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Original article
peer-reviewed

Transient Tumor Volume Increase in Vestibular Schwannomas after Radiotherapy



Abstract

Background:  Transient tumor progression is difficult to diagnose and is challenging for the physician.

Objectives:  To report and review the transient tumor progression rate and induced toxicities in patients treated for vestibular schwannomas (VS).

Materials and Methods:  From January 2005 to February 2010, 43 patients with VS were consecutively treated at our institution. Twenty patients (46.5%) were treated with fractionated stereotactic radiation therapy (FSRT) using a LINAC or a CyberKnife technique with doses varying between 18 and 50.4 Gy.  Radiosurgery (SRS) on a conventional LINAC and on a CyberKnife were performed in 13 patients (30%) (median dose of 12 Gy).  Tumor volume increase was calculated from the first tumor volume increase until tumor stability or regression. A Fisher’s exact test and Mann-Whitney U test were used for statistical analysis.

Results:  Transient tumor volume increase occurred in 10 patients (25%) with a median time to tumor enlargement of 5.5 months (1-25 months).  Prior surgical resection was significantly associated with transient tumor volume increase (Fisher exact, p=0.02). Increased rates of facial and trigeminal neuropathies were associated with transient tumor volume increase (p=0.04 and p=0.08, respectively).  The pseudoprogression rate and the cranial nerve toxicity were not associated with any dosimetric factor.

Conclusions:  Transient tumor volume increase is frequent (25%) after radiotherapy and significantly associated with previous resection possibly due to the surgical microvascular insult.  Cranial nerve toxicities are significantly correlated with, and possibly caused by, transient tumor progression.

Introduction

Vestibular schwannomas (VS) are benign intracranial tumors, which represent 8% of adult intracranial tumors. With a growth rate approaching 2 mm per year [1], tumor progression can lead to progressive hearing loss, tinnitus and vestibular ataxia.

With the exception of large tumors with acute mass effect, management options can lead to controversy. Surgical resection is often proposed to medically fit patients [1] for whom it has a low mortality rate (0.3-0.6%) [2, 3], a high rate of complete tumor removal and a low probability of recurrence [4-7]. Hearing preservation is achieved in 32-50% of cases, while permanent facial neuropathy and postoperative CSF leak occur in 14-29% and 6-11%, respectively [2, 3, 8, 9].

Conservative management with serial MRIs is valid option in older patients with a short life expectancy, slow growing, small to medium-sized tumors, and a low symptomatic burden. Whether of not delayed treatment results in worse ultimate cranial nerve function is debatable. In observed patients, tumor growth will lead to further permanent hearing loss [10] in 29-54 % of patients. Sixteen to twenty-six percent of observed patients will eventually require tumor-directed treatment [2, 11-15].

New studies with Bevacizumab reported promising results in patients with type 2 Neurofibromatosis and evidence of progressive VSs that were considered poor candidates to surgery and radiation therapy [16]

Stereotactic radiosurgery (SRS) is a common alternative to surgical resection. It can be delivered using an isocentric linear accelerator (LINAC), a GammaKnife or a CyberKnife robotic radiosurgery device (CK). Patients with small (<2.5 cm) tumors without significant brainstem compression are eligible for stereotactic radiosurgery (12-13 Gy).

Fractionated stereotactic radiotherapy (FSRT) is a safe alternative for selected patients ill-suited to radiosurgery because of tumor size or mild brainstem compression, Controversy exists as to the relationship of fractionation and hearing preservation - most departments where FSRT is available will recommend fractionation to patients with serviceable hearing.  Dose schedules vary considerably - 18-54 Gy in three to 30 fractions. Independent of the selected schedule, local control is expected in 90-98% [17-21]. The main advantage of CK over other radiation techniques is that there is no technical compromise when delivering a fractionated course of radiation.

Transient tumor progression following radiation is commonly reported, although the underlying physiopathology is poorly acknowledged. Such transient progression, which can last up to two years, has been well-described after single fraction SRS. There is limited data concerning transient progression following FSRT. 

The objective of our study is first to report our transient tumor progression rate as well as the contributing factors in patients treated with stereotactic radiotherapy. Second, we will review the correlation between transient tumor progression and the adverse reactions observed after radiation.

Materials & Methods

Characteristics of the patients

From January 2005 to February 2010, 43 patients with VS were consecutively treated with FSRT or SRS at our institution with a minimum follow up of two years. Radiation was used as primary treatment in 23 patients (53.5%), as salvage treatment following surgery in nine patients (21%) and at progression following observation in 11 patients (25.5%). Five patients with neurofibromatosis type 2 were included in our study. Median age at diagnosis was 56 years. Prior to RT, 16 patients (37.2%) had serviceable hearing - Gardner-Robertson Grade 1-2. Patient and tumor characteristics are detailed in Table 1.

Characteristics Patients (%)
Neurofibromatosis type 2 5 (12%)
Tumor localisation
Right 24 (56%)
Left 16 (37%)
Cranial nerve neuropathy at diagnosis
CN V 8 (19%)
CN VII 5 (12%)
CN VIII 42 (98%)
CN IX, X and XII 8 (19%)
Tumor size  
< 2cm 28 (65%)
2-4 cm 11 (26%)
> 4cm 2 (5%)
Radiation therapy fractionation
12-30 fraction FSRT 18 (42%)
3 fraction FSRT 10 (23%)
SRS 15 (35%)

Surgical resection prior to radiotherapy had been performed in 9 patients (20.9%) for a total of 12 surgeries (3 patients had 2 surgeries prior to RT) of whom 3 had gross total resection and 9 had subtotal resection.

