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10.1245/s10434-007-9405-9
Annals of Surgical Oncology 14:2036-2044 (2007)
© 2007 Society of Surgical Oncology
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Original Article

Patients with Locally Advanced Esophageal Carcinoma Nonresponder to Radiochemotherapy: Who Will Benefit From Surgery?

Guillaume Piessen1, Nicolas Briez1, Jean-Pierre Triboulet1,2 and Christophe Mariette1,2

1 Department of Digestive and Oncological Surgery, University Hospital Claude Huriez—Centre Hospitalier Régional Universitaire, Lille, France
2 University of Lille II, Lille, France

Correspondence: Address correspondence and reprint requests to: Christophe Mariette; E-mail: c-mariette{at}chru-lille.fr


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Background: In patients who are nonresponders to primary radiochemotherapy (RCT), prognosis is poor, leading mostly to palliation. Salvage surgery may have a survival benefit otherwise complete. Our aim was to identify predictors of R0 resection in these patients.

Methods: In 98 nonresponders with locally advanced infracarinal tumors, curative salvage surgery was attempted. Resection was R0 in 62.2% and incomplete in 37.8% of cases. Univariate and multivariate analyses included pre-RCT and post-RCT variables collected prospectively.

Results: Overall survival was higher in the R0 resection group (18.4 vs 8.6 months, P < .001). Independent predictors of R0 resection were tumor height ≤ 5 cm on barium swallow (P = .045) and aortic contact ≤ 90° on computed tomography (P = .039) evaluated after RCT. Three groups of patients were constructed: 1, tumor height ≤ 5 cm with aortic contact ≤ 90° (n = 43); 2, tumor height between 6 and 10 cm with aortic contact ≤ 90° (n = 32); and 3, aortic contact > 90°, irrespective of tumor height (n = 23). Rates of R0 resection were 81%, 53%, and 39%, respectively (P = .001).

Conclusion: Salvage esophagectomy should be systematically attempted in nonresponders with tumor height ≤ 5 cm on barium swallow and aortic contact ≤ 90° on computed tomography and discussed case by case for other patients.

Key Words: Esophageal carcinoma • Treatment • Radiochemotherapy • Salvage surgery


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Esophageal carcinoma is a highly malignant disease with a poor prognosis, reflecting the natural history of this disease to disseminate early. Most patients have locally advanced disease at the time of diagnosis1 with primary radiochemotherapy (RCT) used as the standard treatment for those tumors.2 Because two recent multicentric randomized trials comparing neoadjuvant RCT followed by surgery to exclusive RCT showed no survival benefit to adjuvant surgery, exclusive RCT is thought to be the treatment of choice for locally advanced tumors3,4 with median survival from 14.9–19.3 months. However, after RCT treatment, 11–26% of those patients do not exhibit any morphological response,4–6 leading to a dismal prognosis with a median survival of 9 months.7 Consequently, most of nonresponders are engaged in a palliative approach.8 However, salvage esophagectomy may have a survival benefit in those patients.3,9 Since palliative surgery has not demonstrated any survival advantage, salvage esophagectomy should be considered only if a complete (R0) resection can be performed.10

Consequently, the purpose of our study was to individualize predictive factors of R0 resection in patients with locally advanced infracarinal esophageal carcinoma nonresponder to RCT, in order to identify those who will exhibit a survival benefit from salvage surgery.


   PATIENTS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Patient Population
Between January 1994 and January 2004, 1214 consecutive patients with esophageal carcinoma were referred to our digestive oncological unit of C. Huriez University Hospital, in Lille, France. Patients with esophagogastric junction tumors and rare histological subtypes were not included. Among the 1214 patients, 472 were not deemed to be resectable according to the following criteria: (i) nonresectability criteria: invasion of trachea-bronchi or recurrent laryngeal nerve, subclavian or cervical metastatic lymph node enlargement, or visceral metastasis; (ii) nonoperability criteria: cirrhosis associated with portal hypertension, respiratory failure (forced expiratory volume < 1000 mL/s), weight loss more than 20%, heart failure (New York Heart Association functional class III to IV), or an American Society anesthesiologists (ASA) score III to IV. The remaining 742 patients underwent surgery with curative intent. Among them, based on endoscopic ultrasound (EUS) and computed tomography (CT) (used alone in case of tumor stenosis precluding full EUS examination), 329 (44.3%) had locally advanced tumors (T3 or T4, N0 or N1, M0) at initial work-up. Those patients were proposed for neoadjuvant RCT with two cycles of 5-fluorouracil (800 mg/m2 per 24 hours over 4 or 5 days) and cisplatin (75 mg/m2 per 24 hours over 1 day, or 15 mg/m2 per 24 hours over 5 days), in combination with concomitant radiotherapy (30–46 Gy over 5 weeks). After a post-RCT work-up, 128 patients exhibited tumoral stability according to the RECIST criteria and were considered nonresponders. Among these patients, 98 (median age, 56.0; range 38–76 years old) had infracarinal esophageal tumor (67 at the middle third and 31 at the lower third) and were included in our study. The 30 nonresponder patients with upper-third esophageal tumor were excluded because of well-known worse resectability rate and prognosis in relation with specific extension to neighboring organs and bidirectional lymphatic spread.11,12

