Stereotactic radiosurgery for trigeminal neuralgia secondary to tumor: a single-institution retrospective series

Jennifer C. HallDepartments of Radiation Oncology and

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Timothy H. UngNeurosurgery, Stanford University, Palo Alto, California

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Tamra-Lee McClearyNeurosurgery, Stanford University, Palo Alto, California

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Cynthia ChuangDepartments of Radiation Oncology and

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Iris C. GibbsDepartments of Radiation Oncology and

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Scott G. SoltysDepartments of Radiation Oncology and

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Melanie Hayden GephartNeurosurgery, Stanford University, Palo Alto, California

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Gordon LiNeurosurgery, Stanford University, Palo Alto, California

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Erqi L. PollomDepartments of Radiation Oncology and

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Steven D. ChangNeurosurgery, Stanford University, Palo Alto, California

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Antonio MeolaNeurosurgery, Stanford University, Palo Alto, California

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OBJECTIVE

Trigeminal neuralgia (TN) secondary to tumor represents a rare and diverse entity, and treatment for secondary TN remains controversial. This report reviews a single institution’s experience in treating secondary TN with stereotactic radiosurgery (SRS) and focuses on the durability of pain relief with respect to various treatment targets, i.e., the trigeminal nerve, offending tumor, or both.

METHODS

Between the years 2009 and 2021, 21 patients with TN secondary to benign (n = 13) or malignant (n = 8) tumors underwent SRS. Barrow Neurological Institute (BNI) pain intensity scale scores were collected from patient electronic medical records at baseline, initial follow-up, and 1 and 3 years post-SRS. The interval change in BNI scale score (ΔBNI) at the various follow-up time points was also calculated to assess the durability of pain relief following SRS.

RESULTS

The median follow-up period was 24 (range 0.5–155) months. Five patients (24%) received treatment to the trigeminal nerve only, 10 (48%) received treatment to the tumor only, and 6 (29%) had treatment to both the nerve and tumor. The overall radiation dosage ranged from 14 to 60 Gy delivered in 1–5 fractions, with a median overall dose of 26 Gy. The median dose to the tumor was 22.5 (range 14–35) Gy, delivered in 1–5 fractions. Of the treatments targeting the tumor, 25% were delivered in a single fraction with doses ranging from 14 to 20 Gy, 60% were delivered in 3 fractions with doses ranging from 18 to 27 Gy, and 15% were delivered in 5 fractions with doses ranging from 25 to 35 Gy. The most common dose regimen for tumor treatment was 24 Gy in 3 fractions. The median biologically effective dose (with an assumed alpha/beta ratio of 10 [BED10]) for tumor treatments was 43.1 (range 13.3–60.0) Gy. There was a significant difference in the proportion of patients with recurrent pain (ΔBNI score ≥ 0) at the time of last follow-up across the differing SRS treatment targets: trigeminal nerve only, tumor only, or both (p = 0.04). At the time of last follow-up, the median ΔBNI score after SRS to the nerve only was −1, 0 after SRS to tumor only, and −2 after SRS to both targets.

CONCLUSIONS

SRS offers clinical symptomatic benefit to patients with TN secondary to tumor. For optimal pain relief and response durability, treatment targeting both the tumor and the trigeminal nerve appears to be most advantageous.

ABBREVIATIONS

BCC = basal cell carcinoma; BED = biologically effective dose; BNI = Barrow Neurological Institute; CBZ = carbamazepine; GBP = gabapentin; LTG = lamotrigine; MVD = microvascular decompression; NSCLC = non–small cell lung cancer; SCC = squamous cell carcinoma; SRS = stereotactic radiosurgery; TN = trigeminal neuralgia.

OBJECTIVE

Trigeminal neuralgia (TN) secondary to tumor represents a rare and diverse entity, and treatment for secondary TN remains controversial. This report reviews a single institution’s experience in treating secondary TN with stereotactic radiosurgery (SRS) and focuses on the durability of pain relief with respect to various treatment targets, i.e., the trigeminal nerve, offending tumor, or both.

METHODS

Between the years 2009 and 2021, 21 patients with TN secondary to benign (n = 13) or malignant (n = 8) tumors underwent SRS. Barrow Neurological Institute (BNI) pain intensity scale scores were collected from patient electronic medical records at baseline, initial follow-up, and 1 and 3 years post-SRS. The interval change in BNI scale score (ΔBNI) at the various follow-up time points was also calculated to assess the durability of pain relief following SRS.

