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M Milosevic

Publications and source records attributed to M Milosevic.

At least 19 recordsLinked to original sources
PubMed2006

Using the Kramers-Kronig method to determine optical constants and evaluating its suitability as a linear transform for near-normal front-surface reflectance spectra.

In this paper, the suitability of using the Kramers-Kronig transform to routinely extract optical constants from near-normal incidence reflectance spectra of solids and liquids is demonstrated. In addition, the possibility of utilizing the Kramers-Kronig transform as a linearizing transform for near-normal incidence reflectance spectra is investigated. Also, several commercial Kramers-Kronig software packages were utilized in determining the optical constants from the near-normal incidence reflectance of Plexiglas. Unexpectedly, the results produced by the various packages differed significantly. The near-normal reflectance of water was measured, the Kramers-Kronig transform was applied to extract the optical constants of water, and the result was compared to values found in the literature. Furthermore, the Kramers-Kronig transforms of near-normal incidence reflectance spectra of various concentrations of sugar in water were calculated to evaluate its use as a linearizing transform for quantitative applications.

Journal Article↗
PubMed2003

Is there a relationship between repopulation and hypoxia/reoxygenation? Results from human carcinoma of the cervix.

Long overall treatment times are detrimental for cure by radiotherapy and it has been argued that this may be due to repopulation occurring during the course of treatment. However, attempts to predict treatment outcome in relation to tumour proliferation, using pretreatment measurements of kinetic parameters such as Tpot or labelling index (LI) have not met with great success. One possible reason is that hypoxia/reoxygenation is linked to the growth of the tumour and its ability to repopulate. Data from studies in animal models have provided support for this possibility. We made measurement of tumour hypoxia, reoxygenation during treatment and pretreatment measurements of both Tpot and LI in groups of patients with cervix carcinoma undergoing radical radiation treatment. The data show a relationship between pretreatment pO2 measurements and treatment outcome, but reoxygenation did not show any association with treatment outcome. There was no significant association between pretreatment kinetic parameters and treatment outcome, nor was there any evidence of a relationship between pretreatment kinetic parameters and pO2. In the small group of 28 patients whose tumours underwent measurements of both pretreatment kinetic parameters (Tpot, LI) and reoxygenation, there was no relationship between these two sets of measurements. There was also no evidence that a combination of kinetic and reoxygenation measurements could be predictive of treatment outcome.

Animals↗
PubMed2002

Tumor hypoxia has independent predictor impact only in patients with node-negative cervix cancer.

PURPOSE: This prospective clinical study was begun in 1994 to validate the independent prognostic impact of tumor hypoxia in patients with cervix cancer treated with definitive radiation therapy. PATIENTS AND METHODS: Between May 1994 and January 1999, 106 eligible patients with epithelial cervix cancer had tumor oxygen pressure (PO(2)) measured using the Eppendorf probe. Oxygenation data are presented as the hypoxic proportion, defined as the percentage of PO(2) readings less than 5 mm/Hg (abbreviated as HP(5)) and the median PO(2). RESULTS: The median HP(5) in individual patients was 48%, and the median PO(2) was HP(5). Progression-free survival (PFS) for patients with hypoxic tumors (HP(5) > 50%) was 37% at 3 years versus 67% in those patients with better oxygenated tumors (P =.004). In multivariate analysis, only tumor size (risk ratio [RR], 1.33; P =.0003) and evidence of pelvic nodal metastases on imaging studies (RR, 2.52; P =.0065) were predictive of PFS. However, an interaction between nodal status and oxygenation was observed (P =.006), and further analysis indicated that HP(5) was an independent predictor of outcome in patients with negative nodes on imaging (P =.007). There was a significant increase in the 3-year cumulative incidence of distant metastases in the hypoxic group (41% v 15% in those with HP(5) < 50%; P =.0023), but not in pelvic relapse (37% v 27%; P =.12). CONCLUSION: Tumor hypoxia is an independent predictor of poor PFS only in patients with node-negative cervix cancer, in addition to tumor size. Its impact appears to be related to an increased risk of distant metastases rather than to an effect on pelvic control.

Cell Hypoxia↗
PubMed2002

The prognostic significance of the tumour infiltrating lymphocyte count in stage I testicular seminoma managed by surveillance.