Pretherapeutic Work-up
Pretherapeutic investigations included physical examination, standard laboratory tests, esophago-gastroduodenal barium study, digestive endoscopy, ultrasonography of the cervical and abdominal areas, CT of the thorax, mediastinum, and abdomen, and EUS. In cases of squamous cell carcinoma or smoking history, ear, nose, and throat examination, pan-endoscopy under general anesthesia and fiberoptic bronchoscopy with biopsies were added.

Locally advanced tumors (T3 or T4, N0 or N1, M0) on this initial work-up were defined by (i) a diameter of 30 mm or more (T3) or suspicion of adjacent organ involvement (T4) on CT or (ii) an invasion of adventia (T3) or adjacent organ (T4) on EUS. Lymph nodes were considered to be involved when the maximum diameter on CT was ≥ 10 mm or they were well delimited and round with a homogenous echostructure and a maximum diameter ≥ 10 mm on EUS.

Post-RCT Work-up
A new work-up had been done 4–6 weeks after the end of RCT and 2 weeks before surgery to evaluate response to neoadjuvant treatment. This included physical examination, digestive endoscopy, barium swallow, and CT of the thorax, mediastinum, and abdomen. EUS restaging was not routinely used because of its poor accuracy after RCT13 and frequent stenosis precluding full EUS examination for advanced esophageal tumors.14 Bronchoscopy was repeated in case of compression of trachea-bronchi on initial work-up. All barium swallow study and CT were reviewed by two radiologists to independently assess the tumor response. The RECIST criteria were used to assess response to neoadjuvant RCT. Included in the present study were patients exhibiting tumor stability, that is, less than 30% reduction or less than 20% progression in tumor size, based on longest tumor height on barium swallow and maximal diameter on CT.

Surgical Approach
Esophagectomy was performed 6–8 weeks after neoadjuvant therapy had ended. Details of the resection technique have been described elsewhere.14 Complete surgical resection consisted of a transthoracic en bloc esophagectomy. Surgery included an abdominal lymphadenectomy and an extended en bloc mediastinal lymphadenectomy. Cervical lymphadenectomy was not routinely undertaken. The esophagus was replaced by the stomach in 97.1% of patients. All patients had a pyloroclasy. All anastomoses were hand sewn and placed above the level of the azygos vein. In case of tumoral residues in the posterior mediastinum, a retrosternal route with cervical anastomosis was used to preclude involvement of gastroplasty in tumor relapse.

Histopathological Analysis
After resection, all carcinomas were staged using the ypTNM classification.15 Resections were designated R0 when clearance was complete both macroscopically and microscopically, R1 when microscopically incomplete with histological evidence of invasion of the longitudinal or lateral margins, and R2 when grossly incomplete with macroscopic residual tumor.

Variables Studied
In this retrospective review of data collected in a prospective database, pre-RCT and post-RCT clinical and tumoral variables (Table 1Go), postoperative course, and long-term survival were analyzed in morphological nonresponder patients after primary RCT. Denutrition was defined as weight loss more than 10%. Tumoral response was studied using usual parameters, that is, longest tumor height on barium swallow and maximal diameter on CT after RCT, as described previously. Moreover we tested other variables to evaluate their pertinence in tumoral response evaluation and resectability, such as (i) dysphagia progression after RCT; (ii) deviation of the esophageal axis, defined as deviation from a virtual axis drawn through the middle of the esophagus lumen over its entire height; (iii) variation of esophageal stenosis (stenosis precluding a 13 mm endoscopic passage without any previous dilatation) and macroscopic residual tumor aspect (without biopsy) after RCT; (iv) a contact of the tumor to the aorta > 90°; and (v) a loss of the fat plane between tumor and neighboring organ and tumor indenting neighboring organs on CT were also evaluated.


