Elective nodal irradiation (ENI) in definitive chemoradiotherapy (CRT) for squamous cell carcinoma of the thoracic esophagus

Background and purpose

There are some reports indicating that prophylactic three-field lymph node dissection for esophageal cancer can lead to improved survival. But the benefit of ENI in CRT for thoracic esophageal cancer remains controversial. The purpose of the present study is to retrospectively evaluate the efficacy of elective nodal irradiation (ENI) in definitive chemoradiotherapy (CRT) for thoracic esophageal cancer.

Materials and methods

Patients with squamous cell carcinoma (SCC) of the thoracic esophagus newly diagnosed between February 1999 and April 2001 in our institution was recruited from our database. Definitive chemoradiotherapy consisted of two cycles of cisplatin/5FU repeated every 5 weeks, with concurrent radiation therapy of 60 Gy in 30 fractions. Up to 40 Gy radiation therapy was delivered to the cervical, periesophageal, mediastinal and perigastric lymph nodes as ENI.

Results

One hundred two patients were included in this analysis, and their characteristics were as follows: median age, 65 years; male/female, 85/17; T1/T2/T3/T4, 16/11/61/14; N0/N1, 48/54; M0/M1, 84/18. The median follow-up period for the surviving patients was 41 months. Sixty patients achieved complete response (CR). After achieving CR, only one (1.0%; 95% CI, 0-5.3%) patient experienced elective nodal failure without any other site of recurrence.

Conclusion

In CRT for esophageal SCC, ENI is effective for preventing regional nodal failure. Further evaluation of whether ENI leads to an improved overall survival is needed.     

Pattern of lymph node metastases and its implication in radiotherapeutic clinical target volume in patients with thoracic esophageal squamous cell carcinoma: A report of 1077 cases

Purpose

To study the pattern of lymph node metastases after esophagectomy and clarify the clinical target volume (CTV) delineation of thoracic esophageal squamous cell carcinoma (ESCC).

Methods and materials

Total 1077 thoracic ESCC patients who had undergone esophagectomy and lymphadenectomy were retrospectively examined. The clinicopathologic factors related to lymph node metastasis were analyzed using logistic regression analysis.

Results

The rates of lymph node metastases in patients with upper thoracic tumors were 16.7% (9/54) cervical, 38.9% (18/54) upper mediastinal, 11.1% (6/54) middle mediastinal, 5.6% (3/54) lower mediastinal, and 5.6% (3/54) abdominal, respectively. The rates of lymph node metastases in patients with middle thoracic tumors were 4.0% (27/680), 3.8% (26/680), 32.9% (224/680), 7.1% (48/680), and 17.1% (116/680), respectively. The rates of lymph node metastases in patients with lower thoracic tumors were 1.0% (5/343), 3.0% (10/343), 22.7% (78/343), 37.0% (127/343), and 33.2% (114/343), respectively. T stage, the length of tumor and the histological differentiation emerged as statistically significant risk factors of lymph node metastases of thoracic ESCC (P < 0.001).

Conclusions

T stage, the length of tumor and the histologic differentiation influence the pattern of lymph node metastases in thoracic ESCC. These factors should be considered comprehensively to design the CTV for radiotherapy (RT) of thoracic ESCC. Selective regional irradiation including the correlated lymphatic drainage regions should be performed as well.     

Details of recurrence sites after elective nodal irradiation (ENI) using 3D-conformal radiotherapy (3D-CRT) combined with chemotherapy for thoracic esophageal squamous cell carcinoma - A retrospective analysis

Purpose

To describe patterns of recurrence of elective nodal irradiation (ENI) in definitive chemoradiotherapy (CRT) for thoracic esophageal squamous cell carcinoma (SqCC) using 3D-conformal radiotherapy.

Methods and materials

One hundred and twenty-six consecutive patients with stages I-IVB thoracic esophageal SqCC newly diagnosed between June 2000 and July 2009 and treated with 3D-CRT in our institution were recruited from our database. Definitive CRT consisted of two cycles of nedaplatin/5FU repeated every 4 weeks, with concurrent radiation therapy of 50-50.4 Gy in 25-28 fractions. Until completion, radiotherapy was delivered to the N1 and M1a lymph nodes as ENI in addition to gross tumor volume.

