Cancer Res Treat.  2020 Jan;52(1):109-116. 10.4143/crt.2019.202.

Secondary Squamous Cell Carcinoma of the Oral Cavity after Nasopharyngeal Carcinoma

• Dai L
• Fang Q
• Li P
• Wu J
• Zhang X

• KMID: 2501206
• DOI: http://doi.org/10.4143/crt.2019.202

Abstract

Purpose
The main goal of this study was to analyze the prognosis of secondary oral squamous cell carcinoma (SCC) with a comparison with sporadic oral SCC by a matched-pair design.
Materials and Methods
Records of patients with surgically treated primary oral SCC were reviewed, and a total of 83 patients with previous history of radiotherapy for nasopharyngeal carcinoma (NPC) were retrospectively enrolled. A matched-pair study was performed, each NPC survivor was matched with two sporadic oral SCC patients by age, sex, primary tumor site, adverse pathologic characteristics, disease stage, neck node status, and tumor stage. The overall survival (OS) and disease-specific survival (DSS) rates were calculated by the Kaplan-Meier method; independent prognostic factors were evaluated by the Cox proportional hazards method.
Results
Compared with sporadic oral SCC patients, NPC survivors were less likely to be smokers (p=0.004), perineural invasion and lymphovascular invasion were more common in NPC survivors (both p < 0.001). The 5-year OS and DSS rates in NPC survivors were 47% and 54%, respectively; the 5-year OS and DSS rates in sporadic oral SCC patients were 62% and 67%, respectively; the difference was significant (both p < 0.05). In survival analysis, disease stage remained to be independent prognostic factor for both the OS and DSS.
Conclusion
NPC survivors had worse OS and DSS than sporadic oral SCC patients, NPC survivors were less likely to be smokers, but had higher opportunity of perineural invasion and lymphovascular invasion. Disease stage was the most important predictor for the survival in NPC survivors.

Keyword

Nasopharyngeal carcinoma; Secondary squamous cell carcinoma; Radiotherapy; Oral squamous cell carcinoma; Head and neck squamous cell carcinoma

Figure

• 

  Fig. 1. Overall survival rates between nasopharyngeal carcinoma (NPC) survivors and matched sporadic oral squamous cell carcinoma (SCC) patients (p=0.001).

• 

  Fig. 2. Disease-specific survival rates between nasopharyngeal carcinoma (NPC) survivors and matched sporadic oral squamous cell carcinoma (SCC) patients (p=0.017).

Reference

References

1. Lee HF, Lan JH, Chao PJ, Ting HM, Chen HC, Hsu HC, et al. Radiation-induced secondary malignancies for nasopharyngeal carcinoma: a pilot study of patients treated via IMRT or VMAT. Cancer Manag Res. 2018; 10:131–41.

2. Oei RW, Ye L, Kong F, Du C, Zhai R, Xu T, et al. Prognostic value of inflammation-based prognostic index in patients with nasopharyngeal carcinoma: a propensity score matching study. Cancer Manag Res. 2018; 10:2785–97.

3. Diallo I, Haddy N, Adjadj E, Samand A, Quiniou E, Chavaudra J, et al. Frequency distribution of second solid cancer locations in relation to the irradiated volume among 115 patients treated for childhood cancer. Int J Radiat Oncol Biol Phys. 2009; 74:876–83.

4. Tubiana M. Can we reduce the incidence of second primary malignancies occurring after radiotherapy? A critical review. Radiother Oncol. 2009; 91:4–15.

5. Fu X, Chen S, Chen W, Yang Z, Song M, Li H, et al. Clinical analysis of second primary gingival squamous cell carcinoma after radiotherapy. Oral Oncol. 2018; 84:20–4.

6. Zhang P, Zhang L, Liu H, Zhao L, Li Y, Shen JX, et al. Clinicopathologic characteristics and prognosis of tongue squamous cell carcinoma in patients with and without a history of radiation for nasopharyngeal carcinoma: a matched case-control study. Cancer Res Treat. 2017; 49:695–705.

7. Sun C, Hu Z, Zhong Z, Jiang Y, Sun R, Fei J, et al. Clinical and prognostic analysis of second primary squamous cell carcinoma of the tongue after radiotherapy for nasopharyngeal carcinoma. Br J Oral Maxillofac Surg. 2014; 52:715–20.

8. Song M, Zhuang SM, Chen SW, Zhang Q, Yang AK, Wang LP, et al. Survival study and treatment strategy for second primary tumors in the oral cavity in patients with nasopharyngeal carcinoma after definitive radiation. Head Neck. 2012; 34:1551–5.

9. Strojan P, Corry J, Eisbruch A, Vermorken JB, Mendenhall WM, Lee AW, et al. Recurrent and second primary squamous cell carcinoma of the head and neck: when and how to reirradiate. Head Neck. 2015; 37:134–50.

