Rapid Advances in Radiotherapy Technology

Current scientific evidence and findings from randomized clinical trials that have enabled new treatment approvals show that, in recent years, radiation oncology has developed rapidly and made meaningful contributions to patients' lives. Below, we present a review summarizing all randomized clinical trials (RCTs) involving radiotherapy from 2018 to 2021 to identify emerging concepts and areas requiring further study.

NOTE: Randomization is performed in all phase-3 and phase-2 clinical trials. It means assigning patients randomly to an experimental treatment or control group, with allocation determined by chance through a computer program or random number table. Randomized clinical trials (RCTs) are human experiments with a low risk of bias and strong evidence.

On August 1, 2022, European Journal of Cancer published this review, whose highlights were briefly as follows:

• How high-tech radiotherapy, such as hypofractionation and stereotactic body radiotherapy, improves outcomes for many patients
• How personalized radiotherapy using imaging-based guidance helps tailor treatment
• The prominence of studies focusing on quality of life and patient satisfaction

In the briefest terms, shorter but more intensive, well-targeted radiotherapy approaches that also prioritize quality of life have better outcomes.

In recent years, hypofractionation and stereotactic technologies have come to the forefront, particularly in oligometastatic cancers (those with a small number of metastases).

Hypofractionation refers to giving high-dose radiotherapy over a reduced, shorter period, whereas

stereotaxis refers to a computerized system used to locate a specific tumor precisely before surgery or radiotherapy. In radiation oncology, this is called stereotactic radiosurgery for brain tumors or metastases and stereotactic radiotherapy outside the brain.

TrueBeam, Elekta Versa, RapidArc, CyberKnife and proton therapy are examples of newer radiotherapy technologies with considerable potential to personalize cancer treatment and improve outcomes.

A Rapidly Evolving Field: Radiation Oncology

The landscape of cancer treatment is changing rapidly. Given the volume of research, the authors set out to identify the most notable recent advances, warnings about some approaches and new directions to pursue. Sophie Espenel and colleagues in the Department of Radiation Oncology at the Gustave Roussy Cancer Campus in Villejuif, France, identified 1347 radiotherapy RCTs conducted from January 2018 to December 2021. They then selected 110 major phase II or III RCTs with data illustrating practice-changing or emerging concepts.

Overall, the studies demonstrated “great dynamism” in radiation oncology research and covered a broad range of radiotherapy practices, according to Dr. Espenel and colleagues.

A central focus of research has been radio-immunotherapy, an approach aiming to enhance the antitumor immune response. For example, one study examined preoperative immunotherapy with the anti-PD-L1 agent durvalumab together with concurrent stereotactic body radiotherapy at 24 Gy over 8 fractions in patients with early-stage lung cancer. Compared with durvalumab alone, major pathological complete response rates increased almost eightfold (53.3% versus 6.7%).

Although promising, not all trials evaluating a concurrent chemoradiotherapy-immunotherapy strategy have shown positive results. For example, an RCT in locoregionally advanced head and neck squamous cell cancer found that adding the anti-PD-L1 agent avelumab to chemoradiotherapy did not increase median progression-free survival. The authors also noted conflicting results in studies of metastatic disease.

Another area of interest involves newer radiosensitizing agents. A study in high-risk, locoregionally advanced head and neck squamous cell cancer highlighted the efficacy of the proapoptotic agent that inhibits apoptosis-inhibiting proteins, xevinapan, also known as (debio 1143) . Xevinapant was used for the first time with standard high-dose cisplatin chemoradiotherapy. Locoregional control at 18 months was achieved in 54% of patients receiving xevinapant and 33% receiving standard care. Side-effect profiles were similar.

High-tech radiotherapy is becoming more widespread. These devices allow patients to receive more targeted treatments at lower doses and over shorter periods. For example, one study found hypofractionated radiotherapy after breast cancer surgery at 26 Gy in 5 fractions as effective and safe as the standard approach of 40 Gy in 15 fractions over 3 weeks. Researchers found no difference between regimens in local recurrence, disease-free survival or overall survival.

Advanced methods such as intensity-modulated radiotherapy, stereotactic radiosurgery and proton therapy also have the potential to improve patient-reported side effects and clinical outcomes. This can be seen in clinical practice and several recently published studies.

Personalized radiotherapy is an emerging field that may allow more tailored treatment with improved outcomes. Researchers highlight a study finding that PMSA PET-CT was better than conventional CT for accurately staging prostate cancer. This approach also reduced radiation exposure. Based on this research, “PMSA PET-CT has since become the standard of care for staging prostate cancer,” the researchers explain.

Dr. Espenel and colleagues also note that as patients survive longer, quality of life and patient satisfaction are increasingly becoming RCT endpoints. Experts are focusing more on treatment sequelae and advances in technology that can spare critical organs from radiation and reduce overall treatment time.

Shared decision-making is also becoming more feasible in many situations. For example, some trials involving different treatment methods allowed patients to choose approaches tailored to their preferences. Outcomes were equivalent, but side-effect profiles differed.

The researchers emphasize that, overall, these data demonstrate “great dynamism in radiation oncology research across most major tumor types”.