Clinical colorectal cancer最新文献

Introduction: Patients with metastatic colorectal cancer (mCRC) respond differently to first-line chemotherapy. Early identification of patients with limited or no clinical benefit could prompt a timelier introduction of second-line therapy and potentially lead to improved overall outcomes. Carcinoembryonic antigen (CEA) is currently the only blood-based marker in clinical use for disease control monitoring in mCRC. Circulating cell-free DNA (cfDNA), including circulating tumor DNA (ctDNA) could become a useful surrogate for oncological outcomes.

Materials and methods: Forty patients with RAS-/BRAF-mutated mCRC from the prospective NORDIC-VII trial (NCT00145314) were included. An exploratory model system was made to describe the early on-treatment kinetics of CEA, cfDNA and ctDNA during first-line oxaliplatin-based chemotherapy, and investigate the associations with radiological response, progression-free survival (PFS) and overall survival (OS).

Results: Summary metrics were made, representing percentage change from treatment start to time-grid day 7 (P₇), day 14 (P₁₄), and day 49 (P₄₉); slope from time-grid day 0 to 7 (S₇), day 8 to 14 (S₁₄), and day 15 to 49 (S₄₉); and area under the curve from time-grid day 0 to 49 (AUC). Notably P₄₉ and S₄₉ for ctDNA and CEA were associated with radiological response and/or PFS. The early dynamics of the two markers differed substantially, with faster and more marked changes in ctDNA compared with CEA. Nine patients did not reach complete/near complete molecular ctDNA response close to first evaluation (∼week 8), a state associated with a short PFS (HR 2.72; 95% CI, 1.22-6.06; P = .01) and OS (HR 3.12; 95% CI, 1.35-7.23; P < .01). Contrary, twenty-two patients did not reach radiological response (i.e., complete or partial response) at first evaluation, but this was not associated with PFS (HR 1.21; 95% CI, 0.64-2.30; P = .55) nor OS (HR 1.37; 95% CI, 0.70-2.68; P = .37).

Conclusion: Early dynamics of ctDNA during first-line oxaliplatin-based chemotherapy hold prognostic value, supporting the idea of prospectively validating a ctDNA-RECIST framework in the early care pathway of mCRC patients.

Trial registration: ClinicalTrials.gov, NCT00145314.

Background: In this large population-based cohort study, we examined the prognostic significance of various clinical, pathological, and contextual variables for their correlation with survival in elderly patients with stage III colon cancer.

Methods: Patients aged ≥ 70 years with stage III colon cancer, diagnosed in Saskatchewan during 2012-2018, were evaluated. A Cox proportional multivariate survival analysis was performed to determine factors correlated with overall survival (OS) and disease-free survival.

Results: Overall, 404 eligible patients with a median age of 79 years and a male-to-female ratio of 1:1 were identified. Among them, 48% were aged ≥ 80 years, 66% had ≥ 1 major comorbid illness, 46% had high-risk disease, and 50% had a node-positive to node-harvested (NPNH) ratio of > 0.1. Forty-three percent of patients received adjuvant chemotherapy. The 5-year disease-free survival with chemotherapy was 49% versus 30% without chemotherapy (P < .001). The 5-year OS with adjuvant chemotherapy was 64% versus 49% without chemotherapy (P < .001). On multivariate analysis a past history of cancer, hazard ratio (HR) 1.47 (95% CI, 1.12-1.94); presence of an ostomy, HR 1.53 (1.16-2.03); NPNH ratio > 0.1, HR 1.51 (1.15-1.98); grade III tumor, HR 1.54 (1.16-2.04); WHO performance status > 1, HR 1.42 (1.06-1.90); no adjuvant chemotherapy, HR 1.82 (1.32-2.50); high-risk stage III disease, HR 1.60 (1.22-2.11), and baseline carcinoembryonic antigen > 5, HR 1.98 (1.50-2.61) were independently correlated with OS.

Conclusions: This study highlights the prognostic importance of several factors in elderly patients with stage III colon cancer, particularly the benefit of adjuvant chemotherapy on survival. Key predictors of poorer OS include a past history of cancer, presence pf an ostomy, and a higher NPNH ratio. These findings emphasize the need for personalized treatment approaches to improve outcomes in this vulnerable population.

Background: There is controversy and limited data the management of rectosigmoid junction cancer (RSJC), especially the role of radiation. We aim to investigate the role of preoperative and postoperative radiation in RSJC and whether this cancer should be treated as a colon cancer or as a rectal cancer.

Methods: The data were extracted from the Surveillance, Epidemiology, and End Results (SEER) database and identified from 2000 to 2018.

