Abstract
This retrospective non-randomized 10-year follow-up study compared 147 patients with squamous cell carcinoma (SCC) of the oral cavity requiring hemimandibulectomy, treated by surgical resection, therapeutic neck dissection and radiotherapy. The 5-year survival rates were compared related to localization, size of the tumour, infiltration of locoregional lymph nodes, distant metastases, histopathological grading, radicality of surgery, and invasion of tumour into the mandible. Occurrence of tumour relapse and its localization was studied. The mean 5-year survival rate was 26%. Patients with SCC of the mandibular alveolar process had higher rates; the lowest rates occurred in SCC of the buccal mucosa. Survival rate was significantly lower with insufficient resection of the tumour (85% relapse). An important number of patients with radical resection died within 3 months of surgery. In almost 55% of the mandibles tumour was not present. In 5% of infiltrated mandibles, dissemination into inferior alveolar nerve was proven. Decreasing survival rate was seen with increasing size of tumour and higher histological grade. Therapeutic neck dissection significantly reduces survival rate and increases the percentage of lymph node relapse. Elective neck dissection should be performed in SCC requiring hemimandibulectomy. Primary reconstruction should reverse the high percentage of postoperative complication arising from increased radicality.
Squamous cell carcinoma (SCC) is the most frequent malignant tumour of the oral cavity. It develops in all parts of the oral cavity; the high-risk areas include the floor of the mouth, posterolateral margin and base of the tongue. SCC presents with a solitary chronic, red or white lesion, indurated lump, fissure, non-healing ulcer, pain, bleeding, tongue fixation, dysphagia, paresthesia or enlarged cervical lymph node . Smoking, alcohol, dietary factors, low social status and poor hygiene contribute significantly to the prevalence of the disease .
The treatment of oral SCC, if operable, is primary surgical resection or radiotherapy, mainly in stage III and IV disease . Combination treatment is the most successful (i.e. the surgical resection of the tumour together with at least a 1-cm margin of clinically normal tissue, followed by radiotherapy) . Post-surgical combined radiotherapy and chemotherapy increases the overall survival rate, but it is associated with a substantial increase in adverse effects, including severe mucositis and osteoradionecrosis .
For the prognosis of SCC, the presence or absence of cervical node metastasis is crucial. Once the tumour involves neck nodes, survival drops by almost 50% . The removal of cervical lymph nodes is performed when lymph node metastasis is not clinically discoverable (elective neck dissection) or in case of verified lymph node metastasis (therapeutic, non-elective, neck dissection). The types of neck dissection are radical (comprehensive), modified (functional), extended or selective . In case of oral SCC attached to the mandible, a unilateral, elective, modified supraomohyoid neck dissection is recommended .
Whether to perform a resection of the mandible is questionable in patients with mandible-attached SCC. It has been shown that insufficiently radical surgery significantly decreases the overall survival of patients with SCC , but too extensive surgery, involving the resection of the mandible, negatively influences the patient’s quality of life .
The aim of this study is to evaluate critically the therapeutic potential of the combination of hemimandibulectomy, therapeutic neck dissection and subsequent locoregional radiotherapy in the treatment of SCC at different locations in the oral cavity, either attached to or invading mandible. To achieve this, the authors undertook a 10-year non-randomized, non-controlled retrospective study of 147 patients.
Materials and methods
185 patients underwent hemimandibulectomy for the diagnosis of malignant tumour in the authors’ department from 1994 to 2004 ( Fig. 1 ). Of these, 147 patients were enrolled into the study. Enrolment criteria were: histologically verified and graded SCC of the oral cavity, attached to and/or suspected or visibly displaying invasion into the mandible; the ability to obtain complete preoperative and postoperative documentation; surgical tumour resection with hemimandibulectomy, followed by therapeutic neck dissection in case of tumour-positive neck lymph nodes; and subsequent radiotherapy ( Table 1 ). Exclusion criteria were: previous or concomitant malignant tumour at any location; subsequent reconstructive surgery; and the known presence of distant metastases.
