Existem benefícios com a cirurgia retardada após radioterapia e quimioterapia neoadjuvante no câncer de reto localmente avançado?

Fang, Chia Bin; Gomes, Caroline Merci Caliari de Neves; Formiga, Fernanda Bellotti; Fonseca, Vanessa Antunes; Carvalho, Marineide Prudêncio de; Klug, Wilmar Artur

doi:10.1590/s0102-67202013000100007

Cited by 10 publications

(2 citation statements)

References 24 publications

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“…The majority of reviewed studies which assessed surgical complications did not find any impact of surgical delay on operative complications [ 7 , 9 , 10 , 28 , 29 , 31 , 36 , 39 , 41 – 43 , 51 , 57 , 61 ], with two papers finding an increase in complications with later surgery [ 46 , 54 ] and another finding that later surgery decreased anastomotic and wound complications [ 53 ]. Only two of the reviewed studies assessed development of metastatic disease in the context of time to surgery after completion of radiotherapy and neither found significant between group differences [ 51 , 53 ].…”

Section: Resultsmentioning

confidence: 99%

Temporal determinants of tumour response to neoadjuvant rectal radiotherapy

et al. 2021

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Introduction In locally advanced rectal cancer, longer delay to surgery after neoadjuvant radiotherapy increases the likelihood of histopathological tumour response. Chronomodulated radiotherapy in rectal cancer has recently been reported as a factor increasing tumour response to neoadjuvant treatment in patients having earlier surgery, with patients receiving a larger proportion of afternoon treatments showing improved response. This paper aims to replicate this work by exploring the impact of these two temporal factors, independently and in combination, on histopathological tumour response in rectal cancer patients. Methods A retrospective review of all patients with rectal adenocarcinoma who received long course (≥24 fractions) neoadjuvant radiotherapy with or without chemotherapy at a tertiary referral centre was conducted. Delay to surgery and radiotherapy treatment time were correlated to clinicopathologic characteristics with a particular focus on tumour regression grade. A review of the literature and meta-analysis were also conducted to ascertain the impact of time to surgery from preoperative radiotherapy on tumour regression. Results From a cohort of 367 patients, 197 patients met the inclusion criteria. Complete pathologic response (AJCC regression grade 0) was seen in 46 (23%) patients with a further 44 patients (22%) having at most small groups of residual cells (AJCC regression grade 1). Median time to surgery was 63 days, and no statistically significant difference was seen in tumour regression between patients having early or late surgery. There was a non-significant trend towards a larger proportion of morning treatments in patients with grade 0 or 1 regression (p = 0.077). There was no difference in tumour regression when composite groups of the two temporal variables were analysed. Visualisation of data from 39 reviewed papers (describing 27379 patients) demonstrated a plateau of response to neoadjuvant radiotherapy after approximately 60 days, and a meta-analysis found improved complete pathologic response in patients having later surgery. Conclusions There was no observed benefit of chronomodulated radiotherapy in our cohort of rectal cancer patients. Review of the literature and meta-analysis confirms the benefit of delayed surgery, with a plateau in complete response rates at approximately 60-days between completion of radiotherapy and surgery. In our cohort, time to surgery for the majority of our patients lay along this plateau and this may be a more dominant factor in determining response to neoadjuvant therapy, obscuring any effects of chronomodulation on tumour response. We would recommend surgery be performed between 8 and 11 weeks after completion of neoadjuvant radiotherapy in patients with locally advanced rectal cancer.

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Section: Resultsmentioning

confidence: 99%

Temporal determinants of tumour response to neoadjuvant rectal radiotherapy

et al. 2021

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“…Stein et al [ 5 ] reported 7% higher ypCR rate in the long interval group (p=0.97). In a study by Fang et al [ 19 ] and colleagues, ypCR rate was 6.6% higher in the short interval group (p=0.37). The recently published GRECCAR-6 trial reported that there was no difference in ypCR rate between the 7-week (15%) and 11-week (17.4%) groups (p=0.60) [ 9 ].…”

Section: Discussionmentioning

confidence: 96%

The Impact of Surgical Timing on Pathologic Tumor Response after Short Course and Long Course Preoperative Chemoradiation for Locally Advanced Rectal Adenocarcinoma

