JTCS Sign the Guestbook
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Author home page(s):
Thomas W. Rice
Malcolm M. DeCamp
Sudish C. Murthy
Eugene H. Blackstone
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Rice, T. W.
Right arrow Articles by Blackstone, E. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rice, T. W.
Right arrow Articles by Blackstone, E. H.
Related Collections
Right arrow Esophagus - cancer

J Thorac Cardiovasc Surg 2003;126:1590-1596
© 2003 The American Association for Thoracic Surgery

General thoracic surgery

Benefit of postoperative adjuvant chemoradiotherapy in locoregionally advanced esophageal carcinoma

Thomas W. Rice, MDa,b,*, David J. Adelstein, MDa,c, Mark A. Chidel, MDa,d, Lisa A. Rybicki, MSa,e, Malcolm M. DeCamp, MDa,b, Sudish C. Murthy, MD, PhDa,b, Eugene H. Blackstone, MDa,b,e

a The Center for Swallowing and Esophageal Disorders, The Cleveland Clinic Foundation, Cleveland, Ohio,USA
b Department of Thoracic and Cardiovascular Surgery, The Cleveland Clinic Foundation, Cleveland, Ohio, USA
c Department of Hematology and Medical Oncology,, The Cleveland Clinic Foundation, Cleveland, Ohio, USA
d Department of Radiation Oncology, The Cleveland Clinic Foundation, Cleveland, Ohio, USA
e Department of Biostatistics and Epidemiology, The Cleveland Clinic Foundation, Cleveland, Ohio, USA

Read at the Twenty-eighth Annual Meeting of The Western Thoracic Surgical Association, Big Sky, Mont, June 19-22, 2002.

Received for publication June 20, 2002; revisions received August 19, 2002; revisions received March 11, 2003; accepted for publication April 10, 2003.

* Address for reprints: Thomas W. Rice, MD, The Cleveland Clinic Foundation, 9500 Euclid Ave/Desk F25, Cleveland, OH 44195, USA
ricet{at}ccf.org


   Abstract
Top
 Abstract
Patients and methods
 Results
 Discussion
 References
 
OBJECTIVE: We sought to determine whether chemoradiotherapy after esophagectomy improves survival.

METHODS: From 1994 to 2000, 31 patients with locoregionally advanced esophageal carcinoma (90% pT3, 81% pN1, and 13% pM1a) received postoperative adjuvant chemoradiotherapy. Concurrently, 52 patients with advanced carcinoma underwent esophagectomy alone and survived at least 10 weeks, the time frame for adjuvant therapy. A propensity score based on demographic, tumor, and surgical factors was used to identify matched pairs to determine the association of adjuvant therapy with outcomes.

RESULTS: For patients receiving adjuvant therapy versus esophagectomy alone, risk-unadjusted median, 1-year, and 4-year survivals were 28 versus 14 months, 68% ± 8.4% versus 60% ± 6.8%, and 44% ± 9.0% versus 17% ± 5.6%, respectively (P = .05). Similarly, risk-unadjusted median time to recurrence was 25 versus 13 months (P = .15), and median recurrence-free survival was 22 versus 11 months (P = .04). Among propensity-matched patients, median, 1-year, and 4-year survivals for those receiving adjuvant therapy versus esophagectomy were 28 versus 15 months, 60% ± 11.0% versus 65% ± 10.7%, and 44% ± 11.3% versus 0% (P = .05). Median time to recurrence was 25 versus 13 months (P = .04), and recurrence-free survival was 22 versus 10 months (P = .02).

CONCLUSION: In patients with locoregionally advanced esophageal carcinoma, addition of postoperative adjuvant chemoradiotherapy to esophagectomy alone doubled survival time, time to recurrence, and recurrence-free survival. Patients with locoregionally advanced carcinoma after esophagectomy should be considered for adjuvant therapy.

