Monoclonal antibody therapy for resected Dukes' C colorectal cancer: seven-year outcome of a multicenter randomized trial.

PURPOSE As previously shown, antibody treatment increased survival of patients with resected colorectal cancer of stage Dukes' C. Since the 5-year analysis was criticized because of the wide range (2.7 to 7.5 years) of follow-up time, we performed a 7-year analysis with only four of 189 patients monitored for less than 5 years. PATIENTS AND METHODS A total of 189 patients with resected Dukes' C colorectal cancer were randomly allocated to infusions of a total of 900 mg 17-1A antibody, 500 mg postoperatively followed by 4 monthly doses of 100 mg (n=99), or to observation only (n=90). Primary end points were overall survival and disease-free interval. Patients were stratified by a dynamic randomization according to center, sex, location of tumor, number of affected lymph nodes, and preoperative carcinoembryonic antigen concentration. RESULTS Randomization produced balanced distribution of risk factors. After 7 years of follow-up evaluation, treatment had reduced overall mortality by 32% (Cox's proportional hazard, P < .01; log-rank, P=.01) and decreased the recurrence rate by 23% (Cox's proportional hazard, P < .04; log-rank, P=.07). The intention-to-treat analysis gave a significant effect for overall survival (Cox's proportional hazard, P < .01; log-rank, P=.02) and disease-free survival (Cox's proportional hazard, P=.02; log-rank, P=.11 ). While distant metastases were significantly reduced (Cox's proportional hazard, P=.004; log-rank, P=.004), local relapses were not (Cox's proportional hazard, P=.65; log-rank, P=.52). This differential effect of 17-1A antibody on disseminated isolated tumor cells versus occult local satellites may explain the increased significance seen in the overall survival. CONCLUSION The now-matured study shows that 17-1A antibody administered after surgery prevents the development of distant metastasis in approximately one third of patients. The therapeutic effect is maintained after 7 years of follow-up evaluation.

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Combination of CDX2 expression and T stage improves prognostic prediction of colorectal cancer

Journal of International Medical Research ◽

10.1177/0300060518819620 ◽

2019 ◽

Vol 47 (5) ◽

pp. 1829-1842 ◽

Cited By ~ 2

Author(s):

Weimin Xu ◽

Yilian Zhu ◽

Wei Shen ◽

Wenjun Ding ◽

Tingyu Wu ◽

...

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Disease Free Survival ◽

Hazard Ratio ◽

Free Survival ◽

T Stage ◽

Cdx2 Expression ◽

Prognostic Prediction ◽

Disease Free

Objective Prognostic prediction of colorectal cancer (CRC) remains challenging because of its heterogeneity. Aberrant expression of caudal-type homeobox transcription factor 2 (CDX2) is strongly correlated with the prognosis of CRC. Methods Tissue samples of patients with CRC who underwent surgery in Xinhua Hospital (Shanghai, China) from January 2010 to January 2013 were collected. CDX2 expression was semiquantitatively evaluated via immunohistochemistry. Results In total, 138 patients were enrolled in this study from a prospectively maintained institutional cancer database. The median follow-up duration was 57.5 months (interquartile range, 17.0–71.0 months). In the Cox proportional hazards model, low CDX2 expression combined with stage T4 CRC was significantly the worst prognostic factor for disease-free survival (hazard ratio = 7.020, 95% confidence interval = 3.922–12.564) and overall survival (hazard ratio = 5.176, 95% CI = 3.237–10.091). In the Kaplan–Meier survival analysis, patients with low CDX2 expression and stage T4 CRC showed significantly worse disease-free survival and overall survival than those with low CDX2 expression alone. Conclusion CDX2 expression combined with the T stage was more accurate for predicting the prognosis of CRC. Determining the prognosis of CRC using more than one variable is valuable in developing appropriate treatment and follow-up strategies.

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What Factors Influence the Outcome of Surgically Treated Soft Tissue Sarcomas of the Hand and Wrist?

Hand ◽

10.1177/1558944716672197 ◽

2016 ◽

Vol 12 (5) ◽

pp. 493-500 ◽

Cited By ~ 4

Author(s):

Matthew T. Houdek ◽

Brian E. Walczak ◽

Benjamin K. Wilke ◽

Sanjeev Kakar ◽

Peter S. Rose ◽

...

