Results of a prospective trial on elective modified radical classical versus supraomohyoid neck dissection in the management of oral squamous carcinoma. Brazilian Head and Neck Cancer Study Group. Elective versus therapeutic radical neck dissection in epidermoid carcinoma of the oral cavity: results of a randomized clinical trial. Prospective randomized study of selective neck dissection versus observation for N0 neck of early tongue carcinoma. Prophylactic neck dissection in squamous cell carcinoma of oral tongue: a prospective randomized study. Supraomohyoid neck dissection in the treatment of T1/T2 squamous cell carcinoma of oral cavity. A randomised multicentre trial of CHART versus conventional radiotherapy in head and neck cancer. [Results of a prospective randomized trial with induction chemotherapy for cancer of the oral cavity and tonsils]. A randomised trial of accelerated versus conventional radiotherapy in head and neck cancer. Concomitant methotrexate and radiotherapy in advanced head and neck cancer: 15-year follow-up of a randomized clinical trial.
Elective treatment of the neck in oral squamous cell carcinoma has changed over the last 20 years. The main object of this report is to present the results of a multi-institutional prospective study designed to compare standard treatment with modified radical classical neck dissection (MRND) to supraomohyoid neck dissection (SOH) in the management of the clinically negative neck in oral cancer patients.
                A total of 148 patients were included in the trial. All patients had previously untreated T2 to T4 N0 squamous cell carcinoma of the oral tongue (62 cases), floor of the mouth (49 cases), inferior gingiva (12 cases), or retromolar trigone (25 cases). Tumor stages were T2, 91; T3, 27; and T4, 30. There were no significant imbalances between groups.
                The false-negative rate was 28%, and most positive nodes were sited at level II and III. Complications were seen in 41% of MRND patients and in 25% of SOH patients (P = 0.043). Median total duration of hospitalization was 9 days in MRND patients and 7 days in the SOH group. To date, 19 and 16 patients presented with local and neck recurrences, respectively. The 60-month actuarial survival rates were 63% in the MRND group and 67% in the SOH group (P = 0.7150).
                This study demonstrates that the recurrence and survival rates were similar in both groups. SOH neck dissection can be recommended as standard elective treatment for patients with T2-T4 oral squamous cell carcinomas. This study concerns 75 patients with squamous cell carcinoma of the oral cavity who were patients at the Gustave-Roussy Institute between December 1966 and July 1973. These patients were divided into two groups. The first group was comprised of 39 patients who underwent elective radical neck dissection; nodal involvement was present in 49% with capsular rupture in 13%. In the second group of 36, neck disease appeared during follow up in 19 cases. Therapeutic radical neck dissection was carried out in 17; the nodes were histologically positive in 15, 9 of which had a capsular rupture. In 2 cases, local or general conditions did not permit operative intervention. In this group, the involvement rate was 47% with a 25% capsular rupture rate. However, the comparison of the survival curves by the log-rank test did not reveal any differences, even though histologic prognostic factors were taken into account. These findings led to the conclusion that in squamous cell carcinoma of the oral cavity staged T1N0, T2N0, or T3N0 (from AJC's and UICC's clinical staging system), it seems possible, without risk, to delay neck dissection until a node is detectable, although it is reasonable to perform elective neck dissection in those cases in which the patient is unavailable for regular followup. There are controversies on the benefits of elective neck dissection (END) for oral tongue carcinoma.
                This is a prospective randomized study of elective selective I, II, III neck dissection versus observation for N0 neck of stage I to II oral tongue carcinoma. There were 35 patients on the observation arm and 36 patients on the END arm. The main outcome assessment parameters are node-related mortality and disease-specific survival rate.
                There were 11 patients in the observed arm and 2 patients in the END arm who developed nodal recurrence alone without associated local or distant recurrence. All 13 patients were salvaged, and no patient died of nodal recurrence. The 5-year disease-specific survival rate was 87% for the observation arm and was 89% for the END arm; the 2% difference was not significant.
                Observation may be an acceptable alternative to END if strict adherence to a cancer surveillance protocol is followed.
