Proton Beam Therapy May Improve Survival Compared to Conventional Radiation in Stage II and III NSCLC Patients

SUMMARY: Lung cancer is the second most common cancer in both men and women and the American Cancer Society estimates that for 2016 about 224,390 new cases of lung cancer will be diagnosed and over 158,000 patients will die of the disease. Lung cancer is the leading cause of cancer-related mortality in the United States. Even though Photon-based external beam radiation plus concurrent chemotherapy is the current standard of care for patients with unresectable stage III NSCLC, Proton beam therapy is emerging as an alternative to conventional Photon beam therapy for many cancer types. Radiation Therapy involves the use of X-Rays, Gamma rays and charged particles for cancer treatment. External beam radiation therapy is most often delivered using a linear accelerator in the form of Photon beams (either X-rays or Gamma rays). Photons have no mass and are packets of energy of an electromagnetic wave. Electrons and Protons are charged particles and Electrons are considered light particles whereas Protons are considered heavy particles. Electron beams are used to irradiate skin and superficial tumors, as they are unable to penetrate deep into the tissues. The different types of external beam radiation treatments include 3-Dimensional Conformal Radiation Therapy (3D-CRT) meant to deliver radiation to very precisely shaped target areas, IMRT or Intensity Modulated Radiation Therapy which allows different areas of a tumor or nearby tissues to receive different doses of radiation, Image Guided Radiation Therapy (IGRT) which allows reduction in the planned volume of tissue to be treated as changes in a tumor size are noted during treatment, Stereotactic RadioSurgery (SRS) which can deliver one or more high doses of radiation to a small tumor, Stereotactic Body Radiation Therapy (SBRT) or CYBERKNIFE® which is similar to SRS but also takes the normal motion of the body into account while treating malignancies involving the lung and liver and Proton beam therapy. Proton beams unlike Photons, enter the skin and travel through the tissues and deposit much of their energy at the end of their path (known as the Bragg peak) and deposit less energy along the way. This is unlike Photons which deposit energy all along the path through the tissues and the deposited dose decreases with increasing depth. As a result, with Proton beam therapy, normal tissues are exposed to less radiation compared with Photons. Despite this advantage, tissue heterogeneity such as organ motion, tumor volume changes during treatment can have a significant negative impact on target coverage for Proton beam therapy and can result in damage to the surrounding tissues and potential complications.

It has remained unclear whether Proton beam therapy improves Overall Survival (OS) in patients with NSCLC. To address this question, the authors conducted a retrospective analysis using the National Cancer Data Base (NCDB) and analyzed outcomes and predictors associated with Proton beam therapy for NSCLC. This analysis included 140,383 patients with stage I to stage IV NSCLC, treated with thoracic radiation from 2004-2012, of whom 59% had stage II and III disease. Of these patients, 140,035 were treated with Photon beam therapy and 348 with Proton beam therapy. The median age was 68 yrs, 57% were males, 85% were Caucasian, 27% were treated at academic centers and 78% in metropolitan areas. To reduce treatment selection bias, propensity score matching method was implemented.

It was noted that patients were less likely to receive Proton beam therapy in community or comprehensive community centers compared to academic centers (P< 0.001). Further, patients who received Proton beam therapy were more likely to have a higher education and income. On multivariate analysis, it was noted that the risk for death was greater with use of Photon beam therapy compared to Proton beam therapy (HR=1.46; P<0.001). Among patients with stage II and III disease, 5 year OS was superior with Proton beam therapy compared with Photon beam therapy (22.3% versus 15%; P=0.01). Patients with stage II and III disease who received Photon beam therapy had worse OS both in multivariate (HR=1.19; P=0.06) and univariate (HR=1.23; P=0.02) analyses, compared with Proton beam therapy. Proton beam therapy was associated with better 5 year OS compared to Photon beam therapy (23% vs. 14%; P=0.02), on propensity matched analysis. The median OS was 11 months with Photon therapy compared to 19 months with Proton therapy.

The authors concluded that in this retrospective database analysis, thoracic radiation with Proton beam therapy was associated with better survival rates for patients with stage II and III NSCLC. An ongoing randomized phase III trial (NRG Oncology 1308) involving stage III NSCLC patients is evaluating if chemotherapy and Proton beam therapy is superior to chemotherapy and Photon beam therapy. National Cancer Data Base analysis of proton versus photon radiotherapy in non-small cell lung cancer (NSCLC). Behera M, OConnell KA, Liu Y, et al. J Clin Oncol 34, 2016 (suppl; abstr 8501)