Clinical colorectal cancer最新文献

Background: The management of colorectal cancer (CRC) is a complex process. Defining the disease burden, assessing the radiological response and identifying the right time for surgery or other locoregional treatments are crucial factors which can require the involvement of a multidisciplinary tumor board (MDTB) comprising several specialists. This study investigates the impact of MDTB on management of CRC in our institution.

Methods: We retrospectively assessed all cases discussed by our MDTB between September 2019 and April 2023. In particular, we collected data concerning radiology, surgery and radiotherapy indication before and after MDTB meetings. The primary endpoint was the overall rate of discrepancy between pre- and post-discussion evaluations.

Results: Our analysis involved 1150 cases. Median age was 64 years (16-90), 629 patients (54.7%) were male and 915 (79.5%) had metastatic disease at the time of the relevant MDTB discussion. After the meetings, 325 treatment decisions were modified, producing an overall discrepancy rate of 28.3%. In particular: (1) of 648 cases discussed for radiological assessment, 156 decisions (24.1%) were altered after a central imaging review; (2) of 327 cases considered for surgical approach, treatment strategy changed in 118 (36.1%); and (3) of the 160 cases discussed regarding radiotherapy, the treatment strategy changed in 51 of them (31.9%).

Conclusions: Our analysis shows significant discrepancies between the radiology and locoregional evaluations from both before and after the MDTB meetings. Our results highlight that the discussions of a MDTB can considerably change the management of CRC, maximizing the treatment strategy.

Background: Both aflibercept and bevacizumab-based regimens are available II-line treatment options for patients with metastatic colorectal cancer (mCRC). However, no head-to-head trials established the optimal anti-angiogenic strategy for this setting.

Methods: We launched a multicenter, retrospective, observational study to assess and compare clinical efficacy of II-line treatments for patients with mCRC. Patients with KRAS/NRAS/BRAF-wild type and KRAS/NRAS mutant tumors were also analyzed separately.

Findings: 348 patients were included, of whom 153 and 195 were treated with bevacizumab- and aflibercept-based regimens, respectively. Patients treated with aflibercept showed an increased risk of death (corrected [co]-HR 1.92, 95 %CI: 1.37-2.68), of disease progression/death (co-HR 1.43, 95 %CI: 1.12-1.82) and a decreased objective response rate (ORR) (21.5 % vs 34.7 %, p=0.007) in comparison to bevacizumab. Patients treated with II-line bevacizumab were more frequently treated in the third line setting after disease progression (91.1 % vs 68.5 %, p<0.0001). In the KRAS/NRAS mutant cohort, treatment with bevacizumab was associated with longer overall survival (OS) (18.0 months vs 12.5 months, p=0.0069), but similar progression free survival (PFS) (p=0.32) and ORR (p=0.57). In the KRAS/NRAS, BRAF wild type cohort, patients treated with bevacizumab achieved longer OS (20.2 months vs 10.6 months, p=0.013), PFS (8.4 months vs 3.7 months, p=0.0002), and higher ORR (48.6 % vs 15.0 %, p=0.0016), compared to those treated with aflibercept. The results were independently confirmed with inverse probability of treatment weighting and with fixed multivariable Cox-regressions.

Conclusion: These findings support the use of bevacizumab-based over aflibercept-based regimens as II-line treatment in mCRC, especially in KRAS/NRAS and BRAF wild type tumors.

Background: Multidisciplinary team (MDT) meetings have been increasingly recognized for enhancing cancer treatment outcomes; however, their specific impact on stage II-III rectal cancer remains to be fully elucidated.

Materials and methods: This retrospective cohort study investigated the influence of MDT meeting on disease-free survival (DFS) and overall survival (OS) in patients with stage II-III rectal cancer. Propensity score matching (PSM) was used to minimize selection bias. Kaplan-Meier survival analysis and Cox proportional hazards models were used to compare DFS and OS between groups.

Results: A total of 502 patients were included, with 176 whose cases were discussed in MDT meetings and 326 who did not undergo MDT discussions. After PSM, 173 patients were matched in each group. The MDT group exhibited a significantly improved DFS compared to the non-MDT group, both before PSM (HR = 0.618, P = .037) and after PSM (HR = 0.545, P = .012). Subgroup analysis indicated notable benefits of MDT discussions for patients with T3 to 4 tumors, low to mid tumor locations, and node-positive tumors. While there was a trend towards improved OS in the MDT group, this did not reach statistical significance. More MDT group patients received MRI staging and neoadjuvant therapy compared to non-MDT group.

Conclusions: Discussion in MDT meetings is associated with improved DFS in stage II-III rectal cancer, particularly among patients with locally advanced, low to mid rectal cancer. These findings underscore the importance of incorporating MDT discussions into routine clinical practice to optimize outcomes for rectal cancer patients.