The degree of lymphocytic infiltration is a significant determinant of outcome for a variety of malignancies, but its role in seminoma is unknown. 150 men with stage I testicular seminoma presenting between 1981 and 1993 were managed by surveillance following orchidectomy. The presence of tumour infiltrating lymphocytes (TILs) in each case was classified as high, intermediate or low. At a median follow-up of 9.4 years, 30 of the 150 men developed recurrent seminoma. On univariate analysis, the risk of relapse was associated with age < or =33 years (P=0.002), tumour diameter >6 cm (P=0.03), lymphatic or vascular invasion (P=0.04), tumour invasion of rete testis (P=0.05), and lower TIL count (P=0.02). On multivariate analysis, statistically significant predictors of risk of relapse were age < or =33 years (hazard ratio (HR) 4.6 (95% confidence intervals (CI): 1.7-12.2)) and tumour diameter >6 cm (HR 2.8 (CI: 1.2-6.5)). Lower TIL count was of borderline statistical significance (HR 1.8 (CI: 0.96-3.44)). The functional role of the lymphocytic infiltrate in testicular seminoma warrants further study.

Adult↗
PubMed2002

The effect of smoking on tumour oxygenation and treatment outcome in cervical cancer.

AIM: Tumour hypoxia is associated with an increased risk of cervical tumour recurrence and death. Because smoking is a modifiable behaviour, it is important to establish the importance of smoking as a prognostic factor. We hypothesized that there is an association between smoking and tumour hypoxia, and that smoking adversely affects radiation response and survival. METHODS: A smoking history was obtained from 100 of 115 patients with cervical cancer entered into a prospective study of tumour oxygenation. Eighty-seven of these had clinically evident disease and radiation therapy alone was the planned treatment. Patients who smoked within 2 weeks of commencing radiation therapy were considered smokers, and the amount that they smoked was recorded in packs per day. Patients who had never smoked or quit at least 2 weeks prior to radiation therapy were considered non-smokers. Tumour oxygenation was determined using the Eppendorf polarographic oxygen electrode and tumour oxygenation is represented by the hypoxic proportion HP5 (% of pO2 measurements <5 mmHg). RESULTS: There was no significant association between smoking and tumour hypoxia (P=0.3), haemoglobin (P=0.6) nor tumour size (P=0.1). Progression-free survival at 3 years was 56% for non-smokers and 44% for smokers (P=0.23). In both univariate and multivariate analysis, neither smoking status nor amount smoked were significant predictors of progression-free survival or local control. CONCLUSIONS: There was no significant association between smoking and tumour hypoxia, treatment response or survival in this study of patients with cervix cancer.

Adult↗
PubMed2001

Tumor size and oxygenation are independent predictors of nodal diseases in patients with cervix cancer.

PURPOSE: To determine the relationships between tumor oxygenation and nodal stage in a prospective study of patients with cervix cancer, controlling for other prognostic factors. METHODS AND MATERIALS: Between 1994 and 1999, 128 eligible patients with cervix cancer were entered into a prospective study of tumor oxygenation assessed by Eppendorf oxygen electrode before primary radiation therapy. Oxygenation was evaluated using the proportion of pO(2) values < 5 mmHg (HP(5)), and tumors were classified as hypoxic if the HP(5) was > 50%. Patients were assigned to one of three groups: those with no imaging evidence of nodal (pelvic or para-aortic) or distant metastatic disease (N group; n = 67), those with equivocal findings (E group; n = 28), and those with nodal or distant metastatic disease (P group; n = 33). RESULTS: The proportion of hypoxic tumors in the P, E, and N groups were 67%, 50%, and 40%, respectively (p = 0.014), with median HP(5) values of 63%, 48%, and 36%, respectively (p = 0.0024). In a multivariate analysis including tumor size, stage, HP(5), and hemoglobin, it was found that tumor size and HP(5) were the only independently significant variables for the finding of metastatic disease (p = 0.009 and 0.017, respectively). CONCLUSION: In this patient population, there was a significantly increased risk of nodal or distant metastases in patients with hypoxic tumors, and this finding was independent of tumor size. These results are consistent with the hypothesis that tumor hypoxia is an adverse prognostic factor associated with selection for a metastatic phenotype.

