Node-positive Esophageal Cancer Research Articles

Expression of Neighbor of Punc E11 (NOPE) in early stage esophageal adenocarcinoma is associated with reduced survival

Current recommendations suggest neoadjuvant treatment in node-positive esophageal cancer or tumors staged T3 and upwards but some T2 N0 patients might benefit from neoadjuvant therapy. It is of clinical relevance to identify this subgroup. Loss of epithelial apicobasal polarity is a key factor in the development of invasive capabilities of carcinoma. The oncofetal stem/progenitor cell marker NOPE is expressed in adult depolarized murine hepatocytes and in murine/human hepatocellular carcinoma. We analyzed NOPE expression in 363 patients with esophageal adenocarcinoma using an RNA Scope Assay on a tissue microarray and correlated results with clinical data. Median follow-up was 57.7 months with a 5-year survival rate of 26.6%. NOPE was detectable in 32 patients (8.8%). In pT1/2 stages, NOPE expression was associated with a significantly reduced median OS of 6.3 months (95% CI 1.2–19.4 months), the median OS is not reached in the NOPE-negative group (calculated mean OS 117.1 months) (P = 0.012). In advanced tumor stages, a NOPE dependent survival difference was not detected. This is the first report of NOPE expression demonstrating a prognostic value in esophageal cancer. Early stage, NOPE positive patients are at a high risk of tumor progression and may benefit from neoadjuvant treatment analogous to advanced stage cancer.

Socioeconomic factors in timing of esophagectomy and association with outcomes.

Disparities in esophageal cancer are well-established. The standard treatment for locally advanced esophageal cancer is chemoradiation followed by surgery. We sought to evaluate the association between socioeconomic factors, time to surgery, and patient outcomes. All patients ≥18 years old diagnosed with T2/3/4 or node-positive esophageal cancer between 2004 and 2016 and who underwent chemoradiation and esophagectomy in the National Cancer Database were included. Multivariable regression was used to assess the association between socioeconomic variables and time to surgery (grouped into <56, 56-84, and 85-112 days). A total of 12 157 patients were included. Five-year overall survival was 39%, 35%, and 35% for the three groups examined. Postoperative 30- and 90-day mortality was increased in both the 56-84 days to surgery group (odds ratio [OR]: 1.30 and 1.20, respectively) and the 85-112 days group (OR: 1.37 and 1.56, respectively) when compared to <56 days. Patients of a minority race, public insurance, or lower income were more likely to have a longer time to surgery. Longer time to surgery is associated with increased postoperative mortality and is more common in patients with lower socioeconomic status. Further research exploring reasons for delays to esophagectomy among disadvantaged patients could help target interventions to reduce disparities.

Adjuvant chemoradiotherapy for patients with pathologic node-positive esophageal cancer following radical resection is associated with improved survival.

BackgroundDepending on the pathological stage, patients with esophageal squamous cell carcinoma (ESCC) can experience poor prognosis after surgery. This study was designed to analyze the effect of various treatments on prognosis in pathologic node-positive esophageal cancer patients who undergo radical surgery.MethodsWe evaluated 210 pathologic stage IIb–IIIc patients (pT1-4aN + M0) who had undergone esophagectomy for thoracic ESCC from January 2013 to October 2015 at our institute. Surgery alone was applied in 65 patients, postoperative chemotherapy alone was applied in 112 patients, and postoperative adjuvant chemoradiotherapy was applied in 33 patients. Kaplan­-Meier and Cox regression analysis were used to compare overall survival (OS) and disease-free survival (DFS). A nomogram was constructed to visualize the multivariate Cox regression analysis model.ResultsThe median follow-up period was 49.4 months. The 3- and 5-year OS rates of the patients in the surgery group, postoperative chemotherapy group, postoperative chemoradiotherapy group were 55.4%, 61.6%, and 75.8%, and 30.1%, 44.0%, and 63.0% respectively. The 3- and 5-year DFS rates of the patients in the surgery group, postoperative chemotherapy group, postoperative chemoradiotherapy group were 44.6%, 52.7%, and 72.7%, and 20.0%, 24.1%, and 39.4%, respectively. Both the OS and DFS of the patients in the postoperative chemoradiotherapy group were better than those of the patients in the surgery and postoperative chemotherapy group. Among them, the OS of the postoperative radiotherapy group was longer than that of the surgery group (P=0.011) and the postoperative chemotherapy group (P=0.190), while the DFS of postoperative chemoradiotherapy group was longer than that of the surgery group and postoperative chemotherapy group, but the difference was not statistically significant (P>0.05).ConclusionsThis study showed that postoperative adjuvant chemoradiotherapy could improve 3-year OS and DFS compared with treatment using surgery alone or postoperative chemotherapy alone. However, an evaluation of long-term prognosis requires a longer follow-up.

