Comparison of BEAMing assays and competitive approaches in the detection of main alteration of RAS in circulating DNA of non small-cell lung cancer (NSCLC) and metastatic colon cancer. Manuscript 2016.

e23056 Background: A number of RAS mutations confer resistance to anti-EGFR therapies routinely used in the treatment of colon cancer. The objective of this study was to evaluate the pertinence of analyzing circulating-free plasma DNA (cfDNA) as an indicator of the mutational status of a tumor, in order to use liquid biopsies instead of invasive and painful tumor biopsies during tumor progression. Methods: A cohort of 24 lung and 25 colon cancer patients was constituted in the Hospices Civils of Lyon. Liquid biopsy plasma samples were collected at diagnosis (colon cancer) and during tumor progression (lung cancer) for the purpose of the current study. KRAS and NRAS somatic alterations were quantified using three different technologies: the Droplet Digital polymerase chain reaction (ddPCR) from BioRad, the BEAMing Digital PCR from Sysmex Inostics, and the NGS NextSeq 500 by Illumina with the Accel-Amplicon 56G Oncology Panel from SWIFT BIOSCIENCES. Results: We observed a high level of sensitivity and specificity with the BEAMing technology, which provided us with excellent matches, around 96% and 73%, between solid and liquid biopsies taken at diagnosis (colon cancer) or during tumor progression (lung cancer), respectively. Indeed, when examining cfDNA from patients displaying one of the KRAS or NRAS mutations, 11 of the 13 mutations were confirmed using this technology, whereas only 5-6 matched the initial NGS status, using the two other technologies. The detection threshold was estimated at 1% for samples containing at least 0.8 ngctDNA/µL for the multiplex screening ddPCR from BioRad and for the 56G Oncology Panel from SWIFT BIOSCIENCES. The threshold was lower, at 0.03%, in samples containing only 0.25 ng ctDNA/µL for the BEAMing technology, which includes a PCR pre-amplification step. Conclusions: The advantage of the Illumina NGS technology is the larger coverage of longer gene regions, and thus the detection of more genetic mutations. Finally, the BEAMing technology enabled us to follow the appearance and disappearance of somatic alterations, with a very high level of sensitivity.

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Delay in time from diagnosis to treatment in metastatic melanoma, lung, and colon cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e23186 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e23186-e23186

Author(s):

Muhammad Salman Faisal ◽

Ahmed Khattab ◽

Vida Jahangiri ◽

Hira Shaikh ◽

Soorih Shaikh ◽

...

Keyword(s):

Lung Cancer ◽

Colon Cancer ◽

Demographic Data ◽

Tertiary Care ◽

The United States ◽

Definitive Treatment ◽

Metastatic Colon Cancer ◽

Female Ratio ◽

Number Of Patients ◽

Delay In Treatment

e23186 Background: Delay in cancer treatment is anxiety provoking both for the patient and clinician. We conducted the study to evaluate the patterns of delay in treatment of patients with metastatic colon cancer, lung cancer and melanoma from diagnosis to the initiation of the treatment, and to identify the causes of delay. Methods: In this retrospective study, patients with metastatic colon cancer, lung cancer and melanoma diagnosed between 01/01/2016 to 12/31/2016 in a tertiary care network in the United States were studied. Data was collected from electronic health record (EHR) database, ‘Epic’. Variables such as demographic data, including patient age and gender, and type of cancer, and treatment received were analyzed. The causes of the delay were also evaluated when available. Results: Total number of patients in the study was 288. Mean age was 68.3 years (median 69 years) and 36% were alive at the time of data analysis. Male to female ratio was 1.4:1. 66.7% people had lung cancer, 30% had colon cancer and 3% had melanoma. 67 (23.6%) of total analyzed patients had denied definitive treatment and chose to undergo palliative management. Of the rest, most started treatment with chemotherapy (39.5%), followed by surgery (22.6%) and then radiation (14.6%). With the time of pathological diagnosis of the tumor taken as the date of diagnosis, mean delay from the day of diagnosis to the start of treatment in this study population observed was 27.7 days. 67 patients (23.3%) had a delay of more than 30 days, with the most common reason being systemic factors in 39 patients (58.2%), followed by patient factors in 23 patients (34.3%) and physician factors in 5 patients (7.5%). On logistic regression analysis, time from diagnosis to treatment didn’t predict mortality (OR = 0.99, 95% CI P = 0.10(0.97-1.002). Conclusions: Delay in treatment is common and the system factors one of the common reasons as exhibited by our study. Time from diagnosis to treatment didn’t predict mortality.

