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Biomedical subjects

J Szanto

Publications and source records attributed to J Szanto.

At least 19 recordsLinked to original sources
PubMed2004

Irinotecan in combination with 5-fluorouracil and folinic acid or with cisplatin in patients with advanced gastric or esophageal-gastric junction adenocarcinoma: results of a randomized phase II study.

BACKGROUND: To identify the most effective of two combinations, irinotecan/5-fluorouracil (5-FU)/folinic acid (FA) and irinotecan/cisplatin, in the treatment of advanced gastric cancer, for investigation in a phase III trial. PATIENTS AND METHODS: Patients were randomized to receive irinotecan [80 mg/m2 intravenously (i.v.)], FA (500 mg/m2 i.v.) and a 22-h infusion of 5-FU (2000 mg/m2 i.v.), weekly for 6 weeks with a 1-week rest, or irinotecan (200 mg/m2 i.v.) and cisplatin (60 mg/m2 i.v.), on day 1 for 3 weeks. RESULTS: A total of 115 patients were eligible for analysis in the per-protocol population. The overall response rate in the irinotecan/5-FU/FA arm (n=59) was 42.4%, with a complete response rate of 5.1%. Corresponding figures for the irinotecan/cisplatin arm (n=56) were 32.1% and 1.8%, respectively. The median time to progression was 6.5 months (irinotecan/5-FU/FA) and 4.2 months (irinotecan/cisplatin) (P < 0.0001), with median survival times of 10.7 and 6.9 months, respectively (P=0.0018). The major toxicity was grade 3/4 neutropenia, which was more pronounced with irinotecan/cisplatin than with irinotecan/5-FU/FA (65.7% versus 27%). Diarrhea was the main grade 3/4 non-hematological toxicity with both irinotecan/5-FU/FA (27.0%) and irinotecan/cisplatin (18.1%). CONCLUSIONS: Both combinations were active, with acceptable safety profiles. Irinotecan/5-FU/FA was selected as the most effective combination for investigation in a phase III trial in advanced gastric cancer.

Adenocarcinoma↗
PubMed2003

[Radiation sensitivity testing and late neurological complications following radiosurgery for AVM: the use of SF2 from fibroblasts as a predictive factor].

PURPOSE: To identify SF2 as a prognostic factor of late complications from radiosurgery in patients treated for AVM. PATIENTS AND METHODS: Five patients with AVM treated in three canadian institutions and who suffered clinically significant neurological sequelaes secondary to radiosurgery were identified. Their fibroblasts were cultured and their radiation sensitivity tested to determine the SF2 for each patient. RESULTS: Patients who developed a neurological complication from radionecrosis, secondary to radiosurgery had an SF2 different than the two control patients with AVM and no complications and also from a group of five cancer patients without late radiation complications (P = 0.005). CONCLUSION: Radiosurgery is an elective procedure. The identification of a subgroup of patients who are radiosensitive and at a higher risk of radiation induced complications can allow the treatment team to reduce the risk of such complications. SF2 as a new predictive factor should be incorporated in predictive models of risk from treatment of AVM by radiosurgery. This work needs to be confirmed in a larger cohort of patients.

Cell Survival↗
PubMed2001

Treatment planning aids in prostate cancer: friend or foe?

BACKGROUND: Rectal barium is commonly used as a treatment planning aid for prostate cancer to delineate the anterior rectal wall. Previous research at the Ottawa Regional Cancer Centre demonstrated that retrograde urethrography results in a systematic shift of the prostate. We postulated that rectal barium could also cause prostate motion. PURPOSE: The study was designed to evaluate the effects of rectal barium on prostate position. METHODS AND MATERIALS: Thirty patients with cT1-T3 prostate cancer were evaluated. Three fiducial markers were placed in the prostate. During simulation, baseline posterior-anterior and lateral films were taken. Repeat films were taken after rectal barium opacification. The prostate position (identified by the fiducials) relative to bony landmarks was compared before and after rectal barium. Films were analyzed using PIPsPro software. RESULTS: The rectal barium procedure resulted in a significant displacement of the prostate in the anterior and superior direction. The mean displacement of the prostate measured on the lateral films was 3.8 mm (SD: 4.4 mm) in the superior direction and 3.0 mm (SD: 3.1) in the anterior direction. CONCLUSIONS: Rectal barium opacification results in a systematic shift of the prostate. This error could result in a geographic miss of the target; therefore, alternate methods of normal tissue definition should be used.

