J Med Discov (2017); 2(4):jmd17041; DOI:10.24262/jmd.2.4.17041; Received September 15th, 2017, Revised September 31st, 2017, Accepted October 2nd, 2017, Published October 3rd, 2017
Impacts of Oral Reconstruction on Patients with Tongue Squamous Cell Carcinoma
Xing Zhang1, 2, #, Tianrun Liu3, #, Fengjiao Li1, 5, Huan Li1, 4, Liping Wang6,Shuwei Chen1, 2, Shimin Zhuang3, Xidi Wang1, 2, Zhipeng Chen1, 2, Ming Song1, 2, *
1State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, P. R. China.
2Department of Head and Neck Surgery, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China.
3Department of Otolaryngology-Head & Neck Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, P.R. China.
4Department of Intensive Care, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China.
5Department of Operating room, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China.
6The People’s Hospital of Bao’an District Shenzhen, Shenzhen, P.R. China.
*Corresponding author: Ming Song, 651 Dongfeng Dong Road, Guangzhou 510060, People’s Republic of China. Phone: 86-20-87343300; Fax: 86-20-87343303;
#These authors contributed equally to this work.
Background: The application of reconstruction techniques in head and neck surgery has become the “workhorse” of head and neck surgeons; however, whether reconstruction is appropriate for all head and neck cancer patients remains as a critical issue. To address this question, this study analyzed the impacts of surgical treatment with immediate reconstruction and postoperative radiotherapy on the survival and functional outcomes of patients with different stages of tongue squamous cell carcinoma (TSCC).
Materials and methods: We collected the clinical data of 184 patients with different stages of TSCC. Sixty-eight patients were immediately reconstructed with a variety of ﬂaps. Thirty-three patients underwent postoperative radiotherapy. The recurrence rate, survival time and functional outcomes, such as speech intelligibility and swallowing capacity, were evaluated and compared.
Results: Reconstruction contributed to a reduced recurrence rate and improved overall survival in the patients with T3/T4 TSCC; but did not significantly affect the recurrence rateor overall survival in T1/T2 TSCC patients. Reconstruction is profitable for postoperative speech intelligibility and swallowing capacity in the patients with T3/T4 TSCC, but not significantly in the patients with T1/T2 TSCC.
Conclusions: Surgical resection with immediate reconstruction resulted in improved oncological outcomes and oral function in the patients with T3/T4 TSCC.
Keywords: tongue squamous cell carcinoma, reconstruction,recurrence rate,overall survival, function.
Squamous cell carcinoma consists of more than 95% of all oral malignant neoplasm, and tongue squamous cell carcinoma (TSCC) is one of the most common types of oral malignant neoplasm [1, 2]. The clustered association of TSCC with relatively old men is gradually being replaced by an association with clusters of young men .Surgical resection remains the primary modality of treatment for the patients with TSCC. Although the 5-year survival rate has been slightly improved with the introduction of new treatments, such as concurrent chemo-radiotherapy, monoclonal antibody targeting epidermal growth factor receptor (EGFR) combined with chemotherapy or radiotherapy [4, 5], TSCC is still associated with poor prognosis due to the high incidence of local and regional recurrence [6, 7].
Extensive resection is critical to achieve a safe surgical margin for patients with advanced TSCC, and it is likely to cause serious functional and cosmetic deficits. Since reconstructive surgery emerged, several studies have demonstrated the reliability and promising outcomes for head and neck defects reconstructed with a variety of ﬂaps [8-10].However, reconstruction is a complex surgical procedure because of the high risk of vascular crisis and donor site morbidity. Additionally, whether reconstruction contributes to improved life quality and overall survival rate in the patients with TSCCremains as a controversial issue [11, 12], and very few researchers have studied on this topic. For this reason, the aim of this study was to analyze more recent data on disease control, survival and functional outcomes in patients with TSCC treated with reconstruction, to make clear the impacts of immediate reconstruction using a variety of flaps in patients with different T stages of TSCC, and to identify which groups of TSCC patients are suitable for reconstruction.
