|Year : 2019 | Volume
| Issue : 1 | Page : 26-31
Survival trends in oral cavity cancer patients treated with surgery and adjuvant radiotherapy in a tertiary center of Northern India: Where do we stand compared to the developed world?
Nishant Lohia1, Sharad Bhatnagar1, Sankalp Singh1, Manoj Prashar1, Anand Subramananiam1, Sundaram Viswanath1, PK Sahu2, Ajay Rai2
1 Department of Malignant Disease Treatment Centre, Command Hospital (CC), Lucknow, Uttar Pradesh, India
2 Department of Ear, Nose and Throat, Command Hospital (CC), Lucknow, Uttar Pradesh, India
|Date of Web Publication||15-Mar-2019|
Consultant Radiation Oncologist, Malignant Disease Treatment Centre, Command Hospital (CC), Lucknow - 226 002, Uttar Pradesh
Introduction: Oral cavity cancer is the third most common cancer in India. It presents a major burden on health services in India due to the widespread and rampant use of tobacco. Moreover, as per the Indian Council of Medical Research 2016 data, it ranks the fifth in overall mortality rate among different cancers prevalent in India. Aims and Objectives: The aim was to study and present our data on patient- and tumor-related factors as well as overall survival (OS) among patients of oral cavity cancer treated with surgery and radiotherapy at our center. The objective was to find the difference in OS in various subgroups of patients at 2 and 5 years from treatment. Materials and Methods: This was a retrospective study carried out in a tertiary care center of North India. The data collected were of patients treated between November 12 and November 16. A total of 112 cases of oral cavity cancers were studied. The patient-related variables that were analyzed included age, gender, history of tobacco or alcohol use, and presence of preexisting comorbidities. The tumor-related factors that were studied were tumor subsite, stage, and histological grade. OS of patients with varying parameters was compared at 2 and 5 years. Results: OS at 5 years for Stage I was 100% and decreased to 85% for Stage II. For Stages III and IV, the 5-year survival was a mere 43% and 42%, respectively. Conclusion: Treatment results at our center were comparable to world literature.
Keywords: Oral cavity cancer, retrospective study, survival
|How to cite this article:|
Lohia N, Bhatnagar S, Singh S, Prashar M, Subramananiam A, Viswanath S, Sahu P K, Rai A. Survival trends in oral cavity cancer patients treated with surgery and adjuvant radiotherapy in a tertiary center of Northern India: Where do we stand compared to the developed world?. SRM J Res Dent Sci 2019;10:26-31
|How to cite this URL:|
Lohia N, Bhatnagar S, Singh S, Prashar M, Subramananiam A, Viswanath S, Sahu P K, Rai A. Survival trends in oral cavity cancer patients treated with surgery and adjuvant radiotherapy in a tertiary center of Northern India: Where do we stand compared to the developed world?. SRM J Res Dent Sci [serial online] 2019 [cited 2019 Apr 23];10:26-31. Available from: http://www.srmjrds.in/text.asp?2019/10/1/26/254245
| Introduction|| |
Cancer occurring in the tissues of oral cavity (beginning at the lips and extending backward up to the anterior part of the tonsils) is termed as oral cancer. It is the most common noncutaneous malignancy of the head and neck and comprises cancers of various subsites such as lips, oral tongue, floor of the mouth, retromolar trigone, buccal mucosa (BM), alveolar ridge, and hard palate. The local and nodal patterns of spread and clinical outcomes vary for different subsites. For the year 2017, surveillance, epidemiology, and result program data have estimated almost 49,670 new cases of oral cancer and 9700 deaths for 2017.
Oral cancer is the third most common type of cancer in India. It is predominately a disease of older men who use tobacco and alcohol. Approximately 95% of carcinomas afflict patients in the sixth to seventh decades of life, and it is twice more common in men than in women. Tobacco causes most oral cavity cancers, and alcohol synergistically increases the risk of these cancers conferred by tobacco use., However, the risk of alcohol consumption without tobacco use is unclear. In India, the habit of chewing pan (mixture of lime and tobacco in betel nut leaves) results in prolonged carcinogen exposure to the oral mucosa and is thought to be the leading cause of oral cancer.