Postoperative adjuvant chemotherapy versus chemoradiotherapy for node-positive esophageal squamous cell carcinoma: a propensity score-matched analysis

Background and purposeAfter esophagectomy, adjuvant chemotherapy (S + CT) and adjuvant chemoradiotherapy (S + CRT) can improve survival in patients with node-positive resectable esophageal cancer. However, we are not aware of any studies that directly compared these adjuvant treatments. This study aimed to compare S + CT and S + CRT for patients with esophageal cancer.Materials and methodsWe retrospectively identified patients with node-positive esophageal squamous cell carcinoma who underwent S + CT or S + CRT at Sichuan Cancer Hospital during 2008–2017. The patients’ characteristics were compared, as well as their overall survival (OS) and disease-free survival (DFS) outcomes. Propensity score matching was used to create balanced patient groups according to adjuvant treatment, and a Cox proportional hazards model was used to identify factors that predicted the survival outcomes.ResultsThe 859 eligible patients underwent S + CRT (250 patients, 29.1%) or S + CT (609 patients, 70.9%). After propensity score matching (247 patients per group), the 5-year OS rates were 41.8% for S + CRT and 26.8% for S + CT (p = 0.028), and the 5-year DFS rates were 37.2% for S + CRT and 25.5% for S + CT (p = 0.012). Multivariate Cox regression analysis of the matched samples revealed that, relative to the S + CT group, the S + CRT group had better OS (hazard ratio: 0.71, 95% CI: 0.56–0.91; p = 0.006) and DFS (hazard ratio: 0.70, 95% CI: 0.56–0.88; p = 0.002).ConclusionAmong patients with node-positive resectable esophageal squamous cell carcinoma, S + CRT was associated with better OS than S + CT. A multicenter randomized clinical trial is warranted to confirm these findings.

Adjuvant chemotherapy for patients with pathologic node-positive esophageal cancer after induction chemotherapy is associated with improved survival

ObjectivesThe study objectives were to identify variables associated with the use of adjuvant chemotherapy among patients with node-positive esophageal cancer who received induction therapy and to evaluate its relationship with overall survival. MethodsTreatment data for patients with esophageal cancer receiving induction chemotherapy ± radiotherapy and esophagectomy were abstracted from the National Cancer Data Base. Pathologic node-positive patients were dichotomized by whether they received 2 or more cycles of adjuvant chemotherapy or none. Kaplan–Meier survival curves were generated, and a Cox proportional hazards model was done to identify factors associated with overall survival. ResultsFrom 2006 to 2012, 3100 patients had pathologic positive nodes after induction therapy and esophagectomy. A total of 2625 patients (84.7%) did not receive adjuvant chemotherapy, and 475 patients (15.3%) did. N3 nodal stage was associated with an increased likelihood of receiving adjuvant chemotherapy (reference: N1, odds ratio, 1.82, 95% confidence interval, 1.15-2.97, P = .01), whereas increasing age (by year, odds ratio, 0.97, confidence interval, 0.96-0.98, P < .001), induction chemoradiation therapy (reference: induction chemotherapy, odds ratio, 0.39, confidence interval, 0.30-0.52, P < .001), and increasing inpatient length of stay after esophagectomy (per day: odds ratio, 0.98, confidence interval, 0.97-0.99, P = .007) were associated with a decreased likelihood. Patients receiving adjuvant chemotherapy had improved overall survival at each pathologic nodal stage: 31.6 months versus 22.7 months for N1 disease (P < .001), 32.4 months versus 19.2 months for N2 disease (P = .035), and 19.5 months versus 10.4 months for N3 disease (P < .001). Adjuvant therapy was independently associated with decreased mortality hazard (hazard ratio, 0.69, 95% confidence interval, 0.57-0.83, P < .001). ConclusionsPatients receiving adjuvant chemotherapy after induction therapy and esophagectomy show a survival benefit at all positive nodal stages. Prospective studies may help further delineate this benefit.

