Impact of systemic inflammatory markers in patients with ALK-positive non-small cell lung cancer treated with crizotinib.

OBJECTIVES: To evaluate the prognostic utility of inflammation-based prognostic scores in patients with ALK-positive metastatic or non-resectable non-small-cell lung cancer (NSCLC) treated with crizotinib. PATIENTS AND METHODS: A total of 82 patients with ALK-positive metastatic or non-resectable NSCLC who received ALK TKI crizotinib were included. Pre-treatment modified Glasgow prognostic score (mGPS), prognostic nutritional index (PNI), and systemic immune-inflammation index (SII) were calculated. Multivariable logistic regression and Cox proportional hazards models were used to assess the impact of pretreatment mGPS, PNI, and SII on overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). RESULTS: The ORR was 77.2%, while 1-year OS and PFS rates were 95.0% and 93.5%, respectively. The univariate analysis revealed significantly higher 1-year PFS (89.4 vs. 64.4%, p=0.043) and OS (92.0 vs. 83.3%, p=0.01) rates in patients with low (<934.7) vs. high (≥934.7) SII scores. Multivariate analysis revealed that PNI ≥0.09 was a significant determinant of poorer 1-year OS rates (hazard ratio [HR]: 2.46, 95% confidence interval [CI] 0.88-4.85, p=0.035). No significant difference was observed in survival rates according to gender, age, smoking status, prior lines of therapy, or mGPS scores, while higher mGPS scores (odds ratio [OR]: 0.1, 95%CI 0.16-1.04; p=0.009) and higher PNI scores (OR: 0.16, 95% CI 0.02-0.55; p=0.035) were associated with poorer ORR. CONCLUSION: Our findings indicate the prognostic significance of PNI and SII in terms of survival outcome and the impact of mGPS and PNI on treatment response in patients with ALK-positive NSCLC treated with crizotinib.

Chemotherapy plus radiotherapy vs. radiotherapy alone in high-risk endometrioid endometrial carcinoma.

OBJECTIVE: Adding chemotherapy to radiotherapy in patients with high-risk endometrioid endometrial cancer (EEC) remains controversial, particularly in stages I-II. We aimed to investigate the effect of treatment modalities on survival in high-risk EEC patients. PATIENTS AND METHODS: Patients with high-risk EEC were evaluated retrospectively between 2010 and 2019. Patients who did not receive adjuvant treatment were excluded. We included seventy patients and formed two groups: patients who received radiotherapy (RT) alone and those who received chemotherapy and radiotherapy (CT and RT). RESULTS: The median follow-up time was 60.3 months (8.0-143.5). 38.5% of the patients had relapsed. Recurrence-free survival (RFS) rates were 97. 1%, 68.3% , and 60.8% at 12-, 36-, and 60-month, respectively. Overall survival rates were 97.1%, 80.6%, and 72.6% at 12-, 36-, and 60-month, respectively. Hematological adverse events and neuropathy were more common in the CT and RT group than in the RT group. Multivariate Cox regression analysis for RFS revealed that the FIGO stage and treatment modalities were statistically independent factors (p=0.031 and p=0.040, respectively). Stage stratified log-rank test revealed that adding chemotherapy improved RFS in patients with stage III (p=0.020) but not in stage I-II disease (p=0.725). The number of chemotherapy cycles administered (≤4 vs. >4) did not affect survival in all patients and stage III disease (p=0.497, and p=0.436, respectively). CONCLUSIONS: Adding chemotherapy to radiotherapy may be considered in high-risk stage III EEC. Further studies are needed to determine the optimal duration of chemotherapy.

Synchrotron Radiation Fourier Transform Infrared (SR-FTIR) spectroscopy in exploring ancient human hair from Roman period Juliopolis: Preservation status and alterations of organic compounds.

