How are you incorporating 68-Ga Dotatate PET scans in the management of grade I/II meningiomas?

Thank you for posing such a leading-edge question. I surmise its answer may have a rather different din a few years from now. However, to date, I am not using DOTATATE PET for meningioma. This is due partly to habit, availability, insurance constraints, and the specific clinical circumstances of the meningioma patients I see, and partly to a desire for additional data, but not to weighty reservations. Your question persuaded me to reconsider the data. This did not convince me to change practice immediately, but did open doors to several clinically meaningful potential uses for DOTATATE PET, exploiting the fact that meningiomas typically express high levels of somatostatin receptors. Please permit a review of some recent data I find interesting. If you desire a less tiresome synopsis, skip immediately to the final paragraph.

Ueberschaer and colleagues¹ compared surgeon-reported Simpson grade with findings from ⁶⁸Ga-DOTATATE PET/CTs obtained within 6 months post-resection for patients with WHO grade I meningioma. Their analysis included retrospective and prospective cohorts. Resections reported as Simpson grade I or II -- by definition gross total -- were often found to have tumor remnants on DOTATATE imaging: 62.5% in the retrospective cohort and 40.5% in the prospective group. Even MRI was falsely negative in 18.9%. Intriguingly, discordant results were more common with convexity (40%) or falcine (46.7%) meningioma than with skull base primaries (18.2%).

Sommerauer and co-authors² analyzed whether ⁶⁸Ga-DOTATATE PET predicts growth in patients with WHO I-III meningioma. Reviewing 64 meningiomas in 23 patients, they found SUVmax a strong growth rate predictor for WHO grades I and II (p<.001). Growing WHO I and II meningiomas had a higher SUVmax, not so with WHO grade III. Trans-osseous growth elicited considerably higher binding (p<.001). The authors opined that DOTATATE PET may enhance RT treatment planning, and noted that the expression of somatostatin receptors on meningioma provides impetus for radionuclide or other targeted therapy.

A recent meta-analysis³ of 6 studies including 111 patients with treatment-refractory meningioma receiving somatostatin receptor radionuclide therapy reported 6-month PFS (PFS-6) 94%, 48%, and 0% for WHO grade I, II, and III, respectively, and found that the risk of death decreased with increased applied activity. They found that this treatment was well tolerated noting limited late renal and pituitary effects. The PFS-6 numbers are potentially inviting, at least for WHO recurrent grade I and II meningioma. A RANO Review of surgery- and radiation-refractory meningioma by Kaley et al⁴ found a weighted average PFS-6 of 29% (95%CI 20.3% - 37.7%) with WHO I and 26% (95%CI: 19.3% - 32.7%) for WHO II/III meningioma.

Investigators from Cornell University, Ivanidze et al⁵, published series of 20 WHO grade II-III meningioma patients for whom ⁶⁸Ga-DOTATATE PET (17 PET/MRI and 3 PET/CT) was employed to evaluate disease extent or to differentiate recurrent meningioma from posttreatment change. They reported that DOTATATE PET was beneficial in assessing disease extent, that it assisted in differentiating treatment change or reactive dural thickening from progressive tumor, and that it identified additional meningiomas not clearly identified on MRI. Similar to Sommerauer et al,² they also found it helpful in delineating osseous invasion.

Roytman and co-authors⁶ evaluated dynamic ⁶⁸Ga-DOTATATE PET/MRI in 18 patients with 15 meningiomas and 5 regions of suspected post-treatment change and found significant differences between meningioma and treatment change, as well as different DOTATATE kinetics between meningioma and pituitary. Others have documented high physiologic somatostatin receptor expression in the pituitary gland.^4,5

These studies and others suggest that somatostatin receptor-based imaging may find beneficial application for our meningioma patients on several fronts, for instance confirming diagnosis with suspected meningioma, helping define which patients may benefit from definitive management versus observation, helping determine optimal intervals for follow-up and imaging, documenting extent of resection, response to treatment, and differentiating tumor progression from treatment change or from imaging findings such as reactive dural thickening or dural tail. Somatostatin PET may attain a deeper role in RT-planning, for instance for skull base meningioma when accurate definition of disease extent can be challenging on MRI. The prevalence of somatostatin receptors with meningioma may also potentially be exploited for targeted management including radionuclide therapy. However, DOTATATE has not yet gained any of these strongholds in clinical practice. Each of its plausible applications requires further study. Let this be encouragement for young investigators wanting to address an impactful clinical quandary for a very common neoplasm.

1. Ueberschaer et al., PMID 32827256.
2. Sommerauer et al., PMID 26865086.
3. Mirian et al., PMID 32859705.
4. Kaley et al., PMID 24500419.
5. Ivanidze et al., PMID 31107591.
6. Roytman et al. American Society of Neuroradiology 58th Annual Meeting 2020: ePoster.

Very nice review by Dr. @Dr. First Last. In addition to his nice review, I also like a new paper from Bashir et al., PMID 33526423 published in Clinical Cancer Research this year where the authors performed dotatatePET for 37 meningioma cases after GTR. They showed that 23/37 cases had PET avid disease, and later confirmed 18 had indeed residual disease or developed focal recurrence, so they estimated the scan had an accuracy of 90%.

I'm currently ordering such scan for very selected situation: complex recurrent meningioma case after prior RT where I'm considering focal SRS for salvage re-irradiation. Thus, I would like to use DotatatePET to estimate the extent of disease before committing on SRS. 

Another situation may be helpful in the future though I've not done it: atypical meningioma s/p GTR who would like to be observed and declined NRG BN003 study, so the scan may be helpful to r/o PET avid disease. Should ideally be studied in a prospective study.

To my knowledge, this scan is available for clinical use and can be approved by insurance with a pre-authorization process. 

This is a very nice synopsis of the available data. We have been using the Ga-68 DOTATATE PET for similar situations and have just over 50 patients now. In our experience, it is extremely useful for target delineation for falx/skull base tumors with osseous involvement, either GTR or STR. I have found it particularly useful for high grade meningioma grade 2/3 tumors. We will be presenting our institutional experience at ASTRO this year as an oral presentation.