Abstract
Patients presenting with head, face and neck (HFN) malignancy over a two year period were studied with the aim of identifying the numbers presenting in advanced stage, the treatment modalities that could be applied and the outcome of these patients.

Out of 73 patients only 17 (23%) reported within 2 months of becoming symptomatic. In 63 (86.2%) of the patients, disease had advanced to stage III or IV. Surgery, though known to be the only curative modality, could be performed in only 47 (64.3%) patients. The quality of life was superior in those subjected to surgery than those receiving chemo or radiotherapy. Follow-up failure was encountered in 30% of patients. Delay in seeking treatment, thus led to advanced stage at diagnosis, unsuitability to receive the best therapeutic option and poor outcome in terms of quality of life and survival.

Introduction
Cancer of the head, face and neck (HFN) is the sixth most common cancer worldwide. But in India, this accounts for as many as 50-70% of all cancers diagnosed. Though the pathology occurs in a region easily available for inspection for both the patient and the clinician, significant number of cases seek treatment only at an advanced stage. Several factors such as lack of health consciousness, low socio economic strata, illiteracy and inadequate number of facilities offering comprehensive care can be the reasons for the delay. The impact of this delay is disastrous for the patient and frustrating for the clinician.
This study was carried out at Lokmanya Tilak Municipal Medical College and Hospital, Mumbai, over a two year period. The aims of the study were:

1. To identify the incidence of advanced stage presentation in patients with HFN malignancies.
2. To study the impact of stage at presentation on the treatment decision.
3. To study the impact of stage and treatment on the outcome in terms of survival and quality of life.

Material and Methods
Patients diagnosed to have HFN malignancy during the two year period from May 2001 to April 2003 were included in the study. A proforma was designed to record the history, presenting symptoms and details of clinicial examination. This included the duration of symptoms, addictions, past treatment along with the clinical staging (TNM classification). The suspicion of malignancy was confirmed by edge biopsy of the lesion in every patient and by FNAC of the affected lymph nodes when indicated. The choice of treatment modality varied according to the stage of the disease and the patient’s wish. The patient subjected to surgery also received postoperative adjunctive therapy in the form of chemotherapy or radiotherapy or both. The patients were followed up over a two year period and were evaluated for loco regional recurrence, systemic metastasis and quality of life. The quality of life was evaluated by the patients himself/herself based on the symptom score of symptoms like : pain, disfigurement, and restriction of activity, difficulty in chewing, difficulty in swallowing, altered speech and shoulder disability. Presence of less than 2 symptoms was rated as good quality of life, 3-5 as fair and more than 5 symptoms as bad quality of life.
The data collected was analyzed at the end of the two year period of follow up.

Results
Seventy-three cases of HFN malignancy diagnosed over the 2 year period of study were treated and followed up. Majority of the patients were males (66%) and most were younger than 60 years (44 i.e. 60.3%). Only 29 i.e. 39.7% of the patients in our study were more than 60 years of age (Table 1). A significant observation was that 46 (63%) of the 73 patients approached the dental surgeons first and were then referred to the surgical service.

Only a couple of patients sought treatment within few days of becoming symptomatic. Majority i.e. 77% of patients sought treatment after a delay of 2 months or more after the appearance of symptoms. The maximum duration of delay was 2 years. Most often the reason for delay was lack of awareness and ignorance on the part of patients about the seriousness of the disease leading to neglect of symptoms. Majority of patients (64 i.e. 88%) had one or more addictions, most often to tobacco (55 patients). The commonest sites of malignancy were buccal mucosa, tongue and alveolus (74.1%). The other sites involved by the lesions were larynx, maxilla, palate and floor of mouth. In 65.7% of the patients the mode of presentation was either exophytic growth or an ulcer. Others presented as neck swelling, trismus and hoarseness of voice. Forty six (63%) of the seventy three patients in our study had first reported to the dentistry department and were then referred to the surgical service.

As is evident in Table 2, at diagnosis the disease had advanced to stage III or IV in 86.3% of patients. Histologically, most were squamous cell carcinomas (94.5%) with 11 (15%) being poorly differentiated, 24 (32.8%) well differentiated and 27% being indeterminate. FNAC of lymph nodes was performed in 20 patients and was indicative of metastasis in 18 patients. Pan tomogram was performed in 53 patients preoperatively.

Surgery was considered as the suitable modality for 53 patients, but six of these declined and opted for other modality. Hence 47 patients (Table 3) underwent surgery. 81.25% of patients with stage III disease and 38.7% of patients with stage IV disease could be subjected to surgery. Wide local excision was considered adequate for 8 patients while neck node dissection was performed in 39 patients undergoing surgery, most of these being modified radical neck dissections with preservation of the accessory nerve (Type I). Five out of the 12 patients in stage IV required bilateral neck dissection.

