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Biomedical subjects

R F Meredith

Publications and source records attributed to R F Meredith.

At least 37 records · Page 2Linked to original sources
PubMed1995

Major geometric variations between multiple high-dose-rate applications of brachytherapy in cancer of the cervix: frequency and types of variation.

PURPOSE: To evaluate major geometric variations in multiple intracavitary applications for carcinoma of the cervix. MATERIALS AND METHODS: Orthogonal radiographs were reviewed of 17 consecutive patients with carcinoma of the cervix treated with 70 applications of high-dose-rate brachytherapy. In seven patients, conscious sedation was used for all applications. In 10 patients, general anesthesia was used for the first application and conscious sedation for subsequent applications. Major geometric variation between applications in axis, length, and slippage in tandem placement and separation, packing, and slippage in colpostats placement were reviewed. A major variation was defined as more than 1.0-cm deviation. RESULTS: Major variations between applications occurred more commonly in colpostats placement than in tandem placement. For tandems, the rates of variation were 5.7% in axis, 4.3% in length, and 1.4% in slippage. For colpostats, rates of variation were 7.1% in separation, 25.7% in vaginal packing, and 7.1% in slippage. No consistent pattern of variation was found between applications except in vaginal packing. CONCLUSION: Awareness of geometric variations should improve proper placement of intracavitary applicators for brachytherapy.

Anesthesia, General↗
PubMed1995

Initial clinical evaluation of iodine-125-labeled chimeric 17-1A for metastatic colon cancer.

UNLABELLED: The internalizing properties of murine antibody 17-1A in human colon cancer cells make it attractive as a carrier for radionuclides with short range emissions such as 125I. Murine 17-1A IgG2a antibody, which reacts against human gastrointestinal cancers, has been chimerized by joining its variable region with human IgG1 k constant region. A pilot clinical trial of increasing doses of 125I-chimeric 17-1A in patients with metastatic colorectal cancer has been conducted. METHODS: Patients were treated in groups of 2-4; 2 patients at Hahnemann University and 26 at the University of Alabama at Birmingham. Groups 1-5 received single administrations with 125I doses of 20, 40, 60, 80 or 100 mCi. Subsequent groups received therapeutic doses of 150, 200 or 250 mCi, with the dose subdivided into infusing of 50 or 100 mCi at 4-day intervals. All treatments were delivered in an outpatient setting using radiation precautions. Labeling at 10 mCi/mg antibody was performed on the day of treatment. RESULTS: Pharmocokinetics of circulating antibody was studied for initial patients, showing alpha T 1/2 of 17-27 hr and beta T 1/2 of 100-190 hr. Whole-body T 1/2 of radioactivity was determined by measuring urinary excretion or gamma emissions. Treatment was well tolerated without significant acute or late side effects. No significant bone marrow suppression or other dose-limiting toxicities were noted over this dose range. No objective responses were noted. CONCLUSION: These results show that high-dose outpatient radioimmunotherapy with an 125I-labeled internalizing antibody can be achieved without significant patient toxicity or radiation hazard.

Ambulatory Care↗
PubMed1994

Conventional four-field pelvic radiotherapy technique without CT treatment planning in cancer of the cervix: potential geographic miss.

The advantage of 4-field radiation to the pelvis is the use of lateral ports which spare the small bowel anteriorly and a portion of the rectum posteriorly from radiation. However, guidelines for the lateral pelvic ports are poorly defined. This is a comparative analysis to determine adequate margins by correlating conventional lateral pelvic treatment portals with CT defined tumor volume. The study included 52 patients treated definitively for carcinoma of the uterine cervix between 1986 and 1991. The most common site of inadequate margin (< or = 1.0 cm) was at the rectal block. The incidence of inadequate margin ranged from 39% to 50% and was independent of the stage of the disease except non-bulky stage IB disease. The next most common site was at the posterior border where frequency of inadequate margin for cervical tumor depended on stage with 8% of stage IB, 27% of stage IIB and 22% of stage IIIB/IVA disease. For the anterior border, an enlarged uterus was the only reason for inadequate margin rather than cervical tumor in 8% of stage IB, 18% of stage IIB, and 27% of stage IIIB/IVA disease. Without knowledge of precise tumor volume, the 4-field pelvic technique is potentially dangerous, risking underdosing of the tumor volume. For 4-field pelvic radiotherapy, we strongly recommend CT treatment planning.