Postoperative adjuvant therapy provides a survival advantage in cancers of the stomach, colon, and rectum.1-3 However, single-modality postoperative adjuvant therapy in esophageal cancer has been limited and potentially harmful,4-6 although postoperative adjuvant radiation therapy may benefit patients with advanced disease.7 Recent clinical experience with modern postoperative adjuvant chemoradiotherapy suggests a survival benefit compared with historical controls.8,9 In the absence of randomized trials, the purpose of this study was to determine whether adjuvant chemoradiotherapy after esophagectomy improves survival compared with esophagectomy alone.


   Patients and methods
Top
 Abstract
 Patients and methods
Results
 Discussion
 References
 
Patients
From 1994 to 2000, 31 patients with pathologically documented locoregionally advanced adenocarcinoma or squamous cell esophageal carcinoma (T3-4, N1, or M1a) underwent esophagectomy and were entered in an institutional review board–approved (IRB 4624) trial of postoperative adjuvant chemoradiotherapy. Patients were eligible for this protocol if they had not received previous radiation or chemotherapy for this cancer, had an Eastern Cooperative Oncology Group performance status of 0 or 1, a white blood cell count of 3000 · mm-3 or greater, and a serum creatinine level of 2.0 mg · dL-1 or less.

During this period, 52 patients with locoregionally advanced carcinoma underwent esophagectomy alone without adjuvant therapy and survived more than 10 weeks after the operation, the time frame for postoperative adjuvant therapy (Tables 1 and 2). Data used for this study came from the Cleveland Clinic esophageal database, which has been approved for research by the institutional review board.


View this table:
[in this window]
[in a new window]
  		TABLE 1. Comparison of patients undergoing postoperative adjuvant therapy with those undergoing esophagectomy alone: Categorical variables

 

View this table:
[in this window]
[in a new window]
  		TABLE 2. Comparison of patients undergoing postoperative adjuvant therapy with those undergoing esophagectomy alone: Continuous variables

 
Esophagectomy
Esophagectomy with thoracotomy and 2-field lymphadenectomy was performed in 27 patients receiving adjuvant therapy and 46 patients receiving esophagectomy alone. Four patients receiving adjuvant therapy and 6 patients receiving esophagectomy alone had transhiatal esophagectomy and lymph node sampling. Gastrointestinal reconstruction in all patients used the stomach, with esophagogastric anastomosis done in the neck.

Postoperative adjuvant chemoradiotherapy
Three to 10 weeks after esophagectomy, each patient received a continuous course of external beam radiation therapy with concurrent chemotherapy. Patients received 50.4 to 59.4 Gy in 1.8-Gy once-daily fractions. Treatments were delivered using a linear accelerator with 6- to 8-MV photons at a distance of 100 cm from the source to the axis of rotation. Computed tomography–based treatment planning was used in all patients. A minimum 5-cm margin was given to the tumor bed, superiorly and inferiorly. Lymph node coverage included mediastinal and celiac lymph nodes for middle thoracic tumors and low mediastinal and celiac lymph nodes for lower thoracic tumors. The maximal spinal dose was 45 Gy, which was accomplished either by a field rearrangement after 39.6 to 41.4 Gy or by treatment with a 3-field technique from the beginning of therapy.

Concurrent with radiotherapy, each patient received two 4-day cycles of intravenous 5-fluorouracil (1000 mg · m-2 · d-1) and cisplatin (20 mg · m-2 · d-1) during the first and fourth week of adjuvant therapy. After completion of chemoradiotherapy, patients were followed at 3-month intervals.

Comparison of outcome
Management of outcome data
Because patients had to survive esophagectomy to receive postoperative adjuvant therapy, those undergoing esophagectomy alone who died within 10 weeks of the operation were not included in this comparative study. Thus, in both groups, 10 weeks postoperatively was taken as time zero for all time-related analysis.

Both Kaplan–Meier (nonparametric) and Cox proportional hazards analyses were used to compare survival, freedom from recurrence, and recurrence-free survival between patients receiving adjuvant therapy and those receiving esophagectomy alone. Nonparametric survival estimates were compared by using the log-rank test. Survival estimates are presented with their SE and number of patients at various intervals and as median survival.