Is esophagectomy indicated after induction therapy in patients with clinical N3 esophageal cancer?

e16073Background: The benefit of inclusion of esophagectomy after induction therapy in patients with node-positive non-metastatic esophageal cancer is well established. It is unclear if that benefi...

Survival benefit of neoadjuvant versus adjuvant radiotherapy in lymph node positive esophageal cancer: a population based analysis.

The impact of radiotherapy on the survival of patients with locally advanced esophageal cancer (EC) is presently insufficiently explored. Thus, using data from the Surveillance, Epidemiology, and End Results (SEER) Registry, this study aimed to compare the survival rates of patients with lymph node (LN) positive EC who received curative resection and were treated by neoadjuvant and adjuvant radiotherapy (RT), respectively. Retrospectively collected data from the SEER database using all 18 SEER registries on patients that underwent esophagectomy for EC was evaluated. All patients with LN positive pathology who received either neoadjuvant or adjuvant RT and curative intent esophagectomy from 2004 to 2007 were included. A comparison of 5-year relative survival outcome among groups categorized by sex, race, age, histology, and tumor size was performed. A total of 933 patients were evaluated; 636 (69%) and 297 (31%) received RT in neoadjuvant and adjuvant setting respectively. Their overall 5-year relative survival rates were 32.8% (95% CI: 28.7-36.9) and 26.5% (95% CI: 21-32.3) (P=0.058). Patients in the neoadjuvant RT group who underwent curative resection for squamous cell carcinoma (SCC) of EC had an improved 5-year relative survival rate of 43.4% (95% CI: 32.5-53.8) compared to 26.5% (95% CI: 15.4-38.9) measured for the adjuvant RT group (P=0.03). The results further revealed a significant increase in the 5-year relative survival rates for stage T3 and Tx when RT was given in neoadjuvant setting compared to adjuvant RT group (T3 28.5% vs. 20.2%, P=0.011; Tx 46.3% vs. 8.9%, P=0.021). When the patients were grouped according to race, sex or age, or based on the timing of radiation relative to surgery, in the other histological or T stage groups, there were no statistically significant differences in the 5-year survival rates. Compared to adjuvant radiotherapy, neoadjuvant radiotherapy results in a better 5-year relative survival in patients with squamous cell neoplasms and/or T3, Tx stage disease.

Positive radial resection margin after esophagectomy for esophageal cancer patients treated at a tertiary center and its impact on survival.

162 Background: Although residual tumor at the radial margin can be expected to have a significant impact on the recurrence or overall survival of patient with node negative esophageal cancer (EC), its impact on recurrence and overall survival of patients with node positive EC has not been well characterized. Methods: A retrospective review of patients who underwent esophagectomy for EC at a single institution over a 16 year period (1999-2015) was performed. Pre-operative clinical parameters, stage as well as oncologic management were reviewed as well as the impact of positive radial margin on overall survival of pre-treatment node positive tumors was analyzed using descriptive statistics. Results: The study group consisted of 437 patients (46%) with pre-treatment stage IIB or III out of 945 patients with EC undergoing esophagectomy. The mean age of patients was 63 years with male predominance (85%). Neoadjuvant therapy (NAT) was administered to 87% of patients. Trans-thoracic surgery was performed in 86% of patients and trans-hiatal in 14%. Positive radial margin on final pathology was identified in 14 patients (3.2%); none of these had squamous histology. Neither the surgical approach nor the use of NAT was associated with radial margin positivity (p = 0.6). The median overall survival was significantly lower in the patients with positive radial margin when compared to the rest of the cohort (13.6 months v/s 41.2 months, p = 0.004). Moreover, when focused only on patients with post treatment pathologic T3 and T4 disease, margin positive disease remained associated with worse survival (p = 0.04). However, when final N status is included in multivariate analysis margin positivity loses significance. Conclusions: Radial margin positive disease after surgical resection for EC is associated with worse overall survival. This finding was significant regardless of the pathologic T stage; however, pathologic nodal staging was the most important factor for prognostication in locally advanced EC. Adenocarcinoma is the predominant pathology identified in patients with positive radial margin and concurrent node positivity.

Survival benefit of neoadjuvant versus adjuvant radiotherapy in lymph node positive esophageal cancer patients undergoing curative resection.

e15516Background: The impact of radiation therapy on the survival of patients with locally advanced esophageal cancer (EC) is not clear. This study investigates the difference in survival benefit c...

