Primary Tumor Location Is a Predictor of Poor Prognosis in Patients with Locally Advanced Esophagogastric Cancer Treated with Perioperative Chemotherapy.

BACKGROUND: Esophagogastric cancer (EGC) is a leading neoplasm worldwide. Perioperative chemotherapy (periCT) is currently a standard of care for most patients (pts). Prevalence of esophagogastric junction (EGJ) tumors is increasing over the last years. METHODS: The aim of this study was to retrospectively search for prognostic factors in pts. with locally advanced EGC treated with periCT. Three-year overall survival (OS) and Event-Free Survival (EFS) were main end-points. HER-2 positive tumors were defined by immunohistochemistry or FISH. RESULTS: Between June/2007 and November/2015, 128 pts. started periCT for esophagogastric junction (EGJ) or gastric adenocarcinoma (GC). Median age was 59.5 y and 64% were male. Primary site was EGJ in 27% and 65% were cN+. Diffuse subtype was seen in 42%. Ninety-seven pts. were assessed for HER-2; 14 (14.4%) were positive. After median follow-up time of 45 m, 48 deaths occurred. The 3-year OS and EFS rate was 61.3% and 51.2%, respectively. Main prognostic factors were: AJCC ypT3-T4yN1-N3 (HR 6.75 p 0.002) and EGJ primary (HR 2.64, p 0.004). Overall HER-2 was not prognostic. Still, a difference in 3-year OS was observed for GC/HER2+ compared to EGJ/HER2+ (88.9% versus 20%, p = 0.002). This difference is greater for 3-year EFS with no patient with EGJ/HER2+ free-of-event against 62.5% for GC/HER+ (p = 0.011). CONCLUSION: In our analysis, pathological staging and primary site were main prognostic factors. Moreover, a small group of EGJ/HER2+ had very poor survival.

KRAS gene mutation in a series of unselected colorectal carcinoma patients with prognostic morphological correlations: a pyrosequencing method improved by nested PCR.

INTRODUCTION: Inhibition of EGFR is a strategy for treating metastatic colorectal cancer (CRC) patients. KRAS sequencing is mandatory for selecting wild-type tumor patients who might benefit from this treatment. DNA from formalin-fixed paraffin-embedded (FFPE) tissues is commonly used for routine clinical detection of mutations, and its amplification succeeds only when all preanalytical histological processes have been controlled. In cases that are not properly processed, the DNA results can be poor, with low peak pyrosequencing findings. We designed and tested a pair of forward and reverse primers for a nested PCR method, followed by pyrosequencing, in a single Latin American institution series of 422 unselected CRC patients, correlating KRAS mutations with pathological and clinical data. MATERIALS AND METHODS: Patient DNA samples from tumors were obtained by scraping or laser microdissection of cells from FFPE tissue and extracted using a commercial kit. DNA was first amplified by PCR using 2 primers that we designed; then, nested PCR was performed with the amplicon from the preamplification PCR using the KRAS PyroMark™ Q96 V2.0 kit (Qiagen). Pathological data were retrieved from pathology reports. RESULTS: KRAS mutation was observed in 33% of 421 cases. Codon 12 was mutated in 76% of cases versus codon 13 in 24%. Right-sided CRCs harbored more KRAS mutations than left-sided tumors, as did tumors that presented with perineural invasion. CONCLUSION: Our findings in this Latin American population are consistent with the literature regarding the frequency of KRAS mutations in CRC, their distribution between codons 12 and 13, and type of nucleotide substitution. By combining nested PCR and pyrosequencing, we achieved a high rate of conclusive results in testing KRAS mutations in CRC samples - a method that can be used as an ancillary test for failed assays by conventional PCR.

RAS mutations vary between lesions in synchronous primary colorectal cancer: testing only one lesion is not sufficient to guide anti-EGFR treatment decisions.

INTRODUCTION: Mutations in KRAS and NRAS genes are negative predictors of anti-EGFR therapies response in metastatic colorectal cancer. There are few reports on RAS testing in synchronous primary colorectal cancer (SP-CRC) and a lack of recommendations on which tissue should be tested for the mutation in this disease. This study analyzed the RAS status of both lesions in SP-CRC patients and in their metastasis. MATERIALS AND METHODS: DNA was obtained from formalin-fixed-paraffin-embedded tissue, and mutations were analyzed by pyrosequencing. RESULTS: RAS status was heterogeneous in 6 (75%) of 8 SP-CRC patients between primary lesions. Five showed heterogeneity regarding RAS mutational status, and from these, four presented with metastasis: 3 cases (75%) had WT metastatic tissue, and 1 case (25%) had mutated metastatic tissue. One patient showed divergence regarding RAS mutation type. DISCUSSION: RAS mutations vary significantly between SP-CRC lesions, and the status of the metastasis is unpredictable. Testing for RAS mutations in only 1 of the primary lesions can misguide clinical decisions and hind the predictive potential of anti-EGFR treatment. A more appropriate approach in metastatic SP-CRC is to test the metastatic tissue or both primary lesions for providing more accurate mutation scenery and support more assertive clinical decisions.

Pathologic complete response with neoadjuvant imatinib for locally advanced pelvic GIST.

There are few data that show pathologic complete response (pCR) to imatinib treatment in gastrointestinal stromal tumors (GISTs). We describe a case of a patient with pCR of a pelvic, locally advanced, high-risk GIST who was treated with neoadjuvant imatinib and ultimately underwent a conservative procedure. A 48-year-old male presented with a pelvic mass 10 cm in diameter. Biopsy revealed a gastrointestinal stromal tumor of rectal origin. Although it was considered initially resectable, an extensive procedure would have been necessary for complete resection. Treatment with imatinib was initiated, resulting in partial response. The patient remained on imatinib for over 15 months, maintaining stable disease. Radical prostatectomy with anal sphincter preservation was performed. Pathological report revealed no viable neoplastic cells. The use of imatinib was held for 6 months after the surgery. At a follow-up 15 months after surgery, the patient had no evidence of disease. Our report may help to guide future studies of neoadjuvant imatinib for large pelvic or rectum GISTs that are initially considered unresectable.