Fusun Tokatli

Using Kaplan-Meier analysis together with decision tree methods (C&RT, CHAID, QUEST, C4.5 and ID3) in determining recurrence-free survival of breast cancer patients

Current evidence supports a clear association between clinical and pathologic factors and recurrence-free survival (RFS) in breast cancer patients. The Cox regression model is the most common tool for investigating simultaneously the influence of several factors on the survival time of patients. But it gives no estimate of the degree of separation of the different subgroups. We propose to analyze different decision tree methods (C&RT, CHAID, QUEST, C4.5 and ID3) and use them additionally to the well-known Kaplan-Meier estimates to investigate the predictive power of these methods. Five hundred patients were included to the study. Two hundred and seventy-nine of them had complete data for prognostic factors and median follow-up is about 40.5 months. First, decision tree methods were analyzed for prognostic factors. Then, according to multidimensional scaling method C4.5 (error rate 0.2258 for training set and 0.3259 for cross-validation) performed slightly better than other methods in predicting risk factors for recurrence. Tumor size, age of menarche, hormonal therapy, histological grade and axillary nodal status are found that an important risk factors for the recurrence. Eight terminal nodes were found and stratified by Kaplan-Meier survival curves. Larger tumor size (>=4.4cm) and receiving no hormonal therapy in a small subgroup of patients were associated with worse prognosis. The five-year RFS is 71.3% in the whole patient population. The sensitivity, specificity and predictive rates calculated by C4.5 method were found 43.8%, 91% and 77.4%, respectively. In this study, C4.5 showed a better degree of separation. As a result, we recommend to use decision tree methods together with Kaplan-Meier analysis to determine risk factors and effect of this factors on survival.

Extrapulmonary Small-Cell Carcinoma Compared With Small-Cell Lung Carcinoma A Retrospective Single-Center Study

The study was conducted with the aim of reviewing the clinical features, therapy, and natural course of patients with extrapulmonary small‐cell carcinoma (EPSCC) and small‐cell lung carcinoma (SCLC) to better define current concepts regarding EPSCCs.

Clinical and prognostic features of plasmacytomas: a multicenter study of Turkish Oncology Group-Sarcoma Working Party.

To identify the outcomes of prognostic factors of solitary plasmacytoma mainly treated with local radiotherapy (RT). The data were collected from 80 patients with solitary plasmacytoma (SP). Forty patients (50.0%) received radiotherapy (RT) alone while 38 of them (47.5%) were treated with surgery (S) and RT. The median radiation dose was 46 Gy (range 30–64). The median follow up was 2.41 years (range 0.33–12.33). Ten‐year overall survival (OS) and local relapse‐free survival (LRFS) were 73% and 94%, respectively. The median progression‐free survival (PFS) and multiple myeloma‐free survival (MMFS) were 3.5 years and 4.8 years, respectively. On multivariate analyses, the favorable factors were radiotherapy dose of ≥50 Gy and RT + S for PFS and younger age for MMFS. For the patients with medullary plasmacytoma, the favorable factor was younger age for MMFS. RT at ≥50 Gy and RT + S may be favorable prognostic factors on PFS. Younger patients, especially with head‐neck lesion and without pre‐RT macroscopic tumor, seem to have the best outcome when treated with RT ± S. Progression to MM remains as the main problem especially for older patients. Am. J. Hematol., 2008.

Prognostic value DCE-MRI parameters in predicting factor disease free survival and overall survival for breast cancer patients

PURPOSE The aim of the study is to assess the predictive power of DCE-MRI semi-quantitative parameters during treatment of breast cancer, for disease-free (DFS) and overall survival (OS). MATERIALS AND METHODS Forty-nine women (age range, 28-84 years; mean, 50.6 years) with breast cancer underwent dynamic contrast enhancement MRI at 1.0T imaging, using 2D FLASH sequences. Time intensity curves (TICs) were obtained from the regions showing maximal enhancement in subtraction images. Semi-quantitative parameters (TICs; maximal relative enhancement within the first minute, E (max/1); maximal relative enhancement of the entire study, E(max); steepest slope of the contrast enhancement curve; and time to peak enhancement) derived from the DCE-MRI data. These parameters were then compared with presence of recurrence or metastasis, DFS and OS by using Cox regression (proportional hazards model) analysis, linear discriminant analysis. RESULTS The results from of the 49 patients enrolled into the survival analysis demonstrated that traditional prognostic parameters (tumor size and nodal metastasis) and semi-quantitative parameters (E(max/1), and steepest slope) demonstrated significant differences in survival intervals (p<0.05). Further Cox regression (proportional hazards model) survival analysis revealed that semi-quantitative parameters contributed the greatest prediction of both DFS, OS in the resulting models (for E(max/1): p=0.013, hazard ratio 1.022; for stepest slope: p=0.004, hazard ratio 1.584). CONCLUSION This study shows that DCE-MRI has utility predicting survival analysis with breast cancer patients.

