Accelerated fraction radiation therapy versus concurrent chemoradiation therapy for locally advanced head and neck cancers: Is there evidence of equivalent effect?

Accelerated fraction radiation therapy versus concurrent chemoradiation therapy for locally advanced head and neck cancers: Is there evidence of equivalent effect?: Snehal Bhupendra Shah, Devendra Arvind Chaukar, Priya Ranganathan



Journal of Cancer Research and Therapeutics 2017 13(1):153-154



Sir,

We read with interest the paper by Gupta et al. comparing accelerated fraction radiation therapy (AFRT) with concurrent chemoradiation therapy (CCRT) for locally advanced head and neck cancers.^[1] This is an important research question, and we commend the authors for conducting a randomized trial to resolve this issue. However, we wish to point out that several vital elements crucial to the interpretation of a clinical trial have not been reported in this paper, and the conclusions of the authors are not congruous with the study results.

The aim of this study was to see whether a similar disease control could be achieved with AFRT as compared with CCRT; however, the authors have not specified whether disease control refers to overall survival or median survival, i.e., what were the primary and secondary objectives of the study? The exact hypothesis has also not been stated clearly – did they expect AFRT to be superior/equivalent/noninferior to CCRT? The study included a sample of 133 patients. On what basis was this sample selected? What was the expected outcome in the standard arm and what sort of treatment effect did they expect in the intervention arm? Unless these important aspects of the study design are specified, it would be difficult to ascertain whether the findings of the study were true or merely a play of chance.

At a median follow-up of 12 months, the disease-free survival was 8% lower in the intervention arm which though not “statistically significant” is extremely important clinically. With a proper sample size and adequate follow-up, it is almost certain that this difference (if it was sustained in a larger sample of patients) would have reached statistical significance, with CCRT being superior to AFRT. Based on this absence of statistical significance, the authors have erroneously concluded that the two treatments have similar efficacy. The power of a superiority trial is defined as its ability to pick up a difference between treatments. This study suffers from a lack of power to pick up the difference between the two groups and the appropriate conclusion should have been that “this study failed to show a difference between the treatments” rather than “we can achieve, same or near to the same local control, with lower toxicities with accelerated six fractions of radiation per week compared with CCRT, especially for Indian population” as the authors concluded. The fundamental difference between “no evidence of effect” and “evidence of no effect” needs to be understood.^[2]

The CONSORT statement was introduced in 2000 and updated since then to help authors to standardize the reporting of clinical trials so that reviewers, editors, and readers could draw valid conclusions from the study reports.^[3] This paper has failed on several fronts to conform to the CONSORT checklist – the most dangerous flaw is to conclude that two treatment options are equivalent (when in reality they are not) due to an inadequate sample size, and thereby advocating that either treatment is acceptable. The conclusions of this study are not justified, have the potential for real harm, and should be interpreted with extreme caution.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 

> References

1.	Gupta M, Mahajan R, Kaushal V, Seem RK, Gupta M, Bhattacharyya T. Prospective randomized trial to compare accelerated (six fractions a week) radiotherapy against concurrent chemoradiotherapy (using conventional fractionation) in locally advanced head and neck cancers. J Cancer Res Ther 2015;11:723-9.
2.	Ranganathan P, Pramesh CS, Buyse M. Common pitfalls in statistical analysis: “No evidence of effect” versus “evidence of no effect”. Perspect Clin Res 2015;6:62-3.   [PUBMED]  [Full text]
3.	Schulz KF, Altman DG, Moher D; CONSORT Group. CONSORT 2010 statement: Updated guidelines for reporting parallel group randomized trials. Ann Intern Med 2010;152:726-32.

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