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  		TABLE 1. Postradiochemotherapy parameters tested for predictive factors of complete resection (R0) identification
 
Statistical Analysis
Follow-up was complete for all patients. The survival status of patients was ascertained in January 2005 and mean (SD) follow-up was 20.8 (29.1) months. Data are shown as mean (SD) or median (range). Continuous data were compared with the Mann-Whitney U test and ordinal data with the {chi}2 or Fisher’s exact test as appropriate. Survival was estimated by the Kaplan-Meier method, including postoperative deaths, using SPSS® version 11.5 software (SPSS, Chicago, IL, USA). The log rank test was used for comparison of survival curves. Predictive factors of complete resection were identified by stepwise logistic regression analysis adjusting all covariates simultaneously; the 0.1 level was defined for entry into the model. Multivariable {chi}2 and P values were used to characterize the independence of these factors; the odds ratio with the 95% confidence interval (CI) was used to quantify the relationship between resection and each independent factor. Groups with different risks were identified using a stepwise procedure starting with the two significant variables from the multivariate analysis. Differences in the rates of R0 resection between the defined groups were analyzed with the {chi}2 test. All statistical tests were two sided with the threshold of significance set at P < .050.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Histopathological Analysis Assessment of the Resected Specimen
Squamous cell carcinoma was found in 89 patients. The nine other patients had adenocarcinoma. On histopathological assessment of the resected specimens, all patients had locally advanced tumors with the lesion invading the adventicia (ypT3) in 76 patients (77.6%) and neighboring structures (ypT4) in 22 patients (22.4%), confirming nonresponse to pre-operative RCT. A mean number (SD) of 15.0 (10.7) lymph nodes (range, 6–49) was dissected from each surgical specimen. Lymph node invasion (ypN1) was found in 72 patients (73.5%), whereas it was present in only 55.1% of the patients on preoperative CT. The mean number (SD) of histopathologically positive lymph node was 2.4 (2.8) (range, 0–12).

Type of Resection
R0, R1, and R2 resections were achieved in 61 patients (62.2%), 14 patients (14.3%), and 23 patients (23.5%), respectively. To analyze factors predictive of complete resection, patients were assigned to two groups: R0 group (n = 61, 62.2%)—patients with complete resection; and R1–R2 group—those with incomplete resection (n = 37, 37.8%).

Postoperative Mortality and Morbidity
The postoperative and in-hospital mortality rates were 2.0% (n = 2) and 3.1% (n = 3), respectively. Significant complications occurred in 32 patients (32.7%). Clinical or radiological anastomotic leak were observed in 7 patients (7.1%). Respiratory complications occurred in 21 patients (21.4%). Re-operation for postoperative complication occurred in 7 patients (7.1%). The median time until resumption of oral feeding was 9 days (range 6–89 days). The median hospital stay was 13 days (range 7–127 days). Postoperative course was significantly worst in the R1–R2 group with more postoperative complications (40.6% vs 27.9%) (P = .022) and deaths (8.1% vs 0%) (P = .024).

Survival
Median survival for the overall population was 14.2 months. Overall survival at 1, 2, and 5 years was 62%, 22%, and 8%, respectively. Survival was significantly better in the R0 group, with 18.4 months compared with 8.6 months in the R1–R2 group (P < .001). The 1-, 2- and 5-year survival rates in the R0 group were 77%, 33%, and 13%, respectively (Fig. 1Go). The 1- and 2-year survival rate in the R1–R2 group were 36% and 4%, respectively. After 26 months of follow-up, there were no more survivors in the R1–R2 group.


Figure 1
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  		FIG. 1. Survival curves for the overall population and for R0 (complete resection) and R1–R2 (incomplete resection) groups. R0 vs R1–R2, P = .001, log rank test.

 
Univariate Analysis
Based on univariate analysis (Table 2Go), five variables were found to be statistically related to R1–R2 resection: (i) Esophageal stenosis precluding endoscopic passage (P = .004), (ii) aortic contact > 90° (P = .009) (Fig. 2Go), (iii) post-RCT dysphagia (P = .015), (iv) tumor height on barium swallow > 5 cm (P = .018) (Fig. 3Go), and (v) macroscopic residual tumor on endoscopy (P = .032).


