{"paper_id":"62242469-9a31-464b-872f-00d2d605870f","body_text":"Received\n 02/27/2018 \nReview began\n 02/27/2018 \nReview ended\n 03/06/2018 \nPublished\n 03/09/2018\n© Copyright \n2018\nTetar et al. This is an open access\narticle distributed under the terms of\nthe Creative Commons Attribution\nLicense CC-BY 3.0., which permits\nunrestricted use, distribution, and\nreproduction in any medium, provided\nthe original author and source are\ncredited.\nPitfalls of Ovarian Ablative Magnetic\nResonance-guided Radiation Therapy for\nRefractory Endometriosis\nShyama Tetar \n \n, \nAnna Bruynzeel \n \n, \nOmar Bohoudi \n \n, \nTheodoor Nieboer \n \n, \nFrank Lagerwaard \n1.\n Radiation Oncology, VU University Medical Center, Amsterdam, The Netherlands \n2.\n Radiation\nOncology, VU University Medical Center, Amsterdam, The Netherlands, amsterdam, NLD \n3.\n Department\nof Gynecology, Radboud University Medical Center\n\n Corresponding author: \nAnna Bruynzeel, \name.bruynzeel@vumc.nl \nDisclosures can be found in Additional Information at the end of the article\nAbstract\nIn this case presentation, we describe the challenges of performing magnetic resonance-guided\nradiation therapy (MRgRT) with plan adaptation in a patient with advanced endometriosis, in\nwhom several prior therapeutic attempts were unsuccessful and extensive pelvic irradiation\nwas regarded as being too toxic. Treatment was delivered in two sessions, first for the\nseemingly only active right ovary, and at a later stage for the left ovary. Some logistical\nproblems were encountered during the preparation of the first treatment, which were\nsubsequently optimized for the second treatment by using transvaginal ultrasound to\ndetermine the optimum time point for simulation and delivery. Using breath-hold gated\ndelivery and plan adaptation, radiation dose to the bowel could be minimized, resulting in good\ntolerance of treatment. Because of the need to simulate and deliver in a brief optimal time span\nfor visibility of the follicles in the ovaries, a single fraction dose of 8 Gy was used in our patient.\nHormonal outcome after her second treatment is still pending.\nIn conclusion, MRgRT with plan adaptation is feasible for the occasional patient with refractory\nendometriosis. Simulation and delivery needs to be synchronized with the menstrual cycle,\nensuring that the Graafian follicles allow the ovaries to be visible on magnetic resonance\nimaging (MRI). Because the ovaries are only visible on T2-weighted MRI for a very brief period\nof time, we suggest that it is preferable to use single fraction radiotherapy with a brief interval\nbetween simulation imaging and delivery.\nCategories:\n Obstetrics/Gynecology, Radiation Oncology, Healthcare Technology\nKeywords:\n mrgrt, endometriosis treatment, ovarian ablation, adaptive radiotherapy, adaptive planning\nIntroduction\nEndometriosis constitutes a benign gynecological condition that is characterized by the\npresence of ectopic endometrial-like tissues. Endometriosis is a chronic inflammatory disorder\nthat can significantly impact upon the quality of life with symptoms ranging from\ndysmenorrhea to pelvic or abdominal bowel symptoms, and in severe cases even obstruction or\nperforation \n[1]\n. Although pain medication, hormonal therapy, or surgery form the mainstay of\ntreatment for symptomatic patients, radiotherapy, usually in the form of extensive pelvic\nirradiation, has been applied in exceptional cases with refractory disease \n[2-3]\n. In this case\npresentation, we describe the challenges of performing magnetic resonance-guided radiation\ntherapy (MRgRT) in a patient with advanced endometriosis, in whom several prior therapeutic\nattempts were unsuccessful and extensive pelvic irradiation was regarded as being too toxic.