A COMPARATIVE STUDY OF ONCOLOGICAL OUTCOME BETWEEN SURGERY ALONE AND NEOADJUVANT CHEMOTHERAPY FOLLOWED BY SURGERY IN LOCALLY ADVANCED ORAL CANCERS

Abstract

: Prevalence of Oral cancers has been increasing across the globe. In India 30% of malignancies are Head and Neck cancers and almost 50% among them are oral squamous cell carcinomas. Oral cancers and their surgery adversely affect quality of life and important functions like speech, mastication, swallowing and aesthetics and are aggressive with a tendency towards rapid infiltration into adjoining tissues and lymph node metastasis. 80 % of our patients present in a locally advanced stage making them inoperable or difficult to resect with resultant post operative morbidity. Neoadjuvant Chemotherapy in such cancers is still controversial. It has been tried in order to control progression of cancer till definitive treatment (surgery + adjuvant treatment) is administered, or to down stage the tumor prior to surgery. In this study we intend to compare the oncological outcome in age and stage matched patients undergoing surgery alone followed by adjuvant treatment and those subjected to Paclitaxel and Carboplatin based Neoadjuvant Chemotherapy followed by surgery and adjuvant treatment in locally advanced oral squamous cell carcinoma staged T4a & T4b. OBJECTIVES: 1. To document the oncological outcome of 2 cycles of Paclitaxel and Carboplatin based Neoadjuvant Chemotherapy given at 3 weekly intervals followed by surgery and adjuvant treatment in locally advanced (T4) oral cancers. xiii 2. To document the oncological outcome of surgery alone (upfront surgery) followed by adjuvant treatment in locally advanced (T4) oral cancers. 3. To compare the oncological outcome with regard to loco-regional control and surgical complications in the above mentioned 2 groups. METHODS: The comparative observational study included 60 patients with locally advanced oral cancer staged T4 according to AJCC classification (8th edition) at R.L. Jalappa Hospital And Research Centre, Kolar from December 2018 to November 2020. Patients were randomized and divided into 2 groups. Group A having patients receiving Neoadjuvant Chemotherapy with 2 cycles of Paclitaxel and Carboplatin followed by surgery and adjuvant treatment. Group B having patients undergoing surgery followed by adjuvant treatment. The surgery included Composite Resection + Neck dissection in all cases. Adjuvant treatment included Radiotherapy or Chemotherapy + Radiotherapy. The complications after treatment and locoregional control was compared between the 2 groups after a minimum follow up of 1 year. RESULTS This comparative study included 30 patients in each group. Majority of the patients were females in the age group of 50-60 years. Patients staged T4a were 37(61.6%) and 23(38.3%) patients were staged T4b. 83.3% patients had N1 & 16.7% had N2b nodal status. The most common location of the primary tumor was buccal mucosa seen in 73.3% patients followed by lower alveolus 16.7%. xiv Infratemporal involvement was seen in about 40% of patients in both groups. In the neoadjuvant chemotherapy group, 30% had partial response, 37% had stable disease and 33% had progressive disease following 2 cycles of Neoadjuvant Chemotherapy. The superior margin was found to be the closest margin in both groups being 5mm with a range from 1-9mm.The mean depth of invasion in both groups was 6-7mm. Perineural invasion and lymphovascular spread was seen in less than 10% patients in each group. Extranodal spread was observed in 23.3% patients in Neoadjuvant Chemotherapy group and 36.7% patients in surgery alone group. The surgical complications encountered were similar in both groups about 10% patients with partial flap necrosis and 26% patients with orocutaneous fistula. After a mean follow up of 18 months and minimum follow up of 1 year, 6.6% had local recurrence, 16% had locoregional recurrence and 13% had regional recurrence in Neoadjuvant chemotherapy group. In the surgery alone group, 16.6% patients had local recurrence, 23% had locoregional recurrence and 13% had regional recurrence. Though, the locoregional control rates were similar both groups, the subset with progressive disease in Neoadjuvant chemotherapy group recurred early and had poor prognosis. The patients with stable disease and partial response with neoadjuvant chemotherapy had lesser frequency of recurrence. The resection of the primary tumor was easier with wider margins among patients who had partial response to neoadjuvant chemotherapy (70%). xv At last follow up 50% patients in the Neoadjuvant Chemotherapy group were alive without disease 36.67% were alive with disease whereas in the surgery alone group 43.33% were alive without disease 50% patients were alive with disease. Average time taken for recurrence was about 9 months. CONCLUSION: Among patients with oral squamous cell carcinoma staged T4, the resectable tumors had better outcome with surgery alone compared to Neoadjuvant chemotherapy followed by surgery. Adjuvant treatment is mandatory in both groups. The frequency of surgical complications is not affected by Neoadjuvant chemotherapy. Similar observations have been made in other studies in literature. Partial responders following Neoadjuvant chemotherapy have wider margins of resection and better loco-regional control compared to surgery alone group. Paclitaxel based Neoadjuvant chemotherapy is advisable in very advanced oral squamous cell carcinoma.