scholarly journals Mechanisms of Immunosuppression in Colorectal Cancer

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3850
Author(s):  
Yang Zhang ◽  
Ashwani Rajput ◽  
Ning Jin ◽  
Jing Wang
Keyword(s):  
Palliative Chemotherapy ◽  
Locally Advanced ◽  
Standard Of Care ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Immune Checkpoint Blockade ◽  
The Us ◽  
Promising Treatment ◽  
Modality Approach ◽  
Improve Treatment Efficacy

CRC is the third most diagnosed cancer in the US with the second-highest mortality rate. A multi-modality approach with surgery/chemotherapy is used in patients with early stages of colon cancer. Radiation therapy is added to the armamentarium in patients with locally advanced rectal cancer. While some patients with metastatic CRC are cured, the majority remain incurable and receive palliative chemotherapy as the standard of care. Recently, immune checkpoint blockade has emerged as a promising treatment for many solid tumors, including CRC with microsatellite instability. However, it has not been effective for microsatellite stable CRC. Here, main mechanisms of immunosuppression in CRC will be discussed, aiming to provide some insights for restoring immunosurveillance to improve treatment efficacy in CRC.

Locally Advanced Rectal Cancer: Time for Precision Therapeutics

2015 ◽  
pp. e192-e196 ◽  
Author(s):  
Martin R. Weiser ◽  
Zhen Zhang ◽  
Deborah Schrag
Keyword(s):  
Rectal Cancer ◽  
Local Recurrence ◽  
Locally Advanced ◽  
Standard Of Care ◽  
Advanced Rectal Cancer ◽  
The United States ◽  
Locally Advanced Rectal Cancer ◽  
Neoadjuvant Chemoradiation ◽  
Current Standard ◽  
Trimodality Therapy

The year 2015 marks the 30th anniversary of the publication of NSABP-R01, a landmark trial demonstrating the benefit of adding pelvic radiation to the treatment regimen for locally advanced rectal cancer with a resultant decrease in local recurrence from 25% to 16%. These results ushered in the era of multimodal therapy for rectal cancer, heralding modern treatment and changing the standard of care in the United States. We have seen many advances over the past 3 decades, including optimization of the administration and timing of radiation, widespread adoption of total mesorectal excision (TME), and the implementation of more effective systemic chemotherapy. The current standard is neoadjuvant chemoradiation with 5-fluorouracil (5-FU) and a radiosensitizer, TME, and adjuvant chemotherapy including 5-FU and oxaliplatin. The results of this regimen have been impressive, with a reported local recurrence rate of less than 10%. However, the rates of distant relapse remain 30% to 40%, indicating room for improvement. In addition, trimodality therapy is arduous and many patients are unable to complete the full course of treatment. In this article we discuss the current standard of care and alternative strategies that have evolved in an attempt to individualize therapy according to risk of recurrence.

Emerging strategies in the initial management of locally advanced rectal cancer

2019 ◽  
Vol 15 (25) ◽  
pp. 2955-2965 ◽  
Author(s):  
Lucy Gately ◽  
Hui-Li Wong ◽  
Jeanne Tie ◽  
Rachel Wong ◽  
Margaret Lee ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Treatment Plan ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Treatment Strategies ◽  
Standard Of Care ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Current Standard ◽  
Initial Management

The initial management of locally advanced rectal cancer continues to evolve and formulating the ideal treatment plan remains challenging, with a multitude of emerging treatment strategies and either limited or inconsistent data to support these. The main objective of neoadjuvant treatment is to maximize disease control and minimize toxicity and impact on quality of life. Ultimately, the optimal approach needs to be personalized to the individual. In this Review, we discuss the various strategies currently used and being further investigated in the initial treatment of patients presenting with locally advanced rectal cancer. We describe the evidence behind the current standard of care recommendations and emerging new options, as well as potential biomarkers that may assist with further refining treatment selection.

scholarly journals A Primer on the Current State-of-the-Science Neoadjuvant and Adjuvant Therapy for Patients with Locally Advanced Rectal Adenocarcinomas

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Jeffrey T. Yorio ◽  
Nishin A. Bhadkamkar ◽  
Bryan K. Kee ◽  
Christopher R. Garrett
Keyword(s):  
Adjuvant Therapy ◽  
Locally Advanced ◽  
Standard Of Care ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Current Standard ◽  
Colon Cancers ◽  
Standard Of Care Treatment ◽  
Rectal Cancers ◽  
State Of The Science

Patients with rectal cancers, due to the unique location of the tumor, have a recurrence pattern distinct from colon cancers. Advances in adjuvant therapy over the last three decades have played an important role in improving patient outcomes. This article serves to review the clinical studies that lay the basis for our current standard-of-care treatment of patients with locally advanced rectal cancer, as well as touch upon future ongoing experimental clinical trials of adjuvant chemoradiation therapy.