Background: Special AT-rich binding protein-2 (SATB2) is a nuclear matrix associated protein regulating gene expression which is normally expressed in colonic tissue. Loss of SATB2 expression in colorectal cancer (CRC) has negative implications for prognosis and has been associated with chemotherapy resistance. Furthermore, recent evidence suggests SATB2 may influence immune checkpoint (IC) expression. We hypothesized that SATB2 expression may be associated with altered expression of chemotherapy resistance associated and IC genes.

Methods: Clinicopathologic and gene expression data were extracted from The Cancer Genome Atlas PanCancer Atlas. SATB2 expression was compared by clinicopathologic characteristic and by using multivariate regression analysis to explore associations with chemotherapy and IC gene expression.

Results: About 553 patients were included for analysis. Lower quartile SATB2 expression was associated with worse disease specific survival (P = .04). MSI (P < .001) and mucinous (P < .001) tumors were associated with reduced SATB2 expression independently. SATB2 varied by consensus molecular subtype (P < .001) and was lowest in CMS1. On multivariate analysis, SATB2 was negatively associated with 5-FU related metabolism genes, while more complex but significant relationships were seen with oxaliplatin and irinotecan related genes. Low SATB2 expression was associated with increased expression of PD-1, PD-L1, TIM-3 and CTLA-4 IC genes.

Conclusion: The positive prognostic influence of SATB2 expression is reaffirmed in this study. This effect may be explained by the negative association between SATB2 and 5-FU-resistance related gene expression. Enhanced IC gene expression in SATB2 low cases suggests a potential role for IC inhibition in this setting, but further study is required.

Background: Panitumumab (pan) plus chemotherapy is a preferred first-line therapy for unresectable RAS and BRAF wild type metastatic colorectal cancer (mCRC). Older patients may not be suitable for combination regimens. We investigated 2 lower intensity pan-containing regimens.

Methods: Prospective, noncomparative, randomized (1:1) phase 2 study of pan alone (Arm A) or pan plus FU (Arm B). Previously untreated mCRC were ≥70 years; RAS/BRAF wild type.

Primary endpoint: 6-month progression-free survival (PFS). Secondary endpoints included: overall survival (OS), response rate (RR), feasibility of geriatric assessments and overall treatment utility (OTU)-a composite measure based on radiological response, clinical progress, toxicity and patient-reported treatment worth. Planned sample size was 40 patients per arm.

Results: 36 patients (Arm A n = 19, Arm B n = 17) were randomized between June 2018 and June 2021. Median age was 79 and 80 years respectively. 6-month PFS 63% (95% CI 38%-80%) arm A 82% (95%CI 55%-94%) Arm B. Median OS 21 months Arm A (95%CI 13-31) 28 (95%CI 14-39) months Arm B. RR 47% and 65% Arms A and B respectively. Baseline comprehensive geriatric assessments were completed in >80% of patients. At week 16, OTU was categorized as good in 92% (Arm A) and 90% (Arm B). No unexpected adverse events were seen.

Conclusions: Six-month PFS in both arms was consistent with that achieved with FU/bev, whilst the rate was numerically higher for Arm B. Baseline comprehensive geriatric assessments were feasible and OTU was high. Both treatment arms might be suitable in appropriately selected patients.

Background: Cytoreductive surgery (CRS) is effective for colorectal cancer peritoneal metastases (CRPM) at increasing overall survival (OS) compared to systemic anticancer treatment (SACT) alone. The addition of Oxaliplatin heated intraperitoneal chemotherapy (HIPEC) has been shown in a randomized controlled trial to result in increased complications without significant OS benefit. This study evaluates outcomes for CRPM patients undergoing CRS+HIPEC with Oxaliplatin (Ox) 368mg/m² (30 min), versus Mitomycin C (MMC) 35mg/m² (90min).  METHODS: A prospective CRPM real-world database was used to collect outcomes for patients undergoing CRS+HIPEC at a single center. OS, recurrence-free (RFS), peritoneal RFS (PeRFS) were compared amongst all patients with histologically proven CRPM, those with completeness of cytoreduction (CC) score =0/1, and those with CC score=0/1 who were SACT naïve.  RESULTS: Between April 2005 and April 2021, 409 patients underwent CRS+HIPEC: 271 (66%) had MMC, 138 (34%) Ox. Of these, 395 (97%) had histologically confirmed CRPM, 336 (85%) achieved CC=0/1, 188 (47%) were SACT naïve; median OS =39.5, 44.4, and 47.2 months respectively. MMC versus Ox median OS in CC0/1=43.7 (95% CI 35.9-48.3) versus 50.1 (39.7-70.2) months, P = .28; Median OS in SACT naïve=45.7 (39.4-65.9) versus 59.9 (38.3-82.0) months, P = .31; multivariable analysis for CC0/1, SACT naïve patients showed Ox was comparable to MMC: HR=0.90, (0.64-1.27) P = .55 versus HR=0.88, (0.53-1.44) P = .60, respectively. Ox resulted in a significantly improved PeRFS in CC0/1 patients (MMC=9.0 versus Ox=12.6months, P = .01). A multivariable model for PeRFS showed a HR=0.63, (0.43-0.95), P = .03 for Ox.  CONCLUSION: This study suggests a role for Ox HIPEC in CRPM which should be explored further in clinical trials.

