Optimizing irradiation protocols for pregnant women is challenging, because there are few cases and a dearth of fetal dosimetry data. We cared for a 36-year-old pregnant woman with tongue cancer. Prior to treatment, we compared three intensity-modulated radiation therapy (IMRT) techniques, including helical tomotherapy, volumetric arc therapy (VMAT), and flattening-filter free VMAT (FFF-VMAT) using treatment planning software. FFF-VMAT achieved the minimum fetal exposure and was selected as the optimal modality. We prescribed 66 Gy to the involved nodes, 60 Gy to the tumor bed and ipsilateral neck, and 54 Gy to the contralateral neck over 33 fractions. To confirm the out-of-field exposure per fraction, surface doses and the rectal dose were measured during FFF-VMAT delivery. Postoperative chemoradiotherapy was delivered using IMRT and a cisplatin regimen. Without any shielding, the total fetal dose was 0.03 Gy, within the limits established by the ICRP. A healthy girl was born vaginally at 37 weeks’ gestation

Abe, Osamu

Haga, Akihiro

Imae, Toshikazu

Nakagawa, Keiichi

Nawa, Kanabu

Ogita, Mami

Okuma, Kae

Takahashi, Wataru

Yamashita, Hideomi

English

Tokushima University Institutional Repository

Clinical and Translational Radiation Oncology 20 (2020) 9–12Contents lists available at ScienceDirectClinical and Translational Radiation Oncologyjournal homepage: www.elsevier .com/locate /c t roCase ReportAcceptable fetal dose using flattening filter-free volumetric arc therapy(FFF VMAT) in postoperative chemoradiotherapy of tongue cancerduring pregnancyqhttps://doi.org/10.1016/j.ctro.2019.10.0022405-6308/ 2019 The Author(s). Published by Elsevier B.V. on behalf of European Society for Radiotherapy and Oncology.This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).q Portions of this study were presented at the 54th Autumn Assembly of the JapanRadiological Society in Fukuoka, Japan in October 2018.⇑ Corresponding author at: Department of Radiology, The University of TokyoHospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.E-mail address: wataru.harry1@gmail.com (W. Takahashi).Wataru Takahashi a,⇑, Kanabu Nawa a, Akihiro Haga b, Hideomi Yamashita a, Toshikazu Imae a,Mami Ogita a, Kae Okuma a, Osamu Abe a, Keiichi Nakagawa aaDepartment of Radiology, The University of Tokyo Hospital, Tokyo, JapanbDepartment of Medical Image Informatics, Tokushima University, Tokushima, Japana r t i c l e i n f o a b s t r a c tArticle history:Received 9 October 2019Accepted 10 October 2019Available online 14 October 2019Keywords:PregnancyTongue cancerFetal doseIntensity-modulated radiation therapyFlattening filter-freeOptimizing irradiation protocols for pregnant women is challenging, because there are few cases and adearth of fetal dosimetry data. We cared for a 36-year-old pregnant woman with tongue cancer. Priorto treatment, we compared three intensity-modulated radiation therapy (IMRT) techniques, includinghelical tomotherapy, volumetric arc therapy (VMAT), and flattening-filter free VMAT (FFF-VMAT) usingtreatment planning software. FFF-VMAT achieved the minimum fetal exposure and was selected as theoptimal modality. We prescribed 66 Gy to the involved nodes, 60 Gy to the tumor bed and ipsilateralneck, and 54 Gy to the contralateral neck over 33 fractions. To confirm the out-of-field exposure per frac-tion, surface doses and the rectal dose were measured during FFF-VMAT delivery. Postoperative chemora-diotherapy was delivered using IMRT and a cisplatin regimen. Without any shielding, the total fetal dosewas 0.03 Gy, within the limits established by the ICRP. A healthy girl was born vaginally at 37 weeks’gestation. 