Erkan Topkan; Efsun Somay; Nilufer Kılıc Durankus; Ugur Selek

doi:10.4143/crt.2024.779

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Correspondence Commentary on “Metronomic S-1 Adjuvant Chemotherapy Improves Survival in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma”: Erkan Topkan¹, Efsun Somay^2,, Nilufer Kılıc Durankus³, Ugur Selek⁴; DOI: https://doi.org/10.4143/crt.2024.779
Published online: November 4, 2024

¹Department of Radiation Oncology, Faculty of Medicine, Baskent University, Adana, Turkey

²Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Baskent University, Ankara, Turkey

³Department of Radiation Oncology, Koc University School of Medicine, Istanbul, Turkey

⁴Department of Radiation Oncology, Koc University School of Medicine, Istanbul, Turkey

Correspondence: Efsun Somay, Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Baskent University, 82 Street No. 26 Bahcelievler, Ankara, Turkey
Tel: 90-505-800-1988 Fax: 90-322-344-4445 E-mail: efsuner@gmail.com

• Received: August 13, 2024 • Accepted: October 27, 2024

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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NOTES
REFERENCES

See the reply "Reply to Commentary on “Metronomic S-1 Adjuvant Chemotherapy Improves Survival in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma”".

See the article "Metronomic S-1 Adjuvant Chemotherapy Improves Survival in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma" on page 1058.

We congratulate Yu and colleagues for their study examining the efficacy and safety of metronomic S1 adjuvant chemotherapy in 474 locoregionally advanced nasopharyngeal carcinoma (LANPC) patients: 64 (13.5%) with and 410 (83.5%) without metronomic S1 [1]. Notably, the metronomic S1 group exhibited significantly improved 3-year locoregional recurrence-free survival (LRFS) (p=0.038), distant metastasis-free sruvival (DMFS) (p=0.002), disease-free survival (DFS) (p < 0.001), and overall survival (OS) (p=0.008) rates compared to the group without metronomic S1. The multivariate analysis established that metronomic S1 is an independent prognostic factor associated with better DMFS, DFS, and OS, but not with LRFS. The study’s findings warrant conducting a randomized controlled trial in LANPC patients. However, it is critical to stress a significant concern regarding the definitions of endpoints, which may have inadvertently influenced the outcomes in this study.

As a general statistical principle, neither LRFS, DMFS, nor DFS can have better median survival durations or outcome rates at any specified time points except for those obtained for the synonymously used cancer-, cause-, or disease-specific survival results [2,3]. In this respect, Yu et al.’s results contradict this statistical thumb rule. For instance, the 3-year LRFS rate of 100% in the metronomic S1 group is superior to the 98.0% OS rate in the same group. This scenario is theoretically improbable, considering that 2% of cases are already dead at this specific time. This finding is directly linked to the endpoint definitions utilized by Yu et al. The authors fail to consider deaths as an event despite being required to do so by definition, a principle that also applies to DMFS and DFS. However, the “S” in LRFS, DMFS, and DFS signifies “survival status,” similar to “S” of OS, indicating that deaths must be considered as events in addition to locoregional failures, distant metastasis, or any relapse, respectively, as shown in Table 1. Thus, the estimates provided by the authors should be regarded as locoregional recurrence–free estimates rather than true LRFS, which are also applicable to DMFS and DFS results. Interestingly, Yu et al.’s methodology is also commonly used by other LANPC researchers for unknown reasons [4,5]. However, this commonality does not justify their endpoint definitions and poses challenges when comparing different studies. Consequently, all survival data should be reanalyzed per established survival endpoint definitions to demonstrate the relevance of the presented outcomes and enable comparisons between similar studies.

NOTES

Author Contributions

Conceived and designed the analysis: Topkan E, Somay E, Durankus NK, Selek U.

Collected the data: Topkan E, Somay E, Durankus NK, Selek U.

Contributed data or analysis tools: Topkan E, Somay E, Durankus NK, Selek U.

Performed the analysis: Topkan E, Somay E, Durankus NK, Selek U.

Wrote the paper: Topkan E, Somay E, Durankus NK, Selek U.

Conflicts of Interest

Conflict of interest relevant to this article was not reported.

Table 1.

Standard versus Yu et al.’s endpoint definitions

Characteristic	Event definition
Characteristic	Standard definition [2,3]	Yu et al.’s definition [1]
LRFS	Locoregional recurrence	Locoregional recurrence
	Death	Death is not an event
DMFS	Distant metastasis	Distant metastasis
	Death	Death is not an event
DFS	Any kind of relapse	Any kind of relapse
	Death	Death is not an event
OS	Death due to any cause	Death due to any cause

DFS, disease-free survival; DMFS, distant metastasis-free survival; LRFS, locoregional recurrence-free survival; OS, overall survival.

REFERENCES

1. Yu YF, Wu P, Zhuo R, Wu SG. Metronomic S-1 adjuvant chemotherapy improves survival in patients with locoregionally advanced nasopharyngeal carcinoma. Cancer Res Treat. 2024;56:1058–67. Article PubMed PMC PDF
2. Prinja S, Gupta N, Verma R. Censoring in clinical trials: review of survival analysis techniques. Indian J Community Med. 2010;35:217–21. Article PubMed PMC
3. Delgado A, Guddati AK. Clinical endpoints in oncology: a primer. Am J Cancer Res. 2021;11:1121–31. PubMed PMC
4. Xiang L, Rong JF, Xin C, Li XY, Zheng Y, Ren PR, et al. Reducing target volumes of intensity modulated radiation therapy after induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma: long-term results of a prospective, multicenter, randomized trial. Int J Radiat Oncol Biol Phys. 2023;117:914–24. Article PubMed
5. Yildirim HC, Kupik GE, Mustafayev TZ, Berber T, Yavuz B, Cetinayak O, et al. A multicenter retrospective analysis of patients with nasopharyngeal carcinoma treated in IMRT era from a nonendemic population: Turkish Society for Radiation Oncology Head and Neck Cancer Group Study (TROD 01-001). Head Neck. 2023;45:1194–205. PubMed

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Commentary on “Metronomic S-1 Adjuvant Chemotherapy Improves Survival in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma”

DOI: https://doi.org/10.4143/crt.2024.779

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Commentary on “Metronomic S-1 Adjuvant Chemotherapy Improves Survival in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma”

Characteristic	Event definition
Characteristic	Standard definition [2,3]	Yu et al.’s definition [1]
LRFS	Locoregional recurrence	Locoregional recurrence
	Death	Death is not an event
DMFS	Distant metastasis	Distant metastasis
	Death	Death is not an event
DFS	Any kind of relapse	Any kind of relapse
	Death	Death is not an event
OS	Death due to any cause	Death due to any cause

Table 1. Standard versus Yu et al.’s endpoint definitions

DFS, disease-free survival; DMFS, distant metastasis-free survival; LRFS, locoregional recurrence-free survival; OS, overall survival.