Singh Discusses the Shift Toward Stereotactic Radiation Therapy in Lung Cancer

Raj Singh, MD

Limited resources and infrastructure impede broader implementation of advanced radiation therapy modalities, particularly in underserved communities. Socioeconomic factors further compound these disparities, necessitating efforts to enhance local access to care, according to Raj Singh, MD. Singh added that the transition from conventionally fractionated radiation therapy to stereotactic body radiation therapy (SBRT), which delivers enhanced local disease control and reduced toxicity, also provides a shortened treatment duration that may help address these barriers for patients.

Singh added that advancements don’t stop at delivery techniques alone, noting that investigators are evaluating the potential of extending this approach to earlier stages of disease to optimize outcomes.

“Hopefully in the coming years we’ll continue to [focus on improving this technology] and really find the patients that benefit from this well tolerated treatment,” Singh said in an interview with OncLive® during The Radiation Oncology Summit: ACRO 2024.

In the interview, Singh discussed the evolving role of radiation therapy, particularly in patients with thoracic malignancies and metastatic disease. Singh is an assistant professor of radiation oncology at The Ohio State University Comprehensive Cancer Center––James in Columbus.

OncLive: How have delivery techniques changed since the advent of conventionally fractionated radiation therapy?

Singh: Radiation therapy has always been a mainstay of lung cancer management and has really started to emerge in terms of [its] indication for metastatic disease, which is a fair amount of the research that I do. Historically, conventionally fractionated radiation therapy given in a six-week course for patients who could not tolerate a lobectomy or other form of surgery [was] an inferior treatment option. With the rising role of SBRT or stereotactic ablative radiotherapy, we’ve been able to vastly improve the therapeutic ratio in terms of local control of disease and minimizing toxicity. The other benefit for this particularly given that I practice in Ohio is patients oftentimes find logistically [that] going to radiation therapy sessions for six weeks is a barrier to care.

The other benefit of a shorter treatment course is the ability to expand access to patients from a large radius across different walks of life. The emerging roles of radiation therapy now tend to be in the realm of combining radiotherapy with immunotherapy. Many speakers have focused on and continue to focus on the evolving role of utilizing radiation as a means to [improve the activity of] immunotherapy, which is proven to improve survival in stage III lung cancer. Why can’t we do that same approach for earlier stages of lung cancer where at the moment patients get surgery or SBRT but don’t receive adjuvant therapy.

The issue we find for these patients is they don’t tend to fail at the site we treat, they tend to fail outside of those areas. What can we do to improve that? Many of the indications of radiation are often synergistic now we’re finding as well. We know that this treatment, based on 20 years of research is well tolerated. But what can we do to continue to improve the therapeutic ratio for patients who are medically inoperable or even medically operable too?

What are the current areas of need that remain in terms of radiation therapy for this patient population?

Still even a course of one treatment can be burdensome for patients [who don’t have access to] centers that have the physics capability to provide the services. Luckily, I’m in a very large academic center, but it’s still a burden for patients when I tell them they need to come for a week and a half of treatment. The efficacy and safety of this treatment approach has been established, but the barrier to care is capability in terms of access to centers that are local to patients. Centers are becoming more accustomed to use of the therapy, but it becomes a capital as well as resources limitation, just as we see in third world countries.

The other challenge is that patients with lung cancer tend to be lower socioeconomic status given that these are patients who have significant smoking histories or struggle with social situations. Ideally this technique will continue to grow in terms of use in local communities so that patients can get care closer to home which I always am an advocate for.

What are some of the recent advancements within this domain that you find noteworthy or that you are eager to explore further?

Many of the advancements now and much of my research outside of patients with primary lung cancers is the use of radiotherapy with respect to its incorporation with standard of care systemic therapy for patients with oligometastatic disease. We are challenging current dogma in terms of the idea of radio[therapy] resistance that used to exist in the era of conventionally fractured radiation therapy, particularly for sarcomas, which most commonly spread to the lung.

I published a study through the radiosurgery society that showed excellent local control exceeding 90% with minimal treatment-related toxicity. This is paramount for patients with sarcoma because the standard of care for metastatic sarcoma still consists of cytotoxic chemotherapy, and limiting interruptions in systemic therapy is key. We’ll continue to lead multi-institutional studies to further validate this approach because I believe it’s of significant benefit for patients.