2019 The Author(s). Published by Elsevier B.V. on behalf of European Society for Radiotherapy andOncology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).1. IntroductionThe rare coincidence of cancer and pregnancy is challenging totreat given the dearth of data on fetal dosimetry. Oral canceraccounts for <2% of all cancers during pregnancy, and there is nostandard treatment approach [1]. For non-pregnant patients withnegative prognostic factors, including surgical margin positivityand extracapsular lymph node extension, postoperative chemora-diotherapy (POCRT) is indicated as adjuvant treatment. BecausePOCRT may incur risk to the fetus [2], minimizing fetal dose is vital.Several intensity-modulated radiotherapy (IMRT) techniquescan reduce fetal dose. Although IMRT is excellent at sparing organsat risk (OARs) in head and neck cancers, it has scatter and leakageissues that must be dealt with [3]. Some studies have focused onthe flattening-filter free mode (FFF) of a linear accelerator toreduce OAR dose [4,5].Herein, we present our phantom simulations and describe ourtreatment of a pregnant woman who underwent POCRT for tonguecancer.2. Case reportA 36-year-old primipara presented with a nodule at the tonguetip, and reported increasing pain. Biopsy and multiple imagingtests revealed a squamous cell carcinoma with involvement ofmultiple ipsilateral cervical lymph nodes (Fig. 1). This cT2N2bM0case was discussed in depth at a multidisciplinary tumor board,and it was decided that surgery should be performed during preg-nancy. At the 17th week of pregnancy, partial glossectomy andlymph node dissection (bilateral levels I–III) were performed.There were no severe operative complications. Pathology con-firmed extracapsular lymph node extension. To reduce the risk oflocoregional failure, our tumor board decided that POCRT duringpregnancy was justified. Written informed consent from thepatient and her family was obtained before the initiation of POCRT.Concomitant with the radiotherapy, the patient was scheduledto receive intravenous tri-weekly cisplatin at 80 mg/m2 based onFig. 1. Pretreatment CT scan. Squamous cell carcinoma in the tongue with involvement of multiple ipsilateral cervical lymph nodes (arrows).10 W. Takahashi et al. / Clinical and Translational Radiation Oncology 20 (2020) 9–12previous studies reporting its safety in the 2nd trimester of preg-nancy [6].2.1. RT planning and optimal modality selectionUsing a thermoplastic mask for immobilization, a planning CTdataset was acquired using a 16-detector scanner (Toshiba Aquil-ion LB, Toshiba Medical Systems, Otawara, Japan). For IMRT plan-ning, CT image data were reconstructed as 2 mm sections andwere then sent to our treatment planning systems (TPS).To find an optimal modality for fetal dose reduction duringIMRT of the pregnant patient, a fetal dosimetric comparison wasperformed among helical tomotherapy (HT), single-arc volumetricarc therapy (VMAT), and FFF-VMAT.Using 6 MV photon beams modulated by binary multileaf colli-mation, the HT plan was simulated on the Tomotherapy PlanningStation software (v5.1.1.6, Accuray Inc. Sunnyvale, CA, USA). TheVMAT and FFF-VMAT plans were created on the Pinnacle3 TPS(v9.10, Philips Medical Systems, Fitchburg WI, USA), with maxi-mum dose rates of 600 and 1,500 MU/min, respectively. One com-plete arc was used for both VMAT techniques using the AgilityMLC, achieving <0.5% leakage.Using a simultaneous integrated boost method, we prescribed66 Gy to the involved nodes, 60 Gy to the tumor bed and ipsilateralnodal levels I–V, and 54 Gy to the contralateral levels I–V over 33fractions. The planning target volume (PTV) was defined by addinga 3-mm margin in all directions. Dose constraints for the PTV andOARs were: median values of D2% (maximum dose received by 2%of the PTV), D10% and D50% were <115%, 110%, and 105% of theprescribed dose, respectively. The three rotational IMRT plans(HT, VMAT, FFF-VMAT) had a mean PTV coverage of 96%. The max-imum dose to the brainstemwas <54 Gy; the maximum dose to thespinal cord was <50 Gy; the mean and median doses to the con-tralateral parotid gland were <26 Gy and <20 Gy.Before FFF-VMAT was performed, we compared the respectiveabsorbed out-of-field doses. Glass dosimeters (Chiyoda Technol.Co., Ltd., Tokyo, Japan) were placed on the umbilicus and pubicsymphysis of an anthropomorphic