Adjuvant Chemotherapy For Colorectal Cancer Research Articles

Individualized tumor-informed circulating tumor DNA analysis for molecular residual disease detection in predicting recurrence and efficacy of adjuvant chemotherapy in colorectal cancer.

3615 Background: Molecular residual disease (MRD) using circulating tumor DNA (ctDNA) may identify recurrent risk and guide adjuvant chemotherapy (ACT) in colorectal cancer (CRC). This study explored the feasibility of a tumor-informed personalized approach to predict recurrence, comparing with tumor-informed (TI) and tumor naïve (TN) fixed panel approaches. Methods: Patients with stage I-IV CRC eligible for R0 resection were recruited. Blood samples were collected preoperatively, at postoperative day 7 and 30 (POD7/30), and every 3-6 months thereafter, which were tested by brPROPHET assay, using up to 50 highly ranked variants identified by whole-exome sequencing of surgical tissue samples. A fixed 168-gene panel was applied for TI and TN fixed panel tests. Results: A total of 214 patients were enrolled. With a median follow-up of 13.2 months, 20 (9.3%) participants relapsed. The brPROPHET assay had a positivity rate of 96% in preoperative samples. ctDNA positivity indicated by brPROPHET predicted worse recurrence-free survival (RFS) at both POD7 (hazard ratio [HR]=7.35, 95% confidence interval [95% CI], 3.04-17.78, P<0.001) and POD30 (HR=5.18, 95% CI, 2.00-13.38, P<0.001). Higher mean tumor molecules (MTM) level >0.0316/mL was observed in surveillance of 15 relapsed patients, which was associated with worse RFS (HR=44.47, 95% CI, 12.83-154.12, P<0.001). In ctDNA positive patients at POD7, patients benefit from ACT (HR=0.23, 95% CI, 0.05-1.00, P=0.03), which was not observed in ctDNA negative patients (HR=1.80, 95% CI, 0.48-6.81, P=0.38). Among the patients with results of all three approaches (n=168), the brPROPHET assay outperformed TI and TN fixed-panel assays in predicting RFS at POD7 (HR, 7.52 vs 3.43 and 5.60). Of note, the brPROPHET assay identified 6 additional relapsed patients beyond the fixed panels, with more than 87.5% of the positive sites derived from personalized designs. Conclusions: The individualized tumor-informed brPROPHET assay effectively identified postoperative patients with high risk of recurrence and benefit from ACT. Using a personalized tumor-informed panel that covers sites outside fixed panels may improve the utility of MRD detection. [Table: see text]

New drugs to prevent oxaliplatin-induced peripheral neuropathy: A double-blind, randomized study.