We explore the preservation status and alterations of organic compounds in Roman period human hairstrandsfrom a specific individual (M196) excavated at Juliopolis (JP). How do these organic compounds present in this c. 2000-year-old human hair compare to those present in modern hair? Alterations to organic compounds in archaeological human hair are caused by biological degradative processes dependent on multifactorial processes acting on the hair since the deposition of a body in a mortuary context. We investigate the type of organic compounds present using Synchrotron Radiation Fourier Transform Infrared (SR-FTIR). Juliopolis (Iuliopolis) is an ancient multiperiod city, located in the Çayirhan district of Nallihan, northwest of Ankara. The Juliopolis necropolis from which M196 was recovered was in use throughout the Hellenistic, Roman, and Byzantine periods, and yielded over 700 tombs with numerous human remains. One tomb (M196) contained human remains of exceptional preservation status, including substantial amounts of hair. Human hair from archaeological contexts is not only extremely rare, but importantly, has high analytical value, with potential for analysis of diet, geographical origins, ancient DNA, metal exposure, and other aspects of life in a time-resolved manner. These data make significant contributions to the life history of the individual (osteobiography), as well as contribute towards key archaeological questions. As these analyses are in their majority destructive, prior evaluation of the preservation of sufficient amounts of the organic compounds on which many such analyses rely upon is crucial, to avoid unnecessary loss of precious ancient samples. The results of our SR-FTIR analyses at SESAME synchrotron show that keratin in the JP M196 is more degraded in comparison to the modern reference sample. However, the results also point to clear potential for further analyses with techniques relying on organic compound preservation, such as C and N isotopic analyses for diet, and aDNA.

The inmunohistochemical expression of c-Met is an independent predictor of survival in patients with lioblastoma multiforme

BACKGROUND AND AIMS: Because the outcome of glioblastoma multiforme (GBM) remains dismal, there is an urgent need for a better molecular characterization of this malignancy. The aim of this prospective study was to investigate the prognostic impact of the expression of c-mesenchymal-epithelial transition (c-Met) a receptor tyrosine kinase implicated in expression growth, survival, motility/migration, and invasion in GMB patients managed according to the established diagnostic and therapeutic protocols. METHODS: Between May 2003 and March 2011, a total of 69 patients (33 males and 36 females; mean age: 52.2 ± 12.9 years, age range: 23-81 years) referred to our Department for the surgical removal of GBM were evaluated immunohistochemically for c-Met expression. Progression-free survival (PFS) and overall survival (OS) served as the main outcome measures. RESULTS: Compared with c-Met- subjects (n = 38), c-Met+ subjects (n = 31) had both a significantly lower OS (15.3 ± 2.3 vs. 22.6 ± 2.5 months, respectively, p < 0.01) and PFS (12.3 ± 2.1 vs. 19.1 ± 2.6 months, respectively, p < 0.05). After allowance for potential confounders, multivariate Cox regression analysis identified c-Met+ as an independent predictor of both OS (hazard ratio = 1.7; 95 % confidence interval = 1.2-1.9, p < 0.01) and PFS (hazard ratio = 1.6; 95 % confidence interval = 1.1-2.3, p < 0.05). CONCLUSIONS: Our findings suggest that c-Met immunohistochemical expression is an independent predictor of outcomes in patients with GBM treated by standard of care (AU)

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The immunohistochemical expression of c-Met is an independent predictor of survival in patients with glioblastoma multiforme.

BACKGROUND AND AIMS: Because the outcome of glioblastoma multiforme (GBM) remains dismal, there is an urgent need for a better molecular characterization of this malignancy. The aim of this prospective study was to investigate the prognostic impact of the expression of c-mesenchymal-epithelial transition (c-Met) a receptor tyrosine kinase implicated in expression growth, survival, motility/migration, and invasion in GMB patients managed according to the established diagnostic and therapeutic protocols. METHODS: Between May 2003 and March 2011, a total of 69 patients (33 males and 36 females; mean age: 52.2 ± 12.9 years, age range: 23-81 years) referred to our Department for the surgical removal of GBM were evaluated immunohistochemically for c-Met expression. Progression-free survival (PFS) and overall survival (OS) served as the main outcome measures. RESULTS: Compared with c-Met- subjects (n = 38), c-Met+ subjects (n = 31) had both a significantly lower OS (15.3 ± 2.3 vs. 22.6 ± 2.5 months, respectively, p < 0.01) and PFS (12.3 ± 2.1 vs. 19.1 ± 2.6 months, respectively, p < 0.05). After allowance for potential confounders, multivariate Cox regression analysis identified c-Met+ as an independent predictor of both OS (hazard ratio = 1.7; 95 % confidence interval = 1.2-1.9, p < 0.01) and PFS (hazard ratio = 1.6; 95 % confidence interval = 1.1-2.3, p < 0.05). CONCLUSIONS: Our findings suggest that c-Met immunohistochemical expression is an independent predictor of outcomes in patients with GBM treated by standard of care.

