Management of Complex CNS Tumours: Impact of Multiple Tumour Board Review

Simple Summary

Decision-making regarding optimal treatment in cancerous or non-cancerous brain tumours can be complex. To obtain multidisciplinary consensus, a patient’s file is commonly reviewed by a tumour board (TB). At our centre, 59 patients were reviewed by multiple TBs in order to arrive at a consensus treatment recommendation. The most common reason for review by more than one TB was proximity to structures required for vision, such as the optic nerves. The final management plan involved conventionally fractionated radiation in 21/59, stereotactic radiosurgery in 18/59, surveillance in 12/59, surgery in 3/59, drug therapy in 3/59, and other approaches in 2. 20/59 patients were treated with palliative intent. Among all patients who ultimately received radiotherapy, the median wait time between the first TB discussion and the first treatment was 56 days.

Abstract

Background. Patients with malignant or benign central nervous system (CNS) tumours are evaluated for suitability of treatment modality based on multiple clinical and tumour-related factors. To obtain multidisciplinary consensus, a patient’s file and imaging are commonly reviewed by a tumour board (TB). There are three relevant weekly TB venues at our institute—gamma knife stereotactic radiosurgery (SRS) intake rounds, CNS rounds, and stereotactic body radiotherapy (SBRT) rounds—which are attended by non-overlapping clinician teams. We explored the clinical parameters prompting multiple TB reviews in patients with complex CNS tumours. Methods. Data were retrospectively obtained from electronic medical records. Patients referred for discussion at SRS rounds (November 2017–June 2020) were cross-referenced with those reviewed in CNS rounds and SBRT rounds. The cohort of interest included patients who underwent review at more than one TB for the same indication. Patient, tumour, and treatment factors were abstracted, and descriptive statistics were calculated. A sub-cohort of patients with pre-plans created for both SRS and conventionally fractionated external beam radiotherapy (EBRT) was identified. Dosimetric data were analyzed. Results. Of 1091 patients, 87 (8.0%) were discussed at more than one TB. 59/87 (67.8%) patients were reviewed at two TBs pertaining to the same CNS lesion and comprised the study cohort. The most common tumour type was meningioma (20/59), and the most common reason for multiple discussions was proximity to optic structures (19/59). After TB discussions, 25/59 patients were seen in consultation by one specialist, 29/59 by two, and 5/59 by none. Overall, the final treatment decisions were conventional EBRT in 21/59; SRS in 18/59; surveillance in 12/59; surgery in 3/59; systemic therapy in 3/59; proton referral in 1/59; and SBRT in 1/59. A total of 20/59 patients were treated with palliative intent. Among all patients who ultimately received radiotherapy, median interval between the first TB discussion and the first RT treatment was 56 days (IQR 7.5–65.5 d). The pre-plan sub-cohort consisted of four patients, all of whom were ultimately treated with conventional EBRT. Conclusions. Evidence to support optimal treatment for some complex CNS tumours can be limited. Multiple radiotherapy modalities may be equally favourable (or unfavourable) options. Proximity to the optic apparatus and previous CNS irradiation are common reasons for clinical equipoise. Tumour board review is an essential tool in formulating a multidisciplinary care plan; however, attention should be paid to ensuring that subsequent consultations and treatment initiation are not unduly delayed.

1. Introduction

Patients with benign or malignant central nervous system (CNS) tumours are evaluated for suitability of treatment based on clinical and tumour-related factors. When multiple modalities are available, such as surgical resection, stereotactic radiosurgery (SRS), or conventionally fractionated external beam radiotherapy (EBRT), the optimal treatment, timing, combination, and sequencing of treatments can be unclear. This is often due to a lack of level-one evidence, resulting in multiple options that are equally favourable (or unfavourable), especially for complex lesions.

CNS lesions are considered complex when in proximity to organs at risk, if there is a cystic component, or if they are large, hemorrhagic, or multicentric [1]. Other challenging situations include recurrence or progression after previous surgery or radiotherapy (RT). Target coverage and healthy tissue sparing are important parameters to consider when determining the optimal RT technique, especially for complex lesions [2]. Advantages and disadvantages of each modality must be weighed carefully, including patient wishes and the risk of side effects, prior to formulating recommendations.

