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Biomedical subjects

R S Benjamin

Publications and source records attributed to R S Benjamin.

At least 91 records · Page 5Linked to original sources

MDA-image: an environment of networked desktop computers for teleradiology/pathology.

MDA-Image, a project of The University of Texas M. D. Anderson Cancer Center, is an environment of networked desktop computers for teleradiology/pathology. Radiographic film is digitized with a film scanner and histopathologic slides are digitized using a red, green, and blue (RGB) video camera connected to a microscope. Digitized images are stored on a data server connected to the institution's computer communication network (Ethernet) and can be displayed from authorized desktop computers connected to Ethernet. Images are digitized for cases presented at the Bone Tumor Management Conference, a multidisciplinary conference in which treatment options are discussed among clinicians, surgeons, radiologists, pathologists, radiotherapists, and medical oncologists. These radiographic and histologic images are shown on a large screen computer monitor during the conference. They are available for later review for follow-up or representation.

Clinical Laboratory Information Systems↗

Response to chemotherapy does not predict survival after resection of sarcomatous pulmonary metastases.

Between 1979 and 1988, 26 patients with pulmonary metastases from adult soft-tissue sarcomas were treated with Adriamycin (doxorubicin hydrochloride), Cytoxan (cyclophosphamide), and DTIC before metastasectomy. Thirty-eight thoracotomies were performed with postoperative complications in 5 patients (5/38, 13.2%) and one postoperative death (1/38, 2.6%). Two patients had benign lesions at thoracotomy and were excluded from further survival analysis. The median survival of the remaining 24 patients after thoracotomy was 18.5 +/- 5.9 months, and the actuarial 5-year survival was 22%. Five patients (5/24, 21%) achieved a clinically complete response with preoperative chemotherapy, but all had recurrence in the lung and underwent resection of pulmonary metastases. Seven patients (7/24, 29%) achieved a partial response and had residual disease resected at thoracotomy. Twelve patients (12/24, 50%) showed either no change or disease progression while receiving chemotherapy and were referred for resection. Postthoracotomy disease-free survival and postthoracotomy overall survival did not differ significantly between the three groups. One patient in the group showing no change or progression of disease while receiving chemotherapy is alive without recurrence 57 months after initial pulmonary metastasectomy. Chemotherapy can be used for the initial treatment of pulmonary metastases from adult soft-tissue sarcomas. However, survival after resection of pulmonary metastases cannot be accurately predicted based on the clinical response to preoperative chemotherapy.

Adolescent↗

Single-dose murine monoclonal antibody ricin A chain immunotoxin in the treatment of metastatic melanoma: a phase I trial.

To determine the maximally tolerated dose of a ricin A chain-conjugated antimelanoma antibody (XomaZyme-Mel), 20 patients with metastatic melanoma were treated with escalating doses of the murine immunotoxin given as single intravenous infusion over 30 minutes. The starting dose was 0.6 mg/kg and was escalated in five groups to a maximum of 1.6 mg/kg. The maximally tolerated dose was 1.25 mg/kg as three of six patients treated at 1.6 mg/kg developed unacceptable toxicity. The dose-limiting toxicity consisted of profound fatigue, myalgias, and arthralgias. These occurred within 4 days and resolved in 7 to 10 days. Other non-dose-limiting toxicities encountered consisted of hypoalbuminemia, weight gain, peripheral edema, mild hypotension, and flu-like syndrome; the severity of these was also dose related. In addition, two allergic reactions occurred, one severe. There was one durable complete response of 12+ months' duration and one brief mixed response lasting 3 months. We conclude that the maximum tolerated single dose of XomaZyme-Mel is 1.25 mg/kg. Phase I studies evaluating 1.25 mg/kg given in multiple doses at 2- to 4-week intervals and phase II studies to determine the response rate of a single 1.25 mg/kg dose are warranted.

Adult↗

Extraskeletal osteosarcoma. A clinicopathologic review of 26 cases.

The clinical records and histopathologic features in 26 cases of extraskeletal osteosarcoma (ESOS) diagnosed at M.D. Anderson Cancer Center (Houston) between 1950 and 1987 were reviewed. Presentation was usually that of an enlarging soft tissue mass. The thigh (11 cases), upper extremity/shoulder girdle (three cases), and retroperitoneum (three cases) were the most common anatomic sites. Tumor size ranged from 2.5 to 30 cm. The predominant histologic pattern was osteoblastic in four cases, chondroblastic in two, fibroblastic or pleomorphic malignant fibrous histiocytoma (MFH)-like in four, giant cell type MFH-like in one, and small cell in one. Various mixtures of these patterns were seen in the remaining 14 tumors. The telangiectatic pattern was not seen as the predominant component in any primary tumor but was observed as a minor component. Thirteen tumors recurred locally and 16 metastasized; five patients had distant metastases at presentation. The lungs, bone, and soft tissue were the most frequent metastatic sites. Sixteen patients died of disease at 2 to 54 months, one patient died of unrelated causes at 61 months, seven patients were alive with no evidence of disease (NED) at 30 to 122 months, and two patients were alive with disease at 28 and 54 months, respectively. Tumor size (less than 5 cm versus greater than or equal to 5 cm) was the main prognostic factor; all patients alive with NED for whom accurate tumor measurements were available (six of seven) had neoplasms measuring less than 5 cm that were amenable to complete surgical excision. Histologic pattern and other clinicopathologic features did not significantly affect outcome.

