Prospective multicenter study of the impact of the 12-gene assay recurrence score on adjuvant chemotherapy treatment recommendations for stage II/III colon cancer in the post-IDEA era: SUNRISE-Decision Impact study.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. TPS868-TPS868
Author(s):  
Takeharu Yamanaka ◽  
Takeo Sato ◽  
Sayoko Nakashima ◽  
Takayuki Yoshino
Keyword(s):  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Recurrence Score ◽  
Recurrence Risk ◽  
Treatment Recommendations ◽  
Stage Ii ◽  
Stage Iii ◽  
Treatment Recommendation ◽  
Gene Assay ◽  
The Impact

TPS868 Background: The results of IDEA collaboration study in ASCO 2017 suggested that adjusting the duration of adjuvant chemotherapy (CTx) for stage III colon cancer may be possible according to patient’s risk (T and N factors) and treatment regimen (FOLFOX and CAPOX) in order to balance the benefit and neurotoxicity of oxaliplatin-based CTx. The 12-Gene Assay Recurrence Score (12-gene RS), known as Oncotype DX, has been validated to predict the recurrence risk of stage II/III colon cancer patients through several studies, including our SUNRISE study (J Clin Oncol, 2016), and thus to personalize adjuvant CTx taking account of individual recurrence risk. The objective of this SUNRISE-DI study is to determine the impact of the 12-gene RS on adjuvant CTx treatment recommendations, including the decision for the duration of oxaliplatin-based CTx in stage III patients as well as that for oxaliplatin-based CTx versus 5FU-based monotherapy in stage II/III patients. This study enables us to evaluate how physicians employ the IDEA collaboration results combined with the 12-gene RS to determine the regimen. Methods: Patients who have a curatively resected Stage II/IIIA/IIIB colon cancer, an age of more than 20, and an ECOG PS of 0-1 are eligible. Treating physicians will formulate a treatment recommendation and complete a pre-assay questionnaire, and the 12-gene assay will be performed. Following receipt of the RS result, the treatment recommendation will be revised and a post-assay questionnaire completed. The primary endpoint is the proportion of changes in treatment recommendations between pre- and post-assay across all patients. Secondary endpoints include the proportion of changes by stage; the proportion of changes in the duration of oxaliplatin-based CTx (3 months vs 6 months); the proportion switched to observation only, 5-FU mono, or 5-FU plus oxaliplatin; and changes in expressed physician confidence level. The enrollment target is 200 patients with stage IIIA/IIIB and 100 patients with stage II from 15 centers in Japan. Clinical trial registry number: UMIN000028784

Prospective evaluation of a 12-gene assay on treatment recommendations in patients with stage II colon cancer.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 453-453 ◽  
Author(s):  
Geetika Srivastava ◽  
Lindsay Anne Renfro ◽  
Robert J. Behrens ◽  
Margarita Lopatin ◽  
Calvin Chao ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Cancer Patients ◽  
Score Test ◽  
Recurrence Score ◽  
Recurrence Risk ◽  
Treatment Recommendation ◽  
Medical Oncologists ◽  
Gene Assay ◽  
Stage Ii Colon Cancer