Female↗
PubMed1994

Tumor associated glycoprotein-72 is highly expressed in prostatic adenocarcinomas.

We examined the expression of two well-characterized oncofetal antigens, the tumor associated glycoprotein-72 (TAG-72) and carcinoembryonic antigen (CEA), in malignant prostatic tissues. Three specific monoclonal antibodies, B72.3, CC49 and CC83, were used to examine the expression of TAG-72. Immunoreactivity was detected in 63% of the malignant specimens using B72.3. CC49 and CC83 were more sensitive than B72.3 in detecting TAG-72 expression. Immunoreactivity was detected in approximately 80% of prostatic adenocarcinomas with CC49 or CC83. The pattern and localization of TAG-72 immunoreactivity were similar for the three antibodies with most immunoreactivity observed within the cytoplasm of malignant cells and within the lumens of malignant glands. TAG-72 immunoreactivity was not detected within benign epithelium or stroma, with the exception of focal epithelial expression in areas of acute prostatitis. The COL-1 antibody to CEA did not detect CEA in benign glands, stroma, or malignant cells of prostate specimens resected for prostatic adenocarcinoma. These results demonstrate that TAG-72, but not CEA, is frequently expressed in prostatic adenocarcinomas.

Adenocarcinoma↗
PubMed1994

Treatment of metastatic prostate carcinoma with radiolabeled antibody CC49.

UNLABELLED: A Phase II trial of 75 mCi/m2 131I-anti-TAG-72 high-affinity antibody CC49 was studied in 15 patients with hormone-resistant metastatic prostate cancer. METHODS: Patients had adequate renal, liver and hematopoietic function. No previous cytotoxic chemotherapy was allowed and previous radiation was limited to 20% of the active bone marrow. RESULTS: No acute adverse reactions occurred, but all patients had evidence of an immune response to CC49 by 4 wk. Six of 10 symptomatic patients had bone pain relief, but no patients met the radiographic or PSA criteria for objective response. Positive imaging of bone and/or soft-tissue lesions was noted for 13 of the 15 patients. CONCLUSIONS: CC49 had a high frequency of tumor localization with evidence of anti-tumor effects (pain relief).

Adenocarcinoma↗
PubMed1993

Malignant epidural spinal cord compression associated with a paravertebral mass: its radiotherapeutic outcome on radiosensitivity.

PURPOSE: To evaluate clinical characteristics and functional outcome of malignant epidural spinal cord compression associated with a paravertebral mass. METHODS AND MATERIALS: Between 1987 and 1990, 136 patients with epidural spinal cord compression were treated with irradiation. Of these, 25 patients (18%) had epidural spinal cord compression associated with a paravertebral mass. This report is based on analysis of these 25 patients. Fourteen patients received 3000 cGy in 10 fractions. Seven received 4000 cGy in 16 fractions. Four received 2000 cGy in 5 fractions. Motor function was evaluated by five grades. RESULTS: Lung cancer accounted for the majority of epidural spinal cord compression with a paravertebral mass (60%) followed by lymphoma (8%) and kidney tumor (8%). This pattern of epidural spinal cord compression has a longer duration of pain before developing neurologic symptoms and has a high propensity of the upper thoracic spine involvement by an apical lung cancers. The functional outcome of radiation treatment reveals a significant difference between moderately radiosensitive tumors (lung, prostate, cervix, esophagus) and very radiosensitive tumor (lymphoma). None of the nonambulatory patients became ambulatory following radiotherapy except for the very radiosensitive tumors. Higher doses of radiation treatment (4000 cGy in 16 fractions) did not improve functional outcome. CONCLUSION: Due to the larger tumor burden, radiation treatment for epidural spinal cord compression associated with a paravertebral mass is not as effective as treatment of epidural spinal cord compression without a paravertebral mass except for the very radiosensitive tumor. Therefore, combined treatment modality might be beneficial for improving functional outcome.

Female↗
PubMed1993

Direct localization comparison of murine and chimeric B72.3 antibodies in patients with colon cancer.