Keyword(s):

Overall Survival ◽

Soft Tissue ◽

Local Recurrence ◽

Soft Tissue Sarcomas ◽

Disease Free Survival ◽

Disease Status ◽

Distant Metastases ◽

Factors Affecting ◽

Disease Free

Background: Soft tissue sarcomas (STS) of the hand are exceedingly rare. The aim of this study was to review our institution’s experience with STS of the hand to identify factors affecting outcomes and survivorship. Methods: We retrospectively reviewed the records of 46 hand STS treated with definitive surgery at our institution between 1992 and 2013. Pertinent demographics as well as information regarding the surgical procedure, and disease status at latest follow-up were reviewed. Mean age at diagnosis was 38 years with a mean follow-up of 5 years. Results: The most common tumor subtypes were epithelioid (n = 10) and synovial sarcoma (n = 8). Sixty-one percent were superficial in location. Thirty-three patients had had a nononcologic resection prior to definitive surgical treatment at our institution. Ultimately, negative margins were obtained in all cases. Local recurrence was observed in 5 patients and distant metastases in 14 patients. Tumor sizes ≥2 cm, American Joint Committee on Cancer (AJCC) grade, and depth of the tumor were found to adversely affect the outcome in terms of disease-free and overall survival. Reexcision of an inadvertently excised tumor at an outside institution did not adversely affect the outcome. The 10-year overall and disease-free survival was 72% and 63%. Conclusions: Local recurrence after a wide excision was observed infrequently; however, distant disease was relatively common. Tumors with a size ≥2 cm were associated with a worse disease-free and overall survival, highlighting the aggressive nature of these tumors.

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O20: PREOPERATIVE INTRAVENOUS IRON THERAPY AND SURVIVAL AFTER COLORECTAL CANCER SURGERY: LONG TERM RESULTS FROM THE INTRAVENOUS IRON IN COLORECTAL CANCER-ASSOCIATED ANAEMIA (IVICA) TRIAL

British Journal of Surgery ◽

10.1093/bjs/znab117.020 ◽

2021 ◽

Vol 108 (Supplement_1) ◽

Author(s):

EA Dickson ◽

BD Keeler ◽

O Ng ◽

A Kumar ◽

MJ Brookes ◽

...

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Disease Free Survival ◽

Intravenous Iron ◽

Cancer Surgery ◽

Colorectal Cancer Surgery ◽

Free Survival ◽

Disease Free

Abstract Background Intravenous iron is now the standard treatment to correct preoperative anaemia. However, iron may promote tumour growth and progression which could influence cancer recurrence and survival. We explore the long term postoperative outcomes of patients receiving oral (OI) or intravenous iron (IVI) as part of a randomised controlled trial. Method The multicentre IVICA trial randomised anaemic colorectal cancer patients in a 1:1 fashion to receive either OI or IVI prior to their elective operation. Follow up analysis of all patients was performed and Kaplan-Meier survival estimates and Cox proportional hazard models were used to compare groups. A pooled analysis comparing patients who did/did not achieve preoperative resolution of anaemia was also undertaken. Result, Data were available for 106 of the 116 IVICA patients (OI n=55, IVI n=51). Median follow up was 61 months (IQR 38-68, [range 1-80]). Overall survival estimates at 3 and 5 years were 82%(95% CI 76-90) and 72%(58-83) respectively for OI and 75%(61-86) and 59%(45-72) for IVI, P=0.106. No significant difference in 5-year overall survival (HR 1.73, 95% CI 0.90-3.34 P=0.102) or disease-free survival (HR 1.50, 95% CI 0.83-2.73 P=0.182) was observed between groups. Those non-anaemic at operation demonstrated improved 5 year overall survival (HR 3.26 [1.01-10.58], P=0.05). Non-significant trends in improved disease-free survival (HR 2.29 [0.91-5.81], p=0.08) were observed for the non-anaemic group Conclusion Preoperative correction of anaemia confers a postoperative survival advantage following elective colorectal cancer surgery. Due to its superior efficacy intravenous iron is recommended as the treatment of choice for this anaemia. Take-home message Preoperative correction of anaemia, achieved most effectively with intravenous iron, may offer improved long term postoperative survival after colorectal cancer surgery.

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TRIM25 regulates oxaliplatin resistance in colorectal cancer by promoting EZH2 stability

Cell Death and Disease ◽

10.1038/s41419-021-03734-4 ◽

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.

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Radical hysterectomy in early cervical cancer in Europe: characteristics, outcomes and evaluation of ESGO quality indicators

International Journal of Gynecological Cancer ◽

10.1136/ijgc-2021-002587 ◽

2021 ◽

pp. ijgc-2021-002587

Author(s):

Felix Boria ◽

Luis Chiva ◽

Vanna Zanagnolo ◽

Denis Querleu ◽

Nerea Martin-Calvo ◽

...