Aged↗
PubMed2000

Severe normal tissue complication correlates with increased in vitro fibroblast radiosensitivity in radical prostate radiotherapy: a case report.

The radiation responses of fibroblasts taken from four patients undergoing radiotherapy for prostate cancer were evaluated in vitro. One patient exhibited a severe normal tissue late reaction after radiotherapy, and the fibroblasts from this patient also showed increased radiosensitivity. The other three patients exhibited a normal clinical response, and their fibroblast response in vitro was also considered normal when compared with previously published data from our laboratory. When cells were allowed to repair potentially lethal damage (PLDR), the differences between cell lines were reduced; therefore, a deficiency in PLDR did not cause the differences in radiosensitivity. Fractionated radiation resulted in elevated survival due to repair of sublethal damage (SLDR), and the differences in radiosensitivity were increased. In addition, the survival curves displayed an upward bending nature, indicative of an adaptive response. Thus, adaptive response and ability to modify it may play an important role in fractionated radiotherapy. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 336-342 (2000).

Aged↗
PubMed2000

A prospective comparison of three systems of patient immobilization for prostate radiotherapy.

PURPOSE: The study compared the setup reliability of 3 patient immobilization systems, a rubber leg cushion, the alpha cradle, and the thermoplastic Hipfix device, in 77 patients with cT1-T3, N0, M0 prostate cancer receiving conformal radiotherapy. METHODS AND MATERIALS: Port films were analyzed and compared to simulation films to estimate the setup errors in the three coordinate axes (anterior-posterior, cranial-caudal, medial-lateral). A total vector error was calculated from these shifts. RESULTS: The Hipfix was found significantly superior to the other two devices in reducing mean setup errors in all axes (p < 0.005). The average field-positioning error with the Hipfix ranged from 1.9 mm to 2.6 mm for all axes, whereas the deviation for the other two systems ranged from 2.7 to 3. 4 mm. Errors greater than 10 mm were virtually eliminated with the Hipfix system. There was a reduction in the mean total vector error in the alpha cradle and Hipfix patient cohorts over time, reflecting improved efficacy as a result of experience. CONCLUSION: There was a significant difference in the performance of each immobilization device. The Hipfix was consistently more reliable in reducing setup errors than the other devices.

Analysis of Variance↗
PubMed2000

Respiratory-induced prostate motion: quantification and characterization.

PURPOSE: The precise localization of the prostate is critical for dose-escalated conformal radiotherapy. This study identifies and characterizes a potential cause of inaccurate prostatic localization-respiratory-induced movement. METHODS AND MATERIALS: Prostate movement during respiration was measured fluoroscopically using implanted gold fiducial markers. Twenty sequential patients with CT(1)-T(3) N(0) M(0) prostate carcinoma were evaluated prone, immobilized in customized thermoplastic shells. A second 20 patients were evaluated both prone (with and without their thermoplastic shells) and supine (without their shells). RESULTS: When the patients were immobilized prone in thermoplastic shells, the prostate moved synchronously with respiration. In the study the prostate was displaced a mean distance of 3.3 +/- 1.8 (SD) mm (range, 1-10.2 mm), with 23% (9/40) of the displacements being 4 mm or greater. The respiratory-associated prostate movement decreased significantly when the thermoplastic shells were removed. CONCLUSION: Significant prostate movement can be induced by respiration when patients are immobilized in thermoplastic shells. This movement presumably is related to transmitted intraabdominal pressure within the confined space of the shells. Careful attention to the details of immobilization and to the possibility of respiratory-induced prostate movements is important when employing small field margins in prostatic radiotherapy.

Algorithms↗
PubMed2000

Effects of urethrography on prostate position: considerations for radiotherapy treatment planning of prostate carcinoma.

