Biomedical subjects

M Milosevic

Publications and source records attributed to M Milosevic.

36 records · Page 2Linked to original sources

PubMed1999

Treatment of early epithelial ovarian cancer with chemotherapy and abdominopelvic radiotherapy: results of a prospective treatment protocol.

PURPOSE: To test the hypothesis that the combination of adjuvant chemotherapy and abdominopelvic radiation (APRT) improves the outcome of patients with early ovarian cancer compared to treatment with APRT alone. METHODS AND MATERIALS: Between 1991 and 1994, 93 patients with Stage I to III, optimally cytoreduced, invasive, epithelial ovarian cancer were treated with sequential chemotherapy and APRT. Treatment was assigned using a prognostic classification that was derived from previous cohorts of patients. Low-risk patients (n = 9) received APRT alone, intermediate-risk patients (n = 66) received two courses of cisplatin followed by APRT, and high-risk patients (n = 18) received 6 courses of cisplatin and cyclophosphamide followed by APRT. RESULTS: Disease recurred in 22 patients, and was confined to the pelvis or abdomen in 15. Nine patients died and the remainder were alive with disease after receiving salvage chemotherapy. The 3-year disease-free and overall survivals were 78% and 91%, respectively. The prognostic classification used to assign treatment was the only factor that predicted disease-free survival (83% and 59% at 3 years for low/intermediate- and high-risk patients, respectively; p = 0.03). There was no detectable difference in outcome between the present series and an historical control group treated with APRT alone. Treatment was well tolerated and only 2 patients (2.5%) developed serious complications. CONCLUSION: APRT is an effective adjuvant treatment for carefully selected patients with early ovarian cancer. The addition of chemotherapy as used in this study to APRT does not significantly improve outcome compared to APRT alone.

Adult↗

PubMed1999

Radiotherapy for the treatment of metastatic granulosa cell tumor in the mediastinum: a case report.

OBJECTIVE: We report a case of metastatic ovarian granulosa cell tumor in the mediastinum with a 2-year disease-free interval after treatment with radiotherapy and review the literature regarding the use of radiotherapy in recurrent and metastatic granulosa cell tumor. METHODS: The patient's medical records, histological slides, and radiological films were reviewed. The pertinent references were obtained using a Medline search and cross-references. RESULTS: A patient with Stage 1A granulosa cell tumor developed a recurrence in the retroperitoneum 10 years after initial surgery. She was treated with chemotherapy followed by surgical resection. She subsequently developed metastatic tumor in the mediastinum which responded completely to radiotherapy. She has remained disease free for 2 years since the completion of radiotherapy. CONCLUSION: Radiotherapy is a treatment option that should be considered in localized recurrent or metastatic granulosa cell tumor that is not amenable to surgery as it can potentially control the disease for several years.

Adult↗

PubMed1999

Hysteroscopic endometrial resection and high-dose-rate brachytherapy: treatment of endometrial cancer in a medically compromised patient.

OBJECTIVE: The use of a combined treatment option for endometrial cancer in a medically compromised patient is outlined. METHODS/RESULTS: A case of a 49-year-old severely medically compromised patient with endometrial cancer is described. A complete hysteroscopic endometrial resection with insertion and suturing in place of an endocervical cannula allowed weekly outpatient delivery of high-dose-rate intracavitary radiation without anesthetic or repeat dilatation of the endocervical canal. CONCLUSION: The use of hysteroscopic endometrial resection with adjuvant high-dose-rate radiation therapy is a feasible treatment option for patients with endometrial cancer in whom surgery is contraindicated.

Adenocarcinoma↗

PubMed1999

Tumour proliferation and apoptosis in human uterine cervix carcinoma II: correlations with clinical outcome.

