Complications of radiation therapy: The genitourinary tract

Complications of Radiation Therapy: The Genitourinary Tract Bernard S. Aron, M.D., and Adolph

R

ADIATION effects on normal tissue are inherent in the radiation treatment of patients with cancer. The aim of the radiation therapist is to achieve the highest possible cure rate with the lowest possible complication rate; to avoid these complications entirely would mean lowering the cure rate. Radiation effects may be acute, occurring during the course of treatment, or subacute or chronic, arising months or years after treatment has been completed. One of the basic problems the clinician and radiologist face is to differentiate radiation effect from recurrence of cancer. The anatomic areas covered in this paper include the kidneys, ureters, bladder, male and female genital tracts, and the embryo and fetus. The clinical conditions include lymphoma and neuroblastoma; cancer of the cervix, uterus, ovary, kidney, bladder, prostrate, and rectosigmoid; and vertebral body and spinal cord tumors. The ovary, testis, embryo, and fetus may also be irradiated inadvertently during diagnositc radiologic examination or radioisotope study. KIDNEY,

URETER,

AND

BLADDER

Kidney

Implication of the urinary system as an aftermath of radiation therapy primarily concerns itself with reactions in the kidney and bladder; the ureters are generally considered to be virtually radioresistant .4 The prevention of radiation injury to the urinary system requires accurate volume determination of the area to be treated and precise renal localization through the use of IV!? or renal scan. A dose of 2300 R in 5 wk to the kidney is Bernard S. Aron, M.D.: Attending Radiation Therapist, Cincinnati General Hospital; Professor of Radiology, b?iversity of Cincinnati College of Medicine, Cincinnati, Ohio 45229. Adolph Schlesinger,M.D.: Associate Radiologist, Jewish Hospital; Assistant Clinical Professor of Radiology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229. 0 1974 by Grune & Stratton, Inc.

Seminars in Roentgenology,

Vol.

IX, No. 1 (January),

1974

Schlesinger, M.D.

considered to be the threshold dose.” Doses of 2800 R in a 5-wk period are too high and will result in radiation damage.S Congenital lesions of the kidney, unusual position, ischemia, and previous infection should be considered when treatment will encompass the kidneys, since these factors adversely influence the radiation reaction.’ Smaller treatment volumes and increased fractionation help to keep radiation reaction to a minimum. It has been shown that intraarterial epinephrine protects the normal renal substance by producing arterial spasm and anoxia during irradiation.23 Actinomycin-D does not appear to enhance the effect of radiation therapy. Triiodothyronine also seems to potentiate the effect of radiation.12 Classically, the changes sustained by the kidney have been categorized as follows: acute radiation nephritis, chronic radiation nephritis, benign hypertension, malignant hypertension, and proteinuria. Acute radiation nephritis. This syndrome usually develops after a latent period of 6-13 mo in adults and a somewhat shorter interval in children.” Luxton reported it in 13 of his 27 casesof radiation nephritis.” Early, the symptoms are minimal except for occasional nocturia.” Later, edema, dyspnea on exertion, hypertension, headache, nocturia, lassitude, and vomiting are frequent complaints attributable to hypertension and uremia. Hypertensive retinopathy also occurs, consisting of white exudates, hemorrhages, and papilledema. Headaches are typical of hypertension. When anemia develops, it is usually normochromic and normocytic. The white blood cell count is within normal limits. The anemia is resistant, responding only to transfusions. The level of hypertension varies from patient to patient. The blood pressure does not appear to be of prognostic significance unless it is associated with anemia and an elevated blood urea nitrogen. The blood urea nitrogen is of some prognostic value since all five patients with levels of more

