J Neurooncol (2014) 120:405–409 DOI 10.1007/s11060-014-1565-4
CLINICAL STUDY
Fetal radiation monitoring and dose minimization during intensity modulated radiation therapy for glioblastoma in pregnancy David P. Horowitz • Tony J. C. Wang • Cheng-Shie Wuu • Wenzheng Feng Daphnie Drassinower • Anita Lasala • Radoslaw Pieniazek • Simon Cheng • Eileen P. Connolly • Andrew B. Lassman
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Received: 27 May 2014 / Accepted: 21 July 2014 / Published online: 6 August 2014 ! Springer Science+Business Media New York 2014
Abstract We examined the fetal dose from irradiation of glioblastoma during pregnancy using intensity modulated radiation therapy (IMRT), and describe fetal dose minimization using mobile shielding devices. A case report is described of a pregnant woman with glioblastoma who was treated during the third trimester of gestation with 60 Gy of radiation delivered via a 6 MV photon IMRT plan. Fetal dose without shielding was estimated using an anthropomorphic phantom with ion chamber and diode measurements. Clinical fetal dose with shielding was determined with optically stimulated luminescent dosimeters and ion chamber. Clinical target volume (CTV) and planning target volume (PTV) coverage was 100 and 98 % receiving 95 % of the prescription dose, respectively. Normal tissue tolerances were kept below quantitative analysis of normal
David P. Horowitz and Tony J. C. Wang have contributed equally to this study. D. P. Horowitz (&) ! T. J. C. Wang ! C.-S. Wuu ! W. Feng ! S. Cheng ! E. P. Connolly Department of Radiation Oncology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA e-mail:
[email protected] D. Drassinower ! A. Lasala Department of Obstetrics and Gynecology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA R. Pieniazek Center for Radiological Research, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA A. B. Lassman Department of Neurology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
tissue effects in the clinic (QUANTEC) recommendations. Without shielding, anthropomorphic phantom measurements showed a cumulative fetal dose of 0.024 Gy. In vivo measurements with shielding in place demonstrated a cumulative fetal dose of 0.016 Gy. The fetal dose estimated without shielding was 0.04 % and with shielding was 0.026 % of the target dose. In vivo estimation of dose equivalent received by the fetus was 24.21 mSv. Using modern techniques, brain irradiation can be delivered to pregnant patients in the third trimester with very low measured doses to the fetus, without compromising target coverage or normal tissue dose constraints. Fetal dose can further be reduced with the use of shielding devices, in keeping with the principle of as low as reasonably achievable. Keywords Dosimetry
Glioblastoma ! Radiation ! Pregnancy ! Fetal !
Introduction Radiation therapy has a well-described role in the treatment of patients with glioblastoma, with multiple trials demonstrating a benefit to adjuvant radiation therapy over supportive care and chemotherapy alone [1–6]. While the incidence of glioblastoma increases with age, approximately 7.5 % of patients diagnosed with glioblastoma are younger than 40 years old [7]. Although rare, cases of glioblastoma have been reported during pregnancy, managed with various regimens of radiation and/or chemotherapy [8, 9]. Radiation exposure in utero is associated with an increased risk of multiple severe toxicities, including
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mental retardation, microcephaly, growth retardation, and cancer [10]. Herein, we describe a case report of a pregnant patient with glioblastoma treated with adjuvant radiation, estimation of fetal radiation dose with the use of anthropomorphic phantom, and the use of shielding devices for fetal dose minimization during radiotherapy. The patient provided consent for publication of this case report, and the Columbia University institutional review board does not require review or approval for case reports.
