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Proton Beam Therapy Reduced Bone Marrow Suppression Compared with IMRT for Patients with Stage III NSCLC Receiving Concurrent Chemotherapy

Reviewer: Curtiland Deville, MD
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: May 28, 2010

Presented by: Ritsuko Komaki, MD
Presenter's Affiliation: University of Texas M.D. Anderson Cancer Center

Background

• Lung cancer is the leading cause of cancer mortality, with a 5-year overall survival of 15%.
• Improvements in radiation treatment planning and delivery, in addition to combined modality treatment, have led to an increase in median survival from 9.8 months to 22.7 months in the recent Phase I/II RTOG protocol 0324. This protocol evaluated concurrent chemotherapy, radiation, and Cetuximab, an IgG1 monoclonal antibody, in patients with Stage III non-small cell lung cancer (NSCLC).
• Multiple prospective randomized trials have demonstrated a survival benefit with concurrent chemotherapy and radiation over sequential treatment, despite increased toxicity, including esophagitis, pneumonitis, and bone marrow suppression with concurrent treatmemt.
• Strategies to improve the therapeutic ratio – increasing the dose to tumor and reducing the dose to normal tissues – continue to be investigated.
• The physical properties of proton therapy allow for unique dose deposition with no exit dose, potentially reducing the dose to normal tissues, including the irradiated thoracic bone marrow.
• The objective of this study was to determine if proton therapy can reduce the amount of bone marrow suppression in comparison to 3D conformal and intensity modulated radiation therapy (IMRT) in lung cancer patients treated with concurrent chemotherapy and radiation.

Methods

• This was a single institution, nonrandomized, retrospective review of NSCLC patients treated at the M.D. Anderson Cancer Center from 2003 – 2008.
• There were 132 patients: 67 in the proton arm and 75 in the 3D/IMRT arm.
• 4D planning was implemented in 2004.
• Inclusion criteria: concurrent chemotherapy, dose > 60 Gy, and no previous radiation
• Patients receiving mixed photon and proton therapy were excluded.
• Toxicity was scored based on CTCAE criteria.
• Median doses prescribed were 63 Gy and 74 Gy(RBE) for the 3D/IMRT and proton therapy arms, respectively.

Results

• There were no differences in baseline demographic data between the 2 arms, except for age, which was slightly increased in the proton therapy arm at 67 versus 62 in the 3D/IMRT arm.
• The photon arm also had a slightly increased number of Stage IIIb patients.
• Concurrent chemotherapy generally consisted of weekly Carboplatin and Taxol.
• Median follow-up was longer in the photon arm at 15.6 months versus 11.4 months in the proton arm.
• Baseline Hgb was slightly lower in the photon arm.
• Regarding the primary outcome, bone marrow suppression was significantly decreased in the proton arm, statistically significant across all parameters, including, hemoglobin, platelets, white blood cells.
• Any grade and grade 2 or greater toxicities were significantly lower in the proton therapy arm.
• Secondary outcomes also showed an increased median survival in the proton arm of 27 months versus 17 months in the photon arm.
• Local-regional control and distant metastasis were not significantly different.

Author's Conclusions

• These data suggest that the reduction in dose to the low dose regions of irradiated normal tissues with proton therapy results in a clinically significant reduction in bone marrow suppression.

Scientific Implications

• This single institution, retrospective, nonrandomized comparison of proton and photon therapy in NSCLC patients provides preliminary evidence for potential improvement in the therapeutic ratio of combined modality treatment with proton therapy, specifically by reducing bone marrow suppression.
• The poorer overall survival in the 3D/IMRT arm merits further investigation and may reflect confounding limitations, such as increased number of patients with Stage IIIb disease and chemotherapeutic dose reductions in the photon arm.
• The ongoing randomized controlled trial of proton versus photon therapy in patients with Stage III NSCLC should further clarify these issues.