[Abstract] Objective analysis T3T4 glottic laryngeal cancer prognosis and related factors. Methods A retrospective analysis of 110 cases T3T4 period glottic laryngeal squamous cell carcinoma clinical data, analysis of survival and prognostic factors of different regimen. Results The overall 5-year survival rate and control rate of 59.1% and 68.6%, respectively. Where the combined therapy group were 72.0% and 76.9%, 50.0% and 60.7% in the surgery alone group, 41.7% and 56% in the radiotherapy alone group, the difference was statistically significant (P <0.05). (≤ 60 years old), and cervical lymph node-negative primary site control patients with 5-year survival rates were 76.5%, 67.8% and 67.3%, higher than the old age (≥ 61 years) (47.9%), and cervical lymph node metastasis ( 16.7%) and the primary site of relapse (10.7%) patients, the difference was statistically significant (P <0.01). The overall recurrence rate of 23.64%. Histological grade and cervical lymph node negative patients, 5-year control rates were 76.6% and 73.6%, higher than the poorly differentiated (48%) and cervical lymph node metastasis (43.6%) patients, the difference was statistically significant (P <0.05) . Univariate and multivariate analysis showed that pathological poorly differentiated cervical lymph node metastasis of tumor recurrence independent predictors (P <0.05); age, cervical lymph node metastases and primary site of recurrence independent predictive factors affecting the survival of patients with (P <0.05). Conclusion T3T4 glottic laryngeal squamous cell therapy better than monotherapy. Poorly differentiated pathological cervical lymph node metastasis affecting independent predictor of T3T4 glottic laryngeal cancer recurrence; senior citizens, cervical lymph node metastases and primary site of relapse is an independent predictor factors affecting the survival of patients.

Key words squamous cell carcinoma of the glottis area laryngeal cancer recurrence prognosis

    T3T4 glottic laryngeal squamous cell carcinoma comprehensive treatment of the 5-year survival rate of 45% to 71% local control rate of 53% to 81% [1  4] T3T4 glottic laryngeal squamous cell carcinoma recurrence and survival factors , there has been no unanimous conclusion [2,5  8]. Authors review admitted to hospital in January 1991 to December 1998 T3T4 glottic area laryngeal squamous cell carcinoma clinical data, analysis of treatment outcome and recurrence and prognosis factors in order to provide a valuable reference for clinical treatment.

    1 Materials and Methods

    1.1 General Information

    According to the UICC (2002) staging criteria, 110 cases T3T4 glottic laryngeal squamous cell carcinoma in 109 cases, male and 1 female. Age 27 to 84 years, the median age (60.9 ± 3.37) years old. All cases confirmed by pathological examination for squamous cell carcinoma, including 72 cases of grade Ⅰ, Ⅱ grade 28 cases, 10 cases, Ⅲ grade. 79 cases of stage T3 and T4 of 31 cases. the cN0 of 99 cases in nine cases, cN1 the, cN2 two cases. Distant metastasis.

    1.2 Treatment

    Surgery alone in the treatment of 48 cases, 15 cases, including 33 cases of total laryngectomy, partial laryngectomy.; Radical neck to clear the 5 sides of neck, preventive base of the throat. Radical radiotherapy in 12 cases, including 11 cases of stage T3, T4 1 cases. Primary tumor dose of 56 ~ 70Gy, mean 68Gy, neck radiotherapy dose was 40Gy and 42Gy.

    Comprehensive treatment of 50 cases (surgery plus radiation therapy of 44 cases, radiotherapy + surgery plus radiotherapy 2 cases, surgery + chemotherapy 4 cases). Among them, 21 cases of 29 cases of total laryngectomy, partial laryngectomy. Partition neck clear 3 sides of neck, the functional neck clear 3 sides of neck. 46 patients received radiotherapy, including 2 cases (dose 36Gy and 40Gy) Preoperative radiation therapy. 44 cases of postoperative radiation therapy, a dose of 38 ~ 68Gy, median dose (62 ± 0.42) Gy. Neck to clear the three cases of postoperative radiation therapy, a dose of 40 ~ 56Gy (46 ± 0.46) Gy, split dose 2Gy / d. 4 cases of postoperative chemotherapy using cisplatin (DDP) +5- fluorouracil (5  Fu) + bleomycin (BLM) program, DDP 30mg intravenous infusion d 1 ~~ 5,5  Fu 0.5 intravenous infusion, d 1 ~ 5, BLM 8mg intravenous injection, d 1,3,5,3 treatment.

    1.3 statistical methods

    Use SPSS10.0 software analysis, Kaplan  Meier method of survival analysis and single factor analysis, multivariate analysis using the Cox proportional hazards model, with P <0.05 as statistically significant.

