Conditional survival for patients with colon cancer: An analysis of National Surgical Adjuvant Breast and Bowel Project (NSABP) trials C-03 through C-06

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 6005-6005 ◽  
Author(s):  
S. J. Wang ◽  
B. A. Zamboni ◽  
H. S. Wieand ◽  
G. Yothers ◽  
J. J. Dignam ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Survival Data ◽  
Survival Probability ◽  
Performance Status ◽  
Disease Free Survival ◽  
Time Interval ◽  
Conditional Survival ◽  
Survival Times ◽  
Prognostic Information ◽  
Disease Free

6005 Background: Survival for cancer patients is usually only reported as survival from time of diagnosis to some time landmark (e.g., 5 yrs). For pts surviving one or more years after diagnosis, however, their survival probability changes, and is more accurately depicted by conditional survival (CS), defined as the probability of surviving for an additional fixed time interval given that the pt has already survived a period of time. The purpose of this study was to determine the 5-yr CS of colon cancer pts in 4 NSABP trials. Methods: We analyzed long-term overall survival data from the 5587 colon cancer pts who were enrolled in fluorouracil (or equivalent) arms of NSABP trials C-03 through C-06. We computed observed 5-yr overall CS for pts who had already survived without disease from 0 to 5 yrs after diagnosis, and stratified the results by age, sex, race, stage, number of positive nodes, number of nodes resected, tumor location, and performance status. Results: The Table below shows the 5-yr overall CS for all pts and for selected subgroups for different survival times since diagnosis. As disease-free survival time since diagnosis increased, 5-yr observed overall CS increased from 76% to 90% at 5 yrs. For pts under age 50, CS increased from 78% to 95% at 5 yrs, but for pts > 70 yrs, CS remained fairly constant (71–82%). For pts with > 10 positive nodes, CS increased from 37% to 81% at 5 yrs, but did not change appreciably for node-negative pts (87–92%). Dukes’ C pts saw an increase in CS from 68% to 88% at 5 yrs, while CS for Dukes’ B pts did not change appreciably. Conclusion: Projected survival probability generally increases with time for colon cancer pts who remain disease-free for a period of time after diagnosis, and conditional survival can provide more informative prognostic information for these pts. An additional effect is that prognostic factors that are important at baseline become less important for conditional survival as the disease-free period increases. [Table: see text] No significant financial relationships to disclose.

scholarly journals Conditional Survival and the Choice of Conditioning Set for Patients With Colon Cancer: An Analysis of NSABP Trials C-03 Through C-07

2010 ◽  
Vol 28 (15) ◽  
pp. 2544-2548 ◽  
Author(s):  
Beth A. Zamboni ◽  
Greg Yothers ◽  
Mehee Choi ◽  
Clifton D. Fuller ◽  
James J. Dignam ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Performance Status ◽  
Disease Free Survival ◽  
Second Primary ◽  
Alternative Measure ◽  
Conditional Survival ◽  
Prognostic Information ◽  
And Performance ◽  
Disease Free ◽  
Over Time

PurposeColon cancer overall survival (OS) is usually computed from the time of diagnosis. Survival gives the initial prognosis but does not reflect how prognosis changes with changing hazard rates over time. Conditional survival (probability of surviving y additional years given they have survived x years [CS or OS|OS]) is an alternative measure that accounts for elapsed time since diagnosis, providing more relevant prognostic information. We extend the concept of CS to condition on the set of patients alive, recurrence-free, and second primary cancer-free (disease-free survival [OS|DFS]).Patients and MethodsUsing data from National Surgical Adjuvant Breast and Bowel Project trials C-03 through C-07, 5-year OS|DFS was calculated on patients who were disease free up to 5 years after diagnosis, stratified by age, stage, nodal status, and performance status (PS).ResultsFor stage II, OS|DFS improved from 87% to 92% at 5 years. For stage III, OS|DFS improved from 69% to 88%. Patients younger than 50 years showed OS|DFS improvement from 79% to 95%; those older than 70 years showed no sustained increase in OS|DFS. Node-negative patients with ≥ 12 nodes resected showed little change (89% to 94%); those with more than four positive nodes showed an improvement (57% to 86%). Patients with a PS of 0 or 1 demonstrated a small improvement; those with a PS of 2 did not (64% to 58%).ConclusionPrognosis improves over time for almost all groups of patients with colon cancer, especially those with positive nodes. OS|DFS is a more relevant measure of prognosis for those who have already survived disease free a period of time after diagnosis.

