scholarly journals Methylation status of p16 and p14 genes in locally advanced rectal cancer: Potential clinical implication

2018 ◽  
Vol 70 (4) ◽  
pp. 681-690
Author(s):  
Bojana Kozik ◽  
Nikola Kokanov ◽  
Slavica Knezevic-Usaj ◽  
Ivan Nikolic ◽  
Radoslav Davidovic ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Overall Survival ◽  
Growth Factor ◽  
Methylation Status ◽  
Locally Advanced ◽  
Growth Factor Receptor ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Vegf Expression ◽  
Egfr Expression

Methylation of p16 and p14 genes is a common event in colorectal cancers; however, their exact role in the prediction of patients? outcome is unclear. We conducted this retrospective study to evaluate their potential predictive and/or prognostic roles. Methylation-specific PCR was used to examine the methylation status of p16 and p14 in pretherapeutic and preoperative biopsy specimens of 60 patients with locally advanced rectal cancer. The methylation status of the examined genes did not affect the response to preoperative chemoradiotherapy (CRT), recurrence rate and overall survival. However, patients with a simultaneous presence of either p16 or p14 methylation and high vascular endothelial growth factor (VEGF) expression showed a significantly worse response to CRT (p=0.005 and p=0.038, respectively). Moreover, patients with both p16 methylation and high VEGF expression had significantly shorter overall survival (p=0.010), while no such association was found in patients with p14 methylation and high VEGF expression. On the other hand, a subgroup of patients with p16 methylation and low VEGF and high epidermal growth factor receptor (EGFR) expression showed a significantly better response to CRT (p=0.024). The obtained results point to the importance of p16 and p14 methylation analyses in combination with VEGF and EGFR expression, aimed at better predicting treatment response and patient outcome.

Induction chemotherapy followed by chemoradiotherapy and total mesenteric excision for locally advanced rectal cancer with resectable metastases.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 526-526 ◽  
Author(s):  
Carla Hajj ◽  
Andrea Cercek ◽  
Leonard Saltz ◽  
Neil Howard Segal ◽  
Diane Lauren Reidy ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Overall Survival ◽  
Adjuvant Chemotherapy ◽  
Induction Chemotherapy ◽  
Primary Tumor ◽  
Tumor Regression ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer

526 Background: Optimal management of patients with locally advanced rectal cancer (LARC) and synchronous, resectable metastases remains controversial and treatment decisions benefit from a multidisciplinary approach. To better characterize the role of induction chemotherapy followed by chemoradiation and surgery, we evaluated patterns of distal progression and overall survival in this subset of patients. Methods: We reviewed records of 25 LARC patients with synchronous resectable metastases treated with induction chemotherapy (ICT) followed by 5-fluorouracil-based concurrent chemoradiation (CRT) at our institution between December 2006 and December 2010. Radiation was delivered using a standardized three-field technique or IMRT. The incidence and sites of failure were analyzed. Overall survival (OS) and progression-free survival (PFS) were calculated from the completion of CRT using the Kaplan-Meier method. Results: Of the 25 patients who received ICT followed by CRT, 21 (84%) underwent total mesorectal excision and metastectomy. Eleven patients (44%) had liver metastases. The median ICT duration was 2.4 months. Twenty patients (80%) received a FOLFOX-based ICT regimen and 5 patients (20%) received irinotecan-based chemotherapy. Two patients had unresectable disease, one was medically inoperable, and surgery was aborted due to intra-operative complications in one patient. Eighteen of the 21 were NED after surgery and metastatectomy (86%) with 24% pathologic complete response rate in the primary tumor; 10 (56%) received adjuvant chemotherapy. None of the patients recurred locally. Six of the 18 (33%) progressed distally, four of whom had received adjuvant chemotherapy. Four distal recurrences were in the lungs. With a median follow-up of 29.6 months, the 3-year OS was 50.4%. Median OS and PFS were 25.1 months and 13.5 months, respectively. Conclusions: ICT prior to CRT is associated with acceptable toxicity, substantial primary tumor regression, and promising clinical outcomes in patients with high-risk LARC with synchronous, resectable metastatic disease.

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