Lee

et al. 2018

Cancer Res Treat

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PurposeA pooled analysis of multi-institutional trials was performed to analyze the effect of surgical timing on tumor response by comparing short course concurrent chemoradiotherapy (CCRT) with long course CCRT followed by delayed surgery in locally advanced rectal cancer.Materials and MethodsThree hundred patients with cT3-4N0-2 rectal adenocarcinoma were included. Long course patients from KROG 14-12 (n=150) were matched 1:1 to 150 short course patients from KROG 10-01 (NCT01129700) and KROG 11-02 (NCT01431599) according to stage, age, and other risk factors. The primary endpoint was to determine the interval between surgery and the last day of neoadjuvant CCRT which yields the best tumor response after the short course and long course CCRT. Downstaging was defined as ypT0-2N0M0 and pathologic complete response (ypCR) was defined as ypT0N0M0, respectively.ResultsBoth the long and short course groups achieved lowest downstaging rates at < 6 weeks (long 20% vs. short 8%) and highest downstaging rates at 6-7 weeks (long 44% vs. short 40%). The ypCR rates were lowest at < 6 weeks (both long and short 0%) and highest at 6-7 weeks (long 21% vs. short 11%) in both the short and long course arms. The downstaging and ypCR rates of long course group gradually declined after the peak at 6-7 weeks and those of the short course group trend to constantly increase afterwards.ConclusionIt is optimal to perform surgery at least 6 weeks after both the short course and long course CCRT to obtain maximal tumor regression in locally advanced rectal adenocarcinoma.

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Meta-analysis of the effect of extending the interval after long-course chemoradiotherapy before surgery in locally advanced rectal cancer

Ryan

O’Sullivan

Kelly

et al. 2019

British Journal of Surgery

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Background The current standard of care in locally advanced rectal cancer (LARC) is neoadjuvant long‐course chemoradiotherapy (nCRT) followed by total mesorectal excision (TME). Surgery is conventionally performed approximately 6–8 weeks after nCRT. This study aimed to determine the effect on outcomes of extending this interval. Methods A systematic search was performed for studies reporting oncological results that compared the classical interval (less than 8 weeks) from the end of nCRT to TME with a minimum 8‐week interval in patients with LARC. The primary endpoint was the rate of pathological complete response (pCR). Secondary endpoints were recurrence‐free survival, local recurrence and distant metastasis rates, R0 resection rates, completeness of TME, margin positivity, sphincter preservation, stoma formation, anastomotic leak and other complications. A meta‐analysis was performed using the Mantel–Haenszel method. Results Twenty‐six publications, including four RCTs, with 25 445 patients were identified. A minimum 8‐week interval was associated with increased odds of pCR (odds ratio (OR) 1·41, 95 per cent c.i. 1·30 to 1·52; P < 0·001) and tumour downstaging (OR 1·18, 1·05 to 1·32; P = 0·004). R0 resection rates, TME completeness, lymph node yield, sphincter preservation, stoma formation and complication rates were similar between the two groups. The increased rate of pCR translated to reduced distant metastasis (OR 0·71, 0·54 to 0·93; P = 0·01) and overall recurrence (OR 0·76, 0·58 to 0·98; P = 0·04), but not local recurrence (OR 0·83, 0·49 to 1·42; P = 0·50). Conclusion A minimum 8‐week interval from the end of nCRT to TME increases pCR and downstaging rates, and improves recurrence‐free survival without compromising surgical morbidity.

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Existem benefícios com a cirurgia retardada após radioterapia e quimioterapia neoadjuvante no câncer de reto localmente avançado?

Abstract: Delayed surgery after chemoradiation offered no clear benefits in terms of complete tumor response or downstaging. Predictive molecular factors should be investigated in the future for the proper selection of patients who will benefit from chemoradiation.

Cited by 10 publications

References 24 publications

Temporal determinants of tumour response to neoadjuvant rectal radiotherapy

Temporal determinants of tumour response to neoadjuvant rectal radiotherapy

The Impact of Surgical Timing on Pathologic Tumor Response after Short Course and Long Course Preoperative Chemoradiation for Locally Advanced Rectal Adenocarcinoma

Meta-analysis of the effect of extending the interval after long-course chemoradiotherapy before surgery in locally advanced rectal cancer

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