Presence of 18q loss of heterozygosity (LOH) and disease-free and overall survival in stage II colon cancer: CALGB Protocol 9581

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4012-4012 ◽  
Author(s):  
M. M. Bertagnolli ◽  
D. Niedzwiecki ◽  
M. Hall ◽  
S. D. Jewell ◽  
R. J. Mayer ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Overall Survival ◽  
Performance Status ◽  
Disease Free Survival ◽  
Patient Characteristics ◽  
Low Risk ◽  
Stage Ii ◽  
Assay Method ◽  
Stage Ii Colon Cancer ◽  
Disease Free

4012 Background: LOH at 18q is associated with poorer overall survival in patients with colon cancer; however available studies are retrospective and vary in analysis methods. We recently completed an 18qLOH assay method validation study, and after standardizing technique, this prospective study investigated the role of 18qLOH among patients with low-risk stage II colon cancer. Methods: In Cancer and Leukemia Group B (CALGB) protocol 9581, we randomized 1738 stage II patients to post-operative treatment with a 500 mg loading dose of monoclonal antibody 17–1A followed by four infusions of 100 mg every 28 days or observation. The primary endpoint was overall survival (OS); disease free survival (DFS) was a secondary endpoint. Status of 18qLOH was assessed in patients with available tissue and interpretable PCR results. Patients were excluded if their tumors were uninformative for 18qLOH or if their tumors displayed microsatellite instability. Results: We report 18qLOH data on 156 patients. Patient characteristics including treatment, age, gender, performance status, site and grade of tumor, were similar between all patients enrolled and the subset of patients with tumor samples analyzed. The DFS and OS for treated and observed patients were no different (5-yr DFS: 0.81 and 0.80, p= 0.96; 5-yr OS: 0.88 and 0.86, p=0.44 at a median of 6.8 yrs of follow-up) and the data were pooled across the study's arms. Of the tumors examined, 101 (65%) were positive for 18qLOH. A significantly lower proportion of patients with 18qLOH-positive tumors had proximal tumors (46.5% vs 65.5%; p=0.02). Significantly decreased DFS and OS were observed in patients with 18qLOH-positive tumors. Five-year DFS among patients with 18qLOH-positive tumors was 0.78 vs 0.93 among patients with 18qLOH-negative tumors [HR 0.39; 95% CI (0.16, 0.94); logrank p=0.03 based on 33 events]. Five-year OS among patients with 18qLOH-positive tumors was 0.85 vs 0.98 among patients with 18qLOH-negative tumors [HR 0.25; 95% CI (0.07, 0.83); logrank p=0.01 based on 24 events]. Conclusions LOH at 18q was prognostic for DFS and OS among patients with available tissue for analysis after resection of low-risk stage II colon cancer who were not treated with chemotherapy in the adjuvant setting. [Table: see text]

scholarly journals Evaluation of Prognostic Factors for Survival in Transverse Colon Cancer

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2457
Author(s):  
Michela Roberto ◽  
Giulia Arrivi ◽  
Francesca Lo Bianco ◽  
Stefano Cascinu ◽  
Fabio Gelsomino ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Prognostic Factors ◽  
Survival Data ◽  
Transverse Colon ◽  
Performance Status ◽  
Disease Free Survival ◽  
Tumor Grade ◽  
Braf V600e ◽  
Significant Prognostic Factor ◽  
Transverse Colon Cancer

