ANTICANCER RESEARCH 34: 2537-2540 (2014)
A Novel Minimally Invasive Technique of High-Dose Rate Image-Based Intracavitary Brachytherapy for Endometrial Cancer Using a Single Fine and Soft, Flexible Applicator KOJI MASUI1, KEN YOSHIDA2, TADASHI TAKENAKA3, TADAYUKI KOTSUMA4, EIICHI TANAKA4, KEIJI TATSUMI5, HIDEYA YAMAZAKI1 and KEI YAMADA1 1Department
of Radiology, Kyoto Prefectural University of Medicine, Kyoto, Japan; of Radiology, Osaka Medical College, Osaka, Japan; Departments of 3Radiology, 4Radiation Oncology, and 5Obstetrics and Gynecology, National Hospital Organization Osaka National Hospital, Osaka, Japan 2Department
Abstract. Aim: We report on a minimally invasive computed tomography (CT)/magnetic resonance imaging (MRI)-based image-guided intracavitary brachytherapy (ICBT) for an elder patient with endometrial cancer, who was unfit for anesthesia, using a fine and soft flexible applicator. Patients and Methods: The patient was an 82-year-old female. She was identified as having T1bN0M0 (stage IB) tumor, and histological findings revealed grade 2 adenocarcinoma. She was contraindicated for surgery because of advanced age and severe pulmonary emphysema; therefore, she was managed with CT/MRI-based ICBT alone. The total treatment dose was 26 Gy (6.5 Gy per fraction). The dose–volume histogram of the gross tumor volume, the clinical target volume, and organs at risk were calculated. Results: The patient safely completed the ICBT
Abbreviations: ICBT: Intracavitary brachytherapy; EBRT: external beam radiation therapy; ABS: American Brachytherapy Society; GEC-ESTRO: The Groupe Européen de Curiethérapie and the European Society for Radiotherapy & Oncology; CT: computed tomography; MRI: magnetic resonance imaging; ONH: National Hospital Organization Osaka National Hospital; UICC: Union for International Cancer Control; DVH: dose–volume histogram; GTV: gross tumor volume; CTV: clinical target volume; OAR: organs at risk; 3D: three-dimensional; D100 (target volume): dose that covered 100% of target volume; D90 (target volume): dose that covered 90% of target volume; 100% PD: 100% prescribed dose; D2cc (OAR): maximally irradiated 2-cc volume of organs at risk; V100 (target volume): target volume covered by 100% prescribed dose. Correspondence to: Koji Masui, MD, Department of Radiology, Kyoto Prefectural University of Medicine, 465, Kajiicho, Kamigyouku, Kyoto-city, Kyoto-prefecture, 602-8566 Japan. Tel: +81 752515620, Fax: +81 752515840, e-mail:
[email protected] Key Words: Intracavitary brachytherapy, endometrial cancer, imagebased brachytherapy, fine and soft applicator.
0250-7005/2014 $2.00+.40
course without pre-medication. Tumor growth was controlled, with complete disappearance after 32 months. No acute or late adverse effects were observed. MRI-guided ICBT can visualize the gross tumor volume in the uterine body, which cannot be detected by CT. Conclusion: We successfully and safely performed minimally invasive CT/MRI-based ICBT without pre-medication in a patient with endometrial cancer with high surgical risks, using a fine and soft, flexible applicator. The standard treatment for early-stage endometrial cancer is surgery. However, patients with advanced age, severe medical conditions (obesity, hypertension, diabetes mellitus, coronary artery disease, etc.) may be contraindicated for surgery. Patients with such conditions are often treated with definitive radiotherapy including intracavitary brachytherapy (ICBT) or external-beam radiation (EBRT). Considering the presence of some risks, we often cannot administer pre-medications such as sedatives and analgesics. In addition, these fragile patients are usually uncomfortable with invasive procedures. In recent years, the American Brachytherapy Society and the Groupe Européen de Curiethérapie and the European Society for Radiotherapy and Oncology (GEC-ESTRO) published recommendations of image-based brachytherapy using computed tomography (CT) or magnetic resonance imaging (MRI) for cervical cancer (1-3), which has led to increased reports on the use of image-based brachytherapy for cervical cancer; however, there have been a few reports for endometrial cancer (4). Therefore, here we describe the minimally invasive CT- and MRI-based ICBT using a fine and soft flexible applicator for the treatment of endometrial cancer.
