Purpose Pancreatic adenocarcinoma is a devastating disease for which there are limited treatment options. Identification of novel agents to enhance the activity of existing regimens are much in need. We hypothesized that the disruption of the DNA damage response by AZD1775, an oral Wee1 inhibitor, added to the nab-paclitaxel and gemcitabine chemotherapy backbone would be safe and effective. Methods A phase I trial to evaluate the dose limiting toxicities and maximum tolerated dose of AZD1775 in combination with nab-paclitaxel and gemcitabine was conducted in patients with metastatic or locally advanced, unresectable pancreatic adenocarcinoma (NCT02194829). A total of 7 patients received nab-paclitaxel and gemcitabine intravenously on days 1, 8 and 15 of a 28-day treatment cycle along with AZD1775 by mouth on days 1, 2, 8, 9, 15 and 16. Toxicities were assessed using CTCAE version 4 criteria. Results Two patients were treated at the initial dose level of nab-paclitaxel, gemcitabine and AZD1775 and both experienced dose limiting toxicities (dehydration, elevated bilirubin, oral mucositis, increased AST and candida intertrigo). Under a revised study design, five patients were treated and two of them also developed dose limiting toxicities (anemia, thrombocytopenia, neutropenia, hyponatremia and febrile neutropenia). Progression-free survival (PFS) and overall survival (OS) among these seven patients was 5.26 months (95% CI [2.73, 12.16]) and 5.29 months (95% CI [2.73, 20.17]) respectively. Conclusion The combination of nab-paclitaxel, gemcitabine and AZD1775 was determined to be too toxic when administered in patients with metastatic or locally advanced, unresectable pancreatic adenocarcinoma.
Background The BRAF V600E mutation in metastatic colorectal cancer (mCRC) is associated with a poor prognosis when treated with conventional chemotherapy regimens. Recent advances in research have shown promise in using combined BRAF inhibitor and EGFR inhibitor to treat BRAF V600E mutated mCRC, with international guidelines recommending this combination for patients who have progressed after chemotherapy. However, there is limited real-world evidence evaluating the uptake and outcomes of this regimen. Hence, we sought to evaluate the baseline characteristics, treatment patterns, outcomes, and health-care resource utilization (HCRU) of BRAF V600E mutated stage IV mCRC patients receiving encorafenib (BRAFi) plus panitumumab (EGFRi) in Alberta, Canada. Materials and Methods We conducted an observational study retrospectively analyzing population-level secondary data supplemented with chart review data from Alberta, Canada. Results We identified a total of 43 patients with stage IV mCRC who received encorafenib plus panitumumab in Alberta, Canada between 2018 and 2023. Median overall survival (OS) was 13.0 months while real-world progression free survival was 5.6 months for this cohort. Dose reductions for panitumumab occurred in 2 patients, and 12 patients had a dose reduction of encorafenib. Healthcare utilization for patients receiving this regimen was low, as the mean number of hospital visits and emergency visits within the first year of treatment was 5.2 and 3.4 visits, respectively. Conclusion Encorafenib and panitumumab can be effectively combined to treat stage IV mCRC in patients with BRAF V600E mutation. Real world outcomes indicate that the combination is tolerated with meaningful clinical efficacy.
Background Accurate preoperative staging is essential for risk stratification and treatment planning in localized colon cancer (lCC), particularly in the context of emerging neoadjuvant strategies. However, the reproducibility of CT-based classification and its concordance with pathology remain incompletely defined. Patients and Methods We analyzed 175 patients with lCC who underwent baseline contrast-enhanced CT followed by curative-intent surgery. Two independent radiologists assessed clinical tumor (cT) and nodal (cN) stages, with discrepancies resolved by consensus. Interobserver agreement was evaluated using Cohen’s kappa. Radiological-Pathological (R–P) concordance was assessed for T, N, and overall stage. Multivariable logistic regression analyses was performed to identify predictors of concordance. Results Interobserver agreement was good for cT classification (κ = 0.77) and excellent for cN classification (κ = 0.94), with overall concordance of 82.9%. R–P concordance was achieved in 78.3% for T staging and 73.7% for N staging, while overall concordance was 57.1%. Most discrepancies reflected adjacent misclassification (29.3%), whereas gross errors were rare (2.3%). CT showed moderate diagnostic performance for T stage (sensitivity 75.7%, specificity 81.6%) and lower sensitivity for nodal involvement (sensitivity 52.3%, specificity 87.3%). Performance varied by tumor location, with higher accuracy in left-sided tumors. Lymphovascular invasion was associated with lower interobserver agreement (OR 0.34; p=0.014), while advanced cT stage predicted reduced R–P concordance for T staging (OR 0.04; p=0.004). Conclusion CT classification demonstrates high interobserver reproducibility but only moderate concordance with pathology in lCC. Misclassification may impact clinical decision-making, underscoring the need for improved staging strategies and multidisciplinary integration.
