Changes Improve Radiation Therapy in SCLC

Investigators are making progress in delineating the optimal use of radiation therapy for the treatment of patients with small cell lung cancer (SCLC), which remains a cornerstone of therapy for the malignancy, particularly in limited-stage disease, according to Billy W. Loo Jr, MD, PhD, FASRO, FACR.

“There are a number of ways that our treatments have been evolving,” Loo said in a recent interview with OncologyLive^®. “Continued optimization of radiation therapy in terms of dose intensity and acceleration, better management of the potential for brain metastases, and combinations with immunotherapy are all under development.”

Loo is a professor of radiation oncology (radiation therapy), director of thoracic radiation oncology, and director of new technologies in the Department of Radiation Oncology at Stanford Cancer Institute, Stanford University School of Medicine in California. He discussed key issues in SCLC during the 23rd Annual International Lung Cancer Congress^® hosted by Physicians’ Education Resource^®, LLC (PER^®) in July.

In contrast to non–small cell lung cancer (NSCLC), few therapies have been introduced in recent years for treating patients with SCLC. Why is there a disparity?

There are some key differences between the clinical behavior of SCLC and NSCLC, one of which is that the pace of growth of SCLC is more rapid. That has been an issue because fewer patients are diagnosed in an earlier stage of SCLC. However, stage for stage, the survival outcomes historically for NSCLC and SCLC treated with definitive therapy are somewhat similar. So, it is very important to be able to treat [patients with] SCLC in a time-efficient way.

For biological differences, we have not been as successful at finding specific molecular subtypes or genetic oncogene drivers in SCLC as we have in NSCLC and that’s part of why there have been fewer new therapies for SCLC. A very active area of investigation, of course, is combinations with immunotherapy, which have shown a dramatic impact in NSCLC. The data are being acquired and emerging in SCLC and we hope that we will see some similar improvements.

What recent developments have the potential to improve outcomes?

Specifically with regard to radiation therapy, which has been one of the key pillars of treatment of limited-stage SCLC with the goal of cure, what has been shown historically is that the pace of the radiation—compressing the treatment interval into a shorter period of time—has been important.

In the past, one of the challenges with accelerated radiation is that it causes more toxicity. However, with modern improvements in the delivery of radiation therapy, we are able to sculpt the dose more carefully [so that it is] concentrated where the tumors are and less where the normal tissues are, and we can ameliorate some of the dose-limiting toxicities. Recent data that have emerged in some pilot randomized trials in Europe and in China^1,2 suggest that we can get to higher doses than we have in the past with accelerated radiation therapy. Those studies seem to be associated with better survival outcomes. That is potentially a very promising approach in terms of optimizing radiation therapy.

What pending studies may make a difference in this space?

One of the important questions is how to manage the risk of brain metastases in SCLC, particularly in the early stage or limited stage. Older historical data have shown a survival benefit to doing prophylactic cranial irradiation as a way of heading off the development of symptomatic metastases. In the past, that has shown a survival benefit, but that is based on older data where we didn’t have as good staging as we do now, for example, with MRI scans. A question now is in a truly earlier stage with proper staging, is there a benefit to prophylactic cranial irradiation? Can it be optimized? That is being studied in an ongoing clinical trial, MAVERICK [SWOG 1827; NCT04155034].

Another emerging area that is still being defined with respect to the treatment of brain metastases—this is more for extensive-stage SCLC that has involved the brain—is the role of stereotactic radiation as opposed to whole brain radiotherapy. Some very interesting data have emerged, somewhat counterintuitive to notions in the past, [showing] that stereotactic radiation may indeed be an effective treatment for brain metastases in SCLC. There is at least 1 ongoing randomized clinical trial including [patients with] both limited- and extensive-stage SCLC and treatment of brain metastases [NRGCC009; NCT04804644].

What is important for your oncology colleagues to know about treating patients with SCLC?

One important [facet] is that the optimal use of radiation therapy, which is my specialty, is still actively evolving. In the care of patients with SCLC, just as with NSCLC, it is critical to have that input and feedback from radiation oncology and to have that multidisciplinary coordination. That is particularly important in the care of patients with SCLC, who tend to have a more aggressive course of disease and who may have more baseline comorbidities.

References

1. Grønberg BH, Killingberg KT, Fløtten Ø, et al. High-dose versus standard-dose twice-daily thoracic radiotherapy for patients with limited stage small-cell lung cancer: an open-label, randomised, phase 2 trial. Lancet Oncol. 2021;22(3):321-331. doi:10.1016/S1470-2045(20)30742-7
2. Qiu B, Li QW, Liu JL, et al. Moderately hypofractionated once-daily compared with twice-daily thoracic radiation therapy concurrently with etoposide and cisplatin in limited-stage smallcell lung cancer: a multi-center, phase II, randomized trial. Int J Radiat Oncol Biol Phys. 2021;111(2):424-435. doi:10.1016/j.ijrobp.2021.05.003