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  		TABLE 2. Pre-RCT and pos-tRCT factors influencing type of resection in univariate analysis
 

Figure 2
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  		FIG. 2. CT scan showing a contact between lower-third esophageal tumor and thoracic aorta > 90° in patient nonresponder to chemoradiation, predictor of incomplete tumoral resection.

 

Figure 3
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  		FIG. 3. Tumor height on barium swallow > 5 cm, predictor of incomplete tumoral resection.

 
Multivariate Analysis
Based on multivariate analysis (Table 3Go), two independent variables were predictive of R0 resection: aortic contact ≤ 90° on CT (P = .039) and tumor height on barium swallow (P = .045).


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  		TABLE 3. Independent post-RCT factors predictive of complete resection (R0) in multivariate analysis
 
Groups
Three groups were constructed with the two variables previously identified in multivariate analysis as predictive of R0 resection: aortic contact ≤ 90° on CT and tumor height on barium swallow (Table 4Go). The first group was composed of 43 patients with tumor height between 0 and 5 cm on barium swallow and with aortic contact ≤ 90° on CT. The second group was composed of 32 patients with tumor height between 6 and 10 cm on barium swallow with aortic contact ≤ 90° on CT. The third group was composed of 23 patients who had aortic contact > 90° on CT, irrespective of tumor height on barium swallow. Rates of R0 resection were 81.4%, 53.1%, and 39.1%, respectively and were significantly different between groups (P = .001) and two-by-two (P < .001). Median survival were 15.7 months in group 1, 14.4 months in group 2, and 12.2 months in group 3, with a trend but nonstatistically significant survival difference between the groups (P = .199). Integrating constructed score, a new multivariate analysis exhibited this score as the only independent predictive factor of R0 resection (odds ratio 2.4, 95% CI 1.3–4.4, P = .004). This confirms the relevance of the score in identifying patients as nonresponders to primary RCT who will benefit from surgery through R0 resection.


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  		TABLE 4. R0 resection rates and survivals in the three groups constructed
 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
Locally advanced esophageal carcinomas are widely treated with primary RCT followed by surgery, despite the lack of evidence-based data.2 However, many arguments, especially higher R0 resection and pathological complete response rates, led to the proposal of neoadjuvant RCT as a standard treatment for locally advanced carcinomas.16 Moreover, two recent multicentric randomized trials, comparing neoadjuvant RCT followed by surgery to exclusive RCT, showed no survival benefit to adjuvant surgery, especially for responder patients.3,4 Whereas most nonresponder patients are engaged in a palliative strategy because of a median survival of 9 months,7,8 we show in this study that (i) salvage esophagectomy can offer a longer median survival of 18.4 months in case of R0 resection for those patients and that (ii) two parameters, aortic contact ≤ 90° on CT and tumor height ≤ 5 or 10 cm on barium swallow, can be used to identify nonresponder patients who will benefit from surgery.

Median survival of 14.1 months observed in our study is significantly better than survival rates reported in studies where nonresponder patients were included in a palliative strategy.7,8 With 2-year survival rate of 33%, nonresponder patients who underwent R0 resection (R0 group) are patients who have the higher survival benefit from salvage esophagectomy. This survival rate compares favorably to those of previous reports studying surgery in nonresponder patients after neoadjuvant treatment.3,8 Another important point is that median and 2-year survival showed in our study after R0 resection in nonresponder patients (18.4 months and 33%, respectively) were similar to those observed in the French randomized trial comparing definitive RCT to RCT followed by surgery in the same patients (locally advanced tumors with a majority of squamous cell carcinomas) but responders to neoadjuvant therapy (18.6 months and 34%, respectively).4 Moreover, nonresponder patients, excluded from the French study, had a median survival of only 11.4 months, worse than responders. Even if the populations could possibly be different between the two studies, because of the median survivals observed we can hypothesize that: (i) Surgery would probably have enhanced survival in nonresponders in the French study, (ii) because of the low survival rate in the responder patients, the strategy tested in the French study, excluding surgery, is suboptimal with a possible loss of chance for nonresected patients. This view has been reinforced by the fact that evaluation of the tumoral response to RCT is frequently suboptimal. Discordance between clinical and histological response is well known.10,17 After primary RCT, differences between residual tumor and postradiation initial inflammation or late fibrosis with conventional exams (i.e., CT and EUS) can not be accurately predicted.18,19 This leads one to question therapeutic strategies based on standard tumoral response evaluation using dysphagia and esophagogram4 or esophagogram combined with CT.3 New technologies should be developed to better define tumoral response to neoadjuvant therapy. Positron emission tomography (PET) seems to be promising in this indication since metabolic imaging correlates well with pathological response and survival.20,21 However, this exam was not available at the time of our study, and in nonresponder patients it is probably better to detect distance metastasis rather than play a role in determining locoregional resectbility.22

