scholarly journals KRAS, NRAS and BRAF mutations detected by next generation sequencing, and differential clinical outcome in metastatic colorectal cancer (MCRC) patients treated with first line FIr-B/FOx adding bevacizumab (BEV) to triplet chemotherapy

Oncotarget ◽  
2018 ◽  
Vol 9 (41) ◽  
pp. 26279-26290 ◽  
Author(s):  
Gemma Bruera ◽  
Francesco Pepe ◽  
Umberto Malapelle ◽  
Pasquale Pisapia ◽  
Antonella Dal Mas ◽  
...  
2021 ◽  
Vol 11 ◽  
Author(s):  
Alec J. Kacew ◽  
Garth W. Strohbehn ◽  
Loren Saulsberry ◽  
Neda Laiteerapong ◽  
Nicole A. Cipriani ◽  
...  

Rising cancer care costs impose financial burdens on health systems. Applying artificial intelligence to diagnostic algorithms may reduce testing costs and avoid wasteful therapy-related expenditures. To evaluate the financial and clinical impact of incorporating artificial intelligence-based determination of mismatch repair/microsatellite instability status into the first-line metastatic colorectal carcinoma setting, we developed a deterministic model to compare eight testing strategies: A) next-generation sequencing alone, B) high-sensitivity polymerase chain reaction or immunohistochemistry panel alone, C) high-specificity panel alone, D) high-specificity artificial intelligence alone, E) high-sensitivity artificial intelligence followed by next generation sequencing, F) high-specificity artificial intelligence followed by next-generation sequencing, G) high-sensitivity artificial intelligence and high-sensitivity panel, and H) high-sensitivity artificial intelligence and high-specificity panel. We used a hypothetical, nationally representative, population-based sample of individuals receiving first-line treatment for de novo metastatic colorectal cancer (N = 32,549) in the United States. Model inputs were derived from secondary research (peer-reviewed literature and Medicare data). We estimated the population-level diagnostic costs and clinical implications for each testing strategy. The testing strategy that resulted in the greatest project cost savings (including testing and first-line drug cost) compared to next-generation sequencing alone in newly-diagnosed metastatic colorectal cancer was using high-sensitivity artificial intelligence followed by confirmatory high-specificity polymerase chain reaction or immunohistochemistry panel for patients testing negative by artificial intelligence ($400 million, 12.9%). The high-specificity artificial intelligence-only strategy resulted in the most favorable clinical impact, with 97% diagnostic accuracy in guiding genotype-directed treatment and average time to treatment initiation of less than one day. Artificial intelligence has the potential to reduce both time to treatment initiation and costs in the metastatic colorectal cancer setting without meaningfully sacrificing diagnostic accuracy. We expect the artificial intelligence value proposition to improve in coming years, with increasing diagnostic accuracy and decreasing costs of processing power. To extract maximal value from the technology, health systems should evaluate integrating diagnostic histopathologic artificial intelligence into institutional protocols, perhaps in place of other genotyping methodologies.


2021 ◽  
Author(s):  
Humaira Sarfraz ◽  
Abeer Arain ◽  
Mukul K. Divatia ◽  
Mary R. Schwartz ◽  
Kirk E. Heyne

Abstract Background: Cardiac metastasis due to colon cancer is extraordinarily uncommon. Given the rarity of diagnosis, there is paucity of evidence and hence, no established guidelines for evaluation or clinical management strategy. Clinical presentation: We present the case of a 59 year old male with a previously treated colonic carcinoma who presented with new onset exertional dyspnea. He was noted to be having a right atrial mass on an echocardiogram performed at his cardiologist’s office. Further workup with CT angiogram of the chest confirmed a right atrial mass measuring 4.0 cm. Serum CEA was normal. Biopsies of the right atrial mass demonstrated metastatic moderately differentiated colonic adenocarcinoma. Mismatch repair protein expression analysis by immunohistochemistry showed no loss of MLH1, MSH2, MSH6 or PMS2 expression. Next generation sequencing for RAS and BRAF mutations was negative. Patient received treatment with FOLFIRINOX/ bevacizumab with noted reduction in size of mass. Conclusion: To the best of our knowledge, this is the first report of next generation sequencing results available on a biopsy of metastatic colorectal cancer to the heart with the largest literature review of 31 reported cases of metastatic colorectal cancer to the heart. It will help direct clinical management and also adds evidence to the potential efficacy of treatment of this rare aggressive disease with chemotherapy in combination with VEGF inhibitors.


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