Lymphovascular invasion of tumor cells in lymph node metastases has a negative impact on survival in esophageal cancer

Lymph node metastases constitute a strong prognostic factor in esophageal cancer. Nevertheless, the mechanisms and relevance of further spread of tumor cells from these already established metastatic sites have not been studied in this disease. The aim of this study was to investigate lymphatic vessel invasion (LVI) of tumor cells and lymphatic microvessel density in lymph node metastases in a large cohort of patients with node-positive esophageal cancer. A total of 120 patients with node-positive esophageal cancer (67 adenocarcinomas, 53 squamous cell carcinomas) and radical esophagectomy were analyzed for LVI and lymphatic microvessel density in primary tumors and lymph node metastases using D2-40 immunostaining. In 18 patients, additional tissue from distant metastases was available. LVI was present in 52.1% (62/119) of primary tumors, 52.5% (63/120) of lymph nodes, and 22.2% (4/18) of distant metastases. LVI in primary tumors strongly correlated with LVI in lymph node metastases (P<.05), regardless of histologic subtype. In univariate analysis, LVI in lymph node metastases was associated with shorter disease-free survival and overall survival in all tumors and in adenocarcinomas, and with shorter disease-free survival in squamous cell carcinomas (P<.05, log-rank test). Multivariable analysis revealed LVI in lymph node metastases as an independent prognostic factor for disease-free survival in the whole cohort and for disease-free and overall survival in patients with adenocarcinomas (P<.05, Cox regression). LVI in lymph node metastasis is a significant prognostic factor in metastatic esophageal carcinoma and seems to play a relevant role in disease progression.

Impact of Adjuvant Chemotherapy on Patients with Lymph Node-Positive Esophageal Cancer who are primarily Treated with Surgery.

Whereas the optimal therapeutic strategy in node positive esophageal cancer primarily treated by surgery remains unknown, the study was designed to evaluate the impact of adjuvant chemotherapy on survival in such population. Among 2944 consecutive patients operated on for esophageal cancer between 2000 and 2010 in 30 European centers, patients with lymph node metastasis treated by adjuvant treatment (n = 178) were compared to patients who did not received adjuvant treatment (n = 378). Multivariable analyses and propensity score matching were used to compensate for differences in baseline characteristics. After matching, patients were comparable between the two groups. When comparing adjuvant treatment and nonadjuvant treatment groups, there was no significant differences in 3-year overall (40.9 vs. 35.8 %, P = 0.560) and disease-free (33.9 vs. 28.5 %, P = 0.190) survivals. Locoregional recurrence was lower in the adjuvant treatment group (14.4 vs. 30.9 %, P = 0.012). In the adjuvant treatment group, 94 patients received chemotherapy and 84 chemoradiotherapy, without significant survival benefit over chemoradiotherapy compared with chemotherapy alone (P = 0.280). Predictive factors of overall survival were age ≥60 years, ASA III-IV score, and pN+ classification. No survival benefit was observed according to histological subtype or occurrence of postoperative complications. Adjuvant chemo(radio)therapy did not offer survival benefit in lymph node-positive esophageal cancer patients primarily treated with surgery.

Outcomes of Preoperative Chemotherapy with Docetaxel, Cisplatin, and 5-Fluorouracil Followed by Esophagectomy in Patients with Resectable Node-Positive Esophageal Cancer

There is a consensus that neoadjuvant therapy is an essential component of treatment for resectable advanced esophageal cancer. The aim of this study was to evaluate the efficacy of preoperative docetaxel/cisplatin/5-fluorouracil (DCF) followed by esophagectomy for patients with node-positive esophageal cancer using a prospective database. Fifty-five consecutive patients with resectable node-positive esophageal cancer were treated with preoperative DCF between August 2008 and December 2010. Of these patients, 54 completed 2 courses of DCF, and 50 underwent esophagectomy after the planned chemotherapy. Clinical and pathologic responses to DCF were investigated, as was patient prognosis. Cox proportional hazard regression was used to determine factors that independently affected recurrence. Complete response, partial response, stable disease, and progressive disease were observed in 5, 24, 24, and 2 patients, respectively. Overall, the clinical response rate was 53 %. Pathologic complete response was achieved in 6 cases (12 %), and the overall pathologic response rate was 36 %. Downstaging was observed in 23 cases (46 %). Two-year overall and disease-free survival rates were 78 and 56 %, respectively. Multivariate analysis revealed that residual tumor [R1/2; hazard ratio (HR) 5.21, 95 % confidence interval (CI) 1.64-17.2], pathologic poor response (grade 1a; HR 3.08, 95 % CI 1.08-11.1), and ypN (M1Lym; HR 13.3, 95 % CI 2.06-116) were independent predictors of recurrence. DCF has strong antitumor activity for esophageal cancer and may confer survival benefits when used as preoperative chemotherapy.

