Advances in radiotherapy for locally advanced NSCLC

Abstract

Radiation therapy plays a central role in patients with locally advanced NSCLC who are not eligible for surgery. In fit patients, radiation is administered with concurrent chemotherapy leading to improved survival compared to either modality alone or the sequence of both. Different strategies to improve local control have been explored. Multiple dose escalation protocols produced higher local control rates and promising 2-year survival rates at radiation doses above 70 or even 80 Gy. However, higher doses are currently not recommended following the results of the recent phase III RTOG 0617 trial comparing standard dose radiotherapy with highdose (74 Gy) conformal radiotherapy which demonstrated a significant increase in the risk of death in the high dose arm. Altered fractionation regimens using concomitant boost or hyperfractionated and/or accelerated radiation therapy have reported to be successful, but logistics limited its use in routine practice. Technical advances in radiation therapy include PET CT planning, visualization of tumour hypoxia by dynamic PET-CT, stereotactic boost on hypoxic areas, proton beam therapy, IMRT and image-guided radiation therapy. The best systemic regimen to be used concurrently with radiation has yet to be defined; as has the role of induction and consolidation therapy in addition to concurrent chemoradiotherapy. Monoclonal antibodies such as bevacizumab and cetuximab have not been able to improve outcomes and the results of the phase III study of the novel anti-folate pemetrexed in combination with cisplatin compared to standard etoposide/cisplatin are awaited. The role of targeted agents in molecularly selected subgroups and the optimal treatment approach in unfit and elderly patients has yet to be defined and are the subject of ongoing clinical trials.