Milton Friedman

A quantitative study of late radiation effect on normal skin and subcutaneous tissues in human beings.

Abstract A retrospective study of late effects of irradiation on skin and underlying connective tissues in 94 testis tumour patients was conducted 5–8 years after irradiation. The late lesions were classified into five degrees of “severity of injury”. Among this population of patients, there was marked variation of “severity of injury” produced by similar dosage; or when viewed differently, each degree of “severity of injury” was produced by a wide range of doses. Therefore, since the late response of connective tissues was not constant, a “tolerance dose” could not be established, but only a “percent probability of threat” of a specific degree of injury. The data also indicate that within certain limits, the late effects are independent of overall time; and that they are dependent on the size of the daily fraction. Furthermore, biological features of non-proliferating connective tissue are not applicable to dynamically proliferating normal epithelial and cancerous tissues.

Hodgkin's disease; a review of two hundred and sixteen cases.

This study covers 216 cases of Hodgkins disease treated at Walter Reed Army Hospital from 1938 through 1948. In every instance the diagnosis was established by histologic study of an excised lymph node. In view of present knowledge regarding Hodgkins disease, it is believed that its best management is based on the concept that it is a malignant neoplasm. The pros and cons of an infectious granulomatous process versus a malignant neo-plastic process cannot be settled by the practicing physician. Certainly, to date, the handling of Hodgkins disease as an inflammatory condition has done nothing but delay its treatment as a cancer. Study of any of these cases from the onset of the disease, through its course, to the postmortem findings will convince one that it meets all the criteria of cancer. The high incidence of primary involvement of a single lymph node, or a small group of nodes, lends support to the belief that Hodgkins disease is unicentric in origin. This is corroborated by the relatively higher ...

Treatment of squamous cell carcinoma of the head and neck with combined methotrexate and irradiation

Nine years experience with 200 patients is analyzed retrospectively. In 76% of cases, pre‐irradiation methotrexate produced shrinkage in tumor volume ranging in amount from 25% to 90%. However, there was only a minor impact on the cure rate, because, as demonstrated by serial biopsies, the residual tumor retained its reproductive integrity. Study of tumor shrinkage curves tends to corroborate the clinical impression that methotrexate does not enhance radiation effect but acts as an independent agent. Combined therapy has cured some advanced cancers which might not have been cured with irradiation alone.

Significance of growth rates, cell kinetics, and histology in the irradiation and chemotherapy of squamous cell carcinoma of the mouth

In eight cases of extended tumors of oral cavity, we have studied the growth rate, the cell kinetics parameters, and the histology before and during treatment. We have found that growth rate and cell kinetics are not useful for clinical purposes because the first is not related to the response to treatment, while the second is unable to give relevant parameters in solid human tumors. New information was obtained from examination of serial biopsies before and throughout the treatment. These data suggest that multiple subpopulation groups of cancer cells with different intrinsic sensitivity to chemotherapy and/or radiotherapy may exist in the same tumor. Resistance of the tumor is related to some groups of cells scarcely sensitive to treatment.

“Seminoma with trophocarcinoma”. A clinical variant of seminoma

Seminoma occasionally contains foci of trophocarcinoma (embryonal carcinoma), or else has histologic features of aggressive growth. The resultant variants are classified into: anaplastic seminoma, borderline seminoma, and seminoma with trophocarcinoma. The latter variant is characterized by specific histologic features and, compared with pure seminoma, by more aggressive clinical behavior, larger required tumor lethal radiation dose, and lower survival rate. The intimate association of primordial trophoblastic structures with seminoma is of histogenetic interest.

Aspects of radiation biology and radiation pathology observed during the treatment of cancer in man

1. The ‘required tumour lethal dose’ for all human cancers treated with irradiation ranges from approximately 500 rads to more than 12,000 rads. Therefore, when attempting to quantify the influence of biological factors such as hypoxia, variation in sensitivity during phases of a cell cycle, growth-rate, fractionation patterns, etc., the transposer must be reminded that these factors must exert their influence over a universe of tumours that vary in radio-sensitivity by as much as 25 to 1. It is probable that many radiobiological laws that are applicable to radio-resistant tumours may not apply to radio-sensitive tumours, and vice-versa. 2. Amongst each type of tumour, the required tumour lethal dose varies most commonly by a factor of 2, and in some tumours by much as 3½. A standard dosage formula or isoeffect curve can provide only a first approximation of the required tumour lethal dose. Serial biopsy studies plus observation of volume growth and regression-rates during and toward the end of treatment ...

Irradiation of meningioma: a prototype circumscribed tumor for planning high-dose irradiation of the brain.

Abstract The purpose of this report is to provide specific data concerning the radiation dose required to destroy meningioma, and to demonstrate that radiation doses much greater than the alleged tolerance dose, can be administered to the brain in some patients. Most meningiomas are not responsive to irradiation, but, some surgically incurable lesions benefit from irradiation with radically high doses to small volumes of tissue. The arrest of 7 of 12 consecutive meningiomas in adults for periods of 2–17 years following maximum tumor doses up to 8800 R in 40 days is reported in this paper. All patients, when irradiated, had active tumor in the form of inoperable primary tumor, recurrence or known postoperative residual tumor. Three of the successful results were achieved with orthovoltage radiation. The incidence of brain damage may be acceptable to the patient when it is related to arrest of tumor growth but he must be forewarned of possible brain damage. The factors influencing the radioresponsiveness of meningioma are: the required tumor lethal dose, histology and vascularity of the tumor, anatomical site in the brain, treatment technique for each tumor site, small size of the treated volume, growth rate of the tumor, displacement of normal brain tissue by tumor, inherent individual variations of tumor and normal tissues, quality of the radiation, and tolerance of normal brain tissues. The role of these factors is discussed in the light of modern radiobiological concepts.

The Relation of Tissue Recovery and the Healing Process to the Periodicity of Radiation Effects

IT has been indicated that the amount of recovery from radiation effects of tissues exposed to daily fractionated doses of radiation is a more or less constant factor for each day. Reisner (1), and Quimby and MacComb (2, 3) have measured experimentally the daily potency of this recovery factor for skin up to a period of 30 days, and their figures more accurately represent the quantitative values of this recovery factor than any hitherto published. The quoted values of the recovery factor after approximately the first week have a somewhat diminished significance because, with increased protraction of fractionated doses of radiation, comes an increase in the variation of individual skin reactions. After approximately the third week of daily treatments, new phenomena begin to manifest themselves and divide the period of treatment into two types of phases, the destructive phase and the healing phase. These phenomena seem to be governed by the healing process, a mechanism which appears to be distinct from the ...

Concepts of radical irradiation therapy

Radical irradiation for advanced can cer, like radical surgery, accepts a de gree of risk of damage to normal tissue in exchange for increased survival rates. Radiation damage may be tolerated as a permanent disability or may be repaired surgically. It can be minimized by special precision techniques based on a knowl edge of the tolerance doses of normal tis sues. Before proceeding with the detailed dis cussion of the techniques, the premises on which they are based must be made clear.