Cardiac tumors prevalence and mortality: A systematic review and meta-analysis.

OBJECTIVES: Cardiac tumors and their associated outcomes are poorly characterized. This study sought to comprehensively assess the epidemiology and natural history of primary and secondary malignant cardiac tumors (PMCT and SMCT), a well as establish predictors of mortality. METHODS: A comprehensive literature review was performed to identify articles reporting on PMCTs and SMCTs. The prevalence of important cardiac tumor (CT) subtypes was evaluated and further stratified based on the continental region. Outcomes of interest included short- and long-term mortality and utilization of heart transplantation (HTX). A random effect model was adopted, and a meta-regression was performed to determine predictors of the prevalence of CTs as well as predictors of operative mortality. RESULTS: Of the 1,226 retrieved articles, 74 were included in our study (n = 8,849 patients). The mean follow-up was 2.27 years, mean age was 42.9 years, and 55% of the patients were females. There was a total number of 7,484 benign primary cardiac tumors (PCTs) (5,140 were myxoma), 862 (9.7%) malignant PCTs, and 355 secondary cardiac tumors. The prevalence of PMCTs among PCTs was 10.83% [95%CI = 09.11; 12.83%] with a trend towards being lower in South America compared to other continents (Prevalence = 5.80%). The prevalence of HTX among all patients was 2.45% [1.36; 4.38%]. The pooled short-term mortality was 5.90% [4.70; 7.39%] and the incidence of late mortality in all CTs, benign CT and PMCTs was 2.55% [1.76; 3.72%], 0.79% [0.46; 1.37%] and 14.77% [9.32; 23.40%], respectively. On meta-regression, the annual volume of cardiac tumor cases per center was the only predictor of lower early mortality (Beta = -0.14 ± 0.03, P < 0.0001). CONCLUSIONS: PMCTs represent the minority of PCT (~10%) and have a higher prevalence in Europe and North America. Survival is higher in benign pathology and is significantly improved by treatment in specialized high-volume centers. Approximately 2% of patients with CTs undergo heart transplantation.

Stenting in Non-Small Cell Lung Cancer: How Does It Affect the Outcomes?

OBJECTIVE: Approximately 30% of lung cancer patients develop central airway obstruction (CAO) that remarkably shortens survival. There is little data about the benefits of stenting within this heterogeneous patient group. Our objective was to review their overall survival (OS) and their risk of hospitalization versus patients who did not have lesions requiring stent placement. METHODS: We retrospectively reviewed charts of 171 non-small cell lung cancer (NSCLC) patients who underwent bronchoscopy in the University of Cincinnati Cancer Center from the year 2011 to 2013. Twenty-five patients with advanced lung cancer were evaluated by interventional pulmonology service for endobronchial stent placement for CAO. Eight patients did not require placement of a stent and 17 had obstructive lesions that required stenting by interventional pulmonology. RESULTS: Demographical parameters such as age and gender did not have a significant impact on the risk of hospitalization or OS of both groups of patients, however, those whose lesions did not mandate stent placement had significantly lower odds of hospitalization compared to patients with CAO requiring a stent (OR: 15.913, 95% CI: 1.211-209.068, P = 0.0352). Patients with advanced NSCLC and CAO that required stent placement had an OS of 13.9 m [3.9-19.9 m] compared to an OS of 23.9 m for patients with CAO not requiring a stent. We found out that patients with less severe CAO have lower odds of hospitalization and better OS compared to patients with CAO mandating stent placement. CONCLUSION: CAO patients with interventional pulmonology (IP) evaluation and management in addition, may have improved OS suggesting that IP consultation might offer both improvement in quality of life and overall survival to patients with advanced NSCLC and CAO. 
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Exosomes as a Surrogate Marker for Autophagy in Peripheral Blood, Correlative Data from Phase I Study of Chloroquine in Combination with Carboplatin/Gemcitabine in Advanced Solid Tumors.

