Prognostic scores in brain metastases from breast cancer

<p>Abstract</p> <p>Background</p> <p>Prognostic scores might be useful tools both in clinical practice and clinical trials, where they can be used as stratification parameter. The available scores for patients with brain metastases have never been tested specifically in patients with primary breast cancer. It is therefore unknown which score is most appropriate for these patients.</p> <p>Methods</p> <p>Five previously published prognostic scores were evaluated in a group of 83 patients with brain metastases from breast cancer. All patients had been treated with whole-brain radiotherapy with or without radiosurgery or surgical resection. In addition, it was tested whether the parameters that form the basis of these scores actually have a prognostic impact in this biologically distinct group of brain metastases patients.</p> <p>Results</p> <p>The scores that performed best were the recursive partitioning analysis (RPA) classes and the score index for radiosurgery (SIR). However, disagreement between the parameters that form the basis of these scores and those that determine survival in the present group of patients and many reported data from the literature on brain metastases from breast cancer was found. With the four statistically significant prognostic factors identified here, a 3-tiered score can be created that performs slightly better than RPA and SIR. In addition, a 4-tiered score is also possible, which performs better than the three previous 4-tiered scores, incl. graded prognostic assessment (GPA) score and basic score for brain metastases (BSBM).</p> <p>Conclusion</p> <p>A variety of prognostic models describe the survival of patients with brain metastases from breast cancer to a more or less satisfactory degree. However, the standard brain metastases scores might not fully appreciate the unique biology and time course of this disease, e.g., compared to lung cancer. It appears possible that inclusion of emerging prognostic factors will improve the results and allow for development and validation of a consensus score for broad clinical application. The model that is based on the authors own patient group, which is not large enough to fully evaluate a large number of potential prognostic factors, is meant to illustrate this point rather than to provide the definitive score.</p

Whole brain radiotherapy with radiosensitizer for brain metastases

<p>Abstract</p> <p>Purpose</p> <p>To study the efficacy of whole brain radiotherapy (WBRT) with radiosensitizer in comparison with WBRT alone for patients with brain metastases in terms of overall survival, disease progression, response to treatment and adverse effects of treatment.</p> <p>Methods</p> <p>A meta-analysis of randomized controlled trials (RCT) was performed in order to compare WBRT with radiosensitizer for brain metastases and WBRT alone. The MEDLINE, EMBASE, LILACS, and Cochrane Library databases, in addition to Trial registers, bibliographic databases, and recent issues of relevant journals were researched. Significant reports were reviewed by two reviewers independently.</p> <p>Results</p> <p>A total of 8 RCTs, yielding 2317 patients were analyzed. Pooled results from this 8 RCTs of WBRT with radiosensitizer have not shown a meaningful improvement on overall survival compared to WBRT alone OR = 1.03 (95% CI0.84–1.25, p = 0.77). Also, there was no difference in local brain tumor response OR = 0.8(95% CI 0.5 – 1.03) and brain tumor progression (OR = 1.11, 95% CI 0.9 – 1.3) when the two arms were compared.</p> <p>Conclusion</p> <p>Our data show that WBRT with the following radiosentizers (ionidamine, metronidazole, misonodazole, motexafin gadolinium, BUdr, efaproxiral, thalidomide), have not improved significatively the overall survival, local control and tumor response compared to WBRT alone for brain metastases. However, 2 of them, motexafin- gadolinium and efaproxiral have been shown in recent publications (lung and breast) to have positive action in lung and breast carcinoma brain metastases in association with WBRT.</p

Carmustine and methotrexate in combination after whole brain radiation therapy in breast cancer patients presenting with brain metastases: a retrospective study

<p>Abstract</p> <p>Background</p> <p>Since 1999, patients presenting with brain metastases (BM) from breast cancer (BC) are treated in our institution with a carmustine (BCNU) - methotrexate (MTX) combination. We report here our clinical experience regarding this combination.</p> <p>Patients and Methods</p> <p>Patients were treated by a combination of BCNU 100 mg/m² on day 1 and MTX 600 mg/m² on day 1 and 15 of a 28 day cycle. Treatment was continued until progression or unacceptable toxicity.</p> <p>Results</p> <p>50 patients were treated between 1999 and 2007. 94% of the patients presented with concomitant extra-cerebral disease. Median number of previous metastatic setting chemotherapy regimens was 2 (0-5). Median number of cycles was 3 (1-20). There were 11 objective responses (23% [95%CI 12-37]) among 48 evaluable patients. Median progression-free survival and overall survival (OS) were 4.2 (95%CI: 2.8-5.3) and 6.9 (4.2-10.7) months respectively, with a one-year OS rate of 32% (20-46). Median Relative Dose Intensity for BCNU and MTX were 0.98 (0.31-1.1) and 0.96 (0.57-1.66) respectively. There were 2 presumed treatment-related deaths. One patient developed febrile neutropenia. Performance status, BS-BM score and presence of liver metastases were associated with OS in univariate analysis.</p> <p>Conclusions</p> <p>This combination appears to be effective and well tolerated in good performance status BC patients presenting with BM.</p

