Locally Advanced Non-Small Cell Lung Cancer: Whether Higher Dose of Radiation is a Winner?

Radiotherapy is a mainstay of treatment of locally advanced Non-Small Cell Lung Cancer (NSCLC). Despite that there is a relative paucity of prospective trials directed on the radiotherapy use in this indication in comparison with prospective studies related to the use of chemotherapy. In this context, a recently published randomized study by [1]. is certainly to be welcomed. This randomized phase II trial (NARLAL: Navelbine and Radiotherapy in Locally Advanced Lung cancer) compared two commonly used radiation dose schedules 60 Gy in 30 fractions (60 Gy/30F) and 66 Gy in 33 fractions (66 Gy/33F) based on a “pick the winner” design. Radiotherapy was given concomitantly with a convenient oral formulation of Vinorelbine administered 50 mg three times weekly. Radio-chemotherapy was preceded by two cycles of full-dose induction chemotherapy Carboplatin and oral Vinorelbine. After demonstration that plan of 66 Gy/33F (with 3-dimensional conformal technique or IMRT at the discretion of treating institution) may fulfill predefined dose constraints criteria patients were randomized to 60 Gy or 66 Gy. All patients had FDG-PET CT performed as a part of initial work-up and at nine months of follow-up as part of the protocol. The primary end-point of this study was Local Progression Free Interval (LPFI). Local failure was defined as a progression within radiation field. Overall Survival (OS) was a secondary endpoint. Of 121 patients included, three were not able to receive 66 Gy/33F, because of dose constraints, one had distant metastases at the inclusion, thus finally 117 stage IIB and III NSCLC cases were considered eligible and were subject to the analysis. The LPFI at 9 months was 54% and 59% for 60 Gy/30Fand 66 Gy/33F arms, respectively (p = 0.55). The median OS was also not different for compared groups, 23.3 months for 60 Gy/30F and 23.7 months for 66 Gy/33F. Toxicity in this trial, partially earlier published in detail [2], was mild and not statistically different in compared schedules. Based on the complex “pick the winner” study design, the 66 Gy/33F was chosen as a winning arm for further phase III studies that will test further dose escalation given as a simultaneous boost to the areas of high FDG uptake within tumor and pathological lymph nodes with a standard arm of 66 Gy/33F concurrently with doublet platinum based chemotherapy [3].