\n1\n1\n2\n3\n1\n \n Open Access Case\nReport\n \nDOI:\n 10.7759/cureus.2294\nHow to cite this article\nTetar S, Bruynzeel A, Bohoudi O, et al. (March 09, 2018) Pitfalls of Ovarian Ablative Magnetic Resonance-\nguided Radiation Therapy for Refractory Endometriosis. Cureus 10(3): e2294. \nDOI 10.7759/cureus.2294\n\nCase Presentation\nA 44-year-old woman with an extensive history of advanced and refractory endometriosis\npresented with abdominal complaints associated with a pseudo-obstruction bowel syndrome.\nShe had previously undergone multiple abdominal surgeries, including a subtotal colectomy.\nShe did not respond to ovarian suppression with gonadotropin-releasing hormone agonist, and\na recent embolization of both ovarian arteries only achieved a partial and temporal hormonal\nresponse. Repeated post-embolization transvaginal ultrasound investigations could only\ndiscriminate the right ovary; the atrophic left ovary could not be visualized. Surgical\novariectomy was considered to be high-risk because of extensive abdominal and pelvic\nadhesions on a diagnostic magnetic resonance imaging (MRI). She subsequently was referred by\nher treating gynecologist for radiation to the right ovary in order to achieve a postmenopausal\nhormonal status. Because the patient suffered from chronic and severe bowel complaints with a\nneed for total parenteral nutrition, extensive pelvis radiation, a historical method for ovarian\nablation, was considered contraindicated. MR-guided radiotherapy, a recently introduced\nadvanced technique, was preferred in order to optimally spare the surrounding bowel and\nselectively treat the right ovary.\nIn preparation of MRgRT, on the day of the initial consultation, a simulation (SIM) MR scan was\nperformed on MRIdian (Viewray Inc., Mountain View, US). The SIM MR scan was acquired in\nshallow breath-hold in order to restrict respiratory artifacts. The MRIdian uses a 0.35 Tesla\nmagnetic field with a balanced steady state free precession (bSSFP) sequence. In this sequence\non the MRIdian, there is heavy T2 weighting, hence the fluid and the ovarian follicles are\nbright. However, as this acquired SIM MR scan did not take the phase in the menstrual cycle\ninto account, none of the ovaries were clearly detectable. This was confirmed by an experienced\nradiologist specialized in abdominal MRI who advised to perform a diagnostic MR scan first.\nThis scan was performed three weeks later and showed multiple follicles in the right ovary,\nwith only a small cyst at the location of the left ovary (Figure \n1\n).\nFIGURE\n 1: Coronal images from the diagnostic magnetic\nresonance imaging (MRI) scan\nCoronal T2-weighted images from the diagnostic MR scan showing the right ovary with three small\nfollicles (thick arrow) with a maximum diameter of 15 mm. The left ovary is not clearly recognizable,\nbut a small cyst is visible with a maximum diameter of 8 mm at the position of the ovary (thin arrow).\nWith the duration of the menstrual cycle in mind, the SIM MR scan was repeated one month\nlater showing a comparable image of the ovaries as on the diagnostic MRI. This SIM MR was\nused for the generation of a baseline plan, prescribing 8 Gy in a single fraction to the right\novary. Several days after the SIM MR, the patient returned for the scheduled treatment.\nUnfortunately, because she appeared to be in a postovulatory phase of her menstrual cycle, the\n2018 Tetar et al. Cureus 10(3): e2294. DOI 10.7759/cureus.2294\n2\n of \n5\n\nright ovary could not be seen on the pretreatment MR scan. Two more attempts in the weeks\nthereafter had to be performed before the right ovary was visible, and treatment could actually\nbe delivered. Plan re-optimization was useful, because both the position and volume of the\nright ovary were different on the SIM MR and the pretreatment MR (Figure \n2\n). Treatment was\ndelivered in shallow inspiration breath-hold with a 3 mm gating boundary between the right\novary and the planning target volume (PTV).\nFIGURE\n 2: Simulation scan versus pretreatment scan\nA coronal and axial view of the simulation scans is displayed on the left panels. On the right, a\ncoronal and axial view of radiotherapy treatment fraction is seen.