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Cancer in Pregnancy: Radiation in pregnancy

Professional Summary
Offspring of survivors of cancer who were treated by radiotherapy appear to be at little risk of childhood cancer or birth defects. Thus, in most instances, survivors of cancer should not be discouraged from having children and can expect a good outcome of pregnancy. To reduce the likelihood of an adverse fetal outcome, it is advisable to delay pregnancy for 12 months following completion of radiation therapy.

Radiologic Modes
The risks of fetal exposure to X-rays have been the subject of numerous studies over the last 50 years. The lack of clear information has given rise to unjustified panic among the public. Indeed, fear of X-ray-induced fetal defects has led some women with unsuspected pregnancy who underwent radiography to terminate the pregnancy. In addition, many doctors tend to refrain from prescribing necessary dental, chest or other X-rays to pregnant women.

The possible embryonic or fetal damage from radiation may be classified into two principal types. The first is teratogenic, or abnormal fetal development, which may occur on exposure to radiation in the first 12 weeks of pregnancy, when the embryo is in the stage of organogenesis. The second type is carcinogenic, or the induction of malignancy, which may occur on exposure to radiation in the second and third trimesters of pregnancy; these effects are manifested in the first decade of life.

The available information on radiation-induced embryonic damage is derived from animal studies, follow-up of individuals exposed to atomic bomb explosions in Japan, and statistical analyses. Based on these studies, the United States National Council on Radiation Protection recommends that even radiation levels of 5 - 10 cGy present no real danger to the embryo-fetus and the advantages gained by clinical diagnosis by far outweigh the negligible risk of embryonic damage.

To gain a proper perspective of the issue, natural radiation should be considered as well. In the Rocky Mountain areas of Colorado, New Mexico and Utah in the United States, the natural uranium content of the soil is very high and the attenuation of cosmic radiation by the atmosphere is diminished by the high altitudes. Thus, the annual level of radiation exposure per person exceeds that in other areas of the country by some 100 millirem. We might conclude that a fetus whose mother-to-be lives in, say, Colorado will receive, during the nine months of pregnancy, a surplus irradiation of 85 millirems. Since a routine chest X-ray of a pregnant woman exposes the fetus to 0.5 millirems, the fetus of a pregnant Colorado resident is exposed to a dose equal to that of 150 chest X-rays! At the same time, while millions of people, obviously including pregnant women, reside in Colorado, the state's incidence of cancer is actually about 35% below the national average. The probability of developmental damage or childhood cancer due to embryonic-fetal irradiation of 1 cGy does not exceed 1:1,000, and may well be only 1:10,000 or even zero. These figures are negligible when compared to the overall 4 - 6% rate of birth defects in the general population. Furthermore, in only one of every 1,000 diagnostic X-ray examinations of pregnant women is the level of radiation to which the fetus is exposed equal to or greater than 1 cGy. In radiologic examinations outside the abdominal region, the dose to the embryo-fetus is almost always lower than 1 cGy (usually much lower) and the risk of damage is negligible, and in pelvic and lower-abdominal X-rays the dose to the fetus is rarely above 5 cGy, i.e., within safe limits.

We conclude that only very rarely, if at all, will the level of embryo-fetal irradiation in diagnostic radiography justify the termination of a pregnancy. Only in women who have undergone several X-ray examinations in which the fetus is directly exposed to radiation, or when both radiographic and fluoroscopic or CT examinations have been performed, is it necessary to calculate or measure the level of radiation; and only when that level is found to be above 5 - 10 cGy should abortion be considered.

Radionuclide Examinations
amount of time radioactive atoms remain in the body depends on the combination of the isotope's biological half-life, or rate of its elimination by excretion, and its physical half-life. In pregnant patients undergoing radionuclide examinations, radiation may reach the embryo-fetus via the penetrating gamma rays and X-rays emitted by radionuclides concentrated in maternal organs or the placenta, or by radionuclides taken up by the fetus after they cross the placenta. In either case, the dose to the embryo-fetus from most nuclear diagnostic examinations will be less than 1 cGy.

When radioactive isotopes of iodine are used, and especially when a pregnant woman is administered a therapeutic dose of I-131, the irradiation of the fetal thyroid depends to a large degree on the amount of radioactive material crossing the placenta, the degree of uptake by the gland itself, and the gestational age (the normal period for onset of thyroid function is 10 - 12 weeks).

