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Biomedical subjects

J R Simpson

Publications and source records attributed to J R Simpson.

At least 91 records · Page 5Linked to original sources

Role of irradiation in the management of superior vena cava syndrome.

The records of 125 patients treated for superior vena cava syndrome secondary to malignant disease were reviewed retrospectively. The mean age of patients was 55 years. Bronchogenic carcinoma was the cause of the syndrome in 79% of cases, malignant lymphoma 18%, and other tumors 6%. Approximately 80% of the patients obtained good to excellent symptomatic relief. High initial dose radiation therapy (300-400 cGy daily for three fractions) yielded good symptomatic relief in less than 2 weeks in 70% of patients; conventional dose radiation therapy (200 cGy daily, five weekly fractions) yielded the same response in 56% of patients (p = 0.09). Lymphoma patients displayed a 1 year survival of 41%, small cell carcinoma 24%, and other types of bronchogenic carcinoma 17%. Combination of radiation and chemotherapy did not improve response rate, degree of symptomatic relief or long-term survival. Patients exhibiting symptomatic relief within 30 days had a significantly better survival rate than those who did not (p = 0.002). Thirteen percent of patients showed a recurrence of superior vena cava syndrome. There was no correlation between tumor regression and symptomatic relief. Side effects of therapy were minimal; dysphagia was the most common complaint (26% of patients).

Adult↗

Large fraction irradiation with or without misonidazole in advanced non-oat cell carcinoma of the lung: a phase III randomized trial of the RTOG. Radiation Therapy Oncology Group.

The Radiation Therapy Oncology Group (RTOG) investigated the use of misonidazole as an hypoxic cell sensitizer in a Phase III prospective randomized trial employing radiotherapy, 600 cGy twice weekly to a total of 3600 cGy with and without misonidazole in the treatment of locally advanced non-metastatic squamous cell, adeno, or large cell carcinoma of the lung. Between January 1980 and July 1983, 117 patients from 21 institutions were enrolled. One-hundred eight patients were evaluable; 53 in the combined treatment arm and 55 in the radiation alone arm. Grade 3 or worse complications associated with radiation occurred in 17% of patients. Esophageal toxicity accounted for the majority of complications. Two (4%) patients in the radiotherapy plus misonidazole group experienced grade 3 peripheral neurotoxicity. Complete or partial responses were produced in 58% of the patients with radiotherapy alone and 36% of those treated with radiotherapy plus misonidazole (p = 0.08). At the time of first progression, over 50% of the patients had persistent local disease. Median survival was 7 months regardless of treatment. Misonidazole in the dose and schedule employed did not enhance the effect of radiotherapy on either local tumor control or overall survival in patients with advanced lung cancer.

Adolescent↗

Postoperative radiation therapy in the management of lung cancer.

Postoperative radiation therapy for lung cancer is still controversial. In a 9-year period, 69 patients with non-oat-cell carcinoma of the lung (16% stage I, 26% stage II, and 58% stage III) received such therapy. The radiation dose was less than 5,000 cGy in 42 patients, 5,000-5,900 cGy in 16, and 6,000 cGy or more in 11; follow-up ranged from 24 to 64 months. Actuarial survival at 2 and 4 years was 50% and 16%, respectively, for squamous cell carcinoma, and 40% and 26% for adenocarcinoma. The 5-year survival for stages I, II, and III cancer was 29%, 17%, and 19%, respectively. Histologic findings and type of surgery did not affect survival, but the radiation dose apparently did. The 3-year survival for patients who received less than 6,000 cGy was 35%, compared with 73% for patients who received higher doses. In eight patients, treatment failed within the irradiated volume: all had received doses of less than 6,000 cGy, and the volume in three was judged to be inadequate.

Adenocarcinoma↗

Adenoid cystic salivary gland carcinoma. A histopathologic review of treatment failure patterns.

