Adjuvant Chemotherapy For Stage Research Articles

Predictors of Timely Initiation and Completion of Adjuvant Chemotherapy in Stage II/III Colorectal Adenocarcinoma.

Background: Adjuvant chemotherapy (AC) for colorectal cancer (CRC) has led to substantial improvement in survival. Several clinical trials advocate the initiation of AC within 6-8 weeks of surgical resection based on evidence of improved survival with early initiation of AC. We aim to evaluate factors that predict initiation and completion of AC, subsequently improving survival. Methods: We identified 451 patients who underwent resection for CRC between 2014 and 2022. One hundred ten patients had stage II/III colorectal cancer who underwent resection followed by AC. Multivariable logistic regression analysis was performed to identify factors significantly predicting delay in AC >8 weeks. Secondary outcomes included chemotherapy completion rate, recurrence-free survival, and overall survival. Results: The final analysis included 110 patients. The median time to initiation of adjuvant chemotherapy (TIAC) was 6.9 weeks (IQR: 5.8-9.5). In total, 36.4% of patients had a delay >8 weeks to initiation of AC, and only 40% completed treatment. The surgical approach (open vs laparoscopic vs robotic) had no effect on the TIAC. On multivariable logistic regression analysis, preoperative albumin ≥3.5 (OR = .31; 95% CI: .12-.80) was an independent predictor of timely initiation of AC. Completion of AC was associated with a higher overall survival. Discussion: Preoperative nutritional status predicted delay in initiation of AC. Patients with a delay in AC beyond eight weeks had a lower rate of AC completions and worse survival. It is imperative to optimize this aspect of treatment as it correlates with survival.

Adjuvant chemotherapy in stage 1 colon cancer: Patient characteristics and survival analysis from the national cancer database

BackgroundA subset of patients in ACS-NCDB with stage-1 colon cancer received adjuvant chemotherapy (AC), in contrast to national guidelines. This study aimed to define this population and evaluate associations between AC and survival. MethodsPatients with T1-2N0 colon cancer from 2004 to 2016 were separated into AC and non-AC groups. Adverse pathological features (APF) included T2, poor differentiation, lymphovascular invasion, positive margin, and inadequate lymph nodes (<12). Cox proportional hazard models were used to estimate prognostic factors for overall survival (OS). ResultsA total of 1745 of 139,857 patients (1.2 %) received AC. Receiving AC was associated with male sex (p = 0.02), uninsured (p < 0.01), low income (p = 0.02), or having ≥2 APFs (p < 0.001). In the total cohort, AC was associated with increased mortality (HR 1.14 [1.04–1.24] P < 0.01). On subset analysis, AC was associated with improved OS for patients with ≥2 APFs (log-rank P=<0.001), and decreased mortality when adjusted for covariates (HR 0.81 [0.69–0.95] P=<0.01). The most significant predictor of mortality was old age (HR 3.78 [3.67, 3.89] p ≤ 0.01), followed by higher Charlson Comorbidity Index (HR 1.73 [1.69, 1.76] (p ≤ 0.01), and higher APF score (HR 1.46 [1.42, 15.2] p ≤ 0.01). ConclusionAC was associated with decreased survival in the total cohort of stage 1 colon cancer patients, but was associated with improved survival for patients with multiple APFs.

Race/Ethnicity and Social Determinants of Health and Their Impact on Receiving Appropriate Chemotherapy for Colon Cancer.

Despite the heightened understanding and improved treatment for colorectal cancer in the United States, social determinants of health (SDH) play a significant role in the colorectal cancer outcomes. We sought to investigate the relationship between SDH and appropriate utilization of adjuvant chemotherapy in stage III colon cancer. For this retrospective study, we utilized data from the National Cancer Data Base (NCDB). Descriptive statistics are reported, including means and 95% confidence intervals for continuous variables and frequency and proportions for categorical variables. Univariate hypothesis testing to identify categorical level factors associated with treatment used Wilcoxon rank sum or Kruskal-Wallis tests, with multivariate analyses performed using regression analysis. Significant differences were as follows: Metro-non-Hispanic White patients received treatment less frequently (69.7%) when compared to Metro-non-Hispanic Black patients (73.4%) (P < .001). Increasing age was a negative predictor of likelihood to receive with those over 65years old having an 83% decrease in likelihood to receive chemotherapy when compared to those under 65 (P < .001). Medicaid patients were 47% less likely and Medicare patients were 40% less likely to receive chemotherapy when compared to those with private insurance (P < .001). Rural patients were statistically more likely to receive chemotherapy (OR 1.42, 1.32-2.52, P < .001) as were urban patients, (OR 1.26, 1.20-1.31, P < .001) when compared to patients residing in metro areas. Age, living in a Metro area, and government insurance status at diagnosis are negatively correlated with the likelihood of receiving chemotherapy. Race was not associated with differences in receiving chemotherapy.