65

66

than 100 mg/lOO ml died.” The severity of the edema and the blood urea nitrogen level are significant in the early evaluation. The urinary changes consist of albuminuria of OS-4 g/liter with specific gravity less than 1.012. Usually, there is no hematuria. Epithelial, granular, or hyaline casts are common. Pathologically, the kidney is normal in size with capsular thickening and subcapsular petechiae. There is widespread damage to glomeruli and tubules. Interstitial fibrosis is increased between the tubules. The disease may regress but the patient never fully recovers. Renal function progressively deteriorates, ultimately leading to chronic radiation nephritis. Serial renograms usually show evidence of impaired renal function despite normal IVP during the latent period. Those who die from acute radiation nephritis do so 5-12 mo after onset of the syndrome. Chronic radiation nephritis. This condition closely resembles chronic glomerulonephritis. It is compatible with long life; 14 of 22 patients reported by Luxton were alive IO-14 yr after therapy.” Chronic radiation nephritis may arise de novo or as an aftermath of the acute stage. The signs and symptoms of acute radiation nephritis persist into this stage. Proteinuria, anemia, and azotemia are invariably present. The blood pressure usually falls but not to normal levels. Casts are generally present in the urine. The IVP is commonly normal. The primary lesion is believed to be glomerular damage with secondary tubular atrophy. Intertubular fibrosis and fibrinoid necrosis of the arterioles and interlobular arteries are also seen.” IVP shows progressive contraction in size of the affected kidney or kidneys (Fig. 1); similar changes are noted with benign or malignant hypertension. Benign and malignant hypertension. Benign hypertension is associated with a variable amount Most individuals are asymptomof proteinuria.” atic and the prognosis is thought to be good. A few go on to develop malignant hypertension.” It is not always possible to attribute the hypertension to radiation treatment, since in some

ARON

AND

SCHLESINGER

individuals the blood pressure prior to therapy was unknown. The exact mechanism for development of the hypertension is unknown. Possibly it relates to endothelial damage that may initiate the release of renin and angiotensin. Radiation may sensitize the vessels to hypertensive changes. Hypertension has also been reported after total body radiation in which the kidneys were shielded.12 Late malignant hypertension usually starts about 12 mo after treatment. In Luxton’s series, it occurred in 15 of 54 patients (28%).’ Deterioration was rapid in two patients, who died within 6 wk after onset of hypertension. This was associated with hypertensive encephalopathy and brain stem hemorrhage. Others have reported latent periods up to 13 yr after treatment. Crummy reported a patient in whom hypertension occurred 18 yr after radiation therapy to both kidneys.’ One kidney that appeared abnormal had received 3300 R. It was removed 24 yr after irradiation and blood pressure returned to normal. The other kidney had received only 600 R. Histologically, both kidneys may be normal, contracted, or only one may be small. The hypertension usually responds to antihypertensive drugs. Proteinuria. Individuals with radiation proteinuria may be asymptomatic for years. The excretion of the protein may be minimal and intermittent. Renal tubular function studies may be within normal limits.12 Radiation Changes of the Bladder With the advent of supervoltage x-ray therapy, the number of complications have become minimal and usually only a mild cystitis ensues. Certain factors, however, contribute to an increased incidence of cystitis such as surgery within 3 wk preceding therapy (transurethral resection, biopsy, suprapubic cystostomy, or sigmoid resection). Other problems, such as obstruction of the bladder neck, urethral stricture, gross infection, extensive ulcerating tumor, previous x-ray therapy to the area, treatment beyond the capabilities of the normal tissues or combinations of these factors, may also contribute to an increased incidence of

THE GENITOURINARY

TRACT

67

Fig. 1. Effect of radiation in the kidney. (A) IVP prior to treatment for lymphosarcoma of the stomach. The stomach There is decreasa in size of the upper pole receive td 3600 rads in 34 wk. (81 Eleven years later. The patient is hypertensive. of the left kidney and compensatory hypertrophy of the right kidney. (Courtesy of Dr. Martha E. Soulhard, Philadelphia, Pa.)