RESULTS

The median follow-up period was 24 (range 0.5–155) months. Five patients (24%) received treatment to the trigeminal nerve only, 10 (48%) received treatment to the tumor only, and 6 (29%) had treatment to both the nerve and tumor. The overall radiation dosage ranged from 14 to 60 Gy delivered in 1–5 fractions, with a median overall dose of 26 Gy. The median dose to the tumor was 22.5 (range 14–35) Gy, delivered in 1–5 fractions. Of the treatments targeting the tumor, 25% were delivered in a single fraction with doses ranging from 14 to 20 Gy, 60% were delivered in 3 fractions with doses ranging from 18 to 27 Gy, and 15% were delivered in 5 fractions with doses ranging from 25 to 35 Gy. The most common dose regimen for tumor treatment was 24 Gy in 3 fractions. The median biologically effective dose (with an assumed alpha/beta ratio of 10 [BED10]) for tumor treatments was 43.1 (range 13.3–60.0) Gy. There was a significant difference in the proportion of patients with recurrent pain (ΔBNI score ≥ 0) at the time of last follow-up across the differing SRS treatment targets: trigeminal nerve only, tumor only, or both (p = 0.04). At the time of last follow-up, the median ΔBNI score after SRS to the nerve only was −1, 0 after SRS to tumor only, and −2 after SRS to both targets.

CONCLUSIONS

SRS offers clinical symptomatic benefit to patients with TN secondary to tumor. For optimal pain relief and response durability, treatment targeting both the tumor and the trigeminal nerve appears to be most advantageous.

Trigeminal neuralgia (TN) is a facial pain syndrome characterized by brief, recurrent episodes of unilateral facial pain resulting from dysfunction of the trigeminal nerve, most commonly due to neurovascular compression of the nerve.1 In rare cases (< 6% of patients with facial pain syndromes),2 nerve dysfunction is secondary to benign or malignant tumors abutting or involving the trigeminal nerve. There are numerous documented cases of such tumors, with those that are most likely to cause secondary TN located within the posterior cranial fossa.35

The standard treatment approach for TN secondary to tumor remains controversial given the rarity of this diagnosis. While resection of the tumor can relieve pain, these procedures are invasive and have morbidity and mortality associations.2,4 In patients with tumors that are unresectable and/or medically inoperable, stereotactic radiosurgery (SRS) has been shown to be effective for both tumor control and pain relief.6 Uncertainty remains, however, about whether targeting the trigeminal nerve or offending lesion yields the most effective and durable pain relief. Treatment decisions are further complicated by discordant results in previous studies that report conflicting findings about the association between tumor progression and clinical symptoms.68

In this study, we evaluate clinical outcomes of patients treated with SRS for TN secondary to benign and malignant tumors and compare our single-institution review to prior published findings. We specifically report SRS treatment targets and their association with the durability of pain relief.

Methods

Patient and Study Criteria

After IRB approval, an initial review of medical records for all patients treated with SRS for TN at Stanford University Hospital and clinics between the years 2009 and 2021 was performed. We included only those patients with TN secondary to either a benign or malignant tumor. Demographic data, tumor histology, radiation treatment data, and clinical outcomes were collected for these patients. Barrow Neurological Institute (BNI) pain intensity scale scores prior to and following completion of SRS were collected from the charts. The time points of BNI scale data collection after SRS were at the initial follow-up appointment and 1 and 3 years following completion of SRS. The biologically effective dose (BED) of SRS was calculated with an assumed alpha/beta ratio of 10 (BED10).9 In all patients, SRS was delivered using the CyberKnife System (Accuray).

Statistical Analysis

For comparison of parametric variables, an independent t-test was utilized. Pearson’s coefficient was used to assess correlations between continuous variables; similarly, Fisher’s exact test was used for categorical data. Only p values ≤ 0.05 were considered statistically significant.

Results

Patient and Tumor Characteristics

We identified 21 patients who met inclusion criteria. The median age at initial SRS treatment was 65 (range 35–79) years, and 11 patients (52%) were female (Table 1). Patients had both benign and malignant tumors that abutted the trigeminal nerve and resulted in TN, consisting of meningiomas (43%), schwannomas (19%), and metastatic tumors (38%). Metastatic tumor histologies included squamous cell carcinoma (SCC; 10%), non–small cell lung cancer (NSCLC; 19%), basal cell carcinoma (BCC; 5%), and breast cancer (5%).

Of the patients with benign tumors, 8 (62%) had pain refractory to medical intervention. Trialed medications included gabapentin (GBP), carbamazepine (CBZ), phenytoin, lamotrigine (LTG), and baclofen. Three patients (14%) underwent microvascular decompression (MVD) prior to treatment with SRS (Table 2).

TABLE 1.

