OBJECTIVE: To investigate the clinical efficacy and complications of stereotactic gamma-ray body treatment system for the treatment of intermediate and advanced pancreatic cancer. METHODS: The gyroknife stereotactic gamma-ray body treatment system was used to treat 71 patients with intermediate to advanced pancreatic cancer in fractions of 50% to 80% of the isodose curve covering the planned target volume (PTV), giving a single dose of 350 cGY to 550 cGY around the PTV and a total dose of 4500 cGY to 5500 cGY in 8 to 13 fractions, treating daily or every other day once.
Results: After 71 patients with intermediate to advanced pancreatic cancer were treated with stereotactic gamma ray body treatment system, local pain relief efficiency: 89.5%; jaundice regression rate: 83%; 67 cases reviewed by imaging (CT/MRI): tumor basically disappeared in 8 cases, significantly reduced in 52 cases, basically no change in size in 4 cases, and locally increased in 3 cases, i.e. local efficiency (CR+PR): 89.5%. The survival rate after treatment was 73.2% at 1 year, 32.4% at 2 years and 8.4% at 3 years, with a median survival period of about 15 months. No serious complications occurred. Conclusion: Stereotactic gamma ray body treatment system is a safe and effective method for the treatment of intermediate and advanced pancreatic cancer because of its satisfactory efficacy and low treatment response, which can significantly improve patients’ clinical symptoms, reduce pain, improve survival quality and increase the local control rate of tumor.
In this paper, we collected 71 cases of intermediate and advanced pancreatic cancer treated with the gyroscopic knife stereotactic gamma ray body treatment system of Shanghai Gamma Star Company between January 2006 and January 2012, and conducted regular follow-up observation on the efficacy and complications, and the efficacy was more satisfactory. The results are reported as follows.
1. Materials and methods
1.1 General information
All 71 cases in this group were patients with intermediate to advanced pancreatic cancer, including 59 males and 12 females, with a minimum age of 29 years and a maximum age of 77 years, and a mean age of 63 years. All patients had Karnofsky score ≥ 60 and normal leukocyte count.
The tumors occurred in the head of the pancreas in 53 cases, the body of the pancreas in 11 cases, and the tail of the pancreas in 7. Among the 53 cases of pancreatic head cancer with obstructive jaundice in 41 cases, 23 of them underwent reduction surgery (external drainage or bile-intestinal anastomosis + gastrointestinal anastomosis) because of heavy obstructive jaundice. Distant metastasis had occurred before treatment in 5 cases. There were 57 cases with clinical abdominal pain and/or low back pain.
1.2 Tumor size
The tumor diameter of this group was minimum 2cm, maximum 7.9cm, average 15cm.
1.3 Treatment method
1.3.1 Positioning and scanning
After the patient was lying flat on the negative pressure bag and the lap band was tightened to limit the breathing dynamics, the patient was fixed and shaped with a vacuum pump, and the lesion area was scanned with spiral CT in 2-5mm thin layer continuous enhancement to clarify the lesion site and the relationship with the surrounding sensitive tissues. The patient’s position, the coordinates of the “N” ruler and the X, Y and Z coordinates of the repeated localization points on the body surface were approved.
1.3.2 Develop treatment plan
Transfer the acquired CT scan image data to the Treatment Planning System (TPS). The body surface contour, tumor target area and sensitive tissues of the patient are outlined. When making the gyroknife 3D TPS plan, the size and location of the lesion, subclinical lesions, respiratory motility, repeated positional errors, and surrounding sensitive tissues are taken into consideration. Adjust the treatment plan and dose distribution according to the patient’s physical condition and treatment purpose. The treatment plan is checked by covering the planned target volume (planning target volume PTV) with a 50% to 80% isodose curve, followed by dose assessment of the lesion and surrounding sensitive tissues by 3D display and DVH histogram.
1.3.3 Prescribed dose
The appropriate treatment dose is determined according to the patient’s general condition, tumor size, location and relationship with the surrounding sensitive tissues. Generally, cover the planned target volume (PTV) with a 50% to 80% isodose curve, give a single dose of 350 cGY to 550 cGY around the planned target volume , and treat in 8 to 13 sessions, daily or every other day, with a total dose of 4500 cGY to 5500 cGY, and the irradiation to the surrounding sensitive tissues should be controlled below their maximum tolerated dose.