Methods of comparisons
Outcomes were compared in 2 ways: risk unadjusted and propensity matched.

Risk-unadjusted comparison of outcomes among patients receiving postoperative adjuvant chemoradiotherapy versus esophagectomy alone was performed using the log-rank statistic.

Propensity-matched comparison was performed because selection of patients for adjuvant therapy or esophagectomy alone was not random.10,11 Therefore, the probability of receiving adjuvant therapy versus esophagectomy alone was estimated by logistic regression using 15 variables representing 13 patient, tumor, procedure, and experience characteristics: sex, race, age at operation, pT (T2 vs T1 and T3-4 vs T1, 2 variables), pN, total number of lymph nodes resected, total number of resected nodes containing metastatic cancer, pM, histopathologic type (adenocarcinoma vs squamous cell carcinoma), histopathologic grade (moderately vs well and poorly vs well differentiated, 2 variables), surgical approach (thoracotomy vs transhiatal), completeness of resection (R0 vs R1), and date of operation. A propensity score was calculated for each patient from the resulting logistic regression equation. Patients undergoing each therapy were then matched by using the above propensity score.12 Because the original 2 groups were of comparable size, there were too few esophagectomy-only patients to match every patient receiving postoperative adjuvant chemoradiotherapy. Thus, 20 well-matched pairs of patients were available for comparison of outcomes (Tables 3 and 4) by using the log-rank and hazard ratio statistics.


View this table:
[in this window]
[in a new window]
  		TABLE 3. Comparison of propensity-matched patients undergoing postoperative adjuvant therapy with those undergoing esophagectomy alone: Categoric variables

 

View this table:
[in this window]
[in a new window]
  		TABLE 4. Comparison of propensity-matched patients undergoing postoperative adjuvant therapy with those undergoing esophagectomy alone: Continuous variables

 
Presentation
Continuous variables are presented as means ± 1 SD. Survival estimates are presented as percentage ± 1 SE. For consistency with these, hazard ratios are presented with 68% confidence limits (CL).


   Results
Top
 Abstract
 Patients and methods
 Results
Discussion
 References
 
Toxicity
Toxicity of the adjuvant chemoradiotherapy is detailed in Table 5. Nutrition was well maintained during adjuvant therapy in part because 28 of the 31 patients had jejunostomy tubes in place throughout treatment. There were no toxic deaths. Unplanned hospitalizations were required in 9 patients: 3 because of uncomplicated neutropenic fever, 2 because of a venous thromboembolic event, 2 because of infections developing with adequate blood counts, and 1 each with presumably unrelated episodes of ischemic colitis and cholecystitis.


View this table:
[in this window]
[in a new window]
  		TABLE 5. Toxicity of adjuvant chemoradiotherapy

 
Outcome
Survival
For patients receiving adjuvant therapy versus esophagectomy alone, risk-unadjusted median, 1-year, and 4-year survivals were 28 months versus 14 months, 68% ± 8.4% versus 60% ± 6.8%, and 44% ± 9.0% versus 17% ± 5.6%, respectively (P = .05; Figure 1, A). Among propensity-matched patients, median, 1-year, and 4-year survivals in the 2 groups of patients were 28 months versus 15 months, 60% ± 11.0% versus 65% ± 10.7%, and 44% ± 11.3% versus 0%, respectively (P = .05; Figure 1, B). The hazard ratio of adjuvant therapy versus esophagectomy was 0.46 (CL 0.31-0.69).



View larger version (20K):
[in this window]
[in a new window]
  		Figure 1. Survival among patients receiving adjuvant therapy compared with esophagectomy alone. Long vertical bars represent CLs of 1 SE. Short vertical bars represent censored patients. Each step in the graph represents an event. A, Unadjusted. Numbers of patients traced at 0, 1, and 4 years were 31, 21, and 5 in the adjuvant therapy group and 52, 31, and 5 in the esophagectomy-alone group. B, Propensity matched. Numbers of patients traced at 0, 1, and 4 years were 20, 12, and 3 in the adjuvant therapy group and 20, 13, and 0 in the esophagectomy-alone group.

