Association of systemic inflammatory markers with prognosis in erlotinib-treated EGFR-mutant non-small cell lung cancer.

BACKGROUND: To evaluate the relationship of overall survival (OS) and progression-free survival (PFS) with the derived neutrophil-lymphocyte ratio (dNLR), neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR), and platelet-lymphocyte ratio (PLR) in patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). METHODS: The study included 43 patients with EGFR-mutant metastatic NSCLC. The dNLR, NLR, LMR, and PLR values were calculated using the baseline complete blood counts before and after treatment with erlotinib. RESULTS: The NLR value had the best diagnostic test performance with a sensitivity of 91.3%. dNLR, NLR, LMR, and PLR were found to be significant for the prediction of OS and PFS. While the delta dNLR and NLR values were significant for OS, only the delta NLR value was significant for PFS. CONCLUSIONS: The dNLR, NLR, LMR, and PLR values were found to be significant in the prediction of OS and PFS in erlotinib-treated metastatic NSCLC. Further clinical studies are needed to determine the ideal target-specific tyrosine kinase inhibitor in cases of metastatic NSCLC presenting with the EGFR-activating mutation.

Brigatinib-associated autoimmune hepatitis: A case report.

INTRODUCTION: Brigatinib is a next-generation anaplastic lymphoma kinase (ALK) inhibitor that targets a wide variety of ALK mutations and ROS1 rearrangements. While pancreatic enzyme elevations due to brigatinib are well known, we wanted to present a case that caused liver toxicity. CASE REPORT: ALK and ROS1 translocations were detected in a 58-year-old patient diagnosed with metastatic lung adenocarcinoma. In the patient who had a good response with brigatinib, more than 5-fold elevation was detected in liver enzymes at the fifth month of treatment. MANAGEMENT & OUTCOME: After excluding other hepatitis factors, the patient was thought to have autoimmune hepatitis, and methylprednisolone was started and liver enzymes were decreased. DISCUSSION: Increased creatine kinase and lipase levels are common side effects associated with brigatinib, while liver toxicity is rare. Autoimmune hepatitis due to brigatinib was considered because of hepatic toxicity that developed in the fifth month of treatment and responded well to steroids.

Effects of enhancer of zeste homolog 2 and mucin 1 expressions on treatment response in breast cancer.

OBJECTIVE: Breast cancer is the most common malignancy in women. In the treatment of these patients, pathological complete response is defined as the absence of invasive cancer in breast or lymph node tissue after the completion of neoadjuvant chemotherapy. In this study, we aimed to investigate the relationship of enhancer of zeste homolog 2 and mucin 1 expressions with pathological complete response in patients with breast cancer receiving neoadjuvant chemotherapy. METHODS: A total of 151 patients were included in the study. Enhancer of zeste homolog 2 and mucin 1 expressions were evaluated in the biopsy materials pre-neoadjuvant chemotherapy and post-neoadjuvant chemotherapy surgical material, and their relationship with pathological complete response was investigated. RESULTS: The pathological complete response rates were significantly higher among the hormone receptor-negative patients, those with a high Ki-67 score, and patients with HER2-positive. Higher pathological complete response rates were obtained from patients with enhancer of zeste homolog 2 expression positivity pre-neoadjuvant chemotherapy. In addition, after neoadjuvant chemotherapy, enhancer of zeste homolog 2 expression was found to be completely negative in materials with pathological complete response; that is, in breast tissues considered to be tumor-free. While there was no significant relationship between mucin 1 expression and pathological complete response pre-neoadjuvant chemotherapy, mucin 1 expression was determined to significantly differ between the tissues with and without pathological complete response among the surgical materials examined. CONCLUSION: In our study investigating the relationship between enhancer of zeste homolog 2 and mucin 1 expression and pathological complete response in patients who received neoadjuvant chemotherapy, we found that enhancer of zeste homolog 2 expression could be used as a predictive marker for pathological complete response. However, mucin 1 expression was not associated with pathological complete response.

Panitumumab Associated Acute Pancreatitis.