    2 Results

    2.1 survival

    110 patients were followed up for 60 to 135 months, the median time of 69.7 months. 5-year overall survival rate and control rate of 59.1% and 68.6%, respectively. T3, T4 of patients survival rates were 63.3% (50/79) and 48.4% (15/31), the difference was not statistically significant (χ2 = 2.046, P = 0.153). The 5-year survival rate of the combined therapy group and control rate were 72.0% and 76.9%, 50.0% and 60.7% in the surgery alone group, 41.7% and 56.0% in the radiotherapy alone group, the difference was statistically significant (Log Rank = 6.671 , P = 0.0376, Log Rank = 6.603, P = 0.0422).

    2.1.1 neck lymph node metastasis the survival rate cN0 and cN1 ~ 2 patients 5-year survival rates were 16.7% and 67.8%, respectively. The difference was statistically significant (Log Rank = 15.78, P = 0.0001).

    2.1.2 primary recurrence and survival rates of the primary site recurrence and relapse-free patients with 5-year survival rates were 10.7% and 67.3%, and the difference was statistically significant (Log Rank = 17.85, P = 0.000) .

    2.1.3 Age and survival rate of old age (≥ 61 years) and younger age (≤ 60 years) patients with 5-year survival rates were 48.0% and 76.5%. The difference was statistically significant (Log Rank = 8.59, P = 0.0034).

    2.2 Recurrence

    2.2.1 The overall recurrence rate of 23.6% (26/110) of the original site of recurrence in 11 cases, in which the primary site of recurrence after total laryngectomy 6 cases, partial laryngectomy five cases. Cervical lymph node recurrence in 15 cases, which cN1 ~ 2 patients, the recurrence rate of 18.2% (2/11), cN0 patients, the recurrence rate of 13.1% (13/99). Relapse patients, 8 cases in Ⅱ, Ⅲ three cases, Ⅳ zone 1 cases, Ⅱ, Ⅲ District 1 case. Poorly differentiated cancer recurrence in 4 cases (40%), well-differentiated carcinoma in 22 patients (22%).

    Relapse treatment: row total laryngectomy four cases, 6 cases of cervical lymph node dissection, four cases to give up treatment, radiotherapy and (or) chemotherapy.

    2.2.2 pathological differentiation level and control the rate of squamous cell carcinoma of grade Ⅰ, Ⅱ stage and grade Ⅲ 5-year control rates were 76.56%, 57.86% and 48%, respectively, compared to different pathological differentiation level, grade Ⅰ was significantly higher than that of squamous cell carcinoma squamous cell carcinoma Ⅲ grade, the difference was statistically significant (Log Rank = 6.64.P = 0.0362).

    2.2.3 neck lymph node metastasis and recurrence-free survival rate cN0 cN1  2 patients with 5-year control rate of 43.64% and 73.61%, respectively, comparing the two, the difference was statistically significant (Log Rank = 5.14, P = 0.0234) .

    2.3 recurrence and survival factors

    2.3.1 The factors associated with recurrence of univariate and multivariate analysis, age, level of pathological differentiation, T, N staging and treatment factors such single factor analysis, the results show the pathological differentiation level, N staging, and treatment and T3T4 glottic laryngeal cancer recurrence related (P <0.05) (only 1 female gender factors are not introduced). The introduction of the above factors the Cox proportional hazards model, multivariate analysis, the results show the level of pathological differentiation, cervical lymph node metastases affect independent predictor of late glottic laryngeal cancer recurrence (P <0.05).

    2.3.2 survival factors univariate and multivariate analysis, age, level of pathological differentiation, T, N staging, treatment methods, the primary site of recurrence and neck lymph node recurrence and other factors were analyzed by univariate analysis, the results show age, N stage and primary site of relapse and treatment associated T3T4 glottic laryngeal cancer survival (P <0.05). The introduction of the above factors the Cox proportional hazards model for multivariate analysis, the results showed that age, cervical lymph node metastases and primary site of relapse is T3T4 glottic laryngeal cancer survival independent predictors (P <0.05), see Table 1. Table 1 Univariate analysis showed survival related factors

