Adjuvant therapy sparing in rectal cancer achieving complete response after chemoradiation

García-Albéniz, Xabier; Gallego, Rosa; Hofheinz, Ralf; Fernández‐Esparrach, Glòria; Ayuso-Colella, Juan Ramón; Bombí, Josep Antoni; Conill, Carles; Cuatrecasas, Míriam; Delgado, Salvadora; Ginés, Àngels; Miquel, Rosa; Pagés, Mario; Pineda, Estela; Pereira, Verónica; Sosa, Aarón; Reig, Òscar; Victoria, Iván; Féliz, Luis; Lacy, Antonio M.; Castells, Antoni; Burkholder, Iris; Hochhaus, Andreas; Maurel, Joan

doi:10.3748/wjg.v20.i42.15820

Cited by 20 publications

(10 citation statements)

References 26 publications

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“…However, the rates of local and systemic recurrence vary significantly after radiotherapy, which illustrates that progression and resistance remain common events . Preoperative chemoradiotherapy results in fewer than 50% of rectal cancer patients achieving complete pathological response . Response to radiation is considered to be a key factor in the success of radiotherapy, but the response to radiation is determined by multifactorial etiologies (tumor pathologic type, tumor volume, tumor hypoxia, clinical stage, radiation dose and radiation modes) .…”

Section: Discussionmentioning

confidence: 99%

RBBP6 increases radioresistance and serves as a therapeutic target for preoperative radiotherapy in colorectal cancer

et al. 2018

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Radiotherapy (RT) can be used as preoperative treatment to downstage initially unresectable locally rectal carcinoma, but radioresistance and recurrence remain significant problems. Retinoblastoma binding protein 6 (RBBP6) has been implicated in the regulation of cell cycle, apoptosis and chemoresistance both in vitro and in vivo. The present study investigated whether the inhibition of RBBP6 expression would improve radiosensitivity in human colorectal cancer cells. After SW620 and HT29 cells were exposed to radiation, the levels of RBBP6 mRNA and protein increased over time in both cells. Moreover, a significant reduction in clonogenic survival and a decrease in cell viability in parallel with an obvious increase in cell apoptosis were demonstrated in irradiated RBBP6‐knockdown cells. Transfection with RBBP6 shRNA improved the levels of G2‐M phase arrest, which blocked the cells in a more radiosensitive period of the cell cycle. These observations indicated that cell cycle and apoptosis mechanisms may be connected with tumor cell survival following radiotherapy. In vivo, the tumor growth rate of nude mice in the RBBP6‐knockdown group was significantly slower than that in other groups. These results indicated that RBBP6 overexpression could resist colorectal cancer cells against radiation by regulating cell cycle and apoptosis pathways, and inhibition of RBBP6 could enhance radiosensitivity of human colorectal cancer.

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Section: Discussionmentioning

confidence: 99%

RBBP6 increases radioresistance and serves as a therapeutic target for preoperative radiotherapy in colorectal cancer

et al. 2018

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“…136 A study in which patients who received neoadjuvant chemoRT and experienced a pCR were observed without additional adjuvant chemotherapy found 5-year DFS and OS rates of 96% and 100%, respectively. 221 In addition, a meta-analysis of 4 randomized trials (1,196 patients) concluded that adjuvant fluorouracil-based chemotherapy (5-FU/LV, capecitabine, or CAPEOX) after preoperative therapy and surgery did not improve OS, DFS, or the rate of distant recurrences in patients with stage II or III rectal cancer. 222 However, more recent trials that found a DFS benefit for the addition of adjuvant oxaliplatin-based adjuvant therapy were not included in this study, and other meta-analyses have come to the opposite conclusion.…”

Section: Watch-and-wait Approach For Clinical Complete Respondersmentioning

confidence: 99%

Rectal Cancer, Version 2.2018, NCCN Clinical Practice Guidelines in Oncology

Benson¹,

Venook²,

Al-Hawary³

et al. 2018

J Natl Compr Canc Netw

830

670

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The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Rectal Cancer address diagnosis, staging, surgical management, perioperative treatment, management of recurrent and metastatic disease, disease surveillance, and survivorship in patients with rectal cancer. This portion of the guidelines focuses on the management of localized disease, which involves careful patient selection for curative-intent treatment options that sequence multimodality therapy usually comprised of chemotherapy, radiation, and surgical resection.

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“…The lack of prospective studies to evaluate the effect of ACT is because a pCR is only achieved in ~10–20% of all rectal cancer patients 14,15 . Additionally, treatment adherence to ACT in this subpopulation is mostly poor given the possibility of treatment-related toxicity, financial burden, and a patient or clinician’s preference for less aggressive treatment 36 . In this clinical setting, a meta-analytic approach with a larger number of patients can help detect a small or absent treatment effect.…”

Section: Discussionmentioning

confidence: 99%

Adjuvant chemotherapy in rectal cancer patients who achieved a pathological complete response after preoperative chemoradiotherapy: a systematic review and meta-analysis

Lim

Kim

Kong

2019

Sci Rep

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This study evaluated the prognostic impact of ACT in patients who achieved a pathological complete response (pCR). Articles published from January 1990 to September 2018 were searched in EMBASE, PubMed, Ovid, Web of Science, and Cochrane Library. Hazard ratios (HRs) and 95% confidence intervals (CIs) of overall survival (OS) were extracted. Thirteen observational studies were included. There were four National Cancer Database studies with overlapping study periods, thus individual pooled analyses of four different datasets were conducted (n = 3,182, 3,330, 3,575, and 4,739 for pooled analysis sets including Dossa et al ., Polanco et al ., Xu et al ., and Shahab et al ., respectively). Although a trend toward improved OS with ACT was observed, statistical significance was not proven ( P = 0.09, P = 0.03, P = 0.12, and P = 0.10, respectively). When we performed a stratified analysis comparing the results from single institution and multicenter studies, there was no significant prognostic benefit of ACT. Publication bias was not observed. Routine use of ACT in patients with a pCR could not be warranted from the present meta-analysis. Further study of individual patient data from randomized trials is needed to clarify the role of ACT.

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Adjuvant therapy sparing in rectal cancer achieving complete response after chemoradiation

Abstract: Withholding adjuvant chemotherapy after complete response following standard neoadjuvant chemoradiotherapy and laparoscopic mesorectal excision might be safe within an experienced multidisciplinary team.

Cited by 20 publications

References 26 publications

RBBP6 increases radioresistance and serves as a therapeutic target for preoperative radiotherapy in colorectal cancer

RBBP6 increases radioresistance and serves as a therapeutic target for preoperative radiotherapy in colorectal cancer

Rectal Cancer, Version 2.2018, NCCN Clinical Practice Guidelines in Oncology

Adjuvant chemotherapy in rectal cancer patients who achieved a pathological complete response after preoperative chemoradiotherapy: a systematic review and meta-analysis

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