Duration Of Adjuvant Chemotherapy Research Articles

Survival analysis in pT1-3 and paracolic lymph-node invasion colorectal cancer: the prognostic role of positive paracolic lymph-node ratio for adjuvant chemotherapy.

Several studies have observed that some stage III colorectal cancer (CRC) patients cannot benefit from standard adjuvant chemotherapy. However, there is no unified screening standard to date. Consecutive patients with pathologically confirmed colon adenocarcinoma treated in 3 centers between January 2016 and December 2018 were included. Patients were divided into four groups according to different stages and positive paracolic lymph-node ratio (P-LNR) [Cohort 1: pT1-3N0M0, Cohort 2: pT1-3N + (P-LNR ≤ 0.15)M0, Cohort 3: pT4N0M0, Cohort 4: stage III patients except for pT1-3N + (P-LNR ≤ 0.15)M0], and further overall survival was compared by Kaplan-Meier method. The univariate and multivariate analyses were employed for cox proportional hazards model. We retrospectively reviewed 5581 consecutive CRC patients with, and 2861 eligible patients were enrolled for further analysis. The optimal cut-off value of P-LNR in our study was 0.15. There was no significant difference in OS (91.36 vs. 93.74%) and DFS (87.65 vs. 90.96%) between stage III patients with pT1-3N + (P-LNR ≤ 0.15)M0 and those with pT1-3N0M0. Further analysis demonstrated that CRC patients with pT1-3N + (P-LNR ≤ 0.15)M0 were less likely to benefit from 8 cycles of CAPOX or FOLFOX chemotherapy and suffered fewer adverse events from declining chemotherapy. Comparing with 0-4 cycles versus 8 cycles, the overall survival rates were 91.35 versus 90.19% (P = 0.79), and with a DFS of 87.50 versus 88.24% (P = 0.49), the duration of adjuvant chemotherapy was not an independent risk factor for patients with pT1-3N + (P-LNR ≤ 0.15)M0 (HR: 0.70, 95% CI 0.90-1.30, P = 0.42). The concept of P-LNR we proposed might have a high clinical application value and accurately enable clinicians to screen out specific CRC patients who decline or prefer limited chemotherapy. The clinical trial registration number: ChiCTR2300076883.

Real-world adoption of 3 months of adjuvant oxaliplatin chemotherapy in patients with stage III colorectal cancer (CRC).

83 Background: Based on the IDEA analysis, 3 months (mos) of adjuvant chemotherapy (ACT) with CAPOX has emerged as an option for both low-risk and high-risk stage III CRC. This has resource utilization, cost and toxicity benefits (particularly less neurotoxicity) without compromising efficacy. This study examines the patterns of uptake of CAPOX vs FOLFOX and duration of ACT in a contemporary post-COVID real-world cohort of patients (pts) in the province of British Columbia (BC), Canada. Methods: The provincial pharmacy database was used to identify pts with resected stage III CRC who received adjuvant CAPOX or FOLFOX between January 2021 and December 2022. Pts with rectal cancer requiring neoadjuvant chemotherapy or radiotherapy were excluded. Demographic, tumor, and treatment information was collected. “High-risk features” were defined as pT4 or pN2 tumors. “Urban” setting was defined based on the population size of the regional health authority. Descriptive statistical analyses were performed to examine baseline characteristics and Fisher’s exact test was used to examine univariate associations. Results: 452 pts were included, of which 234 (52%) and 218 (48%) were planned to receive 3 and 6 mos of ACT respectively (see table). Within the 3 mos group, 226 (97%) received CAPOX. Within the 6 mos group, there was a 51%/49% split between CAPOX/FOLFOX. By univariate analysis, factors associated with 3 mos of CAPOX vs 6 mos of ACT were age >70y (P=0.039), low/intermediate grade (P=0.005) and low-risk stage III disease (P<0.0001). 29% of pts planned for 6 mos of oxaliplatin ACT had low-risk disease, with 52% of these receiving CAPOX. Conclusions: 3 mos of adjuvant CAPOX is an accepted option for nearly all pts with stage III disease with consequent less neurotoxicity and fewer treatment visits. Yet, in this contemporary cohort, use of 3 mos of adjuvant CAPOX remains low and is associated with older age and low-risk disease. 6 mos of oxaliplatin is still being offered to pts with low-risk disease. Exploration of patient preferences, real-world treatment and time toxicities, and resource costs may improve more widespread adoption of 3 mos of adjuvant CAPOX in stage III CRC. [Table: see text]

Safety of early Hartmann reversal during adjuvant chemotherapy in colorectal cancer: a pilot study.

