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Convergence of Precision Oncology and Liquid Biopsy in Non-Small Cell Lung Cancer
This review article illuminates the role of liquid biopsy in the continuum of care for non-small cell lung cancer (NSCLC). We discuss its current application in advanced-stage NSCLC at the time of diagnosis and at progression. We highlight research showing that concurrent testing of blood and tissue yields faster, more informative, and cheaper answers than the standard stepwise approach. We also describe future applications for liquid biopsy including treatment response monitoring and testing for minimal residual disease. Lastly, we discuss the emerging role of liquid biopsy for screening and early detection. (Source: Hema...
Source: Hematology/Oncology Clinics of North America - April 4, 2023 Category: Cancer & Oncology Authors: Ebaa Al-Obeidi, Jonathan W. Riess, Umberto Malapelle, Christian Rolfo, David R. Gandara Source Type: research

Locally Advanced Lung Cancer
Consolidation immunotherapy after concurrent chemoradiation has improved five-year survival rates in unresectable, locally advanced lung cancer, but disease progression and treatment personalization remain challenges. New treatment approaches with concurrent immunotherapy and consolidative novel agents are being investigated and show promising efficacy data, but at the risk of additive toxicity. Patients with PD-L1 negative tumors, oncogenic driver mutations, intolerable toxicity, or limited performance status continue to require innovative therapies. This review summarizes historical data that galvanized new research effo...
Source: Hematology/Oncology Clinics of North America - April 4, 2023 Category: Cancer & Oncology Authors: Sarah Oh, George N. Botros, Milan Patel, Missak Haigentz, Eshan Patel, Iaonnis Kontopidis, John Langenfeld, Matthew P. Deek, Salma K. Jabbour Source Type: research

Targeted Therapy for Non –Small Cell Lung Cancer
This article provides an updated review of the management of oncogene-driven non –small cell lung cancer. The use of targeted therapies for lung cancer driven by EGFR, ALK, ROS1, RET, NTRK, HER2, BRAF, MET, and KRAS are discussed, both in the first-line setting and in the setting of acquired resistance. (Source: Hematology/Oncology Clinics of North America)
Source: Hematology/Oncology Clinics of North America - April 4, 2023 Category: Cancer & Oncology Authors: Elliott Brea, Julia Rotow Source Type: research

What Is New in Small Cell Lung Cancer
Small cell lung cancer (SCLC) is a rare yet aggressive lung cancer subtype with an extremely poor prognosis of around 1 year. SCLC accounts for 15% of all newly diagnosed lung cancers and is characterized by rapid growth with high potential for metastatic spread and treatment resistance. In the article the authors review some of the most notable efforts to improve outcomes, including trials of novel immunotherapy agents, novel disease targets, and multiple drug combinations. (Source: Hematology/Oncology Clinics of North America)
Source: Hematology/Oncology Clinics of North America - April 4, 2023 Category: Cancer & Oncology Authors: Robert Matera, Anne Chiang Source Type: research

Lung Cancer Supportive Care and Symptom Management
Lung cancer carries significant mortality and morbidity. In addition to treatment advances, supportive care may provide significant benefit for patients and their caregivers. A multidisciplinary approach is critical in addressing complications of lung cancer, including disease- and treatment-related complications, oncologic emergencies, symptom management and supportive care, and addressing the psychosocial needs of affected patients. (Source: Hematology/Oncology Clinics of North America)
Source: Hematology/Oncology Clinics of North America - April 4, 2023 Category: Cancer & Oncology Authors: Johnathan Yao, Madison Novosel, Shreya Bellampalli, Jennifer Kapo, Julia Joseph, Elizabeth Prsic Source Type: research

Advances and Opportunities in the Management of Lung Cancer
The past quarter of a century has seen tremendous advances in the diagnosis and management of lung cancer, resulting in patients living significantly longer and better than ever before. Patients with early-stage non –small cell lung cancer (NSCLC) are benefiting from innovation in surgical techniques, which results in improved outcomes and easier recovery, and those who are unable to undergo resection are benefiting from progress in radiation therapy technology, such as stereotactic body radiotherapy. (Source: Hematology/Oncology Clinics of North America)
Source: Hematology/Oncology Clinics of North America - April 4, 2023 Category: Cancer & Oncology Authors: Sarah B. Goldberg, Roy S. Herbst Tags: Preface Source Type: research

State of the Art of Pathologic and Molecular Testing
Advances in the treatment of non-small cell lung carcinoma have resulted in improved histologic classification and the implementation of molecular testing for predictive biomarkers into the routine diagnostic workflow. Over the past decade, molecular testing has evolved from single-gene assays to high-thoroughput comprehensive next-generation sequencing. Economic barriers, suboptimal turnaround time to obtain the results, and limited tissue available for molecular assays resulted in adoption of liquid biopsies (ctDNA) into clinical practice. Multiplex immunohistochemical/immunofluorescence assays evaluating tumor microenvi...
Source: Hematology/Oncology Clinics of North America - March 22, 2023 Category: Cancer & Oncology Authors: Sanja Dacic Source Type: research

Advances in Surgical Techniques for Lung Cancer
Thoracic surgery for non –small cell lung cancer has evolved tremendously in the past two decades. Improvements have come on multiples fronts and include a transition to minimally invasive techniques, an incorporation of neoadjuvant treatment, and a greater utilization of sublobar resection. These advances have reduced t he morbidity of thoracic surgery, while maintaining or improving long-term survival. This review highlights major advances in the surgical techniques of lung cancer and the keys to optimizing outcomes from a surgical perspective. (Source: Hematology/Oncology Clinics of North America)
Source: Hematology/Oncology Clinics of North America - March 22, 2023 Category: Cancer & Oncology Authors: Brooks V. Udelsman, Justin D. Blasberg Source Type: research

