By Charles B. Simone, II, MD, Medical Director, Maryland Proton Treatment Center
Stereotactic body radiation therapy (SBRT) is increasingly used as a result of its ability to spare healthy tissue, as well as for its enhanced tumor control and curative potential. Most oncologists associate SBRT with photon radiation. However, my clinical experience shows that proton SBRT—which I have used to treat lung, liver, kidney, and head and neck primary cancers, as well as mesothelioma and oligometastatic malignancies—is not only feasible but safe and efficacious. Data from other centers support these findings as well.
The Effectiveness of Proton SBRT
With the precision of proton pencil beam scanning (PBS), SBRT to all sites can be performed using protons. In many cases, proton SBRT can offer a significant dosimetric advantage over conventional photon SBRT. PBS allows for dose escalation with pinpoint accuracy and conformality due to the PBS Bragg peak and absence of exit dose, potentially allowing for SBRT to be delivered more safely with fewer toxicities to adjacent healthy tissues.
Delivering ultra-high doses of radiation as with SBRT requires ultra precision: we must know the exact tumor location at all times. With head and neck or prostate cancers, treatment planning does not need to account for intrafractional tumor motion. But for lung and upper gastrointestinal tumors that can have significant tumor motion, there is potential for an interplay effect (between scanning spots and a moving target), which could cause degradation of the target dose. It is critical to account for and adequately mitigate motion when delivering therapy in a limited number of fractions, as is done with SBRT, and repainting should also strongly be considered for proton SBRT.
My colleagues and I found (Figure 1) that as long as we delivered at least 4 fractions of PBS, we could obviate any concerns that we were undertreating the tumor, as the delivered dose precisely tracked the treatment plan. In addition, there was no observable coverage difference for 5, 10, or 35 fractions.1
Conventional photon SBRT has significantly improved outcomes for patients with medically inoperable early stage non-small cell lung cancer (NSCLC).2 There is now even some literature suggesting improvements in outcomes with SBRT approaches versus lobectomy in operable patients.3 Several recent reports, however, question if proton SBRT can be as good as or better than photon for select patients. We recently demonstrated in a dosimetric analysis that proton SBRT for stage I NSCLC can lower doses to organs at risk compared with photon SBRT that is delivered with intensity-modulated radiation therapy (IMRT), volumetric-modulated arc therapy (VMAT), and CyberKnife.4 How this dosimetric advantage translates to clinical benefits will need to be validated in future investigations.
A recent meta-analysis of 72 conventional photon SBRT clinical studies and 9 hypofractionated particle beam therapy (PBT) studies on NSCLC found that hypofractionated PBT may lead to additional clinical benefit when compared with conventional photon SBRT. On multivariate analysis, proton SBRT/hypofractionation was associated with improved 3-year local control (p = 0.03), as well as a lower overall incidence of grade 3-5 toxicities (4.8% vs. 6.9%, p = 0.05), including grade ≥ 3 pneumonitis (0.9% vs. 3.4%, p = 0.001), compared with conventional photon SBRT.4
We recently published our findings on the first application of proton SBRT to treat synchronous bilateral renal cell carcinoma (RCC) in the setting of underlying chronic kidney disease. We were able to deliver an optimal biologically effective dose with protons that can offer a high likelihood of long-term control, while preserving this patient’s normal kidney parenchyma and minimizing skin dose. Our findings offered evidence that proton SBRT is feasible, efficacious, and associated with minimal toxicities at 1 year.5
There are certainly cases where we are literally unable to offer optimal dose to the tumor using conventional photon SBRT. For example, Figure 2 shows a patient whose preexisting left-kidney function was compromised with a large right-sided RCC. I was not able to meet dose kidney constraints to safely deliver conventional photon SBRT, but both two-field (left) and three-field (right) proton plans significantly reduced the dose to the patient’s kidney, and the patient was treated with a two-field plan without acute or subacute damage to the kidney.
I want to stress that in our experience, even for tumors with greater motion magnitude such as those in the lung or liver, effective proton SBRT can be delivered in 5 or fewer fractions safely, accurately, and effectively as long as we can successfully mitigate tumor motion.1,6
Lung: Because tumors greater than 5 cm have often been excluded from treatment with conventional photon SBRT due to concerns of increased toxicities when delivering high doses to large areas of tissue, these patients may be most optimally treated with proton SBRT to reduce the dose to normal tissues. Proton SBRT may also be particularly useful for ultra-central lung cancers and for patients with oligometastatic or oligoprogressive disease who are on systemic therapy, where the side effects of conventional photon SBRT are higher. Proton therapy in these patients can potentially minimize the risks of toxicities such as pneumonitis, esophagitis, and airway or great vessel damage.
