Esophageal stenosis and the Glasgow Prognostic Score as independent factors of poor prognosis for patients with locally advanced unresectable esophageal cancer treated with chemoradiotherapy (exploratory analysis of JCOG0303).

BACKGROUND: The aim of this study was to investigate the possible prognostic factors and predictive accuracy of the Glasgow Prognostic Score (GPS) for patients with unresectable locally advanced esophageal squamous cell carcinoma (LAESCC) treated with chemoradiotherapy. METHODS: One hundred forty-two patients were enrolled in JCOG0303 and assigned to the standard cisplatin and 5-fluorouracil (PF)-radiotherapy (RT) group or the low-dose PF-RT group. One hundred thirty-one patients with sufficient data were included in this analysis. A Cox regression model was used to analyze the prognostic factors of patients with unresectable LAESCC treated with PF-RT. The GPS was classified based on the baseline C-reactive protein (CRP) and serum albumin levels. Patients with CRP ≤1.0 mg/dL and albumin ≥3.5 g/dL were classified as GPS0. If only CRP was increased or only albumin was decreased, the patients were classified as GPS1, and the patients with CRP >1.0 mg/dL and albumin <3.5 g/dL were classified as GPS2. RESULTS: The patients' backgrounds were as follows: median age (range), 62 (37-75); male/female, 119/12; ECOG PS 0/1/2, 64/65/2; and clinical stage (UICC 5th) IIB/III/IVA/IVB, 3/75/22/31. Multivariable analyses indicated only esophageal stenosis as a common factor for poor prognosis. In addition, overall survival tended to decrease according to the GPS subgroups (median survival time (months): GPS0/GPS1/GPS2 16.1/14.9/8.7). CONCLUSIONS: Esophageal stenosis was identified as a candidate stratification factor for randomized trials of unresectable LAESCC patients. Furthermore, GPS represents a prognostic factor for LAESCC patients treated with chemoradiotherapy. CLINICAL TRIAL INFORMATION: UMIN000000861.

Inter-institutional survival heterogeneity in chemoradiation therapy for esophageal cancer: exploratory analysis of the JCOG0303 study.

It is important to examine variation in the treatment effects of patients with esophageal cancer in order to generalize treatment outcomes. We aimed to investigate the range of prognostic differences among hospitals in the treatment of locally advanced esophageal cancer. The JCOG0303 study compared the efficacy of radiotherapy plus low-dose cisplatin and 5-fluorouracil with that of high-dose cisplatin and 5-fluorouracil for unresectable esophageal cancer. Of 32 institutions participating in the JCOG0303 study, the 18 institutions that enrolled three or more patients were included in this study. We predicted the 1-year survival in each institution by using a mixed-effect model. We found that the predicted 1-year survival in the 18 institutions with three or more patients was a median of 60.9%, with a range of 60.9-60.9%. This study is the first to investigated heterogeneity of survival in patients who received definitive chemoradiotherapy for locally advanced esophageal squamous cell carcinoma.

Randomized study of low-dose versus standard-dose chemoradiotherapy for unresectable esophageal squamous cell carcinoma (JCOG0303).

Low-dose cisplatin and 5-fluorouracil (LDPF) chemotherapy with daily radiotherapy (RT) is used as an alternative chemoradiotherapy regimen for locally advanced esophageal carcinoma. We evaluated whether RT plus LDPF chemotherapy had an advantage in terms of survival and/or toxicity over RT plus standard-dose cisplatin and 5-fluorouracil (SDPF) chemotherapy in this study. This multicenter trial included esophageal cancer patients with clinical T4 disease and/or unresectable regional lymph node metastasis. Patients were randomly assigned to receive RT (2 Gy/fraction, total dose of 60 Gy) with SDPF (arm A) or LDPF (arm B) chemotherapy. The primary endpoint was overall survival (OS). A total of 142 patients (arm A/B, 71/71) from 41 institutions were enrolled between April 2004 and September 2009. The OS hazard ratio in arm B versus arm A was 1.05 (80% confidence interval, 0.78-1.41). There were no differences in toxicities in either arm. Arm B was judged as not promising for further evaluation in the phase III setting. Thus, the Data and Safety Monitoring Committee recommended that the study be terminated. In the updated analyses, median OS and 3-year OS were 13.1 months and 25.9%, respectively, for arm A and 14.4 months and 25.7%, respectively, for arm B. Daily RT plus LDPF chemotherapy did not qualify for further evaluation as a new treatment option for patients with locally advanced unresectable esophageal cancer. This study was registered at the UMIN Clinical Trials Registry as UMIN000000861.

