Tumor irradiation, when added to a newly formulated chemotherapy regimen, may lengthen survival in patients with metastatic non-small cell lung cancer (mNSCLC), according to results recently accepted for publication in the journal Oncotarget.
Researchers conducted a retrospective analysis in 69 patients who underwent a regimen with a novel metronomic chemotherapy (mCH) comprised of dose-fractionated cisplatin, oral etoposide, and bevacizumab (mPEBev). This regimen was designed for its immune-modulating and anti-angiogenic effects, and was administered metronomically, spaced out in the safest possible disease to reduce side effects and toxicity. Of these patients, 45 also underwent palliative radiotherapy of one or more metastatic sites.
“We had recently established the safety and anti-tumor activity of the mPEBev regimen in mNSCLC,” said lead researcher Pierpaolo Correale, MD, PhD, director of the Oncology Unit, Metropolitan Hospital, Reggio Calabria, Italy. “We hypothesized that in patients undergoing the mPEBev regimen, the use of radiotherapy could provide additional immunostimulation to improve their long-term survival,” he added.
The authors are a multidisciplinary group of Italian researchers, led by Dr. Correale. They include Luigi Pirtoli, MD, full professor and director, radiation oncology, Siena University Hospital, Italy; and Antonio Giordano, MD, PhD, Director of the Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, Temple University, Philadelphia.
Upon statistical analysis, Dr. Correale and colleagues discovered patients treated with additional radiotherapy (RT) had a longer median survival compared with those treated with only mCH (22.12 vs 12.1 months; P=0.015), with no difference in progression-free survival.
In addition, they found that survival correlated with mPEBev regimen’s ability to induce the percentage of activated dendritic cells (CD3-CD11b+CD15-CD83+CD80+), with the fold to baseline value for ≥ 1 vs > 1 being 4+ vs 56+ months, respectively (P=0.049). Survival also correlated with the ability of the regimen to induce the percentage of central-memory T-cells (CD3+CD8+CD45RA-CCR7+), with fold to baseline value for < 1 vs > 1 being 8+ vs 31+ months, respectively (P=0.045).
“We found that radiotherapy, together with its direct cytolytic effect on tumor tissue, also elicits systemic immunological events, similarly to cancer vaccines,” added Dr. Pirtoli. “This response may result in the regression of distant metastases, known as the abscopal effect, as suggested by immunological mechanisms further investigated by our team in previous research.”
“This is a good example of translational research, from bench to bedside, where a multi-disciplinary collaboration actually developed new operative models of treatment for the most frequent malignant disease based on solid preclinical models,” concluded Dr. Giordano.