Salvage chemotherapy in patients with nonsmall cell lung cancer after prior immunotherapy: a retrospective, real-life experience study.

Patients with advanced nonsmall cell lung cancer (NSCLC) who progress with immune checkpoint inhibitors (ICIs), salvage chemotherapy remains the only viable option for tumors that do not harbor genomic alterations. Data on the efficacy of salvage chemotherapy after immunotherapy (SCAI) are scarce. Our main objective in the current study was to evaluate the efficacy of SCAI. All consecutive patients who were diagnosed as having metastatic NSCLC and received at least one dose of ICIs were retrospectively reviewed. We computed progression-free survival (PFS), overall survival (OS) and objective response rate (ORR) with SCAI. We also analyzed associations between survival and various clinicopathologic factors. We identified 35 patients with advanced NSCLC who received at least one dose of SCAI. The median age was 66 years. Most of patients were male ( n = 26, 74.3%) and former or current smokers ( n = 33, 94.3%). The majority of the patients were Eastern Cooperative Oncology Group Performance Status (ECOG PS) 2 ( n = 22; 62.9%), and there were no patients with driver mutations. SCAI was administered as second-line therapy in 21 (60.0%) patients and third-line in 14 (40.0%) patients. The ORR to SCAI was 20.0% with median PFS and OS were 2.43 (95% CI, 1.69-3.16) months and 4.40 (95% CI, 2.17-6.62) months, respectively. In multivariate analysis, ECOG PS 2 was confirmed as being independently associated with inferior OS. We demonstrated that patients with NSCLC who progressed to ICIs had limited clinical benefit with salvage chemotherapy, particularly for patients who were ECOG PS 2.

Adjuvant treatment with paclitaxel plus trastuzumab for node-negative breast cancer: real-life experience.

Background: In node-negative HER2-overexpressed breast cancers, adjuvant paclitaxel plus trastuzumab treatment is a successful de-escalation approach with excellent survival outcomes. Methods: All patients with HER2+ breast cancer treated in our centers were retrospectively reviewed. Results: We analyzed 173 patients who were treated with adjuvant paclitaxel plus trastuzumab. The mean tumor size was 2.2 cm. There were eight invasive disease events or death: four distant recurrences (2.3%), three locoregional recurrences (1.7%) and one death without documented recurrence after a 52 month follow-up. The 3-year disease-free survival and recurrence-free interval rate was 96.6%. Conclusion: This real-life experience with adjuvant paclitaxel plus trastuzumab demonstrated few distant recurrences and is compatible with the APT trial findings.

Lay abstract In oncology practice, there have been some efforts to avoid the toxicity of combination chemotherapies and reduce the amount of treatment given in recent decades. These strategies have been studied especially for patients with a specific subtype of early-stage breast cancer. We present the results from patients treated in our centers and discuss them in relation to the literature.

Prognostic Importance of Inflammatory Indexes in Patients Treated by Pazopanib for Soft Tissue Sarcoma.

BACKGROUND: The goal of this study was to evaluate the predictive and prognostic importance of the lymphocyte to monocyte ratio (LMR), neutrophil to lymphocyte ratio (NLR), derived neutrophil to lymphocyte ratio (DNLR), and systemic immune inflammation index (SSI) in STS cases treated with pazopanib. METHODS: Thirty STS patients treated with pazopanib were included in this study. SSI, DNLR, LMR, and NLR values were calculated at baseline and in the first month. Median values of these predictors in these patients (SSI (944), DNLR (1.8), LMR (2.7), and NLR (3.0)) were taken as cutoff values. The associations between the survival time (both overall survival (OS) and progression-free survival (PFS)) and cutoff values were evaluated using Kaplan Meier curves and Cox regression models. RESULTS: Patients with low SSI, NLR, and DNLR values at pretreatment and after the initial response had longer OS (for OS - p = 0.024, p = 0.015, and p = 0.041, respectively). Longer OS was also found in patients who showed increasing LMR and decreasing NLR after one month of therapy (for ΔLMR, p = 0.016; for ΔNLR, p = 0.016). Pa-tients with low SSI and NLR values at pretreatment and after the initial response had longer PFS (for PFS, p = 0.014, p = 0.04, p ˂ 0.001, respectively). In terms of initial responses to treatment, SSI, NLR, DNLR, and increased LMR were detected as independent risk factors in univariate analysis, but initial response was found to be the only independent risk factor for PFS in multivariate analysis. CONCLUSIONS: Low values of SSI, NLR, and DNLR at pretreatment and at initial response may predict long-term survival rates. After one month of treatment with pazopanib, decreased NLR and increased LMR are predictive of favorable outcomes in these cases.

