Locally Advanced Colorectal Cancer Research Articles

Neoadjuvant Immunotherapy for Patients With Microsatellite Instability-High or POLE-Mutated Locally Advanced Colorectal Cancer With Bulky Tumors: New Optimization Strategy

ObjectiveTo evaluate the efficacy and safety of neoadjuvant immunotherapy for patients with microsatellite instability-high (MSI-H) or DNA polymerase ε (POLE)-mutated locally advanced colorectal cancer (LACRC) with bulky tumors. PatientsWe retrospectively reviewed 22 consecutive patients with MSI-H or POLE-mutated LACRC with bulky tumors (>8 cm in diameter) who received preoperative programmed death-1 blockade, with or without CapOx chemotherapy. Main Outcome MeasuresPathological complete response (pCR), clinical complete response (cCR), toxicity, R0 resection rate, and complications were evaluated. Survival outcomes were analyzed using the Kaplan-Meier method. Multiplex immunofluorescence analysis were performed before and after treatment. ResultsThe incidence of immune-related adverse events (irAEs) was 36.4% (8/22). Five of 22 patients presented with surgical emergencies, most commonly perforation or obstruction. The 22 patients underwent a median 4 (1-8) cycles. Two patients were evaluated as cCR and underwent a watch and wait strategy. The R0 resection rate was 100.0% (20/20) and pCR rate was 70.0% (14/20). Twelve of 14 cT4b patients (85.7%) avoided multivisceral resection, and 10 of them achieved pCR or cCR. In the two patients with POLE mutations, one each achieved pCR and cCR. No Grade III/IV postoperative complications occurred. The median follow-up was 16.0 months. Two-year event-free and overall survival for the whole cohort was both 100%. ConclusionsPreoperative immunotherapy is the optimal option for MSI-H or POLE-mutated LACRC with bulky tumors, especially cT4b. Preoperative immunotherapy in patients with T4b CRC can reduce multivisceral resection and achieve high CR rate.

Development and validation of prognostic nomograms for overall survival in patients with locally advanced colorectal cancer

BackgroundMany colorectal cancer (CRC) patients are initially diagnosed at an advanced stage. Some evidence indicating that TNM staging may not be entirely reliable in forecasting survival outcomes. The research aims to develop accurate prediction models that can determine the survival outcomes of patients with clinically locally advanced colorectal cancer (LACRC). The study aims to provide valuable insights for clinical professionals to make right clinical decisions. MethodsWe retrospectively analyzed 636 LACRC patients admitted to the General Hospital of Western Theater Command between Jan 1, 2017, and Dec 31, 2019. Significant factors determining the prognosis of LACRC patients screened by lasso regression and multifactorial cox regression analysis. These factors were utilized to develop a nomogram model, which serves as a valuable predictive tool for estimating the overall survival (OS) of LACRC patients. Next, we validated the nomogram in the validation group. ResultsThe nomogram emphasized that the TNM stage holds the most prognostic value, followed by CA19–9 levels, smoking history, and MLR. Multiple assessments confirmed the superior discriminatory ability of the nomograms. ConclusionsWe have developed and verified nomograms that can predict OS cohort 635 LACRC patients. The survival nomogram may assist clinicians in better strategizing the therapeutic options for patients with LACRC.

Neoadjuvant immunotherapy for colorectal cancer: Right regimens, right patients, right directions?