Tumor size was measured according to the cerebellopontine angle maximum method (CPA). The tumor including the extracanalicular component was measured in the maximum anteroposterior and medial-lateral diameters on axial MRI. . The majority of patients (28 patients, 65%) had maximum tumor diameter £ 20 mm, 11 (25.5%) patients had tumors 20-40 mm and 2 (4.6%) had tumors > 40 mm. 

At diagnosis, 8 (18.6%) and 5 (11.6%) patients had a trigeminal or facial neuropathy, respectively. Toxicity was assessed and graded according to the Common Terminology Criteria for Adverse Events (CTCAE v3). Facial nerve palsy was graded according to the House-Brackmann score.

Radiotherapy techniques

All patients had a contrast-enhanced computed tomography (CT) and 3D Gradient Echo Ultrafast MRI with a slice thickness of 1 mm for treatment planning. Thin slice, contrast CT images in the treatment position were co-registered to the MRI. Later in the series, a True Fast Imaging with Steady state Precession (FISP, CISS or FIESTA) sequence was often co-registered to the CT and TI contrast imagines.

Twenty patients (46.5%) were treated with isocentric LINAC-based FSRT using a micro multi-leaf delivery system (Brainlab, Feldkirchen, Germany). The prescription dose was 45-50.4 Gy in 25-28 fractions for 9 patients and 36 Gy in 12 fractions for 9 patients at the isodose line covering 98-100% of the PTV. The fractionation regimen of 36 Gy in 12 fractions was used in 2005 and 2006 in our institution as an equivalent biological dose [17] to 45-50 Gy in 25 fractions using an a/b of 3.  It was mainly used in older patients and in those who had a transportation limitation.

Radiosurgery using conical collimation on a conventional LINAC (Philips/Elekta) was performed in 7 patients (16.3%) using an invasive stereotactic localization frame and in 2 patients using a thermoplastic mask. The median dose delivered was 12 Gy (range 12-14.5 Gy) prescribed to the covering isodose surface and delivered through 3-5 noncoplanar arcs.

FSRT using a Cyberknife technique was performed in ten patients at a dose of 18 Gy in 3 fractions. Six patients received SRS (12-12.5 Gy) with the Cyberknife. The ultra-short course FSRT (associated with the misnomer “staged radiosurgery”) was mainly used in patients with serviceable hearing and/or larger tumors in contact with the brainstem.

For each treatment approach, the dose, fractionation, prescription isodose line, maximal dose for the PTV, conformity index, homogeneity index, PTV and GTV volume were reported.

Post-treatment clinical assessment

Most of the patients were seen 6 weeks after their treatment and thereafter at 3 to 6 months interval for the first 2 years and then annually. With the approval of the local ethics review board, all patients were contacted according to a pre-defined telephone protocol. Serial MRIs were requested every 6 months for the first 2 years then once a year or in accordance to clinical findings. Local control was measured from the end of radiation. As described by Flickinger [22], we defined tumor volume increase as tumor growth of 1 mm in any two directions or 2 mm in one direction. Tumor enlargement due to treatment failure usually occurs several months after radiation and tends to persist for a greater period than two years whereas transient tumor volume increase occurs in a relatively acute setting and stabilizes within two years. Therefore, local control was calculated using the last follow up MRI and transient tumor volume increase was calculated from the first tumor volume increase until stability or regression of the tumor. Patients who had systematic tumor volume increase without stability or regression were considered to have treatment failure. Tumor stability was defined as no change in tumor size on serial MRIs.

Statistical analysis

The Kaplan Meier method was used to estimate local control. A Fisher’s exact test was performed to validate statistical correlation and Mann-Whitney U test was performed to compare the different treatment technique. All tests were two-tailed. SPSS 17.0 was used (IBM, Armonk, New York).

Results

Transient tumor volume increase

In order to estimate the transient tumor volume increase rate, we excluded the three out of the 43 patients who did not have a control MRI after radiation. Transient tumor volume increase occurred in 10 patients (25%) with a median time to tumor enlargement of 5.5 months (one-25 months). Prior surgical resection was significantly associated with transient tumor volume increase (Fisher exact, p=0.02). Indeed, among the 10 patients with transient tumor volume increase, five patients had prior surgery. The median and mean time-length of transient tumor volume increase were 14 (5-45 months) and 17 months (5-29 months) respectively. Two patients had further surgery after radiotherapy because of increased symptoms or significant brainstem compression. The pathological findings were consistent with residual vestibular schwannoma for both patients without evidence of tumor necrosis.

Prescription dose, GTV volume, PTV volume, maximum dose to PTV, BED, gender, age at treatment and the presence of neurofibromatosis type 2 did not significantly influence the rate of pseudoprogression by Mann-Whitney analysis (Table 2).

