Correlation of single nucleotide polymorphisms (SNPs) of hypoxia-related genes with pathologic complete response (pCR) following neoadjuvant chemoradiation (chemoXRT) for locally advanced rectal cancer.

2010 ◽  
Vol 28 (15_suppl) ◽  
pp. 3643-3643 ◽  
Author(s):  
M. Tanaka ◽  
I. Bedrosian ◽  
G. J. Chang ◽  
Y. N. You ◽  
P. Das ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Single Nucleotide Polymorphisms ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Neoadjuvant Chemoradiation ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide

Totally neoadjuvant chemoradiation therapy with mFOLFOX6 in locally advanced rectal cancer: A single arm phase II study (FOTAC).

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. TPS816-TPS816
Author(s):  
Jianwei Zhang ◽  
Yue Cai ◽  
Huabin Hu ◽  
Jian Xiao ◽  
Dianke Chen ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Phase Ii Study ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Neoadjuvant Chemoradiation ◽  
Chemoradiation Therapy ◽  
Neoadjuvant Chemoradiation Therapy

TPS816 Background: Preoperative 5-Fluorouracil based chemoradiotherapy is the standard of treatment for locally advanced rectal cancer. About 15% to 18% of patients would achieve pathologic complete response (pCR) after 5-Fluorouracil based chemoradiation. And the survival outcome of patients with pCR was much better than that of non-pCR. In our previous FOWARC study, in the group of preoperative systemic chemotherapy with mFOLFOX6 combined with radiation, the pCR rate was up to 27.5%. In another study, adding mFOLFOX6 after neoadjuvant chemo radiation in locally advanced rectal cancer improve the pCR rate to 38%. This phase II study aimed to explore whether totally neoadjuvant chemoradiation therapy with mFOLFOX6 could further improve the pCR rate in locally advanced rectal cancer. Methods: The primary endpoint is the pathologic complete response rate (pCR).The secondary endpoint included 3-year disease free survival rate, 3-year local recurrence rate, and safety. We hypothesized that totally neoadjuvant chemoradiation therapy with mFOLFOX6 could improve the pCR rate from 18% to 45% with 5% type I error and 80% power. Fifty patients met inclusion criteria will be enrolled in the trial. All patients will receive long term radiation for 25 times and 50Gy before surgery. Four cycles of mFOLFOX6 would be performed every 2 weeks during radiotherapy, and another 4-6 cycles would be added after radiotherapy and before operation. Totally, the patients will receive 8-10 cycles of chemotherapy before surgery. MRI of the pelvic will be performed every 4 cycles of the therapy to assess clinical response. Then the patient will receive total mesorectal excision at least 8 weeks after radiotherapy. The post-operative chemotherapy will be omitted and all the patients go to surveillance. Clinical trial information: NCT02887313.

scholarly journals Single nucleotide polymorphisms in the HIF-1α gene and chemoradiotherapy of locally advanced rectal cancer

2012 ◽  
Vol 4 (5) ◽  
pp. 1056-1060 ◽  
Author(s):  
BIRGITTE MAYLAND HAVELUND ◽  
KAREN-LISE GARM SPINDLER ◽  
JOHN PLOEN ◽  
RIKKE FREDSLUND ANDERSEN ◽  
ANDERS JAKOBSEN
Keyword(s):  
Rectal Cancer ◽  
Single Nucleotide Polymorphisms ◽  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide

Microsatellite instability (MSI) as an independent predictor of pathologic complete response (PCR) in locally advanced rectal cancer: A National Cancer Database (NCDB) analysis.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 616-616 ◽  
Author(s):  
Shaakir Hasan ◽  
Paul Renz ◽  
Rodney E Wegner ◽  
Gene Grant Finley ◽  
Moses S. Raj ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Microsatellite Instability ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Multivariable Analysis ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Neoadjuvant Chemoradiation ◽  
National Cancer Database

