Exon Publications

Front Matter

Advancements in Cancer Research — 2023-08-17

Foreword

Josef Hager, MD, PhD, Mag. — 2023-08-17

As we stand at the precipice of a new era in cancer research, the need for a comprehensive, precise, and up-to-date resource has never been greater. We are witnessing an era in which our understanding of cancer, its causes, its myriad forms, and its potential cures is undergoing significant expansion and refinement. Advancements in Cancer Research delves into selected aspects of Oral and Maxillofacial Oncology, Radiation Oncology, Pediatric Oncology, and Hematological Oncology. The insightful content has been expertly curated for an audience primarily consisting of clinicians. However, the scope of the book extends beyond this demographic, promising invaluable insights for basic scientists, especially those focusing on cell microarrays. The authors of each chapter have conducted extensive research, assembling the most recent and relevant data, thoughts, and ideas within their respective areas. These chapters explore a range of topics, from the significant yet under addressed side effects of radiotherapy, such as osteoradionecrosis of the jaws and radiation-induced trismus, to the complexities surrounding the treatment of chronic lymphocytic leukemia and neuroblastoma. They shed light on the severe physical and emotional impact these conditions have on the quality of life of patients and delve into innovative therapies, including stereotactic radiosurgery and immunotherapies. The book also offers a distinctive chapter on cell microarray techniques, a novel method that promises profound impacts on drug screening and biomarker tracking. CONTINUE READING…..

Preface

Consolato M. Sergi, MD, PhD, FRCPC, FCAP — 2023-08-17

The book Advancements in Cancer Research focuses on selected areas of Oral and Maxillofacial Oncology, Radiation Oncology, Pediatric Oncology, and Hematological Oncology. The contents are primarily designed for clinicians, although basic scientists will also find considerable value. Chapter 1 explores osteoradionecrosis of the jaws, a severe side effect observed in 2-22% of patients undergoing radiation therapy or concurrent chemo-radiotherapy for head and neck cancers. There is currently no consensus on the precise diagnosis of this condition. The chapter enhances our understanding of its clinical and radiological features, presenting strategies for accurate diagnosis, with particular emphasis on radiological and nuclear medicine techniques. Chapter 2 focuses on radiation-induced trismus, a debilitating consequence of radiotherapy in patients with head and neck cancers, which interferes with daily activities such as eating, speaking, chewing, and maintaining oral hygiene. This chapter elucidates current concepts, debates surrounding the definitions, and challenges encountered in managing this condition due to variations in these definitions. Chapter 3 addresses quality of life as a significant concern arising from radiotherapy, which often leads to facial deformity, pain, fractures, devitalized bone, fistulas, dysesthesia or anesthesia, trismus, and difficulties in chewing and swallowing, along with localized or systemic infections. This chapter compiles data on the physical, social, and emotional effects of osteoradionecrosis of the jaws as determined by general or specific quality of life surveys of head and neck cancer. CONTINUE READING…..

Contributors

List of Contributors — 2023-08-17

AHMET KUCUK, MD
Mersin City Education and Research Hospital, Radiation Oncology Clinics, Mersin, Turkey

BERRIN PEHLIVAN, MD
Department of Radiation Oncology, Bahcesehir University, Istanbul, Turkey

BUSRA YILMAZ, DDS, MSC
Department of Oral and Maxillofacial Radiology, Faculty of Dentistry, Baskent University, Ankara, Turkey

CONSOLATO M. SERGI, MD, PHD, FRCPC, FCAP
Anatomic Pathology Division, Children’s Hospital of Eastern Ontario (CHEO), University of Ottawa, Ottawa, ON, Canada; Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, Canada

DIANA NUNES, MSC
Differentiation and Cancer Group, Institute for Research and Innovation in Health (i3S) of the University of Porto, 4200-135 Porto, Portugal; Toxicology Research Unit (TOXRUN), University Institute of Health Sciences, Polytechnic and University Cooperative (CESPU), 4585-116 Gandra, Portugal

DUYGU SEZEN, MD
Koc University, School of Medicine, Department of Radiation Oncology, Istanbul, Turkey

EFSUN SOMAY, DDS, PHD
Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Baskent University, Ankara, Turkey

ERKAN TOPKAN, MD
Department of Oral and Maxillofacial Radiology, Faculty of Dentistry, Baskent University, Ankara, Turkey