PURPOSE: The prognostic value of tumour proliferation and apoptosis measurements were studied prospectively in patients with carcinoma of the uterine cervix, relative to other established clinical factors. MATERIALS AND METHODS: The labelling index (LI) for bromodeoxyuridine was determined by flow cytometry (fc) and also by immunohistochemistry. Apoptosis was assessed histologically using morphological criteria. Patients were treated with radical radiation therapy (RT). RESULTS: The median/mean LI-fc were 6.7%/7.9% (range 1.52-3.9%). The median/mean apoptosis index (AI) were 1.0%/1.6% (range 0-6.8%). To date, 27 patients have died of disease, and the median follow-up for alive patients is 3.2 years (range 0.4-6.0 years). Among 64 patients who completely responded to treatment, 25 patients have relapsed (six pelvic, 17 distant and two pelvic and distant). In univariate analysis, the most significant factors for disease-free survival (DFS) were large tumour size (P=0.0001), low haemoglobin (P=0.01 ), LI-fc (DFS 67% for LI < 7%, 33% for LI > or = 7%, P=0.03), and T(pot) (DFS 66% for T(pot) > 5 days, 35% for T(pot) < or = 5 days, P=0.04) Stage, overall treatment time (OTT), S-phase fraction, ploidy, T(s), LI by histology, mitotic index, and AI were not significant. Multivariate analysis (Cox's model) showed that the only significant prognostic factors for DFS were tumour size and OTT. However, for small tumours (diameter < 6 cm), either a high LI-fc ( > or = 7%) or a high AI ( > 1%) was associated with poorer DFS, whereas patients with larger tumours (diameter > or = 6 cm) fared poorly regardless of LI-fc and AI. CONCLUSIONS: Tumour size was the most important prognostic factor in cervix carcinoma. Although none of the biologic parameters have independent prognostic significance when the effect of initial tumour size was taken into account, our data suggests that LI and AI may be useful in discriminating outcome for patients with smaller tumours when managed by radical RT. These findings support the hypothesis that rapidly proliferating tumours are less likely to be controlled with a conventional course of RT.

Analysis of Variance↗

PubMed1998

Cervix cancer oxygenation measured following external radiation therapy.

PURPOSE: Tumor hypoxia may be an important factor predicting relapse following radiation therapy. This study was designed to determine the relationship between the oxygenation parameters measured using a polarographic oxygen electrode, prior to and during treatment in patients with cervix cancer, and to assess these results with regard to patient survival. MATERIALS AND METHODS: Forty-three patients had pretreatment oxygen assays performed and measurements repeated following external beam radiation to a median dose of 50 Gy (range 26-52 Gy). Stage distribution showed 15 patients in Stage IB, 17 in Stage II, and 11 in Stage III. The median tumor size was 5 cm (range 3-10 cm). RESULTS: The median proportion of pO2 values <5 mm Hg (the HP5) was 41% following radiation, and the median pO2 was 12 mm Hg. These results were not significantly different from the pretreatment HP5 or pO2 of 37% and 12 mm Hg, respectively. Disease-free survival at 2 years was 50% in patients with posttreatment HP5 < or =50%, compared to 60% when posttreatment HP5 was >50% (p = 0.35). CONCLUSIONS: Unlike pretreatment results, tumour oxygenation measured following external radiation does not appear to be a useful predictive assay in patients with cervical cancer.

Adult↗

PubMed1998

Randomized study of brachytherapy in the initial management of patients with malignant astrocytoma.

PURPOSE: A randomized study was undertaken to assess the role of brachytherapy as a boost to external beam radiation therapy in the initial management of patients with malignant astrocytomas. METHODS AND MATERIALS: Inclusion criteria included the following: biopsy-proven supratentorial malignant astrocytoma of brain < or =6 cm in size, not crossing midline or involving corpus callosum, age 18-70, Karnofsky Performance Status (KPS) > or =70. Patients were randomized to external radiation therapy only delivering 50 Gray (Gy) in 25 fractions over 5 weeks or external radiation therapy plus a temporary stereotactic iodine-125 implants delivering a minimum peripheral tumor dose of 60 Gy. Patients were stratified to age < or =50 or >50, and KPS > or =90 or < or =80. RESULTS: There were 140 patients randomized between 1986 and 1996, 71 to the implant arm and 69 to external irradiation only. Pathologically 125 patients had necrosis noted in their tumor specimen. Factors associated with improved survival in univariate analysis were age < or =50, KPS > or =90, chemotherapy at recurrence, and reoperation at the original tumor site. The Cox proportional hazards model revealed the following significant factors: treatment at recurrence (chemotherapy or reoperation) with a relative risk (RR) of 0.6 (p = 0.004) and KPS > or =90 with a RR 0.6 (p = 0.007). Randomization to the implant arm was associated with a RR of 0.7 (p = 0.07). Median survival for patients randomized to brachytherapy or not were 13.8 vs. 13.2 months, respectively, p = 0.49. CONCLUSIONS: We conclude that stereotactic radiation implants have not demonstrated a statistically significant improvement in survival in the initial management of patients with malignant astrocytoma.

