Thoracic Esophageal Squamous Cell Carcinoma Patients Research Articles

Cancer peptide vaccine to suppress postoperative recurrence in esophageal SCC patients with induction of antigen-specific CD8+ T cell.

e14635 Background: This is a following report of the exploratory phase II study of adjuvant peptide vaccine for thoracic esophageal squamous cell carcinoma (TESCC) (abstract #3087 in ASCO2016), focusing on an association of immunological responses with clinical outcomes. Three HLA-A-24-restricted epitope peptides derived from cancer-testis antigens, up-regulated lung cancer 10 (URLC10), cell division cycle associated 1 (CDCA1) and KH domain-containing protein overexpressed in cancer 1 (KOC1), were used in this study. Methods: TESCC patients who underwent neoadjuvant therapy followed by curative resection (Dec./2009 to Sep./2014) and were found LN metastasis were enrolled. One mg each of three peptides mixed with Montanide was injected to patients with HLA-A*2402 20 times in a 6-months period. No other adjuvant therapy was given until recurrence occurred. Primary endpoint is relapse-free survival (RFS). Immunological responses were examined by ELISPOT assay and immunohistochemistry (IHC). Results: 33 patients were enrolled in the vaccine group (VG) and 30 with non-HLA-A*2402 were used as controls (CG). There was no significant difference in clinical backgrounds between the two groups. 5-year RFS in the VG was 44.6% while that in the CG group was 31.6% (p = 0.207); patients who showed CD8+ CTL induction to multiple peptides tend to show better RFS rate [3/2/1 peptides = 69.0(n = 20)/46.8(n = 11)/0%(n = 2), respectively]. Five-year esophageal cancer-specific survival (ECSS) were 58.4% in the VG compared with 35.4% in the CG (p = 0.156); 90.0% (n = 11) vs. 50.0% (n = 15) and 43.8% (n = 22) vs. 24.0%(n = 15) in pN1 and pN2-3 groups, respectively. Regarding the CD8+ positivity, ECSS was improved only in the negative group (56.6% in VG vs. 26.7% in CG). Classification by T cell positivity and PD-L1 expression [type I(+/+), II(-/-), III(-/+) and IV(+/-)] showed 5-year ECSS to be 100%(n = 3), 66.4%(n = 19), 20.0%(n = 5) and 44.4%(n = 6). Conclusions: Our cancer peptide vaccines induced the antigen-specific CD8+ T cell highly and efficiently, and suppressed recurrence with the strong immune responses. Clinical trial information: UMIN000003557.

Radical esophagectomy for thoracic esophageal squamous cell carcinoma followed by adjuvant radiotherapy with or without chemotherapy: Which is more beneficial?

e15597 Background: The current guidelines of the National Comprehensive Cancer Network for thoracic esophageal squamous cell carcinoma(TESCC) are commended no additional treatments after surgery unless the margins are positive.The optimal therapeutic options in TESCC initially treated after surgery remains controversial .This retrospective study compared the efficacy and side effect profile between postoperative adjuvant radiotherapy(RT) and chemoradiotherapy(CRT) in stage II or III TESCC patients who underwent curative esophagectomy. Methods: From January 2006 to December 2013 , 272 cases with pathological confirmed stage II or III TESCC, who had undergone complete esophagectomy, were eligible for analysis.Of these patients, 148 cases received postoperative CRT–at least 2 courses of cisplatin plus fluorouracil or paclitaxel– while the other 124 cases received RT(≥45Gy) alone.The primary end point was overall survival (OS) and the secondary endpoint were disease free survival (DFS) and toxic reactions. Results: In CRT and RTgroups,the OS rates at 1, 3 and 5 years were 91.8% vs 83.8% , 51.3% vs 31.5% and 25% vs 9.68% , respectively(P < 0.01).In CRT and RTgroups, the median OS were 39 months (95% CI, 31.6 to 46.3 months) and 30 months (95% CI, 21.0 to 38.9 months), respectively(P = 0.213), and the median DFS were 23 months (95% CI, 14.7 to 31.3 months) and 16 months (95% CI, 13.3 to 18.6 months),respectively(P = 0.155). Univariate and multivariate analyses showed stage, N stage and the number of lymph nodes removed were independent prognostic factors for OS. There were no statistically differences between the two groups for both recurrence and metastasis rates(P > 0.05). Toxic reactions, including myelosuppression and gastrointestinal reaction, were significantly more common in the CRT group than in the RT group (P < 0.05). No significant differences in incidence of other toxic reactions were found between the two groups. Conclusions: Our results indicate that, in stage II or III TESCC patients, compared with postoperative RT,CRT has a tendency to improve survival. Toxic reactions were more common with CRT than with RT alone, but patients could tolerate CRT.