Keyword(s):

Cervical Cancer ◽

Overall Survival ◽

Quality Indicators ◽

Radical Hysterectomy ◽

Disease Free Survival ◽

Free Survival ◽

Operative Complications ◽

Early Cervical Cancer ◽

Disease Free

IntroductionComprehensive updated information on cervical cancer surgical treatment in Europe is scarce.ObjectiveTo evaluate baseline characteristics of women with early cervical cancer and to analyze the outcomes of the ESGO quality indicators after radical hysterectomy in the SUCCOR database.MethodsThe SUCCOR database consisted of 1272 patients who underwent radical hysterectomy for stage IB1 cervical cancer (FIGO 2009) between January 2013 and December 2014. After exclusion criteria, the final sample included 1156 patients. This study first described the clinical, surgical, pathological, and follow-up variables of this population and then analyzed the outcomes (disease-free survival and overall survival) after radical hysterectomy. Surgical-related ESGO quality indicators were assessed and the accomplishment of the stated recommendations was verified.ResultsThe mean age of the patients was 47.1 years (SD 10.8), with a mean body mass index of 25.4 kg/m2 (SD 4.9). A total of 423 (36.6%) patients had a previous cone biopsy. Tumor size (clinical examination) <2 cm was observed in 667 (57.7%) patients. The most frequent histology type was squamous carcinoma (794 (68.7%) patients), and positive lymph nodes were found in 143 (12.4%) patients. A total of 633 (54.8%) patients were operated by open abdominal surgery. Intra-operative complications occurred in 108 (9.3%) patients, and post-operative complications during the first month occurred in 249 (21.5%) patients, with bladder dysfunction as the most frequent event (119 (10.3%) patients). Clavien-Dindo grade III or higher complication occurred in 56 (4.8%) patients. A total of 510 (44.1%) patients received adjuvant therapy. After a median follow-up of 58 months (range 0–84), the 5-year disease-free survival was 88.3%, and the overall survival was 94.9%. In our population, 10 of the 11 surgical-related quality indicators currently recommended by ESGO were fully fulfilled 5 years before its implementation.ConclusionsIn this European cohort, the rate of adjuvant therapy after radical hysterectomy is higher than for most similar patients reported in the literature. The majority of centers were already following the European recommendations even 5 years prior to the ESGO quality indicator implementations.

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

The American Surgeon ◽

10.1177/000313480607201007 ◽

2006 ◽

Vol 72 (10) ◽

pp. 875-879 ◽

Cited By ~ 8

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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Ecoendoscopia en la estadificación del cáncer de esófago y de estómago

Revista Argentina de Cirugía ◽

10.25132/raac.v113.n1.1524.ei ◽

2021 ◽

Vol 113 (1) ◽

pp. 32-42

Author(s):

Martín Galvarini Recabarren ◽

◽

Francisco Schlottmann ◽

C. Agustín Angeramo ◽

Javier Kerman Cabo ◽

...

Keyword(s):

Overall Survival ◽

Neoadjuvant Therapy ◽

Preoperative Staging ◽

Disease Free Survival ◽

Perioperative Chemotherapy ◽

Free Survival ◽

Causes Of Mortality ◽

Node Metastases ◽

Disease Free

Background: Gastric adenocarcinoma (GAC) and esophageal adenocarcinoma (EAC) are one of the leading causes of mortality from gastrointestinal cancer worldwide. Endoscopic ultrasound (EUS) has proved to be a valuable tool for preoperative staging of GAC and EAC in selected cases. Objective: The aim of this study was to evaluate the usefulness of EUS for staging of EAC and GAC and selecting patients who are candidates for neoadjuvant therapy, as compared with the previous stage before the implementation of EUS, in a surgical center in Argentina. Material and methods: Consecutive patients with EAC and GAC between 2013-2019 were included. Patients with criteria of unresectable cancer or who underwent emergency surgery were excluded. The sample was divided into four groups G1 and G2 (EAC with and without EUS, respectively) and G3 and G4 (GAC with and without EUS, respectively). The clinical and anatomopathological variables and survival were evaluated in all the groups. Results: A total of 89 patients were included, 40 with EAC (30 in G1 and 10 in G2, and 49 with GAC, 20 in G3 and 29 in G4. Of the patients undergoing EUS staging in G1, 23 (75%) received neoadjuvant therapy vs. 2 patients in G2 (20%) (P ≤ 0.005). Eight patients (40%) in G3 and 2 (7%) in G4 received perioperative chemotherapy (P ≤ 0.005). Lymph node metastases were observed in 9 (30%) of surgical specimens of EAC in G1 and in 60% in G2 (P ≤ 0.005), and in 45% in G3 and G4. After a mean follow-up of 36 months (6-72), we observed a non-significant trend toward higher overall survival and disease-free survival in patients undergoing EUS staging. Conclusion: EUS for preoperative staging pf EAC and GAC is a useful tool. Although the use of EUS use may be a challenging task in many centers in Argentina, future efforts are needed to include this test in selected cases for staging patients with these types of cancers

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TP1.2.3Oncological Outcomes of Organ Preservation Strategies - Local Excision Procedures and ‘Watchful Waiting’ In Management of Low Rectal Cancers – A Systematic Review And Meta-Analysis

British Journal of Surgery ◽

10.1093/bjs/znab362.002 ◽

2021 ◽

Vol 108 (Supplement_7) ◽

Author(s):

A R Aspari ◽

V Ramesh ◽

G Kumar ◽

S N Narayanasamy ◽

A O Gumber ◽

...

