Sharjeel Usmani  ( Department of Nuclear Medicine, Sultan Qaboos Comprehensive Cancer Care and Research Center (SQCCCRC), Muscat Oman. )
Anjali Jain  ( Department of Nuclear Medicine, Sultan Qaboos Comprehensive Cancer Care and Research Center (SQCCCRC), Muscat Oman. )
Syed Furqan Hashmi  ( Radiation Oncology, Sultan Qaboos Comprehensive Cancer Care and Research center (SQCCCRC), Muscat Oman. )
Layth Mula-Hussain  ( Radiation Oncology, Sultan Qaboos Comprehensive Cancer Care and Research center (SQCCCRC), Muscat Oman. )
Khulood Al Riyami  ( Department of Nuclear Medicine, Sultan Qaboos Comprehensive Cancer Care and Research Center (SQCCCRC), Muscat Oman. )
Sofiullah Abubakar  ( Department of Nuclear Medicine, Sultan Qaboos Comprehensive Cancer Care and Research Center (SQCCCRC), Muscat Oman. )
Muhammad Shahzad Shamim  ( Section of Neurosurgery, Department of Surgery, Aga Khan University Hospital, Karachi. )

Meningiomas overexpress somatostatin receptors (SSTR). PET imaging with SSTR ligands such as 68Ga-DOTA-peptide has recently shown high diagnostic accuracy in identification of meningiomas due to lack of normal bone and brain activity. PET-derived parameters, especially gross tumour volume (GTV) delineation improves inter-observer variability and appears to be particularly promising for RT planning. The potential strength of 68Ga-DOTA in the ongoing assessment of treatment response and disease progression in meningioma, particularly in the post-surgical and post-radiation settings is encouraging. More prospective randomized studies with large cohorts of patients are required to define the effective role of this modality.

 

Keywords: 68Ga-DOTA PET/CT; Meningioma; 177Lu-DOTATATE; PET/CT; radiotherapy planning.

 

DOI: 10.47391/JPMA.23-44

 

Review of Literature

 

Meningiomas are the most common primary brain tumour and represent approximately 30% of intracranial tumours. The reported incidence is 8.33 per 100,000.¹ The World Health Organization (WHO) has classified meningiomas into three different grades, on the basis of histologic findings and presence/absence of brain invasion: grade 1, grade 2 (atypical), and grade 3 (anaplastic).²  Atypical and anaplastic meningiomas have 5-years overall recurrence rates of 40% and 80%, respectively.³ Most common treatment options are neurosurgical resection and various radiotherapy options such as radiosurgery and external fractionated radiotherapy. Radiation therapy is the preferred treatment for symptomatic meningiomas not amenable to surgical resection and is delivered in the adjuvant setting following resection of WHO II and III meningiomas.⁴

Contrast-enhanced MRI is currently the modality of choice for characterizing these lesions, evaluating the extent, treatment planning, and monitoring, as well as for follow-up after treatment.⁴ However, the diagnostic accuracy of MRI for these lesions is limited at complex anatomic locations in the brain such as in the skull base and parasagittal regions where invasion of bone or dural sinus is frequently present. Moreover, MRI has less diagnostic accuracy in distinguishing scar tissue or post therapeutic changes from residual viable meningioma due to nonspecific reactive signal abnormalities particularly after radiotherapy.

The majority of meningiomas are known to highly express somatostatin receptors (SSTR).^5,6 Somatostatin receptor subtype 2 has been found to be the most abundant with almost 100% expression in meningiomas, which allows for precise diagnostic and functional imaging of meningiomas.⁷ The most common SSTR ligands (68Ga-DOTA peptides) for PET imaging are 68Ga-DOTATOC, 68Ga-DOTATATE, and 68Ga-DOTANOC. These tracers are also frequently used for imaging of neuroendocrine tumours, due to likewise high expression of SSTR. 68Ga-DOTA peptide binding correlates with tumour growth rate in WHO grades I and II meningiomas, but it is abolished/diminished in grade III meningiomas. 68Ga-DOTA PET provides high sensitivity in diagnosing meningioma with excellent target-to-background contrast images due to low uptake in bone and healthy brain tissue (Figure 1).