BACKGROUND: Autophagy is a catabolic process, utilized constitutionally by body cells to recycle nutrients and to remove unwanted/damaged intracellular constituents. It is enhanced during periods of stress, such as starvation and hypoxia, aiding in cell survival and it is linked to major cellular processes, such as apoptosis and antigen expression. The process has been extensively studied in vitro models or tumor tissue samples with rare application on human subjects. METHODS: Plasma samples from 24 advanced solid tumor patients were collected at different time points before and after chemotherapy. Their exosomes were isolate and blotted for microtubule-associated protein-1 light chain-3 (LC-3B) protein as a marker for autophagy. All the subjects received a standard chemotherapy regimen of carboplatin- gemcitabine with chloroquine (CQ)/ hydroxychloroquine (HCQ) in chronic doses throughout their treatment period as an autophagy modulator. CQ/HCQ was given in 50 mg increments as guided by their tolerability to treatment. RESULTS: A total of 267 plasma samples were obtained for the 24 patients and processed. Each sample corresponds to a single time point. The first group included 6 patients, all received 50 mg of CQ with chemotherapy. LC-3B I was detected in their isolated exosomes, while LC3-BII was not detected in their samples. The second cohort of patients included 3 subjects who re-ceived 100mg of HCQ. They demonstrated both LC3-BI and II on day 15 after chemotherapy in one patient, and on third cycle after 24 hours in the second patient. The third cohort included 3 subjects who received 150 mg of HCQ. All cases demonstrated LC3-BI and II on first cycle of treatment after less than 24 hours. The last cohort included 8 subjects, who received a fixed dose of 100 mg of HCQ with treatment. In this cohort, we were able to detect both LC3-B isoforms on advanced time points of second and third cycles. CONCLUSION: Detection of autophagy protein LC3-B in exosomes serves as a dynamic method to monitor autophagy. It can be utilized to study the effects of anti-neoplastic agents on autophagy and mechanisms of drug resistance, however, to standardize our results a larger specimen of patients should be included.

Corrigendum to "Nivolumab and Ipilimumab in the Treatment of Metastatic Uveal Melanoma: A Single-Center Experience".

[This corrects the article DOI: 10.1155/2019/3560640.].

Papillary renal cell carcinoma: what is missing in research? A case report and a review of literature.

The incidence of renal cell carcinomas in adults ranges has been increasing over the past decades in both men and women. Once the incidence was 2.9%, now is reported to have increased to 3%-5% with male predominance according to the most recent reports of cancer statistics. The disease typically describes a group of different histopathological subtypes; the most common is clear cell carcinoma which accounts for 70%-80% of the diagnosed cases, while papillary renal cell carcinoma and chromophobe types represent 20% and 5%, respectively. In 1996, the renal cell carcinomas Heidelberg classification was introduced by Delahunt et al. It divides renal cell tumors into benign and malignant parenchymal neoplasms, excluding Wilm's tumor and secondary metastases and limiting each subcategory to the most commonly documented genetic abnormalities, if applicable. In this report, we discuss a case of metastatic type I papillary renal cell carcinoma treated with the anti-vascular endothelial growth factor receptor sunitinib and showing marked long-term clinical response. Through this case, we highlight the importance of re-classifying papillary renal cell carcinoma subtypes to prioritize the clinical management of these cases.

Retrospective Study of the Effect of Statins on the Outcome of Lung Cancer Patients, University of Cincinnati Experience.