Neoadjuvant chemoradiotherapy (NACRT) or chemotherapy (NACT) followed by radical resection and then adjuvant therapy is considered the optimal treatment model for locally advanced colorectal cancer (LACRC). A recent total neoadjuvant therapy (TNT) strategy further improved the tumour regression rate preoperatively and reduced local-regional recurrence in locally advanced rectal cancer (LARC). However, distant metastasis was still high, and little overall survival benefit was obtained from these preoperative treatment models. According to mismatch repair protein expression, MSI-H/dMMR and non-MSI-H/pMMR statuses were defined in colorectal cancer (CRC) patients. Due to the special features of biologics in MSI-H/dMMR CRC patients, this subgroup of patients achieved little treatment efficacy from chemoradiotherapy but benefited from immune checkpoint inhibitors (ICIs). The KEYNOTE-177 trial observed favourable survival outcomes in metastatic CRC patients treated with one-line pembrolizumab with tolerable toxicity. Given the better systemic immune function, increased antigenic exposure, and improved long-term memory induction before surgery, neoadjuvant ICI (NAICI) treatment was proposed. The NICHE trial pioneered the use of NAICI treatment in LACRC, and recent reports from several phase II studies demonstrated satisfactory tumour downsizing in CRC. Preclinical rationales and preliminary early-phase human trials reveal the feasibility of NAICI therapy and the therapeutic efficacy provided by this treatment model. Better tumour regression before surgery also increases the possibility of organ preservation for low LARC. However, the optimal treatment strategy and effective biomarker identification for beneficiary selection remain unknown, and potential pitfalls exist, including tumour progression during neoadjuvant treatment due to drug resistance and surgery delay. Given these foundations and questions, further phase II or III trials with large samples need to be conducted to explore the right regimens for the right patients.

Does Pathological T-Factor Affect Long-term Prognosis of Locally Advanced Colorectal Cancer Treated With Laparoscopic Multivisceral Resection?

Locally advanced colorectal cancer (LACC) has poor long-term outcomes. Our hypothesis was that the pathological tumor depth would affect postoperative outcomes in patients who underwent multivisceral resection with clear margins (R0). The aim of this study was to analyze short- and long-term outcomes in patients who underwent multivisceral resection for LACC, comparing between T3 and T4 stages. This was a propensity score-matched, retrospective study. All 8,764 consecutive patients who underwent surgery for colorectal cancer between April 2007 and January 2021 at the Saitama Medical University International Medical Center were screened; 572 underwent multivisceral resection for LACC. We compared the T3 and T4 groups to evaluate outcomes. The 5-year disease-free survival (DFS) rates did not significantly differ between the two groups (hazard ratio=1.344, 95% confidence interval=0.638-2.907, p=0.33). The 5-year overall survival (OS) rates were significantly worse for the T4 group than for the T3 group (hazard ratio=3.162, 95% confidence interval=1.077-11.44), p=0.037). To determine the association between American Society of Anesthesiologists (ASA) score, transfusion, pathological T and OS, we performed univariate and multivariate analyses. ASA, transfusion, and pathological T-stage were associated with worse OS in univariate analysis (T4 vs. T3, respectively). Our study showed that postoperative complications and DFS of the T4 group were similar to those of the T3 group of locally advanced colorectal cancer treated with laparoscopic multivisceral resection. However, OS was worse in the T4 group compared with the T3 group. Multivariate risk factors for poor OS were ASA>2, transfusion, and T4 stage.

Intensification of Local Therapy With High Dose Rate, Intraoperative Radiation Therapy (HDR-IORT) and Extended Resection for Locally Advanced and Recurrent Colorectal Cancer

BackgroundWe report our long-term experience with high dose rate intraoperative radiotherapy (HDR-IORT) in a single, quaternary institution. Patients/MethodsFrom 2004 to 2020, 60 HDR-IORT procedures for locally advanced colorectal cancer (LACC) and 81 for locally recurrent colorectal cancer (LRCC) were done in our institution. Preoperative radiotherapy was done prior to majority of the resections (89%, 125/141). Sixty-nine percent (58/84) of the resections involving pelvic exenterations had >3 en bloc organs resected. HDR-IORT was delivered using a Freiburg applicator. A single 10 Gy fraction was delivered. Margin status was R0 and R1 in 54% (76/141) and 46% (65/141) of the resections, respectively. ResultsWith a median follow-up time of 4 years, 3-, 5-, and 7- year, overall survival (OS) rates were 84%, 58%, and 58% for LACC and 68%, 41%, and 37% for LRCC, respectively. Local progression-free survival (LPFS) rates were 97%, 93%, and 93% for LACC and 80%, 80%, 80% for LRCC, respectively. For the LRCC group, an R1 resection was associated with worse OS, LPFS, and progression-free survival (PFS), preoperative EBRT was associated with improved LPFS and PFS, and ≥2 years disease-free interval was associated with improved PFS. The most common severe adverse events were postoperative abscess (n = 25) and bowel obstruction (n = 11). There were 68 grade 3 to 4 and no grade 5 adverse events. ConclusionsFavorable OS and LPFS can be achieved for LACC and LRCC with intensive local therapy. In patients with risk factors for poorer outcomes, optimization of EBRT and IORT, surgical resection, and systemic therapy are required.

