Evaluation of the efficacy and safety of nivolumab in the second- or later-line treatment of patients with locally advanced/metastatic non-small cell lung cancer in Türkiye: a retrospective multicenter non-interventional registry study.

OBJECTIVE: To evaluate the efficacy and safety of nivolumab in the second-line (2L) or later-line (LL) treatment of patients with locally advanced/metastatic non-small cell lung cancer (NSCLC) in real-life setting in Türkiye. METHODS: This study was designed as a national, multi-center, retrospective study. The study population was evaluated in two groups for the line of nivolumab therapy: those receiving nivolumab in the 2L (Group 2L) and third-line (3L) or LL (Group 3L/LL). Efficacy was evaluated based on one-year overall survival (OS) and progression-free survival (PFS). Safety was evaluated based on treatment-related adverse events (AEs) and nivolumab discontinuation rate. RESULTS: Of 244 patients, 52.9% were in Group 2L and 47.1% were in Group 3L/LL. Demographic and clinical characteristics did not differ between the groups. In Group 2L and Group 3L/LL, one-year OS and PFS rates were 60.8% and 61.4% (p = 0.592) and 31.2% and 21.3% (p = 0.078), respectively. The objective response rate (ORR) was 34.7% in Group 2L and 27.3% in Group 3L/LL (p = 0.262). The percentage of patients reporting at least one AE in Groups 2L and 3L/LL was 34.9% and 43.5%, respectively (p = 0.169). Fatigue was the most common (16.4%) treatment-related AE in each group. The groups were comparable regarding the AE frequency. Nivolumab was discontinued in 61 patients in Group 2L and 53 patients in Group 3L/LL, with the most common reason being disease progression (57.4% and 66.0%, respectively). CONCLUSION: Nivolumab is safe and effective in the 2L or 3L/LL treatment of locally advanced/metastatic NSCLC and associated with acceptable AEs in real-life setting.

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer (around 85% of all lung cancers). Patients with NSCLC are usually diagnosed at advanced or metastatic stages. When cancer cells spread to other areas from where they first formed, it is called metastatic cancer. Surgery may not be a treatment option for such patients. Currently, immunotherapeutic agents are used in the treatment of NSCLC. Nivolumab is one of the approved immunotherapeutic agents in the treatment of patients with metastatic NSCLC, who have failed after receiving chemotherapy. Our study explored the efficacy and safety of nivolumab in real-life setting in Türkiye. Nivolumab effectiveness was evaluated by overall survival (OS) and progression-free survival (PFS) rates. OS indicates the proportion of patients who are still alive at a given time after diagnosis or treatment initiation. PFS refers to "the length of time during and after cancer treatment that a person lives with the disease but does not get worse." In the present study, one-year OS for 244 patients who received nivolumab was 61.1% and one-year PFS was 26.4%. Nivolumab safety was evaluated based on the frequency of adverse events observed during nivolumab therapy. Of the patients 38.9% had at least one side effect, with fatigue being the most common (16.4%). Our results support the earlier studies and showed that nivolumab was a safe and effective agent and is associated with acceptable side effects.

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.

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.

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.

Coexistence of anal malignant melanoma and papillary renal cell cancer: An interesting coexistence.

Coexistence of malignant melanoma and renal cell cancer (RCC) is a rare phenomenon, but this issue becomes increasingly popular. The objective of the current study is to present a case with coexistent anorectal melanoma (ANM) and papillary RCC detected. A 61-year-old female admitted to our clinic with complaints of blood in the stool. ANM diagnosed with colonoscopic biopsy and a mass lession with a size of 57 mm × 53 mm suggesting RCC was detected in the left kidney during staging procedure. Transabdominal resection and radical nephrectomy were performed and diagnoses of ANM and papillary RCC were confirmed. Adjuvant radiotherapy was applied for ANM. The patient is still under follow-up for 6 months and no recurrence or progression was detected. To the best of our knowledge, this is the first report of this interesting coexistency.

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.