phantom (The Phantom Labora-tory, Salem, NY, USA). During actual beam delivery, surface dosesat the umbilicus and pubic symphysis and rectal doses weremeasured.Previous reports have suggested that some patient-specific leadshielding devices could reduce the fetal dose in the setting of con-ventional radiotherapy [7,8]. However, in this IMRT case usingrotational beams, a patient-specific shield above the patient wasnot used because there were safety concerns (it might collapsedue to its own weight) and no general-purpose properties despitethe major expense involved. All three IMRT modalities satisfied thePTV and OAR constraints. Fig. 2 presents the dose distributions.The results of the phantom study are summarized in Fig. 3.VMAT showed large out-of-field doses due to scattered photonsfrom the flattening filter. HT, even with an FFF beam, producedhigh abdominal and pelvic doses, mainly due to a comparably lar-ger number of MUs [9]. Depending on reduced scatter from theflattening filter and less head leakage associated with more effi-cient x-ray generation than conventional VMAT, FFF-VMATachieved the lowest fetal exposure during beam delivery and wasselected as the optimal modality [10]. The total fetal dose fromFFF-VMAT was estimated to be approximately 0.05 Gy [11], whichdid not exceed the 0.1 Gy limit set by the ICRP [12]. The patient andher family consented to the treatment.2.2. Treatment and courseGlass dosimeters on the patient’s ventral surface and in the rec-tum revealed that the observed doses were lower than the phan-tom doses (Fig. 3). At this time, the patient’s weight was 53 kgand height was 160 cm. The final fetal dose of 0.03 Gy (886 lGyper fraction) was below the threshold value associated with cogni-tive abnormalities and physical malformations [11,13,14].Although a second course of cisplatin was cancelled due tograde 4 neutropenia, the planned course of radiotherapy was com-pleted with only two days’ interruption. Non-hematologic acutetoxicities included grade 2 mucositis and dysgeusia.A healthy female infant was born vaginally at 37 weeks’ gesta-tion. Unfortunately, the tumor recurred in the patient’s lung andpleura 3 months after POCRT (1 week after vaginal delivery) with-out any locoregional recurrence. Despite pleural drainage and sal-vage chemotherapy, the patient died from lung metastases6 months after radiotherapy. Her child was vigorous and had nocomplications at the last follow-up at 2 years old. To assess for pos-sible cognitive or growth impairment and the risk of developing amalignancy, long-term follow-up is ongoing.3. Discussion and conclusionsObviously, pregnant women should avoid radiation therapyuntil post parturition since radiation could cause harm the fetus.Given the urgency of the high risk of recurrence, and the patient’sbeing in the second trimester of pregnancy, the risk of inducingradiation damage to the fetus was considered to be low and theneed for immediate radiotherapy to be uppermost. With respectto cisplatin, the second trimester also poses less risk than the firsttrimester [12]. According to a previous report on peripartum com-plications and immediate fetal outcome, chemotherapy can beFig. 2. Treatment plans for helical tomotherapy (HT), volumetric arc therapy (VMAT), and flattening filter-free VMAT (FFF-VMAT). Representative dose distribution with66 Gy (red), 60 Gy (yellow), and 54 Gy (blue) isodoses. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of thisarticle.)Fig. 3. Out-of-field dose per fraction for helical tomotherapy (HT), volumetric arctherapy (VMAT), and flattening filter-free VMAT (FFF-VMAT). Horizontal axis showsthe distance [cm] from the edge of the planning target volume. Rectal doses areshown as ‘‘patient rectum (FFF-VMAT).” Distances of 40 cm and 62.5 cm correspondto the umbilicus and pubic symphysis, respectively, on the phantom. Distances of32 cm and 55 cm correspond to the umbilicus and pubic symphysis, respectively, ofthe patient.W. Takahashi et al. / Clinical and Translational