| Procedure |
| Medical history |
| Clinical examination |
| X-ray, CT, bone scan |
| Biopsy |
| Tumour resection |
| Supraomohyoid lymph node dissection |
| Neck dissection in cases with involved lymph nodes |
| Radiotherapy |
The whole primary tumour was removed, together with the attached part of the mandible. The minimum range of the hemimandibulectomy was from the mental foramen to the mandibular lingula, to prevent possible perineural dissemination into the inferior alveolar nerve region. In all patients, the removal of lymph nodes from the submandibular space (i.e. selective level I suprahyoid neck dissection) was performed.
When the diagnostic methods or clinical examination indicated metastatic involvement of cervical lymph nodes, therapeutic selective (levels I, II, III, and if positive, then also IV and V) neck dissection was performed.
After surgery, all patients underwent securing locoregional radiotherapy with Cobalt 60 External Radiator (Theratron 1000) of 60 Gy (2 Gy/day, 5 days a week) at least 3 weeks after wound healing.
The main goal of the study was to evaluate the survival rate and its dependence on the criteria listed in Table 2 . The localization of the primary tumour was divided into six categories ( Table 3 ).
| 1. | Overall survival rate |
| 2. | Localization of the primary tumour |
| 3. | Size of the primary tumour |
| 4. | Infiltration of locoregional lymph nodes |
| 5. | Occurrence of distant metastases |
| 6. | Histopathological grading |
| 7. | Radicality of the removal of the primary tumour |
| 8. | Positivity of invasion of the tumour into mandible |
| 9. | Tumour relapse |
| 1. | Anterior mouth floor and inferior part of tongue |
| 2. | Tongue margin and lateral floor of mouth |
| 3. | Base of the tongue |
| 4. | Tumour of the retromolar region |
| 5. | Tumour of the buccal mucosa |
| 6. | Mucosa of the mandibular alveolar process |
The overall survival of the patients enrolled in the study was described using the Kaplan–Meier method . The differences between particular groups were compared using log-rank tests. All groups were compared together, then compared by pairs. The statistical significance was stated as P < 0.05. Mean estimated survival time (in months) for each group and median estimated survival times that show the time (in months) in which 50% of patients will probably live were determined.
Results
One hundred and eighty-five hemimandibulectomies were carried out during the 10-year period. The study cohort included 147 hemimandibulectomies, performed for SCC. Of the 147 patients enrolled in study, 115 were males (mean age 57.9 years, range 42–79 years), 32 were females (mean age 64.7 years, range 39–88 years). 78% of patients were males. The mean age of all patients was 59.4 years (range 39–88 years).
Overall survival rate
Fifty percent of deaths occurred within the first 2 years of surgery, the rest occurred within the next 3 years ( Fig. 2 ).
Survival rate and tumour localization
The most frequent localization of SCC requiring hemimandibulectomy was on the anterior mouth floor and inferior part of the tongue, followed by the tumour of the tongue margin and lateral floor of the mouth, together comprising 62% of cases ( Table 4 ).
| Localization | Number of patients | Survival rate | Mean survival (months) | Median survival |
|---|---|---|---|---|
| Anterior mouth floor | 47 (32.0%) | 31% | 47.0 ± 6.4 | 34.0 ± 10.4 |
| Tongue margin | 44 (29.9%) | 20.6% | 37.2 ± 5.9 | 24.0 ± 6.4 |
| Base of tongue | 13 (8.8%) | 26.9 | 37.1 ± 11.7 | 17.0 ± 1.5 |
| Retromolar region | 10 (6.8%) | 17.1% | 43.1 ± 12.0 | 43.0 ± 15.9 |
| Buccal mucosa | 16 (10.9%) | 0% * | 25.0 ± 5.0 | 19.0 ± 8.7 |
| Alveolar mucosa | 17 (11.6%) | 57.8% * | 63.5 ± 12.1 | >60 |
| Total | 147 (100.0%) | 26% | 43.1 ± 3.6 | 24.0 ± 6.0 |
The highest survival rate was found in tumours of the alveolar mucosa and reached almost 58% (out of 17 patients). In nine patients (53%) with tumour of the alveolar mucosa, the surgical margin was negative, in three patients (18%) the tumour was close to the margin and positive in four patients (24%). Ten of these patients were pN0 (59%), five patients were pN1 (29%) and one patient was pN2 (6%).