Possible atezolizumab-associated acute kidney injury and immune thrombocytopenia.

INTRODUCTION: The immune checkpoint inhibitors (ICIs), which are used to activate the immune system and stimulate anti-tumor activity, are preferred in many cancers. Atezolizumab acts by blocking programmed cell death ligand (PD-L1) and may cause immune hyperstimulation in healthy tissues like other ICIs, resulting in immune-related adverse events (irAEs). Hepatitis, colitis, pneumonitis, hypophysitis, hypothyroidism, rash, musculoskeletal problems are the most common irAEs, and on the other hand, acute kidney injury (AKI) and immune thrombocytopenic purpura (ITP) are infrequent. CASE REPORT: We present a case with non-small cell lung cancer (NSCLC) treated with atezolizumab 1200 mg every three weeks for third-line treatment. The patient was admitted with fatigue and back pain. The patient's complaints started one week after the first dose of atezolizumab. The patient had renal injury and thrombocytopenia and was diagnosed with drug-induced AKI and ITP. MANAGEMENT AND OUTCOME: After platelet replacement, intravenous immunoglobulin (IVIG), and steroid therapy, the patient whose platelet count was normalized and creatinine level regressed was discharged, and routine follow-up continues. DISCUSSION: Here, we present a case with NSCLC treated with atezolizumab and with drug-induced ITP and AKI association. Given that atezolizumab and other immune checkpoint inhibitors are being utilized in the treatment of cancers, physicians should be aware of the irAEs, including the AKI and ITP.

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.

The ratio of hemoglobin to red cell distribution width predicts survival in patients with gastric cancer treated by neoadjuvant FLOT: a retrospective study.

BACKGROUND: Hemoglobin (HB) and red cell distribution width (RDW) are known to be prognostic in many cancer types. The HB-RDW ratio (HRR) is a new biomarker that has been shown to be predictive in some cancer types. However, the prognostic significance of HRR in patients with gastric cancer (GC) is unknown. AIMS: In this study, we aimed to demonstrate the prognostic importance of HRR in GC patients treated with neoadjuvant fluorouracil, leucovorin, oxaliplatin, docetaxel (FLOT). METHODS: Eighty-five GC patients who were treated with neoadjuvant FLOT in our center were included in the study, retrospectively. Associations between clinical and histopathological parameters with disease-free survival (DFS) and overall survival (OS) were analyzed using Kaplan-Meier curves and compared by the log-rank test. The optimal cutoff values were determined by a receiver operating characteristic (ROC) curve analysis. Neutrophil-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), and HRR were grouped based on a cutoff points 3.05, 802, and 0.89, respectively. Univariate and multivariate analyses were used to assess their prognostic values for DFS and OS. RESULTS: Low NLR, low SII, and high HRR were found to be associated with longer DFS/OS. In univariate analysis, Eastern Cooperative Oncology Group performance status, grade, stage, response to neoadjuvant treatment, NLR, SII, and HRR were found to be significantly associated with DFS and OS. But in multivariate analysis, only HRR was demonstrated as an independent prognostic factor for DFS/OS (p 0.001, p 0.037, respectively). CONCLUSIONS: HRR is a new biomarker that can predict DFS and OS in GC patients treated with neoadjuvant FLOT.

Colorectal cancer in Lynch syndrome associated with PMS2 and MSH6 mutations.

BACKGROUND: It is known that colorectal cancers (CRC) are frequently seen and constitute an important part of cancer-related deaths. Lynch syndrome (LS) is responsible for 3-5% of CRCs and develops due to mutations in DNA mismatch repair (MMR) genes. The most important MMR genes are MutL homolog1 (MLH1), mutS homolog 2 (MSH2), mutS homolog 6 (MSH6) and postmeiotic segregation increased 2 (PMS2). PMS2 and MSH6 mutations are very rarely seen in LS. CASE PRESENTATION: We present a case that developed metastatic CRC, which we diagnosed as LS in association with a very rarely seen PMS2 and MSH6 germline mutation. Genetic counseling was recommended for the family, and screening programs were initiated for the family of the patient whose chemotherapy was continued after the diagnosis. CONCLUSION: With the increase in daily use of next-generation sequencing (NGS) technology, it is thought that detection rate of both combined mutations and rare mutations will be increased.