1.3.4 Implementation of treatment
Repeat the pose strictly and precisely for the patient, extract the data of the planned results, and strictly check the consistency of the data of each implemented treatment target with the planned coordinates. Patients were also closely observed for postural changes and uncomfortable reactions during irradiation.
1.4 Follow-up method
Patients were followed up monthly after treatment for 3 years to understand the improvement of clinical symptoms and signs. CT/MRI scan of the treated area was performed every 3 months after treatment to observe the changes of tumor size and surrounding tissues, with a total follow-up of 9 months.
1.5 Criteria for determining the efficacy
1.5.1 Clinical criteria
The improvement of clinical symptoms and signs after treatment was used as the standard.
1.5.2 Imaging criteria
CT/MRI scan after treatment: change of tumor size as the standard.
Complete remission (CR): complete disappearance of lesions.
Partial remission (PR): lesions shrunk by more than 50%.
No change (NC): no shrinkage or less than 50% shrinkage of the lesion.
Progression of lesions (PD): lesions increased in size compared with those before treatment.
2. Results
2.1 Changes in clinical symptoms and signs
Within 1 to 3 months after treatment with stereotactic gamma ray body treatment system, the symptoms of abdominal pain and low back pain completely disappeared in 33 cases (57.9% (33/57)); the symptoms of abdominal pain and/or low back pain were significantly reduced in 18 cases and no more analgesics could be used, accounting for 31.6% (18/57); the pain symptoms were aggravated in 6 cases (10.5% (6/57 ); that is, the local analgesic efficiency: 89.5%. The jaundice in 18 patients without the reduction surgery, after treatment from 1 to 3 months, 11 cases of jaundice completely subsided, accounting for 61% (11/18), of which 3 cases within 1 month jaundice completely subsided; 4 cases of jaundice gradually reduced, accounting for 22% (4/18); jaundice no change in 6 cases, that is, the rate of jaundice subsidence: 83%.
2.2 Laboratory changes
Laboratory tests 1 to 3 months after treatment: AKP, GPT, CA19-9, serum bilirubin, etc. gradually decreased close to normal, and urinary bilirubin was negative.
2.3 Imaging changes
After treatment, CT/MRI review of the treated area was performed every 3 months. 67 cases were followed up by CT/MRI within 9 months after treatment, 8 cases (11.9%) had basically disappeared, 52 cases (77.6%) had shrunken tumor (52/67), 4 cases (6%) had no change in tumor size (4/67), and 3 cases (4.5) had increased tumor size (3/67). That is, the local efficiency (CR+PR): 89.5%.
2.4 Treatment response and survival rate
During the treatment, 5 cases showed progressive increase of transaminases and jaundice index (7.7%), which gradually decreased after active liver protection and symptomatic treatment; 38 cases showed more obvious gastrointestinal symptoms such as nausea and vomiting during the treatment (58.5%), which were relieved after symptomatic treatment. In 12 cases, epigastric pain began to appear 3 months after treatment, and mucosal ulcer formation was seen microscopically, which improved with powerful acid-control agent treatment. None of the cases developed serious complications such as gastrointestinal perforation or/and hemorrhage during and after treatment.
Fifty-two cases survived 1 year after treatment, i.e., the 1-year survival rate was 73.2% (52/71); 23 cases survived 2 years after treatment, i.e., the 2-year survival rate was 32.4% (23/71). At 3 years after treatment, there were 6 cases surviving, i.e., the 3-year survival rate was 8.4%. The median survival period was about 15 months.
3. Discussion
Pancreatic cancer is a common clinical malignant tumor of the digestive system, accounting for about 1% to 2% of common malignant tumors. The annual incidence rate of pancreatic cancer in China is about 5.1/100,000, and the literature reports that its incidence rate has been increasing year by year in recent years. According to the statistics of Shanghai and Tianjin, the incidence of pancreatic cancer in men in China has approached the level of developed countries in Europe and America, and its mortality rate has risen to the fifth place.
Currently, the first choice of treatment for pancreatic cancer is still surgical resection, but because of the deep and hidden anatomical location of the pancreas and the complex surrounding anatomical structures, the surgical resection rate is extremely low and there are many complications (pancreatic fistula or gastric and duodenal fistula, etc.). There is no specific clinical manifestation in the early stage of pancreatic cancer, and the disease progresses rapidly. Most of the patients visit the doctor because of obstructive jaundice, abdominal pain or wasting, weakness and other symptoms, and the disease is already in the middle and late stage. In addition, the early laboratory tests lack specific and sensitive tumor markers and the imaging features are atypical, so the early diagnosis rate is low. The literature reports that when patients with pancreatic cancer are seen, about 80% of them are already in advanced stage, about 50% of them have distant metastasis, only 10%-15% of them have the chance of surgical resection, and only 5%-7.5% of them can be completely resected.