10. Fang Q, Li P, Qi J, Luo R, Chen D, Zhang X. Value of lingual lymph node metastasis in patients with squamous cell carcinoma of the tongue. Laryngoscope. 2019; 129:2527–30.

11. Fang QG, Shi S, Liu FY, Sun CF. Squamous cell carcinoma of the oral cavity in ever smokers: a matched-pair analysis of survival. J Craniofac Surg. 2014; 25:934–7.

12. Fang QG, Shi S, Li M, Zhang X, Liu FY, Sun CF. Free flap reconstruction versus non-free flap reconstruction in treating elderly patients with advanced oral cancer. J Oral Maxillofac Surg. 2014; 72:1420–4.

13. Cahan WG, Woodard HQ, Higinbotham NL, Stewart FW, Coley BL. Sarcoma arising in irradiated bone: report of eleven cases. 1948. Cancer. 1998; 82:8–34.

14. Arlen M, Higinbotham NL, Huvos AG, Marcove RC, Miller T, Shah IC. Radiation-induced sarcoma of bone. Cancer. 1971; 28:1087–99.

15. Skulsky SL, O'Sullivan B, McArdle O, Leader M, Roche M, Conlon PJ, et al. Review of high-risk features of cutaneous squamous cell carcinoma and discrepancies between the American Joint Committee on Cancer and NCCN Clinical Practice Guidelines In Oncology. Head Neck. 2017; 39:578–94.

16. Bachar G, Hod R, Goldstein DP, Irish JC, Gullane PJ, Brown D, et al. Outcome of oral tongue squamous cell carcinoma in patients with and without known risk factors. Oral Oncol. 2011; 47:45–50.

17. Kong L, Lu JJ, Hu C, Guo X, Wu Y, Zhang Y. The risk of second primary tumors in patients with nasopharyngeal carcinoma after definitive radiotherapy. Cancer. 2006; 107:1287–93.

18. Chen MC, Feng IJ, Lu CH, Chen CC, Lin JT, Huang SH, et al. The incidence and risk of second primary cancers in patients with nasopharyngeal carcinoma: a population-based study in Taiwan over a 25-year period (1979-2003). Ann Oncol. 2008; 19:1180–6.

19. Zhao W, Lei H, Zhu X, Li L, Qu S, Liang X, et al. The clinical characteristics of secondary primary tumors in patients with nasopharyngeal carcinoma after intensity-modulated radiotherapy: A retrospective analysis. Medicine (Baltimore). 2016; 95:e5364.

20. Chen SW, Zhang Q, Guo ZM, Chen WK, Liu WW, Chen YF, et al. Trends in clinical features and survival of oral cavity cancer: fifty years of experience with 3,362 consecutive cases from a single institution. Cancer Manag Res. 2018; 10:4523–35.

21. Paleri V, Wight RG, Silver CE, Haigentz M Jr, Takes RP, Bradley PJ, et al. Comorbidity in head and neck cancer: a critical appraisal and recommendations for practice. Oral Oncol. 2010; 46:712–9.

22. Sanna G, Lorizzo K, Rotmensz N, Bagnardi V, Cinieri S, Colleoni M, et al. Breast cancer in Hodgkin's disease and non-Hodgkin's lymphoma survivors. Ann Oncol. 2007; 18:288–92.

23. Ng AK, Bernardo MP, Weller E, Backstrand KH, Silver B, Marcus KC, et al. Long-term survival and competing causes of death in patients with early-stage Hodgkin's disease treated at age 50 or younger. J Clin Oncol. 2002; 20:2101–8.

24. Teo PM, Chan AT, Leung SF, Chau RM, Yu PK, King WW, et al. Increased incidence of tongue cancer after primary radiotherapy for nasopharyngeal carcinoma: the possibility of radiation carcinogenesis. Eur J Cancer. 1999; 35:219–25.

25. Bostrom PJ, Soloway MS. Secondary cancer after radiotherapy for prostate cancer: should we be more aware of the risk? Eur Urol. 2007; 52:973–82.

26. Chatzistefanou I, Lubek J, Markou K, Ord RA. The role of perineural invasion in treatment decisions for oral cancer patients: a review of the literature. J Craniomaxillofac Surg. 2017; 45:821–5.

27. Sahu V, Nigam L, Agnihotri V, Gupta A, Shekhar S, Subbarao N, et al. Diagnostic significance of p38 isoforms (p38alpha, p38beta, p38gamma, p38delta) in head and neck squamous cell carcinoma: comparative serum level evaluation and design of novel peptide inhibitor targeting the same. Cancer Res Treat. 2019; 51:313–25.

28. Broeks A, Braaf LM, Wessels LF, van de Vijver M, De Bruin ML, Stovall M, et al. Radiation-associated breast tumors display a distinct gene expression profile. Int J Radiat Oncol Biol Phys. 2010; 76:540–7.