When each field can be delivered in under 10 seconds with Varian’s new RapidScan technology, it will allow for more lesions to be treated with SBRT—more peripheral and caudal/inferior lung lesions and more liver lesions—than are currently able to be treated. This would apply to stage I NSCLC, especially for patients whose tumor motion is not as easily mitigated and in patients who generally have poor lung function who cannot tolerate long periods of breath hold.
Liver: Proton SBRT can be effective for treating larger or more centrally located liver tumors, since for some of these lesions conventional photon SBRT cannot be used without risks of liver failure or even death.
Kidney: Proton SBRT can avoid the incidental irradiation to the uninvolved kidney that may occur with conventional photon-based SBRT. By reducing the volume of the ipsilateral kidney irradiated and eliminating contralateral kidney irradiation, proton SBRT in select patients may reduce the risk of kidney failure. Of course, kidney failure in turn would require chronic hemodialysis, with associated impairments in quality of life and decreased overall survival. For patients with bilateral renal malignancies, these risks are magnified.
Head and Neck: Especially for isolated recurrences, proton SBRT may be an effective option that reduces the reirradiation dose to adjacent tissues that have already received maximum doses.
The PBS on the Varian ProBeam system allows me to sculpt the dose in a precise way. The system includes a 360° gantry, allowing for imaging and treatment at almost any angle, which is particularly important for SBRT. All Varian gantries feature cone-beam computed tomography (CBCT), which is essential for daily tumor visualization and effective SBRT delivery. In fact, my colleagues and I published data showing that planar kV guidance was inadequate for accurate positioning and that CBCT image guidance dramatically improves SBRT accuracy.7 And now that CBCT is increasingly available, I believe we will begin to see a real increase in the number of patients treated with proton SBRT. The ultra-fast treatment delivery of the ProBeam system maximizes both treatment precision and patient convenience.
Proton SBRT is unquestionably underused. It offers an attractive way to reduce risks posed by conventional photon SBRT, either because of the size or location of the tumor, or because reirradiation with photons would be inadvisable. For those patients who are at higher risks from or cannot receive conventional photon SBRT due to toxicity concerns, proton SBRT could be a life-saving option.
Proton SBRT allows us to increase the dose delivered to the tumor, which in select patients can improve tumor control and overall survival. And importantly, it can offer some patients a new chance for cure.
1. Kang M, Huang S, Solberg TD, et al. A study of the beam-specific interplay effect in proton pencil beam scanning delivery in lung cancer. Acta Oncologica. 2017;56:531-540. doi: 10.1080/0284186X.2017.1293287.
2. Videtic GMM, Donington J, Giuliani M, et al. Stereotactic body radiation therapy for early-stage non-small cell lung cancer: Executive Summary of an ASTRO Evidence-Based Guideline. Pract Radiat Oncol. 2017;7(5):295-301. doi: 10.1016/j.prro.2017.04.014.
3. Chang JY, Senan S, Paul MA, et al. Stereotactic ablative radiotherapy versus lobectomy for operable stage I non-small-cell lung cancer: a pooled analysis of two randomised trials. Lancet Oncol. 2015;16(6):630-637. doi:https://doi.org/10.1016/S1470-2045(15)70168-3.
4. Wink KCJ, Roelofs E, Simone CB 2nd, et al. Photons, protons or carbon ions for stage I non-small cell lung cancer: Results of the multicentric ROCOCO in silico study. Radiother Oncol. 2018; 128(1):139-146. doi: 10.1016/j.radonc.2018.02.024.
5. Frick MA, Chhabra AM, Lin L, et al. First ever use of proton stereotactic body radiation therapy delivered with curative intent to bilateral synchronous primary renal cell carcinomas. Cureus. 2017; 9(10): e1799. doi: 10.7759/cureus.1799.
6. Lin L, Souris K, Kang M, et al. Evaluation of motion mitigation using abdominal compression in the clinical implementation of pencil beam scanning proton therapy of liver tumors. Med Phys. 2017;44(2):703-712. doi: 10.1002/mp.12040.
7. Corradetti MN, Mitra N, Bonner Millar LP, et al. A moving target: Image guidance for stereotactic body radiation therapy for early-stage non-small cell lung cancer. Pract Radiat Oncol. 2013;3(4):307-315. doi: 10.1016/j.prro.2012.10.005.