Concurrent preoperative chemotherapy and three-dimensional conformal radiotherapy followed by surgery for oral squamous cell carcinoma: a retrospective analysis of 104 cases

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Abstract

Objectives

The objectives of this study were to assess the clinical effects of an integrated program consisting of concurrent preoperative combined paclitaxel and nedaplatin chemotherapy and three-dimensional conformal radiotherapy followed by surgery intended to cure oral squamous cell carcinoma and to determine whether this integrated program is feasible and effective with respect to the treatment of oral squamous cell carcinoma.

Methods

A total of 104 biopsy-confirmed patients who presented with oral squamous cell carcinoma for the first time were included in this study. Concurrent preoperative combined paclitaxel and nedaplatin chemotherapy and three-dimensional conformal radiotherapy were administered to these patients. The most common treatment regimen consisted of infusions of paclitaxel (135-175 mg/m ²/day), infusions of nedaplatin (150 mg; 80-100 mg/m ²/day), and irradiation at doses ranging from 1.5 Gy twice daily to 30-40 Gy over 3-4 weeks. The clinical variables evaluated herein included the local recurrence rate, distant metastasis rate, postoperative survival rate, and degree of mouth opening restriction.

Results

The median follow-up time for surviving patients was 60 months, and the median time to progression for all patients was 57.69 months (95% confidence interval, 56.09 to 59.29 months, and the 3-year disease-free survival probability was 97.11%). The effectiveness rate of the integrated program was 98.08%, and the surgery resection rate was 100%. Only a few postoperative adverse reactions were observed. The local recurrence and distant metastasis rates were 1.92% (2 patients) and 2.88% (3 patients), respectively. The titanium rejection and infection reaction rate that led to restriction of mouth opening was only 2.88% (3 patients). Finally, the 5-year post-surgery survival rate was 91.35% (95 patients).

Conclusion

Preoperative combined paclitaxel and nedaplatin chemotherapy and three-dimensional conformal radiotherapy have significant clinical effects leading to positive anti-tumor results in patients with oral squamous cell carcinoma. These treatments also increase the likelihood that patients will undergo successful surgical treatment. The integrated program described herein can increase long-term survival and surgery resection rates and is associated with only a limited number of adverse reactions.

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Most cited references 24

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Current concepts in management of oral cancer--surgery.

Jatin P. Shah, Ziv Gil (2015)

Oral cancer is the sixth most common cancer worldwide, with a high prevalence in South Asia. Tobacco and alcohol consumption remain the most dominant etiologic factors, however HPV has been recently implicated in oral cancer. Surgery is the most well established mode of initial definitive treatment for a majority of oral cancers. The factors that affect choice of treatment are related to the tumor and the patient. Primary site, location, size, proximity to bone, and depth of infiltration are factors which influence a particular surgical approach. Tumors that approach or involve the mandible require specific understanding of the mechanism of bone involvement. This facilitates the employment of mandible sparing approaches such as marginal mandibulectomy and mandibulotomy. Reconstruction of major surgical defects in the oral cavity requires use of a free flap. The radial forearm free flap provides excellent soft tissue and lining for soft tissue defects in the oral cavity. The fibula free flap remains the choice for mandibular reconstruction. Over the course of the past thirty years there has been improvement in the overall survival of patients with oral carcinoma largely due to the improved understanding of the biology of local progression, early identification and treatment of metastatic lymph nodes in the neck, and employment of adjuvant post-operative radiotherapy or chemoradiotherapy. The role of surgery in primary squamous cell carcinomas in other sites in the head and neck has evolved with integration of multidisciplinary treatment approaches employing chemotherapy and radiotherapy either sequentially or concurrently. Thus, larynx preservation with concurrent chemoradiotherapy has become the standard of care for locally advanced carcinomas of the larynx or pharynx requiring total laryngectomy. On the other hand, for early staged tumors of the larynx and pharynx, transoral laser microsurgery has become an effective means of local control of these lesions. Advances in skull base surgery have significantly improved the survivorship of patients with malignant tumors of the paranasal sinuses approaching or involving the skull base. Surgery thus remains the mainstay of management of a majority of neoplasms arising in the head and neck area. Similarly, the role of the surgeon is essential throughout the life history of a patient with a malignant neoplasm in the head and neck area, from initial diagnosis through definitive treatment, post-treatment surveillance, management of complications, rehabilitation of the sequelae of treatment, and finally for palliation of symptoms.

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Induction chemotherapy followed by concurrent chemoradiotherapy (sequential chemoradiotherapy) versus concurrent chemoradiotherapy alone in locally advanced head and neck cancer (PARADIGM): a randomised phase 3 trial.