Optimal management of CNS tumours requires a multidisciplinary team [3]. To obtain multidisciplinary input, a patient’s chart is often reviewed in a meeting format called a tumour board (TB) [4]. Tumour boards are regularly scheduled formal discussions of treatment strategies for specific patients, including physician and non-physician providers [5]. Neuro-oncology TBs for benign and malignant brain tumours commonly include neurosurgeons, neuro-oncologists, radiation oncologists, radiologists, clinical trial representatives and a nurse coordinator [4]. Benefits of TBs include efficient coordination of multiple providers, direction for complicated cases, a forum for communication, education, and screening for clinical trial eligibility [4]. As such, TBs are valuable for clinical decision-making in challenging cases [4].

For CNS tumours, there are three relevant TBs at our centre: gamma knife (GK) SRS/fractionated stereotactic radiotherapy (FSRT) rounds, CNS rounds, and stereotactic body radiotherapy (SBRT) rounds. While any clinician can attend any or all of these TB, due to workload and scheduling conflicts, in practice, these TB are attended largely by non-overlapping providers. Therefore, if a patient has a complex CNS history or lesion, discussion in more than one of these settings may be helpful to ensure all expertise is available.

There is a lack of level-one literature to support decision-making for complex CNS patients. In challenging circumstances, preliminary treatment plans (called pre-plans) for more than one RT modality can be calculated. This increases workload for dosimetrists and radiation oncologists but provides a concrete way to compare dosimetry and therefore target coverage and risk of adverse effects.

Our objective was to identify clinical and radiological parameters that correlate with review at multiple TB rounds, indicating a complex CNS tumour presentation. Our aim was to identify, if possible, added benefit of multiple TB reviews, factors which correlated with protracted decision-making, and any resulting delay in the initiation of treatment. We also outlined a practical approach for identifying optimal radiation modality pre-planning in situations of clinical equipoise where explicit literature guidance is lacking.

2. Methods

The patients referred for discussion at GK SRS/FSRT intake rounds between their commencement on 27 November 2017, and 26 June 2020, comprised the initial sampling cohort. At the time a request for discussion is made, the pertinent clinical question(s) are indicated in order to focus discussion. These patients were cross-referenced with patients reviewed at CNS rounds and SBRT rounds over the same time period. The final study cohort included only patients reviewed in two or more multidisciplinary TB settings for the same tumour. Main modalities under consideration included: surgical resection, LINAC-based SRS or FSRT, gamma knife SRS or FSRT, and conventionally fractionated EBRT.

Medical charts and treatment planning software, including Aria MO, Aria RO, Eclipse, Leksell GammaPlan v11, and gamma knife (GK) clinical records, were retrospectively reviewed. Patient, tumour, and treatment factors were collected. The data were anonymized and compiled into an Excel spreadsheet after assigning each patient a unique study ID number. Descriptive statistics were calculated.

A sub-cohort of patients was identified who underwent pre-planning for more than one radiotherapy technique. Dose fractionation schedule, target coverage, optic apparatus (OA) dose, and total beam-on time were extracted. The plans were compared utilizing QUANTEC and HyTEC dose constraints.

Ethics approval was granted by the Health Research Ethics Board of Alberta Cancer Committee.

3. Results

Between November 2017 and June 2020, 1091 patients were discussed at GK SRS rounds. Of those 1091, 87 (8.0%) were discussed at more than one TB. 59/87 (67.8%) of those were reviewed at two TBs pertaining to the same CNS lesion and comprised our study cohort. Fifty patients were discussed at both GK and CNS rounds, seven patients were discussed at both GK and SBRT rounds, and two patients were discussed at both CNS and SBRT rounds. No patient was reviewed by all three TBs.

Patient and tumour characteristics are summarized in

Table 1. Patient and tumour factors. ^Other includes PNET, hemangiopericytoma, and astrocytoma.