Results

All 126 patients were included in this analysis, and their tumors were staged as follows: T1/T2/T3/T4, 28/18/54/26; N0/N1, 50/76; M0/M1a/M1b, 91/5/30. The mean follow-up period for the 63 surviving patients was 28.3 (±22.8) months. Eighty-seven patients (69%) achieved complete response (CR) without any residual tumor at least once after completion of CRT. After achieving CR, each of 40 patients experienced failures (local = 20 and distant = 20) and no patient experienced elective nodal failure without having any other site of recurrence. The upper thoracic esophageal carcinoma showed significantly more (34%) relapses at the local site than the middle (9%) or lower thoracic (11%) carcinomas. The 2-year and 3-year overall survival was 56% and 43%, respectively. The 1-year, 2-year and 3-year disease-free survival was 46%, 38% and 33%, respectively.

Conclusions

In CRT for esophageal SqCC, ENI was effective for preventing regional nodal failure. The upper thoracic esophageal carcinomas had significantly more local recurrences than the middle or lower thoracic sites.     

食管癌二野淋巴结清扫术后复发规律探讨

目的 分析胸段食管癌二野淋巴结清扫术后局部复发规律,为术后放疗提供帮助.方法 搜集本科2004-2009年收治的134例胸段食管鳞癌术后局部复发患者的临床资料,依据放疗前定位CT分析复发类型及各区域淋巴结转移情况.结果 食管癌术后淋巴结转移占94.0%,吻合口复发占9.7%,食管原瘤床复发占3.7%.126例淋巴结转移患者中纵隔、锁骨上、腹部的分别占80.2%、43.7%、13.5%(χ2=113.15,P=0.000).淋巴结转移上纵隔占73.8%,左喉返神经区(1L区、2L区、4L区、5区)占38.9%,右喉返神经区(1R区)占43.7%,隆突下占34.1%,奇静脉占15.1%,锁骨上占43.7%[右锁骨上多于左锁骨上(31.7%和16.7%;χ2=7.81,P=0.005)].结论 淋巴结转移是胸段食管癌术后局部复发最主要的类型,原瘤床和吻合口复发少见.锁骨上、喉返神经区、奇静脉淋巴结及隆突下淋巴结是二野淋巴结清扫术后淋巴结转移的高发区.

Abstract：

Objective To investigate the local-regional recurrence in thoracic esophageal cancer after radical surgery including two-field lymph node dissection and provide evidence for postoperative radiotherapy. Methods We reviewed local-regional recurrence for 134 cases with esophageal squamous cell carcinoma after radical surgery from 2004 to 2009. Results In 134 cases, lymph node metastasis rate,anastomosis recurrence rate and tumor bed recurrence rate was 94. 0%, 9. 7% and 3.7%, respectively. As to the 126 cases with lymph node metastasis, significant difference was detected between mediastinal metastasis, supraclavicular metastasis and abdominal lymph node metastasis (80. 2%, 43.7% and 13.5%,respectively, χ2= 113. 15, P = 0. 000). Furthermore, the relative metastasis rate in upper mediastinum,middle mediastinum and the lower mediastinum was 73.8%, 39.7% and 1.6%, respectively, the difference was statistically significant ( χ2 = 139. 11, P = 0. 000 ). Significant difference was identified between right and left supraclavicular lymph node metastasis (31.7% vs 16. 7%, χ2= 7. 81, P = 0. 005 ).To confirm the analysis above,lymph node metastasis rate of left recurrent laryngeal nerve nodes, (including region 1L, 2L, 4L and 5) ,right recurrent laryngeal nerve nodes, azygos nodes, subcarinal nodes, and 2R region was 38.9%, 43.7%, 15.1%, 34.1% and 25.4%, respectively. Conclusions The main characteristics of local-regional recurrence may be lymph node metastasis for esophageal squamous cell carcinoma after radical surgery. On the contrary, tumor bed recurrence is rare. Dangerous regions include supraclavicular nodes, recurrent laryngeal nerve nodes, azygos nodes as well as subcarinal nodes.     

Recommendation for the definition of postoperative radiotherapy target volume based on a pooled analysis of patterns of failure after radical surgery among patients with thoracic esophageal squamous cell carcinoma

Background

Elective use of radiation therapy to treat regionally involved lymph nodes (LNs) after radical surgery for esophageal squamous cell carcinoma (ESCC) is controversial. We studied metastasis patterns through a pooled analysis of published results to guide post-operative radiotherapy (PORT) target designation.

