LAG-3 expression in tumor microenvironment of triple-negative breast cancer.

BACKGROUND: This study aimed to evaluate the expression of lymphocyte activation gene-3 (LAG-3) and its relationship with programmed cell death ligand-1 (PD-L1) in triple-negative breast cancer (TNBC). METHODS: : LAG-3 and PD-L1 was evaluated in tumor-infiltrating lymphocytes (TILs) using immunohistochemistry (IHC). The chi-square test was used to estimate the associations between LAG-3, PD-L1 and clinicopathological characteristics. Correlation between LAG-3 stromal TIL (sTIL), LAG-3 intraepitelial TIL (iTIL) and PD-L1 was assessed with using the Spearman's correlation coefficient. Survival analysis was performed using the Kaplan-Meier method. RESULTS: The percentages of LAG-3 sTIL+, LAG-3 iTIL+, PD-L1+ tumor cells and PD-L1+ inflammatory cells were 52%, 42%, 14% and 70%, respectively. A strong positive correlation between LAG-3 sTIL and LAG-3 iTIL (r = 0.874, p < 0.001) and a moderate positive correlation between LAG-3 sTIL and PD-L1 (r = 0.584, p < 0.001) were found. LAG-3 and PD-L1 status did not significantly affect overall survival (OS) (HR: 0.56 (95% CI: 0.15-2.11) (p = 0.397), HR: 2.70 (95% CI: 0.56-13.02) (p = 0.215), respectively). DISCUSSION: High levels of LAG-3 and PD-L1 expression were detected in patients with TNBC. Although their contribution to survival could not be determined, the high expression rates of PD-L1 and LAG-3 may help identify the subgroup of TNBC that would benefit from immunotherapy.

Current status of biosimilars in Turkey: A survey among medical oncologists.

INTRODUCTION: To evaluate biosimilar understanding and preference trends of medical oncologists in Turkey. METHODS: A survey consisting of 24 multiple-choice questions with checkbox answers was conducted among medical oncologists. The questionnaire was divided into five parts to some intentions: demographic characteristics, general knowledge about biosimilars, knowledge about local approval and reimbursement issues, individual preference trends, and ranking the knowledge of their own. All answers were analyzed as whole cohort, specialists and fellows. RESULTS: Fellows (n = 47) consisted 42%, and academic clinicians (n = 37) consisted 35% of the participants. In the whole cohort, the overall rate of correct answers was 55.1% in the general knowledge about the biosimilars part, and 26.7% in the local approval and reimbursement issues part. At all, 57.7% of the participants declared that they object to switch from a reference product to a biosimilar product. The rate of those who defined themselves as extremely knowledgeable decreased from 8.1% to 2.7% in the whole cohort at the end of the survey. CONCLUSION: The need for more accurate and clarified local regulations and education emerging in the biotechnology era must be met.

Predictive ability of the G8 screening test to determine probable sarcopenia and abnormal comprehensive geriatric assessment in older patients with solid malignancies.

BACKGROUND: Pre-treatment evaluation for sarcopenia is recommended in cancer patients. New screening tests that are less time-consuming and can identify patients who will potentially benefit from geriatric assessment are being developed; the G8 geriatric screening test is one such example. We aimed to investigate whether the G8 screening test can detect probable sarcopenia and is valid and reliable compared to a comprehensive geriatric assessment (CGA) in Turkish older adults with solid cancers. METHODS: We included solid cancer patients referred to a single center. Probable sarcopenia and abnormal CGA were defined as low handgrip strength. Cut-offs for handgrip strength in the Turkish population have been previously determined to be 32 kg for males and 22 kg for females and impairment in at least one of the CGA tests, respectively. The CGA tests comprised KATZ Basic Activities of Daily Living Scale Lawton-Brody Instrumental Activities of Daily Living Scale, Mini-Mental-State Examination Scale, Geriatric Depression Scale-15, and Mini-Nutritional Assessment Short Form. Receiver operating characteristic curve analyses evaluated the test's predictive ability. Intra-rater and inter-rater reliabilities were assessed. RESULTS: The median age of the 76 patients included was 72 (65-91) years. There was a moderate correlation between handgrip strength and the G8 test total score. The sensitivity and specificity of the G8 test to detect probable sarcopenia alone (cut off score = 12.5) were 50 and 92%, respectively (AUC: 0.747; p < 0.001); to determine abnormal CGA plus probable sarcopenia (cut off score = 13) were 93.33 and 86.89%, respectively (AUC: 0.939; p < 0.001); and to detect abnormal CGA alone (cut off score = 14) were 79.63 and 95.45%, respectively (AUC: 0.893; p < 0.001). The G8 test results agreed with those of CGA (κ = 0.638; p < 0.001). Both inter- and intra-rater assessments of G8 scores revealed a strong agreement (Interclass correlation coefficient = 0.979, p < 0.001 and ρ = 0.994, p < 0.001, respectively). CONCLUSIONS: The Turkish version of the G8 test is a good screening tool to detect probable sarcopenia alone and in conjunction with abnormal CGA in older patients with solid malignancies. The G8 screening tool may thus be useful in detecting probable sarcopenia in Turkish older adults with solid cancers.