EYUB YASAR AKDEMIR, MD
Koc University, School of Medicine, Department of Radiation Oncology, Istanbul, Turkey

LAUREN M. WAINMAN, PHD
Department of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH, USA

MARIANA NUNES, MSC
Differentiation and Cancer Group, Institute for Research and Innovation in Health (i3S) of the University of Porto, 4200-135 Porto, Portugal; Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, 4050 313 Porto, Portugal

NULIFER KILIC DURANKUS, MD
Koc University, School of Medicine, Department of Radiation Oncology, Istanbul, Turkey

PRABHJOT KAUR, MD
Department of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH, USA

SARA RICARDO, PHD
Differentiation and Cancer Group, Institute for Research and Innovation in Health (i3S) of the University of Porto, 4200-135 Porto, Portugal; Toxicology Research Unit (TOXRUN), University Institute of Health Sciences, Polytechnic and University Cooperative (CESPU), 485-116 Gandra, Portugal; Faculty of Medicine from University of Porto (FMUP), 4200-319 Porto, Portugal

SUKRAN SENYUREK, MD
Koc University, School of Medicine, Department of Radiation Oncology, Istanbul, Turkey

UGUR SELEK, MD
Department of Radiation Oncology, MD Anderson Cancer Center, The University of Texas, Houston, TX, USA;7Department of Radiation Oncology, Faculty of Medicine, Baskent University, Adana, Turkey

WAHAB A. KHAN, PHD
Department of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH, USA

YASEMIN BOLUKBASI, MD
Koc University, School of Medicine, Department of Radiation Oncology, Istanbul, Turkey

Challenges in the Radiological Diagnosis of Osteoradionecrosis of the Jaw in Head and Neck Cancer Patients

Busra Yilmaz, DDS, MSC — 2022-10-28

ABSTRACT

One of the most common and severe side effects of radiotherapy or concurrent chemo-radiotherapy for head and neck cancers is osteoradionecrosis of the jaws, which affects 2-22% patients. Correct diagnosis is crucial for the effective and timely management of osteoradionecrosis of the jaws. However, various stages of osteoradionecrosis of the jaws resemble osteomyelitis, medication-related osteonecrosis of the jaw, or tumor recurrences, challenging the diagnostic certainty. The clinical and radiological resemblance of osteoradionecrosis of the jaws to these non-radiotherapy-related conditions are the main contributors to this challenging situation. Nevertheless, it may be possible to avoid diagnostic roadblocks by using image analysis methods such as orthopantomography, computed tomography (CT), magnetic resonance imaging, bone scintigraphy, positron emission tomography, and single-photon emission CT (SPECT). There is no widely accepted consensus on the precise diagnosis of osteoradionecrosis of the jaws, although its general characteristics have been reported in the literature. The current chapter covers osteoradionecrosis of the jaws and its clinical and radiological features and provides information on relevant strategies to be used for an accurate diagnosis, with a specific emphasis on radiological and nuclear medicine techniques.

Definitions of Radiation-induced Trismus in Head and Neck Cancer: Current Concepts and Controversies

Efsun Somay, DDS, PHD — 2022-10-28

ABSTRACT

Radiation-induced trismus is a devastating side effect of radiotherapy in patients with head and neck cancers. It hampers daily activities like eating, speaking, chewing, swallowing, and oral hygiene routines. Radiation induced trismus also negatively affects social interactions, psychological wellbeing, and lowers the quality of life of patients. The most common method for determining radiation-induced trismus is to measure the ‘maximum mouth opening’. Different cut-off values for maximum mouth opening have been employed in studies that assessed radiation-induced trismus, including 40 mm, 35 mm, 30 mm, and 20 mm. The impact and prevalence of radiation-induced trismus are not fully understood because there is no common and reliable objective measure to determine cut-off values of maximum mouth opening. Additionally, regardless of the pretreatment measures, a standard cut-off is applied to all patients, where a change may be substantial for one patient but not necessarily for another. These discrepancies may cause certain patients' conditions to be overstated or understated, misdirecting their prophylactic or therapeutic interventions. This chapter highlights the current concepts and controversies of the definitions of radiation-induced trismus, and the possible challenges in managing radiation-induced trismus because of the varied definitions.