Postoperative course was significantly worse in the R1–R2 group. We can hypothesize that wide local tumor extension is a witness to micrometastatic disease leading to host weakening. Since postoperative morbidity and mortality are higher in the R1–R2 group and since only the R0 resection group exhibit a survival benefit, it is fundamental to identify those patients in whom R0 resection could be performed. To help physicians in this selection, we identified two simple morphological parameters, evaluated after RCT, included in three constructed groups with significant different R0 resection rates. Patients with tumor height between 0 and 5 cm on barium swallow and an aortic contact ≤ 90° on CT (group 1) had a higher R0 resection rate than those who had aortic contact > 90° on CT (group 3) (81% vs 39%, P < .001). Patients with tumor height between 6 and 10 cm on barium swallow with aortic contact ≤ 90° on CT represented an intermediate group (group 2) with a R0 resection rate of 53%, significantly different from the two others (P < .001). We did not find significant differences between groups regarding survival probably because of poor prognosis and small population per group.

Barium swallow remains the usual first step in preoperative work-up, assessing length of tumor, degree, and level of obstruction. In several studies, tumor height on barium swallow is closely correlated with tumor extension,23,24 curative resection,24,25 or survival.24 We demonstrated in our study that barium swallow remains an important tool to evaluate resectability after RCT. An esophageal carcinoma that directly invades the aorta may increase the area of contact between the aorta and the esophagus. Criteria for aortic invasion have included the amount of circumferential contact between the aorta and the tumor. An arc interface of less than 45° predicts absence of invasion, whereas an arc interface greater than 90° suggests invasion before RCT.26 Contact between 45 and 90° is indeterminate. However, this criterion had never been evaluated after RCT. We showed that studying circumferential contact between the aorta and the esophagus remains a determinant criterion to identify patients likely to be resectable after RCT.

Barium swallow and CT are simple, accessible, reproducible, and noninvasive tools that should be available for all patients after RCT, allowing easy classification of nonresponder patients into three groups. In the absence of (i) metastatic disease on post-RCT work-up and (ii) nonoperability criteria, surgery should be systematically proposed for patients who have tumor height between 0 and 5 cm with aortic contact ≤ 90°. In groups 2 and 3, patients having 47% and 61% risk of R1 or R2 resection, respectively, staging should be improved before considering esophagectomy. Unfortunately, neither PET27 nor EUS28 add to the estimation of locoregional resectability after primary RCT. However, preliminary but conflicting results showed that PET could facilitate treatment planning in identifying (i) unsuspected distant metastasis with conventional imaging27 and (ii) patients with a poor long-term prognosis.29 A clinical trial is under investigation in our institution to evaluate the role of PET in therapeutic strategy after neoadjuvant RCT. In case of no clear contraindication for an R0 resection after extensive work-up, we think that an explorative thoracoscopy or thoracotomy should be the first step of the surgical treatment for nonresponder patients belonging to the group 2 to evaluate more accurately tumoral resectability. Then resection should be performed if complete surgery is possible. In our opinion for group 3 patients, selection should be very stringent and surgery proposed case by case, knowing that the vast majority will be engaged in palliation.

To conclude, in the absence of tumor progression, neither the patient nor the treating physician should jeopardize the chance for ultimate cure by denying salvage esophagectomy led by preoperative morphological evaluation. Even if the score presented here may need validation in a different population, we show for the first time that tumor height on the barium swallow and circumferential contact between aorta and the tumor on CT are the most useful tools to determine patients who will benefit from surgery after nonresponse to primary RCT. An equivalent work for nonresponder patients with upper-third esophageal tumors is under investigation, taking into account specific extension to tracheo-bronchial tree, upper thoracic inlet, and bidirectional lymphatic spread.