 

 

68Ga-DOTA PET has been shown to be more sensitive than MRI in detecting meningiomas and it may also be used to confirm the diagnosis in patients with uncertain or equivocal results on MRI. It provides more precise delineation of tumour extent than contrast-enhanced MRI and is certainly more accurate in regions such as the skull base, orbits, and cavernous sinus.⁸ 68Ga-DOTA PET/CT is a particularly useful diagnostic tool when the biopsy is prohibitive due to involved risk, as in the case of suspected optic nerve meningiomas.⁹ Furthermore, 68Ga-DOTA PET also has high diagnostic accuracy (90%) in the detection of residual meningioma and their distinction from postoperative scarring.^10,11 In addition, the role of  68Ga-DOTA in evaluating patients eligibility for radionuclide therapy (neurotheranostics) with 177Lu DOTA-peptide is upcoming.¹² Recently 68Ga-DOTA peptides have gained popularity and might influence treatment planning for meningiomas.

 

Radiation Treatment Planning

 

68Ga-DOTA PET delivers additional information regarding extent and volume contouring of meningioma for fractionated stereotactic radiotherapy target definition. It is helpful in better definition of gross target volume (GTV) and clinical target volume (CTV) as compared to MRI. Studies have shown the incremental value of 68 Ga-DOTA PET/CT for contouring and RT target delineation and demonstrated that it often results in modified treatment volumes compared to those created based upon CT and MRI.¹³ (Figure 2).

 

 

Addition of SSTR-PET to standard imaging with CT and MRI reduces the inter-observer variability (IOV) in radiotherapy planning for patients with meningioma.¹⁴ Milker-Zabel et al., demonstrated an optimized target volume delineation for stereotactic fractionated radiation therapy in grades I–III meningiomas using 68Ga-DOTATOC PET co-registered to CT and MRI.¹⁵ Another recent study of Kowalski ES et al., reported the value of 68Ga -DOTATATE PET/CT in the diagnosis, radiation treatment planning and evaluating the response of meningiomas to radiotherapy.¹⁶ In this study, meningioma uptake of the SSTR2 ligand 68Ga-DOTATATE decreased by three months after RT, even in absence of objective MRI response.

 

Treatment Response

 

68Ga-DOTA PET is superior to CT or MRI in both discriminating meningioma tissue from scars and treatment induced changes. It enables an earlier evaluation of treatment effects than CT or MRI. Rachinger W et al., demonstrated that standard MRI has a lower diagnostic performance than 68Ga-DOTATATE PET: sensitivity, 79% versus 90%; specificity, 65% versus 74%; and positive predictive value, 84% versus 89% in discrimination of scar tissue from viable tumour.⁸ The recent Copenhagen Grading (post-operative PET-MRI imaging with 68Ga-DOTATOC) was proposed to provide more sensitive and specific imaging than MRI following surgery of meningioma.¹⁷

 

Conclusion

 

68Ga-DOTA peptide PET shows promising complementary role in detection and treatment planning of meningiomas. The potential benefits include improved diagnostic sensitivity, treatment planning, determination of the extent of resection, selection of RT target volumes (especially GTV), and differentiation between true and pseudo progression and furthermore, in evaluation of treatment response. Increased awareness of the utility of 68Ga-DOTA PET for meningioma is needed. More prospective randomized studies with large cohorts of patients are required to define the effective role of this modality.

 

Disclaimer: None.

 

Conflict of Interest: None.

 

Source of Funding: None.

 

References

 

1.      Ostrom QT, Gittleman H, Truitt G, Boscia A, Kruchko C, Barnholtz-Sloan JS. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2011–2015. Neuro Oncol. 2018;20(suppl_4):iv1–86.

2.      Louis DN, Perry A, Reifenberger G,  Deimling AV, Figarella-Branger D, Cavenee WK, et al. The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol. 2016;131:803–820.

3.      Rogers L, Gilbert M, Vogelbaum MA. Intracranial meningiomas of atypical (WHO grade II) histology. J Neurooncol. 2010;99:393–405.

