Information concerning radiation-induced malignancies comes from the A-bomb survivors and from medically exposed individuals, including second cancers in radiation therapy patients. The A-bomb survivors show an excess incidence of carcinomas in tissues such as the gastrointestinal tract, breast, thyroid, and bladder, which is linear with dose up to about 2.5 Sv. There is great uncertainty concerning the dose-response relationship for radiation-induced carcinogenesis at higher doses. Some animal and human data suggest a decrease at higher doses, usually attributed to cell killing; other data suggest a plateau in dose. Radiotherapy patients also show an excess incidence of carcinomas, often in sites remote from the treatment fields; in addition there is an excess incidence of sarcomas in the heavily irradiated in-field tissues. The transition from conventional radiotherapy to three-dimensional conformal radiation therapy (3D-CRT) involves a reduction in the volume of normal tissues receiving a high dose, with an increase in dose to the target volume that includes the tumor and a limited amount of normal tissue. One might expect a decrease in the number of sarcomas induced and also (less certain) a small decrease in the number of carcinomas. All around, a good thing. By contrast, the move from 3D-CRT to intensity-modulated radiation therapy (IMRT) involves more fields, and the dose-volume histograms show that, as a consequence, a larger volume of normal tissue is exposed to lower doses. In addition, the number of monitor units is increased by a factor of 2 to 3, increasing the total body exposure, due to leakage radiation. Both factors will tend to increase the risk of second cancers. Altogether, IMRT is likely to almost double the incidence of second malignancies compared with conventional radiotherapy from about 1% to 1.75% for patients surviving 10 years. The numbers may be larger for longer survival (or for younger patients), but the ratio should remain the same.

Radiation-induced second cancers: the impact of 3D-CRT and IMRT

An analysis is,,presented of responses of a variety of normal tissues in animals to fractionated irradiations. It is shown that the influence of fractionation can be described on the basis of a simple formula relating the effectiveness for induction of cellular effects to the dose per fraction: F(D) = 1D + a2D2. The ratio a 1 a 2 is derived as an essential parameter for, the description of fractionation effects. It is concluded that the values of a 1 a 2 for responses of various tissues range widely from 2 to 10 Gy. On the basis of the review of radiobiological data, a formalism is developed for the analysis and prediction of iso-effect relations for tissue tolerance, which can be used as an alternative to the nominal standard dose (NSD) formula of Ellis and its derived equations. An essential characteristic of the formalism is that three groups of tissue responses are distinguished which can be described with respect to fractionation effects by average values of a l a 2 = 10 ; 5 and 2.5 Gy, respectively. These groups comprise a l: a.o. skin and intestine; 2: connective tissue; 3:a.o. lung and vascular system. Dose rate effects can be described by a similar formalism. For the calculation of equivalent total doses to be applied in clinical treatments, a concept denoted Extrapolated Tolerance Dose (ETD) of Extrapolated Response Dose (ERD) is introduced. ETD is the tolerance dose for an infinite number of very small fractions. This concept is shown to be useful for the summation of different fractionated schedules and of low dose rate treatments. A number of examples is presented illustrating similarities and differences in comparison with calculations based on the NSD formula. An important feature of the described formalism is that it is directly based on radiobiological insights and it provides a more logical concept to account for the diversity of tissue responses than the assumption of different exponents of N and T in the NSD formula.

Dose fractionation, dose rate and iso-effect relationships for normal tissue responses

Ascertainment of breast cancer incidence among the cohort of the RERF Life Span Study extended sample identified 574 breast cancers among 564 cases diagnosed during 1950-1980 of which 412 cancers were reviewed microscopically. There were no dose-dependent differences with respect to diagnostic certainty or histological type. As in previous studies, the dose response appeared to be roughly linear and did not differ between the two cities. The most remarkable new finding was the emergence of a radiation-related excess among women under 10 years of age at exposure. The risk of radiogenic breast cancer appears to decrease with increasing age at exposure, whether expressed in relative or absolute terms. These results suggest that exposure of female breast tissue to ionizing radiation at any time during the first four decades of life, even during the premature stage, can cause breast cancer later in life, and that the length of time that tumor promoters such as endogenous hormones operate following exposure has an important influence on the development of radiation-induced breast cancer. An unresolved question is whether breast cancer risk is increased by radiation exposure at ages older than 40.

Incidence of female breast cancer among atomic bomb survivors, Hiroshima and Nagasaki, 1950-1980.

BACKGROUND
Endometrial assessment by means of biopsy or sampling of endometrial cells is a minimally invasive alternative for dilatation and curettage (D&C) or hysteroscopy The use of this technique is believed to reduce the cost of the diagnostic work-up for abnormal uterine bleeding without reducing accuracy Because the authors were not aware of any systematic review of this test, they performed a meta-analysis to assess the accuracy of endometrial sampling devices in the detection of endometrial carcinoma and atypical hyperplasia

METHODS
The authors searched the literature for studies published between 1966 and 1999 comparing the results of endometrial sampling with findings at D&C, hysteroscopy, and/or hysterectomy They found 39 studies that included 7914 women For each study, the fraction of patients was calculated in which endometrial sampling failed Furthermore, the authors calculated the fraction of cases of endometrial carcinoma and atypical hyperplasia that were identified correctly as well as the fraction of women in whom these diseases were diagnosed false positively