Patients and Methods Patient characteristics. An 82-year-old patient with endometrial cancer was treated with ICBT alone at the Department of Radiation Oncology, National Hospital Organization Osaka National Hospital
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ANTICANCER RESEARCH 34: 2537-2540 (2014) (ONH). Using the Union for International Cancer Control (UICC) classification of 2002 (5), she was identified as having T1bN0M0 (stage IB) tumor. Histological findings confirmed grade 2 adenocarcinoma. Pre-treatment MRI proved that the tumor was limited to the uterine body, with a maximum diameter of 2.1 cm. The tumor was judged as being surgically-inoperable considering the high surgical risks, advanced patient age, and the fact the patient had severe pulmonary emphysema with home oxygen therapy. Applicator implantation. The patient was placed in the lithotomy position in the treatment room. Firstly, a sounding tube was inserted from the cervical os to the uterine fundus to measure the length of the uterine cavity to conclude its curvature. We used a fine and soft, flexible applicator (Flexible implant tube 6F, blind end, 30 cm®; Nucletron, Elekta AB, Stockholm, Sweden) that was ordinarily used for interstitial implantation (Figure 1). The shape of a metal obturator was altered to fit the uterine curvature, and the obturator was inserted into it. A plastic button stopper (Radiopaque button, 1.9 mm®; Nucletron) was fixed to the applicator at the position defined by the cavity length. Thereafter, the applicator was inserted into the uterine cavity, and the button stopper was fitted to the cervical os. After complete applicator insertion, we packed gauze into the vaginal cavity to fix the applicator position. Treatment planning and treatment. After the applicator insertion, plain CT and MRI were performed. The metal obturator was extracted after obtaining CT images. MRI examinations included axial and sagittal T2-weighted sequences. Both CT and MRI images were obtained with 2.5-mm slice thickness. In the treatment planning system (Oncentra® brachy; Nucletron), we delineated target volumes [gross tumor volume (GTV), clinical target volume (CTV)] using the planning system function of CT/MR image registration (Figure 2), as well as the organs at risk (OAR: rectum, bladder, and sigmoid). We defined the volume visualized as a relatively high intensity area on T2-weighted MRI as the GTV and the entire uterine body and cervix as the CTV. The external walls of the rectum, bladder, and sigmoid colon were delineated according to GEC-ESTRO recommendations for three-dimensional (3D) image-based brachytherapy on cervical cancer (1-3). We performed CT-based 3D treatment planning and evaluated the tumor coverage, as well as the dose for OAR using dose–volume histograms (DVH). Firstly, we formulated a plan based on the classic Manchester calculation method, and subsequently, we modified the plan using a manual or graphical optimization algorithm to fit the following goals (6): (i) the dose that covered 100% of the GTV [D100(GTV)] was ≥100% prescribed dose (100% PD), (ii) the dose that covered 90% CTV [D90(CTV)] was ≥100% PD, (iii) the minimum dose received by the maximally irradiated 2cc volume of OARs [D2cc(OAR)] was less than 100% PD. The single-fraction dose was 6.5 Gy, and the total prescribed dose was 26 Gy in four fractions. Four scheduled fractions were finished in four weeks. We used the microSelectron-HDR® (Nucletro) for treatment and iridium-192 as the treatment source.
Results Treatment outcome. The patient safely completed the entire ICBT course. No pre-medication was required. The tumor disappeared completely, with no evidence of recurrence at the 32-month follow-up (Figure 3). No acute or late adverse effects were observed.
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DVH analysis. GTV and CTV were 1.1 cc and 47.4 cc, respectively. The dose -distribution curve was formed by CT and MRI guidance, and we almost achieved our dose-specification goals. V100 (GTV) was 100%. Moreover, D90 and D100 (GTV) per fraction were 21.9 Gy and 17.9 Gy, respectively. V100 (CTV) was 85.7%. In addition, D90 and D100 (CTV) per fraction were 6.4 Gy and 3.0 Gy, respectively (Figure 4). Furthermore, D2cc (rectum) per fraction was 6.4 Gy, D2cc (bladder) per fraction was 5.4 Gy, and D2cc (sigmoid colon) per fraction was 3.1 Gy.
