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Journal of Clinical Oncology, Vol 25, No 27 (September 20), 2007: pp. 4315-4316 © 2007 American Society of Clinical Oncology. DOI: 10.1200/JCO.2007.11.8026
For Localized Gastroesophageal Cancer, You Give Chemoradiation Before Surgery, but Then What Happens?The University of Texas M.D. Anderson Cancer Center, Houston, TX
Mayo Clinic, Rochester, MN To the Editor: The article by Rizk et al1 is important and of considerable interest to us (and should be to others) as it confirms observations made by Gibson et al2 and by our group.3-13 Rizk et al, by using recursive partition analyses, conclude that the presence of metastatic nodes in the resected specimen after preoperative chemoradiotherapy is the most important prognostic factor (in addition to M1 cancer). Their observation may be important in the development of future treatment strategies for esophageal cancer but it is not novel.6-8 We have previously demonstrated that documentation of a metastatic lymph node even by an endoscopic technique after chemoradiotherapy but before surgery is an ominous sign,7,8 in addition, the precise location of the metastatic node is also a discriminator of prognosis.7 In their article, Rizk et al note that the American Joint Committee on Cancer (AJCC) staging criteria do not allow discrimination between stages (for example between pathologic complete response [pathCR] and stage I, and so on); however, they do not provide an overall P value for the curves in their Figure 11 and, even though they have used too many subgroups, their Figure 11 certainly shows a nice spread according to stage (the graph looks similar to the one published on our 235 similar patients in 20053). It would be important to obtain P values for several comparisons in Figure 3 (eg, Groups A and B compared T0 with T1 v T2 to T4 with N0M0; Groups C and D compared T0 with T1 v T2 to T4 with N1M0; and finally, Group E compared N1M1 v N0m0). Univariate Cox regression analyses of all covariates would be useful and a Cox multivariate regression including multiple covariates would also be of considerable interest.
Combining data from pathCR patients with patients in other stages may be okay under limited circumstances but in general, it should not be done. Also, their conclusion that data from pathCR patients may be combined with T1N0 patients is not supported concretely by the small number of patients and these two groups, understandably, have traveled together because they are biologic cousins but not twins. Nevertheless, our data suggest that T1N0 tend to group with other patients with residual cancer after chemoradiotherapy.3 Combining these two categories is also problematic for the development of future treatment strategies. Another intriguing aspect is that the amount of residual cancer has not only an influence on the patterns of failure9 but also on the AJCC stage.10 That is to say that a patient with even a higher AJCC stage with microscopic residual cancer tends to fare better than a patient with a lower AJCC stage but with demonstrably more residual cancer.10 These observations might require considerably more elaborations and may truly be reflecting the clinical biology of esophageal cancer with regards to chemoradiotherapy resistance and metastatic potential. The presence of mucin11 or neuroendocrine differentiation5 in the resected specimen also has an influence on patient outcome. It is becoming increasingly clear that what one finds in the resected specimen after preoperative chemoradiotherapy therapy is the determinant of patient survival and the baseline clinical stage in gastroesophageal cancers is not able to predict outcome,3,12 although this article does not provide overall survival data with regards to baseline clinical stage. Rizk et al also state that the estimation of treatment response is subjective and might not correspond to the outcome. This should no longer be considered accurate. We have elaborated on the modifications of the pathology review guidelines,3 but to further con solidate the practicality and accuracy of an exercise to score the resected specimens, our group coordinated a multi-institutional pathology review effort.13 Six pathologists from four institutions reviewed blinded resected specimens from 60 patients who had undergone preoperative chemoradiotherapy at our institution to designate categories (pathCR, 1% to 50% residual cancer representing some response, > 50% residual cancer representing total chemoradiotherapy-resistance, T category, and N category).13 The results demonstrated excellent interobserver concordance (Fig 1).13 AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest.
REFERENCES
1. Rizk NP, Venkatraman E, Bains MS, et al: American Joint Committee on cancer staging does not accurately predict survival in patients receiving multimodality therapy for esophageal adenocarcinoma. J Clin Oncol 25:507-512, 2007 2. Gibson M, Burtness B, Heath E, et al: Effect of neoadjuvant chemoradiotherapy on pathologic stage and survival in patients with locally advanced esophageal cancer. Proc Am Soc Clin Oncol 22:14S, 2004 (abstr 4032) 3. Chirieac LR, Swisher SG, Ajani JA, et al: Posttherapy pathologic stage predicts survival in patients with esophageal carcinoma receiving preoperative chemoradiation. Cancer 103:1347-1355, 2005[CrossRef][Medline] 4. Rohatgi PR, Mansfield PF, Crane CH, et al: Surgical pathology stage by the American Joint Commission on cancer criteria predicts patient survival after preoperative chemoradiation for localized gastric carcinoma. Cancer 107:1475-1482, 2006[CrossRef][Medline] 5. Wang KL, Yang Q, Cleary KR, et al: The significance of neuroendocrine differentiation in adenocarcinoma of the esophagus and esophagogastric junction after preoperative chemoradiation. Cancer 107:1467-1474, 2006[CrossRef][Medline] 6. Gu Y, Swisher SG, Ajani JA, et al: The number of lymph nodes with metastasis predicts survival in patients with esophageal or esophagogastric junction adenocarcinoma who receive preoperative chmoradiation. Cancer 106:1017-1025, 2006[CrossRef][Medline] 7. Malaisrie SC, Hofstetter WL, Correa AM, et al: Endoscopic ultrasonography-identified celiac adenopathy remains a poor prognostic factor despite preoperative chemoradiotherapy in esophageal adenocarcinoma. J Thorac Cardiovasc Surg 131:65-72, 2006 8. Agarwal B, Swisher S, Ajani J, et al: Endoscopic ultrasound after preoperative chemoradiation can help identify patients who benefit maximally after surgical esophageal resection. Am J Gastroenterol 99:1258-1266, 2004[CrossRef][Medline] 9. Rohatgi PR, Swisher SG, Correa AM, et al: Failure patterns correlate with the proportion of residual carcinoma after preoperative chemoradiotherapy for carcinoma of the esophagus. Cancer 104:1349-1355, 2005[CrossRef][Medline] 10. Swisher SG, Hofstetter W, Wu TT, et al: Proposed revision of the esophageal cancer staging system to accommodate pathologic response following preoperative chemoradiation. Ann Surg 241:810-817, 2005[CrossRef][Medline] 11. Chiriaec LR, Swisher SG, Correa AM, et al: Signet-ring cell or mucinous histology after preoperative chemoradiation and survival in patients with esophageal or esophagogastric junction. Clin Cancer Res 11:2229-2236, 2005 12. Rohatgi P, Swisher SG, Correa AM, et al: Characterization of pathologic complete response after preoperative chemoradiotherapy in carcinoma of the esophagus and outcome after pathologic complete response. Cancer 104:2365-2372, 2005[CrossRef][Medline] 13. Wu TT, Chiriaec LR, Abraham SC, et al: Excellent interobserver agreement on grading the extent of residual carcinoma after preoperative chemoradiation in esophageal and esophagogastric junction carcinoma: A reliable predictor of patient outcome. Am J Surg Pathol 31:58-64, 2007[CrossRef][Medline]
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Copyright © 2007 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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