Safety and Efficacy of Hypo fractionated Stereotactic Radiosurgery in Facial Nerve Schwannoma.

doi:10.21203/rs.3.rs-897884/v1

Purpose

In the current era of modern neurosurgery, the treatment strategies have been shifted to “nerve-preservation approaches” for achieving a higher facial and hearing function preservation rate following facial nerve tumors. We have conducted this novel report on determining the outcome of patients with facial nerve schwannomas (FNS) treated with hypo fractionated stereotactic radiosurgery (hfSRS).

Methods

Retrospective chart review of a prospectively maintained database search was conducted. Patients who underwent hfSRS CyberKnife (Accuray Inc, Sunnyvale, California., USA) for FNS were included. Outcomes consisted of tumor control, facial and hearing nerve function as graded by House-Brackmann (HB) and Gardner-Robertson scale, and adverse radiation effects. SPSS 23 was used to perform statistical analysis.

Results

With an institutional board review approval, we retrospectively identified 5 patients with FNS [4 intracranial (80%) and 1 extracranial (20%)] treated with hfSRS (2011–2019). Patients received definitive SRS in 3 patients (60.0%) wile adjuvant to surgical resection in 2 patients (40.0%). A median tumor volume of 7.5 cm³ (range, 1.5–19.6 cm³) received a median prescription dose of 23.2 Gy (range, 21–25 Gy) administered in median of 3 fractions (range, 3–5 session). With a median radiographic follow-up of 31.4 months (range, 13.0–71.0 months) and clinical follow-up of 32.6 months (range, 15.1–72.0 months), the local tumor control was 100.0%. At last clinical follow-up, the facial nerve function improved or remained unchanged HB I-II in 80.0% of the patients, while the hearing nerve function improved or remained stable in 100.0% (Gardner-Robertson I-II) of the patients. Temporary clinical toxicity was seen in 3 patients (60.0%) which resolved. None of the patient developed adverse radiation effect.

Conclusion

hfSRS in FNS is safe and efficacious in terms of local tumor control, improved facial and hearing nerve function, and very low incidence of complications.

Neurology

Oncology

facial nerve

schwannoma

tumor control

stereotactic radiosurgery

The treatment strategy for facial nerve schwannomas (FNS) has evolved from microsurgical resection to facial nerve preservation approaches [1]^,[2]. However, the standard management in terms of weighting the normal or near-normal facial nerve function [House-Brackmann (HB) I-II] over tumor size is still controversial [3]. Stereotactic radiosurgery (SRS) is now considered as a safe and alternative treatment to surgery with excellent tumor control and very low risk of treatment associated facial nerve morbidity [4–6]. Although the studies have established the role of hypo fractionated SRS (hfSRS) on vestibular schwannoma [7], there are has not been previously reported safety and efficacy of hfSRS on confirmed intra- and/or extracranial FNS.

This study determined the impact of hfSRS on facial nerve and hearing function outcomes of intra and extra-cranial FNS. We have conducted this research in order to better inform future-treatment, physician decision making options and patient counselling when discussing about the SRS as treatment options.

Patient Demographics:

The charts of all the patients who were treated with hfSRS were retrospectively reviewed between 2011–2019 in accordance with the institutional IRS policies. Patients were included if they had a histological or radiologically diagnosed FNS and hfSRS was provided as a definitive treatment. In total, 5 patients with facial nerve schwannoma had evaluable imaging follow-up, 2 were females (40.0%). The median age was 41.0 years (range, 37–60 years). Baseline characteristics are described in Table 1.

Table 1

Baseline Characteristics of the Patients
Parameter	N (%)
Gender Male Female	3 (60.0) 2 (40.0)
Age, median (range) years	41.0 (37–60)
Prior surgery	2 (40.0)
Tumor Volume, median (range) cm³	7.5 (1.5–19.6)
Prescription dose, median (range) Gy	23.2 (21–25)
Isodose, median (range) %	81.0 (80.0–82.0)
Follow-up, median (range) months Radiological Clinic	11.0 (3.0–71.0) 12.0 (1.0–72)