Objectives: Numerous studies addressed the effect of statin on cancer patients. The aim of this study is to define the effect of statin administration with chemotherapy on the patients' outcomes. Methods: We retrospectively researched the database of the University of Cincinnati cancer to identify lung cancer patients who received statins (S+, n=41) during their treatment in our institute. We also, retrieved data for contemporaneously treated patients who did not receive statins (S-, n=159) as a control arm. Clinico-demographical data and overall survival (OS) were analyzed using Pearson's Chi-square (χ2) test and Kaplan-Meier survival curves with Log-rank test. Adjustment using Cox proportional hazard ratios (HR) were done based on (age, gender, race and stage) to identify effect of statins on their outcomes. Results: The median age for S+ was 64y (IQR; 55-69) and 71.2% of the patients were white. Histopathology was 55.4% and 31.7% for adenocarcinoma and squamous cell carcinoma, respectively. Fifty-six percent were stage IV in each study arm and the median OS was14.9 m. Median OS was insignificantly lower in S­ve arm (13.7 vs 15.6 months; P=0.652, HR=0.91, 95%CI 0.52-1.57). Our results show that after different types of adjustments, S+ did not show survival advantage (P>0.05) compared to the control arm. Conclusion: While showing an increase in overall survival in patients with advanced lung cancer, the results of this study did not reach statistical significance. This could be due for the small sample size of this retrospective study.

Nivolumab and Ipilimumab in the Treatment of Metastatic Uveal Melanoma: A Single-Center Experience.

BACKGROUND: Metastatic uveal melanoma (MUM) is associated with a poor prognosis, with a median overall survival (OS) of 4-15 months. Despite new insights into the genetic and molecular background of MUM, satisfactory systemic treatment approaches are currently lacking. The study results of innovative treatment strategies are urgently needed. PATIENTS AND METHODS: This was a retrospective case series of 8 patients with MUM managed at the University of Cincinnati between January 2015 and January 2018. The immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) 1.1 criteria were used for patient evaluation, and magnetic resonance imaging was used for evaluation at treatment checkpoints. OBJECTIVE: To assess the clinical outcome of patients with MUM treated with a combination of checkpoint inhibitors. RESULTS: The series included eight patients, six men and two women, with MUM. Their median age at MUM diagnosis was 69 (range, 55-77) years. All patients were treated with ipilimumab and nivolumab combination along with transarterial chemoembolization (TACE), followed by nivolumab maintenance and monthly TACE procedures. The majority of patients had a partial response or stable disease. Two of the patients had partial response, while four others had stable disease. Two other patients experienced disease progression. CONCLUSION: We report the outcomes of eight patients with MUM treated with the combination of ipilimumab and nivolumab. We report the clinical outcome and toxicity associated with this treatment approach. Further studies are warranted to explore immunotherapy in MUM. These findings support the consideration of immunotherapy in MUM.

Cardiotoxicity with immune system targeting drugs: a meta-analysis of anti-PD/PD-L1 immunotherapy randomized clinical trials.

Background: With antiprogrammed death receptor-1 (anti-PD-L1) therapy, a recent meta-analysis reported higher incidence of cutaneous, endocrine and gastrointestinal complications especially with dual anti-PD-L1 immunotherapy (IMM). Methods: Our primary outcome was assessment of all cardiotoxicity grades in IMM compared with different treatments, thus a systemic review and a meta-analysis on randomized clinical trials (RCTs) were done. Results: We included 11 RCTs with 6574 patients (3234 patients in IMM arm vs 3340 patients in the other arm). Three non-small-cell lung cancer RCTs, seven melanoma RCTs and only one prostatic cancer RCT met the inclusion criteria. There were five RCTs that compared monoimmunotherapy to chemotherapy "(n = 2631 patients)". No difference exists in all cardiotoxicity grades or high-grade cardiotoxicity (p > 0.05). Lung cancer exhibited a higher response rate and lower mortality in IMM. Conclusion: There was no reported statistically significant cardiotoxicity associated with anti-PD/PD-L1 use. Lung cancer subgroups showed better response and survival rates.

Pneumonitis as a complication of immune system targeting drugs?-a meta-analysis of anti-PD/PD-L1 immunotherapy randomized clinical trials.