Postmastectomy irradiation in breast in breast cancer patients with T1-2 and 1-3 positive axillary lymph nodes: Is there a role for radiation therapy?

BackgroundWe aimed to evaluate retrospectively the correlation of loco-regional relapse (LRR) rate, distant metastasis (DM) rate, disease free survival (DFS) and overall survival (OS) in a group of breast cancer (BC) patients who are at intermediate risk for LRR (T1-2 tumor and 1-3 positive axillary nodes) treated with or without postmastectomy radiotherapy (PMRT) following modified radical mastectomy (MRM).MethodsNinety patients, with T1-T2 tumor, and 1-3 positive nodes who had undergone MRM received adjuvant systemic therapy with (n = 66) or without (n = 24) PMRT. Patient-related characteristics (age, menopausal status, pathological stage/tumor size, tumor location, histology, estrogen/progesterone receptor status, histological grade, nuclear grade, extracapsular extension, lymphatic, vascular and perineural invasion and ratio of involved nodes/dissected nodes) and treatment-related factors (PMRT, chemotherapy and hormonal therapy) were evaluated in terms of LRR and DM rate. The 5-year Kaplan-Meier DFS and OS rates were analysed.ResultsDifferences between RT and no-RT groups were statistically significant for all comparisons in favor of RT group except OS: LRR rate (3%vs 17%, p = 0.038), DM rate (12% vs 42%, p = 0.004), 5 year DFS (82.4% vs 52.4%, p = 0.034), 5 year OS (90,2% vs 61,9%, p = 0.087). In multivariate analysis DM and lymphatic invasion were independent poor prognostic factors for OS.ConclusionPMRT for T1-2, N1-3 positive BC patients has to be reconsidered according to the prognostic factors and the decision has to be made individually with the consideration of long-term morbidity and with the patient approval.

Colonic Metastasis from Carcinoma of the Breast that Mimicks a Primary Intestinal Cancer

Although the lung, liver, or bones are the most common location for distant metastases in breast cancer patients, metastases to the intestinal tract are very rarely recognized in the clinic. We will present an unusual case of colonic metastasis from a carcinoma of the breast that mimics a primary intestinal cancer, along with a through review of English language medical literature. Despite the fact that isolated gastrointestinal (GI) metastases are very rare and much less common than benign disease processes or second primaries of the intestinal tract in patients with a history of breast cancer, metastatic disease should be given consideration whenever a patient experiences GI symptoms.

The comparisons of random survival forests and Cox regression analysis with simulation and an application related to breast cancer

The objective of this study was to compare the performances of Cox regression analysis (CRA) and random survival forests (RSF) methods with simulation and a real data set related to breast cancer. In the simulations, we compared across the methods under varying sample sizes by using Monte Carlo simulation method. The results showed that the performance of the CRA was a slightly better for analysis based on Harrells concordance index than RSF approaches based on log-rank, conservation of events, log-rank score and approximate log-rank splitting rules. In the real data application, a retrospective analysis was performed in 279 breast cancer patients diagnosed. According to Harrells concordance index, RSF based on approximate log-rank splitting rule to determined major risk factors for disease-free survival (DFS) showed a slightly better performance than other approaches. In general, performances of all the methods were almost similar. The predictive capability of CRA can be used for different sample sizes and potential future suitable survival data problems, whereas RSF provide interpretive results.

