Tumor burden as possible biomarker of outcome in advanced NSCLC patients treated with immunotherapy: a single center, retrospective, real-world analysis.

Aim: The role of tumor burden (TB) for patients with non-small cell lung cancer (NSCLC) receiving immunotherapy is still unknown. The aim of this analysis was to analyze the prognostic value of TB in a real-world sample of advanced NSCLC patients. Methods: Sixty-five consecutive patients with advanced NSCLC treated with immunotherapy as first or second line therapy were retrospectively analyzed between August 2015 and February 2018. TB was recorded at baseline considering sites and number of metastases, thoracic vs. extrathoracic disease, measurable disease (MD) vs. not-MD (NMD) and evaluating dimensional aspects as maximum lesion diameter (cut-off = 6.3 cm), sum of the 5 major lesions diameters (cut-off = 14.3 cm), and number of sites of metastases (cut-off > 4). All cut-offs were calculated by receiver operating characteristic curves. Median overall survival (OS) was estimated using Kaplan-Meier method. A Cox regression model was carried out for univariate and multivariate analyses. Results: Median age was 70 years and most patients (86.2%) had a good performance status (PS-Eastern Cooperative Oncology Group < 2). No significant difference in OS was noted between subgroups of patients according to TB. Bone metastases (BM) had a negative prognostic impact [median OS (mOS), 13.8 vs. 70.0 months, P = 0.0009; median progression free survival in the second line (mPFS2) 2.97 vs. 8.63 months; P = 0.0037]. Patients with NMD had a poorer prognosis (mOS, 15.9 months vs. not reached, P < 0.0001; mPFS2 3.8 vs. 12.2 months; P = 0.0199). Patients with disease limited to the thorax had a better prognosis compared to patients with involvement of extrathoracic sites (mOS, 70 vs. 17.3 months; P = 0.0136). Having more than 4 metastatic sites resulted as a negative prognostic factor (mOS, 15.9 vs. 25.2 months; P = 0.0106). At multivariate analysis, BM, NMD, extrathoracic disease and number of sites of metastases > 4 were negative prognostic factors (P < 0.0001). Conclusions: This study underlines the negative prognostic impact of specific metastatic sites, presence of NMD and extrathoracic disease in advanced NSCLC patients treated with immunotherapy. However, TB does not appear to affect the outcome of these patients.

Irinotecan-Induced Transient Dysarthria: Case Series and Updated Literature Review.

Irinotecan-based regimens are used worldwide for the treatment of several recurrent or advanced gastrointestinal malignancies. In this paper we describe the cases of four patients treated in our institution who developed acute dysarthria while receiving intravenous infusion of irinotecan. In all our cases, dysarthria occurred during the infusion of the first course of irinotecan, and then resolved rapidly without any sequelae. Imaging of the brain was performed, but failed to show any evidence of an acute neurological event. We also reviewed the literature on this very uncommon adverse event. The pathogenesis of irinotecan-induced dysarthria is still unknown and is not completely elucidated by the current pharmacodynamic or kinetic explanations; therefore, we could only hypothesize some assumptions.

Hyponatremia is a Predictor of Clinical Outcome for Resected Biliary Tract Cancers: A Retrospective Single-Center Study.

INTRODUCTION: Biliary tract cancers (BTC) include both gallbladder cancer and cholangiocarcinoma, both of which have a poor prognosis. The aim of our study was to evaluate the main clinical prognostic factors in this setting and to assess their impact on overall survival (OS). METHODS: We retrospectively analyzed data collected on 64 patients with BTC who underwent surgery with radical intent at our institution. OS was estimated using the Kaplan-Meier method. The Cox regression model was used to perform univariate and multivariate analyses. RESULTS: Preoperative hyponatremia was found to be an independent prognostic factor that correlated negatively with prognosis, with hyponatremic patients having a poor OS compared to the group of patients with normal serum sodium levels (9.44 vs. 15.47 months; p = 0.0215). In addition, high preoperative values for carbohydrate antigen 19-9 (Ca19.9), a tumor marker for some gastrointestinal cancers, and lactate dehydrogenase (LDH) were found to be prognostic factors for a significant reduction in OS (Ca19-9: 7.14 vs. 24.22 months, p = 0.0088; LDH: 1.70 vs. 15.47 months, p = 0.0384). CONCLUSION: Identification of these prognostic factors may support strategies to identify, in clinical practice, those subgroups of patients with a favorable or unfavorable prognosis before surgical treatment and, therefore, to guide therapeutic choices. In particular, to our knowledge, this is the first report of the prognostic role of serum sodium level in BTC. Early detection and careful monitoring of hyponatremia and supportive therapy can help to improve the treatment and prognosis of BTC.

Prognostic relevance of programmed cell death protein 1/programmed death-ligand 1 pathway in thymic malignancies with combined immunohistochemical and biomolecular approach.