Pathological response and safety of FOLFOXIRI for neoadjuvant treatment of high-risk relapsed locally advanced colon cancer: study protocol for a single-arm, open-label phase II trial

IntroductionNeoadjuvant chemotherapy (NAC) has been demonstrated effective in several tumours, but its benefit has not yet been elucidated in colorectal cancer, especially locally advanced colorectal cancer (LACRC).Methods and analysisThis is...

Clinical significance of neoadjuvant chemotherapy for locally advanced colorectal cancer patients with deficient mismatch repair: possibly residual value in the era of immunotherapy.

Deficient mismatch repair (dMMR) or microsatellite instability is one of the well-established molecular biomarkers in colorectal cancer (CRC). The efficiency of neoadjuvant chemotherapy (NAC) in locally advanced colorectal cancer (LACC) patients with dMMR is unclear. We assessed the tumor response and clinical outcome in LACC patients with dMMR received NAC. Retrospective, single-center analysis. From 2013 to 2018, a total of 577 LACC patients with dMMR who underwent radical surgery were identified. Among them, 109 patients who received adjuvant chemotherapy were further screened out for analysis. According to whether receiving NAC or not, 109 patients were divided into two groups with the purpose of retrospectively analyzing their characteristics, treatment, and survival results, especially the 5-year disease-free survival (DFS) and 5-year overall survival. Baseline characteristics were matched between the two groups. One of 40 patients in NAC group recurred, while 13 of 69 patients in non-NAC group recurred. Univariate and multivariate analyses showed that NAC (hazard ratio: 0.115; 95% confidence interval: 0.015-0.897; p = 0.039) was independent influence factor for DFS. In NAC group, there were 13/40 (32.5%) patients for tumor regression grade 1 and 27/40 (67.5%) patients converted clinical positive N-stage into negative N-stage. In this study, NAC was associated with better tumor downstaging and longer 5-year DFS in LACC patients with dMMR. Consequently, NAC might be an additional treatment choice when it comes to such patients in the future.

Pathological Complete Response Following Neoadjuvant Tislelizumab Monotherapy in Treatment-Naive Locally Advanced, MMR-Deficient/MSI-High Ascending Colon Cancer: A Case Report

Although recent trials started the use of neoadjuvant immunotherapy (NIT) in instability-high (MSI-H) or mismatch repair deficient (dMMR) early-stage or locally advanced colorectal cancer (LACRC), little data on the treatment strategy of NIT has been shown, and whether the tirelizumab mono-immune checkpoint inhibitor (ICI) can be used as NIT for patients with LACRC has not been reported as yet. In this study we report on a locally advanced ascending colon cancer case with a history of incomplete intestinal obstruction which achieved a pathologic complete response (pCR) after treated with Tirelizumab as NIT. A 32-year-old man was diagnosed with locally advanced ascending colon cancer with MSI-H and dMMR. An incomplete intestinal obstruction accompanied with hyperpyrexia occurred unexpectedly and was eased by symptomatic treatment. There was no peritonitis or other acute complications. NIT (three cycles of Tirelizumab) was suggested by the MDT board and partial response was achieved according to CT scanning, and pCR was further revealed by postoperative pathology. A ctDNA clearance confirmed the R0 resection and some immunotherapy related predictors were also detected using the NGS method. Our case study contributes to the evidence on the feasibility, efficacy, and safety of f Tirelizumab as a mono ICI for an optional neoadjuvant therapy in patients with MSI-H/dMMR LACRC.

