From Local Invasion To Metastatic Cancer

In human solid tumors, nodal status is the most important prognostic indicator for patient outcome. Recent developments in the sentinel lymph node concept have resulted in new procedures to define the first draining node as the primary gateway through which the cancer will spread. In From Local Invasion to Metastatic Cancer: Involvement of Distant Sites Through the Lymphovascular System, a panel of international authorities takes an in-depth look at the role of the lymphovascular system in the spread of cancer. The authors summarize the findings of the Second International Symposium on Cancer Metastasis: Basis for Rational Therapy summit. Specifically, the book presents important developments in the biology and clinical understanding of cancer metastasis, describes the relationship between tumor microenvironment and proliferation, and defines the process of lymphangiogenesis and angiogenesis with special reference to cancer metastasis. From Local Invasion to Metastatic Cancer: Involvement of Distant Sites Through the Lymphovascular System provides oncologists, radiologists, and cancer researchers the necessary information to study and develop new strategies to curb the process of metastasis.

Metastasis of cancer cells from primary tumor site to secondary locations is considered a late event in multistep tumorigenesis, and causes most cancer-related mortality. The process from the spreading of cancer cells to the seeding of newly formed tumor colonizations is governed by sequential events, including local invasion, intravasation into stroma and blood vessels, survival in circulation, extravasation, and colonization at secondary tumor sites. Cancer research provides information on the fate of metastatic cancer cells in each sequential movement or heterogeneous tumor microenvironment. However, the complexity of this mechanism remains the most stringent concept of cancer management. This book provides information for cancer researchers on metastatic phenotypes of cancer cells, and diverse promoting factors and molecular mechanisms of metastasis.

In this volume the process of local invasion and the spl~ad cies, myeloid leukemias, histiocytic tumors, eosinophilic is emphasized. Volumes I-VI have already provided know granulomas, and systemic mastocytosis. ledge pertaining to the importance of tumor invasion and The exploration of local recurrence of neoplasms, and the metastasis in the morbidity and mortality of human neo relationship of recurrence to tumor dormancy, is reviewed plasms. as it relates to local tumor invasion and progression to The characteristics of local, direct tumor spreading at metastasis. The elucidation of the mechanisms underlying various sites, including head and neck, the coelomic surface, local tumor invasion and tumor recurrence, as well as those and neuroendocrine tumors are presented. Emphasis is maintaining tumor dormancy oflocal neoplasms or dissemi placed on the spreading of neoplasm by implantation on nated micrometastases, will not only lead to advances in the epithelial surfaces, the spread of occult primary malignan early detection and treatment of primary neoplasms but also cies, and rare types of neoplastic progression, as well as detection and eradication of disseminated metastatic foci. neoplasms of the immune system, the progression of lymphoproliferative disorders and hematologic malignan- Series Editor Volume Editor Hans E. Kaiser Kenneth W. Brunson Vll ACKNOWLEDGEMENT Inspiration and encouragement for this wide ranging project on cancer distribution and dissemination from a comparative biological and clinical point of view, was given by my late friend E.H. Krokowski.

Metastatic disease is the most lethal aspect of human malignancies, making the understanding and continued research of the process of metastasis a crucial step in treating cancer. The proposed book, entitled “Experimental and Clinical Metastasis: A Comprehensive Review” aims to provide a clear and extensive review of the clinical and experimental implications of metastatic disease. This work focuses on recent contributions to the field of metastasis, and will highlight crucial findings in the molecular understanding of disseminated disease as well as standard and personalized medicine currently being investigated in the clinic. Topics will include, among many, gene properties of metastatic cells, molecular mechanisms of tumour growth and spread, animal models of metastasis, and clinical implications, markers and treatment for metastatic disease. With the participation of worldwide experts in the field of oncology, from major academic and government centres, this book will provide a leading manual for the study of the metastatic process, from benchside science to bedside care. In this light, the proposed book will facilitate classroom learning for both medical and graduate students, as well as serve as a tool for physicians and researchers interested in the metastatic process. In addition, this book will include the latest advances in basic science as well as leading technologies and theories of targeting metastatic cells. Most importantly, not only will basic and clinical aspects be discussed, but furthermore, the translational aspect of research in metastatic diseases will be emphasized.

In the United States in 1993 the American Cancer Society estimated that there were about 1,300,000 new cases of invasive cancer diagnosed. At the time of presentation about 70% of those patients represented limited local regional disease without evidences of distant dissemination. About 30% of the patients had demonstrated metastatic disease at the time of initial diagnosis or about 390,000 patients. Of those patients with local regional disease about 56% would be cured by the best treatment programs including surgery, radiation therapy with or without chemotherapy when given for cure. Therefore, of the 1,300,000 new cases of invasive cancer, about 509,000 would be cured by the best treatments available. However, about 790,000 patients will have metastatic disease as a part of initial presentation or following the completion of definitive treatment. The majority of the patients with metastatic disease will have metastases to bone as the dominant site of metastatic disease primarily from cancers of the breast and lung but other metastatic sites will be common including lung, liver, mediastinal and retro-peritoneallymph node groups as well as brain and spinal cord. It has been suggested by SMITHERS, CARLING and WINDEYER that the management of the patient with metastatic disease or recurrent disease can be a more difficult problem in management than a patient who is treated for cure.

Most cancer deaths are a result of metastasis. The spread of a primary tumor to colonize neighboring and distant organs is the relentless endgame that defines the neoplastic process. Patients who have been diagnosed with cancer are treated to prevent both the recurrence of the tumor at the site of origin and metastasis that would re-stage them as advanced stage IV cancer. Historically and still with some types of cancer, stage IV is perceived by patients as “terminal.” Fortunately, recent molecular therapies have extended the lives of patients with advanced cancer and reassuringly people living with metastatic disease increasingly visit our clinics. What is the path forward? Given that the consilience of science and medicine is a dynamic art from which therapies arise, it would be misguided to consider any single work adequate at capturing the horizon for research. So with humility we constructed this text as primer for scientists. It begins with a broad introduction to the clinical management of common cancers. This is intended to serve as a foundation for investigators to consider when developing basic science hypotheses. Unquestionably, medical and surgical care of cancer patients reveals biology and dictates how novel therapeutics will ultimately be evaluated in clinical trials. The second section of this text offers provocative and evolving insights that underscore the breadth of science involved in the elucidation of cancer metastasis biology. The text concludes with information that integrates scientific and clinical foundations to highlight translational research. This book serves as a framework for scientists to conceptualize clinical and translational knowledge on the complexity of disease that is metastatic cancer.