Abstract 5022: MEDOCC-CrEATE trial: Feasibility of measuring circulating tumor DNA after surgery to guide adjuvant chemotherapy in stage II colon cancer patients

Abstract Introduction: Patients with stage II colon cancer not classified as high risk (pT4 microsatellite stable) do not receive adjuvant chemotherapy (ACT) according to Dutch guidelines. However, 15-20% of patients with stage II colon cancer experience a disease recurrence, indicating that there is an unmet clinical need to identify patients who could benefit from adjuvant treatment. Observational studies demonstrate that postoperative circulating tumor DNA (ctDNA) is indicative of minimal residual disease (MRD) and a strong prognostic biomarker for disease recurrence. Aim: The MEDOCC-CrEATE trial aims to assess 1) the proportion of stage II colon cancer patients with detectable postoperative ctDNA accepting ACT and 2) whether ctDNA-guided ACT reduces 2-year recurrence rate (RR). Methods: MEDOCC-CrEATE is an interventional trial following the ‘trial within cohorts’ design. Participants of the Prospective Dutch Colorectal Cancer cohort with stage II colon cancer and no indication for ACT randomized to the intervention arm undergo postoperative tumor-informed ctDNA testing using next-generation sequencing of 33 genes through the PGDx elio™ liquid biopsy assay. If ctDNA is detected, they are offered 4 cycles of adjuvant capecitabine plus oxaliplatin. Patients in the intervention arm who test ctDNA negative and patients in the control arm receive standard of care follow-up. For all patients, blood is collected every 6 months for 3 years to monitor disease recurrence. The primary endpoint is the proportion of patients with detectable postoperative ctDNA willing to receive ACT. Secondary endpoints include 2-year RR, disease-free and overall survival, quality of life and cost-effectiveness of ctDNA-guided ACT. The study is powered for 2-year RR, randomizing 660 patients to each study arm in order to treat 30 patients in the intervention arm with detectable postoperative ctDNA, assuming 5% ctDNA detection and 10% noncompliance. Results: Logistics for timely multicenter collection of tumor tissue and blood have been optimized across 28 Dutch hospitals. At present, 240 patients have been randomized. Of the 119 patients in the intervention arm, 98 provided consent for immediate postoperative ctDNA analysis (82%). Of the 92 currently available results, 5 (5 %) had detectable ctDNA. The median time from surgery to blood collection was 15 days (IQR 11-19), with a median turnaround time from surgery to ctDNA result of 47 days (IQR 39-54). Conclusion: Multicenter postoperative tumor-informed ctDNA testing for MRD is operationally and technically feasible within the clinically relevant 8-12 week window to start ACT. The observed ctDNA detection rate is in accordance with expectations and the study design. Upon study finalization, the results will be used for health technology assessment to demonstrate the putative clinical utility of ctDNA-guided ACT in stage II colon cancer. Citation Format: Ingrid Franken, Suzanna Schraa, Karlijn van Rooijen, Dave van der Kruijssen, Carmen Rubio-Alarcón, Steven Ketelaars, Sietske van Nassau, Teunise Snetselaar, Bregje Adriaans, Jillian Phallen, Sam Angiuoli, Amy Greer, Ellen Verner, Veerle Coupé, Helena Verkooijen, Miranda van Dongen, Linda Bosch, Mirthe Lanfermeijer, Daan van den Broek, Gerrit Meijer, Victor Velculescu, Mark Sausen, Miriam Koopman, Remond Fijneman, Geraldine Vink, on behalf of the PLCRC-MEDOCC group. MEDOCC-CrEATE trial: Feasibility of measuring circulating tumor DNA after surgery to guide adjuvant chemotherapy in stage II colon cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5022.

