Biomedical subjects

Michael Milosevic

Publications and source records attributed to Michael Milosevic.

24 records · Page 2Linked to original sources

PubMed2003

Estimating hypoxic status in human tumors: a simulation using Eppendorf oxygen probe data in cervical cancer patients.

PURPOSE: To define the minimal number of pO(2) measurements, with 90% sensitivity and 90% specificity, needed to categorize cervical tumors as either hypoxic or oxic. METHODS AND MATERIALS: Using Eppendorf oxygen probe data from our ongoing prospective trial, we simulated the measurement of tumor oxygenation with a smaller number of data points in 135 patients with cervical cancer. The hypoxic proportion, defined as the percentage of pO(2) values <5 mm Hg (HP5), was calculated for each tumor. Hypoxic tumors were defined as those with a median HP5 >50%, and tumors with normal oxygen levels as those with a median HP5 < or =50%. A small number of pO(2) measurements were randomly selected from the Eppendorf measurements in each tumor, or per Eppendorf track, and used to define the tumor as hypoxic or oxic. The sensitivity and specificity were calculated, considering the classification as given by the complete set of Eppendorf measurements as the reference standard. RESULTS: The probability of falsely classifying the tumor decreased as the selected number of pO(2) measurements per tumor increased, and at 16 measurements was approximately 10%. Adding additional measurements per tumor beyond 24 improved the ability to classify the tumor accurately only slightly. The probability of falsely classifying the tumor decreased as the pO(2) measurements per track increased. At five measurements per track, the probability of falsely classifying the tumor was approximately 9%. CONCLUSION: Approximately 20 measurements per tumor, or five measurements per track, using the Eppendorf pO(2) histograph, are sufficient to categorize cervical tumors as hypoxic or oxic. The results of this study will serve as a guide for research clinicians in the use of this and other systems in the assessment of tumor oxygenation in humans.

Adenocarcinoma↗

PubMed2003

Recurrent prostate cancer following external beam radiotherapy: follow-up strategies and management.

All patients who undergo curative therapy for prostate cancer should be followed for a prolonged period of time to determine tumor control and treatment toxicity for quality assurance purposes. Follow-up duties may be reasonably shared between the oncologist and the family doctor or urologist: however, it is probable that some follow-up information specific to the irradiated patient will be lost unless the oncologist maintains regular contact with the patient, especially in the first 5 years of follow-up when late radiation effects are most likely to appear. There is no strong evidence that patients stop being at risk for recurrence at any time after treatment, and because PSA testing is an accurate, simple, and inexpensive method of determining post-RT tumor status, it is recommended that periodic PSA measurements be continued for life. In the absence of a rising PSA, all other tests and visits are unnecessary to determine post-RT tumor control. Because DRE has been shown to be of limited utility in follow-up of irradiated patients, it should be possible to effectively follow patients remotely. This could be done by asking patients to have PSA tests done, forward the results to their physicians, and report treatment toxicity when it occurs. Only abnormal results would trigger an office visit. This strategy is being evaluated in clinical trials. The alternative is to delegate the follow-up to the primary-care physician with guidelines as to when referral back is required. Follow-up frequency, and the most beneficial follow-up investigations vary from scenario to scenario, and are influenced by the likelihood of relapse, time to relapse, and planned intervention. These decisions are influenced in turn by the initial presentation--either with high or low risk factors--and by the patient's general state of health at completion of EBRT. Effective follow-up also requires active patient cooperation that only can be achieved after discussion of the goals of follow-up with the patient and with the patient's full understanding of the process. The follow-up strategy proposed in Fig. 1 is most suitable for a fit patient with low or intermediate risk factors who wishes to consider all salvage options should he relapse, or for the high-risk individual in situations in which the probability of systemic relapse is of major concern. Young patients with very adverse risk factors may benefit from even closer follow-up in the early years after EBRT and the elderly or frail may require only occasional visits to record or treat treatment toxicity and to ensure clinical non-progression.

Biopsy↗

PubMed2002

Stage II endometrial carcinoma: prognostic factors and risk classification in 170 patients.

PURPOSE: Factors affecting outcome in patients with surgicopathologic Stage II endometrial cancer are poorly defined. The purpose of this study was to determine prognostic factors in a series of patients treated according to standardized protocols at a single institution. METHODS AND MATERIALS: One hundred and seventy patients referred to Princess Margaret Hospital after hysterectomy between 1984 and 1995 were retrospectively reviewed. One hundred and twenty patients received postoperative external beam radiotherapy and brachytherapy, 18 received external beam radiotherapy alone, five received brachytherapy alone, and 27 had no radiotherapy. RESULTS: With a median follow-up of 5.1 years, overall and disease-free survival (DFS) at 5 years was 77% and 68%, respectively, and 24% of patients had relapsed. Significant independent adverse factors for DFS included age >65 (p = 0.0001), FIGO Stage IIB (p = 0.02), and capillary-lymphatic space (CLS) involvement (p = 0.0007). Prognostic factors for relapse were age (p = 0.0008), histologic grade (p = 0.01), and CLS (p = 0.01). A prognostic model based on the number of adverse prognostic factors (0-3) revealed that the 5-year survival rates for the four groups were as follows: 0%-85%, 1%-77%, 2%-55%, and 3%-11%. Combining the groups with 0 or 1 adverse factors resulted in a three-group variable that was strongly related to DFS (p < 0.0001). CONCLUSIONS: Patient age, stage, and CLS were significant factors for DFS, and age, grade, and CLS predicted time to relapse in Stage II endometrial cancer. A prognostic model for DFS using these factors can provide clinically meaningful outcome predictions.