CT radiomics identifying non-responders to neoadjuvant chemoradiotherapy among patients with locally advanced rectal cancer.

Early detection of non-response to neoadjuvant chemoradiotherapy (nCRT) for locally advanced colorectal cancer (LARC) remains challenging. We aimed to assess whether pretreatment radiotherapy planning computed tomography (CT) radiomics could distinguish the patients with no response or no downstaging after nCRT from those with response and downstaging after nCRT. Patients with LARC who were treated with nCRT were retrospectively enrolled between March 2009 and March 2019. Traditional radiological characteristics were analyzed by visual inspection and radiomic features were analyzed through computational methods from the pretreatment radiotherapy planning CT images. Differentiation models were constructed using radiomic methods and clinicopathological characteristics for predicting non-response to nCRT. Model performance was assessed for classification efficiency, calibration, discrimination, and clinical application. This study enrolled a total of 215 patients, including 151 patients in the training cohort (50 non-responders and 101 responders) and 64 patients in the validation cohort (21 non-responders and 43 responders). For predicting non-response, the model constructed with an ensemble machine learning method had higher performance with area under the curve (AUC) values of 0.92 and 0.89 as compared to the model constructed with the logistic regression method (AUC: 0.72 and 0.71 for the training and validation cohorts, respectively). Both decision curve and calibration curve analyses confirmed that the ensemble machine learning model had higher prediction performance. Pretreatment CT radiomics achieved satisfying performance in predicting non-response to nCRT and could be helpful to assist in treatment planning for patients with LARC.

Efficacy and Safety of Neoadjuvant Monoimmunotherapy With PD-1Inhibitor for dMMR/MSI⁃H Locally Advanced Colorectal Cancer: A Single-Center Real-World Study.

ObjectiveTo explore the efficacy and safety of single-agent programmed cell death protein-1 (PD-1) inhibitor in the neoadjuvant treatment of patients with mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) locally advanced colorectal cancer (LACRC) through single-center large⁃sample analysis based on real⁃world data in China.MethodsThis study was a retrospective, single-center, case series study. 33 colorectal cancer (CRC) patients with clinical stage of T3~4N0~2M0 treated in Yunnan Cancer Hospital from June 2019 to June 2021 were analyzed retrospectively. Among them, 32 patients were dMMR or MSI-H or both dMMR and MSI-H, and one patient was both dMMR and microsatellite stability (MSS) (excluded in the final analysis). All 32 patients received neoadjuvant immunotherapy (nIT) with single-agent PD⁃1 inhibitor.ResultsAmong the 32 patients, 8 (25%) were locally advanced rectal cancer (LARC) and 24 (75%) were locally advanced colon cancer (LACC); 4 (12.55%) were stage II and 28 (87.5%) were stage III. The median number of cycles of 32 patients with dMMR/MSI-H LACRC receiving nIT with single-agent PD-1 blockade was 6 (4~10), and the median number of cycles to achieve partial response (PR) was 3 (2~4). Among them, three LARC patients achieved clinical complete response (cCR) and adopted the watch-and-wait (W&W) strategy. The objective response rate (ORR) of the other 29 patients with radical surgery was 100% (29/29), the pathological response rate was 100% (29/29), the rate of major pathological response (MPR) was 86.2% (25/29), and the rate of pathological complete response (pCR) was 75.9% (22/29). The incidence of immune-related adverse events (irAEs) in 32 patients during nIT was 37.5% (12/32), while the incidence of irAEs in 22 patients with operation during adjuvant immunotherapy was 27.3% (6/22), all of which were grade 1~2. No grade 3 or above irAEs were occured. The median time from the last nIT to surgery was 27 (16~42) days. There were no delayed radical resection due to irAEs in these patients. All 29 patients achieved R0 resection. The incidence of surgical-related adverse events (srAEs) in perioperative period was 10.3% (3/29).ConclusionsNeoadjuvant monoimmunotherapy with PD-1 inhibitor has favorable ORR and pCR rate, and relatively low incidences of irAEs and srAEs for patients with dMMR/MSI-H LACRC, suggesting that this nIT regimen of single-agent PD-1 inhibitor is significantly effective and sufficiently safe.