Most patients undergoing the Hartmann procedure for complicated colorectal cancer require chemotherapy because of their advanced status. Stoma created during the procedure is typically closed after the completion of postoperative chemotherapy. However, stomas can induce medical or surgical complications and disturb quality of life. This study aimed to evaluate the safety of Hartmann's reversal during postoperative chemotherapy. We conducted a retrospective review of electronic medical records. Between 2017 and 2021, 96 patients underwent Hartmann reversal for after colorectal cancer surgery. Among them, the number of patients who underwent Hartmann procedure with radical resection of complicated colorectal cancer and Hartmann reversal during adjuvant chemotherapy was 13. The clinical, surgical, and pathological characteristics of the patients were evaluated. Eight and five patients had obstructions and perforations, respectively. Two patients with synchronous liver metastases underwent simultaneous liver resection and reversal simultaneously. Five and eight patients received adjuvant chemotherapy with capecitabine and FOLFOX, respectively. The median interval between the Hartmann procedure and reversal was 3.31 months (2.69-5.59). The median operative time for Hartmann's reversal was 190 min (100-335). The median hospital stay was 10 days (7-21). Four patients (30.8%) developed postoperative complications, and the rate of 3 or higher grade according to the Clavien-Dindo classification within 90 days postoperatively was 0%. Except for 1 patient who refused continuation of chemotherapy, 12 patients completed the planned chemotherapy. Median total duration of adjuvant chemotherapy was 6.78 months (5.98-8.48). There was no mortality. Early Hartmann reversal during adjuvant chemotherapy is tolerable and safe in carefully selected patients. In particular, it can be used as a therapeutic option for patients with complicated colorectal cancer with synchronous resectable metastases.

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.

Is 6 Months the Optimal Duration of Adjuvant Chemotherapy for Pancreatic Cancer?

This study evaluated the relationship between the relative dose intensity (RDI) and the prognosis to assess the optimal duration of adjuvant chemotherapy for pancreatic cancer. From 2013 to 2018, 119 patients with pancreatic cancer underwent radical surgery. After excluding five patients who underwent R2 resection, three with stage IV disease, and two with adjuvant chemotherapy other than S-1, 109 cases were evaluated. They were classified into four groups based on the RDI for the total dosage of S-1: group 1: <50%, group 2: 50% to <80%, group 3: 80% to ≤125%, and group 4: >125%. The number of patients in each group were 48, 20, 30 and 11, with median ages of 74, 73, 66 and 74, respectively. Median estimated glomerular filtration rate was 75, 72, 89 and 77 ml/min/1.73 m2, respectively, demonstrating statistically significant differences. The corresponding median and 5-year overall survival rates were: 378 days and 17.9%; 1,011 days and 35.1%; 1,246 days and 41.6%; 1,389 days and 10.6%. Using group 1 as a reference, the adjusted hazard ratio was 0.39 for group 2, 0.36 for group 3, and 0.30 for group 4; all were statistically significant. The higher the RDI of S-1 in adjuvant chemotherapy, the better the overall survival. Therefore, 1 year of adjuvant chemotherapy with S-1 in pancreatic cancer may be preferable to 6 months.

Effect of duration of adjuvant chemotherapy with S-1 (6 versus 12months) for resected pancreatic cancer: the multicenter clinical randomized phase II postoperative adjuvant chemotherapy S-1 (PACS-1) trial.

Six-month adjuvant chemotherapy with S-1 is standard care for resected pancreatic cancer in Japan; however, the optimal duration has not been established. We aimed to evaluate the impact of duration of adjuvant chemotherapy with S-1. We performed a multicenter, randomized, open-label, phase II study. Patients with histologically proven invasive pancreatic ductal carcinoma, pathological stage I-III, and no local residual or microscopic residual tumor were eligible. Patients were randomized 1:1 to receive 6- or 12-month adjuvant chemotherapy with S-1. The primary endpoint was 2-year overall survival (OS). Secondary endpoints were disease-free survival (DFS) and feasibility. A total of 170 patients were randomized (85 per group); the full analysis set was 82 in both groups. Completion rates were 64.7% (6-month group) and 44.0% (12-month group). Two-year OS was 71.5% (6-month group) and 65.4% (12-month group) (hazard ratio (HR): 1.143; 80% confidence interval CI 0.841-1.553; P = 0.5758). Two-year DFS was 46.4% (6-month group) and 44.9% (12-month group) (HR: 1.069; 95% CI 0.727-1.572; P = 0.6448). In patients who completed the regimen, 2-year DFS was 56.5% (6-month group) and 75.0% (12-month group) (HR: 0.586; 95% CI 0.310-1.105; P = 0.0944). Frequent (≥ 5%) grade ≥ 3 adverse events comprised anorexia (10.5% in the 6-month group) and diarrhea (5.3% vs. 5.1%; 6- vs. 12-month group, respectively). In patients with resected pancreatic cancer, 12-month adjuvant chemotherapy with S-1 was not superior to 6-month therapy regarding OS and DFS.