Abstract 2400: Determinants of early recurrence in surgically-resected colon cancer: A multi-omics analysis

Abstract Introduction: Colon cancer is the third most common cancer worldwide. The mainstay treatment for localized disease is surgical resection, often followed by adjuvant chemotherapy in stage III patients, and stage II patients with high-risk features. Unfortunately, some patients experience early local and/or distant recurrence. Besides classic anatomical/pathological tumor features, insight into the genomic determinants of early recurrence in colon cancer is lacking. Herein, we utilize a multi-omics approach to identify early-recurrence-specific features that could aid in more accurate risk stratification. Methods: We utilized the Cancer Genomic Atlas Colon Adenocarcinoma (TCGA-COAD) Database. Clinical, histopathological and genomic data were retrieved through the cBioPortal database. Our analysis was limited to patients with stage 2 or 3 (n = 390) disease based on the American Joint Committee on Cancer Code. Early recurrence (ER) was defined as disease relapse/recurrence within 12 months of sample acquisition post-surgery. Accordingly, patients were categorized into the ER and non-early recurrence (NER) groups based on a cut-off point of 12 months of disease-free survival. Results: The colon cancer ER and NER group included 45 and 345 patients, respectively. Comparable age, sex and race percentages were found between both groups. The ER group had significantly worse overall, progression-free, and disease-specific survival (HR: 0.083 95% CI: 0.031-0.220, HR: 0.035 95% CI: 0.011-0.0109, HR: 0.021 95% CI: 0.006-0.076, respectively). ER patients had a significantly higher proportion of patients with T4 and N2 disease based on the TNM staging system. ER patients had significant (P&amp;lt; 0.05) expression of TRIM46, TRPC4, ELOVL7, CSMD1, BCLAF1, and CD70 mutations, while tumor mutational burden was comparable between both groups (median TMB in ER vs NER: 4.2 vs 3.62, p = 0.28). Differential gene expression analysis revealed 68 genes to be upregulated in the ER group which were found to be enriched in hypoxia and interleukin-11 pathway genes. Genes upregulated in the NER group (n = 49) were enriched in interferon-alpha response and glycolysis/gluconeogenesis pathway genes. Proteomics analysis revealed significantly higher levels of EIF4E, CCNE1, SRSF1, SCD, and PECAM1 proteins in NER patients .Conclusion: Our results highlight insights into molecular and genomic features unique to colon cancer patients with early recurrence. Understanding such predictors for early recurrence will aid in risk stratification and help in determining patients who would derive the most benefit from adjuvant treatment considerations. Citation Format: Salma Al-Aomar, Hassan Abushukair, Alaa Zaitoun, Sara Zytoon, Sara Illeyyan, Husam Almomani, Ghayda'a Al-Majali, Arafat Hammad, Khaled Obeidat, Fuad Turfah, Awni Shahait, Fadwa Ali. Determinants of early recurrence in surgically-resected colon cancer: A multi-omics analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2400.

Who benefit from adjuvant chemotherapy in stage I lung adenocarcinoma? A multi-dimensional model for candidate selection

