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

Survival outcomes of patients with oligometastatic non-small cell lung cancer who were treated with radical therapy: A multicenter analysis

Background/aim: Oligometastatic disease for nonsmall cell lung cancer (NSCLC) patients is generally thought to represent a better prognosis with a quieter biology, limited number of disease sites and long-term disease control. In this study, we aimed to determine the efficacy of radical treatment options for patients with oligometastatic NSCLC. Materials and methods: This retrospective trial included totally 134 patients with oligometastatic NSCLC. The presence of oncodriver mutation, tumor stages and nodal status, the number of metastases and involved metastatic site, treatment of primary tumor and oligometastasis, response rate, overall survival (OS) and progression-free survival (PFS) were evaluated. Results: Of 134 patients 66.4% were defined as adenocarcinoma, 26.1% were squamous cell carcinoma and 7.5% of patients were in other histology. Based on the treatment of primary tumor, in 36 patients (26.9%) curative surgery has undergone, in addition, 19 (14.2%) patients were received chemotherapy, 73 (54.5%) were treated with chemoradiotherapy, while immunotherapy and targeted therapy were used in 1 (0.7%) and 2 (1.4%), respectively. The preferred treatment for oligometastatic lesions were SBRT in 72.4% of patients, surgery in 10.5%, and both SBRT and surgery in 17.1% of patients. At the median follow up of 31.3 months (range: 9.5–48.5), the median PFS and OS times were 17 and 24.4 months, respectively. Moreover, OS-2 after progression was also 7.2 months. Conclusion: Based on our real-life experience, we demonstrated a significant correlation between good response to first treatment and survival in oligometastatic disease, we also understand that local ablative treatment modalities prolong and also delay both OS and PFS in oligometastatic NSCLC patients OS-2

Rare side effect caused by atezolizumab, an immune checkpoint inhibitor: Cold agglutinin disease

Introduction Immune checkpoint inhibitors are drugs that are included in the guidelines of hematological and solid cancer treatments, give highly effective results and increase T cell functionality. However, these drugs can cause immune-related adverse events resembling autoimmune diseases. Case report A 50-year-old male patient was admitted to an external center with complaints of chest pain and dyspnea. Thoracic CT revealed a 97 x 58 mm mass in the left lung, and a diagnosis of Small Cell Lung Cancer (SCLC) was made by biopsy. The PET/CT performed for staging was also evaluated as extensive stage small cell lung cancer. It was decided to give a combination of atezolizumab and carboplatin-etoposide to the patient. Management and outcome: The patient completed 3 cycles without any problem. Discordance was detected in the hemogram of the patient who came to the control for the assessment of response and had a regression in the imaging. Hemoglobin 9.6 g/dl (N: 14-17.5) hematocrit 14.8% (N: 41-51) were detected in the hemogram. Agglutinins were seen in the peripheral smear performed. Cold agglutinin (+4 positive) and indirect coombs (+3 positive) were found positive. Atezolizumab was stopped and methylprednisolone was started. After 10 days of treatment, discordance improved and methylprednisolone was discontinued by decreasing to half dose every 5 days. Discussion With the increasing use of immune checkpoint inhibitors, the variety of side effects has increased and case reports have increased. After detection of cold agglutinin, IgG, cryoglobulin, mycoplasma pneumonia, hepatitis B, hepatitis C and HIV were found negative in the differential diagnosis, Our case appears to be immune checkpoint inhibitor-related Cold Agglutinin Disease (CAD). It should not be forgotten that immune checkpoint inhibitors, which are widely used, may cause CAD, and hemoglobin-hematocrit discordance should be paid attention to in routine controls

Pretreatment platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio as a predictor of pathological complete response to neoadjuvant chemotherapy in patients with breast cancer: Single center experience from Turkey

The aim of this study was to investigate the predictive value of PLR and NLR as an indicator of pathological complete response (pCR) in patients with breast cancer after NACT. One hundred thirty-nine patients with early or LABC and candidates to NACT were retrospectively analyzed. The prognostic significance of PLR and NLR was analyzed. In addition, predictive indicators of pCR to NACT were also evaluated. pCR was obtained in 48.9% of patients. Significant difference was detected between pCR and PLR, tumor grade, clinical lymph node status and molecular subgroup. The higher rate of pCR was significantly achieved for patients with PLRlow (181.7) (68.6% vs. 33.4%; P < 0.001). PLR, tumor grade and pCR to NACT for disease-free survival (DFS), and PLR, NLR, tumor grade and pCR to NACT for overall survival were detected to be prognostic factors by univariate analysis. On the other hand, a logistic regression analysis indicated that PLR and NLR were found to be an independent factors for predicting pCR to NACT (P < 0.001; OR, 0.07; 95% CI, 0.02-0.25 and P = 0.016; OR, 4.66; 95% CI, 1.33-16.2, respectively), as were molecular subtypes (P = 0.001; OR, 0.23; 95% CI, 0.09-0.56). Our results showed that PLRlow and NLRlow before NACT are readily feasible and simple and also inexpensive biomarkers predicting pCR to NACT for patients with LABC

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

..

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