Factor	N = 59 (%)
Female	35 (59.3%)
Relevant comorbidities	42 (71.2%)
Previous surgery	46 (78.0%)
Previous EBRT	17 (28.8%)
Previous SRS/FSRT	4 (6.8%)
Benign	25 (42.4%)
Malignant	32 (54.2%)
Unknown	2 (8.5%)
Recurrent	22 (37.3%)
Tumour type
Meningioma	20 (33.9%)
Metastasis	9 (15.3%)
Pituitary	7 (11.9%)
Glioblastoma	5 (8.5%)
Ependymoma	4 (6.8%)
Chordoma	2 (3.4%)
Pineal	2 (3.5%)
Other^	10 (16.9%)

. There were 19 different diagnoses, the most common being meningioma (20/59). Brain metastases accounted for 9/59 cases, pituitary lesions for 7/59, and glioblastoma multiforme (GBM) for 5/59. On average, the tumours were 2.8 cm (range 0.5–9.9 cm) in greatest dimension; size was not available for eight tumors. In cases where more than one tumour was present, the largest size was recorded.

The most common reason for discussion at multiple TBs was proximity to optic structures (19/59) (

Table 2. Reasons for tumour board discussion. Frequency does not add up to 59, as each patient could have multiple reasons for discussion. Abbreviations: CNS—central nervous system; EBRT—conventionally fractionated external beam radiation therapy; GK—gamma knife; GTR—gross total resection; LINAC—linear accelerator; MRI—magnetic resonance imaging; OA—optic apparatus; RT—radiotherapy; SBRT—stereotactic body radiation therapy; SRS—stereotactic radiosurgery; STR—subtotal resection.

Reasons	GK SRS Rounds	CNS Rounds	SBRT Rounds
Proximity to optic apparatus	19	19
Previous CNS radiotherapy	11	12
Review of all modalities for optimal management plan (surgery, radiotherapy, systemic)	1	11
Treatment options, not a GK candidate		11
Recurrent or progressive tumour	8	8	1
Compare SRS versus EBRT	7	4
Adjuvant treatment options post-STR, no further surgery possible	6	5
Concern regarding normal structures other than OA	6	3
Aggressive tumour	6	2
Adjuvant treatment options post-GTR	6		3
Suitability for SRS	5		7
Treatment options, not a surgical candidate	4	5
Compare surgery versus radiotherapy	4	3
Compare LINAC versus GK SRS		2
Treatment options, not a radiotherapy candidate		2
Compare RT versus surveillance	1	2
Review follow-up MRI: recurrence vs. radiation toxicity	2
Recommended for review by other tumour board	2
Other	2	1
Total	90	90	11

). After the discussion in GK SRS rounds, the recommendation was in support of GK SRS (6/19) or conventionally fractionated EBRT (6/19). After the discussion in CNS rounds, the recommendation was in support of conventionally fractionated EBRT (8/19) or stated equipoise between GK SRS and conventional EBRT (3/19) (

Table 3. Tumour board recommendations. Frequency does not add up to 59, as each patient could have multiple recommendations after discussion. Abbreviations: EBRT—conventionally fractionated external beam radiation therapy; GK—gamma knife; LINAC—linear accelerator; MRI—magnetic resonance imaging; RT—radiotherapy; SBRT—stereotactic body radiation therapy; SRS—stereotactic radiosurgery.

Recommendation	GK SRS Rounds	CNS Rounds	SBRT Rounds
GK SRS	22	14	3
Refer to different rounds setting	21
Conventional EBRT	9	25	2
Not an SRS candidate	9
No radiotherapy	2	5
Surgical resection	4	2
Supportive care only	4
Equivalent options to be presented to patient		4
LINAC SRS			4
Systemic therapy	1	4
Surveillance	3	3	1
No consensus	1	2
Proton therapy		2
Conventional EBRT and GK SRS considered equivalent	1
Review literature for supporting data	1
Surgery followed by adjuvant conventional EBRT	1
Further imaging required (postoperative MRI)	1
Clinical trial		1
Referral to different radiotherapy clinic			1
Total	80	62	11

). After the discussion in SBRT rounds, the patients were most frequently recommended to undergo LINAC-based SRS (4/9) or gamma knife SRS/FSRT (3/9) (Table 3).

After TB discussions, 25/59 patients were seen in consultation by one specialist, 29/59 by two, and 5/59 by none. For patients with metastatic lesions, the median interval between TB discussions was 9 days (IQR 4–12 d), median interval between consults was 14 days (IQR 13–15 d), and median interval from last consult to RT start was 4 days (IQR 1.5–5.8 d) for those undergoing radiation. Corresponding values for non-metastatic patients were: 17 days (IQR 9–70 d), 47 days (IQR 4–86 d), and 26 days (IQR 13–40 days), respectively. Among all patients who ultimately received irradiation, median interval between the first TB discussion and RT treatment initiation was 56 days (IQR 7.5–65.5 d).

