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1.  Adjuvant chemotherapy in rectal cancer: defining subgroups who may benefit after neoadjuvant chemoradiation and resection 
International journal of cancer  2014;137(1):212-220.
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 categorised into 3 groups: pCR (ypT0N0), ypT1-2 tumour and ypT3-4 tumour. Hazard ratios for the effect of aCT were derived from multivariable Cox regression analyses. Primary outcome measure was recurrence-free survival (RFS). 1723(52%) of 3313 included patients received aCT. 898 patients had a pCR, 966 had a ypT1-2 tumour and 1302 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. Hazard ratios 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.
doi:10.1002/ijc.29355
PMCID: PMC4957736  PMID: 25418551
rectal cancer; neoadjuvant treatment; adjuvant chemotherapy; survival; response
2.  Associations of sedentary time and patterns of sedentary time accumulation with health-related quality of life in colorectal cancer survivors 
Preventive Medicine Reports  2016;4:262-269.
Sedentary behavior (sitting/lying at low energy expenditure while awake) is emerging as an important risk factor that may compromise the health-related quality of life (HRQoL) of colorectal cancer (CRC) survivors. We examined associations of sedentary time with HRQoL in CRC survivors, 2–10 years post-diagnosis. In a cross-sectional study, stage I–III CRC survivors (n = 145) diagnosed (2002−2010) at Maastricht University Medical Center+, the Netherlands, wore the thigh-mounted MOX activity monitor 24 h/day for seven consecutive days. HRQoL outcomes were assessed by validated questionnaires (EORTC QLQ-C30, WHODAS II, Checklist Individual Strength, and Hospital Anxiety and Depression Scale). Confounder-adjusted linear regression models were used to estimate associations with HRQoL outcomes of MOX-derived total and prolonged sedentary time (in prolonged sedentary bouts ≥ 30 min), and usual sedentary bout duration, corrected for waking wear time. On average, participants spent 10.2 h/day sedentary (SD, 1.6), and 4.5 h/day in prolonged sedentary time (2.3). Mean usual sedentary bout duration was 27.3 min (SD, 16.8). Greater total and prolonged sedentary time, and longer usual sedentary bout duration were associated with significantly (P < 0.05) lower physical functioning, and higher disability and fatigue scores. Greater prolonged sedentary time and longer usual sedentary bout duration also showed significant associations with lower global quality of life and role functioning. Associations with distress and social functioning were non-significant. Sedentary time was cross-sectionally associated with poorer HRQoL outcomes in CRC survivors. Prospective studies are needed to investigate whether sedentary time reduction is a potential target for lifestyle interventions aiming to improve the HRQoL of CRC survivors.
Highlights
•Sedentary time may negatively affect health outcomes in colorectal cancer survivors.•Thigh-worn accelerometers provided objective and accurate estimates of sedentary time.•Colorectal cancer survivors spent on average 10.2 h/day in sedentary time.•Sedentary time was associated with worse quality of life, fatigue, and disability.•Decreasing sedentary time could be a relevant target for lifestyle intervention.
doi:10.1016/j.pmedr.2016.06.022
PMCID: PMC4941044  PMID: 27419042
β, unstandardized regression coefficient; BMI, body mass index; CI, confidence interval; CIS, Checklist Individual Strength; CRC, colorectal cancer; EnCoRe study, Energy for life after ColoRectal cancer study; EORTC QLQ-C30, European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30; HADS, Hospital Anxiety and Depression Scale; HRQoL, health-related quality of life; ICF, International Classification of Functioning, Disability and Health; MET, metabolic equivalent; MVPA, moderate-to-vigorous physical activity; SD, standard deviation; WHO, World Health Organization; WHODAS II, 12-item World Health Organization Disability Assessment Schedule II; Sedentary Lifestyle; Quality of Life; Colorectal Neoplasms; Survivors
3.  Nodal staging in rectal cancer: why is restaging after chemoradiation more accurate than primary nodal staging? 
Purpose
This study aims to explore the influence of chemoradiation treatment (CRT) on rectal cancer nodes and to generate hypotheses why nodal restaging post-CRT is more accurate than at primary staging.