 
Recurrence
There were 17 recurrences in patients receiving adjuvant chemoradiotherapy. One patient was alive and disease free at follow-up after resection of a solitary brain metastasis. Sixteen patients died with disease: 7 with local metastases, 7 with distant metastases, and 2 with both local and distant metastases. There were 33 cancer recurrences in patients receiving esophagectomy alone. Two were alive at follow-up, one with local and one with distant recurrence. Thirty-one died with disease: 14 with local metastases, 12 with distant metastases, and 5 with both local and distant metastases. Among the 20 propensity-matched patients receiving adjuvant therapy, 12 had recurrences, 4 local and 8 distant. Of the 20 receiving esophagectomy alone, 16 had recurrences, 6 local, 8 distant, and 2 both local and distant.

For patients receiving adjuvant therapy versus esophagectomy alone, risk-unadjusted median, 1-year, and 4-year freedoms from recurrence were 25 months versus 13 months, 65% ± 8.6% versus 53% ± 7.4%, and 44% ± 9.8% versus 23% ± 7.0%, respectively (P = .15; Figure 2, A). Among propensity-matched patients, median, 1-year, and 4-year freedoms from recurrence in the 2 groups of patients were 25 months versus 13 months, 60% ± 11.0% versus 50% ± 1.9%, and 40% ± 12.1% versus 0%, respectively (P = .04; Figure 2, B). The hazard ratio of adjuvant therapy versus esophagectomy was 0.45 (CL 0.30-0.67).



View larger version (21K):
[in this window]
[in a new window]
  		Figure 2. Freedom from recurrence among patients receiving adjuvant therapy compared with esophagectomy alone. Format is as shown in Figure 1. A, Unadjusted. Numbers of patients traced at 0, 1, and 4 years were 31, 19, and 5 in the adjuvant therapy group and 52, 22, and 5 in the esophagectomy-alone group. B, Propensity matched. Numbers of patients traced at 0, 1, and 4 years were 20, 11, and 3 in the adjuvant therapy group and 20, 8, and 0 in the esophagectomy-alone group.

 
Recurrence-free survival
For patients receiving adjuvant therapy versus esophagectomy alone, risk-unadjusted median, 1-year, and 4-year recurrence-free survivals were 22 months versus 11 months, 61% ± 8.8% versus 42% ± 6.8%, and 39% ± 9.3% versus 15% ± 5.0%, respectively (P = .04; Figure 3, A). For propensity-matched patients, median, 1-year, and 4-year recurrence-free survivals in the 2 groups of patients were 22 months versus 10 months, 55% ± 11.1% versus 40% ± 11.0%, and 37% ± 11.6% versus 0%, respectively (P = .02; Figure 3, B). The hazard ratio of adjuvant therapy versus esophagectomy was 0.42 (CL 0.29-1.62).



View larger version (21K):
[in this window]
[in a new window]
  		Figure 3. Freedom from recurrence or death (recurrence-free survival) among patients receiving adjuvant therapy compared with esophagectomy alone. Format is as shown in Figure 1. A, Unadjusted. Numbers of patients traced at 0, 1, and 4 years were 31, 19, and 5 in the adjuvant therapy group and 52, 22, and 5 in the esophagectomy-alone group. B, Propensity matched. Numbers of patients traced at 0, 1, and 4 years were 20, 11, and 3 in the adjuvant therapy group and 20, 8, and 0 in the esophagectomy-alone group.

 

   Discussion
Top
 Abstract
 Patients and methods
 Results
 Discussion
References
 
Rationale for adjuvant therapy
Single-modality preoperative adjuvant therapy (chemotherapy or radiotherapy) for esophageal carcinoma offers no greater survival than esophagectomy alone.13-15 Concurrent preoperative chemoradiotherapy has produced conflicting results despite complete pathologic response in up to 30% of patients.16-18 Single-modality postoperative adjuvant therapy has not improved survival or has been harmful,4-6 except for a recent report of benefit from radiation therapy for stage IIB or III tumors.7 However, recent phase II studies8,9 and this report suggest that postoperative concurrent chemoradiotherapy improves survival compared with historical controls and propensity-matched patients receiving esophagectomy alone. It can be administered with acceptable toxicity and enhances local control in patients with locoregionally advanced esophageal carcinoma.