Four patients, all benign, underwent pre-plan construction to compare GK SRS and conventional EBRT techniques to aid decision-making (

Table 4. Comparison of plan metrics. Abbreviations: CNS—central nervous system; EBRT—external beam radiation therapy; GK—gamma knife; GTR—gross total resection; Linac—linear accelerator; MRI—magnetic resonance imaging; PTV—planning target volume; recommend—recommendation; RT—radiotherapy; SBRT—stereotactic body radiation therapy; STR—subtotal resection; TB—tumour board; UNK—unknown.

	Case 1		Case 2		Case 3		Case 4
Diagnosis	Meningioma		Meningioma		Meningioma		Pituitary
Location	Left temporal extending into cavernous sinus		Cavernous sinus		Right optic canal		Pituitary
Size (cm)	4 cm		3.4 cm		0.8 cm		2.6 cm
Patient wishes	Conventional EBRT		Preserve function of unaffected eye		UNK		UNK
TB recommend	Conventional EBRT		Conventional EBRT and GK SRS equivalent		Conventional EBRT		Conventional EBRT
Radiation Plan Parameters
Modality	Linac	GK	Linac	GK	Linac	GK	Linac	GK
Dose fractionation	54 Gy/30	12 Gy/1	54 Gy/30	13 Gy/1	54 Gy/30	12 Gy/1	54 Gy/30	37.5 Gy/5
% PTV covered by prescription	94.5%	98.9%	79.6%	98.0%	86.1%	98.4%	89.1%	99.3%
Optic nerve dmax (cGy)	5472 cGy	880 cGy	5400 cGy	1330 cGy	5715 cGy	2070 cGy	Left: 5481 cGy Right: 5477 cGy	Left: 3580 cGy Right: 4180 cGy
Optic apparatus dmax (cGy)	5479 cGy	970 cGy	5432 cGy	1330 cGy	5715 cGy	2070 cGy	5481 cGy	4200 cGy
Total beam-on time per course (min)	74 min	147 min	70 min	109 min	90 min	75 min	80 min	250 min

). Three patients had meningiomas, and one had a pituitary tumour. Proximity to the OA was the reason for pre-planning in all cases. All LINAC plans were prescribed as 54 Gy in 30 fractions. GK plans were prescribed as 12–13 Gy in one fraction for the meningiomas and 37.5 Gy in five fractions for the pituitary tumour. Total beam-on time for the LINAC plans, on average, was 80.9 min. Average GK beam-on time was 145.3 min (range 75–250 min). The final treatment decision for all four patients was conventionally fractionated EBRT.

Overall, final treatment decisions were: conventional EBRT in 21/59; SRS in 18/59; surveillance in 12/59; surgery in 3/59; systemic therapy in 3/59; proton referral in 1/59; and SBRT in 1/59 patients. 20/59 patients were treated with palliative intent.

4. Discussion

Upon the radiological diagnosis of a CNS tumour, patients expect prompt management [6]. Most patients with a brain tumour will be seen by many clinicians [3,7]. Clinical management often requires complex decision-making and complicated care [8,9]. Multiple investigations and consultations can be required before definitive treatment can be recommended [7]. Multidisciplinary TB review in a single setting by a range of professionals with different expertise facilitates appropriate, organized care [3,4,8,9]. National Comprehensive Cancer Network guidelines (2025) strongly recommend multidisciplinary TB review for any newly diagnosed, recurrent, or progressive malignant brain tumour, as well as for meningiomas [3]; interestingly, the European Association of Neuro-Oncology 2021 guideline on meningioma does not allude to TB review [10].

The overall effectiveness of multidisciplinary TB meetings depends on structure, function, schedule, and expertise of attendees [11]. A consensus management plan is developed by discussion between different specialties regarding the advantages and disadvantages of various treatment approaches for specific patients [9]. Clarification of, or new, clinical information may be provided by the presence of different clinicians [12], particularly when radiologists and pathologists participate [9]. Sharing TB recommendations with patients supports the informed decision-making process [9].