453 Background: A 12-gene assay (Oncotype DX Colon Cancer) has been clinically validated as a predictor of recurrence risk in stage 2 colon cancer patients following surgery. We conducted the first prospective study to characterize the impact of Recurrence Score results on medical oncologists’ recommendations regarding adjuvant chemotherapy in T3, Mismatch Repair-proficient (MMR-P) stage 2 colon cancer patients. Methods: Consecutive patients with resected stage 2A colon cancer who were candidates for adjuvant chemotherapy were consented and enrolled by 105 medical oncologists from 17 sites in the Mayo Clinic Cancer Research Consortium. Each patient’s tumor specimen was assessed by the Recurrence Score test (quantitative RT-PCR) and MMR (IHC). Prior to and after receiving these results, physicians completed surveys indicating their planned treatments given hypothetical or known MMR results, recorded as Observation (Obs), 5FU-based chemotherapy (5FU), or 5FU + Oxaliplatin (Oxal). Change in treatment recommendation intensity from baseline to follow-up was defined as: increased if change from Obs to 5FU +/- Oxal or from 5FU to 5FU+Oxal, decreased if change from 5FU + Oxal to 5FU or Obs, or from 5FU to Obs, or no change. Results: 187 of 221 patients enrolled were evaluable including 141 who were MMR-P (avg age 63, 65% ECOG PS 0, med tumor size 5 cm, 11% high grade, 91% with 12+ nodes examined). In the primary analysis treatment recommendations changed for 63 (45%) of 141 MMR-P patients, with intensity decreasing for 47 (33%) and increasing for 16 (11%). Recommendations for chemotherapy (5-FU +/- Oxal) decreased from 73 (52%) patients pre-assay to 42 (30%) post-assay. Increased treatment intensity was more likely at higher Recurrence Score values and decreased intensity at lower Recurrence Score values (p=0.011), and any change was more likely when MMR status was unknown at baseline (p = 0.041). Conclusions: In this prospective study, quantitative recurrence risk information provided by the Recurrence Score test was associated with treatment recommendation changes for 45% of T3 MMR-P stage II colon cancer patients. Use of the 12-gene assay may lead to overall reductions in chemotherapy.

Impact of adjuvant chemotherapy on recurrence risk in stage II colon cancer.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 533-533
Author(s):  
Taiwo Adesoye ◽  
Chung-Yuan Hu ◽  
Amanda Cuddy ◽  
Amanda B. Francescatti ◽  
Jessica R. Schumacher ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Overall Survival ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Recurrence Rate ◽  
Recurrence Risk ◽  
Stage Ii ◽  
Stage Iii ◽  
Stage Ii Colon Cancer ◽  
The Impact

533 Background: Although clinical guidelines recommend consideration of adjuvant chemotherapy in high-risk stage II colon cancer, the impact on recurrence risk and cancer related survival is unclear. Furthermore, among Medicare patients, adjuvant chemotherapy was not associated with improved survival. We examine the effect of adjuvant chemotherapy on recurrence risk and overall survival in a diverse cohort. Methods: 6,095 patients who underwent surgery for stage II-III colon cancer (2006-2007) were randomly selected from facilities reporting to the National Cancer Data Base for additional abstraction of tumor information, 5 year recurrence and survival. Death or second cancer within 6 months were excluded. Patients were classified as high or low risk using standard pathologic factors. Multivariate Cox regression with propensity score weighting was performed to compare recurrence risk and overall survival. Results: Of 3,423 patients with stage II colon cancer, 26.9% (n = 883) received chemotherapy compared to 76.2% (n = 1,839) of stage III patients. Among stage II patients, 47.8% (n = 1,636) had at least one high risk feature and 30.8% (n = 481) of these received chemotherapy. Five year recurrence rate in stage II patients was 13% (n = 392), greater in high risk compared to non-high risk patients (13.3% vs 9.3% p < 0.0001) and 24.4% (n = 874) in stage III patients. Chemotherapy did not improve recurrence risk in stage II patients regardless of risk status (High risk: hazard ratio [HR] 1.37; 95% CI 0.96 - 1.97; Non-high risk: HR 1.39; 95% CI 0.91 - 2.11). Chemotherapy was associated with a significant improvement in recurrence risk in stage III patients (HR 0.79; 95% CI 0.63 - 0.96). However, chemotherapy was associated with improved overall survival in both high (HR 0.69; 95% CI 0.51 - 0.92) and non-high risk stage II patients (HR 0.76; 95% CI 0.55 - 1.04), and also in stage III patients (HR 0.47; 95% CI 0.41 - 0.54). Conclusions: Adjuvant chemotherapy was not associated with a lower recurrence rate among stage II colon cancer patients. The observed survival benefit associated with chemotherapy is likely attributable to non-oncologic factors such as patient selection. Decision-making regarding chemotherapy use in this cohort should be carefully approached.