Although the primary causative factors for oral cavity cancers are known to be tobacco and alcohol, the etiology is multifactorial, and many additional risk factors have also been described that have an effect on the final outcome. In addition to the stage of disease and age of patients, the overall health in terms of performance status and presence of comorbid conditions can also result in a change in outcome. Similarly, nutrition plays an important role in prognosis, and history of significant weight loss (>10% of body weight over 3–6 months) is known to affect survival.
The primary treatment for oral cancer remains surgery with radiotherapy used as an adjuvant in locally advanced cases and as radical therapy in inoperable cases. Chemotherapy is used concurrently with radiotherapy in patients with certain adverse pathological factors or in metastatic disease for palliation.
Despite having the highest number of oral cancer cases in the world, very scarce long-term survival data are available from our country. The various reasons contributing to this include poor patient follow-up compliance and lack of diligent record maintenance. At our center, a very meticulous system of follow-up as well as record keeping is maintained. As our patients belong to a restricted subgroup comprising military personnel and their families only, follow-up compliance is significantly higher. We present our data of oral cancer patients treated and followed up for a period of 5 years.
| Materials and Methods|| |
We conducted a retrospective study in a tertiary cancer care hospital in northern India in patients of treatment-naive oral cavity cancers who were treated with surgery and subsequently received adjuvant radiotherapy. Data were collected from treatment and follow-up records of patients diagnosed between November 2012 and November 2016. Only patients with a minimum recorded follow-up of 24 months or who died before that were included in the study. The patient-related variables analyzed were age, gender, history of tobacco and alcohol use, and presence of comorbidities.
As majority of the patients in our study were illiterate, so quantification of tobacco and alcohol history could not be done as per specifications laid out in various western studies. Hence, tobacco use was defined in terms of daily consumption of cigarettes or bidis or smokeless tobacco in any form such as snuff, betel nut, and betel quid for at least 5 years. Similarly, positive alcohol history was defined in terms of regular (three or more times a week) consumption of alcohol for at least 5 years. Patients were defined as having comorbid illness if they had preexisting diagnoses of any one or more of hypertension (HTN), diabetes mellitus (DM), coronary artery disease (CAD), or chronic obstructive pulmonary disease (COPD). The tumor-related factors that were analyzed were tumor subsite, stage, and histological grade.
Any missing records were collected from patients during their follow-up visits and through teleconversation. Patients were evaluated every 3 months for the first 2 years and every 6 months for the next 3 years, and annually thereafter, locoregional status and distant metastases were assessed at baseline and at each follow-up assessment. Outcome data collected were on survival at 2 and 5 years. Overall survival (OS) was defined as time from date of diagnosis till death. Death could be due to any cause.
| Results|| |
A total of 167 patients of oral cavity were treated during the study period out of which 112 were included in the study. The age of the patients ranged from 31 to 90 years. The most common age group was 51–70 years (70%), followed distantly by those ≤50 years (18%) and ≥70 years (13%) [Figure 1]. Male patients were four times more common than female ones [Figure 1].
About 84% of study participants had a history of using tobacco either in smoked or smokeless form. Tobacco consumption was very high in male patients (93% or 82 out of 88), whereas it was much lower in the females with only 50% giving positive history. While in females, smokeless tobacco was the only mode of tobacco use, in male tobacco users, both smoked and smokeless versions were used by almost all. About 21% of patients in the study affirmed for alcohol consumption and all were males. Both alcohol and tobacco usages were recorded in 18% of the cases. Nearly 37% of patients had one or more preexisting comorbidities.
Tongue (39%) and BM (34%) were the two most common subsites encountered. All cancers were staged as per the 7th edition of the AJCC Cancer Staging Manual. While the majority of patients (59) were in locally advanced stages III and IV, 53 were in early stages, i.e., Stages I and II [Table 1]. However, Stage I contributed only 9% of these displaying the lack of awareness and reluctance for early medical attention in the population. The distribution of cases as per subsites and stage is given in [Table 1].
Histological grade of tumors is defined as well, moderately, or poorly differentiated, according to the World Health Organization criteria. In our study, 45% were well-differentiated tumors, 38% were moderately differentiated, and 18% were poorly differentiated.
