Preoperative Valproic Acid and Radiation Therapy for Rectal Cancer
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ABSTRACT:
DISEASE(S): Rectal Neoplasms,Colorectal Cancer,Valproic Acid
PROVIDER: 2148214 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:Using Human WG CodeLink microarrays, we established the expression profiling of 26 LARC without metastasis to gain insight into the molecular signatures associated with response to treatment after CRT. The study initially included a total of 35 consecutive patients with locally advanced rectal cancer (LARC) treated at Virgen de las Nieves Hospital from 2008 until 2010. Written informed consent was obtained from all the patients, and the study protocol was approved by the local Clinical Research (Ethics) Committee. They were distributed in two subgroups following a histological classification of response to treatment. Pretherapeutic staging was performed, including complete medical history and physical evaluation, digital rectal examination, endorectal ultrasound, rigid rectoscopy, colonoscopy, PET/TC and chest x-ray. Tumor samples were prospectively obtained during the rectoscopy. All patients subsequently received a total dose of 50.4Gy of radiatio (28 fractions of 1.8Gy) associated with capecitabine or capecitabine and oxaliplatine. Standardized surgery was performed, including total mesorectal excision, after an interval of 8 weeks after chemoradiotherapy. Tumor response was assessed in surgical specimen by semi-quantitative pathological examination (regression grade) including UICC stage. Histopathological tumor regression was graded based on the semiquantitative 5 point tumor regression grading (TRG) system: TRG1 or a TRG2 scores were considered Responders, whereas TRG3, TRG4, and TRG5 scores were classified as Non-Responders. In addition, the tumor regression or radiotherapy effects were assessed by positron emission tomography (18F-FDG PET). Tumor samples of LARC were collected from 35 patients. Nine patients were finally excluded due to the poor quality of the RNA or contradictory results of MandardM-BM-4s criteria and histopathological downstaging, resulting a total of 26 patients. Complete clinical data regarding, age, sex, stage of disease, response to therapy, and overall survival from 26 patients (10 responders and 16 non-responders) was provided in the sample characteristics field. CRT: Chemoradiation; Cap: Capecitabine; Capox: Capecitabine and Oxaliplatine; cTN: clinical stage; Surg: surgical technique; LAR: Low anterior resection; APR: Abdmino-perineal resection; HART: Hartmann, TRG: Tumor Regression Grade; Downst: Downstaging; Downs: downsizing, Resp: response, CPR: complete pathologic response
2014-01-03 | E-GEOD-53781 | biostudies-arrayexpress
Project description:Background: MicroRNAs (miRNAs) are small, non-coding, RNA molecules which regulate numerous cellular processes. Specific miRNA may be abnormally down-regulated or up-regulated in colorectal cancer and have been found associated with prognosis or response to treatments. However, no study has ever addressed their predictive role in rectal cancer. Therefore, we used microarray technology and RT-PCR to profile miRNA expression patterns in patients (pts) with rectal cancer, with the aim to identify a specific M-bM-^@M-^\signatureM-bM-^@M-^] associated with pathological complete response after neoadjuvant chemo-radiotherapy. Methods: 38 pts with locally advanced rectal cancer (cT3-4/N+) were treated with capecitabine-oxaliplatin and pelvic conformal radiotherapy (45 cGy) followed by surgery (after 6-8 weeks). Pathologic response was scored according to the tumor regression grade (TRG) scale. MiRNA expression profile was analysed by microarray on fresh frozen biopsies obtained before treatment start and confirmed by RT-PCR. The correlation between miRNA expression profile and the TRG coded as TRG1 (pathologic Complete Response-pCR) versus TRG >1 (no pCR) was assessed by statistical analysis methods specifically designed for this study. Findings: 14 miRNAs were selected by arrays analysis as differentially expressed in TRG1 pts and 13 were confirmed by RT-PCR. In particular, 11 miRNAs (miR-1183, miR-483-5p, miR-622, miR-125a-3p, miR-1224-5p, miR-188-5p, miR-1471, miR-671-5p, miR-1909*, miR-630 and miR-765) were significantly up-regulated in TRG1 pts, while 2 miRNAs were under -expressed (miR-1274b and miR-720). miR-622 and miR-630 showed 100% sensitivity and specificity in selecting TRG1 cases and were significantly correlated with EGFR (M-OM-^G2=11M-bM-^@M-"793; p= 0M-bM-^@M-"001) and TS expression (M-OM-^G2=10M-bM-^@M-"589; p= 0M-bM-^@M-"001). Interpretation: A set of 13 miRNAs is strongly associated with pathologic complete response and may represent a specific marker of response to chemo-radiotherapy in locally advanced rectal cancer. Experiments were performed on purified RNA from preoperatory biopsies of 38 patients with histological diagnosis of rectal adenocarcinoma invading through the intestinal wall and/or with pelvic lymph node involvement as evaluated by endorectal ultrasonography (uT3-T4 and/or uN+). Patients were treated with neoadjuvant chemo-radiotherapy (capecitabine + oxaliplatin in combination with 45 Gy of pelvic conformal radiotherapy). Patients have been divided in the following two groups: group A those who had obtained a pathologic complete response M-bM-^@M-^S TRG 1, including the patient without detectable disease who refused surgery, group B any pathologic response other than complete.