Discussion In standard ICBT technique, pre-medication, including sedatives and pain relievers, or spinal anesthesia (4, 7, 8) are usually required because conventional applicators such as single tandem, two-channel ‘Y’ applicator (Rotte ‘Y’) (7, 8) and Inoue applicator (9) are too rigid and thick. To resolve this issue, we used a fine and soft, flexible applicator with a round tip to ensure no injury to the uterine mucosa. Therefore, we were able to safely and easily insert this applicator into uterine fundus without dilating the cervical os and without the need for pre-medication. Bush et al. reported a similar technique using a soft applicator tube in ICBT for cervical cancer (10). However, their technique required minor surgery, such as hernia vesicalis, before applicator implantation, and they performed a 2-D treatment planning. Our presented techniques do not require any pre-medication, and the patient reported no complaints. Furthermore, we are able to use MRI images in assisting CT-based treatment planning by image fusion because our flexible applicator and button complex used nonmagnetic materials. MRI-guided image-based brachytherapy was able to visualize the GTV in the uterine body, which is impossible to do by CT. We successfully delineated the GTV in the uterine body precisely using CT-based planning with the aid of CT/MRI registration (Figure 2) so that we could evaluate the detailed DVH for GTV by MRI-aided planning. Weitmann et al. have reported MRI and CT-based ICBT for various volumes of endometrial cancer (4) using the modified Heyman packing technique. Although these explorations should be appraised, they required spinal anesthesia. Therefore, our minimally invasive technique without any premedication should be a good option for fragile patients. A limitation of our technique is the risk of insufficient dose coverage for large target volumes because only a single applicator was used. In ICBT for endometrial cancer, selection of the applicator type is considered very important for obtaining sufficient coverage to the target volume. Fortunately, in this case, the dose distribution revealed sufficient dose coverage around the target volumes. Therefore, we consider that for small tumors, we can deliver a sufficient dose to the target volume using a single-channel applicator (11).
Masui et al: MRI-ssisted Image-based Brachytherapy for Endometrial Cancer
Figure 1. The left image presents the lateral view, and the right image the end view of the sounding tube (a), flexible applicator with obturator (b), metal tandem (c), tandem of the computed tomographic/magnetic resonance imaging applicator (d). The fine and soft, flexible applicator shown in (b) (broad arrow) has a diameter of 6 Fr, and is finer compared with the sounding tube (a) and tandems (c, d).
Figure 3. The magnetic resonance image was recorded before and after treatment. The left image was recorded before the treatment, and the right image was recorded 14 months after treatment. The tumor in the uterus can be seen to have completely disappeared.
Figure 2. We delineated target volumes using the planning system function of computed tomography/magnetic resonance image registration. The registration image is inside the circle. The gross tumor volume is indicated with arrowheads (red line), and the clinical target volume is indicated by the pink line. The applicator is indicated by an arrow (red dots). The applicator, rectum (*1), and sigmoidal colon (*2) were delineated using computed tomography.
Figure 4. This figure presents the same computed tomography image as in Figure 2. Dose-distribution curves are presented, and arrowheads indicate the 100% prescribed isodose line. The gross tumor volume is indicated with a red line, and clinical target volume is indicated with a pink line. The applicator is indicated with red dots. Rectum (*1) and sigmoidal colon (*2) were delineated using computed tomography.
Conclusion
MD; Chiaki Ban, MD; other staff of the Departments of Radiology, Obstetrics, and Gynecology; and Nursing staff for helping us in many ways for the successful completion of this study.
We were able to safely perform minimally invasive CT/MRIbased ICBT without premedication in a patient with endometrial cancer with high surgical risks, using a fine and soft, flexible applicator.
Acknowledgements We would like to thank Kazumasa Aramoto, RTT; Shunsuke Miyake, RTT; Mari Ueda, RTT; Aki Narikiyo; Shigetoshi Yamada,
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Received January 22, 2014 Revised March 21, 2014 Accepted March 24, 2014