68

reactions.3 Bladder complications occur in 5% of women who receive radiation for cancer of the cervix.” Early bladder changes. Usually, problems arise when utilizing 3000 R over a 3-4-wk period. Some individuals may experience mild dysuria and frequency, usually starting at about 4-6 wk after therapy. r2 Bladder tolerance is in the range of 6500-7500 R in 6-8 wk. When cancericidal ranges of 6000-7000 R are approached, a severe acute reaction usually ensues, lasting 3-4 wk. Pathologically, hyperemia, petechiae, ulcers, and connective tissue edema occur and may progress to desquamation. Clinically, there may be only painless hematuria. Severe cystitis may occasionally lead to toxemia and uremia. Hydronephrosis, pyelonephritis, and even death may follow. The cystitis is commonly associated with infection by gram-negative organisms. Frequently, one of these complications may cause an ascending infection. Bladder ulcers may ensue within 6-24 mo after external radiation therapy, although they can appear later.3 The ulcers are usually localized to the trigone, rarely in the dome and may require 6 mo to heal. Complications can be kept to a minimum by allowing at least 3 wk after surgery before initiating supervoltage therapy, by eliminating urinary obstruction, by localizing the bladder port through the use of cystograms, using proper dosimetry, and by avoiding repeated courses of external radiation therapy. Bilateral ureteral obstruction .is a contraindication to irradiation of the bladder; unilateral obstruction is not.3 There are not any specific radiographic findings of radiation cystitis; usually there is increased irritability and contractility. Occasionally, the bladder capacity may be small in the early stages. Rarely, one seesstasis in the pelvic segments of the ureters.4 Late bladder complications. Radiation reaction in the bladder may develop 1-4 yr after treatment, but with high doses it can appear earlier. The frequency of chronic radiation reaction in the bladder increases with faulty radiation techniques or if an anteflexed uterus is present. Interstitial fibrosis, obliterative endarteritis, and

ARON

AND

SCHLESINGER

telangectasia are frequent pathologic findings within the irradiated bladder. Ischemia leads to epithelial atrophy or necrosis with the development of ulcers, fissures, and/or fistulas. When proper technique for cervical cancer is utilized, there should be few instances of rectal or bladder complications. Occasionally, a small contracted bladder may result from fibrosis and induration of the bladder wall. Ureteral, vesical, rectovesical, and vesicovaginal fistulas are usually the result of poor radiation technique, especially too large a dose. Rarely, intestinal obstruction or necrosis due to adhesions after therapy or overirradiation may occur.4 Figure 2 shows rectovaginal and vesicovaginal fistulas 21 yr after curative therapy in a patient with stage II B carcinoma of the cervix. Hemorrhagic cystitis, developing 2 mo to 2 yr after treatment, seldom shows a bleeding site at cystoscopy. Biopsy is consistent with radiation changes. Diatherapy or urinary diversion alone or with internal iliac artery ligation may not control the bleeding,14 and cystectomy may be necessary. The bladder may become contracted 2 mo to 6 yr after treatment. Generally, the capacity is reduced to less than 50 cc. There is free reflux up the ureters, which are not distensible. Ureteroileostomy is the procedure of choice because the ureters and sigmoid are often involved in the radiation changes. IVP shows a small contracted bladder with a thick wall; bilateral hydronephrosis and hydroureter may also be present. Radiation Changes in the Ureters The ureters appear to have uniformly good tolerance to the effects of radiation; there is a rarity of late complications. In Kottmeier’s series, only 20 of 3484 patients developed hydronephrosis in the absence of recurrent tumor.’ It appears that the actual dose is not the important factor for development of postradiation ureteral changes, since they are also seen with low doses. For this reason, whole pelvic radiation therapy is not thought to lead to ureteral fibrosis.’ If periureteral fibrosis does occur, the reaction is probably due to destruction of cancer tissue with resultant necrosis, fibrosis, and parametritis.

THE

GENITOURINARY

69

TRACT

Fig. 2. Rectovaginal and vesicovaginal fistulas. Lateral film during Renografin-66 enema shows opacification of vagina, bladder, and rectum. Two and one-half years earlier the patient had received 5666 rads whole pelvis 6oCo irradiation in 17 treatments over 37 days, followed by a single 66-hr insertion of an Ernst applicator loaded with 50 mg radium. (Courtesy of Dr. Martha E. ‘Southard. Philadelphia, Pa.)

The strictures may appear either as a localized lesion of the distal ureter or as a long thread-like narrowing of the pelvic ureter. Ureteral catheterization may predispose to stricture formation. Infection is a potent factor in predisposing to ureteral obstruction and in patients with pelvic inflammatory disease. Bilateral salpingo-oophorectomy has been recommended prior to irradiation to circumvent this problem.’ MALE