Adult↗

PubMed1998

Magnetic resonance imaging (MRI) for localization of the prostatic apex: comparison to computed tomography (CT) and urethrography.

BACKGROUND AND PURPOSE: It is necessary to include the entire prostate in the high dose treatment volume when planning radical radiation for patients with prostate cancer. We prospectively compared magnetic resonance imaging (MRI) to computed tomography (CT) and urethrography as means of localizing the prostatic apex. MATERIALS AND METHODS: Thirty patients with clinically localized prostate cancer had a sagittal T2-weighted MRI scan and a conventional axial CT scan performed in the treatment position prior to the start of radiotherapy. Twenty of these patients had a static retrograde urethrogram performed at simulation. The position of the MRI and CT apices were localized independently by two radiation oncologists. In addition, the MRI apex was localized independently by a diagnostic radiologist. The urethrogram apex, defined as the tip of the urethral contrast cone, was easily identified and was therefore localized by only one observer. RESULTS: There was good interobserver agreement in the position of the MRI apex. Interobserver agreement was significantly better with MRI than with CT. There were no systematic differences in the position of the MRI and CT apices. However, the MRI apex was located significantly above and behind the urethrogram apex. There was poor correlation between MRI and CT and between MRI and urethrogram in the height of the apex above the ischial tuberosities. There was 83% agreement between MRI and CT and 80% agreement between MRI and urethrogram in the identification of patients with a low-lying apex. The apex, as determined by MRI, was <2 cm above the ischial tuberosities and therefore potentially under-treated in 17% of the patients. CONCLUSIONS: MRI is superior to CT and urethrography for localization of the prostatic apex. All patients undergoing radiotherapy for prostate cancer should have localization of the apex using MRI or a technique of equal precision to assure adequate dose delivery to the entire prostate and to minimize the unnecessary irradiation of normal tissues.

Adenocarcinoma↗

PubMed1998

Oxygenation predicts radiation response and survival in patients with cervix cancer.

BACKGROUND AND PURPOSE: Hypoxia appears to be an important factor in predicting tumor relapse following radiation therapy. This study measured oxygenation prior to treatment in patients with cervix cancer using a polarographic oxygen electrode to determine if oxygenation was an important prognostic factor with regard to tumor control and survival. MATERIALS AND METHODS: Between May 1994 and June 1997, 74 eligible patients with cervix cancer were entered into an ongoing prospective study of tumor oxygenation prior to primary radiation therapy. All patients were evaluated with an Eppendorf oxygen electrode during examination under anesthesia. Oxygenation data are presented as the hypoxic proportion, defined as the percentage of pO2 readings of <5 mm Hg (abbreviated as HP5). RESULTS: The HP5 ranged from 2 to 99% with a median of 52%. With a median follow-up of 1.2 years, the disease-free survival (DFS) rate was 69% for patients with HP5 of < or =50% compared with 34% for those with HP5 of >50% (log-rank P = 0.02). Tumor size above and below the median of 5 cm was also significantly related to DFS (P = 0.0003) and patients with bulky hypoxic tumors had a significantly lower DFS (12% at 2 years) than either bulky oxygenated or non-bulky oxygenated or hypoxic tumors (65%, P = 0.0001). CONCLUSIONS: Hypoxia and tumor size are significant adverse prognostic factors in a univariate analysis of disease-free survival in patients with cervix cancer. A high risk group of patients with bulky hypoxic tumors have a significantly higher probability of relapse and death.