Methods

We searched the MEDLINE database for literature published from May 1977 to March 2018, and found 14 relevant original studies that included 2738 patients with thoracic ESCC. We calculated probabilities of recurrence and metastasis in local (including anastomoses and tumor bed), LNs and distal areas.

Results

Recurrence rates were 1.88% for local, 13.18% for distal, and 22.16% for LNs. Within LNs, recurrence rates were cervical/supraclavicular: 37.69%, upper mediastinal: 44.30%, middle mediastinal: 21.81%, lower mediastinal: 2.57%, abdominal paraaortic: 25% and upper abdominal: 9.56%. Whereas cervical/supraclavicular and upper mediastinal LNs had the highest recurrence rates, abdominal LNs also had high recurrence rates in patients with lower thoracic ESCC.

Conclusions

PORT volume should include the cervical/supraclavicular and upper mediastinal LNs for all thoracic ESCC, and abdominal paraaortic LNs for lower thoracic ESCC. Anastomoses and tumor beds should not be included in the PORT volume if they are not adjacent to the PORT-LN regions. Upper abdominal LNs might not necessarily be included in the PORT volume for thoracic ESCC.

     

Influence of number of metastatic lymph nodes on survival of curative resected thoracic esophageal cancer patients and value of radiotherapy: report of 549 cases

PURPOSE: To analyze the significance of the number of metastatic lymph nodes on survival with and without the addition of prophylactic postoperative radiotherapy (RT) after radical resection of thoracic esophageal carcinoma. METHODS AND MATERIALS: A total of 549 thoracic esophageal squamous cell cancer patients who had undergone radical resection were randomized by the envelope method into a surgery-alone group (S, n = 275) and a surgery plus RT group (S+R, n = 274). We performed a retrospective review of all patients according to the extent of metastasis. The patients were classified into three groups: Group 1, 269 patients (49.0%) without lymph node involvement; Group 2, 159 patients (29.0%) with one to two positive nodes; and Group 3, 121 patients (22.0%) with three or more positive lymph nodes. RESULTS: For the same T stage (T3), the 5-year survival rate for Groups 1, 2, and 3 was 50.6%, 29.3%, and 11.7%, respectively (p = 0.0000). For patients with Stage III, the 5-year survival rate for Groups 1 (T4N0M0), 2 (T3-T4N1M0), and 3 (T3-T4N2M0) was 58.1%, 30.6%, and 14.4%, respectively (p = 0.0092). The 5-year survival rate of the S and S+R groups with positive lymph nodes (Groups 2 and 3) was 17.6% and 34.1% (p = 0.0378). In the positive lymph node groups, the incidence of failure by intrathoracic lymph node metastasis and supraclavicular lymph node metastasis in the S+R group (21.5% and 4.6%, respectively) was lower than in the S group (35.9% and 19.7%, respectively; p <0.012). In the negative lymph node group, the incidence of failure by intrathoracic lymph node metastasis in the S and S+R groups was 27.8% and 13.3%, respectively (p = 0.006). Hematogenous metastasis was the greatest (27.5%) in Group 3 (three or more positive lymph nodes). CONCLUSION: The number of metastatic lymph nodes is one of the important factors affecting the survival of patients with thoracic esophageal carcinoma. In our study, postoperative RT improved the survival of patients with positive lymph nodes. Additionally, postoperative RT reduced the incidence of intrathoracic recurrence and supraclavicular lymph node metastasis for all patients.     

胸段食管鳞癌根治术后失败模式对放疗野设计的指导作用

目的 分析胸段食管鳞状细胞癌根治术后首次复发部位,为进一步修改和完善术后放疗范围提供重要参考依据。方法 回顾分析1999—2007年间在本院行根治术并有明确复发部位记录的195例胸段食管癌患者不同段的首次复发、转移部位。结果 胸上、中段食管癌以胸腔内复发(83.3%、68.0%)为主要部位,而胸下段食管癌则以胸腔内复发(42.9%)和腹腔淋巴结转移(40.8%)为主。术后病理显示淋巴结有无转移与胸腔内复发、锁骨上淋巴结转移、远处转移均无关(χ²=1.58、0.06、0.04,P=0.134、0.467、0.489),但腹腔淋巴结转移的术后淋巴结阳性比例高于阴性(28.7%∶10.6%,χ²=9.94,P=0.001),其中胸中段食管癌的也如此(20.0%∶5.6%,χ²=5.67,P=0.015)。切缘≤3 cm (52例)与>3 cm (142例)者相比术后吻合口复发率明显增加(25.0%∶11.3%,χ²=5.65,P=0.019)。结论 胸腔内为最常见首次复发部位。建议胸上、中段(淋巴结阴性)食管癌放疗靶区包括锁骨上区、上纵隔和瘤床,胸中段(淋巴结阳性)、下段食管癌包括锁骨上区、全纵隔及胃左、腹腔干淋巴引流区。如切缘≤3 cm建议包括吻合口。     