Prognostic impact of postoperative radiation in patients undergoing radical esophagectomy for pathologic lymph node positive esophageal cancer

PurposeThough postoperative radiation for esophageal squamous cell carcinoma is offered in selected cases, there is conflicting evidence as to whether it improves overall survival (OS). A retrospective investigation was performed to analyze the prognostic impact of postoperative radiation therapy (PORT) in a large cohort of patients.MethodsFrom 2001 to 2009, 725 patients underwent radical esophagectomy (R0) with or without PORT were eligible for retrospective analysis. Patients were grouped into surgery alone (n = 467) and surgery plus PORT (n = 258). Median irradiation doses were 50 Gy (range: 40-56 Gy). Radiation fields encompassed the bilateral supraclavicular fossa, mediastinum, subcarinal area, and the tumor bed for the upper/middle-third disease; the bilateral supraclavicular fossa, mediastinum, the tumor bed, subcarinal area, and lower thoracic paraesophageal area for the lower-third disease. Kaplan-Meier and Cox regression analysis were used to compare OS.ResultsAfter median follow-up of 53 months, the median OS was 29 months in the PORT group and 23 months in the surgery alone group. The addition of PORT improved OS at 3 years from 36.6 to 43.6% compared with surgery alone. The use of PORT was associated with significantly improved OS (p = 0.018). For American Joint Committee on Cancer (AJCC) stage III esophageal cancer (T1-2N2M0, T3N1-2M0, T4N1-3M0), there was significant improvement in OS (p = 0.002) in the PORT group, not only for lymph-node metastatic ratio (LNMR) ≥0.25 (p = 0.001), but also for LNMR <0.25 (p = 0.043). However, for stage IIB disease (T1-2N1M0) there was no significant differences. The addition of POCT didn’t prolong the OS significantly (Surgery alone group, p = 0.079; PORT group, p = 0.111).ConclusionsThis large retrospective analysis supports the use of PORT for pathologic lymph node positive stage III esophageal squamous cell carcinoma. Given the retrospective nature of this study, the results should be confirmed by appropriately powered randomized trials. Further development of adjuvant therapy in EC is warranted.

Adjuvant Therapy for Node Positive Esophageal Cancer at Surgery Does Not Improve Survival

Background: The current standard of care for the management of node positive (N) esophageal cancer is induction chemoradiation therapy followed by definite surgical therapy. The utility of adjuvant therapy in patients with persistent histologic evidence of N1 disease post resection is unclear. In this study, we compare survival rates in patients with postsurgical N disease who undergo adjuvant vs. no further therapy. Methods: Using an IRB-approved endoscopic ultrasound (EUS) database, we conducted a retrospective analysis of 77 patients (62 males, 15 females, mean age 60. 4 ± 9.9 years) with esophageal cancer and node positive (N) disease on EUS from2003 to 2010who subsequently underwent surgical resection. Outcomes of patients with surgical node-positive disease undergoing no further therapy were compared to those who underwent adjuvant therapy in terms of significant morbidity (as determined by hospital admissions) and mortality. Results: After neoadjuvant down-staging, a subgroup analysis of the 50 patients with persistent node positive disease on surgical specimen at esophagectomy was carried out. Of the 50 patients, 22 (44%) underwent adjuvant therapy, 24 (48%) did not undergo further chemotherapy and 4 (8%) were lost to follow-up. Morbidity rates were: 11/22 (50%) for those who underwent adjuvant chemotherapy and 7/24 (29%) for those who did not receive adjuvant therapy (p = 0.23, Fisher's Exact Test). Mortality rates were: 10/22 (45%) for those who underwent adjuvant chemotherapy and 13/24 (54%) for those who did not receive adjuvant therapy (p=0.77, Fisher's Exact Test). A KaplanMeier survival curve comparing adjuvant versus no post-operative therapy demonstrated no survival difference (p=0.83) (Figure 1). Conclusion: The addition of adjuvant therapy to surgical node-positive esophageal cancer did not confer a survival advantage. Morbidity was noted to be higher in the adjuvant therapy group however given the small numbers was not statistically significant. Further study into adjuvant therapy for node positive surgical disease is warranted.

