SABR for Treatment of Ventricular Tachycardia

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With a desire to provide new treatment options for ventricular tachycardia patients with high-risk features, recent early data has suggested that a cardiology and radiotherapy collaboration may provide a viable option. Initial experiences with cardiac SABR have shown promising results and the collection of further data will help drive the future clinical direction

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Ventricular tachycardia

The increased use of modern implantable cardioverter-defibrillators (ICDs) provides better medical and mechanical support for patients suffering from heart failure. As a result, patients with ventricular tachycardia (VT) caused by myocardial scarring, previously subject to significantly increased rates of morbidity and mortality are now living longer. The saving of patient lives by multiple ICD shock treatment has effectively turned cardiac arrest into a chronic symptom rather than a fatal event.

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Catheter ablation

In an attempt to reduce the number of ICD shocks a patient must endure, catheter ablation (CA) is being increasingly used for patients suffering from VT (Cronin et al, 2019).¹ CA is, however, not a quick and simple procedure. Nor is it always successful. The CA clinical procedure typically takes up to 4 – 6 hours. Further, the procedure involves the patient and staff receiving a significant X-ray fluoroscopy exposure and necessitates cumbersome radiation shielding.

For patients with high-risk features, the mortality rate may exceed 5%. Survival at 1 year is <70% and recurrence rates can exceed 50% (Vergarap et al, 2018).² As a result, alternative approaches to reducing the number of VT episodes are very desirable and may be the only treatment option for those whose CA has failed, or is no longer viable.

SABR: A new non-invasive option to treat refractory VT

Stereotactic ablative radiotherapy (SABR)  has initially shown promising results in a very limited number of heart, high-risk feature patients^{3 – 7}

Jumeau et al, 2018

 Cuculich et al, 2017,

Robinson et al, 2019,

Loo et al, 2015,

Cvek J et al, 2014 and

Jumeau et al, 2018

This nascent field has leveraged modern radiotherapy techniques to deliver a single fraction, high dose treatment to specific localised areas of myocardial scar tissue. In a landmark pilot study, five patients who had a cumulative 6577 VT episodes in the preceding 3 months, received a single SABR treatment of 25Gy. Following a 6-week blanking period after treatment, (which contained 680 VT episodes), there were only four VT episodes in the following 46 months, a reduction of 99.9% (Cuculich et al, 2017).^3, Following this initial cohort, the Phase I-II study (ENCORE-VT) also showed promising results in 19 patients. The median number of VT episodes reduced from 119 (range 4-292) to 3 (range 0-31) in 17 of the 18 evaluable patients (Robinson et al, 2019).⁴

Because of the very recent introduction of this novel technique, long term clinical data is still an area of active research. Consequently, the technique should be limited only to patients that have exhausted all other treatment options. Typically, patients will have

• structural heart disease,
• placement of an ICD,
• treatment-refractory ventricular tachycardia,
• persistent episodes of ICD treated VT,
• exhausted medicative options,
• have undergone a failed CA or CA may be too risky

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Methods to identify the target for non-invasive ablation

The treatment target is generally determined using a combination of electrical, structure and metabolic mapping. Each patient will have multiple electrical mapping (such as 12-lead ECG) or invasive mapping (such as that obtained during a previous catheter ablation procedure) which may be relevant. Computed tomography (CT) or magnetic resonance imaging (MRI), with intravenous contrast, may also be used to show structural changes – such as thinning of the ventricle wall. 

Metabolic imaging can be obtained to show either a deficit of myocardial viability or when the VT is due to ischemic heart disease. In the case of non-ischemic heart disease, metabolic imaging is also used to detect inflammation of the myocardium. In both cases, a strict fasting protocol and combined use of glucose and insulin is followed. This is to either increase metabolic uptake in muscle (to view regions of non-viable myocardium) or suppress it (to view inflammatory processes). After the diagnostic tests are completed, a radiotherapy CT simulation session is performed.

Simulation 

The simulation procedure involves acquiring volumetric images of the patient in the treatment position to describe digitally outlines of:

• the target volume,
• critical organs that need to be avoided, and
• the treatment geometry.