Whole brain radiotherapy for brain metastases from breast cancer: estimation of survival using two stratification systems

BACKGROUND: Brain metastases (BM) are the most common form of intracranial cancer. The incidence of BM seems to have increased over the past decade. Recursive partitioning analysis (RPA) of data from three Radiation Therapy Oncology Group (RTOG) trials (1200 patients) has allowed three prognostic groups to be identified. More recently a simplified stratification system that uses the evaluation of three main prognostics factors for radiosurgery in BM was developed. METHODS: To analyze the overall survival rate (OS), prognostic factors affecting outcomes and to estimate the potential improvement in OS for patients with BM from breast cancer, stratified by RPA class and brain metastases score (BS-BM). From January 1996 to December 2004, 174 medical records of patients with diagnosis of BM from breast cancer, who received WBRT were analyzed. The surgery followed by WBRT was used in 15.5% of patients and 84.5% of others patients were submitted at WBRT alone; 108 patients (62.1%) received the fractionation schedule of 30 Gy in 10 fractions. Solitary BM was present in 37.9 % of patients. The prognostic factors evaluated for OS were: age, Karnofsky Performance Status (KPS), number of lesions, localization of lesions, neurosurgery, chemotherapy, absence extracranial disease, RPA class, BS-BM and radiation doses and fractionation. RESULTS: The OS in 1, 2 and 3 years was 33.4 %, 16.7%, and 8.8 %, respectively. The RPA class analysis showed strong relation with OS (p < 0.0001). The median survival time by RPA class in months was: class I 11.7, class II 6.2 and class III 3.0. The significant prognostic factors associated with better OS were: higher KPS (p < 0.0001), neurosurgery (P < 0.0001), single metastases (p = 0.003), BS-BM (p < 0.0001), control primary tumor (p = 0.002) and absence of extracranial metastases (p = 0.001). In multivariate analysis, the factors associated positively with OS were: neurosurgery (p < 0.0001), absence of extracranial metastases (p <0.0001) and RPA class I (p < 0.0001). CONCLUSION: Our data suggests that patients with BM from breast cancer classified as RPA class I may be effectively treated with local resection followed by WBRT, mainly in those patients with single BM, higher KPS and cranial extra disease controlled. RPA class was shown to be the most reliable indicators of survival

Improving survey methods in sero-epidemiological studies of injecting drug users: a case example of two cross sectional surveys in Serbia and Montenegro

BACKGROUND: Little is known about the prevalence of HIV or HCV in injecting drug users (IDUs) in Serbia and Montenegro. We measured prevalence of antibodies to HIV (anti-HIV) and hepatitis C virus (anti-HCV), and risk factors for anti-HCV, in community-recruited IDUs in Belgrade and Podgorica, and determined the performance of a parallel rapid HIV testing algorithm. METHODS: Respondent driven sampling and audio-computer assisted survey interviewing (ACASI) methods were employed. Dried blood spots were collected for unlinked anonymous antibody testing. Belgrade IDUs were offered voluntary confidential rapid HIV testing using a parallel testing algorithm, the performance of which was compared with standard laboratory tests. Predictors of anti-HCV positivity and the diagnostic accuracy of the rapid HIV test algorithm were calculated. RESULTS: Overall population prevalence of anti-HIV and anti-HCV in IDUs were 3% and 63% respectively in Belgrade (n = 433) and 0% and 22% in Podgorica (n = 328). Around a quarter of IDUs in each city had injected with used needles and syringes in the last four weeks. In both cities anti-HCV positivity was associated with increasing number of years injecting (eg Belgrade adjusted odds ratio (AOR) 5.6 (95% CI 3.2-9.7) and Podgorica AOR 2.5 (1.3-5.1) for >or= 10 years v 0-4 years), daily injecting (Belgrade AOR 1.6 (1.0-2.7), Podgorica AOR 2.1 (1.3-5.1)), and having ever shared used needles/syringes (Belgrade AOR 2.3 (1.0-5.4), Podgorica AOR 1.9 (1.4-2.6)). Half (47%) of Belgrade participants accepted rapid HIV testing, and there was complete concordance between rapid test results and subsequent confirmatory laboratory tests (sensitivity 100% (95%CI 59%-100%), specificity 100% (95%CI 98%-100%)). CONCLUSION: The combination of community recruitment, ACASI, rapid testing and a linked diagnostic accuracy study provide enhanced methods for conducting blood borne virus sero-prevalence studies in IDUs. The relatively high uptake of rapid testing suggests that introducing this method in community settings could increase the number of people tested in high risk populations. The high prevalence of HCV and relatively high prevalence of injecting risk behaviour indicate that further HIV transmission is likely in IDUs in both cities. Urgent scale up of HIV prevention interventions is needed