Methods
Thirty-nine patients with locally advanced rectal cancer underwent MRI pre- and post-CRT. All visible mesorectal nodes were measured on a 3D T1-weighted gradient echo (3D T1W GRE) sequence with 1-mm3 voxels and matched between pre- and post-CRT-MRI and with histology by lesion-by-lesion matching. Change in number and size of nodes was compared between pre- and post-CRT-MRI. ROC curves were constructed to assess diagnostic performance of size.
Results
Eight hundred ninety-five nodes were found pre-CRT: 44 % disappeared and 40 % became smaller post-CRT. Disappearing nodes were initially significantly smaller than nodes that remained visible post-CRT: 2.9 mm vs. 3.8 mm. cN+ stage was predicted in 97 % pre-CRT and 36 % of patients had ypN+ post-CRT. ypN+ patients had significantly larger nodes than ypN0 patients both pre- and post-CRT. Optimal size cutoff for post-CRT ypN stage prediction was 2.5 mm (area under the curve (AUC) of 0.78) at MRI.
Conclusions
After CRT, most lymph nodes become smaller, and many disappear. Size predicts disappearance and node positivity. Together with a low prevalence of ypN+, this can explain the higher accuracy of nodal staging after CRT than in a primary staging setting, possibly of use when considering organ-preserving strategies after CRT.
doi:10.1007/s00384-016-2576-8
PMCID: PMC4867151  PMID: 27055660
Rectal cancer; Nodal staging; Chemoradiation; Response; Histopathology
4.  Modeling how substitution of sedentary behavior with standing or physical activity is associated with health-related quality of life in colorectal cancer survivors 
Cancer Causes & Control  2016;27:513-525.
Purpose
Previous research indicates that sedentary behavior is unfavorably associated with health-related quality of life (HRQoL) of colorectal cancer (CRC) survivors. Using isotemporal substitution modeling, we studied how substituting sedentary behavior with standing or physical activity was associated with HRQoL in CRC survivors, 2–10 years post-diagnosis.
Methods
A cross-sectional study was conducted in stage I–III CRC survivors (n = 145) diagnosed at Maastricht University Medical Center+, the Netherlands (2002–2010). Sedentary, standing, and physical activity time were measured by the thigh-mounted MOX activity monitor. HRQoL outcomes comprised global quality of life, physical, role, and social functioning, and disability (scales: 0–100), fatigue (20–140), and depression and anxiety (0–21). Isotemporal substitution modeling was applied to analyze associations with HRQoL of substituting sedentary time with equal time in standing or physical activity.
Results
On average, participants spent 10.2 h/day sedentary (SD, 1.7), 3.4 h/day standing (1.3), and 1.7 h/day in physical activity (0.8). In confounder-adjusted isotemporal models, substituting sedentary time with standing or with physical activity was associated with significantly better physical functioning (regression coefficient [β], i.e., difference in outcome score per 1 h/day of sedentary time substituted with standing or physical activity, 3.1; 95 % confidence interval [CI] 0.5, 5.7; and 5.6; 0.7, 10.6, respectively). Substituting sedentary time with standing was also associated with significantly lower disability (β, −3.0; 95 % CI −4.9, −1.1) and fatigue (−4.0; −7.6, −0.3).
Conclusions
Our results suggest that substituting sedentary behavior with standing or physical activity may be beneficially associated with certain HRQoL outcomes in CRC survivors. Prospective studies are warranted to confirm whether actual substitution of sedentary behavior with these activities may improve HRQoL in CRC survivors.
Electronic supplementary material
The online version of this article (doi:10.1007/s10552-016-0725-6) contains supplementary material, which is available to authorized users.
doi:10.1007/s10552-016-0725-6
PMCID: PMC4796364  PMID: 26892604
Isotemporal substitution modeling; Sedentary behavior; Standing; Physical activity; Health-related quality of life; Colorectal cancer survivor
5.  Good and complete responding locally advanced rectal tumors after chemoradiotherapy: where are the residual positive nodes located on restaging MRI? 
Abdominal Radiology (New York)  2016;41:1245-1252.
Purpose
Aim of this study was to evaluate the distribution of persistent mesorectal lymph node metastases on restaging MRI in patients with a good or complete response of their primary tumor (ypT0-2) after CRT for locally advanced rectal cancer.
