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Haematologica Feb 2024Outcomes after programmed death-1 (PD-1) blockade in B-cell lymphomas are disappointing with few durable responses. Histone deacetylase inhibitors exhibit favorable...
Outcomes after programmed death-1 (PD-1) blockade in B-cell lymphomas are disappointing with few durable responses. Histone deacetylase inhibitors exhibit favorable immunomodulatory effects and demonstrate synergistic anti-tumor immune responses with anti-PD-1 therapy in preclinical models. We, therefore, developed a phase I study to evaluate the safety and preliminary efficacy of pembrolizumab with vorinostat in relapsed/refractory B-cell lymphomas. Patients were treated in a dose-escalation cohort using a Rolling 6 design followed by an expansion cohort at the recommended phase II dose (R2PD). Fifty-two patients were enrolled (32 Hodgkin and 20 non-Hodgkin lymphoma [NHL]). Here, we report safety data from the dose escalation cohort, and the toxicity and efficacy within NHL patients. Vorinostat was administered twice daily on days 1-5 and 8-12 (dose-level [DL]1: 100 mg; DL2: 200 mg) and pembrolizumab (200 mg) was administered on day 1 of each 3-week cycle. Of six patients treated at DL1, one had a dose-limiting toxicity (DLT) (Stevens-Johnson syndrome [SJS]), and one of six had a DLT at DL2 (thromboembolism); therefore, DL2 was the RP2D. The patient developing SJS was treated with corticosteroids, infliximab, and cyclosporine but ultimately died of invasive fungal infection from the extensive immunosuppression used to treat the SJS. The most common adverse events were hypertension, diarrhea, and cytopenias. Of 20 NHL patients, nine had follicular lymphoma (FL) and 11 had diffuse large B-cell lymphoma (DLBCL). Five DLBCL patients had primary mediastinal B-cell lymphoma (PMBL). The complete and overall response rates (CR and ORR) were 11% and 22% for FL and 45% and 55% for all DLBCL. Amongst DLBCL, the CR and ORR was 80% and 80% for PMBL and 17% and 33% for non-PMBL. In conclusion, pembrolizumab with vorinostat was tolerable and produced responses in relapsed/refractory B-cell NHL, with particularly notable efficacy in PMBL (clinicaltrials gov. Identifier: NCT03150329).
Topics: Humans; Vorinostat; Neoplasm Recurrence, Local; Lymphoma, Non-Hodgkin; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular; Antibodies, Monoclonal, Humanized
PubMed: 37470137
DOI: 10.3324/haematol.2023.283002 -
Annals of Thoracic and Cardiovascular... 2024Esophagogastric junction cancer (EGJC) is a rare malignant disease that occurs in the gastroesophageal transition zone. In recent years, its incidence has been rapidly... (Review)
Review
Esophagogastric junction cancer (EGJC) is a rare malignant disease that occurs in the gastroesophageal transition zone. In recent years, its incidence has been rapidly increasing not only in Western countries but also in East Asia, and it has been attracting the attention of both clinicians and researchers. EGJC has a worse prognosis than gastric cancer (GC) and is characterized by complex lymphatic drainage pathways in the mediastinal and abdominal regions. EGJC was previously treated in the same way as GC or esophageal cancer, but, in recent years, it has been treated as an independent malignant disease, and treatment focusing only on EGJC has been developed. A recent multicenter prospective study revealed the frequency of lymph node metastasis by station and established the optimal extent of lymph node dissection. In perioperative treatment, the combination of multi-drug chemotherapy, radiation therapy, molecular targeted therapy, and immunotherapy is expected to improve the prognosis. In this review, we summarize previous clinical trials and their important evidence on surgical and perioperative treatments for EGJC.
Topics: Humans; Esophagogastric Junction; Esophageal Neoplasms; Treatment Outcome; Esophagectomy; Gastrectomy; Stomach Neoplasms; Lymph Node Excision; Chemotherapy, Adjuvant; Lymphatic Metastasis; Risk Factors; Neoadjuvant Therapy
PubMed: 38839368
DOI: 10.5761/atcs.ra.24-00056 -
BMJ Case Reports Sep 2023A male patient in his 30s presented to the emergency room with a 1-week history of dyspnoea that progressed to haemoptysis, having coughed up approximately 200 mL of...