Prognostic Factors in Patients Receiving Neoadjuvant 5-Fluorouracil plus Cisplatin for Advanced Esophageal Cancer (JCOG9907).

OBJECTIVE: Neoadjuvant chemotherapy with 5-fluorouracil plus cisplatin and subsequent esophagectomy with two- to three-field lymphadenectomy is a standard treatment for patients with clinical stage II/III squamous cell carcinoma (SCC) of the esophagus. This study investigates the prognostic factors for patients who received neoadjuvant chemotherapy. METHODS: Of 164 patients assigned to receive neoadjuvant chemotherapy in the JCOG9907 trial, multivariate analyses were performed for 159 and 149 patients to evaluate the preoperative and the combined preoperative and postoperative prognostic factors, respectively. RESULTS: The multivariate analyses using preoperative factors showed that clinical stage T3 [vs. cT1-2; hazard ratio (HR) 3.60, p = 0.0007] and serum albumin (Alb) <4.0 g/dl (vs. ≥ 4.0 g/dl; HR 2.29, p = 0.0005) were associated with a poor prognosis. Four independent prognostic factors were identified by multivariate analysis of both preoperative and postoperative factors: pathological curability B (pB; R0 with stage IV or pD < pN) or pC [microscopic or macroscopic residual tumor (R1/R2)] [vs. pA (R0); HR 1.93, p = 0.015], pathological stage N1 (vs. pN0; HR 3.86, p = 0.0012), cT3 (vs. cT1-2; HR 2.80, p = 0.0073), and serum Alb <4.0 g/dl (vs. ≥ 4.0 g/dl; HR 2.03, p = 0.0069). CONCLUSIONS: Preoperative cT stage, Alb, and postoperative pathological findings are independent prognostic factors for patients undergoing neoadjuvant chemotherapy for advanced thoracic esophageal SCC. This analysis may aid in stratification according to individual patient risk.

Coffee and green tea consumption is associated with upper aerodigestive tract cancer in Japan.

The impact of coffee and green tea consumption on upper aerodigestive tract (UADT) cancer risk has not been established. Evaluation of the possible anticarcinogenic properties of their ingredients is confounded by the potential increase in risk owing to the high temperatures at which these beverages are generally consumed. We conducted a case-control study to evaluate the association between coffee and tea consumption and the risk of UADT cancer. The study enrolled 961 patients with UADT cancer and 2,883 noncancer outpatients who visited Aichi Cancer Center between 2001 and 2005. Information on coffee and green tea consumption and other lifestyle factors was collected via a self-administered questionnaire. Consumption of three or more cups of coffee per day had a significant inverse association with UADT cancer [odds ratio (OR) 0.73, 95% confidence interval (CI) 0.55-0.96]. In contrast, consumption of three or more cups of green tea per day had a significant positive association with UADT cancer (OR 1.39, 95% CI 1.13-1.70). These associations were evident for head and neck cancer but not for esophageal cancer. The association of coffee consumption with head and neck cancer was observed only among never smokers and alcohol drinkers. Similarly, the association of green tea consumption was observed among never smokers and never alcohol drinkers. No change in these associations was seen on stratification by each confounding factors. These findings suggest that consumption of coffee might be associated with a decreased risk of UADT cancer, whereas that of green tea might be associated with an increased risk.

Laparoscopic sleeve gastrectomy followed by laparoscopic adrenalectomy for patients with obesity and primary aldosteronism: Report of two patients.

INTRODUCTION AND IMPORTANCE: Primary aldosteronism (PA) is the most frequent cause of secondary hypertension. Surgical treatment of unilateral PA usually resolves excessive aldosterone secretion. Obesity is an independent factor for postoperative persistent hypertension for patients with unilateral PA. Laparoscopic sleeve gastrectomy has become popular due to its efficacy in resolving obesity. A specific strategy might to be needed for patients with unilateral PA and obesity. CASE PRESENTATION: Two males with PA and obesity (Body Mass Index: BMIs of 35.9 and 39.0, respectively) were referred for evaluation. Both patients had hypertension caused by PA and obesity. We performed laparoscopic sleeve gastrectomy (LSG) prior to adrenalectomy to avoid persistent postoperative hypertension and perioperative obesity related comorbidities. LSG could lead to decreasing of BMIs to 27.7 and 32.1. Comorbidities associated with obesity were also resolved in both patients. Laparoscopic adrenalectomy was then safely performed in these two patients with PA. CLINICAL DISCUSSIONS: Patients with PA developing resistant hypertension were estimated to be 20 % of those who underwent adrenalectomy. Decreased BMI can be an independent preoperative determinant for successful outcome after adrenalectomy regarding hypertension. We need to review with special care the preoperative BMI and the nature of hypertension before performing surgery on patients with unilateral PA. CONCLUSIONS: A successful strategy was used to treat two obese patients with unilateral PA who underwent laparoscopic adrenalectomy after LSG to minimize complications associated with obesity-related comorbidities.

