Colorectal cancer including rectal cancer is the third most common cause of cancer deaths in the western world. For colon carcinoma, laparoscopic surgery is proven to result in faster postoperative ...recovery, fewer complications and better cosmetic results with equal oncologic results. These short-term benefits are expected to be similar for laparoscopic rectal cancer surgery. However, the oncological safety of laparoscopic surgery for rectal cancer remained controversial due to the lack of definitive long-term results. Thus, the expected short-term benefits can only be of interest when oncological results are at least equal.
To evaluate the differences in short- and long-term results after elective laparoscopic total mesorectal excision (LTME) for the resection of rectal cancer compared with open total mesorectal excision (OTME).
We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2013, Issue 2), MEDLINE (January 1990 to February 2013), EMBASE (January 1990 to February 2013), ClinicalTrials.gov (February 2013) and Current Controlled Trials (February 2013). We handsearched the reference lists of the included articles for missed studies.
Only randomised controlled trials (RCTs) comparing LTME and OTME, reporting at least one of our outcome measures, was considered for inclusion.
Two authors independently assessed study quality according to the CONSORT statement, and resolved disagreements by discussion. We rated the quality of the evidence using GRADE methods.
We identified 45 references out of 953 search results, of which 14 studies met the inclusion criteria involving 3528 rectal cancer patients. We did not consider the risk of bias of the included studies to have impacted on the quality of the evidence. Data were analysed according to an intention-to-treat principle with a mean conversion rate of 14.5% (range 0% to 35%) in the laparoscopic group.There was moderate quality evidence that laparoscopic and open TME had similar effects on five-year disease-free survival (OR 1.02; 95% CI 0.76 to1.38, 4 studies, N = 943). The estimated effects of laparoscopic and open TME on local recurrence and overall survival were similar, although confidence intervals were wide, both with moderate quality evidence (local recurrence: OR 0.89; 95% CI 0.57 to1.39 and overall survival rate: OR 1.15; 95% CI 0.87 to1.52). There was moderate to high quality evidence that the number of resected lymph nodes and surgical margins were similar between the two groups.For the short-term results, length of hospital stay was reduced by two days (95% CI -3.22 to -1.10), moderate quality evidence), and the time to first defecation was shorter in the LTME group (-0.86 days; 95% CI -1.17 to -0.54). There was moderate quality evidence that 30 days morbidity were similar in both groups (OR 0.94; 95% CI 0.8 to 1.1). There were fewer wound infections (OR 0.68; 95% CI 0.50 to 0.93) and fewer bleeding complications (OR 0.30; 95% CI 0.10 to 0.93) in the LTME group.There was no clear evidence of any differences in quality of life after LTME or OTME regarding functional recovery, bladder and sexual function. The costs were higher for LTME with differences up to GBP 2000 for direct costs only.
We have found moderate quality evidence that laparoscopic total mesorectal excision (TME) has similar effects to open TME on long term survival outcomes for the treatment of rectal cancer. The quality of the evidence was downgraded due to imprecision and further research could impact on our confidence in this result. There is moderate quality evidence that it leads to better short-term post-surgical outcomes in terms of recovery for non-locally advanced rectal cancer. Currently results are consistent in showing a similar disease-free survival and overall survival, and for recurrences after at least three years and up to 10 years, although due to imprecision we cannot rule out superiority of either approach. We await long-term data from a number of ongoing and recently completed studies to contribute to a more robust analysis of long-term disease free, overall survival and local recurrence.
To evaluate the management and oncological outcomes of rectal cancer patients with local regrowth in a watch-and-wait (W&W) program.
Approximately 15%-30% of patients with a clinical complete ...response after (chemo) radiotherapy who undergo a W&W policy will experience a local regrowth. The risks of these local regrowths have not yet been fully established and main concerns include high postoperative morbidity, requirement of advanced surgery, and pelvic recurrence after regrowth treatment.
All patients with a local regrowth after an initial W&W approach between January 2005 and March 2018 were retrospectively identified from 2 cohorts of rectal cancer patients with a clinical complete response after (chemo) radiotherapy. Type and outcome of regrowth treatment were assessed. Oncological outcome was assessed using Kaplan-Meier estimates.