Methods
Two hundred and twenty eight locally advanced rectal cancer patients underwent CRT, which resulted in a good response (downstaging to yT0-2) in 144 patients. Forty-nine patients were excluded (no surgery/insufficient follow-up or lacking lesion-by-lesion histology results). This resulted in a final study group of 95 yT0-2 patients. For the patients with a yN+-status, a detailed lesion-by-lesion comparison between restaging MRI and histology was performed to evaluate the characteristics and distribution of the individual N+-nodes.
Results
7/95 patients (7%) had a yT0-2N+ status (11/880 (1%) N+ nodes): no N+ were found below the tumor level, 55% of the N+ nodes were located at the level of the tumor, and 45% proximal to the tumor (at a median distance of 1.4 cm above the tumor level). In axial plane, 82% of the nodes were located at the ipsilateral circumference of the tumor, at a median distance of 0.9 cm from the tumor/rectal wall.
Conclusions
The incidence of persistent metastatic mesorectal nodes after CRT in patients with a good tumor response after CRT is very low. No N+ nodes are found below the tumor level. All N+ nodes are located at the level of or proximal to the primary tumor, of which the majority very close to the tumor/lumen.
doi:10.1007/s00261-016-0640-z
PMCID: PMC4912594  PMID: 26814499
Rectal cancer; MRI; Lymph node staging; Response assessment
6.  MRI and diffusion-weighted MRI to diagnose a local tumour regrowth during long-term follow-up of rectal cancer patients treated with organ preservation after chemoradiotherapy 
European Radiology  2015;26:2118-2125.
Objectives
To assess the value of MRI and diffusion-weighted imaging (DWI) for diagnosing local tumour regrowth during follow-up of organ preservation treatment after chemoradiotherapy for rectal cancer.
Methods
Seventy-two patients underwent organ preservation treatment (chemoradiotherapy + transanal endoscopic microsurgery or “wait-and-see”) and were followed with MRI including DWI (1.5 T) every 3 -months during the first year and 6 months during following years. Two readers scored each MRI for local regrowth using a confidence level, first on standard MRI, then on standard MRI+DWI. Histology and clinical follow-up were the standard reference. Receiver operating characteristic curves were constructed and areas under the curve (AUC) and corresponding accuracy figures calculated on a per-scan basis.
Results
Four hundred and forty MRIs were assessed. Twelve patients developed local regrowth. AUC/sensitivity/specificity for standard MRI were 0.95/58 %/98 % (R1) and 0.96/58 % /100 % (R2). For standard MRI+DWI, these numbers were 0.86/75 %/97 % (R1) and 0.98/75 %/100 % (R2). After adding DWI, the number of equivocal scores decreased from 22 to 7 (R1) and from 40 to 20 (R2).
Conclusions
Although there was no overall improvement in diagnostic performance in terms of AUC, adding DWI improved the sensitivity of MRI for diagnosing local tumour regrowth and lowered the rate of equivocal MRIs.
Key Points
• DWI improves sensitivity for detecting local tumour regrowth after organ preservation treatment.
• In particular, DWI can aid in detecting small local recurrence.
• DWI reduces the number of equivocal scores.
doi:10.1007/s00330-015-4062-z
PMCID: PMC4902833  PMID: 26518582
Rectal neoplasms; Magnetic resonance imaging; Diffusion; Recurrence; Organ preservation
8.  Assessment of Clinical Complete Response After Chemoradiation for Rectal Cancer with Digital Rectal Examination, Endoscopy, and MRI: Selection for Organ-Saving Treatment 
Annals of Surgical Oncology  2015;22(12):3873-3880.
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.
doi:10.1245/s10434-015-4687-9
PMCID: PMC4595525  PMID: 26198074
9.  Magnetization transfer imaging to assess tumour response after chemoradiotherapy in rectal cancer 
European Radiology  2015;26:390-397.
Purpose
Single-slice magnetization transfer (MT) imaging has shown promising results for evaluating post-radiation fibrosis. The study aim was to evaluate the value of multislice MT imaging to assess tumour response after chemoradiotherapy by comparing magnetization transfer ratios (MTR) with histopathological tumour regression grade (TRG).