A male patient in his 30s presented to the emergency room with a 1-week history of dyspnoea that progressed to haemoptysis, having coughed up approximately 200 mL of blood on two occasions. On diagnostic investigation, a mediastinal tumour infiltrating the free wall of the right atrium and multiple pulmonary nodules were discovered. The first suspicion was a neoplasm of pulmonary origin, and a bronchoscopy was performed, histology reported a probable cardiac origin for the neoplasm. A subsequent biopsy confirmed the presence of a primary cardiac angiosarcoma. An extension CT scan revealed brain metastases. The patient received chemotherapy treatment, resulting in a partial response to date. This case is one of the few reported instances of cardiac neoplasm presenting with respiratory symptoms.
Topics: Humans; Male; Hemoptysis; Hemangiosarcoma; Cough; Affect; Heart Atria
PubMed: 37734864
DOI: 10.1136/bcr-2023-256596 -
Journal of Medical Case Reports Aug 2023Mediastinal Liposarcoma (ML) is an exceedingly rare neoplasm, accounting for less than 1% of all liposarcomas. Surgical resection is the most effective therapeutic... (Review)
Review
BACKGROUND
Mediastinal Liposarcoma (ML) is an exceedingly rare neoplasm, accounting for less than 1% of all liposarcomas. Surgical resection is the most effective therapeutic modality, while adjuvant radiation therapy may be recommended for unresectable tumors.
CASE PRESENTATION
This case report presents a rare case of a 52-year-old Syrian male patient with well-differentiated mediastinal liposarcoma (ML) who presented with exertional dyspnea, cough, and weight loss. Imaging studies revealed a large tumor causing extrinsic compression on the right lung, as well as compression of the heart and great vessels. CT-guided biopsy confirmed a diagnosis of well-differentiated liposarcoma, and the patient underwent surgical resection. The patient had a rapid postoperative recovery and was discharged on the fourth day post-operation, displaying an excellent postoperative status. The patient was followed up for 3 months postoperatively with no recurrence.
CONCLUSION
This report highlights the significance of incorporating ML into the differential diagnosis of mediastinal masses, particularly in individuals presenting with exertional dyspnea and weight loss. Furthermore, this report provides a comprehensive review of previously reported cases of ML in the medical literature.
Topics: Male; Humans; Middle Aged; Mediastinal Neoplasms; Liposarcoma; Heart; Mediastinum; Dyspnea; Lipoma
PubMed: 37649065
DOI: 10.1186/s13256-023-04121-7 -
Journal of Thoracic Oncology : Official... Dec 2023A TNM-based stage classification system of thymic epithelial tumors was adopted for the eighth edition of the stage classification of malignant tumors. The Thymic Domain...
The International Association for the Study of Lung Cancer Thymic Epithelial Tumor Staging Project: Proposal for the T Component for the Forthcoming (Ninth) Edition of the TNM Classification of Malignant Tumors.
INTRODUCTION
A TNM-based stage classification system of thymic epithelial tumors was adopted for the eighth edition of the stage classification of malignant tumors. The Thymic Domain of the Staging and Prognostics Factor Committee of the International Association for the Study of Lung Cancer developed a new database with the purpose to make proposals for the ninth edition stage classification system. This article outlines the proposed definitions for the T categories for the ninth edition TNM stage classification of thymic malignancies.
METHODS
A worldwide collective database of 11,347 patients with thymic epithelial tumors was assembled. Analysis was performed on 9147 patients with available survival data. Overall survival, freedom-from-recurrence, and cumulative incidence of recurrence were used as outcome measures. Analysis was performed separately for thymomas, thymic carcinomas, and neuroendocrine thymic tumors.
RESULTS
Proposals for the T categories include the following: T1 category is divided into T1a (≤5 cm) and T1b (>5 cm), irrespective of mediastinal pleura invasion; T2 includes direct invasion of the pericardium, lung, or phrenic nerve; T3 denotes direct invasion of the brachiocephalic vein, superior vena cava, chest wall, or extrapericardial pulmonary arteries and veins; and T4 category remains the same as in the eighth edition classification, involving direct invasion of the aorta and arch vessels, intrapericardial pulmonary arteries and veins, myocardium, trachea, or esophagus.
CONCLUSIONS
The proposed T categories for the ninth edition of the TNM classification provide good discrimination in outcome for the T component of the TNM-based stage system of thymic epithelial tumors.