A novel predictor in patients with gastrointestinal stromal tumors: Systemic immune-inflammation index (SII).

PURPOSE: Systemic inflammation and immune response are associated with tumors'prognosis. However, there is little information about inflammatory indexes in patients with gastrointestinal stromal tumor (GIST). In this study, we aimed to determine the prognostic significance of inflammation indexes such as neutrophil to lymphocyte ratio (NLR), systemic immune-inflammation index (SII), prognostic nutritional index (PNI) and Glasgow prognostic score (GPS) in GIST patients. METHODS: Forty-five patients diagnosed with GIST between 2003 and 2018 were included in the study. The effects of NLR, SII, PNI and GPS on progression-free survival (PFS) and overall survival (OS) estimated based on clinicopathological and laboratory data were evaluated by Kaplan-Meier and Cox regression analysis. RESULTS: The optimal cut-off values for NLR, SII and PNI were 2.54, 940, and 37.5, respectively. Low SII and higher PNI values were associated with longer PFS (p=0.041, p=0.018, respectively). In terms of OS, patients with high NLR, high SII and low PNI had a shorter lifespan. In multivariate analysis, only SII was found to be independent prognostic factor. CONCLUSION: In cases with GIST, SII may predict recurrence and survival.

Systemic immune-inflammation index predicting survival outcome in patients with classical Hodgkin lymphoma.

Aim: To evaluate the prognostic significance of neutrophil lymphocyte ratio, prognostic nutritional index, systemic immune-inflammation index (SII) and B2M in Hodgkin Lymphoma (HL). Materials & methods: Neutrophil-lymphocyte ratio, prognostic nutritional index, SII and B2M were analyzed to assess their prognostic value via the Kaplan-Meier method and Cox regression analysis in 122 HL patients, retrospectively. Results: SII was found to have the highest area under curve and the most sensitive and specific among all markers. In univariate analyses, all four parameters were prognostic for overall survival and progression-free survival, in multivariate analyzes only SII was found to be independent factors for both of them. Conclusion: SII can be suggested as a novel independent and better prognostic factor for predicting overall survival and progression-free survival in HL.

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.

Clinical significance of prognostic nutritional index (PNI) in malignant melanoma.

PURPOSE: Nutrition and inflammation play a crucial role in the development of cancer. The prognostic value of the prognostic nutritional index (PNI) has been confirmed in some types of human cancers. However, few studies are available indicating its prognostic power in patients with malignant melanoma (MM). Thus, we aimed to identify baseline peripheral blood biomarkers to predict the outcome of MM patients MATERIAL AND METHODS: Data of 101 patients with MM were evaluated retrospectively. Associations between clinical and histopathological parameters with overall survival (OS) and progression-free survival (PFS) were analyzed using Kaplan-Meier curves and compared by the log-rank test. The optimal cutoff values were determined by a receiver operating characteristic (ROC) curve analysis. Neutrophil-lymphocyte ratio (NLR), systemic immune-inflammation index (SII) and PNI were grouped based on a cutoff points 2.18, 547.1, and 40.1, respectively. Univariate and multivariate analyses were used to assess their prognostic values for overall survival (OS). RESULTS: Lower NLR ( < 2.18), SII ( < 547.1) and higher PNI ( ≥ 40.1) were linked with a longer PFS and OS in patients with MM, as reflected in the Kaplan-Meier analyses. In univariate analysis, TNM stage, Breslow thickness, Clark stage, ulceration, Ki67 status, LDH, NLR, SII, and PNI were significantly associated with OS. Multivariate analysis identified TNM stage, ulceration, LDH and PNI as an independent predictor of OS in patients with MM. CONCLUSION: PNI can be regarded as a novel independent prognostic factor for predicting OS in MM.

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.