A randomized trial comparing postoperative adjuvant chemotherapy with cisplatin and 5-fluorouracil versus preoperative chemotherapy for localized advanced squamous cell carcinoma of the thoracic esophagus (JCOG9907).

BACKGROUND: Patients with esophageal carcinoma receiving postoperative chemotherapy showed superior disease-free survival than those receiving surgery alone in a Japan Clinical Oncology Group trial (JCOG9204). The purpose of this study was to evaluate optimal perioperative timing-that is, before or after surgery-for providing chemotherapy in patients with locally advanced esophageal squamous cell carcinoma. METHODS: Eligible patients with clinical stage II or III, excluding T4, squamous cell carcinoma were randomized to undergo surgery followed (group 1) or preceded (group 2) by chemotherapy consisting of two courses of cisplatin plus 5-fluorouracil. The primary end point was progression-free survival. RESULTS: We randomized 330 patients, with 166 assigned to group 1 and 164 to group 2, between May 2000 and May 2006. The planned interim analysis was conducted after completion of patient accrual. Progression-free survival did not reach the stopping boundary, but overall survival in group 2 was superior to that of group 1 (P = 0.01). Therefore, the Data and Safety Monitoring Committee recommended early publication. Updated analyses showed the 5-year overall survival to be 43% in group 1 and 55% in group 2 (hazard ratio 0.73, 95% confidence interval 0.54-0.99, P = 0.04), where the median follow-up of censored patients was 61.6 months. Concerning operative morbidity, renal dysfunction after surgery in group 2 was slightly higher than in group 1. CONCLUSIONS: Preoperative chemotherapy with cisplatin plus 5-fluorouracil can be regarded as standard treatment for patients with stage II/III squamous cell carcinoma.

Radiotherapy quality assurance review for a multi-center randomized trial of locally advanced esophageal cancer: the Japan Clinical Oncology Group (JCOG) trial 0303.

BACKGROUND AND PURPOSE: The purpose of this study was to evaluate the radiotherapy (RT) quality assurance (QA) for JCOG 0303. METHODS AND MATERIALS: JCOG 0303 was a multi-center phase II/III trial that compared two types of chemotherapy administered concomitantly with RT for locally advanced esophageal cancer. RT requirements included a total dose of 60 Gy in 30 fractions and CTV with a 2-cm margin cranio-caudally to the primary tumor. The QA assessment was given as per protocol (PP), deviation acceptable (DA), violation unacceptable (VU), and incomplete/not evaluable following predefined criteria for quality parameters. RESULTS: A total of 142 cases were accrued. After excluding 36 incomplete/not evaluable, 106 (75%) were fully evaluable for RT quality review. Of these 106, there were 4 VU (4%) and overall RT compliance (PP + DA) was 96%. Comparing the incidence of VU based on the numbers enrolled by institution, the highest quarter of enrollment (≥7 cases) had no VU, while all VU (4; 11%) were from institutions enrolling <7 patients. CONCLUSIONS: The results of the RTQA assessment for JCOG 0303 were sufficient to provide reliable results. Additional improvements will be needed for institutions with low accrual rates.

The benchmark analysis of gastric, colorectal and rectal cancer pathways: toward establishing standardized clinical pathway in the cancer care.

