Absence of extramural venous invasion is an excellent predictor of metastasis-free survival in colorectal carcinoma stage II—a study using tangential tissue sectioning

2012 ◽  
Vol 65 (7) ◽  
pp. 619-623 ◽  
Author(s):  
Klaus Dirschmid ◽  
William Sterlacci ◽  
Frank Oellig ◽  
Michael Edlinger ◽  
Zerina Jasarevic ◽  
...  

AimsExtramural venous invasion (EVI) is an important predictor of haematogenous metastasis in colorectal cancer (CRC). However, remarkable discrepancies in incidence rates indicate major problems regarding EVI assessment. The present prospective study applies tangential vessel preparation to CRC resection specimens and correlates results of EVI with metachronous haematogenous metastatic (MHM) spread.MethodsStage II CRC diagnosed at the Institute of Pathology, University Teaching Hospital Feldkirch, Austria over a period of 30 months were analysed and tangential sectioning of the pericolonic tissue was performed. Confirmation, or exclusion of MHM, as assessed by computerised tomography, sonography or biopsy, was recorded.ResultsIn 50/79 (63%) cases EVI was detected. In 13/50 (26%), MHM developed. Of the 29/79 (37%) patients without EVI, only one (3.5%) developed MHM. Statistically, the rate of MHM for patients with EVI was independent of adjuvant chemotherapy.ConclusionsTangential sectioning of the tumour periphery in CRC stage II yields a high rate of histologically evaluable extramural veins and permits proper assessment of EVI. Absence of EVI is significantly associated with metastasis-free survival, a finding of potential therapeutic value. On the other hand, one-third of the patients with EVI and circumferential tumour growth develop MHM, a setting in which the option for adjuvant chemotherapy should be considered. This study emphasises the importance of tangential sectioning of the invasive tumour front in CRC compared with the recommended perpendicular technique. The sensitivity and specificity of this method regarding MHM are characterised.

2015 ◽  
Vol 32 (5) ◽  
pp. 338-343 ◽  
Author(s):  
Chiyo Maeda ◽  
Eiji Hidaka ◽  
Yuichi Mori ◽  
Shumpei Mukai ◽  
Hideyuki Miyachi ◽  
...  

Background/Aims: Adjuvant chemotherapy for stage II colorectal cancer (CRC) can generally be administered to high-risk subgroups. To better identify these patients, we aimed at assessing factors that affect recurrence. Methods: In our hospital, 432 colon and 96 rectal stage II cancer patients who underwent surgical resection between 2001 and 2011 were divided into recurrence and non-recurrence groups. Age, sex, lymphatic vessel invasion, venous invasion, tumor diameter, tumor depth, histological type, preoperative carcinoembryonic antigen level, number of sampled nodes, adjuvant chemotherapy, morphology, surgical approach, anastomotic leakage, preoperative bowel obstruction, and preoperative perforation were retrospectively compared between the groups. Results: For colon cancer, multivariate analysis revealed a significant association between tumor diameter ≥40 mm and recurrence (p = 0.039). For rectal cancer, multivariate analysis revealed that tumor diameter ≥50 mm (p = 0.001) and ≤12 sampled nodes (p = 0.021) were associated with recurrence. Tumor diameter in rectal cancer was associated with worse disease-free survival (p = 0.026). Conclusion: Tumor diameter is a significant predictor of recurrence in stage II CRC. This is an important finding because tumor diameter is easy to evaluate clinically and might help to identify candidates for adjuvant chemotherapy.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3548-3548
Author(s):  
Brandon Matthew Meyers ◽  
Humaid Obaid Al-Shamsi ◽  
Alvaro Tell Figueredo

3548 Background: Colon cancer is potentially curable by surgery in the early stages of the disease. Adjuvant chemotherapy improves disease-free and overall survival in patients with stage III disease, but the magnitude of benefit in stage II colon cancer is less clear. A previous Cochrane systematic review and meta-analysis (SR/MA) found improved disease-free, but not overall survival (Figueredo et al., 2008). An updated SR/MA was performed to determine the effects of adjuvant chemotherapy on disease-free and overall survival in patients with stage II colon cancer. Methods: Relevant databases (MEDLINE, EMBASE, and Cochrane) were independently searched by all authors, using the same search strategy employed in the original study (1/1988 to 9/2012). Randomized trials containing data on stage II colon cancer patients undergoing adjuvant 5-fluorouracil (5FU) chemotherapy versus observation were included. Pooled results were expressed as hazard ratios (HR) whenever possible, or risk ratios (RR), with 95% confidence intervals (95%CI) using a random effects model. Results: Seven studies were identified, and included in the final SR/MA. Six of the 7 studies were included in the disease-free survival analysis (n=4587). Adjuvant 5FU was associated with better disease-free survival (RR 0.84 (95%CI 0.75-0.94)). All 7 studies (n=5353) were included in the overall survival analysis showing an improvement with adjuvant 5FU (HR 0.87 (95%CI 0.78-0.97)). There was no evidence of heterogeneity across the studies (I2 = 0% for all analyses). Conclusions: In stage II colon cancer, adjuvant 5FU chemotherapy statistically improves both disease-free and overall survival. Our SR/MA demonstrates, for the first time, an overall survival advantage with adjuvant chemotherapy in stage II colon cancer.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15765-e15765
Author(s):  
Tao Ma ◽  
Xueli Bai ◽  
Qichun Wei ◽  
Shunliang Gao ◽  
Bingfeng Huang ◽  
...  

