p 300predictive value of circulating tumor derived dna ctdna in patients with locally advanced rectal cancer larc treated with neoadjuvant chemoradiotherapy ct rt preliminary results

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GZMKhigh CD8+ T effector memory cells are associated with CD15high neutrophil abundance in non-metastatic colorectal tumors and predict poor clinical outcome.

CD8(+) T cells are a major prognostic determinant in solid tumors, including colorectal cancer (CRC). However, understanding how the interplay between different immune cells impacts on clinical outcome is still in its infancy. Here, we describe that the interaction of tumor infiltrating neutrophils expressing high levels of CD15 with CD8(+) T effector memory cells (T(EM)) correlates with tumor progression. Mechanistically, stromal cell-derived factor-1 (CXCL12/SDF-1) promotes the retention of neutrophils within tumors, increasing the crosstalk with CD8(+) T cells. As a consequence of the contact-mediated interaction with neutrophils, CD8(+) T cells are skewed to produce high levels of GZMK, which in turn decreases E-cadherin on the intestinal epithelium and favors tumor progression. Overall, our results highlight the emergence of GZMK(high) CD8(+) T(EM) in non-metastatic CRC tumors as a hallmark driven by the interaction with neutrophils, which could implement current patient stratification and be targeted by novel therapeutics

Biomarkers in anal cancer: from biological understanding to stratified treatment

Squamous cell carcinomas of the anus and anal canal represent a model of a cancer and perhaps the first where level 1 evidence supported primary chemoradiotherapy (CRT) in treating locoregional disease with curative intent. The majority of tumours are associated with infection with oncogenic subtypes of human papilloma virus and this plays a significant role in their sensitivity to treatment. However, not all tumours are cured with CRT and there remain opportunities to improve outcomes in terms of oncological control and also reducing late toxicities. Understanding the biology of ASCC promises to allow a more personalised approach to treatment, with the development and validation of a range of biomarkers and associated techniques that are the focus of this review

Transarterial Embolization with Small-Size Particles Loaded with Irinotecan for the Treatment of Colorectal Liver Metastases: Results of the MIRACLE III Study

Purpose: This pilot study was performed to investigate safety and local tumor control following transarterial embolization with small-size particles loaded with irinotecan (DEB-IRI) in patients with colorectal liver metastases (CRLM). Materials and Methods: Patients with pretreated CRLM with mono- or bilobar lesions involving less than 60% of the liver parenchyma and Eastern Cooperative Oncology Group performance status 0 or 1 underwent superselective DEB-IRI embolization with 40 \ub5m diameter embolic microspheres. Results: Eighteen patients (11 males, 7 females, median age 61 years) underwent 80 embolization procedures (mean 4.4, range 2\u201312 per patient). No serious adverse events were reported within 30 days. A total of 39 treatment-related AEs occurred across all embolization procedures. No G4 or G5 treatment-related AEs occurred. Local tumor control, defined as complete response, partial response, or stable disease, was achieved in 16/18 (88.9%), 7/17 (41.2%), and 3/17 (17.6%) patients at 3, 6, and 12 months, respectively. Median liver progression-free survival was 5.9 months (range 27\u2013409 days), and median overall survival was 13.5 months. Conclusion: In this small series, DEB-IRI embolization with small beads was demonstrated a safe procedure in the treatment of patients with CRLM. The promising results in terms of liver-specific progression-free survival and overall survival reported deserve further confirmation in larger prospective trials. Level of Evidence: Level 4, case series

Lung metastases from colorectal cancer: analysis of prognostic factors in a single institution study

BACKGROUND: The aim of our study was to evaluate retrospectively in a large single institution setting all cases of lung resections for colorectal metastases from 1998 to 2008 and to assess clinicopathologic factors influencing outcome. METHODS: In all, 199 patients, 125 men and 74 women, with lung metastases of colorectal cancer, 120 colon and 79 rectum, underwent resection with curative intent; mean interval between primary surgery and lung metastasis was 35 months. Carcinoembryonic antigen preoperative value was abnormal in 52 patients; K-RAS wild-type was detected in 60 of 97 examined cases; 75 patients received preoperative or postoperative chemotherapy or both. A solitary lesion was described in 95 patients (47.7%), two or three metastases in 72 (36.2%), and more than three metastases in 26 (13.1%). Nodal status was reported in 130 patients (73%). One hundred twenty patients (60.3%) underwent wedge resection, 27 (13.6%) underwent segmentectomy, and 52 (26.1%) had lobectomy. An R0 resection was achieved in 178 cases (89.4%). RESULTS: Median overall survival was 4.2 years (95% confidence interval: 3.1 to 5.1) with a 5-year overall survival of 43% (95% confidence interval: 36% to 50%). An R1 resection (log rank p = 0.0001), thoracic nodal involvement (log rank p = 0.0002), and preoperative abnormal carcinoembryonic antigen value (log rank p < 0.001) were significantly associated with poor outcome in univariate analysis. In multivariate analysis, the same variables plus the number of lesions (single versus multiple, p = 0.04) were shown to affect outcome. CONCLUSIONS: An R0 resection, preoperative carcinoembryonic antigen, nodal involvement, and number of lesions represent strong prognostic factors in patient with lung metastases of colorectal cancer. The role of systemic treatments and biomolecular tests deserve future prospective investigations