BackgroundDespite promising overall survival of stage I lung adenocarcinoma (LUAD) patients, 10-25 % of them still went through recurrence after surgery. [1] While it is still disputable whether adjuvant chemotherapy is necessary for stage I patients. [2] IASLC grading system for non-mucinous LUAD shows that minor high-grade patterns are significant indicator of poor prognosis. [3] Other risk factors, such as, pleura invasion, lympho-vascular invasion, STAS, etc. are also related to poor prognosis. [4-6] There still lack evidence whether IASLC grade itself or together with other risk factors can guide the use of adjuvant therapy in stage I patients. In this article, we tried to establish a multi-variable recurrence prediction model for stage I LUAD patients that is able to identify candidates of adjuvant chemotherapy. MethodsWe retrospectively collected patients who underwent lung surgery from 2018.8.1 to 2018.12.31 at our institution and diagnosed with lung adenocarcinoma pT1-2aN0M0 (stage I). Clinical data, manifestation on CT scan, pathologic features, driver gene mutations and follow-up information were collected. Cox proportional hazards regression analyses were performed utilizing the non-adjuvant cohort to predict disease free survival (DFS) and a nomogram was constructed and applied to the total cohort. Kaplan-Meier method was used to compare DFS between groups. Statistical analysis was conducted by R version 3.6.3. FindingsA total of 913 stage I LUAD patients were included in this study. Median follow-up time is 48.1 months.4-year and 5-year DFS are 92.9 % and 89.6 % for the total cohort. 65 patient experienced recurrence or death. 4-year DFS are 97.0 %,94.6 % and 76.2 %, and 5-year DFS are 95.5 %, 90.0 % and 74.1 % in IASLC Grade1, 2 and 3, respectively(p < 0.0001). High-risk patients defined by single risk factors, such as, IASLC grade 3, pleura invasion, STAS, less LN resected could not benefit from adjuvant therapy. A LASSO-COX regression model was built and patients are divided into high-risk and low-risk groups. In the high-risk group, patients underwent adjuvant chemotherapy have longer DFS than those who did not (p = 0.024), while in the low-risk group, patients underwent adjuvant chemotherapy have inferior DFS than those who did not (p < 0.001). InterpretationIASLC grading is a significant indicator of DFS, however it could not guide adjuvant therapy in our stage I LUAD cohort. Growth patterns and T indicators together with other risk factors could identify high-risk patients that are potential candidate of adjuvant therapy, including some stage IA LUAD patients.

Outcome of patients with stage I immature teratoma after surveillance or adjuvant chemotherapy.

Immature teratomas are rare malignant ovarian germ cell tumours, typically diagnosed in young women, where fertility-sparing surgery is the treatment of choice. The role of adjuvant chemotherapy in stage I disease remains controversial. We evaluated the impact of surveillance versus chemotherapy on the recurrence rate in stage I immature teratomas. We collected a single centre retrospective series of patients with stage I immature teratomas treated with fertility-sparing surgery at San Gerardo Hospital, Monza, Italy, between 1980 and 2019. Potential risk factors for recurrence were investigated by multivariate logistic regression. Of the 74 patients included, 12% (9/74) received chemotherapy, while 88% (65/74) underwent surveillance. Median follow-up was 188 months. No difference in recurrence was found in stage IA/IB and IC immature teratomas [10% (6/60) vs. 28.6% (4/14) (P=0.087)], grade 1, grade 2, and grade 3 [7.1% (2/28) vs. 14.3% (4/28) vs. 22.2% (4/18) (p=0.39)], and surveillance versus chemotherapy groups [13.9% (9/65) vs. 11.1% (1/9)) (p = 1.00)]. In univariate analysis, the postoperative approach had no impact on recurrence. The 5-year disease-free survival was 87% and 90% in the surveillance and chemotherapy groups, respectively; the overall survival was 100% in both cohorts. Our results support the feasibility of surveillance in stage I immature teratomas. Adjuvant chemotherapy may be reserved for relapses. However, the potential benefit of chemotherapy should be discussed, especially for high-risk tumours. Prospective series are warranted to confirm our findings. To date, no consensus has been reached regarding the role of adjuvant chemotherapy in stage I immature teratomas of the ovary. Some studies suggest that only surveillance is an acceptable choice. However, guidelines are not conclusive on this topic. No difference in terms of recurrence was observed between the surveillance and the adjuvant chemotherapy group. All patients who relapsed were successfully cured with no disease-related deaths. Adjuvant chemotherapy should be appropriately discussed with patients. However, it may be reserved for relapse according to our data.

Influence of High-Risk Pathological Factors and their Interaction on the Survival Benefit of Adjuvant Chemotherapy in Stage II Rectal Cancer: A Retrospective Study

Influence of High-Risk Pathological Factors and their Interaction on the Survival Benefit of Adjuvant Chemotherapy in Stage II Rectal Cancer: A Retrospective Study

Inadequate Lymph Node Yield: An Inadequate Indication for Adjuvant Chemotherapy in Stage II Colon Cancer.