Demographic overview

CharacteristicTotalBenign TumorMalignant Tumor
Sex, n (%)
 Female11 (52)8 (38)3 (14)
 Male10 (48)5 (24)5 (24)
Median age at initial SRS (range), yrs 64.5 (35.2–78.9)66 (45–79)59 (35–70)
Symptom laterality, n (%)
 Rt9 (43)6 (29)3 (14)
 Lt11 (52)7 (33)4 (19)
 Bilat1 (5)0 (0)1 (5)
Preexisting facial sensory dysfunction, n (%)
 Numbness8 (38)3 (14)4 (19)
 Paresthesia2 (10)2 (10)0 (0)
Prior intervention, n (%)
 Medical8 (38)8 (38)0 (0)
 MVD3 (14)3 (14)0 (0)
Tumor pathology, n (%)13 (62)8 (38)
 Meningioma9 (43)
 Schwannoma4 (19)
 SCC2 (10)
 NSCLC4 (19)
 BCC 1 (5)
 Breast1 (5)
Median baseline BNI score (range)IV (I–V)IV (I–V)III (I–V)
SRS target, n (%)
 Nerve only5 (24)4 (19)1 (5)
 Tumor only 10 (48)3 (14)7 (33)
 Both 6 (29)6 (29)0 (0)
SRS prescribed dose, Gy
 Targeting nerve (single fraction)
  Mean (SD)60 (0)60 (0)60 (0)
  Median (range) 60 (60–60)60 (60–60)60 (60–60)
 Targeting tumor (BED10)
  Mean (SD)41.6 (9.2)34.9 (8.7)38.0 (17.5)
  Median (range)43.1 (13.3–60.0)35.7 (13.7–43.2)43.2 (13.3–60.0)
SRS vol, cm3
 Treated nerve
  Mean (SD)0.044 (0.019)0.039 (0.018)0.060 (0)
  Median (range) 0.049 (0.023–0.060)0.035 (0.020–0.080)0.060 (0.060–0.060)
 Treated tumors
  Mean (SD)3.734 (2.607)3.093 (2.664)4.120 (4.272)
  Median (range)3.008 (0.15–13.705)2.625 (0.690–9.040)3.390 (0.150–13.710)
TABLE 2.

Patient cohort at presentation

Pt No.Age (yrs), SexPathologySide of TumorPresenting SymptomsPrevious Treatments
Facial NumbnessParesthesia
158, FMeningRtYesYesMVD, CBZ
258, MSchwanRtYesNo
368, MSchwanLtNoNoGBP, CBZ, MVD
435, MSCCLtNoNoSystemic therapy
578, FMeningLtNoNoPhenytoin, CBZ, GBP
665, FMeningRtNoNoGBP, CBZ, LTG, baclofen
752, FNSCLCBilatNoNoSystemic therapy
857, MNSCLCRtYesNoSystemic therapy
979, FMeningLtNoNoCBZ, GBP
1066, FMeningLtNoNo
1162, MSchwanRtNoNo
1273, FMeningLtYesNoCBZ, GBP
1355, FSchwanLtYesNo
1445, MMeningRtYesNo
1570, MSCCNoNoSystemic therapy
1661, MNSCLCLtNoNoSystemic therapy
1756, FBreastRYesYesSystemic therapy
1867, FNSCLCLtYesYesSystemic therapy
1976, MMeningRtYesNoMVD, GBP
2076, FMeningLtNoNoGBP
2170, MBCCLtYesNoSystemic therapy

Mening = meningioma; pt = patient; Schwan = schwannoma.

Eight patients with metastatic tumors continued on systemic therapy options at the time of SRS treatment; systemic therapies included chemotherapy, immunotherapy, and other targeted therapeutic agents for treatment of malignancy.

Approximately half (52%) of the patients had left-sided tumors, and 1 patient had NSCLC metastases affecting bilateral trigeminal nerves. Symptoms at presentation included facial sensory disruptions and pain associated with the laterality of the tumor or tumors. Ten patients (48%) experienced facial numbness, and 3 (14%) experienced facial paresthesia prior to treatment with SRS (Table 2).

SRS: Doses and Targets

The median time to initial follow-up after SRS was 6 (range 0.5–21) months, while the median overall follow-up period after SRS was 24 (range 0.5–155) months. Thirteen patients (62%) were treated with a single course of SRS, and the remaining 8 patients with two total courses of SRS. All twice-treated patients experienced recurrent symptoms after their initial course; the median time between first and second courses was 26 (range 5–113) months.

Five patients (24%) received treatment to the trigeminal nerve only, 10 patients (48%) received treatment to the tumor only, and 6 patients (29%) received treatment to both the nerve and the tumor. The overall radiation dosage ranged from 10 to 60 Gy delivered in 1–5 fractions with a median overall dose of 26 Gy (Table 3). The median dose to the tumor was 22.5 (range 14–35) Gy, delivered in 1–5 fractions. Of the treatments targeting the tumor, 25% were delivered in a single fraction with doses ranging from 14 to 20 Gy, 60% were delivered in 3 fractions with doses ranging from 18 to 27 Gy, and 15% were delivered in 6 fractions with doses ranging from 25 to 35 Gy. The most common dose regimen for treatment of a tumor was 24 Gy in 3 fractions. The median BED10 for treatments to the tumor was 43.1 (range 13.3–60.0) Gy (Fig. 1). When comparing mean BED10 across tumor histologies, there was no significant difference between BED10 dose to malignant versus benign histologies (r = 0.51, p = 0.16).

