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Pericardial Effusion with Tamponade, an Immune-Related Adverse Event Associated with Nivolumab Therapy: A Case Report and Review of the Literature

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Journal of Cancer Therapy 2018年第12期9卷 1039-1047页

作者： Fauzia F. Naime Leforte Oncologia Sao Paulo Brazil Instituto do Cancer Dr Arnaldo Vieira de Carvalho Sao Paulo Brazil

Immune checkpoint inhibitors have shown to be very effective when treating lung cancer. Nivolumab, a programmed death-1 (PD-1) inhibitor has been approved for the treatment of metastatic non-squamous and squamous NSCLC. Immunotherapy with checkpoint inhibitors are associated with toxicities defined as immune-related adverse events (irAEs). The most common irAEs are rash, colitis, hepatitis, pneumonitis, and endocrinopathies. Although any organ system can be affected, other rare irAEs can occur and affect the bone marrow, pancreas, and the neurologic and cardiac systems. Pericardial effusion induced by immunotherapy is uncommon and has been described only in a few case reports. Immune-related adverse events usually develop within the first weeks to months after treatment initiation. This is a case report of a 52-year-old male patient with metastatic squamous-cell lung cancer who had a massive pericardial effusion secondary to treatment with nivolumab as second line treatment. During his hospital stay, the patient underwent pericardiocentesis and treatment with corticosteroids. A CT scan after these treatments revealed complete tumor response and minimal pericardial effusion. Nivolumab was definitively ceased. The patient continues to show complete response for 16 months. In general, Nivolumab is well-tolerated and has an excellent safety profile. However, it is important to be aware of life-threatening immune-related adverse events, particularly cardiac toxicity. Consensus guidelines regarding the treatment of the most common irAEs have been established. The optimal management of irAEs is based on clinical experience. It’s crucial to report new or rare irAEs to conduct prospective trials to evaluate the best treatment strategy.

关键词： Pericardial Effusion Immunotherapy Nivolumab non-small Cell Lung Cancer (NSCLC) Immune Related Adverse Events

CD8 T cell response in a phase I study of therapeutic vaccination of advanced NSCLC with allogeneic tumor cells secreting endoplasmic reticulum-chaperone gp96-Ig-peptide complexes

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Advances in Lung Cancer 2013年第1期2卷 9-18页

作者： Luis E. Raez Gail R. Walker Paulette Baldie Eva Fisher Jorge E. Gomez Khaled Tolba Edgardo S. Santos Eckhard R. Podack Department of Medicine Division of Hematology/Oncology University of Miami Miller School of Medicine Miami USA Department of Microbiology and Immunology University of Miami Miller School of Medicine Miami USA Sylvester Comprehensive Cancer Center Biostatistics Core Facility University of Miami Miller School of Medicine Miami USA

Antigen containing, allogeneic cells secreting the genetically modified protein and peptide-chaperone gp96-Ig cross, prime and expand antigen specific CD8 T cells with therapeutic antitumor activity in mice. In a first in man phase I study, we now report the results of therapeutic vaccination of non-small cell lung cancer (NSCLC) patients with an established, allogeneic non-small cell lung adenocarcinoma cell line secreting gp96-Ig. Advanced NSCLC-patients stage IIIB or IV of any histological subtype were enrolled and treated with up to 36 vaccinations over the course of 18 weeks. Primary endpoint was safety, secondary endpoints tumor response and overall survival. Measurement of tumor antigen specific CD8 CTL responses is precluded by the lack of known NSCLC associated antigens. Therefore, we measured patient CD8 T cell-IFN-γ responses to allo-antigens of the vaccine cells as surrogate for tumor antigen specific CD8 CTL. In 7 of 18 treated patients tumor growth was stabilized, however none of the 18 patients had an objective tumor response by RECIST criteria. Of 15 patients evaluable for immune response, 11 responded to vaccination with more than twofold increase in CD8-IFN-γ frequency above baseline. These patients had a median survival time of 16.5 months. Four patients who had no CD8 response above base line had survival times from 2.1 to 6.7 months. Our data are consistent with the concept that generation of CD8 CTL by therapeutic vaccination may delay tumor growth and progression and mediate prolonged survival even in the absence of objective tumor responses. Further studies will be required to test this concept and promising result.