BACKGROUND: The aim of the study was to investigate Programmed cell Death protein 1 (PD-1) and Programmed Death-Ligand 1 (PD-L1) and their mRNA expression in thymic epithelial tumors (TETs). RESEARCH DESIGN AND METHODS: We analyzed 68 samples of formalin-fixed paraffin-embedded tissue (63 thymomas and 5 thymic carcinomas). PD-1 and PD-L1 protein expression were evaluated by immunohistochemistry, and mRNA expression was evaluated by real-time PCR. RESULTS: M/F ratio was 33/35, and median age was 60.5 years. Twenty patients had Myasthenia Gravis (MG). In the subgroup with large tumors (>5 cm), PD-L1 mRNA overexpression was significantly associated with worse prognosis vs. patients with no mRNA overexpression (p = 0.0083) and simultaneous PD-L1 immunostaining (>1%); PD-L1 mRNA overexpression was significantly associated with worse prognosis, respect to patient with PD-L1 negative immunostaining, and no PD-L1 mRNA overexpression (p = 0.0178). The elderly patients (>60 years) with large tumors showed worse prognosis (p = 0.0395). PD-L1 immunostaining (>50%) resulted to be significantly associated with MG. CONCLUSIONS: Our data suggest the potential involvement of the PD-1 and PD-L1 pathway in TETs' progression. According to our results, it may be helpful to design future trials with anti-PD-1 drugs to establish high-risk patients after surgery.

Scientia Potentia Est: How the Italian World of Oncology Changes in the COVID-19 Pandemic.

PURPOSE: After coronavirus disease 2019 (COVID-19) was declared a pandemic by the WHO, a response from the Italian Health System to react to an unprecedented condition became necessary and sudden. The COVID-19 pandemic has required oncologists to redefine clinical organization and patient management. The purpose of our study was to document the difficulties emerging during the SARS-CoV-2 pandemic in Italian oncology. METHODS: We broadcasted an electronic survey to oncologic health care professionals. It consisted of 45 questions ranging from individual perception of pandemic management by hospital centers to physicians' and nurses' psychological distress and patient care. RESULTS: A total of 383 oncology health workers participated in the survey. The majority were female (71.8%) and from central Italy (46.2%). Impressively, a total of 357 (93%) participants declared the oncologic department reorganized routine clinical activity, but only 40.5% were adequately trained about the required procedures; 20% of the survey respondents think they have not received adequate and timely protective devices. CONCLUSION: Our survey demonstrated the flexibility of oncologic teams. However, the emergency response quality has been heterogeneous, and several drawbacks have emerged from the first analyses investigating how the world of oncology changes in the COVID-19 pandemic. Information, protection, testing, and training of health care professionals are key words that should be kept in mind to encourage recovery after this tragedy and to be ready to face a similar emergency in the future.

Electrolyte disorders in advanced non-small cell lung cancer patients treated with immune check-point inhibitors: A systematic review and meta-analysis.

BACKGROUND: Aim of this meta-analysis was to determine the relative risk (RR) of electrolyte disorders (EDs) in advanced non-small cell lung cancer (aNSCLC) patients treated with immune check-point inhibitors (ICIs). METHODS: We searched for phase II/III randomized controlled trials (RCTs) comparing ICIs (alone or combined with chemotherapy) with standard chemotherapy in aNSCLC. Summary incidence and RR were calculated. RESULTS: Six RCTs with data on all-grade hyponatremia were identified (n = 3257). The incidence was 8.7 % in the study group and 4.9 % in the control group (RR 1.78, 95 %CI 1.12-2.80). Looking at all-grade hypokalemia, 7 RCTs were included (n = 4119). Incidence was 10.4 % in ICIs-treated patients and 5.9 % in the control arms (RR 1.62, 95 % CI 1.30-2.02). CONCLUSIONS: Treatment with ICIs in aNSCLC is associated with a significant increased risk of hyponatremia and hypokalemia compared to chemotherapy. Monitoring of electrolyte levels should be emphasized in this setting.

The role of angiogenetic single-nucleotide polymorphisms in thymic malignancies and thymic benign lesions.

BACKGROUND: We previously showed that selected single-nucleotide-polymorphisms (SNPs) of genes involved in angiogenesis influence the aggressiveness of thymic epithelial tumors (TETs). This study analyzes their role in TETs and in thymic benign lesions, in order to investigate potential correlation with risk and outcome. METHODS: Genomic DNA was extracted from paraffin-embedded tissue of 92 patients, undergoing surgery at our Institution. We investigated by Real-Time PCR the SNPs of the following genes: platelet-derived growth factor receptor-α (PDGFRα), hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor A (VEGF-A), vascular endothelial growth factor receptor-2 and 3 (VEGF-2, VEGFR-3), excision repair cross-complementation group-1 (ERCC1). RESULTS: Fifty-seven TETs and 35 thymic benign lesions were included into the study. Frequency of SNPs was as follows: rs2057482 C, rs11158358 C and rs11549465 C polymorphisms of HIF1-a: thymomas < general population (P=0.008, P=0.007, and P=0.044 respectively). HIF1-a alleles: general population > study groups, rs1951795C SNP (P=0.026 for benign lesions and P=0.0007 for thymomas), rs10873142T SNP (P=0.008 and P=0.001 respectively), rs12434438 A SNP (P=0.034 and P=0.0007) and rs2301113A SNP (P=0.027 and P=0.010). rs699947C polymorphism of VEGF-A: benign lesions > general population (P=0.012). CONCLUSIONS: This is the first study investigating the angiogenetic polymorphisms in thymic benign lesions and TETs. SNPs analysis may represent a further asset in identification of patients who could benefit from anti-angiogenetic therapy.