The lowest survival rate was present in SCC of the buccal mucosa; none of 16 patients with this localization survived 5 years. In 13 patients (81%) with tumour of the alveolar mucosa, the surgical margin was negative, in 3 patients (19%) the tumour was close to the margin. In none of these patients, the surgical margin was positive. Seven of these patients were pN0 (44%), six patients were pN1 (38%) and three patients were pN2 (19%).
The size of the tumour in both groups (pT) was almost the same ( Table 5 ). Patients with buccal mucosa cancer had worse histopathological grades ( Table 6 ). The 5-year survival rate was significant only between SCC of the buccal mucosa and SCC of the mandibular alveolar process mucosa ( P = 0.026). Differences between other groups were not significant ( Table 4 ).
| Localization | pTis | pT1 | pT2 | pT3 | pT4 | Together |
|---|---|---|---|---|---|---|
| Buccal mucosa | 0 (0%) | 2 (12%) | 6 (38%) | 5 (31%) | 3 (19%) | 16 (100%) |
| Alveolar mucosa | 1 (6%) | 2 (12%) | 7 (41%) | 3 (18%) | 4 (23%) | 17 (100%) |
| Localization | G1 | G2 | G3 | Together |
|---|---|---|---|---|
| Buccal mucosa | 7 (44%) | 9 (56%) | 0 (0%) | 16 |
| Alveolar mucosa | 12 (70%) | 4 (24%) | 1 (6%) | 17 |
Five-year survival rate and tumour staging
Of all patients enrolled in the study the highest number had pT2 tumour (33%), followed by pT4 in almost 27% of patients and pT3 in almost 25% of patients. All patients with pTis and pT1 comprised no more than 16% together. All four patients with pTis were originally clinically evaluated as pT1 and the final diagnosis of pTis was made retrospectively. Most patients requiring hemimandibulectomy have advanced-stage tumour. The best survival rate was in the group of pTis patients with SCC; the worst in the pT4 group. The difference was more than 33%, but was not statistically significant ( Table 7 ).
| pT | Number of patients | Survival rate | Mean survival (months) | Median survival (months) |
|---|---|---|---|---|
| Is | 4 (2.7%) | 50.0% | 55.3 ± 24.0 | More than 60 |
| 1 | 19 (12.9%) | 30.9% | 47.7 ± 9.6 | 42.0 ± 15.4 |
| 2 | 49 (33.3%) | 29.6% | 41.0 ± 5.9 | 23.0 ± 9.7 |
| 3 | 36 (24.5%) | 26.7% | 43.7 ± 7.1 | 24.0 ± 4.5 |
| 4 | 39 (26.5%) | 16.5% | 37.3 ± 5.9 | 34.0 ± 12.5 |
| Total | 147 (100.0%) | 26% | 43.1 ± 3.6 | 24.0 ± 6.0 |
Five-year survival rate and infiltration of locoregional lymph nodes
Cervical lymph node infiltration was suspected clinically and/or by imaging methods in 73 patients (50%) and therefore therapeutic neck dissection was performed. In 13 of them (18%), histopathological findings in terms of locoregional metastasis were negative. Of 74 patients (50%) with clinically negative locoregional metastasis, 11 patients (15%) had histopathologically positive level I lymph nodes. Cervical lymph node metastases were present in more than 48% of patients enrolled in the study. Most positive lymph node metastases were staged as pN1, whereas a quarter of tumours with positive lymph nodes were staged as pN2. The highest 5-year survival was present in patients with pN0 as expected, followed by patients with pN2 (not by patients with pN1). The difference in the 5-year survival rate between pN0 and pN1 groups almost reached statistical significance ( P = 0.053) ( Table 8 ).