First-time use of deep hyperthermia in local advanced Colo-rectal cancer: A preliminary insight into its role in improving quality of life and survival time.

First-time use of deep hyperthermia in local advanced Colo-rectal cancer: A preliminary insight into its role in improving quality of life and survival time.

Neoadjuvant Immunotherapy for MSI-H/dMMR Locally Advanced Colorectal Cancer: New Strategies and Unveiled Opportunities.

Patients with locally advanced colorectal cancer (LACRC) have a high risk of recurrence and metastasis, although neoadjuvant therapy may provide some benefit. However, patients with high microsatellite instability/deficient mismatch repair (MSI-H/dMMR) LACRC receive little benefit from neoadjuvant chemoradiotherapy (nCRT) or neoadjuvant chemotherapy (nCT). The 2015 KEYNOTE-016 trial identified MSI-H/dMMR as a biomarker indicative of immunotherapy efficacy, and pointed to the potential use of immune checkpoint inhibitors (ICIs). In 2017, the FDA approved two ICIs (pembrolizumab and nivolumab) for treatment of MSI-H/dMMR metastatic CRC (mCRC). In 2018, the CheckMate-142 trial demonstrated successful treatment of mCRC based on “double immunity” provided by nivolumab with ipilimumab, a regimen that may become a standard first-line treatment for MSI-H mCRC. In 2018, the FDA approved nivolumab alone or with ipilimumab for patients who progressed to MSI-H/dMMR mCRC after standard chemotherapy. The FDA then approved pembrolizumab alone as a first-line treatment for patients with MSI-H/dMMR CRC that was unresectable or metastatic. There is now interest in using these drugs in neoadjuvant immunotherapy (nIT) for patients with MSI-H/dMMR non-mCRC. In 2020, the NICHE trial marked the start of using nIT for CRC. This novel treatment of MSI-H/dMMR LACRC may change the approaches used for neoadjuvant therapy of other cancers. Our review of immunotherapy for CRC covers diagnosis and treatment, clinical prognostic characteristics, the mechanism of nIT, analysis of completed prospective and retrospective studies, and ongoing clinical trials, and the clinical practice of using nIT for MSI-H/dMMR LACRC. Our team also proposes a new organ-preservation strategy for patients with MSI-H/dMMR low LARC.

Comparison of the prognostic value of prognostic nutritional index in colorectal cancer deaths:a retrospective cohort study

Evidences showed that Prognostic Nutritional Index (PNI) is one important predictive factor for some cancers. However, the association between PNI and colorectal cancer is still unclear. In this study, we aim to explore the association between PNI and death in patients with locally advanced colorectal cancer. We enrolled 400 patients with colorectal cancer. The pathological results was used to confirm it. The patients received radical resection. The PNI at baseline was set as the exposure variable, death was the outcome variable, and other potential confounders were also analyzed. There was no association between PNI and the deaths of local advanced colorectal cancer and radical resection of colorectal cancer (HR=0.88; 95% CI, 0.78-1.00).Applying the cubic spline function, we found that it is not linear between PNI and death. Two-piecewise cox model showed that there was 68% decrease of risk of deaths when PNI change per 1 (HR=0.32; 95% CI, 0.13-0.79) on the left side of the inflection point (41.35). On the right of the inflection point, there was no association between PNI and death. PNI and deaths are linear correlation. Within a certain range (PNI=26-41), PNI is an independent protective factor for death risk.

