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Cancer occurs in approximately 1 per 1000 pregnancies. This rate is rising, likely due to delayed childbearing and increased detection. , Common cancers during pregnancy include melanoma, cancers of breast and cervix, lymphomas and leukemias. While pregnancy is not a risk factor for malignancy, , diagnosis may be delayed if symptoms are falsely attributed to pregnancy. Managing cancer during pregnancy requires a multidisciplinary, patient-centered approach. The American Society of Clinical Oncology (ASCO) provides a framework for navigating the medical, legal, and ethical challenges of cancer care during pregnancy, balancing optimal patient outcomes and fetal risk. ASCO recommends standard-of-care when possible and weighing risks to the patient and the fetus when considering deviation.

Oftentimes patients and physicians are uncomfortable with fetal exposure to radiation or chemotherapy. However, deviating from standard of care treatments can significantly impact maternal health. For example, treatment delays of 4 months or longer in cervical cancer are associated with a 2.31 times increased mortality risk. In most cases, pregnancy itself will not worsen prognosis unless treatment is declined by the patient due to fetal concerns. Unless indicated for the health of the pregnant patient, the American College of Obstetricians and Gynecologists and ASCO recommend avoiding delivery before 37 weeks. , This highlights the critical importance of contextualizing fetal risk from cancer treatments, and the impact of any deviations from standard of care on both maternal and fetal health.

While there are ample resources for determining the role of systemic therapies, surgery, and other non-radiation treatments during pregnancy, the guidance for radiotherapy is sparse and scattered. Radiotherapy is a cornerstone of cancer treatment, and radiotherapy is beneficial in ∼50% of cancer cases. In many cases, it can be delivered with very low doses to the fetus. The goal of this paper is to discuss how radiation can be safely considered for certain pregnant patients, including the vital importance of diagnostic imaging in appropriate staging, and to discuss the best practices to deliver treatment using modern approaches to minimize fetal risk. It concludes with discussions of patient-centered care and access issues surrounding termination. We use terms like “pregnant individuals” and “patients” to acknowledge that not all pregnant people identify as women.

Fetal risk depends on gestational age at time of exposure and radiation dose , (). Effects vary based on gestational age and stage of organogenesis at the time of exposure. Prior to 10 weeks from last menstrual period, spontaneous abortion, growth restriction, congenital anomalies, and anatomic malformations can occur at thresholds of 200 mGy or more. However after 10 weeks, the organs have been formed and are essentially immutable. Therefore, starting at 11 weeks, the fetal risks include seizure, growth restriction, spontaneous abortion, and intellectual deficits of varying degrees in accordance with dose, occurring at a range of dose thresholds from 100 to 2000 mGy. Deterministic radiation effects occur above a threshold dose, while stochastic effects may occur at any dose, and the probability of occurrence typically increases with dose. Stochastic effects include radiation-induced cancer, but the limited data suggest cancer risk from gestational exposure is significantly lower than exposure during early childhood. A 10-20 mGy fetal dose may increase the risk of leukemia by a factor of 1.5-2.0 over a background rate of ∼1 in 3000. Restated, there is a greater than 99% chance that a fetus exposed to 20 mGy will be unaffected, and a ∼98% chance at 50 mGy. However, uncertainties in estimates below 100 mGy prevent accurate risk quantification.

Pregnancy screening for imaging is discussed in . Screening is recommended prior to radiation therapy and each practice should develop a standardized policy. Screening should focus on the patient’s physical and endocrinologic capacity for childbearing and participation in behaviors which can result in pregnancy. For external beam radiotherapy (EBRT), a negative pregnancy test should be secured within 14 days prior to treatment initiation. For therapeutic I-131 administration, a negative serum pregnancy test should be obtained 72 hours prior to treatment. , Though urine pregnancy tests can be used, serum pregnancy tests can detect pregnancy earlier and with higher sensitivity. Knowledge of state regulations is helpful for pregnancy testing in minors, as the definition of minor and requirement for parental consent varies. It is important to counsel patients to prevent pregnancy during treatment and after radiopharmaceutical administration. , Some radiopharmaceuticals are excreted in breastmilk and, generally, breastfeeding should cease for all I-131 labeled radiopharmaceuticals, Ga-67 citrate, and therapeutic administrations. Recommendations regarding the duration of interruption/cessation of breastfeeding following radiopharmaceuticals vary, and an Authorized User/Nuclear Medicine Physician should be consulted.

Imaging is critical in cancer screening, diagnosis, staging, and monitoring of treatment response. Clinicians should carefully consider the use of imaging modalities that may impact the patient’s course of treatment, in the context of fetal risk from ionizing radiation. Dose optimization in imaging pregnant patients should include the same approaches used in non-pregnant patients: proper x-ray field collimation and patient positioning, limiting the number of views and phases to those necessary, and only performing exams that will impact the course of care. , describes imaging protocol modifications for specific modalities.

summarizes typical fetal doses for exams associated with cancer screening, diagnosis, and staging, , , though the exact dose depends on imaging parameters, pregnancy stage, and patient habitus. Any x-ray-based exam where the gravid uterus is not in the field-of-view (FOV) results in a fetal dose below 1 mGy; no imaging protocol modifications are necessary. For most x-ray-based exams where the fetus is in the FOV, fetal dose is under 10 mGy. Exceptions include computed tomography (CT) and fluoroscopy-guided interventions (FGIs), where doses can exceed 50 mGy. If multiple imaging exams are necessary, cumulative dose should be considered. Given that fetal doses are typically well below 100 mGy, deterministic radiation effects are not relevant , , , , and stochastic risk is negligible or non-existent. External shielding of the fetus for x-ray-based imaging is no longer recommended as it minimally reduces dose but may interfere with dose optimization tools or degrade image quality.

