Metastatik küçük hücre dışı akciğer kanseri hastalarının ikinci veya ileri sıra tedavisinde immünoterapinin gerçek yaşam analizi

Background: Immunotherapy agents such as atezolizumab and nivolumab are appropriate option for non-small cell lung cancer (NSCLC) accounts in the absence of driver mutation, regardless of PDL-1 expression in second and later line setting. Herein we aimed to evaluate the efficacy and safety of immunotherapy for the second and later line settings in metastatic NSCLC patients as a single center experience. Methods: Totally, 37 patients with metastatic NSCLC who received atezolizumab or nivolumab in the second or later lines were included. Clinicopathological features of patients and survival outcomes were analyzed. The safety profile and the factors that may predict survival were also evaluated. Results: Twenty-nine (78.4%) of patients were men and 8 of patients (21.6%) were woman with median age of 61 years (range:42-80). Atezolizumab was preferred in 22 (59.5%) of these patients and nivolumab in 15 (40.5%) of them. Objective response rate was 35.1%. At a median follow up of 22.5 months, median progression-free survival (PFS) was 4.7 months, median overall survival (OS) was 24.1 months. Univariate analysis for PFS revealed that gender (p=0.03), age (p=0.005), the presence of brain metastasis (p=0.02), PDL-1 status >1% (p=0.035), ECOG PS (p=0.04) and the good response to frontline treatment (p=0.015) were found to be significant prognostic indicators. It also showed that the presence of brain metastasis (p=0.03), PDL-1 status >1% (p=0.027), good response to frontline treatment (p=0.022) and atezolizumab preference (p=0.018) were prognostic factors for OS. Conclusion: Our real-life analysis indicated that atezolizumab and nivolumab improved survivals with good safety profile in second and later lines treatment of metastatic NSCLC patients.Atezolizumab ve nivolumab, driver mutasyon yokluğunda, küçük hücre dışı akciğer kanserinin (KHDAK) ikinci ve sonraki basamak tedavisinde PDL-1 durumundan bağımsız olarak kullanılabilen iyi bir seçenektir. Burada, metastatik KHDAK’li hastalarda ikinci ve sonraki sıra tedavide immünoterapinin etkinliğini ve güvenliğini değerlendirmeyi tek Merkez deneyimi olarak amaçladık. Gereç ve yöntem: Çalışmaya, ikinci veya sonraki sıralarda atezolizumab veya nivolumab alan toplam 37 metastatik KHDAK hastası dahil edildi. Hastaların klinikopatolojik özellikleri ve sağkalım sonuçları analiz edildi. Güvenlik profili ve sağkalımı öngörebilecek faktörler değerlendirildi. Bulgular: Hastaların 29'u (%78.4) erkek, 8'i (% 21.6) kadın, ortanca yaş 61 (aralık: 42-80) idi. Bu hastaların 22'sinde (%59.5) atezolizumab, 15'inde (% 40.5) nivolumab tercih edilmişdi. Objektif yanıt oranı %35.1 idi. Medyan 22.5 aylık takipte, medyan progresyonsuz sağkalım 4.7 (PSK) ay iken, medyan genel sağkalım (OS) 24.1 ay olarak bulundu. PFS için tek değişkenli analizde, cinsiyet (p=0.03), yaş (p=0.005), beyin metastazı varlığı (p=0.02), PDL-1 durumu >%1 (p=0.035), ECOG PS (p=0.04) ve ilk sıra tedaviye iyi yanıt varlığı (p=0.015) anlamlı prognostik göstergeler olarak bulundu. OS için ise, beyin metastazı varlığı (p=0.03), PDL-1 durumu >%1 (p=0.027), ilk sıra tedaviye iyi yanıt varlığı (p=0.022) ve atezolizumab tercihi (p=0.018) prognostik faktörler olarak bulundu. Sonuçlar: Gerçek hayat analizimiz, atezolizumab ve nivolumabın, metastatik KHDAK hastalarının ikinci ve sonraki basamak tedavilerinde iyi güvenlik profili ile sağkalımı iyileştirdiğini gösterdi

Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio as prognostic markers in patients with extensive-stage small cell lung cancer treated with atezolizumab in combination with chemotherapy

