scholarly journals Evolving paradigms in locally advanced rectal cancer: Review of the non-operative approach and future directions

2014 ◽  
Vol 61 (2) ◽  
pp. 23-29
Author(s):  
Monica Polcz ◽  
Jesse Smith ◽  
Philip Paty
Keyword(s):  
Rectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
The United States ◽  
Locally Advanced Rectal Cancer ◽  
Neoadjuvant Chemoradiation ◽  
Operative Approach ◽  
Future Directions ◽  
Operative Recovery

The standard treatment of locally advanced rectal cancer in the United States is neoadjuvant chemoradiation, surgical resection with total mesorectal excision, and adjuvant chemotherapy. In recent years, a non-operative approach has been suggested for patients achieving a complete clinical response with chemoradiation alone to avoid the morbidity that accompanies radical excision. This approach is justified by the observation that a significant proportion of patients (15-40%) have achieved a pathological complete response by the time of surgery. We review the most recent literature to determine if the oncologic outcomes are comparable. We also discuss future directions in management, including the consolidation of chemotherapy with neoadjuvant chemoradiation. Currently, distant recurrence rates exceed those of local recurrence and adjuvant chemotherapy is often delayed pending post-operative recovery. Offering chemotherapy up-front would simultaneously treat both the primary tumor and any micrometastatic disease without delay. A trial is currently underway at our center evaluating these treatment modalities.

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.

Outcomes of elderly patients receiving neoadjuvant chemoradiation and adjuvant chemotherapy for locally advanced rectal cancer in a retrospective cohort.

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. e15145-e15145
Author(s):  
Pablo Reguera Puertas ◽  
Vanessa Pachón Olmos ◽  
Reyes Ferreiro Monteagudo ◽  
Federico Longo ◽  
Carmen Guillen ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Elderly Patients ◽  
Retrospective Cohort ◽  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Neoadjuvant Chemoradiation

scholarly journals Multidisciplinary Management of Early-Stage Rectal Cancer

2012 ◽  
Vol 10 (12) ◽  
pp. 1577-1585 ◽  
Author(s):  
John G. Phillips ◽  
Theodore S. Hong ◽  
David P. Ryan
Keyword(s):  
Rectal Cancer ◽  
Adjuvant Therapy ◽  
Early Stage ◽  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
The United States ◽  
Locally Advanced Rectal Cancer ◽  
Neoadjuvant Chemoradiation ◽  
Current Standard ◽  
Recurrence Rates

Because patients with locally advanced rectal cancer are at high risk for both recurrence and distant disease, they require adjuvant therapy. In the United States, the current standard of care is neoadjuvant chemoradiation followed by surgery and adjuvant chemotherapy. Neoadjuvant chemoradiation has been shown to improve local recurrence rates and decrease toxicity. However in the era of total mesorectal excision surgery, no study has shown a survival benefit to either chemoradiation or postoperative chemotherapy. Newer biologic therapies, although promising in initial early trials, have yet to show a significant benefit in adjuvant therapy for rectal cancer.

Association of adjuvant chemotherapy with clinical outcomes in patients treated with neoadjuvant chemoradiation for locally advanced rectal cancer.

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. 3628-3628 ◽  
Author(s):  
Michael M. Vickers ◽  
Jamison Mercer ◽  
Aalok Kumar ◽  
Gillian Gresham ◽  
Rachel Anne Goodwin ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Clinical Outcomes ◽  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Neoadjuvant Chemoradiation

Role of adjuvant chemotherapy in locally advanced rectal cancer with ypT0-3N0 after neoadjuvant chemoradiation therapy.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 760-760
Author(s):  
Chang-gon Kim ◽  
Minkyu Jung ◽  
Inkyung Jung ◽  
Sang Joon Shin ◽  
Seung Hoon Beom ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Neoadjuvant Chemoradiation ◽  
Chemoradiation Therapy ◽  
P Value ◽  
Neoadjuvant Chemoradiation Therapy

760 Background: Clinical benefit of adjuvant chemotherapy (AC) is still controversial in locally advanced rectal cancer (LARC) after neoadjuvant chemoradiation therapy (CRT) followed by total mesorectal excision (TME). We aim to explore the role of adjuvant chemotherapy with fluoropyrimidine for ypT0-3N0 patients. Methods: Patients with ypT0-3N0 rectal cancer after neoadjuvant CRT and TME were included using retrospective cohort of Yonsei Cancer Center. Patients were categorized according to receipt of adjuvant chemotherapy (AC vs. no AC). Disease free survival (DFS) and overall survival (OS) between treatment groups were compared using all patients’ cohort (APC) and propensity score-matched patients’ cohort (PSMPC). Results: total of 339 patients were evaluated. Of all, 87 patients (25.7%) did not receive AC. There was no difference in DFS between two groups [hazard ratio (HR) = 1.079, p-value = 0.782 in APC; HR = 1.22, p-value in PSMPC]. Also there was no difference in OS between two groups (HR = 1.140, p-value 0.717 in APC; HR = 1.366, p-value 0.472 in PSMPC). Advanced T stage and positive resection margin were associated with inferior DFS and OS by multivariate analysis. In subgroup analysis by baseline characteristics, we could not find any group with benefit of adjuvant chemotherapy. Conclusions: AC did not improve DFS and OS of patients with ypT0-3N0 rectal cancer after neoadjuvant CRT followed by TME. The role of AC in LARC with ypT0-3N0 after preoperative CRT should be evaluated in prospective randomized trials with larger sample size.

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.

Adjuvant Chemotherapy After Preoperative Chemoradiation Improves Survival in Patients With Locally Advanced Rectal Cancer

2017 ◽  
Vol 60 (10) ◽  
pp. 1050-1056 ◽  
Author(s):  
Zhifei Sun ◽  
Brian Gilmore ◽  
Mohamed A. Adam ◽  
Jina Kim ◽  
Shiao-wen D. Hsu ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Preoperative Chemoradiation
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