Background Neoadjuvant immunotherapy has shown remarkable efficacy in mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) locally advanced rectal cancer (LARC), whereas mismatch repair-proficient/microsatellite stable (pMMR/MSS) tumors have historically been resistant because of an immunosuppressive tumor microenvironment. Recently, immune checkpoint inhibitor (ICI)-based combinations with chemoradiotherapy or total neoadjuvant therapy have shown encouraging activity in pMMR/MSS LARC, though their efficacy, safety, and optimal design remain unclear. Methods PubMed, Embase, Web of Science, Cochrane Library, ClinicalTrials.gov, and major conference proceedings were searched for trials evaluating neoadjuvant ICI-based therapy in pMMR/MSS LARC. The primary endpoint was pathological complete response (pCR), with major pathological response (MPR), clinical complete response (cCR), sphincter-preserving surgery (SPS), and adverse events as secondary endpoints. Data were synthesized using single-arm, pairwise, and network meta-analytical approaches to evaluate the efficacy, safety and relative treatment rankings. Results Twenty-nine studies (1,865 patients) were included. Pooled pCR, MPR, cCR, and SPS rates were 34%, 62%, 32%, and 80%, respectively, while grade ≥ 3 treatment-related adverse events (TRAEs) and immune-related adverse events (irAEs) occurred in 19% and 4% of patients. Subgroup analyses indicated higher pCR with short-course radiotherapy (SCRT) and higher MPR and SPS with concurrent radioimmunotherapy. Compared with non-ICI controls, ICI-based regimens significantly improved pCR (OR 2.12) and MPR (OR 2.03) without increasing severe toxicity. The network meta-analysis ranked SCRT plus chemoimmunotherapy highest for achieving pCR (P-score = 0.95). Conclusions ICI-based neoadjuvant therapy, particularly SCRT plus chemoimmunotherapy, shows promising efficacy without a significant increase in severe toxicity in pMMR/MSS LARC, warranting validation in large-scale trials.
INTRODUCTION:Lateral lymph node dissection (LLND) in low rectal cancer is technically demanding due to the narrow pelvis and risk of nerve injury. Robotic surgery may improve visualization and precision, but evidence on domestic Chinese robotic systems for this procedure is limited. This study compared the safety and short-term outcomes of the KangDuo Surgical Robot-01 (KD-SR-01) robotic system with conventional laparoscopic surgery in patients undergoing radical resection with LLND. PATIENTS AND METHODS:This retrospective single-center study included 278 patients with low rectal cancer who underwent radical resection plus LLND from June 2022 to June 2025. Patients were divided into robotic (n = 120, KangDuo KD-SR-01) and laparoscopic (n = 158) groups. Perioperative, pathological, postoperative, and short-term oncological outcomes were compared. RESULTS:Baseline characteristics were comparable between groups. After 1:1 propensity score matching (119 pairs), the robotic group showed significantly shorter total operation time (238.7 ± 45.9 vs. 304.1 ± 58.9 minutes, P < .001), shorter LLND time (86.5 ± 23.2 vs. 121.1 ± 27.2 minutes, P < .001), lower blood loss (134.5 ± 52.3 vs. 351.8 ± 183.2 mL, P < .001), and higher lateral lymph node yield (7.87 ± 2.19 vs. 5.87 ± 2.34, P < .001) compared with the laparoscopic group. These advantages persisted in the matched cohort. Robotic surgery was also associated with, borderline lower overall complication rate (P = .047), and nominally lower sexual dysfunction (P = .047). Pathological outcomes and DFS (log-rank P = .163) were comparable. CONCLUSION:The domestic KangDuo KD-SR-01 robotic system is safe and feasible for radical resection with LLND in low rectal cancer. It provides significant perioperative and functional benefits compared to laparoscopy without compromising short-term oncological results.