3568 Background: Postoperative adjuvant chemotherapy for colorectal cancer reduces postoperative recurrence; however, it often causes undesirable adverse events. Oxaliplatin, the mainstay of postoperative adjuvant chemotherapy is particularly likely to cause chemotherapy-induced peripheral neuropathy (CIPN) and hypersensitivity reactions (HSR) that may make it difficult to continue treatment. Various agents have been tested for prevention or treatment of CIPN caused by oxaliplatin, but none have proven effective. Reactive oxygen species contribute oxaliplatin-induced PN; therefore, super oxide dismutase (SOD) could potentially suppress them, but its very short serum half-life has made clinical application difficult. We developed a lecithinized human copper/zinc SOD (Cu/Zn-SOD) (PC-SOD) in which four phosphatidylcholine derivative molecules are bound covalently to each SOD dimer. Compared with SOD, PC-SOD enhanced stability in plasma and stronger tissue affinity, and exerts therapeutic effects in animal models of several diseases, including CIPN. Methods: This double-blind, randomized study included 90 patients with stage II/III colorectal cancer. All patients were slated to receive 12 cycles of mFOLFOX6. In each cycle, patients received PC-SOD or a placebo immediately before oxaliplatin. The primary endpoint of this study was the number of cycles before NCI-CTCAE Grade 2 (G2) CIPN occurred. One of the secondary endpoints was the number of cycles before DEB-NTC G2 PN occurred. Results: Forty-three patients received PC-SOD. No serious adverse events were observed that could be related to PC-SOD. The incidence of neutropenia, diarrhea, stomatitis, and malaise were lower in the study group, but the differences were not significant. Additionally, 3 patients (7.0%) in the study group and 11 (23.4%) in the placebo group had HSR. Although there was no difference in the number of cycles between the two groups until NCI-CTCAE G2 PN occurred, the study group had a significantly greater number of cycles before DEB-NTC G2 PN compared to the placebo group (P=0.08). The study group had a significantly greater number of cycles before NCI-CTC G1 PN (P=0.01) and HSR (P=0.03) compared to the placebo group. The number of cycles before HSR or NCI-CTCAE G2 PN occurred was greater in the study group , but the difference was not significant. The average total oxaliplatin dose was higher in the study group but the difference was not statistically significant. Conclusions: The primary endpoint did not occur; however, the study group had a significantly greater number of cycles before DEB-NTC G2 PN. Notably, the study group also had a significantly greater number of cycles before HSR. These results show that PC-SOD may suppress HSR as well as PN, both of which limit administration of oxaliplatin. Thus, this drug is expected to improve not only patient quality of life, but also the prognosis of patients. Clinical trial information: 2031210466.

An expatiate review on adjuvant chemotherapy of colorectal cancer

Colorectal cancer is the second leading cause of cancer-related death and the third most common cancer globally. For loco regional colon cancer, surgery is the sole curative option. Adjuvant chemotherapy aims to eliminate micro metastases and increase survival. It has been most convincingly proven in stage III illness, even though there is ongoing debate on the usefulness of adjuvant chemotherapy for stage II illness. For the past fifteen years, six months of adjuvant chemotherapy with an oxaliplatin-based chemotherapy has been the accepted standard of care for stage III colon cancer. It is still advised to use 6 months of adjuvant chemotherapy for individuals with stage II illness and high clinicopathological risk. Chemo radiation therapy (CRT) is frequently used as neoadjuvant or adjuvant therapy in the treatment of stage II and stage III rectal cancers because this cancer type has a higher risk of local recurrence than other cancer types.

Low skeletal muscle radiodensity is a risk factor for adjuvant chemotherapy discontinuation in colorectal cancer.

Previously, we reported SMR (skeletal muscle radiodensity) as a potential prognostic marker for colorectal cancer. However, there have been limited studies on the association between SMR and the continuation of adjuvant chemotherapy in colorectal cancer. In this retrospective study, 143 colorectal cancer patients underwent curative surgery and adjuvant chemotherapy using the CAPOX regimen. Patients' SMRs were measured from preoperative CT images and divided into low (bottom quarter) and high (top three quarters) SMR groups. We compared chemotherapy cycles, capecitabine and oxaliplatin doses, and adverse effects in each group. The low SMR group had significantly fewer patients completing adjuvant chemotherapy compared to the high SMR group (44% vs. 68%, P < 0.01). Capecitabine and oxaliplatin doses were also lower in the low SMR group. Incidences of Grade 2 or Grade 3 adverse effects did not differ between groups, but treatment discontinuation due to adverse effects was significantly higher in the low SMR group. Logistic regression analysis revealed Stage III disease (odds ratio 18.09, 95% CI 1.41-231.55) and low SMR (odds ratio 3.26, 95% CI 1.11-9.56) as factors associated with unsuccessful treatment completion. Additionally, a higher proportion of low SMR patients received fewer than 2 cycles of chemotherapy (50% vs. 12%). The low SMR group showed higher treatment incompletion rates and received lower drug doses during adjuvant chemotherapy. Low SMR independently contributed to treatment non-completion in colorectal cancer patients.