PURPOSE: Retrograde urethrography is commonly used to define the prostate apex at simulation. This study evaluated the hypothesis that urethrography causes prostate displacement, resulting in an error in treatment planning. METHODS AND MATERIALS: Forty-five patients with carcinoma of the prostate were evaluated. Gold seeds were placed in the apex, posterior wall, and base of the gland. In the first 20 patients, the position of the seed-defined apex was compared at simulation (with urethrogram) and on day 1 of treatment (without urethrogram). In the second cohort of 25 patients, the effects of urethrography on prostate position were evaluated directly at simulation by comparing the position of apex pre- and post-urethrography. An analysis was performed to estimate the possible impact of urethrogram-induced prostate motion on target coverage. RESULTS: The mean superior displacement in the first and second cohort was 5.2 mm and 6.8 mm, respectively (combined mean shift 6.1 mm). With a 10-mm field margin below the tip of the urethrogram cone, 56% of patients in this study would have inadequate planning target volume (PTV) coverage. CONCLUSION: Retrograde urethrography causes a significant superior shift of the prostate. Strict reliance on urethrography in determining the inferior field margin could result in inadequate treatment.

Adenocarcinoma↗
PubMed1999

Maintenance treatment with medroxyprogesterone acetate in patients with advanced breast cancer responding to chemotherapy: results of a randomized trial. Essen Breast Cancer Study Group.

The purpose of this randomized phase III trial was to study whether medroxyprogesterone acetate (MPA) maintenance treatment prolongs the time to progression in advanced breast cancer patients responding to an induction chemotherapy. Patients with progressive advanced breast cancer previously untreated with anthracylines and progestins were given epirubicin (30 mg/m2) and ifosfamide (2 g/m2) on days 1 and 8 at 3-weekly intervals. Patients without disease progression after 6 cycles of chemotherapy were randomly assigned to receive, until progression, either no treatment or MPA at a daily total dose of 500 mg. Ninety patients were randomized: 46 to the MPA arm and 44 to the observation arm. Median time to progression was longer in the MPA arm: 4.9 months versus 3.7 months in the intent-to-treat analysis (p = 0.02), and 4.9 months versus 3.0 months in the secondary efficacy analysis (p = 0.012). Seven patients were removed from MPA due to side effects. The changes in patient-rated quality of life scores were similar in both groups. The median length of survival from randomization was 17.4 months for patients receiving MPA and 18.3 months for patients randomized to observation (p = 0.39). In conclusion, in patients with advanced breast cancer achieving remission or non-progression with 6 cycles of epirubicin and ifosfamide chemotherapy, MPA maintenance treatment led to a significant, though modest, prolongation of the time to progression without affecting overall survival of the study patients.

Aged↗
PubMed1996

Epirubicin and ifosfamide in metastatic breast cancer.

In a randomized, phase II trial, we evaluated the effectiveness of continued chemotherapy with epirubicin/ ifosfamide versus unmaintained treatment interruption in advanced metastatic breast cancer. Three hundred fifty-seven patients were enrolled and 331 were evaluable for response. Complete response was achieved in 25 patients (8%) and partial response in 121 patients (37%). Pretreatment status correlated significantly with response (complete and partial response). While 54% of unpretreated patients responded, only 42% of the patients responded who had been pretreated with adjuvant chemotherapy and 33% who had been pretreated in the metastatic stage of disease; 69 patients (21%) had disease progression. Of 11 patients pretreated in both the adjuvant and metastatic setting, only two responded. Toxicity of treatment was mild, with leukopenia being the treatment-limiting factor. Thrombocyte levels were not altered significantly by treatment. Thus, there seems to be room for dose escalation using granulocyte colony-stimulating factor. There was no considerable cardiotoxicity, central nervous system toxicity, or cystitis observed. The low rate of cardiotoxicity appeared to be related to dose fractionation of epirubicin. After randomization of patients to treatment interruption versus continuation of chemotherapy, a longer relapse-free survival was observed for patients who continued chemotherapy (mean relapse-free survival, 2+ months); however, this did not translate into prolonged survival. The cumulative scores of toxicity and quality of life parameters showed increasing superiority for treatment interruption. Therefore, a strategy of treatment until maximum response and subsequent treatment interruption seems to be superior to treatment continuation.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Asymmetric arc technique for posterior pharyngeal wall and retropharyngeal space tumors.