Eighty-one out of 112 patients were still alive till completion of this study, with 31 patients having died of which 17 succumbed to cancer. The remaining 14 died of either myocardial infarction (4), COPD (3), pneumonia and other infections (3), neutropenia (2), or cerebrovascular accident (CVA) (1). Among patients who developed recurrent disease, 23% had local, 5% had nodal, while 10% had distant recurrences. The minimum OS seen was of 2 months and was of a patient who died of pneumonia while under radiotherapy treatment. The maximum recorded OS was 84 months. Median OS of the entire study population seen at 2 years was 88% with gradual decline seen at 3 years (78%), 4 years (71%), and 5 years (66%) of the follow-up period. The median OS at 2, 3, 4, and 5 years for the subgroups of study patients with different variables is compared and displayed in [Table 2].
|Table 2: Clinical and tumor characteristic-wise distribution of yearly survival rates in study population|
Click here to view
Patients with early stages fared well with good OS. A 100% OS was seen at 5 years for all patients of Stage I. Only two of these patients died and that too beyond the study period of 60 months. Similarly, an excellent OS of 94% at 2 years and 85% at 5 years was seen in pathological Stage II. However, a steep decline in OS was seen in the advanced stages. Median OS in Stages III and IV at 5 years was 43% and 42%, respectively.
Poorly differentiated tumors had very low OS as compared to moderately differentiated squamous cell carcinoma (MDSCC) and well-differentiated squamous cell carcinoma (WDSCC). OS in poorly differentiated squamous cell carcinoma (PDSCC) at 2 years was only 45% and was 20% at 3 years. Maximum survival seen in this subgroup was 38 months. In comparison, median OS at 5 years for MDSCC and WDSCC was 53% and 75%, respectively.
| Discussion|| |
Oral cancer is a global health problem. The increasing burden of this cancer in our country is a cause of major concern because of high morbidity and poor quality of life.
Although, oral cancer is historically believed to be a disease of people of older age groups, recent studies including our own have observed cases as early as the third decade. This increased incidence in younger age group is likely due to exposure to tobacco and alcohol at an early age (as early as 10 years as per history given by our patients), especially in the low socioeconomic strata. Men everywhere in the world have a 2-fold to 5-fold greater risk of head-and-neck cancer (HNC) than women. This difference can be directly attributed to higher usage of tobacco and alcohol among men than women. Even in our study, both tobacco consumption and incidence of oral cancer were much higher in males. Among tobacco products, smokeless tobacco plays an important role in causation of oral cancers in our country as it is cheaper and more widely prevalent.
An interesting observation in our study was that while in carcinoma tongue patients, 57% presented in early stage (27% in Stage I) and 32% presented in Stage IV, only 5% of BM cancers presented in Stage I. More than 50% of the patients with BM cancers and 65% of patients with alveolar cancers presented in Stage IV. The probable explanation for this variation in temporal presentation of these subsites is that oral cavity malignancies usually occur at the sites where tobacco is in prolonged contact with the mucosa. Chewing of betel nut quid, gutka, or khaini are popular forms of tobacco use in India. These forms of tobacco use not only allow prolonged exposure but also cause discoloration, which camouflage early changes over the mucosa resulting in late presentation of disease of BM and alveolus as evident in our study also. Oral cavity cancers, especially of BM and alveolus, are the most common head-and-neck malignancies in India as a result of these habits. The risk of developing a carcinoma is almost 8-fold higher in pan chewers and relates to the duration of the mucosal exposure to the quid. Studies of HNC in nontobacco users have reported a higher proportion of women patients and that the tumors develop preferentially in the tongue.,
Alcohol consumption has been shown to act synergistically with tobacco in the increased risk of development of oral cancer. Although tobacco and alcohol are independent risk factors, it is often difficult to separate their contribution since they usually coexist. However, in our study, we found that 5-year OS in patients who consumed both alcohol and tobacco was 29% as compared to patients who consumed only tobacco where 5-year OS was 75%. Continued tobacco use during radiation therapy has been associated with decreased OS and inferior response to treatment. We too had 3 patients who continued using tobacco throughout treatment despite repeated counseling and all three developed recurrences within 3 months of treatment completion.
