Correlation of Neutrophil to Lymphocyte Ratio and Absolute Neutrophil Count With Outcomes With PD-1 Axis Inhibitors in Patients With Advanced Non–Small-Cell Lung Cancer

Introduction

Programmed death-1 (PD-1) axis inhibitors have become standard therapy in advanced non–small-cell lung cancer (NSCLC). Response might be delayed and pseudo-progression occasionally occurs in patients who eventually benefit from treatment. Additional markers beyond programmed death ligand 1 (PD-L1) expression are needed to assist in patient selection, response evaluation, and treatment decisions.

Prognostic Value of Pretreatment Albumin-to-Globulin Ratio in Patients With Non–Muscle-Invasive Bladder Cancer

Purpose

To investigate the relationship between albumin-to-globulin ratio (AGR) and oncologic outcomes in patients with non–muscle-invasive bladder cancer (NMIBC).

Tolerability,Safety, and Outcomes of Neoadjuvant Chemoradiotherapy With Capecitabine for Patients Aged ≥ 70 Years With Locally Advanced Rectal Cancer

Introduction

In studies of colorectal cancer, the elderly have been frequently underrepresented because comorbid conditions and functional status often lead to study exclusion. For elderly patients with an indication for neoadjuvant chemoradiotherapy (nCRT), physicians usually decide using clinical factors whether nCRT should be offered. The aim of the present retrospective study was to assess the tolerability of nCRT with capecitabine and the surgical outcomes in patients aged ≥ 70 years with locally advanced rectal cancer.

Prevalence,Outcome, and Management of Risk Factors in Patients With Breast Cancer With Peripheral Arterial Disease: A Tertiary Cancer Center’s Experience

IntroductionThe risk factors of breast cancer overlap with those of peripheral arterial disease (PAD), with increasing prevalence. In addition, there is under-utilization of risk factor modification measures in patients with PAD.Materials and MethodsElectronic medical records of patients with breast cancer with International Classification of Diseases 9/10 codes for PAD spanning 10 years from June 1, 2009 to June 1, 2019 were reviewed.ResultsA total of 248 patients, 98% women, with a median age of 75 years and with a median follow-up of 76 months, were included. PAD risk factors were identified as smoking (44%), obesity (38%), hyperlipidemia (68%), hypertension (HTN) (74%), and diabetes (42%). Overall, survival was significantly impacted by smoking (P = .0301) and HTN (P = .0052). In a Cox proportion hazard ratio regression, HTN (overall death hazard ratio [HR], 3.1784; 95% CI, 1.0291-6.7490; P = .0070; cancer-related death HR, 2.6354; 95% confidence interval [CI], 1.0291-6.7490; P = .0434) and smoking (overall death HR, 1.7452; 95% CI 1.0707-2.8444; P = .0255; cancer-related death HR, 2.7432; 95% CI, 1.4190-5.3030; P = .0027) were predictors of overall death and cancer-related death. Of all patients, 48% were on statins and 54% were on antiplatelet therapies. Of the patients, 62% of current smokers were offered a smoking cessation program, 27% of obese patients were offered a nutrition consult, 42% of patients with diabetes had blood glucose controlled, and 54% of patients with HTN had blood pressure controlled.ConclusionSmoking and HTN are risk factors associated with decreased survival and predictive of overall death and cancer-related death. In this population, risk factor modification was under-utilized.     

Real-World Treatment Patterns,Overall Survival,and Occurrence and Costs of Adverse Events Associated With First-line Therapies for Medicare Patients 65 Years and Older With Advanced Non–small-cell Lung Cancer: A Retrospective Study

Purpose

This study sought to better understand real-world treatment patterns, overall and non–small-cell lung cancer (NSCLC)-specific survival, adverse event (AE) occurrence, and economic impact of first-line cancer therapies in Medicare patients.

Incorporation of the SUVmax Measured From FDG PET and Neutrophil-to-lymphocyte Ratio Improves Prediction of Clinical Outcomes in Patients With Locally Advanced Non–small-cell Lung Cancer

IntroductionThe aim of the present study was to investigate the value of incorporation 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) maximum standardized uptake value (SUVmax) and neutrophil-to-lymphocyte ratio (NLR) for improving prediction of clinical outcomes of patients with locally advanced non–small-cell lung cancer (LA NSCLC).Materials and MethodsWe retrospectively enrolled 138 patients with unresectable LA NSCLC at our institution from July 2010 to August 2017. Spearman correlation analyses were used to estimate the correlations between SUVmax and NLR level. The univariate and multivariate Cox survival analyses were used to evaluate the prognostic indicators, including the incorporation of SUVmax and NLR. We defined the SUVmax and NLR grade (SNG = 0, 1, or 2) score as the number of risk factors among (1) SUVmax > 11.95 and (2) NLR > 3.82. The SNG score prognostic value was evaluated for overall survival (OS) and progression-free survival (PFS).ResultsUnivariate analysis showed that tumor stage, SUVmax, SUVmean, NLR, and SNG score were significantly associated with OS and PFS in patients with LA NSCLC. Kaplan-Meier analysis and log-rank test demonstrated significant differences in both OS and PFS among patients in SNG score (OS, P < .001; PFS, P < .001). Spearman correlation analyses showed that SUVmax had a correlation with the NLR (r = 0.237; P = .005). In subgroup analyses for patients with tumor pathologic stage IIIA/IIIB, we found that the SNG score was significantly associated with OS and PFS in each subgroup (P < .001, P < .001 for OS and P = .027, P < .001 for PFS, respectively). Multivariate analysis showed that the SNG score was a significantly independent prognostic factor for OS (hazard ratio, 1.612; 95% confidence interval, 1.157-2.246; P = .005) and PFS (hazard ratio, 2.241; 95% confidence interval, 1.486-3.379; P < .001).ConclusionIncorporation of the SUVmax and NLR improves prediction of clinical outcomes in patients with LA NSCLC.     

