The prognostic significance of PD-1 and its ligands in non-small cell lung cancer.

Background: In this study, we aimed to investigate the prognostic value of programmed cell death protein 1 (PD-1), programmed cell death ligand 1 (PD-L1), and programmed cell death ligand 2 (PD-L2) expressions on immune and cancer cells in terms of survival in patients with lung adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. Methods: Between January 2000 and December 2012, a total of 191 patients (172 males, 19 females; mean age: 60.3±8.4 years; range, 38 to 78 years) who were diagnosed with non-small cell lung cancer and underwent anatomic resection and mediastinal lymph node dissection were retrospectively analyzed. The patients were evaluated in three groups including lung squamous cell carcinoma (n=61), adenocarcinoma (n=66), and large-cell carcinoma (n=64). The survival rates of all three groups were compared in terms of immunohistochemical expression levels of PD-1, PD-L1, and PD-L2. Results: The mean follow-up was 71.8±47.9 months. In all histological subtypes, PD-1 expressions on tumor and immune cells were observed in 33% (61/191) and in 53.1% (102/191) of the patients, respectively. Higher expression levels of PD-L1 and PD-L2 at any intensity on tumor and immune cells were defined only in lung adenocarcinomas, and PD-L1 and PD-L2 values were detected in 36.4% (22/64) of these patients. The PD-L1 expressions on tumor and immune cells were observed in 41.7% (10/24) and 25% (6/24) of the patients, respectively. The PD-L2 expressions on tumor and immune cells were detected in 16.7% (4/24) and 8.4% (2/24) of the patients, respectively. Univariate and multivariate analyses revealed that PD-1 expression in tumor cells was an independent prognostic factor in all histological subtypes. Conclusion: Our study results suggest that PD-1 expression is a poor prognostic factor for overall survival in patients with completely resected adenocarcinoma, squamous cell carcinoma, and large cell carcinoma.

lncRNA XIST Interacts with Regulatory T Cells within the Tumor Microenvironment in Chronic Hepatitis B-Associated Hepatocellular Carcinoma.

OBJECTIVE: Alterations in the expression of several long non-coding RNAs (lncRNAs) have been shown in chronic hepatitis B-associated hepatocellular carcinoma (CHB-HCC). Here, we aimed to investigate the association between the expression of inflammation-associated lncRNA X-inactive specific transcript (XIST) and the type of inflammatory cells within the tumor microenvironment. MATERIAL AND METHODS: Twenty-one consecutive cirrhotic patients with CHB-HCC were included. XIST expression levels were investigated on formalin-fixed paraffin-embedded (FFPE) tumoral and peritumoral tissue samples by real-time polymerase chain reaction (RT-PCR). Immunohistochemical staining for CD3, CD4, CD8, CD25, CD163, CTLA4, and PD-1 were performed. The findings were statistically analyzed. RESULTS: Of the 21 cases, 11 (52.4%) had tumoral and 10 (47.6%) had peritumoral XIST expression. No significant association was found between the degree of inflammation and XIST expression. The number of intratumoral CD3, CD4, CD8 and CD20 positive cells was higher in XIST-expressing tumors, albeit without statistical significance. Tumoral and peritumoral XIST expression tended to be more common in patients with tumoral and peritumoral CD4high inflammation. The number of intratumoral CD25 positive cells was significantly higher in XIST-expressing tumors (p=0.01). Tumoral XIST expression was significantly more common in intratumoral CD25high cases (p=0.04). Peritumoral XIST expression was also more common among patients with CD25high peritumoral inflammation, albeit without statistical significance (p=0.19). CONCLUSION: lncRNA XIST is expressed in CHB-HCC and its expression is significantly associated with the inflammatory tumor microenvironment, particularly with the presence and number of CD25 (+) regulatory T cells. In vitro studies are needed to explore the detailed mechanism.

The Relationship between Exercise Capacity and Muscle Strength, Physical Activity, Fatigue and Quality of Life in Patients with Cancer Cachexia.