Table 2

The clinical and radiographic characteristics of the patients

No	Age (yrs)	Gender	Previous Rx	Tumor size (cm³)	Dose (Gy)	Fractions (n)	Isodose Line (%)	Tumor Location	Preoperative HB Grade	Postoperative HB Grade	Tumor size at last follow up
1	45	M	N	7.5	22.5	3	80	CPA/IAC/GEN	1/6	2/6	decreased
2	41	F	N	8.38	25	5	81	IAC/GEN	2/6	2/6	stable
3	37	M	N	19.6	25	5	82	GEN/MAST/EXTRA	1/6	1/6	stable
4	41	F	Y (s/p MFC for AN)	4.8	22.5	3	80	IAC/GEN	2/6	2/6	stable
5	60	M	Y (s/p MFC)	1.5	21	3	81	CPA/IAC	1/6	1/6	decreased
s/p: status post op, MFC: middle cranial fossa, AN: acoustic neuroma, CPA: cerebellopontine angle, IAC: internal auditory canal, gen: geniculate ganglion, mast: mastoid, extra: extracranial, HB: house Brackmann, Rx: treatment

The indication of hfSRS was definitive treatment in 3 patients (60.0%), while adjuvant to surgical resection in 2 patients (40.0%). None of the patients had prior irradiation. 2 patients (40.0%) presented initially with hemifacial spasm, 1 patient (20.0%) with facial mass, and 2 patients (40.0%) had progression of tumor on their CT-scan or MRI following surgery. The clinical and radiographic characteristics of the patients are included in Table 2.

Following anatomical facial nerve segments were involved: (i) labyrinthine segment-internal auditory canal (IAC) to geniculate ganglion (n = 3), meatal segment (n = 1), and geniculate ganglion to extratemporal segment (n = 1).

The median pre-operative HB among the patients was 1 (range, 1–2). The preoperative hearing status consisted of median pure tone average of 35.5 dB (range, 20.0–78 dB) and speech discrimination of 96.0% (range, 68.0-100.0%).

SRS Planning and Characteristic:

SRS planning and treatments were delivered with CyberKnife robotic radiosurgery system (Accuray Inc, Sunnyvale, California., USA). The median SRS target volume was 7.5 cm³ (range, 1.5–19.6 cm³). The median prescription dose was 23.2 Gy (range, 21–25 Gy) administered in a median of 3 fractions (range, 3–5 session). The most common dose/fractionation schemes were median of 25 Gy in 5 fraction, 22.5 Gy in 3 fractions. The median isodose line was 81.0% (range, 80.0–82.0%) with a median coverage of 98.9% (range, 98.5–99.9%). (Figs. 1 and 2)

Clinical and Radiological Outcome Assessment:

After receiving SRS, patients were evaluated for 6-month and 1-year interval and annually thereafter. The patient’s postoperative neurological status (unchanged, improved or worsened) and radiographic tumor control were compared with their baseline status prior to SRS treatment. The House-Brackmann Classification was used for grading facial nerve outcome and Gardner-Robertson Hearing scale was used for grading VIII nerve.

Statistical Analysis:

Categorical variables were evaluated through frequencies and percentages, median and range were used for continuous variables.

Tumor Control:

The median radiological follow-up was 31.4 months (range, 13.0–71.0 months). The crude incidence of local tumor control was 100.0%, with tumor size unchanged in 3 patients (60.0%) and regression in tumor size in 2 patients (40.0%).

Clinical Outcome and Toxicity:

The median clinical follow-up for our study was 32.6 months (range, 15.1–72.0 months). At last follow-up, the postoperative HB grade remained unchanged or improved (HB grade I-II) in 4 patients (80.0%), while it worsened by 1-grade (HB Grade II) in 1 patient (20.0%). The postoperative SDS and PTA improved (Gardener-Robertson grade I-II) among all the patients (80.0%), except in 1 patient (20.0%) which remained unchanged.

Following SRS 3 patients had temporary clinical toxicity symptoms which included: 1patient had facial nerve weakness of 5/6 which improve to 2/5 within a week, 1-patient had geniculate neuralgia which improved with gabapentin, and 1-patient had diplopia which improved with resolved on its own. None of the patients had adverse radiation effects.