4.      Goldbrunner R, Minniti G, Preusser M, Jenkinson MD, Sallabanda K, Houdart  E, et al. EANO guidelines for the diagnosis and treatment of meningiomas. Lancet Oncol. 2016;17:e383–e391.

5.      Reubi JC, Schaer JC, Waser B, Mengod G. Expression and localization of somatostatin receptor SSTR1, SSTR2, and SSTR3 messenger RNAs in primary human tumors using in situ hybridization. Cancer Res. 1994;54:3455–9.

6.      Graillon T, Romano D, Defilles C, Saveanu A, Mohamed A, Figarella-Branger D, et al. Octreotide therapy in meningiomas: in vitro study, clinical correlation, and literature review. J Neurosurg. 2017;127:660-669.

7.      Klutmann S, Bohuslavizki KH, Brenner W, Behnke A, Tietje N, Kröger S, et al. Somatostatin receptor scintigraphy in postsurgical follow-up examinations of meningioma. J Nucl Med. 1998;39:1913–7.

8.      Rachinger W, Stoecklein VM, Terpolilli NA, Haug AR, Ertl L, Pöschl J, et al. Increased 68Ga-DOTATATE uptake in PET imaging discriminates meningioma and tumor-free tissue. J Nucl Med. 2015;56:347–353.

9.      Kunz WG, Jungblut LM, Kazmierczak PM, Vettermann FJ, Bollenbacher A,  Tonn JC, et al. Improved detection of transosseous meningiomas using 68Ga-DOTATATE PET/CT compared with contrast-enhanced MRI. J Nucl Med. 2017;58:1580–7.

10.    Afshar-Oromieh A, Giesel FL, Linhart HG, Haberkorn U, Haufe S, Combs SE, et al. Detection of cranial meningiomas: comparison of 68Ga-DOTATOC PET/CT and contrast-enhanced MRI. Eur J Nucl Med Mol Imaging. 2012;39:1409–1415.

11.    Bashir A, Larsen VA, Ziebell M, Fugleholm K, Law I. Improved detection of postoperative residual meningioma with [68Ga]Ga-DOTA-TOC PET imaging using a high-resolution research tomograph PET scanner. Clin Cancer Res. 2021;27:2216-2225.

12.    Palmisciano P, Watanabe G, Conching A, Ogasawara C, Ferini G, Bin-Alamer O, et al. The role of [68Ga]Ga-DOTA-SSTR PET radiotracers in brain tumors: a systematic review of the literature and ongoing clinical trials. Cancers (Basel). 2022;14:2925.

13.    Graf R, Nyuyki F, Steffen IG, Michel R, Fahdt D, Wust P, et al. Contribution of 68Ga-DOTATOC PET/CT to target volume delineation of skull base meningiomas treated with stereotactic radiation therapy. Int J Radiat Oncol Biol Phys. 2013;85:68–73.

14.    Kriwanek F, Ulbrich L, Lechner W, Lütgendorf-Caucig C, Konrad S, Waldstein C, et al. Impact of SSTR PET on inter-observer variability of target delineation of meningioma and the possibility of using threshold-based segmentations in radiation oncology. Cancers (Basel). 2022;14:4435.

15.    Milker-Zabel S, Zabel-du Bois A, Henze M, Huber P, Schulz-Ertner D, Hoess A, et al. Improved target volume definition for fractionated stereotactic radiotherapy in patients with intracranial meningiomas by correlation of CT, MRI, and [68Ga]-DOTATOCPET. Int J Radiat Oncol Biol Phys. 2006;65:222-227.

16.    Kowalski ES, Khairnar R, Gryaznov AA, Kesari V, Koroulakis A, Raghavan P, et al. 68Ga-DOTATATE PET-CT as a tool for radiation planning and evaluating treatment responses in the clinical management of meningiomas. Radiat Oncol. 2021;16:151.

17.    Haslund-Vinding J, Skjoth-Rasmussen J, Poulsgaard L, Fugleholm K, Mirian C, Maier AD, et al. Proposal of a new grading system for meningioma resection: The Copenhagen Protocol. Acta Neurochir. 2021;164:229–238.