Objectives
To assess the value of contrast-enhanced (CE) diagnostic CT scans characterized through radiomics as predictors of recurrence for patients with stage II and III colorectal cancer in a ...two-center context.
Materials and methods
This study included 193 patients diagnosed with stage II and III colorectal adenocarcinoma from 1 July 2008 to 15 March 2017 in two different French University Hospitals. To compensate for the variability in two-center data, a statistical harmonization method Bootstrapped ComBat (B-ComBat) was used. Models predicting disease-free survival (DFS) were built using 3 different machine learning (ML): (1) multivariate regression (MR) with 10-fold cross-validation after feature selection based on least absolute shrinkage and selection operator (LASSO), (2) random forest (RF), and (3) support vector machine (SVM), both with embedded feature selection.
Results
The performance for both balanced and 95% sensitivity models was systematically higher after our proposed B-ComBat harmonization compared to the use of the original untransformed data. The most clinically relevant performance was achieved by the multivariate regression model combining a clinical variable (postoperative chemotherapy) with two radiomics shape descriptors (compactness and least axis length) with a BAcc of 0.78 and an MCC of 0.6 associated with a required sensitivity of 95%. The resulting stratification in terms of DFS was significant (
p
= 0.00021), especially compared to the use of unharmonized original data (
p
= 0.17).
Conclusions
Radiomics models derived from contrast-enhanced CT could be trained and validated in a two-center cohort with a good predictive performance of recurrence in stage II et III colorectal cancer patients.
Key Points
•
Adjuvant therapy decision in colorectal cancer can be a challenge in medical oncology.
•
Radiomics models, derived from diagnostic CT, trained and validated in a two-center cohort, could predict recurrence in stage II and III colorectal cancer patients
.
• Identifying patients with a low risk of recurrence, these models could facilitate treatment optimization and avoid unnecessary treatment.
Recently, preclinical and clinical studies targeting several types of cancer strongly supported the key role of the gut microbiota in the modulation of host response to anti-tumoral therapies such as ...chemotherapy, immunotherapy, radiotherapy and even surgery. Intestinal microbiome has been shown to participate in the resistance to a wide range of anticancer treatments by direct interaction with the treatment or by indirectly stimulating host response through immunomodulation. Interestingly, these effects were described on colorectal cancer but also in other types of malignancies. In addition to their role in therapy efficacy, gut microbiota could also impact side effects induced by anticancer treatments. In the first part of this review, we summarized the role of the gut microbiome on the efficacy and side effects of various anticancer treatments and underlying mechanisms. In the second part, we described the new microbiota-targeting strategies, such as probiotics and prebiotics, antibiotics, fecal microbiota transplantation and physical activity, which could be effective adjuvant therapies developed in order to improve anticancer therapeutic efficiency.
Data regarding clinical outcomes of patients undergoing hepatic resection for BRAF-mutated colorectal liver metastases (CRLM) are scarce. Most of the studies report an impaired median overall ...survival (OS) in BRAF-mutated patients, but controversial Results regarding both recurrence-free survival (RFS) and recurrence patterns. The purpose of this updated meta-analysis was to better precise the impact of BRAF mutations on clinical outcomes following liver surgery for CRLM study, especially on recurrence.
A systematic literature review was performed to identify articles reporting clinical outcomes including both OS and RFS, recurrence patterns, and clinicopathological details of patients who underwent complete liver resection for CRLM, stratified according to BRAF mutational status.
Thirteen retrospective studies, including 5192 patients, met the inclusion criteria. The analysis revealed that both OS (OR = 1.981; 95% CI = 1.613–2.432) and RFS (OR = 1.49; 95% CI 1.01–2.21) were impaired following liver surgery for CRLM in BRAF-mutated patients. Risks of both hepatic (OR = 0.42; 95% CI 0.18–0.98) and extrahepatic recurrences (OR = 0.53; 95% CI 0.33–0.83 were significantly higher in BRAF-mutated patients. These patients tended to have higher rates of right-sided colon primary tumors, primary positive lymph nodes, and multiple CRLM.
This meta-analysis confirms that BRAF mutations impair both OS and RFS following liver surgery. Therefore, BRAF mutational status should probably be included in further prognostic scores for the assessment of the expected clinical outcomes following surgery for CRLM.