Factors evaluated Transient tumor progression
Prescription dose P=0.35
GTV volume P=0.55
Maximum dose to PTV P=0.24
BED P=0.71
Age at treatment P=0.59
NF 2 P=0.96
Gender P=0.7
Previous surgery P=0.01
Facial nerve toxicity P=0.04
Trigeminal nerve toxicity P=0.08

Cranial nerve toxicities

Among the 16 (37.2%) patients who had a serviceable hearing prior to RT, seven patients (47%) preserved a serviceable hearing and nine patients (53%) presented with hearing loss (Gardner-Robertson grade 3-5) at a mean clinical follow-up of 32 months.

Transient trigeminal neuropathy grade 1-2 according to the CTCAE was observed in four patients (9%) at two years. Patients with prior trigeminal neuropathy did not experience a worsening of their symptoms after RT. No grade 3-4 trigeminal neuropathy was observed.

Among our cohort of patients, three (7%) developed transient facial neuropathy (grade 2-3) after treatment according to the House-Brackmann score. No grade 4 facial neuropathy was reported. All the patients with radiation-induced cranial nerve toxicities had transient neuropathy, and therefore no medical treatment was needed.

Transient tumor volume increase was statistically associated with an increased rate of facial neuropathy (p=0.04). There was a trend for increased trigeminal neuropathy with transient tumor volume increase (p=0.08) but no association was found with serviceable hearing loss.  The prescription dose, homogeneity index, conformity index, isodose line and maximum dose received by the PTV were not correlated with any cranial nerve toxicity.

Discussion

Discriminating transient tumor volume increase from local failure is difficult but important if one is to avoid unnecessary surgery. In a large series of 452 patients treated over a 10-year period, 13 patients (3%) underwent surgery after radiosurgery of whom 10 patients (77%) had postoperative House Brackmann grade III to VI facial neuropathy [23]. In our study, two patients (4.7%) had further surgery following radiotherapy.

Transient increase in tumor volume occurred in 10 patients (25%) of whom five were treated with FSRT (18%) and five with SRS (33%). Previous studies reported transient tumor volume increase rates varying between 5-74% among patients treated with SRS [24-31] and a 48% rate among patients treated with FSRT [32].  A recent study showed that transient tumor progression after FRST can occur up to three years and is more frequent in larger tumors (> 3 cm) [33].  Some studies found a correlation between tumor enlargement and initial tumor volume after SRS [28], others did not [26,29,31]. In our study, GTV volumes were not associated with transient tumor volume increase (p=0.5) after SRS or FSRT.

Interestingly, women might have a higher rate of transient tumor volume increase [28]. Seven female patients (32%) and four male patients (27%) had transient tumor volume increase (p=0.7 for the correlation of gender and transient tumor increase).

On a Mann Whitney analysis, the prescribed dose, the biological effective dose [17], neurofibromatosis type 2, and age at treatment were not correlated to transient tumor volume increase. The lack of correlation may be due to the size of our cohort and the heterogeneity of treatments.

In our series, prior surgical resection was significantly associated with transient tumor progression (p=0.01). This is a new finding. Transient progression may be due to vascular injury. In autopsies of patients dying within weeks of radiation, peri-vascular edema is seen along with thickening of arterial walls. These arterial walls are rich in fibrin, and platelet-fibrin thrombi may be found [34]. These pathologic changes might be exacerbated by previous surgical insult to capillaries and their endothelium.

Another hypothesis as to the pathogenesis of transient post-radiation progression is that radiation injury to tumor cells leads to necrosis and the subsequent release of thrombosis promoting cytokines, cytokines that may also lead to blood-brain barrier disruption. With increased resistance to intravascular outflow, tumors may become congested with blood and increased in size [35]. Indeed, surgical resection of tumors that had tumor volume increase after SRS showed hyalinised thrombosis, thickening of the vascular wall, vascular obstruction, and granulomatous changes [24, 36, 37]. Patients that had initial surgery and needed further treatment had either incomplete tumor resection or tumor recurrence. Such “aggressive tumors” with higher cell turnover may suffer greater necrosis and inflammation following radiation.

In our cohort, the median time to transient tumor volume increase after SRS and FSRT was 5.5 months with subsequent tumor shrinkage occurring at a median of 14 months (range: 5-45 months). Similar results have been reported in the literature; the median time to tumor enlargement after SRS varying between six and 13 months [24, 26, 29, 31, 38] with a peak at four to six months [24, 31, 39, 40] followed by tumor shrinkage occurring within two to three years [24, 28, 29]. Therefore, it is reasonable to delay surgery for two years or more [23] in clinically stable and asymptomatic patients.

Little is known about transient tumor volume increase and cranial nerve toxicities. The hearing preservation rate was 47% at 2 years among patients treated with FSRT and SRS. Hearing preservation rates ranged between 53 and 94% [19, 41-44] and between 44 and 96% [43, 45-50] in patients treated with FSRT and SRS, respectively. Although many factors have been analyzed, no statistical association with hearing loss was found. Some studies have associated hearing loss and transient tumor progression [33], other studies did not report a correlation [31]. Predictors of hearing loss after SRS were significant hearing loss before SRS, tumor recurrence and the prescription isodose line, according to a recent study by Wowra et al. [51].  

