Neoadjuvant and adjuvant therapy in patients with oral squamous cell carcinoma: Long-term survival in a prospective, non-randomized study

doi:10.1016/j.bjoms.2007.08.006

British Journal of Oral and Maxillofacial Surgery

Volume 46, Issue 1, January 2008, Pages 1-5

https://doi.org/10.1016/j.bjoms.2007.08.006 Get rights and content

Abstract

Introduction

Recently new concepts for the treatment of oral squamous cell carcinomas (SCC) have been developed, which include preoperative simultaneous neoadjuvant radiochemotherapy (RCT) and one stage operation with excision of the tumour and reconstruction. When we consider long-term survival, we find substantial evidence that combined treatment based on neoadjuvant radiochemotherapy is superior to adjuvant treatment including operation and postoperative radiation.

Patients and methods

We studied two groups consisting of 74 patients given neoadjuvant treatment and 54 treated surgically. Ninety-nine patients suffered from stage III and IV diseases according to the UICC-criteria. Long-term survival was estimated by the Kaplan–Meier method.

Results

Neoadjuvant treatment increased the prospect of a long-term survival free of tumour. Kaplan–Meier curves estimated a 5-year tumour-free survival in oral squamous cell carcinoma category T1 as 83% in the neoadjuvant group and 70% in the adjuvant group; the corresponding figures for T2 were 79% and 57%, for T3 68% and 33% and for T4 51% and 30%, respectively. The difference for T1, T2 and T4 tumours were significant. The preoperative radio- and chemotherapy were shown to be effective by the fact that pathohistologically resection specimens were free of tumour in 28 patients in the neoadjuvant group. Four patients died during the preoperative combination treatment. Of the patients, 65% in the adjuvant group and 72% in the neoadjuvant group survived the observation period.

Conclusion

The neoadjuvant treatment results in better 5-year-survival rate than adjuvant treatment.

Introduction

Today the treatment of primary oral squamous cell carcinomas (SCC) includes various combinations of radiotherapy, chemotherapy and surgery.1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 The main goal of any kind of combined treatment in carcinomas of the oral cavity is to guarantee long tumour-free survival with as little loss of function as possible. Any mutilation of the patient should be avoided. As well as function, the aesthetic result of any treatment in this area must be acceptable.7, 8, 9, 11, 12, 13, 14 From the surgical point of view different strategies are possible: the choices include resection of the tumour after a preoperative course of radiotherapy or radiochemotherapy. Adjuvant treatment is the standard treatment based on resection followed by radiotherapy or radiochemotherapy. The extent of the resection can be influenced by the level of radiation and the treatments may be based on preoperative doses of radiation between 35 and 63 Gy.7, 9, 12, 14, 15, 16

In neoadjuvant treatment of oral SCC free flap and microvascular procedures are essential for the reconstruction after resection of the tumour.7, 9, 12, 14 For the treatment to be considered successful, the side effects should not reduce the quality of life of these patients more than necessary. This means that short-term and long-term effects such as the development of osteoradionecrosis (particularly in the mandible) must be considered when planning the treatment.¹⁴

The aim of this study was to discuss the 5-year survival rate in a neoadjuvant and an adjuvant combination treatment in patients with primary oral SCC. The data were gathered prospectively in a non-randomised study. It is not ethical to compare randomised, evidence-based results with standard treatment in patients with oral SCC.

Section snippets

Patients and methods

From January 1997 until March 2005, a total of 128 patients with primary SCC of the oral cavity that had not been treated previously were included in the study. Seventeen were female and 111 male. The mean age on admission to hospital was 58 years (range 33–77). Seventy-one patients had SCC of the floor of the mouth and 25 carcinoma of the tongue. In 32 patients, the alveolar process including the retromolar region of the mandible was affected (Table 1). Heavy smoking and alcohol misuse, which

Results

The cumulative survival rate for all T-categories was 72% for patients in the neoadjuvant group and 56% for those in the adjuvant group (Fig. 1). The survival rate was 83.1% for T1 tumours in the neoadjuvant group and 70.1% in the adjuvant group. In T2 tumours it was 79.6% for the neoadjuvant group and 57.7% for the adjuvant group. InT3 and T4 tumours the figures were 68.2% and 33.2%, and 51.4% and 30.5%, in favour of the neoadjuvant treatment. For the T-categories the results were confirmed by

Discussion

During the past 30 years relevant progress in the treatment of oral SCC has been achieved by introducing multidisciplinary treatment and by developing microvascular techniques for free flap reconstruction.7, 9 The combination of different treatments has the advantage that the effectiveness of each one can be limited to preserve as much function and cosmesis as possible.1, 10, 17 However, there are certain limitations: unfortunately patients with oral SCC are referred to the clinic with a poor