Neoadjuvant versus adjuvant chemoradiation for stage II-III esophageal squamous cell carcinoma: a single institution experience.

Esophageal cancer is the eighth most common cancer worldwide. It is the fourth most common cause of cancer death in China and esophageal squamous cell carcinoma (ESCC) is the most prevalent histologic type. Many clinical trials have explored the value of neoadjuvant or adjuvant chemoradiation therapy in potentially resectable ESCC; however, these studies have produced conflicting results. This retrospective study was performed to investigate whether patients with resectable stage II/III ESCC should receive neoadjuvant or adjuvant therapy in addition to surgery. A review of stage II/III thoracic ESCC patients who underwent esophagectomy and either neoadjuvant or adjuvant chemoradiation was performed. Chemotherapy regimen consisted of cisplatin 75 mg/m2 divided into 3 days and fluorouracil 500 mg/m2 on days 1 to 5. The patients who underwent neoadjuvant therapy were treated with one cycle of chemotherapy concurrently with radiotherapy (40 Gy in 20 fractions, 5 days/week), and those receiving adjuvant therapy were treated with two cycles of chemotherapy concurrently with radiotherapy (46-50 Gy in 23-25 fractions, 5 days/week). A total of 122 patients met inclusion criteria, of which 49 underwent neoadjuvant chemoradiation and 73 underwent adjuvant chemoradiation. Median follow up was 36.5 months. The median survival times and 3, 5-year overall survival (OS) rates for the neoadjuvant and adjuvant groups were 39.3 versus 31.5 months, and 53.0%, 45.7% versus 42.9%, 29.7%, respectively (P = 0.091). For the patients with stage III ESCC, the median survival times and 5-year OS rates for the neoadjuvant and adjuvant groups were 39.3 versus 21.3 months, and 43.4% versus 21.0%, respectively (P = 0.021). Among lymph node-positive patients, the median survival times and 5-year OS rates for the neoadjuvant and adjuvant groups were 55.6 versus 23.7 months, and 43.0% versus 25.7%, respectively (P = 0.085). The incidence of perioperative and postoperative complications was comparable between the two groups (P > 0.05). For patients with resectable stage II/III ESCC, neoadjuvant chemoradiation does not increase postoperative complications and is associated with a trend toward better OS when compared to adjuvant chemoradiation.

Analysis of postoperative failure model in patients with stage pN0 esophageal squamous cell carcinoma and its effect on postoperative radiotherapy