The relationship between clinical and pathological findings and FDG - PET uptake in metastatic colorectal cancers.

BACKGROUND: In metastatic colorectal cancer (mCRC), the genetic structure and cell metabolism of the primary tumor lesion might be different from metastatic lesions. It is thought that cell-level glucose metabolism may differ due to the difference in RAS wild and mutant mCRC patients' prognosis. In this study, we aimed to compare 2-deoxy-2-[fluorine-18]-fluoro-D-glucose Positron Emission Tomography (18F-FDG PET/CT) uptake levels for KRAS mutation status and primary-metastatic tumor localization. METHODS: Our study is a retrospective cohort analysis that included RAS mutation status study and staging-oriented 18F-FDG PET/CT conducted on mCRC patients. RESULTS: There was no significant relationship between metastasis and primary tumor maximum Standardized uptake value (SUVmax) values according to the KRAS mutational status (P > 0.05). Patients with liver metastasis along with mutant BRAF mutation status had significantly higher SUVmax values in PET-CT scans (P = 0.04). There was a negative correlation between SUVmax values of lung metastases and overall survival (r = -0.35, P = 0.04). Patients with high carcinoembryonic antigen (CEA) levels had significantly higher SUVmax values of lung metastasis than patients with normal CEA levels (P = 0.009). Patients with high CA19-9 levels had significantly higher SUVmax values of liver, peritoneal, and bone metastasis than patients with normal CA19-9 levels (P = 0.002, P = 0.001, P = 0.004, respectively). There was no significant correlation between SUVmax values of metastasis and Lactate dehydrogenase (LDH) values. Liver metastasis of right-sided mCRCs had significantly higher SUVmax values (P = 0.03). CONCLUSION: We could not demonstrate a significant association between KRAS mutation and SUVmax values of PET scan in primary or metastatic tumor sites in advanced CRC.

Cachexia index in predicting outcomes among patients receiving immune checkpoint inhibitor treatment for metastatic renal cell carcinoma.

INTRODUCTION: Immune checkpoint inhibitors (ICI) have transformed treatments for patients with metastatic renal cell carcinoma (mRCC). Although some patients benefit greatly from ICI treatments, an effective marker to determine which patients will benefit from these treatments is lacking. Moreover, chronic inflammation and sarcopenia have been associated with poor survival rates among cancer patients. Accordingly, in this study, we investigated how the cachexia index (CXI), used as a combined score for sarcopenia and chronic inflammation, affects the survival outcomes of patients with mRCC receiving ICI. METHODS: We retrospectively screened data from 52 mRCC patients who had followed up between October 2010 and October 2021 after receiving ICI as a second-line or later treatment. Patients' respective basal CXI score were calculated according to the following formula, based on their L3 vertebral skeletal musculoskeletal area (SMI), neutrophil-lymphocyte ratio (NLR), and albumin (Alb) levels: CXI = (SMI x Alb) / NLR. Additionally, we analyzed how patients' subcutaneous adipose tissue (SAT), body mass index (BMI), ECOG performance status, The International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk score, nephrectomy status, sites of metastasis, and histological subtypes affected survival outcomes. RESULTS: Our univariate analysis significantly associated CXI score, NLR, nephrectomy status, and patient age with overall survival (OS). However, only CXI scores' significance was confirmed through multivariate analysis. The median OS (mOS) was 7 months for patients whose CXI score < the median value and 48 months for patients with a CXI score ≥ the median value. (HR 4.5, 95% CI [1.9-11], p = 0.001). Only CXI was significantly associated with progression-free survival (PFS) outcomes. The median progression-free survival (mPFS) was 4 months for patients whose CXI score < the median value and 17 months for patients with a CXI score ≥ the median value. (HR 2.6, 95% CI [1.3, 5.3], p = 0.007). Sarcopenia, sarcopenic obesity, and sarcopenia combined with NLR were not found to significantly affect OS. CONCLUSION: Our findings suggest that CXI score, a combined indicator of sarcopenia and chronic inflammation parameters, may serve as a useful marker in predicting the outcomes of ICI-based treatments for mRCC patients.