616 Background: The relationship between microsatellite instability (MSI) and response to neoadjuvant chemoradiation in rectal cancer is not well understood. We therefore utilized the national cancer database (NCDB) to investigate the association between MSI and pathologic complete response (pCR) in this patient population. Methods: We analyzed 5,086 patients between 2010-2015 with locally advanced rectal cancer who were tested for MSI and treated definitively with chemoradiation followed by surgery. Primary comparison groups were between 4,450 MSI-negative(-) and 636 MSI-positive(+) patients. Multivariable regression analysis was conducted to identify demographic, therapeutic, and clinical characteristics predictive of pCR. Cox proportional hazard ratios were used for survival. Results: All patients were treated with definitive chemoradiation (median dose 50.4 Gy) followed by resection within 4 months. MSI(+) patients were associated with earlier year of diagnosis and higher grade tumors (P < 0.05). The overall pCR rate was 8.6%, including 8.9% for MSI(-) and 5.9% for MSI(+) tumors (P = 0.01). Along with lower T stage, MSI(+) cases were significantly associated with a reduced pCR rate (OR = 0.65, 95% CI 0.43 – 0.96) with multivariable analysis. The 5-year survival for patients with pCR was 93% compared to 73% without it (< 0.001). Conclusions: Microsatellite instability was independently associated with a reduction in pathologic complete response for locally advanced rectal cancer following neoadjuvant chemoradiation in this NCDB-based analysis.[Table: see text]

Pathologic complete response rate after neoadjuvant chemoradiation in patients with locally advanced rectal cancer affects survival in patients with prolonged radiation-surgery interval.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3608-3608
Author(s):  
Benjamin Mitchell Motz ◽  
Patrick Daniel Lorimer ◽  
Danielle Boselli ◽  
I'sis N Perry ◽  
Joshua S. Hill ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Residual Disease ◽  
Cox Model ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Neoadjuvant Chemoradiation ◽  
National Database

3608 Background: The current standard of care in locally advanced rectal cancer is neoadjuvant chemoradiation and R0 resection. An optimal radiation-surgery interval (RSI) has not been established. A small institutional dataset showed RSI > 49 days improved pathologic complete response (pCR) rates and disease free survival. However, in a national dataset, RSI greater than 60 days was associated with increased rates of positive margins and impaired overall survival. Because pCR is associated with improved survival, we used a national database to evaluate the relationship between RSI, pCR and survival after neoadjuvant therapy for rectal cancer. Methods: The NCDB was queried for cases 2004-2013 of AJCC stage II or III rectal adenocarcinoma that underwent neoadjuvant radiation followed by radical resection. We excluded patients with missing and outlier RSI. pCR was defined as ypT0N0M0. Chi-square, univariate, multivariable Cox model, and Cochran-Armitage time trend analyses were performed. Results: 23475 patients were identified. 7901 (33.7%) had RSI ≥60 days. pCR occurred in 1766 (11.3%) of the < 60 group and 1174 (14.9%) of the ≥60 group (p < 0.001). RSI ≥60 days has increased over time, from 22.1% in 2004 to 45.4% in 2013 (p < 0.001), as have pCR rates, from 8.4% in 2004 to 14.2% in 2013 (p < 0.001). Multivariable Cox model of the total cohort showed that RSI ≥60 days (HR = 1.11, 95% CI = 1.04-1.19) and residual disease (HR = 2.04, 95% CI = 1.78-2.34) were associated with increased mortality. Subgroup analysis of patients with pCR showed RSI ≥60 days was not associated with worse survival (HR = 1.07, 95% CI = 0.82-1.41). However, analysis of patients with residual disease showed RSI ≥60 days was associated with worse survival (HR = 1.13, 95% CI = 1.06-1.21). Conclusions: In a large national database, RSI ≥60 days worsens survival in patients who have residual disease after neoadjuvant therapy for locally advanced rectal cancer, while there is no difference in those with pCR. Emphasis should be placed on identifying patients who are unlikely to have pCR and to prioritize resection in these patients within 60 days of completion of chemoradiation.

The frequencies and clinical implications of mutations in 33 kinase-related genes in locally advanced rectal cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3549-3549
Author(s):  
Khairun Izlinda Abdul Jalil ◽  
Katherine M Sheehan ◽  
Sinead Toomey ◽  
Jasmin Schmid ◽  
Anthony O'grady ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Clinical Outcomes ◽  
Mapk Pathway ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Pi3k Pathway ◽  
Locally Advanced Rectal Cancer ◽  
Nucleotide Polymorphisms