Optimal therapy for stage II colon cancer remains unclear, and national guidelines recommend "consideration" of adjuvant chemotherapy (ACT) in the presence of high-risk features, including inadequate lymph node yield (LNY, <12 nodes). This study aims to determine whether the survival benefit of ACT in stage II disease varies based on the adequacy of LNY. We used the National Cancer Database (NCDB) to identify adults who underwent resection for a single primary T3 or T4 colon cancer between 2006 and 2018. Multivariable logistic regression tested for associations between ACT and prespecified demographic and clinical characteristics, including the adequacy of LNY. We used Cox proportional hazards models to assess overall survival and restricted cubic splines to estimate the optimal LNY threshold to dichotomize patients based on overall survival. Unadjusted 5- and 10-year survival rates were 84% and 75%, respectively, among patients who received ACT and 70% and 50% among patients who did not (log-rank P < 0.01). Inadequate LNY was independently associated with both receipt of ACT (odds ratios, 1.50; P < 0.01) and decreased overall survival [hazard ratio (HR), 1.56; P < 0.01]. ACT was independently associated with improved survival (HR, 0.67; P < 0.01); this effect size did not change based on the adequacy of LNY (interaction P = 0.41). Results were robust to re-analysis with our cohort-optimized threshold of 18 lymph nodes. Consistent with contemporary guidelines, patients with inadequate LNY are more likely to receive ACT. LNY adequacy is an independent prognostic factor but, in isolation, should not dictate whether patients receive ACT.

Prognostic factors for pure ovarian immature teratoma and the role of adjuvant chemotherapy in stage I diseases

Background The prognostic factors for patients with pure ovarian immature teratoma (POIT) and the role of adjuvant chemotherapy in stage IA G2-G3 and IB-IC POIT remains controversial. Methods We conducted a retrospective study of 155 POIT patients treated in our hospital between 2000 and 2022. The recurrence-free survival (RFS), disease-specific survival (DSS), and potential prognostic factors of POIT patients were evaluated. Subgroup analysis was conducted in stage I other than stage IA G1 POIT. Results The median age at diagnosis was 23.0 years (range: 4.0 − 39.0), and 126 (81.3%), 2 (1.3%), 26 (16.8%), and 1 (0.6%) patients had FIGO stage I, stage II, stage III, and stage IV disease, respectively. Twenty-three patients relapsed and five died of the diseases after a median follow-up of 7.6 years, with a 5-year RFS and DSS rate of 86.0% and 97.0%, respectively. Multivariate analysis showed that positive postoperative tumour markers (TM) were the risk factor for recurrence in the overall cohort (hazard ratio [HR] 4.058, 95% CI 1.175 − 14.019, p = 0.027) and subgroup (HR 10.237, 95% CI 2.175 − 48.179, p = 0.003), and FIGO stage II–IV was the only factor for DSS in overall cohort (HR 7.751, 95% CI 1.281 − 46.895, p = 0.026). In 110 patients subjected to subgroup analysis, 29 patients received surveillance without chemotherapy and 81 patients were administered adjuvant chemotherapy. Multivariate analysis revealed active surveillance significantly increased the recurrence rate (5-year RFS of 75.7% vs. 93.6%, HR 7.562, 95% CI 2.441 − 23.424, p < 0.001) but not the death related to POIT (p = 0.338). Conclusion Positive postoperative TM and FIGO stage II–IV were the prognostic factors for POIT. Active surveillance in stage I POIT of any grade may be practical for those with negative postoperative TM.

SIOG2023-1-P-204 - Adjuvant chemotherapy in stage III colorectal cancer: predictors of recurrence and toxicity

SIOG2023-1-P-204 - Adjuvant chemotherapy in stage III colorectal cancer: predictors of recurrence and toxicity

Impact of safety-net hospital burden on achievement of textbook oncologic outcomes following resection in for stage I-IV colorectal cancer.

