Concurrent Chemotherapy, Proton Therapy May Improve Survival in Patients With Advanced Lung Cancer

Key Points

  • At 5 years, the median overall survival was 26.5 months, and the corresponding 5-year overall survival was 29%.
  • Median progression-free survival was 12.9 months, with a 5-year progression-free survival of 22%.
  • In sum, 39 patients experienced a relapse, with distant sites representing 62% of all recurrences. Local and regional recurrence rates were low, 16% and 14%, respectively.

For patients with advanced, inoperable stage III lung cancer, concurrent chemotherapy and proton-beam radiotherapy offers improved survival compared to historical data for standard of care, according to a new study from The University of Texas MD Anderson Cancer Center.

The research, published by Chang et al in JAMA Oncology, reported an overall survival of 26.5 months. In contrast, the historical overall survival rate with standard-of-care concurrent chemotherapy and traditional radiation therapy was 16 months at the time when the study was designed.   

The findings are the final results of the single-institution, phase II study and represent the longest follow-up to date of stage III lung cancer patients who have received proton therapy, said Joe Y. Chang, MD, Professor of Radiation Oncology at MD Anderson and the study’s corresponding author.

Proton Therapy

“Advanced lung cancer patients with inoperable disease traditionally have been treated with concurrent chemotherapy and conventional photon radiation therapy. However, the therapy can be very difficult for patients due to associated toxicities and because many patients are also dealing with comorbidities,” explained Dr. Chang.

Proton therapy is an advanced type of radiation treatment that uses a beam of protons to deliver radiation directly to the tumor, destroying cancer cells while sparing healthy tissues. Protons enter the body with a low radiation dose and stop at the tumor, matching its shape and volume or depth. They deposit the bulk of their cancer-fighting energy right at the tumor, thereby reducing the dose to cardiopulmonary structures, which impacts the toxicity, functional status, quality of life, and even survival for patients, explained Dr. Chang.

“With our study, we hypothesized that proton therapy would offer a survival benefit to patients and reduce treatment-associated toxicities, which can be very serious,” he said.

The study opened at MD Anderson in 2006; in this research, Dr. Chang and his colleague report on the study’s 5-year results.

Major Findings

For the prospective phase II trial, 64 patients with inoperable, stage III non–small cell lung cancer were enrolled. The study’s primary endpoint was overall survival. The researchers hypothesized that the median overall survival would increase from historical data of 16 months on standard therapy to 24 months. Secondary endpoints included distant metastasis and local and regional recurrence rates. Toxic effects of treatment in both the acute and late settings also were analyzed.

Median follow up was 27.3 months for all patients, and 79.6 months for alive patients. At 5 years, the median overall survival was 26.5 months, and the corresponding 5-year overall survival was 29%. Median progression-free survival was 12.9 months, with a 5-year progression-free survival of 22%.

In sum, 39 patients experienced a relapse, with distant sites representing 62% of all recurrences. Local and regional recurrence rates were low, 16% and 14%, respectively.

Acute and late toxic effects diagnosed in patients included esophagitis, pneumonitis, and cardiac arrhythmia. Of note, said Dr. Chang, no patients developed the most severe (grade 5) toxicities, as seen in patients who receive standard of care.

Study Limitations

Dr. Chang noted his study is not without limitations. Of greatest significance, the study was designed more than a decade ago. While the study’s survival, recurrence rates, and toxic effects are still favorable when compared to rates associated with the most advanced traditional photon radiation therapy, intensity-modulated radiation therapy, technology to diagnose and stage the disease, as well as all treatment modalities have significantly improved. 

“When the study opened, positron-emission tomography imaging had just been approved for lung cancer staging. The image quality was poor, and didn’t include a computed tomography component in most facilities across the country,” said Dr. Chang. “Obviously, the technology has improved dramatically over the past decade and has made a significant impact on diagnosis and staging. Also, delivery of both the conventional intensity-modulated radiation therapy and proton therapy, have improved, thereby reducing side effects for both treatment modalities.”  

Dr. Chang also noted the advancements in cancer biology and immunotherapy and that both are important areas of research focus in combination with proton therapy.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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