Robert I Haddad, Anne O’Neill, Guilherme Rabinowits … (2013)

The relative efficacy of the addition of induction chemotherapy to chemoradiotherapy compared with chemoradiotherapy alone for patients with head and neck cancer is unclear. The PARADIGM study is a multicentre open-label phase 3 study comparing the use of docetaxel, cisplatin, and fluorouracil (TPF) induction chemotherapy followed by concurrent chemoradiotherapy with cisplatin-based concurrent chemoradiotherapy alone in patients with locally advanced head and neck cancer. Adult patients with previously untreated, non-metastatic, newly diagnosed head and neck cancer were eligible. Patients were eligible if their tumour was either unresectable or of low surgical curability on the basis of advanced tumour stage (3 or 4) or regional-node stage (2 or 3, except T1N2), or if they were a candidate for organ preservation. Patients were randomly assigned (in a 1:1 ratio) to receive either induction chemotherapy with three cycles of TPF followed by concurrent chemoradiotherapy with either docetaxel or carboplatin or concurrent chemoradiotherapy alone with two cycles of bolus cisplatin. A computer-generated randomisation schedule using minimisation was prepared and the treatment assignment was done centrally at one of the study sites. Patients, study staff, and investigators were not masked to group assignment. Stratification factors were WHO performance status, primary disease site, and stage. The primary endpoint was overall survival. Analysis was by intention to treat. Patient accrual was terminated in December, 2008, because of slow enrolment. The trial is registered with ClinicalTrials.gov, number NCT00095875. Between Aug 24, 2004, and Dec 29, 2008, we enrolled 145 patients across 16 sites. After a median follow-up of 49 months (IQR 39-63), 41 patients had died-20 in the induction chemotherapy followed by chemoradiotherapy group and 21 in the chemoradiotherapy alone group. 3-year overall survival was 73% (95% CI 60-82) in the induction therapy followed by chemoradiotherapy group and 78% (66-86) in the chemoradiotherapy alone group (hazard ratio 1·09, 95% CI 0·59-2·03; p=0·77). More patients had febrile neutropenia in the induction chemotherapy followed by chemoradiotherapy group (16 patients) than in the chemoradiotherapy alone group (one patient). Although survival results were good in both groups there was no difference noted between those patients treated with induction chemotherapy followed by chemoradiotherapy and those who received chemoradiotherapy alone. We cannot rule out the possibility of a difference in survival going undetected due to early termination of the trial. Clinicians should still use their best judgment, based on the available data, in the decision of how to best treat patients. The addition of induction chemotherapy remains an appropriate approach for advanced disease with high risk for local or distant failure. Sanofi-Aventis. Copyright © 2013 Elsevier Ltd. All rights reserved.

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Oral cancer.

Deepak Kademani (2007)

Five percent of all tumors occur in the head and neck, and approximately half of those occur specifically in the oral cavity. Of the 615,000 new cases of head and neck [corrected] tumors reported worldwide in 2000, 300,000 were primary oral cavity squamous cell carcinomas. Recent data from the Surveillance, Epidemiology, and End Results Program suggest that 28,900 new cases of oral cancer will be identified and 7400 deaths attributed to oral cancer each year in the United States. The sixth leading cause of cancer-related mortality, oral cancer accounts for 1 death every hour in the United States. However, despite advances in screening tools, imaging technology, and access to primary care physicians, a considerable percentage of patients present with advanced-stage disease. Clinical signs and symptoms of head and neck tumors are often nonspecific and may be mistaken for other common ailments. Primary care physicians must be aware of the possibility of oral cancer, particularly the increasing incidence in young patients without traditional risk factors of alcohol and tobacco abuse. To improve survival, all patients should be routinely and vigilantly screened for oral mucosal lesions.

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Author and article information

Journal

Journal ID (nlm-ta): Oncotarget

Journal ID (iso-abbrev): Oncotarget

Journal ID (publisher-id): Oncotarget

Journal ID (publisher-id): ImpactJ

Title: Oncotarget

Publisher: Impact Journals LLC

ISSN (Electronic): 1949-2553

Publication date Collection: 26 September 2017

Publication date (Electronic): 21 April 2017

Volume: 8

Issue: 43

Pages: 75557-75567

Affiliations

¹ Department of Oral and Maxillofacial Surgery, Fuzhou General Hospital of Nanjing Command, PLA, Fuzhou, China

² School and Hospital of Stomatology, Fujian Medical University, Fuzhou, China

Author notes

Correspondence to : Sheng Fu, shengfu62@ 123456163.com

Hongbing Lv, hongbinglu@ 123456126.com

[*]

These authors have contributed equally to this work

Article

Publisher ID: 17363

DOI: 10.18632/oncotarget.17363

PMC ID: 5650445

SO-VID: c302be62-3c82-4626-bf14-42c49dbf0620

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

History

Date received : 17 October 2016

Date accepted : 3 April 2017

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Concurrent preoperative chemotherapy and three-dimensional conformal radiotherapy followed by surgery for oral squamous cell carcinoma: a retrospective analysis of 104 cases

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Most cited references 24

Current concepts in management of oral cancer--surgery.

Induction chemotherapy followed by concurrent chemoradiotherapy (sequential chemoradiotherapy) versus concurrent chemoradiotherapy alone in locally advanced head and neck cancer (PARADIGM): a randomised phase 3 trial.

Oral cancer.

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