e15765 Background: Although adjuvant chemotherapy with gemcitabine has for years been the standard of care for resected pancreatic cancer, the role of adjuvant radiation is still debatable. We aimed to investigate the efficacy of gemcitabine combined with stereotactic body radiation therapy (SBRT) as adjuvant therapy for resected stage II pancreatic cancer. Methods: This single center randomized controlled trial was designed to enroll 512 patients with stage II pancreatic cancer that underwent curative-intended radical resection from a large-volume tertiary pancreatic center in China. Patients were randomly assigned to gemcitabine-alone adjuvant chemotherapy or adjuvant SBRT (25 Gray in 5 fractions) followed by gemcitabine chemotherapy. The primary endpoint was recurrence-free survival (RFS). Secondary endpoints included locoregional recurrence-free survival (LRFS), overall survival (OS), and incidence of adverse events. Interim analysis was planned at the time of 2.5-years’ enrollment. Results: 40 patients were randomly assigned to treatment between Sep 1, 2015, and Mar 31, 2018 (21 to the gemcitabine group and 19 to the gemcitabine plus SBRT group). Of these, one was excluded because of ineligibility and one did not receive any treatment. The median RFS was 12.4 (9.3-15.6) months in the gemcitabine group and 14.7 (9.2-20.1) months in the gemcitabine plus SBRT group ( P= 0.753), with median LRFS of 18.2 (14.6-21.7) months in the gemcitabine group and 13.1 (9.1-16.8) months in the gemcitabine plus SBRT group ( P= 0.333). The median OS was 21.7 (19.5-24.0) months in the gemcitabine group and 16.9 (12.8-20.9) in the gemcitabine plus SBRT group ( P= 0.066). Grade 3 or 4 neutropenia, thrombocytopenia, nausea or vomiting, and liver dysfunction were all comparable between the two groups. Evaluation of data from the first 40 enrolled patients indicated that the addition of adjuvant SBRT was not associated with either better local disease control or recurrence free survival. And because of failure to achieve the accrual target, the trial was terminated prematurely. Conclusions: Adjuvant SBRT neither provided a survival benefit nor improved local disease control in resected stage II pancreatic cancer. Clinical trial information: NCT02461836.


2015 ◽  
Vol 2015 ◽  
pp. 1-10
Author(s):  
Shahab Hajibandeh ◽  
Shahin Hajibandeh

Background. Recent meta-analysis of 21 randomised controlled trials (RCTs) supports the use of adjuvant chemotherapy for nonmetastatic rectal carcinoma. In order to define a subgroup of patients who can potentially benefit from postoperative adjuvant chemotherapy, this study aims to review trials investigating adjuvant chemotherapy with respect to stage of disease in patients with locally advanced rectal cancer who had undergone surgery for cure (stage II and stage III). Methods. We searched electronic information sources to identify randomised trials evaluating adjuvant chemotherapy in patients with stages II and III rectal cancer with overall survival or disease-free survival as outcomes. Scottish Intercollegiate Guidelines Network notes on methodology were used to assess the methodological quality of the selected studies. Random-effects models were applied to calculate pooled outcome data. Results. Eight studies reporting total of 5527 patients were selected for analysis. Adjuvant chemotherapy was associated with statistically significant improvement in disease-free survival and overall survival compared to surgery alone in both stage II and stage III cancer. Conclusions. This study indicates that both stage II and stage III rectal cancer patients may benefit from postoperative adjuvant chemotherapy. However, the benefits of adjuvant chemotherapy for patients who already had neoadjuvant chemoradiation still remain unknown.


2011 ◽  
Vol 29 (33) ◽  
pp. 4387-4393 ◽  
Author(s):  
Mitsuru Sasako ◽  
Shinichi Sakuramoto ◽  
Hitoshi Katai ◽  
Taira Kinoshita ◽  
Hiroshi Furukawa ◽  
...  