BACKGROUND: Exercise capacity is a significant determinant of mortality for cancer patients, so knowing the possible determinants of exercise capacity will produce physical and psychological benefits for individuals with cancer cachexia. PURPOSE: To investigate the relationship between exercise capacity on peripheric and respiratory muscle strength, physical activity, fatigue and quality of life in subjects with cancer cachexia. METHODS: The study included 31 patients diagnosed with cancer cachexia. Functional capacity was assessed by 6-Minute Walk Test, hand grip strength and proximal muscle mass by hand dynamometer, respiratory muscle strength by the Maximum Expiratory Pressure and Maximum Inspiratory Pressure measurements, physical activity by International Physical Activity Questionnaire Short Form, fatigue by Brief Fatigue Inventory, and quality of life by EORT-QLQ-C30. The relationship between functional capacity and continuous independent variables was determined using Spearman's or Pearson's tests. RESULTS: A strong positive correlation was observed between exercise capacity and expiratory muscle strength (r = 0.75, p < 0.001), activity level (r = 0.68, p < 0.001), and quality of life global health status (r = 0.74, p < 0.001). Conversely, a strong negative correlation was found between exercise capacity and fatigue severity (r = -0.64, p < 0.001). CONCLUSION: Higher exercise capacity in cancer cachexia patients is linked to reduced fatigue, improved respiratory muscle strength, increased physical activity levels, and enhanced quality of life. When designing rehabilitation programs or exercise interventions for individuals with cancer cachexia, it is crucial to assess their exercise capacity and tailor the programs accordingly.

The Prognostic Nutritional Index (PNI): A New Biomarker for Determining Prognosis in Metastatic Castration-Sensitive Prostate Carcinoma.

Prognostic nutritional index (PNI), which is calculated using the albumin level reflecting nutritional status and lymphocyte count reflecting immune status, is useful in showing nutritional and immunological status related to survival and prognosis in many cancers. In this study, we aimed to evaluate the biomarker potential and effect of PNI in determining the prognosis of metastatic castration-sensitive prostate cancer (mCSPC). This retrospective observational study included the complete data of 108 patients with mCPSC who were treated for at least three months between 1 January 2010, and 1 June 2021. The relationships between cancer-specific survival (CSS), overall survival (OS), progression-free survival (PFS), and PNI were evaluated. The Kaplan-Meier method for OS, PFS, and CSS, as well as univariate and multivariate Cox regression models, were used for the statistical analyses. The median age of 108 patients included in the study was 68.54 (61.05-74.19) years. A value of 49.75 was determined to be the best cut-off point for the PNI. OS (months) was found to be significantly lower in patients with low PNI (median: 34.93, 95% CI: 21.52-48.34) than in patients with high PNI (median: 65.60, 95% CI: 39.36-91.83) (p = 0.016). Patients with high PNI (median: 48.20, 95% CI: 34.66-61.73) had significantly better CSS (months) than patients with low PNI (median: 27.86, 95% CI: 24.16-31.57) (p = 0.001). There was no statistically significant difference in PFS between patients with high PNI values (median: 24.60, 95% CI: 10.15-39.05) and patients with low PNI values (median: 20.03, 95% CI: 11.06-29.03) (p = 0.092). The PNI is a good predictor of OS and CSS in patients with mCSPC. The prediction of PFS, albeit showing a trend towards significance, was not statistically significant, probably due to the small number of cases.

The prognostic indicator in breast cancer treated with CDK4/6 inhibitors: the prognostic nutritional index.

Aims: The aim of this study was to evaluate the effect of prognostic nutritional index (PNI) on prognosis in patients with hormone receptor-positive, HER2-negative metastatic breast cancer who received CDK4/6 inhibitor + endocrine therapy. Methods: Patients receiving a CDK4/6 inhibitor were evaluated retrospectively. The PNI was calculated as: (10 × serum albumin [g/dl]) + (total lymphocyte count [×109/l] × 5). Results: In a study of 106 patients, a statistically significant survival advantage was observed in the high-PNI group over the low-PNI group (mean overall survival: 28.03 ± 0.487 months vs 22.46 ± 1.14 months; p = 0.013). Conclusion: For the first time in the literature, this study demonstrated the prognostic role of PNI in patients with hormone receptor-positive, HER2-negative metastatic breast cancer treated with CDK4/6 inhibitors.