Textbook oncologic outcome (TOO) is a benchmark for high-quality surgical cancer care but has not been studied at safety-net hospitals (SNH). The study sought to understand how SNH burden affects TOO achievement in colorectal cancer. The National Cancer Database was queried for colorectal cancer patients who underwent resection for stage I-III plus stage IV with liver-only metastases (2010-2019). TOO was defined as R0 resection, AJCC-compliant lymphadenectomy (>12 nodes), no prolonged LOS, no 30-day mortality/readmission, and receipt of stage-appropriate adjuvant chemotherapy. Of 487,195 patients, 66.7% achieved TOO. Lower achievement was explained by adequate lymphadenectomy (87.3%), non-prolonged LOS (76.3%), and receipt of adjuvant chemotherapy in stage III (60.3%) and IV (54.1%). Treatment at high burden hospitals (HBH, >10% Medicaid/uninsured) was a predictor of non-TOO (Stage I/II: OR 0.83, III: OR 0.86, IV: OR 0.83; all p < 0.001). Achieving TOO was associated with decreased mortality (Stage I/II: HR 0.49, III: HR 0.48, IV: HR 0.57; all p < 0.001), and HBH treatment was a predictor of mortality (Stage I/II: HR 1.09, III: HR 1.05, IV: HR 1.07; all p < 0.05). Treatment at higher SNH burden hospitals was associated with less frequent TOO achievement and increased mortality. Quality improvement targets include receipt of adjuvant chemotherapy and avoidance of prolonged LOS.

164P Early evaluation of effectiveness and cost-effectiveness of ctDNA-guided selection for adjuvant chemotherapy in stage II colon cancer

164P Early evaluation of effectiveness and cost-effectiveness of ctDNA-guided selection for adjuvant chemotherapy in stage II colon cancer

Using oral tegafur/uracil (UFT) plus leucovorin as adjuvant chemotherapy in stage II colorectal cancer: a propensity score matching study from Taiwan

BackgroundEarly-stage colorectal cancer had excellent outcomes after curative resection, typically. However, a perplexing survival paradox between stage II and stage III was noted. This paradox could be influenced by the administration of routine postoperative adjuvant chemotherapy and the presence of high-risk factors in stage II CRC. The objective of the study was to investigate the influence of high-risk factors on patients with stage II CRC and assess the efficacy of oral tegafur/uracil (UFT) plus leucovorin as adjuvant chemotherapy for stage II CRC patients.MethodsA retrospective study was conducted using propensity score matching at a single medical institution. A total of 1544 patients with stage II colorectal cancer who underwent radical surgery between January 2004 and January 2009 were included. The intervention used was tegafur/uracil plus leucovorin as adjuvant chemotherapy. The main outcome measures were disease-free survival and overall survival.ResultsAfter propensity score matching, 261 patients were included in three groups: no-treatment, half-year treatment, and one-year treatment. The clinical characteristics of each group tended to be more consistent. The Cox proportional hazard models showed that tegafur/uracil treatment or not was a significant independent factor for oncological outcome. Kaplan–Meier analysis also showed significantly better disease-free survival and overall survival. Further investigation revealed that tegafur/uracil duration was an independent factor for oncological outcome. While the survival curve did not reach statistical significance, the one-year UFT treatment group demonstrated the best treatment trend.ConclusionsThis study suggests that tegafur/uracil plus leucovorin is a feasible adjuvant chemotherapy regimen for patients with stage II colorectal cancer after curative surgical treatment. Prolonged tegafur/uracil plus leucovorin treatment for 12 months showed a trend towards better outcomes in patients with stage II colorectal cancer.

Variations in the definition and perceived importance of positive resection margins in patients with colorectal cancer – an EYSAC international survey

IntroductionMicroscopically positive resection margins (R1) are associated with poorer outcomes in patients with colorectal cancer. However, different definitions of R1 margins exist. It is unclear to what extent the definitions used in everyday clinical practice differ within and between nations. This study sought to investigate variations in the definition of R1 margins in colorectal cancer and the importance of margin status in clinical decision-making. Materials and methodsA 14-point survey was developed by members of The European Society of Surgical Oncology (ESSO) Youngs Surgeons and Alumni Club (EYSAC) Research Academy targeting all members of the multidisciplinary team (MDT) treating patients with colorectal cancer. The survey was distributed on social media, in ESSO's monthly newsletter and via national societies. ResultsIn total, 137 responses were received. Most respondents were from Europe (89.7%), with the majority from Denmark (56.9%). Less than 2/3 of respondents defined R1 margins as the presence of viable cancer cells ≤1 mm of the margin. Only 60% reported that subdivisions of R1 margins (primary tumour vs tumour deposit vs metastatic lymph node) are routinely available. More than 20% of respondents reported that pathology reports are not routinely reviewed at MDT meetings. Less than half of respondents considered margin status in decision-making for type and duration of adjuvant chemotherapy in Stage III colon cancer. ConclusionThe definitions and perceived clinical importance of microscopically positive margins in patients with colorectal cancer appear to vary. Adoption of an international dataset for pathology reporting may help to standardise current practices.

