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Neoadjuvant chemotherapy in local advanced rectal cancer

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https://www.readbyqxmd.com/read/28537875/n-myc-downstream-regulated-gene-1-promotes-oxaliplatin-triggered-apoptosis-in-colorectal-cancer-cells-via-enhancing-the-ubiquitination-of-bcl-2
#1
Xiao Yang, Fan Zhu, Chaoran Yu, Jiaoyang Lu, Luyang Zhang, Yanfeng Lv, Jing Sun, Minhua Zheng
N-myc downstream-regulated gene1 (NDRG1) has been identified as a potent tumor suppressor gene. The molecular mechanisms of anti-tumor activity of NDRG1 involve its suppressive effects on a variety of tumorigenic signaling pathways. The purpose of this study was to investigate the role of NDRG1 in the apoptosis of colorectal cancer (CRC) cells. We first collected the clinical data of locally advanced rectal cancer (LARC) patients receiving oxaliplatin-based neoadjuvant chemotherapy in our medical center. Correlation analysis revealed that NDRG1 positively associated with the downstaging rates and prognosis of patients...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28503826/prospective-randomised-trial-of-neoadjuvant-chemotherapy-during-the-wait-period-following-pre-operative-chemoradiotherapy-for-rectal-cancer-results-of-the-wait-trial
#2
James Moore, Tim Price, Scott Carruthers, Sudarsha Selva-Nayagam, Andrew Luck, Michelle Thomas, Peter Hewett
AIMS: To determine whether the addition of additional cycles of chemotherapy during the "wait "period following neoadjuvant chemo-radiotherapy for rectal cancer improves the pathologic complete response rate (pCR). METHODS: Rectal cancer patients were randomly allocated to either a standard 10 week wait period before surgery (standard chemo-radiotherapy, SCRT) or to receive 3 cycles of 5FU based chemotherapy following chemo-radiotherapy during a similar 10 week wait (extended chemo-radiotherapy, XCRT)...
May 15, 2017: Colorectal Disease: the Official Journal of the Association of Coloproctology of Great Britain and Ireland
https://www.readbyqxmd.com/read/28501970/cancer-center-volume-and-type-impact-stage-specific-utilization-of-neoadjuvant-therapy-in-rectal-cancer
#3
Emily F Midura, Andrew D Jung, Meghan C Daly, Dennis J Hanseman, Bradley R Davis, Shimul A Shah, Ian M Paquette
BACKGROUND: Neoadjuvant chemoradiation reduces local recurrence in locally advanced rectal cancer, and adherence to national and societal recommendations remains unknown. OBJECTIVE: To determine variability in guideline adherence in rectal cancer treatment and investigate whether hospital volume correlated with variability seen. DESIGN: We performed a retrospective analysis using the National Cancer Database rectal cancer participant user files from 2005 to 2010...
May 13, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28497757/safety-and-tolerability-of-veliparib-combined-with-capecitabine-plus-radiotherapy-in-patients-with-locally-advanced-rectal-cancer-a-phase-1b-study
#4
Brian G Czito, Dustin A Deming, Gayle S Jameson, Mary F Mulcahy, Houman Vaghefi, Matthew W Dudley, Kyle D Holen, Angela DeLuca, Rajendar K Mittapalli, Wijith Munasinghe, Lei He, John R Zalcberg, Samuel Y Ngan, Philip Komarnitsky, Michael Michael
BACKGROUND: Further optimisation of present standard chemoradiation is needed in patients with locally advanced rectal cancer. Veliparib, an oral poly(ADP-ribose) polymerase inhibitor, has been shown to enhance the antitumour activity of chemotherapy and radiotherapy in preclinical models. We aimed to establish the maximum tolerated dose and establish the recommended phase 2 dose of veliparib combined with neoadjuvant capecitabine and radiotherapy. METHODS: This phase 1b, open-label, multicentre, dose-escalation study was done at six hospitals (one in Australia and five in the USA)...
June 2017: Lancet. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28476941/systemic-chemotherapy-as-salvage-treatment-for-locally-advanced-rectal-cancer-patients-who-fail-to-respond-to-standard-neoadjuvant-chemoradiotherapy
#5
Francesco Sclafani, Gina Brown, David Cunningham, Sheela Rao, Paris Tekkis, Diana Tait, Federica Morano, Chiara Baratelli, Eleftheria Kalaitzaki, Shahnawaz Rasheed, David Watkins, Naureen Starling, Andrew Wotherspoon, Ian Chau
BACKGROUND: The potential of chemotherapy as salvage treatment after failure of neoadjuvant chemoradiotherapy for locally advanced rectal cancer (LARC) has never been explored. We conducted a single-center, retrospective analysis to address this question. PATIENTS AND METHODS: Patients with newly diagnosed LARC who were inoperable or candidates for extensive (i.e., beyond total mesorectal excision [TME]) surgery after long-course chemoradiotherapy and who received salvage chemotherapy were included...
