Biomedical subjects

S Leibel

Publications and source records attributed to S Leibel.

60 records · Page 4Linked to original sources

PubMed1983

Phase I trial of intravenous L-phenylalanine mustard plus the sensitizer misonidazole.

Misonidazole (MISO), a hypoxic cell radiosensitizer, has been shown in vivo to enhance tumor cell killing by melphalan (LPAM) with little or no enhancement of normal tissue injury. A Phase I trial was conducted using MISO p.o. 2 hr before i.v. LPAM. The highest doses used were the single maximum tolerated doses of MISO, 4 g/sq m, and LPAM, 0.6 mg/kg. Thirty-five patients were entered; 30 were evaluable for assessment of hematological toxicity, which was predicted to be the dose-limiting toxicity. The median age was 60 years (range, 28 to 72 years). Mild to moderate nausea and vomiting occurred in 80% of patients. Five developed serious hematological toxicity defined as nadir white blood cell count less than 1000/cu mm, platelets less than 20,000/cu mm or 4-week posttreatment white blood cell count less than 2000/cu mm, platelets less than 50,000/cu mm. Four of the toxicities occurred at the LPAM dose of 0.6 mg/kg but were independent of MISO dose. One patient died of infection. Two patients whose tumor demonstrated an objective response to therapy and 10 others with disease stabilization received additional courses. Four patients developed mild MISO neuropathy. Pharmacokinetic studies demonstrated that MISO did not appear to affect the pharmacokinetics of LPAM in plasma. Both LPAM and MISO can be given safely at their individual maximum tolerated dose. This combination will proceed to Phase II trials.

Adult↗

PubMed1981

The integration of new therapies and radiation in the management of ovarian cancer.

New biologic information has led to a therapeutic program in Stage III ovarian cancer that considers the whole peritoneal cavity the tumor-bearing region and that uses intraperitoneal administration of ovarian cancer antiserum, intraperitoneal P-32, delayed split abdominal irradiation, and chemotherapy. The survival for those patients completing irradiation was 85%. Forty-nine patients with advanced (Stage III, IV, or recurrent) ovarian cancer have been treated with combinations of the present agents. Twenty-two patients have received intraperitoneal ovarian cancer antiserum without significant toxicity. Extensive staging has been a requirement for initial evaluation and includes maximal surgical resection, omentectomy, TAH and BSO, nodal biopsies, and peritoneal cytology. Nineteen patients had 5-mm nodules or less residual disease and were treated with colloidal P-32, abdominal irradiation, and chemotherapy; five of these patients received intraperitoneal antiserum before cytotoxic therapy. The four-year cumulative survival is 84%, and the disease-free survival 43%. A randomized prospective study is now examining the value of antiserum therapy. New experimental data from our laboratory indicate 1) the value of 2/3 biomarkers (alpha globulin and free secretory protein) in following patients for remission of disease and 2) the probability of the development of more effective antiserum with high specific titer. Studies of the radiosensitivity of ovarian cancer indicate the tumor was not different from other solid tumors. Our studies indicate the role of radiation therapy as a cytoreductive agent should be integrated in multimodality therapy and that the immune system offers new possibilities in amplifying therapeutic results.

Alpha-Globulins↗

PubMed1980

The value of ultrasonic imaging and CT scanning in planning the radiotherapy for prostatic carcinoma.

Forty-four consecutive patients with potentially curable carcinoma of the prostate were localized with an Old Delft Simulator with the methods described by Bagshaw. The isocenter and the treatment portal were marked on the skin of the patient. Subsequently, the adequacy of the portal was checked by ultrasonography and/or CT scanning. Of 30 patients who underwent ultrasonography, five patients (17%) were found to have tumor extending beyond the initially simulated treatment portals. Using CT scanning, three of 22 patients were found to have tumor extending beyond the initially simulated portals. As a result, 1-2 cm were added to the initially simulated treatment portals for adequate coverage of the tumor volumes. Eight of our 44 patients underwent both studies and results were similar with ultrasonography and CT scanning. Only patients in the group presenting with clinical stage C disease had modifications of the initially simulated treatment portal. It is recommended that conventional simulation should be done first in order to establish the isocenter and treatment volume, which then should be confirmed by ultrasonography or CT scanning.

Aged↗

PubMedDate not supplied

Clinically relevant optimization of 3-D conformal treatments.

In this paper a method of computer-aided optimization of 3-D conformal treatment plans is presented which incorporates models to predict the clinical consequences of resulting dose distributions. Even though these models are simplistic, it is submitted that their intelligent use leads to treatment plans which indicate lower normal tissue complications and higher tumor control. Dose distribution data, biological models, and observed normal tissue and tumor response data are used to compute tumor control and normal tissue complication probabilities for each of the critical normal structures encountered in a treatment plan. These quantities are combined into a single score using an objective function which incorporates the importance of each end point as assessed by the physician. Using the "simulated annealing" method of optimization, the beam weights are adjusted to maximize the score. Additional constraints are applied to ensure consistency of the results of optimization with the judgment of the physician. These optimization methods have been applied to conformal treatment plans consisting of multiple fixed fields with conformal field shaping. The results indicate that the methods presented have considerable potential.

Aged↗

PubMedDate not supplied

Risk profiles to predict PSA relapse-free survival for patients undergoing permanent prostate brachytherapy.