In our study, cranial nerve toxicities rates were low and transient with no permanent facial or trigeminal nerve toxicity. A statistically significant correlation and a trend towards association were found between transient tumor volume increase and increased facial neuropathy (p=0.04) and trigeminal neuropathy, respectively (p=0.08). Nagano et al. [31] reported a strong trigeminal and facial nerve dysfunction with transient tumor expansion (p=0.018 and p=0.035, respectively). On the other hand, Hayhurst et al. [52] did not find an association between tumor pseudoprogression and cranial nerve toxicities. It would seem logical that transient tumor volume increase can cause local compression leading to temporary or permanent cranial neuropathy. Further larger studies are needed to confirm the correlation between transient tumor volume increase and cranial nerve toxicity. 

Conclusions

Transient tumor volume increase is frequent after both SRS and FSRT in VS (25%). The median time to transient tumor progression was 5.5 months. Transient tumor volume increase was significantly correlated with previous surgery and an increased rate of facial and trigeminal nerve toxicity. The main challenge to the treating physician is to discriminate tumor progression from transient tumor volume increase after radiotherapy in order to avoid unnecessary brain surgery. Conservative management with serial MRIs is recommended for clinically stable patients. 


References

  1. Mirz, F., Jorgensen, B., Fiirgaard, B., Lundorf, E., Pedersen, C. B. : Investigations into the natural history of vestibular schwannomas. Clin Otolaryngol Allied Sci. 1999, 24:13-18.
  2. Yamakami, I., Uchino, Y., Kobayashi, E., Yamaura, A: Conservative management, gamma-knife radiosurgery, and microsurgery for acoustic neurinomas: a systematic review of outcome and risk of three therapeutic options. Neurological Research. 2003, 25:682-690.
  3. Kaylie, D. M., Horgan, M. J., Delashaw, J. B., McMenomey, S. O: A meta-analysis comparing outcomes of microsurgery and gamma knife radiosurgery. The Laryngoscope. 2000, 110:1850-1856.
  4. Gormley, W. B., Sekhar, L. N., Wright, D. C., Kamerer, D., Schessel, D: Acoustic neuromas: results of current surgical management. Neurosurgery. 1997, 41:50-58.
  5. Samii, M., Matthies, C: Management of 1000 vestibular schwannomas (acoustic neuromas): The facial nerve--preservation and restitution of function. Neurosurgery. 1997, 40:684-694.
  6. Falcioni, M., Mulder, J. J., Taibah, A., De Donato, G., Sanna, M: No cerebrospinal fluid leaks in translabyrinthine vestibular schwannoma removal: Reappraisal of 200 consecutive patients. Am J Otol. 1999, 20:660-666.
  7. Darrouzet, V., Martel, J., Enee, V., Bebear, J. P., Guerin, J: Vestibular schwannoma surgery outcomes: our multidisciplinary experience in 400 cases over 17 years. The Laryngoscope. 2004, 114:681-688.
  8. Pollock, B. E., Driscoll, C. L., Foote, R. L., Link, M. J., Gorman, D. A., Bauch, C. D., Mandrekar, J. N., Krecke, K. N., Johnson, C. H: Patient outcomes after vestibular schwannoma management: a prospective comparison of microsurgical resection and stereotactic radiosurgery. Neurosurgery. 2006, 59:77-85.
  9. Samii, M., Gerganov, V., Samii, A: Improved preservation of hearing and facial nerve function in vestibular schwannoma surgery via the retrosigmoid approach in a series of 200 patients. Journal of Neurosurgery. 2006, 105:527-535.
  10. Arthurs, B. J., Fairbanks, R. K., Demakas, J. J., Lamoreaux, W. T., Giddings, N. A., Mackay, A. R., Cooke, B. S., Elaimy, A. L., Lee, C. M: A review of treatment modalities for vestibular schwannoma. Neurosurg Rev. 2011, 34:265-277.
  11. Yoshimoto, Y: Systematic review of the natural history of vestibular schwannoma. Journal of Neurosurgery. 2005, 103:59-63.
  12. Sughrue, M. E., Yang, I., Aranda, D., Lobo, K., Pitts, L. H., Cheung, S. W., Parsa, A. T: The natural history of untreated sporadic vestibular schwannomas: a comprehensive review of hearing outcomes. Journal of Neurosurgery. 2010, 112:163-167.
  13. Battaglia, A., Mastrodimos, B., Cueva, R: Comparison of growth patterns of acoustic neuromas with and without radiosurgery. Otol Neurotol. 2006, 27:705-712.
  14. Selesnick, S. H., Johnson, G: Radiologic surveillance of acoustic neuromas. Am J Otol. 1998, 19:846-849.