May 5, 2017: Oncologist
https://www.readbyqxmd.com/read/28464745/diffusion-weighted-magnetic-resonance-imaging-of-rectal-cancer-tumour-volume-and-perfusion-fraction-predict-chemoradiotherapy-response-and-survival
#6
Kine Mari Bakke, Knut Håkon Hole, Svein Dueland, Krystyna Kotanska Grøholt, Kjersti Flatmark, Anne Hansen Ree, Therese Seierstad, Kathrine Røe Redalen
BACKGROUND: In locally advanced rectal cancer (LARC), responses to preoperative treatment are highly heterogeneous and more accurate diagnostics are likely to enable more individualised treatment approaches with improved responses. We investigated the potential of diffusion-weighted magnetic resonance imaging (DW MRI), with quantification of the apparent diffusion coefficient (ADC) and perfusion fraction (F), as well as volumetry from T2-weighted (T2W) MRI, for prediction of therapeutic outcome...
June 2017: Acta Oncologica
https://www.readbyqxmd.com/read/28439842/controversies-in-the-multimodality-management-of-locally-advanced-rectal-cancer
#7
REVIEW
Robert Díaz Beveridge, Dilara Akhoundova, Gema Bruixola, Jorge Aparicio
Neoadjuvant radiotherapy previous to radical surgery, both as short-course radiotherapy and as long-course radiotherapy combined with 5-FU-based chemotherapy (LCRCT), is routinely used in the management of locally advanced rectal cancer, with consistent benefits in the reduction in the local relapse risk. Unfortunately, survival benefits have been elusive to demonstrate with this approach, especially in the setting of radical surgery in the form of total mesorectal excision (TME). Concerns about over-treating early-stage patients and about the possible long-term side effects have also cast more doubts in a blanket approach of treating all patients with neoadjuvant radiotherapy, especially with LCRCT...
June 2017: Medical Oncology
https://www.readbyqxmd.com/read/28423720/meta-analysis-of-oxaliplatin-based-versus-fluorouracil-based-neoadjuvant-chemoradiotherapy-and-adjuvant-chemotherapy-for-locally-advanced-rectal-cancer
#8
Xing-Li Fu, Zheng Fang, Liang-Hui Shu, Guo-Qing Tao, Jian-Qiang Wang, Zhi-Lian Rui, Yong-Jie Zhang, Zhi-Qiang Tian
A meta-analysis was conducted to compare oxaliplatin-based with fluorouracil-based neoadjuvant chemoradiotherapy and adjuvant chemotherapy for locally advanced rectal cancer. MEDLINE, EMBASE and CENTRAL were systematically searched for relevant randomized controlled trials (RCTs) until January 31 2017. Review Manager (version 5.3) was used to analyze the data. Dichotomous data were calculated by odds ratio (OR) with 95% confidence intervals (CI). A total of 8 RCTs with 6103 stage II or III rectal cancer patients were analyzed, including 2887 patients with oxaliplatin+fluorouracil regimen and 3216 patients with fluorouracil alone regimen...
May 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28420585/adjuvant-chemotherapy-is-associated-with-improved-overall-survival-in-locally-advanced-rectal-cancer-after-achievement-of-a-pathologic-complete-response-to-chemoradiation
#9
Danish Shahab, Emmanuel Gabriel, Kristopher Attwood, Wen Wee Ma, Valerie Francescutti, Steven Nurkin, Patrick M Boland
BACKGROUND: In locally advanced rectal adenocarcinoma, 15% to 20% of patients treated with neoadjuvant chemoradiation (nCRT) achieve a pathologic complete response (pCR). The benefit of adjuvant chemotherapy is controversial in rectal cancer. Our objective was to evaluate the effect of clinical risk factors and adjuvant chemotherapy usage on the outcomes of the pCR patient population. PATIENTS AND METHODS: We performed a retrospective study using the National Cancer Data Base from 2006 to 2013...
March 18, 2017: Clinical Colorectal Cancer
https://www.readbyqxmd.com/read/28386670/the-impact-of-pathologic-complete-response-in-patients-with-neoadjuvantly-treated-locally-advanced-rectal-cancer-a-large-single-center-experience
#10
A M Dinaux, R Amri, L G Bordeianou, T S Hong, J Y Wo, L S Blaszkowsky, J N Allen, J E Murphy, H Kunitake, D L Berger
Small cohort studies demonstrated better oncologic outcomes for patients with pathologic complete response (PathCR) after neoadjuvant treatment for locally advanced rectal cancer. This study reviews long-term outcomes of a large cohort of clinically stage II/III rectal cancer patients who received neoadjuvant chemoradiation and surgery. This is a retrospective analysis of a single-center cohort, including all clinical stage II/III rectal cancer patients who received neoadjuvant chemoradiation and surgery between 2004 and 2014 (n = 271)...
