Treatment of Metastatic Colorectal Cancer With or Without Bevacizumab: Can the Neutrophil/Lymphocyte Ratio Predict the Efficiency of Bevacizumab?

Background: The purpose of this study was to analyze the predictive value of neutrophil/lymphocyte ratio (NLR) to better clarify which patient groups will benefit the most from particular treatments like bevacizumab. Materials and Methods: A total of 245 treatment-naive metastatic colorectal cancern (mCRC) patients wereretrospectively enrolled and divided into 2 groups: 145 group A patients were treated with chemotherapy in combination with bevacizumab, and 100 group B patients were treated as above without bevacizumab. Results: Group A patients had better median overall survival (OS) and progression-free survival (PFS) (24.0 and 9.0 months) than group B patients (20 and 6.0 months) (p=0.033; p=0.015). In patients with low NLR, OS and PFS were significantly longer in group A patients (27 vs 18 months, p=0.001; 11 vs 7 months, p=0.017). Conclusions: We conclude that NLR, a basal cancer related inflammation marker, is associated with the resistance to bevacizumabbased treatments in mCRC patients.     

Outcomes in Patients With Non–small-cell Lung Cancer With Brain Metastases Treated With Pembrolizumab-based Therapy

BackgroundPatients with metastatic non–small-cell lung cancer (mNSCLC) and untreated brain metastases (BM) have been excluded from most trials of immune checkpoint inhibitors (ICIs). Real-world evidence on efficacy and survival outcomes of ICIs in patients with BM is limited.Patients and MethodsWe conducted a single-center retrospective study of patients with mNSCLC treated with pembrolizumab with or without chemotherapy and compared progression-free survival (PFS) and overall survival (OS) between patients with and without BM using Kaplan-Meier and Cox methodology. We also characterized systemic and intracranial objective response rate (ORR) and treatment details, including timing of cranial irradiation.ResultsBetween Augutst 2013 and December 2018, 570 patients with mNSCLC treated with pembrolizumab-based therapy were analyzed. Of 126 (22.1%) patients with BM, 96 (76.2%) had treated BM (local therapy prior to pembrolizumab), and 30 (23.8%) had untreated BM. Of patients with untreated BM, 17 (56.7%) underwent radiation within 30 days after pembrolizumab initiation. In the remaining 13 (43.3%) treated with pembrolizumab-based therapy alone, intracranial ORR was 36.4%. Patients with and without BM did not have significantly different systemic ORR (27.8% vs. 29.7%; P = .671), PFS (mPFS 9.2 vs. 7.7 months; P = .609), or OS (mOS 18.0 vs. 18.7 months; P = .966). Factors associated with improved survival on Cox analysis included female gender, performance status, adenocarcinoma histology, and first-line therapy.ConclusionsPatients with BM did not have inferior survival to patients without BM after treatment with pembrolizumab-based therapy. In the current era, BM may not automatically confer inferior survival, and should not exclude patients from receiving pembrolizumab-based therapy.     

Neutrophil–Lymphocyte Ratio as a Prognostic Factor in Laryngeal Carcinoma

Aim of this study; investigate whether neutrophils/lymphocyte ratio (NLR) could be used as a prognostic factor in larynx cancer. The correlation between preoperative peripheral blood NLR and age, gender, smoking, alcohol use, clinical stage and differentiation degree was examined. One hundered fourty-four patients in Dicle University Department of Otorhinolaryngology between the years of 2005 and 2014 were included in the study. Clinical and preoperative laboratory data of patients were screened retrospectively from archive files of otorhinolaryngology and the pathology results were screened retrospectively from archive files of pathology. The study was approved by the local ethics committee of the department and carried out in accordance with the declaration of Helsinki as amended in 2013. Statistical analyses were performed using the SPSS 15.0 software package for Windows (SPSS inc., Chicago, IL, USA). There was a significant difference between NLR and clinical stage (p = 0.003) smoking (p = 0,001) and alcohol use (p = 0.001). When NLR was analyzed in detail according to the degree of tumor differentiation; significant differences were observed between G1 and G2 (p = 0.007) and between G1 and G3 (p = 0.001). Light of these findings, NLR is a cheap and easily accessible marker which can be used as a prognostic faxtor in laryngeal cancer. It is thougkt to shed light on the studies which will be conducted with more patients.     

Living With Cancer Alone? The Experiences of Singles Diagnosed With Colorectal Cancer

This paper seeks to understand the experiences of single colorectal cancer patients. This study consisted of 12 semi-structured interviews that were digitally voice-recorded, transcribed, and analyzed. Six main themes emerged: (a) gradual shift in view of cancer diagnosis from fatalistic to normalized, (b) perception of cancer as a nadir experience, (c) concerns of singlehood, (d) factors influencing cancer experiences, (e) factors influencing coping with cancer, and (f) range of responses towards cancer diagnosis. Singles with colorectal cancer require short- to long-term individualized care plans, and psycho-emotional support. This may help enhance their individual coping and adjustment to the diagnosis.     