GENITAL

TRACT

Testes Radiation destruction of the relatively sensitive seminiferous epithelium causes loss of sperm

production without loss of sex hormone production. Significant postirradiation damage is seen first in the spermatogonia, which are reduced in number; the amount of reduction depends on the dose of radiation. The more resistant spermatocytes and spermatids are less affected by radiation, so that spermatogenesis may proceed normally. The spermatogonia may regenerate, depending on the radiation dose, over a period of weeks or months, so that fertility may be recovered. There is little damage to Sertoli and Leydig cells; testosterone production, which maintains secondary sexual characteristics, is thus unaffected. Although there is a range of dose effects in the human testis,

70

it appears that a single dose of 250 R causes temporary sterility for about 12 mo with eventual recovery of spermatogonia,20 a single dose of 600 R causespermanent loss of spermatogonia and permanent sterility. Clinically, there is no overt sign of radiation injury to the testes; eventually they become smaller and softer. There is no apparent change in beard, voice, or social behavior. Although potency is retained, seminal and prostatic fluid are produced without spermia. Diagnosisof radiation injury is made on sperm count in the semen. Radiation castration is not a useful procedure in the treatment of patients with metastatic carcinoma of the prostate becausetestosteroneproduction persists; surgical castration is necessary. Protection of the testes by a lead shield is an absolute necessity when curative radiation is used to treat the femoral, inguinal, or pelvic nodes, as in Hodgkin’s disease-even then the dose to the testes may be 5%-10% of the tumor dose (4000 rads). Prostate and Seminal Vesicles

These structures are relatively radioresistant,and symptomatic radiation damageis rarely produced in the adult even after very high dosesof irradiation. Potency was maintained in 70% of 96 patients treated for carcinoma of the prostate using dosesof 7500-7800 rads in 7-8 wk.” Penis and Urethra

The prostatic urethra is relatively resistant and radiation injury is rare even after high doses of radiation. In the management of prostatic carcinoma,” urethral stricture occurred in 12 of 310 patients (4%). All of these patients received more than 7800 rads in 8 wk or had more than two transurethral resectionsbefore radiation. The penile skin shows the gamut of acute and chronic skin reactions after irradiation. Tumoricidal doses that cured 18 of 20 patients with squamouscell carcinoma of the penis resulted in skin necrosis in two and urethral stricture in six.’ It should be noted that the alternative treatment would have been amputation of the penis in all 20 patients.

ARON

FEMALE

GENITAL

AND

SCHLESINGER

TRACT

Radiation destruction of the relatively sensitive ovarian epithelium produces both loss of ovum production (sterility) and loss of sex hormone production (artificial menopause).Significant postirradiation damageis seenfirst in the proliferating granulosa cells with subsequent loss of follicles. The early graafian follicles are more sensitivethan the late ones.After granulosacell injury, the oocyte degeneratesand the follicle becomesatrophic. Small dosesof radiation (170-250 R) may cause temporary amenorrheawith reduction in the number of mature and developing follicles. Recovery of the follicles may take severalyears and is often incomplete, resulting in premature menopause. With higher doses of irradiation (500-625 R), there is permanent sterility and the ovaries show complete absenceof primordial follicles, atrophic follicles, degeneration of corpora lutea and interstitial gland cells, progressivevascularsclerosis,and replacementfibrosis.is Single dosesof about 500 R yield permanent sterility in 9% of women over 40; doses of 625 R appear necessaryto achieve this in younger women. The usual clinical dose employed in radiation castration for metastatic breast carcinoma is in the range of 1000-1500 R delivered in 1 wk. Clinically, the patient usually showsone normal menstrual period after radiation; subsequently one or two short periods with scanty menstrualflow may occur. The menopausalchanges that occur are similar to those of normal physiologic menopause (hot flashes, etc.). Changesin hormone production after irradiation are similar to those after bilateral oophorectomy.6 Oophoropexy, surgicalplacement of both ovaries and their attached pedicles in the midline of the pelvis so that they may be shielded during radiation to the pelvic nodes for Hodgkin’s disease,has resulted in preservation of ovarian function in 12 of 22 women; one has delivered a normal child.lg Uterus

Both the corpus and cervix are very radioresistant and are an ideal radium container in the managementof cervical and corpus carcinoma.As

