|Year : 2016 | Volume
| Issue : 2 | Page : 76-80
Survival outcomes of buccal mucosa carcinoma patients with multimodal therapy: An institutional study
Ramasamy Padma1, Ramamurthy Thilagavathi2, Sivapatham Sundaresan1
1 Department of Medical Research, SRM Medical College Hospital and Research Centre, SRM University, Kanchipuram, Tamil Nadu, India
2 Department of Public Health, SRM Medical College Hospital and Research Centre, SRM University, Kanchipuram, Tamil Nadu, India
|Date of Web Publication||11-Apr-2016|
Department of Medical Research, SRM Medical College Hospital and Research Centre, SRM University, Kattankulathur, Kanchipuram, Tamil Nadu
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background/Objectives: The buccal mucosa carcinoma is the most common site for oral squamous cell carcinoma. Treatment of oral squamous cell carcinoma has classical method of surgical resection and post-operative adjuvant chemo and radiotherapy. Despite, this multimodality treatment five year survival remains poor. Therefore, this study had been conducted to assess survival outcome of buccal mucosa carcinoma by different treatment strategies. Materials and Methods: Demographic, pathologic, treatment and survival data was retrieved from hospital registries from 2013-2015 in Arignar Anna Memorial Cancer Hospital and Research Centre, Kanchipuram. Actuarial overall and relapse-free survivals were estimated with Kaplan-Meier method. Results and Discussion: A total of 198 buccal mucosa carcinoma subjects comprised 125(63.1%) male and 73(36.9%) female in 1.7:1 ratio. Type of treatment had significant association of subjects age, cellular differentiation, clinical stage of disease and regional lymph nodes by chi-square analysis (P < 0.05). Three years estimated overall survival and time to recurrence (TTR) was 96.46% and 3.54% respectively. Subjects receiving multimodality treatment (post operative radiotherapy and with adjuvant chemotherapy) improved overall and time to recurrence (TTR) compared to radio and chemo radiotherapy alone (P < 0.05). Conclusion: This study shows that adding adjuvant chemotherapy with post operative radiotherapy improves better survival outcomes.
Keywords: Chemotherapy, oral cancer, prognosis, radiotherapy, relapse-free, survival
|How to cite this article:|
Padma R, Thilagavathi R, Sundaresan S. Survival outcomes of buccal mucosa carcinoma patients with multimodal therapy: An institutional study. Int J Nutr Pharmacol Neurol Dis 2016;6:76-80
|How to cite this URL:|
Padma R, Thilagavathi R, Sundaresan S. Survival outcomes of buccal mucosa carcinoma patients with multimodal therapy: An institutional study. Int J Nutr Pharmacol Neurol Dis [serial online] 2016 [cited 2019 Jun 24];6:76-80. Available from: http://www.ijnpnd.com/text.asp?2016/6/2/76/179967
| Introduction|| |
Oral cancer has become a global health problem, and its increasing incidence and mortality rates are particularly relevant in certain parts of Europe and South-Eastern Asia especially in Sri Lanka, Pakistan, Bangladesh, and India.  An estimate according to National Cancer Control Programme shows that total cancer burden in India for all sites will increase from 7 lakhs new cases per year to 14 lakhs by 2026.  Oral cancer is the sixth most common cancer worldwide with 575,000 new cases each year and 200,000 deaths annually. 
Oral cancer occurs in all sites of oral cavity such as tongue, cheeks, lips, soft palate, tonsils, salivary glands, oropharynx, and floor of the mouth. Buccal mucosa, the membrane lining of the inner surface of the cheeks is one of the most common sites of oral cancer, which has a poor prognosis because of its aggressive nature than other oral subsites.  However, buccal mucosa carcinoma had poor prognosis than other oral subsites, which required multimodality treatment.
The United States and Europe demonstrated that compared to postoperative radiotherapy (PORT) alone, adjuvant concurrent chemo-radiotherapy (RT) for advanced stage oral squamous cell carcinoma was more efficacious in local and regional control as well as disease-free survival. , Based on these landmark trials, many centers today have adopted triple modality therapy consisting of surgery and adjuvant concurrent chemotherapy and RT for the advanced stage of oral squamous cell carcinoma. 