Background: Although most of the analyses included transverse colon cancers (TCC) among right colon cancer (RCC), it is not completely clear if they present total similarities with RCC or if they have their specific features. Therefore, we present an observational study to evaluate clinicopathological characteristics and survival data of patients with TCC. Methods: We retrospectively reviewed 450 RCC, of whom 97 stages I–IV TCC were included in this multicenter study; clinicopathological and molecular parameters were analyzed to identify prognostic factors for disease-free survival (DFS) and overall survival (OS). Results: Most of TCC cases were male (61%), with ≤70 years old (62%), and good performance status (ECOG PS 0, 68%). According to WHO classification, 41 (49%) and 40 (48%) tumors were classified as well to moderate and poorly/undifferentiated respectively, regardless of mucinous component (30%). About molecular data, 8 (26%), 45 (63%), and 14 (24%) were MSI-H, KRAS wild-type, and BRAF V600E mutant, respectively. With a median follow-up of 34 months, there were 29 and 50 disease recurrences and deaths respectively. Charlson comorbidity index ≥5 was a significant prognostic factor for DFS (HR = 7.67, 95% CI 2.27–25.92). Colon obstruction/perforation (HR = 2.65, 95% CI 1.01–7.01), and BRAF mutant (HR = 3.03, 95% CI 0.97–9.50) cases showed a worst, despite not statistically significant, DFS. Whereas for OS, at the multivariate model, only tumor grade differentiation (HR = 5.26, 95% CI 1.98–14.01) and BRAF mutation status (3.71, 95% CI 1.07–12.89) were independent prognostic factors. Conclusions: Poorly/undifferentiated tumor grade and BRAF V600E mutation are independent prognostic factors for OS in TCC. Further prospective clinical trials are needed to better define TCC treatment in order to improve patient outcome.

Radiomic Signature-Based Nomogram to Predict Disease-Free Survival in Stage II and III Colon Cancer

2019 ◽  
Author(s):  
Xun Yao ◽  
Caixia Sun ◽  
Fei Xiong ◽  
Xinyu Zhang ◽  
Chao Wang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Disease Free Survival ◽  
Stage Ii ◽  
Free Survival ◽  
Disease Free

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.

High Expression of H3K9me3 Is a Strong Predictor of Poor Survival in Patients With Salivary Adenoid Cystic Carcinoma

2013 ◽  
Vol 137 (12) ◽  
pp. 1761-1769 ◽  
Author(s):  
Ronghui Xia ◽  
Rongrui Zhou ◽  
Zhen Tian ◽  
Chunye Zhang ◽  
Lizhen Wang ◽  
...  
Keyword(s):  
Adenoid Cystic Carcinoma ◽  
Distant Metastasis ◽  
Survival Data ◽  
Histone H3 ◽  
Disease Free Survival ◽  
Rank Test ◽  
Free Survival ◽  
Salivary Adenoid Cystic Carcinoma ◽  
Adenoid Cystic ◽  
Disease Free

Context.—Histone methylation and acetylation play important roles in the carcinogenesis and progression of cancer. Objective.—To investigate whether histone modifications influence the prognosis of patients with salivary adenoid cystic carcinoma (ACC). Design.—The expression of histone H3 lysine 9 trimethylation (H3K9me3) and histone H3 lysine 9 acetylation (H3K9Ac) was assessed by immunohistochemistry in 66 specimens of primary ACC. Tests were used to determine the presence of any correlation between H3K9me3 and H3K9Ac levels and clinicopathologic parameters. Log-rank test and Cox proportional hazards regression models were used to analyze the survival data. Results.—H3K9me3 expression was positively correlated with solid pattern tumors (P = .002) and distant metastasis (P = .001). Solid pattern tumors had lower H3K9Ac expression levels than cribriform-tubular pattern tumors (P = .03). Patients whose tumors showed high H3K9me3 expression and a solid pattern had a significantly poorer overall survival (OS) (P < .001 and P < .001, respectively) and disease-free survival (P < .001 and P = .01, respectively). Low H3K9Ac expression was correlated with poor OS (P = .05). The multivariate analysis indicated that high levels of H3K9me3 expression and solid pattern tumors were independent prognostic factors that significantly influenced OS (P = .004 and P = .04, respectively). H3K9me3 expression was identified as the only independent predictor of disease-free survival (P = .006). Conclusions.—Our results suggest that high levels of H3K9me3 expression are predictive of rapid cell proliferation and distant metastasis in ACC. Compared with histologic patterns, H3K9me3 might be a better predictive biomarker for the prognosis of patients with salivary ACC.

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

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.

Disease-free and overall survival in nonmetastatic esophageal or gastroesophageal junctional cancer after treatment with curative intent: A nationwide population-based study.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 246-246
Author(s):  
Marieke Pape ◽  
Pauline A.J. Vissers ◽  
Laurens Beerepoot ◽  
Mark I. Van Berge Henegouwen ◽  
Sjoerd Lagarde ◽  
...  
Keyword(s):  
Overall Survival ◽  
Performance Status ◽  
Disease Free Survival ◽  
Disease Recurrence ◽  
Rank Test ◽  
R0 Resection ◽  
Real World Data ◽  
Curative Intent ◽  
Netherlands Cancer Registry ◽  
Disease Free