Objective To investigate the failure model of patients with stage pN0 thoracic esophageal squamous cell carcinoma (TESCC) after surgery alone and to discuss the feasibility of postoperative radiotherapy. Methods A retrospective analysis was performed on 473 patients with TESCC who received surgery alone from January 2007 to December 2010. The feasibility of adjuvant radiotherapy forpN0 TESCC patients was investigated through the failure model of postoperative patients. Results Of all patients, there were 57 cases with chest-regional recurrence (12.1%), most of which occurred in the mediastinal lymph nodes(52 case). There were 42 (8.9%) patients were identified as distant metastasis (DM), of which 13 cases were found to have both local recurrence and DM, and the total failure rate was 20.9%. The chest-regional recurrence rate of upper TESCC was statistically significantly higher than middle and lower (χ2=7.469, P 0.05). The chest-regional recurrence rate and DM rate of the advanced T stage were significantly higher than those of the early T stage(χ2=10.247, 7.886, P<0.05). The result of univariate analysis showed that disease site, the degree of adhesion, postoperative stump were significant factors of chest-regional recurrence rate(χ2=14.232, 9.486, 7.546, P<0.05). Gender, smoking and preoperative weight loss ≥5 kg significantly influenced DM(χ2=10.823, 10.275, 6.065, P<0.05). In addition, the T stage was the significant influence factor of chest-regional recurrence and DM(χ2=15.994, 12.885, P<0.05). The result of multivariate analysis showed that T stage and postoperative stump were independent factors of chest-regional recurrence(P<0.05). Smoking was an independent factor of DM(P<0.05). Conclusions There was a high rate of chest-regional recurrence in patients with stage pN0 TESCC who received surgery alone. Postoperative radiotherapy was recommended for patients with upper TESCC, advanced T stage, severe local adhesion , positive margin in and postoperative stump. Male, smoking and preoperative weight loss≥5 kg were associated with higher DM rate. Key words: Esophageal neoplasms; Prognosis; Failure model

Patterns of recurrence in patients with stage Ⅲ thoracic esophageal squamous cell carcinoma after radical resection

Objective: To evaluate the patterns of recurrence and their value on target delineation for postoperative radiotherapy (RT) in patients with stage Ⅲ thoracic esophageal squamous cell carcinoma (ESCC) after esophagectomy. Methods: 395 patients (302 male and 93 female) of stage Ⅲ thoracic ESCC after radical resection were enrolled in this study. Among them, 375 patients were treated with two-field and other 20 with three-field esopahgectomy. 97 patients were treated with surgery alone, 212 with adjuvant postoperative chemotherapy (CT), 56 with radiotherapy (RT) and 30 with CT plus RT. Diagnosis of recurrence was primarily based on CT images, some of which were biopsy confirmed. The location and patterns of tumor recurrence were analyzed. Results: The overall failure rates was 75.7% (299/395). Locoregional recurrence (LR) was found in 48.4% of the patients, distant metastasis (DM) in 16.2%, and LR plus DM in 4.3%. There were 208 patients occurred with LR, 26.9% (56) recurred in supraclavicular/neck (51 in supraclavicular), 69.7% (145) in mediastinum (88.7% in upper-mediastinum), and 19.7% (41) in upper abdomen (38 in para-aortic lymph node). Chi-square test and logistic multivariate regression analysis showed that TNM stage and adjuvant therapy were significantly associated with LR (P<0.05). Postoperative RT reduced LR (mainly LR in mediastinum), but postoperative CT did not decrease LR. Conclusions: The recurrence rate is very high in stage Ⅲ thoracic ESCC patients, LR is the main pattern of failure. TNM stage is one of the most important factors for LR. Postoperative radiotherapy can reduce LR but postoperative chemotherapy does not decrease LR. Upper-mediastinum is the most common site of recurrence, followed by supraclavicular and para-aortic regions; these areas should be considered as the key target of postoperative radiotherapy.

TNM Staging Matched-pair Comparison of Surgery After Neoadjuvant Chemoradiotherapy, Surgery Alone and Definitive Chemoradiotherapy for Thoracic Esophageal Squamous Cell Carcinoma.

