Clinical colorectal cancer最新文献

Background: More than 50% of patients diagnosed with colorectal cancer (CRC) will develop liver metastases (CRCLM), which is the main cause of death for more than 60% of these patients. The aim of this study was to correlate the clinical and pathological characteristics of the primary CRC and CRCLM, with emphasis in predicting the histological growth pattern of the CRCLM.

Methods: Cohort of 73 patients with CRC. Analysis of clinical data and blinded pathological review was performed related with primary tumor and CRCLM features. The analysis was performed in SPSS (version 27) with a significance level of 5%.

Results: A statistically significant association was found between tumor size and metastasis growth pattern (P = .002), with larger tumors giving rise to metastases with a nondesmoplastic growth pattern. Lymphovascular invasion (LVI) was associated with metachronous CRCLM (P = .043). In the absence of LVI, the time required for CRCLM to appear was significantly longer (P = .011). The number of metastases was significantly higher (P = .049) in tumors without LVI when compared to tumors with LVI. There was a statistically significant association between CRC high-grade inflammation and the desmoplastic metastases growth pattern of the CRCLM (P = .017).

Conclusion: The possibility of predicting the CRCLM histological growth pattern resorting to primary CRC characteristics would be useful for proper patient selection for surgery and adapting biological therapies.

Introduction: Extramural vascular invasion (EMVI) is associated with distant recurrence after treatment of locogionally advanced rectal adenocarcinomas (LARCs), but its use as a marker for response to neoadjuvant therapy is less well understood. We examined the relationship between EMVI and tumor or nodal category downstaging after treatment of LARCs with neoadjuvant therapy.

Methods: Patients with EMVI categorized on initial staging pelvic MRI for LARC who underwent curative-intent surgery after neoadjuvant therapy at MD Anderson Cancer Center from 2016 to 2022 were identified. Patients received either preoperative chemoradiation or total neoadjuvant therapy (TNT). Associations between EMVI and demographic, radiologic, and clinicopathologic variables were analyzed.

Results: EMVI was associated with higher rates of lymphovascular invasion (LVI) (46.2% vs. 27.8%, P = .001) and perineural invasion (PNI) (51.9% vs. 28.4%, P < .001) on final pathology. Patients with EMVI were more likely to have cT4 tumors (31.7% vs. 16.3%, P = .004) and cN+ status (86.8% vs. 66.3%, P = .001) and more likely to be treated with TNT rather than chemoradiation alone (62.3% vs. 41.9%, P = .005). EMVI was associated with a lower rate of pathologic complete or near-complete response (20.1% vs. 34.2%, P = .018), downstaging to ypT0-2 from cT3/4 tumors (14.9% vs. 44.4%, P = .0001), and downstaging to ypN0 from cN+ status (47.9% vs. 66.4%, P = .015).

Conclusions: Rectal tumors with EMVI are more likely to have higher clinical stage, less likely to respond to neoadjuvant therapy despite increased use of TNT, and more likely to have high-risk features for recurrence. This suggests EMVI is a marker of disease with poorer response to neoadjuvant therapy. Disease biology should be strongly considered in treatment decision-making, and new treatment strategies are needed to improve disease response.

Background: The application of fluoropyrimidine-based chemotherapy in colorectal cancer treatment is known to pose significant toxicity risks, which can be mitigated by tailoring treatment according to DPYD gene variants. This study evaluates the impact of DPYD genotype-guided dosing on treatment-related toxicities and patient outcomes.

Methods: A retrospective analysis was conducted on CRC patients treated with fluoropyrimidines in adjuvant setting at The Wellbeing Services County of Ostrobothnia. Patients were divided into two cohorts based on the implementation of routine DPYD genotyping: pregenotyping (2016-2018) (n = 80) and postgenotyping (2020-2022) (n = 69). The incidence of side effects, treatment discontinuation, hospitalization, and 90-day mortality were compared between groups.

Results: The study revealed a reduction in 90-day mortality rates among patients who underwent DPYD genotyping before treatment. Patients with pathogenic DPYD variants received ≥50% reduced doses initially, leading to no severe toxicities (grade ≥3). Class 3 variants showed similar side effect profiles and hospitalization rates as untested patients but had a lower rate of treatment discontinuation.

Conclusions: Upfront DPYD genotyping appears to improve patient safety in CRC patients treated with adjuvant fluoropyrimidines, leading to personalized dosing that reduces severe toxicities and early mortality. These findings underscore the importance of integrating pharmacogenetic testing in clinical oncology to optimize treatment regimens and enhance patient care.

Background: The aim of this post hoc study was to assess the prognostic value of 18F-FDG PET/CT quantitative parameters recorded before and after treatment for anal canal neoplasm for the disease free survival.

