News | Lung Cancer | September 18, 2019

Radiation After Immunotherapy Improves Progression-free Survival for Some Metastatic Lung Cancer Patients

Treating a single tumor with high-dose radiation boosts the immune system and shrinks distant tumors for some patients

Radiation After Immunotherapy Improves Progression-free Survival for Some Metastatic Lung Cancer Patients

September 18, 2019 — Adding precisely aimed, escalated doses of radiation after patients no longer respond to immunotherapy reinvigorates the immune system in some patients with metastatic non-small-cell lung cancer (NSCLC), increasing progression-free survival (PFS). Findings of the phase II randomized trial were presented at the 61st Annual Meeting of the American Society for Radiation Oncology (ASTRO), Sept. 15-18 in Chicago.1

“This study provides one more important piece of data that indicates that, for some patients, the immune system can be a really powerful tool to combat metastatic lung cancer,” said Allison M. Campbell, M.D., Ph.D., a resident in the Department of Therapeutic Radiology at Yale New Haven Hospital and lead author on the study. “It points us in the direction of places to look for biomarkers that might predict which patients would best respond to this type of therapy."

NSCLC accounts for roughly 80-85 percent of all lung cancers. Approximately 57 percent of patients with NSCLC have already progressed to stage IV cancer at the time of diagnosis, meaning that tumors have spread to other parts of the body, making it difficult to cure. This type of cancer may be treated with radiation therapy, immunotherapy, surgery, chemotherapy or targeted drug therapy to relieve symptoms and allow patients to live longer. 

This phase II prospective trial explored the benefits of treating one cancerous lesion with stereotactic body radiotherapy (SBRT) in patients with NSCLC whose cancer had continued to spread after treatment with pembrolizumab, a type of immunotherapy. Campbell and her team looked to see if tumors outside the treated area would also shrink, how long patients lived before their disease progressed after treatment, and what was happening to the immune systems of those patients who responded well to the combination of SBRT and immunotherapy.

The study included 56 patients with NSCLC, all of whom had two or more measurable tumors at enrollment. Of these, six patients had already received immunotherapy and were immediately treated with SBRT, which delivers precise, intense doses of radiation. The other 50 patients had not yet been treated with immunotherapy; of these, 16 were treated with SBRT after their disease progressed after treatment with pembrolizumab (also known by its brand name Keytruda).

A total of 21 patients completed both treatments and lived, on average, five months longer without their disease progressing any further. In two patients (9.5 percent), tumors outside the treated area shrank by 30 percent or more and stayed that way for more than a year. Ten patients (47.6 percent) experienced disease stabilization (tumors neither grew nor shrank) following the addition of SBRT. 

“We weren’t surprised to see that some patients had tumors shrink outside the field of radiation,” said Campbell, who added that the research team really wanted to learn more about what was happening in the immune systems of those patients. “There’s been a lot of interest in how radiation can stimulate the immune system. We wanted to learn all we could from our very best responders.” 

A closer analysis of the peripheral blood cells in patients whose tumors shrank or did not grow suggested that T cells played an important role in the immune system response, said Campbell. “We found that there were two things that correlated with patients living longer without their disease progressing,” she said. “Those two things were T cells infiltrating the tumor before immunotherapy was given, and the presence of immune-related side effects at any time during the course of treatment, such as inflammation of the lung or inflammation of the GI tract. Patients who experienced these side effects lived a longer period of time before the disease progressed.”

Campbell and her team were able to identify two different types of T cells performing important functions in fighting the tumors. In patients who responded well to the combination therapy, they found both CD8 T cells, which can kill cancer cells directly, and CD4 T cells, which help the immune system organize its response to threats such as cancer. “We saw different proportions of these cells in our good responders versus our bad responders,” she said, “as well as different activation statuses. In people who responded well to the combination therapy, we saw a population of CD8 T cells that looked more excited, and in those with poor responses, we saw a population of CD4 T cells with inhibitory markers. The bigger picture here is that there are signatures in the peripheral blood that are promising avenues for future identification of people who will respond well to SBRT combined with immunotherapy.”

The next step, she said, will be to validate these findings in a larger population.

“We are starting to see that the combination of immunotherapy and radiation is safe, and there are some hints that for certain patients, radiation might be an important option when immunotherapy no longer curbs disease progression,” said Campbell. “Our study lays the groundwork for a phase III randomized trial, which is the gold standard for changing guidelines and clinical practice.”

