Surgery in cancer can be considered to have arrived now at or near its maximum efficiency. Thanks to progress in operative techniques, and to advances in pre- and post operative care, ultraradical surgery is available today. The propensity of cancer to spread far from its original site has made such surgery obligatory in many cases if there is to be an effort to eliminate all malignant cells. Yet ultraradical surgery has not sufficiently increased the cure rate to justify horrifying mutilations, especially when the face is involved. With few exceptions, surgical procedures do not prevent the patient from dying of cancer sooner or later. The so called five year cure rate represents, to say the least, an unrealistic appraisal. Many authors consider that even the rate of five year survival is not improved by surgical procedures, and the ultimate fate of these five year survivors, with few exceptions, is still disastrous. Most of the "cured" cases still die from cancer.

Other recently discovered facts have increased skepticism about the value of surgery in cancer. The polycentric origin of cancer, especially in cases where the lesions are far apart—considered by some workers to be true even in malignant melanoma, for instance—would greatly limit the value of surgery as a means of eliminating all cancerous cells. It is recognized that to operate on a lymphoma is useless. Furthermore, it is known today that cancer cells are present in the circulating blood. Surgical manipulation has been found to induce a flow of these cells into the blood even from relatively small primary tumors.

In view of all this, cancer cannot be considered to be a condition for which surgery is a major hope. Surgery represents only an expedient—to be tried so long as nothing better can be offered. It is probable that in the future it will be reserved, in cancer treatment, for the correction of mechanical complications, such as intestinal or other duct occlusion.

Unfortunately, radiation has not been much more successful in its long range results. In order to control cancer, it is necessary that radiation destroy all the cancer cells present in the organism while producing minimal damage to normal tissue. It appears that such high selectivity of action cannot be obtained. The lack of it may be implicit in the nature of the effects achieved by radiation. A study of the biological effects of radiation, which is to be presented later in this monograph, has shown that an important part of the action of radiation is to induce changes in certain constituents of the body, principally fatty acids. These changes are largely responsible for the favorable effects of radiation but they also are largely responsible for the undesired effects. It is the nature of these changes which limits qualitatively the capacity of radiation to influence cancerous processes, and makes it dubious that progress in technique can ever greatly improve the qualitatively insufficient effectiveness of radiation. Clinical results to date provide confirmation of this pessimistic view. The recent use of extremely high voltage radiation, of radioactive cobalt, and of other radioactive particles has not greatly improved results over those obtained with older forms of radiation twenty years ago, except for reducing some harmful immediate skin and systemic effects. Now, as earlier, with few exceptions, the benefits of radiation are no more than temporary. Long lasting good effects still are limited to only a few radio sensitive tumors.

The resort to isotopes, in which the scientific world has put so much hope and millions of dollars, also has proved greatly disappointing. Of the thousands of cases of various kinds of cancer in which isotope therapy has been tried, only a very limited number of cancers of the thyroid have responded. Not only because of its continuing failures, but because of its inherent qualitative inadequacy, radiation does not appear, any more than surgery, to represent the solution for the problem of cancer.

With surgery and radiation therapy incapable of resolving the problem, more and more research workers have turned their efforts in other directions. The existence of some cases of spontaneous remission has led many investigators to believe that immunological procedures related to cancer would be able to resolve these problems. Unfortunately the existing knowledge in this specific field is too meager to permit more than some tentative investigations, usually only repetitions of similar researches made many years ago with limited success. Fruitful development of this approach would have to follow the normal pathway, starting with more knowledge of the complex immunological processes intervening in cancer.

An enormous amount of cancer research in recent years has been directed toward chemotherapy. It is a fact that many agents and groups of agents have shown the capacity to influence tumor evolution. However, each has had limited usefulness. Results of treatment have been characterized by inconsistency. Even in seemingly susceptible types of cancers, results have been good in one case, poor in another and have varied even for the same patient at different times. The inability to explain and remedy these variations has discouraged many workers. Although it appears evident that the source of discrepancies resides in the patients themselves, the general tendency among researchers has been to try to resolve the problem by finding agents able to act independently of any differences which exist between subjects.