Even for the few patients who have been completely resected, the chance of recurrence after surgery is high, and the average survival time after surgery is only 11 to 15 months. Patients who cannot be completely resected or cannot tolerate surgery are often treated with palliative surgery or symptomatic treatment, and the prognosis is even worse, with a median survival time of only 3 to 6 months after diagnosis. In recent years, the use of conventional radiotherapy + chemotherapy for those who cannot tolerate surgery has extended the median survival of patients, but the survival rate has not been improved. The National Institutes of Health (NIH) has reported that the one-year survival rate of pancreatic cancer is about 8%, the five-year survival rate is 3%, and the median survival is only 2-3 months. Studies have shown that the 5-year survival rate after surgery for small pancreatic cancer with tumor diameter ≤50px and no lymph node metastasis is 19%-41%; the 5-year survival rate after surgery for pancreatic cancer with diameter >50px is nearly 0.
Pancreatic cancer is not sensitive to chemotherapy, and the recent efficacy of many drugs is only about 20%, with large toxic side effects. Because the surrounding organs such as small intestine, bile duct, stomach and blood vessels are more sensitive to radiation, the target dose cannot be effectively increased and it is difficult to reach the radical dose, so the efficacy is also poor, and there are many comorbidities, the median survival is short and the prognosis is often poor. Patients with advanced pancreatic cancer have even shorter survival time and poorer quality of life. In recent years, with the birth of new technology and equipment of radiotherapy, the application of radiotherapy in the treatment of pancreatic cancer has gradually increased and has become one of the main treatment means.
As a precise radiation therapy, stereotactic gamma ray treatment system adopts the principle of rotational focused stereotactic irradiation, which greatly reduces the amount of surrounding sensitive tissues subjected to destructive irradiation, resulting in rapid reduction of tumor volume within a short period of time, gradual opening of the common bile duct with reduced pressure, and gradual disappearance of obstructive jaundice, achieving a treatment effect similar to surgery with slight damage to patients. This has enabled most of the patients with obstructive jaundice who cannot be resected in the middle and late stages to rapidly improve their clinical symptoms, reduce their pain and improve their quality of life. For more than four years, we have used Shanghai GammaStar gyroscopic knife stereotactic gamma ray body treatment system to perform local palliative irradiation treatment on 71 patients with intermediate and advanced pancreatic cancer.
Through clinical and CT/MRI follow-up review, most of the patients had obvious pain relief, better reduction of early obstructive jaundice of pancreatic head cancer, significant shrinkage or disappearance of masses, and improved survival quality. In our group of 71 patients with intermediate to advanced pancreatic cancer, 52 patients survived for 1 year, 23 patients survived for 2 years and 4 patients survived for 3 years after treatment. According to the literature, in recent years, the median survival time can be extended by about 3 months with conventional radiotherapy + Kinselective chemotherapy. The median survival of our group was about 15 months, and the survival rates of 1 year and 2 years were 73.2% and 32.4%, respectively, which were much higher than that of conventional radiotherapy + chemotherapy, which was about 33% and 10%. At 3 years after treatment, 6 cases survived, with a 3-year survival rate of 8.4%. 4-year survival rate is under follow-up.
Through clinical follow-up, we noticed that when pancreatic head cancer is accompanied by obstructive jaundice, the clinical efficacy is better than that of stereotactic radiation therapy alone after firstly performing the yellowing reduction surgery (external drainage or bile-intestinal anastomosis + gastrointestinal anastomosis). Because it helps to reduce the damage of jaundice to the liver, thus obtaining higher efficacy, lower damage and prolonging the survival period.
Stereotactic gamma radiation body treatment system for the treatment of middle and advanced pancreatic cancer can not only strictly protect the important organs adjacent to the lesion, but also expose the lesion to high-dose destructive irradiation, which can achieve the purpose of accurate and safe removal of the lesion. It has satisfactory efficacy, few side effects and complications, short treatment time, and patients can tolerate the whole treatment. It can significantly improve clinical symptoms, relieve patients’ pain, reduce the damage of normal tissues around the pancreas, improve the local control rate of tumor, improve the quality of survival and prolong the survival time, and is a safe and effective treatment for middle and late stage pancreatic cancer.