  15. Smouha, E. E., Yoo, M., Mohr, K., Davis, R. P: Conservative management of acoustic neuroma: a meta-analysis and proposed treatment algorithm. The Laryngoscope. 2005, 115:450-454.
  16. Plotkin, S. R., Stemmer-Rachamimov, A. O., Barker, F. G., 2nd, Halpin, C., Padera, T. P., Tyrrell, A., Sorensen, A. G., Jain, R. K., di Tomaso, E: Hearing improvement after bevacizumab in patients with neurofibromatosis type 2. NEJM. 2009, 361:358-367.
  17. Andrews, D. W., Werner-Wasik, M., Den, R. B., Paek, S. H., Downes-Phillips, B., Willcox, T. O., Bednarz, G., Maltenfort, M., Evans, J. J., Curran, W. J., Jr: Toward dose optimization for fractionated stereotactic radiotherapy for acoustic neuromas: comparison of two dose cohorts. Int J Radiat Oncol Biol Phys. 2009, 74:419-426.
  18. Chan, A. W., Black, P., Ojemann, R. G., Barker, F. G., 2nd, Kooy, H. M., Lopes, V. V., McKenna, M. J., Shrieve, D. C., Martuza, R. L., Loeffler, J. S: Stereotactic radiotherapy for vestibular schwannomas: Favorable outcome with minimal toxicity. Neurosurgery. 2005, 57:60-70.
  19. Combs, S. E., Volk, S., Schulz-Ertner, D., Huber, P. E., Thilmann, C., Debus, J: Management of acoustic neuromas with fractionated stereotactic radiotherapy (FSRT): long-term results in 106 patients treated in a single institution. Int J Radiat Oncol Biol Phys. 2005, 63:75-81.
  20. Koh, E. S., Millar, B. A., Menard, C., Michaels, H., Heydarian, M., Ladak, S., McKinnon, S., Rutka, J. A., Guha, A., Pond, G. R., Laperriere, N. J: Fractionated stereotactic radiotherapy for acoustic neuroma: single-institution experience at The Princess Margaret Hospital. Cancer. 2007, 109:1203-1210.
  21. Thomas, C., Di Maio, S., Ma, R., Vollans, E., Chu, C., Clark, B., Lee, R., McKenzie, M., Martin, M., Toyota, B: Hearing preservation following fractionated stereotactic radiotherapy for vestibular schwannomas: prognostic implications of cochlear dose. Journal of Neurosurgery. 2007, 107:917-926.
  22. Flickinger, J. C., Kondziolka, D., Niranjan, A., Maitz, A., Voynov, G., Lunsford, L. D: Acoustic neuroma radiosurgery with marginal tumor doses of 12 to 13 Gy. Int J Radiat Oncol Biol Phys. 2004, 60:225-230.
  23. Pollock, B. E., Lunsford, L. D., Kondziolka, D., Sekula, R., Subach, B. R., Foote, R. L., Flickinger, J. C: Vestibular schwannoma management. Part II. Failed radiosurgery and the role of delayed microsurgery. Journal of Neurosurgery. 1998, 89:949-955.
  24. Kim, K. M., Park, C. K., Chung, H. T., Paek, S. H., Jung, H. W., Kim, D. G: Long-term Outcomes of Gamma Knife Stereotactic Radiosurgery of Vestibular Schwannomas. J Korean Neurosurg Soc. 2007, 42:286-292.
  25. Noren, G: Long-term complications following gamma knife radiosurgery of vestibular schwannomas. Stereotact Funct Neurosurg. 1998, 70 :65-73.
  26. Pollock, B. E: Management of vestibular schwannomas that enlarge after stereotactic radiosurgery: treatment recommendations based on a 15 year experience. Neurosurgery. 2006, 58:241-248.
  27. Delsanti, C., Tamura, M., Galanaud, D., Regis J: Changing radiological results, pitfalls and criteria of failure. Neurochirurgie. 2004, 50:312-319.
  28. Hasegawa, T., Kida, Y., Yoshimoto, M., Koike, J., Goto, K: Evaluation of tumor expansion after stereotactic radiosurgery in patients harboring vestibular schwannomas. Neurosurgery. 2006, 58:1119-1128.
  29. Nakamura, H., Jokura, H., Takahashi, K., Boku, N., Akabane, A., Yoshimoto, T: Serial follow-up MR imaging after gamma knife radiosurgery for vestibular schwannoma. AJNR. 2000, 21:1540-1546.
  30. Yu, C. P., Cheung, J. Y., Leung, S., Ho, R: Sequential volume mapping for confirmation of negative growth in vestibular schwannomas treated by gamma knife radiosurgery. Journal of Neurosurgery. 2000, 93:82-89.
  31. Nagano, O., Higuchi, Y., Serizawa, T., Ono, J., Matsuda, S., Yamakami, I., Saeki, N: Transient expansion of vestibular schwannoma following stereotactic radiosurgery. Journal of Neurosurgery. 2008, 109:811-816.
  32. Sakanaka, K., Mizowaki, T., Arakawa, Y., Araki, N., Oya, N., Takahashi, J. A., Mikuni, N., Miyamoto, S., Hashimoto, N., Hiraoka, M: Hypofractionated stereotactic radiotherapy for acoustic neuromas: safety and effectiveness over 8 years of experience. Int J Clin Oncol. 2011, 16:27-32.
  33. Aoyama, H., Takeichi, N., Onodera, S., Taguchi, H., Sawamura, Y., Shirato, H: Conventionally Fractionated Stereotactic Radiotherapy for Vestibular Schwannoma: A Single Institutional Long-term Outcomes. Int J Radiat Oncol Biol Phys. 2010, 78:S8-S9.