The comparisons of prognostic indexes using data mining techniques and Cox regression analysis in the breast cancer data

The purpose of this study is to determine new prognostic indexes for the differentiation of subgroups of breast cancer patients with the techniques of decision tree algorithms (C&RT, CHAID, QUEST, ID3, C4.5 and C5.0) and Cox regression analysis for disease-free survival (DFS) in breast cancer patients. A retrospective analysis was performed in 381 breast cancer patients diagnosed. Age, menopausal status, age of menarche, family history of cancer, histologic tumor type, quadrant of tumor, tumor size, estrogen and progesterone receptor status, histologic and nuclear grading, axillary nodal status, pericapsular involvement of lymph nodes, lymphovascular and perineural invasion, adjuvant radiotherapy, chemotherapy and hormonal therapy were assessed. Based on these prognostic factors, new prognostic indexes for C&RT, CHAID, QUEST, ID3, C4.5 and C5.0 and Cox regression were obtained. Prognostic indexes showed a good degree of classification, which demonstrates that an improvement seems possible using standard risk factors. We obtained that C4.5 has a better performance than C&RT, CHAID, QUEST, ID3, C5.0 and Cox regression to determine risk groups using Random Survival Forests (RSF).

Amifostine use in radiation-induced kidney damage. Preclinical evaluation with scintigraphic and histopathologic parameters.

Purpose:To assess the degree of protective effects of amifostine on kidney functions via semiquantitative static renal scintigraphy and histopathologic analysis.Material and Methods:30 female albino rats were divided into three equal groups as control (CL), radiotherapy alone (RT), and radiotherapy + amifostine (RT+AMI). The animals in the CL and RT groups were given phosphate-buffered saline, whereas the animals in the RT+AMI group received amifostine (200 mg/kg) by intraperitoneal injection 30 min before irradiation. RT and RT+AMI groups were irradiated with a single dose of 6 Gy using a 60Co unit at a source-skin distance of 80 cm to the whole right kidney. They were followed up for 6 months. CL, RT, and RT+AMI groups underwent static kidney scintigraphy at the beginning of the experiment and, again, on the day before sacrificing. Histopathologically, tubular atrophy and fibrosis of the kidney damage were evaluated.Results:After irradiation, the median value of right kidney function was 48% (44–49%) and 50.5% (49%–52%) in RT and RT+AMI groups, respectively (p = 0.0002). Grade 1 kidney fibrosis was observed to be 60% in the RT group, while it was only 30% in the RT+AMI group. Grade 2 kidney fibrosis was 30% and 0% in the RT and RT+AMI group, respectively. Grade 1 tubular atrophy was 70% and 50% in the RT and RT+AMI group, respectively. Grade 2 tubular atrophy effect was the same in both groups (10%).Conclusion:Static kidney scintigraphy represents an objective and reproducible method to noninvasively investigate kidney function following irradiation. Amifostine produced a significant reduction in radiation-induced loss of renal function.Ziel:Beurteilung der protektiven Wirkung von Amifostin auf die Nierenfunktion mittels semiquantitativer statischer szintigraphischer und histopathologischer Analyse.Material und Methodik:30 weibliche Albinoratten wurden in drei Gruppen mit jeweils zehn Tieren aufgeteilt: Kontrolle (CL), alleinige Radiotherapie (RT) und Radiotherapie + Amifostin (RT+AMI). Die Ratten in der CL- und RT-Gruppe erhielten eine Plazebosalzlösung, die Ratten in der RT+AMI-Gruppe 200 mg/kg Amifostin intraperitoneal 30 min vor der Bestrahlung. Die rechten Nieren in der RT- und RT+AMI-Gruppe wurden mit 6 Gy Einzeldosis mit einem 60Co-Gerät bestrahlt. Die Nachbeobachtungszeit betrug 6 Monate. Eine Nierenszintigraphie wurde direkt vor der Bestrahlung und vor Sektion bei den Tieren der RT- und RT+AMI-Gruppe durchgeführt. Der Nierenschaden wurde in der histopathologischen Untersuchung mit Tubulusatrophie und Fibrose qualitativ beurteilt.Ergebnisse:Die mediane Nierenfunktion der rechten Niere betrug in der RT- und RT+AMI-Gruppe 48% (44–49%) und 50,5% (49–52%; p = 0,0002). Grad-1-Fibrose lag in der RT-Gruppe bei 60% und in der RT+AMI-Gruppe bei 30%. Grad-2-Fibrose betrug in der RT-Gruppe 30% und in der RT+AMI-Gruppe 0%. Tubulusatrophie Grad 2 war in beiden Gruppen vergleichbar (10%).Schlussfolgerung:Die statische Nierenszintigraphie ist eine objektive, wiederholbare und nichtinvasive Methode zur Beurteilung der Nierenfunktion nach Bestrahlung. Im Tiermodell konnte Amifostin die strahleninduzierten Nierenschäden verringern.