Eighty-nine out of 385 patients developed a local regrowth after a median of 9 (interquartile range 7-14) months. Median follow-up time was 28 (interquartile range 19-41) months. Eighty-four (94%) patients underwent surgical treatment of the local regrowth: total mesorectal excision was performed in 58 out of 84 (69%) patients and local excision was performed in 26 (31%) patients. The 2-year local recurrence-free rate, distant metastasis-free rate, disease-free survival, and overall survival in the patients undergoing surgical treatment were 97.8%, 91.8%, 90.3%, and 98.4%, respectively.
The vast majority (97%) of patients with regrowth after a W&W policy were able to undergo treatment with curative intent for local regrowth. Uncontrolled pelvic disease was very rare.
Recent literature suggests that the benefit of adjuvant chemotherapy (aCT) for rectal cancer patients might depend on the response to neoadjuvant chemoradiation (CRT). Aim was to evaluate whether the ...effect of aCT in rectal cancer is modified by response to CRT and to identify which patients benefit from aCT after CRT, by means of a pooled analysis of individual patient data from 13 datasets. Patients were categorized into three groups: pCR (ypT0N0), ypT1‐2 tumour and ypT3‐4 tumour. Hazard ratios (HR) for the effect of aCT were derived from multivariable Cox regression analyses. Primary outcome measure was recurrence‐free survival (RFS). One thousand seven hundred and twenty three (1723) (52%) of 3,313 included patients received aCT. Eight hundred and ninety eight (898) patients had a pCR, 966 had a ypT1‐2 tumour and 1,302 had a ypT3‐4 tumour. For 122 patients response, category was missing and 25 patients had ypT0N+. Median follow‐up for all patients was 51 (0–219) months. HR for RFS with 95% CI for patients treated with aCT were 1.25(0.68–2.29), 0.58(0.37–0.89) and 0.83(0.66–1.10) for patients with pCR, ypT1‐2 and ypT3‐4 tumours, respectively. The effect of aCT in rectal cancer patients treated with CRT differs between subgroups. Patients with a pCR after CRT may not benefit from aCT, whereas patients with residual tumour had superior outcomes when aCT was administered. The test for interaction did not reach statistical significance, but the results support further investigation of a more individualized approach to administer aCT after CRT and surgery based on pathologic staging.
What's new?
Most patients with locally advanced rectal cancer receive adjuvant chemotherapy after neoadjuvant treatment and surgery. Based on a pooled analysis of individual patient data from 13 datasets, this study however shows that the benefit of adjuvant chemotherapy differs between subgroups, based on the response of patients to previous neoadjuvant chemoradiation. Patients with a complete response after chemoradiation may not benefit from adjuvant chemotherapy, whereas patients with residual tumour have superior outcomes when adjuvant chemotherapy was administered. The results support further investigation of a more individualized approach based on pathologic staging for the administration of adjuvant chemotherapy after chemoradiation and surgery.
Background
The response to chemoradiotherapy (CRT) for rectal cancer can be assessed by clinical examination, consisting of digital rectal examination (DRE) and endoscopy, and by MRI. A high accuracy ...is required to select complete response (CR) for organ-preserving treatment. The aim of this study was to evaluate the value of clinical examination (endoscopy with or without biopsy and DRE), T2W-MRI, and diffusion-weighted MRI (DWI) for the detection of CR after CRT.
Methods
This prospective cohort study in a university hospital recruited 50 patients who underwent clinical assessment (DRE, endoscopy with or without biopsy), T2W-MRI, and DWI at 6–8 weeks after CRT. Confidence levels were used to score the likelihood of CR. The reference standard was histopathology or recurrence-free interval of >12 months in cases of wait-and-see approaches. Diagnostic performance was calculated by area under the receiver operator characteristics curve, with corresponding sensitivities and specificities. Strategies were assessed and compared by use of likelihood ratios.
Results
Seventeen (34 %) of 50 patients had a CR. Areas under the curve were 0.88 (0.78–1.00) for clinical assessment and 0.79 (0.66–0.92) for T2W-MRI and DWI. Combining the modalities led to a posttest probability for predicting a CR of 98 %. Conversely, when all modalities indicated residual tumor, 15 % of patients still experienced CR.
Conclusions
Clinical assessment after CRT is the single most accurate modality for identification of CR after CRT. Addition of MRI with DWI further improves the diagnostic performance, and the combination can be recommended as the optimal strategy for a safe and accurate selection of CR after CRT.