Introduction: We used the TNM staging matched-pair approach to compare the efficacies of surgery after neoadjuvant chemoradiotherapy (NCT), surgery alone and definitive chemoradiotherapy (CCRT) in patients with localized advanced thoracic esophageal squamous cell carcinoma (ESCC). Methods: A total of 642 patients with ESCC from previous studies were studied. Patients whose treatment involved NCT + surgery and surgery alone were compared with patients receiving CCRT. Prospensity score matched-pair comparison based on pre-treatment TNM staging was developed to assess the efficacies of these treatment options. Results: Prospensity score matched-pair comparison to control for bias generated a cohort of 274 patients who were eligible for comparison. The 3-year OS rate was 70.0% in the NCT + surgery group, compared to 51.7% in the surgery group (p=0.000) and 61.9% in the CCRT group (p=0.082). With the TNM staging matched-pair approach, the CCRT group had more upper thoracic ESCC patients (43/92, 46.7%), while the surgery group had more lower thoracic ESCC patients (37/92, 40.2%). The 3-year OS rates were comparable between the surgery alone group and CCRT group (p=0.109). Conclusions: NCT plus surgery was superior in OS to surgery alone or CCRT. The 3-year OS rates were comparable between the surgery alone group and CCRT group with TNM staging matched-pair approach. Further investigation is warranted to confirm these findings.

Adjuvant chemotherapy with paclitaxel and cisplatin in lymph node-positive thoracic esophageal squamous cell carcinoma.

ObjectiveNo standard postoperative adjuvant chemotherapy has ever been established in node-positive esophageal squamous cell carcinoma (ESCC). This is a study to explore the effect of postoperative paclitaxel (PTX) and cisplatin (DDP) in lymph node-positive, completely resected thoracic ESCC patients.MethodsWe conducted a prospective phase II trial. Patients had pathologically node-positive thoracic ESCC with negative margins. Outcomes of disease-free survival (DFS) and overall survival (OS) were compared with a matched historical control cohort. The postoperative chemotherapy regimen consisted of 4 to 6 cycles of PTX 150 mg/m2 administered intravenously on d 1 followed by DDP 50 mg/m2 on d 2 every 14 d. ResultsForty-three patients were accrued from December 2007 to May 2012 at Cancer Hospital of Chinese Academy of Medical Sciences for adjuvant chemotherapy. The historical control group consisted of 80 patients who received complete resection but no adjuvant chemotherapy during the same period of time. Of the 43 patients with adjuvant chemotherapy, 37 (86.0%) patients completed 4 to 6 cycles of chemotherapy. The 3-year DFS rates were 56.3% in the adjuvant group and 34.6% in the control group (P=0.006). The 3-year OS rates were 55.0% in the adjuvant group and 37.5% in the control group (P=0.013). Multivariate analysis revealed that postoperative chemotherapy was the significant predictor for improved OS (P=0.005).ConclusionsBiweekly adjuvant PTX and DDP might improve 3-year DFS and OS in lymph node-positive, curatively resected thoracic ESCC patients. These conclusions warrant further study in randomized phase III clinical trials.

Genetic variants in CHEK1 gene are associated with the prognosis of thoracic esophageal squamous cell carcinoma patients treated with radical resection.

CHEK1 gene is known to play an important role in tumor progression by cell cycle control. However, the association between CHEK1 and the prognosis of esophageal squamous cell carcinoma (ESCC) is unclear. In this study, we explored the association between genetic variants in CHEK1 gene and prognosis of ESCC patients treated with radical resection. A total of 131 thoracic ESCC patients who underwent radical resection were included in this retrospective study and genotyped using the MassArray method. According to the univariate Cox hazard analysis, the GT/TT genotype of CHEK1 rs555752 was shown to be strongly related to a decreased overall survival (OS) (HR=2.560, 95% CI: 1.415-4.631, P=0.002) and disease-free survival (DFS) (HR=2.160, 95% CI: 1.258-3.710, P=0.005). Furthermore, according to the multivariate Cox hazard analysis and multiple testing, patients with the GT/TT genotype of CHEK1 rs555752 had a notably decreased OS (HR=2.735, 95% CI: 1.468-5.096, P=0.002, Pc=0.006) and DFS (HR=2.282, 95% CI: 1.292-4.023, P=0.004, Pc=0.012). In conclusion, genetic variants of the CHEK1 gene are significantly related to OS and DFS of ESCC patients, and may therefore be predictors of the prognosis of thoracic ESCC after surgery.