Background Colorectal malignant polyps (MPs) appear benign endoscopically but display cancer cell invasion beyond the muscularis mucosae. Their recognition is challenging, as most lack overt signs of submucosal invasion (SMI) despite advances in optical diagnosis. This study aimed to identify the endoscopic features associated with curative resection of MPs. Methods We conducted a retrospective analysis of patients undergoing colonoscopy at our institution, and those with resected MPs were included. Results A total of 165 patients were analyzed, 57.6% males, with a mean age of 65 ± 10 years. A total of 170 MPs were resected with a global curative resection rate of 33.5%. Pedunculated polyps demonstrated a significantly higher curative resection rate (50.8%) compared with nonpedunculated lesions (23.4%; P < .001; OR 3.4, 95% CI, 1.74-6.6). On multivariate analysis, piecemeal resection was independently associated with noncurative outcomes for both pedunculated (P = .027) and nonpedunculated polyps (P = .013). In the latter group, indirect signs of deep SMI were also significantly associated with a noncurative resection (P = .01). Supporting these results, the major causes for a noncurative resection were specimen fragmentation (35.5% in pedunculated, 57% in nonpedunculated polyps) and insufficient margins, defined as a vertical margin < 1 mm or R1 resection (41.9% in pedunculated, 36.7% in nonpedunculated polyps). Conclusions Polyp morphology and resection strategy are key determinants of curative outcomes in MPs. En bloc resection should be achieved in lesions suspected of SMI, as piecemeal removal is a leading cause of noncurative outcomes.
Background A nonoperative (watch-and-wait) approach is increasingly accepted for patients with rectal cancer who achieve a complete clinical response to neoadjuvant treatment. This study aimed to investigate the effect of surgery—compared with a watch-and-wait strategy—on long-term quality of life among rectal cancer survivors following chemoradiotherapy. Patients and Methods This cross-sectional study included survivors of resectable rectal cancer treated with long-course chemoradiotherapy between 2011 and 2019 at Flinders Medical Centre, Australia. Participants were categorized as sustained watch-and-wait, surgery after regrowth, or standard surgery after chemoradiotherapy. Patient-reported outcome measures were collected by mail or during clinic visits. Primary multivariable analyses examined the effect of surgery on patient-reported outcomes. Linear regression models were adjusted for receipt of adjuvant chemotherapy, sex, age at assessment, tumor distance from the anal verge, comorbidity burden, and time from treatment completion. Results Of 190 eligible participants approached, 78 were enrolled. Median age was 70 years; 33.3% were female. A total of 32 (41.0%) were in the watch-and-wait group, 8 (10.3%) had been managed with surgery due to regrowth after initial watch-and-wait, and 38 (48.7%) were in the standard surgery group. The comorbidity burden had a negative impact on quality of life (P < .05). Surgery was independently associated with lower QLQ-C30 summary and social functioning scores (both P < .05), and with higher pain, bowel-function, urinary, and embarrassment symptom scores (all P < .05). Conclusion Surgery was associated with worse quality of life, higher symptom burden, and poorer psychosocial outcomes. This study highlights the need for long-term symptom monitoring and personalized care in survivors of rectal cancer.
