Cancer Res Treat.  2022 Jan;54(1):84-95. 10.4143/crt.2020.1197.

Oncological and Functional Outcomes of Larynx-preserving Surgery for Hypopharyngeal Cancer: A Comparison with Definitive Radiation-based Treatment

• Kim D
• Kim N
• Koh S
• Chung MK
• Son YI
• Oh D
• Jeong HS
• Ahn YC

• KMID: 2524590
• DOI: http://doi.org/10.4143/crt.2020.1197

Abstract

Purpose
Larynx-preserving surgery (LPS) have recently gained popularity and achieved comparable oncologic outcomes to conventional radical surgery for localized hypopharyngeal cancer (HPC). In the current study, the role of LPS has been assessed thoroughly in comparison with upfront radiation therapy (RT).
Materials and Methods
We retrospectively reviewed 185 candidates for LPS with cT1-2 disease; 59 patients underwent upfront LPS while 126 patients received upfront RT, respectively. Oncological and functional outcomes were investigated and compared.
Results
Following LPS, safe margin (≥ 5 mm) was achieved in 37.3% of patients. Overall, better clinical outcomes at 5 years were achieved following upfront LPS than those following upfront RT: overall survival (OS) (72.7% vs. 59.0%, p=0.045), disease-free survival (DFS) (59.8% vs. 45.0%, p=0.039), and functional laryngeal preservation (100% vs. 89.7%, p=0.010). Although similar outcomes were observed in patients with cT1 disease, better 5-year DFS was achieved following upfront LPS in patients with cT2 disease (57.0% vs. 36.4%, p=0.023) by virtue of better local control. Despite frequent cN2-3 disease in upfront LPS group, comparable outcomes were observed between upfront RT and LPS group. However, multivariable analyses revealed that performance status and double primary cancer diagnosed within 6 months of HPC diagnosis affected OS significantly, while treatment modality per se did not.
Conclusion
Although upfront LPS could provide better local control than upfront RT in patients with cT2 disease, overall outcomes were comparable following either modality. Treatment selection of larynx-preserving approach for HPC should be individualized based on tumor and patient factors.

Keyword

Hypopharyngeal carcinoma; Surgery; Laryngeal preservation; Radiation; Outcomes; Survival

Figure

• 

  Fig. 1 Study scheme and subject enrollment. CCRT, concurrent chemoradiation therapy; HPC, hypopharyngeal cancer; LPS, larynx-preserving surgery; RT, radiation therapy.

• 

  Fig. 2 Survival plots: overall survival (A) and disease-free survival (B). LPS, larynx-preserving surgery; RT, radiation therapy.

• 

  Fig. 3 Disease-free survival plots according to T and N status: cT1 (A), cT2 (B), cN0–1 (C), and cN2–3 (D). LPS, larynx-preserving surgery; RT, radiation therapy.

Reference

References

1. Pracy P, Loughran S, Good J, Parmar S, Goranova R. Hypopharyngeal cancer: United Kingdom National Multidisciplinary Guidelines. J Laryngol Otol. 2016; 130:S104–10.

2. Carvalho AL, Nishimoto IN, Califano JA, Kowalski LP. Trends in incidence and prognosis for head and neck cancer in the United States: a site-specific analysis of the SEER database. Int J Cancer. 2005; 114:806–16.

3. Newman JR, Connolly TM, Illing EA, Kilgore ML, Locher JL, Carroll WR. Survival trends in hypopharyngeal cancer: a population-based review. Laryngoscope. 2015; 125:624–9.

4. Chirila M, Bolboaca SD, Cosgarea M, Tomescu E, Muresan M. Perineural invasion of the major and minor nerves in laryngeal and hypopharyngeal cancer. Otolaryngol Head Neck Surg. 2009; 140:65–9.

5. Deleyiannis FW, Piccirillo JF, Kirchner JA. Relative prognostic importance of histologic invasion of the laryngeal framework by hypopharyngeal cancer. Ann Otol Rhinol Laryngol. 1996; 105:101–8.

6. Kim JW, Kim MS, Kim SH, Kim JH, Lee CG, Kim GE, et al. Definitive chemoradiotherapy versus surgery followed by adjuvant radiotherapy in resectable stage III/IV hypopharyngeal cancer. Cancer Res Treat. 2016; 48:45–53.

7. Dikshit RP, Boffetta P, Bouchardy C, Merletti F, Crosignani P, Cuchi T, et al. Risk factors for the development of second primary tumors among men after laryngeal and hypopharyngeal carcinoma. Cancer. 2005; 103:2326–33.

8. Clayman GL, Weber RS, Guillamondegui O, Byers RM, Wolf PF, Frankenthaler RA, et al. Laryngeal preservation for advanced laryngeal and hypopharyngeal cancers. Arch Otolaryngol Head Neck Surg. 1995; 121:219–23.

9. Rades D, Schroeder U, Bajrovic A, Schild SE. Radiochemotherapy versus surgery plus radio(chemo)therapy for stage T3/T4 larynx and hypopharynx cancer: results of a matched-pair analysis. Eur J Cancer. 2011; 47:2729–34.

