Abstract
Background
Oral squamous cell carcinoma (OSCC) is an invasive cancer with a high recurrence rate. Most clinical studies have focused on the prognosis of patients with OSCC, few have investigated the causes and interventions that affect the recurrence. Our study is to explore the temporal and spatial patterns of recurrence in OSCC.
Methods
234 OSCC patients with recurrence in our hospital and 64 OSCC patients with recurrence in TCGA database were included in the study. Log-rank test and Multivariate Cox Regression Analysis were used to determine whether there was a significant difference between each selected demographic or clinical factors and recurrence. The Kaplan–Meier method was used to plot survival curves for each recurrence interval.
Results
The proportion of OSCC patients in clinical and TCGA with early recurrence was 93.6% and 84.4%, respectively. Age, chewing betel nut, previous radiotherapy, histopathological grading of the primary tumor (poorly differentiated), lymph node metastasis and postoperative infection were found to be associated with the timing of recurrence. It was found that tongue cancer has more regional recurrences, while buccal cancer is mostly local and loco-regional recurrences. The earlier the recurrence, the greater the possibility of local-regional recurrence and the worse the prognosis.
Conclusion
Most of recurrent OSCC patients present early recurrence (< 18 months) with poor prognosis, and early recurrence is more prone to local recurrence. Moreover, recurrence site is related with primary site of OSCC.
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Background
Oral cancer is one of the most common malignancies, ranking the top 10 of all malignant tumors, with more than 450,000 new cases worldwide each year, accounting for 2.4% of all cancer deaths. More than 90% of oral cancers are oral squamous cell carcinoma (OSCC)[1]. The mainstays of OSCC treatment are surgery, chemotherapy, radiotherapy or a combination of these modalities. Unfortunately, despite the various efforts that have been made for OSCC [2, 3], the survival rate of OSCC has not remarkably increased in the last three decades, which remains below 60%[4].Recurrence (especially early recurrence) is one of the major causes of low survival rates of OSCC after definitive therapy. It has been reported that the cure rates of salvage surgery for patients with recurrence is 15%~67%, suggesting the role for surgical treatment after recurrence with both palliative and curative intent [5,6,7,8,9]. Therefore, regular and close follow-up examinations are particularly important for early diagnosis of recurrence and improvement of survival of OSCC patients [10]. At present, “one-size-fits all” follow up program cannot meet the clinical needs. First, this regimen may not be appropriate for some patients who may be at higher risk for a second event than others [11,12,13]. In addition, personalized follow-up schedule after primary tumor treatment has never been investigated [13]. While longer follow-up time and shorter follow-up interval may help us diagnose relapse early, they may also place an undue burden on patients, especially those in remote areas or with poor economic conditions.
Many literatures stated that the recurrence rate of OSCC varies from 7–47.4%[7, 14,15,16,17,18]. Despite the enormous impact of recurrence (local, loco-regional and regional) on the prognosis of OSCC, limited understanding is currently available about its frequency, exact location and development pattern [19,20,21,22]. Many clinicopathological factors and molecular markers are associated with recurrence of OSCC, including smoking, advanced clinical stage, poorly differentiated tumors, radiotherapy, microvascular invasion, and high positive lymph node ratio, etc. [7, 17, 19, 23,24,25]. However, the prognostic value of these clinicopathological factors is always uncertain and controversial [19, 25,26,27]. It is also worth noting that it’s not clear which clinicopathological factors and molecular biomarkers could identify the patients at high risk of early recurrence.
Materials and methods
Data collection methods
The patients’ data was collected and sorted from our hospital’s electronic database, which contains prior medical records and postoperative follow-up information.
Study design and clinical samples
The study was approved by the Ethics Committee of Second ** to tailor selective lymphadenectomy in cN0 tongue carcinoma: beyond the sentinel node concept. Eur J Nucl Med Mol Imaging. 2006;33(8):900–5." href="/article/10.1186/s12903-023-03204-7#ref-CR61" id="ref-link-section-d8999442e3062">61]. Unlike tongue cancer, buccal cancer has been shown to develop in an orderly progression, skip metastasis was rare [62], however, its specific biological mechanism is still unclear and needs further study. It is worth noting that our results of clinical samples showed that buccal cancer was more prone to regional recurrence (P = 0.035) but results of TCGA database showed no statistical difference in the probability of regional recurrence between the two groups (P > 0.05) (Table 6). Differences in ethnicity, number of cases, and dietary habits (for example, most Chinese OSCC patients chew betel nut while Americans do not) could contribute to the above difference.
More and more studies have shown that the recurrence interval and recurrence location were related to the prognosis of OSCC patients [5, 9, 18, 20, 37]. However, there are currently few studies on the relationship between the recurrence interval and the recurrence site. In this study, we found that the earlier the recurrence, the more likely it is to be loco-regional recurrence (Fig. 3A and B). Further, a survival analysis of patients who underwent secondary surgery after recurrence showed that the earlier the recurrence, the lower the survival rate (Fig. 3C, 3D). These results indicated that patients with local-regional recurrence have a wide range of second tumors, rapid tumor progression, and poor prognosis. The cause has nothing to do with the complete resection of the primary tumor, may be related to tumor heterogeneity [63, 64]. Considering the postoperative quality of life and survival rate, we should be cautious about reoperation for such patients.
Conclusion
In the study, we found that not only recurrence interval, but also recurrence site was associated with the OS of OSCC.
Considering that most patients relapse within 18 months(nearly 90%), it is recommended to pay regular examination every month for 1year after the operation. Follow-up examinations will be performed every 3 months in the second year, and then every 6 months in the third to fifth years. For the surveillance of patients with OSCC after primary surgery, we believe that MRI/CT/PET-CT examination, especially for patients with deep neck pain, MRI/CT examination or even PET-CT should be performed immediately to confirm the diagnosis. At 1 year after surgery, it is also desirable to perform PET-CT to rule out early microscopic lesions. In addition, considering the poor prognosis of patients with earlier recurrence, re-operation should be cautious.
Data Availability
All the data in the manuscript are available from the corresponding author on reasonable request.
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Acknowledgements
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Funding
This study was supported by grant A2022037 from the Health Commission of Guangdong Province and grant 2023JJ41028 from the Department of Science and Technology of Hunan Province.
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Yannan Wang, Feiya Zhu and Tianru Yang designed the study. Yannan Wang, Tianru Yang , Chengwen Gan and Feiya Zhu collected the data and conducted the study. Feiya Zhu and Yannan Wang performed analyses. Yannan Wang, Tianru Yang, Chengwen Gan, Kai Wang, Bincan Sun and Mengxue Wang and Feiya Zhu wrote the manuscript. All authors have read and approved the final manuscript.
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The study was approved by the Ethics Committee of Second **angya Hospital of Central South University. All the authors confirm that all methods were carried out in accordance with relevant guidelines and regulations. Signed informed consent was obtained from all individual participants included in the study.
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Wang, Y., Yang, T., Gan, C. et al. Temporal and spatial patterns of recurrence in oral squamous cell carcinoma, a single-center retrospective cohort study in China. BMC Oral Health 23, 679 (2023). https://doi.org/10.1186/s12903-023-03204-7
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DOI: https://doi.org/10.1186/s12903-023-03204-7