BACKGROUND:KRAS mutations in metastatic colorectal cancer (mCRC) are a factor of poor prognosis, partly because of associated resistance to anti-EGFR therapies. Liver metastases (LM) were also described as a factor of poor prognosis. This study aims to compare the outcomes of patients treated in third-line setting with placebo or Trifluridine/Tipiracil or regorafenib (TToR) and to assess the impact of LM and KRAS mutations on prognosis. METHODS:Data were pooled from five placebo-controlled randomized trials of the ARCAD CRC database (CORRECT, RECOURSE, CONCUR, TERRA, and J003). Overall survival (OS) and progression-free survival (PFS) were analyzed using Kaplan-Meier estimates and adjusted Cox models. Interaction tests were conducted to evaluate the combined effects of LM and KRAS mutations. RESULTS:The study included 2,207 patients: 1,464 treated with TToR and 743 with placebo. A total of 73% had LM and 51% had KRAS mutations. Patients with LM had significantly lower OS and PFS compared to those without LM in both TToR (HR = 0.48 for OS; HR = 0.55 for PFS) and placebo groups (HR = 0.49 for OS; HR = 0.58 for PFS). Patients with KRAS mutations had worse OS compared to wild-type KRAS in TToR-treated patients (HR = 1.18), but not in placebo-treated patients (HR = 1.03). Interaction tests were not significant between LM and KRAS status in both TToR and placebo groups. CONCLUSIONS:In patients with refractory mCRC, LM are a major poor prognosis factor, while KRAS mutations have no clinically relevant additive impact. These results underline the importance to stratify clinical trials on liver metastases rather than on RAS status in latter lines.
INTRODUCTION:Immune checkpoint inhibitors (ICI) are standard for MSI-H/dMMR metastatic colorectal cancer (mCRC). We compared their efficacy and sought subgroups deriving greater benefit from ICI combination. PATIENTS AND METHODS:All patients with MSI/dMMR mCRC treated by anti-PD-1 ± anti-CTLA-4 in the prospective monocenter immunoMSI cohort were analyzed. Treatment choice followed trials availability and regulatory approvals. Main endpoints were progression-free survival (PFS, iRECIST) and overall survival (OS). Landmark analysis at 6 months, restricted mean survival time (τ = 7 years) and piecewise Cox models were used. Interactions were tested in a single Cox model including subgroup terms, treatment, and interaction terms. RESULTS:Among 210 patients, 97 received ICI combination and 113 monotherapy with anti-PD-1. Median follow-up was 4.4 years (4.1 combo; 5.4 mono). About 165 patients (78.5%) received ICI in second line or latter. Combination improved PFS (hazard ratios [HR] 0.48, 95% CI 0.31-0.76) and OS (HR 0.49, 0.29-0.84). RMST was 5.27 versus 3.91 years (+1.36 years, 0.55-2.17). Piecewise HRs showed an early benefit (0-6 months HR 0.32, 0.16-0.66) that attenuated thereafter. Objective responses were 78% versus 60%; progressive disease 5% versus 15%. Interactions were observed for sex (PFS HR 0.21 vs. 0.87 for females vs. males; P-interaction = .0067), liver metastases (0.30 vs. 0.79; 0.0479) and sidedness (0.27 vs. 0.64; 0.0922). CONCLUSION:Dual CTLA-4/PD-1 blockade improved PFS and OS versus anti-PD-1 alone, driven by higher early response rates. Female sex, absence of liver metastases, and left-sided tumor location may predict greater benefit from combination.
Advanced gastrointestinal cancers remain a major global health challenge, with rising incidence especially among younger populations. Systemic chemotherapy continues to be the mainstay of care for most patients, but balancing treatment benefit with tolerability is an ongoing concern. Many patients, especially older adults and those with significant medical comorbidities, may struggle with standard dosing due to side effects, yet they are often underrepresented in clinical trials. As a result, real-world practice often relies on adjusting drug doses and schedules to reduce toxicity without compromising outcomes. Personalizing systemic therapy based on patient factors like age, fitness, and individual response can help improve tolerability and maintain quality of life. Emerging evidence supports the use of modified dosing and frequency, but prospective data remain limited. In this review, we discuss current approaches to optimizing systemic therapy for advanced gastrointestinal cancers and the need for practical, patient-centered care pathways.
