scholarly journals Impact of Tumor LINE-1 Methylation Level and Neoadjuvant Treatment and Its Association with Colorectal Cancer Survival

2020 ◽  
Vol 10 (4) ◽  
pp. 219
Author(s):  
Hatim Boughanem ◽  
Gracia María Martin-Nuñez ◽  
Esperanza Torres ◽  
Isabel Arranz-Salas ◽  
Julia Alcaide ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cox Regression ◽  
Interactive Effect ◽  
Survival Rates ◽  
Neoadjuvant Treatment ◽  
Disease Free Survival ◽  
Pathological Features ◽  
Tumor Line ◽  
Free Survival ◽  
Disease Free

Recent studies suggest that long-interspersed nucleotide element-1 (LINE-1) hypomethylation is commonly found in colorectal cancer (CRC), and is associated with worse prognosis. However, the utility of LINE-1 methylation on the prognosis of CRC is still controversial, and may be due to the fact that some clinical and pathological features may affect LINE-1 methylation. Thus, the aim of this study was to assess the prognostic value of tumor LINE-1 methylation in CRC, through their association with the CRC clinical and pathological characteristics. Survival of sixty-seven CRC patients was evaluated according to the median of tumor LINE-1 methylation, as well as pathological and oncological variables. We also studied the association between LINE-1 methylation and pathological features, and finally, we assessed the overall and disease-free survival of LINE1 methylation, stratified by neoadjuvant treatment and further checked by multivariate Cox regression to assess the statistical interactions. LINE-1 was hypomethylated in the CRC tumor with respect to the tumor adjacent-free area (p < 0.05), without association with any other clinical and oncological features, nor with overall and disease-free survival rates for CRC. Relevantly, in neoadjuvant treatment, LINE-1 methylation was associated with survival rates. Thus, disease-free and overall survival rates of treated CRC patients were worse in the hypomethylated LINE-1 tumors than those with normal LINE-1 methylation (p = 0.004 and 0.0049, respectively). Indeed, LINE-1 was hypermethylated more in the treated patients than in the non-treated patients (p < 0.05). The present study showed that tumor LINE-1 hypomethylation was associated with worse survival rates in only treated patients. Our data suggest an interactive effect of neoadjuvant treatment and tumor LINE-1 methylation, which could be a specific-tissue biomarker to predict survival of the treated patients, and help to personalize treatment in CRC.

Validation of neoadjuvant rectal cancer(NAR) score as a surrogate endpoint for disease free survival in Chinese FOWARC study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15162-e15162
Author(s):  
Yanhong Deng ◽  
Yue Cai ◽  
Jianwei Zhang ◽  
Huabin Hu ◽  
Jiayu Ling ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Cox Regression ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Disease Free Survival ◽  
Surrogate Endpoint ◽  
Chinese Patients ◽  
Significant Prognostic Factor ◽  
Free Survival ◽  
Disease Free

e15162 Background: NAR score is considered as a surrogate endpoint for survival in patients with locally advanced rectal cancer who received neoadjuvant treatment. Here we validate it in Chinese FOWARC study, especially in the chemotherapy alone arm. Methods: NAR score is calculated based on cT, ypT, ypN as reported for patients who received surgery in FOWARC study. NAR score is correlated to DFS with COX regression and Kaplan-Meier analysis. Results: 451 patients had surgery, 147 in FU-RT group, 152 in FOLFOX-RT arm and 152 in FOLFOX arm. NAR score is a significant prognostic factor in COX regression (P=0.000, HR 1.034, 95% CI 1.024-1.045) and in FOLFOX alone group (p=0.001, HR 1.030, 95% CI 1.013-1.047). When NAR score is quartile to <5, 5-10, 10-15,>15, the survival of patients is listed below, and similar to pathological staging. Conclusions: NAR score can be used as a surrogate endpoint for disease free survival Chinese patients. But it is not superior to pathological stage, especially in patients who received chemotherapy alone. [Table: see text]

scholarly journals Long-term Oncologic Outcome of Postoperative Complications After Colorectal Cancer Surgery