Introduction to the Thalassemia Syndromes
Thalassemia is a heterogeneous group of inherited anemias having in common defective biosynthesis of one or more of the globin chain subunits of human hemoglobin. Their origins lie in inherited mutations that impair the expression of the affected globin genes. Their pathophysiology arises from the consequent insufficiency of hemoglobin production and the imbalance in the production of globin chains resulting in the accumulation of insoluble unpaired chains. These precipitate and damage or destroy developing erythroblasts and erythrocytes producing ineffective erythropoiesis and hemolytic anemia. Treatment of severe cases r...
Source: Hematology/Oncology Clinics of North America - March 11, 2023 Category: Cancer & Oncology Authors: Edward J. Benz Source Type: research

Remembering the Contributions of Professor David J. Weatherall
We dedicate this issue of the Hematology/Oncology Clinics of North America to the memory of Professor Sir David J. Weatherall (Fig.  1). The field of thalassemia research has, for the past 75 years, been marked by seminal discoveries that laid the foundation for molecular medicine. It has been populated by many of the world’s most outstanding scientists. Among these, David Weatherall stands out, universally acknowledged as th e individual who contributed more than anyone. He provided foundational insights into the mechanisms underlying these severe inherited anemias and advanced an entire field through his laboratory an...
Source: Hematology/Oncology Clinics of North America - March 11, 2023 Category: Cancer & Oncology Authors: Edward J. Benz Tags: Dedication Source Type: research

Molecular Basis and Genetic Modifiers of Thalassemia
Thalassemia syndromes are common monogenic disorders and represent a significant health issue worldwide. In this review, the authors elaborate on fundamental genetic knowledge about thalassemias, including the structure and location of globin genes, the production of hemoglobin during development, the molecular lesions causing α-, β-, and other thalassemia syndromes, the genotype-phenotype correlation, and the genetic modifiers of these conditions. In addition, they briefly discuss the molecular techniques applied for diagnosis and innovative cell and gene therapy strategies to cure these conditions. (Source: Hematology/...
Source: Hematology/Oncology Clinics of North America - March 11, 2023 Category: Cancer & Oncology Authors: Nicol ò Tesio, Daniel E. Bauer Source Type: research

Fetal Hemoglobin Regulation in Beta-Thalassemia
β-thalassemia is caused by mutations that reduce β-globin production, causing globin chain imbalance, ineffective erythropoiesis, and consequent anemia. Increased fetal hemoglobin (HbF) levels can ameliorate the severity of β-thalassemia by compensating for the globin chain imbalance. Careful cli nical observations paired with population studies and advances in human genetics have enabled the discovery of major regulators of HbF switching (i.e. BCL11A, ZBTB7A) and led to pharmacological and genetic therapies for treating β-thalassemia patients. Recent functional screens using genome editing and other emerging tools hav...
Source: Hematology/Oncology Clinics of North America - March 11, 2023 Category: Cancer & Oncology Authors: Henry Y. Lu, Stuart H. Orkin, Vijay G. Sankaran Source Type: research

Clinical Classification, Screening, and Diagnosis in Beta-Thalassemia and Hemoglobin E/Beta-Thalassemia
This article reviews the classification of beta-thalassemia syndromes, correlating clinical severity and genotype in the earlier classification, and broadening it recently based on clinical severity and transfusion status. The classification is dynamic, and individuals may progress from transfusion-independent to transfusion-dependent. Early and accurate diagnosis prevents delays in instituting treatment and comprehensive care, and precludes inappropriate and potentially harmful interventions. Screening can inform risk in an individual and subsequent generations when partners may be carriers as well. This article discusses...
Source: Hematology/Oncology Clinics of North America - March 11, 2023 Category: Cancer & Oncology Authors: Morgan Pines, Sujit Sheth Source Type: research

The Clinical Phenotypes of Alpha Thalassemia
Clinical manifestations of α-thalassemia range from no symptoms to severe transfusion-dependent anemia. Alpha thalassemia trait is deletion of 1 to 2 α-globin genes, whereas α-thalassemia major (ATM; Barts hydrops fetalis) is the deletion all 4 α genes. All other genotypes of intermediate severity are categorized as HbH d isease, a vastly heterogenous group. Clinical spectrum is classified as mild, moderate, and severe by symptoms and need for intervention. Anemia in prenatal period may be fatal without intrauterine transfusions. New therapies to modify HbH disease or provide cure for ATM are under development. (Source...
Source: Hematology/Oncology Clinics of North America - March 11, 2023 Category: Cancer & Oncology Authors: Ashutosh Lal, Elliott Vichinsky Source Type: research

Pathogenic Mechanisms in Thalassemia I
Erythropoiesis is the physiological process that results in the production of red blood cells (RBCs). In conditions of pathologically altered erythropoiesis or ineffective erythropoiesis, as in the case of β-thalassemia, the reduced ability of erythrocytes to differentiate, survive and deliver oxygen stimulates a state of stress that leads to the ineffective production of RBCs. We herein describe the main features of erythropoiesis and its regulation in addition to the mechanisms behind ineffective e rythropoiesis development in β-thalassemia. Finally, we review the pathophysiology of hypercoagulability and vascular dise...
Source: Hematology/Oncology Clinics of North America - March 11, 2023 Category: Cancer & Oncology Authors: Rayan Bou-Fakhredin, Stefano Rivella, Maria Domenica Cappellini, Ali T. Taher Source Type: research