Effect of Oncotype DX colon cancer test results on treatment recommendations in patients with stage II colon cancer: Preliminary results.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 398-398
Author(s):  
Thomas H. Cartwright ◽  
Calvin Chao ◽  
Margarita Lopatin ◽  
Tanya GK Bentley ◽  
Michael Samuel Broder ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Patients ◽  
Adjuvant Treatment ◽  
Recurrence Score ◽  
Treatment Recommendations ◽  
Oncotype Dx ◽  
Stage Ii ◽  
Medical Oncologists ◽  
Stage Ii Colon Cancer ◽  
The Impact

398 Background: The Oncotype DX Colon Cancer Recurrence Score (RS) has been clinically validated as an independent predictor of individual recurrence risk in stage II colon cancer patients following surgery. As a result, physicians have been ordering the Oncotype DX assay for stage II colon cancer patients since January 2010, yet no data exist on the assay’s impact on adjuvant treatment planning in practice. We performed a survey to characterize the impact of the assay on adjuvant treatment recommendations in stage II colon cancer. Methods: U.S. medical oncologists (N=277) who ordered Oncotype DX for ≥3 patients with stage II colon cancer were contacted and asked to complete a web-based survey regarding the single most recent stage II colon cancer patient for whom the assay was ordered. The survey was developed through cognitive interviews with four medical oncologists, and the protocol was institutional review board approved. Results: As a planned preliminary analysis, we analyzed surveys from 92 eligible physicians. Physicians were more often in community (85%) than academic or other practices, and had a median of 14.5 years (range, 2-40) of practice experience. The median patient age was 62 years (range, 34–81). 84% of patients had T3 disease. Patients had ≤8, 9-11 and ≥12 nodes examined 2%, 14% and 84% of the time and 36% had comorbidities. Of the 60 patients tested for MMR/MSI, 9 (15%) were MMR-D or MSI-high and 37 (62%) were MMR-P or MSI-low; 14 (23%) unknown. Median RS was 20 (range, 1-77). Before obtaining the RS, chemotherapy was planned in 38 (41%) patients, observation in 35 (38%), and there was no recommendation in 19 (21%). For the 73 patients with pre-assay recommendations, recommended treatment changed after obtaining the RS for 23 patients (32%), including changes from chemotherapy to observation and vice-versa. Conclusions: These preliminary findings indicate that for stage II colon cancer patients, treatment recommendations were changed by RS results approximately one-third of the time. Final results will be reported to include accrual through December 2011.

Uptake of adjuvant chemotherapy for colon cancer in older and younger patients in the Irish population.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 478-478
Author(s):  
Seamus Coyle ◽  
Zia Rehman ◽  
Chalen Lee ◽  
Sandra Deady ◽  
Harry Comber ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Clinical Practice ◽  
Adjuvant Chemotherapy ◽  
Adjuvant Therapy ◽  
Older Patients ◽  
The Elderly ◽  
Stage Ii ◽  
Stage Iii ◽  
Younger Patients ◽  
The Impact