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Aldo-keto reductases are biomarkers of NRF2 activity and are co-ordinately overexpressed in non-small cell lung cancer

British Journal of Cancer ◽

10.1038/bjc.2016.363 ◽

2016 ◽

Vol 115 (12) ◽

pp. 1530-1539 ◽

Cited By ~ 19

Author(s):

A Kenneth MacLeod ◽

Lourdes Acosta-Jimenez ◽

Philip J Coates ◽

Michael McMahon ◽

Frank A Carey ◽

...

Keyword(s):

Lung Cancer ◽

Cell Lines ◽

Mutant Cell ◽

Immunohistochemical Analysis ◽

Lung Tumour ◽

Data Sets ◽

Related Factor ◽

Nrf2 Pathway ◽

Mutational Status ◽

Somatic Alterations

Abstract Background: Although the nuclear factor-erythroid 2-related factor 2 (NRF2) pathway is one of the most frequently dysregulated in cancer, it is not clear whether mutational status is a good predictor of NRF2 activity. Here we utilise four members of the aldo-keto reductase (AKR) superfamily as biomarkers to address this question. Methods: Twenty-three cell lines of diverse origin and NRF2-pathway mutational status were used to determine the relationship between AKR expression and NRF2 activity. AKR expression was evaluated in lung cancer biopsies and Cancer Genome Atlas (TCGA) and Oncomine data sets. Results: AKRs were expressed at a high basal level in cell lines carrying mutations in the NRF2 pathway. In non-mutant cell lines, co-ordinate induction of AKRs was consistently observed following activation of NRF2. Immunohistochemical analysis of lung tumour biopsies and interrogation of TCGA data revealed that AKRs are enriched in both squamous cell carcinomas (SCCs) and adenocarcinomas that contain somatic alterations in the NRF2 pathway but, in the case of SCC, AKRs were also enriched in most other tumours. Conclusions: An AKR biomarker panel can be used to determine NRF2 status in tumours. Hyperactivation of the NRF2 pathway is far more prevalent in lung SCC than previously predicted by genomic analyses.

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Metastatic Colon Cancer from Lung Cancer which Demonstrated Rapid and Aggressive Growth: A Case Report

Nippon Daicho Komonbyo Gakkai Zasshi ◽

10.3862/jcoloproctology.61.410 ◽

2008 ◽

Vol 61 (7) ◽

pp. 410-414 ◽

Cited By ~ 5

Author(s):

Hiroki Akamatsu ◽

Nobuo Ogino

Keyword(s):

Lung Cancer ◽

Colon Cancer ◽

Case Report ◽

Metastatic Colon Cancer

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A case of aseptic meningitis in a cetuximab-experienced patient with metastatic colon cancer

Journal of Oncology Pharmacy Practice ◽

10.1177/1078155217739685 ◽

2017 ◽

Vol 24 (8) ◽

pp. 632-633 ◽

Cited By ~ 1

Author(s):

Chelsea L Rohrer ◽

Zunilda Grullon ◽

Sarah K George ◽

Raul Castillo ◽

Kelli Karasiewicz

Keyword(s):

Colorectal Cancer ◽

Lung Cancer ◽

Colon Cancer ◽

Case Report ◽

Aseptic Meningitis ◽

Growth Factor Receptor ◽

Small Cell ◽

Metastatic Colon Cancer ◽

Small Cell Lung ◽

Epidermal Growth

Cetuximab is a monoclonal antibody against epidermal growth factor receptor and is used in the treatment of head and neck cancer, non-small cell lung cancer, and colorectal cancer. This case report describes a rare (<1% incidence) side effect of cetuximab administration: aseptic meningitis. We report a case which is, to our knowledge, the only case at the time of submission of this manuscript of aseptic meningitis in a patient being treated for metastatic colon cancer who was not cetuximab-naïve. This case report may help inform clinicians about the identification and outcome of this adverse event.