Adult↗
PubMed2001

Interstitial fluid pressure predicts survival in patients with cervix cancer independent of clinical prognostic factors and tumor oxygen measurements.

The purpose of this study was to determine the independent prognostic significanceof interstitial fluid pressure (IFP) measurements in cervix cancer. A total of 102 patients with newly diagnosed cervix cancer were accrued to this prospective study. There were 31 International Federation of Gynecology and Obstetrics stage IB or IIA tumors, 40 IIB tumors, and 31 IIIB tumors. The median size was 5 cm (range, 2-10 cm). Pelvic lymphadenopathy was identified radiographically in 20 patients. IFP was measured at examination under anesthesia using a wick-in-needle technique. Multiple measurements were made in each tumor. The mean IFP in individual tumors ranged from -3 to 48 mm Hg, and the median for the entire cohort was 19 mm Hg. Treatment consisted of external beam and intracavitary radiation without chemotherapy. Median follow-up was 2.5 years. The 3-year disease-free survival of all of the patients was 53%. Disease-free survival was 34% in patients with IFP >19 mm Hg, and 68% in those with lower IFP (P = 0.002). To evaluate rigorously the independent prognostic significance of IFP measurements relative to established clinical factors, a multivariate model was first developed using stepwise selection of clinical covariates. Tumor size (P = 0.0003) and pelvic lymph node status (P = 0.0016) comprised the clinical model. IFP, when added to this model, provided additional independent prognostic information (P = 0.0013). IFP was also significant (P = 0.0027) when the clinical factors and hypoxic proportion as determined with the Eppendorf electrode were analyzed together. Patients with high IFP were more likely to recur both locally and at distant sites. This study is the first to document a strong, independent prognostic importance of pretreatment IFP measurements in cervix cancer. Patients with high IFP are significantly more likely than those with low IFP to recur after radiotherapy and die of progressive disease, independent of clinical prognostic factors and the results of tumor oxygen measurements.

Adult↗
PubMed2001

A prospective study of factors predicting clinically occult spinal cord compression in patients with metastatic prostate carcinoma.

BACKGROUND: The objective of this study was to identify clinical parameters that predict occult subarachnoid space or spinal cord (SAS/SC) compression, as determined by magnetic resonance imaging (MRI), in patients with metastatic prostate carcinoma. METHODS: A prospective study was performed in which 68 patients with bone metastases from prostate carcinoma and a normal neurologic examination underwent MRI of the entire spine after documentation of clinical, X-ray, and bone scan parameters potentially predictive of occult SAS/SC compression. RESULTS: Occult SAS/SC compression was diagnosed in 22 patients (32%) using MRI. Nine patients (13%) had compressions at two discontinuous spinal levels. Extensive disease on bone scan, the duration of continuous hormonal therapy prior to study entry, and hemoglobin concentration were found to predict SAS/SC compression by univariate analysis. The extent of disease on bone scan and the duration of continuous hormonal therapy were independent predictors of SAS/SC compression by multivariate analysis (P = 0.02 and P = 0.04, respectively). The risk of occult SAS/SC compression increased from 32% to 44% in patients with a bone scan that showed > 20 metastases as the duration on hormones increased from 0 to 24 months. The risk in patients with fewer metastases increased from 11% to 17% over the same interval. The presence or absence of back pain was not predictive of SAS/SC compression. CONCLUSIONS: Patients who are at high risk for occult SAS/SC compression can be identified using clinical parameters and readily available diagnostic tests. These high-risk patients should undergo MRI screening with the aim of diagnosing and treating spinal cord compression before the development of neurologic deficits that may be irreversible.

Aged↗
PubMed2001

Intratumoral sickling in a patient with cervix cancer and sickle trait: effect on blood flow and oxygenation.

BACKGROUND: Sickle trait affects approximately 8% of the black population in the United States and up to 40% of individuals in some parts of tropical Africa, but rarely causes clinically significant illness. This report provides the first conclusive evidence that erythrocytes in patients with sickle trait may sickle in the microvasculature of solid tumors, leading to impaired perfusion and hypoxia. CASE: A black woman who was sickle trait positive presented with stage IIIB squamous cell carcinoma of the cervix. A biopsy showed extensive intravascular sickling of erythrocytes. An aspirate of blood obtained directly from the tumor also showed numerous sickled cells. A peripheral blood smear was normal. Direct measurement of oxygen tension using the Eppendorf electrode revealed the tumor to be markedly hypoxic, with 93% of a total of 142 individual oxygen reading <5 mm Hg. CONCLUSIONS: Erythrocytes in patients with sickle trait may sickle in the microvasculature of solid tumors and contribute to reduced blood flow and the development of hypoxia. Hypoxia is a strong independent prognostic factor in patients with cervix cancer, and further study is needed to evaluate the impact of intratumoral sickling on long-term outcome.