Effect of reducing groundwater on the retardation of redox-sensitive radionuclides

Laboratory batch sorption experiments were used to investigate variations in the retardation behavior of redox-sensitive radionuclides. Water-rock compositions were designed to simulate subsurface conditions at the Nevada Test Site (NTS), where a suite of radionuclides were deposited as a result of underground nuclear testing. Experimental redox conditions were controlled by varying the oxygen content inside an enclosed glove box and by adding reductants into the testing solutions

Prognostic indices for brain metastases – usefulness and challenges

<p>Abstract</p> <p>Background</p> <p>This review addresses the strengths and weaknesses of 6 different prognostic indices, published since the Radiation Therapy Oncology Group (RTOG) developed and validated the widely used 3-tiered prognostic index known as recursive partitioning analysis (RPA) classes, i.e. between 1997 and 2008. In addition, other analyses of prognostic factors in groups of patients, which typically are underrepresented in large trials or databases, published in the same time period are reviewed.</p> <p>Methods</p> <p>Based on a systematic literature search, studies with more than 20 patients were included. The methods and results of prognostic factor analyses were extracted and compared. The authors discuss why current data suggest a need for a more refined index than RPA.</p> <p>Results</p> <p>So far, none of the indices has been derived from analyses of all potential prognostic factors. The 3 most recently published indices, including the RTOG's graded prognostic assessment (GPA), all expanded from the primary 3-tiered RPA system to a 4-tiered system. The authors' own data confirm the results of the RTOG GPA analysis and support further evaluation of this tool.</p> <p>Conclusion</p> <p>This review provides a basis for further refinement of the current prognostic indices by identifying open questions regarding, e.g., performance of the ideal index, evaluation of new candidate parameters, and separate analyses for different cancer types. Unusual primary tumors and their potential differences in biology or unique treatment approaches are not well represented in large pooled analyses.</p

3 Tesla multiparametric MRI for GTV-definition of Dominant Intraprostatic Lesions in patients with Prostate Cancer – an interobserver variability study

PURPOSE: To evaluate the interobserver variability of gross tumor volume (GTV) - delineation of Dominant Intraprostatic Lesions (DIPL) in patients with prostate cancer using published MRI criteria for multiparametric MRI at 3 Tesla by 6 different observers. MATERIAL AND METHODS: 90 GTV-datasets based on 15 multiparametric MRI sequences (T2w, diffusion weighted (DWI) and dynamic contrast enhanced (DCE)) of 5 patients with prostate cancer were generated for GTV-delineation of DIPL by 6 observers. The reference GTV-dataset was contoured by a radiologist with expertise in diagnostic imaging of prostate cancer using MRI. Subsequent GTV-delineation was performed by 5 radiation oncologists who received teaching of MRI-features of primary prostate cancer before starting contouring session. GTV-datasets were contoured using Oncentra Masterplan® and iplan® Net. For purposes of comparison GTV-datasets were imported to the Artiview® platform (Aquilab®), GTV-values and the similarity indices or Kappa indices (KI) were calculated with the postulation that a KI > 0.7 indicates excellent, a KI > 0.6 to < 0.7 substantial and KI > 0.5 to < 0.6 moderate agreement. Additionally all observers rated difficulties of contouring for each MRI-sequence using a 3 point rating scale (1 = easy to delineate, 2 = minor difficulties, 3 = major difficulties). RESULTS: GTV contouring using T2w (KI-T2w = 0.61) and DCE images (KI-DCE = 0.63) resulted in substantial agreement. GTV contouring using DWI images resulted in moderate agreement (KI-DWI = 0.51). KI-T2w and KI-DCE was significantly higher than KI-DWI (p = 0.01 and p = 0.003). Degree of difficulty in contouring GTV was significantly lower using T2w and DCE compared to DWI-sequences (both p < 0.0001). Analysis of delineation differences revealed inadequate comparison of functional (DWI, DCE) to anatomical sequences (T2w) and lack of awareness of non-specific imaging findings as a source of erroneous delineation. CONCLUSIONS: Using T2w and DCE sequences at 3 Tesla for GTV-definition of DIPL in prostate cancer patients by radiation oncologists with knowledge of MRI features results in substantial agreement compared to an experienced MRI-radiologist, but for radiotherapy purposes higher KI are desirable, strengthen the need for expert surveillance. DWI sequence for GTV delineation was considered as difficult in application