2020 ◽  
Vol 36 (4) ◽  
pp. 273-280
Author(s):  
Chang Kyu Oh ◽  
Jung Wook Huh ◽  
You Jin Lee ◽  
Moon Suk Choi ◽  
Dae Hee Pyo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Risk Factors ◽  
Postoperative Complications ◽  
Survival Rates ◽  
Disease Free Survival ◽  
Major Complication ◽  
Cancer Surgery ◽  
Colorectal Cancer Surgery ◽  
Free Survival ◽  
Disease Free

Purpose: The impact of postoperative complications on long-term oncologic outcome after radical colorectal cancer surgery is controversial. The aim of this study was to examine the risk factors and oncologic outcomes of surgery-related postoperative complication groups.Methods: From January 2010 to December 2010, 310 patients experienced surgery-related postoperative complications after radical colorectal cancer surgery. These stage I–III patients were classified into 2 subgroups, minor (grades I, II) and major (grades III, IV) complication groups, according to extended Clavien-Dindo classification system criteria. Clinicopathologic differences between the 2 groups were analyzed to identify risk factors for major complications. The diseasefree survival rates of surgery-related postoperative complication groups were also compared.Results: Minor and major complication groups were stratified with 194 patients (62.6%) and 116 patients (37.4%), respectively. The risk factors influencing the major complication group were pathologic N category and operative method. The prognostic factors associated with disease-free survival were preoperative perforation, perineural invasion, tumor budding, and receiving neoadjuvant therapy. With a median follow-up period of 72.2 months, the 5-year disease-free survival rates were 84.4% in the minor group and 78.5% in the major group, but there was no statistical significance between the minor and major groups (P = 0.392).Conclusion: Advanced cancer and open surgery were identified as risk factors for increased surgery-related major complications after radical colorectal cancer surgery. However, severity of postoperative complications did not affect disease-free survival from colorectal cancer.

Intensive Systemic Chemotherapy Combined With Surgery for Metastatic Colorectal Cancer: Results of a Phase II Study

2005 ◽  
Vol 23 (3) ◽  
pp. 502-509 ◽  
Author(s):  
Julien Taïeb ◽  
Pascal Artru ◽  
François Paye ◽  
Christophe Louvet ◽  
Nathalie Perez ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
Cancer Progression ◽  
Survival Rates ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Curative Surgery ◽  
Free Survival ◽  
Disease Free

Purpose To evaluate the efficacy and tolerability of the metastatic irinotecan plus oxaliplatin (MIROX) strategy (adjuvant FOLFOX-7 followed by FOLFIRI), in patients with resectable metastatic colorectal cancer. Patients and Methods Forty-seven patients with resectable metastases of colorectal cancer were prospectively enrolled onto this study. Treatment consisted of six cycles of leucovorin 400 mg/m2, oxaliplatin 130 mg/m2 in a 120-minute infusion, and fluorouracil (FU) 2,400 mg/m2 in a 46-hour infusion, every 2 weeks (FOLFOX-7), followed by six cycles of leucovorin 400 mg/m2, irinotecan 180 mg/m2 in a 90-minute infusion, bolus FU 400 mg/m2, and FU 2,400 mg/m2 as a 46-hour infusion, every 2 weeks (FOLFIRI). Surgery was performed before chemotherapy in 25 patients and after six cycles of FOLFOX-7 in 22 patients (six cycles of FOLFIRI were administered after surgery). Results All but one of the patients underwent curative surgery. Two patients refused postoperative chemotherapy. Tolerability was generally good. The main toxicities were grade 3 to 4 neutropenia (13%) and thrombocytopenia (11%); no febrile neutropenia or bleeding occurred, and there were no deaths caused by toxicity. Two pathologically confirmed complete responses and 15 partial responses were obtained with FOLFOX-7 in the 22 patients who received this regimen before surgery (overall response rate, 77%; 95% CI, 68 to 86). The median disease-free survival time was 21 months; the median overall survival has not yet been reached. The 2-year overall and disease-free survival rates were 89% and 47%, respectively. Conclusion The MIROX strategy is feasible and well tolerated by patients with resectable metastatic colorectal cancer. Progression-free and overall survival rates are promising, with a median of 38 months of follow-up. This strategy currently is being compared with the leucovorin and FU regimen in a phase III trial.

