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

Abstract

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.

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

“…). A total of 26 publications, including four RCTs and 25 445 patients with rectal cancer were eligible for inclusion ( Table ). Twenty‐four of the 26 studies (22 650 patients) reported the primary endpoint of pCR based on the predefined wait interval and were included in the qualitative and quantitative analysis for this outcome variable; 15·9 per cent (1522 of 9551) and 11·3 per cent (1481 of 13 099) had achieved pCR in the extended and classical intervals respectively.…”

“…Twenty‐four of the 26 studies (22 650 patients) reported the primary endpoint of pCR based on the predefined wait interval and were included in the qualitative and quantitative analysis for this outcome variable; 15·9 per cent (1522 of 9551) and 11·3 per cent (1481 of 13 099) had achieved pCR in the extended and classical intervals respectively. All patients underwent neoadjuvant 5FU‐based (5FU–capecitabine–folinic acid) nCRT, except in seven trials that included some patients treated with concomitant oxaliplatin (5 trials) or irinotecan (2) in addition to 5FU or had a proportion of patients who had nSCRT (1 trial). The number of participants in the included trials ranged from 31 to 16 915; apart from the RCTs and one phase II non‐randomized trial, all were retrospective or prospective observational series.…”

“…Thirty-day mortality and local recurrence, distant metastasis, RFS and overall survival (OS) rates were also evaluated. Stein et al 21 Tran et al 22 Tulchinsky et al 23 De Campos-Lobato et al 24 Evans et al 32 Garcia-Aguilar et al 31 Wolthuis et al 25 Saglam et al 33 Jeong et al 43 You et al 44 Zeng et al 46 Sirohi et al 45 Probst et al 47 Mihmanlı et al 49 Timudom et al 48 Akbar et al 26 Lefevre et al 35 Kwak et al 51 Foster et al 34 Garrer et al 50 Lee et al 52 Kuan et al 53 Akgun et al 36 Kim et al 54…”

Comparison of long course and short course preoperative radiotherapy in the treatment of locally advanced rectal cancer: a systematic review and meta-analysis

“…Twelve studies (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25), with a total of 1,723 participants, reported a reduction in T or N stage based on the pretreatment clinical staging by CT or MRI versus the final pathological staging. As shown in figure 2.2, significant heterogeneity was observed (I 2 = 79%, p < 0.05) and a random effect model was applied.…”

Practical recommendation for treatment of patients with colon cancer during covid-19 pandemic

“…Probst et al, хоть и ретроспективного, на выборке в 17 255 больных показано, что частота полных патоморфологических эффектов была значимо выше при интервале между двумя методами лечения более 8 недель в сравнении с интервалом в 6 недель -13,2% против 8,7%, р < 0,001 [26]. Аналогичные находки описаны и в отношении короткого курса предоперационной лучевой терапии (5 х 5 Гр) [27]. Выявленные закономерности особенно актуальны в контексте возможности наблюдения за пациентами, у которых достигнут полный клинический эффект.…”