Prognostic significance of estrogen receptor, progesterone receptor, HER2/neu, Ki-67, and nm23 expression in patients with invasive breast cancer.

PURPOSE: To determine the prognostic significance of estrogen receptor (ER), progesterone receptor (PR), HER2/neu, Ki-67, and nm23 immunohistochemical expression with respect to progression free survival (PFS) and overall survival (OS) in Turkish patients with invasive breast cancer (IBC). METHODS: Patients with IBC (n = 81; mean age = 51.9 ± 11.1 years) were prospectively enrolled at the Department of Oncology, Uludag University Medical Center, Bursa, Turkey. Immunohistochemistry was performed on formalin- fixed, paraffin-embedded tissue sections. RESULTS: We did not find any significant association between immunohistochemical expression of ER, PR, HER2/ neu, Ki-67, and nm23 and the baseline characteristics of IBC patients. The median patient PFS was 30 months (range 22-45), and the median OS was 32 months (range 23-46). Stratification of the patient population according to nm23 immunohistochemical expression revealed a statistically significant difference in terms of both OS (p < 0.05) and DFS (p < 0.05). Multivariate Cox regression analysis indicated that tumor grade, axillary lymph node status, and nm23 immunohistochemical expression were the 3 main independent prognostic factors for PFS and OS in IBC patients. CONCLUSION: Reduced nm23 immunohistochemical expression is an independent negative prognostic factor for OS and PFS. Patients with negative nm23 expression may require a more intensive follow-up.

A multi-institutional evaluation of carboplatin plus docetaxel regimen in elderly patients with advanced gastric cancer.

PURPOSE: Albeit the majority of gastric cancers occur at advanced age, little is known regarding the optimal systemic treatment of elderly patients with advanced gastric cancer (AGC). METHODS: Patients with AGC who were ≥ 65 years old and were treated with carboplatin (area under the curve/AUC 5,on day 1, every 3 weeks) plus docetaxel (75 mg/m(2), on day 1, every 3 weeks) at 3 institutions were included in this retrospective analysis. The efficacy and the safety data of the regimen were analyzed. RESULTS: A total of 30 patients were enrolled. They received 128 cycles of chemotherapy, with a median of 4 cycles (range 2-8). Complete response (CR) and partial response (PR) were observed in 2 (6.7%) and 10 patients (33.3%), respectively, amounting to an overall objective response rate (ORR) of 40%. Seven patients (23.3%) had disease stabilization (SD), and 11 (36.7%) showed disease progression (PD). The most common grade 3-4 toxicity was neutropenia occurring in 19 patients (63.3%). The mean progression-free survival (PFS) was 6.0 ± 0.5 months (95% CI: 5.0-7.4), and the mean overall survival (OS) 12.0 ± 1.0 months (95% CI: 9.2-12.1). CONCLUSION: Carboplatin plus docetaxel seems to be an active and well-tolerated regimen, representing a valuable alternative to cisplatin- and/or fluoropyrimidine-containing regimens for the treatment of elderly patients with AGC.

Prognostic significance of c-erbB2 overexpressionin patients with metastatic gastric cancer