To compare radiolocalization of murine B72.3 (m-B72.3) and mouse/human chimeric B72.3 (ch-B72.3) antibodies, five patients with biopsy confirmed adenocarcinoma of the colon received both radiolabeled antibodies 4 or 7 days before laparotomy. Following antibody administration, preoperative gamma camera images showed localization to sites of disease in four of the five patients. Autoradiography of resected specimens showed that both labeled antibodies localized specifically to the tumor with only minimal amounts in normal tissues. Radioactivity from each isotope in biopsy specimens of tumor and normal tissues was quantitated by scintillation gamma counting. Comparison of the percentages of injected activities for each antibody in resected tumor and normal tissue yields tumor to normal tissue radiolocalization ratios of 2.7-13.3 and 0.9-6.3 for murine and chimeric antibodies, respectively. The higher ratios for murine antibody were due to lower normal tissue levels, reflecting its faster clearance from the circulation, whereas the quantitative uptake of labeled antibody was always greater with the chimeric antibody. The chimera to murine antibody ratios in tumor of 1.1-2.7 suggest modest enhancement of tumor localization with chimeric antibody because of its longer half-life.

Aged↗
PubMed1992

Treatment of recurrent head and neck cancer with 5-fluorouracil, hydroxyurea, and reirradiation.

Head and neck cancer locally recurrent after previous irradiation and surgery presents a difficult management problem. Conventional treatment alternatives include chemotherapy, reirradiation with interstitial implant, and hyperthermia. Reirradiation with external beam is generally not considered because of previous high radiation dose and limited tissue tolerance. In this study, 21 patients with recurrent and previously irradiated head and neck cancer were treated in a Phase I-II fashion. Patients received 5 days of 5-fluorouracil, 300 mg/m2/day IV bolus, Hydroxyurea 1.5 or 2 g/day by mouth and external beam radiation therapy every 2 weeks for up to four courses. Of 20 evaluable patients, 9 have attained a complete response (CR) and 6 a partial response (PR). Fifteen patients completed all planned therapy, eight on time, seven patients with delays. With a median follow-up of 7 months, 13 patients are alive, 7 disease-free (3 after salvage surgery) and 6 with recurrence. Eight patients have died. The 1-year survival is 56%. Treatment toxicity was mainly neutropenia. No major early or late radiation related side effects have been observed at a median follow-up of 7 months. Neither previous radiation dose, time since first radiation, prior chemotherapy, or site of recurrence was predictive of response or treatment tolerance. Patients with a performance status of at least 80 had a significant higher CR rate, with 7/10 patients in this group, as compared to 2/10 patients in patients with a performance status less than 80, achieving a CR. Reirradiation with 5-fluorouracil and hydroxyurea is a well tolerated outpatient treatment program for patients with recurrent and previous irradiated head and neck cancer that produces a high response rate and can provide significant palliation of symptoms.

Adult↗
PubMed1992

A phase I study of high-dose cisplatin, prolonged infusion 5-fluorouracil, and concomitant conventional fraction radiation therapy in patients with inoperable squamous cell carcinoma of the head and neck.

Cisplatin (CDDP) and 5-fluorouracil (5-FU) have been used alone, in combination, and in various doses and sequences with radiation therapy in attempts to improve local control and survival of patients with advanced head and neck cancer. This study was undertaken to determine the toxicity and maximum tolerated dose of high-dose CDDP plus prolonged infusion 5-FU with concomitant conventional radiation therapy. Twenty-two patients with inoperable Stage III and IV squamous cell cancer were treated with CDDP (30 or 35 mg/m2 for 5 days every 4 weeks for three courses) and 5-FU (200 or 300 mg/m2 per day continuous i.v. infusion for 12 weeks) with concomitant conventional radiation therapy. This aggressive treatment regimen is accompanied by severe mucositis, myelosuppression, and chronic neuropathy. CDDP, 35 mg/m2/day x 5, and 200 mg/m2/day of 5-FU infused over 12 weeks were identified as potential doses for future Phase II studies.

Adult↗
PubMed1992

Dose fractionation of radiolabeled antibodies in patients with metastatic colon cancer.