PURPOSE: Combined risk profiles are helpful in assessing the likelihood of prostate-specific antigen relapse-free survival (PSA-RFS) for patients with localized prostate cancer. This retrospective analysis reports the 5-year biochemical outcome of a large cohort of patients according to prognostic factors and risk profiles for patients undergoing ultrasound-guided transperineal interstitial permanent prostate brachytherapy (TIPPB). PATIENTS AND METHODS: Seven hundred seventeen consecutive patients with clinically localized prostate cancer treated between June 1992 and November 1997 underwent TIPPB. Palladium-103 (103Pd) (n = 539) or iodine-125 (125I) (n = 178) sources were utilized to a prescribed dose of 120 Gy and 144 Gy, respectively. One hundred eleven patients received combined external-beam irradiation (41.4 or 45 Gy) and TIPPB (103Pd, 90 Gy, and 125I, 108 Gy). One hundred twelve patients received androgen ablation therapy in advance of TIPPB. Patients were grouped into risk profiles based on pretreatment factors that consisted of PSA < or = 10 and Gleason score < or = 6. Patients meeting both criteria were classified as favorable (n = 334). Those not fulfilling one criteria were classified as intermediate risk (n = 261), and those not fulfilling two criteria were classified as unfavorable risk (n = 261). PSA-RFS was calculated based on the American Society of Therapeutic Radiology and Oncology consensus conference definition of PSA failure. The median follow-up was 41 months (range, 14-82 months). RESULTS: The actuarial PSA-RFS survival at 5 years was 82%. Multivariate Cox regression analysis identified PSA and Gleason score as highly significant factors predicting for biochemical outcome. Hazard risk ratios using a nadir definition of the PSA as < or = 1.0 ng/mL and < or = 0.5 ng/mL were each significant predictors of outcome with the 0.5 ng/mL nadir level only slightly better (risk ratio for nadir < or = 1.0 = 2.78; risk ratio for nadir < or = 0.5 = 3.57). Favorable-risk patients had a 5-year actuarial PSA-RFS of 93%, whereas intermediate-risk and unfavorable-risk groups had 5-year PSA-RFSs of 77% and 62%, respectively. Four hundred ninety-three patients underwent brachytherapy without external-beam irradiation or androgen ablation. From this group, the 5-year PSA-RFSs for the favorable-risk, intermediate-risk, and unfavorable-risk patients were 92%, 74%, and 55%, respectively. DISCUSSION: This retrospective study examining TIPPB demonstrated excellent 5-year actuarial PSA-RFS rates. The assignment of risk profiles based on the results of multivariate analysis of prognostic factors identifies the expected PSA-RFS for patients undergoing TIPPB.

Adenocarcinoma↗

PubMedDate not supplied

Final report of the 70.2-Gy and 75.6-Gy dose levels of a phase I dose escalation study using three-dimensional conformal radiotherapy in the treatment of inoperable non-small cell lung cancer.

PURPOSE AND OBJECTIVE: Three-dimensional conformal radiotherapy (3D-CRT) is a mode of high-precision radiotherapy designed to increase the tumor dose and decrease the dose to normal tissues. This study reports the final results of the first two dose levels (70.2 Gy and 75.6 Gy) of a phase I dose-escalation study using 3D-CRT for the treatment of non-small cell lung cancer. PATIENTS AND METHODS: Fifty-two patients were treated with 3D-CRT without chemotherapy. The median age was 67 years (range, 39-82 years). The majority of patients had locally advanced cancer. Tumor was staged as I/II in 10%, IIIA in 40%, and IIIB in 50%. Radiation was delivered in daily fractions of 1.8 Gy, 5 days a week. A radiation dose level was considered complete when 10 patients received the intended dose without unacceptable acute morbidity. Toxicity was scored according to the Radiation Therapy Oncology Group grading scheme. RESULTS: Twenty patients were initially assigned to the 70.2-Gy level; 14 of them received the intended dose. Three patients experienced severe acute toxicity, two with grade 3 (requiring steroids or oxygen) and a third with grade 5 (fatal) acute radiation pneumonitis. Because of the grade 5 pulmonary toxicity, the protocol was modified, and only patients with a calculated risk of normal tissue complication of less than 25% were eligible for dose escalation. Patients who had a normal tissue complication probability (NTCP) of greater than 25% received a lower dose of radiation. An additional 18 patients were entered on the modified study; 11 of them received 70.2 Gy. One patient experienced grade 3 acute pneumonitis. Despite dose reduction in four patients because of an unacceptably high NTCP, two additional patients developed grade 3 pulmonary toxicity. Fourteen patients were accrued to the 75.6-Gy dose level, and 10 received the intended dose. One of the 10 patients experienced grade 3 pulmonary toxicity and one developed grade 3 esophageal toxicity. Three patients were treated to lower doses as a result of their calculated NTCP without toxicity, and one patient refused treatment. The 2-year local control, disease-free survival, and overall survival rates were 37%, 12%, and 24%, respectively. The median survival time was 11 months. DISCUSSION: Treatment to 70.2 Gy and 75.6 Gy using 3D-CRT was delivered with acceptable morbidity when NTCP constraints were observed. Local control was encouraging in these patients with locally advanced disease. Patients are currently being accrued to the 81-Gy level of the study.

Adult↗