INTRODUCTION: The addition of panitumumab to chemotherapy in wild-type metastatic colon cancer contributes to survival. While the skin related side effects of panitumumab are well known, we wanted to present a case where it was a possible cause of acute pancreatitis. CASE REPORT: The FOLFOX regimen was started in a 67-year-old patient with sigmoid colon cancer and multiple liver metastases. After 2 cycles, genetic tests were concluded and panitumumab 6 mg/kg was added to the treatment. The patient who presented with abdominal pain 2 days after the treatment was hospitalized with acute pancreaatitis. MANAGEMENT & OUTCOME: Abdominal tomography of the patient was compatible with acute pancreatitis. Oral intake was stopped, IV hydration was started. The patient, whose complaints regressed, was discharged on the 3rd day of hospitalization. DISCUSSION: Skin side effects related to panitumumab are observed quite frequently. Although panitumumab related gastrointestinal side effects have been reported, there is no data on acute pancreatitis. Panitumumab was added to the chemotherapy regimen he received, and it was thought that panitumumab might be the etiological factor in the case who developed pancreatitis.

Sarcoma - correlation between CD73 and PD-L1 and their relationship with prognosis.

This study aimed to evaluate CD73 and PD-L1 and determine their relationship with each other and with overall survival (OS) in sarcoma patients. The paraffin blocks of 101 patients were analysed. 56.4% were female, and the mean age was 51.39 years. The mean OS was 20.73 months, and the Ki-67 proliferative index was 41.45. A positive correlation was found between CD73 tumour and CD73 tumour-infiltrating lymphocyte (TIL) findings. CD73 tumour and TIL findings were also positively correlated with PD-L1 percentages and PD-L1 intensity. An inverse correlation was detected between OS and CD73 tumour and TIL groups of 5-25%, 25-50%, 50-75%, 75-90%, and > 90%, but no such correlation was found for the ≤ 5% group. There was an inverse correlation between OS and the PD-L1 percentages of  50% and the PD-L1 intensity of weak-moderate and strong, but no correlation was found for the negative values. Lastly, an inverse correlation was found between OS and the Ki-67 proliferative index. We found CD73 and PD-L1 positivity to be associated with decreased OS in sarcoma patients and determined a significant correlation between these parameters. This result is promising in terms of achieving better survival and disease control with anti-CD73 and anti-PD-L1 therapy in selected patients.

The effect of preferentially expressed antigen in melanoma (PRAME) expression status on survival in stage II and stage III colon cancer.

PURPOSE: There are no studies showing PRAME expression in stage II and III colon adenocarcinoma. In this study, we aimed to determine the frequency of PRAME expression and the relationship with survival and clinicopathological data in stage II and III colon adenocarcinoma that need adjuvant therapy. METHODS: Included were 81 patients with stage II and III colon cancer with adjuvant therapy without a second malignancy and systemic inflammatory diseases. RESULTS: A statistically significant relationship was detected between PRAME expression and disease progression and survival (p=0.01 and p=0.003, respectively). Shorter disease-free survival (DFS) and overall survival (OS) were detected in right colon tumors in patients with lymph node metastasis, metastatic lymph node >3, N1 or N2 according to the TNM staging system, with lymphovascular invasion, perineural invasion and PRAME expression (p=0.004, p=0.023, p=0.002, p=0.004, p=0.001, p=0.006, p=0.01, respectively and p=0.009, p=0.037, p=0.001, p=0.004, p=0.003, p=0.004, p=0.006, respectively). In multivariate analysis, it was determined that right colon tumor (HR: 0.488, 95% CI, 0.201-0.998, p=0.049) and PRAME expression (HR: 0.423, 95% CI, 0.170-1.052, p=0.046) were independent risk factors for short DFS. For the OS, only the presence of PRAME expression was determined as an independent risk factor. (HR:0.332, 95%CI, 0.129-0.856, p=0.022). CONCLUSION: PRAME can be a potential target in immunotherapy in colon cancer treatment.

Carotid-femoral pulse wave velocity is significantly increased in newly diagnosed hypertensive patients with primary hyperparathyroidism and significantly related with serum calcium level.

BACKGROUND: Primary hyperparathyroidism (PHP) is a rare cause of secondary hypertension (HT), but in patients with PHP, HT is very common and 20-80% of patients have HT. The aim of this study was to evaluate the change in carotid-femoral pulse wave velocity (CF-PWV) in hypertensive patients with PHP, and was to determine the clinical, laboratory, and echocardiographic parameters associated with CF-PWV. METHODS: The study included 83 newly diagnosed hypertensive patients with PHP and 83 patients with newly diagnosed essential HT without PHP. All patients underwent echocardiography and CF-PWV measurements. RESULTS: In patients with PHP, blood urea nitrogen, hs-CRP, uric acid, serum and urine calcium, parathyroid hormone level, CF-PWV value, LV wall thickness, LVMI, aortic and left atrium (LA) diameter, and presence of LVH and CF-PWV > 10 m/s were higher, and serum phosphorus levels were lower. Serum calcium, LA diameter, and LVMI values were closely correlated with CF-PWV. In the ROC analysis, the AUROC was calculated as 0.825 for calcium level to determine the patients with increased CF-PWV. When the serum calcium value was taken as 10 mg/dL, it was determined with CF-PWV > 10 m/s were 79.5% sensitivity and 78.2% specificity. CONCLUSION: CF-PWV significantly increases in newly diagnosed hypertensive patients with PHP and significantly related to serum calcium level. To protect against target organ damage, high serum calcium levels should be monitored as well as blood pressure in hypertensive patients with PHP.

