Nabeel Humayun Hassan  ( Department of Otolaryngology/ENT, )
Bushra Ayub  ( Department of Surgery and Allied, Patel Hospital, Karachi, Pakistan, )
Talha Ahmed Qureshi  ( Department of Otolaryngology/ENT, )
Shafqat Ali Shaikh  ( Department of Otolaryngology/ENT, )
Maliha Kazi  ( Department of Otolaryngology/ENT, Newcastle Freeman Hospital, United Kingdom, )
Rahila Usman  ( Department of Radiology, Dow University of Health Sciences, Karachi, Pakistan. )
Umer Saeed Haroon  ( Department of Otolaryngology/ENT, )

Objective: To determine the association of clinical and pathological parameters on recurrence of treated stage T4squamous cell carcinoma of oral cavity patients managed with surgery followed by concomitant chemo and radiation therapy.

 

Method: The retrospective, cohort study was conducted at Patel Hospital, Karachi, and comprised data of patients diagnosed with oral squamous cell carcinoma and admitted between January 1, 2014, and January 30, 2019. Patients of either gender aged 20-80 years who had a minimum follow-up of one year were included. Data was collected using the Head and Neck Cancer registry form and the medical record files. The subjects were also contacted by telephone when needed. The study end-points were disease-free survival and overall survival. Data was analysed using SPSS 21.

 

Results: Out of the 83 patients, 65(78%) were male. The overall median(range) age was 46(20-80) years, and 43(52%) of them were aged 31-50 years. Overall, 15(18%) patients had positive margins and 48(58%) had proven cervical node metastasis on histopathology. Overall survival was 42.2% with the median(range) follow-up time was 14(9-21) months and 5-year disease-free survival was 45.8% with the median (range) follow-up time was 13(7-19). The factor that affected the final outcome was found to be the increasing nodal ratio (p=0.043).

 

Conclusion: Among T4 oral squamous cell carcinoma patients treated with surgery and adjuvant therapy, the rate of disease recurrence was found to be high. Tumours with a high cervical nodal disease burden and/or margin involved were at substantially higher risk of recurrence.

 

Keywords: Squamous cell carcinoma, Oral cancer, Recurrence, Survival. (JPMA 72: 2399; 2022)

 

DOI: https://doi.org/10.47391/JPMA.3374

 

Introduction

 

Squamous cell carcinoma (SCC) of the oral cavity is a globally prevalent disease with 2% incidence and 1.8% mortality reported in 20201 and has significantly high recurrence. As such, there is a lot of room for researchers to identify the factors that can improve outcomes.2 Oral cancer, especially of the cheek, is the most common cancers in Pakistan and among the 10 most common malignant tumours in Asia.2 In our region, chewable tobacco is widely consumed, resulting in the higher prevalence of oral cancers.3 The age of most of the patients with oral cavity squamous cell carcinoma (OCSCC) ranges 50-70 years, the mean age being 51-55 years. Clinicopathological parameters have a vital role in prognosis, recurrence and survival, following oral squamous cell carcinoma(OSCC).4 The tumour, nodes, metastasis (TNM) classification is used clinically to decide the treatment pathway and access its response and prognosis.5 However, in reality, the prognosis of the disease and the outcome is not described. Tumours of similar stage can have a different behaviour.6 The best curative treatment for OCSCC is wide local excision when the tumour is regarded resectable, with or without reconstruction and neck dissection. Adjuvant treatment, mostly radiation therapy (RT), is often required, but chemotherapy has a limited role and is most commonly used as a radiosensitiser or in a neo-adjuvant setting.7 Since the past many years, the survival of locally advanced oral cancers has remained the same despite the different aggressive combined treatments used. At the same time, different studies have reported variable survival rates for stage III and IV oral cancers mainly due to the heterogeneous treatment pathways applied.8

The current study was planned to determine the association of clinical and pathological parameters on recurrence of treated stage T4 OCSCC patients managed with surgery followed by concomitant chemo and radiation therapy.

 

Materials and Methods

 

The retrospective, cohort study was conducted at Patel Hospital, Karachi, and comprised data of patients diagnosed with OCSCC and admitted between January 1, 2014,and January 30, 2019, after obtaining exemption from the institutional ethics review committee.

Those included were stage T4 tumour patients of both genders aged 20-80 years who were histopathologically proven cases of OCSSC and had undergone surgical treatment, and had a minimum follow-up of one year. Patients who underwent any treatment modality before the surgical treatment were excluded. Tumour staging was done in accordance with the 8th edition of the American Joint Committee on Cancer (AJCC) staging guidelines.5

Patients' demographic data, including age, gender, addiction habits, the primary site of tumour and trismus, and presenting features were noted. Histopathological parameters, including tumour size, tumour grade, tumour margins, depth of invasion, perineural invasion, bone involvement, vascular invasion, extracapsular spread, and nodal stage were also retrieved. Patients after surgical excision of the tumour had been referred to get adjuvant treatment. Head and Neck Cancer registry form was used for data collection, while missing data was retrieved from the medical record files. The patients or their families were contacted by telephone when needed.

The study end-points were disease-free survival (DFS) and overall survival (OS). Disease recurrence included regional, local, and/or distant metastasis as shown by histopathology report. DFS was defined as an interval from surgery to disease recurrence within 5 years of treatment. OS was considered the time interval from surgical tumour resection to death or completed five-year follow-up.

Data was analysed using SPSS 21. Descriptive statistics were used to summarise the data in terms of frequency and percentages of qualitative variables. Local, regional and distant recurrences of the disease were all noted to assess DFS. Kaplan Meier was used to analyse DFS and OS. Univariate analysis (UVA) and multivariate analysis (MVA) were performed using Cox proportional hazards regression to identify patient-, tumour- and treatment-related variables associated with inferior DFS. P<0.05 was considered significant.

 

Results

 

Out of the 83 patients, 65(78%) were male. The overall median (range) age was 46 (20-80) years, and 43(52%) of them were aged 31-50 years. Overall, 13(16%) patients had positive margins and 48(58%) had proven cervical node metastasis on histopathology. The two most frequently involved sub-sites were buccal mucosa 44(53%) and lower alveolus 20(24%). Furthermore, 51(61%) patients had restricted mouth opening either due to submucosal fibrosis or direct invasion of the disease. However, involvement of pterygoid muscle was evident in only 5(6%) patients. All patients were advised post-op adjuvant radiotherapy (RT), but 12(14%) were not compliant. Besides, 15(18%) patients also received concurrent cisplatin-based chemotherapy (FIGURE-1).

 

Overall survival was 42.2% with the median (range) follow-up time was 14 (9-21) months, and 5-year disease-free survival was 45.8% with the median (range) follow-up time was 13 (7-19) months (Figure-1). Using MVA, the factor that affected the final outcome was found to be the increasing nodal ratio (p=0.043) (Table-2).

Five-year DFS for patients with increasing nodal stage (p=0.024) and positive margin (p=0.038) had worst outcome compared to those without these risk factors (Figure-2).