BACKGROUND: Overexpression of the gene c-erbB2, which encodes a receptor tyrosine kinase, has been associated with prognosis and response to therapy in several solid tumors. This study was designed to test whether c-erb-B2 overexpression can be related to prognosis of patients with metastatic gastric cancer. METHODS: Between 2005 and 2010, 46 cases of metastatic gastric cancer were evaluated immunohistochemically for c-erb-B2 overexpression. Overall survival (OS) and time-to-progression (TTP) served as the main outcome measures. RESULTS: c-erbB2 was overexpressed in 19 (41.3 %) cases and 8 patients (17.4 %) had a c-erbB2 score of 3+ (a strong complete membrane staining observed in >10 % of the tumor cells). c-erbB2 expression was not associated with the clinicohistological characteristics of the study participants. The mean OS was 11.48 ± 1.03 months, whereas the mean TTP was 8.28 ± 0.8 months. Compared with patients with a score of 2+ or less (n = 38), those with a c-erbB2 score of 3+ (n = 8) had both a significantly lower OS (15.55 ± 1.63 vs. 8.22 ± 0.88 months, respectively, p < 0.05) and TTP (10.72 ± 1.81 vs. 6.11 ± 0.61 months, respectively, p < 0.05). After allowance for potential confounders, Cox regression analysis identified a c-erbB2 score of 3+ as an independent predictor of both OS (hazard ratio = 1.9; 95 % confidence interval = 1.1-3.7, p < 0.05) and TTP (hazard ratio = 1.8; 95 % confidence interval = 1.1-4.1, p < 0.05). CONCLUSION: Our results suggest that c-erbB-2 overexpression may have a prognostic significance in patients with metastatic gastric cancer (AU)

Identification of prognostic factors in patients with metastatic gastrointestinal stromal tumors.

PURPOSE: Gastrointestinal stromal tumors (GISTs) have a complex biology which is reflected by a marked clinical heterogeneity. Thus, there has been great interest in identifying prognostic factors influencing tumor recurrence and survival. The aim of this study was to identify potential clinical and immunohistochemical prognostic factors that may affect survival and treatment outcomes in patients with metastatic GISTs. METHODS: Between 2000 and September 2011, a total of 41 patients with metastatic GISTs (29 males and 12 females; mean age: 57.4±11.8 years; range 29-74) were referred to the Department of Oncology, Uludag University Medical School. Survival analysis for a number of potential prognostic factors was made with the main outcome results of progression-free survival (PFS) and overall survival (OS7rpar;. RESULTS: The most common sites of isolated metastases comprised the liver (n=18), followed by lymph nodes (n=5), the omentum (n=1), and the mesothelium (n=1). The remaining patients had metastases at multiple sites. Cox regression analysis identified ileal location as the only significant predictor of poor PFS both after first-line (p=0.023) and second-line therapy (p=0.016). Tumor location in the ileum (p=0.025) and S100 immunoreactivity (p=0.041) were both independent predictors of OS. CONCLUSION: Tumor site and S100 positivity were the main significant independent predictors of clinical outcomes in patients with metastatic GISTs treated by standard of care.

Immunohistochemical expression of excision repair cross-complementing 1 (ERCC1) in non-small-cell lung cancer: implications for patient outcome.

INTRODUCTION The identification of novel prognostic markers may help to better assess survival probability in different subgroups of patients with non-small-cell lung cancer (NSCLC) and to tailor treatment according to the molecular profile of the tumour. AIM We sought to examine whether the immunohistochemical expression of excision repair cross-complementing 1 (ERCC1), an essential component of the nucleotide excision repair pathway, may predict prognosis in NSCLC. MATERIAL AND METHOD Formalin-fixed paraffin-embedded tumour samples from 44 Turkish patients with NSCLC treated by adjuvant platinum-based chemotherapy were included in the study. Immunohistochemical expression levels of ERCC1 were correlated with clinical outcomes by Kaplan-Meier curves and multivariable Cox proportional hazards regression analysis. RESULTS A total of 29 patients had ERCC1-negative tumours while 15 had ERCC1-positive tumours. The mean progression- free survival (PFS) was significantly lower in patients with ERCC1-positive tumours (13±2 months) than in those with ERCC1-negative tumours (27±5 months, p<0.05). Similarly, the mean overall survival (OS) was significantly lower in patients with ERCC1-positive tumours (20±3 months) than in those with ERCC1-negative tumours (33±5 months, p<0.05). After allowance for potential confounders, Cox regression analysis demonstrated that ERCC1 expression was significantly associated with both PFS and OS (both p<0.05). CONCLUSION This study provides support for the prognostic value of ERCC1 immunohistochemical expression in patients with NSCLC treated by adjuvant platinum-based chemotherapy. If independently confirmed, these findings may improve prognostic stratification in this group of patients.