In our cohort, TB review could have occurred at any point in the treatment pathway: prior to confirmation of diagnosis; after confirmation of diagnosis but prior to treatment initiation; after primary treatment but prior to adjuvant treatment; or at progression or recurrence. Main participant differences between tumour board settings in our study were the presence of a pathologist at one TB, a neuroradiologist at a different one, and neither present at the third. Two TB meeting settings were localized in the same facility, while the third was located in a different institution with its own electronic medical record and treatment delivery software. Accessing separate health care systems poses challenges in terms of collaboration, communication, and information-sharing, potentially exacerbating delay; fragmentation, in the worst case, leads to the duplication of intervention [7].

Pillay et al. systematically reviewed English literature published from 1995 to 2015 to evaluate potential benefits of TB meetings [9]. While 27 articles included a range of countries and types of cancer, none were from Canada or included CNS tumours. Patients reviewed at multidisciplinary TBs, versus those not reviewed, after controlling for demographic and tumour factors: had complete staging more frequently; received treatment more often; received adjuvant therapy more often; had a higher frequency of adherence to guidelines; and possibly even longer survival [9]. Similar to our study, whether patients are presented for case discussion at TB depends on institutional policy, national guidelines, and, particularly, the direction of the treating clinician [9]. Physicians choose to present patients who are more complex, interesting, or those more likely to benefit. While TB review has several benefits, since meetings occur on a weekly or biweekly basis, awaiting this multidisciplinary input can introduce delays in treatment initiation. However, literature results are conflicting regarding whether TB consistently increases or decreases time from diagnosis to treatment [9].

Practice guidelines have thus far not specified what should be considered maximum allowable delay to the initiation of therapy [6,13]. Literature findings are heterogeneous on recommended timing of resection, for example, suggesting this may differ by CNS tumour type [13]. From the perspective of RT, according to the Canadian Institute for Health Information, patients should start radiation treatment within 28 days of being assessed as ready to do so; in 2024, 83% nationally met this benchmark [14]. Our centre has a target wait time of less than 20 days between RT consult and first fraction. Patients who required multiple TB discussions had a median wait time of 56 days to treatment initiation. Several additional factors at the patient, provider, and system levels also contribute to the interval between radiological diagnosis and treatment start [6,15]. Evidence for the impact of wait time on patient outcomes in neuro-oncology is sparse and mainly inconclusive [15,16]. Prolonged time to treatment increases the risk of tumour progression, symptom worsening, functional decline, subtotal resection (STR), more complex surgery, postoperative complications, and ultimately decreased tumour control and potentially shorter survival [6,17]. Uncertainty around the diagnosis and prognosis awaiting intervention for a newly diagnosed brain tumour causes significant anxiety for patients and families [6,17].

Two meta-analyses have investigated the impact of delay of surgery, radical and adjuvant RT [15,18]. Multiple tumour types were included in both reviews, but neither included CNS tumours. However, Chen et al. postulated that the fundamental mechanism by which delay might affect local control is common to all types of cancer [18]. Most of the included studies reported an increase in local recurrence with increasing wait time [18]. There was also a consistent association of surgical delay with increased mortality for all indications studied, with a hazard ratio between 1.06 and 1.08 for each four weeks (i.e., 6–8% increased chance of death for each 4-week delay in treatment initiation) [15]. No studies have quantitatively examined the relationship between wait time and quality of life to date.

However, poorer outcomes after the shortest wait times have been observed in other malignancies, which is termed the ‘waiting time paradox’ [19]. Patients with rapidly progressive and/or severe symptoms presenting through the emergency department are selected for expedited investigation and treatment [18]. Conversely, longer wait times are associated with better survival [16]. Some patients with mild or stable symptoms, improvement on steroids, or smaller tumours can tolerate waiting for intervention [6,13,20]. It can be challenging to decide whether to schedule expedited surgery or first proceed with medical and psychological optimization of the patient [6,13,17].