Assessment of the Impact of Osteoradionecrosis on Quality-of-Life Measures in Patients with Head and Neck Cancer

Efsun Somay, DDS, PHD — 2022-10-28

ABSTRACT

Osteoradionecrosis of the jaws is a serious complication of radiotherapy that frequently results in facial deformity, pain, fracture, devitalized bone, fistulas, dysesthesia or anesthesia, trismus, difficulty chewing, swallowing, and localized or systemic infections. Osteoradionecrosis is defined as "a potentially severe, delayed radiation-induced injury characterized by bone necrosis, failure to heal, and exposed bone for at least three months in the absence of primary tumor progression or recurrence, or metastatic disease". The incidence rate of osteonecrosis among patients with head and neck cancers treated with radiotherapy or concurrent chemo radiotherapy is 2-22%. Although the incidence of osteoradionecrosis of the jaws has decreased as a result of recent improvements in radiotherapy procedures, it is still a very challenging task to predict, prevent, and treat osteoradionecrosis of the jaws and its consequences on patients' quality of life. Despite the negative impacts of osteoradionecrosis of the jaws on sufferers' physical appearance and functioning, and social relationships, there is a paucity of research on the quality-of-life that is specific to this condition. This chapter provides a summary of the available data on the physical, social, and emotional effects of osteoradionecrosis of the jaws as determined by general or head and neck cancer-specific quality of life surveys, which may be used to evaluate and treat such patients in radiation oncology and dentistry practices.

Combined Stereotactic Radiosurgery and Immune Checkpoint Inhibitors for the Treatment of Brain Metastasis

Ahmet Kucuk, MD — 2023-01-03

ABSTRACT

Metastasis of solid tumors to the brain occurs in about 30% of cases. Surgery and whole-brain radiotherapy have been the standard treatments with very limited success rates. As a result of the unsatisfactory local control and long-term survival outcomes, stereotactic radiosurgery has been used as an alternative to surgery and whole-brain radiotherapy, or to improve the outcomes in conjunction with other treatments. However, stereotactic radiosurgery does not produce the desired survival results despite the striking increases in local control rates, primarily because of deaths attributed to extracranial systemic disease progression or unavoidably fatal distant brain recurrences. Lately, immunotherapy has become a part, or mainstay, of treatment algorithms for many cancer types. Several authors have proposed the integration of stereotactic radiosurgery and immunotherapy for the treatment of brain metastasis. This chapter evaluates the efficacy and safety of combining novel immunotherapeutics with traditional stereotactic radiosurgery for the treatment of brain metastasis.

Preoperative Radiosurgical Management of Brain Metastases: Evidence and Challenges

Erkan Topkan, MD — 2023-01-10

ABSTRACT

About 30% of all adult patients with solid tumors will develop brain metastases. The prognosis of patients with brain metastasis is poor, with a median overall survival of 4–7 months. Nevertheless, with efficient systemic and local therapies, some specific patient groups may experience longer survival times. Currently, the options for the management of brain metastasis include surgery, systemic chemotherapy, targeted therapies, stereotactic radiosurgery (SRS), postoperative stereotactic radiosurgery, whole-brain radiotherapy (WBRT), and their combination variants. Given the severe neurotoxic effects of WBRT, increased risk of radionecrosis, leptomeningeal dissemination after postoperative SRS, and the ineligibility of certain patients for SRS during the postoperative period (usually first 21 days), an active search for alternative treatment strategies for such patients ensued. It has been suggested that novel preoperative stereotactic radiosurgery, which has a lower risk of radionecrosis and leptomeningeal dissemination, would provide at least equivalent local control rates in this regard. The purpose of the current chapter is to outline the justification and available evidence for the novel preoperative stereotactic radiosurgery in the management of brain metastasis while accepting the paucity of related literature.

Chronic Lymphocytic Leukemia: Current Knowledge and Future Advances in Cytogenomic Testing

Lauren M. Wainman, PHD — 2023-02-08

ABSTRACT

Chronic lymphocytic leukemia (CLL) is the most common leukemia in Western countries. CLL remains incurable despite improvements in clinical outcomes from the identification of prognostic markers and the introduction of targeted therapies. Recent studies have identified differences in the epigenetic and the regulatory landscape of CLL that may provide molecular targets for future therapies. Optical genome mapping (OGM) is a new method that may improve clinical testing and CLL patient care because it can provide greater sensitivity and resolution of structural variation (SV) that is currently detected by chromosome banding analysis (CBA). The practical issues around diagnosis, molecular cytogenetic prognostic markers, pathobiology, and targeted therapies are discussed with brief reference to OGM.

