MR-Linac: Especially useful in prostate cancer treatment

I was invited to discuss the promising new radiotherapy MR-Linac by the EAUN Special Interest Group on Prostate Cancer for the session they organised at EAUN22. It was 1999 when Jan Lagendijk – working as a clinical physicist at the radiotherapy department of the University Medical Centre Utrecht – suggested to integrate an MR scanner into a linear accelerator. The resulting device would enable MR imaging at the moment of treatment and was called the MR-Linac.

Radiotherapy with CT-guidance

Back then, the most advanced external beam radiotherapy treatment was performed with CT-guidance before any radiotherapy fraction. The lack of soft tissue contrast and the inability to perform imaging during the radiotherapy fraction limited the accuracy of this treatment. [1] Most tumours move during radiotherapy. Therefore, the radiotherapy target volume consisted of the tumour with a substantial margin around it to ensure that the tumour would remain within the target during radiation dose delivery. Because of these margins, there is healthy tissue in the target volume that may be susceptible to radiation damage, resulting in unwanted side effects.

Impossible?

At first, Professor Lagendijk’s idea was received by his peers with scepticism, as they deemed it impossible. The powerful magnet of the MR scanner would uncompromisingly influence the functioning of the accelerator, while the metal of the rotating accelerator would distort the magnetic homogeneity of the MRI. Nevertheless, Professor Lagendijk and his team persisted and were able to present a prototype of the MR-Linac in 2009. [2]  From then on, the development took flight. Currently, two commercially available MR-Linac systems are in clinical use worldwide. [3,4]

Prostate cancer treatment

Among urological malignancies treated with the MR-Linac are bladder and kidney cancer, but most patients are treated for prostate cancer. [5] The prostate’s anatomic position, surrounded by the bladder and bowel, causing movement and deformation of the prostate, makes it a suitable treatment site for the MR-Linac. [6] MR imaging before and during the radiotherapy fractions enables more accurate radiotherapy, reducing the target volume margin and radiation to surrounding healthy organs. [7] The hypothesis is that this will lead to fewer side effects.

Improved visualisation

“Seeing what you treat” can also serve hypofractionation and dose escalation, meaning higher radiotherapy doses in fewer fractions. The standard radiotherapy treatment for intermediate-risk prostate cancer used to be delivered in 25 to 35 fractions. A great deal of radiotherapy clinics now perform the treatment in only five fractions. Trials are investigating whether the MR-Linac can reduce the treatment to two fractions without increasing side effects and tumour recurrence. [8,9] Another advantage of integrated MR imaging during radiotherapy is the improved visualisation  of soft tissue structures that may contribute to the erectile function. Sparing these structures, such as the neurovascular bundle and the internal pudendal artery, may reduce erectile dysfunction after radiotherapy – a frequent problem among prostate cancer patients. The effect of neurovascular-sparing radiotherapy using an MR-Linac is currently under investigation at the University Medical Centre Utrecht (ERECT trial). [10]

Compared with other treatments

The technical development of the MR-Linac is ongoing, aiming for optimum real-time target tracking postand treatment adaptation. [11] Simultaneously, current MR-Linac treatment is being evaluated in trials and prospective registries. It is compared with conventional radiotherapy and other treatment modalities, such as prostatectomy in prostate cancer. [12-14] The outcomes of these studies will show the effect of MR-Linac treatment and help define its place in the treatment of prostate cancer and other (urological) malignancies.

References

1. Grégoire V, Guckenberger M, Haustermans K, et al. Image guidance in radiation therapy for better cure of cancer. Mol Oncol. 2020;14(7):1470. doi:10.1002/1878-0261.12751
2. Raaymakers BW, Lagendijk JJW, Overweg J, et al. Integrating a 1.5 T MRI scanner with a 6 MV accelerator: proof of concept. Phys Med Biol. 2009;54(12):N229. doi:10.1088/0031-9155/54/12/N01.
3. Klüter S. Technical design and concept of a 0.35 T MR-Linac. Clin Transl Radiat Oncol. 2019;18:98-101.doi:10.1016/J.CTRO.2019.04.007.
4. Lagendijk JJW, Raaymakers BW, van Vulpen M. The Magnetic Resonance Imaging-Linac System. Semin Radiat Oncol. 2014;24(3):207-209. doi:10.1016/j.semradonc.2014.02.009.
5. de Mol van Otterloo SR, Christodouleas JP, Blezer ELA, et al. Patterns of Care, Tolerability, and Safety of the First Cohort of Patients Treated on a Novel High-Field MR-Linac Within the MOMENTUM Study: Initial Results From a Prospective Multi-Institutional Registry. Int J Radiat Oncol Biol Phys. 2021;111(4):867-875. doi:10.1016/J.IJROBP.2021.07.003.
6. de Muinck Keizer DM, Kerkmeijer LGW, Willigenburg T, et al. Prostate intrafraction motion during the preparation and delivery of MR-guided radiotherapy sessions on a 1.5T MR-Linac. Radiother Oncol. 2020;151:88-94. doi:10.1016/j.radonc.2020.06.044.
7. Winkel D, Bol GH, Kroon PS, et al. Adaptive radiotherapy: The Elekta Unity MR-linac concept. Clin Transl Radiat Oncol. 2019;18:54-59. doi:10.1016/j.ctro.2019.04.001.
8. Westley R, Hall E, Tree A. HERMES: Delivery of a Speedy Prostate Cancer Treatment. Clin Oncol (Royal Coll Radiol (Great Britain). 2022. doi:10.1016/J.CLON.2022.01.003.
9. Randomized Trial of Five or Two MRI-Guided Adaptive Radiotherapy Treatments for Prostate Cancer. ClinicalTrials.gov identifier: NCT04984343. Updated 30 June 2022. https://www.clinicaltrials.gov/ct2/show/NCT04984343. Accessed 28 July 2022.
10. EREctile Function Preservation for Prostate Cancer Radiation Therapy (ERECT). ClinicalTrials.gov identifier: NCT04861194. Updated 25 August 2021. https://www.clinicaltrials.gov/ct2/show/NCT04861194. Accessed 28 July 2022.
11. Pathmanathan AU, van As NJ, Kerkmeijer LGW, et al. Magnetic Resonance Imaging-Guided Adaptive Radiation Therapy: A “Game Changer” for Prostate Treatment? Int J Radiat Oncol Biol Phys. 2018;100(2):361-373. doi:10.1016/j.ijrobp.2017.10.020.
12. de Mol van Otterloo SR, Christodouleas JP, Blezer ELA, et al. The MOMENTUM Study: An International Registry for the Evidence-Based Introduction of MR-Guided Adaptive Therapy. Front Oncol. 2020;10. doi:10.3389/fonc.2020.01328.
13. Ma TM, Lamb JM, Casado M, et al. Magnetic resonance imaging-guided stereotactic body radiotherapy for prostate cancer (mirage): a phase iii randomized trial. BMC Cancer. 2021;21(1):1-13. doi:10.1186/S12885-021-08281-X/TABLES/3.
14. Teunissen FR, Willigenburg T, Meijer RP, van Melick HHE, Verkooijen HM, van der Voort van Zyp JRN. The first patient-reported outcomes from the Utrecht Prostate Cohort (UPC): the first platform facilitating “trials within cohorts” (TwiCs) for the evaluation of interventions for prostate cancer. World J Urol. July 2022. doi:10.1007/S00345-022-04092-2.

Drs. Freek Teunissen, UMC Utrecht, Dept. of Radiotherapy, Utrecht (NL), f.r.teunissen@umcutrecht.nl