Current possibilities of predicting the therapeutic response to neoadjuvant chemoradiotherapy in rectal cancer

2020 ◽  
Vol 74 (5) ◽  
pp. 393-403
Author(s):  
Filip Pazdírek ◽  
Marek Minárik ◽  
Lucie Benešová ◽  
Jiří Hoch ◽  
Radka Lohynská
Keyword(s):  
Rectal Cancer ◽  
Therapeutic Response ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Therapy Response ◽  
Standard Of Care ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Dna And Rna ◽  
Post Radiation

Neoadjuvant chemotherapy in combination with radiation is currently the standard of care for patients with locally advanced rectal cancer. The main purpose of the treatment is to reduce the risk of recurrence, however at the same time it may be accompanied by severe adverse effects due to post-radiation pelvic damage. An effort towards finding markers allowing the prediction of the therapy response has been undertaken by many groups. In this review we have performed a literature search to identify the main studies directed at the use of clinical, radiological, immunological and molecular (protein, DNA and RNA) markers. We present a summary for each group with an overall conclusion that a certain level of ambiguity and disunity in interpretation of the results currently exists among the reported findings. Apparently, even in the most promising direction of circulating molecular bio­markers further work is needed before a clinical utility can be established.

Effect of short course radiation followed by four cycles of FOLFOX as preoperative therapy for rectal cancer on rate of PCR: A phase II trial.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 471-471
Author(s):  
Robert J. Myerson ◽  
Parag J. Parikh ◽  
Steven R. Hunt ◽  
Benjamin Tan
Keyword(s):  
Rectal Cancer ◽  
Residual Disease ◽  
Locally Advanced ◽  
Standard Of Care ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Cytotoxic Agents ◽  
Preoperative Treatment ◽  
Short Course ◽  
Grade 3

471 Background: Preoperative radiotherapy (RT) with 5FU chemotherapy (CT) is a standard of care for cT3-4 rectal cancer. Studies incorporating additional cytotoxic agents have resulted in increased morbidity with little benefit. We evaluate a template that seeks to (1) include the benefits of preoperative RT on local response/control, (2) provide preoperative multi-drug CT, (3) avoid the morbidity of concurrent RT and multi-drug CT. Methods: Patients with cT3-4, any N, any M rectal cancer were eligible. Patients were confirmed to be candidates for surgery, provided the response was sufficient. Preoperative treatment was 5 fractions RT (25 Gy to involved mesorectum, 20 Gy to elective nodes), followed by 4 cycles of mFOLFOX6. Postoperative CT was at the discretion of the medical oncologist. The principal objectives were to achieve T stage down staging (ypT < cT) and acute grade 3+ gastrointestinal (GI) morbidity equal or better than historic controls. Results: 80 patients were enrolled from 11/2009 through 4/2012. All have had sufficient time for principal endpoint analysis. Four are inevaluable for response: 1 patient withdrew consent after completing RT and never received CT and 3 did not undergo surgery (new comorbidity in 2 cases, progression of distant metastatic disease in 1 case). Grade 3 preoperative GI morbidity occurred in 7 cases (9%) (no grade 4 or 5). The 76 evaluable cases included 7 cT4 and 69 cT3; 59 (78%) cN+, 8 cM1. Sphincter preserving surgery was performed on 49 (64%) cases. At surgery 53 (70%) had ypT0-2 residual disease including 21 (28%) ypT0; 24 (32%) were ypN+. For M0 evaluable cases 2 year NED survival is 91+/-6% with no local failures. Cases were sub-analyzed by whether disease met requirements for the recently activated ACOSOG preoperative FOLFOX vs. 5FU-RT trial. Thirty eight cases met ACOSOG eligibility and achieved 16 ypT0 (42%) and 33 ypT0-2 (87%). Conclusions: This regimen achieved high response and low morbidity rates that compare favorably with conventionally fractionated RT and concurrent CT. The ongoing RAPIDO trial compares a similar regimen to conventional chemoradiation in poor risk locally advanced rectal cancer patients.