  34. Fajardo, L. F., Berthrong, M., Anderson, R. E: Radiation Pathology. Oxford University Press, New York, NY; 2001.
  35. Suzuki, H., Toyoda, S., Muramatsu, M., Shimizu, T., Kojima, T., Taki, W: Spontaneous haemorrhage into metastatic brain tumours after stereotactic radiosurgery using a linear accelerator. J Neurol Neurosurg Psychiatry. 2003, 74:908-912.
  36. Hirato, M., Inoue, H., Nakamura, M., Ohye, C., Hirato, J., Shibazaki, T., Andou, Y: Gamma Knife radiosurgery for acoustic schwannoma: Early effects and preservation of hearing. Neurol Med Chir (Tokyo). 1995, 35,:737-741.
  37. Kobayashi, T., Tanaka, T., Kida, Y: The early effects of gamma knife on 40 cases of acoustic neurinoma. Acta Neurochir Suppl. 1994, 62:93-97.
  38. Oyama, H., Kobayashi, T., Kida, Y., Tanaka, T., Mori, Y., Iwakoshi, T., Niwa, M., Kai, O., Hirose, M: Early changes in volume and non-enhanced volume of acoustic neurinoma after stereotactic gamma-radiosurgery. Neurol Med Chir (Tokyo). 1994, 34:607-611.
  39. Okunaga, T., Matsuo, T., Hayashi, N., Hayashi, Y., Shabani, H. K., Kaminogo, M., Ochi, M., Nagata, I: Linear accelerator radiosurgery for vestibular schwannoma: Measuring tumor volume changes on serial three-dimensional spoiled gradient-echo magnetic resonance images. Journal of Neurosurgery. 2005, 103:53-58.
  40. Carai, A., Green, S., Delman, B., Blacksburg, S. R., Maloney-Lutz, K., Lo, Y., Sheu, R., Germano, I: Tumor Volume Increase after Stereotactic Radiosurgery for Vestibular Schwannoma: Expected Radiographic Finding or Exception?. Int J Radiat Oncol Biol Phys. 2010, 78:S280.
  41. Meijer, O. W., Vandertop, W. P., Baayen, J. C., Slotman, B. J: Single-fraction vs. fractionated linac-based stereotactic radiosurgery for vestibular schwannoma: a single-institution study. Int J Radiat Oncol Biol Phys. 2003, 56:1390-1396.
  42. Sawamura, Y., Shirato, H., Sakamoto, T., Aoyama, H., Suzuki, K., Onimaru, R., Isu, T., Fukuda, S., Miyasaka, K: Management of vestibular schwannoma by fractionated stereotactic radiotherapy and associated cerebrospinal fluid malabsorption. Journal of Neurosurgery. 2003, 99:685-692.
  43. Combs, S. E., Welzel, T., Schulz-Ertner, D., Huber, P. E., Debus, J: Differences in clinical results after LINAC-based single-dose radiosurgery versus fractionated stereotactic radiotherapy for patients with vestibular schwannomas. Int J Radiat Oncol Biol Phys. 2010, 76:193-200.
  44. Shirato, H., Sakamoto, T., Sawamura, Y., Kagei, K., Isu, T., Kato, T., Fukuda, S., Suzuki, K., Soma, S., Inuyama, Y., Miyasaka, K: Comparison between observation policy and fractionated stereotactic radiotherapy (SRT) as an initial management for vestibular schwannoma. Int J Radiat Oncol Biol Phys. 1999, 44:545-550.
  45. Spiegelmann, R., Gofman, J., Alezra, D., Pfeffer, R: Radiosurgery for acoustic neurinomas vestibular schwannomas. IMAJ. 1999, 1:8-13.
  46. Spiegelmann, R., Lidar, Z., Gofman, J., Alezra, D., Hadani, M., Pfeffer, R: Linear accelerator radiosurgery for vestibular schwannoma. Journal of Neurosurgery. 2001, 94:7-13.
  47. Chang, S. D., Gibbs, I. C., Sakamoto, G. T., Lee, E., Oyelese, A., Adler, J. R., Jr: Staged stereotactic irradiation for acoustic neuroma. Neurosurgery. 2005, 56:1254-1261.
  48. Rutten, I., Baumert, B. G., Seidel, L., Kotolenko, S., Collignon, J., Kaschten, B., Albert, A., Martin, D., Deneufbourg, J. M., Demanez, J. P., Stevenaert: A. Long-term follow-up reveals low toxicity of radiosurgery for vestibular schwannoma. Radiother Oncol. 2007, 82:83-89.
  49. Chopra, R., Kondziolka, D., Niranjan, A., Lunsford, L. D., Flickinger, J. C: Long-term follow-up of acoustic schwannoma radiosurgery with marginal tumor doses of 12 to 13 Gy. Int J Radiat Oncol Biol Phys. 2007, 68:845-851.
  50. Combs, S. E., Thilmann, C., Debus, J., Schulz-Ertner, D: Long-term outcome of stereotactic radiosurgery (SRS) in patients with acoustic neuromas. Int J Radiat Oncol Biol Phys. 2006, 64:1341-1347.
  51. Wowra, B., Muacevic, A., Furweger, C., Schichor, C., Tonn, J. C: Therapeutic profile of single-fraction radiosurgery of vestibular schwannoma: Unrelated malignancy predicts tumor control. Neuro-oncology. 2012, 14:902-909.
  52. Hayhurst, C., Zadeh, G: Tumor pseudoprogression following radiosurgery for vestibular schwannoma. Neuro-oncology. 2012, 14:87-92.
Original article
peer-reviewed

