Consolidation Chemotherapy after Concurrent Radiochemotherapy in Locally Advanced Non–small-Cell Lung Cancer May Have Been Beneficial if We Only Knew Where It Have Worked

Abstract

In a recent article by Tsujino et al.1Tsujino K Kurata T Yamamoto S et al.Is consolidation chemotherapy after concurrent chemo-radiotherapy beneficial for patients with locally advanced non-small-cell lung cancer? A pooled analysis of the literature.J Thorac Oncol. 2013; 8: 1181-1189Crossref PubMed Scopus (97) Google Scholar pooled the data from the literature investigating the effectiveness of consolidation chemotherapy (CHT) after concurrent radiochemotherapy (RT-CHT) in locally advanced non–small-cell lung cancer (NSCLC). They found no difference (survivals, toxicity) between RT-CHT followed by consolidation CHT and exclusive RT-CHT, adding to previous observations that concurrent RT-CHT is the standard treatment in locally advanced NSCLC.2Aupérin A Le Péchoux C Rolland E et al.Meta-analysis of concomitant versus sequential radiochemotherapy in locally advanced non-small-cell lung cancer.J Clin Oncol. 2010; 28: 2181-2190Crossref PubMed Scopus (1324) Google Scholar, 3O'Rourke N Roqué I Figuls M Farré Bernadó N Macbeth F Concurrent chemoradiotherapy in non-small cell lung cancer.Cochrane Database Syst Rev. 2010; 6 (CD002140)PubMed Google Scholar, 4Liang HY Zhou H Li XL Yin ZH Guan P Zhou BS Chemo-radiotherapy for advanced non-small cell lung cancer: concurrent or sequential? It's no longer the question: a systematic review.Int J Cancer. 2010; 127: 718-728Crossref PubMed Scopus (21) Google Scholar Another recent data5Jeremić B Miličić B Milisavljević S Radiotherapy alone vs. radiochemotherapy in patients with favorable prognosis of clinical stage IIIA non-small-cell lung cancer.Clin Lung Cancer. 2013; 14: 172-180Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar showed that concurrent RT-CHT can also be considered as one of standards in clinical stage IIIA NSCLC patients. Although reasons for inefficiency of consolidation CHT may be multiple, it is challenging to disclose some aspects that may have adversely influenced the outcome. Although these studies presented very detailed pattern of failure in general, this was done for the whole time period of the study (treatment plus follow-up). This way we only learned about the total patterns of failure and not about which type of failure was observed when, that is, after concurrent or after consolidation part, and particularly in which patients. Why exact pattern of failure is so important? First, there are several types of patients after the initial (concurrent) part of RT-CHT and they can easily be separated regarding the response. Although it is extremely unlikely that those achieving a stable disease would benefit from the consolidation CHT, those with either a complete response (CR) or a partial response (PR) seem as likely candidates (although not all of them) to benefit from the consolidation CHT. Therefore, separation of pattern of failure occurring in likely (CR and PR) and unlikely (stable disease) candidates could be used for further studies using similar design with respect to, for example, eligibility criteria. Second, and more importantly, among likely candidates (CR and PR) to benefit from consolidation CHT, a distinction should be made between those achieving CR and those achieving PR after concurrent RT-CHT. This is so because different mechanisms (precisely, different location) of action of consolidation CHT would be expected. In the CR patients, consolidation CHT would target only a microscopic disease both intrathoracically and extrathoracically, whereas in the PR patients, it would have also to address clinically overt intrathoracic disease. Pattern of failure in these two distinct groups of patients would then clearly show how and where consolidation CHT actually acts and to what extent (clinical versus subclinical). In addition, we would be able to investigate the determinants of treatment outcome such as cross-resistance between drugs or drugs and RT. Although identifying pattern of failure in patients achieving different response after concurrent RT-CHT would place additional burden on investigators and hospitals, this effort would be eventually rewarding. This way we would be able to identify different patient subsets and different options and to proceed (or not) with a consolidation CHT, an approach which would ultimately lead to a better patient-tailored treatment sequence, a must for a future clinical research in lung cancer.