A randomized phase II trial of consolidation chemotherapy after preoperative chemoradiation (preop CRT) versus CRT alone for locally advanced rectal cancer (LARC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3606-3606
Author(s):  
Sun Young Kim ◽  
Tae Won Kim ◽  
Yong Sang Hong ◽  
Jeong Eun Kim ◽  
Keun Wook Lee ◽  
...  
Keyword(s):  
Anal Verge ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Dose Intensity ◽  
Standard Of Care ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Consolidation Chemotherapy ◽  
Ecog Ps

3606 Background: In LARC, preop CRT followed by total mesorectal excision (TME) is a standard of care. Recently consolidation chemotherapy after CRT was shown to be safe and to improve pathologic complete response (pCR) rate in LARC. We aimed to evaluate downstaging (DS) rate (the proportion of ypT0-2N0M0) of CRT followed by consolidation chemotherapy (capecitabine and oxaliplatin: CapOx) compared to that of CRT alone. Methods: Patients (pts) with adenocarcinoma of rectum(≤ 12cm from anal verge), ECOG PS 0 or 1, and cT3-4NxM0 were enrolled. CRT (50-50.4Gy/25-28fx) with Cap (825mg/m2/day for 5 days per week throughout CRT) followed by TME was planned in Arm A (control arm). In Arm B, 2 cycles of CapOx was given a week after completion of CRT before TME (Cap 850mg/m2/day from day 1 to day 14; Ox 100mg/m2on day 1; q 3w). 110 pts (55 per arm) were needed to show improvement of DS rate in per-protocol population (PP set) from 30% to 50% in arm B with one-sided α = 0.15, 1- β = 0.85, and follow-up loss in 5%. Results: From 9/2014 Sep to 2/2016, 110 (56 in arm A; 54 in arm B) were enrolled; 108 (55 in arm A; 53 in arm B) were randomized and started study treatment. Median age was 56 years; male/ECOG PS 1/cT4 was 76%/70%/18%. 100 pts (54 in arm A; 46 in arm B) completed CRT ± CapOx and surgery (R0 or R1 resection), while 8 (1 in arm A, 7 in arm B) dropped out mainly due to consent withdrawal. 2 of each arm underwent non-TME; that leaves 96 (52 in arm A and 44 in arm B) in PP set. Relative dose intensity of CapOx was 96% (Cap) and 95% (Ox). The main treatment outcome is described in table. The mean interval days between completion of CRT and surgery was significantly longer in arm B (52.9 vs 61.3, p < 0.0001). Conclusions: 2 cycles of CapOx after completion of CRT was feasible and safe, and it showed improvement in DS rate, even with high dropout rates (13%). Clinical trial information: NCT01952951. [Table: see text]

scholarly journals A Non-Operative Approach to Rectal Cancer after Chemo-Radiotherapy:

2019 ◽  
Vol 12 (1) ◽  
pp. 17-19
Author(s):  
Abeer Arian
Keyword(s):  
Rectal Cancer ◽  
Watchful Waiting ◽  
Locally Advanced ◽  
Standard Of Care ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Operative Approach ◽  
Pathological Complete Remission ◽  
Care Approach ◽  
Rectal Cancers

Introduction. Chemotherapy administered concurrently withradiotherapy for locally-advanced rectal cancer prior to surgeryis a standard of care approach. A fraction of patients after chemoradiotherapyachieve pathological complete remission. Our aim wasto evaluate patients treated only with a non-operative approach ofonly chemo-radiotherapy followed by observation at a communitycancer center.Methods. Medical charts of the patients who were treated for locallyadvanced rectal cancer and treated with chemo-radiation therapyalone from January 1, 2000 through May 1, 2017 at a Midwesterncancer center were reviewed. The clinical course of the patients wasfollowed from the time of the cancer diagnosis through their last availableclinical record.Results. A series of three cases were reviewed with locally-advanceddistal rectal cancers treated with a non-operative approach.Conclusions. Watchful waiting for patients with locally advanceddistal rectal cancer who have complete clinical response with neoadjuvantchemotherapy and radiation might be an effective treatmentstrategy. Kans J Med 2019;12(1):17-19.