The Association of Oxaliplatin-Containing Adjuvant Chemotherapy Duration with Overall and Cancer-Specific Mortality in Individuals with Stage III Colon Cancer: A Population-Based Retrospective Cohort Study.

Few studies have examined the relationship between duration of oxaliplatin-containing adjuvant chemotherapy for stage III colon cancer and mortality in routine practice. We examined the association between treatment with 50% versus >85% of a maximal course of adjuvant therapy (eight cycles of CAPOX, twelve cycles of FOLFOX) and mortality in stage III colon cancer. Using linked databases, we identified Ontarians aged ≥18 years at diagnosis of stage III colon cancer between 2007 and 2019. In the primary comparison, we compared patients who received 50% or >85% of a maximal course of adjuvant therapy; in a secondary comparison, we evaluated a dose effect across patients who received FOLFOX in one-cycle increments from six to ten cycles against >85% (more than ten cycles) of a maximal course of FOLFOX. The main outcomes were overall and cancer-specific mortality. Follow-up began 270 days after adjuvant treatment initiation and terminated at the first of the outcome of interest, loss of eligibility for Ontario's Health Insurance Program, or study end. Overlap propensity score weights accounted for baseline between-group differences. We determined the hazard ratio, estimating the association between mortality and treatment. Non-inferiority was concluded in the primary comparison for either outcome if the upper limit of the two-sided 95% CI was ≤1.11, which is the margin used in the International Duration Evaluation of Adjuvant Chemotherapy Collaboration. We included 3546 patients in the analysis of overall mortality; 486 (13.7%) received 50% and 3060 (86.3%) received >85% of a maximal course of therapy. Median follow-up was 5.4 years, and total follow-up was 20,510 person-years. There were 833 deaths. Treatment with 50% of a maximal course of adjuvant therapy was associated with a hazard ratio of 1.13 (95% CI 0.88 to 1.47) for overall mortality and a subdistribution hazard ratio of 1.31 (95% CI 0.91 to 1.87) for cancer-specific mortality versus >85% of a maximal course of therapy. In the secondary comparison, there was a trend toward higher overall mortality in patients treated with shorter durations of therapy, though confidence intervals overlapped considerably. We could not conclude that treatment with 50% of a maximal course is non-inferior to >85% of a maximal course of adjuvant therapy for mortality in stage III colon cancer. Clinicians and patients engaging in decision-making around treatment duration in this context should carefully consider the trade-off between treatment effectiveness and adverse effects of treatment.

Differences in adjuvant chemotherapy and oncological outcomes according to margin status in patients with stage III colon cancer

Background Microscopically positive margins to lymph node metastases (R1LNM) are associated with poorer oncological outcomes in patients with Stage 3 colon cancer. These poorer outcomes were seen despite a greater proportion of these patients receiving adjuvant chemotherapy when compared to those with microscopically negative (R0) margins. We sought to determine if differences in the type or duration of adjuvant chemotherapy could account for the differences in outcomes seen between patients with R0 and R1LNM margins. Methods A multicentre retrospective study including patients undergoing surgery for Stage 3 colon cancer between 2016–2019 at specialist centres. Patients were stratified according to margins status (R0 vs R1LNM). Type/duration of chemotherapy and oncological outcomes were compared between groups. Results 718 patients were included, of whom 100 had R1LNM margins (13.1%). Patients with R1LNM margins had significantly poorer 3-year distant metastases-free (R0 78.2% (95% CI 74.5–81.3) versus R1LNM 58.8% (95% CI 47.2–68.6), p < 0.001) and disease specific survival (R0 88.3% (95% CI 85.2–90.9) versus R1LNM 78.5% (95% CI 68.0–85.8), p < 0.001) when compared to those with R0 margins. No differences were noted in the proportion of patients who completed long-course chemotherapy or were treated with oxaliplatin-based combinations between the R1LNM and R0 groups. Differences in outcomes between R0 and R1LNM groups persisted even when only those patients who completed long-course chemotherapy were compared. Discussion Differences in adjuvant chemotherapy do not appear to account for the poorer oncological outcomes seen in patients with R1LNM margins after surgery for Stage 3 colon cancer. This suggests that adjuvant chemotherapy may be less effective in this patient group. Further studies to elucidate a potential biological basis for this difference are warranted.