Topics: Humans; Lung Neoplasms; Neoplasm Staging; Vena Cava, Superior; Thymus Neoplasms; Neoplasms, Glandular and Epithelial; Thymoma; Neuroendocrine Tumors; Lung; Prognosis
PubMed: 37634808
DOI: 10.1016/j.jtho.2023.08.024 -
Cancer Imaging : the Official... Dec 2023The presence of mediastinal lymph node metastasis is important because it is related to the treatment and prognosis of lung cancer. Although prevalently used, evaluation... (Review)
Review
BACKGROUND
The presence of mediastinal lymph node metastasis is important because it is related to the treatment and prognosis of lung cancer. Although prevalently used, evaluation of lymph nodes is not always reliable. We introduced sphericity as a criterion for evaluating morphologic differences between metastatic and nonmetastatic nodes.
METHODS
We reviewed the cases of 66 patients with N2 disease and of 68 patients with N0-1 disease who underwent lobectomy with mediastinal dissection between January 2012 and December 2021. The sphericity of the dissected station lymph nodes, which represents how close the node is to being a true sphere, was evaluated along with the diameter and volume. Each parameter was obtained and evaluated for ability to predict metastasis.
RESULTS
Metastatic lymph nodes had a larger short-axis diameter (average: 8.2 mm vs. 5.4 mm, p < 0.001) and sphericity (average: 0.72 vs. 0.60, p < 0.001) than those of nonmetastatic lymph nodes. Short-axis diameter ≥ 6 mm and sphericity ≥ 0.60 identified metastasis with 76.2% sensitivity and 70.2% specificity (AUC = 0.78, p < 0.001) and 92.1% sensitivity and 53.9% specificity (AUC = 0.78, p < 0.001), respectively. For lymph nodes with a short-axis diameter ≥ 5 mm, sphericity ≥ 0.60 identified metastasis with 84.1% sensitivity and 89.3% specificity.
CONCLUSION
By using 3D-CT analysis to examine sphericity, we showed that metastatic lymph nodes became spherical. Our method for predicting lymph node metastasis based on sphericity of lymph nodes with a short-axis diameter ≥ 5 mm could do so with higher sensitivity than the conventional method, and with acceptable specificity.
Topics: Humans; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Lymphatic Metastasis; Tomography, X-Ray Computed; Lymph Nodes; Neoplasm Staging
PubMed: 38105231
DOI: 10.1186/s40644-023-00635-x -
Frontiers in Oncology 2024Malignant cells are known to evade immune surveillance by engaging immune checkpoints which are negative regulators of the immune system. By restoring the T-lymphocyte... (Review)
Review
Malignant cells are known to evade immune surveillance by engaging immune checkpoints which are negative regulators of the immune system. By restoring the T-lymphocyte mediated anti-tumor effect, immune checkpoint inhibitors (ICI) have revolutionized the treatment of solid tumors but have met rather modest success in hematological malignancies. Currently, the only FDA approved indications for ICI therapy are in classic hodgkin lymphoma and primary mediastinal B cell lymphoma. Multiple clinical trials have assessed ICI therapy alone and in combination with standard of care treatments in other lymphomas, plasma cell neoplasms and myeloid neoplasms but were noted to have limited efficacy. These trials mostly focused on PD-1/PDL-1 and CTLA-4 inhibitors. Recently, there has been an effort to target other T-lymphocyte checkpoints like LAG-3, TIM-3, TIGIT along with improving strategies of PD-1/PDL-1 and CTLA-4 inhibition. Drugs targeting the macrophage checkpoint, CD47, are also being tested. Long term safety and efficacy data from these ongoing studies are eagerly awaited. In this comprehensive review, we discuss the mechanism of immune checkpoint inhibitors, the key takeaways from the reported results of completed and ongoing studies of these therapies in the context of hematological malignancies.
PubMed: 38322418
DOI: 10.3389/fonc.2024.1323914 -
Japanese Journal of Radiology Sep 2023The purpose of the study was to explore the importance of quantitative characteristics of spectral CT between invasive thymic epithelial tumors (TETs) and mediastinal...
PURPOSE
The purpose of the study was to explore the importance of quantitative characteristics of spectral CT between invasive thymic epithelial tumors (TETs) and mediastinal lung cancer.
METHODS
We analyzed 54 patients (28 with invasive TETs and 26 with mediastinal lung cancer) who underwent spectral CT. During the arterial and venous phase, we measured the CT, effective atomic number (Zeff), iodine concentration (IC), and water concentration (WC) and calculated the slope of the spectral curve (K). We compared the clinical findings and spectral CT parameters of both groups and performed receiver operating characteristic analysis to evaluate the diagnostic efficacy and the optimal cutoff values of the spectral CT parameters.