To investigate the role of minimally invasive surgery for gastric cancer and determine surgical, clinical, and oncological outcomes.
This is a propensity score-matched case-control study, comparing ...three treatment arms: robotic gastrectomy (RG), laparoscopic gastrectomy (LG), open gastrectomy (OG). Data collection started after sharing a specific study protocol. Data were recorded through a tailored and protected web-based system. Primary outcomes: harvested lymph nodes, estimated blood loss, hospital stay, complications rate. Among the secondary outcomes, there are: operative time, R0 resections, POD of mobilization, POD of starting liquid diet and soft solid diet. The analysis includes the evaluation of type and grade of postoperative complications. Detailed information of anastomotic leakages is also provided.
The present analysis was carried out of 1026 gastrectomies. To guarantee homogenous distribution of cases, patients in the RG, LG and OG groups were 1:1:2 matched using a propensity score analysis with a caliper = 0.2. The successful matching resulted in a total sample of 604 patients (RG = 151; LG = 151; OG = 302). The three groups showed no differences in all baseline patients characteristics, type of surgery (
= 0.42) and stage of the disease (
= 0.16). Intraoperative blood loss was significantly lower in the LG (95.93 ± 119.22) and RG (117.91 ± 68.11) groups compared to the OG (127.26 ± 79.50,
= 0.002). The mean number of retrieved lymph nodes was similar between the RG (27.78 ± 11.45), LG (24.58 ± 13.56) and OG (25.82 ± 12.07) approach. A benefit in favor of the minimally invasive approaches was found in the length of hospital stay (
< 0.0001). A similar complications rate was found (
= 0.13). The leakage rate was not different (
= 0.78) between groups.
Laparoscopic and robotic surgery can be safely performed and proposed as possible alternative to open surgery. The main highlighted benefit is a faster postoperative functional recovery.
Prognostic stratification of patients with colorectal cancer liver metastasis based solely on tumor-related factors has only moderate discriminatory ability. We hypothesized that the inclusion of ...nontumor related factors can improve prediction of long-term prognosis of patients with colorectal cancer liver metastasis.
Nontumor related laboratory markers were assessed utilizing a training cohort from 2 U.S. institutions (n = 1,205). Factors independently associated with prognosis were used to develop a nontumor related prognostic score. The discriminatory ability, assessed by Harrell’s C-statistics (C-index) and net reclassification improvement, was validated and compared with 3 commonly used tumor-related clinical risk scores: Fong clinical risk scores, m-clinical risk scores, and Genetic and Morphological Evaluation (GAME) score in an external validation cohort from 5 Asian (n = 1,307) and 3 European (n = 1,058) institutions. The discriminatory ability of nontumor related prognostic score combined with each of these 3 tumor-related prognostic scores was also estimated.
Alkaline phosphatase (hazard ratio 1.43; 95% confidence interval, 1.11–1.84), albumin (hazard ratio 0.71; 95% confidence interval, 0.57–0.89), and mean corpuscular volume (hazard ratio 19.0, per log unit; 95% confidence interval, 4.79–75.0) were each independently associated with increased risk of death after resection of colorectal cancer liver metastasis (all P < .05). In turn, alkaline phosphatase, albumin, and mean corpuscular volume were combined to form a nontumor related prognostic score (2.942 × mean corpuscular volume + 0.399 × alkaline phosphatase-0.339 × albumin-12) × 10 (median, 16; range, 1–30). The nontumor related prognostic score had good-to-modest discriminatory ability in the external cohort (C-index = 0.58), which was comparable to the 3 established tumor-related prognostic scores (C-index: Fong clinical risk scores, 0.53, m-clinical risk scores, 0.55, GAME, 0.58). The addition of the nontumor related prognostic score to the tumor-related prognostic scores enhanced the discriminatory ability in the entire study cohort (C-index: nontumor related score+Fong, 0.60, nontumor related score+m-clinical risk scores, 0.61, nontumor related score+GAME, 0.64), as well reclassification improvement (42.5, 42.7%, and 21.2%, respectively).
Nontumor related prognostic information may help improve the prognostic stratification of patients after resection of colorectal cancer liver metastasis. The nontumor related prognostic score may be combined with tumor-related prognostic tools to enhance prognostic stratification of patients with colorectal cancer liver metastasis.
