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To access the clinical and subclinical response of patients with pituitary adenoma by Gamma knife in Choray Hospital. Subjects and methods: A clinical, intervention study with no control group on 81 patients with definite diagnosis of recurrent or residual pituitary adenoma at Gamma Knife Unit, Choray Hospital from January 2012 to December 2016. Results: 23 patients with functioning tumours and 58 patients with nonfunctioning tumours. The average age was 43.35 ± 11.98 years, the youngest was 18, the oldest was 73 years old. Average volume of pituitary adenoma was 5,553.73 ± 2,991.15 mm3 . PLR increased in 15 cases and GH increased in 10 cases. After radiotherapy, 52 cases (64.2%) responded to radiotherapy. The time when the tumour started to decrease in response to radiotherapy from the 12th month after radiotherapy was noted.
Journal of military pharmaco-medicine no7-2019 ASSESSMENT OF CLINICAL AND SUBCLINICAL RESPONSE OF PATIENTS WITH PITUITARY ADENOMA BY GAMMA KNIFE IN CHORAY HOSPITAL Nguyen Van Do1; Vu Van Hoe2; Nguyen Van Hung2; Nguyen Van Khoi3 SUMMARY Objectives: To access the clinical and subclinical response of patients with pituitary adenoma by Gamma knife in Choray Hospital Subjects and methods: A clinical, intervention study with no control group on 81 patients with definite diagnosis of recurrent or residual pituitary adenoma at Gamma Knife Unit, Choray Hospital from January 2012 to December 2016 Results: 23 patients with functioning tumours and 58 patients with nonfunctioning tumours The average age was 43.35 ± 11.98 years, the youngest was 18, the oldest was 73 years old Average volume of pituitary adenoma was 5,553.73 ± 2,991.15 mm PLR increased in 15 cases and GH increased in 10 cases After radiotherapy, 52 cases (64.2%) responded to radiotherapy The time when the tumour started to decrease in response to radiotherapy from th the 12 month after radiotherapy was noted There was an increase in the tumour size after the follow-up period in patients, the rate of tumour control was 79/81 (97.5%) GH concentrations were normal in 13.3% of patients and 46.7% of patients at 36 and 40 months after radiotherapy, respectively The time of treatment response to GH concentration was from 12 months after radiotherapy The PLR levels were normal in 10% of patients and 20% of patients at 18 and 36 months after radiotherapy, respectively The treatment response time of PRL concentration was from months after radiotherapy Complications after radiotherapy accounted for 66.7% Conclusion: Radiotherapy for recurrent or residual pituitary adenomas had good results, the rate of tumour control was very high after long follow-up period Clinical symptoms and endocrine blood levels responded appropriately to radiotherapy * Keywords: Pituitary tumours; Radiotherapy; Clinical, subclinical response INTRODUCTION The pituitary adenomas are common benign tumours, accounting for 10 - 15% of the primary intracranial neoplasms It develops from pituitary tissue or from the embryonic vestiges of Rathke's pouch with an estimated disease rate of 15 18/100,000 people, which is the third place after glioma and meningioma [2] Due to the anatomical location and endocrine function of the pituitary gland, pituitary adenomas are only diagnosed in cases of disturbances, two common kinds are tumour syndrome and endocrine syndrome However, many tumours not cause any symptoms, therefore they are never diagnosed throughout life In recent years, Choray Hospital 103 Military Hospital Vietnam Military Medical University Corresponding author: Nguyen Van Do (docrhvn@gmail.com) Date received: 10/07/2019 Date accepted: 27/08/2019 142 Journal of military pharmaco-medicine no7-2019 thanks to the development of imaging diagnostics, especially MRI, pituitary adenomas have been early detected The main purpose of treatments was to remove or control the tumour, but still ensure the endocrine function of the pituitary gland, inhibit or reduce the tumour-induced hormone secretion, with the least invasion [3, 4] Radiotherapy for pituitary adenoma has been carried out worldwide since the 1900s, its technique has been increasingly improved and developed with satisfactory results of treatment and long-term followup after radiotherapy [5] In recent years, in Vietnam radiotherapy has been applied in some clinic cneters in treatment of pituitary adenoma in combination with surgery However, there have been any studies on Gamma knife radiotherapy for patients with recurrent or residual pituitary adenomas after surgery Hence, this research was conducted with aims: Assessment of clinical and subclinical response of patients with pituitary adenoma by Gamma knife in Choray Hospital SUBJECTS AND METHODS Subjects 81 patients with a recurrent or residual pituitary adenoma after surgery All patients had examined, treated and followed up at Gamma Knife Unit, Choray Hospital from 01 - 2012 to 12 - 2016 The patient was diagnosed with pituitary adenoma and underwent surgery The result of pathology was pituitary adenoma The patient received a MRI to discover the recurrent or residual pituitary tumour The patient was combined complementary treatment with radiosurgery by Leksell Gamma knife radiology system at Gamma Knife Unit, Choray Hospital Methods A clincal intervention study with no control group was carried out * The diagnostic criteria of residual tumour: The presence of the pituitary in the procedure and its image on the MRI at least months after surgery * The diagnostic criteria for post-operative recurrence tumours: Pituitary tumours were removed completely from surgery, there were evidences of MRI that tumour increased in size compared to the previous months Diagnosis of pituitary tumours was based on either American Association of Brain Tumours (ABTA) criteria [2] and histopathology or pituitary adenoma on MRI Diagnosis of pituitary tumour types was based on hormones: Secreting tumour: one or more hormones (PRL, ACTH, TSH, FSH, GH, LH); nonfunctioning tumour: No increase in pituitary hormones Patients were followed up after radiotherapy with MRI and endocrine tests at times of 3, 6, 12, 18, 24, 36, 40, 46 and 60 months after radiotherapy Criteria for normal hormone levels in the adults are assessed according to Molina [6] (American Clinical Endocrine Society) Hypopituitarism was diagnosed when one or more pituitary hormones decreased below the threshold of lower limit in the reference group, except for GH and ACTH hormones The diagnostic criteria for hypopituitarism was based on Nemes [7] Dose radiation was accordance with RTOG 90-05 (Radiotherapy oncology group) 143 Journal of military pharmaco-medicine no7-2019 guidelines [8]: The radiation dose was based on the size and volume of the tumour Adoption of tumour size according to RECIST standard Clinical and paraclinical features, tumour images on MRI were collected during the treatment The data were processed by SPSS 20.0 RESUTLS Table 1: Clinical and paraclinical characteristics of patients Functioning tumour ( n = 23) Nonfunctioning tumour (n = 58) Total (n = 81) p value Male 11 (47.8) 27 (44.6) 38 (46.9) Female 12 (52.2) 31 (53.4) 43 (53.1) 39.48 ± 12.12 44.88 ± 11.67 43.35 ± 11.98 9.39 ± 4.06 10.26 ± 5.66 10.01 ± 5.25 0.506 Dementia (4.3) 12 (20.7) 13 (16) 0.071 Headache 18 (78.3) 50 (86.2) 68 (84) 0.380 Visual disorders (30.4) 37 (63.8) 44 (54.3) 0.007 Galactorrhe (21.7) (1.7) (7.4) 0.002 Menstrual irregularities (8.7) (10.8) (9.9) 0.823 Decreased libido (13) (13.8) 11 (13.6) 0.929 14 (60.9) 14 (17.3) < 0.001 4,835.26 ± 2,722.11 5,835.64 ± 3,066.98 5,553.73 ± 2,991.15 0.175 Degree (4.3) (3.4) (3.7) 0.357 Degree 1 (4.3) (1.2) Degree (34.8) 17 (29.3) 25 (30.9) Degree 12 (52.2) 30 (51.7) 42 (51.9) Degree (4.3) (15.5) 10 (12.3) 11 (47.8) 32 (53.1) 17.74 ± 2.28 15.55 ± 2.07 Gender ( n, %) Age (year) Duration from surgery to radiation (weeks) Compress syndrome (n; %) Endocrine syndrome (n; %) Acromeagaly Tumour size (mm ) KNOSP classification Hypopituitarism (n; %) Radiation dose (Gy) 144 0.550 16,17 ± 2.33 < 0.001 Journal of military pharmaco-medicine no7-2019 