Adult↗

A phase II trial of taxol in metastatic melanoma.

Taxol is an investigational new drug which is currently undergoing Phase II evaluation in various tumors. It is a plant alkaloid extracted from the western Yew, Taxus brevifolia. In this study, patients with metastatic melanoma who were previously untreated, received Taxol at a starting dose of 250 mg/m2 delivered as a continuous intravenous (IV) infusion over 24 hours, at 3-week intervals. All patients were premedicated with oral dexamethasone and IV diphenhydramine hydrochloride as prophylaxis against allergic reactions. Three of 25 patients had a partial response (PR) for a response rate of 12% (CI, 3%-31%). In addition four patients had objective regression of tumor that failed to qualify for a PR but these responses were as durable, lasting 6 to 17 months. No patient experienced acute allergic reactions. The major toxicity of Taxol was neutropenia requiring dose reduction to 200 mg/m2 in a majority of the patients. Our data confirm that Taxol has definite although limited activity against metastatic melanoma.

Adult↗

Radioimaging of melanoma using 99mTc-labeled Fab fragment reactive with a high molecular weight melanoma antigen.

Twenty patients with metastatic malignant melanoma were studied with 99mTc-labeled monoclonal antibody (MoAb) Fab fragment (NR-Ml-05) reactive with a high molecular weight (Mr 240,000) melanoma associated antigen. Patients received 40 mg unlabeled irrelevant MoAb (NR-2AD-IgG) and 7.5 mg unlabeled NR-Ml-05 (whole IgG) prior to infusion of 10 mg 99mTc-labeled (10-25 mCi) NR-Ml-05 Fab. Unlabeled MoAb were given to block nonspecific and specific binding sites. Gamma camera scans and single photon emission computed tomography were performed at 8 and 24 h postadministration. Of 172 preexisting lesions, 136 were imaged for a sensitivity of detection of 79%. Imaging was site and size dependent with the greatest sensitivity for liver lesions (100%) and the least for bowel (0%). Six sites (2 skin, 1 lung, 3 liver) were detected by single photon emission computed tomography that were missed on routine planar images. Forty-one additional unconfirmed sites were seen. Of these, 7 (17%) have been confirmed as tumor after a median follow-up time of 6 months. False positive scans included scar tissue, areas of chronic inflammation, an infected femoral aneurysm, and septic emboli. Nonspecific uptake of radioactivity occurred in kidney, gallbladder, bowel, thyroid, and myocardium. Human anti-mouse antibodies were detected in up to 69% of patients. In summary, radioimaging with 99mTc-NR-Ml-05 is a sensitive test, especially for detecting liver lesions. It is safe, simple to administer, and convenient for the patient. Biodistribution and imaging sensitivity differ significantly from studies in which 111In-labeled anti-melanoma MoAb have been used.

Adult↗

Malignant melanoma of soft parts (clear cell sarcoma). A study of 17 cases, with emphasis on prognostic factors.

Seventeen cases of malignant melanoma of soft parts (clear cell sarcoma) are reported. The patients ranged from 9 to 70 years of age, but 13 were between 10 and 40 years of age. There were eight male patients and nine female patients. The most common tumor location (seven patients) was the foot, followed by the area around the knee (four patients). The usual histologic pattern was that of variably sized nests of uniform plump spindle cells with clear to pale cytoplasm separated by fine to coarse fibrous septa; however, variants with a substantial proportion of epithelioid cells, moderate to marked nuclear pleomorphism, predominantly diffuse growth, or a microcystic pattern were seen. Patient survival was relatively poor overall (median, 49 months; ten deaths due to tumor) and was determined mainly by distant metastasis (11 patients). Both survival and distant metastasis were correlated with tumor size (P less than 0.01 for patients with tumors greater than or equal to 5 cm versus less than 5 cm). Other clinical and pathologic factors, including patient age, sex, and race, tumor location, duration of symptoms, initial therapy, mitotic rate, tumor necrosis, proportion of epithelioid cells, and nuclear pleomorphism had no significant relation to survival or distant metastasis when tumor size was taken into account. Local recurrence and regional lymph node metastasis each occurred in four patients.

Adolescent↗

Intracarotid cisplatin-based chemotherapy in patients with malignant melanoma and central nervous system (CNS) metastases.