Cell-Free Plasma DNA-Guided Treatment With Osimertinib in Patients With Advanced EGFR-Mutated NSCLC

Introduction

Osimertinib is standard treatment for patients with advanced EGFR T790M-mutated non–small-cell lung cancer who have been pre-treated with EGFR–tyrosine kinase inhibitors (TKIs). We studied whether cell-free plasma DNA for T790M detection can be used to select patients for osimertinib treatment in the clinical routine.

Neutrophil gelatinase-associated lipocalin immunoexpression in colorectal carcinoma: A stage-specific prognostic factor?

TNM post-surgical staging is considered to be one of the most powerful prognosticators for colorectal carcinoma. Although patient survival mostly decreases concomitantly to stage increase, in a percentage of cases TNM stage appears only to express the anatomic extent of the neoplasia with no correlation with clinical outcome. Thus, the identification of additional prognostic markers for colorectal cancer is required. Neutrophil gelatinase-associated lipocalin (NGAL) is a 25-kDa protein that appears to play an important role in colorectal cancer progression. In order to evaluate whether NGAL expression may be considered as a predictor of colorectal cancer progression, we analyzed its correlation with clinicopathological characteristics, as well as with patient progression-free survival in a series of surgically resected colorectal carcinomas. A variable NGAL immunoexpression was found in 24 out of the 64 analyzed cases. When only the positive cases were considered, a significant association was found between a high NGAL expression and the presence of distant metastases or high tumor stage. In addition, the presence of NGAL was a significant negative prognostic marker correlated with a shorter progression-free survival in stage I colorectal carcinoma, but not in the remaining TNM stages. If our findings are confirmed in more extensive analyses on stage I colorectal carcinoma, NGAL assessment may be used in order to select those patients with a higher progression risk and to submit them to adjuvant therapies useful to prevent adverse outcome.     

How Do I Deal With the Axilla in Patients With a Positive Sentinel Lymph Node?

Optimal management of the axilla in a patient with a positive sentinel node biopsy is not yet defined.     

Neoadjuvant Chemotherapy With Docetaxel-Cisplatin in Patients With Stage III N2 Non–Small-Cell Lung Cancer

IntroductionTo assess the efficacy and potential prognostic factors of patients with stage III N2 non–small-cell lung cancer (NSCLC) treated with neoadjuvant docetaxel-cisplatin (DP) chemotherapy followed by surgical resection.MethodsSixty-two patients with NSCLC treated with DP as neoadjuvant chemotherapy between November 2003 and December 2009 were identified and reviewed in this study. Tumor response, survival, and clinicopathologic data were collected retrospectively. The time to event was analyzed by fitting Cox proportional hazards models.ResultsFifty-eight (94%) of 62 patients eventually underwent surgical resection after DP. The overall clinical response rate to induction DP chemotherapy was 42%. Patients with squamous cell carcinoma (SCC) histology were more likely to response to the DP regimen than those with adenocarcinoma histology (68% vs. 33%, P = .006). With a median follow-up of 82.4 months among the 58 patients, there were 41 (71%) tumor relapses and 27 (47%) deaths. The median event-free survival was 27.5 months (95% CI, 22.3-32.7 months), and the median overall survival was 66.7 months (95% CI, 35.1-98.3 months). In multivariate analysis, when fitting the Cox proportional hazards model, SCC histology (hazard ratio [HR] 0.234 [95% CI, 0.098-0.560]; P = .001) and mediastinal downstaging to N0 (HR 0.451 [95% CI, 0.226-0.898]; P = .024) were independent predictors of better event-free survival.ConclusionsNeoadjuvant chemotherapy with the DP regimen is both active and well tolerated in patients with stage III N2 NSCLC. SCC histology predicted a better treatment response and survival outcome than adenocarcinoma histology in this patient group. Further investigation of combined-modality treatment is warranted to improve survival in the adenocarcinoma subset of stage III N2 NSCLC.     

Analysis of Early Death in Japanese Patients With Advanced Non–small-cell Lung Cancer Treated With Nivolumab

Background

The increased risk for early death owing to anti-programmed cell death 1 inhibitors is a major disadvantage that requires special management. We evaluated the frequency, causes, and risk factors of early death during nivolumab treatment for non-small cell lung cancer (NSCLC) in a Japanese clinical setting.

Soluble c-Met Levels Correlated With Tissue c-Met Protein Expression in Patients With Advanced Non–Small-Cell Lung Cancer

Background

Immunohistochemistry (IHC) and fluorescent in situ hybridization are reliable methods for identifying c-Met protein expression or c-Met gene amplification. However, each technique requires a high-quality tissue sample, which might not be available. The aim of the present study was to investigate the correlation between the soluble c-Met level and tissue c-Met protein expression and the relationship between these markers and patient prognosis.