Materials and methods: Consecutive, previously untreated patients with histologically proved anal cancer, with 18F-FDG PET/CT pre- and 2 months post treatment were included. The following criteria were analyzed: baseline primary tumor lesion glycolysis (TLG), metabolic tumor volume (MTV), standardized tumor volume (SUV) max and mean, SUV normalized by lean body mass (SUL) max, mean and peak, variations between pre- and post-treatment examinations for SUVmax (Delta SUVmax), TLG (Delta TLG), MTV (Delta MTV), as well as post-treatment SULpeak and SUVmax for the primary tumor, and baseline sum of lesions TLG and MTV.

Results: About 78 consecutive patients were included in this study. Median follow-up was 49 months. Baseline TLG, SUVmax, SULpeak, SULmax, sum of lesions for TLG and MTV, Delta SUVmax, and post-therapeutic SULpeak and SUVmax for the primary tumor, were statistically significant for disease free survival.

Conclusion: Pretherapeutic 18F-FDG PET/CT has a statistically significant prognostic value. The wide variability of results published in literature compels us to specifically explore the interest of uptake variations between pre- and post-treatment examinations.

Objective: To assess the impact of external iliac lymph node (N1b) metastasis on anal carcinoma (AC) staging and refine the Tumor-Node-Metastasis (TNM) system without modifying existing criteria.

Methods: This retrospective study was performed utilizing the data of 3,815 patients with AC included in the Surveillance, Epidemiology, and End Results (SEER) registry from 2018 to 2021. We compared the TNM8th and 9th editions with our proposed system, focusing on overall survival (OS) and cancer-specific survival (CSS). The Kaplan-Meier survival analysis and time-dependent C-index measures were employed to evaluate the 3 staging systems.

Results: The SEER registry identified only 42 patients with solitary N1b metastasis, with lymph node (LN) metastasis rates rising with higher T stages. No significant survival differences were found among N1a to N1c subgroups, yet N1a showed better OS and CSS than N1b+c (hazard ratio [HR] = 1.306, 95% confidence interval (CI): 1.011-1.687, P = .041 for OS; HR = 1.432, 95% CI: 1.088-1.886, P = .011 for CSS). The proposed TNM system, reclassifying T 1N1M0 as stage I and defining T3-T4 with LN status as stages IIIA and IIIB, showed marginally improved predictive accuracy (C-index: 0.684 vs. 0.683 for OS; 0.635 vs. 0.634 for CSS).

Conclusions: N1b metastasis minimally affects AC staging. We introduce a simplified TNM system for clinical use: M Staging: Distant metastasis presence as M1. T Staging: T1 as stage I, T2 as stage II, T3-T4 as stage III. N Staging: N status noncontributory for stage I; N negative as stage A (IIA or IIIA), N positive as stage B (IIB or IIIB).

Liquid biopsies offer the possibility to evaluate cancer patients using noninvasive approaches. Circulating cell-free DNA (ccfDNA) is 1 of the most used and promising sources. Detecting tumor DNA among ccfDNA (ctDNA) can be used for early cancer detection, treatment response assessment, prognosis, and predictive evaluations. Providing analyses that can increase the quality of patient treatment is very much a joint effort between laboratory scientists and clinicians. With its use approaching clinical practice, it is important for clinicians to be familiar with the basic concepts and analyses behind ctDNA results in a similar way as laboratory scientists should have knowledge of the clinical needs to provide relevant analyses. In this Perspective, we describe the whole process of ctDNA analyses, from the preanalytical standards to reporting/analyzing results, and highlight some important factors that need to be addressed in the process of implementing them to clinical practice.

Background: Colorectal cancer (CRC) remains a leading cause of death despite notable advancements through guideline-based management. We present data on changes of CRC care during the COVID-19 pandemic in Germany.

Methods: Retrospective data from 22 AIO CCs and an academic Institute of Pathology compared the first (fw, 03-05.2020) and second wave (sw, 11-12.2020) of the pandemic with corresponding 2019 periods. Parameters were: number of cases diagnosed, age, sex, tumor stage, surgical procedures, quality criteria of CRC care (presentation in multidisciplinary tumor boards (MTB), psychological or social consultation), number of precancerous and malignant colorectal lesions (CRL). Data points were compared as mean values with confidence intervals estimated according to Clopper and Pearson (1934). Hypothesis tests were conducted using Poisson regression models that included interaction terms (year*sex or year*age over70). Statistical significance was considered at P < .05.

Results: A total of 4316 cases diagnosed (AIO CC) revealed a substantial reduction (fw -20.58%; sw -23.48%). Hypothesis test showed a significant decline in incidence due to the fw and sw of the pandemic. Quality criteria of cancer care remained stable except for trial participation. Analysis from 60,695 CRL detected a decrease in precancerous (fw: -16 %/sw: -4 %) and malignant (fw: -18 %) lesions while malignant CRL increased in the sw (+8 %). Hypothesis test revealed a significant decline only for the fw 2020 and detected age > 70 as independent risk factor in both waves.

Conclusion: We detected substantial alterations in cancer care during the pandemic, including detected precancerous CRL. CCs showed high resilience in quality criteria for CRC care.

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.