Clinical Test Report for Medical Equipment
Name of Product: Gyro-Rotating Co60 Radio surgical Therapy System.
Practitioner: Shanghai Gamma Star Science and Technology Development Co. Ltd.
Institution Responsible for Clinical Test: Xijing Hospital Affiliated to the Fourth Militarily Medical University.
Classification of Clinical Test: Clinical Verification.
Functionary for the Clinical Test (Signature): August 5, 2006
Clinical Test Report for the Gyro-Rotating Co60 Radio surgical
Background for the Clinical Test
In 1950, the Swedish neurosurgeon Leksellst first proposed the innovative idea of the stereotaxic radio surgery principle. Then in 1968, the world’s first ?-ray dependent stereotaxic radiological system, or the so-called ? knife, was given to birth in Elekta Co., Sweden. In the middle of 1990’s, the ? knife technology and its equipment were introduced into China, and on the basis of that system, we have developed a more advanced ? knife that can be used in the head and body. Currently, approximately more than 300?knives were in service around the world and 350,000 patients have been treated with that system. In China, those numbers are more than 300 and 120,000 respectively. When using the gyro-rotating Co60 Radiosurgical Therapy System (or GyroStar), the radioactive source Co60 was installed in a gyro which rotates in synchronism at the mutually vertical directions. It rotates around the human body’s axis at any angle and during the rotating process, the ray always focuses on the target site. Therefore the lesion site can receive the high radiation dose while the normal tissues are relatively little-affected. In this way, we can fulfill the therapeutic aim of clearing the lesion site and preserving the normal tissues. This system has been under the type test carried out by Beijing Center for Medical Device Quality Supervision and Testing of State Drug Administration, accords with the registration requirement for medical equipment and can be subject to clinical test. The purpose of the clinical test is to evaluate the effectiveness and safety of GyroStar?s use in treating cancer patients.
(1) The Design Blueprint and Grouping Method of the Clinical Test the GyroStar is a ?-ray dependent stereotaxic radiosurgical therapy system, devised mainly to treat tumors in thorax, abdomen and pelvis. Thus typical tumors in these regions were selected to be the test objects. The random treatment and control grouping method was adopted in the test of lung and liver cancers. In the treatment group, the treatment strategy was devised according to the protocol of the GyroStar, while in the control group, the strategy was devised according to the therapy protocol of the accelerator. In order to evaluate the treating effectiveness and facilitate the contrast, all illnesses were radiated with the CT-modeling type. During the testing process, we also chose some other cancer illnesses suitable for ? knife treatment to be treated by GiroStar, so as to observe its therapy effectiveness.
(2) Grouping Requirements
1. Above 70 grade should be achieved in Karnofsky evaluation.
2. Blood cells counting are in normal range
3. Cardiopulmonary and hepatorenal functions are normal. Abnormalities can be accepted if they are confined in the normal radiotherapy requirements
4. No tumor metastasis is discovered in physical examination. No fluidity occurs in the thoracic and abdominal cavities
5. Easy localization and good repetitiveness. Calculable distance exists between the lesion site and possibly-affected organs. Possibility of radiation complication occurrence tends to be zero
