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 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 ◽  
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 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,

scholarly journals Local recurrence after surgery of locally advanced rectal cancer treated with or without preoperative chemoradiotherapy

2020 ◽  
Vol 26 (2) ◽  
pp. 30-34
Author(s):  
Mladen Djuric ◽  
Dejan Lukic ◽  
Zoran Radovanovic ◽  
Aleksandar Ðermanovic ◽  
Milan Ranisavljevic ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Local Recurrence ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Neoadjuvant Chemoradiotherapy ◽  
Treatment Protocol ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Number Of Patients ◽  
Study Results

Introduction: The ?gold standard? for patients with locally advanced rectal cancer is neoadjuvant chemoradiotherapy followed by surgery. Aim: Evaluation of local recurrence after surgery for locally advanced rectal cancer. Methods and patients: Retrospective study included 189 patients, who were operated at Oncology Institute of Vojvodina from January 1st 2012 until December 31st 2017. Patients were divided into two groups. In the first group 73 patients who received chemoradiotherapy were included, while 116 patients without neoadjuvant treatment were in the second group. All patients were diagnosed with locally advanced rectal cancer. The existence of operable metastases in the liver and/or lungs did not exclude patients from the study. Patients who had undergone resection of the rectum by Miles, Hartmann or local tumor excision were excluded from the study. Results: The median follow-up period was 48 months (range 13-84). In total, 23 (12.2%) patients developed local recurrence. In the chemoradiotherapy group, 15.1% (11 of 73 patients) had a local recurrence, as compared with 10.3% (12 of 116 patients) in the group without neoadjuvant treatment. In both groups, there were no correlation between rate of local recurrence with other clinical and pathological parameters such as gender, tumor location, T and N stage, histological differentiation, or lymphovascular and perineural invasion (p>0.05). We confirmed significant association between circumferential resection margin with local recurrence in patients who were treated by preoperative chemoradiation (p=0.014). Conclusion: This study has not shown reduced risk of local recurrence after neoadjuvant therapy most likely due to small number of patients. Despite our results, neoadjuvant treatment followed by surgery remains the best treatment protocol for patients with locally advanced rectal cancer.

Oxaliplatin-based neoadjuvant chemoradiation for locally advanced rectal cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15102-e15102
Author(s):  
S. S. Kazmi ◽  
M. Azfar ◽  
A. A. Syed ◽  
M. A. Yusuf
Keyword(s):  
Rectal Cancer ◽  
Local Recurrence ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Neoadjuvant Chemoradiation ◽  
R0 Resection ◽  
Resection Rate ◽  
Number Of Patients

e15102 Background: Preoperative chemoradiation improves local recurrence in patients with locally advanced rectal cancer1. The survival benefit of 5-FU based chemotherapy with radiation has been questioned2. Oxaliplatin based protocols have shown promise but the optimal regime remains to be defined3,4. We report our experience with addition of Oxaliplatin to neoadjuvant chemoradiation for rectal cancer. Methods: For this retrospective study, thirty-six consecutive patients referred for neoadjuvant chemoradiation for rectal cancer between May 2007 and March 2008 were identified. All patients had histologically proven adenocarcinoma, and were clinical stage T3/T4 or N+, except for one who was T2N0. Outcomes of interest were R0 resection rate and pathological complete response rate(pCR). Neoadjuvant treatment consisted of upto 4 cycles of CapOx(oxaliplatin 130 mg/m2, IV, D1, capecitabine (2,000 mg/m2/day, D1–14, q3 weeks), followed by capecitabine(1650mg/m2/day) with concurrent pelvic radiation(50.4Gy/28 fractions). Restaging to assess resectability was done at 4–6 weeks and definitive TME surgery was undertaken 6–8 weeks after end of chemoradiation Results: Thirty patients(oxaliplatin group) received at least 1 cycle of CapOx(range 1–8). Radical radiotherapy to 50.4Gy/28# was completed in 29/36 patients(81%). Surgical resection was undertaken in 24/36 patients(67%). Resection rate, R0 resection rate, pCR and local recurrence rate were 63%(19/30), 95%(18/19), 32%(6/19), and 5%(1/19) in the oxaliplatin group. In patients with low rectal cancer (0–5cm from anal verge), 16/26(62%) underwent resection. Sphincter sparing surgery was carried out in 7 patients, all of whom had received oxaliplatin, giving a sphincter sparing surgery rate of 64%(7/11) in the oxaliplatin group. Conclusions: Addition of oxaliplatin to neoadjuvant chemoradiation results in a significant number of patients achieving R0 resection, pCR and sphincter sparing surgery, compared to historical controls. No significant financial relationships to disclose.

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