Results: Of the 50,779 patients, 87% were ≥50 years old, 56.2% were male, 80.8% were White. Regarding tumor characteristics, 76% were Grade II, while 22.7% had distant-stage. 16.4% of patients were treated with multimodal therapy (surgery with chemoradiation), 47.9% surgery alone, 6.5% of patients received preoperative radiation, and 9.9% received postoperative radiation. Regarding prognostic significance of pre-operative and postoperative radiation factors, we evaluated factors, such as age, gender, race, tumor size, histologic variants of adenocarcinoma, and tumor grade. Patients with distant-staged tumors who received preoperative radiation had lower mortality compared to those who received postoperative radiation (95% CI, 0.73 - 0.97, (hazard ratio (HR) = 0.85, p = 0.04). There were no survival differences for localized or regional disease regarding pre and postoperative radiation, or when sub-stratifying for any other significant demographic or tumor characteristics.

Conclusion: Surgery with adjuvant chemoradiation had the best prognosis for all demographic and tumor characteristics. Preoperative radiation had a good prognosis only in distant disease. However, further randomized evidence is required to demonstrate the efficacy of pre-and post-operative radiation in rectosigmoid junction cancer.

Background: Patients with recurrent or metastatic advanced colorectal cancer (mCRC) often face the clinical dilemma as this unresectable disease is continuously progressing and endangering the patients' lives. In the current study, we explored the clinical feasibility of KH903 in combination with FOLFIRI chemotherapy as a new clinical indication for mCRC.

Methods: Patients (N = 122) were randomized 1:1 to 4mg/kg q1w KH903 or 5mg/kg q2w KH903, and both groups of patients were treated with the fixed regimen of FOLFIRI (every 2 weeks) along with the KH903 therapy. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were Overall Survival (OS), objective response rate (ORR), and disease control rate (DCR).

Results: As of December 30, 2020, median (m)PFS was 5.68 months (95% CI, 4.67-7.13) with 4mg/kg q1w versus 5.19 months (95% CI, 4.04, 5.78) with 5mg/kg q2w (HR, 0.76; 95% CI, 0.50-1.16),and mOS was 13.14 months (95% CI, 10.61-19.52) versus 16.03 months (95% CI, 10.28- NE), respectively (HR, 1.11; 95% CI, 0.65-1.89), The ORR was 15.9% and 11.9% for both groups, respectively, and The DCR for both groups was 85.7% and 83.1%, respectively. Grade 3 or higher treatment-related adverse event rates for both groups were 68.3% vs.52.5%, respectively.

Conclusions: KH903 in combination with FORFIRI in second-line treatment of patients with mCRC showed prolonged mPFS and mOS, comparing to the similar agents (Avastin®, ZALTRAP®, Cyramza®) and no new safety signals were observed.

Background: The multi tyrosine kinase inhibitor regorafenib is active in metastatic colorectal cancer. Improvement in clinical outcome by adding regorafenib to long-course chemoradiotherapy (LcCRT) was investigated in molecularly undefined LARC.

Methods: Patients with T3-4 and/or N+ but M0 rectal cancer were included. Neoadjuvant LcRCT consisted in capecitabine (C) 825mg/m² d1-d38 and 28 fractions of 1.8Gy (50.4Gy). Regorafenib was added d1-14 and d22-35 in 3 dose escalation (DE) cohorts (40mg/80mg/120mg). The recommended dose (RD) was used for the expansion (EXP) cohort. Primary endpoints were dose-limiting toxicity (DLT) for DE and pathological response (near-complete regression [npCR] or complete regression [pCR]) for EXP.

Results: Overall, 25 patients were included. Two DLTs occurred at the regorafenib dose level of 120 mg, thereby establishing the RD at 80mg daily. Among the 19 patients who were treated at the RD, 8 (42.1%; 1-sided 80% confidence interval [CI] (lower bound): 30.7%; 95% CI, 20.3%-66.5%) reached the primary endpoint (5 [26.3%] had npCR and 3 [15.8%] pCR). One additional patient received no surgery due to clinical complete response. All patients had R0 resections and clear circumferential margins. Postoperative complications occurred in 6 patients (35.3%). The most common grade ≥ 3 treatment-related adverse event in the EXP cohort was diarrhea (2 patients).

Conclusion: Adding regorafenib 80 mg to LcCRT in LARC resulted in both primary endpoints being met and yielded an expected pathological response rate. Toxicity was manageable, and postoperative complications were as expected.

Background: Surgery improves long-term survival for resectable, liver-only metastatic colorectal cancer (mCRC). With no consensus definition of "resectable" disease, decisions regarding resectability are reliant on the expertise and judgement of the treating clinician working in consultation with a multidisciplinary team (MDT). This study examines the clinical outcome versus initial assessment of resectability in an Australian population with mCRC.