Pregnant patients should follow breast cancer screening guidelines for the general population. , , While physiologic changes of pregnancy and lactation may degrade the diagnostic efficacy of mammography, this does not warrant a screening delay. Screening mammography is essential in detecting subclinical breast cancers during pregnancy.

Ultrasound has 100% sensitivity in patients with a palpable breast mass. Specificity may be reduced, as breast cancer in pregnant patients is more likely to mimic benign lesions on ultrasound than in non-pregnant patients. Any solid mass identified on ultrasound should proceed to biopsy. Contrast-enhanced ultrasound (CEUS) is useful for assessing tumors and lymph nodes with metastatic infiltration and for imaging patients with cardiotoxic chemotherapy regimens. Limited studies have shown that microbubbles in ultrasound contrast agents do not cross the placental barrier, and no adverse reactions have been observed. Despite no known risks, the American College of Radiology (ACR) only recommends CEUS use when there is a clear patient benefit.

Non-contrast MRI is considered safe during pregnancy when the static magnetic field is 3 T or less and the scanner is in normal operating mode (whole body-averaged specific absorption ratio [SAR] limited to 2 W/kg). Despite limited evidence of fetal risk from gadolinium-based contrast agents (GBCA), current recommendations discourage their use except in situations where the anticipated clinical benefit justifies the unknown risk of fetal exposure to GBCA. ,

Diagnostic fluoroscopy may facilitate cancer diagnosis or treatment through biopsy or port placement for chemotherapy and is used to treat or manage conditions that are common in pregnancy, such as iliofemoral deep vein thrombosis and embolism. When the fetus is outside the FOV, FGI fetal dose will be below 1 mGy. However, if the fetus is in the FOV during a prolonged procedure, fetal dose may exceed 100 mGy. The benefits and risks should be weighed against alternative treatments. Fetal time in the FOV should be limited.

No protocol adjustments are required when the fetus is outside the FOV as fetal doses are below 1 mGy. For multi-phase exams where the fetus is inside the FOV, modifications should be considered, eg, reducing the scan range or conducting a single-phase study.

Iodinated contrast crosses the placenta but does not affect short-term neonatal thyroid stimulating hormone (TSH). Long-term effects on TSH function are unknown, but iodinated contrast agents are recommended during pregnancy when needed for accurate diagnosis. Importantly, management of contrast reactions may be different for pregnant patients. ,

Fetal doses in nuclear medicine depend on radiopharmaceutical accumulation in the fetus and nearby patient organs. Positron emission tomography (PET) is the most common diagnostic nuclear medicine exam in this population as cancers that are common during pregnancy exhibit strong F-18-FDG uptake. Most diagnostic nuclear medicine studies use low administered activities of radiopharmaceuticals with short half-lives, resulting in fetal doses below 5 mGy. Fetal thyroid doses can be substantial for I-131 (over 40 Gy), which is contraindicated for diagnosis and therapy during pregnancy. ,

Many cancers outside the pelvis may be safely treated with radiation (), while pelvic radiation may cause severe or lethal fetal consequences. , While no strict dose limitation guidelines exist, most sources claim deterministic effects may occur above 100 mGy. , Therapeutic radiation should aim to keep fetal dose below this threshold. For extremity, head and neck, and brain sites fetal doses can be kept below 100 mGy with few additional accommodations, but fetal dose should still be closely monitored. For chest, abdomen, and upper thigh sites, fetal doses may exceed 100 mGy, necessitating shielding and other fetal-dose reduction strategies (see below). When fetal dose is likely to exceed 100 mGy, patient risks from foregoing radiation should be weighed against fetal risks.

Several relevant guidelines from professional organizations and consensus groups exist , ; however, many contain limited radiation-specific information , or are outdated. The American Association of Physicists in Medicine (AAPM) Task Group Report 36 contains recommendations for estimating and reducing fetal dose, but does not discuss modern treatment modalities. The French Society for Radiation Oncology practice guidelines on radiotherapy and pregnancy reported that supradiaphragmatic radiation can be safely delivered, and phantom and in vivo dose measurements should be performed. Multiple review papers have also been published, , but many contain limited and/or misleading radiation information (eg, avoiding radiation except in “rare scenarios in which the benefits exceed the risk”). In many cases the benefit of radiotherapy outweighs the fetal risks. Recommendations specific to common disease sites are described below.