ASO Visual Abstract: Factors Associated with Receipt of Adjuvant Chemotherapy in Stage II Colon Cancer.

ASO Visual Abstract: Factors Associated with Receipt of Adjuvant Chemotherapy in Stage II Colon Cancer.

Predictive models of recurrence from transcriptomic signatures of the tumor microenvironment and cell cycle in stage III colon cancer from PETACC-8 and IDEA France trials.

3523 Background: The objective of this work was to establish predictive models of the risk of recurrence in stage III colon cancer (CC) based on transcriptomic signatures of the tumor microenvironment (TME) and cell cycle from the PETACC-8 (training set) and IDEA- France (validation set) trials. Methods: 3'RNAseq was performed in 1733 patients from the PETACC-8 trial (85%) and 1263 patients from the IDEA-France trial (63%). 4 transcriptomic signatures were analyzed: a signature reflecting T-cells infiltration named "Immunoscore-Like", a signature reflecting M2 macrophage infiltration named "M2-like", the expression of CXCL13 (reflecting B cells infiltration) and a score based on the Oncotype DX® Colon Cancer RS using the same formula from the stromal score and the cell cycle score, named “Oncotype DX Like”. In the 1st multivariate model, we analyzed the 4 signatures separately with a dichotomization into "high" and "low" with the best cut point value for the prediction of time to recurrence (TTR) in PETACC-8 trial. In the 2nd multivariate model, we defined a score named “IPS” (Immune Proliferative Stromal), corresponding to the number of deleterious signatures (“high” or “low” depending on the signatures), ranging from 0 to 4. Results: The 1st multivariate model, built from PETACC-8 trial, showed that these 4 signatures were significantly associated with TTR with a protective effect of Immunoscore Like and CXCL13 "high" (HR: 0.66, p = 0.003 and 0.60, p &lt; 0.001 respectively) and a deleterious effect of M2 Like and Oncotype Like “high” (HR: 1.28, p = 0.05 and HR: 1.37, p = 0.01, respectively), independently of known prognostic factors, with a C-index of 0.73. This model was applied to the IDEA-France cohort by calculating a predictive score for each patient, with TTR significantly different depending on the quartile of this score with a 3-year TTR ranging from 55% for the lowest quartile to 90% for the highest quartile (p &lt; 0.001). In the 2nd model, in the 2 cohorts, IPS score was independently associated with TTR with a HR increasing with the IPS score, independently of T and N stage and intra-tumoral CMS heterogeneity (Table). Conclusions: Using transcriptomic data of patients with stage III CC from 2 large-scale adjuvant trials, two predictive models based on signatures of the TME and the cell cycle, provide important information in addition to known prognostic factors for patient stratification on risk of recurrence. Beyond T and N stage, for the decision of adjuvant chemotherapy in stage III CC, the combination of these different variables could be exploited in the future for personalized care (de-escalation, intensification). [Table: see text]

PACE: A phase III trial of CAPOX versus anti-PD-1 inhibitor as adjuvant therapy for patients with dMMR/MSI-H stage III colon cancer.

TPS3637 Background: Approximately 12% of stage III colon cancer are deficient mismatch repair (dMMR), leading to high levels of microsatellite instability (MSI-H). In the KEYNOTE-177 study, the anti–PD-1 inhibitor Pembrolizumab alone significantly improved progression free survival (PFS) versus chemotherapy as first-line therapy for metastatic colorectal cancer (mCRC) patients with MSI-H/dMMR. We are conducting a phase III randomised trial to determine whether anti-PD-1 inhibitor Sintilimab monotherapy can improve disease free survival (DFS) compared with standard adjuvant chemotherapy in stage III colon cancer patients with dMMR. Methods: This is an open-label, multicentre, randomised phase III study. Patients aged ≥ 18 years with completely resected, stage III colon cancer confirmed to have dMMR/MSI-H and ECOG performance status 0-1 are eligible. Approximately 323 patients will be randomly assigned 1:1 to either Sintilimab monotherapy (200 mg IV every 3 weeks for 8 cycles) or CAPOX regimen (capecitabine, oxaliplatin for 4 or 8 cycles according to current standard practice). Adverse events (AEs) will be assessed throughout treatment and for 30 days thereafter (90 days for serious AEs) and graded per NCI CTCAE v4.0. Primary endpoint is 3-year DFS. The study was estimated to provide approximately 80% power to detect a hazard ratio of 0.56 for DFS at a two-sided alpha of 0.05. Secondary endpoints include OS, safety profile, toxicity, and quality of life. Archived tumor tissue and blood samples will be collected for correlative studies. Study enrollment is ongoing. Clinical trial information: NCT05236972 .