Phase II Trial of Dose-dense Pemetrexed,Gemcitabine, and Bevacizumab in Patients With Advanced,Non–Small-cell Lung Cancer

Introduction

Platinum-based chemotherapy is standard for untreated, advanced non-small-cell lung cancer (NSCLC). We investigated the activity and tolerability of the novel combination of dose-dense pemetrexed, gemcitabine, and bevacizumab in patients with advanced NSCLC.

Validation of Neutrophil-to-lymphocyte Ratio in a Multi-institutional Cohort of Patients With T1G3 Non–muscle-invasive Bladder Cancer

Introduction

The aim of this multicenter study was to investigate the prognostic role of neutrophil-to-lymphocyte ratio (NLR) and to validate the NLR cutoff of 3 in a large multi-institutional cohort of patients with primary T1 HG/G3 non–muscle-invasive bladder cancer (NMIBC).

Natural Disease History,Outcomes, and Co-mutations in a Series of Patients With BRAF-Mutated Non–small-cell Lung Cancer

BackgroundBRAF mutations occur in 1% to 4% of non–small-cell lung cancer (NSCLC) cases. Previous retrospective studies have reported similar outcomes for BRAF-mutated NSCLC as compared with wild-type tumors without a known driver mutation or tumors harboring other mutations. However, select cases of prolonged survival have also been described, and thus, the natural history of BRAF-mutated NSCLC remains an area of ongoing study. The aim of this series was to describe the natural history, clinical outcomes, and occurrence of co-mutations in patients with BRAF-mutated NSCLC.Patients and MethodsPatients with BRAF-mutated NSCLC seen at Stanford University Medical Center from January 1, 2006 through July 31, 2015 were reviewed. The Kaplan-Meier method was used to calculate median overall survival, and the generalized Wilcoxon test was used to compare median survivals across subgroups of patients.ResultsWithin a cohort of 18 patients with BRAF-mutated NSCLC, V600E mutations were most common (72%; 13/18). Clinicopathologic features were similar between patients with V600E versus non-V600E mutations, although there was a trend toward more patients with non-V600E mutations being heavy smokers (80% vs. 31%; P = .12). Co-occurring mutations in TP53 were identified most commonly (28%; 5/18). The median overall survival for the entire cohort was 40.1 months, and the median survival from the onset of metastases (n = 16) was 28.1 months. Survival rates at 2 and 5 years from the onset of metastases were 56% and 13%, respectively.ConclusionThe clinical behavior of BRAF-mutated NSCLC is variable, but favorable outcomes can be seen in a subset of patients.     

Prognostic Impact of Preoperative Albumin–Globulin Ratio on Oncologic Outcomes in Upper Tract Urothelial Carcinoma Treated With Radical Nephroureterectomy

Purpose

To identify the impact of albumin–globulin ratio (AGR) on pathologic and survival outcomes in patients with upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU).

Giant Circulating Cancer-Associated Macrophage-Like Cells Are Associated With Disease Recurrence and Survival in Non–Small-Cell Lung Cancer Treated With Chemoradiation and Atezolizumab

BackgroundCancer-associated macrophage-like cells (CAMLs) are a potential peripheral blood biomarker for disease progression. This study used data from a phase 2 clinical trial to evaluate prognostic utility of CAMLs for locally advanced non–small-cell lung cancer treated with definitive chemoradiotherapy (CRT) and atezolizumab (DETERRED; ClinicalTrials.gov NCT02525757).Patients and MethodsSample collection occurred at baseline (T0), during CRT (T1), at end of CRT (T2), and at first follow-up (T3). CAMLs were captured and quantified by the CellSieve system using multiplex immunostaining. Giant CAMLs were defined as characteristic CAMLs ≥ 50 μm. Kaplan-Meier methodology estimated progression-free survival, distant failure-free survival, relapse-free survival, and overall survival at 30 months.ResultsThirty-nine patients were evaluated between December 2015 and March 2018. Median follow-up was 27 months. Most disease was stage III (85%) and comprised squamous-cell carcinoma (38%) or adenocarcinoma (59%). In total, 267 blood samples were analyzed. Giant CAMLs were identified in 57%, 60%, 64%, and 63% of patients at T0, T1, T2, and T3, respectively. Patients with giant CAMLs at T3, occurring at a median of 30 days after completion of CRT, had significantly worse distant failure-free survival (hazard ratio [HR] 4.9, P = .015), progression-free survival (HR 2.5, P = .025), recurrence-free survival (HR 2.4, P = .036), and overall survival (HR 3.5, P = .034) compared to patients with small or no CAMLs.ConclusionsPresence of giant CAMLs after CRT completion was associated with development of metastatic disease and poorer survival despite the use of maintenance immunotherapy. Monitoring CAMLs may help risk-stratify patients for adaptive treatment strategies.     