The Effect of Inflammatory Markers on Survival in Advanced Biliary Tract Carcinoma Treated with Gemcitabine/Oxaliplatin Regimen.

BACKGROUND: In advanced biliary tract carcinoma (BTC), the prognosis is very poor, and the overall survival is less than 1 year. This study aimed to determine the effect of neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), C-reactive protein (CRP)/albumin ratio (CAR), and prognostic nutritional index (PNI) on the survival of BTC patients treated with gemcitabine/oxaliplatin (GEMOX) regimen. METHODS: Data of 53 patients with advanced BTC were evaluated retrospectively. Association between inflammatory markers and 6-month PFS and 12-month OS were compared by the log-rank test. The optimal cutoff values were determined by a receiver operating characteristic (ROC) curve analysis. NLR, dNLR, CAR, and PNI were grouped based on cutoff points 1.95, 1.15, 0.57, and 33, respectively. Univariate and multivariate analyses were used to assess their prognostic values for survival. RESULTS: Lower dNLR (< 1.15) was prognostic for higher 6-month PFS and 12-month OS rates, while lower NLR (< 1.95) was prognostic for higher 6-month PFS rates only. CAR and PNI did not have statistically significant effects on survival. CONCLUSIONS: Pretreatment dNLR and NLR values in advanced BTC can be used as predictive markers for survival in patients undergoing the GEMOX regimen.

Advanced Biliary Tract Cancer Treated with Gemcitabine plus Cisplatin (GEMCIS) and Novel Inflammatory Markers.

OBJECTIVE: It is known that chronic inflammation plays an important role in the etiopathogenesis of biliary tract carcinoma (BTC). In this study, we wanted to examine the effect of neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), and prognostic nutritional index (PNI) on survival in advanced BTC treated with gemcitabine plus cisplatin (GEMCIS) regimen. METHODS: Forty-two patients with advanced BTC treated with GEMCIS regimen were included in the study. Measurements for NLR, dNLR and PNI were calculated with available formulas. NLR, dNLR, and PNI values were dichotomized based on receiver operating characteristic curve analysis (cut-off values 3.94, 2.66, and 46, respectively). Univariate and multivariate analyses were performed to identify prognostic factors for 6-month progression free survival (PFS) and overall survival (OS) using a Cox proportional hazards model. RESULTS: The mean PFS was 5.3 (median 5) months, and the mean OS was 10.7 (median 11) months. The pre-treatment increased NLR (≥ 3.94) value was prognostic for lower 6-month PFS and 12-month OS rates. dNLR was not found to be important for survival times. Low PNI (< 36) value was prognostic for lower 6-month PFS and 12-month OS rates. In the multivariate analysis, increased NLR value was determined as an independent prognostic factor for 6-month PFS. CONCLUSION: In patients with advanced BTC using GEMCIS as the first-line chemotherapy regimen, NLR and PNI can be used as prognostic inflammatory markers for 6-month PFS and 12-month OS.

Inflammatory Markers Predicting Pathological Complete Response in Cases with Breast Cancer Treated by Neoadjuvant Chemotherapy.