Use of circulating tumor DNA analysis to predict recurrence and need for adjuvant chemotherapy in stage I-IV colorectal cancer.

e15537 Background: Circulating tumor DNA (ctDNA) has emerged as a biomarker that can define the risk of recurrence after curative-intent surgery for patients with colorectal cancer (CRC). However, beyond the predictive power of postoperative ctDNA detection, the efficacy and potential limitations of ctDNA detection urgently need to be fully elucidated in a large cohort of CRC. Methods: We enrolled 309 patients with stages Ⅰ to Ⅳ CRC who underwent definitive surgery. Tumor tissues from those patients were sequenced by a custom-designed next-generation sequencing (NGS) panel to identify somatic mutations, and plasma was analyzed using ctDNA-based molecular residual disease (MRD) assay which integrated tumor genotype–informed and tumor genotype–naïve ctDNA analysis. Results: ctDNA was detected after surgery in 5.4%, 13.8%, 15% and 30% of patients with stage Ⅰ, Ⅱ, Ⅲ and Ⅳ disease, respectively, and in 17.5% of all longitudinal samples. Detection of MRD after surgery and in serial plasma samples during follow-up were associated with shorter disease-free survival (DFS) (hazard ratio [HR], 13.17; P &lt; 0.0001 and HR, 14.44; P &lt; 0.0001, respectively) independent of tumor site, stage, and MSI status. Within the population, only 13 patients (6.6%) with longitudinal undetectable MRD recurred, resulting in a negative predictive value of 93.4%. Correspondingly, the positive predictive value of longitudinal detectable MRD was 79.6%, with a median lead time of 10.1 months. Further subgroup analyses revealed that adjuvant therapy did not confer a superior survival for patients with undetectable or detectable MRD. Moreover, lung-only and peritoneal metastases were less detectable by MRD. Conclusions: Postoperative ctDNA status is a strong predictor of recurrence independent of stage and MSI status. Longitudinal undetectable MRD could be used to define the potentially cured population in CRC patients undergoing curative-intent surgery.

Factors Associated with Receipt of Adjuvant Chemotherapy in Stage II Colon Cancer.

The benefits of chemotherapy in stage II colon cancer remain unclear, but it is recommended for high-risk stage II disease. Which patients receive chemotherapy and its impact on survival remains undetermined. The National Cancer Database was surveyed between 2004 and 2016 for stage II colon cancer patients. Patients were categorized as high- or average-risk as defined by the National Comprehensive Cancer Network. The demographic characteristics of high- and average-risk patients who did and did not receive chemotherapy were compared using univariate and multivariable analyses. The survival of high- and average-risk patients was compared based on receipt of chemotherapy with Cox hazard ratios and Kaplan-Meier curves. Overall, 84,424 patients met the inclusion criteria. A total of 34,868 patients were high-risk and 49,556 were average-risk. In high-risk patients, the risk factors for not receiving chemotherapy included increasing age, distance from the treatment facility, Charlson-Deyo score, and lack of insurance. In average-risk patients, factors associated with receipt of chemotherapy were decreasing age, distance from the treatment facility, Charlson-Deyo score, and non-academic association of the treatment facility. In both, chemotherapy was significantly associated with increased survival on the Kaplan-Meier curve. In the Cox hazard ratio, only high-risk patients benefited from chemotherapy (hazard ratio 1.183, confidence interval 1.116-1.254). Factors associated with not receiving chemotherapy in high-risk stage II colon cancers included increasing age, medical comorbidities, increasing distance from the treatment facility, and lack of insurance. Chemotherapy is associated with improved overall survival in high-risk patients.