|Year : 2020 | Volume
| Issue : 1 | Page : 19-25
Short-term results of treatment outcome and toxicities following gamma knife surgery in cerebellopontine angle tumors
Nishant Lohia1, Arti Sarin2, Manoj Kumar Semwal3, Virender Suhag4, Sukhvir Singh1, Sankalp Singh3, Pankaj Goyal5, Tejas Pandya5
1 Department of Radiation Oncology, Command Hospital (CC), Lucknow, Uttar Pradesh, India
2 Department of Radiation Oncology, INHS Asvini, Mumbai, Maharashtra, India
3 Department of Radiation Oncology, Army Hospital (R&R), Delhi, India
4 Department of Radiation Oncology, Command Hospital (SC), Pune, Maharashtra, India
5 Department of Radiation Oncology, Command Hospital (EC), Kolkata, West Bengal, India
|Date of Submission||11-Nov-2019|
|Date of Acceptance||04-Jun-2020|
|Date of Web Publication||2-Jul-2020|
Dr. Arti Sarin
INHS Asvini, Mumbai - 400 005, Maharashtra
Source of Support: None, Conflict of Interest: None
Introduction: About 5% to 10% of all intracranial neoplasms are located at the cerebellopontine (CP) angle. The most common of these is the vestibular schwannoma (VS).
Aims and Objectives: The primary objective was to assess treatment outcomes in CP angle tumor post-Gamma Knife radiosurgery (GKS). Secondary objectives were the assessment of dose conformity and gradient indices for target coverage and organs-at-risk sparing along with the assessment of hearing function preservation post-GKS. We also assessed facial and trigeminal nerve function and quality of life (QoL) post-GKS.
Materials and Methods: This was a retrospective study carried out in a tertiary care center of North India for 2 years and 3 months. All patients were followed up for 24 months posttreatment with a minimum follow-up at least 12 months. Tumor expansion was assessed post-GKS along with hearing preservation rates, facial and trigeminal nerve function and QoL.
Results: No significant relationship between age, sex, and study variables was made out. The target tumor coverage ranged from 94% to 100%, with a mean of 97.24%. The conformity index ranged from 1.17 to 1.92, and the gradient index ranged from 1.35 to 1.73. Tumor expansion occurred in 52% of the patients (13) 6 months after GKS, though the increase in size was minimal with a standard deviation of 0.59 and did not result in any clinical deterioration of patients. Positive correlation was seen between maximum tumor size and loss of hearing function. The hearing preservation rate at 12 months post-GKS is 80%. This study also showed that GKS for VS has little impact in the deterioration of the function of the trigeminal and facial nerve and the general QoL.
Conclusion: The radiation changes after GKS are generally seen after 6–12 months post-GKS and about 3–5 years are required to ascertain tumor control and any meaningful change in hearing levels and other toxicities. Thus, a longer period of follow-up is needed to validate the findings of this study.
Keywords: Cerebellopontine angle tumors, Gamma Knife radiosurgery, vestibular schwannoma
|How to cite this article:|
Lohia N, Sarin A, Semwal MK, Suhag V, Singh S, Singh S, Goyal P, Pandya T. Short-term results of treatment outcome and toxicities following gamma knife surgery in cerebellopontine angle tumors. Int J Neurooncol 2020;3:19-25
|How to cite this URL:|
Lohia N, Sarin A, Semwal MK, Suhag V, Singh S, Singh S, Goyal P, Pandya T. Short-term results of treatment outcome and toxicities following gamma knife surgery in cerebellopontine angle tumors. Int J Neurooncol [serial online] 2020 [cited 2020 Aug 10];3:19-25. Available from: http://www.Internationaljneurooncology.com/text.asp?2020/3/1/19/288788
| Introduction|| |
The cerebellopontine (CP) angle is a triangular space located posterior to the pyramid, inferior to the tentorium, lateral to the pons, and ventral to the cerebellum. Vestibular schwannomas (VSs) are oncologically benign, typically slow-growing tumors. They occur in two different forms: sporadic unilateral (95%) and bilateral, and the latter is associated with neurofibromatosis 2 (5%). The patients with sporadic VS usually present in their fifth or sixth decades of life.
The clinical presentations include unilateral high-frequency sensorineural hearing loss, tinnitus, and pressure in the ear, disequilibrium, otalgia, and occasionally vertigo. Hearing loss occurs in >95% of patients for this disease. Progressive hearing loss is to be expected in untreated patients, regardless of tumor growth.,
The diagnosis of VS is made with history, physical examination, audiometry, and neuroradiological examination. Magnetic resonance imaging (MRI) has revolutionized the diagnosis of CP angle pathology.