Purpose
To compare the performance of advanced radiomics analysis to morphological assessment by expert radiologists to predict a good or complete response to chemoradiotherapy in rectal cancer using ...baseline staging MRI.
Materials and methods
We retrospectively assessed the primary staging MRIs prior to chemoradiotherapy (CRT) of 133 rectal cancer patients from 2 centers. First, two expert radiologists subjectively estimated the likelihood of achieving a “complete response” (ypT0) and “good response” (TRG 1–2), using a 5-point score (based on TN-stage, MRF/EMVI-status, size/signal/shape). Next, tumor volumes were segmented on high
b
value DWI (semi-automated, corrected by 2 non-expert and 2-expert readers, resulting in 5 segmentations), copied to the remaining sequences after which a total of 2505 radiomic features were extracted from T2W, low and high
b
value DWI and ADC. Stability of features for noise due to inter-reader and inter-scanner and protocol variations was assessed using intraclass correlation (ICC) and the Kruskal–Wallis test. Using data from center 1 (
n
= 86; training set), top 9 features were selected using minimum Redundancy Maximum Relevance and combined in a logistic regression model. Finally, diagnostic performance of the fitted models was assessed on data from center 2 (
n
= 47; validation set) and compared to the performance of the radiologists.
Results
The Radiomic models resulted in AUCs of 0.69–0.79 (with similar results for the segmentations performed by expert/non-expert readers) to predict response, results similar to the morphologic prediction by the expert radiologists (AUC 0.67–0.83). Radiomics using semi-automatically generated segmentations (without manual input) did not result in significant predictive performance.
Conclusions
Radiomics could predict response to therapy with comparable diagnostic performance as expert radiologists, regardless of whether image segmentation was performed by non-expert or expert readers, indicating that expert input is not required in order for the radiomics workflow to produce significant predictive performance.
Retrospective single-center studies have shown that diffusion-weighted magnetic resonance imaging (DWI) is promising for identification of patients with rectal cancer with a complete tumor response ...after neoadjuvant chemoradiotherapy (CRT), using certain volumetric thresholds.
This study aims to validate the diagnostic value of these volume thresholds in a larger, independent, and bi-institutional patient cohort.
A total of 112 patients with locally advanced rectal cancer (2 centers) treated with a long course of CRT were enrolled. Patients underwent standard T2W-magnetic resonance imaging and DWI, both pre- and post-CRT. Two experienced readers independently determined pre-CRT and post-CRT tumor volumes (cm) on T2W-magnetic resonance image and diffusion-weighted magnetic resonance image by means of freehand tumor delineation. Tumor volume reduction rates (Δvolume) were calculated. Previously determined T2W and DWI threshold values for prevolume, postvolume, and Δvolume were tested to "prospectively" assess their respective diagnostic value in discriminating patients with a complete tumor response from patients with residual tumor.
Twenty patients had a complete response. Using the average measurements between the 2 readers, areas under the curve for the pre-/post-/Δvolumes was 0.73/0.82/0.78 for T2W-magnetic resonance imaging and 0.77/0.92/0.86 for DWI, respectively. For T2W-volumetry, sensitivity and specificity using the predefined volume thresholds were 55% and 74% for pre-, 60% and 89% for post-, and 60% and 86% for Δvolume. For DWI volumetry, sensitivity and specificity were 65% and 76% for pre-, 70% and 98% for post-, and 70% and 93% for Δvolume.
Previously established DWI volume thresholds can be reproduced with good results. Post-CRT DWI volumetry offers the best results for the detection of patients with a complete response after CRT with an area under the curve of 0.92, sensitivity of 70%, and specificity of 98%.
Previously, it was shown in patients with low rectal cancer that a short-axis (SA) lateral node size of 7 mm or greater on primary magnetic resonance imaging (MRI) resulted in a high lateral local ...recurrence (LLR) rate after chemoradiotherapy or radiotherapy (CRT) with total mesorectal excision (TME) and that this risk was lowered by a lateral lymph node dissection (LLND). The role of restaging MRI after (C)RT with regard to LLR risk and which specific patients might benefit from an LLND is not fully understood.
To determine the factors on primary and restaging MRI that are associated with LLR in low rectal cancer after (C)RT and to formulate specific guidelines on which patients might benefit from an LLND.