Clinical Characteristics,Treatments, and Concurrent Mutations in Non–Small Cell Lung Cancer Patients With NF1 Mutations

ObjectivesMetastatic non–small cell lung cancer (mNSCLC) is characterized by complex genomic alterations. NF1 mutations may confer distinct clinical characteristics within NSCLC, and real-world evidence on concurrent mutations, treatment patterns, and health outcomes is lacking.Materials and MethodsThis retrospective study was performed in patients with mNSCLC treated in the Flatiron Health network who underwent the FoundationOne tumor-sequencing. Anticancer therapies, concurrent mutations, real-world progression-free survival (rwPFS), and overall survival (OS) were assessed.ResultsOf the 1663 patients, 103 patients were identified with NF1 mutation. Concurrent mutations with Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (16.5%) and epidermal growth factor receptor fusion (6.8%) were the most frequent. In patients with NF1 mutation only (n = 57), 42% were women, 86% patients had smoking history, and 70% had non-squamous cell carcinoma type. Most (51%) of the patients with NF1 mutations received a single line of therapy versus other mutations and the overall treated population (44%). Platinum-based chemotherapy was the predominant first-line therapy, with programmed cell death-1/programmed cell death-ligand-1 inhibitors as subsequent lines of therapy. The NF1 mutation only group had numerically the shortest median rwPFS (82 days) than other mutation groups. Median OS for the NF1 mutation group in first, second, and third lines of therapy was 321, 498, and 210 days, respectively.ConclusionsNF1 mutations confer distinct clinical characteristics in patients with mNSCLC. These patients may have different trajectories for progression and survival than seen for other mutations, experience less systemic therapy after first-line therapy, and may have shorter survival.     

Incidence,Risk Factors,and Effect on Survival of Immune-related Adverse Events in Patients With Non–Small-cell Lung Cancer

Background

The risk factors for immune-related adverse events (irAEs) remain undefined. Recently, a correlation between irAEs and clinical benefit was suggested. We examined the risk factors for irAEs and their effect on survival in patients with non–small-cell lung cancer (NSCLC) who had received immunotherapy.

Phase II Study of Cetuximab,Docetaxel, and Gemcitabine in Patients With Previously Untreated Advanced Non–Small-Cell Lung Cancer

BackgroundTargeting epidermal growth factor receptors (EGFRs) has been a novel strategy in treating non–small-cell lung cancer (NSCLC). This multicenter, community-based trial was designed to examine the role of cetuximab in combination with a nonplatinum regimen.Patients and MethodsEligibility criteria were newly diagnosed unresectable stage III/IV NSCLC, all histologies, measurable disease, and Eastern Cooperative Oncology Group performance status (ECOG PS) 0-2. Treatment premedication included dexamethasone 20 mg orally 12 and 6 hours before treatment, and 4 mg 12 hours following treatment; diphenhydramine 50 mg intravenously (I.V.) and cimetidine 300 mg I.V. before cetuximab. Treatment medication included docetaxel 30 mg/m² I.V. days 1 and 8; gemcitabine 1000 mg/m² I.V. days 1 and 8; and cetuximab 400 mg/m² I.V. day 1, then 250 mg/m² I.V. weekly. Patients received up to 6 cycles with restaging every 6 weeks. The primary endpoint was an overall response rate (ORR) ≥ 25%.ResultsSixty-nine patients enrolled from July 2005 to October 2007. Patients had a median age of 69 years; 70% were male and 30% were female; ECOG PS was 0 in 42%, 1 in 51%, and 2 in 7%; patients had adenocarcinoma (42%), squamous cell (30%), large cell (6%), mixed (1%), and not otherwise specified (20%) disease. The ORR was 17% (95% CI, 9%-29%). Thirty-five patients (54%) had stable disease; 14 patients (22%) had progressive disease. With a median follow-up of 17.8 months, the median progression-free and overall survivals were 4 months and 9.4 months, respectively. The most common (> 10%) grade 3/4 toxicities were neutropenia (25%), rash (22%), and fatigue (12%). Accrual in our middle Tennessee offices was temporarily suspended and ultimately stopped because of a higher-than-anticipated rate of cetuximab-related severe hypersensitivity reactions (HSRs) in 4 patients among the first 12 enrolled, including 1 fatal event.ConclusionCetuximab/docetaxel/gemcitabine was relatively well-tolerated and associated with efficacy similar to chemotherapy alone. Additional study with cetuximab/chemotherapy in NSCLC should focus on new potentially predictive biomarkers. Also, additional study is needed to better understand and prevent the severe HSRs that appear to be endemic to specific regions of the United States.     

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.