BACKGROUND:Risk-stratified colorectal cancer (CRC) screening may improve benefit-risk ratios and alleviate colonoscopy demands. Utilizing previous faecal immunochemical tests (FIT) values below positivity thresholds is promising due to its high predictive value and availability. This study aims to estimate and compare resources and costs between standard screening (SS and 2-year interval) and risk-stratified protocol (RS and 4-year interval) among low-risk participants (cumulative f-Hb ≤ 3.8 µg/g in 2 consecutive episodes) using retrospective data. METHODS:The Barcelona colorectal cancer screening programme biennially invites people aged 50 to 69 years to a FIT (cut-off point 20 µg/g). Negative results lead to reinvitation in 2 years; positive results prompt a colonoscopy appointment. Low-risk participants who underwent 2 additional screenings from 2009-2019 were considered. The SS scenario utilized real resources and costs, whereas the RS simulated outcomes using natural history probabilities. Direct screening and stage-specific CRC treatment costs were obtained. RESULTS:Compared to SS, RS showed a 50% reduction in invitation letters and FITs, less than 4% reduction in nurse visits and colonoscopies, and 49 fewer low-risk and 24 fewer high-risk lesions per 100,000 screenees, with an increase in local CRC and interval cancers. The RS protocol was estimated to generate a 17.4% decrease in screening costs and a 22.6% increase in treatment costs compared to the SS, resulting in an excess cost of 8.5%. CONCLUSIONS:These findings will inform the results of experimental studies, and need to be assessed in the context of the entire strategy, since the high-risk group could notably reduce treatment costs through earlier detection.
INTRODUCTION:Circulating tumor DNA (ctDNA) is a promising biomarker for monitoring metastatic colorectal cancer. Tumor fraction, defined as the proportion of tumor-derived DNA within total circulating cell-free DNA (cfDNA), has been used as a quantitative measure of tumor-derived DNA burden. However, because tumor fraction is a relative metric, its relationship with absolute ctDNA dynamics remains unclear. PATIENTS AND METHODS:We conducted a retrospective longitudinal study of patients with metastatic colorectal cancer harboring RAS or BRAF mutations who underwent systemic therapy with serial ctDNA monitoring. Plasma samples were analyzed using droplet digital PCR to quantify absolute ctDNA, expressed as mutant copies/mL of plasma, and tumor fraction. Longitudinal dynamics were assessed by comparing each sample with the preceding measurement. Dilution was defined as increased absolute ctDNA, with fold change ≥ 1.5 and increase ≥ 313 mutant copies/mL of plasma, accompanied by decreased tumor fraction. RESULTS:Fifty-five patients with 246 evaluable plasma samples were included. Among 120 samples with preceding measurements, 7 dilution events were identified in 5 patients, occurring predominantly during progressive disease. Although absolute ctDNA and tumor fraction increased concordantly at the population level during progression, individual-level analyses revealed discordant dynamics in which absolute ctDNA increased while tumor fraction decreased. Higher absolute ctDNA levels were associated with dilution in mixed-effects logistic regression analysis (odds ratio, 3.25; 95% CI, 1.16-9.15; P = 0.025). CONCLUSION:Tumor fraction may decrease despite increasing tumor-derived ctDNA during treatment monitoring. Simultaneous evaluation of absolute ctDNA and tumor fraction may improve interpretation of ctDNA dynamics in metastatic colorectal cancer.
BACKGROUND AND AIM:Colon capsule endoscopy (CCE) is a noninvasive technique for colon evaluation. Although previous research has demonstrated high accuracy of CCE in detecting polyps, the impact of colonic transit time (CTT) on polyp detection remains unclear. We aimed to identify the lowest acceptable CTT for an optimal polyp detection rate (PDR). METHODS:This study analyzed data from colorectal cancer screening participants with complete CCE examinations, as part of the CareForColon2015 trial. A multivariate logistic regression model was employed to investigate the relationship between CTT and PDR. RESULTS:Among the 2,031 participants who underwent CCE, 1,266 (62.3%) were eligible for analysis. CTTs ≤ 20 minutes were significantly associated with lower PDR for polyps of any size (OR 0.36, 95% CI 0.22; 0.59, P < .001) and polyps > 5 mm (OR 0.54, 95% CI 0.34; 0.85, P = .007) compared to a CTT of > 60 minutes. A nonsignificant trend was observed for CTTs 21-40 minutes and PDR for polyps > 5 mm (OR 0.68, 95% CI 0.46; 1.01, P = .053). No significant differences in PDR for polyps > 9 mm was found across the CTT categories. A sensitivity analysis with size-adjusted polyps revealed no significant differences in PDR for polyps > 5 mm across CTT categories. CONCLUSIONS:CTTs of ≤ 20 min are correlated with lower PDR for polyps of any size and those exceeding > 5 mm, but not for polyps > 9 mm. After size-adjustments of polyps, detection rates of clinically significant polyps were deemed CTT independent.