                (c) 2009 Wiley Periodicals, Inc. This paper presents the first report of an ongoing prospective randomised clinical trial in early T1T2N0 carcinoma of the oral tongue. The problems of regular follow-up in an indigent population from the vast rural expanse of India has been successfully overcome in this trial by close personal follow-up. The trial addresses itself specifically to prophylactic vs. therapeutic surgical management of the neck in T1T2N0 patients with cancer of the oral tongue. Overall disease, free survival (median follow-up 22 months) is higher (64% vs. 47%) in the group receiving prophylactic neck dissection. Disease-free survival for those with positive nodes at prophylactic neck dissection was twice that of those who underwent a subsequent therapeutic neck dissection (57% vs. 28%). Contralateral neck node metastasis has been identified as a significant factor in neck failures in those patients undergoing simultaneous prophylactic neck dissection. Recent studies in patients with previously untreated T1 and T2 squamous cell carcinoma (SCC) of the tongue and floor of the mouth have shown a relationship between tumor thickness, neck metastasis, and survival. Our study was conducted to determine the indication of elective neck dissection in patients with early oral cavity SCC.
                Sixty-seven patients were stratified by stage (T1 and T2 NO), and those in each stage were randomized to receive one of two types of treatment; resection alone (RA) or resection plus elective supraomohyoid neck dissection (RSOND). Fifty-two patients (78%) were men and 15 (22%) were women. The median age was 57 years old (range 34 to 95).
                Twenty-six (39%) patients had tumor in the floor of the mouth and 41 (61%), in the tongue. Using the criteria of the Union Internationale Contre le Cancer (UICC), 1987, we classified 31 tumors (46%) as T1 lesions and 36 (54%) as T2 lesions. Thirty patients had a tumor thickness < or = 4 mm and 37 had a tumor thickness > 4 mm. Thirty-three (49%) patients were treated with RA, and 34 patients (51%) were treated with RSOND. Seven (21%) patients of the RSOND group had occult cervical metastasis. There were recurrences in 14 (42%) patients of the RA group and 8 (24%) patients of the RSOND group. The disease-free survival rates at 3.5 years for RA and RSOND patients were 49%, and 72%, respectively. The impact of sex, age, site, cancer stage, and tumor thickness was assessed by the Mantel-Haenszel chi-square procedure. Later stage (P = 0.05) and increased tumor thickness (P = 0.005) were significantly associated with treatment failures.
                Neck dissection remains mandatory in the early stage of oral SCC, because of better survival rates compared to RA and the poor salvage rate. In particular, patients with tumor thickness > 4 mm treated with RSOND had significant benefit on disease-free survival. Continuous, hyperfractionated, accelerated radiotherapy (CHART) has shown promise of improved tumour control and reduced late morbidity in pilot studies and has now been tested in a multicentre randomised controlled clinical trial.
                Patients with squamous cell cancer in the main sites within the head and neck region with the general exception of early T1 N0 tumours were entered into the study by 11 centres. There was a 3:2 randomisation to either CHART, where a dose of 54 Gy was given in 36 fractions over 12 days, or to conventional therapy where 66 Gy was given in 33 fractions over 6.5 weeks. A total of 918 patients were included over a 5 year period from March 1990.
                ACUTE MORBIDITY: Acute radiation mucositis was more severe with CHART, occurred earlier but settled sooner and was in nearly all cases healed by 8 weeks in both arms. Skin reactions were less severe and settled more quickly in the CHART treated patients. TUMOUR CONTROL AND SURVIVAL: Life table analyses of loco-regional control, primary tumour control, nodal control, disease-free interval, freedom from metastasis and survival showed no evidence of differences between the two arms. In exploratory subgroup analyses there was evidence of a greater response to CHART in younger patients (P = 0.041) and poorly differentiated tumours appeared to fare better with conventional radiotherapy (P = 0.030). In the larynx there was evidence of a trend towards increasing benefit with more advanced T stage (P = 0.002). LATE TREATMENT RELATED MORBIDITY: Osteoradionecrosis occurred in 0.4% of patients after CHART and 1.4% of patients after conventional radiotherapy. The incidence of chondritis or cartilage necrosis was similar in both arms. Life table analysis showed evidence of reduced severity in a number of late morbidities in favour of CHART. These were most striking for skin telangiectasia, superficial and deep ulceration of the mucosa and laryngeal oedema.