Immunohistochemical expression of excision repair cross-complementing 1 (ERCC1) in non-small-cell lung cancer: implications for patient outcome

INTRODUCTION The identification of novel prognostic markers may help to better assess survival probability in different subgroups of patients with non-small-cell lung cancer (NSCLC) and to tailor treatment according to the molecular profile of the tumour. AIM We sought to examine whether the immunohistochemical expression of excision repair cross-complementing 1 (ERCC1), an essential component of the nucleotide excision repair pathway, may predict prognosis in NSCLC. MATERIAL AND METHOD Formalin-fixed paraffin-embedded tumour samples from 44 Turkish patients with NSCLC treated by adjuvant platinum-based chemotherapy were included in the study. Immunohistochemical expression levels of ERCC1 were correlated with clinical outcomes by Kaplan-Meier curves and multivariable Cox proportional hazards regression analysis. RESULTS A total of 29 patients had ERCC1-negative tumours while 15 had ERCC1-positive tumours. The mean progression- free survival (PFS) was significantly lower in patients with ERCC1-positive tumours (13±2 months) than in those with ERCC1-negative tumours (27±5 months, p<0.05). Similarly, the mean overall survival (OS) was significantly lower in patients with ERCC1-positive tumours (20±3 months) than in those with ERCC1-negative tumours (33±5 months, p<0.05). After allowance for potential confounders, Cox regression analysis demonstrated that ERCC1 expression was significantly associated with both PFS and OS (both p<0.05). CONCLUSION This study provides support for the prognostic value of ERCC1 immunohistochemical expression in patients with NSCLC treated by adjuvant platinum-based chemotherapy. If independently confirmed, these findings may improve prognostic stratification in this group of patients (AU)

The access rate to diagnosis and treatment modalities in breast cancer patients in Turkey; multicenter observational study.

PURPOSE: To determine the time elapsed between the first notification of the disease and the access to the diagnosis and treatment modalities and the associated factors in female patients with breast cancer in Turkey. METHODS: Data was acquired from a questionnaire involving 535 patients who applied to 14 various oncology clinics in Turkey between 1st and 28th of February 2010. Analyses were performed by the participating clinics and were divided into 3 groups: centers located in metropolitan areas formed group 1 (n=161), those located in Marmara and central Anatolia region formed group 2 (n=189), and centers located in Karadeniz and East-Southeast Anatolia region formed group 3 (n=185). The groups of these centers were formed according to the socioeconomic development of the provinces. RESULTS: The median patient age was 48 years, 56.1% of patients were less than 50 years of age. Eighty-five percent of the patients detected a mass in their breast by self examination and 27% of the patients older than 50 years never had breast imaging until the definite diagnosis was established. The median time elapsed between disease noticed by the patient and application to a health care center was 10 days, between application and biopsy 19 days, between biopsy and surgery 10 days, and between surgery and systemic therapy 31 days. The median time elapsed between patients applying for surgery in groups 1 and 2 centers was 11 and 21 days, respectively (p=0.01). The median time elapsed between biopsy and surgery in groups 1,2 and 3 centers was 14,1.5, and 12 days, respectively (p<0.05). CONCLUSION: A high level of awareness regarding breast cancer in our country is related with the time that is defined as 10 days between disease recognition and medical application. The time elapsed between the application and biopsy, surgery and systemic therapy was longer compared with the corresponding figures in developed countries.

Subwavelength resolution in a two-dimensional photonic-crystal-based superlens.

We experimentally and theoretically demonstrate single-beam negative refraction and superlensing in the valence band of a two-dimensional photonic crystal operating in the microwave regime. By measuring the refracted electromagnetic waves from a slab shaped photonic crystal, we find a refractive index of -1.94 that is very close to the theoretical value of -2.06. A scanning transmission measurement technique is used to measure the spatial power distribution of the focused electromagnetic waves that radiate from a point source. The full width at half maximum of the focused beam is measured to be 0.21 lambda, which is in good agreement with the finite difference time domain method simulations. We also report a subwavelength resolution for the image of two incoherent point sources, which are separated by a distance of lambda/3.