Closure with primary mucosal approximation or local mucosal advancement flaps and/or split skin grafts was achieved in 20 patients subjected to surgery. In remaining 27 patients reconstruction was done using single flap in 18 (38%) and double flap in 7 (15%). One failed PMMC flap was reconstructed with radial artery free flap. The postoperative complications were recorded in 23 (49%) patients subjected to surgery and these were wound infection in 8, flap failure in 4, fistula formation in 5, shoulder weakness in 4 patients and there were 2 deaths in the postoperative period.

Twenty patients (27.5%) were considered unsuitable for surgery due to locally advanced disease (19 pts in stage IV and 1 pt in stage III) and were offered palliative therapy along with the six cases declining surgical option. The modality of adjuvant therapy was decided on an individual basis for every patient. As seen in Table 4, 70.3% of patients received postoperative adjuvant therapy. Fourteen patients (29.7%) were subjected to composite resection with adjuvant chemo radiotherapy. 8 patients (3 in stage IV and 5 in stage III) out of these were also administered induction chemotherapy.

The overall survival rate at the end of follow-up period was longest in stage I and stage II disease (100% and 62.5% respectively). The survival rate declined with advancing stage with 50% survival for Stage IV disease (Table 5). The overall incidence of loco regional recurrence was 31.9% and this was mainly associated with stage III and IV disease (Table 6). The possibility of disease free survival diminished significantly with advancing stage from 50% in stage II to 25% in stage IV (Table 6).

As is evident from Table 7, 37 i.e. 50.7% of the patients in this series had good or fair quality of life as evaluated by symptom score. 89.1% (33 out of 37) of these patients had undergone surgery. Out of 26 patients who were offered only palliative therapy, 7 (26.9%) patients had bad quality of life with symptom score of more than 5, whereas 15 (57.6%) patients did not come for follow up. The 2 patients who died in early postoperative period were in stage IV of disease and were included as the patients with bad quality of life.

Discussion
Cancer of the head, face and neck is more common in Asians1 and is one of the commonest malignancies in India. Western literature reports median age at diagnosis as 63 years.2 But in our study, 60% of our patients had oral malignancy before the age of 60 and 15% of our patients were below 40 years of age. This early occurrence may be due to early exposure to tobacco. A study from Orissa observed maximum cases in 4th to 5th decade of life.3 Males dominated our series (66%) as well as others (75%).2 Over 75% of HFN malignancies are associated with smoking and drinking that cause 15-40 fold rise in relative risk.¹ In our study 88% of the patients had addictions and 86% of these were addicted to tobacco.

Eighty six per cent of the lesions were seen in oral cavity with Taneja reporting 65% of lesions in the oral cavity² and Parija observing 51.5% lesions in the buccal mucosa.³ In our study 65.7% of patients presented with an ulcer or exophytic growth and 13.7% presented with a neck swelling. While over 90% of all head and neck cancers are observed to be squamous cell carcinomas,¹ in our study 94% of the lesions were squamous cell carcinomas. 33% of the patients in our series had a well differentiated malignancy, but this grading has not been shown to be of relevant prognostic significance.¹

Literature has reported presentation in early stages (I and II)¹ in one third of the patients. But in our group of patients only 13.8% presented at an early stage. Taneja observed advanced regional disease in 43% and distant metastasis in 10% at presentation.² But we had a much larger number (86%) of patients in stage III and IV of the disease at the diagnosis. This difference has a direct impact on possible therapeutic intervention and outcome.

Surgery as the sole treatment modality will cure upto 90% of stage I patients.⁴ Hick et al found high survival rates with surgery as the only modality of treatment for cancers of the oral tongue.⁵ Tumour margins of 2 cm are considered to be adequate.¹ However since 86% of our patients were in stage III and stage IV, surgery as the sole treatment modality could be adopted in only 29.7% of the cases.

In our study 47 (64.3%) patients accepted surgery as the primary modality of treatment. Of these only 8 (17%) patients were considered suitable for surgical excision of primary alone. In all others this had to be combined with one or other type of neck node dissection. The size of the defect demanded flap reconstruction in 27 (57.5%) patients. Four out of the twenty five pedicled flaps in our study showed evidence of failure. Free flaps were performed in 2 patients as a primary method of reconstruction in our study.

Seventy per cent (70.3%) of patients undergoing surgery, required postoperative adjuvant therapy in the form of radiation, chemotherapy or both due to either multiple positive lymph nodes, extracapsular spread, perineural, lymphatic or vascular invasion or positive margins. Eight patients out of forty seven subjected to surgery, were given preoperative induction chemotherapy aiming at better loco regional control. Postoperative chemotherapy was administered to 25 patients while 14 patients received postoperative chemoradiation. Johnston et al6 observed 30 month overall survival of 58% with post operative chemoradiation, 40% with surgery and radiation alone as compared to 17% in patients subjected to surgery only.