Wait times in a cohort of multiple subtypes of CNS tumours from 32 high volume neurosurgical centres were reported by the Pakistan Brain Tumour Epidemiology Study [17]. The 1474 patients included had a recorded date of first radiological diagnosis and first surgery. Longer average wait times for surgery were associated with public hospital vs. private sector (94.1 vs. 75.1 days respectively, p < 0.001), regardless of tumour type. Patients undergoing gross total resection (GTR) had a significantly longer wait time than those undergoing STR (p < 0.001), regardless of tumour type. Patients with meningioma had the longest waiting period of 106 days (95%CI 76–95 days) versus those with hemangioblastoma, metastases, and brainstem gliomas (range 59.5–61.3 days). Patients surviving longer after surgery tended to have waited longer for resection (91.9 vs. 77.4 days, p < 0.001). Wait times for adjuvant RT were not available [17].

Meningiomas comprised the most common diagnosis in our cohort. The vast majority (>90%) of meningiomas are WHO grade I [3]. Meningiomas are often incidentally diagnosed during the evaluation for other disorders, as an extra-axial dural-based mass that uniformly and markedly enhances with contrast [21]. While grade cannot be definitively determined prior to surgery [13], most incidental (asymptomatic) meningiomas do not demonstrate clinically significant growth on long term follow-up and can be safely observed without treatment [21,22,23,24]. As such, observation is the primary strategy in asymptomatic patients with a newly diagnosed or slowly growing meningioma [3,10]. Annual MRI scans should be undertaken in suspected meningioma for 5 years; thereafter, intervals can be increased [10]. Optimal duration of monitoring is unclear [22]. If a presumed meningioma shows rapid growth during observation, a higher grade (or alternative diagnosis) must be considered [10].

Most natural history studies on incidental meningiomas have found a slow rate of growth (average < 5% volumetric increase per year) [22]. 60–65% of patients have a self-limiting growth pattern, with no growth over several years [21,23,25]. However, 5–10% of patients will develop new symptoms over a mean follow-up period of approximately 5 years [21,22]. Imaging features such as peritumoural edema, hyper- or isointense signal on T2 MRI, size > 3 cm, and a lack of calcification predict a higher risk of progression [21,22,24]. Although most meningiomas that progress will do so within 2–5 years, some can remain indolent for longer periods before demonstrating accelerated growth [21,22,25]. However, radiographic growth will not become clinically significant until size reaches a certain threshold or nears eloquent brain [22]. In one cohort, while 75% of tumours increased by 15% or more in volume, all patients remained asymptomatic [23]. In another study, 25.4% of tumours showed rapid growth [24]. In the setting of NF2, approximately 10% of meningiomas will grow rapidly (defined as ≥2 cm³/year) [22].

Therapy is indicated in symptomatic or growing meningiomas [10]. However, in many patients, the optimal timing of such intervention is not certain, and institution of therapy to control a tumour prior to neurological compromise is ideal [25]. Grade I meningiomas may have a low proliferative index, but the location can cause significant neurological compromise due to mass effect [25]. It can be unclear what constitutes growth sufficient to trigger intervention—in one study, progression required >5 mm absolute increase in the largest CT diameter, as agreed by two clinicians [21]. Decisions to treat depend on tumour factors, clinical status, physician judgement, referral timing, literature evidence, available expertise, and patient wishes [3,22,25,26]. The primary treatment modality is surgery, which rapidly relieves mass effect and neurological symptoms and provides tissue to confirm the diagnosis [10]. The extent of resection depends on tumour location, consistency, size, and involvement of critical neurovascular structures [10]. While there are no randomized trials comparing surgery to other therapies, RT can be an alternative in specific clinical situations, particularly if tissue confirmation is not required [10].

Depending on the WHO grade, RT may be the primary treatment, or as an adjunct to surgery, either immediately following surgery (adjuvant) or delayed until progression/recurrence (salvage) [22]. For many indications, the optimal timing of adjuvant RT is not known [22], and early postoperative evaluation by a radiation oncologist is recommended [3]. Patients with incompletely resected WHO grade I meningioma without neurological deficits typically embark on surveillance [10]. While patients with grade II tumours generally exhibit shorter intervals to recurrence, some patients with grade I tumours show unexpectedly early tumour relapse, while some with grade II tumours can have a long clinical course without requiring further treatment [10]. RT may prevent the need for further surgery, but this must be balanced against the potential risks of long-term radiotherapy toxicity [10].