OBJECTIVE: Response to neoadjuvant chemotherapy (NAC) is predictive for survival times in some patients with breast cancer (BC). The aim of this study is to explore the predictive value of some inflammatory markers including neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), monocyte-to-high density lipoprotein ratio (MHR) and prognostic nutritional index (PNI) in cases with BC treated with NAC. MATERIALS AND METHODS: One hundred and ten patients with BC treated with NAC were included in the study. Measurements for NLR, dNLR, MHR and PNI were calculated with available formulas. The value of NLR, dNLR, MHR and PNI in predicting pCR to NAC in BC was analyzed using receiver operating characteristic (ROC) curve analysis. All analyses were performed using the SPSS statistical software package (SPSS statistics 21.0). RESULTS: Mean NLR values were 2.2±0.8 vs. 2.6±1.3 for pCR (+) and pCR (-) groups (p=0.603). Mean dNLR values were 1.5±0.5 vs. 1.9±0.8 for pCR (+) and pCR (-) groups, respectively and this was statistically significant (p=0.022). Mean MHR values were 15.4±17.2 vs. 13.2±10.1 for pCR (+) and pCR (-) groups (p=0.406). Mean PNI values were 52±5.1 vs. 49±5.8 for pCR (+) and pCR (-) groups, and this was statistically significant (p=0.015). In multiple logistic regression analysis PNI was found to be independent factor for pCR. CONCLUSION: In this study pre-treatment dNLR and PNI were found to be predictive for pCR while NLR and MHR were not found to be associated with pCR. PNI and dNLR are simple but useful biomarkers predicting response to NAC.

Prognostic significance of EGFR, MUC1 and PD-L1 expressions in cases with triple negative breast cancer.

PURPOSE: Twenty percent of the breast cancers are triple negative (TNBC). Despite the impressive progression in the biology of this subgroup, data is limited as compared to hormone and/or HER2 positive cases. Thus, the aim of this study was to detect the expression levels and to identify the prognostic values of MUC1, EGFR and PD-L1 in TNBC. METHODS: MUC1, EGFR and PD-L1 expressions were detected by immunohistochemistry in 97 cases with TNBC. Associations between clinical and histopathological parameters with overall survival (OS) and progression-free survival (PFS) were analyzed using the Kaplan-Meier method and compared by the log-rank test. Prognostic effects were analyzed by Cox proportional hazard models. RESULTS: During a median follow-up of 93 months (0.6-168.7) the mean PFS was 110.1 and OS was 121.8 months. Tumor diameter (T), involved lymph node status (N) and TNM were found to be prognostic for PFS and OS. PD-L1 in microenvironment (PD-L1 ME) and EGFR expression were found to be associated with longer PFS and OS, but MUC1 and tumor PD-L1 (PD-L1 TM) expressions were not. All combined analyses showed that in the subgroups of MUC1, PD-L1 TM or ME positive, EGFR expression was correlated with longer PFS and OS than those who were not. Older age (≥70 years), T and N status and also EGFR expression were found to be independent prognostic factors for OS in Cox regression analysis. CONCLUSION: EGFR expression was found to be one of the most important prognostic factors in addition to T and N status in cases with TNBC.

Performance of Positron Emission Tomography-Computed Tomography and Bone Marrow Biopsy in Detecting Bone Marrow Infiltration in Lymphoma Cases

Objective: Bone marrow infiltration (BMI) affects the stage diagnosis, and treatment of lymphoma. We aimed to evaluate the performance of bone marrow biopsy (BMB) and positron emission tomography-computed tomography (PET/CT) in detecting BMI in lymphoma patients. Materials and Methods: A total of 269 non-Hodgkin's lymphoma (NHL) and 110 Hodgkin's lymphoma (HL) patients were evaluated retrospectively. Sensitivity, negative predictive value (NPV), and accuracy were calculated for PET/CT and BMB in detecting BMI.ensitivity, negative predictive value (NPV) and accuracy were calculated for PET/CT and BMB in detecting BMI. Results: Sensitivity, NPV, and accuracy for PET/CT in detecting BMI in NHL cases were 65%, 78%, and 84.4%, respectively, while they were 55%, 73.4%, and 79.9% for BMB. PET/CT performance for diffuse large B-cell lymphoma and follicular lymphoma was better than that of BMB, whereas the performance of BMB was better for mantle-cell lymphoma, Burkitt's lymphoma, and primary mediastinal B-cell lymphoma. Sensitivity, NPV, and accuracy for PET/CT in HL cases were 91.3%, 97.75%, and 98.18%, respectively, while they were 56.52%, 89.69%, and 90.91% for BMB. Due to BMB, 43 (15.9%) patients in the NHL group and 2 (1.8%) patients in the HL group were protected from downstaging. Conclusion: Although their results vary according to NHL subtypes, PET/CT and BMB are complementary methods in determining BMI. In HL, PET/CT is an important diagnostic tool for detecting BMI, and BMB is not necessary in a significant proportion of cases.

Correction to: Brentuximab vedotin use in a jaundiced case with resistant Hodgkin lymphoma.