Exploratory randomized phase II trial for optimizing treatment dosage and duration of adjuvant S‐1 plus oxaliplatin in patients with stage III colon cancer: YCOG1402 (SOAP trial)

AbstractIntroductionConventionally, the recommended duration of adjuvant chemotherapy of colon cancer had been 6 months. The IDEA Collaboration suggested that shortening capecitabin and oxaliplatin (CAPOX) adjuvant chemotherapy may be possible. S‐1 and oxaliplatin (SOX) treatment is standard treatment in metastatic colorectal cancer in Japan. The aim of this study was to optimize treatment dosage and duration of adjuvant SOX in stage III colon cancer.MethodsThis trial was as open‐label multi‐center randomized phase II study. Patients with stage III colon cancer were randomly assigned to 3 months or 6 months of adjuvant SOX treatment in different doses: 130 mg/m2 (3 months) or 100 mg/m2 (6 months) of oxaliplatin. The primary endpoint was 3‐year disease‐free survival (DFS) and the null hypothesis for the primary endpoint was that the 3‐year DFS was ≤72% in each arm and was tested with a one‐sided significance level of 10%.ResultsEighty‐two patients were assigned to the 6 months arm and 81 to the 3 months arm. The 3‐year DFS was 75.0% (80% CI 67.95–80.72, p = 0.282) in the 6 months arm and 76.9% (80% CI 70.1–82.38, p = 0.171) in the 3 months arm. Treatment completion rate and relative dose intensity (RDI) were higher in 3 months than 6 months arm. The adverse events (AE) were similar in both arms.ConclusionsThe 3‐year DFS was not significantly superior to null hypothesis in both 3 months and 6 months arms for the stage III colon cancer. Primary endpoint was not achieved. The SOX regimen was not feasible in long‐term outcomes.

European Cancer Summit 2022 submission for Quality Cancer Care NetworkVariations in the definition and perceived importance of positive resection margins in patients with colorectal cancer: a survey study

BackgroundMicroscopically positive resection margins (R1) have a well-recognized association with poorer outcomes in patients with colorectal cancer. However, different definitions of positive margins have been proposed and it is currently unclear to what extent these definitions used in everyday clinical practice differ both within and between nations. This study sought to investigate variations in the definition of positive margins in colorectal cancer and the importance of margin status in clinical decision making. MethodsA prospective survey-based study conducted by The European Society of Surgical Oncology (ESSO) Young Surgeons and Alumni Club (EYSAC) Research Academy. A 14-point survey was developed and distributed via social media and ESSO’s newsletter in June 2022. The survey was aimed at any clinician involved in colorectal cancer care. ResultsA total of 120 responses were received, the majority from surgeons (53.3%) and from European nations (89.2%). The most commonly reported definition of positive resection margin was the presence of cancer cells within ≤ 1mm of the margin, although less than 2/3 of respondents use this definition. 23.9% of respondents stated that pathology reports are not routinely reviewed at MDT meetings. Less than half (46.7%) reported that positive margins were a factor used to determine the type and duration of adjuvant chemotherapy, with variations also noted in other histopathological factors such a T stage, N stage and mismatch repair (MMR) status. ConclusionThe results of this survey suggest that significant variations in the definition and perceived clinical importance of positive margins in colorectal cancer exist. Development and acceptance of a uniform definition of positive margins is necessary and further work must be done to incorporate the presence of positive margins into decision making with regard to adjuvant chemotherapy.

Do differences in adjuvant chemotherapy account for poorer oncological outcomes in patients with R1LNM margins after surgery for Stage 3 colon cancer?

Background: Microscopically positive margins to lymph node metastases (R1LNM) have recently been shown to be associated with poorer oncological outcomes in patients with Stage 3 colon cancer. These poorer outcomes were seen despite a greater proportion of these patients receiving adjuvant chemotherapy when compared to those with microscopically negative (R0) margins. We sought to determine if differences in the type or duration of adjuvant chemotherapy could account for the differences in outcomes seen between these two groups.