Most clinical pathways in treating cancers in Japan are based on individual physician's personal experiences rather than on an empirical analysis of clinical data such as benchmark comparison with other hospitals. Therefore, these pathways are far from being standardized. By comparing detailed clinical data from five cancer centers, we have observed various differences among hospitals. By conducting benchmark analyses, providing detailed feedback to the participating hospitals and by repeating the benchmark a year later, we strive to develop more standardized clinical pathways for the treatment of cancers. The Cancer Quality Initiative was launched in 2007 by five cancer centers. Using diagnosis procedure combination data, the member hospitals benchmarked their pre-operative and post-operative length of stays, the duration of antibiotics administrations and the post-operative fasting duration for gastric, colon and rectal cancers. The benchmark was conducted by disclosing hospital identities and performed using 2007 and 2008 data. In the 2007 benchmark, substantial differences were shown among five hospitals in the treatment of gastric, colon and rectal cancers. After providing the 2007 results to the participating hospitals and organizing several brainstorming discussions, significant improvements were observed in the 2008 data study. The benchmark analysis of clinical data is extremely useful in promoting more standardized care and, thus in improving the quality of cancer treatment in Japan. By repeating the benchmark analyses, we can offer truly clinical evidence-based higher quality standardized cancer treatment to our patients.

Comparison between self-reported facial flushing after alcohol consumption and ALDH2 Glu504Lys polymorphism for risk of upper aerodigestive tract cancer in a Japanese population.

Some Japanese exhibit facial flushing after drinking alcohol. Facial flushing was considered to be caused by acetaldehydemia. The concentration of blood acetaldehyde was concerned with the catalytic activity of acetaldehyde dehydrogenase (ALDH). Acetaldehyde dehydrogenase (ALDH)-2 polymorphism (rs671, Glu504Lys) was known to be associated with upper aerodigestive tract (UAT) cancer due to modulation of ALDH2 enzyme activity. It remains controversial whether facial flushing is useful in predicting UAT cancer risk as a surrogate marker of ALDH2 polymorphism. We conducted a case-control study to assess the risk of UAT cancer and facial flushing and ALDH2 polymorphism. Cases and controls were 585 UAT cancer patients and matched 1170 noncancer outpatients of Aichi Cancer Center Hospital. Information on facial flushing and other lifestyle factors was collected via a self-administered questionnaire. Association between facial flushing, polymorphism, and UAT cancer was assessed by odds ratios and 95% confidence intervals by using conditional logistic regression models. The facial flushing had no significant association with UAT cancer, although ALDH2 Lys allele was significantly associated with UAT cancer. No significant interaction between facial flushing and alcohol consumption was observed in this study, whereas ALDH2 Lys allele had significant association with UAT cancer. The misclassification between facial flushing and ALDH2 genotype was observed in 18% of controls with ALDH2 Glu/Glu genotype and in 16% of controls with ALDH2 Glu/Lys genotype. Facial flushing was less useful to predict UAT cancer risk than genotyping ALDH2 polymorphism.

Heavy smoking history interacts with chemoradiotherapy for esophageal cancer prognosis: a retrospective study.

Smoking is a well-known risk factor for esophageal cancer. However, there are few reports that directly evaluate smoking as a prognostic factor for esophageal cancer. Moreover, scarce evidence is available on whether smoking interacts with major treatment modalities of esophageal cancer. In this study we retrospectively analyzed 364 patients with esophageal squamous cell cancer who were treated between 2001 and 2005 at our institution. Background characteristics, including smoking history, were analyzed as potential prognostic factors. Of the 363 patients, 76 patients (20.9%) were non-smokers or light smokers (non-heavy), whereas 287 patients (79.1%) were heavy smokers. The 5-year survival rate for non-heavy smokers and heavy smokers was 61.8% (95% confidence interval [CI]: 49.1-72.2) vs 44.6% (95% CI: 38.2-50.9), respectively. In a multivariate Cox model (adjusted for age, gender, performance status, alcohol consumption, histology, tumor length, International Union Against Cancer [UICC] stage, and treatment), the hazard ratio for heavy smokers in comparison with non-heavy smokers was 1.73 (95% CI: 1.12-2.68; P = 0.013). When we stratified by treatment method, heavy smoking was significantly associated with poor survival only in patients treated by chemoradiotherapy (hazard ratio, 2.43; 95% CI: 1.38-4.27; P = 0.002). More importantly, a statistically significant interaction between heavy smoking history and treatment modality was observed (P = 0.041). Our results indicated that smoking history is strongly associated with poor prognosis in patients with esophageal cancer, especially those treated by chemoradiotherapy. Further investigation is warranted to explain this different prognosis.

Determination of the irradiation field for clinical T1-T3N0M0 thoracic/abdominal esophageal cancer based on the postoperative pathological results.

