A deep-learning framework to predict cancer treatment response from histopathology images through imputed transcriptomics.

Advances in artificial intelligence have paved the way for leveraging hematoxylin and eosin-stained tumor slides for precision oncology. We present ENLIGHT-DeepPT, an indirect two-step approach consisting of (1) DeepPT, a deep-learning framework that predicts genome-wide tumor mRNA expression from slides, and (2) ENLIGHT, which predicts response to targeted and immune therapies from the inferred expression values. We show that DeepPT successfully predicts transcriptomics in all 16 The Cancer Genome Atlas cohorts tested and generalizes well to two independent datasets.

Lymphocyte-Directed Immunomodulation Remits Thymoma-Associated Autoimmune Pneumonitis.

Background: Thymoma presents with several autoimmune manifestations and is associated with secondary autoimmune regulator (AIRE) deficiency. Pneumonitis has recently been described as an autoimmune manifestation associated with thymoma presenting with similar clinical, radiographic, histological, and autoantibody features as seen in patients with inherited AIRE deficiency who suffer from Autoimmune PolyEndocrinopathy-Candidiasis-Ectodermal Dystrophy (APECED) syndrome.

Objectives: To treat two patients with biopsy-proven thymoma-associated pneumonitis with lymphocyte-directed immunomodulation.

Role of ALK Inhibitors in Anaplastic Large Cell Lymphoma-Experience from an Indian Center.

Perumal Kalaiyarasi JayachandranAnaplastic large cell lymphoma (ALCL) is the second most common type of peripheral T cell lymphoma and an aggressive mature T cell lymphoma. About 50 to 70% of systemic ALCLs are anaplastic lymphoma kinase positive (ALK +), the proportion even higher in the pediatric population. The 5-year survival after chemotherapy is around 70 to 80%.

Immunotherapy for Thymomas and Thymic Carcinomas: Current Status and Future Directions.

Thymic epithelial tumors are a histologically diverse group of cancers arising from the epithelial compartment of the thymus. These tumors are characterized by a low tumor mutation burden, a lack of actionable genomic changes, and, especially with thymomas, defects in immune tolerance. Surgery is the mainstay of the management of resectable disease, whereas advanced, unresectable tumors are treated with platinum-based chemotherapy.

Anti-Interleukin-23 Autoantibodies in Adult-Onset Immunodeficiency.

Background: Autoantibodies against interleukin-12 (anti-interleukin-12) are often identified in patients with thymoma, but opportunistic infections develop in only some of these patients. Interleukin-12 (with subunits p40 and p35) shares a common subunit with interleukin-23 (subunits p40 and p19). In a patient with disseminated infection, the identification of both anti-interleukin-23 and anti-interleukin-12 prompted further investigation.

Efficacy, safety, and biomarker analyses of bintrafusp alfa, a bifunctional fusion protein targeting TGF-β and PD-L1, in patients with advanced non-small cell lung cancer.

Background: Bintrafusp alfa, a first-in-class bifunctional fusion protein targeting transforming growth factor-β (TGF-β) and programmed cell death ligand 1, has demonstrated encouraging efficacy as second-line treatment in patients with non-small cell lung cancer (NSCLC) in a dose expansion cohort of the phase 1, open-label clinical trial (NCT02517398). Here, we report the safety, efficacy, and biomarker analysis of bintrafusp alfa in a second expansion cohort of the same trial (biomarker cohort).

Methods: Patients with stage IIIb/IV NSCLC who were either immune checkpoint inhibitor (ICI)-naïve (n=18) or ICI-experienced (n=23) were enrolled.

Liquid biopsy epigenomic profiling for cancer subtyping.

Although circulating tumor DNA (ctDNA) assays are increasingly used to inform clinical decisions in cancer care, they have limited ability to identify the transcriptional programs that govern cancer phenotypes and their dynamic changes during the course of disease. To address these limitations, we developed a method for comprehensive epigenomic profiling of cancer from 1 ml of patient plasma. Using an immunoprecipitation-based approach targeting histone modifications and DNA methylation, we measured 1,268 epigenomic profiles in plasma from 433 individuals with one of 15 cancers.

Prediction of cancer treatment response from histopathology images through imputed transcriptomics.

Advances in artificial intelligence have paved the way for leveraging hematoxylin and eosin (H&E)-stained tumor slides for precision oncology. We present ENLIGHT-DeepPT, an approach for predicting response to multiple targeted and immunotherapies from H&E-slides. In difference from existing approaches that aim to predict treatment response directly from the slides, ENLIGHT-DeepPT is an indirect two-step approach consisting of (1) DeepPT, a new deep-learning framework that predicts genome-wide tumor mRNA expression from slides, and (2) ENLIGHT, which predicts response based on the DeepPT inferred expression values.

Dataset for reporting of thymic epithelial tumours: recommendations from the International Collaboration on Cancer Reporting (ICCR).

Aims: Thymic epithelial tumours (TET), including thymomas and thymic carcinomas and thymic neuroendocrine neoplasms, are malignant neoplasms that can be associated with morbidity and mortality. Recently, an updated version of the World Health Organization (WHO) Classification of Thoracic Tumours 5th Edition, 2021 has been released, which included various changes to the classification of these neoplasms. In addition, in 2017 the Union for International Cancer Control (UICC) / American Joint Committee on Cancer (AJCC) published the 8th Edition Staging Manual which, for the first time, includes a TNM staging that is applicable to thymomas, thymic carcinomas, and thymic neuroendocrine neoplasms.

The therapeutic relevance of a mutation in a patient with recurrent thymoma: a case report.

