Evaluation of the role of remission status in a heterogeneous limited disease small-cell lung cancer patient cohort treated with definitive chemoradiotherapy

The aim of this retrospective analysis was to establish the role of remission status in LD SCLC patients treated with chemotherapy and TRT without surgery and to compare survival parameters in the different subgroups defined by remission status. This study demonstrates a clear correlation between achieved remission after primary multimodality treatment and systemic disease control as well as overall survival. Especially our results show that complete response following CRT was associated with prolonged TTP, DMFS and OS when compared to partial remission.

Disease control becomes of prime importance in the treated LD SCLC due to the early onset of metastases. A number of studies have reported that the absolute majority of patients with LD SCLC will develop a recurrence [1, 12, 16, 17]. Our analysis on the timing of treatment failure in LD SCLC has demonstrated that in more than half of the patients with distant relapse, failure occurred in the first year from initial diagnosis [18]. Hence previous clinical trials have addressed the question of the correlation between treatment response, disease control and outcome after CRT. A phase III trial published in 1997 by Jeremic et al. firstly showed higher complete remission rates in patients treated with early compared to late concurrent CRT correlated with better long-term survival [9]. However, remission status itself was not analyzed as a prognostic factor. Sixteen years later Sun et al. conducted a phase III study on the timing of TRT concurrent with chemotherapy with complete remission rate as the primary endpoint. Early and late TRT arms were found to be identical concerning remission status and survival rates. The trial demonstrated that complete responders independent of the timing of TRT have significantly better prognosis compared to the rest of the treated patients [8]. In contrast to the above mentioned studies, the present analysis was conducted in a heterogeneous patient cohort and aimed to compare survival parameters between complete, partial and non-responders. The importance of the achievement of complete remission for the TTP, DMFS and OS was emphasized. This fact may be considered in the planning and assessment of future multimodality trials for LD SCLC.

The relevance of tumor shrinkage or downstaging during the course of CRT was already investigated in several smaller studies [19‐21]. A correlation between early metabolic (before start of TRT) and CT changes of the tumor volume and survival in LD SCLC was described by van Loon et al. [19]. Go et al. revealed that downstaging during CRT can be considered as an independent prognostic factor [20]. Also Fujii et al. reported that the achievement of remission after the first cycle of chemotherapy applied simultaneously with TRT was associated with significantly better 2-year survival rate [21].

A major limitation of the present study is its retrospective nature. However, described treatment response rates and survival correlated well with reported historical data. Another important critical point is the heterogeneity of the analyzed cohort but only 3 % of patients presented with primary tumors <5 cm without lymph-node involvement (UICC Stage I). Comprehensive retrospective acquisition of the treatment toxicity was not possible and we decided to analyze only medical charts of the patients who completed definitive CRT without interruptions. Moreover an integration of the PET-CT (Positron emission tomography–computed tomography) could not be exactly evaluated, because fewer than 20 % percent of patients received PET-CTs at initial staging. Nevertheless, present results point out a clinical relevance of the complete remission after definitive CRT and suggest that remission status may be considered as an additional factor in the planning and assessment of multimodality clinical trials for LD SCLC.