2012-04-24 | E-GEOD-29298 | biostudies-arrayexpress
Project description:Background: MicroRNAs (miRNAs) are small, non-coding, RNA molecules which regulate numerous cellular processes. Specific miRNA may be abnormally down-regulated or up-regulated in colorectal cancer and have been found associated with prognosis or response to treatments. However, no study has ever addressed their predictive role in rectal cancer. Therefore, we used microarray technology and RT-PCR to profile miRNA expression patterns in patients (pts) with rectal cancer, with the aim to identify a specific “signature” associated with pathological complete response after neoadjuvant chemo-radiotherapy. Methods: 38 pts with locally advanced rectal cancer (cT3-4/N+) were treated with capecitabine-oxaliplatin and pelvic conformal radiotherapy (45 cGy) followed by surgery (after 6-8 weeks). Pathologic response was scored according to the tumor regression grade (TRG) scale. MiRNA expression profile was analysed by microarray on fresh frozen biopsies obtained before treatment start and confirmed by RT-PCR. The correlation between miRNA expression profile and the TRG coded as TRG1 (pathologic Complete Response-pCR) versus TRG >1 (no pCR) was assessed by statistical analysis methods specifically designed for this study. Findings: 14 miRNAs were selected by arrays analysis as differentially expressed in TRG1 pts and 13 were confirmed by RT-PCR. In particular, 11 miRNAs (miR-1183, miR-483-5p, miR-622, miR-125a-3p, miR-1224-5p, miR-188-5p, miR-1471, miR-671-5p, miR-1909*, miR-630 and miR-765) were significantly up-regulated in TRG1 pts, while 2 miRNAs were under -expressed (miR-1274b and miR-720). miR-622 and miR-630 showed 100% sensitivity and specificity in selecting TRG1 cases and were significantly correlated with EGFR (χ2=11•793; p= 0•001) and TS expression (χ2=10•589; p= 0•001). Interpretation: A set of 13 miRNAs is strongly associated with pathologic complete response and may represent a specific marker of response to chemo-radiotherapy in locally advanced rectal cancer.
2012-04-25 | GSE29298 | GEO
Project description:We found that ERY974 shows only moderate antitumor efficacy in MKN45 non-inflamed tumor in huNOG mice. We also observed that ERY974 + capecitabine increases antitumour efficacy in non-inflamed MKN45 tumours. To identify a mechanism of combination effect, we compared RNA expression of MKN45 tumors treated with ERY974, capecitabine, or combination.
2022-08-21 | GSE211373 | GEO
Project description:Primary objectives: The main objective of the trial is to evaluate the activity, in terms of pathologic complete response, of the addition of temozolomide to standard concurrent capecitabine-based chemoradiation, in moleculary selected patient with low-risk locally advance rectal cancer molecularly selected formicrosetellite stability, MGMT negative IHC and MGMT promoter methylation.
Primary endpoints: Pathologic complete response (pCR), defined as complete histological regression with no available tumor cells (yT0N0) in the intention-to-treat population.
| 2541423 | ecrin-mdr-crc
Project description:Specific immune subsets from orthotopic murine rectal tumors were sequenced to explore the effect that short course radiotherapy has on the immune response.
2023-02-08 | GSE211991 | GEO
Project description:Specific cell types from orthotopic murine rectal tumors were sequenced to explore the effect that short course radiotherapy has on the immune response.
