Abstract
OBJECTIVE The purpose of the study was to examine the efficacy of treating patients with advanced gastric cancer using iodine-125 (125l) brachytherapy.
METHODS Ten patients with unresectable advanced gastric cancer were selected based on their pattern of CT scans. We utilized a brachytherapy planning system to determine the distribution of the (125l) seeds, their activity and quantity. The matched peripheral dose (MPD) was 110-135 Gy. (125l) seeds were implanted in a single plane or biplane by an intraoperative small incision or percutaneous puncture. The postoperative hemogram, CT, KPS, pain-relieving period and survival period were recorded.
RESULTS One patient developed a complete response (CR), 4 patients a partial response (PR), 3 patients showed no change (NC) and 2 patients developed progressive disease (PD). The overall response rate (CR+PR) was 50% (5/10). The pain-relieving rate was 89% (8/9). The patients' appetite and KPS were improved. The longest survival period was 10 months and median life span was 4 months. There were 8 patients whose seeds fell off resulting in an expulsion rate of 3.8% (26/692). The patients showed 0-1 degree acute radio-therapeutic side-effects without other symptoms such as abdominal pain, vomitus cruentes or intestinal obstruction etc.
CONCLUSION Applying (125l) implantation to treat advanced gastric cancer with a reasonable seed distribution can significantly improve clinical symptoms and their quality of life. The radioactive damage is mild. This method can be used as an important supplementary treatment for unresectable advanced gastric cancer.
keywords
At present, gastric cancer ranks high in frequency of all malignant tumors, although its incidence and morbidity are slowly decreasing. When found, most patients are in an advanced stage and even in developed countries only 10% of gastric cancers are in Stage I. Surgical excision is the preferred method of treatment, but the recurrence rate is still 70%, and is especially high for cases in Stage IIIb~IV with a 5-year survival rate of only 10%~20% after treatment with a radical operation and adjuvant chemotherapy. Radiotherapy has not become a regular therapeutic method for gastric cancer[1-3] and 125I brachytherapy has not been reported in China or abroad. Here we report the results of 10 patients with unresectable gastric cancer treated with 125I brachytherapy.
Materials And Methods
Equipment
Computer 3D treatment planning system: Prowess 3D Version 3.02 brachytherapy planning system (BPS), produced by SSGI Co. Ltd, USA.
Implant needle: Eighteen G type and 1820-C type, implant gun: Mick 200-TPV applicator kit, made by Mick Radio-Nuclear Inc., USA.
125I radioactive seeds were provided by Shanghai Xinke Medical Co., type: 125I-6711-99, length: 4.5 mm, diameter: 0.8 mm, activity: 1.85xl07~2.96xl07 Bq, energy: 27-35 keV, half life: 59.6 days.
All instruments were dry heated and autoclaved before use, under 121 °C, 15 kPa for 30 min. 125I seeds were soaked with 2% glutaral for 30 min. Doctors wore protective clothing while doing the operations.
Patients
Ten Chinese (male 7, female 3) unresectable gastric carcinoma patients in Stages III~IV were treated in the Department of Oncology, Hebei Provincial People’s Hospital, China from March 2004 to October 2005. Their ages ranged from 36 to 76 years (median 66). Through gastroscopy and pathological examination, 7 cases displayed poorly differentiated adenocarcinoma and 3 cases moderately differentiated adenocarcinoma. Maximum and minimum sizes were 10x2x3 cm and 5x6x3 cm respectively. One patient refused an operation, 6 patients had abdominal metastasis and 3 patients had hepatic metastasis. The patients did not receive an operation, chemo-radiotherapy, or other interventional treatment post implant.
Radioactive dosage and implant methods
Based on the features of brachytherapy dosage, the matched peripheral dose (MPD) was 110~130 Gy.
CT images were sent to the computer 3D-treatmentplanning system via a scanner, then treatment targets were decided, 3D isodose curves were drawn and the quantity of radioactive seed implants administered Table 1.
The treatment of ten patients with unresectable gastric cancer
First, small surgical incisions of 5 cm were made under general anesthesia in the center of the abdomen. Using guided ultrasound, the location of the tumor and its relation to surrounding structures was explored to identify important tumor blood vessels. Under TPS-guidance, 125I radioactive seeds were implanted as single plane or biplanes at 0.5 and 0.8 cm intervals, to strictly control the high dose within the treatment volume and to manage to make the low dosage consistent with the MPD. Pressure was used to stop bleeding, a drainage tube inserted, the abdomen closed and an examination made to determine whether there were lost seeds in the operating field. At 1 month postoperation, film X-ray or CT scans were conducted to determine the seed distribution and defluxion, and to evaluate through 3D BPS whether the dosage had been reached.
Observation index and curative evaluation
Blood routine tests, hepatic function, renal function and CT examinations were conducted.
Tumor objective effectiveness: CR, tumor completely disappeared, after 4 weeks; PR, tumor diminution exceeded 50%, after 4 weeks; NC, tumor increased less than 25% or diminished less than 50% ; PD, tumor increased more than 25%.
Karnofsky performance status (KPS) standard: evaluated by WHO schedule recommended by the Chinese Medical Association.
Pain-relieving time: from the effective date to advanced date.
Survival time: from the therapeutic date to the date of death or loss of follow-up.