                Similar local turnout control was achieved by CHART as compared with conventional radiotherapy despite the reduction in total dose from 66 to 54 Gy supporting the importance of repopulation as a cause of radiation failure. The effects seen in advanced laryngeal cancer and those related to histological differentiation need further study. Reduced late morbidity is a factor which together with patient preference should be considered in the decision as to the programme of radiotherapy to employ in the curative treatment of head and neck cancer. Although induction chemotherapy administered prior to local therapy produces encouraging initial response rates in head and neck cancer, randomized studies have failed to demonstrate an improvement in survival rates. All randomized studies included only patients with advanced stage III and IV disease. In our opinion, this is the main reason for the low rate of complete responses demonstrated in the randomized trials (maximum 18%). Frei et al. estimate that a 40%-50% complete response rate is necessary before improved survival rates are seen. To date, such complete response rates with induction chemotherapy have only been attainable in resectable T2-T3, N0-N2 disease. Therefore, we initiated a prospective randomized trial including only patients with the mentioned disease stages. Patients (pts) were randomized to receive either induction chemotherapy with three cycles of carboplatin/5-FU prior to surgery and radiotherapy (arm A, 70 pts) or standard treatment with surgery and radiotherapy (arm B, 74 pts). Patients were classified according to primary tumour site and neck disease. The observed remission rate after chemotherapy confirmed the primary estimated rate for this subgroup of patients with head and neck cancer (CR: 43%, PR: 37%, NR: 15%, PD: 5%). After a follow-up of 12-96 months overall survival was 58% in arm A and 45% in arm B (n.s.). Disease-free survival in arm A (61%) is statistically significantly better than in arm B (43%, P=0. 03). Therefore, we recommend further controlled trials to investigate the role of induction chemotherapy in patients with primary resectable carcinomas of the oral cavity and tonsils and stage T2-T3 and N0-N2 disease prior to surgery. To study the effect of accelerated radiation treatment in locally advanced head and neck cancer, a prospective randomised trial was conducted comparing two fractionation schemes which differed only in the overall treatment time; fraction size and total dose were the same in both arms.
                Eighty-two patients with stage 3 or 4 squamous cell cancer of the oral cavity, oropharynx, hypopharynx or larynx considered suitable for radical radiotherapy as primary treatment were stratified by site and stage and randomised to receive 66 Gy in 33 2 Gy daily fractions in 45-48 days (o.d.) or 66 Gy in 33 2 Gy twice daily fractions in 22-25 days (b.i.d.).
                An initial improved clinical response in tumour control in the b.i.d. arm was not sustained and the 3 year recurrence free survival and overall survival rates were similar and not significantly different. The actuarial recurrence free survival was 49.1% in the b.i.d. arm and 44.3% in the o.d. arm. The disease free 3 year survival was 59.4% and 56.8%, respectively. The acute and late normal tissue effects were scored using the RTOG scale. As expected the acute effects were much greater in the b.i.d. arm. The combined grade 3 and 4 late effects were similar but the proportion of grade 4 reactions was significantly higher in the b.i.d. arm. The increase in grade 4 toxicity caused the trial to be discontinued after 82 of the planned 226 patients had been randomised.
                The severity of the normal tissue effects and a failure to demonstrate sustained local control does not support this fractionation scheme in patients with such extensive head and neck cancer. Long-term follow-up for patients who receive chemoradiation for head and neck cancer is lacking from most studies reported in the literature. This report gives a 15-year review of the use of concomitant methotrexate and radiation in advanced head and neck cancer. Although there has not been any significant benefit in overall survival, the primary control rate is higher in patients who received methotrexate in addition to radiotherapy. However, in those with oropharyngeal cancer, both primary control and survival were significantly improved when chemotherapy was used. The other most significant benefit from chemoradiation is the much lower rate of salvage operations for primary recurrence. The addition of methotrexate failed to show any effect on the development of metastatic neck nodes. The rate of block dissection of the neck was similar in both arms of the study and is comparable with the historical data collected at this institute. There has not been any significant increase in serious late morbidity. The timing of the methotrexate with radiotherapy has a significant influence on primary control and survival in head and neck cancer.
Seven included trials evaluated neck dissection surgery in patients with oral cavity cancers. The review found weak evidence that elective neck dissection of clinically negative neck nodes at the time of removal of the primary tumour results in reduced locoregional recurrence, but there is insufficient evidence to conclude that elective neck dissection increases overall survival or disease free survival compared to therapeutic neck dissection. There is very weak evidence from one trial that elective supraomohyoid neck dissection may be associated with increased overall and disease free survival. There is no evidence that radical neck dissection increases overall survival compared to conservative neck dissection surgery. Reporting of adverse events in all trials was poor and it was not possible to compare the quality of life of patients undergoing different surgeries.