Immobilisation of the patient is decided during the simulation process. Proper immobilisation ensures the patient is consistently in a stable, reproducible and comfortable position for the initial imaging and for the treatment session. Because patients are often quite sick, immobilisation must be customised for each patient to provide optimum stability and comfort whilst remaining efficient to set up. 

Motion management plays a critical role due to the presence of two asynchronous rhythms. The heart will move both with respiration and with its own cardiac cycle. Depending on the target location, this may be negligible or significant. A typical motion management approach is to measure all forms of respiratory and cardiac motion of the target using 4D imaging, and then treat an internal target volume (ITV) to encompass this motion. Current clinical motion management options include using an internal target volume (ITV) that encompasses all respiratory and cardiac motion of the target, coupled with abdominal compression to reduce target motion, respiratory gating or dynamic tracking such as with the CyberKnife. The appropriate motion management should be assessed on a per-patient basis alongside consideration of the available equipment and intended treatment modality. With the relevant immobilisation in place, a 4DCT, preferably using intravenous contrast should be obtained.

The use of intravenous contrast during simulator imaging enhances visualisation of the blood flow through the heart. This allows the treatment team to accurately define the border between the myocardium and blood pool, and each of the anatomical heart components.

Treatment planning

From the radiotherapy simulation images obtained, the left ventricle is divided into 17 segments, depending on the distance from base to apex of the ventricle. The procedure is in accordance with the American Heart Association (AHA) model. Based on the results of the diagnostic imaging and testing, the target segments are defined directly on the simulation images. This process keeps the simulation imaging as the geometrical reference frame and avoids the use of image registration, which in this scenario is extremely challenging due to lack of consistency of patient position, respiratory and cardiac phase, and inability of radiotherapy software to handle electrical mapping and generally nonstandard patient orientation.

As with all SABR treatments, the organs at risk (OAR) must be carefully considered. In general, normal SABR planning principles take preference and dose escalation within the target is not actively avoided. A strong emphasis is placed on achieving steep dose gradients and a rapid dose fall-off outside the target. The specific OAR of concern for each patient depends on the location of the target to the ventricle and often includes lungs, stomach and oesophagus. In addition, the left anterior descending (LAD) artery is usually listed as a structure to avoid in radiotherapy. The LAD is often included in the target volume during VT ablation and, when possible, no X-ray dose hotspots should concentrate on this structure. However, there’s insufficient evidence about this at this stage. An example of some typical planning aims, constraints and Dose Volume Histograms are described in detail by Knutson et al.⁸

For linac based centres, VMAT is typically the delivery method of choice and FFF is beneficial to reduce treatment time. This is particularly important as patients will often struggle to lie supine for long periods. Multiple non-coplanar partial arcs are a common choice for linac solutions. But other technologies such as CyberKnife, and the MR linac have been used for these clinical treatments. Due to the complex, non-routine nature of the treatment, specific QA for the patient receiving treatment must be carried out to verify the delivered dose. 

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Treatment

On the day of treatment, the parameters involving patient motion must be reconsidered. The target segments move during the respiratory and cardiac cycles. The respiratory component is typically the dominant motion effect. A 4DCBCT, gated CBCT or slow scan speed CBCT, is repeated and matched against the original simulation images. The heart’s silhouette shown on the CBCT and simulator images are compared to confirm the accuracy of the patient’s set-up. Patients often have ICD leads in the heart or calcified blood vessels which can potentially assist checking the alignment of the treatment and simulator images. The ‘surrogate markers’ can be used for target positioning during IGRT, if available. But preference should be given to the outline of the heart tissue. Fluoroscopy is also beneficial when matching a moving target. The high fluoroscopy frame rate is particularly useful for imaging the cardiac and respiratory motion.

During the treatment, there’s a busy multi-disciplinary medical team attending. The High Acuity Team consisting of cardiology nursing, cardiology monitoring and the cardiologist, attend with the radiation oncologist, medical physicist and at least two radiation therapists.