Seventy-one cases of adenoid cystic salivary gland carcinoma were reviewed according to treatment modality and clinical course. Thirty-six patients (51%) were treated by combined surgery and radiation therapy. The tumors were classified by their histologic patterns into tubular, cribriform, and solid forms. Distant metastases, in 52%, were the most frequent and ominous sources of failure. In 35% of cases, distant metastases developed despite local control at the primary site. In this group, the disease had a more fulminant course with shorter survival. Histopathologically, the cribriform subtype was associated with multiple local recurrences, greater local aggressiveness, and a poorer salvage rate as compared with the tubular subtype. Late onset of local recurrences and distant metastases was especially associated with the cribriform subtype. Overall prognosis in terms of distant metastases and survival was worst for the solid subtype. Control of local disease is best achieved with combined surgery and radiation therapy. The high incidence of distant metastases may not be affected by this regimen. The ultimate outcome of therapy is poorly predicted. Survival appears to be based on the pattern in which distant metastases develop. Overly aggressive and mutilating surgical approaches for these tumors are not recommended in many instances. The need for the development of new, more effective forms of therapy is emphasized.

Aged↗

Improved treatment of salivary adenocarcinomas: planned combined surgery and irradiation.

The treatment outcome of 47 patients with adenocarcinoma of major and minor salivary gland origin treated at the Washington University Medical Center between 1960 and 1980 was retrospectively reviewed by site, histologic grade, and treatment modality. Planned irradiation with surgery was the initial treatment for 21 patients, irradiation alone for 14 patients, surgery alone for 11 patients, and chemotherapy for 1. Four patients presented with distant metastases at diagnosis and were not treated definitively. Twenty-seven patients had tumors histologically graded at the time of original treatment; one-third of these were low-grade, and two-thirds were high grade. Treatment results were analyzed in terms of local control as well as overall survival. Median survival for the entire group was 4.1 years. Local-regional disease control was significantly improved in the combination therapy group (81%) compared with the groups treated with irradiation alone (29%) and surgery alone (8%). Disease free survival was also significantly improved with combination therapy. Patients with low-grade adenocarcinoma had better local control and survived longer than those with high-grade. However, one-third of the patients with high-grade tumors survived 5 years. We conclude that both local disease control and survival of patients with adenocarcinoma of salivary gland origin were improved with the planned combination of irradiation and surgery.

Actuarial Analysis↗

Dosimetry of CT-guided volumetric IR-192 brain implant.

Over the past 2 years, an afterloading technique has been developed and refined to implant radioactive Ir-192 sources into brain tumors. The implantation procedure integrates a stereotaxic system with computerized tomography (CT), which provides tumor position, volume, and guides the placement of catheters. A radiolucent ring-frame immobilizes the head as holes are made at 1 cm intervals with the aid of a template. Catheters containing dummy sources 1 cm apart are then inserted to the desired depth, and their position verified in three dimensions to insure complete coverage of visible tumor volume as defined by contrast enhancement. Once catheters are secured, the anesthetized patient is moved to the intensive care unit where the dummy sources are replaced by ribbons of Ir-192 seeds (specific activity 0.6-1.0 mg Ra eq). CT scans with the dummy sources in place are used to designate spatial coordinates of the active sources. A computer program converts position data and source strength into isodose contours in any plane. The implant duration (70-100 hours) for the desired dose to the tumor periphery (60-120 Gy) is then calculated. Dose rate contours are superimposed on preimplant CT scans. Maximum and minimum doses are determined in each of the various planes. Verification dosimetry has been carried out with thermoluminescent dosimeters placed in a catheter located in a plane along the tumor periphery. In vivo isodose values compared to idealized plans agree within +/-5%-10%.

Brachytherapy↗

Palliative radiotherapy for inoperable carcinoma of the lung: final report of a RTOG multi-institutional trial.

