2 Materials and methods
2.1 Patients
Under the guidance of the Ethics Committee of Peking University School and Hospital of Stomatology, 7 pediatric patients with DT in HN treated with 125I seed brachytherapy from January 2008 to June 2018 in the Peking University School of Stomatology were included in this study. All the pediatric patients’ guardians signed their informed consents, which were well documented. Among the included patients, 4 were male and 3 were female. The median age was 3 years old, ranging from 3 to 8 years old. The median of maximum diameter of the primary tumor was 6.0 cm, ranging from 2.5 to 10.0 cm. The median follow-up time was 57 months, ranging from 43 to 135 months. The site tumor involved including 4 at the parapharyngeal region and 3 at the skull base region. The detailed patients’ characteristics were listed in Table 1. The R stage was classified as R0 with microscopically negative margin according to pathological examination, R1 with macroscopically negative margin according to the surgeon but microscopically positive margin, and R2 with macroscopically positive margin.
2.2 Treatment
After evaluation by an experienced medical group, 4 to 6 weeks before brachytherapy, 2 patients underwent surgery with R2 margin for vital organ preservation, and 1 to 2 weeks before brachytherapy, biopsies were performed on the other five patients with tumors invading the critical structures in HN, such as skull base, facial nerves and any other vital nerves or vessels. The pathological specimens were examined and diagnosed by two centers with expert pathologists in consensus. Then the computed tomography (CT) scanning of the HN with a slice thickness of 0.75 mm, tube voltage of 120 kV, and tube current of 225–300 mA was performed on all patients using a GE Optima CT680 scanner. Then all the Digital Imaging and Communications in Medicine (DICOM) data were transferred into a brachytherapy treatment planning system (BTPS, Beijing Atom and High Technique Industries). Referring to the tumor boundary based on the magnetic resonance imaging (MRI), the planning target volume (PTV) were contoured by extending the gross tumor volume (GTV) with a distance of 0.5 to 1.0 cm in the BTPS based on CT imaging. The prescription doses were set from 10 000 cGy to 12 000 cGy according to the size, subsite and the tolerance doses of the adjacent vital structures, with a median of 12 000 cGy, in the BTPS, using the 125I seeds with a surface radioactivity of 18.5 MBq per seed (type 6711, t1/2, 59.4 days, Beijing Atom and High Technique Industries, Beijing, China).
Three-dimensional printed individual templates12 along with intraoperative CT or a far-infrared navigation guidance system (iPlan 3.0, Brainlab, Feldkirchen, Germany) were used to assist the 125I seeds distribution. Then the 125I brachytherapy were performed under general anesthesia according to the previous design. Finally, the post-implant dosimetry parameters were calculated based on the post-implant CT by BTPS (Figure 1).
2.3 Follow-up
Patients received physical examination, CT and (or) MR every two months in the first half year, and every three or six months thereafter, and core-needle biopsy when confirmation for tumor response was needed. The safety were evaluated with radiation-relevant toxicities according to the Radiation Therapy Oncology Group (RTOG) grading system13. The effectiveness was evaluated with local control (LC) rate. And LC were defined as the absence of tumor after surgery combined with brachytherapy, or complete response (CR) and partial response (PR) according to the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.114 after sole brachytherapy.