|Variable||No. of Patients (%)|
|≤ 53||94 (51.1)|
|> 53||90 (48.9)|
|Lymph node metastasis (N)|
Table 1. Clinicopathological features of the 184 TSCC patients.
|Variable||No. of Patients (%)|
|Neck dissection||175 (95.1)|
|Ipsilateral RND||13 (7.4)|
|Ipsilateral MRND||20 (11.4)|
|Ipsilateral SND||139 (79.4)|
|Ipsilateral RND and contralateral SND||1 (0.6)|
|Ipsilateral SND and contralateral SND||2 (1.1)|
|Anterolateral thigh flap (ALTF)||46 (67.6)|
|Radial forearm flap (RFF)||17 (25.0)|
|Pectoralis major myocutaneous flap (PMMF)||3 (4.4)|
|Rectus abdominis ﬂap (RAF)||1 (1.5)|
|Latissimus dorsi flap (LDF)||1 (1.5)|
Abbreviations:RND, radical neck dissection;MRND, modiﬁed radical neck dissection;SND,selective neck dissection (usually supraomohyoid neck dissection).
Table 2. Surgical treatment for the 184 TSCC patients
Patients and Methods
Patients with TSCC initially treated between January 1, 2005 and April 13, 2010 were recruited in this review. The patients included in this study met the following criteria: (1) histologically proven, untreated resectable primary TSCC; (2) an absence of confounding variables (second primary tumor, prior history of other cancers). Patients with distant metastasis were excluded. Finally, a total number of 184 patients met the inclusion criteria and were enrolled into this study. Follow-up ended on April 30, 2012.
The patients included 112 males and 72 females with an age range of 20 to 81 years (mean, 52.5 years). The TNM classiﬁcation and staging were based on the 7th International Union Against Cancer (UICC) staging criteria (2010). The patients’ detailed characteristics are summarized in Table 1. All of the 184 patients underwent surgical resection with or without neck dissection.Sixty-eight of the patients underwent simultaneous reconstruction of intraoral defects and the rest 116 patients did not. Seventeen of the 71 (23.9%) patients with T1 TSCC, 26/78 (33.3%) patients with T2 TSCC, 18/22 (81.8%) patients with T3 TSCC and 7/13 (53.8%) patients with T4 TSCC underwent reconstruction. In this study, 175 patients underwent neck dissection, including ipsilateral neck dissection in 172 patients and bilateral neck dissection in 3 patients.
The standard indications for postoperative irradiation were applied, including one or more of the following pathologic findings (risk factors): T3/T4 stage; N2/N3 stage; pathologic lymph nodes of level IV/V; close margins (< 5 mm); perineural invasion or vascular space invasion. Sixty-four of the 184 patients met the indications for postoperative irradiation. Because of the limited financial resources or some other reasons, only 33 of these 64 patients underwent postoperative radiotherapy. The radiotherapy dosage ranged from 50 Gy to 76 Gy. Twenty-three of the 33 patients were still alive at the last follow-up, and the 23 patients received postoperative radiotherapy with a dose range of 50 Gy to 66 Gy (detailed data are presented in Table 2).
