scholarly journals Intra-tumoral genomic heterogeneity in rectal cancer: mutational status is dependent on preoperative biopsy depth and location.  

2020 ◽  
Author(s):  
Floris A. Vuijk ◽  
Carlijn van de Water ◽  
Shannon van Lent - van Vliet ◽  
Maxime J.M. van der Valk ◽  
Femke Simmer ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Next Generation Sequencing ◽  
Neoadjuvant Therapy ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Next Generation ◽  
Biopsy Material ◽  
Mutational Status ◽  
Number Of Patients ◽  
Generation Sequencing

Abstract BackgroundNeoadjuvant therapy before surgical resection is indicated for patients with locally advanced rectal cancer. However, a significant number of patients show minimal or no response to neoadjuvant therapy. Unfortunately, we are currently unable to predict response and identify non-responding patients before neoadjuvant treatment is given. Genomic mutational status might provide valuable prognostic information. However, it is unclear whether predictions based on genomic mutational status in single preoperative biopsies are reliable due to intra-tumoral heterogeneity. In this study we aim to investigate the reliability of genomic mutations found in single pre-operative biopsies by comparing these genomic mutations to 4 other locations within the same tumor using next generation sequencing.Methods Rectal cancer patients undergoing primary resection, without neoadjuvant therapy, were included. Of all patients, one biopsy, two deep and two superficial samples were obtained and sequenced using a targeted next generation sequencing gene panel. Concordance between these 5 samples was assessed.Results In this feasibility study we included 11 patients. In 7 out of 11 (64%) patients, all 5 samples showed concordant mutations. In 4 out of 11 patients (36%) discordant mutations were observed. ConclusionsIn conclusion, assessment of mutational status on a single pre-operative biopsy shows discordance with tumor tissue from other locations in 36% of cases. These results warrant careful interpretation of biopsy material analysis, as these might be influenced by tumor heterogeneity.

scholarly journals Intra-Tumoral Genomic Heterogeneity in Rectal Cancer: Mutational Status Is Dependent on Preoperative Biopsy Depth and Location

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2271
Author(s):  
Floris A. Vuijk ◽  
Carlijn van de Water ◽  
Shannon Lent-van Vliet ◽  
Maxime J. M. van der Valk ◽  
Femke Simmer ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Next Generation Sequencing ◽  
Neoadjuvant Therapy ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Next Generation ◽  
Biopsy Material ◽  
Mutational Status ◽  
Number Of Patients ◽  
Generation Sequencing

Neoadjuvant therapy before surgical resection is indicated for patients with locally advanced rectal cancer. However, a significant number of patients show minimal or no response to neoadjuvant therapy. Unfortunately, we are currently unable to predict response and identify non-responding patients before neoadjuvant treatment is given. Genomic mutational status might provide valuable prognostic information. However, it is unclear whether predictions based on genomic mutational status in single preoperative biopsies are reliable due to intra-tumoral heterogeneity. In this study we aim to investigate the reliability of genomic mutations found in single pre-operative biopsies by comparing genomic mutations to four other locations within the same tumor using next generation sequencing. Rectal cancer patients undergoing primary resection without neoadjuvant therapy were included. From each patient, one biopsy, two deep and two superficial samples were obtained and sequenced using a targeted next generation sequencing gene panel. Concordance between these five samples was assessed. In this feasibility study we included 11 patients. In 7 out of 11 (64%) patients, all 5 samples showed concordant mutations. In 4 out of 11 patients (36%) discordant mutations were observed. In conclusion, assessment of mutational status on a single pre-operative biopsy shows discordance with tumor tissue from other locations in 36% of cases. These results warrant careful interpretation of biopsy material analysis, as these might be influenced by tumor heterogeneity.

scholarly journals Intra-tumoral genomic heterogeneity in rectal cancer: mutational status is dependent on preoperative biopsy depth and location.