In this retrospective, multicenter, pooled cohort study, patients who underwent surgery for cT3 or cT4 low rectal cancer with a curative intent from 12 centers in 7 countries from January 2009 to December 2013 were included. All patients' MRIs were rereviewed according to a standardized protocol, with specific attention to lateral nodal features. The original cohort included 1216 patients. For this study, patients who underwent (C)RT and had a restaging MRI were selected, leaving 741 for analyses across 10 institutions, including 651 who underwent (C)RT with TME and 90 who underwent (C)RT with TME and LLND.
The main purpose was to identify the factors on primary and restaging MRI associated with LLR after (C)RT with TME. Whether high-risk patients might benefit in terms of LLR reduction from an LLND was also studied.
Of the 741 included patients, 480 (64.8%) were male, and the mean (SD) age was 60.4 (12.0) years. An SA lateral node size of 7 mm or greater on primary MRI resulted in a 5-year LLR rate of 17.9% after (C)RT with TME. At 3 years, there were no LLRs in 28 patients (29.2%) with lateral nodes that were 4 mm or less on restaging MRI. Nodes that were 7 mm or greater on primary MRI and greater than 4 mm on restaging MRI in the internal iliac compartment resulted in a 5-year LLR rate of 52.3%, significantly higher compared with nodes in the obturator compartment of that size (9.5%; hazard ratio, 5.8; 95% CI, 1.6-21.3; P = .003). Compared with (C)RT with TME alone, treatment with (C)RT with TME and LLND in these unresponsive internal nodes resulted in a significantly lower LLR rate of 8.7% (hazard ratio, 6.2; 95% CI, 1.4-28.5; P = .007).
Restaging MRI is important in clinical decision making in lateral nodal disease. In patients with shrinkage of lateral nodes from an SA node size of 7 mm or greater on primary MRI to an SA node size of 4 mm or less on restaging MRI, which occurs in about 30% of cases, LLND can be avoided. However, persistently enlarged nodes in the internal iliac compartment indicate an extremely high risk of LLR, and an LLND lowered LLR in these cases.
To determine diagnostic performance of diffusion-weighted (DW) magnetic resonance (MR) imaging for assessment of complete tumor response (CR) after combined radiation therapy with chemotherapy (CRT) ...in patients with locally advanced rectal cancer (LARC) by means of volumetric signal intensity measurements and apparent diffusion coefficient (ADC) measurements and to compare the performance of DW imaging with that of T2-weighted MR volumetry.
A retrospective analysis of 50 patients with LARC, for whom clinical and imaging data were retrieved from a previous imaging study approved by the local institutional ethical committee and for which all patients provided informed consent, was conducted. Patients underwent pre- and post-CRT standard T2-weighted MR and DW MR. Two independent readers placed free-hand regions of interest (ROIs) in each tumor-containing section on both data sets to determine pre- and post-CRT tumor volumes and tumor volume reduction rates (volume). ROIs were copied to an ADC map to calculate tumor ADCs. Histopathologic findings were the standard of reference. Receiver operating characteristic (ROC) curves were generated to compare performance of T2-weighted and DW MR volumetry and ADC. The intraclass correlation coefficient (ICC) was used to evaluate interobserver variability and the correlation between T2-weighted and DW MR volumetry.
Areas under the ROC curve (AUCs) for identification of a CR that was based on pre-CRT volume, post-CRT volume, and volume, respectively, were 0.57, 0.70, and 0.84 for T2-weighted MR versus 0.63, 0.93, and 0.92 for DW MR volumetry (P = .15, .02, .42). Pre- and post-CRT ADC and ADC AUCs were 0.55, 0.54, and 0.51, respectively. Interobserver agreement was excellent for all pre-CRT measurements (ICC, 0.91-0.96) versus good (ICC, 0.61-0.79) for post-CRT measurements. ICC between T2-weighted and DW MR volumetry was excellent (0.97) for pre-CRT measurements versus fair (0.25) for post-CRT measurements.
Post-CRT DW MR volumetry provided high diagnostic performance in assessing CR and was significantly more accurate than T2-weighted MR volumetry. Post-CRT DW MR was equally as accurate as volume measurements of both T2-weighted and DW MR. Pre-CRT volumetry and ADC were not reliable.
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