Detailed information regarding both x-ray exposure and radionuclide examination can be found in "Exposure of the pregnant patient to diagnostic radiation: A guide to medical management", by L.K. Wagner, R.G. Lester, L.R. Saldana (Medical Physics Publishing, Madison, Wisconsin, 1997).

Radiotherapy
Physicians faced with a pregnant woman who requires radiation therapy for cancer may be inclined to advocate abortion for fear of possible injury to the fetus. Radiation doses used in cancer therapy are usually in the range of 4000 - 7000 cGy, i.e., 104 - 105 times the level in diagnostic radiology.

The dose to the embryo-fetus will depend on several factors:

  1. the teletherapy machine used and its leakage;
  2. the target dose;
  3. the size of the radiation fields;
  4. the distance from the edges of the fields to the embryo-fetus; and
  5. the use of wedges, lead blocks, compensators and other scattering objects.

Lesser leakage, lower target dose, smaller radiation fields, greater distance of the edges of the radiation fields from the embryo-fetus, and avoidance of wedges and other scattering objects will all decrease the radiation dose to the embryo-fetus. A distance of over 30 cm from the field edges will yield an exposure of the embryo-fetus to only 4 - 20 cGy. Thus, many areas (head and neck, breast, extremities) can be treated with radiation without significantly irradiating the embryo. Lead shielding over the embryo-fetus can also be used to reduce the dose. A qualified medical physicist should be consulted, and the dose levels to the embryo-fetus should be determined for every case.

Types of Cancer Requiring Radiotherapy
The following sections discuss specific cancers complicating pregnancy that may require radiation therapy.

Treatment
Breast Cancer
When breast or chest wall irradiation is necessary for tumor control, a risk assessment must be performed by an experienced medical physicist and a radiation oncologist. Successful breast cancer radiation therapy during pregnancy has been reported in the literature 1,2.

We believe that radiation therapy to the breast or chest wall is not an absolute contraindication for pregnancy. The risk-benefit assessment should be presented to the patient, and the final decision should depend on the strength of the indication for treatment and the woman's desire to continue the pregnancy. The use of wedges and/or lead blocks should be avoided to decrease external scatter to the fetus. In the second and third trimesters, when adjuvant chemotherapy can be safely administered, radiation therapy should be postponed until after delivery.

Hodgkin's Disease
Although definitive radiation therapy (4000 cGy) is still considered the standard for early stages of Hodgkin's disease, some authors have recently recommended a combination of chemotherapy alone or with low-dose, low-volume radiation fields 3. This approach in pregnant women can reduce the fetal dose or delay irradiation until delivery.

In conclusion, radiotherapy is an appropriate treatment for supradiaphragmatic presentation of Hodgkin's disease during pregnancy, provided special attention is paid to shielding and treatment techniques. The outcome of treatment for women with early-stage disease is not adversely affected by pregnancy, and the risk to the fetus appears to be minimal 4-16.

Cervical Carcinoma
The treatment of carcinoma of the cervix should be stage-related regardless of the presence of a pregnancy. Surgery and radiotherapy (for advanced disease) should be utilized in the same manner as in nonpregnant patients. However, the timing of treatment may be adjusted according to the gestational age. Late second- or early third-trimester pregnancies should be allowed to continue to 35 weeks unless there is evidence of a rapidly growing tumor. Vaginal delivery should be avoided because of the risk of tumor implantation in the episiotomy site.

Patients in whom cervical cancer is diagnosed in the first or second trimester are not good candidates for delay of treatment and should be given external radiotherapy immediately, with the fetus in situ. Usually, spontaneous abortion will occur after a few days and intracavitary radiation can be added. In case no spontaneous abortion occurs, curettage of the fetus should be performed.The majority of reports indicate that survival is not altered by pregnancy.

Hereditary effects of radiation
The gonads are one of the most radiosensitive organs in the human body. The threshold radiation dose for permanent sterility in men is 350 - 600 cGy, and for women 250 - 600 cGy. In a retrospective cohort study of survivors of cancer, it was found that radiation therapy directed below the diaphragm depressed fertility in both sexes by about 25%.