RESULTS
Hemograms, hepatic and renal functions had no statistically significant abnormal values (P>0.05) at 1 week preoperation or 1 and 2 weeks or 1 month postoperation. Results were as follows: CR: 1 patient; PR: 4 patients; NC: 3 patients; PD: 2 patients. The total effective rate was 50% (5/10) and the pain-relieving rate was 89% (8/9). The patients' appetite increased and KPS scores were improved significantly with the highest KPS score increasing by 30 points. The longest and the shortest survival time of the patients was 10 months and 4 months respectively and the mid survival time was 4 months. Cases 2, 3, 6 and 8 developed mild nausea in the second week but with no vomiting. Acute radiotherapeutic side-effects of 0~1 degree occurred without other symptoms such as abdominal pain, vomitus cruentes or intestinal obstruction etc. A few seeds in 8 patients became dislodged. The expulsion rate was 3.8% (26/692). Because some of the seeds were transplanted to the ulcer of the tumor, a portion of the seeds were expelled into the abdominal cavity which did not cause any complications. No seeds were found in the digestive tract.
Typical patient: Case 1 was a 71-year old male with gastric carcinoma. He was postoperative for 8 years and had complained of dysphagia and abdominal pain for 2 months, resulting in a pathologic diagnosis of remnant gastric cancer. CT showed retroperitoneal lymph node metastasis Fig.1. Explored abdomen: an ulcer-type tumor (7x6x3 cm) on the lesser curvature side of the cardia which was local and unresectable. 125I radioactive seeds were implanted in a biplane with 135 Gy (MPD) and 1.85xl07~2.59xl07Bq activity under ultrasonic-guidance. His abdominal pain disappeared postoperatively at 24 h. He began to eat at 3 days postoperatively and his dysphagia markedly improved. Postoperatively at 3 weeks, his appetite improved and he gained 2 kg of weight with no complications. Postoperatively at 2 months, a CT scan showed that the gastric wall had became soft and the tumor had almost disappeared, but the peripheral lymph nodes were still swollen Fig.2. His KPS score had increased from 60 points to 90 points. The patient survived for 8 months.
Shows the shrunken stomach remnant, irregular bump on the lesser curvature side of the stomach remnant of the cardia. Its boundary was vague.
Shows that the gastric wall became soft and the tumor mostly disappeared, but there was hepatic metastasis.
Discussion
Radiotherapy for gastric carcinoma has not been recommended as a regular adjuvant therapy. But recently some reports[4-5] have indicated that adjuvant radiotherapy can slow the rate of tumor growth and improve the survival rate. When the gastric radiation dosage surpassed 55 Gy, 30% -40% of the patients suffered postradiotherapy complications.[6] 125I implantation can solve those problems by emitting tumoricidal low energy gamma rays to break DNA double chains and suppress tumor growth. The internal dosage of radiation to the tumor is higher, but normal surrounding tissues are subject to a lower dosage and the damage is repaired in a short time. Undoubtedly, 125I implantation is more reasonable and effective than general radiation.
In recent years, 125I implantation has been used to treat prostate cancer, digestive tract malignant cancer etc.17'111 But as to whether it can be utilized for visceral tumor therapy has become a question of increased interest. At present, the reasonable MPD for gastric carcinoma is the key feature for brachytherapy. According to the criteria recommended by American Brachytherapy Committee, the MPD of 125I seed implantation in prostate cancer is 140~145 Gy. Peretz et al.[7] reported that 98 unresectable pancreatic cancer patients received MPD as high as 136.6 Gy. Montinez et al.P1 reported that 29 recurrent colorectal cancer patients received a MPD of 140 Gy and produced a better therapeutic effect. Therefore, in our work we set 110-130 Gy as the MPD for gastric cancer.
In our study at 2 months postoperatively, a CT scan of cases 1 and 7 showed that the gastric wall became soft and the tumor mostly disappeared. Their pathological changes were limited. These curative effects may be related to gradual improved techniques and a reasonable dosage distribution. The tumors of cases 2, 3, 6, 8 and 10 was in the paries anterior gastricus and posterior gastricus, the pathological changes were widespread, the boundary was not clear and the distribution of the radiation was not even, resulting in the patient’s death with a short period of symptoms. Therefore, the curative effect using seed implantation for diffuse pathological changes is not good and does prolong survival. From these results, the authors suggest the following: (1) 125I implantation is the modus operandi to alleviate pain. After 48 h of implantation, the patient’s pain was markedly relieved, but the reason needs further study. With time, the pain was reduced even more, perhaps due to the mitigation of tension in adjacent tissues. (2) Employing only a small incision to implant the needles and using an albumin gel to overlie the punctures can relieve surgical operation damage, prevent movement of the tumor cells and shorten the patient hospitalization. The damage to normal tissues is small.
No patients in our study had a stomach ulcer or perforation, bleeding or bowel obstruction etc. At 1~2 weeks postoperation, half of the patients appeared to have a mild acute side-effect associated with the upper gastrointestinal tract such as light nausea but with no vomiting, a problem considered to be related to gastric wall edema. These findings are in accord with the report of Guo et al.[12] showing that 125I implantation had no general complications. The seed expulsion rate was 4%, which did not cause complications. Seed expulsion might be related to neoplastic necrosis, gastrointestinal motility and the implantation technique etc.
In conclusion, 125I implantation brachytherapy applied for advanced gastric cancer is feasible. It results in few post-radiotherapy complications and has a local curative effect. At present due to a limited number of cases, there are no relevant reports from China or abroad. Therefore in the future we need further studies on the MPD and the production of radioactive damage.
- Received December 13, 2005.
- Accepted May 18, 2006.
- Copyright © 2006 by Tianjin Medical University Cancer Institute & Hospital and Springer
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