Adenocarcinoma↗

PubMed1997

Heterogeneity of polarographic oxygen tension measurements in cervix cancer: an evaluation of within and between tumor variability, probe position, and track depth.

PURPOSE: To evaluate the heterogeneity of cervix cancer oxygenation as measured using the Eppendorf polarographic electrode and define the optimal number of measurements required to adequately sample a cervix cancer. METHODS AND MATERIALS: Two to 6 tracks with 20-30 measurements per track were obtained in each of the 44 patients evaluated. One hundred sixty-eight tracks and 4719 measurements formed the basis of this analysis. Median pO2 and hypoxic proportion (HP5), defined as the percentage of pO2 values <5 mmHg, were calculated for each track and for each tumor. Within-tumor (W) and between-tumor (B) variability in oxygenation was evaluated using a variance component analysis. The standard error of the measured HP5 with each additional track in each patient was analysed as a function of the total number of tracks. RESULTS: The ratio W/W + B was 0.67 and 0.76 for median pO2 and HP5, respectively, indicating that multiple measurements are needed to adequately sample a tumor. The median value of the standard error of the HP5 decreased from 7.0 to 4.0% from the first to the fifth track, respectively. It was estimated that adding the sixth track would only result in a small change (<0.3%) in the standard error. There was no significant difference in oxygen tension measurements as a function of the location of the measurements around the circumference of the cervix or the depth along the measurement tracks. CONCLUSIONS: There is significant within tumor variability in oxygen tension in cervix cancer. Five tracks with 20-30 measurements per track is optimal to sample the oxygenation status of a cervix cancer. The present data does not suggest that there is a significant difference related to the position in the tumor at which the pO2 measurements were taken.

Adult↗

PubMed1997

Improvement in total positioning error for lateral prostatic fields using a soft immobilization device.

PURPOSE: To prospectively measure the total positioning error present in lateral pelvic fields of patients undergoing prostatic irradiation, and to evaluate the effect of a rigid table insert and soft immobilization on the magnitude of the measured error. MATERIALS AND METHODS: Sixty-one consecutive patients receiving radical prostatic irradiation with a four field technique underwent a total of 234 lateral portal films during the first, third, fifth and seventh week of treatment. The position of the isocentre was compared to the isocentre on the corresponding simulator films and the magnitude and direction of deviations recorded. The patients were divided in to three cohorts of 15 patients, 15 patients and 31 patients. The first cohort was treated on a standard treatment couch, the second cohort treated with the table top stiffened using a 1 cm polycarbonate insert, and the third cohort treated with a soft immobilization device supporting the lower legs, and the polycarbonate insert. RESULTS: There was no difference in the mean deviation of the vector of the isocentre displacement in the y and z directions identified at any of the four times when measurements were taken during therapy between the cohorts treated with or without the polycarbonate insert, but without immobilization. The overall mean deviation for these first two cohorts of patients was 3.9 mm. The positioning of patients treated with immobilization was compared to those treated without, and the immobilized patients had a significantly improved overall mean deviation of 2.6 mm (P = 0.002). This was a result of improvement in both the random and systematic components of the total error. In addition, the proportion of errors greater than 5 mm was reduced from 17% of set-ups to 8% of set-ups. The time during the course of treatment when the measurement was taken had no effect on positioning error for any of the treatment groups. CONCLUSION: Stiffening the treatment couch with a 1 cm thick polycarbonate insert had no effect on reducing total positioning error, but immobilization with an inexpensive and non-customized foam rubber leg support reduced total positioning error in a statistically significant way.

Humans↗

PubMed1997

Post-operative radiotherapy for recurrent dermoid cysts of the spine: a report of 3 cases.