Effect of Different Durations of Adjuvant Capecitabine Monotherapy on the Outcome of High-Risk Stage II and Stage III Colorectal Cancer: A Retrospective Study Based on a CRC Database.

(1) Background: The duration of adjuvant chemotherapy recommended by the NCCN guidelines is 6 months. However, patients are not compliant with intravenous chemotherapy for many reasons; therefore, one approach is to obtain a survival benefit by prolonging the duration of capecitabine monotherapy. (2) Methods: A total of 355 qualified colorectal cancer (CRC) patients from January 2010 to December 2020 at West China Hospital of Sichuan University were selected to receive capecitabine monotherapy for 6−9 months and >12 months. The main endpoints were overall survival (OS) and disease-free survival (DFS). (3) Results: Among stage III patients, in the >12 months (12M) and 6−9 months (6M) groups, the 5-year DFS rates were 80.7%% and 66.8%, respectively, and the 5-year OS rates were 94.7%% and 88.8%, respectively. Among high-risk stage II patients, in the >12 months (12M) and 6−9 months (6M) groups, the 5-year DFS rates were 81.5% and 78.6%, respectively, and the 5-year OS rates were 93.1% and 84.2%, respectively. (4) Conclusions: Twelve months of chemotherapy demonstrated superior OS and DFS to that of six months in the stage III group but showed no difference in the high-risk stage II group. The better OS and DFS observed in the 12-month treatment period could be of value in selected cases.

Lymphovascular invasion represents a superior prognostic and predictive pathological factor of the duration of adjuvant chemotherapy for stage III colon cancer patients

BackgroundLymphovascular invasion (LVI) and perineural invasion (PNI) can indicate poor survival outcomes in colorectal cancer, but few studies have focused on stage III colon cancer. The current study aimed to confirm the prognostic value of LVI and PNI and identify patients who could benefit from a complete duration of adjuvant chemotherapy based on the two pathological factors.MethodsWe enrolled 402 consecutive patients with stage III colon cancer who received colon tumor resection from November 2007 to June 2016 at Sun Yat-sen University Cancer Center. Survival analyses were performed by using Kaplan–Meier method with log-rank tests. Risk factors related to disease-free survival (DFS) and overall survival (OS) were identified through Cox proportional hazards analysis.Results141 (35.1%) patients presented with LVI, and 108 (26.9%) patients with PNI. The LVI-positive group was associated with poorer 3-year DFS (86.5% vs. 76.3%, P = 0.001) and OS (96.0% vs. 89.1%, P = 0.003) rates compared with the LVI-negative group. The PNI-positive group showed a worse outcome compared with the PNI-negative group in 3-year DFS rate (72.5% vs. 86.7%, P < 0.001). Moreover, LVI-positive group present better 3-year DFS and OS rate in patients completing 6–8 cycles of adjuvant chemotherapy than those less than 6 cycles (3-year DFS: 80.0% vs. 64.9%, P = 0.019; 3-year OS: 93.2% vs. 76.3%, P = 0.002).ConclusionsLVI is a superior prognostic factor to PNI in stage III colon cancer patients undergoing curative treatment. PNI status can noly predict the 3-year DFS wihout affecting the 3-year OS. Furthermore, LVI also represents an effective indicator for adjuvant chemotherapy duration.

Impact of S-1 adjuvant chemotherapy longer than 6months on survival in patients with resected pancreatic cancer: a nationwide survey by the Japan Pancreas Society based on real-world data.

Based on the Japan Adjuvant Study Group of Pancreatic Cancer 01 study, the standard duration of adjuvant chemotherapy with S-1 (an oral 5-fluorouracil prodrug consisting of tegafur, gimeracil, and oteracil) in patients with resected pancreatic ductal adenocarcinoma (PDAC) was considered to be 6months, but the impact of increasing its duration on postoperative survival was unknown. Here, the authors investigated this question by reviewing real-world data from a large cohort of patients with PDAC. In total, 3949 patients who underwent surgery for PDAC during the study period followed by S-1 adjuvant chemotherapy in board-certified institutions were included. Based on the duration of S-1 chemotherapy, two subgroups were defined: a standard-duration group that included patients who were treated for 180±30days and a longer duration group that included patients who received treatment for >210days. The median duration of S-1 chemotherapy was 167days, with a mean±standard deviation of 200±193days. After excluding patients who had a recurrence within 210days after the initiation of adjuvant chemotherapy, postoperative recurrence-free survival (RFS) and overall survival (OS) in the standard-duration group (n=1473) and the longer duration group (n=975) were compared. RFS and OS did not differ significantly between the standard-duration and longer duration groups (5-year RFS: 37.8% vs. 36.2% respectively; p=.6186; 5-year OS: 52.8% vs. 53.4%, respectively; p=.5850). The insignificant difference was verified by multivariate analysis and propensity-score matching analysis. The current findings suggest that extending S-1 adjuvant chemotherapy beyond 6months has no significant additional effect on survival in patients with PDAC. This could be useful in determining whether to extend S-1 chemotherapy in patients who have completed the standard 6-month treatment.