Blood Flow Velocity↗
PubMed2001

Adjuvant and salvage radiation therapy after radical prostatectomy for adenocarcinoma of the prostate.

PURPOSE: To evaluate the outcome of adjuvant and salvage radiotherapy (RT) after radical prostatectomy (RP) for clinically localized prostate cancer using conventional clinical end-points, and the biochemical relapse-free rate (bRFR). METHODS: Between 1987 and 1994, 113 node negative, hormonally naïve men received RT 1 month to 12 years after RP. Adjuvant RT was given for positive resection margins and/or pT3 disease. Salvage RT was given for a persistently elevated prostatic specific antigen (PSA), a rising PSA, or palpable recurrence post RP. Clinical and biochemical endpoints determined outcome. Log-rank testing and the Cox proportional hazards model identified factors predictive for biochemical relapse free rate. RESULTS: Median follow-up after RT was 3.7 years (range 0.2-9 years). Five-year clinical local control was 95% for patients with no palpable evidence of disease and 59% for those with palpable recurrence (P < 0.0001). 5-year bRFR was 81% for adjuvant RT, 19% for salvage of biochemical recurrence, 0% for patients with palpable disease (P < 0.0001). Improved bRFR for adjuvant and salvage RT was predicted by a Gleason score < 7 vs. 7 vs. > 7 (hazard ratio 1.53; 95% CI 0.99-2.35) and an undetectable pre-RT PSA vs. PSA < 2.0 ng/ml vs. PSA > 2.0 ng/ml (hazard ratio 3.81; 95% CI 2.47-5.87). Seminal vesicle involvement was not a statistically significant independent predictor of bRFR. CONCLUSIONS: The most favourable bRFR was observed for adjuvant therapy. Salvage was most successful with a pre-RT PSA < 2.0 ng/ml, or Gleason score < 7. Few patients with a pre-RT PSA > 2.0 ng/ml were salvaged, and none with palpable recurrence. These patients require investigation of alternative salvage strategies.

Adenocarcinoma↗
PubMed2001

Surveillance for stage I testicular seminoma. a review.

There is good evidence that patients with stage I seminoma can be managed equally well after orchidectomy with surveillance and adjuvant retroperitoneal radiation therapy. There is considerable reluctance amongst many physicians to accept surveillance as a management option in stage I seminoma and this is largely based on the excellent results achieved with adjuvant retroperiteonal radiation for many years. However, patients with stage I seminoma have a long life span and it is possible that the long-term sequelae of radiation treatment could have a negative impact on quality of life and longevity. It is of utmost importance to continue the study of the long-term effects of all current treatment approaches, in particular the risk of induction of second malignancies. However, the psychosocial impact on patients of surveillance and other management strategies must also be assessed. Stage I testicular seminoma is highly curable with currently available management approaches and the current challenge for clinicians is to maintain these excellent results while minimizing toxicity and individualising treatment to the specific social, economic and emotional circumstances of each patient. Surveillance should be one of the management options offered to patients with stage I seminoma.

Journal Article↗
PubMed2001

Interstitial fluid pressure in cervical cancer: guide to targeted therapy.

Interstitial fluid pressure (IFP) is elevated in most malignant tumors, mainly as a result of the abnormal tumor vasculature that develops from unregulated angiogenesis. Theoretical models predict that IFP should correlate with capillary flow resistance in tumors, and therefore also with perfusion and oxygenation. However, a prospective clinical study in patients with cervical cancer at Princess Margaret Hospital failed to demonstrate a relationship between IFP and oxygenation. Despite this, high IFP was strongly associated with inferior survival after radiotherapy independent of clinical prognostic factors and tumor oxygen status. This suggests that IFP and direct needle oxygen measurements may provide information about different aspects of tumor oxygenation, such as chronic versus intermittent hypoxia. Alternatively, IFP may reflect an aspect of tumor biology that is largely unrelated to perfusion and oxygenation. One possibility is that tumors with high pretreatment angiogenesis levels, as indicated by high IFP, may be more radioresistant because the vascular endothelium is more likely to survive during and after treatment. The mechanistic link between elevated IFP and the abnormal tumor vasculature and the strong prognostic effect of IFP in our cervix study together suggest that drugs targeted at angiogenesis, when combined with radiotherapy, may lead to improved tumor control and patient survival.