TABLE 3.

Patient SRS overview

Pt No.No. of SRS CoursesTargetTarget Vol (cm3)Tumor BED10Prescribed Dose (Gy)FractionsInitial FU (mos)Overall FU (mos)
12Tumor

Nerve
1.172

0.022
43.2024

60
3

1
2121
21Nerve0.040601719
32Nerve

Nerve
0.080

0.070


60

60
1

1
661
41Nerve0.06060100
52Tumor

Nerve
0.918

0.023
43.20

24

60
3

1
629
61Tumor

Nerve
0.690

0.035
33.60

14

60
1

1
625
72Tumor

Tumor
0.150

0.250
28.80

28.80
18

18
3

3
48
81Tumor1.08050.40181236
91Nerve

Tumor
0.049

1.360


37.50
60

15
1

1
622
101Nerve

Tumor
0.034

9.040


33.60
60

14
1

1
624
111Tumor3.59035.702131024
122Tumor

Nerve
2.625

0.020
35.70

21

60
3

1
7115
131Tumor3.44335.70255324
141Tumor5.00013.705243736
151Tumor7.20059.5035536
161Tumor0.22060.00201415
172Tumor

Tumor
7.038

1.20
48.00

13.33
30

10
5

3
141
181Tumor4.10051.30273466
192Nerve

Nerve
0.040

0.040


60

60
1

1
614
202Nerve

Nerve
0.024

0.030


60

60
1

1
367
211Tumor

Tumor

Tumor
7.011

13.705

3.391
43.20

20.53

20.53
24

14

14
3

3

3
338

FU = follow-up.

A hypothetical BED3 (with assumed alpha/beta ratio of 3) for treatments to the nerve was omitted given the uniformity of all patients and unclear biological significance.

FIG. 1.
FIG. 1.

SRS treatment planning was conducted prior to all treatments utilizing coregistered CT scans and MRI, allowing for limiting the dose to nearby organs at risk, including the brainstem (yellow outline) and optic apparatus. The SRS plan depicts conformal contouring of dose targeting both the left trigeminal nerve (red outline) and an offending meningioma of the left cavernous sinus (pink outline) in a 66-year-old woman. Both targets were treated in the same course of SRS and received a single fraction; the trigeminal nerve was prescribed 60 Gy, whereas the tumor was prescribed 14 Gy.

All trigeminal nerve targets were treated with single-fraction SRS to a prescribed dose of 60 Gy to the 80% isodose line for a maximum dose of 75 Gy. This dose regimen was utilized for all treatments to the trigeminal nerve, including cases in which patients received treatment to both the trigeminal nerve and tumor. The median target volume for treatments to the trigeminal nerve was 0.049 (range 0.023–0.06) cm3. The median target volume for treatments to the tumor was 3.008 (range 0.15–13.705) cm3. There was no significant difference between treated tumor volume for benign versus malignant tumors (r = 0.33, p = 0.38).

Pain Relief and Response Durability

BNI pain intensity scale scores were collected at baseline, initial follow-up, and 1 and 3 years after SRS (Table 4). The median baseline BNI scale score (prior to treatment with SRS) was IV. There was no significant difference in baseline BNI scale scores for patients with benign and malignant tumor types. There was no significant correlation between tumor volume and baseline BNI scale score (r = 0.08, p = 0.78).

TABLE 4.

BNI pain intensity scale scores for patients treated with SRS

BNI ScorePain DescriptionTotal, Benign, Malignant, n (%)
Baseline, n = 21Initial FU, n = 271 yr Post-SRS, n = 223 yrs Post-SRS, n = 12
ILittle to no pain, no medication5 (24), 1 (5), 4 (19)10 (37), 5 (19), 5 (19)3 (14), 1 (5), 2 (9)5 (42), 3 (25), 2 (17)
IIOccasional pain not requiring medication0 (0)3 (11), 1 (4), 2 (7)6 (27), 2 (9), 4 (18)1 (8), 0 (0), 1 (8)
IIISome pain adequately controlled w/ medication2 (9), 1 (5), 1 (5)6 (22), 4 (15), 2 (7)5 (23), 2 (9), 3 (14)1 (8), 0 (0), 1 (8)
IVSome pain not adequately controlled w/ medication5 (24), 4 (19), 1 (5)8 (30), 8 (30), 0 (0)8 (36), 8 (36), 0 (0)4 (33), 4 (33), 0 (0)
VSevere pain, no relief9 (43), 7 (33), 2 (10)0 (0)0 (0)1 (8), 1 (8), 0 (0)

This table includes patients treated with more than one course of SRS; separate courses were treated independently from one another in terms of follow-up BNI assessment. Percentages reflect percentage of total cases.