Predictors of the 6-min walk test in patients with ovarian cancer.

PURPOSE: To identify the predictors of the 6-min walk test (6MWT) and investigate the relationship between 6MWT, performance status, functional mobility, fatigue, quality of life, neuropathy, physical activity level, and peripheral muscle strength in patients with ovarian cancer (OC). METHODS: Twenty-four patients diagnosed with stage II-III ovarian cancer were included in the study. Patients were assessed using the following measurement methods: 6MWT for walking capacity, Eastern Cooperative Oncology Group Performance Scale (ECOG-PS) for performance status, an armband physical activity monitor for physical activity level, Checklist Individual Strength (CIS) for fatigue, Functional Cancer Treatment Evaluation with Quality of Life-Extreme (FACT-O) for quality of life, Functional Evaluation of Cancer Treatment/Gynecological Oncology-Neurotoxicity (FACT/GOG-NTX) for neuropathy, a hand-held dynamometer for peripheral muscle strength, and 30-s chair-stand test for functional mobility. RESULTS: The mean 6MWT distance was 578.48 ± 115.33 meters. 6MWT distance correlated with ECOG-PS score (r = -0.438, p = 0.032), handgrip strength (r = 0.452, p= 0030), METs (r = 0.414, p = 0.044) 30s-CST (r= 0.417, p= 0.043), and neuropathy score (r = 0.417, p = 0.043) significantly. There was no relationship between 6MWT distance and other parameters (p> 0.05). Multiple linear regression analysis demonstrated that performance status was the sole predictor of 6MWT. CONCLUSION: The walking capacity seems to be associated with performance status, peripheral muscle strength, level of physical activity, functional mobility, and severity of neuropathy in patients with ovarian cancer. Evaluating these may help clinicians to understand factors behind the decreased walking capacity.

Diagnostic performance of magnetic resonance imaging in preoperative local staging of rectal cancer after neoadjuvant chemoradiotherapy

PURPOSE: This paper aims to investigate the diagnostic performance of magnetic resonance imaging (MRI) in predicting the pathologic stage of locally advanced rectal cancer (LARC) after neoadjuvant chemoradiotherapy (CRT) and the role of MRI in selecting patients with a pathologic complete response (ypCR). METHODS: Restaging MRI (yMRI) examinations of 136 patients with LARC treated with neoadjuvant CRT followed by surgery were retrospectively analyzed by two radiologists. All examinations were performed on a 1.5 Tesla MRI machine with a pelvic phased-array coil. T2-weighted turbo spin-echo images and diffusion-weighted imaging were obtained. Histopathologic reports of the surgical specimens were the reference standard. The accuracy, sensitivity, specificity, positive and negative predictive values (PPV and NPV) of yMRI in predicting the pathologic T-stage (ypT), N-stage, and ypCR were calculated. The inter-observer agreement was evaluated using kappa statistics. RESULTS: The yMRI results showed 67% accuracy, 59% sensitivity, 80% specificity, 81% PPV, and 56% NPV in identifying ypT (ypT0-2 versus ypT3-4). In predicting the nodal status, the yMRI results revealed 63% accuracy, 60% sensitivity, 65% specificity, 47% PPV, and 75% NPV. In predicting ypCR, the yMRI results showed 84% accuracy, 20% sensitivity, 92% specificity, 23% PPV, and 90% NPV. The kappa statistics revealed substantial agreement between the two radiologists. CONCLUSION: Utilization of yMRI showed high specificity and PPV in predicting the tumor stage and high NPV in predicting the nodal stage; in addition, yMRI revealed moderate accuracy in the T and N classifications, mainly due to underestimating the tumor stage and overestimating the nodal status. Finally, yMRI revealed high specificity and NPV but low sensitivity in predicting the complete response.

The Prognostic Significance of Circulating Tumor Cells in Patients with Pancreatobiliary Cancer.