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An earlier prospective randomised multicentre study (ARTSCAN) in head and neck cancer patients that compared conventionally fractionated radiotherapy (CF) with accelerated radiotherapy (AF) was inconclusive. In the subgroup of oral cavity squamous cell cancer (OCSCC) a large absolute, but not statistically significant, difference in local control was seen in favour of AF. This difference was more pronounced in resectable tumours. The finding raised the hypothesis that AF could be beneficial for OCSCC patients. In addition, the longstanding controversy on pre- or postoperative radiotherapy was addressed.
Patients with OCSCC, judged to withstand and likely benefit from combined therapy, were recruited. Subjects were randomised to either preoperative AF with 43 fractions given as a concomitant boost with two fractions/day to the tumour bearing volume to a total dose of 68 Gy in 4.5 weeks followed by surgery, or primary surgery with postoperative CF, total dose 60 or 66 Gy in 6–7 weeks. For patients whose tumours had high-risk features, 66 Gy and concomitant cisplatin was prescribed.
250 patients were randomised. Median follow-up was 5 years for locoregional control (LRC) and 9 years for overall survival (OS). There were no statistically significant differences between the two treatment arms regarding LRC and OS. LRC at five years was 73% (95% CI, 65–82) in preoperative AF and 78% (95% CI, 70–85) in postoperative CF.
Toxicity was more pronounced in preoperative AF.
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Silencing circular RNA hsa_circ_0004491 promotes metastasis of oral squamous cell carcinoma
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Oral squamous cell carcinoma (OSCC) is an oral cavity malignancy which is the eighth most common cancer. However, the molecular mechanisms underlying the pathogenesis of OSCC remain largely unknown, and effective methods for the prognosis and diagnosis of this disease are lacking. Circular RNAs (circRNAs) are widely expressed among mammals. A growing number of studies have shown that circRNA expression is altered in cancers. In this study, we investigated the role of hsa_circ_0004491 in OSCC cell migration and invasion and examined the clinical characteristics associated with its expression.
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The expression level of hsa_circ_0004491 affects the migration and invasion of OSCC cells. Hsa_circ_0004491 may therefore play a role in the progression of oral squamous cell carcinoma.
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The 5-year overall survival rate for all patients was 48 %. In univariate analysis, patient's age and data compiled from the histopathological examination as margin status, extracapsular spread, ypT, ypN, ypUICC, number of positive lymph nodes and lymph node ratio (LNR) had a statistically significant impact on overall survival. Multivariate analysis revealed an independent significant impact of patient age, ypT, margin status and LNR on OS. ypN showed no statistical significant impact on OS.
Our results show that LNR is an important predictor for OS in patients with OSCC that were treated with neoadjuvant radiochemotherapy and radical surgery.
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The purpose of this retrospective study was to analyze the factors that had a significant effect on securing a successful surgical resection (surgical margin) in oral cancer surgery. One hundred forty-eight consecutive patients who underwent planned radical resection of oral squamous cell carcinoma (SCC) were analyzed. Successful resection was judged if pathological examination of the surgical specimen revealed a clear surgical margin (no SCC within 5 mm, n = 116), while an unsuccessful resection was judged if there was a close and involved surgical margin (SCC within 5 mm, n = 21; and SCC at margin, n = 11). Univariate analyses showed that gender, age, and T-classification had significant influence on successful surgical resection. The results of multivariate logistic regression analysis showed that age (odds ratio [OR] = 1.042, 95% CI = 1.001-1.084), T-classification (OR = 1.656, 95% CI = 1.060-2.587), and the presence of preoperative treatment (OR = 2.868, 95% CI = 1.047-7.85) had significant effects on successful surgical resection. The results of this study suggested that successful resection of oral SCC was difficult in patients with either older age or advanced (T4) tumor. It is also suggested that preoperative therapy had a positive effect on securing a pathologically clear surgical margin.
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Neoadjuvant and adjuvant therapy in patients with oral squamous cell carcinoma: Long-term survival in a prospective, non-randomized study

Abstract

Introduction

Patients and methods

Results

Conclusion

Introduction

Section snippets

Patients and methods

Results

Discussion

Eur J Cancer

Int J Radiat Oncol Biol Phys

Radiother Oncol

Lancet

Am J Surg

Radiother Oncol

Oral Oncol

Int J Radiat Oncol Biol Phys

Mature results of a phase III randomized trial comparing concurrent chemoradiotherapy with radiation therapy alone in patients with stage III and IV squamous cell carcinoma of the head and neck

Cancer

Patterns of failure following radiation with and without chemotherapy in patients with nasopharyngeal carcinoma

Onkologie

Preliminary results of Radiation Therapy Oncology Group 97-03: a randomized phase II trial of concurrent radiation and chemotherapy for advanced squamous cell carcinoma of the head and neck

J Clin Oncol