To better understand differences in the durability of pain relief, we calculated the change in BNI scale score (ΔBNI) between consecutive time points and SRS treatment targets (Fig. 2). There was a significant difference in the proportion of patients with recurrent pain (ΔBNI score ≥ 0) at the time of last follow-up across the differing SRS treatment targets, i.e., trigeminal nerve only, tumor only, or both (p = 0.04). At the time of the last follow-up, the median ΔBNI score for patients who received SRS to the trigeminal nerve only was −1 (range −1 to 0); for patients who received SRS to the tumor only, 0 (range −2 to 2); and for patients who received SRS to both targets, −2 (range −4 to −1).

FIG. 2.
FIG. 2.

ΔBNI score allows for assessment of symptom relief over time compared across treatment targets irrespective of baseline BNI scale score. Trends in ΔBNI score with respect to time illustrate differences in the efficacy and durability of pain relief associated with the various treatment targets, i.e., trigeminal nerve only, tumor only, and both. Treatments to the trigeminal nerve (including nerve only and both) resulted in the most notable pain relief at initial follow-up, but treatments targeting both the trigeminal nerve and tumor are shown to sustain the most negative ΔBNI score to the 3-year post-SRS time point.

Adverse Effects

Nine patients (43%) were documented as having new or worsened trigeminal symptoms following treatment with SRS; these symptoms included pain flare, paresthesia, dysesthesia, facial numbness, and facial nerve palsy (Table 5). The relationship between SRS target and these adverse effects was also explored.

TABLE 5.

Adverse effects after SRS

VariableNew or Worsened Facial Symptom
ParesthesiaFacial NumbnessDysesthesiaFacial Nerve PalsyPain Flare
No. (%)2 (10)5 (24)3 (14)2 (10)2 (10)
Benign/malignant, n (%)2 (100)/0 (0)4 (80)/1 (20)2 (66)/1 (33)0 (0)/2 (100)2 (100)/0 (0)
Median mos to onset (range)25 (6–44)6 (5–44)3 (2–35)6.5 (5–8)2 (1–3)
No. resolved by last FU, n (%)1 (50)0 (0)2 (67)0 (0)2 (100)
Nerve only, n (%)2 (10)2 (10)1 (5)0 (0)1 (5)
Tumor only, n (%)0 (0)1 (5)1 (5)2 (10)1 (5)
Both, n (%)0 (0)2 (10)1 (5)0 (0)0 (0)

Pain flare was the adverse event with the earliest onset and most rapid resolution. Facial numbness was the most reported adverse event and failed to completely resolve in all reported occurrences.

Discussion

TN secondary to tumor is distinct from classic or idiopathic TN and represents a diverse entity. Tumor pathologies can range from benign, slow-growing lesions to metastatic lesions. Accordingly, there remains a lack of consensus as to the most effective treatment modality, particularly in patients with notable comorbidities or contraindications to resection of the offending tumor. As demonstrated within our single-institution review of SRS for secondary TN, radiosurgery offers patients clinical symptomatic benefit, but there also remains diversity in treatment technique within this single treatment modality.

Specifically, our review focused on SRS treatment targets, distinguishing between SRS to the tumor, trigeminal nerve, or both. Symptomatic improvement was assessed via calculation of ΔBNI, in which a negative ΔBNI score (ΔBNI score < 0) corresponds to a decrease in the patients’ overall BNI pain scale score. Our findings suggest treatment with SRS targeting both the trigeminal nerve and the offending tumor is associated with the most substantial decrease in ΔBNI score over time, with increased durability observed as long as 3 years after SRS.

A review of the prior literature was performed to compare these findings with previously documented outcomes (Table 6). Chivukula et al. addressed the current debate regarding the best treatment approach among targets to the trigeminal nerve only, tumor only, or both.10 In their report they state that radiation to the tumor—without causing significant morbidity—could at best only achieve volume reduction, but this would not be of great benefit because the electrical propagation will inevitably continue. This was evident in their study, in which 50% of the patients experienced incomplete relief with short durability. For this reason, Chivukula et al. affirm that targeting the nerve may provide the best symptom relief, because patients reported excellent outcomes maintained over more than a mean of 2 years of follow-up. However, it is important to highlight that 10 of the 12 patients in their cohort underwent radiosurgery or radiation therapy targeting the tumor prior to receiving treatment to the nerve. These data could confirm that a two-stage approach targeting both the tumor and nerve might offer the best outcome, as the initial pain relief went from 50% after tumor target to 83.3% after treatment to the nerve.

TABLE 6.