6. Patients tend to accept the therapy plan and sign the Test-Taker Knowing and Agreeing Pact.
(3) Clinical Cases and Grouping
1. Glioma Group: 115 patients were included in the study and 37 of them undertook the stereotactic brain tissue biopsy. The pathological results were as follows. Among the astroma group, 19 cases belonged to grade I, 28 cases grade I-II, 35 cases grade II, 9 cases grade II-III, 3 cases grade III, 8 cases grade III-IV, and 5 cases grade IV. 5 cases belonged to ependymoblastoma. 3 cases belonged to medulloblastoma. 85 cases occurred in supratentorium and 30 in infratentorium. 30 cases occurred in temporal lobe, 26 in frontal lobe, 21 in parietal lobe, 9 in occipital lobe, 12 in thalamus, 16 in cerebellum, 6 in brain stem and 4 in optic chiasm. The minimal volume of the tumor was 3cm3, the maximal one 32cm3 and the average 10.38cm3. 39 males and 27 females were included with an average age of 31.6 years old (8-82 years old). Clinical manifestation: 49 cases suffered from headache, 65 cases deficiency in neural function and 20 cases epilepsy. Therapy: 60 cases were chosen as treating group and the remaining 55 were control group. The lesion was localized by Simenz 1.5T MRI with a slice thickness of 2.0mm and slice distance of 2.5mm. T1 and T2 axial and coronal images were acquired. Target scope: the verge for the lowly malignant tumors was 1mm out of the tumor’s border and the verge for the highly malignant tumors was 2mm out of the tumor’s border. Dosage: the maximal dosage in the surrounding areas was 25Gy and the minimal one was 6Gy. The dosage in the surrounding areas for most tumors was between 12 and 16Gy and the average was 14.73Gy. The dosage in the central region was 25-30Gy (14-55Gy) with an equivalent dosage curve of 40%-60% and an average of 50%. At most 13 and at least 1 equal central point’s existed and the average number was 5.48. Anti-epilepsy treatment was carried out for those cases that had lesions in the motor region or had an epilepsy history. The control group undertook radiotherapy by varian-23EX accelerator with an equal dosage as describe above. Radiological imaging tests like CT and MRI were taken before and after treatment and the results were analyzed with SAS 6.0 software package. 20 cases were not treated, among which 8 cases were suffered from increased cranial pressure and the remaining 12 cases had a Karnofsky score that was lower than 60.
2. Pituitary Adenoma Group: 77 cases were included in this group, among which 36 cases were male and 80 were female. The ages were between 11-80 (36.5}5.3) years old. The diameters of the tumors were between 5-30 (15.2}3.4) mm. The distances between the tumor and the optic nerve as well as the optic chiasm were 2-5mm. In 13 cases, the cavernous sinus was invaded. 45 cases belonged to adenoma that had secreting functions, including 23 cases of PRL-secreting adenoma, 11 cases of GH-secreting adenoma, 6 cases of ACTH-secreting adenoma, 5 cases of multiple-hormone adenoma. 32 cases belonged to adenoma that had no secreting functions. There were also 38 cases of menopause, 42 cases of galactorrhea, 18 cases of abnormal menstruation, 16 cases of acromegaly, 8 cases of sexual hypoactivity, 10 cases of Cushion’s syndrome, 31 cases of tiredness, 4 cases of cold, 9 cases of blood glucose higher than 7mmol/L, 7 cases of polydrinking and polyuria and 6 cases of hypertension. 36 cases were chosen as treatment group and 41 cases as control group. The dosage in the treatment group was as follows. The dosage in the surrounding areas was between 12 and 35 Gy and the average was 21.3 Gy (NFA: 15.9 Gy; FA: 27.6 GY). The dosage in the central region was 24-70Gy with an average of 46.6 Gy (NFA: 31.8 Gy, FA: 50.3 Gy). The control group undertook radiotherapy by varian-23EX accelerator with an equal dosage as describe above. Endocrine function and radiological imaging tests like CT and MRI were taken before and after treatment. Complications were treated similarly between the two groups. The results were analyzed by SAS6.0 software package.
3. Arteriovenous Malformation in the Brain: 5 cases were included. They were treated with the central dosage of 50Gy and the dosage of 18-25 Gy in the surrounding areas. Since small number of cases were included, the control group was not established.
4. Lung Cancer Group: 56 patients suffered from lung cancer, with an age range of 35-82 years old, a median age of 65 years old, 37 males and 19 females. 47 cases were diagnosed pathologically as primary lung cancer. 9 cases were primary malignant tumors with pathological proof plus metastasis cancer in lung (within 4 metastasis site). 34 cases were in the treatment group, treated with GyroStar. On the 50%-60% equal dose curve, the radiation dose for tumor was 3-10Gy/time, 3-5times/week, 4-15 times treatment and the total dose was 40-45Gy, equivalent to the biological dose of 52-88Gy. 22 cases were in the control group, treated with 6MV X ray multiple-area adaptability radiotherapy, varian-23EX accelerator. The radiation dose for tumor was 3Gy/time, 5times/week, a total of 60-72Gy, equivalent to the biological dose of 76-88Gy. All patients took the pulmonary function test before and after therapy to prevent and be treated with complications, this measure is both taken in two groups.