We report three cases of recurrent, intraspinal dermoid cysts managed with post-operative radical radiotherapy. In all cases, the period between last surgery and cystic re-accumulation has been lengthened by the use of involved-field radiotherapy. This combined-modality approach could be beneficial in decreasing the probability of recurrence associated with incompletely-resected tumours, or in patients whose co-morbidities put them at increased operative risk for serial neurosurgical procedures.

Adult↗

PubMed1996

[Changes in somatosensory evoked potentials after sevoflurane and isoflurane. A randomized phase III study].

Monitoring of somatosensory evoked potentials (SEP) is used to identify critical phases of cerebral ischaemia by means of characteristic changes in the signal patterns. A correct interpretation of the results is possible, however, only if the influence of drugs that act on the central nervous system is known. We were able to show that volatile anaesthetics have an impact on latencies and stimulus amplitudes. In this study, we examined the influence of sevoflurane as compared with isoflurane on the conduction of SEP by the median nerve at various concentrations. In addition, we determined how the addition of nitrous oxide (N2O) influenced the stimulus response of median-nerve SEP. Both isoflurane and sevoflurane caused a dose-dependent increase in latency of the primary cortical complex, while the influence on the cervical components of the SEP with respect to increased latency was only slight. No significant difference was found between both study groups. Under the influence of N2O, there were marked reductions in amplitude of the cortical stimulus response. Thus, it can be recommended that supplementation with N2O should be avoided in the presence of low initial amplitudes. Based on our results, the use of isoflurane and sevoflurane concentrations up to 1.0 MAC seems to be compatible with intraoperative monitoring of SEP.

Anesthetics, Inhalation↗

PubMed1995

Recurrent intracranial epidermoid cyst treated with radiotherapy.

We report the case of a 58 year old woman with an epidermoid cyst of the right cerebello-pontine angle that was subtotally excised. She recurred 2 years later and received radiotherapy with resolution of symptoms and shrinkage of the cyst. The natural history of epidermoid cysts and the role of radiotherapy in their management is discussed.

Brain Diseases↗

PubMed1994

Radiation myelopathy following single courses of radiotherapy and retreatment.

PURPOSE: To assess the latent time, survival and dose-fractionation factors associated with permanent radiation myelopathy following single and multiple courses of radiotherapy to the spinal cord. METHODS AND MATERIALS: A retrospective analysis was undertaken of all patients who were registered at the Princess Margaret Hospital between 1955 and 1985, and who developed permanent radiation myelopathy. There were 22 males and 13 females with ages ranging from 30 to 72 years. Twenty-four patients developed permanent myelopathy after one course of radiation therapy and 11 patients following retreatment. Seven patients had histological confirmation of radiation myelopathy at autopsy. RESULTS: The actuarial survival was 14% at 5 years (median: 8.3 months) from the date of diagnosis of radiation myelopathy. Latent times for myelopathy following a single course of treatment (mean: 18.5 months, 7-57 months), were significantly longer than those after reirradiation (mean: 11.4 months, 4-25 months), p = 0.03. There was not a single incident of myelopathy in patients who received fractionated radiotherapy given once daily to an extrapolated response dose (ERD) of < or = 100 Gy2 (equivalent to 50 Gy in 25 daily fractions). Four patients who developed myelopathy after an ERD of < 100 Gy2 were all treated on accelerated fractionation protocols with multiple fractions given per day. Patients who were reirradiated received significantly higher doses (mean ERD of 148 Gy2) than those who had a single course of treatment (mean ERD of 121 Gy2), p = 0.001. CONCLUSION: We conclude that the risk of radiation myelopathy following conventionally fractionated radiotherapy to the spinal cord is extremely small; giving multiple fractions per day reduces the spinal cord tolerance; latent time to myelopathy decreases following retreatment; and there is possible long-term recovery of radiation damage in the human spinal cord.

Adult↗

PubMed1993

Spinal cord ependymomas: a retrospective analysis of 59 cases.

