Evaluating the effectiveness of computed tomography-guided 125I seed interstitial implantation in patients with secondary adrenal carcinoma
ABSTRACT
Aim: This study aimed to evaluate the feasibility, safety, and clinical efficacy of computed tomography (CT)-guided 1251 seed interstitial implantation in patients with secondary adrenal carcinoma.
Materials and Methods: Twenty patients with secondary adrenal carcinoma received CT-guided 125| seed interstitial implantation. A three-dimensional treatment planning system was used to calculate the dose distribution before 1251 seed interstitial implantation. CT scans were performed every 2 months after the treatment to evaluate local therapeutic efficacy according to the Response Evaluation Criteria in Solid Tumors.
Results: The mean follow-up time was 23.65 months (5-102 months). The mean maximum tumor diameter was 34.16 ± 18.94 mm at the beginning of follow-up and 14.42 ± 24.07 mm at the end of follow-up. Eleven patients had complete response (CR), seven had partial response (PR), one had stable disease, and one had progressive disease. Local control rate (CR + PR) was 90% (18/20). The median survival time was 19 months (5-71 months). The 1-, 2-, 3-, and 5-year overall survival rates were 83.70%, 46.8%, 20.80%, and 20.80%, respectively.
Conclusion: CT-guided 125| radioactive seed interstitial implantation may be a feasible, safe, effective, and minimally invasive treatment for secondary adrenal carcinoma.
KEY WORDS: Adrenal gland, brachytherapy, computed tomography-guided, iodine 125, secondary carcinoma
INTRODUCTION
Malignant adrenal tumors can be primary tumors or secondary metastases, with metastases representing the most common malignancy. Most patients diagnosed with secondary adrenal tumors were not considered for surgery due to the lack of symptoms in the early stage.[1,2] In recent years, 125I seed interstitial implantation has been widely used in the treatment of recurrent head and neck tumor, prostate cancer, liver cancer, pancreatic cancer, lung cancer, and metastatic cancers, with obvious local therapeutic efficacy.[3-5] In this study, we aimed to examine the effectiveness of computed tomography (CT)-guided interstitial 125I seed implantation in patients with secondary adrenal malignancies.
MATERIALS AND METHODS
Patient information and selection
Twenty consecutive patients received CT-guided 125I seed percutaneous interstitial implantation
treatment in our department from December 2009 to January 2018. Of the total patients, 16 were male and 4 were female, with a mean age of 57 years (range: 10-81 years). The following patients had secondary adrenal carcinoma: one with bilateral lesions and 19 with unilateral lesion (7 had lesions at the left side and 12 had lesions at the right side). Eighteen patients had metastasis to the adrenal gland (nine with lung cancer, four with hepatocellular carcinoma, two with esophagus cancer, one with colon cancer, one with gastric cancer, and one with renal cancer). One patient had primitive neuroectodermal tumor and one had lymphoma. All patients were diagnosed by pathological biopsy. All patients underwent systemic
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Zheng-Yu Lin*, Jia-You Yang1*, Jin Chen, Jian Chen
Department of Interventional Radiology, First Affiliated Hospital of Fujian Medical University, Fuzhou, ‘Department of Radiology, Fujian Provincial Nanping First Hospital, Nanping, China
For correspondence: Dr. Zheng-Yu Lin, Department of Interventional Radiology, First Affiliated Hospital of Fujian Medical University, 20 Chazhong Road, Fuzhou 350005, China. E-mail: linsinlan@ aliyun.com
*Zheng-Yu Lin and Jia- You Yang contributed equally to this work and should be considered co-first authors
Access this article online
Website: www.cancerjournal.net
DOI: 10.4103/jcrt.JCRT_6_19
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Cite this article as: Lin ZY, Yang JY, Chen J, Chen J. Evaluating the effectiveness of computed tomography-guided 125I seed interstitial implantation in patients with secondary adrenal carcinoma. J Can Res Ther 2019;15:813-7.
| Parameter | Number of patients |
|---|---|
| Age (years) | |
| Mean age | 56.85±16.94 |
| ≤60 | 7 |
| ≥60 | 13 |
| Gender | |
| Male | 16 |
| Female | 4 |
| Primary tumor | |
| Primitive neuroectodermal tumor | 1 |
| Lymphoma | 1 |
| Lung cancer | 9 |
| Hepatocellular carcinoma | 4 |
| Esophagus cancer | 2 |
| Colon cancer | 1 |
| Gastric cancer | 1 |
| Renal cancer | 1 |
| Location of secondary tumor | |
| Right adrenal gland | 12 |
| Left adrenal gland | 7 |
| Bilateral adrenal gland | 1 |
| Tumor size (21 lesions) (mm) | |
| Mean size | 34.16±18.94 |
| ≤20 | 6 |
| 20-30 | 5 |
| 30-40 | 4 |
| >40 | 6 |
| Pretreatment | |
| Chemotherapy | 4 |
| Surgery + chemotherapy | 9 |
| Targeted therapy | 1 |
| Surgery + targeted therapy | 4 |
| Surgery + TACE+targeted therapy | 2 |
| Existence of other distant metastasis | |
| No | 7 |
| Yes | 13 |
TACE=Transarterial chemoembolization
therapy (such as chemotherapy and targeted therapy) for primary and metastasis lesions prior to implantation. Thirteen patients had other distant metastases apart from secondary adrenal carcinoma [Table 1], which were effectively controlled except the adrenal lesions. Hypertension did not occur before the operation. This study was approved by the Ethics Committee of the First Affiliated Hospital of Fujian Medical University, and all patients signed a written informed consent form.