Atezolizumab is now the standard treatment for extensive-stage small cell lung cancer (ES-SCLC). Herein, we investigated the prognostic role of inflammatory markers in patients treated with atezolizumab plus chemotherapy and evaluated the efficacy and safety of adding atezolizumab to chemotherapy for patients with ES-SCLC and prognostic and predictive factors as a real-life experience. This retrospective study included 55 patients who received front-line atezolizumab with etoposide plus platin regimen for ES-SCLC. We analyzed the survival outcomes and factors that may predict response and survival. The objective response rate (ORR) was 81.8%. At a median follow-up of 23.5 months, the median progression-free survival (PFS) time was 10.8 months, and the median overall survival (OS) time was 15.2 months. In univariate analysis for PFS, limited-stage disease at the time of diagnosis, the presence of prophylactic cranial irradiation (PCI), the presence of liver metastasis, neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) were found to be prognostic factors (P = .041, P = .034, P = .031, P = .004, and P = 135.7. Similarly, median PFS was 14.9 months in patients with NLR ≤ 3.43, while it was 9.6 months in patients with > 3.43. Univariate analysis for OS revealed that limited stage at the time of diagnosis, NLR and PLR were significant prognostic indicators (P = .01, P = .006, and P = .007, respectively). Median OS time for patients with both NLR ≤ 3.43 and PLR ≤ 135.7 was significantly better than that of patients with NLR > 3.43 and PLR > 135.7 (16.9 vs 11.3 and 16.9 vs 11.5 months, respectively). Logistic regression analysis demonstrated that PLR was an independent significant predictive factor for the response to atezolizumab plus chemotherapy (OR: 0.07, P = .028). The patients with PLR ≤ 135.7 were significantly good responders to atezolizumab plus chemotherapy treatment. Real-life data demonstrated a significant correlation between survival and NLR and, PLR in ES-SCLC patients treated with atezolizumab. In addition, PLR was a significant predictive indicator of response to atezolizumab plus chemotherapy

Acute Renal Failure due to Leukaemic Infiltration in Chronic Lymphocytic Leukaemia

Chronic lymphocytic leukemia (CLL) is a malignancy characterized by clonal proliferation and accumulation of B lymphocytes. Although leukaemic infiltration of the kidney is well recognized in CLL, acute renal failure (ARF) due to leukaemic infiltration is extremely rare. Here we present a case of ARF as the initial manifestation of CLL. The diagnosis was made by a kidney biopsy. Treatment with cyclophosphamide and prednisolone resulted in a completely improved renal function

An Unusual Case of Cushing’s Syndrome: Coexistence of Functional Pituitary and Adrenal Adenoma

A case of adrenocorticotropic hormone (ACTH)-independent Cushing’s syndrome, which develops in the course of ACTH-dependent Cushing’s disease, is presented in this report. A 47-year-old woman with a past history of surgery and gamma knife radiosurgery because of Cushing’s disease was admitted to the endocrinology clinic with weight gain and unregulated blood glucose levels. Hypercortisolemia was still persisting and diagnostic work-up indicated ACTH-independent Cushing’s syndrome. Along with the rare possibility of this coexistence, longstanding ACTH hypersecretion can play a role in functional transition of adrenal adenomas. Further studies are needed to clarify the underlying mechanisms

Platelet to lymphocyte ratio is associated with tumor localization and outcomes in metastatic colorectal cancer

The aim of this study was to investigate the predictive and prognostic value of PLR, and the relationship between PLR and tumor localization. A total of 229 patients with de-novo metastatic CRC were retrospectively analyzed. The cutoff value for PLR was defined by the receiver operating characteristic (ROC) curve analysis and threshold value of 196.5 as best cut-off value was found. The higher rate of BRAF mutation was significantly detected for patients with PLRhigh (> 196.5) compared to those with PLRlow (<= 196.5) (P = .001). PLR was significantly higher in tumors located on the right colon (P = .012). PLR, tumor localization, the presence of surgery for primary tumor, the presence of curative surgery, the presence of metastasectomy for progression-free survival (PFS) and PLR, gender, BRAF mutation, tumor localization, the presence of surgery for primary tumor, the presence of metastasectomy for overall survival (OS) were found to be prognostic factors by univariate analysis. Multivariate analysis showed that PLR, the presence of curative surgery and the presence of metastasectomy for both PFS and OS were found to be independent prognostic factors. Moreover, a logistic regression analysis indicated that PLR and tumor localization were found to be an independent factors for predicting response to systemic treatment (P P = .023 respectively). Our results showed that pretreatment PLR was readily feasible and simple biomarker predicting response to treatment and survival, in addition it was significantly associated with tumor localization

Prognostic significance of primary tumor localization in patients with metastatic colorectal cancer: Is it beneficial to select targeted treatment? Real-life experience from Turkey