PURPOSE: Tumors of the posterior pharyngeal wall and nasopharyngeal cancer with retropharyngeal extension can partly encircle the cervical vertebrae. Treating the patient within spinal cord tolerance can cause a geographic miss. A simple technique has been developed to avoid this problem. METHODS AND MATERIALS: The standard fields for posterior pharyngeal wall and nasopharyngeal tumors are used up to 36-40 Gy. A planning computed tomography (CT) scan is taken during the second or third week of treatment with the patient fitted in a new shell ensuring that the cord is straight and parallel to the treatment couch. The asymmetric arc technique consists of two posterior arcs with closure of one jaw beyond the central axis. Each arc delivers the total dose to each ipsilateral side, while the median region of the U-shaped volume is treated by the summation of both arcs. RESULTS: We have treated 10 patients using asymmetric arcs in the last 3 years. This technique proved to be a versatile way of treating targets wrapped around the spine. The technique allows better individualization for target volume irregularities than the partial rotation with a central bar.

Humans↗
PubMed1995

Lateral electron equilibrium and electron contamination in measurements of head-scatter factors using miniphantoms and brass caps.

The head-scatter factor (Sh) can be measured with a narrow miniphantom or a metal cap provided it is completely covered by the photon beam and its lateral size is thick enough to prevent electron contamination contributions. The effects of lateral electron equilibrium (LEE) and electron contamination on the Sh values were studied. The EGS4 Monte Carlo technique was used to calculate the minimum beam radii (rLEE) required to achieve complete LEE for photon beams ranging from 60Co to 24 MV. The measurement shows that the error introduced to the Sh value due to lateral electron disequilibrium is negligible. The radii of the miniphantoms or the sidewall thicknesses of the caps can be reduced below rLEE provided they are thick enough to prevent the effect of electron contamination.

Biophysical Phenomena↗
PubMed1994

A translating-bed technique for total-body irradiation.

Total-body irradiation (TBI) is a therapy modality that is being used with increasing frequency, in conjunction with chemotherapy, for patients undergoing bone-marrow transplantation. At the Ottawa Regional Cancer Centre a technique has been developed for the delivery of TBI to patients prior to bone-marrow transplantation. In this technique patients are treated on a mobile couch at approximately 195 cm SSD with a field size of 66.5 cm wide by 57 cm long. A computer-controlled stepping motor drives the patient couch at a user-selectable speed. The total dose delivered to the patient is a function of couch velocity, field size and patient separation. Treatment times are of the order of 10 min for each of the anterior and posterior fields for a 400 cGy fraction. It has been found that the conventional central axis tissue maximum ratio (TMR) and percentage depth dose (PDD) functions are not appropriate for describing dose delivered during dynamic treatment. To this end we have developed dynamic TMR and PDD functions. Extensive measurements have been performed in an anthropomorphic water phantom to determine the dose distributions in three dimensions and the efficacy of polymethyl methacrylate (PMMA) beam spoilers as a replacement for anterior and lateral bolus. It has been found that 2.4 cm PMMA spoilers do provide full skin dose and negate the requirement for lateral bolus. This TBI procedure is simple, rapid and appears to be well tolerated by the patients. 55 patients have been treated since the introduction of this technique in 1991.

Bone Marrow Transplantation↗
PubMed1992

The clinical use of thermocouple thermometry.

The development of a clinical thermometry system entails solving both clinical and technical problems. A thermometry system will, in general, be comprised of a temperature transducing element, a mechanism for interrogating the transducer temperature, and a means of interpreting, reporting and recording the measured temperature. Thermocouples are thermometers which report their own temperature, while the parameter of interest is the temperature of the medium. The two key questions which arise are then: (1) is the thermometer correctly reporting its own temperature, and (2) what is the relationship between the medium temperature and the thermometer temperature? In this work some of the important parameters influencing the temperature of the thermometer and the thermal relationship between the thermometer and the medium are investigated.

Body Temperature↗
PubMed1987

Efficacy of dichlorvos, fenbendazole, and ivermectin in swine with induced intestinal nematode infections.