Twenty-three patients with malignant melanoma metastatic to the central nervous system (CNS) were treated with intracarotid cisplatin-based chemotherapy. Twenty-two had failed prior cranial radiation therapy (one patient refused radiation therapy) and had progressive brain metastases documented by computerized tomography (CT). Intracarotid cisplatin 40-75 mg/m2 was administered alone (seven patients) with 1,3-bis(2-Chloroethyl)-1-nitrosourea (BCNU) (13 patients) or bleomycin (three patients). Courses were repeated monthly with CT scan. Seven patients (30%) had objective improvement in CT scans and three patients (13%) had stabilization of disease. The median time to tumor progression for responding patients was 20 weeks (range 8-34 weeks) while stable disease ranged from 9-12 weeks. In three patients the extracranial disease progressed while the brain metastases responded. Neurological and retinal toxicity were potential complications of therapy. Intracarotid cisplatin-based chemotherapy may be useful for palliation in selected patients with malignant melanoma and CNS metastases.

Adult↗

Preoperative chemotherapy for soft-tissue sarcomas of the extremities.

Forty-six patients with extremity soft-tissue sarcomas were treated with a mean of 4.4 cycles of preoperative adriamycin-based combination chemotherapy, followed by definitive local surgery and radiotherapy. All tumors were larger than 5 cm and of histologic type having significant risk of metastasis. Eighteen patients (40%) had an objective clinical response to the chemotherapy, while 27 patients (60%) did not respond. Patients with tumors responsive to chemotherapy had significantly improved overall survival (median 60 + months versus 32.7 months; p = 0.02), continuous disease-free survival (median 60 + months versus 15.1 months; p = 0.04), and distant metastasis-free survival (median 60+ months versus 28.5 months; p = 0.006) compared to the nonresponding patients. Tumor response to preoperative chemotherapy provides strong prognostic information and identifies a subgroup of patients most likely to benefit from chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

Osteosarcoma: MR imaging after preoperative chemotherapy.

The authors reviewed 76 magnetic resonance (MR) images of 38 patients with osteosarcoma treated with preoperative chemotherapy (intraarterial cisplatin with or without systemic chemotherapy). Histologic maps of the surgical tumor specimens in 33 cases were correlated with either late-chemotherapy or postchemotherapy MR images. There were four MR patterns--dark, mottled or speckled, homogeneous, and cystic--that corresponded to different amounts of tumor matrix, granulation tissue, hemosiderin deposits, fluid-filled cysts, and residual viable tumor. Nested foci of residual viable tumor could not be specifically identified, although tumor progression or skip metastases were accurately depicted in four patients. Other findings included (a) peritumoral edema in the soft tissues and intramedullary space that shrank with chemotherapy, (b) chemotherapy effect in the surrounding soft tissues, (c) a dark rim around the extramedullary component of the tumors corresponding to a collagenous capsule continuous with the periosteum, (d) development of metaphyseal hemorrhages and bone marrow infarcts, and (e) intramedullary vascular channels.

Adolescent↗

Recovery of sperm production after chemotherapy for osteosarcoma.

Because treatment with surgery and combination chemotherapy produces a high cure rate in young men with osteosarcoma, their subsequent reproductive function is an important concern. Semen analyses of osteosarcoma patients, therefore, were performed before, during, and after treatment with the PADIC regimen consisting of cisplatin, Adriamycin (doxorubicin), and dacarbazine or, in some cases, the PADIC regimen plus additional drugs. Results showed that semen volume was not affected and that sperm motility was reduced only during treatment. Although nearly all patients were rendered azoospermic during treatment, sperm production resumed in 30 of 32 patients examined at least 2 years after treatment. Analysis with correction for censored data indicates that, in 78% of treated men, sperm counts will return to more than 10 million/ml. The percentage of men whose sperm counts recovered to normal was lower for those receiving cisplatin dosages greater than or equal to 600 mg/m2; no trends were observed with Adriamycin and dacarbazine dosages. The inclusion of additional drugs such as methotrexate, bleomycin, dactinomycin, or cyclophosphamide (less than 4 g/m2) did not significantly affect the recovery of spermatogenesis. We conclude that the risk of long-term infertility from treatment with the PADIC regimen is low.

Adolescent↗

Advanced basal cell carcinoma and successful treatment with chemotherapy.

The patient presented in this report has a large basal cell carcinoma on the wrist and thigh. The lesion on the wrist was nonresectable without amputation. The patient showed an impressive response to chemotherapy with systemic cyclophosphamide, adriamycin, and intra-arterial cisplatin. The tumor could be excised by a simple excision on both sites and showed no residual tumor on the hand and only a microscopic focus on the thigh. The patient continues to be free of disease 3 years after the initiation of the therapy.