Historically, tumor resection has been the treatment of choice for VS. However, now with an early diagnosis with smaller size tumor, goal of the treatment has changed from surgery to prophylactic management of future morbidity. Serial surveillance with MRI scans performed annually with a “wait-and-scan” principle seems to be a safe treatment strategy for a small-to-medium-sized benign tumors and is being followed nowadays. This approach consists of performing repeated MRI scans, and the first one generally 6 months after diagnosis and if there are no significant changes, once every year.,, Along with MRI, audiometric testing is also done at each review. Different radiotherapy techniques for VS are stereotactic radiosurgery (SRS) in a single shot and fractionated stereotactic radiotherapy with hypofractionation or conventional fractionation. The most common radiotherapeutic approach is by computer-aided single-dose cobalt irradiation, the so-called Gamma Knife radiosurgery (GKS). The goal of GKS is to achieve tumor growth control. The recommended current doses are in the 12–14 Gy range, and MRI is used for dosimetry planning. In the current era, VS is treated with GKS, and surgery is reserved for those needing urgent decompression or in very young patients. Thus, treatment options of VS include “wait and scan,” radiotherapy, and microsurgical removal via one of the several operative approaches.
Complications seen with GKS for VS are much lower than those with microscopic open surgery and comprise hearing deficits, facial palsy, hydrocephalus, and brain stem damage. However, treatment of any condition can only be justified if the results of treatment are better than the natural course of the disease. In this context, symptom progression and quality of life (QoL) are most important for the patients.
This study was undertaken to observe and assess treatment outcomes and toxicities following GKS in CP angle tumors and compare them with the published literature and also compare the overall impact on QoL post-GKS.
| Materials and Methods|| |
We conducted a retrospective study at a tertiary cancer care hospital in Northern India. The study included patients of CP angle tumor with tumor size <3 cm and between the age group of 18–70 years with no history of any invasive malignancies within the past 5 years. Patients with prior history of brain surgery or prior GKS or features of symptomatic brain stem compression were excluded from the study. The study was carried out for 2 years and 3 months. Patient selection and treatment was made from March 2014 to May 2015. Follow-up of patients, data collection and analysis were carried out till May 2016 (minimum follow-up 12 months posttreatment).
The patients were evaluated at initial diagnosis before GKS and every 3 months post-GKS thereafter. They were asked for the cardinal symptoms, as well as if there were other complaints. The clinical examination included cranial nerves with a special focus on the trigeminal and facial nerves function. Facial nerve function was assessed using the House-Brackmann Scale [Table 1]. The hearing assessment was done by both the Rinne test and the Weber test. Pure-tone audiometry (PTA), MRI with Gadolinium contrast scan, and QoL assessment by the Glasgow Benefit Inventory (GBI) Questionnaire were also carried out.
Rinne and Weber's tests determine whether a patient has conductive or sensorineural hearing loss. PTA is the average of hearing sensitivity at 500, 1000, and 2000 Hz. The minimum presentation level at which the subject responds at least 50% times (3 responses out of 6 tone presentations), is taken as the hearing threshold. The preservation of hearing has been codified, and the most popular grading system in the current use is that of Gardner and Robertson. An easier way of documentation of hearing is by using only the pure tone averages, which was included in this study. Here, the average of four frequency of air conduction is taken, and hearing is graded as follows [Table 2].
There is no validated disease-specific questionnaire for the evaluation of QoL in VS patients. QoL questionnaire used was the GBI questionnaire. It contains 18 postintervention items, eliciting responses based on a five-point scale. The scores range from −100 to 100, with a score of 0 indicating no health change after an intervention and −100, a worsened health state after treatment.
All patients underwent SRS using GKS as an elective daycare procedure. The tumor volume and tumor dimension were recorded while planning the dose on the “Gamma Plan” console.
All patients were followed up for a period of at least 96 weeks after the completion of treatment of CP angle tumor with minimum follow-up of at least 48 weeks. Patients were reviewed and assessed on outpatient department basis at base line at the time of presentation, every 12 weeks subsequently. At every follow-up, assessment of cranial nerve V and VII was done. Tumor size was assessed by contrast-enhanced MRI at 6 months post-GKS. Assessment of hearing by PTA was made at 3, 6, and 12 months post-GKS. The assessment of QoL was also done post-GKS at every follow-up.