BACKGROUND: Anti-PD/PD-L1-targeted immunotherapy is associated with remarkably high rates of durable clinical responses in patients across a range of tumor types, although their high incidence of skin, gastrointestinal, and endocrine side effects with their use. The risk of pneumonitis associated with checkpoint inhibition therapy is not well described. METHODS: A systematic review of the literature was conducted on randomized clinical trials (RCTs) comparing anti-PD/PD-L1 mono-immunotherapy (IMM) to chemotherapy (CTH) protocols in cancer patients. The primary endpoint was the pneumonitis rate in IMM compared to CTH. Secondary endpoints were (I) high-grade pneumonitis rate in IMM compared to CTH and (II) tumor response rate, progression-free survival (PFS), and overall survival (OS) between IMM and CTH. Random model and leave-one-out-analysis were performed. RESULTS: Thirteen RCTs studying 7,246 patients were included; 3,704 (51.12%) patients in the IMM arm and 3,542 (48.88%) patients in the chemotherapy arm. Seven non-small cell lung cancer (NSCLC) RCTs were included with 4,164 patients; 2,101 in the IMM arm and 2,063 patients in the CTH arm. Three RCTs were on melanoma patients (n=1,390). Nine RCTs compared mono-immunotherapy to CTH [docetaxel in 5 studies (38.5%), platinum-based in 2 studies (15.4%), dacarbazine in 1 study (7.7%) and everolimus in 1 study]. Both high-grade and all-grade pneumonitis were higher among patients in the IMM arm when compared to the CTH arm (OR =4.39, 95% CI: 1.65-11.69, P=0.003 and OR =2.46, 95% CI: 1.29-4.6, P=0.007). Tumor response rate was significantly better in the immunotherapy arm (OR =2.31, 95% CI: 1.62-3.29, P<0.001). PFS and OS were longer in patients who received IMM compared to patients in the CTH arm (HR =0.75, 95% CI: 0.65-0.85, P<0.001, and HR =0.71, 95% CI: 0.66-0.77, P<0.001). CONCLUSIONS: The incidence of high-grade and all-grade pneumonitis is higher in anti-PD-1 therapy but not in anti-PD-L1 therapy when compared to traditional CTH regimens for NSCLC and melanoma. High-grade adverse events were otherwise more common in the CTH arm. Tumor response rate, PFS, and OS are all substantially improved with IMM over CTH. These results can be used to guide therapy selection and set expectations for treatment effect in these patients.

Myeloid Sarcoma.

Hematological malignancies can manifest as extramedullary soft tissue masses in relatively rare cases. The rarity of it causes a diagnostic and therapeutic challenge. One of the rarest manifestations is myeloid sarcoma (MS). MS develops as part of acute myeloid leukemia, myeloproliferative neoplasm, or myelodysplastic syndrome or at relapse, especially following allogeneic hematopoietic stem cell transplant. The tumor displays high myeloperoxidase expression, hence the color green, and is called chloroma. It most commonly appears in lymph nodes, skin and soft tissues, bone, testes, gastrointestinal tract, and peritoneum. Immunohistochemistry shows CD68-KP1 as the most commonly expressed marker, then myeloperoxidase, CD117, CD99, CD68/PG-M1, lysozyme, CD34, terminal deoxynucleotidyl transferase, CD56, CD61, CD30, glycophorin A, and CD4. Different chromosomal abnormalities including MLL rearrangement, t(8; 21), monosomy 7, trisomy 8, trisomy 11, trisomy 4, inversion (16), monosomy 16,16q deletion, 5q deletion, and 20q deletion were reported. Most of the literature about MS are case reports and small retrospective studies, thus there is limited clinical knowledge of the cases and their presentation and management plans. Here, we provide a review of what has been reported in the literature about MS in the light of our experiences.

Small or Non-Small Cell Lung Cancer Based Therapy for Treatment of Large Cell Neuroendocrine Cancer of The Lung? University of Cincinnati Experience.