In despair at the lack of progress in this approach, many workers today are using the screening enterprise mentioned above as a kind of last resort. For this project, they have renounced the scientific concept that pharmacodynamic activity must serve as the basis on which an agent is to be tried in therapy. They have fastened into a purely empiric approach. Now, all available chemical substances—and many others which will be synthesized especially for the purpose—are to be screened indiscriminately, for their effects on animal tumors with no reason for this test other than that the agents are, or can be made, available. We will not dwell here on the assumption that routine technique is more likely than imaginative brain power to resolve the problem of cancer. The results of this screening to date have shown it to be an invalid procedure, as expected by most critical workers. With tens of thousands of substances already tested, the busy screeners are obliged to recognize that the approach itself is fundamentally erroneous. Experience has proved that an agent can be wonderfully effective against one tumor and still be entirely inactive in others. Of tens of thousands of agents tested, less than a hundred have shown effects on tumors in animals. None appears to have significant value when applied in humans.

These results have emphasized again the importance of factors other than the agent itself. One factor lies in the differences which exist between various tumors. Some of the other factors include variations between species, between individuals of the same species, between origins of tumors, between spontaneous and transplanted tumors, and even variations in any one individual at different times.

Faced with this situation, some workers have concluded that not one treatment but at least hundreds of different treatments must be found in order to cope with the huge variety of conditions.

Taking cognizance of these considerations, it has seemed to us that a more realistic and logical approach is to try to understand the nature of the existing differences and to attempt to make the treatment adequate on the basis of that understanding. It has been this approach which has been followed in our research.

We have studied the problem of cancer for the last thirty years from an entirely different vantage point than that used by other workers. Attention has been focused on the physiopathological aspect of cancer, on the basic changes that occur in the different patients, with the ultimate aim of understanding the part played by these changes in the response of cancer to therapeutic attempts. This emphasis on the physiopathological aspect of cancer has been made possible by applying a more general overall idea of the nature of the disease.

This approach is based under various new concepts. They concern,

1) The role of the organization in the pathogenesis of the conditions.

2) A dualistic systematization of the manifestations related to normal and abnormal physiology.

3) The predominant intervention of certain constituents such as lipoids and chemical elements in the induction of the opposite manifestations.

4) The possibility to integrate the occurring processes into a system of defense mechanism against the noxious influence exerted by the environment.

Many general and special problems of physiopathology, some of them concerning cancer and other conditions, have been analyzed in this framework.

The application of this approach to therapy has resulted from a logical development of that approach. The recognition of the intervention of a variety of pathogenic factors, not only differing from one subject to the other, but even changing in the same subject during the evolution of the condition has emphasized the need for individualized therapy. As opposed to the tendency to overcome the differences existing between individual subjects through a standard therapy, the "guided therapy" utilizes the knowledge of the occurring different pathogenic particularities in order to correct them. A high degree of flexibility in the treatment has appeared necessary.

As part of this approach to therapy, has appeared the need for more complete knowledge of the existing differences and their interpretation in terms of the pathogenesis of the condition. The search for adequate analytical tests has thus represented the first task. The development of day by day analysis of the condition has been possible by choosing relatively simple but reliable procedures. The information they offered was used to determine the nature of the agents able to correct with a certain specificity, the encountered pathological conditions. These two parts, the recognition of the existing condition and the adequate agents, have concretized this approach.

These considerations explain also why the new developed "guided therapy" cannot be understood and correctly applied without a sufficient knowledge of its physiopathological and pharmacological basis. These same considerations have led us to present the research concerning this approach as a block, instead of fragmented communications. The form of a monograph has appeared consequently the best suited. In a further effort to achieve a cohesive presentation, we have separated from the text most of the technical and experimental data, and presented them as notes at the end of the text.