5. Liver Cancer Group: 55 patients suffered from liver cancer, with an age range of 38-79 years old, a median age of 54 years old, 38 males and 17 females. Liver cancer was determined by hepatic biopsy. And cancer metastasis in liver was determined by diagnostic imaging accompanied with proof of primary cancer. The cancers cannot be excised of the patients didn’t accept surgical operation. 32 cases were in the treatment group, treated with GyroStar. On the 50%-60% equal dose curve, the radiation dose for tumor was 3-6Gy/time, 3-5times/week, 8-15 times treatment, equivalent to the biological dose of 76-88Gy. 23 cases were in the control group, treated with 6MV X ray multiple-area adaptability radiotherapy, varian-23EX accelerator. The radiation dose for tumor was 3Gy/time, a total of 39-45Gy, equivalent to the biological dose of 48-56Gy.
6. Other Tumor Groups: 12 patients suffering from other tumors were treated, with an age range of 35-67 years old, a median age of 51 years old, 5 males and 7 females. Among them are 2 cases of mediastinal tumor, 6 cases of cervical cancer, 1 case of postpeitoneal tumor, 2 cases of pancreatic cancer and 1 case of renal cancer. They were treated with GiroStar. On the 50%-60% equal dose curve, the radiation dose for tumor was 2.5-4Gy/time, 5times/week, 10-18 times treatment, total dose in the margin 40-45Gy, equivalent to the biological dose of 76-88Gy. No control group was set because of the small volume of cases.
The same standard was adopted in determining the target region in the treatment and control groups. The tumor border can be defined in the GTV-CT localization image. And the CTV-GTV was extended to 0.5-1.0cm. All the borders were depicted by the same doctor.
Clinical Testing Methods
I. Major observation indications in the test The recent effectiveness and incidence of side effects were used as the clinical evaluation indicators in accordance with the standardized methods for the clinical test enacted by RTOG.
(1) Observation of the tumor size: Normal or enhanced CT scan was used to compare the tumor sizes before and after therapy. The tumor size was determined by double or single diameter measurement. a: Double diameter measurement: in the single lesion case, the tumor size was determined by multiplying the two biggest diameters that were mutually vertical. In multiple lesion case, the size was determined by the sum of the products of the individual tumor’s biggest diameters in the vertical or close to vertical direction. b: Single diameter measurement: the acquired value of the linear tumor
(2) Observation of the therapy effectiveness: the change in the tumor size was determined by the comparison of the tumor sizes 1-3 months after treatment and those before the treatment.
(3) Observation of the side effects as a result of radiotherapy: Acute toxicity test: the overall or regional reaction to radiation in the treatment and control groups during the clinical testing period. Besides overall response to radiation, symptoms and radiological expression of the radiation esophagitis, radiation pneumonia, radiation myocarditis and pericarditis were observed in the lung cancer patients. For those liver cancer patients, Symptoms and laboratory indicators of radiation hepatitis and radiation gastro-enteritis were observed.
(1) We communicated with the patients and their relatives to let them know the illness conditions, side effects, complications and all other possible accidents, and let the patients know the whole therapy process, so that they would fully cooperate to receive the treatment.
(2) Before localization, the position of the lesion and its activity when under the treatment should be determined.
(3) Well-matched subpressurization bag was used. The body surface of the patients should keep
contact with the subpressurization bag in the maximum extent, so as to let the patients have body position that would make them comfortable and have the best repeatability.
(4) We trained and modulated the patients’ tranquil breathing to make sure the best repeatability in each treatment and localization. Belly belt might be used to confine the breathing magnitude if it was too large.
(5) We fixed the patients on the localizing bed that was adaptive to the CT scanning bed.
(6) The coordinate localization was recorded by the locating gauge.
