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.
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ASSESSMENT OF CLINICAL AND SUBCLINICAL RESPONSE
OF PATIENTS WITH PITUITARY ADENOMA BY GAMMA KNIFE
IN CHORAY HOSPITAL
Nguyen Van Do 1 ; Vu Van Hoe 2 ; Nguyen Van Hung 2 ; Nguyen Van Khoi 3
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 3 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 12 th month after radiotherapy was noted There was an increase in the tumour size after the follow-up period in 2 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 6 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 do not cause any symptoms, therefore they are never diagnosed throughout life In recent years,
1 Choray Hospital
2 103 Military Hospital
3 Vietnam Military Medical University
Corresponding author: Nguyen Van Do (docrhvn@gmail.com)
Date received: 10/07/2019
Date accepted: 27/08/2019
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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
follow-up 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
1 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
2 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 3 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 6 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)
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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
Gender ( n, %)
Duration from surgery to
radiation (weeks)
Compress syndrome (n; %)
Endocrine syndrome (n; %)
KNOSP classification
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Table 2: Post radiotherapy complications
Functioning tumour
(n = 23)
Nonfunctioning tumour
(n = 58)
Total
Chart 1: Clinical response to radiothepary in functioning pituitary adenomas (n = 23)
Chart 2: Clinical response to radiothepary in nonfunctioning pituitary adenomas (n = 58)
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Chart 3: Tumour size response to radiotherapy
Chart 4: Tumour size response according to RECIST classification.
Chart 5: Treatment response of endocrine after radiotherapy (n = 23)
P<0.001
p < 0.01
Time of follow-up
(month)
Time of
follow-up (month)
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Chart 6: Hypopituitarism during the follow-up after radiotherapy
6 patients with galactorrhe and 8
patients with menstrual disorders were
followed up after treatment returned to
normal, 2 patients after radiotherapy had
pregnancy and gave normal birth
14 cases had acromegaly, however,
there was no improvement in the course
of treatment Clinical symptoms of memory
loss, headache, visual disturbances
decreased gradually compared to pre
treatment
After radiotherapy, 52 cases (64.2%)
responded to radiotherapy with reduced
tumour size The period when the tumour
size started to decrease in response to
radiotherapy from the 12th month after
radiotherapy In the study, there was an
increase of the tumour size after the
follow-up period, the rate of tumour control was 79/81 (97.5%)
GH concentrations were recorded at normal levels in 13.3% of patients and 46.7% of patients at 36 and 40 months after radiotherapy, respectively The period
of treatment response to GH concentration was from the 12th month after radiotherapy 10% of patients and 20% of patients had normal PLR levels in the 18th and the 36th months after radiotherapy The treatment response time of PRL concentration was from the 6th month after radiotherapy Complications after radiotherapy accounted for 66.7% of the total study subjects, of which the most symptoms were dry mouth Headache, nausea, loss
of appetite, dry mouth, insomnia were
Time of follow-up (month)
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similar in the two groups of patients,
particularly hair loss symptoms in the
functioning tumour group were higher than
in nonfunctioning tumour with statistically
significant difference
DISCUSION
We studied 81 patients with recurrent
or residual pituitary adenomas The
average volume of tumour was 5,553
mm3 Chui Bum Cho [9] reported that the
mean tumour volume was 2.6 cm3, they
also found that the volume of
nonfunctioning pituitary adenomas was
statistically significantly higher than the
secretory tumour (3.06 cm3 compared to
1.69 cm3) Bir [5] also showed that the
volume of nonfunctioning pituitary
adenomas before radiotherapy was quite
large, an average volume of 3.7 cm3
Guadalupe [10] also showed that pituitary
tumour volume before radiotherapy was
10,306 mm3 In addition, we found that
the volume of tumour > 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
Symptom of headache started to decrease after 3 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
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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 2 patients
had visual disturbances before surgery,
2 out of 3 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
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