Postoperative evaluation of oral function
All survived patients received a postoperative speech and swallowing evaluation using themethod described by Yanai . In short, speech intelligibilitywas estimated by a speech therapist who graded the patients after a conversation as: 5, no sound errors and speech can be easily understood; 4, speech is occasionally misunderstood; 3, speech is understood only when the context of the text is known to the listener; 2, speech is occasionally understood; and 1, speech is completely unintelligible. Speech intelligibilitywas then classified as good (scores 5–4), acceptable (score 3) or poor (scores 1–2). Swallowing capacity was evaluated using the MTF classification based on the method of food intake (M), the time required for food intake (T) and the consistency of food (F) . The method of food intake (M) was classiﬁed and scored as: M5, swallowing is unlimited (5 points); M4, capacity for swallowing anything, but occasional aspiration (4 points); M3, capacity to swallow anything prepared in a suitable form (3 points); M2, capacity to swallow small portions of food, but stomach tube is the main means of ingestion (2 points); and M1, capacity to swallow nothing and stomach tube is the only method of ingestion (1 point). The time required for food intake (T) was assessed according to the average time required to eat a daily meal (irrespective of its nature and consistency) as: T5, food intake time is not signiﬁcantly different before and after therapy. (5 points); T4, food intake time is prolonged by 0 to 10 min (4 points); T3, food intake time is prolonged by 10 to 20 min (3 points); T2, food intake time is prolonged by 20 to 30 min (2 points); and T1, food intake time is prolonged by more than 30 min or is impossible (1 point). The consistency of food that a patient was able to ingest (F) was classiﬁed as: F5, capacity to ingest any food (5 points); F4, capacity to ingest soft, chewable food (4 points); F3, capacity to ingest gruel (3 points); F2, capacity to ingest viscous ﬂuids (2 points); and F1, capacity to ingest only non-viscous ﬂuids (1 point). Finally, the M, T and F scores were added and swallowing capacity was classified as good (scores 13–15), acceptable (scores 9–12) or poor (scores ≤8) according to the sum MTF value.
Statistical analysis was performed using Statistical Program for Social Sciences (SPSS) PASW Statistics for Windows version 18.0 (SPSS Inc., USA). The influence of clinicopathological characteristics and treatment strategy on recurrence and survival rates were assessed using Chi-square test. The Kaplan–Meier method was used to plot survival and disease-free interval curves, and log-rank method was used for comparisons between groups. P values were subject to a global signiﬁcance at the level of 0.05.
|Lymph node metastasis (N)||<0.001||<0.001|
Table 3. Influence of clinicopathological characteristics on recurrence and survival in TSCC.
Relationship between clinicopathological characteristics and prognosis in TSCC.
Recurrence was signiﬁcantly associated with N-stage (P < 0.001), T-stage (P = 0.001), pathological stage (P < 0.001) and tumor grade (P = 0.017) in patients with TSCC. N-stage (P < 0.001), T-stage (P = 0.018), pathological stage (P < 0.001) and tumor grade (P = 0.002) were also signiﬁcantly associated with overall survival (Table 3). A lower loco-regional recurrence rate (P = 0.015) and higher overall survival rate (P = 0.001) were observed in T3/T4 TSCC patients who received immediate reconstruction, compared to T3/T4 patients who did not undergo immediate reconstruction (Fig 1). However, immediate reconstruction did not significantly affect the recurrence rate (P = 0.513) or overall survival in T1/T2 TSCC patients (P = 0.354; Fig 2), detailed data is presented in Table 4. The recurrence rate (P = 0.397) and overall survival rate (P = 0.150) were not significantly different in TSCC patients who received preoperative chemotherapy and those who did not.
Effect of reconstruction on functional outcomes in stage T1/T2 TSCC patients.
Speech Intelligibility: There was no significant difference inspeech intelligibility between the reconstruction group and the group without reconstruction (P = 0.309; Table 5).
Swallowing Capacity: The surviving patients underwent postoperative swallowing capacity evaluation using the MTF method. None of the surviving patients was stomach tube dependent during the functional survey. There was no significant improvement in patients who received reconstruction, compared to patients who did not undergo reconstruction (P = 0.746; Table 5).
Figure 1. Disease-free interval (1a; P=0.015) and overall survival (1b; P=0.001) of T3/T4 TSCC patients after surgical treatment with (n =17) and without reconstruction (n = 18).
Figure 2. Disease-free interval (2a; P=0.513) and overall survival (2b; P=0.354) of T1/T2 TSCC patients after surgical treatment with (n = 43) and without reconstruction (n = 106).
Effect of reconstruction on functional outcomes in stage T3/T4 TSCC patients.