Prognostic Factors for Post-Recurrence Survival in Patients with Thoracic Esophageal Squamous Cell Carcinoma after Curative Resection

Background/Aims: We investigated factors affecting the post-recurrence prognosis in order to develop adequate therapeutic guidelines for determining the indication for treatment of recurrent esophageal squamous cell carcinoma (ESCC). Methods: Ninety-three thoracic ESCC patients who developed postoperative recurrence after undergoing curative esophagectomy with 3-field lymphadenectomy at our institute and who received treatment for recurrence were enrolled in this study. Results: A univariate analysis showed that distant organ recurrence, the number of recurrent tumors, the longest diameter of the largest recurrent tumor, the sum of all of the longest diameters of the recurrent tumors, invasion into adjacent structures and the speed of growth of the representative recurrent tumors were significantly associated with the post-recurrence prognosis. A multivariate analysis showed that distant organ recurrence, the longest diameter of the largest recurrent tumor, invasion into adjacent structures and the speed of growth of the representative recurrent tumors were significantly associated with the prognosis. The patients whose recurrent tumor(s) did not meet all 4 of these factors showed a better prognosis. In contrast, the prognosis of the patients whose recurrent tumor(s) demonstrated all 4 factors was almost the same as that observed in the patients who did not receive any treatment for recurrence. Conclusions: The evaluation of these 4 factors may potentially be used to determine the indication for treatment for recurrence.

Precise delineation of clinical target volume for crossing-segments thoracic esophageal squamous cell carcinoma based on the pattern of lymph node metastases.

This work aims to investigate lymph node metastases (LNM) pattern of crossing-segments thoracic esophageal squamous cell carcinoma (ESCC) and its significance in clinical target volume (CTV) delineation. From January 2000 to December 2014, 3,587 patients with thoracic ESCC underwent surgery including esophagectomy and lymphadenectomy at Shandong Cancer Hospital and Institute. Information of tumor location based on preoperative endoscopic ultrasonography (EUS) and postoperative pathological results were retrospectively collected. The extent of the irradiation field was determined based on LNM pattern. Among the patients reviewed, 1,501 (41.8%) were crossing-segments thoracic ESCC patients. The rate of LNM were 12.1%, 15.2%, 8.0%, 3.0%, and 7.1% in neck, upper mediastinum, middle mediastinum, lower mediastinum, and abdominal cavity for patients with upper-middle thoracic ESCC, 10.3%, 8.2%, 11.0%, 4.8%, 8.2% for middle-upper thoracic ESCC, 4.8%, 4.8%, 24.1%, 6.3%, 22.8% for middle-lower thoracic ESCC and 3.9%, 3.1%, 22.8%, 11.9%, 25.8% for lower-middle thoracic ESCC, respectively. The top three sites of LNM were 105 (12.1%), 108 (6.1%), 101 (6.1%) for upper-middle thoracic ESCC, 108 (8.2%), 105 (7.5%), 106 (6.8%) for middle-upper thoracic ESCC, 1 (18.8%), 108 (17.9%), 107 (9.6%) for middle-lower thoracic ESCC, 1 (21.3%), 108 (16.1%), 107 (10.1%) for lower-middle thoracic ESCC. Crossing-segments thoracic ESCC was remarkably common among patients. When delineating their CTV, tumor location should be taken into consideration seriously. For upper-middle and middle-upper thoracic ESCC, abdominal cavity may be free from irradiation. For middle-lower and lower-middle thoracic ESCC, besides irradiation of relative mediastinal, irradiation of abdominal cavity can't be neglected.