478 Background: Colon cancer is predominantly a disease of the elderly, with recent evidence supporting the use of adjuvant chemotherapy in the older population. However, it remains unclear to what degree such patients are receiving adjuvant therapy in clinical practice. We examined uptake of adjuvantchemotherapy and it’s impact on survival in older patients with stage II and stage III colon cancer in a national cohort. Methods: Using the National cancer Registry of Ireland, we identified 3,486 patients with stage II and III colon cancer who were treated with curative resection from 2004-2009. Clinopathological features and chemotherapy use were compared between those ≥70 years and those < 70 years. Results: A total of 2,026 patients with stage II disease were identified, 56% male and 60% ≥ 70 years. T3 tumors accounted for 81%, T4 19% and 89% were grade 2/3. Adjuvant chemotherapy was utilized in 10% and 40% of ≥ 70 and <70 years, respectively (p<0.0001). A benefit for chemotherapy over observation alone was seen in both the older [HR 0.36; 95% CI 0.36 – 0.68; p <0.0001] and younger patient groups [HR 0.43; 95% CI 0.2701 - 0.6881; p<0.0004]. Of 1,460 patients with stage III disease, 51% were ≥ 70 years, 54% male. 34% of older and 83% of younger patients received adjuvant therapy (p<0.0001). A similar magnitude of benefit from chemotherapy compared to observation was seen in patients ≥ 70 years [HR 0.30; 95% CI 0.29 - 0.45 ; p <0.0001] and <70 years [HR 0.22 95%CI 0.1 – 0.2; p<0.0001] with stage III disease. Conclusions: Adoption of adjuvant chemotherapy appears to be associated with significant survival benefit in older patients (age ≥ 70 years), however, is still underutilized in clinical practice. The impact of sociodemographic and clinicopathological features as potential drivers of treatment decisions in a cohort of this population will be reported.

scholarly journals Validation of the 12-Gene Colon Cancer Recurrence Score in NSABP C-07 As a Predictor of Recurrence in Patients With Stage II and III Colon Cancer Treated With Fluorouracil and Leucovorin (FU/LV) and FU/LV Plus Oxaliplatin

2013 ◽  
Vol 31 (36) ◽  
pp. 4512-4519 ◽  
Author(s):  
Greg Yothers ◽  
Michael J. O'Connell ◽  
Mark Lee ◽  
Margarita Lopatin ◽  
Kim M. Clark-Langone ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Therapy ◽  
Cox Regression ◽  
Cancer Recurrence ◽  
Recurrence Score ◽  
Recurrence Risk ◽  
Stage Ii ◽  
Stage Iii ◽  
Treatment Benefit ◽  
Stage Ii Colon Cancer

Purpose Accurate assessments of recurrence risk and absolute treatment benefit are needed to inform colon cancer adjuvant therapy. The 12-gene Recurrence Score assay has been validated in patients with stage II colon cancer from the Cancer and Leukemia Group B 9581 and Quick and Simple and Reliable (QUASAR) trials. We conducted an independent, prospectively designed clinical validation study of Recurrence Score, with prespecified end points and analysis plan, in archival specimens from patients with stage II and III colon cancer randomly assigned to fluorouracil (FU) or FU plus oxaliplatin in National Surgical Adjuvant Breast and Bowel Project C-07. Methods Recurrence Score was assessed in 892 fixed, paraffin-embedded tumor specimens (randomly selected 50% of patients with tissue). Data were analyzed by Cox regression adjusting for stage and treatment. Results Continuous Recurrence Score predicted recurrence (hazard ratio for a 25-unit increase in score, 1.96; 95% CI, 1.50 to 2.55; P < .001), as well as disease-free and overall survival (both P < .001). Recurrence Score predicted recurrence risk (P = .001) after adjustment for stage, mismatch repair, nodes examined, grade, and treatment. Recurrence Score did not have significant interaction with stage (P = .90) or age (P = .76). Relative benefit of oxaliplatin was similar across the range of Recurrence Score (interaction P = .48); accordingly, absolute benefit of oxaliplatin increased with higher scores, most notably in patients with stage II and IIIA/B disease. Conclusion The 12-gene Recurrence Score predicts recurrence risk in stage II and stage III colon cancer and provides additional information beyond conventional clinical and pathologic factors. Incorporating Recurrence Score into the clinical context may better inform adjuvant therapy decisions in stage III as well as stage II colon cancer.

scholarly journals Impact of Patient Factors on Recurrence Risk and Time Dependency of Oxaliplatin Benefit in Patients With Colon Cancer: Analysis From Modern-Era Adjuvant Studies in the Adjuvant Colon Cancer End Points (ACCENT) Database