The Impact of Colon Cancer Sites on Survival Rates after Curative Resection and Adjuvant Chemotherapy: A SingleCenter Study

Background: Most recent studies indicate that right-sided colon cancer is associated with a significantly higher mortality rate. Multivariate analyses showed that the patient’s age, sex, mode of presentation, co-morbidity, and the stage had significantly influenced their survival. Although the primary tumor location has an impact on the overall survival in metastatic settings, the laterality of early-stage colon cancer might also affect the disease-free survival and determine the duration of adjuvant chemotherapy for each side. This study aimed to compare overall survival and disease-free survival between left-sided and right-sided high-risk stage II and stage III colon cancer in patients from a single institute. Methods: This retrospective cohort study was conducted between January 2004 and December 2017. Data on 153 patients who underwent curative resection and adjuvant chemotherapy for colon cancer were retrieved from an existing database. Results: We found that the five-year disease-free survival rates were 63.20% for left-sided colon cancer and 51.11% for right-sided colon cancer (P-value &lt; 0.05). The five-year overall survival rates were 66.98% for left-sided colon cancer and 57.77% for right-sided colon cancer (P-value 0.063). The right-sided primary tumor location was associated with a significantly higher mortality rate (HR: 2.28; 95%CI 1.38–5.8; P-value: 0.004). Conclusion: The results of this study confirmed that patients with high-risk stage II and stage III colon cancer who had right-sided tumors were significantly more likely to have decreased disease-free survival and overall survival. Further prospective studies should focus on tumor genetics and proper durations of adjuvant chemotherapy to maximize the benefit of treatment with acceptable toxicity.

Analysis of treatment outcomes according to the cycles of adjuvant chemotherapy in gastric cancer: a retrospective nationwide cohort study

BackgroundOne-year S-1 or six-month capecitabine/oxaliplatin (CAPOX) has been the standard adjuvant chemotherapy for gastric cancer (GC). We investigated outcomes according to the cycles of adjuvant chemotherapy, using data from the Korean Health Insurance and Assessment Service.MethodsA total of 20,552 patients, including 13,614 patients who received S-1 and 6,938 patients who received CAPOX extracted from 558,442 patients were retrospectively analyzed. The five-year overall survival rate was evaluated according to the duration of adjuvant chemotherapy.ResultsThe five-year overall survival rate gradually increased according to the increase in adjuvant chemotherapy cycles in both the S-1 (≤ 5 cycles: 48.4%, hazard ratio [HR] 4.06, 95% confidence interval [CI] 3.74–4.40, P < 0.0001; 5 < cycles ≤ 6: 55.4%, HR 3.08, 95% CI 2.65–3.57, P < 0.0001; 6 < cycles ≤ 7: 64.1%, HR 2.11, 95% CI 1.84–2.41, P < 0.0001; 7 < cycles < 8: 71.1%, HR 1.60, 95% CI 1.39–1.84, P < 0.0001; ≥ 8 cycles: 77.9%) and the CAPOX groups (≤ 4 cycles: 43.5%, HR 3.20, 95% CI 2.84–3.61, P < 0.0001; 5 cycles: 45.3%, HR 2.63, 95% CI 2.11–3.27, P < 0.0001; 6 cycles: 47.1%, HR 2.09, 95% CI 1.76–2.49, P < 0.0001; 7 cycles: 55.3%, HR 1.63, 95% CI 1.35–1.96, P < 0.0001; ≥ 8 cycles: 67.2%).ConclusionsReducing the treatment cycles of adjuvant chemotherapy in GC with S-1 or CAPOX showed inferior survival outcomes. Completing the standard duration of adjuvant chemotherapy with S-1 or CAPOX would be strongly recommended.

