Luc A. Heijnen

Long-term Outcome of an Organ Preservation Program After Neoadjuvant Treatment for Rectal Cancer

BACKGROUND The aim of this study was to establish the oncological and functional results of organ preservation with a watch-and-wait approach (W&W) and selective transanal endoscopic microsurgery (TEM) in patients with a clinical complete or near-complete response (cCR) after neoadjuvant chemoradiation for rectal cancer. METHODS Between 2004 and 2014, organ preservation was offered if response assessment with digital rectal examination, endoscopy, and MRI showed (near) cCR. Watch-and-wait was offered for cCR, and two options were offered for near cCR: TEM or reassessment after three months. Follow-up included endoscopy and MRIs every three months during the first year, and every six months thereafter. Long-term outcome was assessed with Kaplan-Meier curves. Functional outcome was assessed with colostomy-free survival and Vaizey incontinence score (0 = perfect continence, 24 = totally incontinent). RESULTS One hundred patients were included, with median follow-up of 41.1 months. Sixty-one had cCR at initial response assessment. Thirty-nine had near cCR, of whom 24 developed cCR at the second assessment and 15 patients underwent TEM (9 ypT0, 1 ypT1, 5 ypT2). Fifteen patients developed a local regrowth (12 luminal, 3 nodal), all salvageable and within 25 months. Five patients developed metastases, and five patients died. Three-year overall survival was 96.6% (95% confidence interval [CI] = 89.9% to 98.9%), distant metastasis-free survival was 96.8% (95% CI = 90.4% to 99.0%), local regrowth-free survival was 84.6% (95% CI = 75.8% to 90.5%), and disease-free survival was 80.6% (95% CI = 70.9% to 87.4%). Colostomy-free survival was 94.8% (95% CI = 88.0% to 97.8%), with a good continence after watch-and-wait (Vaizey = 3.4, SD = 3.9) and moderate after TEM (Vaizey = 9.7, SD = 5.1). CONCLUSIONS Organ preservation appears oncologically safe for selected rectal cancer patients with a cCR or near cCR after neoadjuvant chemoradiation when applying strict selection criteria and frequent follow-up, including endoscopy and MRI. The low colostomy rate and the good long-term functional outcome warrant discussing this option with the patient as an alternative to major surgery.

MRI and Diffusion-weighted MRI Volumetry for Identification of Complete Tumor Responders After Preoperative Chemoradiotherapy in Patients With Rectal Cancer: A Bi-institutional Validation Study.

Background: 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. Objective: This study aims to validate the diagnostic value of these volume thresholds in a larger, independent, and bi-institutional patient cohort. Methods: 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 (cm3) on T2W-magnetic resonance image and diffusion-weighted magnetic resonance image by means of freehand tumor delineation. Tumor volume reduction rates (&Dgr;volume) were calculated. Previously determined T2W and DWI threshold values for prevolume, postvolume, and &Dgr;volume were tested to “prospectively” assess their respective diagnostic value in discriminating patients with a complete tumor response from patients with residual tumor. Results: Twenty patients had a complete response. Using the average measurements between the 2 readers, areas under the curve for the pre-/post-/&Dgr;volumes 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 &Dgr;volume. For DWI volumetry, sensitivity and specificity were 65% and 76% for pre-, 70% and 98% for post-, and 70% and 93% for &Dgr;volume. Conclusions: 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%.

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.

CT texture analysis in colorectal liver metastases: A better way than size and volume measurements to assess response to chemotherapy?

Background Response Evaluation Criteria In Solid Tumors (RECIST) are known to have limitations in assessing the response of colorectal liver metastases (CRLMs) to chemotherapy. Objective The objective of this article is to compare CT texture analysis to RECIST-based size measurements and tumor volumetry for response assessment of CRLMs to chemotherapy. Methods Twenty-one patients with CRLMs underwent CT pre- and post-chemotherapy. Texture parameters mean intensity (M), entropy (E) and uniformity (U) were assessed for the largest metastatic lesion using different filter values (0.0 = no/0.5 = fine/1.5 = medium/2.5 = coarse filtration). Total volume (cm3) of all metastatic lesions and the largest size of one to two lesions (according to RECIST 1.1) were determined. Potential predictive parameters to differentiate good responders (n = 9; histological TRG 1–2) from poor responders (n = 12; TRG 3–5) were identified by univariable logistic regression analysis and subsequently tested in multivariable logistic regression analysis. Diagnostic odds ratios were recorded. Results The best predictive texture parameters were Δuniformity and Δentropy (without filtration). Odds ratios for Δuniformity and Δentropy in the multivariable analyses were 0.95 and 1.34, respectively. Pre- and post-treatment texture parameters, as well as the various size and volume measures, were not significant predictors. Odds ratios for Δsize and Δvolume in the univariable logistic regression were 1.08 and 1.05, respectively. Conclusions Relative differences in CT texture occurring after treatment hold promise to assess the pathologic response to chemotherapy in patients with CRLMs and may be better predictors of response than changes in lesion size or volume.