Postoperative adjuvant therapy has theoretic advantages and disadvantages. Potential advantages include the following: (1) therapy can be based on pathologic stage rather than potentially inaccurate clinical stage; (2) patients who might benefit from adjuvant therapy can be identified, avoiding toxicity in those who do not need or will not benefit from it; (3) delay resulting from induction therapy is avoided, and resection is ensured; (4) dysphagia is relieved early in treatment; (5) nutrition can be maintained with feeding tubes placed at operation; and (6) induction therapy toxicity does not affect surgery. Potential disadvantages include the following: (1) blood supply to the resected area is reduced, decreasing delivery of chemotherapy to the locoregional tumor bed; (2) the radiation therapy target is removed at operation, complicating the definition of radiation fields; (3) postoperative complications preclude adjuvant therapy; (4) early postoperative death precludes adjuvant therapy, possibly biasing survival data; and (5) the effect of induction therapy on resectability is eliminated.

Postoperative chemoradiotherapy requires balancing advantages with disadvantages and treatment toxicity with improved survival. For the majority of patients in this report, postoperative chemoradiotherapy was advantageous. However, when to use this strategy is not clearly defined.

Treatment strategies
A single-treatment strategy for all patients with locoregionally contained esophageal carcinoma is an outdated approach.19 Detection of cancer at an earlier stage with Barrett surveillance, accurate clinical staging, and development of new treatments allows a tailored stage-dependent approach to be used.

At one end of the cancer spectrum—high-grade dysplasia and intramucosal cancers without regional lymph node metastases—esophagectomy alone offers excellent survival.20 For these patients, the toxicity of adjuvant therapy outweighs any small survival advantage.21

At the opposite end of the cancer spectrum—marginally operable tumors because of either bulky T3 or T4 disease or significant regional lymph node metastases (R2 resection likely)—esophagectomy alone offers no hope of cure. Induction therapy will downstage about one third of these patients, and subsequent resection will offer responders an intermediate survival.22 The survival advantage in responders far outweighs the toxicity of treatment. If nonresponders are identified after induction therapy, esophagectomy might be avoided and best palliation offered. In the future, identification of likely responders before therapy will further refine this approach.

Esophageal carcinoma between these 2 ends of the spectrum affects many patients, with variable survival after esophagectomy alone. Esophagectomy followed by postoperative adjuvant therapy should be considered in the following clinical situations: (1) patients with incorrect clinical staging who have esophagectomy and are found to have more advanced disease (T3 or N1 or M1a); (2) patients with T3 or N1 cancers (few regional nodal metastases) who appear technically resectable (R0 resection possible); and (3) patients with deep submucosal invasion (T1bN0M0) or invasion into the muscularis propria (T2N0M0) without regional nodal metastases.

Strengths and weaknesses
This is a small, single-institution, nonrandomized phase II study. Two methods of comparison were used, unadjusted and propensity matched to minimize selection bias. Results were consistent. Because esophagectomy was the first treatment, accurate pathologic stage was available for all patients and is fundamental to this comparison, unlike preoperative induction therapies in which potentially inaccurate clinical staging complicates comparisons. The absence of staging inaccuracies and good matching based on 15 variables allowed outcome comparisons to be influenced principally by postoperative adjuvant therapy. Nevertheless, propensity matching does not guard against unknown factors. Among potential and unmeasured factors that might have influenced patient selection were subjective ones, such as vigor, mental status, ability to cooperate with and consent to treatment protocols, referral and physician bias, and the unblinded nature of the treatments. These factors influence not only nonrandomized comparisons but also randomized trials.23

Clinical inference
In patients with locoregionally advanced esophageal cancer in whom an R0 resection is clinically possible, the strategy of esophagectomy followed by postoperative adjuvant chemoradiotherapy should be considered. Compared with esophagectomy alone, it improves survival, decreases recurrent cancer, and increases recurrence-free survival.