BACKGROUND: Circulating tumor cells (CTCs) are cancer cells which separate from the primary tumor and enter systemic circulation. In this study, it was aimed to examine the relationship between CTCs isolated and identified from the peripheral blood of patients with pancreatobiliary cancer, with the clinicopathological characteristics of the patients and their overall survival. METHODS: A total of 21 patients were included the study. Density gradient centrifugation with the OncoQuick® assay was performed for isolation of CTCs from peripheral blood. In order to identify CTCs, enriched samples underwent flow cytometric analysis. RESULTS: The rate of patients with positive surgical margin in the high CTC group (CTC <15) was identified to be statistically significantly high compared to the group with low CTC (CTC ≤15) (83.3% vs. 16.7%; P = .041). Median neutrophil/lymphocyte ratio (NLR) was found to be higher in the high CTC group compared to the low CTC group, which was close to statistical significance (2.37 vs. 1.41; P = .055). CONCLUSIONS: Circulating tumor cells were identified to have a significant relationship with surgical margin positivity in our study for the first time, suggesting that the CTCs count in peripheral blood in preoperative patients may be a biomarker predicting positive surgical margin. Due to the very low number of studies assessing the relationship between CTCs and NLR, our study which identified relationship close to statistical significance between CTCs and NLR, significantly contributes to the literature on the topic of the possible role of lymphocytes in CTC clearance.

Association of Serum Hepatocyte Growth Factor Level with Systemic Inflammatory Biomarkers in Patients with Pancreatobiliary Cancer.

BACKGROUND: Hepatocyte growth factor is a cytokine secreted by the stromal cells in the tumor microenvironment. There is little information about the clinical significance of serum hepatocyte growth factor level in patients diagnosed with pancreatobiliary cancer. The objective of the current study was to investigate the relationship between serum hepatocyte growth factor level with inflammation markers and the clinical features of patients with pancreatobiliary cancer. METHODS: A total of 62 patients with pancreatobiliary cancer were included in this study. Serum hepatocyte growth factor concentrations were evaluated utilizing the enzyme-linked immunosorbent assay method. RESULTS: The median serum hepatocyte growth factor level was 329.1 ng/mL (1.4-1051.1). The patients were categorized into 2 groups as those below the median hepatocyte growth factor level (low hepatocyte growth factor) and those above the median hepatocyte growth factor level (high hepatocyte growth factor). While 40.9% of the patients without metastasis were observed to be in the high hepatocyte growth factor group, 72.2% of the metastatic patients were observed to be in the high hepatocyte growth factor group (P = .025). The median levels of monocyte, monocyte-to-lymphocyte ratio, C-reactive protein, and C-reactive protein-to-albumin ratio were found to be significantly higher in the high hepatocyte growth factor group as compared to the low hepatocyte growth factor group (P < .050). CONCLUSION: The significant relationship between serum hepatocyte growth factor level and systemic inflammation markers in patients with pancreatobiliary cancer is shown for the first time in our study. This study, which showed a significant relationship between the presence of metastasis and serum hepatocyte growth factor level, suggests that serum hepatocyte growth factor level may be a prognostic biomarker in patients who are diagnosed with pancreatobiliary cancer.

The percentage of ALK-positive cells and the efficacy of first-line alectinib in advanced non-small cell lung cancer: is it a novel factor for stratification? (Turkish Oncology Group Study).

