Molecular landscape and sub-classification of gastrointestinal cancers: A review of literature

The historical approach of diagnosing cancer types based entirely on anatomic origin and histologic features, and the one-size-fit-all therapeutic approach, are inadequate in modern cancer treatment. From decades of research we now know that cancer is a highly heterogeneous disease driven by complex genetic or epigenetic alterations. The advent of various high throughput molecular tools has now enabled us to view and sub-classify each cancer type based on their distinct molecular features, in addition to histologic classification, with the promise of individualized treatment strategies tailored towards each specific subtype to improve patient outcomes. In this review, we have made an effort to systematically review the most up-to-date, leading literature in molecular analysis and/or subtyping of major gastrointestinal cancers. These include esophageal squamous cell carcinoma (ESCC), gastric cancer (GC) adenocarcinoma, pancreatic ductal adenocarcinoma (PDAC), hepatocellular carcinoma (HCC), gallbladder cancer (GBC), and colorectal cancer (CRC). For each cancer type we summarized the global mutational landscape, subgroup classification based on genomics, epigenetics, gene expression and/or proteomic analysis, and their salient clinicopathological features. We have highlighted the actionable mutations or mutational pathways that could help guide targeted therapies in the future

The frequency of four common cancers in Kermanshah City, Iran, during the years 2004-2011

BACKGROUND: Cancer is one of the most prevalent diseases in today’s civilized world, with an increasing number of sufferers with each passing day. The aim of this study was to determine the prevalence of common cancers in Kermanshah City, Iran, in a period of eight years between 2004 and 2011.METHODS: This was a historic cohort study. Data were collected from Kermanshah Province Health Center (Cancer Registry). Data analysis was performed using SPSS software.RESULTS: 6,146 people were diagnosed with cancer in Kermanshah during these eight years. The prevalence of skin, stomach, breast, and bladder cancers, without considering the patients’ genders, was 35.24, 24.58, 23.73, and 16.45 percent, respectively. The highest frequency belonged to skin cancer with 309 persons in 2007.CONCLUSION: Considering the fact that cancer has increased in the city of Kermanshah, it is necessary to change the lifestyle of all the people in order to prevent and reduce different types of cancer. Managers, officials, and health professionals are the most suitable individuals that can start changing the lifestyle, habits, and the improper way of living in this community

The frequency of skin cancers in Kermanshah City, Iran, during the years 2003-2012

BACKGROUND: Skin cancer is the most common malignancy in the world, and besides the malignant type that has a high mortality rate, other cancers causes many complications and deaths as well. The incidence of skin cancer has increased over the recent decades. The present study aimed to assess the incidence of skin cancers in the city of Kermanshah, Iran, in a period between 2003 and 2012.METHODS: This was a retrospective cohort study, for which all the data was collected from the Cancer Registry Health Center in Kermanshah Province. The study population consisted of 2,660 individuals that had been diagnosed with skin cancer between the years 2003 and 2012. Analysis of obtained data was performed using SPSS statistical software.RESULTS: The prevalence of skin cancer in Kermanshah was 2,660 people over the last ten years. Skin cancer had a uniform trend, but it had increased from 212 individuals to 282 over the past decade. Although this cancer could be found in all ages, but in 2004, it was mostly diagnosed in the seventh decade of life.CONCLUSIONS: The results showed that the prevalence of skin cancer is in fact high. Given that skin cancer is one of the most common cancers, it is necessary to take steps toward reducing the risk factors of this cancer by management and proper planning

The frequency of four common cancers in Kermanshah City, Iran, during the years 2004-2011

BACKGROUND: Cancer is one of the most prevalent diseases in today’s civilized world, with an increasing number of sufferers with each passing day. The aim of this study was to determine the prevalence of common cancers in Kermanshah City, Iran, in a period of eight years between 2004 and 2011. METHODS: This was a historic cohort study. Data were collected from Kermanshah Province Health Center (Cancer Registry). Data analysis was performed using SPSS software. RESULTS: 6,146 people were diagnosed with cancer in Kermanshah during these eight years. The prevalence of skin, stomach, breast, and bladder cancers, without considering the patients’ genders, was 35.24, 24.58, 23.73, and 16.45 percent, respectively. The highest frequency belonged to skin cancer with 309 persons in 2007. CONCLUSION: Considering the fact that cancer has increased in the city of Kermanshah, it is necessary to change the lifestyle of all the people in order to prevent and reduce different types of cancer. Managers, officials, and health professionals are the most suitable individuals that can start changing the lifestyle, habits, and the improper way of living in this community

The role of acalabrutinib in adults with chronic lymphocytic leukemia.