April 6, 2017: Journal of Gastrointestinal Surgery: Official Journal of the Society for Surgery of the Alimentary Tract
https://www.readbyqxmd.com/read/28333014/single-nucleotide-polymorphism-tgf%C3%AE-1-r25p-correlates-with-acute-toxicity-during-neoadjuvant-chemoradiotherapy-in-rectal-cancer-patients
#11
J Joshua Smith, Isaac Wasserman, Sarah A Milgrom, Oliver S Chow, Chin-Tung Chen, Sujata Patil, Karyn A Goodman, Julio Garcia-Aguilar
PURPOSE: To validate the finding of an association between single nucleotide polymorphisms (SNPs) and toxicity during chemoradiotherapy (CRT) in rectal cancer patients, in an independent population. METHODS AND MATERIALS: The cohort consisted of 165 patients who received CRT for rectal cancer from 2006 to 2012. Prospectively recorded toxicity information, graded according to the Common Terminology Criteria for Adverse Events version 3.0, was retrieved from the medical record...
April 1, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/28304150/additional-chemotherapy-and-salvage-surgery-for-poor-response-to-chemoradiotherapy-in-rectal-cancers
#12
Reena Engineer, Vikas Ostwal, Supreeta Arya, Priyamvada Gupta, Supriya Chopra, Prachi Patil, Sudhir Jatal, Avanish Saklani
AIM: A proportion of locally advanced rectal cancer patients who receive neoadjuvant chemoradiotherapy (NACRT) are still unresectable. This study was undertaken to assess the outcomes of giving additional chemotherapy to rectal cancer patients with unresectable disease after NACRT. METHODS: Patients with poor response to NACRT where mesorectal fascia was still involved on MRI and R0 resection was doubtful, received additional four cycles of chemotherapy with either CAPOX or FOLFIRINOX regimen, and the response was reevaluated with MRI and reassessed for surgical resection...
March 17, 2017: Asia-Pacific Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28295220/total-neoadjuvant-therapy-for-rectal-cancer-an-emerging-option
#13
REVIEW
Ethan B Ludmir, Manisha Palta, Christopher G Willett, Brian G Czito
The treatment of locally advanced rectal cancer (LARC) has benefited from improved surgical techniques and from the implementation of neoadjuvant chemoradiotherapy (CRT), which have markedly decreased the rates of local recurrence. However, distant metastatic disease remains the most significant cause of death for these patients. Although adjuvant chemotherapy (ChT) after neoadjuvant CRT and definitive surgery is commonly recommended, the value of adjuvant systemic therapy remains less clear. Trials evaluating adjuvant ChT for rectal cancer have been handicapped by poor compliance rates and inconsistent survival results...
March 10, 2017: Cancer
https://www.readbyqxmd.com/read/28281215/neoadjuvant-treatment-for-locally-advanced-rectal-cancer-new-concepts-in-clinical-trial-design
#14
REVIEW
Nitesh Rana, A Bapsi Chakravarthy, Lisa A Kachnic
Treatment for locally advanced rectal cancer has evolved from surgery alone to surgery plus adjuvant therapy. Preoperative 5-fluorouracil- or capecitabine-based chemoradiation with standard fractionated radiation, surgery utilizing total mesorectal excision, and further chemotherapy has become the standard of care in the USA. Preoperative adjuvant chemoradiation treatment sequencing has allowed for decreased toxicity, more sphincter-sparing surgery, and improved local control rates as compared to delivering the chemoradiation postoperatively...
February 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28273303/association-between-incomplete-neoadjuvant-radiotherapy-and-survival-for-patients-with-locally-advanced-rectal-cancer
#15
Kyle Freischlag, Zhifei Sun, Mohamed A Adam, Jina Kim, Manisha Palta, Brian G Czito, John Migaly, Christopher R Mantyh
Importance: Failing to complete chemotherapy adversely affects survival in patients with colorectal cancer. However, the effect of incomplete delivery of neoadjuvant radiotherapy is unclear. Objective: To determine whether incomplete radiotherapy delivery is associated with worse clinical outcomes and survival. Design, Setting, and Participants: Data on 17 600 patients with stage II to III rectal adenocarcinoma from the 2006-2012 National Cancer Database who received neoadjuvant chemoradiotherapy followed by surgical resection were included...