2016 ◽  
Vol 34 (8) ◽  
pp. 843-853 ◽  
Author(s):  
Manish A. Shah ◽  
Lindsay A. Renfro ◽  
Carmen J. Allegra ◽  
Thierry André ◽  
Aimery de Gramont ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Therapy ◽  
Time Course ◽  
Recurrence Risk ◽  
Post Treatment ◽  
Stage Ii ◽  
Stage Iii ◽  
Risk Of Recurrence ◽  
Risk Of Death ◽  
The Impact

Purpose Fluorouracil plus leucovorin (FU + LV) adjuvant chemotherapy reduced the risk of recurrence and death across all time points in a pooled analysis of 20,898 patients with colon cancer from 18 randomized studies. The impact of oxaliplatin added to FU + LV on the time course of recurrence and survival remains unknown. Patients and Methods A total of 12,233 patients enrolled to the randomized trials C-07, C-08, N0147, MOSAIC (Adjuvant Treatment of Colon Cancer), and XELOXA (Adjuvant XELOX) were pooled to examine the impact of oxaliplatin and tumor-specific factors on the time course of recurrence and death. For each end point, continuous-time risk was modeled over 6 years post treatment in all oxaliplatin-treated patients and patients concurrently randomized to FU + LV with or without oxaliplatin; the latter analyses supported time-dependent treatment comparisons. Results Addition of oxaliplatin significantly reduced the risk of recurrence within the first 14 months post treatment for patients with stage II disease and within the first 4 years for patients with stage III disease. Oxaliplatin also significantly reduced risk of death from 2 to 6 years post treatment for patients with stage III disease, with no differences in timing of outcomes between treatment groups (ie, oxaliplatin did not simply postpone recurrence or death compared with FU + LV alone). Patients with stage II disease receiving oxaliplatin did not exhibit a significant reduction in risk of death in the first 6 years post treatment. Recurrence risk peaked near 14 months for both treatments, and risk of recurrence and death increased with increased tumor and nodal burden. Conclusions These analyses support the addition of oxaliplatin to fluoropyrimidine-based adjuvant therapy in patients with stage III disease and underscore the need for adequate surveillance of patients with colon cancer during the first 3 years after adjuvant therapy.

The 55 STAR study: Prognostic and predictive value of the 55-gene classifier (55GC) in stage III colon cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3597-3597
Author(s):  
Toshiaki Ishikawa ◽  
Eiji Oki ◽  
Eiji Shinto ◽  
Mototsugu Shimokawa ◽  
Shigeki Yamaguchi ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Propensity Score ◽  
Propensity Score Matching ◽  
Recurrence Risk ◽  
Stage Ii ◽  
Stage Iii ◽  
Recurrence Rates ◽  
Curative Surgery ◽  
Cancer Subtypes

3597 Background: Patient prognosis can be predicted based on cancer subtypes classified according to DNA microarray results. The most robust classification system involves the consensus molecular subtypes, which uses over 600 genes for classification. To simplify this classification, we recently constructed a 55-gene classifier (55GC) to classify colon cancer (CC) into three subtypes with different recurrence rates: “microsatellite instability (MSI)-like,” “chromosomal instability (CIN)-like,” and “stromal” colon cancers. The 55GC has been reported to be a useful and reproducible grading system for stage II CC recurrence risk stratification. This study aimed to explore the usefulness of 55GC for classifying stage III CC patients. Methods: We retrospectively identified stage III CC patients aged 20-79 years who underwent curative surgery and received adjuvant chemotherapy with or without oxaliplatin (OX) between 2009 and 2012 from 15 institutions. Propensity score matching was used to adjust for the number of lymph node metastases, tumor location, sex, and age. Results: Among 938 eligible patients, 203 and 201 cases involving adjuvant chemotherapy with and without OX were selected, respectively, using propensity score matching. Ninety-five cases each from groups were analyzed after exclusion of cases involving low-quality specimens and those involving chemotherapy for < 3 months. The 5-year relapse-free survival (RFS) in patients receiving adjuvant chemotherapy with and without OX were 77.1% and 73.7%, respectively. Classification of the stage III CC according to 55GC and related 5-year RFS rates were as follows: stromal (N = 60), 66.6%; CIN-like (N = 78), 80.5%; and MSI-like (N = 52), 78.4%. The HRs for 5-year RFS for adjuvant chemotherapy with and without OX in each subtype were as follows: stromal, HR = 0.791 (95% CI = 0.329-1.901); CIN-like, HR = 1.241 (95% CI = 0.465-3.308); and MSI-like, HR = 0.495 (95% CI = 0.145-1.692). Conclusions: The stromal subtype showed poor prognosis in stage III as well as stage II patients. Oxaliplatin had a good additive effect in adjuvant chemotherapy for MSI-like subtype. The 55GC is useful for predicting the efficacy of adjuvant chemotherapy for CC.

