Evaluation of the outcomes of treating pituitary tumor by rotating gamma knife at the Nuclear Medicine and Oncology Center, Bachmai hospital

Objectives: To evaluate treatment outcomes of rotating Gamma knife radiosurgery (RGKR) for pituitary adenomas at the Nuclear Medicine and Oncology Center, Bachmai Hospital. Subjects and methods: A prospective interventional study was conducted on 48 patients, whowere treated with rotating Gamma knife for pituitary tumor. All patients had size of tumor < 5 cmon MRI and recruited in between April, 2008 and April, 2016.

Journal of military pharma-medicine no6-2017 EVALUATION OF THE OUTCOMES OF TREATING PITUITARY TUMOR BY ROTATING GAMMA KNIFE AT THE NUCLEAR MEDICINE AND ONCOLOGY CENTER, BACHMAI HOSPITAL Nguyen Thi Minh Phuong*; Mai Trong Khoa** Doan Van De***; Tran Quoc Hung* Summary Objectives: To evaluate treatment outcomes of rotating Gamma knife radiosurgery (RGKR) for pituitary adenomas at the Nuclear Medicine and Oncology Center, Bachmai Hospital Subjects and methods: A prospective interventional study was conducted on 48 patients, who were treated with rotating Gamma knife for pituitary tumor All patients had size of tumor < cm on MRI and recruited in between April, 2008 and April, 2016 Results: Male/female ratio was 1/2, patient age ranged from 21 - 78 years old with median of 44.58 ± 12.84 years old Clinical symptoms were reduced gradually after radiosurgery: the percentage of patients with headache symptom at baseline after the time of months, 12 months, 24 months and 36 months accounted for 70.8%, 50%, 36.4%, 20.5% and 8.6%, respectively Abnormal hormone level had been improved after radiosurgery Size of the tumor was reduced Severe side effects or death were not reported in the follow-up period Conclusion: Radiosurgery with rotating Gamma knife is an effective and safe treatment method for pituitary tumor * Keywords: Pituitary tumor; Rotating Gamma knife; Outcomes INTRODUCTION The pituitary gland tumors are tumors that occur in the anterior pituitary, which account for 10 - 15% of the intracranial tumors, more than 99% of the pituitary tumors are benign tumors and grow slowly Pituitary tumors are mainly seen in adults, very rarely seen before puberty, and the incidence rate of men compared to women is 1/2 Different methods for treatment of pituitary tumors are available such as surgery, medicine, radiation therapy, and radiotherapy by rotating Gamma knife The main purpose of these methods is to remove or inhibit tumor growth, to maintain the endocrine function of the pituitary gland, to suppress or reduce the secretion of hormones caused by tumors, and with minimum of invasion to the surrounding areas In previous decades, * 198 Hospital ** Bachmai Hospital *** 103 Hospital Conresponding author: Nguyen Thi Minh Phuong (drminhphuong198@gmail.com) Date received: 20/04/2017 Date accepted: 25/07/2017 169 Journal of military pharma-medicine no6-2017 treatment of pituitary tumors was mainly with medications When medical treatment fails, surgery may be performed to open the cranium but it was done only in some major hospitals with high rate of postoperative complications and the mortality rate over 10% In recent decades, surgical removal of the tumor by endoscopy through the sinus fracture has partially reduced the mortality rate [1, 2] but the rate of recurrence after surgery is still high Globally, the application of rotating Gamma knife for treatment is widely accepted in the United States, Japan, Singapore, France, Hungary [3, 4, 5, 6] Since 2007, the American rotating Gamma knife system has been introduced at the Center for Nuclear Medicine and Oncology, Bachmai Hospital for the treatment of brain tumors and some cranial diseases including pituitary tumors This treatment method is less invasive, requires no anesthesia, with less complication rate and short hospital stay In Vietnam, there has been no studies evaluating the role of rotating Gamma knife for the treatment of pituitary tumors Therefore, this study aims to: Evaluate the treatment results of pituitary tumors by rotating Gamma knife at the Center of Nuclear Medicine and Oncology, Bachmai Hospital SUBJECTS AND METHODS Subjects * Inclusion criteria: The study enrolled 48 patients aged ≥ 18 years diagnosed with pituitary tumor based on cranial MRI and treated with rotating Gamma knife at the Center for Nuclear Medicine and Oncology, Bachmai Hospital from April, 2008 to April, 2016 170 * Exclusion