Materials and Methods
Thirty patients with locally advanced rectal cancer (cT3-4 and/or cN2) underwent routine restaging MRI 8 weeks post-chemoradiotherapy, including multislice MT-sequence, covering the entire tumour bed. Two independent readers delineated regions of interest on MTR maps, covering all potential remaining tumour and fibrotic areas. Mean MTR and histogram parameters (minimum, maximum, median, standard deviation, skewness, kurtosis, and 5-30-70-95th percentiles) were calculated. Reference standard was histological TRG1-2 (good response) and TRG3-5 (poor response).
Results
24/30 patients were male; mean age was 67.7 ± 10.8 years. Mean MTR rendered AUCs of 0.65 (reader1) and 0.87 (reader2) to differentiate between TRG1-2 versus TRG3-5. Best results were obtained for 95th percentile (AUC 0.75- 0.88). Interobserver agreement was moderate (ICC 0.50) for mean MTR and good (ICC 0.80) for 95th percentile.
Conclusions
MT imaging is a promising tool to assess tumour response post-chemoradiotherapy in rectal cancer. Particularly, 95th percentile results in AUCs up to 0.88 to discriminate a good tumour response.
Key Points
• The mean MTR can differentiate between good and poor responders after chemoradiation.
• In addition to measurement of the mean value, histogram analyses can be beneficial.
• The histogram parameter 95thpercentile can reach AUCs of 0.75–0.88.
doi:10.1007/s00330-015-3856-3
PMCID: PMC4712249  PMID: 26065396
Magnetization transfer imaging; Rectal cancer; Response assessment; Tumour regression grade; Interobserver agreement
10.  Whole-liver CT texture analysis in colorectal cancer: Does the presence of liver metastases affect the texture of the remaining liver? 
Background
Liver metastases limit survival in colorectal cancer. Earlier detection of (occult) metastatic disease may benefit treatment and survival.
Objective
The objective of this article is to evaluate the potential of whole-liver CT texture analysis of apparently disease-free liver parenchyma for discriminating between colorectal cancer (CRC) patients with and without hepatic metastases.
Methods
The primary staging CT examinations of 29 CRC patients were retrospectively analysed. Patients were divided into three groups: patients without liver metastases (n = 15), with synchronous liver metastases (n = 10) and metachronous liver metastases within 18 months following primary staging (n = 4). Whole-liver texture analysis was performed by delineation of the apparently non-diseased liver parenchyma (excluding metastases or other focal liver lesions) on portal phase images. Mean grey-level intensity (M), entropy (E) and uniformity (U) were derived with no filtration and different filter widths (0.5 = fine, 1.5 = medium, 2.5 = coarse).
Results
Mean E1.5 and E2.5 for the whole liver in patients with synchronous metastases were significantly higher compared with the non-metastatic patients (p = 0.02 and p = 0.01). Mean U1.5 and U2.5 were significantly lower in the synchronous metastases group compared with the non-metastatic group (p = 0.04 and p = 0.02). Texture parameters for the metachronous metastases group were not significantly different from the non-metastatic group or synchronous metastases group (p > 0.05), although – similar to the synchronous metastases group – there was a subtle trend towards increased E1.5, E2.5 and decreased U1.5, U2.5 values. Areas under the ROC curve for the diagnosis of synchronous metastatic disease based on the texture parameters E1.5,2.5 and U1.5,2.5 ranged between 0.73 and 0.78.
Conclusion
Texture analysis of the apparently non-diseased liver holds promise to differentiate between CRC patients with and without metastatic liver disease. Further research is required to determine whether these findings may be used to benefit the prediction of metachronous liver disease.
doi:10.1177/2050640614552463
PMCID: PMC4245301  PMID: 25452849
Colorectal cancer; liver metastases; CT texture; occult disease; metachronous metastases
11.  The CARTS study: Chemoradiation therapy for rectal cancer in the distal rectum followed by organ-sparing transanal endoscopic microsurgery 
BMC Surgery  2011;11:34.
Background
The CARTS study is a multicenter feasibility study, investigating the role of rectum saving surgery for distal rectal cancer.
Methods/Design
Patients with a clinical T1-3 N0 M0 rectal adenocarcinoma below 10 cm from the anal verge will receive neoadjuvant chemoradiation therapy (25 fractions of 2 Gy with concurrent capecitabine). Transanal Endoscopic Microsurgery (TEM) will be performed 8 - 10 weeks after the end of the preoperative treatment depending on the clinical response.
