Abstract
This is a significant study that shows that definitive chemo-radiotherapy is an effective treatment option for cervical esophageal squamous cell carcinoma. We are curious, though, whether local control has any effect on survival.
We read with interest the article by De Virgilio et al. (De Virgilio et al. 2022) on the oncological outcomes of patients treated with definitive chemo-radiotherapy (CRT) for cervical esophageal squamous cell carcinoma (CESCC). We would like to express our gratitude to the authors for conducting the first and only meta-analysis to summarize the oncologic outcomes of 22 studies and over 1200 patients with this extremely rare disease treated with definitive CRT. Overall survival (OS) and progression-free survival (PFS) rates were 35.3 and 29.8%, respectively, after 5 years. Finally, they concluded that definitive CRT is an effective treatment option for CESCC. This is an important article that adds to the body of knowledge, but we have some concerns that need to be addressed for better comprehension.
Radiation therapy (RT), either alone or in combination with chemotherapy, is primarily used to achieve improved local control (LC) of the primary tumor. Local failure has previously been demonstrated to be a significant prognostic factor for survival in the treatment of CESCC (Hoeben et al. 2016). As a result, improved LC of the primary tumor followed by definitive CRT may result in an increase in OS and PFS. Additionally, a multicenter phase II trial found a statistically significant difference in 3 year OS between patients with and without CR (74.6% vs. 25%; p = 0.002) (Zenda et al. 2016). Additionally, other retrospective studies have demonstrated the effect of LC on CESCC patient survival (Uno et al. 2007). However, there was no information about LC or failure patterns in the current meta-analysis. It would be quite instructive if the authors could report on the outcomes of LC rather than focusing exclusively on survival. Additionally, we are curious as to whether LC has any effect on PFS or OS in this meta-analysis.
The appropriate RT dose and technique for CESCC patients are still debatable. According to the authors, there was no difference in OS between CESCC patients treated with intensity modulated RT (IMRT) or 3-D conformal RT. This is a significant finding indicating that definitive CRT could be used in areas lacking new technological RT options such as IMRT/IGRT. The defined dose for the definitive treatment of esophageal cancer is 50.4 Gy, but NCCN guidelines recommend higher radiation doses (60–66 Gy) due to the LC advantage over conventional doses. (National Comprehensive Cancer Network. Clinical practice guidelines in oncology (NCCN Guidelines). Esophageal and Esophagogastric Junction Cancers 2022. NCCN.org.). In the literature, there are conflicting findings regarding increased radiation doses and their potential impact on outcomes. In the current meta-analysis, the authors reported a median RT dose of 61.2 Gy. However, there is no evidence that higher doses are associated with better oncological outcomes. We believe that reporting the radiation dose and outcome relationship in a rare disease meta-analysis is important for shedding light on the literature.
In the first sentence of the discussion, the authors emphasize that “over the last decades, surgical treatment has represented the first choice” in the treatment of CESCC patients. Finally, they reach the conclusion that definitive CRT is the “current preferred therapeutic option” for these patients. However, the NCCN and European Society of Medical Oncology (ESMO) guidelines recommend definitive CRT as the standard treatment modality. (Lordick et al. 2016; National Comprehensive Cancer Network. Clinical practice guidelines in oncology (NCCN Guidelines). Esophageal and Esophagogastric Junction Cancers Network and Clinical practice guidelines in oncology (NCCN Guidelines). , 2022. NCCN.org.). To clarify this issue, it would be better to address the fact that definitive concurrent CRT is the standard treatment for CESCC patients.
In conclusion, this is a significant study of a large database in patients with CESCC treated with definitive CRT, as well as the first and only meta-analysis of such patients. We believe that explaining our concerns will improve the study’s readability.
Funding
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Declarations
Conflict of interest
All authors declare no conflicts of interest related to this article.
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References
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