criteria: - Patients with other endocrine diseases such as Basedow disease, adrenal tumors - Patients taking prolonged steroids, pregnant women, breast-feeding women - Patients < 18 years old Research methods Interventional study with repeatedmeasures analysis * Study procedures: - Baseline evaluations: + Record clinical and laboratory information in study case report forms + Clinical: functional and physical symptoms + Para-clinical tests: hormone levels, size and nature of tumors on brain MRI - Steps for conducting the operation: + Step 1: prepare the patient + Step 2: fix the patient's head using the Fraim frame + Step 3: MRI simulation + Step 4: plan the radiosurgery + Step 5: proceed with radiotherapy - Post-treatment evaluation: based on clinical and paraclinical symptoms of the patient being examined, compared before and after treatment + Clinical characteristics: age, sex, history of treatment, clinical symptoms before treatment and months, 12 months, 24 months and 36 months after treatment + Clinical features: Evaluation of size, nature and extent of invasive on MRI before treatment, Journal of military pharma-medicine no6-2017 months, 12 months, 24 months, 36 months after treatment Hormonal tests: PRL, GH, ACTH, LH, TSH, FSH before treatment, months, 12 months, 24 months, 36 months after treatment + Patients underwent pituitary hormone quantification using morning venous blood (fasting condition) + Investigation of TSH, FSH, PRL, ACTH, LH, GH by electrochemistry immunoassay on Elecsys 2010 with Roche reagent at Biochemistry Department, Bachmai Hospital * Data analysis and processing: The collected information is encrypted and processed on SPSS 16.0 software RESULTS AND DISCUSSIONS Patient disposition by age group 18 - 30 years old: patients (8.3%); 31 - 45 years old: 21 patients (43.8%); 46 - 60 years old : 16 patients (33.3%); > 60 years old: patients (14,6%) The study on 48 patients with pituitary tumors using rotating Gamma radiography at the Center for Nuclear Medicine and Oncology, Bachmai Hospital showed that: The majority of patients in the age group of 31 - 45 years old, the lowest age was 21, the highest age was 78, the average was 44.58 ± 12.84 years old The percentage of male accounted for 33.3%; females accounted for 66.7% Distribution of patients by gender Figure 1: Patient distribution In the study group, the proportion of male patients was 33.3% male, female was 66.7% Heng Wan's study (2007) [3] reported that the average age of patients with pituitary tumors was 44.58 ± 12.84 years old and the proportion of women was higher than men Medical history before surgery No interventions: patients medication interventions: 30 (12.5%); patients (62.5%); surgical interventions: 12 patients (25.0%) Most patients have received medication or surgical treatment for recurrence 12.5% of the patients who received no treatment were indicated to use radiotherapy According to Faglia G, 92% of patients with pituitary gland tumors who had been treated with Gamma irradiation had failed to response to prior medication treatments 171 Journal of military pharma-medicine no6-2017 Irradiation dosages Table 1: Dose (Gy) Mean dose (X) Standard deviation (SD) Min Max Gamma knife group (n = 48) 13.6 2.2 11 22 Hormonally active (n = 21) 14.0 2.9 11 22 Clinically non-functioning (n = 27) 13.3 1.3 12 16 Group p > 0.05 The mean surgical irradiation dose of 13.6 ± 2.2 Gy The dose was used in the hormonally active group was higher than that in the hormonally non-active group, but the difference was not statistically significant (p > 0.05) Time to follow-up after surgery Table 2: Follow-up time (month) Value Mean (X ± SD) 38.9 ± 10.9 Minimum 12 Maximum 63 The mean postoperative follow-up time was 38.9 ± 10.9 months (from 12 months to 63 months) after radiosurgery We found that all of the clinical signs of postoperative irradiation were significantly improved Clinical symptoms before and after the radiosurgery Table 3: Symptoms (n = 48) Baseline (n = 48) months (n = 46) n 12 months (n = 44) % n 24 months (n = 39) % n % 36 months (n = 35) n % n % Headache 34 70.8 23 50 16 36.4 20.5 8.6 Visual disturbance 25 52.1 17 37.0 10 22.7 17.9 17.1 Libido 12.5 13.3 4.4 4.8 2.7 Menstrual disorder 10 20.8 11 23.9 11.4 12.5 11.4 Lactation 16.7 13.0 4.5 5.1 0 Clinical symptoms decreased over time Headache was one of the most common symptoms before treatment (70.8% of patients) and this had decreasead to 50%, 36.4%, 20.5%, and 