Even if fertility is preserved, there is concern regarding the induction of genetic abnormalities (germ-line mutation, chromosomal aberrations) which could potentially produce birth defects and cancer in the offspring. However, a 40-year follow-up of survivors of the nuclear blasts in Japan showed no significant increase in genetically-linked disorders in children born thereafter compared to matched controls of the general population. Based on animal experiments, the estimated dose of gonadal radiation required to produce a mutation rate equal to the baseline spontaneous rate in humans (mutation doubling dose) is between 100 and 150 cGy, with an approximate risk of 100 per 10,000 live-born infants per 100 cGy exposure. Yet, recent studies of children of cancer treatment survivors have found no more birth defects than expected for healthy parents, although an increase in low-birth-weight infants or spontaneous abortions was noted, particularly if conception occurred less than one year after cessation of radiation.

Table 1 --
Estimated Average Dose to Fetus per Radiographic Examination (in millirems)

Note: Values listed here are averages. The precise amount of fetal irradiation depends upon the device, the operator, the site, etc.
Dental 0.06 Upper G.I. series 170
Head <0.5 Femur (distal) 1
Cervical spine <0.5 Lumbar spine 720
Extremities <0.5 Pelvis 210
Shoulder 0.5 Hip and femur (proximal) 120
Thoracic spine 11 Intravenous pyelography 590
Chest 0.5 Cystography 1,500
Mammography <10 Barium enema 900
Abdominal CT 2000 Abdomen 220
Chest CT 20 Pelvimetry 1,270

References

  1. Antypas C, Sandilos P, et al. Fetal dose evaluation during breastcancer radiotherapy. Int J Radiat Oncol Biol Phys 40:995-999, 1998.
  2. Ngu SL, Duval P, Collins C. Foetal radiation dose in radiotherapy for breast cancer. Austral Radiol 36:321-322, 1992.
  3. Hoppe RT. Treatment of early-stage Hodgkin's disease: consideration in the use of radiation therapy. American Society of Clinical Oncology Educational Book 188-200, 1998.
  4. Becker MH. Hodgkin's disease and pregnancy. Radiol Clin North Am 6:111-114, 1968.
  5. Becker MH, Hyman GA. Management of Hodgkin's disease coexistent with pregnancy. Radiology 85:725-728, 1965.
  6. Conley JG, Jacobson A. Modified radiation therapy regimen for Hodgkin's disease in the third trimester of pregnancy. AJR 128:666-667, 1977.
  7. Covington EE, Baker AS. Dosimetry of scattered radiation to the fetus. JAMA 209:414-415, 1969.
  8. Jacobs C, Donaldson SS, et al. Management of the pregnant patient with Hodgkin's disease. Ann Intern Med 95:669-675, 1981.
  9. Nisce LZ, Tome MA, et al. Management of coexisting Hodgkin's disease and pregnancy. Am J Clin Oncol 9:146-151, 1986.
  10. Sharma SC, Williamson JF, Khan FM, Lee CK. Measurement and calculation of ovary and fetus dose in extended field radiotherapy for 10 MV x-rays. Int J Radiat Oncol Biol Phys 7:843-846, 1981.
  11. Spitzer M, Citron M, Ilardi CF, Saxe B. Non-Hodgkin's lymphoma during pregnancy. Gynecol Oncol 45:309-312, 1991.
  12. Tawil E, Mercier JP, Dandavino A. Hodgkin's disease complicating pregnancy. J Can Assoc Radiol 36:133-137, 1983.
  13. Thomas PRM, Peckham MJ. The investigation and management of Hodgkin's disease in the pregnant patient. Cancer 38:1443-1451, 1976.
  14. Wong PS, Rosemark PJ, et al. Doses to organs at risk from mantle field radiation therapy using 10 MV x-rays. Mt Sinai J Med 52:216-220, 1985.
  15. Woo SYH, Fuller LM, et al. Radiotherapy during pregnancy for clinical stages IA - IIA Hodgkin's disease. Int J Radiat Oncol Biol Phys 23:407-412, 1992.
  16. Zacali R, Marchesini R, De Palo G. Abdominal dosimetry for supradiaphragmantic irradiation of Hodgkin's disease in pregnancy. Experimental data and clinical considerations. Tumori 67:203-208, 1981.
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