Purpose: The purpose of this study was to investigate the prognostic value,and the effect of primary tumor location on targeted therapy selection in patients with metastatic colorectal cancer (mCRC). Methods: A total of 201 patients with de novo mCRC who received first line treatment were retrospectively analyzed. Clinicopathological features, treatment outcomes, the primary tumor surgery, metastasectomies/local therapies and survivals were evaluated in terms of both RAS mutation status and primary tumor sidedness. Results: Tumor localization showed 140 (69.7%) patients with left-sided and 61 (30.3%) with right-sided tumors. Median progression-free survival (PFS) and overall survival (OS) were significantly shorter in patients with right-sided tumor than those with left-sided tumors (10.1 vs 12.9 months, p=0.005; 25 vs 44.4 months, p=0.008, respectively). In addition,the median OS interval of patients receiving anti-VEGF containing regimen was better than those treated with anti-EGFR containing regimen (50.7 vs. 26.9 months, p=0.001). Multivariate analysis indicated that age (HR:0.41,p=0.045), primary tumor resection (HR:0.41,p=0.037) and primary tumor localization (HR:0.38,p=0.021) for PFS and age (HR:0.39, p=0.09), the presence of BRAF mutation (HR:0.59,p=0.019) and the type of targeted therapy (HR:3.16,p=0.025) for OS were independent prognostic factors. Conclusions: Our results showed that primary tumor location is a prognostic factor in mCRC patients regardless of RAS status. Primary tumor location before treatment decision may be a simple indicator predicting survival and in choosing targeted agent

Real-life analysis of immunotherapy as the second or later lines treatment in patients with metastatic non-small cell lung cancer

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Interferon Induced Focal Segmental Glomerulosclerosis

Behçet’s disease is an inflammatory disease of unknown etiology which involves recurring oral and genital aphthous ulcers and ocular lesions as well as articular, vascular, and nervous system involvement. Focal segmental glomerulosclerosis (FSGS) is usually seen in viral infections, immune deficiency syndrome, sickle cell anemia, and hyperfiltration and secondary to interferon therapy. Here, we present a case of FSGS identified with kidney biopsy in a patient who had been diagnosed with Behçet’s disease and received interferon-alpha treatment for uveitis and presented with acute renal failure and nephrotic syndrome associated with interferon

Impact of SPARC expression on treatment response of pembrolizumab and brain metastasis in patients with metastatic non-small cell lung cancer

Background: Non-small cell lung cancer (NSCLC) often exhibits elevated Secreted Protein Acidic and Cysteine-Rich (SPARC) expression. In this study, we investigated the impact of SPARC expression on clinicopathologic features, pembrolizumab response, and prognosis in metastatic NSCLC patients. Methods: Thirty-six patients diagnosed with metastatic NSCLC without actionable driver mutation and who received pembrolizumab with or without chemotherapy were included in this study. PD-L1 and SPARC expression were evaluated, with PD-L1 expression categorized based on tumor proportion score and SPARC staining intensity graded as 1+, 2+, and 3 +. Patients’ characteristics were compared across groups, and possible predictive markers were determined by binary logistic regression analysis. Results: No significant associations were found between SPARC expression and smoking status, histopathological tumor type, T and N status, and liver and bone metastasis. Higher SPARC expression was significantly linked to lower brain metastasis rates but higher CNS progression rates (p = 0.022 and p = 0.011, respectively. The objective response rate (ORR) showed a trend of being higher in the SPARC 1 + group (85.7% vs. 43.8% and 50.0% in 2 + and 3 + groups, respectively, p = 0.052. Univariate analysis did not find SPARC expression to be a significant prognostic factor for progression-free survival (PFS) (p = 0.7) and overall survival (OS) (p = 0.07).SPARC 1 + expression negatively affected the pembrolizumab response(p = 0.04,OR:0.11, 95%CI 0.01–0.92). Conclusions: Our study sheds light on a novel aspect of SPARC expression as a potential predictor of pembrolizumab response and a marker for CNS progression in metastatic NSCLC patients treated in the first-line setting

Anti-Ri-associated paraneoplastic neurological syndrome: Initial symptom of breast cancer with HER2 overexpression and treatment by dual HER2 blockade

Paraneoplastic neurological syndrome is associated with anti-Ri antibodies, which are typically present with opsoclonus–myoclonus–ataxia. Human epidermal growth factor receptor 2 (HER2) overexpression is present in 15%–25% of breast cancer and is associated with poor prognosis. There are a few reports of paraneoplastic neurological syndrome associated with HER2-positive breast cancer in the literature, of which most are anti-Yo-associated paraneoplastic neurological syndrome. We present herein the case of a female patient with HER2-positive breast cancer who had atypical anti-Ri antibody associated with opsoclonus–myoclonus paraneoplastic neurological syndrome. Following the diagnosis of paraneoplastic syndrome, chemotherapy with dual HER2 blockade and immunomodulating treatment including intravenous immunoglobulin and oral prednisolone were administered. Although the patient was negative for serum anti-Ri antibodies, there was partial clinical improvement and her neurological deficit persisted. To our knowledge, this is the first case report of female patient with HER2-positive breast cancer who had atypical anti-Ri antibody associated with opsoclonus–myoclonus paraneoplastic neurological syndrome and treated with dual HER2 blockade