Postoperative Intensity-Modulated Radiotherapy Improved Survival in Lymph Node-Positive or Stage III Thoracic Esophageal Squamous Cell Carcinoma

Background: The aim of this study was to retrospectively analyze the effect of postoperative intensity-modulated radiotherapy (IMRT) on recurrence and survival in lymph node-positive or stage III thoracic esophageal squamous cell carcinoma (TESCC) patients, and evaluate its role in TESCC therapy. Methods: We enrolled 538 patients who underwent radical resection with (S + R) or without (S) postoperative IMRT. The median total postoperative IMRT dose was 60 Gy. The Kaplan-Meier method, log-rank test, and chi-square test were used for survival rate calculation, univariate analysis, and sites of failure analysis, respectively. Results: The 5-year overall survival (OS) and disease-free survival rates were 32.7 and 27.3%, respectively. The 5-year OS rates of lymph node-positive S and S + R patients were 28.4 and 38.8%, respectively (p < 0.001). The 5-year OS rates of stage III S and S + R patients were 24.0 and 38.0%, respectively (p = 0.001). Postoperative IMRT resulted in significantly decreased intrathoracic and supraclavicular recurrence, and obviously delayed median local recurrence and systemic metastases. Systemic metastases increased following postoperative IMRT. Conclusion: Postoperative IMRT reduces local recurrence and improves survival in lymph node-positive or stage III TESCC patients, providing a rationale for selection criteria for postoperative IMRT in TESCC.

Postoperative Radiation Therapy With or Without Concurrent Chemotherapy for Node-Positive Thoracic Esophageal Squamous Cell Carcinoma

To retrospectively compare the efficacy of radiation therapy (RT) and chemotherapy plus RT (CRT) for the postoperative treatment of node-positive thoracic esophageal squamous cell carcinoma (TESCC) and to determine the incidence and severity of toxic reactions. We retrospectively reviewed data from 304 patients who had undergone esophagectomy with 3-field lymph node dissection for TESCC and were determined by postoperative pathology to have lymph node metastasis without distant hematogenous metastasis. Of these patients, 164 underwent postoperative chemotherapy (cisplatin 80 mg/m(2), average days 1-3, plus paclitaxel 135 mg/m(2), day 1; 21-day cycle) plus RT (50 Gy), and 140 underwent postoperative RT alone. The 5-year overall survival rates for the CRT and RT groups were 47.4% and 38.6%, respectively (P=.030). The distant metastasis rate, the mixed (regional lymph node and distant) metastasis rate, and the overall recurrence rate were significantly lower in the CRT group than in the RT group (P<.05). However, mild and severe early toxic reactions, including neutropenia, radiation esophagitis, and gastrointestinal reaction, were significantly more common in the CRT group than in the RT group (P<.05). No significant differences in incidence of late toxic reactions were found between the 2 groups. Our results show that in node-positive TESCC patients, postoperative CRT is significantly more effective than RT alone at increasing the overall survival and decreasing the rates of distant metastasis, mixed metastasis, and overall recurrence. Severe early toxic reactions were more common with CRT than with RT alone, but patients could tolerate CRT.

Explore the Radiotherapeutic Clinical Target Volume Delineation for Thoracic Esophageal Squamous Cell Carcinoma from the Pattern of Lymphatic Metastases

Esophageal carcinoma is characterized by a high frequency of lymph node metastasis (LNM). It is difficult to accurately define the radiotherapeutic clinical target volume in patients with thoracic esophageal squamous cell carcinoma (ESCC), because the LNM rate and the included node level varied greatly among previous studies. This study aimed to determine which node level should be included for radiotherapy by analyzing LNM rate in thoracic ESCC patients. The clinicopathological factors related to LNM were analyzed using the χ test. The sites with LNM rate higher than 15%, an empirical cutoff value, were considered as high-risk areas and were included in clinical target volume of thoracic ESCC patients for radiotherapy. This study included 1893 thoracic ESCC patients treated at Shandong Cancer Hospital, Jinan, China. The rates of LNM in patients with upper thoracic tumors were 14.6% cervical, 29.3% upper mediastinal, 8.5% middle mediastinal, 9.8% lower mediastinal, and 7.3% abdominal, respectively. The rates of LNM in patients with middle thoracic tumors were 4.3%, 5.0%, 32.9%, 2.5%, and 14.9%, respectively. The rates of LNM in patients with lower thoracic tumors were 2%, 2.2% 15.4%, 38.1%, and 27.5%, respectively. Independent prognostic factors for LNM included length of tumor, histologic differentiation, and depth of tumor invasion (p < 0.001). Irradiation of the selective regional lymph node and the correlated lymphatic drainage regions should be performed according to the clinicopathological factors. For the large, deeply invasive longer tumors and poorly differentiated thoracic ESCC, the irradiation field should be enlarged appropriately.