Three-dimensional conformal radiation therapy for squamous cell carcinoma of the esophagus: A prospective phase I/II study

Purpose

A prospective phase I-II study was conducted to determine the tolerance and local control rate of three-dimensional conformal radiotherapy (3-DCRT) for esophageal squamous cell carcinoma (SCC).

Methods and materials

Thirty patients underwent 3-DCRT for thoracic esophageal SCC. PTV1 composed of a 1.2-1.5 cm margin lateral around GTV and 3.0 cm margin superior/inferior of GTV. PTV2 encompassed GTV with a margin of 0.5-0.7 cm. The dose for PTV1 was 50 Gy in 2 Gy daily fractions; PTV2 received a boost of 16 Gy in 2 Gy daily fractions to a total dose of 66 Gy.

Results

Median follow-up time was 18 months. The most common acute toxicity was esophagitis in 63% of patients with RTOG grades 1-2, and in 3% with grade 3. RTOG grades 1-2 radiation pneumonitis developed in 27% of patients. One patient developed pulmonary fibrosis RTOG grade 2 and another patient experienced grade 3 pulmonary fibrosis. Two patients developed mild esophageal stricture requiring dilatation. Two-year overall survival, local disease progression-free rate, and distant metastasis-free rate were 69%, 36% and 56%, respectively.

Conclusions

Although 3-DCRT to 66 Gy for esophageal SCC was well tolerated, the local control was disappointing. The result supports the use of chemoradiation as the standard care for esophageal SCC.     

胸段食管鳞癌术后复发模式及辅助治疗的意义

目的:探讨胸段食管鳞癌术后复发模式,临床病理指标与复发模式的关系及术后辅助治疗的意义。方法:回顾性分析具有完整随访资料,行手术治疗的胸段食管鳞癌256 例,全部病例均按TNM分期（1997年UICC分期法）,率的比较采用χ2检验。结果:全组中141 例术后复发（55.08%）,复发平均时间15.1 个月（4～58个月）,其中淋巴结转移82例（58.16%）;血行性转移15例（10.64%）;混合型转移（血行转移伴淋巴结转移或吻合口复发）26例（18.44%）;吻合口复发18例（12.77%）。 胸段食管癌术后复发与肿瘤浸润深度、临床分期及局部淋巴结转移相关（P=0.034,P=0.037,P=0.004）。 胸上段食管癌术后淋巴结转移主要发生于颈部;胸下段食管癌术后腹部及中、下纵隔淋巴结转移率明显大于上纵隔和颈部淋巴结转移率;胸中段食管癌术后上纵隔和颈部淋巴结转移率大于中、下纵隔和腹部。辅助放化疗组淋巴结转移及吻合口复发33例,与无辅助治疗组比较差异有统计学意义（P=0.012）,辅助放化疗组血行及混合转移13例,与无辅助治疗组比较差异无统计学意义（P=0.065）。 结论:胸段食管鳞癌术后复发主要为局部淋巴结转移;肿瘤浸润深度、临床分期及局部淋巴结转移与术后复发相关;胸上段食管癌术后颈部淋巴结转移率高,胸下段食管癌术后腹部淋巴结转移率高;术后放化疗治疗对局部控制具有统计学意义。      

Accuracy of preoperative diagnosis of lymph node metastasis for thoracic esophageal cancer patients from JCOG9907 trial

Background

Accurate clinical evaluation of lymph nodes is crucial for selection of the optimum treatment strategy for individual esophageal cancer patients. This study investigated the accuracy of preoperative clinical diagnosis of lymph node metastasis for patients with clinical stage II/III esophageal squamous cell carcinoma.