Patients and methods: Patients with liver-only mCRC diagnosed January 2009 to December 2022 were identified from the Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) registry. Patients were classified based on prospectively documented treatment assessment as "resectable," "potentially resectable," or "unresectable." The correlation between initial assessment of resectability and clinical outcome, and any impact of clinicopathologic factors were examined. Kaplan-Meier analysis assessed overall survival based on initial resectability assessment and resection status.

Results: Of 4437 patients with mCRC identified through TRACC, 1250 (28%) had liver-only disease at presentation, with 497 (43%), 277 (24%), and 374 (33%) classified as "unresectable," "potentially resectable," and "resectable," respectively. In total, 516 (41%) ultimately underwent surgical resection, including 30 (6%) of the "initially unresectable," 148 (53%) of the "potentially resectable," and 338 (90%) of the "resectable" at a median of 9.5, 5.9, and 2.4 months from the diagnosis of liver metastases, respectively. Resection in the "unresectable" patient population was associated with younger age (mean age 63 vs. 69, P = .0006), better performance status (ECOG 0-1 100% vs. 74%, P = .0017), and fewer comorbidities (Charlson index 0-3 in 73% vs. 53%, P = .0296) compared with no resection. Median overall survival was longer for resected versus nonresected patients across all categories: "unresectable" (59.2 vs. 17.6 months, P < .0001), "potentially resectable" (57.2 vs. 22.8 months, P < .0001), and "resectable" (108 vs. 55 months, P < .0001).

Conclusions: This real-world study demonstrates the potential for "initially unresectable" patients to become surgical candidates following systemic therapy, more likely in younger and fitter patients, with overall excellent survival outcomes in resected patients. This highlights the value of routine, repeated MDT assessments for patients with liver-only disease who are continuing to respond to systemic therapy, even for those initially considered never to be surgical candidates.

Introduction: Total neoadjuvant treatment (TNT) with induction chemotherapy (ICT) followed by chemoradiotherapy (CRT) has improved long-term outcomes for patients with locally advanced rectal cancer (LARC). However, long-term outcomes have not been investigated for patients with incomplete (R1) resection separately. This study investigates overall survival (OS), disease-free survival (DFS) and local and distant recurrence rates in patients with R1 resection after preoperative treatment with ICT and CRT or CRT.

Patients and methods: From the NORD database 689 patients with LARC who received treatment between 2006 and 2017 were screened for inclusion. All patients with R1 resection were included. ICT consisted of at least 1 cycle of capecitabine and oxaliplatin (CAPOX) and was followed by radiotherapy concomitant with capecitabine.

Results: Among 46 patients with R1 resection, 27 (59%) received both ICT and CRT, and 19 (41%) patients received CRT. The 5-year OS was 44% (95% CI, 26%-63%) (ICT + CRT) versus 37% (95% CI, 15%-59%) (CRT) (P = .25) and 5-year DFS was 44% (95% CI, 26%-63%) (ICT + CRT) versus 32% (95% CI, 11%-53%) (CRT) (P = .22). The local recurrence rates showed a small nonstatistical significant difference in local control in the ICT group: 15% compared to 26% in the CRT group (P = .22). Distant recurrence rates were similar: 41% (ICT + CRT) versus 47% (CRT) (P = .48).

Conclusion: There was no significant difference in OS, DFS or local and distant recurrence rates between patients who received ICT + CRT versus patients who received CRT only.

Background: Para-aortic lymph node metastasis (PALNM) is a rare occurrence in colorectal cancer (CRC), and the high risk of radical lymphadenectomy leads to persistent debate about the best treatment strategy. This study aims to evaluate the predictor for PALNM and the clinical value of para-aortic lymph node dissection (PALND) in CRC patients with radiologically suspected synchronous PALNM.

Methods: Patients who have synchronous radiologically suspected PALNM and underwent primary tumor resection were included. Logistic regression and receiver operating characteristic curve analysis were used to assess the predictive value of lymph node short axis in preoperative CT, identifying the optimal cut-off value. Propensity score matching and Cox regression explored factors affecting overall and disease-free survival, while Kaplan-Meier curves and decision tree models identified patient characteristics suitable for synchronous para-aortic lymph node dissection.