Between June 1973 and February 1979, 409 patients with inoperable advanced non-oat cell carcinoma of the lung were randomized on RTOG protocol 73-02. Three treatment arms were evaluated: 40 Gy split course, 30 Gy continuous course, and 40 Gy continuous course. Patients were also randomized to receive cytoxan or no further therapy following irradiation. Three hundred sixteen patients were evaluable. Palliation of symptoms was achieved in 60% with 1/4 of the patients becoming symptom-free. Complete regression of local and regional tumor was produced in 15% and partial regression in 26%. There is no significant difference between the treatment arms in these objective response rates. Median survival times were approximately 6 months. No significant benefit was demonstrated by the adjuvant use of Cytoxan. Although the number of complete responses produced was relatively small, patients achieving a complete response had a significantly longer median survival than the remaining patients, i.e., 14.5 months versus 6 months. Significant toxicity occurred in fewer than 6% of patients. Radiation pneumonitis counted for the majority of these adverse reactions. Toxicity occurred somewhat more often in the group treated with 40 Gy split course therapy. Implications for further studies are discussed.

Adenocarcinoma↗

Expression in normal adult, fetal, and neoplastic tissues of a carbohydrate differentiation antigen recognised by antigranulocyte mouse monoclonal antibodies.

The distribution in paraffin fixed human tissues of a carbohydrate antigen defined by two monoclonal antibodies raised against human granulocytes has been studied by means of an immunoperoxidase technique. In addition to granulocytes, the antigen has been detected in adult tissues on identifiable cell types of the stomach, kidney, adrenal medulla, and brain and on the mucins of the gastrointestinal tract and other secretions. In fetal tissue, epithelial cells of the alimentary tract, lung, brain, and kidney express the antigen. Adenocarcinoma of the colon, stomach, breast, and lung are stained strongly, as are other types of lung cancer. The monoclonal antibodies give a staining pattern similar but not identical to other monoclonal antibodies raised against granulocytes or neoplastic cell lines which recognise the antigen 3-fucosyl N-acetyllactosamine. The use of antibodies against this oncofetal antigen in the study of differentiation and as tumour markers is discussed.

Adrenal Medulla↗

Adenoid cystic salivary gland carcinoma: treatment with irradiation and surgery.

The records of 71 patients with adenoid cystic carcinoma of the salivary glands were reviewed to determine the dose response relationships for this aggressive tumor. Local control after treatment was determined for all patients and analyzed with respect to extent of surgery and dose of radiation. Of 70 patients who were available for evaluation of local control, 28 (40%) had a local recurrence and 42 (60%) did not. The highest control rates were found in patients who underwent both radiation therapy and surgery. Patients who received a dose equal to or greater than 6,000 rad (60 Gy) in addition to surgery had significantly higher local control rates than those who received less than 6,000 rad (60 Gy). Distant metastases developed in 50% of patients regardless of local control, with the following distribution: 39% lung, 19% bone, and 10% disseminated soft-tissue metastases. Lymph node involvement was rare. Implications for combined modality treatment are discussed.

Adult↗

Adenoid cystic carcinoma of major and minor salivary gland origin.

The records of 76 patients with adenoid cystic carcinoma of major and minor salivary gland origin seen at the Washington University Medical Center from 1963-1980 were reviewed to determine factors involved in local control, development of distant metastasis, and survival. Twenty-four (32%) patients were initially treated with surgery alone, 36 (47%) with combined surgery and irradiation, and 16 (21%) with irradiation alone. Local control after treatment was determined for all patients and was analyzed with respect to extent of surgery and dose of irradiation. Of 75 patients evaluable for local control, 30 (40%) failed with a median time of less than 5 years. There was no significant difference for patients treated vigorously for local recurrences after surgery. Patients who had a complete surgical resection (i.e., negative margins) survived significantly longer than patients treated by incomplete resection or biopsy alone followed by irradiation. Distant metastases developed in 50% of patients regardless of local control. Median survival after development of distant metastases was 40 months. There was no difference between major and minor gland sources for development of metastases. Lymph node involvement was rare. Our data indicate that complete and radical surgery results in the best survival. Combined modality therapy with surgery and irradiation optimizes the control of local disease. However, since distant metastases develop in spite of local control, in most instances we cannot recommend mutilating surgery for this disease entity.

Adult↗

Cerebellar medulloblastoma: the importance of posterior fossa dose to survival and patterns of failure.