Primary objective is to determine the number of patients with a (near) complete pathological response after chemoradiation therapy and TEM. Secondary objectives are the local recurrence rate and quality of life after this combined therapeutic modality. A three-step analysis will be performed after 20, 33 and 55 patients to ensure the feasibility of this treatment protocol.
Discussion
The CARTS-study is one of the first prospective multicentre trials to investigate the role of a rectum saving treatment modality using chemoradiation therapy and local excision. The CARTS study is registered at clinicaltrials.gov (NCT01273051)
doi:10.1186/1471-2482-11-34
PMCID: PMC3295682  PMID: 22171697
12.  Tumour ADC measurements in rectal cancer: effect of ROI methods on ADC values and interobserver variability 
European Radiology  2011;21(12):2567-2574.
Objectives
To assess the influence of region of interest (ROI) size and positioning on tumour ADC measurements and interobserver variability in patients with locally advanced rectal cancer (LARC).
Methods
Forty-six LARC patients were retrospectively included. Patients underwent MRI including DWI (b0,500,1000) before and 6–8 weeks after chemoradiation (CRT). Two readers measured mean tumour ADCs (pre- and post-CRT) according to three ROI protocols: whole-volume, single-slice or small solid samples. The three protocols were compared for differences in ADC, SD and interobserver variability (measured as the intraclass correlation coefficient; ICC).
Results
ICC for the whole-volume ROIs was excellent (0.91) pre-CRT versus good (0.66) post-CRT. ICCs were 0.53 and 0.42 for the single-slice ROIs versus 0.60 and 0.65 for the sample ROIs. Pre-CRT ADCs for the sample ROIs were significantly lower than for the whole-volume or single-slice ROIs. Post-CRT there were no significant differences between the whole-volume ROIs and the single-slice or sample ROIs, respectively. The SDs for the whole-volume and single-slice ROIs were significantly larger than for the sample ROIs.
Conclusions
ROI size and positioning have a considerable influence on tumour ADC values and interobserver variability. Interobserver variability is worse after CRT. ADCs obtained from the whole tumour volume provide the most reproducible results.
Key Points
• ROI size and positioning influence tumour ADC measurements in rectal cancer
• ROI size and positioning influence interobserver variability of tumour ADC measurements
• ADC measurements of the whole tumour volume provide the most reproducible results
• Tumour ADC measurements are more reproducible before, rather than after, chemoradiation treatment
• Variations caused by ROI size and positioning should be taken into account when using ADC as a biomarker for tumour response
doi:10.1007/s00330-011-2220-5
PMCID: PMC3217149  PMID: 21822946
Diffusion magnetic resonance imaging; Rectal neoplasms; Observer variation; Methodology; Apparent diffusion coefficient
13.  T-staging of rectal cancer: accuracy of 3.0 Tesla MRI compared with 1.5 Tesla 
Abdominal Imaging  2011;37(3):475-481.
Objectives
Magnetic resonance imaging (MRI) is not accurate in discriminating T1-2 from borderline T3 rectal tumors. Higher resolution on 3 Tesla-(3T)-MRI could improve diagnostic performance for T-staging. The aim of this study was to determine whether 3T-MRI compared with 1.5 Tesla-(1.5T)-MRI improves the accuracy for the discrimination between T1-2 and borderline T3 rectal tumors and to evaluate reproducibility.
Methods
13 patients with non-locally advanced rectal cancer underwent imaging with both 1.5T and 3T-MRI. Three readers with different expertise evaluated the images and predicted T-stage with a confidence level score. Receiver operator characteristics curves with areas under the curve (AUC) and diagnostic parameters were calculated. Inter- and intra-observer agreements were calculated with quadratic kappa-weighting. Histology was the reference standard.
Results
Seven patients had pT1-2 tumors and six had pT3 tumors. AUCs ranged from 0.66 to 0.87 at 1.5T vs. 0.52–0.82 at 3T. Mean overstaging rate was 43% at 1.5T and 57% at 3T (P = 0.23). Inter-observer agreement was κ 0.50–0.71 at 1.5T vs. 0.15–0.68 at 3T. Intra-observer agreement was κ 0.71 at 1.5T and 0.76 at 3T.