BACKGROUND:Sotorasib 960 mg plus panitumumab (soto960+pani) was investigated in chemorefractory KRAS G12C-mutated metastatic colorectal cancer (mCRC) in the phase 3 CodeBreaK 300 and phase 1b CodeBreaK 101 studies. In CodeBreaK 300, soto960+pani significantly improved progression-free survival (PFS) versus investigator's choice therapy (trifluridine/tipiracil [T/T] or regorafenib). The phase 3 SUNLIGHT study evaluated T/T plus bevacizumab (T/T+bev) in patients with unselected refractory mCRC and found longer survival times with T/T+bev than T/T monotherapy. Matching-adjusted indirect treatment comparisons (MAIC) were performed to compare the efficacy and safety of soto960+pani with new standard-of-care T/T+bev treatment. MATERIALS AND METHODS:Clinical outcomes and adverse events (AEs) from CodeBreaK 300 and 101 (for soto960+pani) were compared with those from SUNLIGHT (for T/T+bev). By reweighting individual patient-level data from the pooled CodeBreaK studies, differences in baseline characteristics were adjusted. Odds ratios (ORs) were estimated for objective response rates; hazard ratios (HRs) were used for PFS and overall survival (OS). RESULTS:From a pool of 93 patients, the effective sample size of soto960+pani with matched characteristics was 29 patients. Soto960+pani increased the likelihood of treatment response, with an adjusted OR of 5.7 (95% CI, 2.6-12.8) versus T/T+bev. HR for PFS was 0.77 (95% CI, 0.47-1.25); HR for OS was 0.44 (95% CI, 0.22-0.87), suggesting a survival benefit favoring soto960+pani. Grade ≥ 3 AEs occurred in 58% and 72% of soto960+pani-treated and T/T+bev-treated patients, respectively. CONCLUSION:In this MAIC analysis, soto960+pani demonstrated statistically significant improvement in response rates and OS in patients with chemorefractory KRAS G12C-mutated mCRC.
Metastatic colorectal cancer (mCRC) remains a major clinical challenge, particularly for patients with disease progression after multiple lines of therapy. Advances in molecular profiling have transformed the therapeutic landscape, enabling personalized treatment selection and expanding third- and later-line options. Targeted therapies such as BRAF inhibitors, anti-HER2 agents, and KRASG12C inhibitors are utilized in patients whose tumors harbor specific molecular alterations, with their use increasingly being explored across various lines of therapy. Agents such as trifluridine/tipiracil, regorafenib, and fruquintinib offer additional benefit in heavily pretreated mCRC. The integration of broad molecular testing, including emerging rare biomarkers, further supports individualized management. Despite these developments, prognosis in late-line mCRC remains poor, underscoring the need for ongoing research and clinical trial participation. This review summarizes contemporary evidence supporting third- and later-line therapies, highlights key clinical trial data, and discusses practical considerations in treatment sequencing. Potential treatment algorithms designed to aid clinicians in the selection and sequencing of therapies for refractory mCRC are also proposed. Anticipated paradigm shifts with novel agents may further refine management strategies and improve outcomes for these patients. As the landscape evolves, ongoing multidisciplinary collaboration will be essential in optimizing both patient selection and therapy sequencing as new options become available.