Case report The patient is a 37 year old woman, G5P3013, who initially presented at 26 weeks gestation with severe headaches in January 2013 and was managed with pain medications which provided minimal relief. Her headaches worsened and were associated with nausea and vomiting. An MRI revealed a large right parietal solid and cystic mass and she underwent a gross total resection while she was at 23 weeks gestation. Pathology showed
Fig. 1 Isodose lines of the intensity modulated radiotherapy treatment plan in the axial, sagittal, and coronal planes
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glioblastoma, WHO grade IV. O6-Methylguanine-DNA methyltransferase (MGMT) promoter was unmethylated. She was then treated with postoperative radiotherapy to 60 Gy in 30 fractions using intensity modulated radiation therapy (IMRT) with three right-sided coplanar 6 MV beams. Every reasonable effort was made to minimize total monitor units (410 MU per fraction, 2.05 MU/cGy) while providing adequate coverage to the tumor volume and respecting dose constraints to normal critical structures. One hundred percent of the clinical target volume (CTV) received 95 % of the prescription dose and 98 % of the planning target volume (PTV) received 95 % of the prescription dose, brainstem maximum dose was 56 Gy, right optic nerve maximum dose was 51 Gy, left optic nerve maximum dose was 24 Gy, and chiasm maximum dose was 53 Gy (Fig. 1). Treatment planning was performed with Pinnacle TPS (Philips Radiation Oncology Systems, Fitchburg, WI). A custom made mobile shielding device consisting of 2 inch thick lead plate, representing 3.4 halfvalue layers, suspended from a two-ton Hoyer lift, was placed vertically on the patient’s right side in order to
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Fig. 2 Actual patient setup with custom made mobile shielding device placement
minimize fetal exposure from treatment head leakage (Fig. 2). The patient began radiotherapy while at 27 weeks gestation. She completed adjuvant radiotherapy without acute toxicity. Weekly obsterical sonogram showed normal fetal growth during the course of radiation. Postradiation therapy, the patient reported no acute toxicity, and the child was delivered 35 weeks, gestation with no complications noted. After delivery, the patient was started on adjuvant temozolomide (150 mg/m2 by mouth, given in 28 day cycles). Sixteen months after the completion of radiotherapy, the patient has no evidence of disease recurrence.
Phantom dosimetric measurements It is important to estimate dose to the fetus using phantom measurement before the treatment is given. A very important factor in fetal dose is the distance from the edge of the radiation field. Compared to in vivo measurement one advantage using phantom measurement is that dose measurements with ion chamber and diode can be made for multiple fractions and more reliable dosimetry results can be obtained. The ATOM anthropomorphic phantom (CIRS, Norfolk, VA) measurement was used to estimate fetal dose without shielding (Fig. 3a, b). Both ion chamber and diode (Sun Nuclear Corp.) were used to measure dose, and were placed under 2 cm of tissueequivalent bolus material in order to simulate the position of the gravid uterus. Based on measurements from the isocenter position within the patient’s head to the uterine fundus, ion chamber and diode were placed 40 cm from the isocenter. Five fractions of treatment fields were delivered to the ATOM phantom, and measured dose was used to estimate the fetal dose for the full course
Fig. 3 Anthropomorphic phantom measurement was used to estimate fetal dose without shielding
treatment. For the full course of radiation, without shielding, the estimated fetal dose using the phantom measurements was 0.024 Gy from diode measurement and 0.021 Gy from ion chamber measurement. With shielding in place, ion chamber dose measurement for the full course was estimated at 0.02 Gy, a 5 % reduction in dose due to shielding.
Patient dosimetric measurements On the first day of radiation therapy, optically stimulated luminescent dosimeters (OSLDs) badges with 1 cm bolus were placed on the patient’s superior midline, umbilicus, right and left abdomen. Ion chamber with 2 cm bolus was also placed right next to the abdomen. With mobile shielding in place, the estimated fetal dose during the full course of radiation therapy was 0.018 Gy from OSLD badges (average 0.6 mSv/fraction), and 0.016 Gy from ion chamber measurement (0.53 mGy/fraction). Repeated OSLD measurement during the course of radiation showed the estimated fetal dose to be 0.015 Gy in total. Additional OSLDs used for every treatment were read at the end of the course of radiation therapy, and showed a total dose equivalent delivered to average 24.21 mSv at the midplane of the patient’s abdomen (third party reading performed by Landauer, Glenwood, IL).