OBJECTIVE: In patients with thoracic/abdominal esophageal cancer with no clinical evidence of lymph node metastasis, there is no consensus about whether the irradiation field should include regional lymph nodes. In this study, the extent of the irradiation field for clinical stage T1-3N0M0 esophageal cancer was determined based on the postoperative pathological results. METHODS: From July 1989 to June 2008, 103 patients diagnosed with clinical stage T1-3N0M0 thoracic/abdominal esophageal cancer underwent standard esophagectomy and regional lymph node dissection at the Aichi Cancer Center Hospital. Of these 103 patients, the pathological results of the resected specimens could be confirmed in 95 (92%) patients. The pathological lymphatic spread was reviewed retrospectively, and the extent of the irradiation field was determined based on the postoperative pathological results. RESULTS: Of 95 patients with clinical stage T1-3N0M0 esophageal cancer, 40 (42.1%) had pathological lymph node metastases, and the frequency of nodal metastases was studied by tumor location. The rates of lymph node metastases for the upper, middle, lower and abdominal esophagus were 37.5%, 32.5%, 46% and 70%, respectively. CONCLUSIONS: Pathological lymph nodes metastases are often seen after operation in clinical stage T1-3N0M0 esophageal cancer. In the present study, the optimal lymph nodes to be included in the irradiation field were determined according to the primary site in the esophagus.

A phase II trial of chemoradiotherapy for stage I esophageal squamous cell carcinoma: Japan Clinical Oncology Group Study (JCOG9708).

OBJECTIVE: The study objective was to evaluate the efficacy and toxicity of chemoradiotherapy with 5-fluorouracil (5-FU) plus cisplatin in patients with Stage I esophageal squamous cell carcinoma (ESCC). The primary endpoint was proportion of complete response (%CR). METHODS: Patients with Stage I (T1N0M0) ESCC, aged 20-75 years, without indication of endoscopic mucosal resection were eligible. Treatment consisted of cisplatin 70 mg/m(2) (day 1) and 5-FU 700 mg/m(2)/day (days 1-4) combined with 30 Gy radiotherapy (2 Gy/day, 5 days/week, days 1-21). The cycle was repeated twice with 1-week split. Salvage surgery was recommended for residual tumor or local recurrence. RESULTS: From December 1997 to June 2000, 72 patients were enrolled. No ineligible patient or major protocol violation was observed. There were 63 CRs for %CR of 87.5% [95% confidence interval (CI): 77.6-94.1]. Six patients with residual tumor successfully underwent esophagectomy. There was no Grade 4 toxicity. Four-year survival proportion was 80.5% (95% CI: 71.3-89.7), and 4-year major relapse-free survival proportion was 68% (95% CI: 57.3-78.8) (mucosal recurrence removed by endoscopy was not counted as an event). CONCLUSIONS: High CR proportion and survival proportion with mild toxicity suggest that this regimen could be considered as a candidate of new standard treatment to be compared with surgery in patients with Stage I ESCC.

[Feasibility and response of gemcitabine and carboplatin biweekly combination chemotherapy for patients with postoperative recurrence non-small cell lung cancer].

BACKGROUND: In advanced non-small cell lung cancer(NSCLC), the standard treatment is chemotherapy with platinum doublet. Gemcitabine (GEM)is one of the major drugs administered in combination with platinum. We studied the feasibility and response of GEM and Carboplatin(CBDCA)biweekly combination chemotherapy for patients with / postoperative recurrence NSCLC. METHOD: Patients received GEM(1,000 mg/m(2))over 30 minutes and CBDCA(AUC =3)over 60 minutes intravenously on day 1 biweekly. Response was evaluated with RECIST. RESULT: Between April 2005 and December 2006 thirteen patients with PS 0 or 1 were entered in the study. All patients received 4 or more cycles. Eight patients received 8 cycles. Of them, only two patients required dose-reduction for hematologic toxicity. / Grade 3/4 hematologic or non-hematologic toxicities and more than grade 2 thrombocytopenia did not occur in any patients. The overall response rate was 20%. SD was seen in 6 patients. CONCLUSION: GEM and CBDCA biweekly combination chemotherapy is a well-tolerated regimen with promising activity against NSCLC.

Opposite impact of NKG2D genotype by lifestyle exposure to risk of aerodigestive tract cancer among Japanese.

