2022 ASTRO Round-Up: A Shift Toward a New Standard of Care in Radiotherapy and Reducing Cancer Treatment Duration

Data from recent studies may have confirmed the benefits of decreasing the amount of radiation used to treat a variety of solid cancers, according to experts.

Findings presented at this year’s American Society for Radiation Oncology (ASTRO) Annual Meeting covered an array of topics, such as using certain types radiation therapy to decrease treatment duration and manage pain, as well as its role in certain disease types such as breast cancer, prostate cancer, and even for oligometastatic disease.

“If one was to take away an overall theme from the meeting, it was the continued acceleration of hypofractionation—the idea of using fewer treatments for any particular disease,” Louis Potters, MD, FACR, FASTRO, FABS, said in an interview.

Following the meeting’s completion, CancerNetwork^® sat down with Potters, deputy physician-in-chief and Marilyn and Barry Rubenstein Chair in Cancer Research at Northwell Health Cancer Institute, and professor and chair of the Department of Radiation Medicine at Donald and Barbara Zucker School of Medicine at Hofstra, and James Yu, MD, a professor and executive vice chair at Columbia University Irving Medical Center, who shared their key takeaways from the meeting, spotlighting which studies other experts in the radiation oncology space should know.

Using Prophylactic Radiation to Decrease Skeletal Events in Asymptomatic Bone Metastases

One set of phase 2 data highlighted that prophylactic radiation therapy significantly reduced the occurrence of skeletal events in addition to subsequent pain and hospitalizations in patients with asymptomatic, high-risk bone metastases.¹

Investigators reported that skeletal events—defined as pathologic fracture, cord compression, surgery for instability, or radiotherapy for pain—occurred in 1.6% of patients who received radiation therapy (n = 39) vs 29.0% of patients who had no radiation therapy (n = 39; P <.001).

“We know that metastases to the long bone are associated with impending fractures. Generally speaking, radiation is utilized when erosion of the long bone is significant or after a patient has had a fracture,” Potters explained. “This study was able to demonstrate an overall improvement following prophylactic treatment of these patients earlier upstream in their disease course, which not only impacted the risk of bony fracture, but…[resulted in] an overall survival [OS] benefit as well.”

After a median follow-up 2.41 years, the median OS was 0.99 years (95% CI, 0.78-1.87) among patients who didn’t receive radiotherapy vs 1.67 years (95% CI, 1.26-not reached [NR]) among those who did (HR, 0.49; 95% CI, 0.27-0.89; P = .018). Moreover, there were 4 hospitalizations in the no radiotherapy arm vs 0 hospitalizations in the radiotherapy arm (P = .045).

In the no radiotherapy arm, common grade 2 adverse effects (AEs) included fatigue (8%) and diarrhea (3%), and grade 3 AEs included nausea (5%) and emesis (5%). In comparison, grade 2 AEs in the radiotherapy arm included nausea (8%), emesis (5%), erythema (3%), fatigue (10%), and diarrhea (5%).

“After the first 3 months, the patients who got radiation had less pain than those who did not,” Yu noted. “There were no statistically significant differences in quality of life. But when you add together [OS] and less initial pain, it certainly looks like radiating asymptomatic but high-risk bony lesions was beneficial to the patient. I think this is the biggest potentially practice-changing study [from this year’s meeting] because metastatic disease is an extraordinarily common indication for radiotherapy and all across the country, we're all going to start thinking that maybe patients with a high-risk lesion should get radiation before they are in pain.”

Assessing Long-Term Data of Conventional vs Hypofractionated Radiotherapy in Prostate Cancer

With 7 years of follow-up, investigators reported positive oncologic outcomes from the phase 3 PCS5 trial (NCT01444820) for patients treated with conventional radiotherapy vs hypofractionated radiotherapy.² The findings demonstrated that there were no differences in toxicity or outcomes with the use of moderate hypofractionation in patients with high-risk prostate cancer. This has raised questions from study investigators as to whether the treatment should be considered as the new standard of care for this population.