Results: A total of 578 patients were enrolled, and 125 patients received synchronous PALND. We found that simultaneous PALND significantly improved overall survival (HR, 0.56; 95% CI, 0.35-0.91; P = .019) in multivariate analysis, while disease-free survival showed no significant difference (P = .41). The short axis diameter of PALN on preoperative CT is a crucial predictor of PALNM (P < .001, AUC = 0.759) with a threshold of > 7 mm. N-stage and distant metastasis were included as independent predictors in the diagnostic model to enhance accuracy. A larger short axis diameter of PALN correlated with advanced tumor stage and poorer prognosis. Subgroup analysis revealed that PALND offers survival benefits for colorectal cancer patients at all stages with a short axis diameter >10 mm on preoperative CT (P = .037) and for stage III patients with a diameter between 7 to10 mm (P < .001, AUC = 0.810).

Conclusion: Synchronous PALND can improve overall survival in CRC patients with suspected PALNM, with the maximum short axis diameter of PALN serving as a key criterion for selecting patients for surgery.

Background: The vast majority of colon cancers occur in pre-existing adenomas. Little is known about the impact of adenoma type on behavior and outcome of subsequent carcinomas. The present study aimed to assess characteristics, behavior, and outcome of colon adenocarcinoma based on histologic type of pre-existing adenoma.

Methods: US-National Cancer Database was searched between 2005 and 2019 for patients with colonic adenocarcinoma with known adenoma type who underwent colectomy. Patients were divided into 3 groups according to type of adenoma in which carcinoma developed: tubular adenoma (TA), villous adenoma (VA), and tubulovillous adenoma (TVA)-associated carcinomas. The main outcome of the study was 5-year overall survival (OS).

Results: 66,854 patients were included. 79.3% of carcinomas originated from TVA, 10.2% from VA, and 0.5% from TA. Patients with adenocarcinoma in VA were more often female whereas carcinomas in TA affected patients of Asian race more often. Approximately one-third of carcinomas in villous and tubulovillous adenomas were in the cecum whereas one-third of carcinomas in tubular adenomas were in the sigmoid colon. More TA-associated carcinomas were of clinical T1-2 stage (30.2% vs. 20.8%; P < .001), clinical N0 stage (69% vs. 62.2%, P < .001), and high grade (15.9% vs. 11.5%, P < .001) compared to VA-associated carcinomas. Patients with TA-associated carcinomas had longer mean OS than patients with VA and TVA-associated carcinomas (130.1 vs. 116.9 vs. 123.5 months, P < .0001).

Conclusions: Adenocarcinomas that arose in TA had more T1-2 stage and N0 stage, higher grade, and longer OS than did adenocarcinomas that arose in VA and TVA.

Background: Whether HCV infection is associated with colorectal cancer (CRC) development remains inconclusive.

Methods: A nationwide population-based cohort study of the Taiwan National Health Insurance Research Database was conducted.

Results: From 2003 to 2012, 1:2:2 propensity score-matched HCV-treated [interferon-based therapy ≥ 6 months, surveys for CRC (n = 9017), colon cancer (CC) (n = 9,022) and rectal cancer (RC) (n = 9,033), HCV-untreated and HCV-uninfected cohorts CRC (n = 18034), CC (n = 18,044) and RC (n = 18,066) were enrolled. The HCV-uninfected cohort had the lowest cumulative incidence of CRC (0.117%; 95% CI: 0.062%-0.207%), whereas the HCV-treated (0.966%; 0.375-2.122%) and HCV-untreated (0.807%; 0.485%-1.280%) cohorts had similar incidences (P = .0662); HCV infection [reference: HCV-untreated cohort, HCV-treated: hazard ratio (HR): 0.598; 95% CI HR: 0.337-1.059; HCV-uninfected: 0.250; 0.138-0.456] and age ≥ 49 years (3.128;1.751-5.59) were associated with CRC development. The HCV-untreated cohort had the highest cumulative incidence of CC (0.883%; 0.371-1.839%), while HCV-treated (0.478%; 0.110-1.518%) and HCV-uninfected cohorts (0.147%; 0.071-0.284%) had similar incidences (P = .4853); HCV infection (HCV-treated: 0.474; 0.232-0.971; HCV-uninfected: 0.338; 0.184-0.62), male sex (2.18; 1.301-3.654), age≥ 49 years (4.818; 2.123-10.936) and diabetes (1.983; 1.205-3.262) were associated with CC development. A higher RC cumulative incidence was noted in the HCV-untreated cohort (0.332%; 0.151-0.664%) than in the HCV-uninfected cohort (0.116%; 0.054-0.232%) (P = .0352); HCV infection (HCV-treated: 0.691; 0.295-1.617; HCV-uninfected: 0.424; 0.207-0.867), age ≥ 49 years (3.745, 1.576-8.898) and stroke (3.162; 1.366-7.322) were associated with RC development.

Conclusions: The baseline associations were HCV infection and age ≥ 49 years with CRC; male sex and diabetes with CC; and stroke with RC. Anti-HCV therapy might reverse the risk of HCV-related CC but not RC.