It was reported that there are 2 haplotypes in natural killer complex (NKC) region. One of them could be divided by NKG2D polymorphism into 2 haplotype alleles (high and low natural killer (NK) cell activity) and were associated with overall cancer risks. However, its impact on a specific cancer is unclear. Therefore, by a case-control study, we analyzed the association between NKG2D genotype and aerodigestive tract cancer risk. Subjects were 502 aerodigestive tract cancer patients (276 with head and neck, 226 with esophageal) and 1,004 sex-age matched noncancer controls. Exposures to 2 lifestyle factors, smoking and drinking, were evaluated by a self-administered questionnaire. The genotype of NKG2D was determined by the TaqMan method, and its impact was assessed by multivariable logistic regression models. Association strength was measured by the odds ratio (OR) and its confidence intervals (CI). An overall analysis revealed no statistically significant association between NKG2D genotype and the risk of aerodigestive tract cancer. However, we found protective effects of G allele among never smokers (OR 0.35; 95% CI 0.15-0.84) and never drinkers (0.42; 0.19-0.94). In contrary, increased risks were observed for G allele among heavy smokers (5.92; 3.23-10.85) and heavy drinkers (4.13; 2.29-7.47). Interactions between NKG2D genotype and lifestyle exposure were statistically significant (interaction p = 0.001 for smoking, 0.005 for drinking). The same trends were observed in both sexes, and in head and neck cancer and esophageal cancer independently. These results suggest an opposite impact of NKG2D genotype by lifestyle exposure to the risk of aerodigestive tract cancer among a Japanese population.

Correction to: Thoracic and cardiovascular surgery in Japan during 2001 : Annual report by the Japanese Association for Thoracic Surgery.

The original publication of the articles cited above included incorrect values.

Mutations of the epidermal growth factor receptor gene predict prolonged survival after gefitinib treatment in patients with non-small-cell lung cancer with postoperative recurrence.

PURPOSE: To evaluate the relationship between mutations of the epidermal growth factor receptor (EGFR) gene and the effectiveness of gefitinib treatment in patients with recurrent lung cancer after pulmonary resection. PATIENTS AND METHODS: We sequenced exons 18-21 of the EGFR gene using total RNA extracted from 59 patients with lung cancer who were treated with gefitinib for recurrent lung cancer. Gefitinib effectiveness was evaluated by both imaging studies and change in serum carcinoembryonic antigen (CEA) levels. RESULTS: EGFR mutations were found in 33 patients (56%). Of these mutations, 17 were deletions around codons 746-750 and 15 were point mutations (12 at codon 858, three at other codons), and one was an insertion. EGFR mutations were significantly more prevalent in females, adenocarcinoma, and never-smokers. Gefitinib treatment resulted in tumor shrinkage and/or CEA decrease to less than half of the baseline level in 26 patients, tumor growth and/or CEA elevation in 24 patients, and gefitinib effect was not assessable in nine patients. Female, never-smoking patients with adenocarcinoma tended to respond better to gefitinib treatment. Gefitinib was effective in 24 of 29 patients with EGFR mutations, compared with two of 21 patients without mutations (P < .0001). Of note, del746-750 might be superior to L858R mutations for prediction of gefitinib response. Patients with EGFR mutations survived for a longer period than those without the mutations after initiation of gefitinib treatment (P = .0053). CONCLUSION: EGFR mutations were a good predictor of clinical benefit of gefitinib in this setting.

Clinical aspects of multimodality therapy for resectable locoregional esophageal cancer.

Radical resection has been considered the only possible way to save the lives of patients with esophageal cancer. Therefore, tremendous efforts have been made in order to improve the surgical results for resectable locoregional esophageal cancer. Various surgical approaches have been developed. Combination therapies such as neoadjuvant, adjuvant chemotherapy, and neoadjuvant chemoradiation have been extensively investigated in numerous randomized clinical trials. Due to insufficient surgical results and high postoperative mortality rates, definitive chemoradiation has been studied as alternative treatment in selected patients, based on the concept that combined-modality therapy allows simultaneous treatment of locoregional disease and systemic micrometastases. Chemoradiation has shown survival rates equivalent to surgery in some non-randomized comparative studies. Presently, concerns appear to be shifting to the question of whether definitive chemoradiation could be an alternative to surgery in the primary treatment of resectable locoregional esophageal cancer. Recently, 2 randomized trials, comparing definitive chemoradiation with chemoradiation and surgery were published. These trials seem to show at first glance that definitive chemoradiation can achieve results comparable to surgery with neoadjuvant chemoradiation. More sophisticated trials should be conducted as treatment modalities used in these trials are far from routine.