10. Kim S, Wu HG, Heo DS, Kim KH, Sung MW, Park CI. Advanced hypopharyngeal carcinoma treatment results according to treatment modalities. Head Neck. 2001; 23:713–7.

11. Habib A. Management of advanced hypopharyngeal carcinoma: systematic review of survival following surgical and non-surgical treatments. J Laryngol Otol. 2018; 132:385–400.

12. Bonner J, Giralt J, Harari P, Spencer S, Schulten J, Hossain A, et al. Cetuximab and radiotherapy in laryngeal preservation for cancers of the larynx and hypopharynx: a secondary analysis of a randomized clinical trial. JAMA Otolaryngol Head Neck Surg. 2016; 142:842–9.

13. Jang JY, Kim EH, Cho J, Jung JH, Oh D, Ahn YC, et al. Comparison of oncological and functional outcomes between initial surgical versus non-surgical treatments for hypopharyngeal cancer. Ann Surg Oncol. 2016; 23:2054–61.

14. Iwae S, Fujii M, Hayashi R, Hasegawa Y, Fujii T, Okami K, et al. Matched-pair analysis of patients with advanced hypopharyngeal cancer: surgery versus concomitant chemoradiotherapy. Int J Clin Oncol. 2017; 22:1001–8.

15. Vilaseca I, Blanch JL, Bernal-Sprekelsen M, Moragas M. CO2 laser surgery: a larynx preservation alternative for selected hypopharyngeal carcinomas. Head Neck. 2004; 26:953–9.

16. De Virgilio A, Iocca O, Malvezzi L, Di Maio P, Pellini R, Ferreli F, et al. The emerging role of robotic surgery among minimally invasive surgical approaches in the treatment of hypopharyngeal carcinoma: systematic review and meta-analysis. J Clin Med. 2019; 8:256.

17. Joo YH, Cho KJ, Park JO, Nam IC, Kim MS. Role of larynx-preserving partial hypopharyngectomy with and without postoperative radiotherapy for squamous cell carcinoma of the hypopharynx. Oral Oncol. 2012; 48:168–72.

18. Cho WK, Oh D, Lee E, Kim TG, Lee H, Nam H, et al. Feasibility of selective neck irradiation with lower elective radiation dose in treating nasopharynx cancer patients. Cancer Res Treat. 2019; 51:603–10.

19. De Bodt MS, Wuyts FL, Van de Heyning PH, Croux C. Test-retest study of the GRBAS scale: influence of experience and professional background on perceptual rating of voice quality. J Voice. 1997; 11:74–80.

20. Stenson KM, MacCracken E, List M, Haraf DJ, Brockstein B, Weichselbaum R, et al. Swallowing function in patients with head and neck cancer prior to treatment. Arch Otolaryngol Head Neck Surg. 2000; 126:371–7.

21. Ho CM, Ng WF, Lam KH, Wei WJ, Yuen AP. Submucosal tumor extension in hypopharyngeal cancer. Arch Otolaryngol Head Neck Surg. 1997; 123:959–65.

22. Ansarin M, Santoro L, Cattaneo A, Massaro MA, Calabrese L, Giugliano G, et al. Laser surgery for early glottic cancer: impact of margin status on local control and organ preservation. Arch Otolaryngol Head Neck Surg. 2009; 135:385–90.

23. Steiner W, Ambrosch P, Hess CF, Kron M. Organ preservation by transoral laser microsurgery in piriform sinus carcinoma. Otolaryngol Head Neck Surg. 2001; 124:58–67.

24. Martin A, Jackel MC, Christiansen H, Mahmoodzada M, Kron M, Steiner W. Organ preserving transoral laser microsurgery for cancer of the hypopharynx. Laryngoscope. 2008; 118:398–402.

25. Park YM, Kim WS, De Virgilio A, Lee SY, Seol JH, Kim SH. Transoral robotic surgery for hypopharyngeal squamous cell carcinoma: 3-year oncologic and functional analysis. Oral Oncol. 2012; 48:560–6.

26. Mazerolle P, Philouze P, Garrel R, Aubry K, Moriniere S, El Bedoui S, et al. Oncological and functional outcomes of trans-oral robotic surgery for pyriform sinus carcinoma: a French GETTEC group study. Oral Oncol. 2018; 86:165–70.

27. Ma DJ, Price KA, Moore EJ, Patel SH, Hinni ML, Garcia JJ, et al. Phase II evaluation of aggressive dose de-escalation for adjuvant chemoradiotherapy in human papillomavirus-associated oropharynx squamous cell carcinoma. J Clin Oncol. 2019; 37:1909–18.

28. Isaacs JH Jr, Stiles WA, Cassisi NJ, Million RR, Parsons JT. Postoperative radiation of open head and neck wounds: updated. Head Neck. 1997; 19:194–9.

29. Pelucchi C, Gallus S, Garavello W, Bosetti C, La Vecchia C. Alcohol and tobacco use, and cancer risk for upper aerodigestive tract and liver. Eur J Cancer Prev. 2008; 17:340–4.

30. 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.