Long-Qi Chen

Lack of EGFR mutations benefiting gefitinib treatment in adenocarcinoma of esophagogastric junction

BackgroundThe epidermal growth factor receptor (EGFR) inhibitor, gefitinib, has been reported to successfully treat advanced non-small cell lung cancer patients with genetic mutations in EGFR. The aim of this study was to investigate the existence of EGFR mutations in carcinoma of esophagogastric junction, and also to explore the possibility of treating carcinoma of esophagogastric junction using gefitinib.MethodsFrom Aug. 2009 to Jun. 2010, 65 patients with carcinoma of esophagogastric junction underwent surgical resection. The tumor tissue and corresponding blood specimens were collected from all cases. The DNA was extracted and PCR amplification was accomplished based on designed primers for exons 18, 19, 20, and 21. EGFR exons 18, 19, 20 and 21 of both cancer cell and white blood cell were finally successfully sequenced.ResultsIn exon 20, a variant from CAG to CAA at codon 787 (2361G-> A) was identified in 19 patients, which was a genomic variation of EGFR since it was found in both cancer tissue and white blood cells. This EGFR alteration was a synonymous single nucleotide polymorphism (SNP) since CAA and CAG were encoding the same amino-acid of Glutamine (Q787Q, NCBI database 162093G > A, SNP ID: rs10251977). No genetic alteration was found in exons 18, 19 or 21.ConclusionsAdenocarcinoma of esophagogastric junction rarely presents EGFR mutation, especially gefitinib-associated mutations such as L858R, or delE746-A750. This means that the gefitinib-based gene target therapy should not be recommended for treating carcinoma of esophagogastric junction.

Factors influencing response enthusiasm to telephone follow-up in patients with oesophageal carcinoma after oesophagectomy.

Response enthusiasm to telephone follow-up is a precondition for obtaining exhaustive information; however, no study has yet examined this specific issue. This study aimed to investigate possible factors influencing response enthusiasm to telephone follow-up in patients with oesophageal carcinoma after oesophagectomy and to propose corresponding countermeasures. A telephone follow-up was conducted on patients who underwent oesophagectomy. The possible factors influencing response enthusiasm grades were investigated by univariate and logistic regression analyses. The study enrolled 346 eligible patients. Univariate analysis showed that the tumour, nodes, metastasis (TNM) staging (P = 0.004); survival status (P < 0.001); survival time (P < 0.001); complications/co-morbidities (P = 0.001); and the relationship between the patient and his/her contact person (P < 0.001) were significantly different among the three groups. The first group of patients had high response enthusiasm, the second group had moderate response enthusiasm, and the third group had low response enthusiasm. Logistic regression analysis demonstrated that only the complications/co-morbidities [confidence interval (CI) = -2.310 to -0.665, P < 0.001] and dysphagia status (CI = 0.039-1.509, P = 0.039) were independent factors affecting the response enthusiasm grades. The primary therapeutic results and the current complications and co-morbidities, especially the dysphagia status, were important factors influencing response enthusiasm grades. Planning a follow-up schedule with proper health instructions could be crucial to the quality of follow-up.

Impact of lymph-node metastasis site in patients with thoracic esophageal cancer: Does the lymph node metastasis site matter?

Dear Editor: In a recent paper in Journal of Surgical Oncology, Kunisaki et al. [1] reported the ‘‘Impact of lymph-node metastasis site in patients with thoracic esophageal cancer.’’ They concluded that ‘‘the surgical outcomes in these patients depend on the number, but not the site, of metastatic lymph nodes after curative esophagectomy.’’ However, we have several concerns about their conclusion as stated below:

The role of definitive chemoradiotherapy versus surgery as initial treatments for potentially resectable esophageal carcinoma

BackgroundWe performed a meta-analysis to compare the efficacy of definitive chemoradiotherapy (dCRT) and esophagectomy as initial treatments for potentially resectable esophageal cancer.MethodsTo assess both strategies, the combined odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Thirteen studies (N = 2071; dCRT = 869 and surgery = 1202) were included. In all, 90.39% of the patients were diagnosed with esophageal squamous cell carcinoma (ESCC).ResultsThe 2-year (OR = 1.199, 95% CI 0.922–1.560; P = 0.177) and 5-year overall survival (OS) rates (OR = 0.947, 95% CI 0.628–1.429; P = 0.796) were not significantly different. No significant differences were identified in the 2-year OS among patients with stage I disease (OR = 1.397, 95% CI 0.740–2.638; P = 0.303) or stage II–III (OR = 0.418, 95% CI 0.022–7.833; P = 0.560). Patients with lymph node metastases tended to have a better 5-year OS when treated with dCRT than with surgery (OR = 0.226, 95% CI 0.044–1.169; P = 0.076); however, the difference between the two methods was not significant. Western patients who received dCRT had poorer prognoses than patients who underwent surgery (OR = 1.522, 95% CI 1.035–2.238; P = 0.033). dCRT and surgery led to similar 5-year progression-free survival rates (OR = 1.06, 95% CI 0.79–1.42; P = 0.70).ConclusionsdCRT and surgery are equally effective as initial treatments for potentially resectable esophageal cancer. These results apply primarily to Asian populations as they have an increased incidence of ESCC.