关键词： Heat Shock Protein Chaperone Gp-96 non-small Cell Lung Cancer Gene Transfer Immunotherapy Allogeneic Vaccine Cytotoxic CD8 T Cells

Significance of Multimodality Therapy in Patients with a Superior Sulcus Tumor of the Lung: A Review Article

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Journal of Cancer Therapy 2014年第1期5卷 115-123页

作者： Gouji Toyokawa Mitsuhiro Takenoyama Yukito Ichinose Department of Thoracic Oncology National Kyushu Cancer Center Fukuoka Japan

Despite the aggressive pursuit of diagnostic and treatment modalities for lung cancer, the treatment outcomes are still not satisfactory, and even patients with surgically resectable non-small cell lung cancer (NSCLC) are often at considerable risk of suffering recurrence and/or death from lung cancer. Regarding the treatment of patients with locally advanced, resectable NSCLC, several retrospective and prospective studies have shown the significance of multimodality treatments with preoperative chemoradiotherapy and surgical treatment. However, no definitive treatment strategies for locally advanced NSCLC patients have yet been established. One of the reasons for the lack of established treatment strategies for patients with locally advanced NSCLC is considered to be the heterogeneity of the population, i.e., cT4N0, cT3-4N1 and cT1a-3N2 tumors are included in stage IIIA disease, and superior sulcus tumors (SSTs) are also included in this classification. With regard to SST, two representative prospective phase II trials indicated the efficacy of surgical treatment following concurrent radiation and chemotherapy. In a study conducted by the Southwest Oncology Group, 110 patients with superior sulcus NSCLC were treated with two cycles of cisplatin and etoposide concurrently with 45 gray (Gy) of radiation, followed by surgical treatment and two additional cycles of chemotherapy postoperatively. The response rate (RR) to the preoperative chemoradiotherapy was 86%, and 83 patients (76%) were able to undergo complete resection. A pathological complete response (CR) was observed in 61 patients (56%), and the five-year survival of all patients and those undergoing complete resection was 44% and 54%, respectively. A phase II study conducted by the Japan Clinical Oncology Group examined the safety and efficacy of preoperative concurrent chemoradiotherapy using mitomycin, vinblastin and cisplatin followed by surgical treatment. Seventy-six patients with SST were enrolled in th

关键词： Locally Advanced non-small Cell Lung Cancer Superior Sulcus Tumor Multimodality Therapy

Estimation of the effect of target and normal tissue sparing based on equivalent uniform dose-based optimization in hypofractionated radiotherapy for lung cancer

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Oncology and Translational Medicine 2019年第5期5卷 197-203页

作者： Ying Shao Fuli Zhang Shi Wang Weidong Xu Jing Jiang Deparment of Radiotherapy The Seventh Medical CenterPLA General Hospital/Beijing Tsinghua Changgeng Hospital affiliated to Tsinghua UniversityBeijing 102218China Department of Radiotherapy The Seventh Medical CenterPLA General HospitalBeijing 100700China Department of Engineering Physics Tsinghua UniversityBeijing 100084China

Objective This study aims to investigate the dosimetric differences among four planning methods of physical and biological optimization in hypofractionated radiation therapy for non-small cell lung cancer(NSCLC).Methods Ten NSCLC patients receiving radiation therapy were chosen for this retrospective *** modulated arc treatment plans for each patient were remade with dose-volume(DV)functions,biological-physical functions,and biological functions,using the same constraint parameters during *** dosimetric differences between the four types of plans were calculated and *** For the target,equivalent uniform dose(EUD)of the EUD and EUD+DV groups was approximately 2.8%–3.6%and 3.2%–3.7%higher than those of the DV and DV+EUD groups,*** average tumor control probability(TCP)of the EUD and EUD+DV groups was also significantly higher than those of the other two groups(P0.05).For the organs at risk,the differences of EUD,V5,V10,V20,V30 of normal lung tissues were not statistically significant(P>0.05);however,the mean lung dose of the EUD and EUD+DV groups was slightly lower than those of the other two *** The biological optimization method has obvious advantages of improving EUD and TCP of the target,while decreasing the exposed dose of normal *** result is meaningful in choosing plan optimization methods in routine work.