In Situ Neuroblastoma: The Intriguing "Tumor" of Neuroectodermal Origin and the Putative Cancer Stem Cells

Consolato M. Sergi, MD, PhD, FRCPC, FCAP — 2023-02-27

ABSTRACT

Neuroblastoma is the most prevalent solid tumor encountered outside of the central nervous system in infancy. It is considered an embryonal tumor arising from pluripotent sympathetic cells called neuroblasts with characteristic neurosecretory granules. They are positive for chromogranin A, and are double membrane bounded ultra-structurally. In rare occurrences, it can be identified at neonatal age or at very early infancy. In situ labelling of neuroblastoma has been used, but there is a remarkable controversy around it, because most of these clusters of neuroblastic cells do not exhibit a neoplastic potential. These clusters often regress, and these pediatric patients should not receive chemotherapy. This chapter reviews the challenges of this tumor and report on the heterogeneity of this kind of pediatric neoplasm with a focus on putative cancer stem cells.

Radiotherapy and Dental Implant Applications in Patients with Head and Neck Cancer

Efsun Somay, MD — 2023-04-11

ABSTRACT

Head and neck cancers are aggressive malignancies, with surgery, radiotherapy, and chemoradiotherapy being current therapeutic options. Multiple tooth loss due to rampant caries, ineffective oral hygiene or care, xerostomia, and changes in saliva content are among the common side effects of radiotherapy. Multiple tooth loss will significantly reduce the quality of life by negatively affecting oral activities such as eating, drinking, speaking, chewing, and grinding, as well as social interactions and psychological well-being. Because less saliva is produced after radiotherapy, the use of conventional prostheses would be difficult for various reasons. As a result, dental implant-supported prostheses have gained popularity as a reliable oral rehabilitation option for patients who have received radiotherapy. However, the potential risks of dental implant applications and the appropriate scheduling for patients who have undergone or will undergo radiation therapy remain a source of concern. In light of this, the purpose of this chapter is to present a multidisciplinary perspective on dental implant applications, ideal application timing, and considerations in patients with head and neck cancer from the perspectives of radiation oncology and dentistry.

Cell Microarray: An Approach to Evaluate Drug-Induced Alterations in Protein Expression

Mariana Nunes, MSC — 2023-05-04

ABSTRACT

Designing reliable in vitro assays is crucial to obtain impactful results in oncology research. Here, we describe a histology-based method to evaluate the changes in biomarker expression after being subjected to several drug conditions and explore the mechanisms of therapy resistance in a chip-like tool, such as a cell microarray. This methodology has great potential in cancer research because we can evaluate a variety of cell culture conditions on a single microscope slide, enabling rapid screening of biomarkers using microscopic images of cultured cells. Indeed, the cell microarray presents several advantages over the Western blot option to evaluate protein expression in cell cultures, enabling visualization of the protein cellular localization and side-by-side condition comparison of the results. This chapter summarizes the main technical aspects of cell microarray construction, addressing the advantages and limitations, and its potential applications in the screening of biomarkers and tracking the phenotypic modifications on cancer cell lines after being exposed to different therapeutical conditions.

Index

Index — 2023-08-17

About the Editor

Consolato M. Sergi, MD, PhD, FRCPC, FCAP — 2023-08-17

Consolato M. Sergi, MD, PhD, MPH, FRCPC, FCAP, is chief of pathology at the Children’s Hospital of Eastern Ontario, full professor of pathology and an adjunct professor of pediatrics at the Universities of Ottawa, Ontario, and Alberta, Canada. He is also a consultant for Standards and Guidelines in Carcinogenesis of Chemical Compounds published by the World Health Organization/International Agency on Research on Cancer (WHO/IARC monographs), Lyon, France. His research interests include hepatic tumors, metabolic diseases, cholangiopathies, organ transplantation, and gut/bile microbiome using cell lines, animal models, and clinical samples. He identified the role of apoptosis in ductal plate malformation of the liver, characterized sialidosis, and found two new genes, WDR62, which encodes a centrosome-associated protein (Nat Genet 2010) and OTX2, mutations of which can contribute to dysgnathia (J Med Genet 2012). Professor Sergi has published more than 350 research/review articles and several books and book chapters. All the royalties from his books go to charities of families and children. He has supervised and mentored many PhD students and clinical fellows. He is also on the editorial boards of several scientific journals.