Prognostic value of pretreatment immune inflammation indices in patients with immune-related tumors.

BACKGROUND: Pretreatment high levels of lactate dehydrogenase (LDH), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR), modified Glasgow prognostic scores (mGPS), prognostic nutritional index (PNI), and other prognostic biomarkers have been associated with poor overall survival (OS) in immune-related tumor types. Therefore, we explored a simple, inexpensive and effective method for cancer prognosis. METHODS: Between March 2017 and June 2022, 111 individuals who had immunotherapy were retrospectively examined. Oncologic outcomes of patients with immune-related tumor types, include OS and progression-free survival (PFS), and response rates (RR). RESULTS: Pretreatment ECOG (Eastern Cooperative Oncology Group) performance quality was independently linked with poor OS ECOG ≥2 (HR 4.80, 95% CI 2.57-8.96, p < .001) and inferior PFS (HR 3.31, 95% CI 2.023-5.445, p < .001). Additionally, a high LDH status prior to therapy was independently linked to an inferior OS (HR 1.004, 95% CI 1.001-1.007, p = .003) and inferior PFS (HR 1.004, 95% CI 1.002-1.006, p < .001). Higher MLR at baseline was a prognostic factor for both shorter PFS (HR = 3.691, 95% CI 1.582-8.610, p = .003) and OS (HR = 2.876, 95% CI 1.127-7.342, p = .027). CONCLUSIONS: In our cohort, elevated pre-treatment MLR, LDH and ECOG ≥2 were associated with poor OS and PFS. Prospective studies need to determine the utility of them.

Sixth-Week Immune-Nutritional-Inflammatory Biomarkers: Can They Predict Clinical Outcomes in Patients with Advanced Non-Small Cell Lung Cancer Treated with Immune Checkpoint Inhibitors?

BACKGROUND: We investigated the relationships between inflammatory markers such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), Lung Immune Prognostic Index (LIPI), and modified Glasgow prognostic score (mGPS) to determine whether they could predict treatment response to pembrolizumab or nivolumab (immunotherapy) 6 weeks after the start of treatment (post-treatment). METHODS: We included all patients with lung cancer treated with immunotherapy. We examined the biomarker trends and explored their associations with progression-free survival (PFS), overall survival (OS), and response rate (RR) at 6 weeks. RESULTS: Eighty-three patients were enrolled in the study. The presence of liver metastasis, low post-treatment NLR (<5), low post-treatment PLR (<170), intermediate post-treatment LIPI, and immune-related adverse events were significantly associated with the response. The multivariate analysis revealed that high post-treatment NLRs ≥ 5 (p = 0.004) and PLRs ≥ 170 (p ≤ 0.001) were independent prognostic factors of shorter OS. A good LIPI status was associated with better PFS (p = 0.020) and OS (p = 0.065). Post-treatment mGPS (0-2) was significantly associated with improved PFS (p = 0.009) and OS (p = 0.064). CONCLUSIONS: Post-treatment NLR, PLR, LIPI, and mGPS are associated with worse OS and recurrence. These findings should be independently and prospectively validated in further studies.