Conclusions
This is the first study to compare 3T with 1.5T MRI for T-staging of rectal cancer within the same patients. Our results showed no difference between 3T and 1.5T-MRI for the distinction between T1-2 and borderline T3 tumors, regardless of expertise. The higher resolution at 3T-MRI did not aid in the distinction between desmoplasia in T1-2-tumors and tumor stranding in T3-tumors. Larger studies are needed to acknowledge these findings.
doi:10.1007/s00261-011-9770-5
PMCID: PMC3345180  PMID: 21674192
Rectal cancer; MRI; T-stage; 3 Tesla; Medicine & Public Health; Hepatology; Gastroenterology; Imaging / Radiology
14.  What is the most accurate whole-body imaging modality for assessment of local and distant recurrent disease in colorectal cancer? A meta-analysis 
Purpose
The objective of this study was to compare the diagnostic performance of positron emission tomography (PET), PET/CT, CT and MRI as whole-body imaging modalities for the detection of local and/or distant recurrent disease in colorectal cancer (CRC) patients who have a (high) suspicion of recurrent disease, based on clinical findings or rise in carcinoembryonic antigen (CEA).
Methods
A meta-analysis was undertaken. PubMed and Embase were searched for studies on the accuracy of whole-body imaging for patients with suspected local and/or distant recurrence of their CRC. Additionally, studies had to have included at least 20 patients with CRC and 2 × 2 contingency tables had to be provided or derivable. Articles evaluating only local recurrence or liver metastasis were excluded. Summary receiver-operating characteristic (ROC) curves were constructed from the data on sensitivity and specificity of individual studies and pooled estimates of diagnostic odds ratios (DORs) and areas under the ROC curve (AUCs) were calculated. To test for heterogeneity the Cochran Q test was used.
Results
Fourteen observational studies were included which evaluated PET, PET/CT, CT and/or MRI. Study results were available in 12 studies for PET, in 5 studies for CT, in 5 studies for PET/CT and in 1 study for MRI. AUCs for PET, PET/CT and CT were 0.94 (0.90–0.97), 0.94 (0.87–0.98) and 0.83 (0.72–0.90), respectively. In patient based analyses PET/CT had a higher diagnostic performance than PET with an AUC of 0.95 (0.89–0.97) for PET/CT vs 0.92 (0.86–0.96) for PET.
Conclusion
Both whole-body PET and PET/CT are very accurate for the detection of local and/or distant recurrent disease in CRC patients with a (high) suspicion of recurrent disease. CT has the lowest diagnostic performance. This difference is probably mainly due to the lower accuracy of CT for detection of extrahepatic metastases (including local recurrence). For clinical practice PET/CT might be the modality of choice when evaluating patients with a (high) suspicion of recurrent disease, because of its best performance in patient based analyses and confident prediction of disease status.
doi:10.1007/s00259-011-1785-1
PMCID: PMC3126998  PMID: 21468765
Colorectal cancer; Whole-body imaging; Recurrence; Staging
15.  Diffusion-Weighted MRI for Selection of Complete Responders After Chemoradiation for Locally Advanced Rectal Cancer: A Multicenter Study 
Annals of Surgical Oncology  2011;18(8):2224-2231.
Purpose
In 10–24% of patients with rectal cancer who are treated with neoadjuvant chemoradiation, no residual tumor is found after surgery (ypT0). When accurately selected, these complete responders might be considered for less invasive treatments instead of standard surgery. So far, no imaging method has proven reliable. This study was designed to assess the accuracy of diffusion-weighted MRI (DWI) in addition to standard rectal MRI for selection of complete responders after chemoradiation.
Methods
A total of 120 patients with locally advanced rectal cancer from three university hospitals underwent chemoradiation followed by a restaging MRI (1.5T), consisting of standard T2W-MRI and DWI (b0-1000). Three independent readers first scored the standard MRI only for the likelihood of a complete response using a 5-point confidence score, after which the DWI images were added and the scoring was repeated. Histology (ypT0 vs. ypT1-4) was the standard reference. Diagnostic performance for selection of complete responders and interobserver agreement were compared for the two readings.
