Definitive Surgery after Neoadjuvant Chemotherapy for Locally Advanced Oral Cavity Cancers: Experience from a Tertiary Care Center

Abstract

Mansi Agrawal

Vidya Konduru

Background Oral cavity cancers require definitive surgical resection as the primary treatment, but with advanced T stage, complete resection with pathologically negative margins might be difficult to achieve. Induction chemotherapy helps achieve the balance between resection and morbidity in locally advanced technically unresectable tumors. The aim of this study was to analyze the impact of surgery in locally advanced, technically unresectable oral cavity cancers after neoadjuvant chemotherapy (NACT).

Materials and Methods A retrospective analysis of patients with borderline resectable, locally advanced oral cavity cancers who were given NACT between February 2017 and December 2021 was conducted. Data regarding clinical and pathological characteristics, NACT, surgery, adjuvant therapy, and recurrences was analyzed.

Results Of the 69 patients in the study, 69.6% had tongue cancer, rest were gingivobuccal complex cancers. All tumors were resected based on the post-NACT tumor volume and clear margins were achieved in 42% of cases. About 85.4% of the tongue cancers required a lesser resection than anticipated, thereby following the concept of organ and functional preservation post-NACT as proposed by Licitra et al. About 30.4% had ypT0 and 17.4% had ypN0. Recurrence and survival rates noted in our study were comparable to those reported in literature. Lymph node density of more than or equal to 0.07 was found in all recurrent cases.

Conclusions Induction chemotherapy offers a chance of achieving adequate surgical resection while reducing morbidity and improving functional outcomes for patients with technically unresectable oral cavity cancers. Nodal disease may not respond to chemotherapy as well as the primary tumor. There is a need for comprehensive evaluation of prognostic factors, which could help identify the patients who will most benefit with NACT.

Keywords

oral squamous cell carcinoma - neoadjuvant chemotherapy - induction chemotherapy - oral cavity cancer - NACT - borderline resectable oral cancer - technically unresectable cancer

Note

Interim analysis was presented at:

1. Oral presentation at Annual Research Day—2019, Christian Medical College, Vellore, India—awarded first place.

2. E-poster presented at Annual FHNO Conference, 2019 at Chennai, India.

Ethical Approval

This study has been approved by Institutional Review Board of Christian Medical College, Vellore; IRB No: 12662 [Retro].

Authors' Contributions

M.A., V.K., and A.J.T. conceptualized and designed the study. M.A., R.J. helped in data acquisition. V.K., R.K., A.S., and A.J. contributed to quality control of data and algorithms. M.A., V.K., R.J., R.K., A.S., and A.J. helped in data analysis and interpretation. M.A., V.K., and R.K. helped in statistical analysis. M.A. and V.K. prepared the manuscript. V.K. and A.J.T. edited the manuscript. A.J.T., A.S., and A.J. reviewed the manuscript.