Amifostine Use in Radiation-Induced Kidney Damage

Purpose:To assess the degree of protective effects of amifostine on kidney functions via semiquantitative static renal scintigraphy and histopathologic analysis.Material and Methods:30 female albino rats were divided into three equal groups as control (CL), radiotherapy alone (RT), and radiotherapy + amifostine (RT+AMI). The animals in the CL and RT groups were given phosphate-buffered saline, whereas the animals in the RT+AMI group received amifostine (200 mg/kg) by intraperitoneal injection 30 min before irradiation. RT and RT+AMI groups were irradiated with a single dose of 6 Gy using a 60Co unit at a source-skin distance of 80 cm to the whole right kidney. They were followed up for 6 months. CL, RT, and RT+AMI groups underwent static kidney scintigraphy at the beginning of the experiment and, again, on the day before sacrificing. Histopathologically, tubular atrophy and fibrosis of the kidney damage were evaluated.Results:After irradiation, the median value of right kidney function was 48% (44–49%) and 50.5% (49%–52%) in RT and RT+AMI groups, respectively (p = 0.0002). Grade 1 kidney fibrosis was observed to be 60% in the RT group, while it was only 30% in the RT+AMI group. Grade 2 kidney fibrosis was 30% and 0% in the RT and RT+AMI group, respectively. Grade 1 tubular atrophy was 70% and 50% in the RT and RT+AMI group, respectively. Grade 2 tubular atrophy effect was the same in both groups (10%).Conclusion:Static kidney scintigraphy represents an objective and reproducible method to noninvasively investigate kidney function following irradiation. Amifostine produced a significant reduction in radiation-induced loss of renal function.Ziel:Beurteilung der protektiven Wirkung von Amifostin auf die Nierenfunktion mittels semiquantitativer statischer szintigraphischer und histopathologischer Analyse.Material und Methodik:30 weibliche Albinoratten wurden in drei Gruppen mit jeweils zehn Tieren aufgeteilt: Kontrolle (CL), alleinige Radiotherapie (RT) und Radiotherapie + Amifostin (RT+AMI). Die Ratten in der CL- und RT-Gruppe erhielten eine Plazebosalzlösung, die Ratten in der RT+AMI-Gruppe 200 mg/kg Amifostin intraperitoneal 30 min vor der Bestrahlung. Die rechten Nieren in der RT- und RT+AMI-Gruppe wurden mit 6 Gy Einzeldosis mit einem 60Co-Gerät bestrahlt. Die Nachbeobachtungszeit betrug 6 Monate. Eine Nierenszintigraphie wurde direkt vor der Bestrahlung und vor Sektion bei den Tieren der RT- und RT+AMI-Gruppe durchgeführt. Der Nierenschaden wurde in der histopathologischen Untersuchung mit Tubulusatrophie und Fibrose qualitativ beurteilt.Ergebnisse:Die mediane Nierenfunktion der rechten Niere betrug in der RT- und RT+AMI-Gruppe 48% (44–49%) und 50,5% (49–52%; p = 0,0002). Grad-1-Fibrose lag in der RT-Gruppe bei 60% und in der RT+AMI-Gruppe bei 30%. Grad-2-Fibrose betrug in der RT-Gruppe 30% und in der RT+AMI-Gruppe 0%. Tubulusatrophie Grad 2 war in beiden Gruppen vergleichbar (10%).Schlussfolgerung:Die statische Nierenszintigraphie ist eine objektive, wiederholbare und nichtinvasive Methode zur Beurteilung der Nierenfunktion nach Bestrahlung. Im Tiermodell konnte Amifostin die strahleninduzierten Nierenschäden verringern.