Patients in the standard fractionation arm received 46 Gy/23 to the pelvis plus a 30 Gy/15 sequential boost followed by 28 months of androgen deprivation therapy (ADT), and the hypofractionation arm was given 45 Gy/25 to the pelvis plus a 68 Gy simultaneous boost and 28 months of ADT.

Figure 1. Schema for the phase 3 PCS5 trial

Previously reported findings from the trial indicated that hypofractionation was non-inferior to conventional fractionation. Moreover, 8% of those in the conventional fractionation arm vs 9% of those in the hypofractionation arm experienced grade 2 or higher gastrointestinal toxicities. Additionally, 7% and 2%, respectively, experienced grade 2 or higher genitourinary toxicities.

Additional findings indicated that the biochemical recurrence-free survival rate was 87.4% in the conventional fractionation arm compared with 85.1% of those in the hypofractionation arm. The metastases-free survival was 91.5% vs 91.8% in each respective arm.

“This further validates the utilization of a shorter treatment course, as definitive care for prostate cancer,” Potters noted.

Examining Length of Radiotherapy Treatment in High-Risk, Early-Stage Breast Cancer

In a population of patients with high-risk early breast cancer who were set to receive breast conserving surgery, treatment with concomitant boost and hypofractionated whole breast irradiation (H-WBI) resulted in a reduced treatment time and non-inferior in-breast recurrence (IBR), as well as no significant difference in toxicity and physician-rated cosmetic outcomes vs WBI and sequential boost.³

Figure 2. Study schema for the phase 3 NRG RTOG 1005 study

The data were from the phase 3 NRG RTOG 1005 trial (NCT01349322), and demonstrated that the 5-year estimated IBR rates were 2.0% (95% CI, 1.4%-2.9%) compared with 1.9% (95% CI, 1.3%-2.7%) and the 7-year estimated IBR rates were 2.2% (95% CI, 1.5%-3.0%) and 2.6% (95% CI, 1.9%-3.5%) in the WBI (n = 1124) and H-WBI cohorts (n = 1138), respectively. The median time to IBR was 2.05 years in the WBI cohort and 3.04 years in the H-WBI cohort (HR, 1.32; 90% CI, 0.84-2.05; P = .039). Moreover, the physician-rated cosmesis score was considered excellent/good in 86% of those in the WBI group vs 82% in the H-WBI group, as well as fair/poor in 14% and 18% of patients, respectively.

Explaining the significance of the NRG RTOG 1005 study and PCS5 trial, Yu concluded, “[These trials] show that radiation oncologists are very interested in improving the convenience of our treatments to our patients. It is really interesting to see how much time and resources are being spent to shorten therapy when in the current fee for service model, shortening therapy reduces revenue for a radiation oncology practice. It's a very altruistic thing that radiation oncologists are trying to do to really have a patient centered treatment that is more efficient, more sensitive to healthcare resources, and emphasizes the value of radiation oncology.”

References

1. Gillespie EF, Mathis NJ, Marine C, et al. Prophylactic radiation therapy vs. standard-of-care for patients with high-risk, asymptomatic bone metastases: a multicenter, randomized phase II trial. Int J Rad Oncol. 2022;114(5):P1059. doi:10.1016/j.ijrobp.2022.09.005
2. Niazi TM, Nabid A, Malagon T, et al. Conventional vs. hypofractionated, radiotherapy for high-risk prostate cancer: 7-year outcomes of the randomized, non-inferiority, phase 3 PCS5 Trial. Int J Rad Oncol. 2022;114(3):S3. doi:10.1016/j.ijrobp.2022.07.2323
3. Vicini FA, Winter K, Freedman GM, et al. A phase III trial of hypofractionated whole breast irradiation with concurrent boost versus conventional whole breast irradiation plus sequential boost following lumpectomy for high risk early-stage breast cancer. Presented at 2022 American Society for Radiation Oncology (ASTRO) Annual Meeting; October 23-26, 2022; San Antonio, TX. Abstract 1. Accessed October 28, 2022.