THE GENITOURINARY

71

TRACT

these tumors frequently occur in postmenopausal women or in women who undergo postirradiation menopause, the loss of ability to carry a pregnancy to term is of no serious consequence. The standard intrauterine and intravaginal radium systems deliver a dose of lO,OOO-20,000 rads to the mucosa. The usual results are scarring, fibrosis, and atrophy. Severe cervical necrosis is rare in the absence of recurrent carcinoma. When present, it usually responds quickly (within l-2 wk) to antibiotics and hydrogen peroxide douches. If necrosis persists, biopsy for recurrent neoplasm is indicated. Vagina and Vulva The response of vaginal mucosa to radiation is similar to that of mucous membranes elsewhere in the body, with the production of acute erythema, moist desquamation, confluent mucositis, and healing with fibrosis. Severe late scarring with fibrosis and atrophy creates problems for the patient, as sexual intercourse becomes difficult and painful. Also it is difficult for the physician to visualize the cervix on follow-up examinations. The incidence of these vaginal complications can be lowered by topical estrogen therapyl’j and the use of a vaginal dilator. Vesicovaginal and rectovaginal tistulas have already been discussed. The response of perineal tissues, vulva, labia, and clitoris to radiation is similar to skin; however, due to the intertriginous and moist nature of the’ perineum, these tissues tolerate radiation poorly. Moist desquamation occurs after doses lower than those expected to cause skin reaction and necrosis in other areas. Extensive tumors of the labia are usually treated surgically (radical vulvectomy), with radiation (radium needle implants) reserved for small lesions. Occasionally, edema of the genitalia and the lower extremities is a sequela of radiation treatment. No systemic or local cause is found. Fibrosis of the lymphatics, lymph nodes, and iliac vessels has been found at autopsy in such cases, and is probably the cause. THE

EMBRYO

AND

FETUS

Many congenital abnormalities have been experimentally induced by irradiation of mammalian

embryos (especially the mouse and rat). Direct information concerning irradiation effects on human embryos is inadequate. Extrapolation of experimental data from animal to man should be regarded with great caution. Although there are qualitative similarities between experimental and human anomalies attributed to radiation, these anomalies are not specific for radiation, and quantitative dose relationships have not been accurately defined for man. This section is a general summary of the radiation effects. For a detailed description, the excellent review of Rugh should be consulted.2L Irradiation of any embryo or fetus may result in the death of the embryo or in the production of congenital anomalies. The basic mechanism is either cell destruction or sublethal irreparable damage that interferes with the normal proliferation and differentiation of cells. Different effects are produced when irradiation is given at different times during gestation. The three major effects are death of the embryo, congenital anomalies, and reduced growth with associated functional deficits and carcinogenesis. Within each time period, larger doses increase the incidence of these effects. The most radiosensitive period for the lethal effect of irradiation is the first 3 wk of human embryonic development. Doses in the range of 5-l 5 R increase lethality in rat zygotes but produce few gross congenital anomalies. The period of organ differentiation and formation in the human is the first trimester, especially from 3-6 wk after fertilization. This is the most sensitive time for radiation induction of congenital anomalies. Sensitivity to radiation lethality is less than in the first 3 wk. A wide range of congenital anomalies may be produced, primarily involving the central nervous system but also affecting the eyes, skeleton, and other organ systems. Significant anomalies include anecephaly, microcephaly, encephalocele, mental retardation, microphthalmia, absence of lens, abnormal limbs, situs inversus, and absence of kidneys. Rugh lists 50 major abnormalities found in the mammal following fetal irradiation.2’ After the organs have differentiated and are primarily involved in growth, susceptibility to radiation lethality and congenital anomalies is re-

72

ARON

duced. Radiation now producespathologic damage with loss of cells in tissues and organs, growth disturbances,functional deficits, and induction of malignancy. Mayer et al. produced abortion in 96%of patients in early pregnancy(6-16-wk gestation) with 400 R

AND

single dose to the fetus.r3 The interval between radiation and induced abortion was about 4, wk. Reactions to treatment were minimal; febrile and toxic symptoms did not develop. If spontaneous abortion does not occur, surgical abortion is indicated as an abnormal fetus will frequently result.