(7) Non-separation thin layer Spiral CT was used. (Layer thickness 5mm/spiral distance 5mm)
III. Make Therapy Strategy
The CT image was put into the 3D therapy strategy system. By acquiring the localization site, the image was uniformed, the 3D image was reconstructed, the target region was depicted and the therapy plan was made.
(1) Target region: The target region was depicted in accordance with the principles in ICRU50 and No.60 Report, including 1, mechanical error, 2, relation between the lesion characteristic and vulnerable organs. 3, technician’s placing operation, 4 error of voluntary or involuntary movement of the tumor (2) Dose: The therapy dose was determined according to the equivalent curve surrounding the planned target region. It was generally regulated with reference to single separation dose. limited radiation dose on vulnerable organ and the therapy objectives.
All patients were followed with illness tracking, in which clinical syndromes, laboratory test result and radiological imaging were carried out just one month after radiotherapy.
Statistics Process and Evaluation Methods
(1) Statistics Process The SSPS10.0 stastics software package was used. The effectiveness (CR+PR) was x2-tested, evaluation level a (P)=0.05
(2) EvaluationMethods for Clinical effectiveness;
1. Change in tumor size: evaluated by the radiological images before and after therapy
2. Side effects and complications of the radiotherapy: determined according to the RTOG standard
Recent Therapy Effect and Side Effect Evaluation Standard
Evaluation was taken according to WHO tumor evaluation standard 1-3 months after therapy.
1. Change in Lesion Site;
(1) Completely Relieved (CR): lesion disappears completely
(2) Partial Relieved (PR): lesion disappears at a more than 50% ratio.
(3) No change (NC): lesion doesn’t shrink or shrinks less than 50% ratio
(4) Progressive Degree (PD): lesion is bigger than that before therapy
Clinical Testing Results
1). All cases were tracked after therapy. The tracking rate is 100%.
2). Lesion changes
1, Glioma Group
The effectiveness for treatment group (CR+PR) was 91.67% (95%CI:84.68-98.66%). The effectiveness for control group (CR+PR) was 61.82% (95%CI:48.98-74.66%). The effectiveness for treatment group was greater than Control group (x2=14.61 P>0.05). The difference is not statistically significant.
2, Pituitary Tumor Group
The effectiveness for treatment group (CR+PR) was 86.11% (95%CI:74.81-97.41%). The effectiveness for control group (CR+PR) was 65.85% (95%CI:51.33-80.37%). The effectiveness for treatment group was greater than Control group (x2=4.23 P>0.05). The difference is not statistically significant.
3, Lung Cancer Group
The effectiveness for treatment group (CR+PR) was 88.24% (95%CI:88.13-88.35%). The effectiveness for control group (CR+PR) was 72.27% (95%CI:77.09-77.45%). The effectiveness for treatment group was greater than Control group (x2=1.19, P=0.275). The difference is not
4, Liver Cancer Group
The effectiveness for treatment group (CR+PR) was 81.25% (95%CI:81.18-81.32%). The effectiveness for control group (CR+PR) was 78.26% (95%CI: 78.17-78.35%). The effectiveness for treatment group was greater than Control group (x2=0.075, P=0.785). The difference is not statistically significant.
5, Other Cancer Group
The effectiveness for the 12 cases (CR+PR) was 83.33%.
The Abnormal Incidents and Side Effects Observed in the Clinical Test and the Handling
1. Among the 115 glioma cases, radiation brain lesion: 2 cases of moderate radiation brain infection in the treatment group, 2 cases of moderate radiation brain infection in the control group, 1 case of severe radiation brain infection. Radiation neural function lesion: 0 case in treatment group, 1 case in control group. Overall incidence of side effects: 2/60(2.33%) in treatment group; 4/41(9.75%) in control group. The difference in these two groups is not statistically significant (x2=2.11, P=0.146). (Table 6) All those effects and abnormalities were reverse after the anti-infection and adequate hormone therapy.