Effects of tumour budding on adjuvant chemotherapy in colorectal cancer.

High tumour budding has been indicated as a risk factor of poor survival in colorectal cancer. This study aimed to investigate the impact of tumour budding grades and the use of adjuvant chemotherapy on prognosis in patients with colorectal cancer. This study included consecutive colorectal cancer patients who underwent radical surgery for primary colorectal adenocarcinoma at The Sixth Hospital of Sun Yat-sen University between 2009 and 2019. Tumour budding was assessed based on the recommendations of the International Tumor Budding Consensus Conference using haematoxylin and eosin (H&E)-stained slides with tumour samples. The primary outcome of interest was to correlate tumour budding with disease-free survival and overall survival; the secondary outcome was investigation of the impact of adjuvant therapy on different tumour budding grades. In addition, a subgroup analysis was performed for the effects of lymphocytic infiltration on adjuvant chemotherapy in patients with Bd3. Of 709 eligible patients, 412 with colorectal cancer were included. According to the International Tumor Budding Consensus Conference, 210 (50.9 per cent), 127 (30.8 per cent) and 75 (18.2 per cent) were classified as low budding (Bd1), intermediate budding (Bd2) and high budding (Bd3) respectively. Patients with Bd1, Bd2 and Bd3 had 5-year disease-free survival rates of 82.9 per cent, 70.1 per cent and 49.3 per cent respectively, and 5-year overall survival rates of 90 per cent, 79.5 per cent and 62.7 per cent respectively (P <0.001). Adjuvant chemotherapy yielded a significant survival benefit in patients with Bd3 (5-year disease-free survival, 65 per cent versus 31.4 per cent, P <0.001; 5-year overall survival, 84.4 per cent versus 63.1 per cent, P <0.001), but not in those with Bd1 or Bd2. In patients with Bd3, the benefit of adjuvant chemotherapy was maintained in those with low, but not high lymphocytic infiltration. High grade of tumour budding was strongly correlated with poorer survival outcomes in colorectal cancer. Patients with Bd3 benefited from adjuvant chemotherapy, with the exclusion of patients with high lymphocytic infiltration.

PTEN-induced kinase 1 gene single-nucleotide variants as biomarkers in adjuvant chemotherapy for colorectal cancer: a retrospective study

BackgroundFluoropyrimidine-based postoperative adjuvant chemotherapy is globally recommended for high-risk stage II and stage III colon cancer. However, adjuvant chemotherapy is often associated with severe adverse events and is not highly effective in preventing recurrence. Therefore, discovery of novel molecular biomarkers of postoperative adjuvant chemotherapy to identify patients at increased risk of recurrent colorectal cancer is warranted. Autophagy (including mitophagy) is activated under chemotherapy-induced stress and contributes to chemotherapy resistance. Expression of autophagy-related genes and their single-nucleotide polymorphisms are reported to be effective predictors of chemotherapy response in some cancers. Our goal was to evaluate the relationship between single-nucleotide variants of autophagy-related genes and recurrence rates in order to identify novel biomarkers that predict the effect of adjuvant chemotherapy in colorectal cancer. MethodsWe analyzed surgical or biopsy specimens from 84 patients who underwent radical surgery followed by fluoropyrimidine-based adjuvant chemotherapy at Saitama Medical University International Medical Center between January and December 2016. Using targeted enrichment sequencing, we identified single-nucleotide variants and insertions/deletions in 50 genes, including autophagy-related genes, and examined their association with colorectal cancer recurrence rates.ResultsWe detected 560 single-nucleotide variants and insertions/deletions in the target region. The results of Fisher’s exact test indicated that the recurrence rate of colorectal cancer after adjuvant chemotherapy was significantly lower in patients with the single-nucleotide variants (c.1018G > A [p < 0.005] or c.1562A > C [p < 0.01]) of the mitophagy-related gene PTEN-induced kinase 1.ConclusionsThe two single-nucleotide variants of PINK1 gene may be biomarkers of non-recurrence in colorectal cancer patients who received postoperative adjuvant chemotherapy.