Development of a Novel Predictive-Prognostic Scoring Index for Immune Checkpoint Inhibitors in Advanced Non-small Cell Lung Cancer.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have become the standard of care for the treatment of patients with driver mutation absent advanced non-small cell lung cancer (NSCLC). The present study aimed to develop a reliable, reproducible, and practical scoring system to prognosticate and predict response to ICI response in patients with advanced NSCLC. PATIENTS AND METHODS: All patients who were diagnosed as having unresectable/advanced stage NSCLC and were treated with at least one cycle of ICIs at the Medical Oncology Departments of Dr. Burhan Nalbantoglu State Hospital (Nicosia, Cyprus) and Near East University Hospital (Nicosia, Cyprus) were included in the study. The association between variables and OS was evaluated using a Cox proportional hazards regression model. Variables with a P-value less than 0.05 in the univariate analysis were included in the multivariate model. A prognostic scoring system was developed.  Survival estimates were calculated using the Kaplan-Meier method. The value of the Concordance index (C-index) and the area under the curve (AUC) was used to evaluate the discriminative ability of scoring systems. RESULTS: One hundred fifty consecutive patients with unresectable/metastatic NSCLC who received PD-1 inhibitors between March 2017 and November 2022 were included. In the multivariate Cox regression model, serum lactate dehydrogenase (LDH), C-reactive protein (CRP) levels, and Eastern Cooperative Oncology Group Performance Status (ECOG PS) were significantly associated with OS. We generated a new score using CRP ³1.0 mg/dL, ECOG PS ³2, and LDH level >ULN. Relative weight was based on the HRs of multivariate analyses (CRP ³1.0 mg/dL 2 points, ECOG PS ³2 2.5 points, and LDH level >ULN 1.5 points). The cohort was divided into three risk groups based on the sum of factors present: 0-2.5 (good risk), 3.5-4.5 (intermediate risk), or 6 (poor risk). The median OS was 18.9, 7.4, and 2.9 months for good, intermediate, and poor risk categories, respectively (log-rank test, p<0.001). The Harrell C-index of CEL to predict OS and PFS was 0.73 and 0.69, respectively, indicating significant predictability. The AUC of the scoring index for predicting the responses was 0.765 (95% CI: 0.685-0.845). CONCLUSION: The CEL score is a promising prognostic and predictive index consisting of serum CRP levels (C), ECOG PS (E), and serum LDH levels (L). This represents another step forward in the treatment of patients with advanced NSCLC.

A Multicenter Study of Genotype Variation/Demographic Patterns in 2475 Individuals Including 1444 Cases With Breast Cancer in Turkey.

Objective: Breast cancer (BC) is the most common cancer type in women and may be inherited, mostly in an autosomal dominant pattern. The clinical diagnosis of BC relies on the published diagnostic criteria, and analysis of two genes, BRCA1 and BRCA2, which are strongly associated with BC, are included in these criteria. The aim of this study was to compare BC index cases with non-BC individuals in terms of genotype and diagnostic features to investigate the genotype/demographic information association. Materials and Methods: Mutational analyses for the BRCA1/BRCA2 genes was performed in 2475 individuals between 2013-2022 from collaborative centers across Turkey, of whom 1444 with BC were designated as index cases. Results: Overall, mutations were identified in 17% (421/2475), while the percentage of mutation carriers in cases of BC was similar, 16.6% (239/1444). BRCA1/BRCA2 gene mutations were detected in 17.8% (131/737) of familial cases and 12% (78/549) of sporadic cases. Mutations in BRCA1 were found in 4.9%, whereas 12% were in BRCA2 (p<0.05). Meta-analyses were performed to compare these results with other studies of Mediterranean-region populations. Conclusion: Patients with BRCA2 mutations were significantly more common than those with BRCA1 mutations. In sporadic cases, there was a lower proportion with BRCA1/BRCA2 variants, as expected, and these results were consistent with the data of Mediterranean-region populations. However, the present study, because of the large sample size, revealed more robust findings than previous studies. These findings may be helpful in facilitating the clinical management of BC for both familial and non-familial cases.

First-line pembrolizumab efficacy in patients with advanced non-small cell lung cancer: A Bi-center retrospective, real-life experience study.

PURPOSE: Immune checkpoint inhibitors (ICIs) have caused a paradigm shift in the treatment landscape of advanced non-small cell lung cancer (NSCLC). Real-world practice may be different from randomized studies. The purpose of this study was to investigate the real-world pembrolizumab efficacy with or without chemotherapy. METHODS: All consecutive patients aged over 18 years who were diagnosed as metastatic NSCLC and received at least one dose of first-line pembrolizumab treatment were retrospectively reviewed. The patients hadn't received no previous systemic therapy. RESULTS: A total of 44 patients treated with pembrolizumab were enrolled. Just over half (51.2%) of the patients had an Eastern Cooperative Oncology Group Performance Status (ECOG PS) 2, and 36.4% had liver metastasis. There were no patients with driver mutations, 18.2% had programmed death ligand-1 (PD-L1) 50% expression and 82.3% were treated with pembrolizumab plus chemotherapy. The median progression-free survival (PFS) and overall survival (OS) were 3.0 months (95% CI: 0.9-5.0 months) and 6.6 months (95% CI: 0.7-12.4 months), respectively. Multivariate analysis identified liver metastasis and adrenal metastasis as independent predictors of OS. CONCLUSIONS: PFS, OS, objective response and disease control rate results were significantly worse than in randomized studies. ICIs are not an infallible treatment option to be used for every patient with advanced NSCLC encountered in daily clinical practice. Attention should be payed to stringent eligibility criteria used in randomized studies as much as possible and try to manage patients according to these criteria.