Read more about clinical trials presented at ASTRO 2019.

For more information: www.astro.org

 

Reference

1. Campbell A.M., Cai W.L., Burkhardt D., et al. Final Results of a Phase II Prospective Trial Evaluating the Combination of Stereotactic Body Radiotherapy (SBRT) with Concurrent Pembrolizumab in Patients with Metastatic Non-Small Cell Lung Cancer (NSCLC). Red Journal, published online Sept. 1, 2019. https://doi.org/10.1016/j.ijrobp.2019.06.453

Related Content

Varian received FDA clearance for its Ethos therapy in February 2020. It is an adaptive intelligence solution that uses onboard AI in the treatment system to take the cone beam CT imaging on the system, compare it to the treatment plan and deliver an entire adaptive treatment plan in a typical 15-minute treatment time slot, from patient setup through treatment delivery.

Varian received FDA clearance for its Ethos therapy in February 2020, shown here displayed for the first time at ASTRO 2019. It is an adaptive intelligence solution that uses onboard AI in the treatment system to take the cone beam CT imaging on the system, compare it to the treatment plan and deliver an entire adaptive treatment plan in a typical 15-minute treatment time slot, from patient setup through treatment delivery.

Feature | Treatment Planning | April 03, 2020 | Dave Fornell, Editor
The traditional treatment planning process takes days to create an optimized radiation therapy delivery plan, but new
#COVID19 #Coronavirus #2019nCoV #Wuhanvirus #SARScov2 New studies use SIRD model to forecast COVID-19 spread; examine patient CT scans to correlate clinical features with mortality

Fig 1. A sample scoring on CT images of a 63-year-old woman from mortality group demonstrated a total score of 63. It was calculated as: for upper zone (A), 3 (consolidation) × 3 (50–75% distribution) × 2 (both right and left lungs) + 2 (ground glass opacity) ×1 (< 25% distribution) × 2 (both right and left lungs); for middle zone (B), 3 (consolidation) × 2 (25–50% distribution) × 2 (both right and left lungs) + 2 (ground glass opacity) × 2 (25–50% distribution) × 2 (both right and left lungs); for lower zone (C), 3 (consolidation) × (2 (25–50% distribution of the right lung) + 3 (50–75% distribution of the left lung)) + 2 (ground glass opacity) × (2 (25–50% distribution of the right lung) + 1 (< 25% distribution of the left lung)) Yuan et al, 2020 (CC BY 4.0)

News | Coronavirus (COVID-19) | April 01, 2020
April 1, 2020 — A new study, ...
Women are more likely to be cured of cancer by radiotherapy but the side effects are worse.

Women are more likely to be cured of cancer by radiotherapy but the side effects are worse. Image by Mark Kostich

News | Radiation Therapy | March 30, 2020
March 30, 2020 — Women undergoing radiotherapy for
A new framework from an international team of experts aims to help protect patients and providers, and conserve protective equipment for frontline healthcare workers #COVID19 #Coronavirus #2019nCoV #Wuhanvirus #SARScov2
News | Prostate Cancer | March 30, 2020
March 30, 2020 — In the wake of the COVID-19 pan
Novel scanners may open door for prognostic assessment in patients receiving cochlear implants

Iva Speck, MD, explains research showing that novel, fully digital, high-resolution positron emission tomography/computed tomography imaging of small brain stem nuclei can provide clinicians with valuable information concerning the auditory pathway in patients with hearing impairment. The research is featured in The Journal of Nuclear Medicine (read more at http://jnm.snmjournals.org/content/current). Video courtesy of Iva Speck, University Hospital Freiburg, Germany.

News | PET-CT | March 26, 2020
March 26, 2020 — Novel, fully digital, high-resolution...
Age‐standardized, delay‐adjusted overall cancer incidence rates for 2012 through 2016 are illustrated among males and females by racial/ethnic group

Age‐standardized, delay‐adjusted overall cancer incidence rates for 2012 through 2016 are illustrated among males and females by racial/ethnic group. Racial/ethnic groups are mutually exclusive. Data for the non‐Hispanic American Indian/Alaska Native (AI/AN) population are restricted to Indian Health Service Purchased/Referred Care Delivery Area (PRCDA) counties. API indicates Asian/Pacific Islander. Chart courtesy of ACS Journals 

News | Radiation Oncology | March 16, 2020
March 16, 2020 — The Ann...