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.

Circulating Tumor DNA as a Minimal Residual Disease Assessment and Recurrence Risk in Patients Undergoing Curative-Intent Resection with or without Adjuvant Chemotherapy in Colorectal Cancer: A Systematic Review and Meta-Analysis.

Emerging data have suggested that circulating tumor DNA (ctDNA) can be a reliable biomarker for minimal residual disease (MRD) in CRC patients. Recent studies have shown that the ability to detect MRD using ctDNA assay after curative-intent surgery will change how to assess the recurrence risk and patient selection for adjuvant chemotherapy. We performed a meta-analysis of post-operative ctDNA in stage I-IV (oligometastatic) CRC patients after curative-intent resection. We included 23 studies representing 3568 patients with evaluable ctDNA in CRC patient post-curative-intent surgery. Data were extracted from each study to perform a meta-analysis using RevMan 5.4. software. Subsequent subgroup analysis was performed for stages I-III and oligometastatic stage IV CRC patients. Results showed that the pooled hazard ratio (HR) for recurrence-free survival (RFS) in post-surgical ctDNA-positive versus -negative patients in all stages was 7.27 (95% CI 5.49-9.62), p < 0.00001. Subgroup analysis revealed pooled HRs of 8.14 (95% CI 5.60-11.82) and 4.83 (95% CI 3.64-6.39) for stages I-III and IV CRC, respectively. The pooled HR for RFS in post-adjuvant chemotherapy ctDNA-positive versus -negative patients in all stages was 10.59 (95% CI 5.59-20.06), p < 0.00001. Circulating tumor DNA (ctDNA) analysis has revolutionized non-invasive cancer diagnostics and monitoring, with two primary forms of analysis emerging: tumor-informed techniques and tumor-agnostic or tumor-naive techniques. Tumor-informed methods involve the initial identification of somatic mutations in tumor tissue, followed by the targeted sequencing of plasma DNA using a personalized assay. In contrast, the tumor-agnostic approach performs ctDNA analysis without prior knowledge of the patient's tumor tissue molecular profile. This review highlights the distinctive features and implications of each approach. Tumor-informed techniques enable the precise monitoring of known tumor-specific mutations, leveraging the sensitivity and specificity of ctDNA detection. Conversely, the tumor-agnostic approach allows for a broader genetic and epigenetic analysis, potentially revealing novel alterations and enhancing our understanding of tumor heterogeneity. Both approaches have significant implications for personalized medicine and improved patient outcomes in the field of oncology. The subgroup analysis based on the ctDNA method showed pooled HRs of 8.66 (95% CI 6.38-11.75) and 3.76 (95% CI 2.58-5.48) for tumor-informed and tumor-agnostic, respectively. Our analysis emphasizes that post-operative ctDNA is a strong prognostic marker of RFS. Based on our results, ctDNA can be a significant and independent predictor of RFS. This real-time assessment of treatment benefits using ctDNA can be used as a surrogate endpoint for the development of novel drugs in the adjuvant setting.

China special issue on gastrointestinal tumor: Regulatory-immunoscore-A novel indicator to guide precision adjuvant chemotherapy in colorectal cancer.