\nGreen = the right ovary. Red = treatment boundary.\nThe patient reported mild symptoms of an inflated belly and some fatigue for which no\nintervention was required in the first days following treatment, both scored as grade 1 toxicity\n(CTCAE criteria v. 4.3). She experienced neither nausea nor diarrhea. Hormonal assessment at\nfour months follow-up revealed a serum estradiol (E2) of 40 pmol/L and serum follicle\nstimulating hormone (FSH) level of 70 U/L, indicating that she biochemically had reached a\npostmenopausal status. In addition to the hot flushes she experienced, the patient also\nreported having fewer abdominal complaints. Unfortunately, at six months follow-up, the\npatient appeared to have regained a biochemical premenopausal status. In addition, this was\nconfirmed by a transvaginal ultrasound that showed follicles, this time in an apparently active\nleft ovary. As a result of this finding, the patient was referred for local treatment by\nradiotherapy, now for her left ovary.\nHaving learned from the first procedure, this time the MRgRT was synchronized with her\nmenstrual cycle by performing weekly transvaginal ultrasound in order to determine the\nappropriate treatment window. As soon as the follicle was visible in the left ovary, the patient\nwas seen at our department with immediate MR simulation. After quick planning, the patient\nwas treated within 24 hours of the SIM MR scan with a single dose of 8 Gy. Similar to the first\ntreatment, the patient noticed mild abdominal complaints and fatigue in the first days\n2018 Tetar et al. Cureus 10(3): e2294. DOI 10.7759/cureus.2294\n3\n of \n5\n\nfollowing the second treatment. Toxicity did not impact upon her daily activities and was\ntherefore scored as grade 1. At one month after treatment, she reported that her bowel\nsymptoms were better than in previous years. She had even been able to discontinue total\nparenteral nutrition. The biochemical results after radiotherapy on the left ovary are pending.\nDiscussion\nThis case report describes an uncommon indication for radiotherapy with the goal to obtain\novarian ablation in a patient with refractory and advanced endometriosis. Given the extensive\nbowel complications in this patient, neither surgical ovariectomy nor extensive pelvic radiation\nwas considered feasible. It was contemplated that MR-guided focal radiotherapy directed\ntowards the remaining active right ovary might be beneficial in order to diminish potential\ngastro-intestinal side effects. One main difference between conventional radiotherapy (such as\ne.g., extensive pelvic irradiation) and MRgRT is that setup and radiation delivery is delivered to\na specific target rather than a region. Contrary to conventional radiotherapy, this necessitates\nthat the ovary is discernible on SIM and pretreatment MR scans.\nDiagnostic MR imaging of the normal ovaries is usually performed using T2-weighted imaging,\nwhich makes the bSSFP sequence of the MRIdian suitable for visualizing the ovaries. During the\nmenstrual cycle, the Graafian follicles can be seen as bright cysts within the ovarian stroma, and\nthis pre-ovulatory phase is ideal for imaging. Both simulation and MR-guided delivery,\ntherefore, have to take place in the last days of this relatively short time slot. During the first\ntreatment fraction, we used ‘trial and error’ and the irregular cycle of our patient necessitated\nseveral visits. In anticipation of the second treatment, simulation and delivery were\nsynchronized with her menstrual cycle by performing sequential transvaginal ultrasound\ninvestigations. Once the follicles were visible on this imaging, simulation and delivery took\nplace within 24 hours. For the same reason, we used single fraction radiotherapy, rather than a\nmore prolonged fractionation scheme. Clinical experience of ovarian ablative radiotherapy is\nmostly derived from older literature