Evaluation of Neutrophil–Lymphocyte Ratio as a Prognostic Factor in Cervical Intraepithelial Neoplasia Recurrence

Background: Immune system status is a factor related to cervical intraepithelial neoplasia (CIN) recurrence.neutrophil-lymphocyte ratio (NLR) is a useful factor in assessing the immune status. The aim of this study was toevaluate the prognostic value of NLR factor for CIN recurrence in patient who underwent excisional procedure and itsrelationship with recurrence free survival (RFS). Methods: In this historical cohort study, a population of 307 patientswith CIN (confirmed by excisional pathology) from 2009 to 2017 were selected. NLR and hematologic factors weremeasured before surgery and the follow-up records of these patient were analyzed. The recurrence rate and RFS wereassessed during the follow-up phase. Results: The NLR cut-off point of 1.9 was determined using the Youden Index.NLRUnivariate analysis showed that higher NLR values (P<0.001), absolute neutrophilic counts (ANC) (P<0.001) andplatelet lymphocytic ratios (PLR) (P=0.002) were significantly associated with reduction in RFS. The results of Coxregression showed that removing more tissue during excision (HR = 0.325; 95% CI (0.936-0.136) significantly reducedthe hazard of recurrence, higher NLR (HR = 4.55; 95% CI) (1.97-10.51) and white blood cell (WBC) count levels (HR=1.27; 95% CI, 1.04-1.55), significantly decreased RFS, but PLR and ANC associated with RFS were not confirmedby Cox regression. Conclusion: NLR and total WBC count might be prognostic factors involved in the prediction ofrecurrence and RFS in CIN patient underwent excisional procedure. To confirm these results, more prospective studieswith larger sample sizes are needed.     

Immune-related Adverse Events of Pembrolizumab in a Large Real-world Cohort of Patients With NSCLC With a PD-L1 Expression ≥ 50% and Their Relationship With Clinical Outcomes

BackgroundThe role of immune-related adverse events (irAEs), as a surrogate predictor of the efficacy of checkpoint inhibitors, has not yet been described in the setting of first-line, single-agent pembrolizumab for patients with metastatic non–small-cell lung-cancer (NSCLC) with a programmed death-ligand 1 (PD-L1) expression of ≥ 50%.Patients and MethodsWe previously conducted a multicenter retrospective analysis in patients with treatment-naive metastatic NSCLC and a PD-L1 expression of ≥ 50% receiving first-line pembrolizumab. Here, we report the results of the irAE analysis and the potential correlation between irAEs and clinical outcomes.ResultsA total of 1010 patients were included in this analysis; after a 6-week landmark selection, 877 (86.8%) patients were included in the efficacy analysis. Any grade irAEs (P < .0001), grade 3/4 irAEs (P = .0025), leading to discontinuation irAEs (P = .0144), multiple-site and single-site irAEs (P < .0001), cutaneous irAEs (P = .0001), endocrine irAEs (P = .0227), pulmonary irAEs (P = .0479), and rheumatologic irAEs (P = .0018) were significantly related to a higher objective response rate. Any grade irAEs (P < .0001), single-site irAEs (P < .0001), multiple-site irAEs (P = .0005), cutaneous irAEs (P = .0042), endocrine irAEs (P < .0001), gastrointestinal irAEs (P = .0391), and rheumatologic irAEs (P = .0086) were significantly related to progression-free survival. Any grade irAEs (P < .0001), single-site irAEs (P < .0001), multiple-site irAEs (P = .0003), cutaneous irAEs (P = .0002), endocrine irAEs (P = .0001), and rheumatologic irAEs (P = .0214) were significantly related to overall survival.ConclusionsThis study confirms the feasibility and the safety of first-line, single-agent pembrolizumab, in a large, real-world cohort of patients with NSCLC with PD-L1 expression ≥ 50%. The occurrence of irAEs may be a surrogate of clinical activity and improved outcomes in this setting.     

Challenges With Serum Protein Electrophoresis in Assessing Progression and Clinical Response in Patients With Waldenström Macroglobulinemia

Accurate determination of the immunoglobulin (Ig) M paraprotein concentration is crucial to evaluating response in patients with Waldenström macroglobulinemia (WM). In most clinical laboratories, M-spike quantitation is performed by serum protein electrophoresis, which is the same method used to quantitate IgG and IgA paraproteins in patients with multiple myeloma (MM). However, the migration pattern and propensity of IgM paraproteins to form higher-order complexes in serum makes laboratory evaluation of samples from patients with WM especially challenging. We review examples of patients whose IgM paraprotein is particularly ill-suited to M-spike quantitation by serum protein electrophoresis: a case of “sticky M,” a case of IgM multimers that cannot be resolved, and a case of an IgM in the β region. In these and similar cases, a method other than M-spike quantitation, such as IgM heavy chain nephelometry, should be considered in laboratory evaluation of paraprotein concentration.     

Distinct MET Protein Localization Associated With MET Exon 14 Mutation Types in Patients With Non–small-cell Lung Cancer

Background

The MET gene has been recognized as a potential important therapeutic target in non–small-cell lung cancer (NSCLC). We sought to investigate the MET exon 14 mutations in a cohort of Chinese patients with NSCLC.