2020 ◽  
Author(s):  
Floris A. Vuijk ◽  
Carlijn van de Water ◽  
Shannon van Lent - van Vliet ◽  
Maxime J.M. van der Valk ◽  
Cornelis J.H. van de Velde ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Next Generation Sequencing ◽  
Neoadjuvant Therapy ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Advanced Rectal Cancer ◽  
Next Generation ◽  
Mutational Status ◽  
Number Of Patients ◽  
Generation Sequencing

Abstract Background Neoadjuvant therapy is indicated for patients with locally advanced rectal cancer, even though a significant number of patients show minimal or no response. Adequate response prediction before the start of neoadjuvant treatment might reduce unnecessary waiting periods and therapy related toxicity in non-responders. Genomic mutational status might provide a means to predict response to neoadjuvant therapy. However, it is unclear whether predictions based on genomic mutational status in single preoperative biopsies are reliable due to intra-tumoral heterogeneity. In this study we aim to investigate the reliability of genomic mutations found in single pre-operative biopsies by comparing these genomic mutations to 4 other locations within the same tumor using next generation sequencing. Methods Rectal cancer patients undergoing primary resection, without neoadjuvant therapy, were included. Of all patients, one biopsy, two deep and two superficial samples were obtained and sequenced using a targeted next generation sequencing gene panel. Concordance between these 5 samples was assessed. Results 
In this feasibility study we included 11 patients. In 7 out of 11 (64%) patients, all 5 samples showed concordant mutations. In 4 out of 11 patients (36%) disconcordant mutations were observed. Conclusions Evaluation of genomic mutational status on a single pre-operative biopsy shows disconcordance in a substantial amount of patients.

scholarly journals Intra-tumoral genomic heterogeneity in rectal cancer: mutational status is dependent on preoperative biopsy depth and location.

2020 ◽  
Author(s):  
Floris A. Vuijk ◽  
Carlijn van de Water ◽  
Shannon van Lent - van Vliet ◽  
Maxime J.M. van der Valk ◽  
Cornelis J.H. van de Velde ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Next Generation Sequencing ◽  
Neoadjuvant Therapy ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Advanced Rectal Cancer ◽  
Next Generation ◽  
Mutational Status ◽  
Number Of Patients ◽  
Generation Sequencing

Abstract Background Neoadjuvant therapy is indicated for all patients with locally advanced rectal cancer, even though a significant number of patients show minimal or no response. Adequate response prediction before the start of neoadjuvant treatment might reduce unnecessary waiting periods and therapy related toxicity in non-responders. Genomic mutational status might provide a means to predict response to neoadjuvant therapy. However, it is unclear whether predictions based on genomic mutational status in single preoperative biopsies are reliable due to intra-tumoral heterogeneity. In this study we aim to investigate the reliability of genomic mutations found in single pre-operative biopsies by comparing these genomic mutations to 4 other locations within the same tumor using next generation sequencing. Methods Rectal cancer patients undergoing primary resection, without neoadjuvant therapy, were included. Of all patients, one biopsy, two deep and two superficial samples were obtained and sequenced using a targeted next generation sequencing gene panel. Concordance between these 5 samples was assessed. Results 
In this feasibility study we included 11 patients. In 7 out of 11 (64%) patients, all 5 samples showed concordant mutations. In 4 out of 11 patients (36%) disconcordant mutations were observed. Conclusions Evaluation of genomic mutational status on a single pre-operative biopsy is inadequate in a substantial amount of the patients and is therefore insufficient to predict response to neoadjuvant therapy. Predictive algorithms including multiple parameters might be required to further stratify patients to optimal treatment regimens.

scholarly journals Differences in Mutational Profile between Follicular Thyroid Carcinoma and Follicular Thyroid Adenoma Identified Using Next Generation Sequencing

2019 ◽  
Vol 20 (13) ◽  
pp. 3126 ◽  
Author(s):  
Martyna Borowczyk ◽  
Ewelina Szczepanek-Parulska ◽  
Szymon Dębicki ◽  
Bartłomiej Budny ◽  
Frederik A. Verburg ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
P Value ◽  
Thyroid Adenoma ◽  
Next Generation ◽  
Mutational Status ◽  
Follicular Thyroid Adenoma ◽  
Ffpe Samples ◽  
Formalin Fixed Paraffin Embedded ◽  
Follicular Lesions ◽  
Generation Sequencing