Lung metastases from colorectal cancer: Analysis of prognostic factors in a single institution study

Background. The aim of our study was to evaluateretrospectively in a large single institution setting allcases of lung resections for colorectal metastases from1998 to 2008 and to assess clinicopathologic factorsinfluencing outcome.Methods. In all, 199 patients, 125 men and 74 women,with lung metastases of colorectal cancer, 120 colon and 79rectum, underwent resection with curative intent; meaninterval between primary surgery and lung metastasis was35 months. Carcinoembryonic antigen preoperative valuewas abnormal in 52 patients; K-RAS wild-type wasdetected in 60 of 97 examined cases; 75 patients receivedpreoperative or postoperative chemotherapy or both. Asolitary lesion was described in 95 patients (47.7%), two orthree metastases in 72 (36.2%), and more than three metastasesin 26 (13.1%). Nodal status was reported in 130patients (73%). One hundred twenty patients (60.3%) underwentwedge resection, 27 (13.6%) underwent segmentectomy,and 52 (26.1%) had lobectomy. An R0 resectionwas achieved in 178 cases (89.4%).Results. Median overall survival was 4.2 years (95%confidence interval: 3.1 to 5.1) with a 5-year overallsurvival of 43% (95% confidence interval: 36% to 50%).An R1 resection (log rank p [ 0.0001), thoracic nodalinvolvement (log rank p [ 0.0002), and preoperativeabnormal carcinoembryonic antigen value (log rankp &lt; 0.001) were significantly associated with pooroutcome in univariate analysis. In multivariate analysis,the same variables plus the number of lesions(single versus multiple, p [ 0.04) were shown to affectoutcome.Conclusions. An R0 resection, preoperative carcinoembryonicantigen, nodal involvement, and number oflesions represent strong prognostic factors in patient withlung metastases of colorectal cancer. The role of systemictreatments and biomolecular tests deserve future prospectiveinvestigations

Treatments for colorectal liver metastases: A new focus on a familiar concept

A major challenge for the management of advanced-colorectal-cancer is the multidisciplinary approach required for the treatment of liver metastases. Reducing the burden of liver metastases with liver-directed therapy has an important impact on both survival and health-related quality of life. This paper debates the rationale and current liver-directed approaches for colorectal liver metastases based on the evidence of literature and new clinical trials. Surgery is the gold standard, when feasible, and it's the main treatment goal for patients with potentially-resectable disease as a means of prolonging progression-free survival. Better tumor response rates with modern systemic therapy mean that more unresectable patients are now down-staged for radical resection following conversion therapy but for other patients, additional procedures are needed. In multiple unilobar disease, when the projected remnant liver is &lt;30% of the total liver, portal embolization or selective-internal-radiation-therapy (SIRT) can induce hypertrophy of the healthy liver, leading to resectability. In multiple bilobar disease, in situ destruction of non-resectable lesions by minimally invasive techniques may be associated with liver resection to achieve potential curative intent. Other palliative liver-directed approaches, such as SIRT or intra-hepatic chemotherapy (HAI), which are associated with higher response rates, may also have role in down-staging patients for resection. Until recently, such technologies have not been validated in prospective controlled trials. However in the light of new Phase 3 data for SIRT as well as for HAI combined with modern therapies or radiofrequency ablation in the first- and second-line setting, the clinical value of these treatments needs to be re-appraised

Location and condition based reconstruction of colon cancer microbiome from human RNA sequencing data

Abstract Background The association between microbes and cancer has been reported repeatedly; however, it is not clear if molecular tumour properties are connected to specific microbial colonisation patterns. This is due mainly to the current technical and analytical strategy limitations to characterise tumour-associated bacteria. Methods Here, we propose an approach to detect bacterial signals in human RNA sequencing data and associate them with the clinical and molecular properties of the tumours. The method was tested on public datasets from The Cancer Genome Atlas, and its accuracy was assessed on a new cohort of colorectal cancer patients. Results Our analysis shows that intratumoural microbiome composition is correlated with survival, anatomic location, microsatellite instability, consensus molecular subtype and immune cell infiltration in colon tumours. In particular, we find Faecalibacterium prausnitzii, Coprococcus comes, Bacteroides spp., Fusobacterium spp. and Clostridium spp. to be strongly associated with tumour properties. Conclusions We implemented an approach to concurrently analyse clinical and molecular properties of the tumour as well as the composition of the associated microbiome. Our results may improve patient stratification and pave the path for mechanistic studies on microbiota-tumour crosstalk