Statistical analysis was conducted using SPSS software (Version 16.0). Histogram was generated to assess data distribution. Continuous variables were expressed as mean ± standard deviation (SD) and were analyzed using paired and unpaired Student t-tests. Comparison of quantitative variables between the two groups was made by two-tailed Student's t-test. The association between different parameters was assessed using Pearson correlation.
| Observations and Results|| |
Most of the patients in this study were diagnosed with vestibular (Acoustic) schwannoma-23 cases (92.0%), while two cases (8.0%) were of CP angle meningioma. The most common age group of patients was 41–50 years, with eight patients (32.0%) falling in this group, with a mean age of 49 years. The median age was 50 years. The male-to-female ratio was 1:1.5 showing a female preponderance.
The tumor volume was analyzed by the Gamma Plan software during treatment planning. The tumor volume included in the study ranged from a maximum of 7.1 cc and minimum 0.13 cc. Tumors with a volume of ≥4.0 cc were considered to be of larger volume. There is a negative correlation with maximum tumor volume and change in hearing function in decibels between pre-GKS and at 3, 6, and 12 months post-GKS. Deterioration in hearing function was seen from pre-GKS to 12 months post-GKS for larger volume tumors. However, the changes are statistically insignificant, as shown in [Table 3]. Maximum dose to Cochlea was 9.5 Gy and minimum was 1 Gy with a mean of 6.5 Gy. Decline in hearing function was seen in patients who received dose >10 Gy to the cochlea.
|Table 3: Relation of hearing loss with tumor volume, tumor dimensions, dose to cochlea|
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An increasing trend was seen in PTA value from pre- to post-GKS with mean values of 49.50 in pre-GKS patients (min PTA-16; max PTA-78), 52.44 at 3 months post-GKS (min-16; max-82) subsequently increasing to 54.44 at 6 months postGKS (min-17; max-90), and 57.32 at 12 months postGKS (min-19; max-90) [Figure 1]. However, this minimal deterioration in the hearing was not statistically significant, as shown in [Table 4].
|Figure 1: Chart showing mean pure tone audiometry values pre- and post-Gamma Knife radiosurgery|
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|Table 4: Changes in hearing grades from pregamma knife radiosurgery to postgamma knife radiosurgery at 3, 6 and 12 months|
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V th cranial nerve was intact in all the patients both pre- and post-GKS, with only 1 patient having a sensory deficit in the distribution area of the V th cranial nerve, which was the same both before and after GKS. Hence, no change in the V th cranial nerve function was noticed post-GKS. Out of the 25 patients, 21 patients (84%) had House-Brackman Grade 1 facial nerve function, 3 (12%) had Grade 2 function, and 1 (4%) had Grade 3 function pre-GKS. post-GKS 21 patients had Grade 1 facial nerve function, and 2 each had Grade 2 and 3 facial nerve function with a P = 0.327, which is statistically insignificant [Table 5] and [Figure 2].
|Table 5: Pre- and Post-gamma knife radiosurgery comparison of facial nerve grade|
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|Figure 2: Chart showing pre- and post-Gamma Knife radiosurgery Facial nerve Grade|
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Eleven patients (44%) had a GBI score of 0,1 each (4%) had a score of 24 and 25.3 patients (12%) had a GBI score of 28 and rest 9 patients (36%) had a GBI score of 50 The mean total GBI score of 23.32 in this study indicates no negative change in the overall QOL after GKRS.
Only two cases were diagnosed as CP Angle Meningioma with tumor volume of 2.5 and 1 cm, respectively. One of them presented with a headache, and the other patient presented with hearing loss. They received doses of 12 Gy and 13 Gy, respectively, to the tumor margin at 50% isodose line. Trigeminal and facial nerve function was intact in both cases and no change in tumor volume was seen at 6 months post-GKS.
| Discussion|| |
VSs are the most common CP angle tumor and account for 80% to 94% of them, followed by meningioma (3%–10% of CP angle tumors) and the epidermoids (2%–4%). Several authors have reported that the typical age for VS diagnosis is during the fifth to sixth decades of life. Chung et al. reported a median age of 51 years (11–82). Chung et al. reported female-to-male ratio of 113:82 in their 10 years study of 195 cases of VS. No significant relationship between age and sex could be made out by us. The published literature also fails to give any conclusive deduction on age and sex.
The most common presenting otological symptoms of VS are considered to be hearing loss. We had 21 (84%) patients who complained of hearing loss as a presenting symptom of VS. Most literature reviewed is in agreement that tinnitus is the second most common presenting symptom of VS. We had 2 (8%) patients who presented with tinnitus and one, each with the primary symptom of headache and giddiness.