Cigarette Smoking and hOGG1 Ser326Cys Polymorphism are Associated with 8-OHdG Accumulation on Mitochondrial DNA in Thoracic Esophageal Squamous Cell Carcinoma

We examined whether cigarette smoking affects the degrees of oxidative damage (8-hydroxyl-2'-deoxyguanosine [8-OHdG]) on mitochondrial DNA (mtDNA), whether the degree of 8-OHdG accumulation on mtDNA is related to the increased total mtDNA copy number, and whether human 8-oxoguanine DNA glycosylase 1 (hOGG1) Ser326Cys polymorphisms affect the degrees of 8-OHdG accumulation on mtDNA in thoracic esophageal squamous cell carcinoma (TESCC). DNA extracted from microdissected tissues of paired noncancerous esophageal muscles, noncancerous esophageal mucosa, and cancerous TESCC nests (n = 74) along with metastatic lymph nodes (n = 38) of 74 TESCC patients was analyzed. Both the mtDNA copy number and mtDNA integrity were analyzed by quantitative real-time polymerase chain reaction (PCR). The hOGG1 Ser326Cys polymorphisms were identified by restriction fragment length polymorphism PCR and PCR-based direct sequencing. Among noncancerous esophageal mucosa, cancerous TESCC nests, and metastatic lymph nodes, the mtDNA integrity decreased (95.2 to 47.9 to 18.6 %; P < 0.001) and the mtDNA copy number disproportionally increased (0.163 to 0.204 to 0.207; P = 0.026). In TESCC, higher indexes of cigarette smoking (0, 0-20, 20-40, and >40 pack-years) were related to an advanced pathologic N category (P = 0.038), elevated mtDNA copy number (P = 0.013), higher mtDNA copy ratio (P = 0.028), and increased mtDNA integrity (P = 0.069). The TESCC mtDNA integrity in patients with Ser/Ser, Ser/Cys, and Cys/Cys hOGG1 variants decreased stepwise from 65.2 to 52.1 to 41.3 % (P = 0.051). Elevated 8-OHdG accumulations on mtDNA in TESCC were observed. Such accumulations were associated with a compensatory increase in total mtDNA copy number, indexes of cigarette smoking, and hOGG1 Ser326Cys polymorphisms.

A phase I/II clinical trial of preoperative short‐course carbon‐ion radiotherapy for patients with squamous cell carcinoma of the esophagus

Carbon-ion radiotherapy (CIR) has been under development. We report the results of a phase I/II clinical trial of preoperative CIR for esophageal squamous cell carcinoma (ESCC). Thirty-one thoracic ESCC patients were enrolled. They were first treated with CIR. The radiation dose was escalated from the initial dose of 28.8 GyE up to 36.8. Four to 8 weeks after CIR followed by clinical evaluation of the therapy, surgery was performed. Thereafter, a pathological evaluation was made. Acute toxicity was not seen except in one case (3.2%), and there were no late toxicities. Throughout the study period, there were no cases of withdrawal due to the effects of preoperative CIR. Twelve out of 31 (38.7%) patients achieved a clinical complete response (CR) and 13 patients (41.9%) achieved a partial response. Twelve out of 31 patients (38.7%) achieved a pathological CR. The overall 1-, 3-, and 5-year survival rates in the stage I cases were 91%, 81%, and 61%, and was 100%, 85%, and 77% for the stage II, and 71%, 43%, and 29% for the stage III cases, respectively. CIR showed strong local tumor control and is highly effective as a neoadjuvant therapy without severe adverse events.