scholarly journals Sentinel Node Biopsy after Neoadjuvant Chemotherapy for Breast Cancer: Preliminary Experience with Clinically Node Negative Patients after Systemic Treatment

2021 ◽  
Vol 11 (3) ◽  
pp. 172
Author(s):  
Alejandro Martin Sanchez ◽  
Daniela Terribile ◽  
Antonio Franco ◽  
Annamaria Martullo ◽  
Armando Orlandi ◽  
...  
Keyword(s):  
Lymph Node ◽  
False Negative ◽  
Neoadjuvant Treatment ◽  
Disease Free Survival ◽  
Lymph Node Biopsy ◽  
Axillary Lymph ◽  
Free Survival ◽  
Oncological Outcomes ◽  
Node Biopsy ◽  
Disease Free

Sentinel lymph node biopsy (SLNB) following neoadjuvant treatment (NACT) has been questioned by many studies that reported heterogeneous identification (IR) and false negative rates (FNR). As a result, some patients receive axillary lymph node dissection (ALND) regardless of response to NACT, leading to a potential overtreatment. To better assess reliability and clinical significance of SLNB status on ycN0 patients, we retrospectively analyzed oncological outcomes of 399 patients treated between January 2016 and December 2019 that were either cN0-ycN0 (219 patients) or cN1/2-ycN0 (180 patients). The Endpoints of our study were to assess, furthermore than IR: oncological outcomes as Overall Survival (OS); Distant Disease Free Survival (DDFS); and Regional Disease Free Survival (RDFS) according to SLNB status. SLN identification rate was 96.8% (98.2% in patients cN0-ycN0 and 95.2% in patients cN+-ycN0). A median number of three lymph nodes were identified and removed. Among cN0-ycN0 patients, 149 (68%) were confirmed ypN0(sn), whereas regarding cN1/2-ycN0 cases 86 (47.8%) confirmed an effective downstaging to ypN0. Three year OS, DDFS and RDFS were significantly related to SLNB positivity. Our data seemed to confirm SLNB feasibility following NACT in ycN0 patients, furthermore reinforcing its predictive role in a short observation timing.

scholarly journals EPEN-49. RESPONSE OF RECURRENT EPENDYMOMA TO MEMMAT BASED METRONOMIC ANTIANGIOGENIC COMBINATION THERAPY UTILIZING TAPERED BEVACIZUMAB AND MAINTENANCE THERAPY WITH CELECOXIB AND FENOFIBRATE

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii317-iii317
Author(s):  
Eileen Gillan
Keyword(s):  
Combination Therapy ◽  
Maintenance Therapy ◽  
Survival Rates ◽  
Disease Free Survival ◽  
Time To Progression ◽  
Free Survival ◽  
Dismal Prognosis ◽  
Recurrent Ependymoma ◽  
Disease Free

Abstract Recurrent ependymomas have a dismal prognosis (2 year survival rates 29% OS and 23% EFS) and are relatively resistant to conventional chemotherapy. We previously reported five relapsed ependymoma patients treated with a MEMMAT based metronomic antiangiogenic combination therapy. All patients are currently alive, including four patients who were multiply relapsed with at least three recurrences. These four patients received between 44–52 weeks of therapy with minimal toxicity. Three had recurrent disease within an average of 44 months (median 42 months) after discontinuation of therapy. One patient who received the following tapering bevacizumab schedule: q3 weeks x 3, q4 weeks x 4 and q5 weeks x 5 followed by maintenance therapy with fenofibrate and celecoxib is in complete remission 12 months post treatment. This regimen was well tolerated with good quality of life in this patient population. Our results suggest that the chosen anti-angiogenic drug combination prolonged the time to progression in these multiply relapsed patients and thus may be particularly beneficial for patients with recurrent ependymoma. Tapered bevacizumab and maintenance therapy with celecoxib and fenofibrate may be modifications worth further investigation for prolonged disease free survival in relapsed ependymoma patients.