Transient Tumor Volume Increase in Vestibular Schwannomas after Radiotherapy


Author Information

Lara Hathout Corresponding Author

Department of Radiation Therapy, CHUM – Hôpital Notre-Dame, Centre hospitalier de l'Université de Montréal (CHUM)

Carole Lambert

Department of Radiation Oncology, Centre hospitalier de l'université de Montréal (CHUM) - Hôpital Notre-Dame

Jean-Francois Carrier

Department of Radiation Oncology, Centre hospitalier de l'Université de Montréal (CHUM)

Jean-Paul Bahary

Department of Radiation Oncology, Centre hospitalier de l'Université de Montréal (CHUM)

Yannick Hervieux

Department of Radiation Oncology, Centre hospitalier de l'Université de Montréal (CHUM)

Robert A. Moumdjian

Department of Neurosurgery, CHUM – Hôpital Notre-Dame, Centre hospitalier de l'Université de Montréal (CHUM)

Marie-Andree Fortin

Department of Radiation Oncology, Centre hospitalier de l'Université de Montréal (CHUM)

David Roberge

Radiation Oncology, University of Montreal Health Centre, Montréal, CAN


Ethics Statement and Conflict of Interest Disclosures

Human subjects: Consent was obtained by all participants in this study. The Ethics Committee of the Centre Hospitalier de l'Université de Montréal issued approval # 10.053. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.

Acknowledgements

We would like to thank Dr. Daniel Taussky for his collaboration and for his support in this study.


Original article
peer-reviewed

Transient Tumor Volume Increase in Vestibular Schwannomas after Radiotherapy


Figures etc.

Original article
peer-reviewed

Transient Tumor Volume Increase in Vestibular Schwannomas after Radiotherapy


Patient Reported Outcome

Patient name: Rodney Walker

In 2009 I experienced a continuing sensation of blocked hearing, similar to that of having water in one’s ear, which would not go away. After a series of visits to an ear, nose and throat specialist and close to a year of nasal sprays intended to clear the eustachian tube (which was originally believed to be the cause), I was sent for an MRI. This revealed a schwannoma tumor that had damaged my right side auditory nerve, causing the effect I was experiencing.
 
I was then referred to the Montreal Neurological Hospital where, after a number of exams and hearing tests, I was given the option of either surgery to remove the tumour, or a series of CyberKnife radiation treatments at the CHUM hospital to “kill” it. It was explained to me that there was some risk associated with surgery of damage to the nerves controlling facial muscles, while the only long term downside to the CyberKnife treatments was a requirement for annual MRIs afterwards to verify that the tumour had stopped growing. After reading information about CyberKnife and viewing a video about it on the web, I decided to go that route.
 
The first step in preparation for the CyberKnife radiation treatments was the creation of a facial mask at CHUM designed to immobilize me during treatment. Essentially, a technician applied what appeared to be wet, cloth-like webbing over my face while lying down. It was stretched very tight to ensure an exact fit to my face and the web structure of the material ensured that my breathing was unhindered. After a short delay the hardened mask was removed and holes were cut out for the eyes. The mask was very long, reaching back about 12 inches from the front of my face, and terminated in a frame that could be rigidly secured.
 
On August 5th, 6th and 9th of 2010, I subsequently received the CyberKnife treatments. The process, while at first unnerving, was painless and quite easy. The machine consists of a single articulated mechanical arm, as is seen in robotic automobile assembly plants, with a unit on the end that emits the radiation. It is a huge device in a large room with a raised table in the center, where the patient lies down. I was asked to lie on this table on my back and the mask described above was secured over my head and firmly attached to the table. There was no requirement to wear a hospital gown. The secured mask completely immobilized my head, although I could see, hear and speak with no difficulty. Directly above me on the ceiling was a screen where a very calming video was projected throughout the treatment.
 
After explaining the process to me, the technician left the room and went to an adjacent control room where he spoke with me through an intercom system. The treatment lasted approximately 30 minutes, during which time the robotic arm moved the radiation head from one position to the other around my head, at varying angles and elevations, pausing at each to irradiate the tumour. I was advised that it moved to many tens of positions over the course of the treatment. I felt almost nothing throughout, although at the end I did notice a heating effect at the position of the tumour.
 
I underwent three identical sessions and the process was complete.
 
In closing I would like to say how impressed I was with the staff that did everything possible to make the process as easy as possible. This helped enormously.


Supplemental files


Patient name: Stuart Kogan

Hi, my name is Stuart Kogan. I live in Montreal, Quebec and this is the story of my tumour. It all started in September of 2010. I was 41 years old, sitting at my desk at work, talking on the phone. I could barely make out what the person on the other end was saying. The volume seemed very low, so I tried to raise it. It didn't help. After a few more phone calls, I assumed my phone was defective. Just by chance, during a call, I switched ears. Wow! Suddenly I could hear perfectly. That led to the quick conclusion that I was having a problem hearing from my left ear. On top of that, I started getting a terrible ringing from the same ear - tinnitus. After that came a slew of doctor appointments. My first MRI was in early November and with it came the terrifying results - I had a benign tumour called an acoustic neuroma or schwannoma. I started exploring different options, and stumbled upon a device called a CyberKnife. More research confirmed that there was one in Montreal, but only in the CHUM (Centre Hospitalier de l'Université de Montréal) - and I was currently going through the MUHC (McGill University Health Centre). The two different systems did not share resources or information. However, I was fortunate enough to have a doctor who was able to refer me to Dr. David Roberge, who was in charge of the CyberKnife program at Hopital Notre-Dame, part of the CHUM. 