Osteoblastic bone metastases from neuroendocrine tumor (NET) of unknown origin detected by 18fluorocholine PET/CT and its comparison with 68gallium-DOTATOC PET/CT: Case report and review of the literature.

RATIONALE: Choline (CH) positron emission tomography (PET)/computed tomography (CT) with fluorine 18 (F) CH is increasingly used not only to evaluate patients with biochemically recurrent prostate cancer but also to assess metastatic lesions that are difficult or impossible to identify using more conventional modalities. Our experience with CH PET/CT has shown that it can also be used for many other malignancies. PRESENTING CONCERNS: A 71-year-old male with a neuroendocrine tumor (NET) of unknown origin showed osteoblastic bone metastases positive to F-CH PET. INTERVENTIONS: Diffuse bone and liver metastases were gallium-DOTATOC PET-positive with only mild uptake on FDG PET/CT. An increased prostate specific antigen (8 µg/L) gave rise to a suspicion of concurrent prostate cancer and the patient underwent F-CH PET/CT which showed diffuse uptake in the bone. A CT-guided bone biopsy confirmed osteoblastic bone metastases from NET. OUTCOMES: Given the aggressiveness of the tumor, the patient underwent treatment with temozolomide from July 2015 to December 2015, maintaining stable disease. However, progression was documented in January 2016 and the patient was enrolled onto a phase II peptide receptor radionuclide therapy retreatment trial, which is currently ongoing. MAIN LESSON: Our study highlights that NETs should be taken into consideration in the differential diagnosis of osteoblastic bone metastases showing F-CH uptake. A prognostic role for this imaging technique can also be hypothesized.

Bordetella bronchiseptica pneumonia in a patient with lung cancer; a case report of a rare infection.

BACKGROUND: Bordetella bronchiseptica (B.bronchiseptica) is a frequent cause of respiratory infections in animals but rarely causes serious infection in humans. We present a rare case of B. bronchiseptica pneumonia in a patient with lung cancer. CASE PRESENTATION: A 52-year-old white male with non small cell lung cancer developed fever during treatment with nivolumab. A persistent productive cough and a deterioration in his clinical condition led to his hospitalization for evaluation. Bronchoscopy was performed and a diagnosis of B. bronchiseptica pneumonia was made. The infection was successfully managed by antiobiotic therapy. CONCLUSIONS: B. bronchiseptica is a pathogen that can cause serious infection in humans, especially in immunocompromised or immunoincompetent individuals. In our patient it showed unusual resistance to cephalosporins and poor sensitivity to amikacin. To our knowledge this is the first case of such an infection in a lung cancer patient undergoing treatment with nivolumab. When B. bronchiseptica is identified, the possibility of a nosocomial transmission must be considered.

Impact of VEGF, VEGFR, PDGFR, HIF and ERCC1 gene polymorphisms on thymic malignancies outcome after thymectomy.

We aimed to analyze genotypes of VEGF-A, VEGFR2, Flt4, PDGFRα, HIF-1α and ERCC1 and their correlation with thymic tumor risk and patient outcome. DNA of 57 consecutive patients (43 thymomas and 14 thymic carcinomas) who underwent total thymectomy at our Institution was extracted from paraffin-embedded tissue. We selected polymorphisms in the following genes:HIF1-α (rs2057482T > C, rs1951795A > C, rs2301113C > A, rs10873142C > T, rs11158358G > C, rs12434438G > A, rs11549465C > T, rs11549467G > A), VEGF-A (rs2010963G > C, rs699947A > C), VEGFR-2 (rs2305948C > T, rs1870377T > A), VEGFR-3 (rs307826T > C, rs307821C > A), PDGFR-α (rs35597368C > T) and ERCC1 (rs11615A > G). Gene polymorphisms were determined by Real-Time PCR using TaqMan assays. As compared to the general population, the allele frequency of PDGFR-α rs35597368T was significantly higher (95% vs. 87%, p = 0.036), while the frequency of alleles HIF1-α rs2057482C (78% vs. 90%), rs1951795C (69% vs. 87%), rs2301113A (70% vs. 83%), rs10873142T (70% vs. 87%), rs11158358C (75% vs. 88%), rs12434438A (67% vs. 84%) were significantly lower. VEGFR-3 rs307821C frequency was significantly higher in thymomas vs. thymic carcinomas (79% vs. 72%, p = 0.0371). The following factors were significantly correlated with a longer overall survival: VEGFR-3 rs307826C, VEGFR-2 rs1870377A, PDGFR-α rs35597368T/C, HIF1-α rs2301113C, rs2057482C/T, rs1951795C, rs11158358G/C and rs10873142T/C, ERCC1 rs11615A (p < 0.05). Our results suggest, for the first time, that PDGFR-α, HIF-1α and VEGFR-3 SNPs are associated with thymic cancer risk and survival.