The treatment landscape of chronic lymphocytic leukemia (CLL) has significantly changed in the past decade. This paradigm shift is due to the introduction of novel agents to the field. The two major classes of drugs that have contributed to this dramatic evolution include the Bruton tyrosine kinase (BTK) inhibitors and BCL2 inhibitors. Ibrutinib was the first-in-class drug which was initially approved by the US Food and Drug Administration (FDA) for the treatment of patients with relapsed/refractory and later for patients with treatment-naïve CLL. Despite encouraging efficacy outcomes, its use has been associated with cardiovascular and gastrointestinal toxicities likely due to off-target inhibition of ITK, TEC and EGFR family kinases. The next generation of BTK inhibitors was developed to be more selective with less off-target inhibition with the prospect to improve tolerability without compromising efficacy. Acalabrutinib, a selective covalent BTK inhibitor, is a second generation BTK inhibitor. The focus of this review is on two major phase III trials that resulted in the FDA approval of acalabrutinib in 2019. The ELEVATE TN trial investigated acalabrutinib with or without obintuzumab versus chlorambucil-obinutuzumab in older and frail patients with previously untreated CLL. The ASCEND trial explored acalabrutinib versus chemoimmunotherapy in patients with relapsed/refractory CLL. Both trials demonstrated superiority of the acalabrutinib-containing arms in terms of both efficacy and tolerability. Unfortunately, the availability of new generation BTK inhibitors has not resulted in mitigating the financial toxicities associated with these potentially life-long treatments

The role of acalabrutinib in adults with chronic lymphocytic leukemia.

The treatment landscape of chronic lymphocytic leukemia (CLL) has significantly changed in the past decade. This paradigm shift is due to the introduction of novel agents to the field. The two major classes of drugs that have contributed to this dramatic evolution include the Bruton tyrosine kinase (BTK) inhibitors and BCL2 inhibitors. Ibrutinib was the first-in-class drug which was initially approved by the US Food and Drug Administration (FDA) for the treatment of patients with relapsed/refractory and later for patients with treatment-naïve CLL. Despite encouraging efficacy outcomes, its use has been associated with cardiovascular and gastrointestinal toxicities likely due to off-target inhibition of ITK, TEC and EGFR family kinases. The next generation of BTK inhibitors was developed to be more selective with less off-target inhibition with the prospect to improve tolerability without compromising efficacy. Acalabrutinib, a selective covalent BTK inhibitor, is a second generation BTK inhibitor. The focus of this review is on two major phase III trials that resulted in the FDA approval of acalabrutinib in 2019. The ELEVATE TN trial investigated acalabrutinib with or without obintuzumab versus chlorambucil-obinutuzumab in older and frail patients with previously untreated CLL. The ASCEND trial explored acalabrutinib versus chemoimmunotherapy in patients with relapsed/refractory CLL. Both trials demonstrated superiority of the acalabrutinib-containing arms in terms of both efficacy and tolerability. Unfortunately, the availability of new generation BTK inhibitors has not resulted in mitigating the financial toxicities associated with these potentially life-long treatments

Donor-Derived Smoldering Multiple Myeloma following a Hematopoietic Cell Transplantation for AML

Posttransplant Lymphoproliferative Disorder (PTLD) is one of the most common malignancies complicating solid organ transplantation. In contrast, PTLD accounts for a minority of secondary cancers following allogeneic hematopoietic cell transplantation (HCT). Here we report on a 61-year-old woman who received an ABO-mismatched, HLA-matched unrelated donor hematopoietic cell transplantation from a presumably healthy donor for a diagnosis of acute myeloid leukemia (AML). Eighteen months following her transplant, she developed a monoclonal gammopathy. Bone marrow studies revealed 10% plasma cells, but the patient lacked clinical defining features of multiple myeloma (MM); thus a diagnosis of smoldering multiple myeloma (SMM) was established. Cytogenetic and molecular studies of the bone marrow confirmed the plasma cells were donor-derived. The donor lacks a diagnosis of monoclonal gammopathy of undetermined significance, SMM, or MM

Bones in Multiple Myeloma: Imaging and Therapy

Bone disease is the most frequent disease-defining clinical feature of multiple myeloma (MM), with 90% of patients developing bone lesions over the course of their disease. For this reason, imaging plays a major role in the management of disease in patients with MM. Although conventional radiography has traditionally been the standard of care, its low sensitivity in detecting osteolytic lesions has called for more advanced imaging modalities. In this review, we discuss the advantages, indications, and applications of whole-body low-dose CT (WBLDCT), 18F-fluorodeoxyglucose (FDG)-PET/CT, MRI, and other novel imaging modalities in the management of disease in patients with plasma cell dyscrasias. We also review the state of the art in treatment of MM bone disease (MMBD) and the role of bisphosphonates and denosumab, a monoclonal antibody that binds and blocks the activity of receptor activator of nuclear factor-kappa B ligand (RANKL), which was recently approved by the U.S. Food and Drug Administration for MMBD