Large cell neuroendocrine cancer (LCNEC) of the lung exhibits morphological and immunohistochemical characteristics of both neuroendocrine and large cell carcinomas. No defined optimal therapy has been described for this subset of patients and the question of whether these patients should be treated with non-small cell lung cancer (NSCLC) treatment protocols, according to the National Comprehensive Cancer Network (NCCN) guidelines, or with small cell lung cancer (SCLC) due to histological and clinical similarities is still uncertain. We conducted a retrospective review of patients identified with diagnosis of LCNEC of the lung at the University of Cincinnati Cancer Center from the year 2002 to 2012 to determine which treatment approach resulted in improved outcomes in this rare category of disease. Patients who received chemotherapy whether NSCLC (group A) or SCLC (group B) protocols did not show significant changes in OS (P=0.911). Meanwhile, patients who underwent surgery (group C) had better OS compared to groups A and B (P= 0.027 and 0.024, respectively). This analysis reveals that outcomes for SCLC or NSCLC treatment strategies in LCNEC patients did not result in survival advantages and future research should be addressing it as a separate entity.

Lung cancer patients have the highest malignancy-associated suicide rate in USA: a population-based analysis.

PURPOSE: Previous studies have reported that psychological and social distresses associated with a cancer diagnosis have led to an increase in suicides compared to the general population. We sought to explore lung cancer-associated suicide rates in a large national database compared to the general population, and to the three most prevalent non-skin cancers [breast, prostate and colorectal cancer (CRC)]. METHODS: The Surveillance, Epidemiology and End Results (SEER) database (1973-2013) was retrospectively reviewed to identify cancer-associated suicide deaths in all cancers combined, as well as for each of lung, prostate, breast or CRCs. Suicide incidence and standardised mortality ratio (SMR) were estimated using SEER*Stat-8.3.2 program. Suicidal trends over time and timing from cancer diagnosis to suicide were estimated for each cancer type. RESULTS: Among 3,640,229 cancer patients, 6,661 committed suicide. The cancer-associated suicide rate was 27.5/100,000 person years (SMR = 1.57). The highest suicide risk was observed in patients with lung cancer (SMR = 4.17) followed by CRC (SMR = 1.41), breast cancer (SMR = 1.40) and prostate cancer (SMR = 1.18).Median time to suicide was 7 months in lung cancer, 56 months in prostate cancer, 52 months in breast cancer and 37 months in CRC (p < 0.001).We noticed a decreasing trend in suicide SMR over time, which is most notable for lung cancer compared to the other three cancers. In lung cancer, suicide SMR was higher in elderly patients (70-75 years; SMR = 12), males (SMR = 8.8), Asians (SMR = 13.7), widowed patients (SMR = 11.6), undifferentiated tumours (SMR = 8.6), small-cell lung cancer (SMR = 11.2) or metastatic disease (SMR = 13.9) and in patients who refused surgery (SMR = 13). CONCLUSION: The cancer-associated suicide rate is nearly twice that of the general population of the United States of America. The suicide risk is highest among the patients with lung cancer, particularly elderly, widowed, male patients and patients with unfavourable tumour characteristics. The identification of high-risk patients is of extreme importance to provide proper psychological assessment, support and counselling to reduce these rates.

Clinical Presentation and Treatment Options for Clear Cell Lung Cancer: University of Cincinnati A Case Series and Literature Review of Clear Cell Lung Cancer

Clear cell carcinomas are common finding in renal, ovarian and uterine carcinomas. However, clear cell lung cancer (CCLC), first described by Liebow and Castleman in 1963, is considered an extremely rare variant of lung tumors. The 2011 WHO classification of lung tumors considered CCLC as a rare cytologic feature of squamous cell or adenocarcinomas. It is no longer recognized as a formal subtype, albeit it can be referred to in the pathological diagnosis as "with clear cell features" even with marginal fractions of the tumor cells. Such recognition is needed since the variation in clinical features and outcome in this subset of patients. The disease has a clinically vague natural history, is characterized by slight female predominance and is often seen in the elderly. As frequently encountered with rare diseases, its clinical course and treatment options have many questions still yet to be answered. In this paper, we review both the natural history and treatment options mentioned in literature, in the light of our experience by reporting a case series of four patients diagnosed with CCLC and highlight their aspects.