Twelve patients with metastatic colon cancer were treated with 131I-chimeric B72.3 (IgG-4) at total doses of 28 or 36 mCi/m2 in two or three weekly fractions. Bone marrow suppression was the only significant side effect. The degree of bone marrow suppression adjusted for whole-body dose was modestly but statistically significantly (p = 0.04) less than that seen with identical doses given as a single infusion for the total dose of 36 mCi/m2. Nine of twelve patients developed an antibody response to ch B72.3, which altered the kinetics of radiolabeled antibody in four patients given a second course of therapy. One patient had a minor response that lasted 4 mo. Fractionation of this particular radiolabeled antibody at the dose schedule used produced a modest increase in the therapeutic window in regard to administered dose.

Adult↗
PubMed1992

Phase I trial of iodine-131-chimeric B72.3 (human IgG4) in metastatic colorectal cancer.

Twelve patients with metastatic colorectal cancer participated in a Phase I trial of 131I-labeled chimeric B72.3 (human IgG4). Consecutive groups of patients received 18 mCi/m2, 27 mCi/m2 and 36 mCi/m2. No acute side effects related to antibody administration were noted. Bone marrow suppression was the only side effect; it was dose-dependent and correlated with whole-body radiation dose estimates. The lowest dose level produced no marrow suppression, whereas 27 mCi/m2 resulted in Grade 1 and 2 marrow suppression in two of three patients. The maximum tolerated dose was 36 mCi/m2 with all six patients at this dose level having at least Grade 1 and two patients with Grade 3 and 4 marrow suppression. Eight of 12 patients had radioimmune imaging of tumor sites at 5-22 days. Seven patients had an antibody response to initial infusion. On retreatment, whole-body kinetics and imaging were altered for patients with a high anti-ch-B72.3 response. Thus, chimeric B72.3 (IgG4) has limited utility as a means of delivering multiple therapeutic doses of 131I in the majority of patients; alternative strategies including second generation anti-TAG-72 monoclonal antibodies, other radioisotopes and other chimeric human isotypes will need to be pursued.

Adenocarcinoma↗
PubMed1991

Pharmacokinetics and immune response of 131I-chimeric mouse/human B72.3 (human gamma 4) monoclonal antibody in humans.

Chimeric B72.3, composed of the V-regions of murine B72.3 and the constant regions of human immunoglobulin G4 heavy and kappa light chain, was administered as a 131I-labeled conjugate to 12 patients with metastatic colon cancer. Seven of these patients had an antibody response after initial infusion, and the immune response was primarily directed to the murine V-region, although a small proportion of the antibody response was directed to topographical epitopes requiring the presence of both murine V-region and human CH-1 and kappa constant regions (neo-epitopes). The pharmacokinetics included a plasma disappearance curve best fit by a two-compartmental model with an alpha t 1/2 of 18 +/- 7 h and a beta t 1/2 of 224 +/- 66 h. A second infusion of the same dose of 131I-chimeric B72.3 was administered to four of these patients 8 wk after the first infusion. Two patients who had a high antibody response to initial infusion had an anamnestic antibody response, and the infused ch-B72.3 rapidly disappeared from the circulation with associated immune complexes and free 131I in the plasma. One patient with no initial antibody response had no antibody response and identical pharmacokinetics on second infusion. One patient with a modest transient antibody response to initial infusion had no antibody response on second infusion and a modest shortening of plasma circulation. Thus, the human immunoglobulin G4 isotype chimeric B72.3 monoclonal antibody has a plasma half-life 6 to 8 times as long as murine B72.3 and retains considerable immunogenicity in some patients which can adversely affect repetitive infusions.

Animals↗
PubMed1991

A phase I study of prolonged infusion 5-fluorouracil and concomitant radiation therapy in patients with squamous cell cancer of the head and neck.

The radiosensitization properties of 5-FU are well documented, and clinical trials have suggested improved local control and survival in head and neck cancer. Clinical trials to date have used bolus injection or short term (less than or equal to 5 days) 5-FU infusions. To determine the maximum tolerated dose (MTD) of 5-FU given as continuous intravenous infusion for 12 weeks concomitant with conventional radiation therapy, 18 patients with advanced inoperable head and neck cancers were treated with conventional irradiation and 100, 200, 250, or 300 mg/m2/day of 5-FU. A dose of 250 mg/m2/day was determined to be the maximum tolerated dose and is recommended for Phase II studies.

Adult↗
PubMed1991

Expedient set-up of tangential breast fields with a simple gantry attachment.

