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 Pathologic response after neoadjuvant chemoradiotherapy in Sudanese patients with locally advanced rectal adenocarcinoma

2015 ◽  
Vol 3 (2) ◽  
pp. 53
Author(s):  
Ahmed Abdalla ◽  
Awad Alawad ◽  
Hussein Abdalla M. Ali
Keyword(s):  
Rectal Cancer ◽  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Neoadjuvant Chemoradiation ◽  
Pathologic Response ◽  
Response To Therapy ◽  
Clinical Staging ◽  
Preoperative Treatment ◽  
Surgical Specimen

<p><strong>Background:</strong> Locally advanced rectal cancer can be down staged by neoadjuvant therapy and the resultant tumor response can be quantified histologically.</p><p><strong>Objective:</strong> This study aimed to assess pathologic response of neoadjuvant chemoradiation in patients with locally advanced rectal cancers treated in Wad Medani Teaching Hospital (WMTH) and National Cancer Institute (NCI), Wad Medani, Sudan.</p><p><strong>Patients and Methods:</strong> A total of 36 consecutive patients with locally advanced rectal cancer that were managed in WMTH and NCI during the period from 2006-2011 were reviewed. Preoperative pelvic radiotherapy was delivered.  The total of 46 Grays were delivered concurrently with 5- fluorouracil (5-FU) on the first and last week of radiation. Total mesorectal excision of the rectal tumour either by anterior or abdominoperineal resections was planned at 6-8 weeks from completion of preoperative treatment. The pathological response to therapy was assessed by histopathology examination of the surgical specimen.</p><p><strong>Results:</strong> Initial clinical staging of patients revealed 58.3% of them were stage T3/T4N2M0 and 41.7% were stage T3N0M0. Down-staging to stage T1/T2N0M0 was found in 36.1% and stages T3N0M0 in 30.6%. No response was seen in 8.3% of cases with stage T3/T4N2M0 while a complete clinical response (no residual) was seen in 25.0%. Complete histological response was observed 13.8%. Positive lymph-nodes metastasis was confirmed in 8.3% of cases.</p><p><strong>Conclusion:</strong> Neoadjuvant chemoradiation is a reasonable option for cases of rectal cancer and deserves further evaluation.</p>

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.

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.

scholarly journals Neoadjuvant chemoradiation alters biomarkers of anticancer immunotherapy responses in locally advanced rectal cancer

2021 ◽  
Vol 9 (3) ◽  
pp. e001610
Author(s):  
Incheol Seo ◽  
Hye Won Lee ◽  
Sang Jun Byun ◽  
Jee Young Park ◽  
Hyeonji Min ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Locally Advanced ◽  
Enrichment Analysis ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Neoadjuvant Chemoradiation ◽  
Cytolytic Activity ◽  
Gene Set Enrichment Analysis ◽  
Preoperative Treatment ◽  
Rna Seq

BackgroundNeoadjuvant chemoradiation therapy (CRT) is a widely used preoperative treatment strategy for locally advanced rectal cancer (LARC). However, a few studies have evaluated the molecular changes caused by neoadjuvant CRT in these cancer tissues. Here, we aimed to investigate changes in immunotherapy-related immunogenic effects in response to preoperative CRT in LARC.MethodsWe analyzed 60 pairs of human LARC tissues before and after irradiation from three independent LARC cohorts, including a LARC patient RNA sequencing (RNA-seq) dataset from our cohort and GSE15781 and GSE94104 datasets.ResultsGene ontology analysis showed that preoperative CRT significantly enriched the immune response in LARC tissues. Moreover, gene set enrichment analysis revealed six significantly enriched Kyoto Encyclopedia of Genes and Genomes pathways associated with downregulated genes, including mismatch repair (MMR) genes, in LARC tissues after CRT in all three cohorts. Radiation also induced apoptosis and downregulated various MMR system-related genes in three colorectal cancer cells. One patient with LARC showed a change in microsatellite instability (MSI) status after CRT, as demonstrated by the loss of MMR protein and PCR for MSI. Moreover, CRT significantly increased tumor mutational burden in LARC tissues. CIBERSORT analysis revealed that the proportions of M2 macrophages and CD8 T cells were significantly increased after CRT in both the RNA-seq dataset and GSE94104. Notably, preoperative CRT increased various immune biomarker scores, such as the interferon-γ signature, the cytolytic activity and the immune signature.ConclusionsTaken together, our findings demonstrated that neoadjuvant CRT modulated the immune-related characteristics of LARC, suggesting that neoadjuvant CRT may enhance the responsiveness of LARC to immunotherapy.

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