Methods

Patients assigned to receive surgery and postoperative chemotherapy in JCOG9907 trial were studied to evaluate the concordance between clinical and pathological nodes. Preoperative diagnosis was based on computed tomography or magnetic resonance imaging.

Results

Among 166 patients in the postoperative group, 160 with sufficient pathological data were studied. The patient background characteristics were: male/female, 147/13; median age, 61 years (range 39–75 years); primary tumor site (upper/middle/lower), 15/76/69; cN0/cN1, 53/107. The sensitivity and specificity of clinical nodes for diagnosis of pathological nodes were 72.7 and 51.3 %, respectively; the positive and negative predictive values were 82.2 and 37.7 %, respectively. The lymph nodes overestimated in the preoperative diagnosis included thoracic paratracheal lymph nodes (#106) (n = 8), middle thoracic paraesophageal lymph nodes (#108) (n = 4), lymph nodes along the lesser curvature (#3) (n = 4), right cardiac lymph nodes (#1) (n = 3), and left cardiac lymph nodes (#2) (n = 2).

Conclusion

Diagnosis of clinical nodes has low specificity and low negative predictive value for prediction of pathological node category in the preoperative diagnosis of lymph node metastasis for patients with locally advanced resectable esophageal cancer. Clinical staging techniques must therefore be improved for accurate preoperative diagnosis.

     

Brachytherapy with permanent gold grain seeds for squamous cell carcinoma of the lip

Purpose

To describe the use of radioactive gold grain implantation for squamous cell carcinoma of the lip.

Methods

Retrospective review of 51 patients treated with permanent gold (¹⁹⁸Au) grain implant brachytherapy. The seed arrangement delivered a dose of 5500 cGy at 0.5 cm from a single plane. Primary endpoints were local recurrence and cosmetic outcome.

Results

Median follow-up was 27 months. Median age was 69 years. The majority (90%) were T1 lesions. None of the patients had evidence of regional lymph node or distant metastasis. Twelve patients had recurrent disease with prior surgery and five patients had previous head and neck radiation. Local control was achieved in 49 patients. Good cosmesis was achieved in 48 patients. Two-year actuarial estimates for local failure-free survival, disease-free survival and overall survival were 97.9%, 94.1% and 87.9%, respectively; no deaths were attributable to lip cancer.

Conclusions

Gold grain interstitial low-dose rate brachytherapy provides excellent local control and cosmesis in patients with squamous cell carcinoma of the lip. This technique provides an excellent option for patients that are elder or live remotely. It is particularly useful for lesions that are small, in previously radiated areas, or treated with prior surgery.     

Impact on survival of the number of lymph nodes removed in patients with node-negative gastric cancer submitted to extended lymph node dissection

Purpose

This study was designed to establish whether the number of lymph nodes removed has an effect on prognosis in patients with node-negative gastric cancer.

Patients and Methods

We retrospectively analysed data of 114 consecutive patients who underwent gastrectomy and extended lymph node dissection for node-negative adenocarcinoma of the stomach between 2000 and 2005. Standard survival methods and restricted cubic spline multivariable Cox regression models were applied.

Results

Median age was 63 years and 67 patients out of 114 (59%) were males. Median number of dissected LNs was 22 (range 2-73). Median follow-up was 76 months. Patients who had ≤15 nodes removed had significantly worse distant disease-free survival, disease-free survival and overall survival at multivariable analysis than other patients. The results did not change when pT1 and pT2-3 cancer patients were analysed separately. The risk of distant metastases decreased as the number of dissected lymph nodes increased (>15).

Conclusions

More extended lymph node resection offered survival benefit even in the subgroup of patients with early stage disease. Lymphadenectomy involving more than 15 lymph nodes should be performed for the treatment of node-negative gastric cancer.

Synopsis

The impact on survival of the number of lymph nodes removed in patients with node-negative gastric cancer has not been established. This study suggests that more extended lymph node resection offers protection, as patients who had ≤15 nodes removed had significantly worse disease-free survival and overall survival at multivariate analysis than patients in whom >15 nodes were removed.     