RT can be delivered via conventionally fractionated conformal EBRT, SRS, or FSRT [10]. Deep and midline lesions, along with those near the OA, pose challenges for radiation, similar to the constraints imposed by these factors on resectability. Conventionally fractionated EBRT is preferred for large target volumes such as surgical cavities, multifocal or diffuse tumours, and when margins are required to encompass subclinical extension [26]. EBRT utilizes a thermoplastic mask but not stereotactic guidance [26]. For conventional LINAC plans, the optimization goal is to deliver 100% of the prescribed dose to 95% of the target volume [27]. SRS is a method of radiation delivery that uses stereotaxis and image guidance to precisely deliver a high biologically effective dose using either GK or LINAC platforms [28,29,30]. Additional margins are not utilized, and, therefore, SRS carries a risk of regional treatment failure [26]. SRS is generally considered for small (<3 cm) lesions with distinct margins located away from highly functional areas [28,30,31]. A major benefit of SRS is the delivery of high doses per fraction to the target with a steep dose gradient outside, minimizing irradiation of surrounding normal brain [26,29,30]. Conventionally fractionated EBRT and SRS have comparable control rates for benign meningiomas [32,33], with differences in number of fractions required and potential side effects [32]. FSRT (multiple fractions delivered with stereotactic precision) is an alternative strategy for large tumour volumes [10].

In terms of utilization of SRS for WHO grade I meningiomas, Bowden et al. retrospectively analyzed 238 patients (1995–2019) with at least 2 years of follow-up [25]. They evaluated whether the timing of adjuvant SRS affected outcomes for residual or recurrent tumours. 12% had GTR, 88% had STR, and 9% had multiple prior surgical procedures. The median time between last craniotomy and SRS was 22.4 months (range 0.1–282 months). Prior to SRS, neurological symptoms or signs were reported in 60% of patients, of whom 15% (21 patients) experienced symptom improvement subsequently, correlating significantly with shorter interval to adjuvant SRS. There was no difference in tumour control between groups having SRS within 3 months, or by 6, 12, or 24 months after surgery regardless of extent of resection [25]. After SRS, 58% of patients had stable tumour, and 27% had a decrease in size. 15% progressed within or directly adjacent to the treatment field, at an average of 6.3 years (range 1–24.4 yrs). The authors acknowledged the likely effect of selection bias, noting that patients referred earlier may have been deemed at higher risk of tumour progression and neurological compromise [25].

Atypical meningiomas (WHO grade II) are typically characterized by a mean growth rate of 124.2% per year [34]. In atypical meningioma, therapy is mandatory, with surgery as the primary modality [10]. Whether early adjuvant RT reduces the risk of recurrence after GTR remains unanswered; however, after STR and in the setting of recurrence, RT is recommended [10]. Either fractionated conventional EBRT or SRS can be utilized, which differ in target volume, schedule, immobilization, and biologically equivalent dose [26]. However, in one retrospective cohort analysis, there was no difference in local control or toxicity between modalities, after matching for location, brain invasion, and necrosis [26]. Sun et al. reported that salvage RT at a mean of 32.1 months after surgery showed similar local control as adjuvant RT at a mean of 4.3 months postoperatively [26]. They concluded that RT modality and timing should be individualized for a given patient by the multidisciplinary team [26].

WHO grade III meningiomas are characterized by rapid growth, early recurrence, and risk of metastasis, and radical surgery followed by fractionated EBRT is recommended [3,10].

Exemplifying the challenge of determining the optimal therapeutic modality and timing in meningiomas is a case report published by Tan et al. [7]. They describe a 70-year-old female who presented with a 4-year history of progressive occipital headaches. The initial MRI demonstrated a 3.7 × 3.5 cm right inferior clival meningioma projecting into the anterior lip of the foramen magnum, encasing the right vertebral artery, posteriorly displacing the medulla and compressing the cerebellar tonsils [7]. Multiple consultations were pursued in three different regions regarding the roles of neurosurgery, SRS, and conventional EBRT. She was not reviewed in a multidisciplinary TB until after consultation with the initial radiation oncologist, SRS team, and three neurosurgeons. All specialists ultimately recommended the same management plan (fractionated EBRT). By the time of the RT treatment planning MRI, the tumour measured 4.2 × 3.9 cm [7]. The process of obtaining multiple opinions lasted approximately 12 months. Over this time, she developed worsening headaches, decreased energy, generalized limb weakness, dysphagia, and a significant decline in balance. As it is far from certain that RT will shrink meningiomas, but more likely only halt further growth, earlier treatment could have prevented her clinical and functional deterioration. Although providing patients with the best possible treatment is important, this must be balanced with timeliness and local resource availability [7].