Adult↗

PubMed2002

Expression of hypoxia-inducible factor-1alpha in cervical carcinomas: correlation with tumor oxygenation.

PURPOSE: To investigate the relations between hypoxia-inducible factor-1 (HIF-1), tumor oxygenation, and clinical correlates in patients with locally advanced carcinoma of the uterine cervix. METHODS AND MATERIALS: Biopsies from 42 patients with invasive cervical carcinoma and previous polarographic O2 measurements were assessed for the expression of HIF-1alpha using digitized microscopic imaging and analysis. RESULTS: The HIF-1alpha expression levels ranged from <0.1% to 10.7% of the total tumor area; the positive staining was localized exclusively to the nuclei. Three distinct arrangement patterns of HIF-1alpha-positive cells in relation to blood vessels were identified using spatial image mapping: (1) most HIF-1alpha-positive cells were located within the typical oxygen diffusion distance in tissue (< or =150 microm to the nearest blood vessel); (2) most HIF-1alpha-positive cells were located in the vicinity (< or =60 microm) of the blood vessels; and (3) no apparent spatial relationship was found between HIF-1alpha-positive cells and blood vessels. A statistically significant association was found between HIF-1alpha expression and tumor oxygenation (Spearman correlation coefficient = 0.4, p <0.01), as determined with the Eppendorf pO2 histograph. No correlation was found between the level of HIF-1alpha expression and patient outcome, using disease-free survival as the end point. CONCLUSION: Our results suggest that HIF-1alpha expression may represent a useful biologic marker for hypoxia in uterine cervical cancer.

Aged↗

PubMed2002

Interobserver variation in postimplant computed tomography contouring affects quality assessment of prostate brachytherapy.

PURPOSE: Permanent seed implants are accepted treatment of early stage prostate cancer. Implant quality is assessed by post implant CT-based dosimetry but prostate contours on CT images are obscured by metallic seed artefact and edema. Outcome depends on implant quality, but perceived implant quality depends on accurate prostate contouring. This study documents inter observer variation in prostate contouring on post implant CT scans. METHODS AND MATERIALS: Ten patients had implant dosimetry calculated on 4 copies of the post implant CT scan. Prostate contours from MRI-CT fusion were the gold standard for prostate edge identification. CTs were contoured by an experienced prostate brachytherapist matching CT images to the pre implant TRUS, and by 2 GU radiation oncologists experienced in conformal radiotherapy planning. Dosimetry was compared to that obtained using MRI-CT fusion in terms of D90 and V100. RESULTS: Contours and dosimetry were not reproducible among the 3 observers. The V100's of the experienced brachytherapist differed from that of MRI-CT fusion by a mean of 2.4% compared to 9.1% and 4.4% for observers 1 and 2, and the D90 by a mean of 9.3 Gy compared to 30.3 and 14.4 Gy for observers 1 and 2. CONCLUSIONS: Quality assessment of prostate brachytherapy based on 1 month post implant CT is difficult. This may obscure the dose-response relationship in brachytherapy as well as create problems for quality assurance in multicentre trials evaluating brachytherapy against standard modalities. Whenever possible, MRI-CT fusion should be employed to verify prostate contours post implant.

Brachytherapy↗

PubMed2002

Clinical and biochemical outcome of conventional dose radiotherapy for localized prostate cancer.

PURPOSE: To retrospectively review the results of conventional dose radical radiotherapy for clinical stage T1 and T2 prostate cancer, and to identify the factors that predict the biochemical relapse-free rate. METHODS: The records were reviewed of 706 hormonally-naïve men with clinical stage T1T2 prostate cancer treated with radical radiotherapy (RT) between 1987-1994 at the Princess Margaret Hospital. The median prostate RT dose was 65 Gy in 35 fraction (range 52 Gy in 20 fractions to 67 Gy in 37 fractions). Pelvic lymph nodes were included in the treatment volume and treated to a median dose of 45 Gy in 25 fractions for 283 cases (40%). The primary end-point was biochemical relapse-free survival from RT using the American Society of Therapeutic Radiology and Oncology (ASTRO) consensus criteria. Favourable, intermediate and unfavourable pre- treatment prognostic groupings were derived from the initial PSA, T-category, and Gleason score using Cox regression analysis. Secondary end-points included survival, metastases-free survival and clinical local control. RESULTS: The overall biochemical relapse-free rate at 2 and 5 years was 63% and 45% respectively. Overall survival at 5 years was 87%, and metastases-free survival was 86%. Local control by DRE was 72% at 5 years. Multivariate analysis of variables associated with time to biochemical failure after RT showed that pre-RT PSA, T-category and Gleason score were significant independent predictors with hazard ratios of 1.33 (P = 0.0001), 1.22 (P = 0.01) and 1.33 (P = 0.029) respectively. PSA nadir was an early indicator of biochemical failure. The biochemical failure rate at 3 years was 20% for a PSA nadir < or = 0.5 ng/ml and 85% for a PSA nadir > or = 2.0 ng/ml (P < 0.0001). CONCLUSION: The results of conventional dose RT were unsatisfactory for all risk categories, and overall, less than half of the treated patients remained in biochemical remission at 5 years. These men require more aggressive therapy, that may include dose escalation with conformal techniques, and neoadjuvant/adjuvant androgen deprivation therapy. These results highlight the need to support new and on-going clinical trials for management of localized disease.

Aged↗