Equipment
Toshiba Aquilion M16-slice spiral CT scanning was used in this study, and HGGR 3000 three-dimensional Treatment Planning System (TPS; HOKAI, Zhuhai, China) was used to calculate the dose distribution. The 17-G coaxial implantation needle (11 cm, Gallini), 18-G PTC needle (20 cm, Hakko), and seed implantation device (HTA, Beijing, China) were utilized for seed implantation. The 125I radioactive seeds (length: 4.5 mm, external diameter: 0.8 mm, nominal activity: 0.8 mCi, half-life: 59.6 days; HTA, Beijing, China) were used.
Pretreatment planning
Before the adrenal brachytherapy was initiated, the patients were routinely examined to determine the lesion size and the
surrounding tissue of the lesion under plain and enhanced CT scanning. The informations obtained were transferred to the TPS. The total number, distribution, and activity of 125I seeds were calculated; the matched peripheral dose within the target volume was 120 Gy, with a 1.5-cm margin external to the GTV. Routine blood test and blood coagulation index were used to rule out bleeding disorders.
Computed tomography-guided implantation
The appropriate position for the implantation was selected for each patient. A positioning grid was placed on the puncture side, and puncture path and entry point were determined by CT scan; three-dimensional reconstruction was conducted if necessary. The surgical area was disinfected and draped, and local anesthesia (2% lidocaine) was administered. A 17-G coaxial needle was gradually inserted 2 cm proximal to the lesion in the adrenal gland, and the needle core was pulled out; then, an 18-G PTC needle was gradually inserted distally into the lesion to implant one 125I radioactive seed. Direction and location of the needle were gradually adjusted under CT guidance, and the 125I radioactive seed implantation was performed according to the preoperative TPS. The different puncture paths used were as follows: transhepatic approach in two patients [Figure 1], trans-perirenal space by posterior approach in nine patients [Figures 2 and 3], and transpleural cavity after artificial pneumothorax in nine patients [Figure 4]. With regard to the transpleural cavity approach, 200-400 ml filtered air was injected into the pleural cavity to produce an artificial pneumothorax. After fully compressing the lung tissue, the coaxial needle was inserted proximal to the lesions via the transpleural cavity and diaphragm. Air was aspirated out of the pleural cavity at the end of treatment. Routine postoperative CT scans were conducted to assess the seed distribution and complications.
Follow-up
Tumor size was evaluated by adrenal CT scan every 2 months after seed implantation. The endpoint of this study was overall survival (OS). The objective response rate of brachytherapy, including complete response (CR), partial response (PR), stable disease, and progressive disease, was calculated according to the Response Evaluation Criteria in Solid Tumors. Local control rate was defined as the proportion of CR + PR.
RESULTS
General characteristics
In total, 836 125I radioactive seeds (8-82 seeds/lesion) were implanted into 21 lesions, with a mean dose of 27.84 ± 19.90 mCi (range: 6.4-65.6 mCi). After treatment, two patients had mild bleeding in the chest, three had peri-nephric hematoma, and four had a very small amount of residual air in the thoracic cavity after the transpleural cavity approach. No massive bleeding caused by injury to the liver, kidneys, lungs, and other organs and no postoperative hypertension
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occurred. The patients who underwent 125I implantation in both adrenal glands required long-term glucocorticoid therapy to prevent adrenal failure.
Therapeutic effect
The mean follow-up time was 23.65 ± 23.81 months (5-102 months). The median survival time was 19 months (5-71 months), and 11 patients died during follow-up. The 1-, 2-, 3-, and 5-year OS rates were 83.70%, 46.8%, 20.80%, and 20.80%, respectively [Figure 5]. New metastases in other organs were found in 16 patients. Eleven patients had CR, seven had PR, one had SD, and one had PD. The local control rate was 90% (18/20). The remission rate was 90.0% (CR + PR). The mean maximum tumor diameter was 34.16 ± 18.94 mm
at the beginning of follow-up and 14.42 + 24.07 mm at the end of follow-up (t = 5.226, P < 0.05).