关键词： non-small cell lung cancer(NSCLC) equivalent uniform dose(EUD) hypofractionated radiotherapy plan optimization

Influence of Smoking Status and Body Mass Index on Serum Carcinoembryonic Antigen Concentration in Patients with Thoracic Diseases

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Surgical Science 2017年第7期8卷 279-286页

作者： Masaki Tomita Takanori Ayabe Kazuyo Tsuchiya Kunihide Nakamura Department of Thoracic and Breast Surgery Faculty of Medicine University of Miyazaki Miyazaki Japan Department of Cardiovascular Surgery Faculty of Medicine University of Miyazaki Miyazaki Japan

BACKGROUND: Although the serum carcinoembryonic antigen (CEA) concentration is the well-known prognostic marker of non-small cell lung cancer (NSCLC), serum CEA concentration has been reported to be affected by smoking status and body mass index (BMI). There are no previous investigations that examined the relationship between BMI and serum CEA concentration in thoracic disease, including NSCLC. METHODS: Consecutive 384 NSCLC patients and 87 patients with benign thoracic disease were enrolled. The relationship between serum CEA concentration and smoking status and BMI in patients with benign thoracic benign disease and NSCLC was examined. RESULTS: In patients with benign thoracic disease, serum CEA concentration significantly increased with smoking status and Brinkman index. However, serum CEA concentration was not related with BMI. Serum CEA concentration of patients with NSCLC was significantly higher than those with benign disease. In NSCLC patients, the relationship between serum CEA concentration and smoking status was also found. A significant relationship between serum CEA concentration and smoking status was also found in patients with adenocarcinoma which is known to have weaker associations with smoking in carcinogenesis. On the other hand, we failed to find the relationship between serum CEA concentration and BMI in NSCLC patients. CONCLUSION: Serum CEA concentration may be affected by smoking status but not BMI in our Japanese patients with thoracic disease.

关键词： CEA Smoking Status Body Mass Index Benign Thoracic Disease non-small Cell Lung Cancer

Gender Does Not Have a Potential Predictive Value for the Presence of Epidermal Growth Factor Receptor Mutation in Lung Adenocarcinoma

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Advances in Lung Cancer 2014年第4期3卷 82-87页

作者： Masaki Tomita Takanori Ayabe Eiichi Chosa Katsuya Kawagoe Kunihide Nakamura Department of Surgery II Faculty of Medicine University of Miyazaki Miyazaki Japan

Background: Previous studies reported that non-small cell carcinoma patients characterized by female gender, never-smoking status and adenocarcinoma histology were more likely to harbor epidermal growth factor receptor (EGFR) mutations. However, some studies failed to find the relationship between EGFR mutation and gender. Methods: One hundred and eighty-four consecutive patients (90 men and 94 women) of resected lung adenocarcinoma were studied retrospectively. Since the smoking rate is significantly higher in men, we assumed that gender difference might be a seeming factor affected by smoking. Therefore we subdivided the patients into 2 groups: never- and ever-smokers. Results: The number of ever-smokers was 94.44% in men, whereas 8.51% in women. EGFR mutation was positive in 48.9%. For overall patients, EGFR mutation status was associated with gender, pStage, pT status, lepidic dominant histologic subtype, pure/mixed groundglass opacity (GGO) on computed tomography (CT) and smoking status. However, in ever-smokers, EGFR mutation status was associated with lepidic histologic subtype and GGO on CT, but not others including gender. Similar results were also found in never-smokers, and gender was not also related to EGFR mutation in never smokers. Conclusion: The EGFR mutational frequency among men and women was not significantly different when lung adenocarcinoma patients were stratified into never- and ever-smokers.

关键词： Epidermal Growth Factor Receptor Mutation Smoker Gender non-small Cell Lung Cancer Adenocarcinoma Brinkman Index

Correlation of serum GDF-15 and MIF contents with the malignant behaviors of cancer cells in patients with NSCLC

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Journal of Hainan Medical University 2018年第8期24卷 40-43页

作者： Tian-Ming Zheng Li-Juan Lin Thoracic Surgery Department Kashgar Prefecture First People's Hospital in the Xinjiang Uygur Autonomous RegionKashgarXinjiang844000 Clinical Teaching and Research Office Kashgar Prefecture Health School in the Xinjiang Uygur Autonomous RegionKashgarXinjiang844000