Background: The efficacy of trifluridine/tipiracil (FTD/TPI) + bevacizumab compared to FTD/TPI for treatment of refractory metastatic colorectal cancer (mCRC) was demonstrated in the SUNLIGHT trial. This analysis of SUNLIGHT investigated the impact of treatment with FTD/TPI + bevacizumab on patient quality of life (QoL) and Eastern Cooperative Oncology Group performance status (ECOG PS).

Methods: Questionnaires (EORTC QLQ-C30 and EQ-5D-5L) and ECOG PS assessments were conducted at baseline and on Day 1 of each treatment cycle. Time to definitive deterioration (TTDD) of QoL and time to ECOG PS worsening between treatment arms was assessed. A repeated-measures mixed-effects model was used to compare changes in QoL and ECOG PS from baseline. Kaplan-Meier and Cox regression methods were used to assess TTDD of QoL, time to ECOG PS worsening to ≥ 2, and overall survival (OS) and progression-free survival (PFS) in patients maintaining an ECOG PS of 0-1.

Results: Both treatment arms showed similar QoL scores from baseline to cycle 6, with no clinically relevant change over time. Patients receiving FTD/TPI + bevacizumab had a longer TTDD of QoL than patients receiving FTD/TPI, as well as longer time to ECOG PS worsening. In patients with maintained ECOG PS, median OS and PFS was prolonged in the FTD/TPI + bevacizumab arm compared to the FTD/TPI arm.

Conclusion: This analysis of SUNLIGHT showed that patients treated with FTD/TPI + bevacizumab had no clinically relevant changes in QoL, and prolonged TTDD and time to ECOG PS worsening, compared to patients treated with FTD/TPI.

Introduction: Data regarding the incidence and outcomes of mismatch repair deficient (dMMR) rectal cancer is limited. This study characterizes dMMR rectal cancer patients, comparing response after neoadjuvant radiotherapy and oncological outcomes to mismatch repair proficient (pMMR) rectal cancer patients.

Method: A retrospective cross-sectional cohort study was conducted in 67 Dutch centers. Data including patient and tumor characteristics, radiological and pathological reports and oncological follow-up outcomes were gathered from documentation in electronic patient files for patients who underwent a curative resection for primary rectal cancer in 2016. MMR-status was verified in pathology reports from immunohistochemistry or PCR microsatellite instability testing.

Results: MMR-status was determined in 1645 (54.9%) of 3001 stage I-IV rectal cancer patients, of which 46 (2.8%) were dMMR. Median follow up was 50 months (IQR 38-55). MMR-status was determined more often in younger patients. DMMR tumors were more locally advanced (cT4 23.9% vs. 8.8%, P = .010), and more distally located (mean distance to anorectal junction 3.6 cm vs. 5.3 cm, P = .004) than pMMR tumors. While radiological response after neoadjuvant (chemo)radiotherapy was similar, pathological complete response was significantly higher in dMMR compared to pMMR tumors (24.0% vs. 10.0%, P = .039). Four-year local recurrence, distant metastases, cancer-specific or overall survival rate between patients with dMMR or pMMR tumors were similar.

Conclusion: In this population-based cohort, 2.8% of rectal cancers in which MMR-status was determined were subtyped as dMMR. Surprisingly, dMMR was associated with higher pathological complete response rate to neoadjuvant (chemo) radiotherapy than pMMR. MMR-status did not impact oncological outcomes.

Background: Current American Joint Committee on Cancer (AJCC) staging for colorectal cancer utilizes TNM framework groups disease based on extent and provides prognostic information, ideally with a hierarchical logic. We sought to evaluate survival as a function of stage within the 8^th edition AJCC staging system for colon and rectal cancer.

Methods: Patients with primary colon or rectal cancer diagnosed 2010-2016 were identified from the National Cancer Database (NCDB). Survival curves were used to determine staging hierarchy for colon and rectal cancer. Multivariable modeling was used to identify relative contributions of variables (z-score) to survival, and hazard ratio (HR)-based groupings were constructed.

Results: Among 270,584 colon and 53,846 rectal cancer patients, AJCC summary staging was non-hierarchical (e.g. HR IIC=2.92, HR IIIA=0.85-1.31). Multivariable analysis demonstrated high T category (T4a, T4b) confers the greatest mortality (colon: T4a HR 2.76, T4b HR 3.04; rectum: T4a HR 3.29, T4b HR 3.73), while high T category as well as high N category (colon: T4a z=66.9, T4b z=64.6, N2b z=55.7; rectum: T4b z=31.1, N2b z=25.1) contributed substantially to the survival model. HR based TN groupings resulted in hierarchical stage organization.

Conclusions: Current AJCC stage groups for colorectal cancer are non-hierarchical. High T category has a greater impact on survival than N category for patients with early N disease, while high N category was more important for patients with early T disease. An organizational framework based on HR groupings is hierarchical and provides more accurate prognostic information.