Novel biomarkers are essential to improve the treatment efficacy and overall survival of stage II and III colorectal cancer (CRC), allowing for personalized treatment decisions. Here, the densities of CD8+ and FOXP3+ T cells in the tumor and invasive margin were processed by immunohistochemistry and digital pathology to form a scoring system named regulatory-Immunoscore (RIS). Cox proportional hazards regression models were used to determine the risk factors associated with time to recurrence. Harrell's concordance index and the time-dependent area under the curve were used to assess model performance. A total of 1213 stage I-III DNA mismatch repair-proficient colorectal cancer (pMMR CRC) patients were randomly assigned to a training set (n = 642) and a validation set (n = 571). From the Cox multivariable analysis, the association of RIS with survival was independent of patient age, sex and anatomy-based tumor risk parameters (P < .0001). For stage II patients, chemotherapy was significantly associated with better recurrence time in patients with low (95% confidence interval [CI]: 0.11-0.54, P = .001) and intermediate (95% CI = 0.25-0.57, P < .001) RIS values. In stage III patients treated with adjuvant chemotherapy, a treatment duration of 6 or more months was significantly associated with better recurrence time in patients with intermediate RIS values (95% CI = 0.38-0.90, P = .016) when compared with duration under 6 months. Therefore, these findings suggest that RIS is reliable for predicting recurrence risk and treatment responsiveness for patients with stage I-III pMMR CRC.

LEANOX: Lean body mass normalization of oxaliplatin-based chemotherapy for patients with stage III colon cancer treated in adjuvant setting: Impact on oxaliplatin-induced sensitive neurotoxicity—A multicenter phase II randomized trial.

92 Background: Adjuvant chemotherapy is the current worldwide standard of care for stage III colorectal cancer (CRC) but it leads to significant neurotoxicity. We have shown in 2 cohorts of CRC patients treated with Oxaliplatin (Ox) that Ox-due neuropathy occurred in patients receiving an excess of 3.09 mg Ox/ kg Lean Body Mass (LBM). The aim of this trial was to determine whether the Ox dose adaptation based on the LBM index can reduce neurotoxicity, in patients treated for a stage III CRC. Methods: LEANOX is a randomized phase II multicentre study in patients eligible for an Ox regimen as adjuvant chemotherapy for CRC. Patients without sarcopenia (LBM index &lt;3.09mg/kg, group 1) received a dosage of Ox according to Body Surface Area (BSA) (85 mg/m²).Patients with sarcopenia (LBM index ≥3.09mg/kg) were randomized in 2 groups, group 2: dosage of Ox according to BSA (similar to group 1) and group 3: a dosage of Ox according to LBM (3.09 mg Ox/ kg LBM). Randomization (1:1) was stratified by center, age and weight loss. The primary endpoint was the percentage of patients without grade ≥2 neurotoxicity during the first 6 cycles of adjuvant Ox-based chemotherapy. The study required 108 randomized patients (bilateral α=0.05, 80% power) to compare the primary endpoint between groups 2 and 3 with P2=55% and P3=80%. Secondary endpoints included time to onset of grade≥2 chronic cumulative neurotoxicity, duration of the chronic cumulative neurotoxicity, cumulative Ox doses that can be delivered without reaching the dose-limiting chronic neurotoxicity, tolerance, disease free survival, overall survival and quality of life. Results: A total of 160 patients were included in 18 french centers: 33 in group 1, 64 in group 2 and 63 in group 3. Median age was 63 years, 52.5 % male, 89.3 % OMS 0 and tumoral stage was T3 (57.5%), T4 (33.8%), N1 (60.6%) and N2 (38.1%). Grade 3-4 AE events occurred in 58.0% in group 2 and 59.7% in group 3. The percentage of patients without experiencing grade ≥ 2 of neurotoxicity during the first 6 cycles of adjuvant Ox-based chemotherapy was 43.9% in group 2 vs 67.2% in group 3 (p=0.01). Conclusions: We wish to avoid severe adverse reactions to Ox regimen by personalization of cancer chemotherapy. Clinical trial information: NCT03255434 .