Chemotherapy-induced toxicities and treatment efficacy in advanced esophageal cancer treated with neoadjuvant chemotherapy followed by surgery

Neoadjuvant chemotherapy (NACT) followed by surgery is a promising treatment strategy for advanced esophageal cancer. Response to NACT is a strong predictor for prognosis, but no studies have examined the relationship between toxicity and efficacy of NACT. We retrospectively analyzed the treatment results of 105 patients with clinically node-positive esophageal cancer treated with NACT followed by surgery and examined the correlation between adverse events and treatment efficacy. Chemotherapeutic response was evaluated by the reduction rate of the primary tumor in CT scans. Adverse events were graded using the Common Terminology Criteria for Adverse Events version 3. The clinical response rate was 40%, and responders displayed a significantly better survival than nonresponders. Major adverse events (grade 3 or 4) during NACT were leukopenia (24.8%), neutropenia (42.9%), nausea (30.5%), and mucositis (27.9%). There were no chemotherapy-related deaths. In a univariate analysis, responders had significantly more severe adverse events including leukopenia, neutropenia, anemia, thrombocytopenia, and nausea than nonresponders. A multivariate analysis demonstrated that neutropenia was the only independent factor significantly associated with a clinical response (P = 0.027). Concerning prognosis, patients with grade 2–4 neutropenia showed significantly better survival than those with grade 0–1 neutropenia. Antitumor efficacy of NACT for advanced esophageal cancer is significantly associated with the severity of neutropenia. To elucidate the mechanisms underlining these observations, pharmacokinetic and genetic chemosensitivity analyses are needed in future studies.

Phase II study of induction chemotherapy with docetaxel, cisplatin, and 5-fluorouracil for patients with node-positive esophageal cancer.

e14535 Background: Despite an extended radical surgery, the prognosis of patients with esophageal cancer is still unsatisfactory, especially in cases with lymph node metastasis. Although the usefulness of neoadjuvant chemotherapy for node-positive esophageal cancer has been reported, an optimal regimen has not yet been established. This phase II study explores the efficacy and toxicity of docetaxel/cisplatin/5-FU (DCF) as induction chemotherapy for node-positive esophageal cancer. Methods: The modified DCF consisted of 60 mg/m2 of docetaxel on day1, given intravenously for 2 hours, 350 mg/m2 of 5-FU on day 1-5 as a 24-hour continuous intravenous infusion, and 6 mg/m2 of cisplatin on day 1-5, given intravenously for 1 hour. The regimen was given every 3 weeks and 2 scheduled courses has completed in all cases. Eligibility criteria were: i) a pathlogically defined esophageal cancer, ii) lymph node metastasis observed with PET/CT or US, iii) no previous treatment, iv) ECOG PS of 0 to 2, v) an age of 20 -80, and iv) adequate bone marrow, renal and hepatic function. Primary endpoint Treatment effect was evaluated according to RECIST v1.0. Changes in SUV with FDG-PET scan and tumor markers (SCC, CEA) were also used for the evaluation of efficacy, while adverse events were assessed according to CTCAE v3.0. Pathological response was evaluated in 26 resected cases. Results: CR and PR were observed in 5 (9.8%) and 25 (49.0%), respectively. SUV of the primary tumors reduced in 46 cases (90.2%) during the chemotherapy and the mean value was decreased from 14.1 to 7.0 (p < 0.0001). SCC was decreased in 25 out of 30 elevated cases (p = 0.029), while CEA reduced in 14 out of 16 elevated cases (p = 0.17). Down-staging was observed in 15 resected cases (57.7%), including 10 cases (38.7%) with pathlogical N0. Pathological complete response was observed in 3 cases. Grade 3 or 4 neutropenia was seen in 43 cases (84.3%), but neither treatment-related death nor delay in the treatment was observed. Conclusions: Induction chemotherapy with modified DCF is highly efficient with acceptable toxicity for patients with node-positive esophageal cancer. No significant financial relationships to disclose.