Radiation Oncology 20 (2020) 9–12 11safely administered to women during the second trimester ofpregnancy [15]. After the multidisciplinary meeting, we decide todeliver POCRT to her.In this pre-treatment assessment, we did not test 3-dimensionalconformal radiotherapy or opposing fields with/without wedges forless scattering due to less primary fluence. We wished to administerIMRT to the patient because of its reduced rate of side effects such asxerostomia. If an unacceptable fetal dose had been calculated forIMRT, we would have had to consider 2- or 3-dimensional RT tech-niques. However, in our assessment, FFF-VMAT would deliver alow fetal dose without unacceptable doses to the organs at risk. InFFF-VMAT, the removal of the flattening filter reduced the out-of-field dose near the treatment field because of decreased collimatorscatter, relative to the usual VMAT technique with the filter. In FFF-VMAT, the removal of the flattening filter reduced the out-of-fielddose because of decreased collimator scatter, relative to the usualVMAT technique with the filter. As for HT, regardless of using FFFbeams, the more-than-expected scattered radiation were detected.This could be due to the shielding in its accelerator design, thesmall-bore size of HT, and its longer beam-on time than VMAT.In summary, the fetal exposure to radiation during FFF-VMATwas exceedingly low, compared to the other rotational IMRTtechniques. Therefore, we identified FFF-VMAT as a good choicefor pregnant patients needing radiation therapy, at least in thehead and neck region. However, the accuracy of the findingsmight not be representative of the entire pregnant population,and it is therefore still necessary to perform accurate modelexperiments in each case. To our knowledge, this is the firstreport of a successful live birth in a patient with locally advancedtongue cancer who successfully underwent postoperative FFF-VMAT as part of POCRT.DeclarationsAvailability of data and materialsAll data generated or analyzed during this study are included inthis published article. The datasets used and/or analyzed during12 W. Takahashi et al. / Clinical and Translational Radiation Oncology 20 (2020) 9–12the current study are available from the corresponding author onreasonable request.Consent for publicationWritten informed consent was obtained from the patient forpublication of this case report and accompanying images.FundingThis research did not receive any specific grant from fundingagencies in the public, commercial, or not-for-profit sectors.Authors’ contributionsWT participated in the radiation management of the patient,collected patient’s data, reviewed literature and drafted the manu-script. KN, AH, TI, KO CK performed the radiation treatment, anddosimetrical measurement and calculations for this patient. HY,OA, KN revised the article. All authors read and approved the finalmanuscript.Ethics approval and consent to participateThis report has been performed in accordance with the Declara-tion of Helsinki.We would like to thank Dr. Mizuo Ando, Dr. Masafumi Yoshida,and Dr. Yuki Saito for establishing the treatment strategy and forhelpful discussions. We thank Libby Cone, MD, MA, from DMCCorp. (www.dmed.co.jp <http://www.dmed.co.jp/>) for editingdrafts of this manuscript.Declaration of Competing InterestThe authors declare that they have no known competing finan-cial interests or personal relationships that could have appearedto influence the work reported in this paperReferences[1] Layton SA, Rintoul M, Avery BS. Oral carcinoma in pregnancy. 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Acceptable fetal dose using flattening filter-free volumetric arc therapy (FFF VMAT) in postoperative chemoradiotherapy of tongue cancer during pregnancy

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Acceptable fetal dose using flattening filter-free volumetric arc therapy (FFF VMAT) in postoperative chemoradiotherapy of tongue cancer during pregnancy

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