Fifty patients with biopsy-proven cerebellar medulloblastoma were retrospectively analyzed for prognostic factors, survival and patterns of failure. Five- and ten-year actuarial survivals for the entire group were 51% and 42%. Survival and local control were significantly better for the 21 patients who received doses greater than 5000 rad to the posterior fossa (85% and 80% respectively) than for the remaining patients (38% and 38%, respectively). Significant prognostic factors included achievement of local control in the posterior fossa (p = .0001) and dose to the posterior fossa (p = .0005). Sex, age, duration of symptoms, extent of surgery and initial T-stage of disease were not significant. Posterior fossa was the predominant site of failure (71% of failures), but 10% of patients failed in the cerebrum and 12% outside the CNS. This experience confirms that survival rates of 70-80% are achievable with current treatment policies but accurate and consistent dose delivery to the posterior fossa is essential.

Adolescent↗

Large fraction radiotherapy plus misonidazole for treatment of advanced lung cancer: report of a phase I/II trial.

From August 1978 through December 1979, 51 patients with advanced non-oat cell carcinoma of the lung were enrolled in a Phase I/II trial sponsored by the Radiation Therapy Oncology Group (RTOG) employing misonidazole (a 2-nitroimidazole) as a hypoxic cell sensitizer and radiation. The purpose of this study was to test drug and radiation tolerance and to assess the short term efficacy of this unconventional treatment. Tumor doses of 600 rad wer given twice weekly for three weeks for a total of 3600 rad, preceded four to six hours by misonidazole in a dose of 2 gm/m2 or 1.75 gm/m2, administered orally. Forty-nine patients were evaluable. Serious toxicity from this treatment was rare. Grade 2 or 3 peripheral neuro-toxicity occurred in eight of 24 patients (33%) with drug doses of 2 gm/m2 and in four of 26 patients (15%) who received 1.75 gm/m2. Grade 3 or 4 central nervous system toxicity occurred in two patients. Two patients developed serious late radiation complications: one patient had a transverse myelitis that appeared one year following delivery of 3600 rad to the spinal cord; a second patient developed a tracheoesophageal fistula and pericarditis eight months following treatment. Objective responses were reported in 67% of patients (complete in 18%); 70% of the patients died with a median survival time of nine months. Of 32 patients eligible for 12 month follow-up, 34% survived more than one year. Patterns of relapse after initial treatment and comparison with results from other RTOG trials using conventional fractionation are discussed.

Adenocarcinoma↗

Twenty-four-hour fluid intake and renal handling of electrolytes after various doses of ethanol.

The effects of single ethanol doses on fluid and electrolyte metabolism were studied in 31 male mongrel dogs. The animals were given either 0.75 g/kg 1.50 g/kg, or 2.25 g/kg of a 25% (v/v) ethanol solution or isovolumetric quantities of water. Fluid intake, urine output, and electrolyte (Na, K, Cl, Mg) excretions were measured at 0--3, 3--8, and 8--24 hr. During the ascending portion of the plasma ethanol curve (0--3 hr) there was a diuresis and renal magnesium loss in the two highest dosage ethanol groups. During the initial portion of the descending plasma ethanol curve (3--8 hr), each ethanol group had a significant elevation in voluntary intake. At 8--24 hr, renal retention of sodium, potassium, and chloride was found in the 1.5 and 2.25 g/kg groups, and magnesium excretion was also reduced in the 2.25 g/kg group. Over the 0--24 hr, none of the ethanol groups showed fluid loss, while the 2.25 g/kg ethanol group had significant retention of water. The administration of the 2.25 g/kg ethanol dose also resulted in 24-hr retention of sodium and potassium.

Animals↗

Recruitment of patients to cooperative group clinical trials.

One of the prerequisites for a successful clinical trial is the accrual of a sufficient number of patients for study. Because the sample-size requirements for a randomized clinical trial can rarely be met by a single institution in a short period of time, cooperative groups have taken in a major role in conducting clinical trials. In this paper, the recruitment of patients at our institution to a lung cancer clinical trial is evaluated. A total of 653 lung cancer cases were reviewed. Of the 77 cases which were eligible for the trial, 41 were accessioned. The reasons why eligible patients were not accessioned to the trial are discussed.

Clinical Trials as Topic↗