Table 2: Post radiotherapy complications Functioning tumour (n = 23) Nonfunctioning tumour (n = 58) Total (n = 81) p value Total complication 16 (69.9) 38 (65.5) 54 (66.7) 0.727 Headache (21.7) 12 (20.7) 17 (21.0) 0.917 Nausea (21.7) 10 (17.2) 15 (18.5) 0.638 Anorexia (26.1) 16 (27.6) 22 (27.2) 0.891 Dry mouth (34.8) 18 (31.0) 26 (32.1) 0.745 Insomnia (17.4) 15 (25.9) 19 (23.5) 0.417 Hair loss (30.4) (10.3) 13 (16.0) 0.026 Chart 1: Clinical response to radiothepary in functioning pituitary adenomas (n = 23) Chart 2: Clinical response to radiothepary in nonfunctioning pituitary adenomas (n = 58) 145 Journal of military pharmaco-medicine no7-2019 P 4,500 mm3 accounted for a high rate (54.3%) The mean radiation dose was 16.17 Gy, which revealed that the secreting pituitary adenomas had a higher radiation dose than the non-functioning pituitary adenomas (17.74 Gy compared to 15.55 Gy, p < 0.001) Sheehan [11] studied 512 patients with nonfunctioning pituitary adenomas, with an average tumour size of 3.3 cm3, indicating an average radiation dose of 16.4 Gy The author also found the relation between the dose radiation and the free-disease survival rate over the follow-up time, the patients who received radiotherapy < 12 Gy or > 20 Gy would have a lower rate of free-disease survival than the group of 12 - 20 Gy 148 Symptom of headache started to decrease after months of radiotherapy (86.2% at radiotherapy and 81% at the 3rd month) and then decreased sharply from the 6th month (65.5%) until the 18th month only 5.2% and was stable in the follow-up months This symptom reduction was statistically significant Bir [12] performed radiotherapy for 57 patients with pituitary tumours without increased secretion, headache symptoms decreased from 49.1% before radiotherapy to 3.5% after radiotherapy, with statistical significance, p < 0.001 Chai Hong Rim [13] reported 60 patients with an average follow-up time of 5.7 years, indicating a remarkable decrease in headache symptoms (74%) Nguyen Thi Minh Phuong [1] showed that headache symptoms decreased slowly within the first 12 months of follow-up but by 24 months, headache symptoms decreased significantly We recorded that pituitary adenomas completely responded to radiotherapy accounting for 13.6%, partially responding accounted for 50.6%, stable disease made up 33.3% and 2.5% of progressive disease, tumour increased in size The rate of pituitary tumour control was 97.5% Nguyen Thi Minh Phuong [1] recorded that tumour response with radiotherapy according to RECIST criteria occured in 44 patients with pituitary tumours: Complete response accounted for 6.3%, partial response presented in 41.7%, stable disease explained for the highest proportion (43.8%), progressive disease was found in 8.3% of patients Sallabanda [14] gave the treatment for 30 patients with pituitary tumours, 63% of patients, whose tumours did not change in size Journal of military pharmaco-medicine no7-2019 after radiotherapy, 30% of them decreased in size and 7% of them increased the size after radiotherapy Yuan-Hao Chen [3] treated 22 patients by radiotherapy with an average followed up of 58.1 months showed that 39.1% of patients had reduced tumour size, 60.9% of them had stabilized tumour size and none of them had increased tumour size after follow-up period The period when endocrine responded to treatment returned to normal level was the 18th month for PRL and the 30th month for GH hormone after radiotherapy However, according to Nguyen Thi Minh Phuong [1], this point of time was the 6th month after radiotherapy Grant et al [16] reported that 31 patients with secreting pituitary adenomas were treated with radiotherapy with an everage follow-up of 40.2 months and found that 70% of patients with endocrine concentrations returned to normal level after everage follow-up of 17.7 months The author revealed that mean time of endocrine substances at normal level: ACTH was 11.7 months, GH was 18.4 months and PLR was 57 months Visual complications were not obseved in our study In Sebastian’s et al research [14] on 117 patients with pituitary adenoma, visual complications after radiotherapy were 5.3% In multivariate analysis, the author demontrated that risk factors for visual complications after radiotherapy were traditional radiotherapy (OR = 10.36, p = 0.04) Gopalan [17] recorded that visual complications after radiotherapy was 6.2% (3/48 patients), of which patients had visual disturbances before surgery, out of patients had progressive disease after radiotherapy CONCLUSION Radiotherapy for pituitary adenomas has brought good results with high rate of tumour control after long-term follow-up period Clinical symptoms and endocrine levels respond to radiotherapy Radiological complications are transient and disappear after a few days REFERENCES Nguyễn Thị Minh Phương Nghiên cứu biến đổi triệu chứng lâm sàng, hình thái, chức tuyến yên bệnh nhân u tuyến yên trước sau điều trị dao Gamma quay Luận án Tiến sỹ Y học, Học viện Quân y 2018, tr.62 American Brain Tumour Association Pituitary tumours, ISBN 0-944093-90-6 2015 Chirag G, Hayden M, Katznelson L et al Non-surgical management of hormonesecreting pituitary tumours Journal of Clinical Neuroscience 2009, 16, pp.985-993 Camara Gomez R Non-functioning pituitary tumours: 2012 update Endocrine Nutrition 2014, 61 (3), pp.160-170 Wan H, Chihiro O, Yuan S MASEP Gamma knife radiosurgery for secretory pituitary adenomas: Experience in 347 consecutive cases Journal of Experimental & Clinical Cancer Research 2009, 28 (1), p.36 Molina P.E Anterior pituitary gland th Endocrine Physiology edition, McGraw-Hill Companies, Inc, New York 2013, 1, pp.49-72 Nemes O Hypopituitarism due to pituitary adenomas, traumatic brain injury and stroke Clinical Medical Sciences Hungary 2016, pp.10-13 149 Journal of military pharmaco-medicine no7-2019 Moose B.D, Shaw E.G Radiotherapy of pituitary tumours Diagnosis and Management of Pituitary Tumours Humana Press, Springer Science 2008, pp.269- 274 13 Chai Hong Rim et al Radiotherapy for pituitary adenomas: Long-term outcome and complication Radial Oncol J 2011, 29 (3), pp.156-163 Chul Bum Cho et al Stereotactic radiosurgery with the Cyber knife for pituitary adenomas J Korean Neurosurg Soc 2009, 45, pp.157-163 14 Sallabanda K et al Stereotatic radiosurgery in pituitary adenomas: Long-term single institution experience and role of the hypothalamic-pituitary axis Journal of Radiosurgery and SBRT 2011, 1, pp.213-220 10 Guadalupe V, Gonzalez B, Ramirez C et al Clinical characteristics and treatment outcome of 485 patients with unfunctioning pituitary macroadenomas International Journal of Endocrinology 2015, pp.1-7 15 Yuan-Hao Chen et al Multisession Cyber knife radiosurgery for post-surgical residual and recurrent pituitary adenoma: Preliminary result from one center Journal of Radiosurgery and SBRT 2013, 2, pp.105-117 11 Sheehan J.P et al Gamma knife radiosurgery for the management of nonfunctioning pituitary adenomas: A multicenter study J Neurosurg 2013, 119, pp.446-456 16 Grant R.A et al Efficacy and safety of higher dose stereotatic radiosurgery for functional pituitary adenoma: A preliminary Report World Neurosurg 2014, 82 (1-2), pp.195-201 12 Bir S.C et al Clinical and radiologic outcome of Gamma knife radiosurgery on nonfunctioning pituitary adenomas J Neurol Surg B 2015, 76, pp.351-357 17 Gopalan R et al Long-term outcome after Gamma knife radiosurgery for patients with a nonfunctioning pituitary adenoma Nerosurgery 2011, 69 (2), pp.284-293 150 ... pituitary adenomas after surgery Hence, this research was conducted with aims: Assessment of clinical and subclinical response of patients with pituitary adenoma by Gamma knife in Choray Hospital. .. in some clinic cneters in treatment of pituitary adenoma in combination with surgery However, there have been any studies on Gamma knife radiotherapy for patients with recurrent or residual pituitary. .. SUBJECTS AND METHODS Subjects 81 patients with a recurrent or residual pituitary adenoma after surgery All patients had examined, treated and followed up at Gamma Knife Unit, Choray Hospital