ABSTRACT
The traditional view of progression of disease in cancer is the sequential spread of tumour to locoregional lymph nodes and then to distant metastases. However, this view may need to be challenged and modern pathology techniques such as immunohistochemistry and tumour profiling can provide us with a greater insight into the pathways and mechanisms of distant spread. Professor Nagtegaal discusses the evidence for reconsidering the current paradigm and reflects on the need for further investigation into mechanisms of distant metastatic spread.
Subject(s)
Cause of Death , Colorectal Neoplasms/pathology , Liver Neoplasms/secondary , Lymph Nodes/pathology , Colorectal Neoplasms/mortality , Colorectal Neoplasms/surgery , Disease Progression , Female , Humans , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Lymphatic Metastasis , Male , Neoplasm Invasiveness , Neoplasm Staging , Prognosis , Risk Assessment , Survival AnalysisSubject(s)
Guidelines as Topic , Pathology , Research Report/standards , Histological Techniques , HumansABSTRACT
BACKGROUND: KRAS mutation is a negative predictive factor for treatment with anti-epidermal growth factor receptor antibody in metastatic colorectal cancer (CRC). KRAS mutation analysis is usually performed on primary tumour tissue because metastatic tissue is often not available. However, controversial data are available on the concordance of test results between primary tumours and corresponding metastases. We assessed the concordance of KRAS mutation status in a study of 305 primary colorectal tumours and their corresponding liver metastases. METHODS: Patients with histologically confirmed CRC who underwent surgical resection of the primary tumour and biopsy or surgical resection of the corresponding liver metastasis were included. KRAS mutation analysis was performed for codons 12 and 13. RESULTS: KRAS mutation was detected in 108 out of 305 primary tumours (35.4%). In 11 cases (3.6%), we found a discordance between primary tumour and metastasis: 5 primary tumours had a KRAS mutation with a wild-type metastasis, 1 primary tumour was wild type with a KRAS mutation in the metastasis, and in 5 cases the primary tumour and the metastasis had a different KRAS mutation. CONCLUSION: We observed a high concordance of KRAS mutation status of 96.4% (95% CI 93.6-98.2%) between primary colorectal tumours and their corresponding liver metastases. In only six patients (2.0%; 95% CI 0.7-4.2%), the discordance was clinically relevant. In this largest and most homogenous study to date, we conclude that both primary tumours and liver metastases can be used for KRAS mutation analysis.
Subject(s)
Carcinoma/genetics , Colorectal Neoplasms/genetics , DNA Mutational Analysis/methods , Genes, ras , Liver Neoplasms/genetics , Aged , Carcinoma/pathology , Cohort Studies , Colorectal Neoplasms/pathology , Female , Humans , Liver Neoplasms/secondary , Male , Matched-Pair Analysis , Middle Aged , Models, Biological , Multicenter Studies as Topic , MutationABSTRACT
BACKGROUND: Peripheral sensory neurotoxicity is a frequent and potentially debilitating side effect of oxaliplatin treatment. Calcium and magnesium (Ca/Mg) infusions are frequently used to prevent this toxicity. However, concerns about a negative impact of Ca/Mg infusions on outcome have been raised. We retrospectively assessed the effect of Ca/Mg infusions on the incidence of neurotoxicity and on clinical outcome in advanced colorectal cancer (ACC) patients treated in the phase III CAIRO2 study. MATERIALS AND METHODS: Seven hundred and fifty five previously untreated ACC patients were randomised between treatment with capecitabine, oxaliplatin and bevacizumab or the same combination with the addition of cetuximab. Patients were retrospectively divided into two groups: patients in the Ca/Mg(+) group received Ca/Mg at least during their first treatment cycle, and patients in the Ca/Mg(-) group did not. RESULTS: Seven hundred and thirty two patients were evaluable for this analysis. The Ca/Mg(+) group consisted of 551 patients, the Ca/Mg(-) group consisted of 181 patients. The incidence of all grade neurotoxicity in the Ca/Mg(+) group and the Ca/Mg(-) group was 85% and 92%, respectively (p = 0.02), and the incidence of grade ≥ 2 neurotoxicity was 40% and 45%, respectively (p = 0.22). The median PFS in the Ca/Mg(+) versus Ca/Mg(-) group was 10.1 versus 10.7 months (p = 0.92), the median OS was 19.8 versus 20.7 months (p = 0.10), and the response rate was 43.1% versus 50% (p = 0.11), respectively. CONCLUSIONS: In this largest retrospective analysis to date we observed that Ca/Mg infusions significantly reduced all grade oxaliplatin-related neurotoxicity. Ca/Mg infusions did not affect the clinical efficacy of treatment.
