IntroductionDespite durable responses from immune-checkpoint blockade (ICB) in a subset of patients with advanced non-small cell lung cancer (NSCLC), the majority of patients do not derive benefit from this treatment. In this analysis we evaluated the impact of concomitant administration of antibiotics during initiation of ICB on clinical outcome.MethodsAdvanced non-squamous NSCLC patients receiving ICB as second- or later line between 2015 and 2017 at our tertiary cancer center in Salzburg (Austria) were included. Concomitant use of antibiotics was defined as administration of antibiotics within a time frame of one month before or one month after initiation of ICB (AB+-group).ResultsOf the 30 patients included, 11 (36.7%) received antibiotics one month before or one month after start of ICB (AB+-group). Median PFS on ICB was in favor of the AB--group (AB-: 3.1 months [95%CI: 3.0-16.3]; AB+: 2.9 months, [95%CI: 1.9-NA]; HR=0.46 [95%CI: 0.12-0.90], p=0.031). Furthermore, median OS was significantly longer in the AB--group (AB-: 15.1 months [95%CI: 11.1-NA]; AB+: 7.5 months [95%CI: 6.3-NA]; HR=0.31 [95%CI: 0.02-0.78], p=0.026). In a multivariate analysis, the antibiotic treatment status was identified as the only parameter statistically significantly associated with PFS (p=0.028) and OS (p=0.026).ConclusionsStratification of patients according to the antibiotic treatment status is warranted in future trials investigating ICB.
D5F3 with OptiView exclusively stained rearranged cases with strong intensity, without a single false-positive or false-negative case. The number of subsequent ALK FISH analyses required would have decreased from 303 to 14 cases (-95.4%), reducing significantly the time, work and costs without any loss of diagnostic quality and accuracy.
Immune-checkpoint blockade in front-line or second-line treatment improves survival in advanced non-small cell lung cancer (aNSCLC) when compared with chemotherapy alone. However, easily applicable predictive parameters are necessary to guide immune-checkpoint inhibition in clinical practice. In this retrospective bi-centric analysis, we investigated the impact of baseline patient and tumor characteristics on clinical outcome in aNSCLC patients treated with programmed cell death protein 1(PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors. Between May 2015 and January 2018, 142 unselected consecutive NSCLC patients received PD-1/PD-L1 inhibitors during the course of disease. In multivariate analysis, we identified the Eastern Cooperative Oncology Group (ECOG) performance status (ECOG > 1 versus ECOG ≤ 1, HR: 3.23, 95%CI: 1.58–6.60, P = 0.001), baseline absolute lymphocyte count (ALC; high: >0.93 × 109/L versus low: ≤ 0.93 × 109/L, HR: 0.38, 95%CI: 0.23–0.62, P < 0.001), prior or concomitant anti-vascular endothelial growth factor (VEGF) targeting therapy (yes versus no, HR: 2.18, 95%CI: 1.15–4.14, P = 0.017) and TNM stage (IV versus III, HR: 4.18, 95%CI: 1.01–17.36, P = 0.049) as the most relevant parameters for survival. Neither antibiotic exposure (antibiotic-positive versus antibiotic-negative, HR: 0.90, 95%CI: 0.56–1.45, P = 0.675), nor PD-L1 expression on tumor cells (≥1% versus <1%, HR: 0.68, 95%CI: 0.41–1.13, P = 0.140) was associated with survival. Baseline ECOG performance status and ALC were associated with survival in aNSCLC patients treated with PD-1/PD-L1 inhibitors and assessment of these parameters could be suitable in clinical practice.
Purpose: Chemotherapy can be an integral component of the adjuvant management strategy for women with early stage breast cancer. To date, no tool is available to predict or monitor the efficacy of these therapies. The aim of this proof-of-principle study was to assess whether NEUROD1 DNA methylation is able to predict the response to neoadjuvant and adjuvant chemotherapy. Experimental Design: Recently, we showed that NEUROD1 DNA is differentially methylated in neoplastic versus nonneoplastic breast tissue samples. In this study, we used MethyLight and analyzed NEUROD1methylation in (a) 74 breast cancer tissue samples, (b) two independent sets of pretreatment core biopsies of 23 (training set) and 21 (test set) neoadjuvantly treated breast cancer patients, and (c) pretherapeutic and posttherapeutic serum samples from 107 breast cancer patients treated with adjuvant chemotherapy. Results: High-grade tumors showed higher NEUROD1 methylation levels. Estrogen receptorn egative breast cancers with high NEUROD1 methylation were 10.8-fold more likely to respond with a complete pathologic response following neoadjuvant chemotherapy. Patients with positive serum pretreatment NEUROD1 methylation, which persisted after chemotherapy, indicated poor relapse-free and overall survival in univariate and multivariate analyses (relative risk for relapse, 6.2; 95% confidence interval, 1.6-24; P = 0.008, and relative risk for death, 14; 95% confidence interval, 1.6-120; P = 0.02). Conclusions: These data support the view that NEUROD1 methylation is a chemosensitivity marker in estrogen receptor^negative breast cancer.Breast cancer is the most frequent malignancy among women in the industrialized world. To date, the presence or absence of metastatic involvement in the axillary lymph nodes is still the most powerful prognostic factor available for patients with primary breast cancer (1), although this is just an indirect measure reflecting the tendency of the tumor to spread. Recently, we showed that RASSF1A DNA methylation in serum is a marker of poor prognosis in women with breast cancer (2) and that this cancer-specific DNA alteration allows the monitoring of adjuvant tamoxifen therapy (3), which is applied mainly in estrogen receptor (ER) -positive tumors. To date, no tool is available to sufficiently predict or monitor the efficacy of neoadjuvant or adjuvant systemic chemotherapy which is frequently applied in ER-negative breast cancer.We recently reported that stem cell polycomb group targets (PCGT) are up to 12-fold more likely to have cancer-specific promoter DNA hypermethylation compared with nontargets (4). This supports the idea of a stem cell origin of cancer whereby reversible gene repression is replaced by permanent silencing, forcing the cell into a perpetual state of self-renewal and therefore increasing the possibility for subsequent malignant transformation (4). A large number of PCGT genes have not yet been described to play a role in cancer and this could explain why non -tumor suppressor genes are found t...
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