Are patients with ulcerative colitis still at increased risk of colon cancer?
Lancet. 2020 01 11;395(10218):92-94
Authors: Damas OM, Abreu MT
PMID: 31929018 [PubMed - indexed for MEDLINE]
Targeting EGFR pathway in metastatic colorectal cancer- tumour heterogeniety and convergent evolution.
Crit Rev Oncol Hematol. 2019 Nov;143:153-163
Authors: Khan K, Valeri N, Dearman C, Rao S, Watkins D, Starling N, Chau I, Cunningham D
Despite significant progress in management of metastatic colorectal cancer (mCRC) pertaining to better screening procedures and amelioration of the therapeutic armamentarium with targeted therapies, prognosis remains poor. Targeting epidermal growth factor receptor (EGFR) has been of particular interest owing to favourable efficacy benefits demonstrated by monoclonal antibodies (cetuximab and panitumumab) in various clinical settings and development of predictive biomarkers informing treatment decisions respectively. In spite of optimal patient selection based on RAS mutation status, primary and secondary resistance to monoclonal antibodies is higher than desired. Further research into predictive biomarkers is therefore essential, but has, to date, been conducted with considerable limitations. Whilst molecular heterogeneity has been demonstrated by several studies in mCRC, for incomprehensible reasons, multiple resistant genetic alterations that emerge under the selective pressure of EGFR-targeted therapies are somehow able to influence the biological and clinical behaviour of cancer cells, despite being detectable at extremely low frequencies. Intriguingly, these subclonal events largely seem to converge on RAS/RAF/MAPK pathway in patients treated with EGFR-targeted monoclonal antibodies. This review describes the clinical and biological evolution and development of EGFR targeted therapies in mCRC, the challenges in the presence of molecular complexities, the role of cell free (cf)-DNA and future strategies that could lead to further optimal discovery of clinically meaningful biomarkers and application of precision medicine.
PMID: 31678702 [PubMed - indexed for MEDLINE]
Lesion detection performance of an abbreviated gadoxetic acid-enhanced MRI protocol for colorectal liver metastasis surveillance.
Eur Radiol. 2019 Nov;29(11):5852-5860
Authors: Canellas R, Patel MJ, Agarwal S, Sahani DV
OBJECTIVE: To assess the lesion detection performance of an abbreviated MRI (AMRI-M) protocol consisting of ultrafast SE T2W, DWI, and T1W-HBP at 20 min for colorectal liver metastasis (CRLM) surveillance.
METHODS: In this Institutional Review Board (IRB)-approved retrospective study, gadoxetic acid-enhanced MRI scans of 57 patients (43 with pathologically proven CRLMs) were assessed. Two readers independently evaluated two sets of images per patient and commented on the number, location, and size of liver lesions. Set 1 included ultrafast spin-echo (SE) T2-weighted (T2W) + T1-weighted (T1W) hepatobiliary phase (HBP) at 20 min sequences + diffusion-weighted imaging (DWI), and set 2 consisted of the standard MRI protocol. A maximum of 10 lesions per patient were recorded. Cohen's kappa analysis, sensitivity, areas under the curve (AUCs), and the MRI cost analysis of the AMRI-M protocol were assessed.
RESULTS: Between 198 and 209 lesions were assessed with each set of images. The inter-observer agreement for the abbreviated protocol was reported excellent (κ = 0.91). The sensitivity and AUCs for the lesion characterization of AMRI-M protocol were very high (over 90%) for both readers. No statistically significant differences in sensitivity (assessed by mixed-effects logistic regression) and AUCs for lesion characterization (by ROC regression) were found between both protocols. The AMRI-M acquisition time was estimated to be less than 10 min, which translated into 59% cost of standard MRI.
CONCLUSION: Our proposed AMRI-M protocol (ultrafast SE T2W, DWI, and T1W-HBP at 20 min) is fast, low-cost alternative to the standard MRI protocol and has a high lesion detection performance.
KEY POINTS: • Gadoxetic acid-enhanced protocol has increased the accuracy, sensitivity, and specificity of MRI for detecting colorectal liver metastases. • Our proposed abbreviated MRI protocol is fast, low-cost alternative compared with the standard MRI protocol and has a high lesion detection performance. • Adoption of our protocol may translate to substantial savings for patients and payers.
PMID: 30888485 [PubMed - indexed for MEDLINE]
Evaluation of the clinical impact of concomitant acid suppression therapy in colorectal cancer patients treated with capecitabine monotherapy.
J Oncol Pharm Pract. 2019 Dec;25(8):1839-1845
Authors: Rhinehart HE, Phillips MA, Wade N, Baran A
BACKGROUND: Capecitabine is an oral chemotherapeutic agent used in colorectal cancer. Two prior studies found a negative impact with the concomitant use of proton pump inhibitor agents during treatment with capecitabine in patients with early colorectal and gastroesophageal cancers.
OBJECTIVE: To determine if there is a clinical impact of the concomitant use of capecitabine and acid suppression therapy in patients with local and metastatic colorectal cancer.
METHODS: This was a single-center retrospective cohort study of adult patients with colorectal cancer on capecitabine monotherapy between 2011 and 2017. Progression-free survival (PFS) and overall survival were compared between patients on acid suppression therapy and those not on acid suppression therapy.
RESULTS: A total of 70 patients were included. Patients on acid suppression therapy at capecitabine initiation (21%) had decreased progression-free survival versus those not on acid suppression therapy (HR 2.24, 95% CI 1.06-4.41, p = 0.035), after adjusting for disease severity and age. Acid suppression therapy use was associated with a numerical decrease in overall survival (HR 1.86, 95% CI 0.81-3.91, p = 0.14). In patients on any concomitant acid suppression therapy (25%), there was a decreased rate of progression-free survival (HR 6.21, 95% CI 2.56-14.32, p = 0.0001) but not overall survival (HR 1.64, 95% CI 0.68-3.54, p = 0.25) versus those without concomitant acid suppression therapy, after adjusting for age and disease severity.
CONCLUSIONS: Concurrent use of acid suppression therapy and capecitabine was associated with decreased progression-free survival, and there was a trend towards decreased overall survival. Due to the demonstrated potential of decreased efficacy, concurrent use of proton pump inhibitors or histamine 2 receptor antagonists should be avoided in colorectal cancer patients on treatment with capecitabine monotherapy.
PMID: 30551722 [PubMed - indexed for MEDLINE]