The most commonly affected subsites seen were tongue and buccal mucosa, similar to findings in other Indian studies., Recent studies have demonstrated that in patients not exposed to smoking and alcohol, the lesions tended to be well or moderately differentiated, whereas in individuals who are exposed to either smoking or alcohol, a lower degree of cell differentiation has been observed., Even in our patients, the histology pattern seen in the majority of nontobacco users was WDSCC (11% or 65%) or MDSCC (5% or 29%) with only one (6%) case of PDSCC. On the other hand, in the 18 cases who consumed both alcohol and tobacco, 67% (12) were PDSCC, 22% (4) were WDSCC, and 11% (2) were MDSCC. The said pattern suggests a poorer degree of cell differentiation in smokers and alcoholics. However, a larger patient population is required to establish a correlation between tumor grades and smoking and alcohol.
Overall, 5-year survival rates in oral cavity cancers have been reported as 57.7% by Kim et al. and 63.2% by Lee et al. Two- and five-year survival rates for our patients were 88% and 66% which are comparable with the published literature. No significant sex difference in OS was observed as displayed in [Table 2]. While no significant difference in survival at 2 or 5 years was seen in the age groups <50 and 50–70 years, the age group above 70 years clearly did have a poorer survival at both 2 and 5 years. This is probably attributable to the presence of more comorbid diseases, poorer nutritional status, greater frailty, and worse treatment tolerance in the elderly age group. Further corroborating this hypothesis, OS at 5 years in patients without comorbidities was 84% which drastically decreased to 16% in those with comorbidities. An important aspect which we noticed was that patients with diabetes fared poorly compared to other comorbidities. We had 20 patients with type II DM out of which only 5 were alive till completion of the study.
Median OS at 2 years in both tobacco users (84%) and nonusers (88%) was comparable, but it declined at 5 years from 72% in nonusers to 43% in users. This reflects the possibility that the tobacco-related tumors were less responsive to treatment by radiotherapy with higher chances of mortality. Other reasons could be increased mortality due to other diseases related to tobacco such as CAD, CVA, and HTN. An interesting fact is that the survival rates are identical at 2 years between users and nonusers but falls away after that. A possible reasoning for this could be the restarting of tobacco use by those who had reformed during treatment and for a short while after that.
In terms of tumor subsite, patients with tongue cancers had a better OS when compared to buccal mucosa and alveolus. This is likely due to 56% of tongue cancers presenting to us in early Stage (I and II) with the remaining in locally advanced Stages (III and IV). In BM cancers, this ratio is reversed with only 43% of patients presenting in early stages and 57% in advanced stages. The trend was even poorer in those with alveolar cancers as only 24% presented in early stages and majority (76%) presented in advanced stage.
Patients with early-stage oral cavity cancer and Grade I tumor generally have an excellent prognosis. Tumor stage and grade were very strongly related to the level of survival in our study too. OS at 5 years varied from excellent (100%) in Stage I to 85% in Stage II to a mere 43% and 42% in Stage III and IV, respectively. Similarly, OS in WDSCC (Grade I), MDSCC (Grade II), and PDSCC (Grade III) at 5 years was 75%, 53%, and 0%, respectively. PDSCC had higher local and distant recurrences in our study as compared to MDSCC and WDSCC. However, the prognostic significance of grade independently is difficult to ascertain due to wide variation in pathological interpretation and patient characteristics.
Another important prognostic factor for outcome in oral cavity carcinoma is the presence of cervical metastases. Five-year survival is decreased by almost 50% in node-positive cases as compared to node-negative cases. In a study by Myers et al., 5-year OS for pathologically node-negative patients was 75% which decreased to 50% in node-positive cases but without extra capsular extension (ECE). The results in our study were comparable as 5-year OS in node-negative cases was 71%, and in node-positive cases, 5-year OS was 54%.
| Conclusion|| |
Oral cavity cancer has one of the largest burdens in India due to the high prevalence of tobacco use, especially in rural areas and in the lower socioeconomic bracket. Lack of awareness, absence of a widespread screening program, and lack of adequate diagnostic and therapeutic facilities result in presentation of most cases in advanced stages resulting in poor treatment results and high mortality rates. Lack of follow-up for the majority of patients not only leads to late detection of recurrences but also is the reason for the lack of substantial survival and treatment data from our country. Our study shows that establishment of the practice of regular follow-up and careful maintenance of records can help in recognizing the impact of treatment on patient survival. Our data also reflect that standard treatment results at our center are comparable to world literature.