scholarly journals TRIM25 regulates oxaliplatin resistance in colorectal cancer by promoting EZH2 stability

2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Sha Zhou ◽  
Jianhong Peng ◽  
Liuniu Xiao ◽  
Caixia Zhou ◽  
Yujing Fang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Disease Free Survival ◽  
Free Survival ◽  
Epigenetic Regulator ◽  
Crc Management ◽  
Disease Free ◽  
Resistance To Chemotherapy

AbstractResistance to chemotherapy remains the major cause of treatment failure in patients with colorectal cancer (CRC). Here, we identified TRIM25 as an epigenetic regulator of oxaliplatin (OXA) resistance in CRC. The level of TRIM25 in OXA-resistant patients who experienced recurrence during the follow-up period was significantly higher than in those who had no recurrence. Patients with high expression of TRIM25 had a significantly higher recurrence rate and worse disease-free survival than those with low TRIM25 expression. Downregulation of TRIM25 dramatically inhibited, while overexpression of TRIM25 increased, CRC cell survival after OXA treatment. In addition, TRIM25 promoted the stem cell properties of CRC cells both in vitro and in vivo. Importantly, we demonstrated that TRIM25 inhibited the binding of E3 ubiquitin ligase TRAF6 to EZH2, thus stabilizing and upregulating EZH2, and promoting OXA resistance. Our study contributes to a better understanding of OXA resistance and indicates that inhibitors against TRIM25 might be an excellent strategy for CRC management in clinical practice.

Phase I Study of Fludarabine Plus Cyclophosphamide in Patients With Previously Untreated Low-Grade Lymphoma: Results and and Long-Term Follow-Up—A Report From the Eastern Cooperative Oncology Group

2000 ◽  
Vol 18 (5) ◽  
pp. 987-987 ◽  
Author(s):  
Howard S. Hochster ◽  
Martin M. Oken ◽  
Jane N. Winter ◽  
Leo I. Gordon ◽  
Bruce G. Raphael ◽  
...  
Keyword(s):  
Phase Ii ◽  
Bone Marrow Involvement ◽  
Survival Rates ◽  
Eastern Cooperative Oncology Group ◽  
Disease Free Survival ◽  
Low Grade ◽  
Survival Times ◽  
Free Survival ◽  
Disease Free

PURPOSE: To determine the toxicity and recommended phase II doses of the combination of fludarabine plus cyclophosphamide in chemotherapy-naive patients with low-grade lymphoma. PATIENTS AND METHODS: Previously untreated patients with low-grade lymphoma were entered onto dosing cohorts of four patients each. The cyclophosphamide dose, given on day 1, was increased from 600 to 1,000 mg/m2. Fludarabine 20 mg/m2 was administered on days 1 through 5. The first eight patients were treated every 21 days; later patients were treated every 28 days. Prophylactic antibiotics were required. RESULTS: Prolonged cytopenia and pulmonary toxicity each occurred in three of eight patients treated every 3 weeks. The 19 patients treated every 28 days, who were given granulocyte colony-stimulating factor as indicated, did not have undue nonhematologic toxicity. Dose-limiting toxicity was hematologic. At the recommended phase II/III dose (cyclophosphamide 1,000 mg/m2), grade 4 neutropenia was observed in 17% of all cycles and 31% of first cycles. Grade 3 or 4 thrombocytopenia was seen in only 1% of all cycles. The median number of cycles per patient was six (range, two to 11) for all patients enrolled. The response rate was 100% of 27 patients entered; 89% achieved a complete and 11% a partial response. Nineteen of 22 patients with bone marrow involvement had clearing of the marrow. Median duration of follow-up was more than 5 years; median overall and disease-free survival times have not been reached. Kaplan-Meier estimated 5-year overall survival and disease-free survival rates were 66% and 53%, respectively. CONCLUSION: The recommended dosing for this combination in patients with previously untreated low-grade lymphoma is cyclophosphamide 1,000 mg/m2 day 1 and fludarabine 20 mg/m2 days 1 through 5. The regimen has a high level of activity, with prolonged complete remissions providing 5-year overall and disease-free survival rates as high as those reported for other therapeutic approaches in untreated patients.