The 12-gene colon cancer assay validation and utility: Summary of clinical evidence.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 523-523
Author(s):  
Emily Burke ◽  
Haluk Tezcan ◽  
Margarita Lopatin ◽  
Kim Michelle Clark-Langone ◽  
Mark Lee ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Tumor Biology ◽  
Stage Ii ◽  
Stage Iii ◽  
Clinical Validation ◽  
Cancer Specific Survival ◽  
Colon And Rectal Cancer ◽  
Gene Assay

523 Background: The 12-gene colon cancer assay is the first commercially available molecular assay to predict the risk of recurrence in stage II/III colon and rectal cancer. Rigorous evidence for clinical validity and utility of an assay is imperative since the result is used for treatment decision-making. This summary outlines the studies that meet an established definition of clinical validation and additional studies that support the utility of the assay. Methods: Prospectively designed studies using archival tissue with pre-specified methods, clinical outcomes, and analysis plan were considered clinical validation studies (Simon et al. JNCI 2009). Additional studies that demonstrated the utility of the assay in a clinical setting were considered supportive. Results: The assay has been clinically validated in four independent studies with 3315 patients (2390 stage II/628 stage III colon and 130 stage II/167 stage III rectal). All four studies demonstrated a significant association (p<0.05) between the result and outcome (e.g. recurrence risk and cancer specific survival). The score was examined in the context of other variables, including T and N stage, MMR status, number of nodes examined, lymphovascular invasion, and tumor grade; across all studies, the result consistently contributed to risk stratification beyond these variables. Three clinical utility studies with 502 patients showed that 29-45% of initial treatment recommendations in stage IIA colon cancer were changed, with a net reduction in use of adjuvant chemotherapy. Conclusions: Clinical validation of the 12-gene assay followed a now-standard approach of using archived tissue from multiple large, prospectively-designed studies with documented long-term outcomes; the 12-gene colon assay meets level IB evidence criteria. Subsequent studies showed the assay has impact on clinical practice. The underlying tumor biology assessed by the score is relevant in both colon (stage II and III) and rectal cancer, providing information beyond conventional features, and can help guide treatment decisions regarding adjuvant chemotherapy.

scholarly journals Duration of FOLFOX Adjuvant Chemotherapy in High-Risk Stage II and Stage III Colon Cancer With Deficient Mismatch Repair

2020 ◽  
Vol 10 ◽  
Author(s):  
Huabin Hu ◽  
Zehua Wu ◽  
Chao Wang ◽  
Yan Huang ◽  
Jianwei Zhang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Propensity Score ◽  
Mismatch Repair ◽  
Therapy Group ◽  
Stage Ii ◽  
Stage Iii ◽  
Deficient Mismatch Repair ◽  
The Impact

