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The prognostic significance of tumor epidermal growth factor receptor (EGFR) expression change after neoadjuvant chemoradiation in patients with rectal adenocarcinoma.

Richter I, Dvořák J, Urbanec M, Bluml A, Čermáková E, Bartoš J, Petera J - Contemp Oncol (Pozn) (2015)

Bottom Line: Progression was reported in 5 patients.The median disease-free survival was 64.9 months, median overall survival was 76.4 months.Increased EGFR expression was found in 12 patients (26.1%).

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology, Regional Hospital Liberec, Liberec, Czech Republic.

ABSTRACT

Aim of the study: The aim of this retrospective study was to determine the prognostic impact of epidermal growth factor receptor (EGFR) expression changes during neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer.

Material and methods: Fifty patients with locally advanced rectal cancer were evaluated. All the patients were administered the total dose of 44 Gy. Capecitabine has been concomitantly administered in the dose 825 mg/m(2) in two daily oral administrations. Surgery was indicated 4-8 weeks from the chemoradiotherapy completion. Epidermal growth factor receptor expression in the pretreatment biopsies and in the resected specimens was assessed with immunohistochemistry.

Results: All of 50 patients received radiotherapy without interruption up to the total planned dose. In 30 patients sphincter-saving surgery was performed, 20 patients underwent amputation of the rectum. Downstaging was described in 30 patients. Four patients have had complete pathologic remission. Twenty-six patients have had partial remission, the disease was stable in 15 patients. Progression was reported in 5 patients. The median disease-free survival was 64.9 months, median overall survival was 76.4 months. Increased EGFR expression was found in 12 patients (26.1%). A statistically significantly shorter overall survival (p < 0.0001) and disease-free survival (p < 0.0001) was found in patients with increased expression of EGFR compared with patients where no increase in the expression of EGFR during neoadjuvant chemoradiotherapy was observed.

Conclusions: The overexpression of EGFR during neoadjuvant chemoradiotherapy for locally advanced rectal adenokarcinoma associated with significant shorter overall survival and disease free survival.

No MeSH data available.


Related in: MedlinePlus

Disease-free survival in months (red curve: patients without increase of EGFR expression, blue curve: patients with increase of EGFR expression)
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Figure 0005: Disease-free survival in months (red curve: patients without increase of EGFR expression, blue curve: patients with increase of EGFR expression)

Mentions: All of the 50 patients received radiotherapy without interruption up to the total planned dose. No patient died during the treatment. Concomitant chemotherapy was discontinued prematurely in four patients because of haematological and gastrointestinal toxicity. No patient was hospitalised because of acute treatment toxicity. Non-haematological toxicity evaluation did not achieve grade III or IV. Anaemia grade III was found in one patient. The median time between chemoradiotherapy completion and surgery was 44 days (6.3 weeks). In 30 patients sphincter-saving surgery was performed, and 20 patients underwent amputation of the rectum. R0 resection was performed in 47 patients, and microscopically positive margin was described by a pathologist in 3 patients. There was no surgically macroscopic residue left in any patient. According to the pathological TNM classification, 14 patients were at the first clinical stage, 24 patients in the second clinical stage, and 8 patients in the third clinical stage after the operation. Four patients achieved complete pathological remission. Complete pathological response was defined as the absence of tumour tissue in the specimen. No patient had the generalisation of the disease described intraoperatively. Downstaging was described in 30 patients. Four patients had complete pathologic remission. Twenty-six patients had partial remission. The disease was stable in 15 patients. Progression was reported in 5 patients. At the time of assessment (31 December 2013) median follow-up was 51.3 months. A recurrence occurred in 25 patients, and 25 patients had no signs of recurrence. Local recurrence was found in 8 patients, and generalisation of disease was reported in 17 patients. The most common sites of metastases were the liver (eight patients) and lungs (seven patients). One patient suffered from brain metastases, and metastatic involvement of retroperitoneal lymph nodes was found in one patient. The median DFS was 64.9 months (95% CI: 26.1 to 67.8 months). The 3-year DFS was 56%. A total of 21 patients died, and 29 patients remained alive. The median OS was 76.4 months (95% CI: 57.3 to 76.9 months). The 3-year OS was 92%. Epidermal growth factor receptor expression was examined both by endobiopsy and in resection specimens after neoadjuvant chemoradiotherapy (Table 1). Forty-six patients were enrolled into the evaluation of EGFR expression changes. In four patients no change in expression of EGFR was evaluated because pathologic complete response was achieved after neoadjuvant chemoradiotherapy. Increased EGFR expression was found in 12 patients. In 34 patients no increased expression of EGFR was observed (23 patients without any change of EGFR expression, 11 patients with a decrease of EGFR expression). Statistically significantly shorter OS and DFS was found in patients with increased expression of EGFR compared with patients in whom no increase in expression of EGFR during neoadjuvant chemoradiotherapy was observed. The median OS in patients with increased EGFR expression was 41.1 months (95% CI: 39.1 to 47.0 months). The median OS for patients without increased expression of EGFR was 76.9 months (95% CI: 76.4 to 76.9 months, log-rank test: p < 0.0001). The median DFS in patients with increased EGFR expression was 13.7 months (95% CI: 3.8 to 15.8 months). The median DFS in patients without increased EGFR expression was 67.8 months (95% CI: 55.7 to 67.8 months, log-rank p < 0.0001). Kaplan-Meier curves are presented in Figures 4 and 5.