Background: Thymomas are characterized by a low tumor mutation burden and a paucity of actionable mutations. Clinical behavior can vary from relatively indolent to very aggressive and impact survival. Platinum-based chemotherapy is the primary treatment modality for inoperable disease and is palliative in intent.

Phase 1 trial of CV301 in combination with anti-PD-1 therapy in nonsquamous non-small cell lung cancer.

CV301, a poxviral-based vaccine, has been evaluated in a phase 1 clinical trial (NCT02840994) and shown to be safe and immunologically active (phase 1a). Preclinical data support a combination of CV301 with programmed death-1 inhibitors, which has been evaluated in the phase 1b part of this trial and is reported here. Patients with advanced nonsquamous non-small cell lung cancer (NSCLC) without actionable genomic alterations received two priming doses of modified vaccinia Ankara-BN-CV301 (MVA) 4 weeks apart, followed by boosting doses of fowlpox-CV301 (FPV) at increasing time intervals for a maximum of 17 doses in combination with nivolumab for cohort 1 (C1) and 15 doses in combination with pembrolizumab for cohort 2 (C2).

Unraveling the Pharmaceutical Benefits of Freshly Prepared Amino Acid-Based Schiff Bases Via DFT, In Silico Molecular Docking and ADMET.

A series of amino acid-based Schiff bases have been synthesized using a facile condensation between benzil (a diketone) and amino acid in the presence of a base. The formation of Schiff base compounds has been ensured by elemental analysis, FT-IR, H-NMR, C-NMR and UV-Vis. spectra.

Immunotherapy for Management of Thymic Epithelial Tumors: A Double-Edged Sword.

Thymic epithelial tumors (TETs) are rare thoracic cancers that are broadly classified as thymomas and thymic carcinomas. Surgery is the cornerstone of management for early-stage disease. There are a limited number of effective treatment options for patients with advanced or recurrent disease.

Heterogeneity of neuroendocrine transcriptional states in metastatic small cell lung cancers and patient-derived models.

Molecular subtypes of small cell lung cancer (SCLC) defined by the expression of key transcription regulators have recently been proposed in cell lines and limited number of primary tumors. The clinical and biological implications of neuroendocrine (NE) subtypes in metastatic SCLC, and the extent to which they vary within and between patient tumors and in patient-derived models is not known. We integrate histology, transcriptome, exome, and treatment outcomes of SCLC from a range of metastatic sites, revealing complex intra- and intertumoral heterogeneity of NE differentiation.

Joint-Predominant Rheumatic Complications of Immune Checkpoint Inhibitor Therapy in Patients with Thymic Epithelial Tumors.

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced cancers. However, activation of the immune system can occasionally cause life-threatening toxicity involving critical organs. Induction of immune-mediated toxicity is a significant concern for patients with thymic epithelial tumors (TETs) due to defects in immune tolerance.

Mechanistic Investigation of GHS-R Mediated Glucose-Stimulated Insulin Secretion in Pancreatic Islets.

Ghrelin receptor, a growth hormone secretagogue receptor (GHS-R), is expressed in the pancreas. Emerging evidence indicates that GHS-R is involved in the regulation of glucose-stimulated insulin secretion (GSIS), but the mechanism by which GHS-R regulates GSIS in the pancreas is unclear. In this study, we investigated the role of GHS-R on GSIS in detail using global mice (in vivo) and -ablated pancreatic islets (ex vivo).

The 2021 WHO Classification of Tumors of the Thymus and Mediastinum: What Is New in Thymic Epithelial, Germ Cell, and Mesenchymal Tumors?

This overview of the fifth edition of the WHO classification of thymic epithelial tumors (including thymomas, thymic carcinomas, and thymic neuroendocrine tumors [NETs]), mediastinal germ cell tumors, and mesenchymal neoplasms aims to (1) list established and new tumor entities and subtypes and (2) focus on diagnostic, molecular, and conceptual advances since publication of the fourth edition in 2015. Diagnostic advances are best exemplified by the immunohistochemical characterization of adenocarcinomas and the recognition of genetic translocations in metaplastic thymomas, rare B2 and B3 thymomas, and hyalinizing clear cell carcinomas. Advancements at the molecular and tumor biological levels of utmost oncological relevance are the findings that thymomas and most thymic carcinomas lack currently targetable mutations, have an extraordinarily low tumor mutational burden, but typically have a programmed death-ligand 1 phenotype.

JNJ-64041757 (JNJ-757), a Live, Attenuated, Double-Deleted -Based Immunotherapy in Patients With NSCLC: Results From Two Phase 1 Studies.

Introduction: JNJ-64041757 (JNJ-757) is a live, attenuated, double-deleted -based immunotherapy expressing human mesothelin. JNJ-757 was evaluated in patients with advanced NSCLC as monotherapy (phase 1) and in combination with nivolumab (phase 1b/2).

Methods: Patients with stage IIIB/IV NSCLC who had received previous therapy were treated with JNJ-757 (1 × 10 or 1 × 10 colony-forming units [CFUs]) alone (NCT02592967) or JNJ-757 (1 × 10 CFU) plus intravenous nivolumab 240 mg (NCT03371381).

Autologous Stem Cell Transplantation in Testicular Germ Cell Tumor-Preliminary Experience from a Single Center.

Germ cell tumor (GCT) of the testis is one of the highly curable solid organ malignancies. Those who experience relapse after platinum-based chemotherapy can be salvaged with systemic therapy followed by high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT). Complete remission can be obtained in approximately 50 to 60% of patients treated with HDCT.