The rest 26 patients were provided palliative therapy, the reasons being inoperability (20) and refusal of surgery (6). Most of the stage IV patients (61.3%) could only be offered palliation.

In our study, the overall survival rate was 59.5% with mortality due to disease being 21.2%. This is comparable with Bensadoun’s study with 54% overall survival at 2 years.⁷ The overall survival rate in Stage III and Stage IV was 61.5% and 50% respectively. A retrospective review conducted by the University Medical Centre, St Louis, Mo, USA demonstrated a 5-year survival rate of 38%, which decreased from 67% in stage I to 31% in stage III, and 32% in stage IV.⁸ Patients with positive surgical margins are at high risk of loco regional failure and death from disease.⁹

In this study, disease free survival was 40.4% with recurrences occurring in 36.1% cases. This higher rate of recurrence can be attributed to advanced stage of disease at diagnosis. Nair et al10 identified regional lymph node involvement, histological type and intra oral site of lesion as independent predictors of response. Gleich11 concluded that age and N stage were the most important predictors of survival. Patients subjected to surgery showed better survival compared to only radiation group.¹¹ Taneja reported increased incidence of distant failure as the first event as loco regional control improved with overall survival of 42% at 5 years.² The reported cure rate for Stage III cancers from 10 to 65% as compared to 52 to 100% for patients with Stage I and II.²

Quality of life (QOL) in patients with HFN cancers depends upon the anatomical location of the disease, morbidity associated with the modalities of treatment and its side effects and the type of reconstructive procedures.¹² Its assessment is difficult and several model questionnaires like FACT, RAND-36 and SF-36 have been utilized to study this. Without a theoretical model, the outcome of research on this multidimensional construct depends on the assumptions made by the researchers, and the assessment tools used.¹² Patients undergoing composite resection will develop large defects in the face area. Even after reconstruction, patient may not be rehabilitated well enough as regards to speech and swallowing. In view of the above factors, we have evaluated the symptom score in our patients based on the following factors : pain, disfigurement, restriction of activity, recreation, chewing, swallowing, speech disability. Forty nine patients were available for evaluation of symptom score at 2 years after diagnosis. Fifty one per cent (37) of patients had good to fair score. Eighty nine per cent (33) of these had undergone surgical treatment. Seven of the twenty six patients who were offered only palliative therapy had bad symptom score while fifteen patients from this group failed to follow up.

Fifteen (57.7%) of twenty six patients who had been offered palliative therapy failed to follow up. Despite attempts at establishing contact using various methods of communication, these patients could not be retrieved. The reasons can be several - change of address, illiteracy, resource crunch making travel to hospital impossible. Considering the advanced stage of disease in these patients, possibility of death or physical inability to report for follow up cannot be overlooked. 38 out of 47 patients (81%) subjected to surgery completed the follow up period of 2 years. The difference in follow up compliance in operated and palliated group suggests that use of surgery as the treatment modality results in better post operative symptom score and better follow up.

Conclusions

• HFN cancer was observed to occur at younger age in Indians with male preponderance.
• Tobacco consumption was once again confirmed as the single most aetiological factor.
• Majority of the patients reported with a minimum delay of 2 months and in advanced stage.
• Due to advanced stage at diagnosis, surgery could not be offered to 20 (27.4%) patients, thus eliminating the best therapeutic choice. In those subjected to surgery, reconstruction was required in 27 (57.5%) patients, which consequently increased the morbidity and affected the quality of life adversely. Surgery at advanced stage was seen to be associated with high incidence of local recurrence, again affecting the QOL and survival adversely.
• Due to advanced stage at presentation, adjuvant therapy had to be administered to 33 (70.3%) patients. This not only prolonged the duration and the cost of therapy, but also had adverse effect on QOL.
• The best symptom score was obtained in patients subjected to surgery. Those receiving palliation had the worst symptom score and very poor follow up.
  

This study underscores the deleterious impact of advanced stage at diagnosis of HFN malignancy, on treatment decision and outcome. Delay in seeking treatment impose elimination of the best therapeutic option, makes adjuvant therapy mandatory and in some, palliation may be the only recourse. The QOL and survival probability is directly dependent on the stage at presentation. Constant and continued efforts to create awareness about positive impact of early diagnosis along with carcinogenic potential of tobacco are urgently warranted. Training of health care personnel and creation of comprehensive facilities more easily accessible to the population also needs to be addressed to.

Occurrence of malignancy at early age needs to be studied from genetic predisposition angle. Search also deserves to be directed towards the molecular specifics of the tumour, in view of progress to advanced stage.

Acknowledgement

• Dr. ME Yeolekar, Dean, LTMGH and LTMMC, Sion, Mumbai.
• Department of Plastic Surgery, LTMGH and LTMMC, Sion, Mumbai.
• Dr. HL Dhusia Department of Dentistry, LTMGH and LTMMC.
• Department of Oral Diagnosis, Government Dental College, Mumbai.

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