From my very first visit to the hospital, I felt that I was being very well taken care of. Dr. Roberge was punctual, and he took the time to explain everything to me. We went over all of my options many times before finally agreeing that the CyberKnife would be my best choice. I needed to go through another round of MRIs with contrast - loud, confining, and somewhat annoying, but with no claustrophobia issues not really a big deal. Next came the mask. In order to perform the CyberKnife procedure, they needed to make a perfect mask of my face. The nurses who were in charge of this procedure were amazing. They were very reassuring that the process would not be too uncomfortable, and would be over quite quickly. I needed to lie down on my back on a small bed. The nurses prepared what seemed like a hot towel, but was really a special molding substance. They gave me warning that the towel would need to cover my entire face, including my mouth and nose, for a few seconds - preventing me from breathing. They placed the towel over my face, and removed it quickly. From that, they were able to make the mask. The whole thing was over before I knew it, and I was able to keep the final product after my radiation treatment was done. The mask looks like a hard plastic mesh, perfectly shaped to my face. 

The day finally arrived that my CyberKnife treatment was to begin. The operators were very friendly and reassuring. The showed me the actual CyberKnife, their computer operating room, everything. They must have confirmed with me that they had the correct side - my left ear - at least 3 times. I lay down on my back on the soft table; they placed the mask over my head and strapped it down. Keeping my head perfectly still is imperative to the whole system. There was a television screen on the ceiling above me showing a relaxing nature video throughout. They put on a music CD of my choosing from their small collection for me to listen to during the procedure. Then they covered me with a blanket as it was cold in the room - it has to stay cold to keep the machinery running well. The entire bed lifted up off the ground, thereby allowing the arm to move 360o around every side of my head. Then they left the room, heading into the computer operating room and spoke to me over a loudspeaker system. They let me know when it was about to begin, and then it started. The robot arm delivering the radiation in very precise beams to my tumour began moving around my head. It would move into position, stop for a moment to deliver the radiation, and then continue on to the next location. Despite being more then just a little bit freaked out by the diagnosis and subsequent doctor visits, as well as fairly physically uncomfortable on the table, I had to admit that the coolness of the robot was amazing.  I was absolutely astounded at what it was able to do. The entire process only took about 40 minutes - 15 minutes of prep time and about 25 minutes of radiation. The technicians came in when it was done, lowered the bed and unstrapped me. They were great the whole time. They let me know that I could bring my own music for the following treatments. I had a total of three treatments, each one being easier than the last one. Not that they were any shorter, just that I knew what to expect. I also knew that I could wear a warm sweatshirt and listen to what I enjoyed. 

The three treatments were completed as scheduled, and my follow-up MRI and visit with Dr. Roberge went very well. The entire staff at Hopital Notre-Dame treated me with the utmost respect and care. I would give extra thanks to the CyberKnife crew who were especially sympathetic and caring, not to mention knowledgeable and professional. I still see Dr. Roberge on a regular basis (yearly) and he never ceases to impress me with his intelligence and straightforward answers to my questions or concerns.

Today, my tumour is slightly smaller than when it was first diagnosed, but not significantly. My tinnitus is still there, but I have learned to ignore it. My hearing is still mostly gone from my left ear, but it is not completely finished. I can actually hear a little bit better, and listening to music through headphones works well. My balance was never affected, nor did I ever experience any facial paralysis or ticks that are common with these tumours. The biggest side effect from the radiation was weariness. For about a year and a half after the treatments I became extremely tired almost every afternoon. I would be feeling fine, and then all of a sudden I would get very sleepy. The sensation would only last at most a couple of hours and did not seem connected to how much sleep I got the night before. The sleepy spells were never so bad that I could not work through them, but if I were able to I would take break and sit for a bit. Another side effect I experienced was dizzy spells. They started around 6 months after the treatments and continued for about 8 months. They would come upon me suddenly, often many times during the same day. They would usually only last a few seconds, and then I would be fine. They were never that severe, and left no lasting problems. The worst one I had made me stop what I was doing - grocery shopping - and sit down for a few minutes. The only other minor side effect I still suffer from is a lower tolerance for alcohol. I used to be able to drink a few beers or glasses of wine without feeling any adverse effects. Now, after one drink I start feeling a little woozy in my head. Good thing I was never a big drinker! 

Getting the acoustic neuroma diagnosis was the most terrifying experience of my life. It shook me to my very core, and changed my life forever. I was absolutely shaken, and my future outlook was bleak. However, the treatment I received was top notch and the people who treated me made me feel confident that I would soon be back to normal - or as close to normal as I could get. I will be forever grateful to Dr. Roberge and the entire CyberKnife team for treating me with incredible compassion combined with amazing skill. I look forward to leading the rest of my life with the same amount of passion and energy as I did before the diagnosis. Overall, while I would not wish to go through the whole thing again, it was not as bad as it could have been, and it gave me a good story to tell friends and family!


Supplemental files


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