Prognostic power of lymph node station ratio for resected esophageal squamous cell carcinoma patients deserves additional investigation

Dear Editor, We read with great interest the report by Fu et al on the investigation of the prognostic value of the lymph node (LN) station ratio (SR, metastatic LN stations/examined LN stations) in esophageal squamous cell carcinoma (ESCC) patients. This study developed a new N category, which was demonstrated to provide more detailed prognostic information than the current N category. A standard staging system should be encompass the following major aspects: (1) the difference in survival time is small among patients classified into the same group by that criterion (homogeneity); (2) there are much greater differences in the survival times among patients classified into different groups (discriminatory ability); (3) mean survival time for a group classified as favorable is longer than the survival time for less favorable groups (monotonicity of gradients). In this study, log-rank test and c-index were used for measuring both the discriminatory power and monotonicity of the gradient, and the homogeneity was explored by performing the likelihood ratio (LR) test. Thus, this study has demonstrated statistically convincing evidence for that SR category has a superior prognostic ability relative to the AJCC pN category in ESCC patients. However, some points of the manuscript warrant discussion. First, since the radical two-field lymph node dissection with a qualified number of resected lymph nodes (>15) was done for each patient included, the value of LN stations was confinedwithin a certain narrow range (median 7, mean ± SD 7.67 ± 2.25). In this case, the prognostic power of examined LN stations was limited considerably, and the main determinant of SR was the metastatic LN stations. Second, the authors did not describe the process to select the arithmetic method to describe metastatic LN stations and examined LN stations. Readers might argue that other statistical models should be examined, such as arithmetic addition (metastatic stations + 1/ examined stations). Simple combination may produce adverse effects by impairing the homogeneity, discrimination, or monotonicity of each predictable marker. To further prove the point that the SR stage can properly represent both the quantitative accuracy and extent of LN metastasis, evaluation of the separate prognostic performance of examined LN stations and metastatic LN stations is mandatory to be added in the results section Another notable limitation is the lack of an external validation cohort to access the prognostic performance of this modified N category. A validation cohort is needed to further prove the improved prognostic ability of the new T-SR-M staging system into daily clinical practice. In short, the authors have proposed a revised N category which was demonstrated with a superior prognostic ability as compared with the AJCC pN category in ESCC patients after radical esophagectomy. Given the above-mentioned potential limitations, the prognostic power of this new N staging needs further investigation.

The effect of interaction between lymphovascular invasion and lymph node metastasis

To the Editors: We read with great interest the report by Schiefer et al on the investigation of lymphovascular invasion (LVI) of lymph node metastases (LNM) in a large cohort of patients with esophageal cancer. We have conducted a similar study with a larger cohort (n = 347) but focused on the predictive value of LVI in the primary tumor. Our study highlighted that LVI has a significant impact on the overall survival of patients with resected esophageal squamous cell carcinoma. Theoretically, the LVI is a phase of lymph node metastasis. In other words, the presence of LVI is a necessary condition, not a sufficient condition, for LNM. Thus, there is considerable effect of interaction between LVI and LNM. Given that LNM constitute a strong prognostic factor in esophageal cancer, it is reasonable for LVI in LNM to be a significant prognostic factor as well. We think that LVI in LNM may be a prognostic marker that is basically equivalent to the LNM. This hypothesis may explain the results in our study and some other studies that LVI in primary tumor failed to be an independent prognostic factor for overall survival in patients with node-positive esophageal cancer. Even though multivariable analysis revealed LVI in LNM as a significant prognostic factor for disease-free survival in the whole cohort and for disease-free and overall survival in patients with adenocarcinomas (P < .05, Cox regression), it is insufficient to deduce the conclusion that LVI in LNM can provide additional prognostic value to the current nodal categories in the 7th American Joint Committee on Cancer staging system. Further analysis for the effect of interaction between LVI and LNM by testing an interaction term between LVI and LNM should be carried out within the context of the multivariate Cox regression model. Our previous study has demonstrated that the nodal categories for esophageal squamous cell carcinoma should be based on the number of metastatic lymph node stations, which represent the extent of LNM and have a better reliability and generalizability than the nodal categories in the 7th American Joint Committee on Cancer staging system. To further explore the prognostic value of LVI in lymph node-positive patients, the number of LN stations with LVI can be taken into consideration.