Mitochondrial dysfunction induces radioresistance in colorectal cancer by activating [Ca2+]m-PDP1-PDH-histone acetylation retrograde signaling

Mitochondrial retrograde signaling (mito-RTG) triggered by mitochondrial dysfunction plays a potential role in regulating tumor metabolic reprogramming and cellular sensitivity to radiation. Our previous studies showed phos-pyruvate dehydrogenase (p-PDH) and PDK1, which involved in aerobic glycolysis, were positively correlated with radioresistance, but how they initiate and work in the mito-RTG pathway is still unknown. Our further genomics analysis revealed that complex I components were widely downregulated in mitochondrial dysfunction model. In the present study, high expression of p-PDH was found in the complex I deficient cells and induced radioresistance. Mechanistically, complex I defects led to a decreased PDH both in cytoplasm and nucleus through [Ca2+]m-PDP1-PDH axis, and decreased PDH in nucleus promote DNA damage repair (DDR) response via reducing histone acetylation. Meanwhile, NDUFS1 (an important component of the complex I) overexpression could enhance the complex I activity, reverse glycolysis and resensitize cancer cells to radiation in vivo and in vitro. Furthermore, low NDUFS1 and PDH expression were validated to be correlated with poor tumor regression grading (TRG) in local advanced colorectal cancer (CRC) patients underwent neoadjuvant radiotherapy. Here, we propose that the [Ca2+]m-PDP1-PDH-histone acetylation retrograde signaling activated by mitochondrial complex I defects contribute to cancer cell radioresistance, which provides new insight in the understanding of the mito-RTG. For the first time, we reveal that NDUFS1 could be served as a promising predictor of radiosensitivity and modification of complex I function may improve clinical benefits of radiotherapy in CRC.

Neoadjuvant chemotherapy for locally advanced colon cancer patients: Long-term results from a single institutional experience.

e15598 Background: Neoadjuvant chemotherapy (NAC) is an emerging alternative in the management of patients with locally advanced colorectal cancer (LACRC), with promising results in terms of R0 resection rates, compliance, postoperative morbidity and a trend towards reduced risk of relapse. However, more mature data are required. We evaluated the long-term outcome of this strategy in our institution. Methods: We retrospectively analysed LACRC patients treated preoperatively with either biweekly FOLFOX or XELOX at standard doses as a follow-up of our previous experience with this neoadjuvant approach. Patients were identified from a prospectively collected tumor registry database from our institution. Clinical staging was based on colonoscopy and CT-scan. Only patients with radiological signs of lymph node involvement and/or extramural invasion > 5 mm were included. The uracil/dihidrouracil ratio was calculated at baseline as a surrogate marker of DPD deficiency. Pathological tumor regression was graded according to the MSKCC and toxicity with the NCI-CTCAE 4.0. Results: From February 2006 to November 2019 91 pts with MSS LACRC (M/F: 62/29; median age 66. Clinical stage; T3: 60.4%, T4: 37.4%, N+: 75.8%; Sideness: 82.4% left located were analysed. Preoperative chemo was FOLFOX in 46 pts and CAPOX in 45 pts. Median number of preoperative cycles was 4 (range 1-10). Side effects profile included G3-4 diarrhea (3.3%), G2 sensitive neuropathy (12.1%) and G2 neutropenia (4.4%). 9 pts had a treatment delay due to haematological toxicity. No progressive disease was noted during neoadjuvant chemotherapy. All patients underwent surgery, most of them (63.7%) by a laparoscopic approach. pCR was found in 11 pts (12.1%). Grade 3, 3+ and 4 tumor regression according to MSKCC score was reached in 50.5% of the patients (Median number of harvested nodes was 17 (range 7-51), with 75.8% being ypN0. Lymphovascular and perineural invasion were found in 7.7% and 6.6% of the patients, respectively. The median hospital stay was 7 days (3-36) and 13 pts develop any surgical complication. 37.4% received adjuvant treatment. After a median follow-up of 63 months, median progression-free (PFS) and overall survival (OS) have not been reached. 5-year actuarial PFS for right and left LACRC was 77 and 87%, respectively. Conclusions: Our data add to the growing evidence suggesting that NAC may play a meaningful role in LACRC patients

Low MicroRNA-19b Expression Shows a Promising Clinical Impact in Locally Advanced Rectal Cancer.