Table 1. Dose From Roentgenography

and F~uoroscopyl Gonadal

Examination

Lumbar spine

Lumbosacral spine Pelvis

Sacrum Thigh Abdomen

IVP

Chest

Upper GI series

Small bowel series

Barium

enema

Hysterosalpingography

Myelography

Projection

AP Lateral Tomo. AP Lateral AP Lateral Oblique Tomo. AP Lateral AP Lateral AP PA Lateral Oblique AP (KUB) AP bladder Tomo. PA Fluoro. konv.) Fluoro. (image) Fluoro. konv.) Fluoro. (image) spot AP Fluoro. konv.) Fluoro. (image) spot AP AP Fluoro. (conv.) Fluoro. (image) Fluoro. konv.1 Fluoro. (image) spot Oblique AP stereo Fluoro. (conv.) Fluoro. spot

(image)

SCHLESINGER

KVP

100 120 80 120 100 120 100 120 100 120 100 100 100 100 120 100 120 120 120 100 90 90 90 90 90 100 90 90 90 120 120 90 90 90 90 90 120 120 120 120 90

Male

MA

30 60 160 70 30 70 40 20 30 60 20 20 20 20 60 30 30 30 20 5 3.0 0.5-l .o 3.0 0.5-l .o PHT 20 3.0 0.5-l .o PHT 20 20 3.0 0.5-l .o 3.0 0.5-I .o PHT 30 30 3.0 0.5-I .o PHT

Added filtration 2.5 mm Al,except for image fluoro.-3.0 mm Al, F.F.D.-36 film size-8 X 10 in to 14 X 17 in. Collimators used in all radiography. PHT, phototimer.

Dose-m

rad Female

14.7 9.8 31 55 83 55 110 85 83 55 108 16.7 11.6 3-3 9.8 17

16

70.4 61.5 148 82 79 82 110 81 79 82 60 14 51 16 61.5 77 132 105 80 0.04 1.52/min 0.36/min 81.1 lmin 12.8/min 2.68 51.1 320Imi n 77Imin 52 68 132 562/min 140lmin 560/min 140/min 61 110 73 200/min 45/min 94

to 40 inches,except

for chest (72 in). Usual

60.2 181 12 0.02 0.34/min

O.O3/min 12.4/min 0.35/min 0.07 11.6 37/min 5.7/min 15 30 60.2 62/min lllmin

25lmin Blmin

THE

GENITOURINARY

73

TRACT

Tabla 2. Dose From Radioisotope

Diagnostic

Procedures* Gonadal

Radioisotope

Examination Brain

99mTc O4 t97Hgchlormerodrin

Thyroid

131 , 123,

Lung

Liver

Pancreas Bone Kidney

Spleen Blood pool (placenta and cardiac) Myocardium Schilling test Tumor scan

99mTc 04 99mTc-M.A.A. 131 I-M.A.A. 133 Xe t98Au colloid 99mTc SC 139mln colloid 1st I rose bengel 7sSe methionine 8sSr l*F 197 Hgchlormerodrin 99mTc-DTPA 131 I-Hippuran slCr labeled RBC 99mTc-HSA 99mTc 04 131 I-HSA s1Cr labeled RBC 124 cs 57Co B12 67Ga citrate

Subsequent sterility and amenorrhea are common in patients treated with this dose of radiation. This method of inducing abortion has an obvious advantage over surgical interference in severely debilitated patients. There is very little information as to recommendations for therapeutic abortion after incidental irradiation to a pregnant woman. Saenger** has summarized the recommendations of Hammer and Jacobsen, based on 11 cases, as: (1) Dose of less than 1 R: therapeutic abortion not indicated. (2) Dose of l-10 R: individual evaluation, therapeutic abortion probably advisable. (3) Dose greater than 10 R: therapeutic abortion is urged. Radiation exposure of pregnant females may be avoided by limiting diagnostic radiologic procedures in the first 2 wk after menses, but this is not a practical approach. Avoidance of unnecessary exposure of known pregnant women is desirable; the radiation dose to the fetus and gonads from different diagnostic procedures is presented in

Amount 15mCi 500 mCi 100 &i 300 j.rCi 3 mCi 3 mCi 300 I.rCi 10 mCi 150 &i 3 mCi 3 mCi 300 CrCi 200 /.&i 100 &i 4 mCi 100 &i 2 mCi 200 pCi 300 j&i 1 mCi 300 pCi 5 I.tCi 20 /.rCi 4 mCi 0.5 jrtci 3 mCi