Male Breast Cancer: Clinical, Demographical, and Pathological Features in a Cohort of 41 Patients.

Background and objective Male breast cancer (MBC) is a rare malignancy, and it accounts for less than 1% of all cancers in men. The pathogenesis of MBC remains unclear, with most available data obtained from single-center studies and retrospective series. The aim of this study was to share our experiences of MBC cases and to describe the characteristics of MBC patients. Materials and methods We retrospectively reviewed the records of 41 MBC cases and recorded the pathological, clinical, and demographic features of the patients. Data on progression-free survival (PFS) and overall survival (OS) were also recorded. Results The mean age of the patients was 64.1 ± 10.0 years. The most common histopathological subtype was invasive ductal carcinoma. Hormone receptor positivity was detected in 39 (95.1%) patients. Human epidermal growth factor receptor 2 (HER2) positivity was present in five (12.2%) patients. Most of the patients had early-stage disease. Surgery was the treatment of choice for most primary tumors. Thirty-nine (95.1%) patients received hormonotherapy, and 21 (51.2%) received systemic chemotherapy. OS was found to be 126.4 months and PFS was 83.2 months. The OS and PFS time in patients with a Nottingham Prognostic Index (NPI) score of <5.4 were longer than those with an NPI score of >5.4. Conclusion The hormone receptor status of most of the MBC patients was positive, and their HER2 status was negative. A multimodality approach was associated with longer survival, which has been reported in female patients with breast cancer as well. The NPI score is a useful tool for predicting survival time in MBC patients.

Neutrophil-to-lymphocyte ratio is prognostic in recurrent glioblastoma multiforme treated with bevacizumab plus irinotecan.

Aim: We intended to survey the prognostic utility of pretreatment neutrophil-to-lymphocyte ratio (NLR) as a novel prognostic index in recurrent glioblastoma multiforme (R-GBMs) treated with bevacizumab plus irinotecan (BEVIRI). Patients & methods: The present retrospective investigation incorporated the R-GBMs patients who underwent BEVIRI. The pre-BEVIRI NLR was calculated for each patient by utilizing the complete blood count tests obtained on the first day of BEVIRI. Results: The data of a total of 103 patients were analyzed. The ideal cutoff was identified at 3.04 (area under the curve: 60%; sensitivity: 60.3%; specificity 60%) for the pre-BEVIRI NLR. Low-NLR group had significantly longer overall survival times than the high-NLR group (15.8 vs 9.3 months; p = 0.015). Conclusion: NLR might be utilized as a novel biomarker in the prognostic stratification of the R-GBMs treated with BEVIRI.

Efficacy of Palbociclib and Endocrine Treatment in Heavily Pretreated Hormone Receptor-positive/HER2-negative Advanced Breast Cancer: Retrospective Multicenter Trial

Background: The synthesis of CDK4/6 inhibitors with endocrine treatment in two series of treatment has been widely accepted as the standard for patients with estrogen receptor-positive metastatic breast cancer. In spite of this, the activity of CDK4/6 inhibitors in patients with metastatic breast cancer who have progressed despite receiving multiple lines of treatment is not well understood. Aims: To report the activity and safety of a CDK4/6 inhibitor (palbociclib) in patients in whom at least three lines of treatment for ER+ metastatic breast cancer had failed. Study Design: Multicenter retrospective observational cohort study. Methods: In this retrospective observational cohort study, we included 43 patients who received palbociclib after at least three lines of systemic treatment for ER+/HER2− metastatic breast cancer. Results: The median progression-free survival in our population was 7 months (25th-75th percentile, 4-10), and the median overall survival was 11 months (25th-75th percentile, 6-19). Although there were some adverse events, palbociclib was generally well tolerated, so dose reduction was needed for only six patients (14%). Conclusion: The efficacy of palbociclib among heavily treated hormone receptor-positive/HER2− patients with advanced breast cancer was acceptable in terms of clinical benefit, and it was generally well tolerated among this population.