Therefore, this study was conducted to assess survival outcomes of buccal mucosa carcinoma by different treatment strategies.
| Materials And Methods|| |
The retrospective analytical study was carried out at Regional Cancer Centre, Arignar Anna Memorial Cancer Hospital and Research Centre, Kanchipuram during the year of 2013-2015. The Institutional Ethical Committee Permission from Directorate of Medical Education, Tamil Nadu was obtained to conduct the study (Ref No. 24984).
The study included 198 buccal mucosa carcinoma subjects among both sexes. The standardized questionnaire was used to retrieve demographic, clinical and histopathological variables and their follow-up details from hospital registries. The relevant clinical data, stage of buccal mucosa carcinoma according to Union for International Cancer Control (UICC). 
Histopathology confirmed premalignant lesions/conditions and other oral subsites were excluded.
A total of four treatment groups were analyzed. (1) RT only, (2) PORT, (3) chemo and RT (4) PORT with adjuvant chemotherapy. Group 1 subjects were treated RT alone, Group 2 subjects received surgical resection with adjuvant RT within 6-8 weeks postoperatively, Group 3 subjects were treated with chemo and RT, and Group 4 subjects underwent surgical resection and postoperative adjuvant chemoradiotherapy within 6-8 weeks of their operation. Doses for curative RT ranged from 63 to 80 Gy in 33-35 fractions and for adjuvant RT from 55 to 70 Gy (3 Gy per fraction, once a day). (5) Fluorouracil and Cisplatin or carboplatin-based chemotherapy were used as an adjuvant for most of the subjects.
All patients were followed at regional cancer treatment centers of Kanchipuram, Tamil Nadu at regular intervals. Dates of follow-up up to October 2015 were recorded.
The follow-up outcome measure was set overall survival which was calculated as the time from the 1 st date of treatment to the date of death, or last known date of subjects was alive. Time to recurrence (TTR) was calculated from the first day of treatment to the date of disease recurrence.
SPSS version 16.0 was used for statistical analysis (SPSS Inc., Chicago, IL, USA). The demographic and clinicopathologic characteristics based on treatment strategies among buccal mucosa carcinoma subjects were analyzed using Chi-square test (P < 0.05). Overall survival and TTR was performed using Kaplan-Meier method and log-rank test were used to determine significant difference among different treatment groups (P < 0.05).
| Results|| |
The study consists of 198 buccal mucosa carcinoma subjects. Of these, 125 (63%) subjects were male and 73 (37%) female subjects, among them 60 (30.3%) subjects were undergone surgical resection and rest of the subjects were not fit for surgery or refused for surgery. A total of 138 (70%) subjects were planned for palliative care of either RT alone or radio-chemotherapy because these subjects medically not fit for surgery, 25 (12.6%) subjects were planned for surgery with adjuvant RT (PORT) and 35 (17.7%) had undergone for PORT with adjuvant chemotherapy.
[Table 1] demonstrates patient demographic, clinical, and histopathological characteristics. As curative care 30 (15.1%) subjects were undergone surgery with adjuvant radio and chemotherapy among the old age group of > 50 years and rest of the subjects had palliative care. Type of treatment exists significantly association with different age groups (P < 0.049). However, gender was not associated with type of treatment groups.
|Table 1: Sociodemographic and clinical characteristics by treatment groups |
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Clinical staging in accordance with the tumor nodal stage (TNM) system of the UICC staging were recorded. On the basis of staging, patients were divided into 2 groups: Group 1 with early stage disease at presentation (i.e., stage I and II) and Group 2 with late stage disease at presentation (i.e. stage III and IV). In our study, 170 (86%) most of the subjects were diagnosed late stage, and 41 (20.7%) had regional lymph nodes. The treatment strategies differ based on the stage of diseases and medical fitness. In our study, 32 (16%) subjects with advanced stages and 27 (13.6%) subjects with regional lymph nodes were treated with postoperative adjuvant chemotherapy. Clinical stage and nodal involvement exist association with type of treatments at P < 0.01 [Table 1].