Overview of previous studies

Authors & YearNo. of CasesAge (range), yrsTumor Pathology %Treatment Target % or Vol, cm3 (range)Dose, Gy (range)Initial Response Rate (%)Recurrent or Persistent Pain (%)Mean FU (range), mos
Chivukula et al., 2017101259.8 (47.7–84.7)Mening 66.7, SCC 16.7, VS 8.3, Hemang 8.3Mening 14 (13–14), SCC 57.6 (50.4–57.6)83.35055.6 (10.3–125.3)
Cho et al., 2016115054 (33–87)Mening 60, VS 22, TS 14, epidermoid cyst 2, AVM 2Tumor 84%, nerve 4%, tumor & nerve 12%Mening 13.25 (10–25), VS 12.5 (12–15), TS 14 (12–15), epidermoid cyst 90, AVM 329228.354.8 (13–142)
Kano et al., 201161254 (37–68)Mening 100Tumor 3.8 (1.0–15.9)13 (11–16)832568 (25–180)
Huang et al., 200872154.5 (18–79)Mening 57.1, Schwan 42.9Mening 8.2 (1.1–21), Schwan 5.6 (2–9.2), nerve 60.7 (40–70)Mening 12.7 (12–15), Schwan 13 (11.5–16)813857.8 (36–94)
Pollock et al., 200082457 (33–79)Mening 67, malignant cranial base tumors 33Mening 9.7 (1.9–27.2), cranial base 15.6 (7.0–27.2)Mening 18 (16–20), cranial base 15.0 (12.0–16.0)5012.545 (12–90)
Squire et al., 2012122167 (41–80)Mening 67, VS 24, TS 9Tumor 2.3 (0.16–14.5)12 (11–13)816645.6 (4.8–111.6)
Tanaka et al., 2013133162 (17–81)Mening 84, Schwan 1630 (20–60)5822.650 (12–184)

AVM = arteriovenous malformation; Hemang = hemangiopericytoma; TS = trigeminal schwannoma; VS = vestibular schwannoma.

Several other groups have evaluated the outcomes of different target approaches. Two main limiting factors shared among most of these studies are the relatively small cohorts and short follow-up periods. To better evaluate the best treatment approaches, it is imperative to study larger cohorts over a significant period. We understand that the size of the cohort presented here (n = 21) along with the follow-up duration (mean 24 months) is a valuable contribution to enhance the available data. Our results regarding the benefit of targeting both the tumor and the nerve are similar to those published by Cho et al. in 2016.11 In their report, Cho et al. presented a larger sample size (n = 50) and longer follow-up period (mean 54.8 months), in which patients who received a second SRS treatment also had favorable symptom results. They concluded that a second SRS treatment could be effective without an increase in comorbidities or complications. Similarly, in our series, there was no increase in adverse effects for patients treated at both targets compared with those treated only at the tumor or nerve targets. The results published by Huang et al. also support targeting both the tumor and nerve.7 They showed that a repeat treatment to the nerve could enhance pain relief without medication, from 57% to 76.2%; however, they did find a high incidence of facial numbness.

In a series by Kano et al. focusing only on treatment to tumor targets, symptom relief was underwhelming, albeit good tumor control was achieved.6 Nevertheless, efficacy with tumor targets can still be tested, as Pollock et al. found that for most patients, SRS provides both symptom improvement and long-term tumor growth control, with a mean dose of 18 (range 16–20) Gy for benign tumors.8 Squire et al. further studied the outcomes in patients who received SRS targeted to the tumor.12 The authors in this series excluded all patients with malignant tumors or previous radiation treatment. Benign tumors in this report were treated with a mean dose of 12 (range 11–13) Gy, and the authors found a favorable initial treatment response of 81%, with a high recurrence rate of 66% at 1 year after treatment. Tanaka et al. also presented a successful patient series with tumor-only targets.13 In their cohort, they reported 2 patients who received a second SRS treatment targeting the trigeminal nerve in which they obtained pain relief, with only 1 of these patients experiencing a recurrence at 6 years after treatment. Therefore, they concluded that it is reasonable to consider a second SRS treatment for tumor-related intractable trigeminal pain.

The literature presented strongly suggests that SRS targeting both the offending tumor and the trigeminal nerve could yield the best results for pain relief in TN secondary to tumor. This was also found by Peciu-Florianu et al. in their systematic review and meta-analysis of SRS for TN in benign tumors.14 The authors illustrate the current heterogeneity in targeting policy and reporting of results, while also indicating that targeting both the tumor and the nerve appears to achieve better long-term results, but the rate of complications seems to be higher. Despite these findings, the authors raise further questions that must be addressed. Although our series could contribute to the notion that it might be most favorable to target both tumor and nerve, further long-term prospective inquiries are necessary to better characterize the clinical presentations and correlate these with the appropriate target for best results. The questions of suitable targets, sequence of treatment, and timing between sessions remain.