Prognostic Significance of the Number of Lymph Node Metastases in Esophageal Cancer

Regional lymph node (LN) involvement is one of the most important predictors of survival for patients with esophageal cancer. The current staging classification differentiates only between the presence and absence of LN metastasis. In this study, we examined whether involvement of a higher number of LNs is associated with worse survival among esophageal cancer patients. We identified all patients who underwent operations for node-positive esophageal cancer between 1988 and 2003 from the Surveillance, Epidemiology and End Results cancer registry. Because the number of positive LNs is confounded by the total number of LNs removed, patients were classified into three groups by the ratio of positive-to-total number of LNs removed (LN ratio [LNR]): <or= 0.2, 0.21 to 0.5, and>0.5. Esophageal cancer-specific survival was compared among these groups using Kaplan-Meier curves. Stratified and Cox regression analyses were used to evaluate the relationship between the LNR and survival after adjusting for potential confounders. The study cohort included 838 esophageal cancer patients. Disease-specific survival rates decreased with higher LNR. Five-year disease-specific survival was 30% among patients with an LNR<or=0.2, compared with 16% and 13% for those with LNs of 0.21 to 0.5 and>0.5, respectively (p < 0.001). In stratified and multivariable analyses controlling for age, race, gender, histology, tumor-status, and postoperative radiotherapy, a higher LNR was independently associated with worse disease-specific survival. These data suggest that a higher LNR among patients with node-positive esophageal cancer is associated with worse survival. If validated, this prognostic criterion may be included in staging classifications.

Impact of Solitary Involved Lymph Node on Outcome in Localized Cancer of the Esophagus and Esophagogastric Junction

Node-positive esophageal cancer is associated with a dismal prognosis. The impact of a solitary involved node, however, is unclear, and this study examined the implications of a solitary node compared with greater nodal involvement and node-negative disease. The clinical and pathologic details of 604 patients were entered prospectively into a database from1993 and 2005. Four pathologic groups were analyzed: node-negative, one lymph node positive, two or three lymph nodes positive, and greater than three lymph nodes positive. Three hundred and fifteen patients (52%) were node-positive and 289 were node-negative. The median survival was 26 months in the node-negative group. Patients (n = 84) who had one node positive had a median survival of 16 months (p = 0.03 vs node-negative). Eighty-four patients who had two or three nodes positive had a median survival of 11 months compared with a median survival of 8 months in the 146 patients who had greater than three nodes positive (p = 0.01). The survival of patients with one node positive [number of nodes (N) = 1] was also significantly greater than the survival of patients with 2–3 nodes positive (N = 2–3) (p = 0.049) and greater than three nodes positive (p < 0001). The presence of a solitary involved lymph node has a negative impact on survival compared with node-negative disease, but it is associated with significantly improved overall survival compared with all other nodal groups.

Preoperative chemotherapy for clinically node-positive patients with squamous cell carcinoma of the esophagus

Lymph node metastasis is one of the strongest prognostic factors for patients with esophageal cancer. Whether neoadjuvant chemotherapy is effective for metastatic nodes and improves the prognosis of clinically node-positive patients is unknown. Seventy-seven patients with clinically node-positive esophageal cancer, who were given preoperative chemotherapy (5-fluorouracil, cisplatin and adriamycin) followed by surgery, were retrospectively analysed. The histological effectiveness of the chemotherapy against the main tumor in the resected specimen was correlated with nodal status and prognosis. Of the 77 patients, the histological effects in the main tumors were grade 3 in one patient (1.3%), grade 2 in 10 (13.0%), grade 1b in seven (9.1%), grade 1a in 50 (64.9%) and grade 0 in nine (11.7%). Eleven patients (14.3%) were found to be pathologically node-negative. The pathological stages were significantly earlier in responders (grades 3-1b) than in non-responders (grades 1a-0) (P = 0.0001). The responders showed a significantly lesser degree of lymph node metastasis (P = 0.0005), fewer metastatic nodes (2.2 +/- 3.1 vs. 12.0 +/- 20.5, P = 0.0482) and better survival (P = 0.002) than the non-responders. The most common failure pattern for the non-responders was lymphatic recurrence, with an incidence of 47.5% (28/59), while that for the responders was 16.7%. Responders to neoadjuvant chemotherapy show fewer metastatic nodes and better prognosis than non-responders. Neoadjuvant chemotherapy may offer clinical benefit to responders.

222 - VEGF expression as a prognostic factor in node-positive esophageal cancer

222 - VEGF expression as a prognostic factor in node-positive esophageal cancer