Pancreaticobiliary maljunction (PBM) and choledochal cysts (CC) are rare and little-known diseases. Several definitions have been proposed for the PBM, but the most widely accepted is an excessive ...length of the common pancreaticobiliary duct due to the abnormal convergence of the pancreatic and biliary ducts out of the duodenal wall. This anomaly, thought to develop during embryogenesis, is associated with a loss of regulation of the Oddi’s sphincter leading to a pancreaticobiliary or biliopancreatic backflow. This reflux could be responsible, or associated with cystic dilatation of the bile ducts and biliary tract cancers, to various biliary or pancreatic events such as cholangitis or pancreatitis. For the diagnosis of PBM, magnetic resonance cholangiopancreatography has now become the gold standard as a noninvasive imaging tool. However, the main risk of PBM is the development of bile duct cancer, most often on a distended area. PBM without CC increase the occurrence of gallbladder cancer and require a preventive cholecystectomy. Surgical treatment of PBM with concomitant CC is more complex and depends on localization of the dilatation(s) as reported in the Todani’s classification. This review describes the pathogenesis, embryogenesis, clinical features, investigation and management of PBM and CC.
Intratumoral bacteria flexibly contribute to cellular and molecular tumor heterogeneity for supporting cancer recurrence through poorly understood mechanisms. Using spatial metabolomic profiling ...technologies and 16SrRNA sequencing, we herein report that right-sided colorectal tumors are predominantly populated with Colibactin-producing
(CoPEC) that are locally establishing a high-glycerophospholipid microenvironment with lowered immunogenicity. It coincided with a reduced infiltration of CD8
T lymphocytes that produce the cytotoxic cytokines IFN-γ where invading bacteria have been geolocated. Mechanistically, the accumulation of lipid droplets in infected cancer cells relied on the production of colibactin as a measure to limit genotoxic stress to some extent. Such heightened phosphatidylcholine remodeling by the enzyme of the Land's cycle supplied CoPEC-infected cancer cells with sufficient energy for sustaining cell survival in response to chemotherapies. This accords with the lowered overall survival of colorectal patients at stage III-IV who were colonized by CoPEC when compared to patients at stage I-II. Accordingly, the sensitivity of CoPEC-infected cancer cells to chemotherapies was restored upon treatment with an acyl-CoA synthetase inhibitor. By contrast, such metabolic dysregulation leading to chemoresistance was not observed in human colon cancer cells that were infected with the mutant strain that did not produce colibactin (11G5
). This work revealed that CoPEC locally supports an energy trade-off lipid overload within tumors for lowering tumor immunogenicity. This may pave the way for improving chemoresistance and subsequently outcome of CRC patients who are colonized by CoPEC.
The gut microbiota acts as a real organ. The symbioticinteractions between resident micro-organisms and thedigestive tract highly contribute to maintain the guthomeostasis. However, alterations to ...the microbiomecaused by environmental changes （e.g. , infection, dietand/or lifestyle） can disturb this symbiotic relationshipand promote disease, such as inflammatory boweldiseases and cancer. Colorectal cancer is a complexassociation of tumoral cells, non-neoplastic cells and alarge amount of micro-organisms, and the involvementof the microbiota in colorectal carcinogenesis isbecoming increasingly clear. Indeed, many changes inthe bacterial composition of the gut microbiota havebeen reported in colorectal cancer, suggesting a majorrole of dysbiosis in colorectal carcinogenesis. Somebacterial species have been identified and suspectedto play a role in colorectal carcinogenesis, such asStreptococcus bovis , Helicobacter pylori , Bacteroides fragilis , Enterococcus faecalis , Clostridium septicum ,Fusobacterium spp. and Escherichia coli . The potentialpro-carcinogenic effects of these bacteria are nowbetter understood. In this review, we discuss thepossible links between the bacterial microbiota andcolorectal carcinogenesis, focusing on dysbiosis andthe potential pro-carcinogenic properties of bacteria,such as genotoxicity and other virulence factors,inflammation, host defenses modulation, bacterialderivedmetabolism, oxidative stress and antioxidativedefenses modulation. We lastly describehow bacterial microbiota modifications could representnovel prognosis markers and/or targets for innovativetherapeutic strategies.
PDF