Despite its effectiveness for pain control, SRS should be recommended pragmatically. The clinical decision-making for patients with TN secondary to tumors must necessarily consider all the clinical variables of the TN, tumor, and patient. A multidisciplinary approach and comprehensive individualized patient assessment are warranted, including (among others) tumor histology and prognosis, tumor size and mass effect on neurovascular structures, any preexisting or evolving neurological deficits, clinical functional status, prior medical and surgical treatments, goals of care, and patient expectations. When there is risk for neurological worsening due to tumor size or mass effect, open surgery may be preferable over SRS. Conversely, when there is no concern for neurological worsening, SRS is a versatile and safe option for treating TN secondary to a broad range of tumors. In our experience, SRS has been safely used to treat TN secondary to metastases in neurologically stable patients who could not tolerate or did not choose invasive cranial procedures.

Limitations of the Study

The limitations of this single-institution review are compounded by the scarcity of the diagnosis of TN secondary to tumor, as well as by the constraints of retrospective review. The size of the presented cohort limits more detailed analysis of the differences between benign versus malignant tumors in terms of baseline characteristics and pain outcome measures. Additionally, patients lost to long-term follow-up represent a weakness in our analyses given the potential for introducing selection bias. Furthermore, although SRS is an established standard of care for treatment of TN and intracranial tumors, the relative novelty of this treatment modality limits more prolonged follow-up assessment. Future studies may aim to better characterize the impacts of different SRS treatment targets by analyzing a larger sample size or employing prospective techniques with optimized follow-up intervals. Nonetheless, based on our single-institution review of SRS for TN secondary to tumor, treatment to both the trigeminal nerve and offending tumor appears to derive most symptomatic benefit and durability of pain control.

Conclusions

SRS offers patients with TN secondary to tumor clinical symptomatic benefit. For optimal pain relief and response durability, treatment targeting both the tumor and the trigeminal nerve appears to be most advantageous.

Disclosures

Dr. Gibbs reports receiving honoraria from Accuray, Inc. Dr. Soltys reports being a consultant to Accuray, Inc., and receiving support of non–study-related clinical or research effort from Novocure, Inc.

Author Contributions

Conception and design: Meola, Ung. Acquisition of data: Hall, McCleary, Chuang. Analysis and interpretation of data: Hall, Ung, McCleary. Drafting the article: Hall, McCleary. Critically revising the article: Meola, Hall, Ung. Reviewed submitted version of manuscript: all authors. Approved the final version of the manuscript on behalf of all authors: Meola. Statistical analysis: Hall, Ung. Administrative/technical/material support: Hall, Gibbs, Soltys, Hayden Gephart, Li, Pollom, Chang. Study supervision: Meola, Ung.

Supplemental Information

Previous Presentations

An abstract for this paper was accepted for presentation as a poster to the annual meeting for the American Society for Radiation Oncology (ASTRO), October 23–26, 2022, in San Antonio, Texas.

References

  • 1

    Maarbjerg S, Di Stefano G, Bendtsen L, Cruccu G. Trigeminal neuralgia—diagnosis and treatment. Cephalalgia. 2017;37(7):648657.

  • 2

    Barker FG II, Jannetta PJ, Babu RP, Pomonis S, Bissonette DJ, Jho HD. Long-term outcome after operation for trigeminal neuralgia in patients with posterior fossa tumors. J Neurosurg. 1996;84(5):818825.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3

    Bullitt E, Tew JM, Boyd J. Intracranial tumors in patients with facial pain. J Neurosurg. 1986;64(6):865871.

  • 4

    Cheng TM, Cascino TL, Onofrio BM. Comprehensive study of diagnosis and treatment of trigeminal neuralgia secondary to tumors. Neurology. 1993;43(11):22982302.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5

    Shulev Y, Trashin A, Gordienko K. Secondary trigeminal neuralgia in cerebellopontine angle tumors. Skull Base. 2011;21(5):287294.

  • 6

    Kano H, Awan NR, Flannery TJ, et al. Stereotactic radiosurgery for patients with trigeminal neuralgia associated with petroclival meningiomas. Stereotact Funct Neurosurg. 2011;89(1):1724.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7.

    Huang CF, Tu HT, Liu WS, Chiou SY, Lin LY. Gamma Knife surgery used as primary and repeated treatment for idiopathic trigeminal neuralgia. J Neurosurg. 2008;109(suppl):179-184

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8

    Pollock BE, Iuliano BA, Foote RL, Gorman DA. Stereotactic radiosurgery for tumor-related trigeminal pain. Neurosurgery. 2000;46(3):576583.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9

    Santacroce A, Kamp MA, Budach W, Hänggi D. Radiobiology of radiosurgery for the central nervous system. BioMed Res Int. 2013;2013:362761.

  • 10

    Chivukula S, Kim W, Zhuo X, et al. Radiosurgery for secondary trigeminal neuralgia: revisiting the treatment paradigm. World Neurosurg. 2017;99:288294.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11

    Cho KR, Lee MH, Im YS, et al. Gamma knife radiosurgery for trigeminal neuralgia secondary to benign lesions. Headache. 2016;56(5):883889.

  • 12

    Squire SE, Chan MD, Furr RM, et al. Gamma knife radiosurgery in the treatment of tumor-related facial pain. Stereotact Funct Neurosurg. 2012;90(3):145150.