RESULTS
During the AP and VP, the CT, Zeff, IC, and K were significantly higher in patients with invasive TETs than those in patients with mediastinal lung cancer (p < 0.05). WC was not statistically significantly different between the two groups (p > 0.05). ROC curve analysis revealed that all quantitative parameters combined in the AP and VP provided the best diagnostic performance in identifying invasive TETs from mediastinal lung cancer (AUC = 0.88, p = 0.002, sensitivity = 0.89 and specificity = 0.77). The cutoff values in the AP for CT, IC, Zeff, and K to differentiate invasive TETs from mediastinal lung cancer were 75.55, 15.86, 8.45, and 1.71, respectively. The cutoff values in the VP for CT, IC, Zeff, and K to differentiate them were 67.06, 15.74, 8.50, and 1.81, respectively.
CONCLUSIONS
Spectral CT imaging has potential value in the differential diagnosis of invasive TETs and mediastinal lung cancer.
Topics: Humans; Tomography, X-Ray Computed; Lung Neoplasms; Lung; Thymus Neoplasms; Thymoma; ROC Curve; Mediastinal Neoplasms; Iodine; Retrospective Studies
PubMed: 37071247
DOI: 10.1007/s11604-023-01428-9 -
Medicine Nov 2023Paragangliomas are rare and can occur in many places throughout the body, but mediastinal paragangliomas are even rarer, accounting for less than 0.3% of mediastinal... (Review)
Review
RATIONAL
Paragangliomas are rare and can occur in many places throughout the body, but mediastinal paragangliomas are even rarer, accounting for less than 0.3% of mediastinal masses. Extremely susceptible to misdiagnosis and mistreatment, which may lead to the death of the patient.
PATIENT CONCERNS
We report a case of a giant paraganglioma of the middle mediastinum. A 40-year-old woman was admitted to the hospital with a rib fracture and a chest computed tomography suggesting a giant occupying tumor in the middle mediastinum.
DIAGNOSIS
Immunohistochemistry revealed positive for S100 fraction and Syn, focally positive for CgA, while negative for CKp and succinate dehydrogenase complex iron sulfur subunit B gene, and Ki67index ≈ 5%. The imaging and immunohistochemical features suggested a final diagnosis of Paragangliomas.
INTERVENTIONS
This patient underwent lateral open heart surgery to remove a mediastinal mass.
OUTCOMES
One month after being discharged, the patient was contacted by phone for a follow-up visit and reported feeling OK. Unfortunately, as of the date of submission, the patient did not come to our hospital for review.
LESSONS
Mediastinal paraganglioma as a rare and potentially malignant tumor susceptible to misdiagnosis and mistreatment. Organ pathology examination is the gold standard for diagnosis, and surgery is an important treatment method. A clear diagnosis and thorough preoperative examination are important guarantees for the success of surgery.
Topics: Female; Humans; Adult; Mediastinum; Paraganglioma; Paraganglioma, Extra-Adrenal; Mediastinal Neoplasms; Tomography, X-Ray Computed
PubMed: 38013330
DOI: 10.1097/MD.0000000000036327 -
Japanese Journal of Radiology Jan 2024Machine learning (ML) analyses using F-fluorodeoxyglucose (F-FDG) positron emission tomography (PET)/computed tomography (CT) radiomics features have been applied in the... (Review)
Review
Machine learning (ML) analyses using F-fluorodeoxyglucose (F-FDG) positron emission tomography (PET)/computed tomography (CT) radiomics features have been applied in the field of oncology. The current review aimed to summarize the current clinical articles about F-FDG PET/CT radiomics-based ML analyses to solve issues in classifying or constructing prediction models for several types of tumors. In these studies, lung and mediastinal tumors were the most commonly evaluated lesions, followed by lymphatic, abdominal, head and neck, breast, gynecological, and other types of tumors. Previous studies have commonly shown that F-FDG PET radiomics-based ML analysis has good performance in differentiating benign from malignant tumors, predicting tumor characteristics and stage, therapeutic response, and prognosis by examining significant differences in the area under the receiver operating characteristic curves, accuracies, or concordance indices (> 0.70). However, these studies have reported several ML algorithms. Moreover, different ML models have been applied for the same purpose. Thus, various procedures were used in F-FDG PET/CT radiomics-based ML analysis in oncology, and F-FDG PET/CT radiomics-based ML models, which are easy and universally applied in clinical practice, would be expected to be established.
Topics: Humans; Fluorodeoxyglucose F18; Positron Emission Tomography Computed Tomography; Radiopharmaceuticals; Radiomics; Neoplasms; Machine Learning
PubMed: 37526865
DOI: 10.1007/s11604-023-01476-1