246 Background: Among patients with potentially curable esophageal cancer (EC) or gastroesophageal junctional cancer (GEJC) treated with curative intent, survival remains poor and around half of these patients have disease recurrence within a few years. This study addresses the need for real-world data on disease-free survival (DFS) and overall survival (OS) in patients with EC or GEJC who underwent potentially curative treatment. Methods: Patients selected from the nationwide Netherlands cancer registry (NCR) had received a primary diagnosis of non-metastatic EC or GEJC (excluding patients with T4b tumors) in 2015 or 2016 and received treatment with curative intent. Curative intent was defined as receiving resection (with or without [neo]adjuvant therapy) or definitive chemoradiotherapy (dCRT) without surgery. DFS and OS were analysed using Kaplan-Meier curves with Log-Rank test from resection date or end of dCRT. A sub-analysis was performed for NCR patients selected to align with the population of the CheckMate-577 phase 3 study of adjuvant nivolumab, i.e. patients with non-cervical stage II/III disease, R0 resection and residual pathological disease after neoadjuvant CRT (nCRT) and surgery. Results: We identified 1916 patients of median age of 67 years and predominantly male (76%). The majority (79%) received surgery and 21% of patients received dCRT. In resected patients, 83% received nCRT, 10% neoadjuvant chemotherapy (with or without adjuvant CRT) and 7% received no (neo)adjuvant treatment. Compared to the resected group, the population receiving dCRT had significantly fewer males (65% vs 78%), a higher median age (72 vs 65 years) and worse performance status. Patients receiving dCRT significantly shorter median DFS (14.2 months) and OS (20.9 months) compared to resected patients (DFS: 26.4 months, p < 0.001; OS: 40.5 months, p < 0.001). The 1- and 3-year DFS probabilities were 68% and 44%, respectively, in resected patients, and 56% and 24%, respectively, in patients receiving dCRT. In patients receiving nCRT followed by surgery, the median DFS and OS were 25.2 and 38.0 months, respectively, and 1- and 3-year DFS probabilities were 67% and 43%, respectively. In the sub-analysis (n = 725) the median DFS and OS were 19.2 and 29.4 months, respectively, and the 1- and 3-year DFS rates were 62% and 36%, respectively. Conclusions: Although patients are treated with curative intent, a considerable amount of patients with non-metastatic EC or GEJC experienced recurrence within two years. Resected patients had a higher DFS and OS compared to patients receiving dCRT.

Effective treatment of small-noncleaved-cell lymphoma with high-intensity, brief-duration chemotherapy.

1991 ◽  
Vol 9 (6) ◽  
pp. 941-946 ◽  
Author(s):  
M L McMaster ◽  
J P Greer ◽  
F A Greco ◽  
D H Johnson ◽  
S N Wolff ◽  
...  
Keyword(s):  
Poor Prognosis ◽  
Performance Status ◽  
Disease Free Survival ◽  
Poor Performance ◽  
Response To Therapy ◽  
Poor Performance Status ◽  
Inpatient Setting ◽  
Term Survival ◽  
Chemotherapeutic Regimen ◽  
Disease Free

Small-noncleaved-cell (SNC) lymphoma is a high-grade, biologically aggressive neoplasm notable for poor response to therapy, high relapse rate, and less than a 20% long-term survival. We treated 20 patients with SNC lymphoma with a novel chemotherapeutic regimen using intensive doses of chemotherapy at frequent intervals in the inpatient setting. All patients were previously untreated. Sixteen patients (80%) had stage IV disease. Most patients (95%) had at least one other characteristic associated with poor prognosis (bulky [greater than 10 cm] disease, multiple extranodal sites, poor performance status), and 85% had two or more characteristics associated with poor prognosis. Seventeen patients (85%) achieved a complete response (CR) to therapy, including all three patients with human immunodeficiency virus (HIV)-associated disease. There have been three relapses, all occurring less than 18 months after treatment, and two of three relapses occurred in patients who were unable to complete therapy. At a median follow-up of 29 months, 13 patients (65%) remain disease-free; the calculated 5-year actuarial disease-free survival is 60%. Toxicity, chiefly myelosuppression, was severe but manageable. There were two treatment-related deaths, both in elderly patients with poor performance status and advanced-stage disease. These data suggest that such a dose-intensive approach improves the response and survival of patients with SNC lymphoma.

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