INTRODUCTION: Alectinib is an effective second-generation ALK tyrosine kinase inhibitor (TKI) used in the first-line treatment of patients with advanced ALK-positive NSCLC. Recent studies demonstrated that the percentage of ALK-positive tumor cells in patient groups receiving crizotinib might affect outcomes. This study aimed to investigate whether the percentage of ALK-positive cells had a predictive effect in patients with advanced NSCLC who received first-line Alectinib as ALK-TKI. MATERIALS AND METHODS: This retrospective study included patients with advanced-stage NSCLC who received alectinib as a first-line ALK-TKI and whose percentage of ALK-positive cells was determined by FISH at 27 different centers. Patients who received any ALK-TKI before alectinib were not included in the study. Patients were separated into two groups according to the median (40%) value of the percentage of ALK-positive cells (high-positive group ≥ 40% and low-positive group < 40%). The primary endpoint was PFS, and the secondary endpoints were OS, ORR, and PFS of the subgroups based on different threshold values for the percentage of ALK-positive cells. RESULTS: 211 patients were enrolled (48.3% female, 51.7% male) to study. 37% (n = 78) of the patients had received chemotherapy previously. After a median of 19.4 months of follow-up, the median PFS was not reached in the high-positive group (n = 113), but it was 10.8 months in the low-positive group (n = 98) (HR 0.39; 95% CI 0.25-0.60, p < 0.001). The median OS in the high-positive group was not reached, whereas it was 22.8 months in the low-positive group (HR 0.37; 95% CI 0.22-0.63, p < 0.001). ORR was significantly higher in the high-positive group (87.2 vs. 68.5%; p = 0.002). According to the cut-off values of < 20%, 20-39%, 40-59%, and ≥ 60%, the median PFS was 4.5, 17.1, and 26 months, respectively, and could not be reached in the ≥ 60% group. CONCLUSION: Our study demonstrated that the efficacy of alectinib varies significantly across patient subgroups with different percentages of ALK-positive cells. If these findings are prospectively validated, the percentage of ALK-positive cells may be used as a stratification factor in randomized trials comparing different ALK-TKIs.

Erratum to: Evaluation of gene expression levels in the diagnosis of lung adenocarcinoma and malignant pleural mesothelioma.

[This corrects the article DOI: 10.5606/tgkdc.dergisi.2020.17279.].

Real-world data on efficacy and safety of first-line alectinib treatment in advanced-stage, ALK-positive non-small-cell lung cancer patients: a Turkish Oncology Group study.

Aims: In this multicenter study, the authors aimed to determine the real-life efficacy and safety of first-line alectinib. Materials & methods: This retrospective trial included advanced-stage, ALK-positive non-small-cell lung cancer patients who were treated with first-line alectinib in terms of ALK-tyrosine kinase inhibitors, regardless of previous chemotherapy. The co-primary end points were progression-free survival both for all patients and for the treatment-naive population. The secondary end points were overall response rate, overall survival, rate of CNS progression and safety. Results & conclusion: A total of 274 patients (n = 177 for treatment-naive patients) were enrolled in the study. The median progression-free survival was 26 and 28.8 months for all patients and the treatment-naive group, respectively. The overall response rate, CNS progression rate and 1-year overall survival ratio were 77.9, 12.4 and 77%. Alectinib is a highly effective therapy with a favorable safety profile.

The advancements in cancer treatment, particularly in the last two decades, have been promising. Non-small-cell lung cancer (NSCLC) is one of the most important diseases experiencing these promising developments. ALK positivity, which is caused by the rearrangement of different gene fragments between two chromosomes, affects about 5% of NSCLC patients. This provides a target for next-generation therapies. One of these targeted therapy drugs is alectinib. The authors examined the outcomes of 271 patients with body-disseminated NSCLC who received alectinib as initial targeted therapy. These patients were not chosen to participate in a clinical phase study. They were treated with an approved drug; the study also included 97 patients who had previously received chemotherapy. The median duration of survival without disease worsening was 26 months for all patients receiving alectinib treatment. This value was 28.8 months in 177 patients who had not received any treatment before alectinib. Regardless of disease status, 77% of all patients were found to be alive at the end of the first year. Alectinib treatment resulted in a significant improvement of the disease in approximately four out of five patients. The treatment's side effects were generally tolerable or manageable. Only four patients were reported to have discontinued their medication due to treatment-related side effects. These real-world findings are compatible with previous clinical research. Alectinib is an important first-line treatment option for patients with advanced, ALK-positive NSCLC.

Tumoral and Parenchymal Morphological Assessment in Liver Metastases of Colorectal Carcinoma: Micrometastasis, Peritumoral Lymphocytes, Tumor Budding and Differentiation are Potential Prognostic Factors.