Value of the number and distribution of metastatic lymph nodes in postoperative radiotherapy for thoracic esophageal squamous cell carcinoma

Objective To analyze the relationship between the number as well as distributions of positive lymph nodes, and the clinical outcomes of postoperative radiotherapy for thoracic esophageal squamous cell carcinoma (TESCC) , And to evaluate the efficacy of postoperative radiotherapy . Methods From January 1993 to March 2007,945 patients with TESCC treated with three-field lymphadenectomy were involved in this study. All patients were with lymphoid metastasis but without distant metastasis. Among them, 590 patients received surgery alone and the other 355 received surgery plus postoperative radiotherapy. The radiotherapy were begun in the third or fourth week after operation and the median total radiation dose was 50 Gy in 25 fractions of 2 Gy, 5 fractions per week. Results The follow-up rate was 94.5%. 189 patients finished minimal follow-up of five years. The 5-year survival rates in the surgery alone group and in the postoperative radiotherapy group were 29.6% and 38.0%, respectively (χ~2 = 10.44 ,P = 0.001). In stratification analysis, compared with the surgery alone, postoperative radiotherapy could increase the 5-year survival rate of the patients with 3 to 5 (30.5% : 23.1%, χ~2 = 4.11, P = 0.043) or > 5 positive nodes (16.7% : 8.9%, χ~2= 6.87, P= 0.009) , or metastastatic node in the region of supraclavicular or upper mediastinum (45.5% : 34.9%, χ~2= 5.37, P = 0.020). In patients with positive nodes number less than 3, or with medium mediastinum or lower mediastinum lymph nodes metastasis, postoperative radiotherapy could not increase the 5-year survival rates (50.7% : 41.2%, χ~2 = 3.30, P = 0.069 ; 32.0% : 27.7% , χ~2= 2.22 , P = 0. 137) , Though could decrease lymph nodes metastasis in supraclavicular and medium-upper mediastinum (15 : 76, χ~2 = 18.10, P = 0.000; 18 : 97, χ~2= 26.81, P = 0.000). Conclusions In TESCC patients with positive lymph nodes number ≥3 or nodes in the region of supraclavicular and upper mediastinum, postoperative radiotherapy can improve the survival after three field lymphadenectomy. And the rate of metastastatic lymph nodes in the supraclavicular region or upper-medium mediastinum can also be decreased. Key words: Esophageal neoplasms/surgery; Esophageal neoplasms/radlotherapy; Metastatic number,lymph nodes; Metastatic distribution,lymph nodes; Prognosis

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.

Prognostic Variables in Thoracic Esophageal Squamous Cell Carcinoma

Thoracic esophageal squamous cell carcinoma (TESCC) is an aggressive malignancy with a poor prognosis. The current American Joint Committee on Cancer (AJCC) TNM cancer staging system focusing on the effect of regional (N1) and nonregional lymph node (M1a and M1b) metastasis may need reappraisal. We investigated the role of the number of dissected and positive nodes in TESCC patients. A total of 109 TESCC patients (97 men; mean age of 62.3 years) who underwent surgical resection were retrospectively analyzed. The current AJCC TNM system and other lymph node classifications were used to subgroup these patients and analyze survival differences. Previously reported prognostic factors were evaluated. Patients with positive lymph node metastasis had a poor prognosis (p < 0.001). There was a significant difference in survival among the 67 node-positive patients subdivided into subgroups with 1 to 3 and 4 or more positive nodes (p = 0.004). Multivariable Cox proportional hazard regression analysis identified four independent prognostic factors: difficulty in swallowing (p = 0.024), cigarette smoking (p = 0.003), number of positive lymph nodes (0, 1 to 3, and > or = 4; p < 0.001), and gastric cardia invasion (p = 0.012). Total dissection of at least 20 lymph nodes was the minimal requirement to achieve accurate nodal staging. Dissection of more than 20 lymph nodes is mandatory in TESCC patients to achieve accurate staging. Positive lymph node metastasis of 4 or higher is a significant independent prognostic factor.