胸段食管癌术后局部复发因素在确定术后放射治疗指征及放疗靶区中的价值

目的:探讨胸段食管癌术后局部复发因素对确定术后放疗指征及术后放疗靶区的指导意义.方法:回顾性分析2009年1月-2011年6月75例胸段食管癌术后局部复发患者的临床病理资料,探讨局部复发规律及其影响因素.结果:75例患者中,男性68例,女性7例;术前病变位于胸上段8例,胸中段53例,胸下段14例;术后病理分期:Tis期0例,T1期6例,T2期17例,T3期48例,T4期4例;N0期35例,N1期40例;临床分期:Ⅰ期5例,ⅡA期26例,ⅡB期7例,Ⅲ期35例,ⅣA期1例,ⅣB期1例;病理分型:鳞癌72例,腺癌2例,鳞癌小细胞癌混合型1例;食管癌根治术中行喉返神经旁淋巴结清扫14例,未行清扫61例;颈部淋巴结清扫9例,未行清扫66例.胸段食管癌根治术后局部复发时间为1～68个月,平均复发时间为13个月.局部复发部位包括双侧锁骨上区27例,上纵隔47例,中纵隔11例,下纵隔为0例,腹腔淋巴结转移4例,吻合口复发8例.结论:胸段食管癌根治术后局部复发位置主要是在双侧锁骨上区、中上纵隔和吻合口,且复发者主要为未行喉返神经淋巴结清扫和颈部淋巴结清扫的患者.建议应结合不同的手术方式及术后病理分期来决定是否应行术后放疗,放疗靶区则以双侧锁上区、中上纵隔和吻合口为主.     

Re-appraisal of N2 disease by lymphatic drainage pattern for non-small-cell lung cancers: by terms of nodal stations, zones, chains, and a composite

Purpose

N2 non-small-cell lung cancer (NSCLC) is a heterogeneous disease with an extremely wide range of 5-year survival rates. A composite method of sub-classification for N2 is likely to provide a more accurate method to more finely differentiate prognosis of N2 disease.

Methods

A total of 720 pN2 (T1-4N2M0) NSCLC cases were enrolled in our retrospective analysis of the proposed composite method. Survival rates were respectively calculated according to the N2 stratification methods: singly by “nodal stations”, “nodal zones”, or “nodal chains”, or by combination of all three. Statistical analysis was carried out by Kaplan-Meier and Cox regression models.

Results

A total of 10,199 lymph nodes (8059 mediastinal; 2140 hilar and intra-lobar) were removed. By nodal station, there were 173 cases of single-station involvement and 547 multi-stations. By nodal zone, there were 413 single-zone involvement and 307 with multiple zones. By nodal chain, there were 311 cases with single-chain and 409 multi-chain involvements. The overall 5-year survival was 20% and median survival time was 27.52 months. The 5-year survival was significantly better for cases of single-zone involvement, as compared to multi-zones (29% vs. 6%, p < 0.0001). The 5-year survival rates of single- and multi-chains involvement were 36% and 8%, respectively (p < 0.0001). When taking all of the above grouping methods into consideration, the N2 disease state could be further sub-classified into two subgroups with respective survival rates of 36% and 7% (p < 0.0001). Subgroup I was composed of individuals with single-chain involvement and having either one or two station metastasis; individuals with any other metastasis combinations formed Subgroup II. Multivariate analysis revealed that the composite sub-classification method, number of positive lymph nodes, ratio of nodal metastasis, and pT information were the most important risk factors of 5-year survival.

Conclusions

By combining the three N2 stratification methods based on “stations”, “zones”, and “chains” into one composite method, prognosis prediction was more accurate for N2 NSCLC disease. Single nodal chain involvement, which may be either one or two nodal stations metastasis, is associated with best outcome for pN2 patients.     

