Effects of postoperative chemotherapy and radiotherapy on patients with squamous cell carcinoma of the oral cavity and multiple regional lymph node metastases

Abstract

Nodal metastasis in oral squamous cell carcinoma (OSCC) is considered to be a predictor of a poor prognosis. The aim of this study was to investigate the relationship between the number of positive lymph nodes and the prognosis in OSCC patients with nodal metastases and to assess the effects of postoperative radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) on this patient group. A retrospective investigation of 98 patients with OSCC who underwent radical neck dissection and had at least three pathologically positive lymph nodes was performed. The 5-year disease-specific survival rate was 66.7% for patients with 3 positive nodes, while it was significantly lower for those with 4 positive nodes and those with ≥5 positive nodes (21.5% and 46.1%, respectively; P < 0.01). The loco-regional control and disease-specific survival rates for the surgery alone, surgery plus RT, and surgery plus CCRT groups were 46.2% and 40.5%, 66.3% and 54.4%, and 81.7% and 52.4%, respectively. For patients with ≥4 positive nodes, the loco-regional control rate after surgery plus CCRT was better than that observed after surgery alone (77.5% vs. 32.6%, P = 0.01). Postoperative RT and CCRT have positive impacts on the prognosis of OSCC patients with advanced stage neck disease.

Introduction

The local control rate of oral squamous cell carcinoma (OSCC) has recently improved due to the development of various treatment modalities, but patients who suffer regional or distant metastasis still have a poor prognosis. Many authors have reported that nodal involvement is one of the most significant prognostic factors in OSCC and that patients with multiple lymph node metastases have an extremely poor prognosis. Radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) is recommended as a postoperative adjuvant therapy for head and neck squamous cell carcinoma (HNSCC) patients with nodal metastasis. However, the effects of such adjuvant therapies on OSCC are still unclear because of the relatively small number of patients examined in previous studies. Only a few studies of OSCC have examined the number of positive lymph nodes as a prognostic factor, and the optimum threshold number of positive nodes for determining the indications for adjuvant therapy is disputed. Furthermore, the use of postoperative RT or CCRT is associated with various adverse events and a reduction in the treatment options for recurrence. Hence, there are no agreed criteria for the use of postoperative adjuvant therapy.

The aim of this retrospective study was to investigate the relationship between the number of positive lymph nodes and the prognosis in OSCC patients with nodal metastasis, and to assess the effects of postoperative RT and CCRT on this patient group.

Materials and methods

A retrospective investigation of 98 OSCC patients who underwent modified radical neck dissection (levels I–V) at any of five participating hospitals between 2001 and 2010, and who had at least 3 pathologically positive lymph nodes, was performed. In most patients, the internal jugular vein and spinal accessory nerve were preserved, but the sternocleidomastoid muscle was resected. The timing of neck dissection was categorized as follows: immediate neck dissection; i.e., dissection was performed as an initial therapy during the resectioning of the primary tumor; secondary neck dissection, which was performed in patients who were initially staged as N0 but progressed to N+ during the observation period; and neck dissection with local recurrence; i.e., patients who were initially staged as N0, but subsequently developed nodal metastasis and local recurrence. Some patients underwent postoperative RT (total 60–70 Gy) or CCRT (RT plus 70–100 mg/m 2 of cisplatin, 60 mg/m 2 of docetaxel, or any dose of 5-fluorouracil) ( Fig. 1 ). No indications or regimen for RT or CCRT were established, therefore the decision to use such therapies was made by each institution. The major inclusion criteria were advanced clinical stage, multiple cervical metastases, extranodular invasion (ENI), or a positive resection margin. The major exclusion criteria were old age, a past history of renal failure and hepatitis, and poor performance status. Most patients were examined each month and underwent computed tomography, magnetic resonance imaging, or ultrasonography every 3 months to check their postoperative status.

Fig. 1
Chemotherapy regimen and radiotherapy dose (Gy).

The major variables evaluated were clinical and pathological T stage, N stage, the number of pathologically positive lymph nodes, ENI, and the type of treatment received (surgery alone (including postoperative chemotherapy alone), postoperative RT, or postoperative CCRT). The major endpoints evaluated included the disease-free survival rate, loco-regional control rate, and type of recurrence. The Kaplan–Meier method was used to draw survival and loco-regional control curves. Statistical analyses were performed with the log rank test and Fisher’s exact test. A multivariate analysis aimed at elucidating prognostic factors for OSCC was performed using Cox regression analysis.