PURPOSE: To determine the outcome of patients with primary spinal ependymoma treated with postoperative radiotherapy and to identify clinical and treatment variables predictive of outcome. METHODS AND MATERIALS: A retrospective chart review was undertaken of 59 spinal ependymoma patients referred to the Princess Margaret Hospital between 1958 and 1987. All patients were treated with radiation therapy to either the site of the primary tumor or the craniospinal axis. There were 23 female and 36 male patients with a median age of 37 years (range: 8-66 years). Median follow-up was 130 months (range: 1-371 months). Clinical variables including age, sex, length of symptoms, functional status, tumor location, and grade as well as treatment variables including extent of surgery, radiation dose and treatment volume were analyzed for influence on outcome. RESULTS: Treatment was well-tolerated with no cases of radiation myelopathy identified. Overall actuarial survival at 5 and 10 years was 83% and 75%, respectively. Eleven patients had recurrent tumor with the 9/11 having a component of their recurrence within the treatment field. Median time to recurrence was 2 years with 9 of the 11 recurrences within the first 3 years. Tumor grade was the only independent variable identified as predictive of outcome. Patients with well differentiated tumors had a 5-year cause-specific survival of 97% compared to 71% for those with intermediate or poorly differentiated tumors (p = 0.005). CONCLUSION: We conclude that postoperative irradiation for patients with spinal ependymomas is associated with a favorable outcome and that tumor grade is a major prognostic factor. Based on results of this series and a review of the literature, specific management recommendations are made for this rare tumor.

Adolescent↗

PubMed1991

Fertility and viability at the Sod locus in Drosophila melanogaster: non-additive and asymmetric selection.

Experiments were designed to test in Drosophila melanogaster the effect of mating type at the Sod locus on fertility and viability. The experiments show that fertility is neither additive (or multiplicative) nor symmetric, i.e. that the fertility of a mating type cannot be predicted from the average fertility of the two genotypes involved in the mating. There is no significant male x female interaction with respect or progeny viability; but the interaction is significant for productivity, i.e. when fertility and viability are jointly taken into account. There is overdominance with respect to female fertility, but not with respect to male fertility or to viability. There also is alloprocoptic selection with respect to fertility and with respect to productivity, i.e. mating between like homozygotes are less fertile and productive than matings between dissimilar homozygotes. Selection at the Sod locus yields stable polymorphic equilibria, with the frequency of the F allele predicted at P = 0.641 or 0.695, respectively for low and high larval density.

Animals↗

PubMed1990

Primary biliary cirrhosis and polymyositis.

We document the rare occurrence of primary biliary cirrhosis (PBC) and polymyositis in a 68-year-old woman. The diagnosis was confirmed by liver biopsy, antimitochondrial antibody, muscle biopsy, and electromyography. We discuss the possible common immunological basis for these two diseases and the risks and benefits of immunosuppressive therapy.

Aged↗

PubMedDate not supplied

Uterine papillary serous carcinoma: evaluation of multimodality treatment with abdominopelvic radiotherapy and chemotherapy.

The aim of this study was to compare overall survival (OS), progression-free survival (PFS), and relapse patterns between different modalities of treatment for uterine papillary serous carcinoma (UPSC). A retrospective review of 124 patients with pathologically confirmed UPSC was performed, of whom, 97 patients were eligible for study. Postoperative treatment groups included adjuvant radiotherapy consisting of whole abdomen and a pelvic boost (abdominopelvic radiotherapy [APRT]) (55 patients), paclitaxel and carboplatin chemotherapy (CT) for six cycles followed by APRT (18 patients), CT only (5 patients), and 19 patients were observed without postoperative adjuvant therapy. Three-year OS was 81% and 63% for the CT followed by APRT and APRT alone, respectively (P= 0.11). After controlling for stage, the group treated with APRT alone had significantly decreased OS and PFS compared to the CT/APRT group (HR 3.6; 1.3-9.8; P= 0.01) and (HR 2.9; 95% CI 1.1-7.3; P= 0.03), respectively. Within the limitations of a retrospective study, the results of this study indicate that multimodality postoperative treatment with paclitaxel and a platinum-based CT followed by APRT may increase the survival of patients with UPSC. However, further prospective studies using these combined modalities are needed to confirm these findings.

Adenocarcinoma, Papillary↗