胸段食管鳞癌淋巴结转移数和区域与术后放疗价值的临床研究

目的 对胸段食管鳞癌根治术患者的淋巴结转移数和区域与术后放疗的疗效进行分析,评价术后放疗价值.方法 选择2007年前14年内我院胸段食管癌根治术后病理诊断鳞癌、淋巴结转移阳性及无远处血道转移的N_1期患者945例,其中单纯手术590例,术后放疗355例.术后3～4周开始2 Gy/次放疗,中位剂量50 Gy分25次5周完成.结果 随访率为94.5%,随访满5年者189例.5年生存率单纯手术组和术后放疗组分别为29.6%和38.0%(X~2=10.44,P=0.001).分层分析术后放疗较单纯手术可提高淋巴结转移数3～5个、>5个和仅有锁骨上区及上纵隔区淋巴结转移的5年生存率(30.5%:23.1%,χ~2=4.11,P=0.043;16.7%:8.9%,χ~2=6.87,P=0.009;45.5%:34.9%,χ~2=5.37,P=0.020),而不能提高淋巴结转移数1～2个和仅有中下纵隔及上腹部区淋巴结转移的生存率(50.7%:41.2%,χ~2=3.30,P=0.069;32.0%:27.7%,χ~2=2.22,P=0.137),但可降低锁骨上区及中上纵隔区淋巴结转移例数(15:76,χ~2=18.10,P=0.000;18:97,χ~2=26.81,P=0.000).结论 N_1期胸段食管鳞癌三野根治术后放疗可提高淋巴结转移数≥13个和仪有锁骨上区及上纵隔区淋巴结转移者的生存率,并能降低锁骨上区及中上纵隔区淋巴结转移率.     

Computed tomography–based distribution of involved lymph nodes in patients with upper esophageal cancer

Background

Delineating the nodal clinical target volume (ctvn) remains a challenging task in patients with cervical or upper thoracic esophageal carcinoma (ec). In particular, the extent of the lymph area that should be included in the irradiation field remains controversial. In the present study, the extent of the ctvn was determined based on the incidence of lymph node involvement mapped by computed tomography (ct) imaging.

Methods

Our study included 468 patients who were diagnosed with cervical and upper thoracic ec and who received staging information between June 2005 and April 2011. The anatomic distribution of metastatic regional lymph nodes was mapped using ct images and grouped using the levels established by the Radiation Therapy Oncology Group. The probability of the various groups being involved was examined. If a lymph node group had a probability of 10% or more of being involved, it was considered at high risk for metastasis, and elective treatment as part of the ctvn was recommended.

Results

Lymph node involvement was mapped by ct in 256 patients (54.7%). Not all lymph node groups should be included in the ctvn. For cervical lesions, the involved lymph nodes were located mainly between the hyoid bone and the arcus aortae; the recommended ctvn should consist of the neck lymph nodes at levels iii and iv (supraclavicular group) and thoracic groups 2 and 3P. In upper thoracic ec patients, most of the involved lymph nodes were distributed between the cricoid cartilage and the subcarinal area; the ctvn should cover the supraclavicular group and thoracic nodal groups 2, 3P, 4, 5, and 7.

Conclusions

Our ct-based study indicates a specific distribution and incidence of metastatic lymph node groups in patients with cervical and upper thoracic ec. The results suggest that regional lymph node groups should be electively included in the ctvn for precise radiation administration.     

胸中段食管鳞癌淋巴结转移度及合理清扫范围的临床研究

目的:本研究通过分析胸中段食管鳞癌淋巴结转移规律及淋巴结转移度对预后的影响,探讨合理的淋巴结清扫范围.方法:对129例经现代二野淋巴结清扫术的胸中段食管鳞癌患者的临床资料进行回顾性分析.结果:全组患者淋巴结转移率为56.6%,总淋巴结转移度(阳性淋巴结数/清扫淋巴结总数,LMR)为11.3%,上纵隔淋巴结转移率为43.4%.最常见的淋巴结受累区域为食管旁、右喉返神经旁、贲门及胃左血管旁、隆突下.影响淋巴结转移的主要因素为肿瘤浸润深度、分化程度及肿瘤长度.无淋巴结转移组、淋巴结转移度≤20%组和淋巴结转移度>20%组患者5年生存率分别为50.4%、31.0%和6.8%,结果差异有统计学意义(P=0.000).结论:淋巴结转移度是判断食管癌预后的一个重要因素,胸中段食管癌应该常规行包括双侧上纵隔的现代二野淋巴结清扫术.     