FNS treatment is challenging due to critical function of the parent nerve as well as the morbidity associated with the growth and mass effect on the surrounding neurovascular structure. The incidence of FNS is 3.0% of all cerebellopontine angle schwannomas [8], therefore the outcome of these tumors remain uncertain due to infrequency. The current case series is the first study reporting the facial nerve and hearing function outcome after hfSRS for patients with confirmed, including those with temporal bone and extra cranial nerve involvement FNS. This study is conducted for better decision making among the patients with this rare tumor. Based on the findings of our series, hfSRS significantly benefit more patients in terms of preservation and/or improvement of facial nerve and hearing function outcome. These findings will help the physician and patients alike in understanding the risks and benefits of hfSRS for treatment of FNS.

hfSRS has proven to have comparable outcomes with respect to tumor control while also lowering the risk of collateral damage to surrounding tissue as that of SRS [9, 10]. In our study, hfSRS has demonstrated its safety and efficacy in terms of preservation of nerve function and perifocal critical tissue. Based on our findings, hfSRS appears to be significantly associated with stable to improved facial and hearing nerve function outcome with no complications. This is however, in contrast to the previous studies with vestibular schwannoma in which the authors did not detect significant difference between SRS and hfSRS [11].

Preoperative facial nerve function is also an important determinant in decision-making in FNS, hence surgeons recommend observation to patients with minimal degradation in facial function; SRS for moderate reduction in facial function; and surgery with or without grafting for poor facial nerve function (HB IV or worse) or for significant mass effect [2, 12, 13]. Studies have suggested that with a treatment goal of preventing the tumor growth while preserving function of facial nerve in FNS, surgery poses a higher risk of facial palsy compared to SRS for facial nerve function [14]. Further, multi-institutional studies have demonstrated that SRS can result in durable tumor control 87.2–92% and facial nerve functional preservation of approximately 90–94% [15–17]. No study to date has assessed the relationship of hfSRS to radiological and functional outcome in FNS.

Given the low estimated tumor recurrence rate and significant nerve preservation, we do believe that hfSRS may be a better option for FNS. The data support that hfSRS should be considered among the primary treatment options for large or growing FNS associated with some degree of facial nerve function. Therefore, hfSRS confers the higher rates of facial and hearing nerve function, with excellent local tumor control and very low incidence of complications. Our current study would support consideration of hfSRS as the predominant first line treatment therapy for FNS, in hope of reducing the incidence of patients developing more severe clinical symptoms or sufficient tumor growth that mandates microsurgical resection.

Our study has a few limitations, which include (i) retrospective report, (ii) small cohort size and statistical power, however it is difficult to ascertain the safety and efficacy of novel treatment in a huge cohort initially. Therefore, our study would guide in the treatment strategy for FNS worldwide, and (iii) although HB grading and Gardner Robertson scale are standardized metric, still there can be inconsistencies inn an inter rater reliability. Further prospective studies using hfSRS on large cohort of FNS are needed.

In this study, we have demonstrated the safety and efficacy of hfSRS on FNS in terms of local tumor control, improved facial and hearing nerve function, and very low incidence of complications. The results suggest that hfSRS should be considered as a front-line option in patients with FNS in order to preserve their facial and hearing nerve function. Further prospective studies should be conducted to investigate the impact of this treatment in large cohort of patients with FNS.

hfSRS: hypo fractionated stereotactic radiosurgery, HB: House-Brackmann, FNS: facial nerve schwannoma, SRS: Stereotactic radiosurgery

Acknowledgments: None
Funding: None.
Conflict of interest/Competing Interest: None
Ethics Approval: IRB Approved House Institute
Availability of data and material: All data generated or analyzed during this study are included in this published article

Consent to Participate: Not Applicable
Consent to Publish: Not Applicable

Authors Contribution: Nida Fatima, Anna La Dine, Gregory P Lekovic: Manuscript Writing; Zachary R Barnard, Kevin Peng, William Slattery: Data Collection, Nida Fatima and Katherine Ko: Data/Statistical Analysis; Nida Fatima and Gregory P Lekovic: Editing and Final Revision; Supervision: Gregory P Lekovic

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Safety and Efficacy of Hypo fractionated Stereotactic Radiosurgery in Facial Nerve Schwannoma.

Status:

Version 1

Abstract

Purpose

Methods

Results

Conclusion

Figures

Introduction:

Patients And Methods:

Patient Demographics:

SRS Planning and Characteristic:

Clinical and Radiological Outcome Assessment:

Statistical Analysis:

Results:

Tumor Control:

Clinical Outcome and Toxicity:

Discussion:

Conclusion:

Abbreviations

Declarations

References

Status:

Version 1