   References
Top
 Abstract
 Patients and methods
 Results
 Discussion
 References
 

  1. Macdonald JS, Smalley SR, Benedetti J, Hundahl SA, Estes NC, Stemmermann GN, et al. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med. 2001;345:725–730[Abstract/Free Full Text]
  2. Moertel CG, Fleming TR, Macdonald JS, Haller DG, Laurie JA, Goodman PJ, et al. Levamisole and fluorouracil for adjuvant therapy of resected colon carcinoma. N Engl J Med. 1990;322:352–358[Abstract]
  3. Fisher B, Wolmark N, Rockette H, Redmond C, Deutsch M, Wickerham DL, et al. Postoperative adjuvant chemotherapy or radiation therapy for rectal cancer: results from NSABP protocol R-01. J Natl Cancer Inst. 1988;80:21–29[Abstract/Free Full Text]
  4. Teniere P, Hay JM, Fingerhut A, Fagniez PL. Postoperative radiation therapy does not increase survival after curative resection for squamous cell carcinoma of the middle and lower esophagus as shown by a multicenter controlled trial. French University Association for Surgical Research. Surg Gynecol Obstet. 1991;173:123–130[Medline]
  5. Fok M, Sham JS, Choy D, Cheng SW, Wong J. Postoperative radiotherapy for carcinoma of the esophagus: a prospective, randomized controlled study. Surgery. 1993;113:138–147[Medline]
  6. Law S, Fok M, Chow S, Chu KM, Wong J. Preoperative chemotherapy versus surgical therapy alone for squamous cell carcinoma of the esophagus: a prospective randomized trial. J Thorac Cardiovasc Surg. 1997;114:210–217[Abstract/Free Full Text]
  7. Xiao ZF, Yang ZY, Liang J, Miao YJ, Wang M, Yin WB, et al. Value of radiotherapy after radical surgery for esophageal carcinoma: a report of 495 patients. Ann Thorac Surg. 2003;75:331–336[Abstract/Free Full Text]
  8. Ebie N, Kang HJ, Millikan K, Murthy AK, Griem K, Hartsell W, et al. Integration of surgery in multimodality therapy for esophageal cancer. Am J Clin Oncol. 1997;20:11–15[Medline]
  9. Bedard EL, Inculet RI, Malthaner RA, Brecevic E, Vincent M, Dar R. The role of surgery and postoperative chemoradiation therapy in patients with lymph node positive esophageal carcinoma. Cancer. 2001;91:2423–2430[Medline]
  10. Rosenbaum PR, Rubin DB. The central role of the propensity score in observational studies for causal effects. Biometrika. 1983;70:41–55[Abstract/Free Full Text]
  11. Blackstone EH. Comparing apples and oranges. J Thorac Cardiovasc Surg. 2002;123:8–15[Free Full Text]
  12. Parsons LS. Reducing bias in a propensity score matched-pair sample using greedy matching techniques. In: Proceedings of the Twenty-Sixth Annual SAS Users Group International Conference. Cary (NC): SAS Institute, Inc; 2001. p. 214-26
  13. Kelsen DP, Ginsberg R, Pajak TF, Sheahan DG, Gunderson L, Mortimer J, et al. Chemotherapy followed by surgery compared with surgery alone for localized esophageal cancer. N Engl J Med. 1998;339:1979–1984[Abstract/Free Full Text]
  14. Ando N, Iizuka T, Kakegawa T, Isono K, Watanabe H, Ide H, et al. A randomized trial of surgery with and without chemotherapy for localized squamous carcinoma of the thoracic esophagus: the Japan Clinical Oncology Group Study. J Thorac Cardiovasc Surg. 1997;114:205–209[Abstract/Free Full Text]
  15. Arnott SJ, Duncan W, Gignoux M, Girling DJ, Hansen HS, Launois B, et al. Preoperative radiotherapy in esophageal carcinoma: a meta-analysis using individual patient data (Oesophageal Cancer Collaborative Group). Int J Radiat Oncol Biol Phys. 1998;41:579–583[Medline]
  16. Walsh TN, Noonan N, Hollywood D, Kelly A, Keeling N, Hennessy TP. A comparison of multimodal therapy and surgery for esophageal adenocarcinoma. N Engl J Med. 1996;335:462–467[Abstract/Free Full Text]
  17. Bosset JF, Gignoux M, Triboulet JP, Tiret E, Mantion G, Elias D, et al. Chemoradiotherapy followed by surgery compared with surgery alone in squamous-cell cancer of the esophagus. N Engl J Med. 1997;337:161–167[Abstract/Free Full Text]
  18. Urba SG, Orringer MB, Turrisi A, Iannettoni M, Forastiere A, Strawderman M. Randomized trial of preoperative chemoradiation versus surgery alone in patients with locoregional esophageal carcinoma. J Clin Oncol. 2001;19:305–313[Abstract/Free Full Text]
  19. Kitajima M, Kitagawa Y. Surgical treatment of esophageal cancer—the advent of the era of individualization. N Engl J Med. 2002;347:1705–1709[Free Full Text]
  20. Rice TW, Blackstone EH, Goldblum JR, DeCamp MM, Murthy SC, Falk GW, et al. Superficial adenocarcinoma of the esophagus. J Thorac Cardiovasc Surg. 2001;122:1077–1090[Abstract/Free Full Text]
  21. Rice TW, Blackstone EH, Adelstein DJ, Zuccaro G, Jr, Vargo JJ, Goldblum JR, et al. Role of clinically determined depth of tumor invasion in the treatment of esophageal cancer. J Thorac Cardiovasc Surg. 2003;125:1091-102
  22. Rice TW, Blackstone EH, Adelstein DJ, Zuccaro G Jr, Vargo JJ, Goldblum JR, et al. N1 esophageal carcinoma: the importance of staging and downstaging. J Thorac Cardiovasc Surg. 2001;121:454–464[Abstract/Free Full Text]
  23. Piantadosi S. Clinical trials: a methodologic perspective. New York: John Wiley & Sons, Inc; 1997.