The degree of differentiation was an important prognostic factor for patient's survival. Poorly differentiated had less survival than moderate and well-differentiated squamous cell carcinoma. In our study, 32 (16.1%) had poorly differentiated among them 29 (14.64%) undergone postoperative adjuvant chemo or RT. However, histopathology of buccal mucosa carcinoma revealed that there was a statistically significant difference between with poorly differentiated and 166 (83.83%) subjects with either moderately or well-differentiated buccal mucosa carcinoma exists significant at P < 0.05 level [Table 1].
The mean follow-up for all patients was 17.4 months. Of 198 subjects, 191 subjects were living without disease until their last follow-up. Hence, the 3 years estimated overall survival rate was 96.46% [Figure 1]. Kaplan-Meier curve (log-rank test) shows an association of different treatment groups and their overall survival. PORT with adjuvant chemotherapy improves better survival outcome than other treatment therapy [Figure 2] and [Table 2]. Similarly, among 198 subjects, seven subjects were found with a reoccurrence of buccal carcinoma. Therefore, the estimated TTR was 3.54% for 3 years as shown in [Table 3] and [Figure 3]. TTR Kaplan-Meier graph also had proved that multimodality therapy had higher survival compared to single treatment therapy [Figure 4].
|Table 2: Overall survival among different treatment strategies of subjects |
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|Table 3: Time to recurrence of subjects among different treatment strategies of subjects |
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|Figure 1: Kaplan-Meier curve shows overall survival of buccal mucosa carcinoma subjects|
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|Figure 2: Kaplan-Meier curve shows association of overall survival among different treatment strategies|
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|Figure 3: Kaplan-Meier curve shows time to recurrence of buccal mucosa carcinoma subjects|
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|Figure 4: Kaplan-Meier curve shows association of time to recurrence among different treatment strategies|
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| Discussion|| |
This study was undertaken to assess the survival of subjects based on the treatment groups. Despite advances in treatment, 50% of 5 years survival was disappointing due to aggressive nature of disease. Previous studies reported that clinical stage, depth and degree of differentiation were the most important prognostic factors. It is best when the primary tumor is small, and there is no evidence of regional lymph node involvement or distant metastasis. The 5 years survival rate of persons with early stage oral squamous according to the TNM staging system may reach 80-90% whereas the 5 years survival rate for advanced stage oral squamous cell carcinoma was about 40%.  In India, Iyer reported that 5 years survival rates for buccal mucosa carcinoma range from 80% for stage I and II disease to 5-15% for locally advanced disease stage III and IV. 
The present study consists of 170 (86%) of subjects with an advanced stage of III and IV, among them 138 (69.7%) were undergone postoperative adjuvant chemotherapy or RT and rest of the subjects were medically not fit for multimodality treatment due to various factors. However, multimodality treated had better survival than other treatment therapy as similar to cooper's report. 
Recent studies had shown that pathological poorly differentiated pT1-2N0 oral squamous cell carcinoma subjects were associated with poor regional control, and such subjects may benefit from PORT.  In this study, also shown PORT adjuvant chemotherapy for poorly differentiated squamous cell carcinoma subjects and had a significant association with degree of differentiation with different treatment modalities.
In general, primary RT and chemotherapy without surgery treated in the early stage of disease to avoid anticipated function and cosmetic defect, unrespectable diseases, high operative risk patients due to co-morbidity or poor performance status and patient's preference.  Similarly, in our study also nearly half of the patients were treated with only and radio and chemotherapy without surgery.
The recurrent and metastatic squamous cell carcinoma is considered the main indication for chemotherapy, especially when the operative and radiotherapeutic approach have been exhausted.  Andreadis et al. revealed in his study chemotherapy alone without surgery as palliative care had increased survival rate and also mention that no significant difference in overall survival has been demonstrated with this modality compared with surgery or radiation alone.  In contrast, our study depicted that overall survival different from based on treatment groups. Multimodality had better survival than single therapy alone.