  • 13

    Tanaka S, Pollock BE, Stafford SL, Link MJ. Stereotactic radiosurgery for trigeminal pain secondary to benign skull base tumors. World Neurosurg. 2013;80(3-4):371377.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 14

    Peciu-Florianu I, Régis J, Levivier M, Dedeciusova M, Reyns N, Tuleasca C. Trigeminal neuralgia secondary to meningiomas and vestibular schwannoma is improved after stereotactic radiosurgery: a systematic review and meta-analysis. Stereotact Funct Neurosurg. 2021;99(1):616.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Collapse
  • Expand
  • View in gallery
    FIG. 1.

    SRS treatment planning was conducted prior to all treatments utilizing coregistered CT scans and MRI, allowing for limiting the dose to nearby organs at risk, including the brainstem (yellow outline) and optic apparatus. The SRS plan depicts conformal contouring of dose targeting both the left trigeminal nerve (red outline) and an offending meningioma of the left cavernous sinus (pink outline) in a 66-year-old woman. Both targets were treated in the same course of SRS and received a single fraction; the trigeminal nerve was prescribed 60 Gy, whereas the tumor was prescribed 14 Gy.

  • View in gallery
    FIG. 2.

    ΔBNI score allows for assessment of symptom relief over time compared across treatment targets irrespective of baseline BNI scale score. Trends in ΔBNI score with respect to time illustrate differences in the efficacy and durability of pain relief associated with the various treatment targets, i.e., trigeminal nerve only, tumor only, and both. Treatments to the trigeminal nerve (including nerve only and both) resulted in the most notable pain relief at initial follow-up, but treatments targeting both the trigeminal nerve and tumor are shown to sustain the most negative ΔBNI score to the 3-year post-SRS time point.

  • 1

    Maarbjerg S, Di Stefano G, Bendtsen L, Cruccu G. Trigeminal neuralgia—diagnosis and treatment. Cephalalgia. 2017;37(7):648657.

  • 2

    Barker FG II, Jannetta PJ, Babu RP, Pomonis S, Bissonette DJ, Jho HD. Long-term outcome after operation for trigeminal neuralgia in patients with posterior fossa tumors. J Neurosurg. 1996;84(5):818825.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3

    Bullitt E, Tew JM, Boyd J. Intracranial tumors in patients with facial pain. J Neurosurg. 1986;64(6):865871.

  • 4

    Cheng TM, Cascino TL, Onofrio BM. Comprehensive study of diagnosis and treatment of trigeminal neuralgia secondary to tumors. Neurology. 1993;43(11):22982302.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5

    Shulev Y, Trashin A, Gordienko K. Secondary trigeminal neuralgia in cerebellopontine angle tumors. Skull Base. 2011;21(5):287294.

  • 6

    Kano H, Awan NR, Flannery TJ, et al. Stereotactic radiosurgery for patients with trigeminal neuralgia associated with petroclival meningiomas. Stereotact Funct Neurosurg. 2011;89(1):1724.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7.

    Huang CF, Tu HT, Liu WS, Chiou SY, Lin LY. Gamma Knife surgery used as primary and repeated treatment for idiopathic trigeminal neuralgia. J Neurosurg. 2008;109(suppl):179-184

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8

    Pollock BE, Iuliano BA, Foote RL, Gorman DA. Stereotactic radiosurgery for tumor-related trigeminal pain. Neurosurgery. 2000;46(3):576583.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9

    Santacroce A, Kamp MA, Budach W, Hänggi D. Radiobiology of radiosurgery for the central nervous system. BioMed Res Int. 2013;2013:362761.

  • 10

    Chivukula S, Kim W, Zhuo X, et al. Radiosurgery for secondary trigeminal neuralgia: revisiting the treatment paradigm. World Neurosurg. 2017;99:288294.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11

    Cho KR, Lee MH, Im YS, et al. Gamma knife radiosurgery for trigeminal neuralgia secondary to benign lesions. Headache. 2016;56(5):883889.

  • 12

    Squire SE, Chan MD, Furr RM, et al. Gamma knife radiosurgery in the treatment of tumor-related facial pain. Stereotact Funct Neurosurg. 2012;90(3):145150.

  • 13

    Tanaka S, Pollock BE, Stafford SL, Link MJ. Stereotactic radiosurgery for trigeminal pain secondary to benign skull base tumors. World Neurosurg. 2013;80(3-4):371377.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 14

    Peciu-Florianu I, Régis J, Levivier M, Dedeciusova M, Reyns N, Tuleasca C. Trigeminal neuralgia secondary to meningiomas and vestibular schwannoma is improved after stereotactic radiosurgery: a systematic review and meta-analysis. Stereotact Funct Neurosurg. 2021;99(1):616.

    • Crossref
    • Search Google Scholar
    • Export Citation

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