Purpose The first planned interim analysis (median follow-up, 3 years) of the Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer confirmed that the oral fluoropyrimidine derivative S-1 significantly improved overall survival, the primary end point. The results were therefore opened at the recommendation of an independent data and safety monitoring committee. We report 5-year follow-up data on patients enrolled onto the ACTS-GC study. Patients and Methods Patients with histologically confirmed stage II or III gastric cancer who underwent gastrectomy with D2 lymphadenectomy were randomly assigned to receive S-1 after surgery or surgery only. S-1 (80 to 120 mg per day) was given for 4 weeks, followed by 2 weeks of rest. This 6-week cycle was repeated for 1 year. The primary end point was overall survival, and the secondary end points were relapse-free survival and safety. Results The overall survival rate at 5 years was 71.7% in the S-1 group and 61.1% in the surgery-only group (hazard ratio [HR], 0.669; 95% CI, 0.540 to 0.828). The relapse-free survival rate at 5 years was 65.4% in the S-1 group and 53.1% in the surgery-only group (HR, 0.653; 95% CI, 0.537 to 0.793). Subgroup analyses according to principal demographic factors such as sex, age, disease stage, and histologic type showed no interaction between treatment and any characteristic. Conclusion On the basis of 5-year follow-up data, postoperative adjuvant therapy with S-1 was confirmed to improve overall survival and relapse-free survival in patients with stage II or III gastric cancer who had undergone D2 gastrectomy.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 6046-6046
Author(s):  
Marc Oliva Bernal ◽  
Shao Hui Huang ◽  
Rachel Taylor ◽  
Jie Su ◽  
Wei Xu ◽  
...  

6046 Background: Total cumulative cisplatin dose (CDDP-D) (concurrent/induction/adjuvant) in multimodality therapy for LA-NPC has been associated with survival at centers in Asia. We evaluated the survival impact of adjuvant chemotherapy (adj chemo) and total CDDP-D in a large, single institution Canadian cohort of LA-NPC. Methods: Patients (Pts) withWHO type II and III LA-NPC treated with concurrent IMRT with high-dose CDDP and adj chemo with CDDP/Carboplatin and 5-FU (maximum total/adjuvant CDDP-D= 540/240 mg/m2) between 2003-2016 were analyzed. EBER status was tested by ISH. Staging was classified by UICC/AJCC7thedition TNM. Kaplan-Meier 5-year (5y) for overall survival (OS) and recurrence-free survival (RFS) were calculated and compared by log-rank test betweenstage, adj chemo (yes vs no) and total CDDP-D (>300 vs ≤300mg/m2). Multivariable analysis (MVA) identified survival predictors. Results: A total of 312 pts were evaluated: median age = 49.8 (range 17.4-75.9); EBER+/-/unknown=67%/1%/32%; stage II/III/IV=2%/51%/47%; T4=36%; N3=17%; adj chemo=83% (21% switched to carboplatin); median total/adjuvant CDDP-D=380/160 mg/m2; median follow-up 7.6 years (range 0.6-14.9). 5y OS differed by stage II-III vs IV (95% vs 80%, p<0.001) and total CDDP-D >300 vs ≤300mg/m2 (89% vs 83%, p=0.02). Adj chemo and total CDDP-D impacted 5y OS in stage IV (table). 5y RFS was higher in stage IV with total CDDP-D >300 vs ≤300mg/m2 (74% vs 59%, p=0.03), with a trend in locoregional control (LRC) (91% vs 80%, p=0.05) but not significant on distant control (DC) (78% vs 72%, p=0.36). Conclusions: Total CDDP-D >300 mg/m2 impacts OS in the overall cohort. The benefit of adj chemo and total CDDP-D on OS and RFS is significant in stage IV but not stage II-III LA-NPC, mainly due to higher LRC rather than DC. [Table: see text]


Genes ◽  
2018 ◽  
Vol 9 (7) ◽  
pp. 361 ◽  
Author(s):  
Zhixun Zhao ◽  
Yibo Gao ◽  
Xu Guan ◽  
Zheng Liu ◽  
Zheng Jiang ◽  
...  