BackgroundWe evaluated the impact of 3 months of mFOLFOX6 adjuvant chemotherapy or surgery alone in comparison with 6 months of mFOLFOX6 on disease-free survival (DFS) in deficient mismatch repair (dMMR) colon cancer (CC) patients.MethodsThis retrospective study identified a cohort of patients with high-risk stage II and III dMMR CC who underwent curative surgery between May 2011 and July 2019. DFS was compared using the Kaplan-Meier survival methods and Cox proportional hazards models. Propensity-score matching was performed to reduce imbalance in baseline characteristics.ResultsA total of 242 dMMR CC patients were identified; 66 patients received 6 months of mFOLFOX6, 87 patients received 3 months of mFOLFOX6, and 89 patients were treated with surgery alone. The 3-year DFS rate was 72.8% in 3-month therapy group and 86.1% in 6-month therapy group, with a hazard ratio (HR) of 2.78 (95CI%, 1.18 to 6.47; P= 0.019). The difference in DFS between surgery alone group and 6-month therapy group was also observed but was nonsignificant (HR= 2.30, 95%CI, 0.99 to 5.38; P=0.054). The benefit of 6-month therapy in DFS compared with 3-month therapy group was pronounced for patients with stage III (HR=2.81, 95%CI, 1.03 to 7.67; P=0.044) but not for high-risk stage II patients. Propensity score matched analysis confirmed a DFS benefit in the 6-month therapy group.ConclusionThis study suggested that a 6-month duration of mFOLFOX6 adjuvant chemotherapy in dMMR CC patients may be associated with improved DFS compared with 3-month therapy, particularly in patients with stage III. The observational nature of the study implies caution should be taken in the interpretation of these results.

12-Gene Recurrence Score Assay Stratifies the Recurrence Risk in Stage II/III Colon Cancer With Surgery Alone: The SUNRISE Study

2016 ◽  
Vol 34 (24) ◽  
pp. 2906-2913 ◽  
Author(s):  
Takeharu Yamanaka ◽  
Eiji Oki ◽  
Kentaro Yamazaki ◽  
Kensei Yamaguchi ◽  
Kei Muro ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Risk Group ◽  
Recurrence Score ◽  
Recurrence Risk ◽  
High Risk Group ◽  
Stage Ii ◽  
Stage Iii ◽  
Stage Iiia ◽  
Resected Stage ◽  
Stage Ii Colon Cancer

Purpose The 12-gene Recurrence Score assay has been validated in resected stage II colon cancer treated with or without chemotherapy and resected stage III disease treated with chemotherapy. This study evaluated the 12-gene Recurrence Score assay for stage II and III colon cancer without chemotherapy to reveal the natural course of recurrence risk in stage III disease. Methods A cohort-sampling design was used. From 1,487 consecutive patients with stage II to III disease who had surgery alone, 630 patients were sampled for inclusion with a 1:2 ratio of recurrence and nonrecurrence. Sampling was stratified by stage (II v III). The assay was performed on formalin-fixed, paraffin-embedded primary cancer tissue. Association of the Recurrence Score result with recurrence-free interval (RFI) was assessed by using weighted Cox proportional hazards regression. Results Overall, 597 of 630 patients were analyzable—247 patients had stage II, and 350 had stage III colon cancer. The continuous Recurrence Score was significantly associated with RFI after adjustment for disease stage (hazard ratio for a 25-unit increase in Recurrence Score, 2.05; 95% CI, 1.47 to 2.86; P < .001). With respect to prespecified subgroups, as defined by low (< 30), intermediate (30 to 40), and high (≥ 41) Recurrence Score risk groups, patients with stage II disease in the high-risk group had a 5-year risk of recurrence similar to patients with stage IIIA to IIIB disease in the low-risk group (19% v 20%), whereas patients with stage IIIA to IIIB disease in the high-risk group had a recurrence risk similar to that of patients with stage IIIC disease in the low-risk group (approximately 38%). Conclusion To our knowledge, this study provides the first validation of the 12-gene Recurrence Score assay in stage III colon cancer without chemotherapy and showed the heterogeneity of recurrence risks in stage III as well as in stage II colon cancer.

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