Manmeet Ahluwalia - Central Nervous System Metastases

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Brain metastases are one of the most challenging complications of cancer. Patients with cancer are living longer, and consequently, brain metastases are seen more often and from primaries not traditionally associated with brain metastases, such as prostate or endometrial cancer. These findings suggest that the central nervous system may be a sanctuary site for solid tumors, much in the way that it is for hematologic malignancies. If so, this suggests that microscopic tumor reaches the brain over the course of the disease, perhaps even by initial diagnosis, and therapies that may control the disease elsewhere cant penetrate an intact blood-brain barrier and eradicate the tumor residing within the brain parenchyma. This can lead to the delayed appearance of brain metastases in some patients, and in others, the brain can be the sole or residual site of disease. The therapy of brain metastases has improved over the years, in part by becoming more focal, but most patients still succumb. Much of the therapeutic challenge of brain metastases comes from the unforgiving nature of the brain itself and its relative vulnerability to the toxicities of standard treatment modalities.

The growing prevalence of brain metastases brings an urgency for better understanding of their biology and treatment. Clarity on the mechanisms of brain metastasis formation may enable the development of preventative and novel therapeutic approaches. Thus, this book is timely because it addresses both the basic mechanisms of brain metastasis formation and the current treatments that have given many patients long-term survival. The authors and editors are to be congratulated for such a comprehensive review of this critically important subject, and it is highly valuable to have the full spectrum of this topic consolidated in a single book. Hopefully, the considerable research effort now being directed towards brain metastases will lead to both improved prevention and therapeutics to reduce the morbidity and mortality associated with this deadly metastatic complication of solid tumors.

In 2011, the first European meeting exclusively dedicated to brain metastases entitled Brain Metastases Research and Emerging Therapies Conference was organized in Marseille, France, on October 5, under the impulsion of Prof. Philippe Metellus with the support of Aix-Marseille Universit. The goal of this meeting was to galvanize neurosurgeons, neurologists, neuro-/medical oncologists, radiation oncologists, pathologists, neuroimaging specialists, and biologists involved in the field to foster new collaborations between physicians, translational researchers, and basic scientists in this wide and growing field of interest in oncology. Interestingly, at the same year, a similar initiative was launched in Cleveland, thanks to Prof. Manmeet Ahluwalia with objectives almost identical to those of the European counterparts. Also, in 2011, the results of the first large phase III randomized clinical trial assessing the role of adjuvant WBRT after both surgery and stereotactic radiosurgery in oligometastatic brain metastatic patients were published by Prof. Riccardo Soffietti and colleagues in the Journal of Clinical Oncology . Since that time, we have had multiple opportunities to interact and share our experience and expertise in the field. Finally, in 2016, during a lunch at the sixth edition of the Brain Metastases Research and Emerging Therapies Conference in Marseille, France, we thought of the idea of editing a book that would represent a source reference for brain metastases.

Indeed, brain metastases are the most common intracranial malignancy, accounting for significant morbidity and mortality in cancer patients. An estimated 2045% of all patients with cancer will develop brain metastases. Metastatic brain disease is ten times more common compared to primary brain tumors. The most frequent cancers that metastasize to the brain include lung, breast, and colorectal cancers, melanoma, or renal cell carcinoma. The number of patients diagnosed with brain metastases has increased recently. This is due to an earlier and better detection of these tumors with the widespread use of modern imaging techniques but also due to the improvement of systemic treatments resulting in an improved overall survival of these patients. Brain metastases are thought to occur via seeding of circulating tumor cells into the brain microvasculature; within this unique microenvironment, tumor growth is promoted, and the penetration of systemic medical therapies is limited. Of all sites of organ colonization, brain metastases are associated with the worst prognosis, with a median survival of less than 1 year on average, associated with an impaired quality of life due to associated physical and cognitive deficits. Despite recent improvements in the treatment of systemic disease and associated brain metastases with multimodal approaches including the combination of surgery, radiotherapy, chemotherapy, immunotherapy, and targeted therapies, the median survival of patients with metastatic brain lesions is approximately 724 months from diagnosis. Therefore, understanding how cells target specific organs, whether differences exist in this targeting, and factors critical to cell survival following dissemination is also important for developing optimal treatments for metastatic and resistant tumors. Hence, a personalized plan for each patient, based on molecular characterization of the tumor used to better target radiotherapy and systemic treatment, is undoubtedly the future of brain metastasis management.