Materials and methods

A retrospective investigation of 98 OSCC patients who underwent modified radical neck dissection (levels I–V) at any of five participating hospitals between 2001 and 2010, and who had at least 3 pathologically positive lymph nodes, was performed. In most patients, the internal jugular vein and spinal accessory nerve were preserved, but the sternocleidomastoid muscle was resected. The timing of neck dissection was categorized as follows: immediate neck dissection; i.e., dissection was performed as an initial therapy during the resectioning of the primary tumor; secondary neck dissection, which was performed in patients who were initially staged as N0 but progressed to N+ during the observation period; and neck dissection with local recurrence; i.e., patients who were initially staged as N0, but subsequently developed nodal metastasis and local recurrence. Some patients underwent postoperative RT (total 60–70 Gy) or CCRT (RT plus 70–100 mg/m 2 of cisplatin, 60 mg/m 2 of docetaxel, or any dose of 5-fluorouracil) ( Fig. 1 ). No indications or regimen for RT or CCRT were established, therefore the decision to use such therapies was made by each institution. The major inclusion criteria were advanced clinical stage, multiple cervical metastases, extranodular invasion (ENI), or a positive resection margin. The major exclusion criteria were old age, a past history of renal failure and hepatitis, and poor performance status. Most patients were examined each month and underwent computed tomography, magnetic resonance imaging, or ultrasonography every 3 months to check their postoperative status.

Fig. 1
Chemotherapy regimen and radiotherapy dose (Gy).

The major variables evaluated were clinical and pathological T stage, N stage, the number of pathologically positive lymph nodes, ENI, and the type of treatment received (surgery alone (including postoperative chemotherapy alone), postoperative RT, or postoperative CCRT). The major endpoints evaluated included the disease-free survival rate, loco-regional control rate, and type of recurrence. The Kaplan–Meier method was used to draw survival and loco-regional control curves. Statistical analyses were performed with the log rank test and Fisher’s exact test. A multivariate analysis aimed at elucidating prognostic factors for OSCC was performed using Cox regression analysis.

Results

Clinical and histological findings in the patients who underwent neck dissection

Ninety-eight patients were included in this retrospective study. The clinical and pathological characteristics of the patients are summarized in Table 1 . There was a male predominance, and the mean age of the patients was 65.4 years. The most common primary site was the tongue, followed by the lower gingiva, upper gingiva, buccal mucosa, and floor of the mouth. Almost half of the patients (45.9%) had T2 tumors, while T1, T3, and T4 tumors were seen in 14.3%, 16.3%, and 23.5% of patients, respectively. The clinical N stage at initial therapy was N0 in 40 patients, N1 in 10, N2b in 27, N2c in 20, and N3 in 1. Regarding neck dissection, an immediate dissection was performed in 65 patients, secondary dissection was carried out in 29 patients, and dissection with local recurrence was performed in four patients. Thirty-eight patients had 3 pathologically positive nodes, 21 had 4 pathologically positive nodes, and 39 had ≥5 pathologically positive nodes. ENI was present in almost half (48.0%) of the patients. The median follow-up period was 19 months (range 2–143 months).

Table 1
Clinical and pathological characteristics of the patients.
Characteristics n (%)
Age, mean (range) 65.4 (27–88) years
Sex
Male 64 (65.3%)
Female 34 (34.7%)
Tumor site
Tongue 52 (53.1%)
Lower gingiva 16 (16.3%)
Upper gingiva 15 (15.3%)
Buccal mucosa 6 (6.1%)
Floor of the mouth 6 (6.1%)
Other 3 (3.1%)
T
1 14 (14.3%)
2 45 (45.9%)
3 16 (16.3%)
4 23 (23.5%)
N
0 40 (40.8%)
1 10 (10.2%)
2 47 (48.0%)
3 1 (1.0%)
Time of neck dissection
Immediate 65 (66.3%)
Secondary 29 (29.6%)
With local recurrence 4 (4.1%)
No. of pathologically positive nodes
3 38 (38.8%)
4 21 (21.4%)
≥5 39 (39.8%)
Extranodular invasion
No 51 (52.0%)
Yes 47 (48.0%)
Follow-up interval, median (range) 19 (2–143) months
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Jan 19, 2018 | Posted by in Oral and Maxillofacial Surgery | Comments Off on Effects of postoperative chemotherapy and radiotherapy on patients with squamous cell carcinoma of the oral cavity and multiple regional lymph node metastases
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