Simple SummaryThe establishment of molecular markers to predict response to neoadjuvant chemoradiotherapy (CRT) would help to avoid unnecessary toxicities and surgery delays in the clinical management of locally advanced rectal cancer (LARC) patients. Our aim here was to in-vestigate the clinical impact of miR-19b in this disease. Interestingly, our findings highlight the potential usefulness of miR-19b as a predictor of response to neoadjuvant CRT and outcome, and suggest PPP2R5E as a relevant miR-19b target in LARC.The standard treatment for patients with locally advanced colorectal cancer (LARC) is neoadjuvant 5-fluorouracil (5-FU) based chemoradiotherapy (CRT) followed by surgical mesorectal excision. However, the lack of response to this preoperative treatment strongly compromises patient outcomes and leads to surgical delays and undesired toxicities in those non-responder cases. Thus, the identification of effective and robust biomarkers to predict response to preoperative CRT represents an urgent need in the current clinical management of LARC. The oncomiR microRNA-19b (miR-19b) has been reported to functionally play oncogenic roles in colorectal cancer (CRC) cells as well as regulate 5-FU sensitivity and determine outcome in CRC patients. However, its clinical impact in LARC has not been previously investigated. Here, we show that miR-19b deregulation is a common event in this disease, and its decreased expression significantly associates with lower tumor size after CRT (p = 0.003), early pathological stage (p = 0.003), and absence of recurrence (p = 0.001) in LARC patients. Interestingly, low miR-19b expression shows a predictive value of better response to neoajuvant CRT (p < 0.001), and the subgroup of LARC patients with low miR-19b levels have a markedly longer overall (p = 0.003) and event-free survival (p = 0.023). Finally, multivariate analyses determined that miR-19b independently predicts both patient outcome and response to preoperative CRT, highlighting its potential clinical usefulness in the management of LARC patients.

The Role of expedited adjuvant intraperitoneal chemotherapy in locally advanced colorectal cancer - a systematic review

Introduction: Locally advanced colorectal cancer (LACRC), defined as T4 N0-2 M0 tumours, frequently metastasizes intraperitoneally. Peritoneal metastases occur in 41% of T4 tumours, and augur significant morbidity and mortality. Adjuvant intraperitoneal chemotherapy targets micro-metastatic deposits from the primary tumour which may progress to peritoneal carcinomatosis. We systematically reviewed the effect of intraperitoneal chemotherapy delivered within a month of cytoreductive surgery on outcomes in LACRC.

CELL MEDIATED IMMUNITY IN PATIENTS WITH STAGE II–IV COLORECTAL CANCER WITH OR WITHOUT CIRCULATING TUMOR CELLS

Nowadays, circulating tumor cells (CTCs) are considered to be one of the most important mechanisms of tumor dissemination. Detection of CTCs in patients` blood is estimated as a prognostic factor for various tumors including colorectal cancer (CRC). However, CTCs may also be a source of tumor antigens capable of inducing both immune response and tolerance and participating in «immmunoediting». The aim of the study was to assess the parameters of cell-mediated immunity in patients with stage IIIV CRC with respect to the presence or absence of CTCs. Materials and Methods . We studied the parameters of cell-mediated immunity in 60 patients with stage IIIV CRC with respect to the presence or absence of CTCs. Before treatment, we evaluated the CTC levels in patients’ blood using CellSearch System™ and lymphocyte subsets: Т-В-NК-cells, T-reg, CD4+ and CD8+ expressing markers of activation (CD69+, СD38+, CD25+, HLA-DR+ СD95+); naïve and memory T-lymphocytes (CD45RA-/CD45RO+); NК-cells expressing CD335, perforin and granzyme B using flow cytometry (FACSCantoII, BD). Results . A difference in the immunologic parameters between patients with CTCs and without CTCs depending on the stage of CRC was found. In СTС-positive patients with locally-advanced CRC, increase in the parameters of innate immunity (CD335+ NK-cells, neutrophils` respiratory burst) and activated Th (CD38+, CD25+, HLA-DR+) was found, while in СTС-positive patients with generalized CRC, suppression of cytotoxic lymphocytes of both innate (CD56/16+) and adaptive (CD8+CD25+) immunity was observed, which is, apparently, an unfavorable prognostic factor. Conclusion . The presence of CTC in CRC patients is accompanied by some immunologic changes rather stimulating Thlink and innate immunity factors in II-III stages and doubtlessly suppressive in patients with IV stage.