Introduction: Various potential prognostic histopathologic factors for colorectal carcinoma liver metastasis have been proposed. However, there is still no consensus on pathological reporting of colorectal carcinoma liver metastasis resection materials. The aim of this study was to investigate the relation between selected tumoral and parenchymal histopathologic features and prognostic factors for better characterization and prognostic prediction of the patients with colorectal carcinoma liver metastasis. Methods: Hematoxylin-eosin stained slides from 100 patients who underwent hepatic resection were evaluated. Pathologic characteristics; including number of tumor nodules, largest tumor size, status of surgical margin, tumor distance to closest margin, tumor necrosis, the presence of tumor capsule, tumor differentiation, perineural and lymphovascular invasion, micrometastasis, tumor budding, peritumoral lymphocytic infiltrate and parenchymal features including steatosis, steatohepatitis, lobular inflammation, confluent necrosis, hepatocyte ballooning, portal inflammation were assessed. For 49 patients who were treated with preoperative chemotherapy, tumor regression grade and chemotherapy-related parenchymal changes such as sinusoidal damage, venous obstruction, nodular regenerative hyperplasia, steatosis and steatohepatitis were also evaluated. Results: The presence of lymphovascular invasion (p < 0.001), micrometastasis (p=0.004), absent or mild peritumoral lymphocytic infiltration (p =0.013), high tumor budding score (p=0.033) and moderate/poor differentiation (p=0.022) were significantly associated with shorter overall survival. Lymphovascular invasion (p < 0.001) was an independent predictor of mortality in multivariate analysis. Conclusions: We conclude that tumor differentiation, lymphovascular invasion, micrometastasis, peritumoral lymphocytic reaction and tumor budding score are potential prognostic histopathological features and candidates for inclusion in pathology reports of colorectal carcinoma liver metastasis resections.

Peritumoral histopathologic findings in patients with chronic viral hepatitis-associated hepatocellular carcinoma.

Data on peritumoral histopathologic findings in patients with hepatocellular carcinoma (HCC) is limited. In this retrospective study, we evaluated the peritumoral histopathologic changes in patients with chronic viral hepatitis (CVH)-associated HCC (CVH-HCC) and their prognostic value. 61 consecutive cirrhotic patients who underwent liver transplantation due to CVH-HCC were included. Histopathologic features within 1 cm distance of the tumor, and their association with clinicopathological characteristics and prognosis were evaluated. A random representative slide of cirrhotic parenchyma unrelated to invasive and/or dysplastic foci was also evaluated for the same histopathologic criteria. The majority (85%, n = 52) were male with a median age of 55 ± 6.38 (range, 39-67). The etiologic agent was only HBV in 90% (n = 55). The most common peritumoral findings were portal inflammation (100%; n = 61), ductular reaction (100%; n = 61) and sinusoidal dilatation (95%; n = 58). Macrovascular invasion was observed only in four cases (7%) with mild peritumoral portal inflammation. Neutrophilic infiltration of the peritumoral portal tracts (n = 18; 30%) was significantly associated with pT4 tumor stage, tumor grade, macrovascular invasion, and pretransplant therapy. Patients with moderate or severe peritumoral sinusoidal dilatation tended to have worse prognosis, albeit not significantly. Peritumoral ballooning degeneration was associated with multifocality, recurrence and recurrence-free survival in both uni- and multivariate analysis. Peritumoral histopathologic changes in CVH-HCC can be classified as: changes related to pathogenesis, changes indirectly affecting prognosis, and changes directly affecting prognosis. Peritumoral prominent ballooning degeneration may be a predictor of recurrence while portal neutrophilic infiltration and sinusoidal dilatation seem to indicate poor prognosis.

Reconsideration of Clinicopathologic Prognostic Factors in Pancreatic Neuroendocrine Tumors for Better Determination of Adverse Prognosis.