The prognostic significance of tumor epidermal growth factor receptor (EGFR) expression change after neoadjuvant chemoradiation in patients with rectal adenocarcinoma.

Richter I, Dvořák J, Urbanec M, Bluml A, Čermáková E, Bartoš J, Petera J - Contemp Oncol (Pozn) (2015)

Disease-free survival in months (red curve: patients without increase of EGFR expression, blue curve: patients with increase of EGFR expression)
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4507892&req=5

Figure 0005: Disease-free survival in months (red curve: patients without increase of EGFR expression, blue curve: patients with increase of EGFR expression)
Mentions: All of the 50 patients received radiotherapy without interruption up to the total planned dose. No patient died during the treatment. Concomitant chemotherapy was discontinued prematurely in four patients because of haematological and gastrointestinal toxicity. No patient was hospitalised because of acute treatment toxicity. Non-haematological toxicity evaluation did not achieve grade III or IV. Anaemia grade III was found in one patient. The median time between chemoradiotherapy completion and surgery was 44 days (6.3 weeks). In 30 patients sphincter-saving surgery was performed, and 20 patients underwent amputation of the rectum. R0 resection was performed in 47 patients, and microscopically positive margin was described by a pathologist in 3 patients. There was no surgically macroscopic residue left in any patient. According to the pathological TNM classification, 14 patients were at the first clinical stage, 24 patients in the second clinical stage, and 8 patients in the third clinical stage after the operation. Four patients achieved complete pathological remission. Complete pathological response was defined as the absence of tumour tissue in the specimen. No patient had the generalisation of the disease described intraoperatively. Downstaging was described in 30 patients. Four patients had complete pathologic remission. Twenty-six patients had partial remission. The disease was stable in 15 patients. Progression was reported in 5 patients. At the time of assessment (31 December 2013) median follow-up was 51.3 months. A recurrence occurred in 25 patients, and 25 patients had no signs of recurrence. Local recurrence was found in 8 patients, and generalisation of disease was reported in 17 patients. The most common sites of metastases were the liver (eight patients) and lungs (seven patients). One patient suffered from brain metastases, and metastatic involvement of retroperitoneal lymph nodes was found in one patient. The median DFS was 64.9 months (95% CI: 26.1 to 67.8 months). The 3-year DFS was 56%. A total of 21 patients died, and 29 patients remained alive. The median OS was 76.4 months (95% CI: 57.3 to 76.9 months). The 3-year OS was 92%. Epidermal growth factor receptor expression was examined both by endobiopsy and in resection specimens after neoadjuvant chemoradiotherapy (Table 1). Forty-six patients were enrolled into the evaluation of EGFR expression changes. In four patients no change in expression of EGFR was evaluated because pathologic complete response was achieved after neoadjuvant chemoradiotherapy. Increased EGFR expression was found in 12 patients. In 34 patients no increased expression of EGFR was observed (23 patients without any change of EGFR expression, 11 patients with a decrease of EGFR expression). Statistically significantly shorter OS and DFS was found in patients with increased expression of EGFR compared with patients in whom no increase in expression of EGFR during neoadjuvant chemoradiotherapy was observed. The median OS in patients with increased EGFR expression was 41.1 months (95% CI: 39.1 to 47.0 months). The median OS for patients without increased expression of EGFR was 76.9 months (95% CI: 76.4 to 76.9 months, log-rank test: p < 0.0001). The median DFS in patients with increased EGFR expression was 13.7 months (95% CI: 3.8 to 15.8 months). The median DFS in patients without increased EGFR expression was 67.8 months (95% CI: 55.7 to 67.8 months, log-rank p < 0.0001). Kaplan-Meier curves are presented in Figures 4 and 5.

Bottom Line: Progression was reported in 5 patients.The median disease-free survival was 64.9 months, median overall survival was 76.4 months.Increased EGFR expression was found in 12 patients (26.1%).

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology, Regional Hospital Liberec, Liberec, Czech Republic.

ABSTRACT

Aim of the study: The aim of this retrospective study was to determine the prognostic impact of epidermal growth factor receptor (EGFR) expression changes during neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer.

Material and methods: Fifty patients with locally advanced rectal cancer were evaluated. All the patients were administered the total dose of 44 Gy. Capecitabine has been concomitantly administered in the dose 825 mg/m(2) in two daily oral administrations. Surgery was indicated 4-8 weeks from the chemoradiotherapy completion. Epidermal growth factor receptor expression in the pretreatment biopsies and in the resected specimens was assessed with immunohistochemistry.

Results: All of 50 patients received radiotherapy without interruption up to the total planned dose. In 30 patients sphincter-saving surgery was performed, 20 patients underwent amputation of the rectum. Downstaging was described in 30 patients. Four patients have had complete pathologic remission. Twenty-six patients have had partial remission, the disease was stable in 15 patients. Progression was reported in 5 patients. The median disease-free survival was 64.9 months, median overall survival was 76.4 months. Increased EGFR expression was found in 12 patients (26.1%). A statistically significantly shorter overall survival (p < 0.0001) and disease-free survival (p < 0.0001) was found in patients with increased expression of EGFR compared with patients where no increase in the expression of EGFR during neoadjuvant chemoradiotherapy was observed.

Conclusions: The overexpression of EGFR during neoadjuvant chemoradiotherapy for locally advanced rectal adenokarcinoma associated with significant shorter overall survival and disease free survival.

No MeSH data available.


Related in: MedlinePlus