8.6% after 6, 12, 24, and 36 months, respectively The study on 172 Journal of military pharma-medicine no6-2017 over 270 patients of Sheehan J.P (2011) [5] showed that rotating Gamma kife treatment improved functional symptoms in 90% of patients and 55% of them improved their physical symptoms Tumor size (on MRI) before and after the radiosurgery Table 4: Baseline (n = 48) months (n = 46) 12 months (n = 44) 24 months (n = 39) 36 months (n = 35) 20.9 ± 10.3 19.5 ± 11.5 15.6 ± 12.3 12.9 ± 12.7 12.9 ± 12.4 Minimum tumor size (mm) 0 0 Maximum tumor size (mm) 48 48 48 50 50 Time-points Mean tumor size (mm) Mean tumor size decreased after treatment, significantly decreased after 12 months compared with pretreatment, difference was statistically significant (p < 0,05) Heng Wan et al (2002) [3] showed that the percentage of patients with tumor size decreased or remained constant after tumor resection was 89.7% Hormone level before and after treatment Table 5: Baseline 36 months after treatment Hormon level Mean SD Medium Mean SD Medium TSH (uU/mL) 3.647 14.224 1.500 1.941 1.141 1.840 LH (mU/mL) 5.97 2.72 5.42 6.09 2.75 5.49 FSH (mU/mL) 10.92 15.55 7.02 8.63 7.61 6.72 Prolactin (ng/mL) 62.27 115.03 12.45 29.99 75.78 13.42 GH (ng/mL) 11.31 24.38 2.35 2.83 1.95 2.19 ACTH (Pg/mL) 27.04 18.95 20.97 25.62 9.81 23.41 The post-treatment hormone levels decreased, especially PRL and GH, these levels significantly decreased and difference was statistically significant (p < 0.01) LH, ACTH, THS and FSH levels were not significantly reduced (p > 0.05) This was probably due to the fact that the number of patients with ACTH, TSH, LH and FSH hypersecretion was not significant Shota Tanaka et al (2010) [6] reported that after the radiotherapy, the PRL concentration decreased from 88.4 ng/mL to 28.4 ng/mL The difference was statistically significant (p = 0.001) There was no cases of death after treatment 173 Journal of military pharma-medicine no6-2017 CONCLUSION The study on 48 patients with pituitary tumors using rotating Gamma radiosurgery at the Center for Nuclear Medicine and Oncology, Bachmai Hospital: - Patient age ranged from 21 - 78 years old with average of 44.58 ± 12.84 years old - Male/female ratio was 1/2 - Clinical symptoms were reduced gradually after radiosurgery: the percentage of patients with headache symptom at the time point of baseline, after months, 12 months, 24 months, 36 months accounted for 70.8%, 50%, 36.4%, 20.5% and 8.6%, respectively - Abnormal hormone level GH, PRL had been improved after radiosurgery - Size of the tumor was reduced - Severe side effects or death were not reported in the follow-up period - Radiosurgery with rotating Gamma knife has been shown as an effective and safe treatment method for pituitary tumor REFERENCES Nguyễn Đức Anh Nhận xét đặc điểm lâm sàng, cận lâm sàng đánh giá kết 174 phẫu thuật u tuyến yên tăng tiết prolactin Luận văn Tốt nghiệp Bác sỹ Nội trú Chuyên ngành Ngoại khoa Trường Đại học Y Hà Nội 2012 Lý Ngọc Liên Nghiên cứu áp dụng phương pháp mổ u tuyến yên qua đường xoang bướm Bệnh viện Việt Đức từ 2000 2002 Luận văn Tốt nghiệp Bác sỹ Chuyên khoa Cấp II Đại học Y Hà Nội 2003 Heng Wan Gamma knife radiosurgery for secretory pituitary adenomas: experience in 347 consecutive cases 2007, 106 (6), pp.980-987 Faglia G Genesis of pituitary adenomas, in Landolt A Vance M.L, Reilly P.L Pituitary adenoma New York, Churchill Livingstone 1996 Sheehan J.P, Pouratian N, Steiner L, Laws E.R, Vance M.L Gamma knife surgery for pituitary adenomas Factors related to radiological and endocrine outcomes Department of Neurological Surgery, University of Virginia Health System, Charlottesville, Virginia 22908, USA jps2f@virginia.edu 2011 Shota Tanaka1, Michael J.Link Gamma knife radiosurgery for patients with prolactinsecreting pituitary adenomas World Neurosurgery 2010, 74 (1), pp.147-152  ... role of rotating Gamma knife for the treatment of pituitary tumors Therefore, this study aims to: Evaluate the treatment results of pituitary tumors by rotating Gamma knife at the Center of Nuclear. .. patients with pituitary tumors using rotating Gamma radiography at the Center for Nuclear Medicine and Oncology, Bachmai Hospital showed that: The majority of patients in the age group of 31 - 45... 6] Since 2007, the American rotating Gamma knife system has been introduced at the Center for Nuclear Medicine and Oncology, Bachmai Hospital for the treatment of brain tumors and some cranial