The question of how successful we are in predicting pancreatic neuroendocrine tumors (panNET) with poor prognosis has not been fully answered yet. The aim of this study was to investigate the effects of clinicopathological features on prognosis and to determine their validity in prediction of prognosis and whether a better prognostic classification can be made. Fifty-six patients who underwent pancreatic resection for pancreatic neuroendocrine tumor were included. The associations between clinicopathological parameters and prognosis were evaluated statistically. Efficiencies of different thresholds for tumor size, mitotic count, and Ki67 proliferation index for prognosis prediction were compared. Vascular invasion was statistically associated with high tumor grade, advanced pT stage, and mortality rate. The presence of non-functional tumor, lymphatic invasion, and > 10 cm tumor size were significantly related to shorter overall survival. Advanced pT stage (pT3-4), > 5 cm tumor size, and high tumor grade (grades 2-3) were significantly associated with shorter disease-free survival. The mortality rate showed the strongest statistical significance with mitotic count when grouped as 1: < 2, 2: 2-10, and 3: > 10 mitosis/ 2 mm2. The 10% threshold value for Ki67 index was more successful in predicting adverse prognosis. Among the morphologic variants, the ductulo-insular variant was the most promising to have positive prognostic value in our series, although no statistical significance was detected. In conclusion, threshold values of 5 cm and 10 cm for tumor size, 10% for Ki67 proliferation index, and 10/2 mm2 for mitotic count and vascular and lymphatic invasion assessed separately are potential prognostic candidates for better stratification of panNETs.

The prognostic role of thyroid transcription factor-1 in lung adenocarcinoma.

AIMS: In this study, we investigated the expression of thyroid transcription factor-1 (TTF-1) in lung adenocarcinoma patients' samples and analyzed the association of TTF-1 with clinicopathological parameters, prognosis, and treatment options in patients with lung adenocarcinoma. SUBJECTS AND METHODS: This retrospective study enrolled 200 patients who were histologically confirmed lung adenocarcinoma with Stage I-IV disease, between 2008 and 2015 years. The cytological archive of these hospitals' Pathology Department was searched. The available slides and the clinical information were reviewed and correlated. All analyses were conducted by SPSS version 15.0 statistical software. RESULTS: Sixty-five (32.5%) of the patients showed TTF-1 negativity and 135 (67.5%) of them showed TTF-1 positivity. The median survival for TTF-1 positive and negative patients was 19.6 and 12.2 months, respectively. We did not find any statistical significance in-between the parameters in terms of the survival data. In TTF-1-negative group, the survival time of epidermal growth factor receptor mutation positive (P = 0.049), cytokeratin 7 (CK7) positive (P = 0.009) patients and those who had received curative radiotherapy (P = 0.028) was significantly better as compared to TTF-1-positive group. We also analyzed the relation between TTF-1 and survival outcome or chemotherapy selection in Stage IV disease. We could not identify any correlation between TTF-1 and survival outcome or treatment selection. CONCLUSIONS: This study suggests that TTF-1 is not a favorable prognostic factor in lung adenocarcinoma patients. The prognostic role of CK7 and relationship between TFF-1 expression in lung adenocarcinoma and predictive role of TTF-1 expression for the selection of first-line treatment in Stage IV lung adenocarcinoma should be validated in prospective and randomized studies.

GLASS: Global Lorlatinib for ALK(+) and ROS1(+) retrospective Study: real world data of 123 NSCLC patients.

Lorlatinib is a third-generation tyrosine-kinases inhibitor (TKI) targeting ALK/ROS1 fusions. The FDA has approved lorlatinib for TKI-pretreated ALK(+) NSCLC, while its approval for ROS1(+) is still pending. Here we present the largest real-world data of NSCLC patients harboring ALK/ROS1 rearrangements treated with lorlatinib. METHODS: 123 patients were enrolled retrospectively (data cut-off 1/1/2019). Lorlatinib was administered through an early access program for patients with no other available therapy. Outcome and response were defined by each investigator upon RECIST 1.1 criteria. RESULTS: 106 ALK(+) and 17 ROS1(+) patients recruited from 8 different countries. The ALK(+) cohort included 50 % males, 73 % never-smokers and 68 % with brain metastases. Extracranial (EC) and intracranial (IC) response rates (RR) were 60 % and 62 %, with disease control rates (DCR) of 91 % and 88 % respectively. Mean duration of therapy (DoT) was 23.9 ±â€¯1.6 months and median overall survival (mOS) was 89.1 ±â€¯19.6 months. ROS1 cohort enrolled 53 % males, 65 % never-smokers and 65 % had brain metastases. EC and IC RR were 62 % and 67 % with DCR of 92 % and 78 % respectively. Median DoT was 18.1 ±â€¯2.5 months and mOS of 90.3 ±â€¯24.4 months. OS and DoT in both cohorts were not significantly correlated with line of therapy nor other parameters. The most common adverse events of any grade were peripheral edema (48 %), hyperlipidemia (47 %), weight gain (25 %) and fatigue (30 %). CNS adverse events such as cognitive effect of grade 1-2 were reported in 18 % of patients. CONCLUSION: Lorlatinib shows outstanding EC/IC efficacy in ALK/ROS1(+) NSCLC. The observed mOS of 89 ±â€¯19 months in ALK(+) NSCLC supports previous reports, while mOS from of 90 ±â€¯24 months is unprecedented for ROS1(+) NSCLC.