Prognostic nutritional index and colorectal cancer deaths: A retrospective cohort study in Chinese patients with locally advanced colorectal cancer.

e15160 Background: The nutrition and immune status-based scoring system PNI was originally used to assess the nutritional status and surgical risk of surgical patients before surgery. Subsequent studies have shown that PNI is an important prognostic indicator for some malignant tumors, including hepatocellular carcinoma, pancreatic cancer, laryngeal cancer, renal cell carcinoma and gastric cancer. We speculated that since PNI is associated with the prognosis of other malignancies, is it also relevant in colorectal cancer? In view of the obvious increase in the incidence of colorectal cancer in China, and the clinical progress of colorectal cancer in the entire colorectal cancer accounted for up to 70% and current studies on PNI and local advanced colorectal cancer prognosis association study in Chinese is limited. In the present study, our primary objective was to explore whether PNI evaluated at baseline was independently associated with colorectal cancer deaths after controlling other potential confounders. Methods: Through a retrospective cohort study, we analyzed the clinical data of 400 patients with pathologically confirmed colorectal cancer and radical resection of colorectal cancer from January 2013 to April 2018.The exposure variable was PNI at baseline, the outcome variable was death, and other covariates of this study include: Continuous variables: age, platelet count, tumor markers (CEA, CA199, CA724, CA242).Categorical variables: gender, survival status, tumor location, histological type, degree of differentiation, TNM staging, and postoperative treatment. Results: Fully-adjusted model demonstrated that PNI was not associated with deaths of local advanced colorectal cancer and radical resection of colorectal cancer (HR = 0.88; 95% CI, 0.78-1.00). By applying the cubic spline function to the model, we found that the relationship between PNI and death is nonlinear.Two-piecewise cox model suggested that On the left side of the inflection point (41.35), PNI per 1 change is associated with the 68% decrease of risk of deaths (HR = 0.32; 95% CI, 0.13-0.79), to the right of the inflection point, PNI and death The association is not detected. Conclusions: PNI and deaths are nonlinearity, and within a certain range (PNI = 26-41), PNI is an independent protective factor for death risk.

The main contributor to the upswing of survival in locally advanced colorectal cancer: an analysis of the SEER database.

Background:There is no conclusion about the most important contributor to the upswing of locally advanced colorectal cancer (LACRC) survival.Methods:Data from the Surveillance, Epidemiology, and End Results (SEER) database was extracted to identify colorectal adenocarcinoma cancer patients at stage II and III diagnosed in the two periods 1989–1990 and 2009–2010. The statistical methods included Pearson’s chi-squared test, log-rank test, Cox regression model and propensity score matching.Results:The Cox regression model showed that hazard ratio (HR) of non-surgery dropped from 11.529 to 3.469 in right colon cancer (RCC), 5.214 to 2.652 in left colon cancer (LCC) and 3.275 to 3.269 in rectal cancer (RC) from 1989–1990 to 2009–2010. The 95% confidence intervals (CIs) for surgical resection in 2009–2010 were narrower than those in 1989–1990. HR became greater in LACRC without chemotherapy (from 1.337 to 1.779 in RCC, 1.269 to 2.017 in LCC, 1.317 to 1.811 in RC). There was no overlapping about the 95% CI of chemotherapy between the two groups. The progress of surgery was not linked to the improvement of overall survival (OS) of RCC (p = 0.303) and RC (p = 0.660). Chemotherapy had a significant association with OS of all colorectal cancer (CRC) patients (p = 0.017 in RCC; p = 0.006 in LCC; p = 0.001 in RC).Conclusions:Advancements in chemotherapy regimen were the main contributor to the upswing of CRC survival. The improvements in surgery had a limited effect on improvements in CRC survival.