2023-08-07 | GSE227738 | GEO
Project description:Background: Radiotherapy is an effective treatment of intermediate/high-risk locally advanced prostate cancer, however,>30% of patients relapse within 5 years. Clinicopathological parameters currently fail to identify patients prone to systemic relapse and those whom treatment intensification may be beneficial. The purpose of this study was to independently validate prognostics assays in a cohort of diagnostic biopsies from patients treated with radical radiotherapy and androgen deprivation therapy. Patients and methods: Independent clinical validation in a cohort of diagnostic biopsies from patients treated with radical radiotherapy and androgen deprivation therapy. Multivariable Cox proportional hazard regression analysis was used to assess assay performance in predicting biochemical failure-free survival (BFFS) and metastasis free survival (MFS). Results: Gene expression analysis was carried out in 248 patients from the independent validation cohort and the Metastatic Assay applied. Ten-year MFS was 72% for Metastatic Assay positive patients and 94% for Metastatic Assay negative patients [HR 3.21 (1.35–7.67); P=0.003]. On multivariable analysis the Metastatic Assay remained predictive for development of distant metastases [HR 2.71 (1.11–6.63); P=0.030]. The assay retained independent prognostic performance for MFS when assessed with the Cancer of the Prostate Assessment Score (CAPRA) [HR 3.23 (1.22–8.59); P=0.019] whilst CAPRA itself was not significant [HR 1.88, (0.52–6.77); P=0.332]. Conclusions: The Metastatic Assay demonstrated significant prognostic performance in patients treated with radical radiotherapy both alone and independent of standard clinical and pathological variables. The Metastatic Assay could have clinical utility when deciding upon treatment intensification in high-risk patients.
2018-07-12 | GSE116918 | GEO
Project description:Interventions: Short course radiotherapy with 25 Gy in 5 fractions with concurrent chemotherapy regimen including Capecitabine 850mg/m2/bid for 5 days and Oxaliplatin 85mg/m2/day for 1 day then one cycle chemotherapy with XELOX regimen (Capecitabine 1000mg/m2/bid for 14 days and Oxaliplatin 130mg/m2/day for 1 day) 3 weeks after completion of radiotherapy then surgery 8 weeks after the radiotherapy last session..;Treatment - Other;Short course radiotherapy with 25 Gy in 5 fractions with concurrent chemotherapy regimen including Capecitabine 850mg/m2/bid for 5 days and Oxaliplatin 85mg/m2/day for 1 day then one cycle chemotherapy with XELOX regimen (Capecitabine 1000mg/m2/bid for 14 days and Oxaliplatin 130mg/m2/day for 1 day) 3 weeks after completion of radiotherapy then surgery 8 weeks after the radiotherapy last session.
Primary outcome(s): Complications. Timepoint: At the Initiation of Radiotherapy up to one month after surgery. Method of measurement: Common terminology criteria for cancer related therapy adverse events.
Study Design: Randomization: N/A, Blinding: Not blinded, Placebo: Not used, Assignment: Single, Purpose: Treatment.
| 2491836 | ecrin-mdr-crc
Project description:Intervention 1: ?1st Arm: Short course radiotherapy with 25 Gy in 5 fractions with concurrent chemotherapy regimen including Capecitabine 625mg/m2/bid for 5 days and Oxaliplatin 50mg/m2/day for 1 day then one cycle chemotherapy with XELOX regimen (Capecitabine 1000mg/m2/bid for 14 days and Oxaliplatin 130mg/m2/day for 1 day) 3 - 4 weeks after completion of radiotherapy then surgery at least 8 weeks after the radiotherapy last session. Intervention 2: 2nd Arm (Control): Long course radiotherapy with 50 Gy in 25 fractions with concurrent Capecitabine 825mg/m2/bid for 5 days each week then one cycle chemotherapy with XELOX regimen (Capecitabine 1000mg/m2/bid for 14 days and Oxaliplatin 130mg/m2/day for 1 day) 3 - 4 weeks after completion of radiotherapy then surgery at least 8 weeks after the radiotherapy last session.;Treatment - Drugs;Treatment - Drugs;?1st Arm: Short course radiotherapy with 25 Gy in 5 fractions with concurrent chemotherapy regimen including Capecitabine 625mg/m2/bid for 5 days and Oxaliplatin 50mg/m2/day for 1 day then one cycle chemotherapy with XELOX regimen (Capecitabine 1000mg/m2/bid for 14 days and Oxaliplatin 130mg/m2/day for 1 day) 3 - 4 weeks after completion of radiotherapy then surgery at least 8 weeks after the radiotherapy last session.;2nd Arm (Control): Long course radiotherapy with 50 Gy in 25 fractions with concurrent Capecitabine 825mg/m2/bid for 5 days each week then one cycle chemotherapy with XELOX regimen (Capecitabine 1000mg/m2/bid for 14 days and Oxaliplatin 130mg/m2/day for 1 day) 3 - 4 weeks after completion of radiotherapy then surgery at least 8 weeks after the radiotherapy last session.
Primary outcome(s): Complications. Timepoint: At the Initiation of Radiotherapy up to one month after surgery. Method of measurement: Common terminology criteria for cancer related therapy adverse events.
Study Design: Randomization: Randomized, Blinding: Not blinded, Placebo: Not used, Assignment: Parallel, Purpose: Treatment.
| 2495080 | ecrin-mdr-crc