Analysis of the Clinical Testing Effects
The results shows that the GiroStar possess a high recent therapy effects on glioma, pituitary adenoma and AVM with an effectiveness rate of 91.67% in glioma and 81.66% in pituitary adenoma. The complication rates are 3.33% in glioma and 5.00% in adenoma. It also possess a high recent therapy effects on tumors in thorax, abdomen and pelvis.The relatively high therapy effects and low side effects incidence are related to the accurate localization of the therapy equipment, high distribution or rays in the tumor regions and low dose of rays in the surrounding normal tissues.
Clinical Testing Conclusion
1. The GiroStar possesses a relatively good focal dose and dose gradation, accurate stereotaxic apparatus and 3 dimensional therapy strategy system. It has the characteristics of 1) accurate localization, 2) high accuracy in repetitive localization, 3) relatively good dose gradation between the target region and the surrounding normal tissues, low ray-absorbance in the extra-target normal tissues, both of which can bring about relatively good therapy benefit, and 4) adaptability in the thoracic, abdominal and pelvic tumor treatment.
2. The Clinical therapy effects of the high-dose separation radiation by GiroStar are equivalent to those of shape-adaptability radiotherapy by linear accelerator. The optimal separation dose should be determined in accordance with the tissue and organ types. For example in the 50%-60% equal dose curve, the tumor’s radiation dose should be 2.5-10Gy/time, plus 4-15 times with a total of 40-48Gy, equivalent to the biological dose of 48-88Gy. The above radiation method should be perfected as result of its wide use in the future.
3. The GiroStar has the characteristic of arc extension, which is more advantageous in protecting the normal tissues. For example, the selection of radiation direction and target point as well as the determination of significance may help protect those important organs such as spinal cord and esophagus. It assures that high radiation dose reaches the tumor region while its surrounding normal tissues are little affected. Therefore it can promote the tumor control percentage, or TCP.
4. The therapy strategy system has a stable performance, is easy to be observed, is to be operated, has DVH evaluation function, has the axial, coronal and sagittal dose distribution analysis and the peculiar advantage of dose limitations in several important organs.
Adaptabilities, Inhibitions and Notices
(1) GyroStar’s Adaptability
2. Meningioma in cranial base, cerebral hemisphere and cerebellum
4. Metastasis in the brain
5. Primary lung cancer and metastatic cancer in the lung
6. Primary liver cancer and metastatic cancer in the liver
7. Mediastinal tumor
8. Cervical cancer, pancreatic cancer, postperitoneal tumor and renal cancer
1. Tumors located in important function region or in the regions that have important arteries
2. Tumors with a large volume or multiple lesion sites in the brain
3. Severe increased cranial pressure
4. Malignant tumors in late stages with multifunction failure
5. Below 70 in Karnofsky evaluation
1. The head should be placed within the localization gauge. Otherwise, the treatment cannot proceed.
2. 6 points should be chosen in the appropriate epidermal region near the lesion site. Their 3 dimensional coordinates should be recorded. Each repetitive 3 dimensional coordinates localization should be matched with the first record.
3. When designing target region, the influence of the patient’s breathing activity, subclinical lesion enclosing should be taken into consideration. Safety border is routinely placed beside the GTV to make sure that the lesion site does not miss the high radiation region. At the same time, safety border should be appropriately placed in order to avoid impairment of the normal tissues.
4. Before and after GyroStar therapy, other accompanying therapies can also be performed, including complementary outside radiation, chemotherapy and even surgery. Till all these measures are paid attention to, good therapy effects can be achieved with little loss and the improvement of therapy and life quality.
Existing Problems and Improvement Suggestion
Considering the current use of GyroStar, the equipment is defect in ensuring QA/QC. If there is a breakthrough in the real-time supervision, the value of the equipment will be well displayed. Clinical Testing Staff Position Title Department Shi Mei Dean Associate Professor Radiotherapy
Lu Jun Associate Dean Physician Radiotherapy Liang Keming Doctor Physician Radiotherapy
Liu Xiaoli Technician Principal Technician Radiotherapy Xiao Feng Engineering Physist Engineer Radiotherapy Suggestions from the Administration in Charge of the Clinical Test.