in breast cancer patients and has only been reported in\ncase reports for refractory endometriosis \n[2-3]\n. While radiotherapy for endometriosis is most\ncommonly delivered in the form of extensive pelvic irradiation in 15-20 Gy in 10 fractions, the\nliterature on hormonal castration in breast cancer patients describes a wider range of\nfractionation schemes, including the use of single-fraction irradiation. Because the most\nfrequently applied radiation scheme in the literature is 15 Gy in 5 fractions \n[4]\n, we selected a\nsingle fraction dose of 8 Gy which has a comparable biological equivalent dose for an \nα\n/\nβ\n of 3\nand slightly lower than that for an \nα\n/\nβ\n of 10.\nFrom a practical standpoint, we performed a scan during the shallow breath-hold and with a\nfull bladder to optimize visibility of the ovary, minimize target (and bowel) mobility, and enable\nbowel spacing. Plan adaptation was used to generate a conformal as possible dose distribution.\nThe cumulative dose distribution from both fractions can be seen in Figure \n3\n, which clearly\nillustrates the resulting relative sparing of the surrounding bowel, especially when compared\nwith conventional extensive pelvis irradiation. Despite two treatments with 8 Gy, the acute\ntoxicity has been minimal with temporary bowel symptoms and some fatigue. The results of\nhormonal outcome in our patient are pending.\n2018 Tetar et al. Cureus 10(3): e2294. DOI 10.7759/cureus.2294\n4\n of \n5\n\nFIGURE\n 3: The cumulative dose distribution\nA coronal and axial view of dose accumulation of both treatments projected on the first simulation\nmagnetic resonance (SIM MR) scan.\nBlue color wash = 4Gy. Inner red color wash = 8 Gy.\nConclusions\nMRgRT with plan adaptation is feasible for the occasional patient with refractory\nendometriosis. Simulation and delivery needs to be synchronized with the menstrual cycle,\nensuring that the Graafian follicles allow the ovaries to be visible on MRI. Because the ovaries\nare only visible on T2-weighted MRI for a very brief period of time, we suggest that it is\npreferable to use single fraction radiotherapy with a brief interval between simulation imaging\nand delivery.\nAdditional Information\nDisclosures\nHuman subjects:\n Consent was obtained by all participants in this study. \nConflicts of interest:\nIn compliance with the ICMJE uniform disclosure form, all authors declare the following:\nPayment/services info:\n Dr. Tetar has nothing to disclose. Dr. Bruynzeel reports speaker grants\nand travel fee from ViewRay, Inc. \nDr. Bohoudi has nothing to disclose. Dr. Nieboer has nothing\nto disclose. Dr. Lagerwaard reports speaker grants and travel fee from ViewRay, Inc. \nFinancial\nrelationships:\n All authors have declared that they have no financial relationships at present or\nwithin the previous three years with any organizations that might have an interest in the\nsubmitted work. \nOther relationships:\n All authors have declared that there are no other\nrelationships or activities that could appear to have influenced the submitted work.\nReferences\n1\n. \nFalcone T, Flyckt R: \nClinical management of endometriosis\n. Obstet Gynecol. 2018, [Epub\nahead of print], \n10.1097/AOG.0000000000002469\n2\n. \nThomas WW, Hughes LL, Rock J: \nPalliation of recurrent endometriosis with radiotherapeutic\nablation of ovarian remnants\n. Fertil Steril. 1997, 68:938–40. \n10.1016/S0015-0282(97)00342-7\n3\n. \nNomiya T, Harada M, Sudo H: \nRadiotherapy for inoperable and refractory endometriosis\npresenting with massive hemorrhage: a case report\n. J Med Case Rep. 2012, 6:308.\n4\n. \nAl Asiri M, Tunio M, Abdulmoniem R: \nIs radiation-induced ovarian ablation in breast cancer\nan obsolete procedure? Results of a meta-analysis\n. Breast Cancer (Dove Med Press). 2016,\n8:109-16. \n10.2147/BCTT.S94617\n2018 Tetar et al. Cureus 10(3): e2294. DOI 10.7759/cureus.2294\n5\n of \n5","source_license":"CC0","license_restricted":false}