Acute Esophageal Reactions from Proton Beam Therapy and Concurrent Chemotherapy for Non-Small Cell Lung Cancer: Reduction in Incidence and Severity Despite Higher Doses

Reviewer: James M. Metz, MD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: May 22, 2007

Presenter: R. Komaki
Presenter's Affiliation: MD Anderson Cancer Center
Type of Session: Scientific

Background
In the United States, concurrent chemotherapy and radiation therapy is standard for unresectable NSCLC. However, there is significantly increased toxicity with concurrent radiochemotherapy as opposed to sequential treatment. There has also been evidence that esophageal toxicity can be reduced when 2D versus 3D treatment planning is utilized, but still remains very high. Protons, due to the better dose distribution, may further reduce toxicity particularly in the era of concurrent chemotherapy and radiation therapy. This study reports on the acute toxicity in the initial patients treated with combined chemotherapy and proton therapy for NSCLC.

Materials and Methods

Initial 25 patients treated at the MD Anderson Proton Therapy Center for NSCLC with combined chemotherapy and proton therapy.
Acute toxicity in the first 90 days after the initiation of treatment is reported.
Patients received carboplatin and taxol based chemotherapy in two separate clinical trials
Comparisons where made to matched patients who received 3D conformal radiation therapy from the same treatment team
Proton dose was 74 CGE while the 3D Conformal radiation dose was 63 Gy

Results

Esophageal reactions for any grade were 60% (Proton) vs 93% (3D)
Esophageal reactions by grade included 16% vs 27% for grade I, 28% vs 45% for Grade 2, 16% vs 20% for GrAD 3, and 0% vs 1% for grade 4, for protons vs 3D Conformal respectively
Patients received their chemotherapy dosing in in 100% of the proton therapy treatments and 93% of the 3D conformal treatments

Author's Conclusions

This is the first report of proton beam therapy and concurrent chemotherapy
The data suggest that higher total doses are achievable with proton beam therapy and concurrent chemotherapy without and increase in incidence or severity of esophageal reactions

Clinical/Scientific Implications

Although preliminary, this study makes an important contribution to the understanding of the combination of chemotherapy and proton therapy. Although a formal statistical comparison was not performed, acute toxicity of combined modality treatment was not increased by giving proton therapy to substantially higher doses then 3D conformal treatment. This is an important concept with moving forward with proton therapy. Proton therapy by itself will most likely not show significant improvements in survival. It is the combination of protons with chemotherapy and targeted biologic agents have the promise to make substantial impacts in overall survival and improve cancer care. We are currently very limited in our ability to combine a number of radiosensitizing chemotherapy agents due to the tolerance of normal tissues to radiation therapy. Proton therapy may completely change this paradigm.