the prognostic variables of age, histology and Karnofsky performance status. In addition, the longer interval of 4.5-8 hr was associated with a worse prognosis than the 4-4.4 hr interval (p = 0.0011). The difference in survival between the 81.6 Gy arm and the lower three arms approached significance (p = 0.078) with inferior survival observed in the 81.6 Gy arm. When therapy was evaluated by radiation therapy dose received (60-74.4 Gy compared with 74.5-84.0 Gy), the p value was 0.062 in favor of the lower dose range. Patients with anaplastic astrocytoma treated with 72 Gy by hyperfractionation + BCNU had at least as good a survival as those treated with 60 Gy by conventional fractionation + BCNU on Radiation Therapy Oncology Group protocols 7401 and 7918. This suggests that 72 Gy delivered by 1.2 Gy twice daily is no more toxic than 60 Gy delivered by conventional fractionation.

Adult

Evaluation of 45 degrees C hyperthermia and irradiation. II. A phase I clinical trial in humans by the Radiation Therapy Oncology Group.

This report describes the experience in 40 evaluable patients entered into a Radiation Therapy Oncology Group (RTOG) study to evaluate the feasibility of administering 45 degrees C for 15 minutes for superficial malignant lesions: 18 patients (45%) tolerated only 1 heat session at 45 degrees C; 7 (17.5%), 2 sessions; 4 (10%), 3 sessions; and 3 (7.5%) tolerated > or = 4 sessions. The overriding reason for discontinuing at 45 degrees C treatment was pain. Of the 40 evaluable patients, 22 (55%) had complete tumor regression, and 8 (20%) had partial regression. Tumors < or = 3 cm in diameter had significantly better complete tumor response than lesions > 3 cm (85% vs 41%) (p = .02). We conclude that 45 degrees C heating is difficult to use in patients chiefly because of pain; this may be due in part to inadequacy of currently available external hyperthermia equipment. Caution must be exercised in the application of thermal isoeffect heat dose concepts in clinical practice until further trials have been performed and a better understanding of the time-temperature relationship is established.

Adenocarcinoma

Appraisal of the clinical value of serotoninergic drugs.

Principal objectives in obesity management comprise the prevention of weight gain, the promotion of weight loss, and the treatment of obesity-related complications, including diabetes, hypertension, and depression. Serotonin agonists reduce food intake. The resultant weight loss is variable and there appears to be no way of predicting good responders, nor is there evidence that additional weight loss attributable to drug therapy is sustained once treatment is discontinued, although nonpharmacological strategies for preventing weight regain are worthy of exploration. Serotonin agonists are of clinical value if there is a short-term need for weight reduction or if long-term pharmacotherapy can be justified. This implies that sometimes the dangers of the obese state outweigh the potential hazards of drug treatment. Clearly, if the same agent also improves diabetic control, blood pressure, or depression then a longer term usage is more readily justified. The extent to which this may be achieved by the currently available 5-HT agonists is discussed.

Appetite Depressants

Phase II trial of combination chemotherapy and irradiation in non-small-cell lung cancer, Radiation Therapy Oncology Group 88-04.

Encouraging results of several clinical trials utilizing combination chemotherapy and irradiation in unresectable non-small-cell lung cancer have been reported. A recent report from a cooperative group study suggested that preirradiation vinblastine and cisplatin improved survival over irradiation alone. In an attempt to enhance the possible effectiveness of combination chemotherapy and irradiation, the Radiation Therapy Oncology Group embarked on a Phase II trial utilizing preirradiation vinblastine (5 mg/m2 weekly x 5) and cisplatin (100 mg/m2) on days 1 and 29 prior to irradiation and on days 50, 71, and 92 during irradiation. The irradiation began on day 50 and consisted of 6300 cGy in 7 weeks. Between May 20, 1988 and May 1, 1989, 30 patients were entered on study. Seventy-two percent of patients had Karnofsky status greater than 90, and 76% had weight loss less than 5%. Forty-eight percent of the patients were younger than 60 years of age. Forty-five percent of the patients had Stage IIIA disease. Eighty-three percent of the patients received at least four courses of vinblastine, and 59% received at least four courses of cisplatin. Seventy-eight percent of the patients received at least 95% of the prescribed irradiation. The major toxicity was hematologic, and there were two fatal complications in the study group. The preliminary survival figures are encouraging. This combination of chemotherapy and irradiation appears to be tolerable and may merit further investigation.

Aged

A case-control study of benign ovarian tumours.

STUDY OBJECTIVE: The aim was to investigate the association between reproductive, contraceptive, and menstrual factors and risk of benign ovarian tumours. DESIGN AND SETTING: This was a case-control study carried out in six London Hospitals. An interviewer administered questionnaire was used. SUBJECTS: 62 women with a benign epithelial ovarian neoplasm, 37 women with a functional ovarian cyst, and 20 women with a dermoid cyst presenting between 1983 and 1985, together with 132 controls, took part in the study. MAIN RESULTS: On average, women with a benign epithelial ovarian neoplasm were older than those with a functional ovarian cyst, who in turn were older than those with a dermoid cyst. Nulliparity and infertility were associated with an increased risk, and multiparity with a reduced risk, of benign epithelial ovarian neoplasms. Infertility and pelvic inflammatory disease were associated with increased risks of functional and dermoid cysts. Recent use of oral contraceptives was associated with a reduced risk of all three tumour types. CONCLUSIONS: The findings suggest that the aetiology of ovarian cysts and benign epithelial ovarian neoplasms may differ. The aetiology of benign and malignant epithelial ovarian neoplasms may be similar, however, since some risk factors are shared.

Adolescent

Construction of synthetic genes using PCR after automated DNA synthesis of their entire top and bottom strands.