GNQ-209P Mutation in Metastatic Uveal Melanoma and Treatment Outcome.

Metastatic prognosis in uveal melanoma is assessed by gene expression profiling (GEP) testing of the tumor cells, usually obtained by fine needle aspiration (FNA). GEP has demonstrated high accuracy in distinguishing class I and II tumors, both having different metastatic potential. Transcriptomic studies identified distinct mutations including somatic mutations in GNAQ and GNA11, detected in more than 80%, and contribute to the upregulation of the mitogen-activated protein kinase (MAPK) pathway and the development of uveal melanoma (UM). The role of these mutations in treatment selection and possible benefit from targeted therapy are somewhat unclear. However, until the discovery of novel agents, local versus systemic therapies remain options for treatment that can still be considered for disease control in certain cases. We report a series of patients with metastatic UM with distinct mutational profiles. One had significant liver metastases with proven GNQ-209P mutation on tissue biopsy while peripheral blood molecular profiling did not show these mutations. The other three cases had no GNQ-209P mutation. All cases received nab-paclitaxel (Abraxane) as a treatment drug, and we record their responses to treatment and their molecular-profiling results.

Pulmonary sarcomatoid carcinoma: University of Cincinnati experience.

OBJECTIVES: To review the outcomes of treatment in patients with pulmonary sarcomatoid carcinoma (PSC) treated at the University of Cincinnati Medical Center (UCMC). RESULTS: There was no significant difference in survival of patients treated with chemotherapy alone (median, 256 days) compared to patients not undergoing treatment (median, 205.5 days). Patients who underwent surgery and adjuvant chemotherapy showed a trend in improvement of survival (median, 457.6 days). Patients requiring only surgery had the longest OS of 713.5 days. CONCLUSIONS: Systemic chemotherapy alone did not improve survival in patients with PSC. Surgery provides the greatest overall survival benefit and adjuvant chemotherapy may also improve survival. METHODS: From 2000 to 2014, twenty-five patients with pathologically confirmed PSC were treated at UCMC. The outcomes were retrospectively analyzed by treatment with overall survival (OS) as the endpoint.

A Case Study in Advanced Lung Cancer Patients with Vimentin Over Expression.

BACKGROUND: Vimentin belongs to an intermediate filament (IF) family of proteins, mainly present in mesenchymal cells and has a crucial role in maintaining cellular integrity. Vimentin can induce epithelial to mesenchymal transition, and thus increase migration and invasion capacity of the cells. It has been shown to be a useful and reliable diagnostic and prognostic marker in several cancers including colon cancers, breast and hepatocellular cancers. Recent studies suggest that it may have a role in distant metastasis of non-small cell lung cancer (NSCLC) accounting for poor survival [1]. METHODS: The aim of the study is to assess the impact of vimentin testing as a diagnostic and prognostic marker in NSCLC. This is a case study of 12 NSCLC patients who had vimentin testing as a part of their work up over the past five years at the University of Cincinnati. A total of 12 patients with advanced lung cancer were included in this case study as they were found to have strong vimentin expression. This was correlated with overall survival of this group of patients. RESULTS: Median survival of the patients was 4.66 months. This is 7.34 months less compared to the median survival of patients with stage IV NSCLC which is reported to be 12 months. CONCLUSIONS: More studies are warranted into the use of vimentin as an emerging useful marker for early diagnosis, aggressive transformation relapse, and prognostication of NSCLC. It may have therapeutic value in NSCLC as observed in other cancers.