By Bradford S. Hoppe, MD
The standard-of-care treatment for patients with locally-advanced, non-small cell lung cancer, or Stage 3 NSCLC, is concurrent chemotherapy and radiation therapy, including proton therapy, as a potentially less-toxic, yet effective, treatment option. Clinical trials for Stage 3 NSCLC are open at the UF Health Proton Therapy Institute examining 1) hypofractionated (an accelerated course of proton treatments delivered over 3 weeks instead of 7 weeks) proton therapy with chemotherapy and; 2) proton therapy versus X-ray radiation. Unfortunately, these clinical trials have been difficult to accrue patients. Two new studies published by UF explored these issues surrounding the accrual.
In the first study, the researchers demonstrated the main barrier for enrolling patients into clinical trials was patient ineligibility, due to several medical issues making them “unfavorable,” including previous lung cancer surgery, poor lung function, weight loss, prior cancers, and other medical comorbidities. Additionally, it was shown that patients getting proton therapy for Stage 3 NSCLC at UF are older than typical Stage 3 NSCLC patients. This finding is likely due to older patients having Medicare, which covers proton therapy for lung cancer, while many private payers are not covering treatment cost—even on clinical trials.
The second study by the UF researchers looked at the outcomes of 90 consecutive patients treated with proton therapy at the UF Health Proton Therapy Institute.
The two-year Stage 3 NSCLC patient outcomes, published last month in Acta Oncologica,  suggest that favorable- and unfavorable-risk patients responded similarly to proton therapy. Patients were categorized as favorable-risk, people who had no other health issues, or unfavorable-risk, people who had one or more of the following risk factors:
- age ≥ 80
- stage IV cancer
- weight loss >10% in 3 months
- performance status ≥2
- FEV1 <1.0 or oxygen dependency
- prior lung cancer
- prior lung surgery
- prior 2nd cancer in the past 3 years
- prior chest irradiation
After two years, the overall survival was 52% and 45% for favorable- and unfavorable-risk patients, respectively. Overall survival measures the percentage of people in the study who are still alive. “Most patients treated with proton therapy for Stage 3 NSCLC have unfavorable risk factors. These patients had similar outcomes to favorable-risk patients,” said researchers. “Enrollment in future clinical trials may improve if eligibility is less restrictive.”
In fact, these study results have led to a re-evaluation of clinical trials eligibility requirements and broadened them for patients with Stage 3 NSCLC.
 He J. Zhu, Romaine C. Nichols, Randal H. Henderson, Christopher G. Morris, Stella Flampouri, Dat C. Pham, Christopher L. Klassen, Vandana Seeram, James D. Cury, Lisa Jones, Lisa McGee & Bradford S. Hoppe (2019) Impact of unfavorable factors on outcomes among inoperable stage II-IV Nonsmall cell lung cancer patients treated with proton therapy, Acta Oncologica, DOI: 10.1080/0284186X.2018.1546060