胸段食管癌术后预防性照射的预后分析

目的 探讨胸段食管癌根治术后预防性照射的范围对长期生存的影响。 方法 回顾分析2000— 2007年间 201例胸段食管癌根治术后行预防性照射患者资料,比较照射范围差异对生存影响,并对可能影响预后的因素行Cox模型多因素分析。Kaplan Meier法计算OS率,Logrank检验差异。结果 5年随访率为97.0%。全纵隔、全纵隔+胃左区、全纵隔+双锁骨上区、中上纵隔+双锁骨上区、全纵隔+双锁骨上+胃左区照射的 5年OS率分别为21.7%、37.1%、38.7%、34.8%、19.8%( P=0.406),多因素分析结果显示仅仅术后N分期为预后影响因素(P=0.009)。预防性照射后锁骨上淋巴结转移11例、中上纵隔淋巴结转移34例、腹腔淋巴结转移10例。结论 胸段食管癌根治术后预防性照射范围应包括中上纵隔和双锁骨上区。     

pT3N0M0期胸段食管鳞癌患者术后失败原因分析及其术后放疗思考

目的 探讨pT₃N₀M₀期胸段食管鳞癌患者术后失败模式,并依据其失败模式讨论术后放疗意义及可行性。方法 对2007-2010年符合入组条件的227例pT₃N₀M₀期食管癌术后患者进行回顾分析,主要分析其单纯手术后失败模式,同时结合相关研究来探讨pT₃N₀M₀期胸段食管鳞癌患者术后辅助性放疗意义及适合人群。应用Kaplan-Meier法计算OS、LR、DM并Logrank法检验和单因素预后分析,Cox模型多因素预后分析。结果 治疗后出现胸腔内LR 58例(25.6%),DM 27例(11.9%),其中10例为LR+DM。单纯胸腔内纵隔淋巴结复发所占比率为50%(29/58)。单因素分析显示胸上段食管癌患者术后3、5年OS率低于胸中、下段患者(P=0.000),而其胸腔-区域复发率高于后两者(P=0.047);低分化鳞癌患者3、5年OS率低于中高分化鳞癌患者(P=0.005),而其DM率高于后者(P=0.000)。多因素分析显示患者不同病变部位、不同病理分化程度为患者OS的影响因素(P=0.014、0.010);病变部位为影响患者胸腔内LR的影响因素(P=0.046);不同病理分化程度为DM的影响因素(P=0.000)。结论 pT₃N₀M₀期胸段食管鳞癌患者行常规胸腹两野根治术后胸腔内LR为其主要治疗失败模式,且胸上段食管癌高于胸中、下段食管癌患者,建议pT₃N₀M₀期胸段食管鳞癌胸上段患者行术后放疗。     

Occult mediastinal lymph node metastasis in NSCLC patients diagnosed as clinical N0-1 by preoperative integrated FDG-PET/CT and CT: Risk factors, pattern, and histopathological study

Background

Integrated F18-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) is widely used for mediastinal lymph node (MLN) staging in patients with non-small cell lung cancer (NSCLC). However, FDG-PET/CT has certain limitations. Prediction of occult MLN metastasis could allow selection of candidates for preoperative cervical mediastinoscopy or endobronchial ultrasound-guided transbronchial needle aspiration. This study defined risk factors for occult MLN metastasis in patients with NSCLC patients who were diagnosed as clinical N0-1 by preoperative integrated FDG-PET/CT and CT.

Methods

Consecutive patients with NSCLC who underwent staging using integrated FDG-PET/CT as an adjunct to CT prior to lung resection from October 2006 to September 2009 were evaluated retrospectively. The prevalence of MLN metastasis in patients diagnosed as clinical N0-1 was analyzed according to clinicopathological factors such as tumor location, tumor size, histology, and FDG uptake by the primary tumor. Risk factors for occult MLN metastasis were defined by multivariate analysis. Patterns of occult MLN metastasis were also analyzed and the involved MLNs were further examined histopathologically.

Results

The incidence of MLN metastasis was 11% (24 patients of 224). Multivariate analysis identified adenocarcinoma (P = 0.04), tumors located in upper or middle lobe (P = 0.02), tumor size >3 cm (P = 0.01), and SUV_max of primary tumor >4.0 g/ml (P = 0.04) as significant risk factors for MLN metastasis. The pattern of occult MLN metastasis was typical for NSCLC cases. The size of metastatic foci were small, with 68% of foci smaller than 4.0 mm.

Conclusions

The present study demonstrated that adenocarcinoma, tumors located in the upper or middle lobe, tumor size >3 cm, and SUV_max of primary tumor >4.0 g/ml are risk factors for occult MLN metastasis in patients with NSCLC who were diagnosed as clinical N0-1 by preoperative integrated FDG-PET/CT and CT. Patients with tumors located in the right upper or middle lobe are considered candidates for cervical mediastinoscopy because the involved metastatic mediastinal lymph nodes are easily accessible by these modalities.