Effect of neoadjuvant IMRT for locally advanced rectal cancer on toxicity and pathologic response.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 693-693 ◽  
Author(s):  
John David ◽  
Salma Jabbour ◽  
Gillian K. Gresham ◽  
Mathew Deek ◽  
Thomassian Shant ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Organs At Risk ◽  
Locally Advanced ◽  
Standard Of Care ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Neoadjuvant Chemoradiation ◽  
Pathologic Response ◽  
Rectal Pain ◽  
Chi Square Analysis

693 Background: Neoadjuvant chemoradiation (NeoCRT) is standard of care for the treatment of locally advanced rectal cancer (LARC). Contemporary radiation techniques may reduce dose to normal organs at risk. Our purpose was to compare clinical outcomes and acute toxicities between standard 3D conformal (3D) and intensity modulated radiation therapy (IMRT). Methods: LARC patients (pts) treated at 4 large academic centers in the US between 2007 and 2016 were reviewed. Pts received 5FU-based NeoCRT concurrently with IMRT or 3D. Pathologic response (PR) was used as a surrogate for clinical outcome, and common terminology for adverse events version 4 was used to grade toxicities, summarized on a 1-5 scale. Toxicity rates were compared using chi-square analysis. Multivariable models were fit adjusting for age, gender, pre-tx CT to identify independent predictors of PR and toxicity. Results: 128 pts were analyzed: 60.1% male and 39.8% female, median age 57.7 years (Range 31-85). Clinical characteristics were similar across RT groups. The outcome of partial and complete PR was similar for IMRT and 3D (48.1%, 23.1% vs 32.2%, 23.7%*), respectively. After adjusting for gender, age, and pre-RT chemotherapy type, IMRT was significantly associated with increased odds for complete and partial response (OR: 2.9, 95%CI 1.2-7.2*). Additionally, IMRT was significantly associated with reduced rates of dehydration, dermatitis, rectal pain, rectal bleeding, diverting ostomy, and trend toward significance for decreased rates of fatigue (p = 0.07) and erythema (p = 0.06) (see table). Overall rates of grade 2 and higher toxicities were significantly reduced in IMRT vs. 3D after adjusting for confounders (OR: 0.27, 95% CI 0.08-0.87*). Conclusions: Neoadjuvant 5FU-based IMRT for LARC leads to reduced acute toxicities and improved PR compared to 3D. Given the challenges associated with prospective validation of these data, IMRT should be considered standard treatment for LARC.[Table: see text]

scholarly journals Tumor microenvironment before and after chemoradiation in locally advanced rectal cancer: Beyond PD-L1

2021 ◽  
Author(s):  
Pritam Tayshetye ◽  
Andrew J. Friday ◽  
Ashten N. Omstead ◽  
Stacey Miller ◽  
Ping Zheng ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Tumor Microenvironment ◽  
Locally Advanced ◽  
Standard Of Care ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Neoadjuvant Chemoradiation ◽  
Growth And Survival ◽  
Before And After

Abstract Background: In rectal cancer treatment, neoadjuvant chemoradiation therapy (CRT) is the standard of care and reduces local failure rate. The tumor microenvironment (TME) is a complex entity comprising of tumor cells, immune cells and surrounding stroma and is closely associated with tumor growth and survival, response to antitumor therapies and also resistance to antitumor therapies. The purpose of this study is to assess the change in biomarkers associated with TME following standard neoadjuvant CRT in rectal cancer. Methods: We accessed archival tissue from rectal cancer patients treated with neoadjuvant CRT at Allegheny Health Network (AHN) facilities over the past 14 years. Pre-treatment and post-treatment biopsies were assayed for PD-L1, CD8+ T-cells, CXCL9, TIM-3, IDO-1, IFN-G, IL17RE, LAG-3, and OX40 in 41 patients. Results: We found statistically significant upregulation in multiple biomarkers namely CD8, IL17RE, LAG3 and OX40 post neoadjuvant CRT and a trend towards upregulation, although not statistically significant, in biomarkers PD-L1, CXCL9, TIM-3, IDO-1 and IFN-G expression. Conclusions: This data has broad implications, not only in rectal cancer but also in other malignancies, and provides a glimpse into the TME before and after neoadjuvant CRT. We hypothesize that the biomarkers which were noted to be upregulated could be used for development of therapeutic targeted drug therapy and designing appropriate clinical trials in an effort to achieve better response to neoadjuvant therapy, increasing pathological complete response rates and improved overall outcomes.

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