Zhang et al., a study supported the radiation therapy oncology group (RTOG) and European Organisation for Research and Treatment of Cancer (EORTC) landmark trials. The addition of postoperative chemotherapy to surgery-RT for advanced oral squamous cell carcinoma improved overall survival by 22% and 18% at 2 and 5 years posttreatment, respectively.  Similarly, the results of this study also support the RTOG and EORTC landmark trials. The addition of postoperative chemotherapy and RT for buccal mucosa carcinoma appears to improve overall survival 96.46% at 3 years of posttreatment.
| Conclusion|| |
In our study, we found the strong influence of treatment strategies on the prognosis of buccal mucosa carcinoma. The present study concluded that multimodality, PORT with adjuvant chemotherapy had better survival than treatment groups. Further studies warranted to emphasize better prognosis of buccal mucosa carcinoma.
Our team would like to acknowledge and thank Arignar Anna Memorial Cancer Hospital and Research Centre, Kanchipuram for permitted sample collection and also we would like to thank Mrs. S. Arivalazhiki Dental hygienist and the entire participant for their support of sample collection.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Warnakulasuriya S. Global epidemiology of oral and oropharyngeal cancer. Oral Oncol 2009;45:309-16.
Dikshit R, Gupta PC, Ramasundarahettige C, Gajalakshmi V, Aleksandrowicz L, Badwe R, et al.
Cancer mortality in India: A nationally representative survey. Lancet 2012;379:1807-16.
O'Sullivan E. Oral and pharyngeal cancer in Ireland. Ir Med J 2009;102:16-9.
Diaz EM Jr., Holsinger FC, Zuniga ER, Roberts DB, Sorensen DM. Squamous cell carcinoma of the buccal mucosa: One institution's experience with 119 previously untreated patients. Head Neck 2003;25:267-73.
Cooper JS, Pajak TF, Forastiere AA, Jacobs J, Campbell BH, Saxman SB, et al.
Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med 2004;350:1937-44.
Bernier J, Domenge C, Ozsahin M, Matuszewska K, Lefèbvre JL, Greiner RH, et al.
Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med 2004;350:1945-52.
Zhang H, Dziegielewski PT, Biron VL, Szudek J, Al-Qahatani KH, O'Connell DA, et al.
Survival outcomes of patients with advanced oral cavity squamous cell carcinoma treated with multimodal therapy: A multi-institutional analysis. J Otolaryngol Head Neck Surg 2013;42:30.
Sobin LH, Wittelund C. TNM Classification of Malignant Tumors. International Union Against Cancer (UICC). Geneva, Switzerland: Wiley-Liss; 2002.
Feller L, Lemmer J. Oral squamous cell carcinoma; epidemiology, clinical presentation and treatment. J Cancer Ther 2012;3:263-8.
Iype EM, Pandey M, Mathew A, Thomas G, Sebastian P, Nair MK. Oral cancer among patients under the age of 35 years. J Postgrad Med 2001;47:171-6.
Cohen EE, Baru J, Huo D, Haraf DJ, Crowley M, Witt ME, et al.
Efficacy and safety of treating T4 oral cavity tumors with primary chemoradiotherapy. Head Neck 2009;31:1013-21.
Huang SH, O'Sullivan B. Oral cancer: Current role of radiotherapy and chemotherapy. Med Oral Patol Oral Cir Bucal 2013;18:e233-40.
Paximadis P, Yoo G, Lin HS, Jacobs J, Sukari A, Dyson G, et al.
Concurrent chemoradiotherapy improves survival in patients with hypopharyngeal cancer. Int J Radiat Oncol Biol Phys 2012;82:1515-21.
Andreadis C, Vahtsevanos K, Sidiras T, Thomaidis I, Antoniadis K, Mouratidou D. 5-Fluorouracil and cisplatin in the treatment of advanced oral cancer. Oral Oncol 2003;39:380-5.
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3]