DISCUSSION
Adrenal anatomical characteristics
The adrenal gland is located inside the upper pole of the kidney; as a retroperitoneal organ, it is encased in the same renal fascia and fat sac with the kidney. Because adrenal tumors are adjacent to the kidneys, lungs, liver, spleen, pancreas, and large blood vessels, which can lead to the damage to adjacent organs during puncture, the surgical removal of adrenal tumors should be performed by an experienced and skilled practitioner.
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Survival Analysis
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Technique
Puncture approach
The following puncture approaches can be used: transliver, translung, or transpleural cavity and trans-perirenal space. The transliver approach is always used when the lesions are small, and the posterior approach is occluded by the adjacent organs, avoiding damage to the large intra-hepatic blood vessels and bile ducts during the procedure. In our study, two patients with lesions <2 cm underwent transliver puncture. However, the posterior approach of the trans-perirenal space was usually selected for larger lesions, thus avoiding injury to the kidneys. If the puncture path is occluded by the kidney, a nonaxial needle path can be used in the posterior
approach. During the procedure, the direction of the needle and the distance between the needle and surrounding vital organs can be guided by CT scan and three-dimensional imaging [Figure 3]. The risk for iatrogenic pneumothorax and pulmonary hemorrhage is higher in patients who underwent a translung puncture path, because the needle tract is adjusted many times and puncture is repeated several times. Owing to lung tissue compression after artificial pneumothorax, the needle is inserted into the lesions by piercing the diaphragm through the aerated pleural cavity, avoiding damage to the visceral pleura and lungs; this approach can significantly reduce the incidence of iatrogenic pneumothorax.[6] No massive hematoma at adjacent organs or iatrogenic pneumothorax occurred after the procedure. Therefore, the performance of appropriate puncture approach and technique for treatment of adrenal tumors can effectively reduce damage to vital organs, promoting surgical safety.
Coaxial needle technique
In this study, 17-G coaxial needles (11 cm) with 18-G PTC needles (20 cm) were used. Due to the length of coaxial and PTC needles, the direction of the PTC needle during insertion was adjusted by simply pushing the coaxial needle, resulting in quick and accurate seed implantation at different locations within the lesion and reduction in the number of punctures and operation time, thus avoiding bleeding and tumor metastasis. Due to the flat head design of the coaxial needle tube, tissue blunt dissection can occur after the core is withdrawn passing through the fat gap, thereby reducing damage to the kidneys, intestines, and blood vessels.
Therapeutic effect
Currently, the treatment of secondary adrenal tumors includes surgery, ablation, chemotherapy, and external beam radiotherapy (EBRT). In Howell et al.’s study, adrenalectomy was performed in 62 patients with adrenal metastasis, and the mean OS was 30 months with 31% 5-year OS.[7] However, the surgical resection of secondary adrenal tumors caused considerable injury, and the metastasis rate in other organs was high; thus, most of the patients were not suitable for adrenalectomy. In this study, 13 of 20 patients had metastases from different organs, and new metastases occurred in 16 patients after the treatment. Since the adrenal gland is close to the kidneys, intestines, and many blood vessels, the risk associated with ablation is high, and some tumor cells may be retained. Hasegawa et al. reported that local tumor progression developed in 8 of 35 (23%) patients with unresectable adrenal metastasis who underwent radiofrequency ablation (RFA).[8] Chemotherapy has a low CR rate and a high relapse rate. Targeted therapy is effective, but may cause drug resistance, side effects, and insensitivity. Our study patients experienced chemotherapy failure or resistance to targeted therapy. As the adrenal gland is located in the deepest region, the surrounding organs are prone to radiation damage from EBRT and radiotherapy is not administered in patients who relapsed. In general, radiotherapy cannot be performed after a recurrence.
Kishi et al.[9] and Bretschneider et al.[10] evaluated the effectiveness of 192Ir (prescription dose 15-20 Gy) percutaneous brachytherapy in five patients with adrenal metastases and showed that the progression-free survival was ≥6 months. As an isotope of iodine, 125I-emitting y-rays can destroy the double-stranded DNA of tumor cells, causing tumor growth inhibition and thus treating tumors effectively. Under CT guidance, percutaneous permanent implantation of 125I radioactive seeds can provide continuous brachytherapy for advanced tumors with less trauma or complications and high target radiation dose; the prescribed dose in this group was 120 Gy, which was higher than the radical dose of EBRT. The radiation dose administered to adjacent tissues is slightly lower and can achieve good local control rate.[11-13] The local control rate in this study was 90% and was better than that of EBRT.
Limitations
Due to the small number of cases in this single retrospective study, multicenter prospective studies with a large sample size are warranted. 125I radioactive seed implantation is only a local treatment and should be combined with systemic comprehensive treatment.
CONCLUSION
CT-guided 125I radioactive seed interstitial implantation has many advantages, such as minimal invasiveness, better local
therapeutic effect, and fewer adverse reactions; therefore, it is an effective treatment for secondary adrenal carcinoma. However, periadrenal structures are complex so that skilled practitioners are required to perform the procedure.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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