BACKGROUND:Immune checkpoint blockers (ICBs) are front-line therapy for mismatch repairdeficient (dMMR)/microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC). Poor ECOG performance status (PS) is widely recognized as a negative prognostic factor, often leading physicians to avoid treatment. We aimed to assess the effect of ECOG PS on patient outcomes in dMMR/MSI-H mCRC receiving ICBs. METHODS:This is an international multicenter retrospective cohort study of ICBs-naïve dMMR/MSI-H mCRC patients who received ICBs between 2014-2024. Exposure variables included best treatment response and patient characteristics including line of treatment, RAS/BRAF status, single-agent versus doublet ICBs, and metastatic sites. The main outcome was overall survival. Kaplan-Meier analysis was used to analyze the association of best treatment response with overall survival according to ECOG PS of 2-3 and 0-1. RESULTS:The study cohort included 51 dMMR/MSI-H mCRC patients with ECOG PS of 2-3 and 633 patients with ECOC PS of 0-1 that were treated with ICBs. Median follow-up time was 35.3 months (IQR 23.9-54.9) and 49.9 months (IQR 46.7-53.8), respectively. For patients with ECOG PS of 2-3 ORR and DCR rates were 37.3% and 60.8%. Median overall survival (mOS) was 14.4 months - not reached for those who achieved CR/PR and 1.7 months for those whose best response was PD. For patients with ECOG PS of 0-1, mOS was not reached, and ORR was 60.0%. CONCLUSIONS:Patients with dMMR/MSI-H mCRC and ECOG PS 2-3 derive durable benefit from ICBs, mainly among those who achieved CR/PR, and should therfore be considered candidates for ICBs.
BACKGROUND:Following the IDEA collaboration, the use of capecitabine and oxaliplatin (CAPOX regimen) for adjuvant colorectal cancer treatment has increased. While CAPOX is associated with higher rates of diarrhea, non-neutropenic enterocolitis (NNE) and related hospitalizations have not been well described. PATIENTS AND METHODS:We performed a retrospective cohort study of patients treated with adjuvant CAPOX, mFOLFOX6 (infusional 5-fluorouracil, leucovorin, and oxaliplatin), and capecitabine between 2015 and 2023 at 2 hospitals in Quebec, Canada. Data on demographics, oncologic treatments, and complications, including NNE (defined as grade ≥ 2 diarrhea with radiologic ileocolitis) were extracted. RESULTS:A total of 223 patients were included, 82.9% of patients had stage III colorectal cancer, 54.3% received CAPOX, and 40.8% mFOLFOX6. NNE occurred in 12.4% of patients treated with CAPOX versus 1.1% with mFOLFOX6 (odds ratio [OR] 12.736, P = .002). All NNE were grade 3 to 4 events and required hospitalization. The median time to CAPOX-induced NNE onset was 36 days after the first chemotherapy dose. Risk factors for NNE included CAPOX use (OR [vs. mFOLFOX6] OR 12.736, P = .002) and age over 65 years (OR 4.214, P = .006). No difference in relapse-free survival was observed for stage III patients with versus without NNE (hazard ratio 0.247, P = .167). CONCLUSION:NNE is a significant complication of CAPOX, particularly in patients over 65 years. It occurs early in the treatment course, leads to a high rate of hospitalization, and necessitates careful patient selection and close monitoring during early cycles.
BACKGROUND:Recent studies have shown an increased incidence of early-onset CRC (EO-CRC), particularly in advanced stages and with metastatic disease. Our study aimed to evaluate the role of metastasectomies related to the clinical and molecular characteristics of EO-CRC patients with liver metastases compared to average-onset CRC (AO-CRC) patients. METHODS:We retrospectively collected data from 1123 stage IV colorectal cancers, including 782 with liver metastases, from 5 different Italian institutions. The main objective of the study was to compare the overall survival of liver metastatic EO-CRC and AO-CRC patients who underwent metastasectomy versus those who were not resected. RESULTS:Liver resected EO-CRCs patients showed a statistically significant lower mOS than liver resected AO-CRCs (44.0 vs. 64.0 months, P < .0001). mPFS was also statistically significant lower in EO-CRCs (13.0 vs. 17.0, P < .0001). Same outcomes were found in RAS mut subgroup (37.0 vs. 52.0 months, P < .0001) and in RAS/BRAF wild-type subgroup (50.0 vs. 81.0 months, P < .0001). EO-CRC patients showed a higher prevalence of TP53 alterations (56.2%) and a lower of APC mutation (29.9%). EO-CRCs presented a higher frequency of ARID1A (4.4%) and CTNNB1 (3.0%) alterations. CONCLUSION:The results indicate a worse overall prognosis for EO-CRC patients undergoing metastasectomy compared to average-onset patients. This outcome appears to occur independently of the molecular status. These observations could have a considerable impact on clinical practice and research.