Certain weaknesses of our paper have been identified:
- The study was a retrospective one with collection of data started after completion of requisite follow-up by patients
- Due to lack of adequate sample size, statistical tests could not be applied to identify the significance of the findings
- Due to lack of adequate laboratory resources, human papillomavirus prevalence in the study population could not be assessed which might have been an important etiological factor, especially in nontobacco users.
We would like to thank Command Hospital (CC), Lucknow Cantt, Uttar Pradesh, India.
Financial support and sponsorship
This study was financially supported by Command Hospital (CC), Lucknow Cantt, Uttar Pradesh, India.
Conflicts of interest
There are no conflicts of interest.
| References|| |
Chi AC, Day TA, Neville BW. Oral cavity and oropharyngeal squamous cell carcinoma – An update. CA Cancer J Clin 2015;65:401-21.
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;7:108-12.
Blot WJ, McLaughlin JK, Winn DM, Austin DF, Greenberg RS, Preston-Martin S, et al.
Smoking and drinking in relation to oral and pharyngeal cancer. Cancer Res 1988;48:3282-7.
Hashibe M, Brennan P, Benhamou S, Castellsague X, Chen C, Curado MP, et al.
Alcohol drinking in never users of tobacco, cigarette smoking in never drinkers, and the risk of head and neck cancer: Pooled analysis in the international head and neck cancer epidemiology consortium. J Natl Cancer Inst 2007;99:777-89.
Pinholt EM, Rindum J, Pindborg JJ. Oral cancer: A retrospective study of 100 Danish cases. Br J Oral Maxillofac Surg 1997;35:77-80.
Secretan B, Straif K, Baan R, Grosse Y, El Ghissassi F, Bouvard V, et al.
A review of human carcinogens – Part E: Tobacco, areca nut, alcohol, coal smoke, and salted fish. Lancet Oncol 2009;10:1033-4.
Jussawalla DJ, Deshpande VA. Evaluation of cancer risk in tobacco chewers and smokers: An epidemiologic assessment. Cancer 1971;28:244-52.
Hodge KM, Flynn MB, Drury T. Squamous cell carcinoma of the upper aerodigestive tract in nonusers of tobacco. Cancer 1985;55:1232-5.
Ng SK, Kabat GC, Wynder EL. Oral cavity cancer in non-users of tobacco. J Natl Cancer Inst 1993;85:743-5.
Browman GP, Wong G, Hodson I, Sathya J, Russell R, McAlpine L, et al.
Influence of cigarette smoking on the efficacy of radiation therapy in head and neck cancer. N Engl J Med 1993;328:159-63.
Modi D, Laishran RS, Sharma LD, Debnath K. Pattern of oral cavity lesions in a tertiary care hospital in Manipur, India. J Med Soc 2013;27:199-202. [Full text]
Mehta NV, Dave KK, Gonsai RN, Goswami HM, Patel PS, Kadam TB. Histopathological study of oral cavity lesions: A study on 100 cases. Int J Res Rev 2013;5:110-6.
Bachar G, Hod R, Goldstein DP, Irish JC, Gullane PJ, Brown D, et al.
Outcome of oral tongue squamous cell carcinoma in patients with and without known risk factors. Oral Oncol 2011;47:45-50.
Kruse AL, Bredell M, Grätz KW. Oral squamous cell carcinoma in non-smoking and non-drinking patients. Head Neck Oncol 2010;2:24.
Kim MY, Kim CS, Lee SH, Kim JW, Jang HJ. A clinicostatistical analysis of oral cancer patients for recent 8 years. J Korean Assoc Oral Maxillofac Surg 2007;33:660-8.
Lee JW, Kim JW, Kim CS. A clinic-statistical study on cervical lymph node metastasis of oral squamous cell carcinoma. J Korean Assoc Oral Maxillofac Surg 2008;34:594-601.
Johnson JT, Barnes EL, Myers EN, Schramm VL Jr., Borochovitz D, Sigler BA, et al.
The extracapsular spread of tumors in cervical node metastasis. Arch Otolaryngol 1981;107:725-9.
Myers JN, Elkins T, Roberts D, Byers RM. Squamous cell carcinoma of the tongue in young adults: Increasing incidence and factors that predict treatment outcomes. Otolaryngol Head Neck Surg 2000;122:44-51.
[Table 1], [Table 2]