Objective:To study the correlation of serum GDF-15 and MIF contents with the malignant behaviors of cancer cells in patients with ***: Patients with non-small cell lung cancer who underwent surgical resection in Kashgar Prefecture First People's Hospital in the Xinjiang Uygur Autonomous Region between January 2015 and November 2017 were selected as lung cancer group for the research, and healthy volunteers who received physical examination in Kashgar Prefecture First People's Hospital in the Xinjiang Uygur Autonomous Region during the same period were selected as the control group. Serum was collected from the lung cancer group before surgery and from the control group during physical examination respectively to determine the contents of GDF-15 and MIF;lung cancer tissue and adjacent tissue were collected from lung cancer group after surgery to determine the expression of tumor suppressor genes, proliferation genes and invasion ***:Serum GDF-15 and MIF contents of lung cancer group were significantly higher than those of control group;TCF21, Bax, GRPC5A and PTEN mRNA expression in lung cancer tissue were significantly lower than those in the adjacent tissue whereas Bcl-2, AQP4, c-myc, CyclinD1, SIRT1, CatL, MMP9, N-cadherin and Vimentin mRNA expression were significantly higher than those in adjacent tissue;serum GDF-15 and MIF contents of patients with lung cancer were negatively correlated with TCF21, Bax, GRPC5A and PTEN mRNA expression, and positively correlated with Bcl-2, AQP4, c-myc, CyclinD1, SIRT1, CatL, MMP9, N-cadherin and Vimentin mRNA expression in lung cancer ***:The abnormal increase of GDF-15 and MIF in patients with NSCLC is closely related to the abnormal proliferation and invasion of cancer cells.

关键词： non-small cell lung cancer Growth differentiation factor 15 Macrophage migration inhibitory factor Proliferation Invasion

Rare Tumors of Ovary: Case Report and Literature Review

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Open Journal of Pathology 2012年第3期2卷 81-84页

作者： El Fatemi Hinde Hammas Nawal Saadi Hannane Brahmi Sami Amarti Afaf Bannani Abdelaziz Mesbahi Omar Department of Gynecology Hassan II Teaching Hospital Fez Morocco Department of Oncology Hassan II Teaching Hospital Fez Morocco Department of Pathology Hassan II Teaching Hospital Fez Morocco

Introduction: Large cell neuroendocrine carcinoma (LCNEC) or non small cell neuroendocrine carcinoma the ovary is a rare entity and is frequently associated with ovarian surface epithelial tumors. However, its association with serous carcinoma is rarer, in our knowledge tree cases has been described in international literature and the first case in Moroccan literature. Case Report: A 54-year-old woman presented with a pelvic mass measuring 15 cm in diameter. She underwent an exploratory laparotomy with resection of the pelvic mass. Diffuse and nodular intra-abdominal disseminations were observed. Immunohistochemistry stain confirmed the diagnosis of large cell neuroendocrine carcinoma with serous carcinoma. The patient received three courses of carboplatin and paclitaxel and she's still alivewith a decline of 6 months. Its clinicopathologic association is discussed and the literature is reviewed. Conclusion: In summary, ovarian LCNEC is an aggressive tumor with a tendency to present at advanced stage and cause death within a mean of 17 months after diagnosis;however, some patients, particularly those with stage I disease and/or those who have received platinum-based therapy, may have a more favorable prognosis.

关键词： Ovary Neuroendocrine Carcinoma non-small Cell Type Serous Carcinoma Immunohistochemistry

Micro RNAs as lung cancer biomarkers

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World Journal of Clinical Oncology 2014年第4期5卷 604-620页

作者： Valerio Del Vescovo Margherita Grasso Mattia Barbareschi Michela A Denti Laboratory of RNA Biology and Biotechnology Centre for Integrative Biology University of Trento Unit of Surgical Pathology Laboratory of Molecular Pathology Trentino Biobank S.Chiara Hospital

Lung cancer is the leading cause of cancer mortality worldwide. Its high mortality is due to the poor prognosis of the disease caused by a late disease presentation, tumor heterogeneities within histological subtypes, and the relatively limited understanding of tumor biology. Importantly, lung cancer histological subgroups respond differently to some chemotherapeutic substances and side effects of some therapies appear to vary between subgroups. Biomarkers able to stratify for the subtype of lung cancer, prognosticate the course of disease, or predict the response to treatment are in high demand. In the last decade, microR NAs(miR NAs), measured in resected tumor samples or in fine needle aspirate samples have emerged as biomarkers for tumor diagnosis, prognosis and prediction of response to treatment, due to the ease of their detection and in their extreme specificity. Moreover, miR NAs present in sputum, in plasma, in serum or in whole blood have increasingly been explored in the last five years as less invasive biomarkers for the early detection of cancers. In this review we cover the increasing amounts of datathat have accumulated in the last ten years on the use of miR NAs as lung cancer biomarkers.

关键词： Lung cancer non-small cell lung carcinomas MicroRNAs Biomarkers