Some tumor regrowth may occur during the early period following radiosurgery for VS, usually between 6 and 24 months after radiation. This initial tumor expansion may be transient and the tumor may decrease in size after the initial expansion. We noticed that increase in tumor size occurred in 13 patients (52%) 6 months after radiosurgery. However, post-GKS there was only a minimal increase in size with an SD of 0.59. However, tumor expansion did not result in any clinical deterioration of patients as only minimal tumor expansion was seen with minimum and maximum size of 0.8 and 2.8, respectively, post-GKS vis a vis 0.6 cm and 2.7 cm pre-GKS tumor dimensions [Table 6]. Nevertheless, longer follow-up is required for assessing long-term rates of tumor control after radiosurgery. It has been documented that delayed tumor growth may occur even in cases where the tumor remained stable for 3 years after treatment.
|Table 6: Pre- and post-gamma knife radiosurgery tumor dimensions and volume, dose to cochlea and tumor coverage|
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The conformity index ranged from 1.17 to 1.92, and gradient index ranged from1.35 to 1.73. Clinical importance of conformity index in terms of tumor control in VS is not known, and further studies are needed for this.
Serviceable hearing is typically defined as a PTA ≤50 dB or SD ≥50%, which corresponds to a Gardner-Robertson (GR) class of I or II. The overall rate of preservation of functional hearing at the long-term follow-up was 71% for patients with hearing classified as GR Class I, and 93% among cases of GR Class I hearing in patients younger than 55 years. Evaluation of hearing function was based on audiometry, ensuring a low risk of observer bias. The hearing preservation rate at 12 months post-GKS is 80%. The hearing preservation rate of 80% in our study far exceeds that achieved by other centers. This may be explained by our consistent use of a lower marginal dose of 12 Gy and shorter follow up. The same reason may help to explain the almost complete absence of trigeminal neuropathy and facial weakness in our series, with only one patient in this study showing deterioration in facial nerve function after GKS, and he received a dose of 14 Gy. Linskey et al. showed a clear inverse relationship between the sizes of tumor and probability of worsening in hearing. In the study by Paek et al., where he examined hearing loss only in patients with serviceable hearing found that a maximum cochlear nucleus dose >10 Gy was a significant predictor of serviceable hearing loss. Baschnagel et al. found that patients who received a mean cochlear dose <3 Gy had a 2-year hearing preservation rate of 91% compared with 59% in those who received a mean cochlear dose of 3 Gy or greater (P = 0.029). No patient who received a mean cochlear dose <2 Gy experienced serviceable hearing loss (P = 0.035).
The tumor coverage in this study ranged from 94% to 100%, with a mean of 97.24%. No meaningful correlation could be elicited from this. Review of literature by various authors also does not suggest any significant relation. A logical assumption is to believe that more the coverage worse the outcome, but the review of literature has shown several authors suggesting no significant relationship. The prescription dose to the tumor volume in almost all our cases has been 12 Gy. It has been already shown by the Pittsburg group that 12–13 Gy is ideal for tumor control and critical in preventing cranial nerve neuropathies and hearing.
Whitmoreet al. found that at 5 years, patients treated with radiosurgery have an overall better QoL than those treated with either microsurgery or those investigated further with serial imaging. In this study, we found that GKRS has a small impact on the general QOL in VS patients. According to the mean total GBI score, the impact of GKRS on the QOL was negligible. However, the range from 0 to 50 points at the presence of large inter-individual variations.
| Conclusion|| |
The radiation changes after GKS are generally seen after 6–12 months post-GKS and about 3–5 years is required to ascertain any meaningful change in both tumor control, hearing levels, and other toxicities. Thus, a longer period of meticulous follow-up is needed to validate the findings of this study. The dose profile applied in this study is one of the lowest reported in the literature. With 12 Gy at the 50% isodose line in GKS, the tumor control rate was comparable at 1-year post-GKS. To validate the merits of further reducing the radiotherapy dose to patients with VSs with measurable hearing, long-term follow-up should be mandatory to monitor any adverse effects on tumor control.
Limitations of the study
- A small sample size and a shorter follow-up is a major limitation of the study. A larger sample size, longer follow-up to assess hearing preservation and treatment outcome along with other toxicities is required to consolidate the role of GKS in VS
- Not all VSs were histologically confirmed because many patients were diagnosed with an MRI; therefore, it is possible that our sample included individuals with other diagnoses such as meningioma or facial nerve schwannoma.
- Not all patients may have reported all relevant symptoms because there are differences in the willingness to report certain symptoms by different patients
- There is no disease-specific disease QoL Questionnaire for VS. Since we have used readymade Questionnaire on QoL from other studies, comparison and any change in QoL between pre- and postGKS status of patients could not be made
- Measuring QOL is difficult. The timing of the interview and the questions asked may be decisive for the patient's responses. Again the posttreatment QOL outcome could be influenced by the doctor's social skills as well.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]