We aimed to identify differences in mutational status between follicular thyroid adenoma (FTA) and follicular thyroid cancer (FTC). The study included 35 patients with FTA and 35 with FTC. DNA was extracted from formalin-fixed paraffin-embedded (FFPE) samples from thyroidectomy. Next-generation sequencing (NGS) was performed with the 50-gene Ion AmpliSeq Cancer Hotspot Panel v2. Potentially pathogenic mutations were found in 14 (40%) FTA and 24 (69%) FTC patients (OR (95%CI) = 3.27 (1.22−8.75)). The number of mutations was higher in patients with FTC than FTA (p-value = 0.03). SMAD4 and STK11 mutations were present only in patients with FTA, while defects in FBXW7, JAK3, KIT, NRAS, PIK3CA, SMARCB1, and TP53 were detected exclusively in FTC patients. TP53 mutations increased the risk of FTC; OR (95%CI) = 29.24 (1.64–522.00); p-value = 0.001. FLT3-positivity was higher in FTC than in the FTA group (51.4% vs. 28.6%; p-value = 0.051). The presence of FLT3 and TP53 with no RET mutations increased FTC detectability by 17.1%, whereas the absence of FLT3 and TP53 with a presence of RET mutations increased FTA detectability by 5.7%. TP53 and FLT3 are candidate markers for detecting malignancy in follicular lesions. The best model to predict FTA and FTC may consist of FLT3, TP53, and RET mutations considered together.

scholarly journals Adjuvant chemotherapy for poor-responders to neoadjuvant therapy in locally advanced rectal cancer: does it improve the prognosis?

2021 ◽  
Author(s):  
KHADIJA DARIF ◽  
ZINEB BENBRAHIM ◽  
JIHANE CHOUEF ◽  
ZAYNAB MAHDI ◽  
ADIL NAJDI ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Neoadjuvant Therapy ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Disease Free Survival ◽  
Advanced Rectal Cancer ◽  
Poor Responders ◽  
Free Survival ◽  
Radio Chemotherapy

Abstract Background: Colorectal cancer is the first cause of cancer death in developed countries. Although colon and rectal cancers are frequently grouped as a single disease entity, these malignancies have important differences in treatment approaches ; The preoperative radio-chemotherapy combination has become the standard for tumors of the middle and lower rectum, improving local control. But unlike colon cancer, currently there is no compelling evidence of the benefit of adjuvant chemotherapy in rectal cancer. This study examines the role of adjuvant chemotherapy after a neoadjuvant treatment and chirurgy in localy advanced rectal cancer, especially in poor responders to neoadjuvant therapy. Patients and Methods: Using the medical files collected at the medical oncology department at the Hassan II Hospital Center in Fez , Morocco; patients with rectal cancer diagnosed in 2014 through 2019 who received neoadjuvant CRT(concomitant radio chemotherapy) and surgery with or without AC(adjuvant chemotherapy) were identified. Kaplan-Meier analysis, log-rank tests were used to assess survival. Results: A total of 90 patients were identified; 70 received AC and 20 did not (observation [OBS] group). Median overall survival(OS) of the general population was 40 months, CI 95% = [25-56], the median disease-free survival (DFS) was 17 months,CI 95% = [7-26]. In the analysis of survival according to the ypT and ypN subgroups: the median OS in the ypT1-2 and ypN0 subgroup was higher than in the ypT3-4 or ypN + group (40 months vs 33 months and 44 months vs. 31 consecutive months); DFS was also better in the ypT1-2 and ypN0 group (29 months vs. 11 months (p = 0.05) and 29 months vs. 13 months respectively).The median OS was 40 months for AC and 23 months for OBS (p = 0.036), by against there was no significant improvement in recurrence-free survival. Conclusions: In this population of patients with LARC (localy advanced rectal cancer) treated with neoadjuvant CRT and surgery,

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