Speech Intelligibility: Nineteen of the 21 (90.5%) patients in the T3/T4 reconstruction group achieved good speech intelligibility; one patient achieved good speech intelligibility and another achieved acceptable speech intelligibility in the group of T3/T4 patients who did not receive reconstruction. As only two patients from the advanced T3/T4 group without reconstruction survived, we did not pursue further statistical analysis. However, the speech intelligibility outcome of these T3/T4 patients after reconstruction was satisfactory (Table 5).
|Reconstruction||Tumor stage(T1, T2)||Tumor stage (T3, T4)|
Table 4. Influence of reconstruction on recurrence and survival inTSCC patientsat different T stages.
Swallowing Capacity: After reconstruction, 15/21 (71.4%) of the T3/T4 patients acquired good swallowing capacity and 6/21 (28.6%) achieved acceptable swallowing capacity. None of the surviving patients was stomach tube dependent during the functional survey. One surviving patient who did not undergo reconstruction achieved good swallowing capacity and another achieved acceptable swallowing capacity. Due to the small number of surviving patients in the group without reconstruction (two patients), we did not pursue further statistical analysis. However, the swallowing capacity outcome of the T3/T4 patients who underwent reconstruction was satisfactory (Table 5).
|Oral function||Evaluation||Tumor stage (T1, T2)||Tumor stage (T3, T4)|
|No ﬂap reconstruction
|No ﬂap reconstruction
Table 5. Influence of ﬂap reconstruction on speech intelligibility and swallowing capacityin TSCC patients at different T stages.
Reconstruction has been used in the surgical treatment of head and neck cancer for more than five decades, and it has recently become more popular; however, many patients with TSCC still do not achieve the desired results. This study suggests that reconstruction should be applied in selected patients with TSCC.
Controversy of which group of patients with TSCC are appropriate for ﬂap reconstruction always exists. Some clinicians suggest that since the patients with advanced TSCC have a high recurrence rate[14, 15], the beneﬁts of reconstruction are very limited. In contrast, others have advocated that larger defects should be reconstructed when there is a functional or aesthetic loss of structure in the oral cavity after tumor ablation [16-18]. Additionally, immediate reconstruction has been reported to signiﬁcantly inﬂuence the survival of patients with advanced TSCC (T3/T4) [11, 12, 19]. Advanced cancer has always been associated with high recurrence rate, and insufficient surgical margin is the major reason for local recurrence [20, 21]. Extensive resection is necessary in patients with advanced TSCC in order to obtain a safe surgical margin. In this study, we investigated the impacts of reconstruction in patients with different T stage of TSCC, and found that proper reconstruction could enable the head and neck surgeons to perform radical resection of advanced primary tumors (T3/T4).All T3/T4 patients who received reconstruction completed surgical resection (a clinical margin of excision of at least 10 mm). Comparing with T3/T4 TSCC patients who did not receive reconstruction, T3/T4 patients who received reconstruction significantly improved overall survival and lowered rate of recurrence. Probably, because the T1/T2 patients have sufficient surgical margins and sutured directly, in the study, reconstruction did not signiﬁcantly affect the overall survival and rate of recurrence in the patients with early stageTSCC (T1/T2).
Patients with advancedTSCC have bad functional outcomes after tumor ablation. Malone et al reportedthat patients with stage III and IV squamous cell carcinoma of the tongue base showed worse results of Normalcy of Diet and Understandability of Speech, compared to patients with early-stage cancer.Zelefskyet al. demonstrated that these subjective functional scores deteriorated with increasing T stage in patients with advanced stage oral cavity and oropharyngeal carcinoma. Reconstruction of oral resections rehabilitated the functions in acceptable levels, improving quality of life in these patients [10, 24]. In most literatures, only the postoperative function of patientswho received reconstruction was evaluated. In this study, speech and swallowingfunction of all patients was evaluated, and there was a comparison between patientswho received reconstruction and patients who did not undergo reconstruction. Additionally, postoperative function of patients was analyzed in different T stage. The results suggested that surgical resection combined with reconstruction tended to offer satisfactory speech and swallowing function in advanced patients, while the speech and swallowing functional outcomes were less satisfactory in T3/T4 TSCC patients who did not receive reconstruction. In contrast to the advanced TSCC patients, immediate reconstruction after tumor ablation had no signiﬁcant effect on speech and swallowing function in early-stage TSCC (T1/T2) patients. Additionally,reconstruction increased the risk of medical complications, including the wound to heal by secondary intention, split-thickness skin or dermal grafting and so on.