Anthelmintic efficacies of dichlorvos, fenbendazole, and ivermectin were compared in specific-pathogen-free crossbred weanling pigs inoculated with Ascaris suum, Trichuris suis, and Oesophagostomum dentatum. On postinoculation day (PID) 50, 24 pigs in each treatment group were treated orally with 43 mg of dichlorvos/kg of body weight, 3 X 3 mg of fenbendazole/kg, or 300 micrograms of ivermectin/kg, SC. Twenty-four pigs were not treated. On posttreatment day 7 (PID 57), 12 pigs from each treatment group (phase I) were slaughtered, and the anthelmintic efficacy of each treatment was determined. Efficacies against A suum, T suis, and O dentatum, respectively, were: dichlorvos, 100%, 99.9%, and 100%; fenbendazole, 100%, 99.8%, and 100%; and ivermectin, 98.7%, 53.9%, and 87.6%. Weight gains and feed conversions of the remaining pigs were monitored until they reached market weight (phase II). The average weight gains (kg) and feed conversions (kg of feed/kg of gain) at posttreatment day 81 (PID 131), respectively, were: 73.6 and 3.44 for nontreated controls, 78.9 and 3.31 for dichlorvos-treated pigs, 72.1 and 3.36 for fenbendazole-treated pigs, and 74 and 3.48 for ivermectin-treated pigs. Differences in average weight gains and feed conversions were not significant (P greater than 0.05).

Animals↗
PubMed1985

Antiparasitic agents. 6. Synthesis and anthelmintic activities of novel isothiocyanatophenyl-1,2,4-oxadiazoles.

The syntheses and anthelmintic activities of 31 3- and 5-(isothiocyanatophenyl)-1,2,4-oxadiazoles are reported. In the primary anthelmintic screen, 3-(4-isothiocyanatophenyl)-1,2,4-oxadiazole (39) showed 100% nematocidal activity and 3-(2-furanyl)-5-(4-isothiocyanatophenyl)-1,2,4-oxadiazole (63), 3-(2-furanyl)-5-(2-chloro-4-isothiocyanatophenyl)-1,2,4-oxadiazole (64), and 3-(2-furanyl)-5-(4-chloro-3-isothiocyanatophenyl)-1,2,4-oxadiazole (66) showed 100% taeniacidal activity when administered orally to mice. The two most active members of this series, 39 and 63, were active against the gastrointestinal nematodes of sheep at 100 mg/kg. In addition, 39 was also found to be active against hookworms in dogs at a single, oral dose of 200 mg/kg.

Ancylostomiasis↗
PubMed1982

Antiparasitic agents. 5. Synthesis and anthelmintic activities of novel 2-heteroaromatic-substituted isothiocyanatobenzoxazoles and benzothiazoles.

The synthesis and antiparasitic properties of 22 isothiocyanato-2-pyridinylbenzoxazoles and benzothiazoles are described; the preparation and anthelmintic activities of 14 isothiocyanato-2-thienyl-, -furyl-, and -pyrrolylbenzoxazoles are outlined. In mice experimentally infected with Nematospiroides dubius (nematode) and Hymenolepis nana (tapeworm), three derivatives, i.e., 5-isothiocyanato-2-(2-furyl)benzoxazole (34), 5-isothiocyanato-2-(5-methyl-2-furyl)benzoxazole (35), and 5-isothiocyanato-2-(1-methyl-1H-2-pyrroly)benzoxazole (37), show 100% nematocidal activity and two, i.e., 5- and 6-isothiocyanato-2-(3-pyridinyl)benzoxazole (5) and 5- and 6-isothiocyanato-2-(3-pyridinyl)benzthiazole (21), show 10% taeniacidal activity at 0.2% in the diet. Two derivatives (5 and 21) show good nematocidal activity in sheep. Maximum activity requires 3-pyridinyl derivatives for both the benzoxazole and benzothiazole series.

Animals↗
PubMed1979

Critical evaluation of taeniacidal antibiotic S15-1 (SQ 21, 704) for removal of natural tapeworm infections in dogs and cats.

The new taeniacidal antibiotic S15-1 (SQ 21,704) was evaluated against naturally occuring infections of Taenia pisiformis in 53 dogs, Dipylidium caninum in 35 dogs, T taeniaformis in 18 cats, and D caninum in 33 cats. It all instances, the compound was administered in gelatine capsules in a single oral dose. The doses tested were between and 200 mg/kg of body weight in dogs and between 15 and 45 mg/kg in cats. In dogs, doses of 25 mg/kg and greater were 100% effective against T pisiformis, whereas a dose of 50 mg/kg was necessary to clear D caninum. In cats, a single oral dose of 22.5 mg/kg was 100% efficacious against T taeniaeformis, and a single dose of 45 mg/kg (the largest dose tested) clearly seven of eight cats of D caninum. The efficacy was limited to tapeworms only; there was no efficacy against nematodes. The antibiotic was well tolerated by both species with no drug-related vomiting or other side-effects observed.

Administration, Oral↗