Angiogenesis Inhibitors↗
PubMed2000

Interrelationship of proliferation and hypoxia in carcinoma of the cervix.

PURPOSE: In human cervix cancer treated with radiotherapy, we have previously shown from separate groups of patients that tumor hypoxia and proliferation rate as measured by bromodeoxyuridine (BrdU) labeling index (LI) are important determinants of clinical outcome. We now examine the relationship of these two pre-treatment predictive assays in 43 patients studied prospectively from 1994-98 where both tests were performed for each patient. MATERIAL AND METHODS: Newly diagnosed patients with carcinoma of the cervix were examined under anesthesia for staging purposes. Patients were given BrdU (200 mg) by intravenous route prior to the procedure. Tumor oxygenation was measured with the Eppendorf pO2 histograph. Biopsy of tumor was then performed and the BrdU LI was obtained by flow cytometry. The degree of tumor hypoxia for each tumor was expressed as median pO2 values, and as the percentage of pO2 readings <5 mm Hg (HP5). RESULTS: The median age was 53 years (range 23-79 years). There were 32 squamous, and 11 non-squamous carcinomas. FIGO stages were: IB and IIA, 8; IIB, 17; IIIB, 18; with a median tumor size of 6 cm (range 2-10 cm). The patients received uniform treatment with radical radiation therapy. There were 22 diploid and 21 aneuploid tumors. The median LI, pO2, and HP5 were 8.0%, 5.4 mm Hg, and 46.8%, respectively. Tests for linear associations showed no significant correlation between median pO2 vs. LI (r = 0.078, p = 0.62), and HP5 vs. LI (r = -0.14, p = 0.38). CONCLUSIONS: The clinical outcome in this group of patients is immature, but these results suggest that tumor hypoxia and proliferation measurements are independent and potentially complementary predictive assays in cervix carcinoma. Further investigations are required to examine the distribution of proliferating tumor cells and its relationship with hypoxic tumor cells in tissue sections with the use of immunohistological techniques and image analysis systems.

Adenocarcinoma↗
PubMed2000

Results of radical radiotherapy for recurrent endometrial cancer.

OBJECTIVES: The aims of this study were to determine the overall survival (OS) and local control (LC) achieved in patients developing a locoregional recurrence of endometrial carcinoma and to define those prognostic factors that predict for improved LC and OS. METHODS: Between 1984 and 1988, 958 women were referred to Princess Margaret Hospital (PMH) with a diagnosis of endometrial carcinoma. Of these, 58 were treated for recurrent disease with radical radiotherapy (RT). Forty-two were referred with recurrence and 16 relapsed during follow-up at PMH for their primary tumor. None had received prior RT. The majority (n = 49) were treated with combined external beam RT followed by an intracavitary cesium insertion. RESULTS: The median time to relapse from original diagnosis was 1.3 years (range 0.2-13.4 years). The actuarial 5- and 10-year OS was 53 and 41%, respectively. The respective results for LC were 65 and 62%. All end-points were measured from the time of relapse. The median total dose received was 81.5 Gy. Univariate analysis showed that favorable histological features at original diagnosis (<50% myometrial involvement, grade 1-2, P = 0.007) and Perez modified staging (P = 0.02) were significant predictors for OS. The Perez staging (P = 0.02) and size of recurrence (<2 cm versus >/=2 cm, P = 0.04) were predictors for LC. CONCLUSION: Patients with localized relapse of endometrial carcinoma in whom radical radiotherapy can be administered should be treated aggressively and may be cured in over half the cases treated. Pathological findings in the original surgical specimen, size of recurrent disease, and a modified vaginal carcinoma staging system are significant predictors of local pelvic control and survival.

Adult↗
PubMed2000

Anemia, hypoxia and transfusion in patients with cervix cancer: a review.