A cross-sectional optical coherence tomography study in patients on taxane-based therapy and a case report with the literature review.

PURPOSE: To evaluate the characteristics of macular retinal and subfoveal choroidal changes in patients already on taxane-based therapy by the help of spectral domain optical coherence tomograpy (SD-OCT) and determine the incidence of taxane- related cystoid macular edema (CME). MATERIALS AND METHODS: In this cross-sectional case-control study, 202 patients who received taxane-based therapy due to treatment of various cancer and age and sex-matched 200 healthy control subjects were examined. Only patients who received at least 4 cycles of taxane-based therapy were taken into consideration for the taxane group. Taxane-based therapy was further divided into two subgroups; paclitaxel group (149 patients) and docetaxel group (53 patients). Central macular thickness (CMT) and central subfoveal choroidal thickness (CCT) were measured just once during their ongoing chemotherapy using SD-OCT and enhanced-depth imaging (EDI) OCT by Heidelberg OCT by a single examiner. RESULTS: Patients received a median of 7 cycles (range, 4-26) of paclitaxel or docetaxel and received a total cumulative dose of 852.81 ± 368.82 mg/m2 (range, 300-2310 mg/m2). Though the mean CMT was significantly thicker in the taxane group (224.9 ± 28.4 µm) than the healthy control group (215.9 ± 19.7 µm), there was no statistically significant difference between the paclitaxel (225.3 ± 28.2 µm) and docetaxel (224.2 ± 20.1 µm) groups. On the other hand, the CCT was not statistically significant different between the taxane versus control eyes and paclitaxel versus docetaxel patients. Taxane-related CME was detected only in one patient on paclitaxel. Overall, incidence of taxane-related maculopathy was 0.5% (1/202) of all patients in the taxane group. CONCLUSION: In our group of taxane receiving patients, incidence of taxane-related CME was 0.5%. In light of our study, we believe that clinicians should be alert on the occurence of taxane-related CME and carefully scrutinize the patients whenever any suspicion is arisen.

EGFR mutation status in a series of Turkish non-small cell lung cancer patients.

Epidermal growth factor receptor (EGFR) mutations are potential markers driving carcinogenesis, and may alter the response to EGFR tyrosine kinase inhibitors in patients with non-small cell lung cancer (NSCLC). The frequency of EGFR mutations in patients with NSCLC differs according to sex, smoking habits and regional-based ethnicity differences. The aim of the present study was to determine the frequency of EGFR mutations in Turkish patients with NSCLC to highlight the importance of regional differences, and their associations with patient characteristics. Genomic DNA was extracted from formalin-fixed and paraffin-embedded tumor tissue sections of 409 NSCLC patients. The most common EGFR mutations in exons 18, 19, 20 and 21 were detected using BioFilmChip-based microarray assay. The overall EGFR mutation frequency was 16.6%, and the highest mutation frequencies were observed in exon 19 (6.4%) and exon 21 (7.3%). There was a higher frequency of EGFR mutations in females compared with males and in never-smokers compared with smokers (both P≤0.05). These results were similar to other European population-based studies, but not consistent Middle-Eastern based studies. The present study may contribute to understanding the gradient frequency of EGFR mutation across different ethnicities, and in designing genome wide-based collaborations that may reveal novel decision making and susceptibility mutations in EGFR in patients with NSCLC.