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Discussion In the use of radiation to treat all patients, every reasonable effort is made to treat the target volume with the prescription dose while minimizing the dose delivered to normal tissues. In the case of radiation treatment delivered to pregnant women, additional care must be taken due to the significant potential for small doses of radiation to cause severe toxicity to the developing fetus. In the first trimester of pregnancy, doses from 0.1 to 0.5 Gy have significant risk of toxicity, such as growth retardation, microcephaly, and mental retardation. As the fetus develops it becomes less sensitive to the detrimental effects of radiation exposure, though doses greater than 0.5 Gy pose a high risk of damage during all trimesters [10]. For radiation-induced malignancies caused by exposure in utero, no threshold below which risk does not exist has been established. It has been estimated that 0.01–0.02 Gy exposure in utero confers a 1.5-fold increase in the risk of childhood leukemia [11]. The American Association of Physicists in Medicine (AAPM) Task Group 36 Report #50 described the fetal dose associated with irradiation of a pregnant patient with glioblastoma [10]. Depending on the distance from the nearest field edge, an unshielded fetus was estimated to receive a total of 0.022–0.03 Gy during a course of 60 Gy to the target. Sneed et al. [12] described fetal dose estimates for two pregnant patients who received brain irradiation, with estimated fetal radiation doses ranging from 0.03 to 0.06 Gy. It should be noted, however, that dose estimates in these cases were determined using conventional lateral opposed fields or bicoronal arcs with physical wedges. The treatment planning undertaken in the above case was for IMRT, and the fetal dosimetric measurements more accurately represent dose from modern radiation treatment to the brain. IMRT optimization in this case was performed not just to ensure appropriate target coverage and normal tissue constraints, but also with care to limit total monitor units. Beams were arranged in a coplanar manner in order to avoid excess fetal dose from a vertex field. There are multiple sources of radiation that contribute to fetal dose. Photon leakage through the treatment head of the machine, scatter from collimators or physical wedges, internal scatter, and neutron contamination of high energy photon beams all contribute to dose outside of the treatment field. The AAPM reports that for distances within the body beyond 30 cm from the field edge, which reflects the distance from an intracranial target to the fetus, head leakage is the predominant contributor to dose [10]. Sneed et al. [12] reported that internal scatter accounted for 13–20 % of fetal dose. The fact that the majority of the fetal dose is derived from machine head leakage or collimator scatter suggests that external shielding can significantly reduce the exposure
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of the fetus to radiation. The AAPM estimates an approximately 50 % reduction in dose to the fetus with the use of 4.5 cm lead blocks (three half-value layers) [10]. Multiple abdominal shields have been created, such as bridges and mobile designs. Practical concerns with the construction of large lead shields have been raised, as well as safety concerns about having immense weights of lead suspended over patients [12]. For this reason, as well as the fact that the above patient’s tumor was well lateralized within the right parietal lobe, we opted for construction of a custom mobile shield to be positioned on the right side of the patient, which was built by an in-house machine shop. Beam angles were optimized to take advantage of the positioning of this shielding device. Measurement of radiation dose with and without use of the shielding device showed a 5–33 % reduction in dose with the use of this shielding device. At the fetal doses measured, there can be significant variability in measurements among different devices, giving rise to the wide range of measured dose reduction due to the shielding device. While the dose without use of shielding was below that associated with severe abnormalities such as mental retardation or microcephaly, its use was in keeping with the principle of as low as reasonably achievable (ALARA). The radiation dose that the fetus was exposed to was on the order of the dose from a CT to evaluate for pulmonary embolus [13]. The use of shielding also minimizes the risk of radiation-induced malignancy, for which no threshold is known to exist. The above patient was treated with antepartum adjuvant radiation therapy followed by postpartum temozolomide (150 mg/m2 by mouth daily in 28 day cycles). The Food and Drug Administration has classified temozolomide as pregnancy category D, with animal studies showing evidence of embryo lethality, and fetal malformations. There are no controlled data in humans informing its use, though case report data has suggested that it can be given without short term fetal toxicity [9]. In light of the tumor having no methylation of the MGMT promoter, the potential fetal risk from temozolomide was thought to outweigh benefit, and its use was withheld until after delivery. In conclusion, we describe a case of a pregnant woman with glioblastoma treated with surgery and IMRT. Measured fetal radiation dose was low, and consistent with data from conventionally planned radiation therapy that has been previously reported. Additionally, the use of mobile shielding devices and optimization of radiation beam angles can further reduce fetal dose to as low as is reasonably achievable.
Conflict of interest The authors declare that they have no relevant conflict of interest. Funding
None.
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