Salvage of progressing pituitary tumours is another common indication for SRS, fractionated radiosurgery, or EBRT [35]. Unresectable pituitary adenomas—for example, those invading the cavernous sinus—can be treated with SRS, which provides a sharper dose fall-off than EBRT [35]. While an SRS plan can be designed to carve the dose away from critical structures, this requires relative underdosing of the target [35,36,37]. For tumours near the OA, which will be treated with high doses per fraction, FSRT and/or relative undertreatment is required to avoid exceeding optic nerve tolerance [28,33,35,36,37]. In such cases, standard fractionation with EBRT is often preferred [33].

Radiation-induced optic neuropathy (RION) is delayed radionecrosis of the optic nerve [38]. This generally occurs within 3 years of radiation and can result in permanent vision loss [38]. According to HyTEC dose tolerances for hypofractionated schedules, the risk of RION is <1% with OA maximum point doses of <10 Gy in one fraction, 20 Gy in three fractions, and 25 Gy in five fractions [39]. QUANTEC dose tolerances for RION after conventional EBRT report a risk < 3% with maximum point doses of <55 Gy [40]. Prior irradiation is associated with a 10-fold increased risk of RION [39]. It is important to recall that HyTEC dose constraints apply to patients who have not received prior radiation. However, prior CNS radiation was the second most common reason for multiple TB discussions in this study.

In our pre-planning sub-cohort, conventional LINAC plans for cases 1, 2 and 4 respected QUANTEC dose constraints at a cost of relative underdosing for cases 2, 3 and 4, shown by the percentage of the PTV encompassed by the prescription isodose. The GK preplan for case 1 also met HyTEC dose constraints (Table 4). Logistic issues and, therefore, cost to the patient are also essential considerations. Conventional EBRT is delivered in 25–30 fractions over 5–6 weeks. SRS requires one to five fractions but entails more time on the treatment couch per fraction, especially with GK. GK beam-on times of 2 or 3 hours can be challenging for even the most cooperative patient to tolerate, and other radiation modalities should be considered in those situations [41]. All patients who underwent pre-planning in this study were ultimately treated with conventional fractionation.

The strengths of our study include a sampling cohort drawn from over 1000 patient referrals spanning almost 3 years. Attendees at the three tumour boards included multiple experienced physician and non-physician providers based at two tertiary hospitals with a catchment area of over 1.5 million people. The limitations of retrospective chart reviews are well-known and, in this study, influenced data availability on specific reasons for TB review and subsequent outcomes. It is unknown whether treatment options were impacted as a consequence of delay (i.e., patients who were initially resectable became unresectable, or lesions initially targetable via SRS ultimately required FSRT or EBRT). All patients referred to the GK programme or for CNS radiation were reviewed in a TB as per standard protocol. Patients under consideration for SBRT by any radiation oncologist could be referred for discussion at SBRT rounds, but this was not mandatory. All three TBs initially took place in-person; however, over the final 6 months of the study period, all transitioned to virtual only due to the COVID-19 pandemic. Information on neurological symptoms, performance status, quality of life, and steroid requirements during the waiting period were not consistently available. Time from initial symptom onset to imaging diagnosis was not consistently available.

Future work includes the evaluation of clinical outcomes, with a plan to compare local control, recurrence rates, salvage treatment, and survival with a matched population reviewed at one TB. It will also be beneficial to examine if TB meetings impacted positively upon communication between health professionals, by examining, for example, rates and timelines of cross-referral between disciplines [9].

5. Conclusions

Level-one evidence supporting optimal treatment recommendations for complex, especially unresectable, CNS tumours, is limited. Multiple radiotherapy modalities may be equally favourable (or unfavourable) options. Proximity to the optic apparatus and previous CNS irradiation are common reasons for clinical equipoise. Tumour board review is an essential tool in formulating a multidisciplinary care plan; however, attention should be paid to ensuring that subsequent consultations and treatment initiation are not unduly delayed. In our cohort, all cases with sufficient uncertainty about the ideal radiation modality to prompt pre-planning ultimately underwent conventionally fractionated external beam radiation treatment.