Publikationsverlauf

Artikel online veröffentlicht:
10. April 2023

• References

• 1 Sankaranarayanan R. Oral cancer in India: an epidemiologic and clinical review. Oral Surg Oral Med Oral Pathol 1990; 69 (03) 325-330
• 2 Sankaranarayanan R, Ramadas K, Thomas G. et al; Trivandrum Oral Cancer Screening Study Group. Effect of screening on oral cancer mortality in Kerala, India: a cluster-randomised controlled trial. Lancet 2005; 365 (9475): 1927-1933
• 3 D'cruz A, Lin T, Anand AK. et al. Consensus recommendations for management of head and neck cancer in Asian countries: a review of international guidelines. Oral Oncol 2013; 49 (09) 872-877
• 4 Scully C, Bagan J. Oral squamous cell carcinoma overview. Oral Oncol 2009; 45 (4-5): 301-308
• 5 Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin 2005; 55 (02) 74-108
• 6 Coelho KR. Challenges of the oral cancer burden in India. J Cancer Epidemiol 2012; 2012: 701932
• 7 Elango JK, Gangadharan P, Sumithra S, Kuriakose MA. Trends of head and neck cancers in urban and rural India. Asian Pac J Cancer Prev 2006; 7 (01) 108-112
• 8 Crombie AK, Farah C, Tripcony L, Dickie G, Batstone MD. Primary chemoradiotherapy for oral cavity squamous cell carcinoma. Oral Oncol 2012; 48 (10) 1014-1018
• 9 Chaudhary AJ, Pande SC, Sharma V. et al. Radiotherapy of carcinoma of the buccal mucosa. Semin Surg Oncol 1989; 5 (05) 322-326
• 10 Ghoshal S, Mallick I, Panda N, Sharma SC. Carcinoma of the buccal mucosa: analysis of clinical presentation, outcome and prognostic factors. Oral Oncol 2006; 42 (05) 533-539
• 11 Larizadeh MH, Shabani M. Survival following non surgical treatments for oral cancer: a single institutional result. Asian Pac J Cancer Prev 2012; 13 (08) 4133-4136
• 12 Bernier J, Cooper JS, Pajak TF. et al. Defining risk levels in locally advanced head and neck cancers: a comparative analysis of concurrent postoperative radiation plus chemotherapy trials of the EORTC (#22931) and RTOG (# 9501). Head Neck 2005; 27 (10) 843-850
• 13 Bernier J, Domenge C, Ozsahin M. et al; European Organization for Research and Treatment of Cancer Trial 22931. Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med 2004; 350 (19) 1945-1952
• 14 Belcher R, Hayes K, Fedewa S, Chen AY. Current treatment of head and neck squamous cell cancer. J Surg Oncol 2014; 110 (05) 551-574
• 15 Vermorken JB, Remenar E, van Herpen C. et al; EORTC 24971/TAX 323 Study Group. Cisplatin, fluorouracil, and docetaxel in unresectable head and neck cancer. N Engl J Med 2007; 357 (17) 1695-1704
• 16 Agarwal JP, Nemade B, Murthy V. et al. Hypofractionated, palliative radiotherapy for advanced head and neck cancer. Radiother Oncol 2008; 89 (01) 51-56
• 17 Mohanti BK, Umapathy H, Bahadur S, Thakar A, Pathy S. Short course palliative radiotherapy of 20 Gy in 5 fractions for advanced and incurable head and neck cancer: AIIMS study. Radiother Oncol 2004; 71 (03) 275-280
• 18 Huang SH, O'Sullivan B. Oral cancer: current role of radiotherapy and chemotherapy. Med Oral Patol Oral Cir Bucal 2013; 18 (02) e233-e240
• 19 Liao CT, Chang JT, Wang HM. et al. Surgical outcome of T4a and resected T4b oral cavity cancer. Cancer 2006; 107 (02) 337-344
• 20 Jerjes W, Upile T, Petrie A. et al. Clinicopathological parameters, recurrence, locoregional and distant metastasis in 115 T1-T2 oral squamous cell carcinoma patients. Head Neck Oncol 2010; 2: 9
• 21 Priya SR, D'Cruz AK, Pai PS. Cut margins and disease control in oral cancers. J Cancer Res Ther 2012; 8 (01) 74-79
• 22 Sutton DN, Brown JS, Rogers SN, Vaughan ED, Woolgar JA. The prognostic implications of the surgical margin in oral squamous cell carcinoma. Int J Oral Maxillofac Surg 2003; 32 (01) 30-34
• 23 National Comprehensive Cancer Network. Head and Neck Cancers (Version 1.2023). Accessed March 20, 2023 at: https://www.nccn.org/professionals/physician_gls/pdf/head-and-neck.pdf
• 24 Paccagnella A, Orlando A, Marchiori C. et al. Phase III trial of initial chemotherapy in stage III or IV head and neck cancers: a study by the Gruppo di Studio sui Tumori della Testa e del Collo. J Natl Cancer Inst 1994; 86 (04) 265-272
• 25 Licitra L, Grandi C, Guzzo M. et al. Primary chemotherapy in resectable oral cavity squamous cell cancer: a randomized controlled trial. J Clin Oncol 2003; 21 (02) 327-333
• 26 Zhong LP, Zhang CP, Ren GX. et al. Randomized phase III trial of induction chemotherapy with docetaxel, cisplatin, and fluorouracil followed by surgery versus up-front surgery in locally advanced resectable oral squamous cell carcinoma. J Clin Oncol 2013; 31 (06) 744-751
• 27 Patil VM, Prabhash K, Noronha V. et al. Neoadjuvant chemotherapy followed by surgery in very locally advanced technically unresectable oral cavity cancers. Oral Oncol 2014; 50 (10) 1000-1004
• 28 Pradhan SA. Surgery for cancer of the buccal mucosa. Semin Surg Oncol 1989; 5 (05) 318-321
• 29 Posner MR, Hershock DM, Blajman CR. et al; TAX 324 Study Group. Cisplatin and fluorouracil alone or with docetaxel in head and neck cancer. N Engl J Med 2007; 357 (17) 1705-1715
• 30 Salama JK, Stenson KM, Kistner EO. et al. Induction chemotherapy and concurrent chemoradiotherapy for locoregionally advanced head and neck cancer: a multi-institutional phase II trial investigating three radiotherapy dose levels. Ann Oncol 2008; 19 (10) 1787-1794
• 31 Haddad R, O'Neill A, Rabinowits G. et al. Induction chemotherapy followed by concurrent chemoradiotherapy (sequential chemoradiotherapy) versus concurrent chemoradiotherapy alone in locally advanced head and neck cancer (PARADIGM): a randomised phase 3 trial. Lancet Oncol 2013; 14 (03) 257-264
• 32 Patel SG, Amit M, Yen TC. et al; International Consortium for Outcome Research (ICOR) in Head and Neck Cancer. Lymph node density in oral cavity cancer: results of the International Consortium for Outcomes Research. Br J Cancer 2013; 109 (08) 2087-2095
• 33 Patil V, Noronha V, Joshi A. et al. Is there a limitation of RECIST criteria in prediction of pathological response, in head and neck cancers, to postinduction chemotherapy?. ISRN Oncol 2013; 2013: 259154
• 34 Freites-Martinez A, Santana N, Arias-Santiago S, Viera A. Using the Common Terminology Criteria for Adverse Events (CTCAE - Version 5.0) to evaluate the severity of adverse events of anticancer therapies. Actas Dermosifiliogr (Engl Ed) 2021; 112 (01) 90-92 (Engl Ed)