https://orcid.org/0000-0001-6195-8624
We thank Rizzo and Brandi for their review and comments [Citation1] on our article [Citation2]. We would like to add that, in addition to the other treatment modalities listed by Rizzo and Brandi, external beam radiation therapy – one of the primary modalities that we reported on in our network meta-analysis – is also a potentially curative treatment options for patients Barcelona Clinical Liver Cancer 0/A hepatocellular carcinoma. Rizzo and Brandi bring up two important points that can be inherent limitations in network meta-analyses, and we encourage careful interpretation from our analyses.
First, we agree with them that network meta-analyses can result in inflated type 1 and 2 errors, most notably type 1 false positive errors [Citation3] and can result in exaggerated relative treatment effects. In our study, however, very few significant differences were noted between treatment modalities, thus leading to our conclusion that all modalities assessed resulted in a similar overall survival. It is also important to note that type 1 and 2 errors are observed in pairwise meta-analyses. An article by Imberger et al. [Citation4] screened 4736 systematic reviews and found, in a sample of 100 network meta-analyses, a false positive rate of 7% and false negative rate of 14%. Cautious interpretation should be encouraged for all meta-analyses, both network meta-analyses and pairwise meta-analyses alike.
Second, we also agree that the included trials have heterogeneous study design, and as stated in our article, even have heterogeneous definition of radiotherapy. This may play a role in the heterogeneous conclusions reported across studies, as stated in our article. Of note, however, the consistency/coherence in the NMA model was found to be generally acceptable.
Ultimately, while we attempted to limit bias as much as possible when comparing results across studies, we agree with Rizzo and Brandi that head-to-head comparisons with randomized trials are needed to more definitively assess which modalities are associated with the best survival, and also to add insight into the differences in toxicity profiles across the modalities. Currently there are no active trials addressing head to head comparisons across all these modalities. Until these trials are completed, hopefully, this analysis can provide evidence-based insight into the decisions health care practitioners and administrators must make now.
References
- Rizzo A, Brandi G. Radiofrequency ablation, radiation therapy, transarterial chemoembolization, and yttrium 90: no differences for local treatment of liver cancer? Acta Oncologica. 2021.
- Chow R, Simone CB 2nd, Jairam MP, et al. Radiofrequency ablation vs radiation therapy vs transarterial chemoembolization vs yttrium 90 for local treatment of liver cancer – a systematic review and network meta-analysis of survival data. Acta Oncologica. 2021;1–11. DOI:https://doi.org/10.1080/0284186X.2021.2009563
- Efthimiou O, White IR. The dark side of the force: multiplicity issues in network meta-analysis and how to address them. Res Synth Methods. 2020;11(1):105–122.
- Imberger G, Thorlund K, Gluud C, et al. False-positive findings in cochrane meta-analyses with and without application of trial sequential analysis: an empirical review. BMJ Open. 2016;6(8):e011890.