RESULTS
The detection rate for endometrial carcinoma was higher in postmenopausal women compared with premenopausal women In both postmenopausal and premenopausal women, the Pipelle was the best device, with detection rates of 996% and 91%, respectively For the detection of atypical hyperplasia, there was only one study that reported explicitly on postmenopausal women, thereby hampering the possibility of subgroup analysis Again, the Pipelle was the most sensitive technique with a sensitivity of 81% The specificity of all devices was > 98%

CONCLUSIONS
Endometrial biopsy with the Pipelle is superior to other endometrial techniques in the detection of endometrial carcinoma and atypical hyperplasia The accuracy of the Pipelle is higher in postmenopausal women compared with premenopausal women Cancer 2000;89:1765–72 © 2000 American Cancer Society

The accuracy of endometrial sampling in the diagnosis of patients with endometrial carcinoma and hyperplasia: a meta-analysis.

Approximately 4000 women per year in the United States require radiotherapy during pregnancy. This report presents data and techniques that allow the medical physicist to estimate the radiation dose the fetus will receive and to reduce this dose with appropriate shielding. Out-of-beam data are presented for a variety of photon beams, including cobalt-60 gamma rays and x rays from 4 to 18 MV. Designs for simple and inexpensive to more complex and expensive types of shielding equipment are described. Clinical examples show that proper shielding can reduce the radiation dose to the fetus by 50%. In addition, a review of the biological aspects of irradiation enables estimates of the risks of lethality, growth retardation, mental retardation, malformation, sterility, cancer induction, and genetic defects to the fetus.

Fetal dose from radiotherapy with photon beams: report of AAPM Radiation Therapy Committee Task Group No. 36.

Influence of Dose and Its Distribution in Time on Dose-Response Relationships for Low–LET Radiations

From 1965 through 1974, 88 patients with Stage B or C prostatic carcinoma were treated with radical megavoltage therapy. Treatment technique was small field arc alone for Stage B and 4 field box whole pelvis irradiation to 4400 or 5000 rad with small field rotational boost for Stage C. All were at risk for 5 years and 30 for 10 years or more. None of the 14 Stage B patients have died of cancer, although one is living with metastases. In Stage C (74 patients) uncorrected actuarial survival was 55% ± 5.8 (5 year) and 28% ± 6.5 (10 year). When corrected for intercurrent deaths, survival was 65 % ± 5.8 (5 year) and 37 % ± 8.1. Survival curves for those patients receiving 6000–6900 rad were not significantly different from those receiving 7000 rad or more. Local control may be better in the latter group, 82.7% (43/52) versus 71.4% (20/28), although this is, not significant. Thirty-one percent of local failures appeared after 5 years. Whole pelvis dose of 5000 rad was associated with a higher 5 and 10 year survival than 4400 rad but the difference was not statistically significant. Comparison between groups treated with radiation alone, versus radiation plus a simultaneous hormonal therapy showed no significant differences in survival, local control or complications. A group of 20 patients who failed hormonal therapy and were then irradiated did less well. Complications were generally mild, but early in the series 2 patients receiving 7500 rad developed ano-rectal necrosis; one of these patients died. More common problems were urethral stricture (12 % ) and ano-rectal stenosis (10%). Changes in technique in 1971 drastically reduced the subsequent complications. The failure of whole pelvic irradiation to improve on the 10 year results of local treatment is discussed.

Radical external radiotherapy for prostatic carcinoma.

The purpose of this study is to assess the accuracy and limitations of the outpatient endometrial biopsy in detection of endometrial carcinoma and atypical hyperplasia. This was done by reviewing all the endometrial material from the 891 women at this clinic whose first endometrial sample in 1974 was by the biopsy technique. The results of this material were correlated with subsequently available additional uterine samples obtained over a three year period by biopsy, dilatation and curettage, or hysterectomy. The detection rate by biopsy for the 21 cases of endometrial carcinoma proven by hysterectomy was 81%. There was a 5% false negative rate and no false positives. For the 25 cases of atypical hyperplasia proven by hysterectomy, the detection rate by biopsy was 68%. There was lack of hysterectomy confirmation in 33% and 24% false negatives. Insufficient material was obtained initially in 9% of the 891 women. Five percent of this group were found at hysterectomy to have either endometrial carcinoma or atypical hyperplasia. With an understanding of its limitations, the endometrial biopsy, although somewhat less accurate than the D & C, is considered to be a useful diagnostic tool for detection of these lesions.

https://acsjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/1097-0142%28197904%2943%3A4%3C1474%3A%3AAID-CNCR2820430438%3E3.0.CO%3B2-9

Evaluation of the office endometrial biopsy in the detection of endometrial carcinoma and atypical hyperplasia.

An Introduction to Physics for Radiologic Technologists by B. J. Graham and W. N. Thomas

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Influence of Dose and Its Distribution in Time on Dose-Response Relationships for Low–LET Radiations

Radical external radiotherapy for prostatic carcinoma.

Evaluation of the office endometrial biopsy in the detection of endometrial carcinoma and atypical hyperplasia.

An Introduction to Physics for Radiologic Technologists by B. J. Graham and W. N. Thomas