Pituitary surgery as alternative to dopamine agonists treatment for microprolactinomas, a cohort study

2021 ◽  
Author(s):  
Bertrand Baussart ◽  
Chiara Villa ◽  
Anne Jouinot ◽  
Marie-Laure Raffin-Sanson ◽  
Luc Foubert ◽  
...  
Keyword(s):  
Dopamine Agonists ◽  
Cox Regression ◽  
Disease Free Survival ◽  
Pituitary Surgery ◽  
Cerebrospinal Fluid Leakage ◽  
Neurosurgical Department ◽  
Free Survival ◽  
Kaplan Meier ◽  
Disease Free

Objective: Microprolactinomas are currently treated with dopamine agonists. Outcome information on microprolactinoma patients treated by surgery is limited. This study reports the first large series of consecutive non-invasive microprolactinoma patients treated by pituitary surgery and evaluates the efficiency and safety of this treatment. Design: Follow-up of a cohort of consecutive patients treated by surgery. Methods: Between January 2008 and October 2020, 114 adult patients with pure microprolactinomas were operated on in a single tertiary expert neurosurgical department, using an endoscopic endonasal transsphenoidal approach. Eligible patients were presenting a microprolactinoma with no obvious cavernous invasion on MRI. Prolactin was assayed before and after surgery. Disease-free survival was modeled using Kaplan-Meier representation. A cox regression model was used to predict remission. Results: Median follow-up was 18.2 months (range: 2.8 to 155). In this cohort, 14/114 (12%) patients were not cured by surgery, including 10 early surgical failures, and 4 late relapses occurring 37.4 months (33 to 41.8) after surgery. From Kaplan Meier estimates, 1-year and 5-year disease free survival were 90.9% (95% CI, 85.6%-96.4%) and 81% (95% CI,71.2%-92.1%) respectively. The preoperative prolactinemia was the only significant preoperative predictive factor for remission (P<0.05). No severe complication was reported, with no anterior pituitary deficiency after surgery, one diabetes insipidus, and one postoperative cerebrospinal fluid leakage properly treated by muscle plasty. Conclusions: In well selected microprolactinoma patients, pituitary surgery performed by an expert neurosurgical team is a valid first-line alternative treatment to dopamine agonists.

Radiofrequency Ablation of Hepatic Metastases from Colorectal Cancer: Are Newer Generation Probes Better?

2006 ◽  
Vol 72 (10) ◽  
pp. 875-879 ◽  
Author(s):  
Aziz Ahmad ◽  
Steven L. Chen ◽  
Maihgan A. Kavanagh ◽  
David P. Allegra ◽  
Anton J. Bilchik
Keyword(s):  
Colorectal Cancer ◽  
Radiofrequency Ablation ◽  
First Generation ◽  
Hepatic Metastases ◽  
Disease Free Survival ◽  
Cancer Center ◽  
Free Survival ◽  
Alive With Disease ◽  
Disease Free

Second-generation radiofrequency ablation (RFA) probes and their successors have more power, shorter ablation times, and an increased area of ablation compared with the first-generation probes used before 2000. We examined whether the use of the newer probes has improved the clinical outcome of RFA for hepatic metastases of colorectal cancer at our tertiary cancer center. Of 160 patients who underwent RFA between 1997 and 2003, 52 had metastases confined to the liver: 21 patients underwent 46 ablations with the first-generation probes and 31 patients underwent 58 ablations with the newer probes. The two groups had similar demographic characteristics. At a median follow-up of 26.2 months, patients treated with the newer probes had a longer median disease-free survival (16 months vs 8 months, P < 0.01) and a lower rate of margin recurrence (5.2% vs 17.4%); eight patients had no evidence of disease and one patient was alive with disease. By contrast, of the 46 patients treated with the first-generation probes, 2 patients had no evidence of disease and 1 patient was alive with disease. Newer-generation probes are associated with lower rates of margin recurrence and higher rates of disease-free survival after RFA of hepatic metastases from colorectal cancer.

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