| pN | Number of patients | Survival rate | Mean survival (months) | Median survival (months) |
|---|---|---|---|---|
| 0 | 76 (51.7%) | 35.8% | 50.2 ± 5.7 | 38.0 ± 8.0 |
| 1 | 53 (36.1%) | 14.9% | 34.4 ± 4.7 | 23.0 ± 5.1 |
| 2 | 18 (12.2%) | 29.2% | 43.1 ± 9.0 | 23.0 ± 17.0 |
| Total | 147 (100.0%) | 26% | 43.1 ± 3.6 | 24.0 ± 6.0 |
Survival rate and occurrence of distant metastases
Distant metastases were present in more than 5% of patients and these were discovered only after surgical treatment, whereas in more than 90% of patients distant metastasis were not present during the entire follow-up period. In six patients (4%), the presence of distant metastases was not clear, so they were excluded from this comparison. More than 25% of patients without distant metastases (M0) and more than 21% of patients with distant metastases (M1) survived 5 years after surgery. No significant difference between these groups of patients was found ( Table 9 ).
| M | Number of patients | Survival rate | Mean survival (months) | Median survival (months) |
|---|---|---|---|---|
| 0 | 133 (90.5%) | 25.4% | 42.8 ± 3.7 | 24.0 ± 7.2 |
| 1 | 8 (5.4%) | 21.4% | 37.3 ± 9.0 | 4.0 ± 20.9 |
| MX | 6 (4.1%) | – | – | – |
| Total | 147 (100.0%) | 26% | 43.1 ± 3.6 | 24.0 ± 6.0 |
Five-year survival rate and histopathological grading
In more than 53% of patients, the primary tumour was histopathologically graded as Grade I, in more than 37% of patients as Grade II. Less than 9% of patients had Grade III. The 5-year survival rate was proportional to the level of grading; as expected patients with grade I tumours had the highest survival rate and patients with grade III tumours had the worst survival rate. The ratio between particular grades was almost 3:2:1, but the differences were not statistically significant ( Table 10 ).
| Grade | Number of patients | Survival rate | Mean survival (months) | Median survival (months) |
|---|---|---|---|---|
| 1 | 79 (53.7%) | 30.8% | 46.5 ± 4.9 | 25 ± 8.1 |
| 2 | 55 (37.4%) | 20.7% | 37.1 ± 5.4 | 23 ± 8.6 |
| 3 | 13 (8.8%) | 11.4% | 30.7 ± 7.4 | 17 ± 18.7 |
| Total | 147 (100.0%) | 26% | 43.1 ± 3.6 | 24.0 ± 6.0 |
Five-year survival rate and radicality of surgery
Radicality of resection was evaluated histopathologically as: negative (>5 mm from the margin); close to the margin (<5 mm); or positive (extending the margin of the tumour). In more than 70% of patients, the surgical margin was negative, in more than 10% it was close to the margin and in 19% it was positive. When marginal resection of the primary tumour was performed, almost 48% of patients survived 5 years, which was the highest survival rate in accordance with the radicality of the primary tumour excision. When the resection margin was negative, with the margin of the tissue completely clear of tumour infiltration, about 24% of patients survived 5 years. The lowest survival rate (about 18%) was present in patients with a positive margin. Statistical significance ( P = 0.04) was found between all groups. The authors found significant differences when the group with marginal resection was compared with either radical ( P = 0.024) or insufficient ( P = 0.006) excision, indicating that either exaggerated or decreased radicality of tumour resection significantly decreases the survival rate of patients with oral SCC ( Table 11 ).
