1978 Annual Plenary Meeting of the European Organization for Research on Treatment of Cancer, Paris, June 1978

P. Denoix and G. Mathe Approximately 70% of cancer patients relapse after surgery before the 5th year and, in most cases, for example in breast carcinoma, they relapse still later up to the 20th year. For some considerable time, the strategy of cancer treatment has been limited to the sophistication of surgery-radiotherapy combinations that maximally decreased the incidence of local and regional relapses in sites that were within their reach. Today, the practice of clinical oncology is unthinkable without the active participation of the medical oncologist. He is the "third man" of the clinical oncology team, and he has recently focused attention on the fact that most relapses arise from distant metastases due to the proliferation of cells seeded there after having left the primary tumor site at the time of operation and, hence, are inaccessible to any form oflocal and/or regional treatment. On this evidence, medical oncologists have proposed the application of medical treatments for disseminated minimal residual disease (MRD). They have two available means: chemother apy and immunotherapy. Medical oncologists in general can be divided into three groups: chemotherapists, immunotherapists, and chemoimmunotherapists. The pure chemotherapists, who had already cured some malignant neoplasias such as Hodgkin's disease, acute lymphoid leukemia, placental choriocarcinoma, and Wilms' tumor, thought they might have the means of attacking the residual disease of common cancers.

Cellular Immune Mechanisms and Tumor Dormancy features the work of internationally recognized experts from various disciplines as they discuss the phenomenon of tumor dormancy in humans. Animal models are described in which cellular and molecular components of the immune control of dormancy have been identified, and the relevance of these models to human cancer patients is recognized. Data derived from studies of organ transplantation, adjuvant chemotherapy, radiotherapy, anaesthesia, surgery, and whole blood transfusion is presented to show the vulnerability of cellular mechanisms maintaining dormancy. The potential for increasing the incidence of dormancy in micro metastases is also shown for non-small cell lung cancer, lymphoma, and leukemia. Cellular Immune Mechanisms and Tumor Dormancy is an important reference volume that will benefit researchers from many disciplines, including immunologists, pathologists, surgeons, and clinicians

The present volume constitutes an attempt to compile contem porary features of diagnosis and treatment of renal and adrenal tumors. A thorough survey of the field is ensured by the authors' considerable scientific experience. Tumors of the kidneys and the adrenal glands are being diagnosed and treated by physicians of different medical disciplines. For both types of tumor, the pathologic cellular substrate is of crucial importance in diagnosis and therapy. In recent years significant diagnostic advances have been made, ranging from angiography through ultrasonography and computer tomography to immunology. New impulses in oncologic therapy have occurred in surgery, radiation therapy, and tumor emboliza tion. A further important topic is renal tumors in infants. Such tumors involve special aspects of both diagnosis and therapy and also have a distinctive prognosis. We are indebted both to Springer-Verlag, who supported us in our intention to write this book, and to our colleagues, whose help is greatly appreciated. For the authors: E. LOHR Essen/Heidelberg, September 1979 Contents (Chapters marked with an asterisk have been translated by H.-U. Eickenberg) Pathology of Renal and Adrenal Neoplasms L.-D. Leder, H.J. Richter, and Chr. Stambolis ...... . 1. Tumors and Tumor-Like Lesions of the Kidney in the Adult 1.1. General Remarks . 1.2. Heterotopic Tissue . . . . l.2.l. Adrenal Tissue . . . . . .

The varying cancer incidence from country to country and region to region suggests that en vironmental factors play a considerable role in the aetiology of cancer. Whether these factors in the environment moderate the effect of car cinogenic chemicals or whether they might them selves be carcinogenic is not known at the present time. What is known is that there are various chemicals, both naturally occurring and man-made, which can induce cancer in man. In the Western world estimates vary as to how much cancer is occupational in origin; the figures range from 1% to 40%. It is our feeling that probably about 10% of cancer has a direct oc cupational origin. Nevertheless this number is considerable and it behoves us therefore to identify those chemicals which are carcinogenic and to reduce human exposure. Recent work on the mode of action of carcinogenic chemicals suggests that the majority exert their effect through an activation step to give elec trophilic metabolites. Such metabolites have as a common feature the ability to react with cel lular nucleophiles to give covalently bound products. Such reaction will occur after carcino gen treatment of animals with nucleic acids par ticularly in target organs. It is reaction with nucleic acids that provides the basis of a num ber of short-term tests for carcinogens, since the basic composition of DNA is similar in micro-organisms and in human cells.

Transplantation of syngeneic (donor is a monozygous twin) or allogeneic (donor is an HLA-identical sibling) marrow provides the opportunity for aggressive antileukemic therapy without regard to marrow toxicity. Until 1975, marrow transplantation was carried out only after failure of all other therapy. Consequently, most patients were in advanced relapse. Six of 16 recipients of syngeneic marrow and 13 of 100 recipients of allogeneic marrow are still in remission after 5. 5-10 years [3, 7]. An actuarial survival curve of the first 100 patients grafted in Seattle after conditioning with cyclophos phamide (60 mg/kg on each of 2 successive days) and total body irradiation (1,000 rad) showed three periods of interest: (1) The first 4 months showed a rapid loss of patients associated with advanced illness, graft-versus-host disease, infections (in particular interstitial pneumonias), and recurrent leukemia; (2) from 4 months to 2 years, the curve showed a much slower rate of decline attributable primarily to recurrent leukemia; and (3) from 2-10 years, the curve was almost flat with a negligible loss of patients and no recurrent leukemia. This flat portion of the curve corresponded to 13% of the patients and indicates a strong probability that the majority of these survivors are cured of their disease [8]. Attempts at reducing the incidence of leukemic relapse after transplantation were made by a number of marrow transplant groups by added chemotherapy.

Traditional cancer diagnosis relies on tissue biopsy, blood testing as well as medical imaging. By the detection moment, in most cases the tumor size may reach several millimeters and the risk of distant metastasis is unavoidable. Even, following drug treatment, there is no accurate and timely way to follow up the success of treatment. New reliable tumor-specific biomarkers/tools that allow non-invasive early cancer detection as well as monitoring of anti-cancer therapeutic regime is highly demanded. To tackle limitations of traditional cancer management, liquid biopsy has emerged which screen bodily fluids using ultrasensitive biosensing systems capable of simultaneous capturing and studying horizontal gene transfer (HGT) materials including circulating tumor cells (CTCs), exosomes, cell-free DNA, and apoptotic bodies. These are messengers and/or delivery systems by which tumor cells are communicating as well as transforming/sharing new phenotypes with each other resulting in drug resistance, distant metastatic outbreaks, and cancer recurrence. Acting as next-generation prognostic and therapeutic tools call for understanding the molecular mechanisms by which HGT works to tran