Keyword(s):

Systematic Review ◽

Overall Survival ◽

Local Recurrence ◽

Organ Preservation ◽

Meta Analysis ◽

Disease Free Survival ◽

Distant Metastases ◽

Free Survival ◽

Rectal Cancers ◽

Disease Free

Abstract Objective To evaluate local recurrence, metastases, and survival outcomes of `wait and watch’ (WW) strategy and local excision (LE) of tumours, in comparison to the present standard practice of total mesorectal excision (TME) for locally advanced rectal cancers. Data Sources MEDLINE, EMBASE, PubMed databases, and sources of Grey literature. Study Selection Randomised and non-randomised prospective studies, retrospective studies with propensity-score-matched analyses. Data Extraction and Synthesis These were carried out independently by two reviewers. A random-effects methodology was used for meta-analyses. Data was presented keeping with the 27-item PRISMA checklist. Main Outcomes The primary outcomes of interest were local recurrence, distant metastases, disease-free-survival and overall-survival, which were assessed in comparison to those associated with radical surgeries (TME). Results 7 of the 16 studies in the systematic review were included for the quantitative synthesis and meta-analysis. Local recurrence rates were comparable amongst patients in WW group and LE group to those undergoing TME. [Risk ratio (RR) 3.07/1.41; 95% Confidence Interval (CI) 0.86-10.95/0.66-3.01; P = 0.08/P=0.89 respectively]. Rates of distant metastases in the WW group and LE group were comparable to those undergoing TME [RR = 0.71/0.94; 95% CI 0.22-2.30/0.55-1.61; P = 0.56/ P = 0.83 respectively]. The median 3-year disease-free survival among patients undergoing WW, LE procedure, and TME were 88%, 80%, and 78.2% respectively; and the median 3-year overall survival among the three groups were 96%, 93%, and 89.5% respectively. Conclusions and Relevance Organ-preservation strategies appear to be a viable treatment option in the management of rectal-cancers. Further research is warranted to provide stronger levels of evidence on organ-preservation strategies.

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Re-Evaluating Disease-Free Survival as an Endpoint vs Overall Survival in Stage III Adjuvant Colon Cancer Trials

JNCI Journal of the National Cancer Institute ◽

10.1093/jnci/djab187 ◽

2021 ◽

Author(s):

Jun Yin ◽

Mohamed E Salem ◽

Jesse G Dixon ◽

Zhaohui Jin ◽

Romain Cohen ◽

...

Keyword(s):

Colon Cancer ◽

Overall Survival ◽

Disease Free Survival ◽

Surrogate Endpoint ◽

Free Survival ◽

A Value ◽

Deficient Mismatch Repair ◽

Disease Free

Abstract Background Disease-free survival with a 3-year median follow-up (3-year DFS) was validated as a surrogate for overall survival with a 5-year median follow-up (5-year OS) in adjuvant chemotherapy colon cancer (CC) trials. Recent data show further improvements in OS and survival after recurrence, in patients who received adjuvant FOLFOX. Hence, re-evaluation of the association between DFS and OS and determination of the optimal follow-up duration of OS to aid its utility in future adjuvant trials are needed. Methods Individual patient data from nine randomized studies conducted between 1998 and 2009 were included; three trials tested biologics. Trial-level surrogacy examining the correlation of treatment effect estimates of 3-year DFS with 5 to 6.5-year OS was evaluated using both linear regression (R2WLS) and Copula bivariate (R2Copula) models and reported with 95% confidence intervals (CIs). For R2, a value closer to 1 indicates a stronger correlation. Results Data from a total of 18,396 patients were analyzed (median age = 59 years; 54.0% male), with 54.1% having low-risk tumors (pT1-3 & pN1), 31.6% KRAS mutated, 12.3% BRAF mutated, and 12.4% microsatellite instability high/deficient mismatch repair tumors. Trial level correlation between 3-year DFS and 5-year OS remained strong (R2 =0.82, 95% CI = 0.67 to 0.98; R2 =0.92, 95% CI = 0.83 to 1.00) and increased as the median follow-up of OS extended. Analyses limited to trials that tested biologics showed consistent results. Conclusion Three-year DFS remains a validated surrogate endpoint for 5-year OS in adjuvant CC trials. The correlation was likely strengthened with 6 years of follow-up for OS.

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