Patients indications selection
Totally 15 patients with 17 lesions from recurrent carcinomas located in retroperitoneal regions who received EBRT were enrolled in this study (Table 1). The pre-RT doses ranged from 30 to 80 Gy. The median tumor volume was 23.1 cc (range, 5.1–68.6 cc). The indications for selected patients in this study were as follow: (1) pathological or radiological diagnosis were confirmed; (2) the diameter ≤ 5 cm and no invasion to intestinal tube or spine; (3) preoperative plan showed that the needle channel pathway and the prescribed doses were satisfactory; (4) predicted survival time ≥ 3 months. The exclusion criteria were as follow: (1) severe coagulation functional disorder; (2) tumor invasion into spine or intestine; (3) preoperative plan showed that there was no satisfied needle puncture pathway. The study was approved by the ethic committee of our hospital.
Table 1
| Number | Percentage (%) |
Gender | | |
male | 7 | 46.7 |
Female | 8 | 53.3 |
Age, years | | |
Median (range) | 58 (38–78) | |
Primary tumor location | | |
Esophagus | 3 | 20 |
Pancreas | 1 | 6.7 |
Cervix | 4 | 26.7 |
Corpus uteri | 3 | 20 |
Liver | 1 | 6.7 |
Colon | 1 | 6.7 |
Ureter | 1 | 6.7 |
Cardia | 1 | 6.7 |
Stage | | |
I | 3 | 20 |
II | 4 | 26.7 |
III | 4 | 26.7 |
IV | 4 | 26.7 |
Pathological type | | |
Squamous cell carcinoma | 7 | 46.7 |
Adenocarcinoma | 2 | 13.3 |
Hepatocellular carcinoma | 1 | 6.7 |
Urothelium carcinoma | 1 | 6.7 |
Endometrioid adenocarcinoma | 3 | 20 |
Neuroendocrine carcinoma | 1 | 6.7 |
Previous treatment | | |
EBRT | 15 | |
Prescribed doses (Median, range) | 50.4(30–80) | |
Implantation Location | | |
Retroperitoneal lymph node | 13 | 76.5 |
Adrenal gland | 3 | 17.6 |
Pancreas | 1 | 5.9 |
Table 2
The deviation of position, angle and distance of needles between preoperative plan and intraoperation plan in B-TPS.
| No. of needles | Deviation of position (mm) | Deviation of angle (°) | Deviation of distance (mm) |
Mean | Range | SD | Mean | Range | SD | Mean | Range | SD |
| 165 | 4.5 | 0–30 | 4.1 | 2.7 | 0–20 | 3.0 | 6.9 | -30 ~ 28.1 | 6.0 |
P | | 0.000 | | | 0.000 | | | 0.000 | | |
Table 3
The dosimetric parameters of 125I seeds implantation (x ± s)
| Preoperative | Intraoperative | Postoperative | P* | P** | P*** |
Number of needles | 10.76 ± 4.05 | 9.76 ± 3.80 | 9.82 ± 3.75 | 0.010 | 0.007 | 0.332 |
Number of seeds | 48.00 ± 16.80 | 46.82 ± 18.25 | 47.88 ± 18.75 | 0.595 | 0.962 | 0.070 |
GTV volume(cm3) | 26.41 ± 16.2 | 26.71 ± 17.43 | 26.72 ± 17.46 | 0.585 | 0.629 | 0.952 |
D90 | 140.55 ± 23.93 | 124.25 ± 28.04 | 128.98 ± 22.75 | 0.036 | 0.102 | 0.338 |
D100 | 66.70 ± 16.77 | 58.14 ± 21.24 | 61.51 ± 15.86 | 0.169 | 0.459 | 0.500 |
V100 | 24.83 ± 15.94 | 22.71 ± 12.1 | 23.64 ± 13.75 | 0.142 | 0.317 | 0.129 |
V150 | 20.02 ± 13.32 | 17.45 ± 10.15 | 18.74 ± 11.53 | 0.058 | 0.302 | 0.056 |
V200 | 14.51 ± 11.02 | 12.38 ± 8.07 | 23.59 ± 8.97 | 0.119 | 0.451 | 0.072 |
CI | 0.54 ± 0.16 | 0.50 ± 0.15 | 0.50 ± 0.17 | 0.68 | 0.342 | 0.985 |
EI | 0.90 ± 1.00 | 0.91 ± 0.90 | 1.06 ± 0.99 | 0.981 | 0.553 | 0.119 |
HI | 0.22 ± 0.07 | 0.25 ± 0.09 | 0.21 ± 0.08 | 0.380 | 0.637 | 0.117 |
Note: P* refers to preoperative vs. intraoperative; P** refers to preoperative vs. postoperative. P*** refers to intraoperative vs. postoperative. |
Table 4
Perioperative and postoperative complication of seeds implantation.
| | RTOG/CTC Scoring Schema |
| | G1 | G2 | G3 | G4 |
Perioperative | Pneumothorax | 0 | 1 | 0 | 0 |
Hematemesis | 1 | 0 | 0 | 0 |
Hemorrhage of digestive tract | 1 | 0 | 0 | 0 |
Fever | 0 | 0 | 0 | 0 |
Infection | 0 | 0 | 0 | 0 |
Postoperative | Skin | 1 | 0 | 0 | 0 |
Patients Preparation And Preoperative Plan
Patients were set-up on the CT simulator and immobilized at prone position with vacuum bad. Both native and contrast CT scan were performed with 5 mm thickness before RSI-BT. The CT scan slices were transferred into B-TPS (Beijing University of Aeronautics and Astronautics and Beijing Astro Technology Co., Ltd) for preoperative plan. Planning system source data originated from the latest official manuscripts of the American Association of Physicists in Medicine (AAPM) [18, 19].
