AT A meeting of the American Medical Association recently held in Cleveland, Dr. Joseph C.Bloodgood, in discussing a paper on radiation therapy, said that “report at my clinic told me that 49 per cent of the patients previously operated on in the clinic now to for radiotherapy. This is based on results. They are not hopeless cases; they are still hopeful and they get well under radiotherapy. This has happened during the last three years, not because I have changed any but because the method of radiotherapy has changed. A great change has taken place. First of all, radium and x-rays are no longer looked on a last resort.”.
The foregoing bears witness to the progress made in the field radiation therapy. The manufacture of more adequate apparatus and the improved technic in its use reflect this improvement. Machines are used generally delivering twenty to thirty milliamperes of current at 200 K.V., while machines operating at 750 to 1,000 200 K.V., using lower milliamperes, have been installed in several places in this country. Since the question of increased voltages began to dominate the field, machines operating at 400 to 600 K.V., using sealed tubes, have been manufactured in this country as well as on the been manufactured in this country as well as on the continent. This higher powered machines occupy little more space than the usual 200 K.V. machine.
The effectiveness of these stronger radiations is thought to be due to (1) the increased penetration and its consequently larger percentage depth doses, (2) the supposed higher selective action of short have length radiation on malignant cells, and (3) greatly increased x-ray output. Clinics using super-voltages report that clinical results are somewhat better than those secured through the use of the lesser voltage machine.
Experimental effort, from the physical and biologic point of view, has been exerted to establish to standard basis for radiotherapy since Roentgens discovery thirtyfive years ago, and its application five years later. Radiotherapists have only recently begun to understand the principles of clinical application or radiotherapy in the treatment of malignant conditions.
Regaud selected the rabbits testicle for his experiments because its histologic cellular structure was highly sensitive to radiation, containing cells which are in a state of active mitosis resembling that of malignant tissue. In 1922, Regaud reported that of malignant, tissue. In 1922, Regaud reported that it was impossible to sterilize the testicle by a single dose of radiation without causing serious damage to the overlying skin.
The dose required to produced such radio necrosis was equivalent to about three radionecrosis was equivalent to about three erythemas when administered in one dose. However, by dividing the dose in such a manner as to prolong the treatment over a period of fourteen days, a total dose of about five erythemas could be given causing complete sterilizations without damage to the skin. Thus it is seen that by prolonging the time of treatment the cutaneous dose could be increased nearly 50 per cent without causing necrosis.
The above experiments were reported, and the same results determined, by Schinz and Slotopolsky in 1926, and again by Regaud and Ferroux in 1927. These experiments formed the foundation for the clinical studies of Pfahler (America), Hohlfelder (Germany) and Coutard (France), who have swung the pendulum from massive radiation, as advocated by the German school, to that of the protected fractional dose method.
Results have been achieved by this method which are superior to previously reported; these are obtained by the improved method of administering a large dose to the (3 days) without causing destructive effects to the surroundings normal structure (or cancer bed); its effect are rather biologic than physical. The clinical application of the method of radiation by Pfahler, Countard, and Berven (Sweden) in the treatment of cancer of the tonsil, pharynx and larynx and have proved the radio-sensitive properties of squamous carcinoma, previously considered incapable of of responding to radiation.
According to Coutard, the neoplasm is exposed to x-rays twice daily, giving a total dose of 350 r to400 r to two areas, using 190 to 200 k.v., four milliamperes, two millimeters of copper and three millimeters of aluminum filtration at a distance of fifty of sixty centimeters, for lesion of the head and neck. For deeply situated lesions, such as cancer of the uterus, the focal distance varies from 80 to 100 centimeters, the area of the field for the head and neck conditions being only 50 to 100 square centimeters, while those of the lower abdomen require on an average of 250 to 300 square centimeters. For the sterilization of the radio-sensitive squamous carcinomatous growth, a depth dose of 3,000 r to 4,000 r is given, while stronger dose is necessary for the radio-resistant tumors.
In the course of treatment of principle guides a radio reaction of the covering epithelium and the radio reaction of the cancer cells. The radio reaction of the cutaneous epithelium is called “radio epidermitis.”characterized by loss of epithelial layers and denudation of the dermis. The reaction of the mucous membrane , called “radio epithelitis,” manifests itself by loss of the epithelial layer sand denudation of the mucous membrane, epithelial layers and denudation of the corium which becomes covered by a fibrinous and false membrane; of clear. The duration of both describe radio reactions is six weeks. Each appears at the beginning of three weeks and disappears at the beginning of the ninth week.
Should the total or daily dose or the intensity per minute be too high, or the filtration or the tension too low, the cancer bed would be modified. the nutrition of the malignant cells becomes impaired The cellular radio- sensitivity, which seems to be linked up not only with the mitosis of the cell but above all with the activity of their interchange with the cell but above all with the activity of their interchange with the surrounding normal structures, becomes diminished and at times suppressed. The cancer cells become incentive to radiation. This phenomenon is called “radio- vaccination” by Regaud.
Observation of clinical facts shows that changes in the surrounding normal tissue result from excessive daily doses and intensity per minute per minute causing radio resistance of the tissue. Conversely, radio- sensitivity would be prolonged with a smaller daily dosage and the resultant extended period.
Realizing that better results may be obtained by prolonged treatment, Coutard and his collaborators in the last few years have begun to extend the duration of treatment of certain so-called radio-resistant cancers from thirty to ninety days, giving weak daily doses in order of about 175, 220, 225 and 250 r per day, dividing the dose in two treatments.
By this method he was able to cure a certain number of lesions on which he had not been able previously to obtain the same results, such as very differentiated epidermoid epithelioma invading the muscles and cartilages, glandular epithelioma of the breast ad the thyroid body, and special round celled epitheliomas of the upper part of the ethmoid and the adjacent sinuses. This mode of prolonged treatment not only controlled the condition locally but it lessened the frequency of metastasis.
When radiating a cancer of very embryonic, very radio-sensitive growths, the energy factor is predominant. The action of the x-rays seems to be direct and rapid; the treatment can be accomplished within fifteen to twenty days. The cells are destroyed and generally normal structures are affected very little. When radiating the less embryonic type of growths, the time of treatment should be longer.
Pursuing these general principles, I have adopted the Countard method with some slight modifications. The cures which I shall illustrate will show that the percentage of cures in a number of most dangerous epidermoid carcinomas has markedly increased and that some conditions formerly considered hopeless have been temporarily cured. In conclusion I wish to emphasize the following facts:.
(1) Cure of cancer by x-rays is still difficult and must not be entered into lightly and causally.
(2) Radiotherapy is just as radical in method as surgery, and requires great skill, judgment and experience.
(3) The cooperation of the pathologist and the radiotherapist is imperative for a proper estimate of the radio-sensitivity in relation to treatment of the lesion.
(4) Daily examination of the patient is necessary; modification of the normal structure and general reaction by the x-ray treatment sometimes appears to quickly that it is often necessary to diminish the daily dose or the size of the field in the course of treatment.
(5) There exists no fixed method of treatment, only a simple clinical treatment for each individual patient and for the special type of tumor..
(6) Improvement in roentgen apparatus of higher voltages, producing more penetrating rays, will permit a better relation between destruction of malignant cells and preservation of the supporting, and the radio sensitivity of the tumor may be prolonged.
Department of Radiation Therapy, Harlem City Hospital, New York City