Antineoplastic Combined Chemotherapy Protocols↗

Phase I clinical trial and pharmacokinetic evaluation of 4'-0-tetrahydropyranyladriamycin (THP-adriamycin).

Tetrahydropyranyladriamycin (THP-adriamycin) is an anthracycline analogue currently under development in Europe and Japan. Preclinical studies suggest that it may have greater activity and less cardiac toxicity than doxorubicin. We conducted a phase I clinical and pharmacologic study of THP-adriamycin given as a weekly 15-min infusion for 3 weeks, followed by 1 week of observation. Therapy was associated with minimal acute toxicity. The dose-limiting toxicity was neutropenia, usually maximal during the 4th week after treatment; alopecia was rare. The maximum tolerated dose was 25 mg/m2; for phase II studies using this schedule, a dose of 20 mg/m2 weekly for 3 weeks is recommended. Pharmacokinetic studies revealed a triphasic elimination of the parent compound with alpha, beta, and gamma half-lives of 5.6 min, 1.4 h, and 9.3 h, respectively. THP-adriamycin was rapidly taken up by blood cell components, with concentrations in red blood cells (RBCs), lymphocytes, and polymorphonuclear cells exceeding those in plasma. In all, less than 10% of the compound was eliminated in the urine within 24 h.

Chromatography, High Pressure Liquid↗

Interleukin-2 alone and in combination with other cytokines in melanoma: the investigational approach at the University of Texas M.D. Anderson Cancer Center.

The clinical data that have been accumulated so far suggests a significant influence of IL-2 dose and schedule on the immunobiological effects and clinical toxicities observed with this cytokine. Consequently, the series of Phase I and Phase II clinical trials conducted at the University of Texas M. D. Anderson Cancer Center in patients with advanced malignant melanoma investigating the use of IL-2 in combination with other cytokines, monoclonal antibodies, or ex vivo activated effector cells have used a common dose and schedule of IL-2 administration for which abundant immunobiological information already exists. This approach allows cross-trial comparison of experience with toxicities, immunobiological observations and clinical activity by a group of investigators within a single institution, and more rapid and valid evolution towards combination biological therapy, which preclinical data suggest will have greater activity than single agent therapy.

Biological Factors↗

A comparative study of doxorubicin and epirubicin in patients with metastatic breast cancer.

Seventy-seven patients with progressive metastatic breast cancer refractory to prior therapy participated in a prospective randomized trial designed to compare the efficacy and toxicity of doxorubicin and epirubicin administered as single agents. In arm 1, 60 mg/m2 of doxorubicin and, in arm 2, 90 mg/m2 of epirubicin were administered by 48-h continuous i.v. infusion every 3 weeks. In arm 3, 90 mg/m2 of epirubicin was administered by bolus every 3 weeks. Patients in the three groups had similar characteristics, except that in arm 3 more patients were premenopausal, had more extensive disease, and fewer patients had been exposed to doxorubicin. Objective remission rates were 29, 26, and 13%, respectively for the three arms. Median response durations ranged from 4-6 months. No significant differences occurred in response rate, remission duration, or survival among patients in the three arms. The incidence of gastrointestinal toxicity and alopecia was evenly distributed. Hematologic toxicity was more severe in arms 2 and 3, and there was a higher incidence of infectious complications in arms 2 and 3 compared to arm 1 (p = 0.05). Two episodes of congestive heart failure occurred in arm 1, one in arm 2, and three in arm 3. Although the total cumulative anthracycline dosage was highest in the arm 2 group, they had the lowest incidence of cardiac toxicity. Epirubicin by bolus and doxorubicin administered by continuous infusion have similar potential for cardiac toxicity. Epirubicin administered by continuous infusion appears less cardiotoxic than doxorubicin by either method of administration or epirubicin given by bolus. Epirubicin appears equally active and less cardiotoxic than the parent compound doxorubicin in patients with metastatic breast cancer.

Adult↗

Osteosarcoma: angiographic assessment of response to preoperative chemotherapy.

Adjuvant chemotherapy prolongs the survival of patients with high-grade osteosarcoma. Preoperative chemotherapy allows identification of effective agents for adjuvant chemotherapy based on response of the primary tumor. Preoperative determination of tumor response has therapeutic implications, and angiography offers a less subjective means of assessing it than do conventional radiography or computed tomography. Changes in tumor vascularity, as seen angiographically, after two courses and at the time of the last of several courses of preoperative chemotherapy were correlated with histologic tumor necrosis of resected specimens in 81 patients. Angiographically, 40% of the histologic responders and 91% of the nonresponders were identified after two courses of preoperative chemotherapy. After a median of four courses of chemotherapy, 91% of the responders but only 50% of the nonresponders were identified angiographically. Angiographic assessment of tumor vascularity, although not of absolute value, offers a useful guideline for determining the preoperative chemotherapy strategy.

Adult↗