The surgical margin is under the direct control of surgeons and has been demonstrated a strong correlation with survival rates [21, 25]. Owing to the advancements of reconstruction, more extensive resections are now available than before. Additionally, T3/T4 TSCC patients who received reconstruction achieve satisfactory speech and swallowing function. Considering the patient’s survival and quality of life, reconstruction is a good choice for patients with advanced TSCC (T3/T4); however,for this circumstance, using a free flap or pedicle flap to reconstruct the oral defect might cause adversities to the patients with early TSCC. So it is still controversial whether to apply a flap reconstruction for the patient with early TSCC, and the decision to perform reconstruction should be made cautiously in patients with early TSCC (T1/T2).
The overall success rate of reconstruction in this study was 97.2%, which is similar to other studies [26, 27]. Flap vascular crisis occurred in six patients due to phlebothrombosis; four of these were successfully salvaged. One patient had total ﬂap necrosis, and as the patient refused repeat reconstruction, the tongue defect was closed directly after the necrotic flap was removed. The other patient had partial ﬂap necrosis. The most commonly observed donor-site morbidity was a broad scar; therefore, to decrease the impact of donor site scarring we suggest the Anterolateral thigh flap (ALTF) is the ideal soft tissue ﬂap for intraoral defect reconstruction, as it has a number of advantages, including enough volume, a flexible shape, secret donor site and long vessel pedicel [10, 28, 29]. Even though many other flaps are available, we usually apply radial forearm flap (RFF) and pectoralis major myocutaneous flap (PMMF) as backup flaps, in case the ALTF fails in vascular crisis.
Compared to patients who did not have the standard risk factors for radiotherapy, the rate of local or regional relapse was signiﬁcantly higher in patients with one or more risk factor, such as T3/T4 stage, N2/N3 stage, pathologic level IV/V lymph nodes, close margins (< 5 mm), perineural invasion or vascular space invasion. Postoperative radiotherapy is efficient to control local or regional relapse,and it has been previously recommended in patients with one or more risk factors [14, 15, 30-34]. In this study, our results are consistent with previous studies. Postoperative radiotherapy has been reported to negatively influence the functional speech and swallowing outcome in patients with TSCC [17, 35, 36]. While some authors have reported that postoperative radiotherapy at 20 to 40 Gy did not prevent the continued recovery of tongue function with respect to speech, the majority of patients recovered gradually and could still achieve an acceptable functional status and quality of life [9, 23, 37-39]. Schultze-Mosgauet al.  reportedthat irradiation at a dose of 40–50 Gy and chemotherapy at a median interval of 1.5 months prior to surgery did not lead to significant histological changes in the recipient vessels. In this study, the impact of postoperative radiation was estimated from two aspect-survival and function. Postoperative radiation improved loco-regional control and overall survival in patients with the risk factors. Speech intelligibility and swallowing capacity were classified as good, acceptable or poor according to the scores. Most patients who underwent postoperative radiation got a low score in the same level, but speech and swallowing capacity was still satisfactory. Postoperative radiation at a dose 50 Gy to 66 Gy partly interfered the life quality for these patients, but the results showed no statistical significance compared to patients who did not undergo postoperative radiotherapy.
In conclusion, it is important to choose the appropriate patients for reconstruction.In this study, immediate oral reconstruction is recommended for advanced TSCC patients. For patients with early TSCC, reconstruction should be reserved and usedselectively, but reconstruction can be considered when there is functional or esthetic loss of the oral cavity. Speech and swallowing functional outcomes are not significantly inﬂuenced by postoperative radiotherapy in patients receiving a dose 50 Gy to 66 Gy. A moderate dose of postoperative radiotherapy is recommended for patients with the common/standard risk factors.
Conflict of interest
The authors have no conflicts of interest to declare.
This research is supported by the Science and Technology Program Fund of Guangdong Province (No. 2014A020212476).
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