March 8, 2017: JAMA Surgery
https://www.readbyqxmd.com/read/28270729/pre-and-post-surgery-treatments-in-rectal-cancer-a-long-term-single-centre-experience
#16
H Ozyurt, A S Ozden, Z Ozgen, C Gemici, G Yaprak
BACKGROUND: Our study evaluated long-term survival outcomes in rectal cancer patients treated with preoperative radiotherapy, and the impact on survival of concomitant and postoperative adjuvant chemotherapy (ctx), among other prognostic factors. METHODS: The study included 196 patients [median age: 58 years (range: 20-86 years); 63.0% men] with locally advanced rectal carcinoma and, in some cases, resectable liver metastasis. Rates of distant metastasis and local recurrence and of 5-year distant metastasis-free survival (dmfs) and overall survival (os) were determined...
February 2017: Current Oncology
https://www.readbyqxmd.com/read/28181384/resection-of-synchronous-liver-metastases-between-radiotherapy-and-definitive-surgery-for-locally-advanced-rectal-cancer-short-term-surgical-outcomes-overall-and-recurrence-free-survivals
#17
K J Labori, M G Guren, K W Brudvik, B I Røsok, A Waage, A Nesbakken, S Larsen, S Dueland, B Edwin, B A Bjørnbeth
AIM: There is debate as to the correct treatment algorithm sequence for patients with locally advanced rectal cancer with liver metastases. The aim of the study was to assess safety, resectability, and survival after a modified "liver-first" approach. METHOD: This was retrospective study of patients undergoing preoperative adjuvant radiotherapy for the primary rectal tumour, followed by liver resection and finally, resection of the primary tumour. Short-term surgical outcome, overall survival (OS) and recurrence-free survival (RFS) are reported...
February 9, 2017: Colorectal Disease: the Official Journal of the Association of Coloproctology of Great Britain and Ireland
https://www.readbyqxmd.com/read/28179091/rectal-cancer-french-intergroup-clinical-practice-guidelines-for-diagnosis-treatments-and-follow-up-snfge-ffcd-gercor-unicancer-sfcd-sfed-sfro
#18
Jean-Pierre Gérard, Thierry André, Frédéric Bibeau, Thierry Conroy, Jean-Louis Legoux, Guillaume Portier, Jean-François Bosset, Guillaume Cadiot, Olivier Bouché, Laurent Bedenne
INTRODUCTION: This document is a summary of the French Intergroup guidelines regarding the management of rectal adenocarcinoma published in February 2016. METHOD: This collaborative work, under the auspices of most of the French medical societies involved in the management of rectal cancer, is based on the previous guidelines published in 2013. Recommendations are graded into 3 categories according to the level of evidence of data found in the literature. RESULTS: In agreement with the ESMO guidelines (2013), non-metastatic rectal cancers have been stratified in 4 risk groups according to endoscopy, MRI or endorectal-ultrasonography...
April 2017: Digestive and Liver Disease
https://www.readbyqxmd.com/read/28150022/efficacy-and-safety-of-neoadjuvant-chemotherapy-with-oxaliplatin-5-fluorouracil-and-levofolinate-for-t3-or-t4-stage-ii-iii-rectal-cancer-the-fact-trial
#19
Junichi Koike, Kimihiko Funahashi, Kazuhiko Yoshimatsu, Hajime Yokomizo, Hayato Kan, Takeshi Yamada, Hideyuki Ishida, Keiichiro Ishibashi, Yoshihisa Saida, Toshiyuki Enomoto, Kenji Katsumata, Masayuki Hisada, Hirotoshi Hasegawa, Keiji Koda, Takumi Ochiai, Kazuhiro Sakamoto, Hiroyuki Shiokawa, Shimpei Ogawa, Michio Itabashi, Shingo Kameoka
PURPOSE: A multicenter phase II clinical study was performed in patients with T3 or T4 stage II/III rectal cancer to evaluate the efficacy and safety of neoadjuvant chemotherapy with 5-fluorouracil, levofolinate, and oxaliplatin (mFOLFOX6). METHODS: Patients received four 2-week cycles of mFOLFOX6 therapy (oxaliplatin at 85 mg/m(2) + leucovorin at 200 mg/m(2) + fluorouracil as a 400 mg/m(2) bolus followed by infusion of 2400 mg/m(2) over 46 h, all on Day 1)...
February 1, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28078118/less-than-12-lymph-nodes-in-the-surgical-specimen-after-neoadjuvant-chemo-radiotherapy-an-indicator-of-tumor-regression-in-locally-advanced-rectal-cancer
#20
Jaiprakash Gurawalia, Kapil Dev, Sandeep P Nayak, Vishnu Kurpad, Arun Pandey
BACKGROUND: The number of lymph node retrieved in the surgical specimen is important for tumor staging and has paramount impact on prognosis in colorectal cancer and imitates the adequacy of lymph node surgical clearance. The paucity of lymph node yields in patients undergoing resection after preoperative chemo radiotherapy (CRT) in rectal cancer has seen. Lower total number of lymph nodes in the total mesoractal excision (TME) specimen after CRT, could a marker of better tumor response...
December 2016: Journal of Gastrointestinal Oncology
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