Proton beam radiotherapy plus chemotherapy for unresectable NSCLC improves survival: 5-year results

In patients with unresectable non-small cell lung cancer (NSCLC), concurrent chemotherapy and proton beam radiotherapy (PBT) may improve survival compared with treatment with concurrent chemotherapy and traditional radiation (26.5 vs 16 months, respectively), with toxic effects similar to those reported in previous studies, according to results published in the journal JAMA Oncology. These data comprise the longest follow-up, to date, of stage III lung cancer patients treated with 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,” said lead author Joe Y. Chang, MD, PhD, professor, radiation oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.

Proton therapy is an advanced type of radiation treatment that delivers radiation directly to tumors via a beam of protons. Cancer cells are destroyed, and healthy tissue spared. With a low dose of radiation, protons enter the body and stop at the tumor, matching its shape, volume, or depth.

“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,” said Dr. Chang.

For this open-label, single-group assignment phase 2 study, he and fellow researchers assessed survival, toxic effects, and patterns of treatment failure achieved with concurrent chemotherapy and high-dose PBT in patients with unresectable stage III NSCLC.

They sought to assess the efficacy of PBT in reducing toxic effects in 64 patients (median age: 70 years; 34% female; 47% stage IIIA; 53% stage IIIB) with unresectable IIIA/IIIB histologically confirmed NSCLC, Karnofsky performance status of 70-100, and a 6-month prediagnosis weight loss of no more than 10%. PET and/or CT were used for staging, and induction chemotherapy was allowed.

All patients underwent concurrent chemotherapy with carboplatin-paclitaxel, and passively scattered PBT (74-Gy relative biological effectiveness). Researchers conducted Kaplan-Meier analysis of overall survival (OS), progression-free survival (PFS), actuarial distant metastasis, and locoregional recurrence. They categorized treatment pattern failures as local/regional or distant.

At last follow-up (median: 27.3 months for all patients, 79.6 months for survivors), 27% of patients (n=17) were alive. Median OS was 26.5 months (5-year OS: 29%; 95% CI: 18%-41%). Five-year PFS was 22% (95% CI: 12%-32%). Five-year actuarial distant metastasis was 54%, and 5-year locoregional recurrence was 28%.

Most treatment failures were distant (48%), and researchers noted low rates of crude local recurrence (16%) and regional recurrence (14%).

Grade 2 esophagitis occurred in 28% of patients, and grade 3 in 8%. Only one patient (2%) had acute grade 2 pneumonitis, and late toxic effects were rare, and included grade 2 esophageal and grade 4 esophagitis each occurring in only one patient. Grade 2 bronchial stricture occurred in two patients (3%), and grade 4 bronchial fistula in one (2%). No acute or late grade 5 toxic effects were seen.

One limitation, noted Dr. Chang, is that this study was designed over 10 years ago, before major improvements in all treatment modalities.

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