18F-FDG PET/CT for primary staging of patients with testicular germ cell tumors: the predictors of 18F-FDG PET positivity and prognostic value of PET derived metabolic parameters.

PURPOSE: The aim of this study was to investigate the role of histopathologic and biochemical parameters for predicting F-FDG PET positivity for primary staging in patients with newly diagnosed testicular germ cell tumors (TGCT). It was also aimed to evaluate the prognostic value of PET derived metabolic features in this patient group. MATERIALS AND METHODS: The imaging findings of 51 patients who were diagnosed as TGCT and underwent F-FDG PET/CT for primary staging after surgery between 2009 and 2019 were evaluated retrospectively. In terms of the presence of F-FDG uptake consistent with metastasis, the patients were divided into two groups as 'PET-positive' and 'PET-negative'. In 'PET-positive' patients, highest maximum standardized uptake values of metastatic lesions, whole-body total metabolic tumor volumes (wb-TMTV) and total lesion glycolysis (wb-TLG) were extracted. Pathological tumor types, pathological T stages (pT), tumor marker (TM) levels (AFP, hCG, LDH) after orchiectomy and overall survival (OS) times in months were also recorded. The predictive value of variables for OS was evaluated using the Kaplan-Meier survival analysis. RESULTS: PET positivity was observed in 28% of pT1 and in 83.3% in pT2-T3 tumors (P < 0.001). In the logistic regression analysis to predict 'PET positivity', pT stage and ≥2 elevated TMs were found as independent significant predictors. Survival analysis demonstrated that wb-TMTV, wb-TLG and TMs were significantly associated with prognosis for OS. CONCLUSION: The likelihood of PET positivity was significantly higher in patients with elevated TMs and pT2-T3 stages compared to those with normal TMs and pT1 tumors. PET derived quantitative metabolic-volumetric parameters can be used as biomarkers to identify patients with poor prognosis in TGCT.

Association of Low Fecal Elastase-1 and Non-Ulcer Dyspepsia.

Non-ulcer dyspepsia (NUD) is a term used to define a set of symptoms that are believed to originate from the gastroduodenal region, and no underlying organic, systemic, or metabolic reason can be found. The majority of patients suffer from chronic symptoms although half of the patients report improvement in symptoms with time. The potential role exocrine pancreatic insufficiency in NUD patients has not been clarified yet. We aimed to identify exocrine pancreas function with pancreatic fecal elastase-1 in patients diagnosed with non-ulcer dyspepsia and no typical exocrine pancreatic insufficiency (EPI) symptoms. Thirty-five patients referred to gastroenterology clinics with NUD and 35 people with no dyspeptic symptoms as a control group were included in this prospective study. Non-ulcer dyspepsia patients were classified as group 1 and control subjects classified as group 2. Upper gastrointestinal endoscopies were performed in both groups. Assessment of exocrine pancreatic function was performed by measuring fecal elastase-1 concentration with a commercial ELISA kit using polyclonal antibodies (BioServ Diagnostics) in NUD patients compared to control subjects. Mean fecal elastase-1 levels were significantly lower in group 1 patients compared with group 2 (367.47 ± 43.27; 502.48 ± 50.94 respectively; p = 0.04). The percentage of the patients with EPI was significantly higher in group 1 (p = 0.02). Patients with NUD should be re-evaluated if they do not show satisfactory improvement with treatment. Exocrine pancreatic insufficiency was significantly higher in patients with NUD in our study. Evaluation for the presence of EPI can be a cost effective approach in management of refractory patients during the process of ruling out organic reasons.