329P Duration of adjuvant therapy in stage III colon cancer: A real world multi-institutional US-based experience

Since the publication of IDEA, the duration of adjuvant chemotherapy (CTX) in stage III colon cancer (CC) has shifted to a risk-stratified approach as 3 months (mo) of CAPOX vs 6 mo was found to be non-inferior in patients (pts) with low risk (LR) (T1-T3/N0-N1). High risk (HiR) (T4 or N2) disease failed to show non-inferiority, however 3-year DFS differences were less than 2% and only .1% when pts received CAPOX. However in the US cohort, pts did not receive CAPOX, possibly due to capecitabine intolerance. Herein, we performed a real-world evaluation of CTX in US pts with stage III CC. A retrospective review of stage III CC pts treated from 2016-2022 from 5 US academic medical institutions was performed. Pts were stratified into 3mo vs 6mo of CTX, HiR vs LR, and CAPOX vs FOLFOX. 3-year DFS and adverse events were recorded. A total of 443 pts were included. In the overall population, no difference in 3-year DFS was observed in 3 vs 6 mo of CTX (69.3 vs 71.0%, hazard ratio [HR] = 1.26, 95% CI (0.74, 2.17), adjusted p [aP] = 0.40), numerically less than was observed in IDEA. HiR pts were observed to have detriment in 3-year DFS with 3mo vs. 6mo CTX (34.0% vs 62.9%, HR = 1.51, 95% CI (0.77, 2.99), aP=0.23). Grade 3 adverse events (AE) of nausea, diarrhea, and hand/foot syndrome from capecitabine were higher than reported in IDEA.Table: 329PDFS by treatment, duration and riskCTXN (Events)36 Months DFS6 mo FOLFOX255 (76)71.8%6 mo CAPOX54 (17)67.5%3 mo FOLFOX37 (9)68.8%3 mo CAPOX97 (16)69.4%HiR vs LR6 mo LR126 (23)82.3%6 mo HiR183 (70)62.9%3 mo LR102 (13)81.2%3 mo HiR32 (12)34.0% Open table in a new tab In this real-world experience we observed no DFS benefit in pts treated with 3 vs 6mo CTX. In HiR pts treated with 3mo CTX, we observed a lower 3-year DFS rate compared to 6mo of CTX. The findings were not statistically significant due to low number of events in this cohort and was significantly lower than reported in IDEA. AEs were more prevalent in US pts compared to non-US pts in IDEA, likely due to capecitabine intolerance. Our study is the first to assess 3mo vs 6mo capecitabine based adjuvant CTX in a risk stratified US population and suggests discrepancies in DFS and AEs compared to IDEA in US pts who received CAPOX.

Conversion of non-inferiority margin from hazard ratio to restricted mean survival time difference using data from multiple historical trials.

The restricted mean survival time measure has gained a lot of interests for designing and analyzing oncology trials with time-to-event endpoints due to its intuitive clinical interpretation and potentially high statistical power. In the non-inferiority trial literature, restricted mean survival time has been used as an alternative measure for reanalyzing a completed trial, which was originally designed and analyzed based on traditional proportional hazard model. However, the reanalysis procedure requires a conversion from the non-inferiority margin measured in hazard ratio to a non-inferiority margin measured by restricted mean survival time difference. An existing conversion method assumes a Weibull distribution for the population survival time of the historical active control group under the proportional hazard assumption using data from a single trial. In this article, we develop a methodology for non-inferiority margin conversion when data from multiple historical active control studies are available, and introduce a Kaplan-Meier estimator-based method for the non-inferiority margin conversion to relax the parametric assumption. We report extensive simulation studies to examine the performances of proposed methods under the Weibull data generative models and a piecewise-exponential data generative model that mimic the tumor recurrence and survival characteristics of advanced colon cancer. This work is motivated to achieve non-inferiority margin conversion, using historical patient-level data from a large colon cancer clinical database, to reanalyze an internationally collaborated non-inferiority study that evaluates 6-month versus 3-month duration of adjuvant chemotherapy in stage III colon cancer patients.