The other indication outside of stage III lung cancer, certainly stage IV lung cancer where consolidated radiotherapy or the idea of allowing patients to remain on the same first-line therapy, because systemic therapy options are generally limited for metastatic non–small cell lung cancer [NSCLC] and small cell lung cancer [SCLC], can be of significant benefit. The recently published CURB trial [NCT03808662] showed this in the setting of oligoprogressive disease, where [patients with] one to five [metastatic] lesions that progress on first-line therapy [experienced] significantly improved progression-free survival with SBRT with limited AEs. Much of my research is hoping to show and really home in on what the specific populations are for which this technique is beneficial. It’s one thing to know that you can offer the technique safely, but who are the patients who are truly going to benefit from it?

What is your approach to treatment decision-making and the development of personalized radiation therapy plans for patients in this population?

In SCLC we’re starting to see that there is a signal towards benefit in terms of survival with use of dose escalation. The standard regimen for limited stage SCLC or [disease that] can be safely encompassed in one field is either 45 Gy in 30 fractions twice daily per the Turrisi regimen, or 66 Gy to 70 Gy with conventional fractionation per the CALGB [30610 (NCT00632853)] and CONVERT [NCT00433563] trials. However, some initial phase 2 trials have shown improved survival if we increase the dose, either with the simultaneous integrative boost method to 254 Gy in 30 fractions or by prolonging the treatment course to 60 Gy in 40 fractions. We don’t see improvements in survival very often with increased radiation dose, so it’s an exciting idea. We don’t have phase 3 data yet to validate this approach [though]. That has been my approach for patients with SCLC because the two dose-limiting structures for these patients tend to be the esophagus and the heart.

For patients who have limited disease burden or disease that’s located away from these structures, I will utilize one of these two dose-escalation methods if they are very good performers or have limited cardiac comorbidities. In patients where either of those [situations] are not the case or we have those volumetric issues, then I’ll use a standard approach. But given the signal we’re seeing, that’s where I’m starting to personalize use of dose. In NSCLC we have yet to see that there truly is a benefit to dose escalation.

There [have] been some promising findings from UCLA that have shown the feasibility of using SBRT as a boost modality to the primary disease in the stage III setting. I haven’t yet incorporated this into my practice [and I won’t] until we start to see that this also results in a benefit in terms of outcomes, but that’s also in the non–small cell space where you might see some emerging indications as well.

One of the sessions featured a discussion on brain metastases in SCLC. What did you find interesting from this portion of the meeting?

[We heard from] Dr Paul Brown who has led many of the studies with respect to neurocognitive outcomes in patients with brain metastases. Many of his studies have shown that the use of stereotactic radiosurgery [for] certain lesions in the brain rather than the historical standard of whole brain radiotherapy, [does not result in a] detriment in terms of survival. But importantly, neurocognitive outcomes were improved.

SCLC is an interesting, unique entity [among] solid tumors where there is the idea that there’s likely micrometastatic disease in the brain. For these patients who have a partial or complete response after chemoradiotherapy up front, the historical standard has been to offer prophylactic cranial radiation where we treat the brain even though we’re not seeing any disease. The criticism of this has been that many of the studies that supported this approach were prior to the MRI era where we did not have accurate staging for patients. There are two very important studies that I as well as Dr Brown would encourage accrual on, one of which is the phase 3 MAVERICK study [NCT04155034], which is randomizing patients with limited stage SCLC to prophylactic cranial radiation or observation with MRIs.

The other emerging and questionable indication for stereotactic radiosurgery is in SCLC with brain metastases. We know that stereotactic radiosurgery is a viable option for these patients compared with whole brain radiotherapy, but in SCLC whole brain radiotherapy has been the standard. The retrospective FIRE-SCLC cohort study did not show a difference in terms of survival for these patients. The currently accruing phase 3 NRG-CC009 study [NCT04804644] is aimed to answer this question for patients with a limited extent of brain metastases by randomizing between stereotactic radiosurgery and the current standard, hippocampal sparing whole brain radiotherapy. We’re hoping that these trials will accrue soon so we’ll have the optimal answer in terms of balancing the therapeutic ratio of being aggressive with these patients’ care, but also maximizing neurocognitive quality of life.

What are the primary takeaways from your presentation from the meeting?

The takeaway with respect to thoracic malignancies and stereotactic radiation is that [radiation] continues to have an increased role, allowing for increased usage of treatment with limited toxicity. The other role [for radiation] is in [the setting of] oligometastatic disease, but it’s limited there. Can we improve outcomes for patients with disease that’s limited to the lung but also spare them the adverse effects [AEs] of surgery that can delay systemic therapy, which we know is also crucial to their outcomes?