This article has been cited by other articles:


Home page
 Ann. Thorac. Surg.Home page
P. D. DiMusto and M. B. Orringer
Transhiatal Esophagectomy for Distal and Cardia Cancers: Implications of a Positive Gastric Margin
Ann. Thorac. Surg., June 1, 2007; 83(6): 1993 - 1999.
[Abstract] [Full Text] [PDF]

Home page
 J. Thorac. Cardiovasc. Surg.Home page
T. W. Rice, D. P. Mason, S. C. Murthy, G. Zuccaro Jr, D. J. Adelstein, L. A. Rybicki, and E. H. Blackstone
T2N0M0 esophageal cancer
J. Thorac. Cardiovasc. Surg., February 1, 2007; 133(2): 317 - 324.
[Abstract] [Full Text] [PDF]

Home page
 Ann. Thorac. Surg.Home page
T. W. Rice, D. Khuntia, L. A. Rybicki, D. J. Adelstein, M. A. Vogelbaum, D. P. Mason, S. C. Murthy, and E. H. Blackstone
Brain Metastases From Esophageal Cancer: A Phenomenon of Adjuvant Therapy?
Ann. Thorac. Surg., December 1, 2006; 82(6): 2042 - 2049.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Author home page(s):
Thomas W. Rice
Malcolm M. DeCamp
Sudish C. Murthy
Eugene H. Blackstone
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Rice, T. W.
Right arrow Articles by Blackstone, E. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rice, T. W.
Right arrow Articles by Blackstone, E. H.
Related Collections
Right arrow Esophagus - cancer

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
ANN THORAC SURG ASIAN CARDIOVASC THORAC ANN EUR J CARDIOTHORAC SURG
J THORAC CARDIOVASC SURG ICVTS ALL CTSNet JOURNALS