Adjuvant Capecitabine and Oxaliplatin for Elderly Patients with Colorectal Cancer

Introduction: Adjuvant chemotherapy improves the prognosis of patients with colorectal cancer (CRC) following radical resection. However, the safety and efficacy of oxaliplatin-based chemotherapeutic regimens for elderly patients remains to be elucidated. The aim of the present study was to examine the tolerability and efficacy of adjuvant CAPOX (capecitabine and oxaliplatin) therapy for elderly patients in comparison with young patients. Methods: We examined 138 Japanese patients who received adjuvant CAPOX therapy for high-risk stage II or III CRC between July 2010 and June 2021 at our hospital. Patients were divided according to an age of 70 years. Treatment details of CAPOX therapy were analyzed in association with age. Moreover, prognosis of stage III CRC was compared between the patient groups. Results: Twenty-three patients (17%) were ≥70 years old. Male patients were predominant in the ≥70 years group (p = 0.006). Patients ≥70 years old had more comorbidities (diabetes, p = 0.014; cardiovascular disease, p < 0.001; renal disease, p = 0.042) than patients <70 years old. There were no age-dependent differences in dose intensity, the number of cycles, or DLTs of CAPOX therapy. CSS and RFS were also similar between the ≥70 and <70 years old patients with stage III CRC. Conclusions: Adjuvant CAPOX therapy was tolerable in elderly Japanese patients. The prognosis of elderly patients with stage III CRC was similar to that of their younger counterparts. Advanced age itself may not be a contraindication for adjuvant chemotherapy in CRC. Future studies with a larger patient cohort are required to confirm the present results.

Diverting ileostomy is a risk factor for renal impairment during CAPOX therapy.

Temporary ileostomy is sometimes created after colorectal surgery and may cause renal impairment. However, the impact of ileostomy on renal function during adjuvant chemotherapy for colorectal cancer (CRC) remains unknown. The aim of the present study was to examine the effects of ileostomy on renal function during adjuvant chemotherapy. We examined 184 patients who received adjuvant CAPOX therapy (capecitabine and oxaliplatin) for CRC with or without ileostomy between January 2011 and December 2020 at the University of Tokyo Hospital. Clinicopathological factors, including renal function, were retrospectively reviewed in association with temporary ileostomy. Factors associated with reductions in the estimated glomerular filtration rate (eGFR) during CAPOX therapy were analyzed. Eighteen patients (10%) underwent temporary ileostomy. The maximum decrease in eGFR during CAPOX therapy was significantly higher in patients with than in those without ileostomy (-16.1 vs. -5.6mL/min/1.73m2, p = 0.003). A multivariate analysis identified ileostomy as one of factors independently associated with reductions in eGFR during CAPOX therapy (p = 0.003). The cumulative number of readmission due to dehydration was also higher in patients with ileostomy (33% vs. 1%, p < 0.001). Ileostomy significantly reduced eGFR during adjuvant CAPOX therapy. Therefore, renal function needs to be monitored during CAPOX therapy, particularly in patients with ileostomy.

Exploratory study on relative dose intensity and reasons for dose reduction of adjuvant CAPOX therapy in elderly patients with colorectal cancer.

Capecitabine plus oxaliplatin, CAPOX, therapy is one of the standardized options for adjuvant chemotherapy for colorectal cancer, but the efficacy and the safety of CAPOX in elderly patients are unclear. In this study, we investigated the relative dose intensity (RDI) and reasons for dose reduction in patients over the age of 70 (elderly group) (n = 12) and those under the age of 70 (non-elderly group) (n = 24) receiving adjuvant CAPOX therapy for colorectal cancer. The median RDIs were 71.1% in the elderly group and 67.9% in the non-elderly group for oxaliplatin (p = 0.416), and 81.6% and 86.4% for capecitabine (p = 0.166), respectively. The rate of peripheral neuropathy which was the reason for dose reduction of oxaliplatin was approximately 4.5-fold higher in the non-elderly group than in the elderly group. In addition, hematologic toxicity was the most common reason for dose reduction at 50.0% in the elderly group. The results of this study suggested that a similar therapeutic intensity can be maintained in elderly patients relative to non-elderly patients by appropriate dose reduction and discontinuation of drug treatments. Elderly patients are more susceptible to hematologic toxicity than to peripheral neuropathy.