The original version of this article contained a mistake in one of the author names. Cem Irili should have been Cem Mirili.

Assessment of potential predictive value of peripheral blood inflammatory indexes in 26 cases with soft tissue sarcoma treated by pazopanib: a retrospective study.

PURPOSE: The aim of this study was to evaluate the prognostic and predictive value of neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (DNLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR) in soft tissue sarcoma (STS) cases treated with pazopanib. MATERIALS AND METHODS: The study population included 26 STS cases treated with pazopanib for at least 3 months. NLR, DNLR, LMR, and PLR were evaluated at baseline, and at third month of therapy and also compared with response to pazopanib. Median measurements were taken as cutoff for NLR (4.8), DNLR (3.1), LMR (3.6), and PLR (195). The associations between these cutoff values and survival times (progression-free survival [PFS] and overall survival [OS]) were assessed by Kaplan-Meier curves and Cox proportional models. RESULTS: Patients with low pretreatment NLR and DNLR had longer OS (P=0.022, P=0.018), but low PLR was found to be associated only with longer OS. Additionally, decrease in NLR and DNLR after 3 months of therapy as compared with pretreatment measurements was found to be associated with an advantage for OS (P=0.021, P=0.010, respectively) and PFS (P=0.005, P=0.001, respectively). Response to pazopanib; changes in NLR, DNLR, LMR, and PLR; and >3 metastatic sites were found to be independent risk factors in univariate analysis, but NLR was the only independent risk factor in multivariate analysis. CONCLUSION: Low pretreatment and decrease in NLR and DNLR values, and regression/stable disease after 3 months of pazopanib are predictive factors for longer OS and PFS.

Prognostic significance of neutrophil/lymphocyte ratio (NLR) and correlation with PET-CT metabolic parameters in small cell lung cancer (SCLC).

PURPOSE: The aim of this study is to detect the prognostic significance of neutrophil/lymphocyte ratio (NLR) in SCLC and to evaluate the relation with 18F-FDG PET-CT metabolic parameters (PET-CT MPs). METHODS: Demographic parameters, laboratory values including NLR and other clinical variables were analyzed in 112 patients with small cell lung cancer (SCLC) and 54 of these patients had results of metabolic parameters detected with 18 FDG PET-CT [including SUVmax, SUVmean, metabolic tumor volume (MTV), whole body MTV (WBMTV), TLG (total lesion glycolysis), whole body TLG (WBTLG)] were evaluated for survival analyses. RESULTS: Mean and median overall survival (OS) and progression-free survival (PFS) were found to be significantly longer in cases with NLR < 4 compared with NLR > 4 in totally. Also stage, performance status, response to first-line therapy, LDH, and lymphocyte count were found to be prognostic for OS and PFS. MTV, WBMTV and WBTLG were found to be prognostic for both OS and PFS, while SUVmax found to be significant for OS. Patients with NLR ≥ 4, MTV ≥ 60.1, WBMTV ≥ 120 and WBTLG ≥ 1000 points had lower OS and PFS. A moderate positive correlation was found between NLR and SUVmean (r: 0.36), SUVmax (r: 0.34), TLG (r: 0.39), MTV (r: 0.51), WBMTV (r: 0.40), and WBTLG (r: 0.46). CONCLUSION: There is relationship between PET-CT metabolic parameters and NLR in SCLC. Highest correlation was found with NLR and MTV, WBMTV, and WBTLG, and evaluation of NLR together with these parameters predicts survival times and tumor biology more clearly in SCLC.

Myeloid Neoplasia and Lymphoblastic Lymphoma with Eosinophilia After Radioactive Iodine: A Case Report.

BACKGROUND: Thyroid cancer is the most common endocrine cancer, with an increasing incidence around the world in the last three decades. The increased risk of secondary cancer is associated with a genetic predisposition or radioactive iodine used in the treatment. CASE REPORT: A 65-year old male patient was operated on for thyroid papillary cancer. He received radioactive iodine on two occasions postoperatively. After six years, he presented with malaise and fatigue with leukocytosis and eosinophlilia. The physical examination revealed inguinal lymphadenopathies and splenomegaly, after examining the bone marrow and lymph node biopsies, he was diagnosed with eosinophilic myeloproliferative neoplasia and T-cell lymphoblastic leukaemia/lymphoma. CONCLUSION: Leukaemia and other haematological malignencies may develop after radioactive iodine treatment. Patients with radioactive iodine ablation history should be monitored for a long time.