    3 Discussion

    3.1 T3T4 glottic laryngeal treatment options

    Treatment programs for advanced laryngeal regional differences. North American countries have chosen surgery, European countries chose radical radiotherapy + surgery to save the domestic use more comprehensive treatment. Ge Junheng [1] reported in the comprehensive treatment of advanced laryngeal cancer 5-year survival rate was 68.2%, surgery alone is 50%. De la Vega [9] hyperfractionated radiation therapy for advanced laryngeal cancer 5-year survival rate was 42%, Johansen [10] reported that Phase III laryngeal cancer radiotherapy treatment of the 5-year survival rate was 44%. In this group, the 5-year overall survival and control rates were 59.1% and 68.6%, respectively. Comprehensive treatment of the 5-year survival and relapse-free survival rate was 72.0% and 76.9%, surgery alone and radiotherapy were 50.0% and 60.7%, 41.7% and 56.0%, consistent with the results reported in [1-4]. Comprehensive treatment than surgery alone and radiation therapy, and the difference was statistically significant (P <0.05). T3T4 glottic laryngeal choose radiotherapy alone for the simple preservation of laryngeal function should be cautious. A wide range of advanced laryngeal tumors, surgery alone is difficult to guarantee the complete removal of the tumor, surgical comprehensive treatment supplemented by radiotherapy or chemotherapy, can significantly increase the survival rate and control rate. Pathological differentiation, neck lymph node metastasis and age should be used as treatment options considerations.

    3.2 Analysis of recurrence and survival factors

    The data showed that the level of pathological differentiation, cervical lymph node metastasis, clinical factors such as age and primary site recurrence T3T4 glottic laryngeal cancer recurrence and survival-related factors.

    Poorly differentiated squamous cell carcinoma of high malignancy, aggressive, poor prognosis [11]. Johansen [10] summarizes 1252 cases of laryngeal cancer information, well-differentiated squamous cell carcinoma and poorly differentiated squamous cell carcinoma of the 5-year control rates were 76% and 44% (P <0.01). In this group, poorly differentiated squamous cell carcinoma compared with well-differentiated squamous cell carcinoma, the recurrence rate is higher (40% vs. 22%), 5-year control rate was significantly lower (76.6% vs 48.0%, P <0.05). Poorly differentiated squamous sensitive radiotherapy for pathological poorly differentiated T3T4 glottic laryngeal should comprehensive treatment program options include radiation therapy to reduce the relapse rate.

    In this group, the primary site of relapse rate of 10% (11/110), the primary site recurrence compared with patients without recurrence, the 5-year survival difference decreased (10.67% vs 67.28%, P <0.001), influence independent prognostic factors (P <0.001), consistent with the results reported in [5]. In 11 patients with relapsed patients, 4 patients reoperation, seven cases due to the tumor a wide range of unresectable, only palliative treatment, the prognosis is poor. T3T4 glottic laryngeal cancer, should ensure the complete removal of the tumor and the possible involvement of the hose outside the organization, cleaning trachea surrounding lymph nodes. Pathological poorly differentiated residual tumor, tumor invasion, lymph node metastasis from more than one lymph node metastasis in patients with postoperative radiotherapy should be given in order to get a good local control. Low recurrence rate in this group than the reported results (35% to 39%), and higher control rates [2  4], which may be associated with this group UICC2002 staging part T2 of cases included in the T3 stage .

    Many scholars reported cervical lymph node metastasis associated with laryngeal cancer prognosis [2,3,6]. In this group, cN1, to 2 patients the 5-year overall survival and relapse-free survival rates were 16.67% and 43.64% than lower cN0 patients (67.84% and 73.61%, respectively), the difference was statistically significant (P <0.05 and P <0.01), only with T3T4 glottic laryngeal cancer recurrence and survival independent predictors, consistent with the conclusion Nguyen  Tan [2]. Neck lymph nodes in 15 cases of patients with recurrence for cN1,  2 patients with a high relapse rate than cN0 (18.18% vs. 13.13%), suggesting that aggressive treatment of cervical lymph node metastases, and improve survival, reduce the relapse rate, and the other , on the partition neck lymph node surgery for advanced laryngeal cervical lymph node metastases role, there may be overestimated. Only partition neck lymph node dissection or poorly differentiated carcinoma neck T3T4 should be considered in patients with lymph node metastasis supplemented by postoperative radiotherapy or chemotherapy.

    processing there is controversy neck lymph cN0 patients [12, 13], this group cN0 patients, 13 cases of recurrence, the recurrence rate of 13.13%, Ⅱ, Ⅲ area accounted for 92.7%. Cervical lymph node metastasis and recurrence and survival is closely related, we advocate a more active treatment of cervical lymph node. Pathological poorly differentiated primary tumor surgery, especially elderly patients, should be held in Ⅱ, Ⅲ lymph nodes to exploration or preventive neck clear, in order to reduce the relapse rate and improve the cure rate.

    In this group, age is associated with the survival of the other clinical factors, the poor prognosis of patients over 61 years old (47.95% vs 76.45%, P <0.05) [14] The results are consistent with Ampil.

    Estimated recurrence and survival has been the focus of cancer clinical research, yet can not accurately determine the prognosis of patients with laryngeal cancer based on clinical factors, in recent years, genes and proteomics and the screening and application of tumor markers may provide a more accurate prediction of tumor the prognosis methods.