A novel technique for setting up tangential fields is described. The technique uses a simple device (Breast Aligner) which attaches to the collimator of the treatment unit. The function of the Breast Aligner is similar to conventional front and back pointers except that the beam edge rather than central ray is defined. By delineating beam entrance and exit points at the posterior field edge, the device greatly simplifies and expedites set-up, and enhances precision of port alignment. Additional advantageous features include: (a) the ability to compensate for small inadvertent variations from the initial set-up position or for patient movement between the set-up of opposing ports, (b) the ability to visually check port alignment in the treatment position immediately before irradiation, and (c) decreased chance of human and equipment error by eliminating the need for measurements and calculations at the time of treatment. Our method can be used for SSD or SAD techniques and, with minor adjustment, is applicable for establishment of coplanar cephalad field borders as required at the junction of a supraclavicular field.

Breast Neoplasms↗
PubMed1991

Three-port perineal sparing technique.

The records were reviewed of 103 patients with low-lying pelvic malignancies irradiated with a skin-sparing technique involving use of a pair of anteroposterior-posteroanterior opposed ports and a direct perineal port. Patients had rectal, anal, cervical, vaginal, urethral, or vulvar cancer. Use of a special lead compensator allowed the three beams to be applied perpendicularly to the surface, while delivery of a homogeneous dose to the pelvis and perineum was maintained. Skin dose with this method was greatly reduced compared with that delivered with simple opposing or four-port techniques, in which irradiation is tangential to the surface at the perineum. Acute perineal skin irritation was assigned a grade between 0 and 3, with grade 0 representing the least amount of irritation. All patients were in the grade 0 or grade 1 category. Patients treated for low-lying rectal carcinoma showed no increase in perineal recurrences when compared with historic control subjects. Use of this approach allowed delivery of adequate doses to the pelvis and perineum and a definite decrease in local toxic effects, and local control was not compromised.

Adenocarcinoma↗
PubMed1991

Pharmacokinetics, immune response, and biodistribution of iodine-131-labeled chimeric mouse/human IgG1,k 17-1A monoclonal antibody.

Pharmacokinetics, immunogenicity, and biodistribution of a 131I-labeled mouse/human chimeric monoclonal antibody (C-17-1A) was studied in six metastatic colon cancer patients. Pharmacokinetics obtained from serum radioactivity or chimera concentration were identical after 5 mCi of 131I-C-17-1A with mean alpha half-lives of 17.6 +/- 2.3 and 19.7 +/- 2.9 and mean beta half-lives of 100.9 +/- 16.1 and 106.4 +/- 14.1 hr, respectively. HPLC analysis documented the monomeric chimeric 17-1A without evidence of immune complexes or free 131I. None of the patients developed antibody after 131I-chimeric 17-1A exposure. Radiolocalization occurred in known areas of disease greater than 4 cm in all patients. The half-life of total-body radioactivity was 58 +/- 7 hr by whole-body counts and 64 +/- 13 hr by urine measurements. Whole-body and bone marrow dose estimates ranged from 0.75-1.03 and 0.76-1.05 rad/mCi, respectively. These studies confirm the prolonged circulation and reduced immunogenicity of chimeric 17-1A versus murine 17-1A. Marrow radiation exposure using antibodies with prolonged circulation is a critical factor in planning for radioimmunotherapeutic applications.

Adenocarcinoma↗
PubMed1990

Extradural spinal cord compression: analysis of factors determining functional prognosis--prospective study.

The treatment results in 59 patients with extradural spinal cord compression (ESCC) who were treated with irradiation between April 1987 and December 1988 were analyzed prospectively. Eighty percent of the patients presented with back pain, which preceded ESCC by an average of 6 weeks. The most common primary tumor was lung cancer (27% of cases), followed by prostate cancer and breast cancer. The prognostic significance of pretreatment motor function, degree of spinal cord block, radiosensitivity of tumor, and radiation dose schedule was determined with multivariate analysis. Only pretreatment motor function was found to be a significant factor in determining functional prognosis (P = .0058). Even with the increasing clinical awareness of ESCC, 78% of the patients in the current series were nonambulatory at presentation. Therefore, computed tomographic myelography or magnetic resonance imaging is recommended for patients with back pain and bone destruction at the site of the complaint if local radiation treatment is not planned.

Adolescent↗