GADD45B acts as a member of the growth arrest DNA damage-inducible gene family, which has demonstrated to play critical roles in DNA damage repair, cell growth, and apoptosis. This study aimed to explore the potential relationship between GADD45B expression and tumor progression and evaluate the clinical value of GADD45B in stage II colorectal cancer (CRC). The expression patterns and prognostic value of GADD45B in CRC were analyzed based on The Cancer Genomic Atlas (TCGA). GADD45B expression features of 306 patients with stage II CRC and 201 patients with liver metastasis of CRC were investigated using immunochemical staining on tissue microarrays. Afterward, survival analysis and stratification analysis were performed in stage II to explore the prognostic and predictive significance of GADD45B. Overexpressed GADD45B is associated with poorer prognosis for CRC patients both in overall survival (OS) (p < 0.001) and disease-free survival (DFS) (p = 0.001) based on the TCGA database. Analysis results according to the stage II CRC cohort and the liver metastatic CRC cohort revealed that GADD45B was gradually upregulated in normal mucosa including primary colorectal cancer (PCC). Colorectal liver metastases (CLM) tissues were arranged in order (normal tissue vs. PCC p = 0.005 and PCC vs. CLM p = 0.001). The low GADD45B group had a significantly longer five-year OS (p = 0.001) and progression-free survival (PFS) (p < 0.001) than the high GADD45B group for the stage II patients. The multivariate Cox regression analysis results proved that the expression level of GADD45B was an independent prognostic factor for stage II after radical surgery (OS: Hazard Ratio (HR) 0.479, [95% confidence interval (CI) 0.305–0.753] and PFS:HR 0.490, [95% CI 0.336–0.714]). In high GADD45B expression subgroup of stage II cohort, the patients who underwent adjuvant chemotherapy had longer PFS than those who did not (p = 0.008). High expression levels of GADD45B is an independent prognostic factor of decreased OS and PFS in stage II CRC patients. The stage II CRC patients with high GADD45B expression might benefit from adjuvant chemotherapy.


1986 ◽  
Vol 4 (8) ◽  
pp. 1162-1170 ◽  
Author(s):  
W Hryniuk ◽  
M N Levine

We have analyzed the relationship between dose intensity of cyclophosphamide, methotrexate, and fluorouracil (CMF)-containing adjuvant chemotherapy of stage II breast cancer and 3-year relapse-free survival. Studies using only one or two drugs of CMF or melphalan instead of cyclophosphamide were included in the analysis by using simple techniques developed for this purpose. There was a clear-cut relationship between relapse-free survival and dose intensity in trials containing all four prognostic groups: less than 50 years, one to three and more than three positive nodes; and greater than or equal to 50 years, one to three and more than three positive nodes (P less than 10(-5)). Relapse-free survival also correlated with dose intensity for each of the four prognostic groups analyzed separately (P less than .005). Dose intensity was an independently significant correlate of relapse-free survival in multivariate analysis (P less than 10(-5)). This is a retrospective study, and the hypothesis that dose intensity contributes to outcome independently of other variables should be tested prospectively. Methods of increasing dose intensity also require testing in randomized trials before they can be applied to routine clinical practice.


2021 ◽  
Vol 94 (1120) ◽  
pp. 20201221
Author(s):  
Xiaoxuan Jia ◽  
Peiyi Xie ◽  
Liang Bi ◽  
Xiaochun Meng ◽  
Ziqiang Wang ◽  
...  

Objective: The goal of this study was to investigate whether neoadjuvant chemoradiotherapy (NCRT) plus total mesorectal excision (TME) would improve the outcome of patients with MRI-defined high-risk rectal cancer compared with TME plus adjuvant chemotherapy (ACT) or TME alone. Methods: We retrospectively enrolled 362 patients with MRI-defined high-risk rectal cancer who were treated with NCRT plus TME, TME plus ACT, or TME alone between January 2008 and August 2018. Cases with a high-risk tumor stage, positive extramural venous invasion, or mesorectal fascia involvement on baseline MRI were considered cases of high-risk rectal cancer. We matched patients treated with NCRT plus TME to patients treated with TME plus ACT and to those treated with TME alone. Kaplan–Meier curves were used to compare local recurrence (LR), disease-free survival (DFS), and overall survival (OS) rates. Results: The cumulative 3 year LR rate in the matched NCRT plus TME group was more favorable than in the TME plus ACT group (0% vs 5.1%; p = 0.037; n = 98) and in the TME alone group (0% vs 11.5%; p = 0.016; n = 61). Patients who received NCRT plus TME demonstrated better cumulative 3 year DFS rates than patients treated with TME plus ACT (85.7% vs 65.3%; p = 0.009) or with TME alone (86.9% vs 68.9%; p = 0.046). No difference in OS was observed among the groups. Conclusion: NCRT may improve DFS and LR rates in patients with MRI-defined high-risk rectal cancer when compared with TME plus ACT or TME alone. Advances in knowledge: This study illustrated the specific benefit of NCRT on the outcome measures of MRI-defined high-risk rectal cancer compared with TME plus ACT or TME alone, which was not clearly clarified in previous studies enrolling all patients with Stage II/III rectal cancer.


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