Circulating tumor DNA (ctDNA) as a minimal residual disease (MRD) assessment and recurrence risk in patients undergoing curative intent resection with or without adjuvant chemotherapy in colorectal cancer: A systematic review and meta-analysis.

3623 Background: Minimal residual disease (MRD) assessment may effectively detect cure in patients with colorectal cancer (CRC). Emerging data have suggested that circulating tumor DNA (ctDNA) can be a reliable biomarker for MRD in patients. Recent studies have shown the ability to detect MRD using ctDNA assay to assess recurrence risk and patient selection for adjuvant chemotherapy. We performed a systematic review and metanalysis of post operative ctDNA in Stage I-IV (oligometastatic) CRC patients after curative intent resection with or without adjuvant chemotherapy. Methods: We searched PubMed/Medline, EMBASE, Web of Science, Cochrane Library, and Google from inception to February 3, 2022 using keywords related to colorectal cancer, ctDNA, and MRD. The search also includes paper and conference presentations. The search resulted in 427 studies after removing the duplicates. Data were extracted to perform a meta-analysis using RevMan 5.4. software. Subsequent subgroup analysis was performed for stages I-III and oligometastatic stage IV CRC patients. Results: After the initial abstract screening, 48 studies were identified. The final review led to the inclusion of 27 studies representing 3459 patients with evaluable ctDNA, with 623 having +ve post-surgery ctDNA levels. Seven studies had analyses of patients specifically with oligometastatic disease, the rest 20 studies subdivided within stages I-III. The pooled HR for RFS in post-surgical ctDNA +ve vs -ve patients in all stages was 7.16 (95% CI 6.12-8.36) p &lt;0.00001. Subgroup analysis revealed pooled HR = 8.27 (95% CI 6.16-11.09) and 6.07 (95% CI 4.54-8.13) for stage I-III and IV CRC, respectively. Only 11 studies did analysis for post adjuvant chemotherapy patients based on ctDNA status. The pooled HR for RFS in post-adjuvant chemotherapy ctDNA +ve versus -ve patients in all stages was 12.40 (95% CI 9.24-16.64) p &lt;0.00001. Subgroup analysis revealed pooled HR = 13.95 (95% CI 9.08-21.43) and 11.39 (95% CI 5.99-21.66) for stage I-III and IV CRC, respectively. Conclusions: This is the largest and most current meta-analysis done on ctDNA levels as MRD assessment in CRC. Our analysis emphasizes that post operative ctDNA is a strong prognostic marker of RFS. Based on our results ctDNA can be a significant and independent predictor of RFS. Several ctDNA-based randomized adjuvant trials are ongoing internationally to confirm the clinical utility of ctDNA in colorectal cancer. [Table: see text]

Impact of the COVID-19 pandemic on cancer incidence and mortality

Impact of the COVID-19 pandemic on cancer incidence and mortality

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.

Perioperative second-line chemotherapy is beneficial for resectable liver metastases that occur during or early after adjuvant chemotherapy for colorectal cancer.

The prognosis of patients with liver metastases during or early after adjuvant chemotherapy for colorectal cancer (CRC) is significantly worse. This study aimed to explore the efficacy of perioperative second-line chemotherapy in prolonging survival in those patients. Patients who underwent liver resection, with resectable liver metastases that occurred within 12months after the last cycle of adjuvant chemotherapy for CRC, from January 2006 to December 2019, were included. The long-term outcome of overall survival (OS) and progression-free survival (PFS) between different groups was analyzed. A total of 200 patients were included, of whom 112 underwent direct hepatectomy and 88 received upfront second-line chemotherapy. OS and PFS were significantly better in patients receiving upfront second-line chemotherapy than direct surgery (PFS, P = 0.016; OS, P = 0.013). Further analysis showed that perioperative second-line chemotherapy could provide a greater survival benefit, which was also confirmed by propensity score matching (OS: P = 0.03; PFS: P = 0.04). Multivariate analysis determined that perioperative second-line chemotherapy was an independent factor influencing OS (OR [95% CI]: 0.468 [0.294-0.744], P = 0.001) and PFS (OR [95% CI]: 0.517 [0.353-0.758], P = 0.001). Perioperative second-line chemotherapy could improve the survival of patients who underwent hepatectomy, with resectable liver metastases that occurred during or early after adjuvant chemotherapy for CRC.