A new method is described for the direct construction of synthetic genes by applying a modified version of the polymerase chain reaction (PCR) to crude oligonucleotide mixtures made by automated solid phase DNA synthesis. Construction of the HIV-1 393 bp rev gene and the 655 bp nef gene by this method is illustrated. The sequences for the entire top and bottom strands of rev were each programmed into an automated DNA synthesizer. Following DNA synthesis, the two crude oligonucleotide solutions were mixed together, specific primers were added, and the target gene was amplified by a modified PCR technique. Although the longer (greater than 200 bases) strands comprise a very small percentage of the total DNA after solid phase synthesis, this method uses PCR to 'find' and amplify such strands to create the target gene. The rev gene constructed by this method was found to contain 4 sequence errors, which were subsequently corrected by site-directed mutagenesis. In order to evaluate the source of sequence errors, several nef genes were made from the top and bottom strand DNA synthesis solutions using independent PCR's. Results suggest that sequence errors arose from both DNA synthesis and PCR. The utility of this method in producing a functional gene is demonstrated by expression of rev in E.coli.

Base Sequence

Corneal ulcer and adverse reaction rates in premarket contact lens studies.

We analyzed clinical data on 22,739 contact lens wearers who were studied and whose lenses were approved under 48 manufacturer-sponsored studies for the Food and Drug Administration between 1980 and 1988. The incidence of corneal ulcers was low in the cosmetic (nontherapeutic) daily-wear soft and rigid gas-permeable lens wearers (1/1,923 and 1/1,471 patient-years, respectively). Corneal ulcers and severe adverse reactions occurred two to four times more frequently in extended-wear cosmetic soft and rigid gas-permeable lens wearers than in cosmetic daily-wear lens wearers. Aphakic extended-wear soft lens users were nine times more likely to develop a corneal ulcer when compared to the soft daily-wear cosmetic group. Corneal abrasions and keratitis accounted for 81 of 159 severe adverse reactions, whereas corneal ulcers accounted for 28 of 159 adverse reactions. The data indicate that overnight extended wear of contact lenses is associated with a greater risk of serious, sight-threatening complications than daily wear.

Aphakia

The relationship of nasopharyngeal carcinomas and second independent malignancies based on the Radiation Therapy Oncology Group experience.

The authors sought to learn if the incidence of second independent malignancies after the irradiation of carcinomas of the nasopharynx is similar to that observed after treatment of tumors arising in other head and neck sites. One hundred twenty-one patients who had primary carcinomas of the nasopharynx who were treated solely by ionizing radiation (according to the specifications of a Radiation Therapy Oncology Group protocol) were identified and their subsequent well-being was reviewed. Overall there was a 4.1% incidence of second malignancies (2% after 3 years, 5% after 5 years, and 8% after 8 years) with most arising in the upper aerodigestive tract. This rate is significantly less than the rate associated with other head and neck sites. It is not significantly different from the rate of first malignancies observed in an age-matched and sex-matched population. When only those patients who were free of all evidence of neoplastic disease 6 months after the completion of radiotherapy are considered, similar analysis leads to similar outcomes. The authors conclude that the risk of second malignancies after the successful irradiation of carcinomas of the nasopharynx is substantially less than after treatment of tumors at other head and neck sites.

Adolescent

Phase I/II study, combination of radiotherapy and hyperthermia in patients with deep-seated malignant tumors: report of a pilot study by the Radiation Therapy Oncology Group.

This is a report of a Phase I/II study activated in March 1984 and completed in October 1988 by the Radiation Therapy Oncology Group on the feasibility/toxicity of hyperthermia in patients with deep-seated malignant tumors. The main objective of this study was to evaluate the morbidity of regional hyperthermia (systemic and regional, acute and late effects); a secondary objective was to evaluate tumor response to combined irradiation and regional hyperthermia. A total of 54 patients with locally advanced abdominal or pelvic malignancy were accrued to this study; 42% were male and 58% female. Seventy-five of the patients had pelvic tumors and 25% abdominal tumors. Acute toxicities included grade 4 in three patients (1 cutaneous, 1 infection and 1 chemical peritonitis) one grade 3 (skin), and 12 grade 2 toxicities (6 skin and 6 gastrointestinal). With regard to late toxicities, grade 4 was noted in one patient (skin), grade 3 (GI) in one, and grade 2 (skin, peripheral neuropathy) in six patients. The prescribed course of hyperthermia was completed in 17 (32%) of patients. In 36 patients (68%) the course of hyperthermia was terminated, primarily because of patient discomfort. Tumor response was assessed by physical examination or radiological studies. Of 44 patients evaluable for response, there were 17 (39%) complete responses and 6 (14%) partial responders. Significant technical problems in heat delivery and thermometry remain.

Abdominal Neoplasms

Community hospital carotid endarterectomy in patients over age 75.

We compared the prevalence of stroke and death in 133 patients aged 75 and older in whom 170 carotid endarterectomies were performed with that in 501 patients less than age 75 in whom 640 carotid endarterectomies were performed. There were three strokes (2%) in patients aged 75 and older and nine strokes (1%) in younger patients (p = 0.7). There were 8 deaths (5%) in patients aged 75 and older and 14 deaths (2%) in younger patients (p = 0.1). After controlling for the possible confounding effects of diabetes, prior stroke, history of angina, prior carotid artery disease, previous vascular surgery, history of myocardial infarction, preoperative hypertension requiring medication, and female gender, a logistic regression model showed that patients aged 75 and older were no more likely to have a stroke or death than patients under age 75. We conclude that age alone is not a contraindication to the safe performance of carotid endarterectomy in the community hospital.

Age Factors