Male

185 55 250 3 37 20 65 4 16.5 57

47 9.6 2000 290 240 1 .l 40 3.2 90 90 5 8.5 4.4 1600 0.39 1920

Dose-m

rad

Female 270 13 150 6 54 20 65 4

37.5 69 56 51.9 2000 290 280 2.6 40 32 60 90 5 8.5 4.4 1600 1.05 1920

Table 1, adopted from Antoku and Russell,’ and Table 2, adopted from Ashare’ and may be used as a general guide to radiation exposure; detailed dose calculations should be made for each individual patient. Coincident cancer and pregnancy occur most frequently with squamous cell carcinoma of the cervix but can be seen with other tumors, such as Hodgkin’s disease and breast cancer. Therapy must be individualized depending on both the stage of the disease and the trimester of the pregnancy. REFERENCES 1. Antoku S, Russell, WJ: Dose to the active bone marrow, gonads, and skin from roentgenography and fluoroscopy. Radiology 101:669-678, 1971 2. Ashare A: Personal communication 3. Bloedorn FG, Young JD, Cuccia CA, et al: Radiotherapy in carcinoma of the bladder: possible complications and their prevention. Radiology 79:576-581, 1962 4. Chau PM, Fletcher GH, Rutledge FN, et al: Complications in high dose whole pelvis irradiation in female pelvic cancer. Am J Roentgen01 87:22110, 1962

74 5. Crummy AB Jr, Hellman S, Stansel HC Jr, et al: Renal hypertension secondary to unilateral radiation damage relieved by nephrectomy. Radiology 84: 108-l 11, 1965 6. Diczfalusy E, Notter G, Edsmyr F, et al: Estrogen excretion in breast cancer patients before and after ovarian irradiation and oophorectomy. J Clin Endocrinol Metab 19:1230-1244,1959 7. Duncan W, Jackson SM: The treatment of early cancer of the penis with megavoltage x-rays. Clin Radio1 23:246-248, 1972 8...Graham JB, Abad RS: Ureteral obstruction due to radiation. Am J Obstet Gynecol99:409-412, 1967 9. Kottmeier HL: Cancer of the Female Genitalia. Baltimore, Williams & Wilkins, 1953 10. Luston RW: Radiation nephritis. Quart J Med 22:215-242,1953 11. Luxton RW, Kunkler PB: Radiation nephritis. Acta Radio1 (Stockh) 2:169-178, 1964 12. Maier JG: Effects of radiation on kidney, bladder and prostate, in Vaeth JW (ed): Frontiers of Radiation Therapy and Oncology, vol 6. Baltimore, University Park Press, 1972, pp 196-227 13. Mayer MD, Harris W, Wimpfheimer S: Therapeutic abortion by means of x-ray. Am J Obstet Gynecol 32:945-957,1936 14. Q’Malley B, D’Angio GJ, Vawter GF: Late effects

ARON

AND

SCHLESINGER

of roentgen therapy given in infancy. Am J Roentgen01 89:1067-1074,1963 15. Peck WS, McGreer JT, Kretzschmar NR, et al: Castration of the female by irradiation: the results in 334 patients. Radiology 34: 176-l 86, 1940 16. Pitkin RM, VanVoorhis LW: Postirradiation vaginitis: an evaluation of prophylaxis with topical estrogen. Radiology 99:417-421, 1971 17. Rams MD: Complications of radiotherapy for carcinoma of the bladder. Proc Roy Sot Med 63:93-95, 1970 18. Ray GR, Cassady JR, Bagshaw MA: Definitive radiation therapy of carcinoma of the prostate: a report on 15 years of experience. Radiology 106:407-418, 1973 19. Ray CR, Trueblood HW, Enright LP, et al: Oophoropexy: a means of preserving ovarian function following pelvic megavoltage radiotherapy for Hodgkin’s disease. Radiology 96: 175-180, 1970 20. Rubin P, Casarett GW: Clinical Radiation Pathology. Philadelphia, Saunders, 1968 21. Rugh P: The impact of ionizing radiations on the embryo and fetus. Am J Roentgen01 89:182-190,1963 22. Saenger EL: Radiologists, medical radiation, and the public health. Radiology 92:681-699, 1969 23. Steckel RJ, Tobin PL, Stein JJ, et al: Intra-arterial epinephrine protection against radiation nephritis: a progress report. Radiology 92:1341-1345,1969