The Principle Of Preoperative Plan Design
The needles should be kept in parallel, with distance of 1-1.5 cm. If the organs at risk (OARs) interference for the needles, no co-planar needles distribution was adapted to satisfy the targets doses conformity and the lowest doses to normal tissue. Then we delineated targets and OARs, and defined prescribed doses and limitation of OARs. Clinical target volume (CTV) was expanded from gross tumor volume (GTV) by 5–6 mm in three dimensions. Prescribed doses were 110–160 Gy, the radioactivity of 125I seed was 0.4–0.7 mCi (The seed model was 6711 − 1985, Shanghai GMS Pharmaceutical Co., Ltd). The principles of seeds distribution were sparse in the center and dense at the peripheral zone of the targets (Fig. 1).
3D-PNCT Design And Production
The B-TPS data were imported into 3D imaging and reverse engineering software for individualized digital modeling design. 3D-PNCT were obtained by a 3D curing rapid prototyping machine and the material processing of medical curing resins. The 3D-PNCT contained certain information such as body-surface characteristics, X, Y axle coordinate, 2–3 stable needles and dummy needles channel holes.
We classified recurrent retroperitoneal carcinoma into 3 subgroups according to the recurrent locations referenced to spinal cord. The definition of subgroup included: (1) Type 1: the recurrent tumors located in left side of spinal cord and the front margin did not spread to the middle line, the needles inserted from left side; (2) Type 2: the recurrent tumor located before the front edges of spinal cord, the needles inserted from two sides; (3) Type 3: the recurrent tumors located in right side of spinal cord and the front margin did not spread to middle line of spinal cord, the needles inserted from right side (Fig. 2).
The Work-flow Of 125I RSI-BT
The procedures of 125I RSI-BT were as follow: (1) patients were set-up again with template fixed on the patient body by 2–3 stable needles; (2) CT-scan was performed to verify the stable needles position. If the deflection errors were ༞2 mm, we adjusted the needles position until the deviation ≤ 2 mm. (3) The other implant needles were inserted into the targets; (4) CT scan was performed again to check the tips of the needles position. If the deflection errors were ༞2 mm, we made a fine adjustment until the errors were ≤ 2 mm; (4) 125I seeds were implanted with applicators according to the preoperative plan and the needles withdraw to the skin below 1 cm; (5) CT scans were conducted again to verify the seeds distribution. If the seeds distribution did not meet the requirements of preoperative plan, seeds savage implantation was performed immediately and all the needles were taken out; (6) CT scan was performed again and transferred the slices into the B-TPS for postoperative doses parameters calculation [17]. After RSI-BT, the patients return to patients wards and received perioperative prophylactic antibiotics and hemostasis one day and discharged 24 hours later.
Postoperative Plan For Dosimetric Verification
The D90, D100, V100, V150 and V200 were recognized as the dosimetric parameters of tumor target. The quality assurance comparison of RSI-BT involved CI, EI and HI among preoperative plan, real-time plan and postoperative plan.
Definition Of End Points:
Main-end points: (1) To evaluate the accuracy of needle distributions, we compared the preoperative planned with intra-operative on B-TPS. The CT images in preoperative plan were confused with intra-operative real-time CT scan images depending on bone construction as the references. The needles tips positions, the needles angles and the tips depth were measured; (2) The D90 (doses delivered to 90% of the target volume), D100, V100 (the percentage of the target volume receiving at least 100% of the prescribed doses), V150 and V200 were calculated; (3) The quality of RSI-BT in preoperative plan, real-time and postoperative plan targets were compared with CI, HI and EI.
Secondary main-point: (1) Peri-operation side effects assessment included bleeding, fever, infection, fistula; (2) The radiation related complications were assessed according to RTOG Common Toxicity Criteria; and (3) Pain relief rate was evaluated.
Follow-up
After RSI-BT, routine follow-up was performed every 3 months in the first 2 years and every 6 months from 3 to 5 year, followed by annual evaluation. CT scans of the thorax and abdomen was part of the follow-up for contrast. Patients underwent clinical evaluation and laboratory testing. The evaluation of efficacy was based on the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, including complete response (CR), partial response (PR), progressive disease (PD), and stable disease (SD). Adverse reactions were evaluated by the Common Terminology Criteria for Adverse Events (CTCAE) v 4.0 (CTCAE 2010) [20, 21]. Pain was assessed using a numerical rating scale (NRS) which was categorized into five grades: 0 for no pain, 1–3 for mild pain, 4–6 for moderate pain, 7–9 for severe pain, and 10 for unbearable pain. The pain score in one month after the treatment was compared with that of pre-operation.
Statistical analysis
The characteristics of patients were expressed as continuous variables and/or categorical variables. Continuous variables were compared using the t-test or rank-sum test, whereas the categorical variables were compared using the chi-square or Fisher’s exact test. ORR was expressed based on the number and percentage of patients. SPSS 21.0 software (SPSS, Chicago, IL) was used for statistical analysis. The P value < 0.05 was considered as statistical significance.