BACKGROUND AND PURPOSE: With the recent development of hemopoietic growth factors and alternatives to transfusion, there has been a renewed interest in the relationships between anemia, tumor hypoxia and treatment outcome in a number of human malignancies. This review is intended to provoke a reconsideration of these issues and their effect on clinical trials, aimed at improving treatment outcome in patients with cervix cancer. MATERIALS AND METHODS: Using data from the literature and from our own prospective series of tumor oxygenation in cervix cancer, we modeled the impact of anemia on tumor blood flow and hypoxia in animal models and human tumors, examined the relationship between anemia and hypoxia and treatment outcome in patients, and reviewed the impact of transfusion on tumor hypoxia and treatment outcome in cervix cancer. RESULTS: Anemia may result in a significant reduction in oxygen delivery to tumors, but compensatory mechanisms reduce the impact on tumor oxygenation. Anemia is associated with inferior treatment outcome in cervix cancer, but hemoglobin levels prior to and during treatment are strongly correlated with tumor size, and this may explain the prognostic impact of anemia in older studies. Transfusion and erythropoietin ameliorate hypoxia in only a proportion of anemic patients. Critical analysis of the published data from the Princess Margaret Hospital randomized trial of transfusion in cervix cancer reveals that, when analyzed by intention-to-treat, transfusion did not result in a benefit to patients. CONCLUSIONS: This review suggests that the relationships among anemia, hypoxia, transfusion and treatment outcome are complex. Further study of anemia as an independent prognostic factor is required and randomized studies of transfusion alternatives, such as erythropoietin, must be of sufficient size to detect small treatment effects.

Anemia↗
PubMed2000

Increased urinary excretion of thioethers as a marker for detecting exposure to herbicide containing 2,4-dichlorophenoxyacetic acid dimethylamine - experimental study on mice.

The possibility that urinary thioethers concentration might be a marker for detecting exposure to herbicide containing 2,4-dichlorophenoxyacetic acid dimethylamine (2,4-DMA) was investigated in animals. Mice were treated with the herbicide containing 2,4-DMA consecutively for 4 days. Urinary concentrations of thioethers related either to body weight or creatinine concentration in urine in the group of animals treated with herbicide were significantly higher compared to control group. Results suggest that thioethers determination in urine might be a noninvasive and simple method for detecting exposure to herbicide containing 2,4-DMA.

2,4-Dichlorophenoxyacetic Acid↗
PubMed2000

Long term outcome and cost in the management of stage I testicular seminoma.

PURPOSE: To validate the use of surveillance as an alternative to adjuvant RT in clinical stage I seminoma, we analyzed our experience with the two approaches in terms of long term outcome and cost. PATIENTS AND METHODS: Between January 1981 and December 1994, 471 patients with stage I testicular seminoma were treated at our institution. Of these, 245 patients received post-operative RT (25 Gy) to the retroperitoneal lymph nodes, and 226 have been managed with surveillance following orchidectomy. Two patients were included in this series twice; both had RT previously for seminoma, were placed on surveillance for a contralateral seminoma and were analyzed for outcome of both primary tumors. The costs associated with both approaches were estimated in 1994 Canadian dollars (C$). RESULTS: With a median follow-up of 7.7 years in the surveillance patients, and 9.7 years in the adjuvant RT cohort, the 5 year actuarial survival for all patients was 97% and the cause-specific survival (CSS) was 99.8%. Of the 226 patients on surveillance 37 patients have relapsed to date; five of those developed a second relapse. One patient has died of disease. Of the 245 patients treated with adjuvant RT, 14 patients have relapsed and none had a second relapse. The CSS was 100%. Thirteen patients on surveillance (5.7%) and 10 patients treated with post-operative RT (4.1%) have received chemotherapy as part of their management. One hundred and eighty-nine patients on surveillance have received no post-orchidectomy treatment to date. Surveillance was more expensive with an average additional cost per patient per year of Can$2620 over 10 years. CONCLUSIONS: Both adjuvant RT and surveillance give excellent results in stage I seminoma. The documented increased risk of second malignant tumors following RT must be taken into account when considering the additional cost of surveillance. The routine use of post-operative RT in stage I seminoma should be reconsidered and a surveillance program offered to all patients as an alternative management option.

Actuarial Analysis↗