The role of folate receptor-positive circulating tumor cell analysis in the diagnosis of colorectal cancer: a retrospective cohort study

To explore the application value of folate receptor-positive circulating tumor cell analysis (FR+-CTC analysis) in the diagnosis of colorectal cancer (CRC). Clinical data of CRC patients and healthy subjects admitted to our hospital from January 2019 to October 2019 were retrospectively collected. CTC result and serological and pathological outcomes of the study patients were collected and analyzed. Receiver operating characteristic curve (ROC curve) was drawn. The CTC levels of cancer patients (9.34 ± 3.53 FU/3ml) were significantly higher than those of healthy subjects (7.00 ± 2.33 FU/3ml). CTC levels could be related to cancer stage and metastasis in patients. ROC curves were drawn and the area under the ROC curve (AUC) was 0.702. The cutoff value was determined to be 8.87 FU/3ml. At this cutoff value, the sensitivity and specificity of FR+-CTC analysis in the diagnosis of colorectal cancer were 61.8% and 82.6%, respectively. The diagnostic efficiency of FR+-CTCs in advanced CRC was significantly higher than that in the early stage. And the cutoff value of early and advanced stage CRC was determined to be 9.66 FU/3ml. FR+-CTC analysis has high potential in recurrence diagnosis and decision of adjuvant chemotherapy for CRC.

Clinical and Socioeconomic Factors that Predict Non-completion of Adjuvant Chemotherapy for Colorectal Cancer in a Rural Cancer Center.

Previous literature demonstrates correlations between comorbidities and failure to complete adjuvant chemotherapy. Frailty and socioeconomic disparities have also been implicated in affecting cancer treatment outcomes. This study examines the effect of demographics, comorbidities, frailty, and socioeconomic status on chemotherapy completion rates in colorectal cancer patients. This was an observational case-control study using retrospective data from Stage II and III colorectal cancer patients offered chemotherapy between January 01, 2013 and January 01, 2018. Data was obtained using the cancer registry, supplemented with chart review. Patients were divided based on treatment completion and compared with respect to comorbidities, age, Eastern Cooperative Oncology Group (ECOG) score, and insurance status using univariate and multivariate analyses. 228 patients were identified: 53 Stage II and 175 Stage III. Of these, 24.5% of Stage II and 30.3% of Stage III patients did not complete chemotherapy. Neither ECOG status nor any comorbidity predicted failure to complete treatment. Those failing to complete chemotherapy were older (64.4 vs 60.8 years, P = .043). Additionally, those with public assistance or self-pay were less likely to complete chemotherapy than those with private insurance (P = .049). Both factors (older age/insurance status) remained significant on multivariate analysis (increasing age at diagnosis: OR 1.03, P =.034; public insurance: OR 1.84, P = .07; and self-pay status: OR 4.49, P = .03). No comorbidity was associated with failure to complete therapy, nor was frailty, as assessed by ECOG score. Though frailty was not significant, increasing age was, possibly reflecting negative attitudes toward chemotherapy in older populations. Insurance status also predicted failure to complete treatment, suggesting disparities in access to treatment, affected by socioeconomic factors.

Adjuvant Chemotherapy for Colorectal Cancer in the Era of Genomic Medicine

Adjuvant Chemotherapy for Colorectal Cancer in the Era of Genomic Medicine