MO1055: Effect of Duration of Adjuvant Chemotherapy for Patients with Colorectal Cancer on the Deterioration of Glomerular Filtration Rate

Abstract BACKGROUND AND AIMS Six-month adjuvant chemotherapy (CTH) is the current standard of care in locally advanced colorectal cancer (CRC). Recent studies have shown that shortening the treatment to 3 months results in moderately worse (0%–4% difference) overall survival. A longer duration of CTH may pose a risk of nephrotoxicity. We aimed to assess the effect of the duration of adjuvant CTH for CRC on kidney excretory function. METHOD We retrospectively studied medical records of 96 patients aged 38–83 (51% males) treated with adjuvant CTH for CRC. Patients underwent CTH either with regimens containing oxaliplatin and 5-fluorouracil/capecitabine (FOLFOX—31.3%; or XELOX—18.8%) or regimens containing 5-fluorouracil only (5-FU/LV; 50%). Glomerular filtration rate (calculated with the CKD-EPI formula) was analysed in three time points: before CTH, after 3 and 6 months of therapy. The deterioration of eGFR by 1.5 mL/min/1.73 m2 or more after 3 months and by 3 mL/min/1.73 m2 or more after 6 months was considered clinically significant. RESULTS We observed a clinically significant loss of eGFR after 3 months in 56.3% of patients. The risk of eGFR loss after 3 months was not related to gender, CTH regimen, clinical stage, initially low eGFR or comorbidities (P &amp;gt; 0.05). However, the clinically significant loss of eGFR was related to age (mean age 65.1 versus 61.3 years without eGFR loss; P = 0.03). Two-thirds (66.8%) of all patients were assessed in a 6-month time point. In this group, a significant eGFR loss was present in 42.4% of cases. Similarly, eGFR deterioration after 6 months was not related to proposed risk factors such as gender, CTH regimen type, clinical stage, low eGFR or comorbidities (P &amp;lt; 0.05), but was associated with age (mean age 66.3 versus 60.9 years without eGFR loss; P = 0.04). We observed a significant deterioration of eGFR more frequently in patients treated with 5-FU/LV regimens than with FOLFOX or XELOX (P = 0.03). However, patients, who underwent CTH with 5-FU/LV were older (P &amp;lt; 0.001), had lower initial eGFR (P = 0.02) and had hypertension more often (P = 0.03) than patients treated with oxaliplatin-containing regimens. In 92.9% of patients with significant eGFR loss after 6 months, we were able to observe rapid eGFR loss earlier, in a 3-month time point. However, one-third (31.6%) of patients with significant eGFR loss after 3 months did not present it after 6 months (P &amp;lt; 0.001). In patients with significant loss after 3 months, further deterioration after the next 3-month period occurred in 8 cases (21.1%), with a mean loss of 7.7 mL/min/1.73 m2. CONCLUSION Adjuvant CTH for CRC may cause a rapid loss of eGFR. The assessment of eGFR after 3 months of CTH is a predictor of further eGFR decline. Further investigation is needed to conclude if the shortage of CTH duration from 6 to 3 months may be beneficial for older patients in the context of nephrotoxicity.

Cancer Trial Impact: Understanding Implementation of the Short Course Oncology Treatment (SCOT) Trial Findings in colorectal cancer at a National Level

AimsThe Short Course Oncology Treatment (SCOT) trial indicated that 3 months of adjuvant doublet chemotherapy was non-inferior to 6 months of treatment for patients with colorectal cancer, with considerably less toxicity. The SCOT trial results were disseminated in June 2017. The aim of this study was to understand if SCOT trial findings were implemented in Scotland. Materials and methodsA retrospective analysis was carried out on a dataset derived from a source population of 5.4 million people. Eligible patients were those with stage II or III colorectal cancer who received adjuvant chemotherapy. Logistic regression was applied to understand the extent of practice change to a 3-month adjuvant chemotherapy duration after the SCOT trial results were disseminated. Interrupted time series analysis was used to visualise differences in prescribing trends before and after June 2017 for the overall cohort, and by SCOT trial eligibility. ResultsIn total, 2310 patients were included in the study; 1957 and 353 treated pre- and post-June 2017, respectively. The median treatment duration decreased from 21 weeks (interquartile range 14–24) prior to June 2017 to 12 weeks (interquartile range 12–21 weeks) after June 2017 (P < 0.001). The proportion of patients receiving over 3 months of adjuvant treatment decreased from 75% to 42% (P < 0.001). This change was most noticeable for patients who met the SCOT trial eligibility criteria, and specifically for those with low-risk stage III disease and those treated with capecitabine and oxaliplatin (CAPOX). Although practice change occurred in all locations, there were differences between regions that could be explained by pre-SCOT trial prescribing trends. DiscussionA significant change in chemotherapy prescribing occurred after dissemination of the SCOT trial results. National, real-world data can be used to capture the extent of implementation of clinical trial results. In this case, implementation was aligned with clinical trial subgroup findings. This type of analysis could be conducted to evaluate the impact of other clinical trials.