Results
Twenty-five of 120 patients had a complete response (ypT0). Areas under the ROC-curve for the three readers improved from 0.76, 0.68, and 0.58, using only standard MRI, to 0.8, 0.8, and 0.78 after addition of DWI (P = 0.39, 0.02, and 0.002). Sensitivity for selection of complete responders ranged from 0–40% on standard MRI versus 52–64% after addition of DWI. Specificity was equally high (89–98%) for both reading sessions. Interobserver agreement improved from κ 0.2–0.32 on standard MRI to 0.51–0.55 after addition of DWI.
Conclusions
Addition of DWI to standard rectal MRI improves the selection of complete responders after chemoradiation.
doi:10.1245/s10434-011-1607-5
PMCID: PMC3136702  PMID: 21347783
16.  Value of MRI and diffusion-weighted MRI for the diagnosis of locally recurrent rectal cancer 
European Radiology  2011;21(6):1250-1258.
Objectives
To evaluate the accuracy of standard MRI, diffusion-weighted MRI (DWI) and fusion images for the diagnosis of locally recurrent rectal cancer in patients with a clinical suspicion of recurrence.
Methods
Forty-two patients with a clinical suspicion of recurrence underwent 1.5-T MRI consisting of standard T2-weighted FSE (3 planes) and an axial DWI (b0,500,1000). Two readers (R1,R2) independently scored the likelihood of recurrence; [1] on standard MRI, [2] on standard MRI+DWI, and [3] on T2-weighted+DWI fusion images.
Results
19/42 patients had a local recurrence. R1 achieved an area under the ROC-curve (AUC) of 0.99, sensitivity 100% and specificity 83% on standard MRI versus 0.98, 100% and 91% after addition of DWI (p = 0.78). For R2 these figures were 0.87, 84% and 74% on standard MRI and 0.91, 89% and 83% with DWI (p = 0.09). Fusion images did not significantly improve the performance. Interobserver agreement was κ0.69 for standard MRI, κ0.82 for standard MRI+DWI and κ0.84 for the fusion images.
Conclusions
MRI is accurate for the diagnosis of locally recurrent rectal cancer in patients with a clinical suspicion of recurrence. Addition of DWI does not significantly improve its performance. However, with DWI specificity and interobserver agreement increase. Fusion images do not improve accuracy.
doi:10.1007/s00330-010-2052-8
PMCID: PMC3088810  PMID: 21240647
MRI; Diffusion magnetic resonance imaging; Rectal neoplasms; Local neoplasm recurrence; Diagnosis
17.  Value of ADC measurements for nodal staging after chemoradiation in locally advanced rectal cancer—a per lesion validation study 
European Radiology  2010;21(2):265-273.
Objectives
To evaluate the performance of diffusion-weighted MRI (DWI) in addition to T2-weighted (T2W) MRI for nodal restaging after chemoradiation in rectal cancer.
Methods
Thirty patients underwent chemoradiation followed by MRI (1.5 T) and surgery. Imaging consisted of T2W-MRI and DWI (b0, 500, 1000). On T2W-MRI, nodes were scored as benign/malignant by two independent readers (R1, R2). Mean apparent diffusion coefficient (ADC) was measured for each node. Diagnostic performance was compared for T2W-MRI, ADC and T2W+ADC, using a per lesion histological validation.
Results
ADC was higher for the malignant nodes (1.43 ± 0.38 vs 1.19 ± 0.27 *10−3 mm2/s, p < 0.001). Area under the ROC curve/sensitivity/specificity were 0.88/65%/93% (R1) and 0.95/71%/91% (R2) using T2W-MRI; 0.66/53%/82% using ADC (mean of two readers); and 0.91/56%/98% (R1) and 0.96/56%/99% (R2) using T2W+ADC. There was no significant difference between T2W-MRI and T2W+ADC. Interobserver reproducibility was good for T2W-MRI (κ0.73) and ADC (intraclass correlation coefficient 0.77).
Conclusions
After chemoradiation, ADC measurements may have potential for nodal characterisation, but DWI on its own is not reliable. Addition of DWI to T2W-MRI does not improve accuracy and T2W-MRI is already sufficiently accurate.
doi:10.1007/s00330-010-1937-x
PMCID: PMC3034880  PMID: 20730540
Nodal restaging; Diffusion-weighted imaging; Apparent diffusion coefficient; MRI; Locally advanced rectal cancer

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