The overall set-up and treatment time for which the patient is in the room is typically 30-60 minutes. It’s largely dependent on the complexity of the patient’s immobilisation equipment, the setting-up and the time taken for the IGRT image matching processes. Once the set-up, safety checks and IGRT procedures are complete, the treatment delivery can take less than 10 minutes. If X-ray beam gating is used, it will take longer.

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Conclusion

As is the case with all new techniques, lessons are learnt and offer better ideas and improvements for future patients treated. In the short term, growth in confidence and experience of the staff in these early cases are expected to reduce the overall time it takes between the initial diagnostic, planning and treatment procedures. Technological advances will hopefully allow us to develop more appropriate measurement techniques, that take into account respiratory and cardiac motion when completing the radiotherapy treatment planning work. This could lead to improved motion management methods for gating or tracking X-ray treatment machines, such as MR linacs or CyberKnife.

As the breadth and depth of clinical evidence grows, it is hoped that fundamental understanding of the biological science aspects will be better understood and used to improve the treatment plan objectives. This should lead to increased consensus and specificity in target delineation on simulator CT images which, will in turn, make the treatment planning more consistent between clinical centres and guide dose prescription. Combined with the long-term clinical evidence gathered in the coming years, cardiac radiotherapy has the potential to continue to improve and become a valuable option for patients with recurrent ventricular tachycardia. 

Overall, this is an exciting new treatment which is providing an opportunity to patients that have exhausted the current medical treatment options. But it’s important to recognise that the biological processes are still not fully understood, and the long-term effects of the treatment need to be confirmed.

Ideally, prospective clinical trials should be arranged to compare SABR to the current standard of care treatments (such as catheter ablation for high-risk heart failure patients). Close monitoring of trials in recognised clinical centres would provide:

• valuable information for establishing the best supportive medical care for inoperable patient cases; and
• would be key to identifying the most appropriate patients for this treatment technique.

In the absence of clinical trials, the organisation of registries will be a fundamental requirement to track how the heart failure patients respond to stereotactic radiotherapy. We must ensure that we learn from every patient who has this treatment.

References

1. Cronin EM, Bogun FM, Maury P, et al. 2019 HRS/EHRA/APHRS/LAHRS expert consensus statement on catheter ablation of ventricular arrhythmias. Heart Rhythm 2019; 21(8):1143-1144.
2. Vergara P, Tzou WS, Tung R, et al. Predictive Score for Identifying Survival and Recurrence Risk Profiles in Patients Undergoing Ventricular Tachycardia Ablation. Circ Arrhythm Electrophysiol 2018;11:e006730.
3. Phillip S. Cuculich, Clifford Robinson, et al. Noninvasive Cardiac Radiation for Ablation of Ventricular Tachycardia. N ENG J MED 377;24
4. Clifford G. Robinson, Phillip S. Cuculich, et al. Phase I/II Trial of Electrophysiology-Guided Noninvasive Cardiac Radioablation for Ventricular Tachycardia. Circulation. 2019;139:313–321 
5. Billy W. Loo, Jr, Paul Zei, et al. Stereotactic Ablative Radiotherapy for the Treatment of Refractory Cardiac Ventricular Arrhythmia. Circ Arrhythm Electrophysiol. 2015;8:748-750
6. Cvek J, Neuwirth R, Knybel L, et al. (July 22, 2014) Cardiac Radiosurgery for Malignant Ventricular Tachycardia. Cureus 6(7): e190.
7. Raphaël Jumeau, Jean Bourhis et al. Rescue procedure for an electrical storm using robotic non-invasive cardiac radio-ablation. Radiotherapy and Oncology 128 (2018) 189–191
8. Knutson NC, Samson P, Hugo G, et al. Radiotherapy Workflow and Dosimetric Analysis from a Phase I/II Trial of Noninvasive Cardiac Radioablation for Ventricular Tachycardia. Int J Radiat Oncol. 2019 104(5)

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Simon Goodall and Nicholas Hardcastle, 7 April 2021

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