Radiotherapy is often important for primary tumor and nodal irradiation. Some sites may require radiotherapy alone or with chemotherapy due to severe toxicities of surgery. Given the distance between the treatment site and the uterus, fetal dose can be kept below 100 mGy, and treatment decisions should focus on optimizing patient outcome.

Radiotherapy during pregnancy is most relevant for high grade primary central nervous system (CNS) tumors and brain metastases. For brain metastases, the primary cancer type, extra- and intracranial extent and location, and systemic therapy options need to be closely weighed, as there are few options that completely obviate the need for radiotherapy. Many aggressive primary brain neoplasms can be surgically resected, but adjuvant radiotherapy improves survival. If diagnosed early in pregnancy, radiotherapy should not be delayed in aggressive histologies as recurrence occurs quickly. Fortunately, the large distance from the uterus typically results in low fetal doses. ,

Most early stage cancers can be managed with surgical resection and/or chemotherapy, and local recurrence risks without radiotherapy are typically low. However, more extensive lung cancers are managed with primary radiotherapy, which can potentially be safely delivered with proper shielding and dosimetric fetal dose reduction strategies. , Treatment planning should consider pregnancy-related changes in pulmonary function.

Diagnosis of breast cancer during pregnancy is often delayed and presents at a more advanced stage than in nonpregnant patients. , A full staging workup is essential as advanced disease may impact treatment decisions. Treatment management should follow standardized protocols for non-pregnant patients as closely as possible, and typically includes surgery followed by radiation and systemic therapy. Radiotherapy decisions should consider gestational age, as fetal exposure increases later in pregnancy as the uterus becomes closer to the treatment field, balanced against the impact of delaying radiation, which may impact local control. There is no consensus of acceptable surgery-to-radiotherapy interval, with evidence for permissible delays varying from 6 to 20 weeks. , Often, the standard treatment course may involve neoadjuvant chemotherapy, which may result in delaying radiotherapy till after pregnancy. If prompt radiotherapy is indicated, breast radiotherapy can be delivered relatively safely during the first and much of the second trimesters, , , and there is ample evidence showing fetal doses are often below 100 mGy using shielding. ,

Treatment options vary depending on the cancer type and stage, gestational age, and maternal symptoms, but generally treatment occurs in the second and third trimester. , , Chemotherapy is the most common treatment, but supradiaphragmatic lymphomas can be safely treated with radiation if necessary. , In some cases of asymptomatic Hodgkin lymphoma, treatment can be deferred until after delivery.

The timing and manner of treatment is based on gestational age, tumor stage, and maternal wishes. , For stages 1B1 or less, options include delay or more limited surgical approaches. For stages greater than 1B1, delivering standard-of-care chemoradiotherapy would induce abortion in 1-2 months. A short treatment delay to allow lung maturation could be considered in some third trimester cases. Local abortion restrictions and fetal personhood laws should be considered to avoid prosecution of the treatment team or the patient. If laws or patient wishes prevent termination, pelvic lymphadenectomy or neoadjuvant systemic therapy could be considered, risking inferior maternal outcomes.

An alternative to photon EBRT is pencil beam scanning proton therapy (PBS-PRT). PBS-PRT can produce fetal equivalent doses over ten times lower than photon EBRT for brain and head and neck cancers. When PBS-PRT is not available, it is possible to deliver photons or electrons using 3D conformal radiotherapy (CRT), intensity modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT), CyberKnife, GammaKnife, and linac-based stereotactic radiosurgery (SRS), while maintaining fetal doses below 100 mGy (). , Though reports during pregnancy are limited, electrons have been used successfully for intraoperative breast cancer treatment and chest wall irradiation. Passive scattering proton therapy (PS-PRT) produces doses ten times greater than photon therapy and is not recommended during pregnancy.

Fetal dose for photon EBRT sites outside the uterus is due to internal patient scatter, treatment head leakage and collimator scatter (). Leakage and collimator scatter can be minimized through shielding and monitor unit (MU) reduction, whereas internal scatter can only be decreased by increasing the distance to the fetus or decreasing field size. Beyond the field edge, out-of field dose decreases approximately exponentially. , For electron beams, out-of field dose is mainly caused by scattered electrons originating from the primary beam or trimmer and collimator scatter. Electron beam out-of-field dose, particularly for certain linear accelerators, can exceed that of photons. For photons and electrons, out-of-field dose is highest superficially, then decreases rapidly with depth, remaining fairly constant at deeper depths. , Secondary neutron dose for electron beams is typically ∼5% of that from similar photon energies. In PRT, fetal dose primarily results from internal neutrons and secondary photons produced from proton interactions in the patient. Neutrons comprise the majority of out-of-field dose with photons contributing ∼10%.

Physicists, dosimetrists and physicians should collaborate to determine the best plan for a given patient and treatment site. 3DCRT features lower out-of-field dose than IMRT/VMAT due to fewer MUs. , In sites that necessitate tight conformality, eg, head and neck or brain, IMRT/VMAT may be used with MU reduction efforts. Flattening filter free beams are preferred due to reduced flattening filter scatter and reduced target current, decreasing fetal dose by ∼50%. , Beam energies of 10 MV or less are preferred to eliminate neutron dose.