   ACKNOWLEDGMENTS
 
The authors thank Dr Isabelle Van Seuningen for critical reading of the manuscript.


   FOOTNOTES
 
Presented in part and rewarded at the Second French-Speaking Conference of Digestive and Hepatobiliary Surgery, Paris, France, December 2006.

Received for publication January 14, 2007. Accepted for publication February 27, 2007.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Brenner B, Ilson DH, Minsky BD. Treatment of localized esophageal cancer. Semin Oncol 2004; 31:554–65.[CrossRef][Medline]
  2. Mariette C, Triboulet JP. Is preoperative chemoradiation effective in treatment of oesophageal carcinoma? Lancet Oncol 2005; 6:635–7.[CrossRef][Medline]
  3. Stahl M, Stuschke M, Lehmann N, Meyer HJ, Walz MK, Seeber S, et al. Chemoradiation with and without surgery in patients with locally advanced squamous cell carcinoma of the esophagus. J Clin Oncol 2005; 23:2310–7.[Abstract/Free Full Text]
  4. Bedenne L, Michel P, Bouché O, Milan C, Mariette C, Conroy T, et al. Chemo-radiation followed by surgery compared to chemo-radiation alone in locally advanced operable oesophageal cancer: a randomised multicentric phase III trial (FFCD 9102). J Clin Oncol. 2007, in press.
  5. Jeremic B, Shibamoto Y, Acimovic L, Matovic Z, Milicic B, Milisavljevic S, et al. Accelerated hyperfractionated radiation therapy and concurrent 5-fluorouracil/cisplatin chemotherapy for locoregional squamous cell carcinoma of the thoracic esophagus: a phase II study. Int J Radiat Oncol Biol Phys 1998; 40:1061–6.[CrossRef][Medline]
  6. Mariette C, Taillier G, Van Seuningen I, Triboulet JP. Factors affecting postoperative course and survival after en bloc resection for esophageal carcinoma. Ann Thorac Surg 2004; 78:1177–83.[Abstract/Free Full Text]
  7. Di Fiore F, Lecleire S, Rigal O, Galais MP, Ben Soussan E, David I, et al. Predictive factors of survival in patients treated with definitive chemoradiotherapy for squamous cell esophageal carcinoma. World J Gastroenterol 2006; 12:4185–90.[Medline]
  8. Ancona E, Ruol A, Santi S, Merigliano S, Sileni VC, Koussis H, et al. Only pathologic complete response to neoadjuvant chemotherapy improves significantly the long term survival of patients with resectable esophageal squamous cell carcinoma: final report of a randomized, controlled trial of preoperative chemotherapy versus surgery alone. Cancer 2001; 9:2165–74.
  9. Murakami M, Kuroda Y, Matsusue S, Okamoto Y, Nakajima T, Nishimura S, et al. Treatment results of esophageal carcinoma of clinical T3, T4M0: historical comparison between neoadjuvant chemoradiotherapy followed by surgery or definitive radiotherapy and conventional surgery. Oncol Rep 2000; 7:571–8.[Medline]
  10. Mariette C, Finzi L, Fabre S, Balon JM, Van Seuningen I, Triboulet JP. Factors predictive of complete resection of operable esophageal cancer: a prospective study. Ann Thorac Surg 2003; 75:1720–6.[Abstract/Free Full Text]
  11. Piessen G, Mariette C, Triboulet JP. Cervical and upper-third thoracic esophageal carcinoma: a single pathological entity? Ann Chir 2005; 130:86–91.[CrossRef][Medline]
  12. Manshanden CG, Hulscher JB, Hovius M, Fockens P, van Lanschot JJ, Obertop H. Limited resection for carcinoma of the upper thoracic oesophagus is not a realistic option. Eur J Surg Oncol 2000; 26:561–6.[CrossRef][Medline]
  13. Westerterp M, van Westreenen HL, Reitsma JB, Hoekstra OS, Stoker J, Fockens P, et al. Esophageal cancer: CT, endoscopic US, and FDG PET for assessment of response to neoadjuvant therapy-systematic review. Radiology 2005; 236:841–51.[Abstract/Free Full Text]
  14. Mariette C, Balon JM, Maunoury V, Taillier G, Van Seuningen I, Triboulet JP. Value of endoscopic ultrasonography as a predictor of long-term survival in oesophageal carcinoma. Br J Surg 2003; 90:1367–72.[CrossRef][Medline]