3549 Background: Locally advanced rectal cancer, LARC (T3/4 and/or N+) is currently treated with pre-operative chemoradiotherapy (pCRT), but responses are not uniform. The phosphatidylinositol 3-kinase (PI3K), MAP-kinase (MAPK) and related pathways have been implicated in rectal cancer tumorigenesis. Here, we investigated the association between genetic variations in these pathways and clinical outcomes in LARC. Methods: We genotyped a total of 234 Single Nucleotide Polymorphisms (SNPs) including potentially clinically relevant mutations in 33 cancer related genes including PIK3CA, PIK3R1, AKT, STK11, KRAS, BRAF, MEK, CTNNB1, EGFR, MET and NRAS using the Sequenom platform. DNA samples utilized herein were extracted from pre-treatment rectal cancer biopsies of 201 patients who were then treated with long-course pCRT followed by surgical resection. Results: 62 different mutations were detected in 15 genes, with the highest frequencies occurring in KRAS (n=93, 47%), PIK3CA (n=29, 14%), MET (n=27, 13%), STK11 (n=13, 6.3%), CTNNB1 (n=12, 6%), BRAF (n=8, 4%) and NRAS (n=7, 3.5%). Mutations were also detected in AKT, PIK3R1, EGFR, GNAS, MEK1, PDGFRA, ALK and TNK2, but at frequencies of less than 2%. Pathologic complete response (pCR) was associated with excellent (97%) 5-year Recurrence-Free Survival (RFS) (Hazard ratio [HR], 0.076; 95% CI, 0.01-0.50, P=0.001). We found: 1) Mutations in PI3K pathway-related genes (PIK3CA, AKT, STK11) were significantly associated with absence of pCR (odd ratio [OR], 5.40; 95% CI, 1.24-23.54, P=0.024). However, mutations in MAPK pathway-related genes (KRAS, BRAF, NRAS, MEK) was not found to be significantly associated with pCR (P=0.805). 2) In contrast, in patients who did not achieve pCR (non-pCR), mutations in PI3K pathway-related genes were not associated with RFS. However, in these patients, codon 12 (G12D/G12V/G12S) and 13 mutations in KRAS were associated with poor RFS (HR, 0.336; 95% CI, 0.115-0.981, P=0.046). Conclusions: These results suggest that mutations in kinase signaling pathways may modulate treatment responsiveness and clinical outcomes in locally advanced rectal cancer and thus may constitute rational targets for novel therapies.

scholarly journals Mutational and Clinical Predictors of Pathologic Complete Response in the Treatment of Locally Advanced Rectal Cancer

2013 ◽  
Vol 45 (1) ◽  
pp. 34-39 ◽  
Author(s):  
Andrea L. Russo ◽  
David P. Ryan ◽  
Darrell R. Borger ◽  
Jennifer Y. Wo ◽  
Jackie Szymonifka ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Clinical Predictors

Intensification of neoadjuvant therapy in patients with locally advanced rectal cancer

2021 ◽  
Vol 11 (2) ◽  
pp. 19-28
Author(s):  
Z. Z. Mamedli ◽  
A. V. Polynovskiy ◽  
D. V. Kuzmichev ◽  
S. I. Tkachev ◽  
A. A. Aniskin
Keyword(s):  
Rectal Cancer ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Disease Free Survival ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Control Group ◽  
Free Survival ◽  
Disease Free

The aim of the study: to increase the frequency of achieving pathologic complete response and increase disease-free survival in the investigational group of patients with locally advanced rectal cancer T3(MRF+)–4N0–2M0 by developing a new strategy for neoadjuvant therapy.Materials and methods. In total, 414 patients were assigned to treatment. Control group I included 89 patients who underwent radiotherapy (RT) 52–56 Gy/26–28 fractions with concurrent capecitabine twice daily 5 days per week. Control group II included 160 patients who underwent RT 52–56 Gy/26–28 fractions with concurrent capecitabine twice daily 5 days per week and oxaliplatin once a week, during the course of RT. Study group III consisted of 165 patients. This group combined RT 52–56 Gy/26–28 fractions with concurrent capecitabine twice daily 5 days per week and additional consecutive CapOx cycles. This group was divided into 2 subgroups: subgroup IIIa included 106 patients with consolidating chemotherapy (after CRT); subgroup IIIb included 59 patients who underwent “sandwich” treatment. Therapy consisted of conducting from 1 to 2 cycles of induction CapOx (up to CRT) and from 1 to 2 cycles of consolidating CapOx with an interval of 7 days. In the interval between the courses of drug therapy, RT 52–56 Gy/26–28 fractions was performed. According to the results of the control examination, further treatment tactics were determined. The primary end points were 5-year disease-free survival and the achievement of a pathologic complete response.Results. Pathologic complete response was significantly more often recorded in patients in the investigational group III (17.48 %; p = 0.021) compared with control groups (7.95 % in the I group and 8.28 % in the II group). 5-year disease-free survival in patients in the study groups was: 71.5 % in the III group, 65.6 % in the II group and 56.9 % in the I group.Conclusion. The shift in emphasis on strengthening the neoadjuvant effect on the tumor and improving approaches to drug therapy regimens have significantly improved disease-free survival of patients with locally advanced rectal cancer.

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