Total Neoadjuvant Therapy: A Shifting Paradigm in Locally Advanced Rectal Cancer Management

Franke, Aaron J; Parekh, Hiral D.; Starr, Jason S.; Tan, Sanda; Iqbal, Atif; George, Thomas J.

doi:10.1016/j.clcc.2017.06.008

Cited by 93 publications

(69 citation statements)

References 93 publications

(105 reference statements)

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“…2 Rectal cancer is the major subtype of colorectal cancer and represents over 30% of all colorectal cancer cases. [4][5][6] Therefore, it is urgent to identify novel biomarkers for predicting prognosis and developing molecular target therapy in rectal cancer patients. [4][5][6] Therefore, it is urgent to identify novel biomarkers for predicting prognosis and developing molecular target therapy in rectal cancer patients.…”

Section: Introductionmentioning

confidence: 99%

LncRNA NKILA correlates with the malignant status and serves as a tumor‐suppressive role in rectal cancer

Tao

Yang

et al. 2018

J of Cellular Biochemistry

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NF-κB interacting lncRNA (NKILA) has been found to function as a tumor-suppressive role in various human cancers. However, the role of NKILA in rectal cancer is still unknown. The objective of this study is to investigate the clinical value and biological function of NKILA in rectal cancer. The association between NKILA expression and clinical variables including prognosis was estimated in rectal cancer patients. The gain-of-function study of NKILA in rectal cancer cell was conducted to evaluate the effect of NKILA on cell proliferation, migration, invasion, and NF-κB signaling pathway. The results suggested NKILA expression was decreased in rectal cancer tissues and cells, and correlated with clinical stage, T classification, N classification and M classification. NKILA low-expression was an independent poor prognostic factor in rectal cancer patients. NKILA-inhibited rectal cancer cell proliferation, migration, and invasion via suppressing NF-κB signaling. In conclusion, NKILA serves as an antioncogenic lncRNA in rectal cancer.

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Section: Introductionmentioning

confidence: 99%

LncRNA NKILA correlates with the malignant status and serves as a tumor‐suppressive role in rectal cancer

Tao

Yang

et al. 2018

J of Cellular Biochemistry

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Section: Principles Of Radiosensitizationmentioning

confidence: 99%

“…Refinements in surgical technique, with the adoption of total mesorectal excision, the incorporation of modern chemotherapy, and advances in timing and dosimetry of radiotherapy (RT), have demonstrated a meaningful impact on local tumor control; however, distant relapse remains the leading cause of mortality in this patient population, with approximately 35% developing metastatic relapse within 5 years of trimodality treatment. 3 After neoadjuvant chemoRT, a pathologic complete response (pCR), defined as no histopathologic evidence of residual cancer cells, has been extensively studied as a standard tool for measuring tumor regression. In the current era of consistently low local tumor recurrence rates, the goal of increasing the pCR rate is driven by our aspiration to move the field forward.…”

Section: Principles Of Radiosensitizationmentioning

confidence: 99%

National Cancer Institute (NCI) state of the science: Targeted radiosensitizers in colorectal cancer

George

Franke

Chakravarthy

et al. 2019

Cancer

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Colorectal cancer (CRC) represents a major public health problem as the second leading cause of cancer‐related mortality in the United States. Of an estimated 140,000 newly diagnosed CRC cases in 2018, roughly one‐third of these patients will have a primary tumor located in the distal large bowel or rectum. The current standard‐of‐care approach includes curative‐intent surgery, often after preoperative (neoadjuvant) radiotherapy (RT), to increase rates of tumor down‐staging, clinical and pathologic response, as well as improving surgical resection quality. However, despite advancements in surgical techniques, as well as sharpened precision of dosimetry offered by contemporary RT delivery platforms, the oncology community continues to face challenges related to disease relapse. Ongoing investigations are aimed at testing novel radiosensitizing agents and treatments that might exploit the systemic antitumor effects of RT using immunotherapies. If successful, these treatments may usher in a new curative paradigm for rectal cancers, such that surgical interventions may be avoided. Importantly, this disease offers an opportunity to correlate matched paired biopsies, radiographic response, and molecular mechanisms of treatment sensitivity and resistance with clinical outcomes. Herein, the authors highlight the available evidence from preclinical models and early‐phase studies, with an emphasis on promising developmental therapeutics undergoing prospective validation in larger scale clinical trials. This review by the National Cancer Institute's Radiation Research Program Colorectal Cancer Working Group provides an updated, comprehensive examination of the continuously evolving state of the science regarding radiosensitizer drug development in the curative treatment of CRC.

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“…Detailed and assiduous histopathological evaluation remains the gold standard. However, it must be noted that both clinical/radiological and pathological response to therapy have been shown to be of prognostic value 1. As a surrogate marker of local control and recurrence, pathological complete response (pCR) is consistent and reliable.…”

Section: Recommendations For Grossingmentioning

confidence: 99%

“…Neoadjuvant chemoradiation (NACR) is now standard fare in many institutions around the world for the treatment of locally advanced rectal cancer allied to surgery in the form of low anterior or abdominoperineal resection encompassing total mesorectal excision (TME) 1. With advances in the drugs used and modes of delivery of NACR together with timing of TME surgery, local recurrences in cases of locally advanced rectal cancer have dropped precipitously from about 25% to approximately 5%–10% 2.…”

Section: Introductionmentioning

confidence: 99%

Neoadjuvant chemoradiation and rectal cancer

Chetty

McCarthy

2018

J Clin Pathol

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Neoadjuvant chemoradiation (NACR) is now standard of care in stage II and III rectal cancer. The advent of this modality of treatment has impacted on the way the pathological evaluation of resection specimens that have been subjected to preoperative chemoradiation is conducted. The gross description, sectioning and microscopic examination have had to be adapted to accommodate the changes induced by NACR. Attempts at introducing a uniform approach to the gross triaging and reporting of these specimens have been met with muted response. There still exists much variation in approach. The purpose of this overview is to highlight some of the newer developments and issues around NACR-treated rectal cancers from a pathological point of view. The NACR-treated resection specimens should be handled in a consistent manner, at least within individual institutions, if not universally. There should be generous sampling with multiple sections taken as tumour is often sequestered deep in the bowel wall. Microscopic examination should be extra vigilant as residual cancer can be present as single cells or small clusters, often deep in the muscularis propria or serosa. Acellular pools of mucin or non-viable tumour cells in mucin within the bowel wall or lymph nodes are not regarded as positive and do not upstage the tumour. The issue of grading of regression has been the subject of much debate, and several approaches have been published. It is recommended that a system that has clinical meaning and use to oncologists be used. Lymph node counts will be reduced after NACR, but reasonable attempts to accrue 12 nodes should be made.

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Total Neoadjuvant Therapy: A Shifting Paradigm in Locally Advanced Rectal Cancer Management

Cited by 93 publications

References 93 publications

LncRNA NKILA correlates with the malignant status and serves as a tumor‐suppressive role in rectal cancer

LncRNA NKILA correlates with the malignant status and serves as a tumor‐suppressive role in rectal cancer

National Cancer Institute (NCI) state of the science: Targeted radiosensitizers in colorectal cancer

Neoadjuvant chemoradiation and rectal cancer

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