  15. In: Greene FL, Page DL, Fleming ID, Fritz AG, Balch CM, Haller DG (edset al. AJCC Cancer Staging Manual 6th ed. New York: Springer Verlag; 2002.
  16. Mariette C, Piessen G, Lamblin A, Mirabel X, Adenis A, Triboulet JP. Impact of preoperative radiochemotherapy on postoperative course and survival in patients with locally advanced squamous cell oesophageal carcinoma. Br J Surg 2006; 93:1077–83.[CrossRef][Medline]
  17. Bedenne L, Seitz JF, Milan C, Renard P, Fraisse J, Conroy T, et al. Cisplatin, 5-FU and preoperative radiotherapy in esophageal epidermoid cancer. Multicenter phase II FFCD 8804 study. Gastroenterol Clin Biol 1998; 22:273–81.[Medline]
  18. Zuccaro G Jr, Rice TW, Goldblum J, Medendorp SV, Becker M, Pimentel R, et al. Endoscopic ultrasound cannot determine suitability for esophagectomy after aggressive chemoradiotherapy for esophageal cancer. Am J Gastroenterol 1999; 94:906–12.[Medline]
  19. Beseth BD, Bedford R, Isacoff WH, Holmes EC, Cameron RB. Endoscopic ultrasound does not accurately assess pathologic stage of esophageal cancer after neoadjuvant chemoradiotherapy. Am Surg 2000; 66:827–31.[Medline]
  20. Brucher BL, Weber W, Bauer M, Fink U, Avril N, Stein HJ, et al. Neoadjuvant therapy of esophageal squamous cell carcinoma: response evaluation by positron emission tomography. Ann Surg 2001; 233:300–9.[CrossRef][Medline]
  21. Levine EA, Farmer MR, Clark P, Mishra G, Ho C, Geisinger KR, et al. Predictive value of 18-fluoro-deoxy-glucose-positron emission tomography (18F-FDG-PET) in the identification of responders to chemoradiation therapy for the treatment of locally advanced esophageal cancer. Ann Surg 2006; 243:472–8.[CrossRef][Medline]
  22. Reed CE, Eloubeidi MA. New techniques for staging esophageal cancer. Surg Clin North Am. 2002; 82:697–710.[CrossRef][Medline]
  23. Woronoff AS, Mercier M, Gignoux M, Triboulet JP, Chaillard G, Bosset JF. Prognostic factors in operable epidermoid esophageal cancers. Gastroenterol Clin Biol 1998; 22:168–74.[Medline]
  24. Elias D, Lasser P, Hatchouel JM, Escudier B, Spielmann M, Girinsky T, et al. A multivariate prospective study of prognostic factors in 200 operated epidermoid cancers of the esophagus. Definition of patients for whom surgical resection was of benefit. Gastroenterol Clin Biol 1993; 17:17–25.[Medline]
  25. Sugimachi K, Watanabe M, Sadanaga N, Ikebe M, Mori M, Kitamura K, et al. Pre-operative estimation of complete resection for patients with oesophageal carcinoma. Surg Oncol 1994; 3:327–34.[CrossRef][Medline]
  26. Picus D, Balfe DM, Koehler RE, Roper CL, Owen JW. Computed tomography in the staging of esophageal carcinoma. Radiology 1983; 146:433–8.[Abstract/Free Full Text]
  27. Downey RJ, Akhurst T, Ilson D, Ginsberg R, Bains MS, Gonen M, et al. Whole body 18FDG-PET and the response of esophageal cancer to induction therapy: results of a prospective trial. J Clin Oncol 2003; 21:428–32.[Abstract/Free Full Text]
  28. Laterza E, de Manzoni G, Guglielmi A, Rodella L, Tedesco P, Cordiano C. Endoscopic ultrasonography in the staging of esophageal carcinoma after preoperative radiotherapy and chemotherapy. Ann Thorac Surg 1999; 67:1466–9.[Abstract/Free Full Text]
  29. Swisher SG, Erasmus J, Maish M, Correa AM, Macapinlac H, Ajani JA, et al. 2-Fluoro-2-deoxy-D-glucose positron emission tomography imaging is predictive of pathologic response and survival after preoperative chemoradiation in patients with esophageal carcinoma. Cancer 2004; 101:1776–85.[CrossRef][Medline]



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Eur. J. Cardiothorac. Surg., June 1, 2008; 33(6): 1117 - 1123.
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