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Metastatic Colon Cancer to the Lung With No Detectable Primary Tumor, Mimicking Advanced Primary Lung Cancer on F-18 FDG PET/CT Imaging

Clinical Nuclear Medicine ◽

10.1097/rlu.0b013e3181cc62fe ◽

2010 ◽

Vol 35 (3) ◽

pp. 184-186

Author(s):

Hae Won Kim ◽

Kyoung Sook Won ◽

Kun Young Kwon ◽

Byung Wook Choi ◽

Seok Kil Zeon

Keyword(s):

Lung Cancer ◽

Colon Cancer ◽

Primary Tumor ◽

Fdg Pet ◽

Primary Lung Cancer ◽

Ct Imaging ◽

Metastatic Colon Cancer ◽

Pet Ct ◽

Fdg Pet Ct

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Association of prognostic value of primary tumor location in stage III colon cancer with RAS and BRAF mutational status.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.3515 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 3515-3515 ◽

Cited By ~ 3

Author(s):

Julien Taieb ◽

Hampig Raphael Kourie ◽

Jean-François Emile ◽

Karine Le Malicot ◽

Ralyath Balogoun ◽

...

Keyword(s):

Colon Cancer ◽

Primary Tumor ◽

Prognostic Value ◽

Disease Free Survival ◽

Tumor Location ◽

Stage Iii ◽

Metastatic Colon Cancer ◽

Tumor Site ◽

Anatomic Site ◽

Mutational Status

3515 Background: Recent data suggest that the anatomic site of colon primary tumor may be an important factor in the interpretation of molecular markers with clinical outcome in metastatic colon cancer (CC) patients (pts). We assessed here the prognostic value of primary location in fully resected stage III CC pts and its relationship to MSI, RAS and BRAF mutational status. Methods: Pts enrolled in the PETACC-8 trial were analyzed. We categorized tumor site as located proximal (left-sided) or distal (right-sided) to the splenic flexure. The association between tumor location and disease free survival (DFS), survival after relapse (SAR) and overall survival (OS) were assessed by Cox models and adjusted for clinical and pathological features, MSI, BRAF and RASmutation status. The outcome of pts receiving FOLFOX or FOLFOX and cetuximab in the adjuvant setting were also determined according to tumor site. Results: Among the 1869 pts with full molecular data available, 755 (40%) had a right-sided tumor, 164 (10%) were MSI, 942 (50%) were mutated for RAS and 212 (11%) were mutated for BRAF. Right-sided tumor was not prognostic for DFS in the whole population but was associated to a shorter SAR (HR: 1.54 [1.23 - 1.93], p = 0.001) and OS (HR: 1.25 [1.02 - 1.54], p = 0.03). Same results were observed for MSS and for MSI pts. However, when looking at pts mutated for RAS or BRAF(MUT) and those double wild type (DWT) for those mutations, we found that right-sided tumors, when compared to left-sided tumors, was associated with a worst DFS in DWT patients (HR:1.39[1.01-1.92], p = 0.04) and a better DFS in MUT patients (HR:0.77[0.63-0.95], p = 0.01). These results were found independently of the treatment received and no beneficial effect of cetuximab on DFS or OS was observed in left-sided tumors. Conclusions: In the whole study population of stage III CC pts, though right-sided tumor location influences OS as previously reported, it does not seem to influence DFS but only SAR, when disease becomes metastatic. Interestingly, sidedness seems to influence DFS when splitting the population in MUT or DWT for RAS and BRAF, with a worst DFS for right-sided tumors in DWT and a worst DFS for left-sided tumors in RAS or BRAF mutants. Clinical trial information: 2005-003463-23.

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