Magnetization transfer ratio: a potential biomarker for the assessment of postradiation fibrosis in patients with rectal cancer.

ObjectivesMagnetization transfer-magnetic resonance imaging (MT-MRI) uses differences in the magnetization interaction of the free “unbound” water protons and the macromolecular-bound protons. The aim of this study was to evaluate whether the magnetization transfer ratio (MTR) may be used to identify fibrosis in patients with rectal cancer treated with chemoradiotherapy. Materials and MethodsThis study was part of a rectal cancer imaging study, which was approved by the local institutional review board. Twenty-six patients, treated with neoadjuvant chemoradiotherapy, underwent a standard MRI including T2-weighted sequences and a diffusion-weighted sequence. An axially oriented MT sequence was performed at the center of the (former) tumor location. Regions of interest were manually drawn on the MT-MRI (with reference to the T2-weighted and diffusion-weighted images), covering areas of residual tumor, fibrosis, or the normal or edematous rectal wall. The results were compared with that of the histopathological examination. Differences in MTR between the 4 tissue types were analyzed, and a receiver operating characteristic (ROC) curve was generated to assess the diagnostic potential. ResultsThirty-eight regions of interest were analyzed on the MT-MRI. The mean (SD) MTR of the fibrosis was 37.7% (2.7%), which was significantly higher than that of the residual tumor (29.6% [4.2%]; P < 0.001), the normal rectal wall (30.3% [4.7%]; P = 0.003), and the edematous rectal wall (18.2% [4.0%]; P < 0.001). The use of MTR resulted in an area under the ROC-curve of 0.96, a sensitivity of 88%, and a specificity of 90% for the diagnosis of fibrosis. ConclusionsMagnetization transfer ratio can be used to discriminate postradiation fibrosis from residual tumor and the normal rectal wall after chemoradiotherapy. Magnetization transfer imaging can thus be a promising tool for the unsolved dilemma of interpreting postradiation fibrosis in rectal cancer.

Whole-liver diffusion-weighted MRI histogram analysis: effect of the presence of colorectal hepatic metastases on the remaining liver parenchyma

Objectives To explore whether whole-liver diffusion-weighted MRI analysis (of the apparently normal liver parenchyma) can help differentiate between patients with colorectal liver metastasis and controls without liver disease. Materials and methods Ten patients with colorectal liver metastasis and 10 controls with no focal/diffuse liver disease underwent liver MRI at 1.5 T including diffusion-weighted imaging (DWI; b-values 0, 50, 100, 500, 750, 1000). Apparent diffusion coefficient (ADC) maps were calculated from the DWI images to carry out quantitative diffusion analyses. An experienced reader performed segmentation of the apparently nondiseased liver (excluding metastases/focal liver lesions) on the ADC maps. Histogram ADC parameters were calculated and compared between the patients and the controls. Results The mean liver ADC was 0.95×10−3 mm2/s for the patients versus 1.03×10−3 mm2/s for the controls (P=0.42). The fifth percentile of the ADC was significantly lower for the patients compared with the controls (0.45 vs. 0.69 10−3 mm2/s, P=0.01). The SD was significantly higher in the patient group (0.30 vs. 0.22, P<0.001). Median, skewness, kurtosis, and 30th–95th percentile were not significantly different between the two groups. Areas under the receiver operator characteristics curves to differentiate patients with metastatic liver involvement from healthy controls without liver disease were 0.79 for the fifth percentile and 0.95 for the SD. Conclusion Whole-liver diffusion-weighted MRI histogram analysis showed a significant shift towards lower fifth percentile ADC values and higher SD in patients with colorectal liver metastasis compared with controls without liver disease.

Adrenal Incidentalomas During Diagnostic Work-up of Colorectal Cancer Patients: What is the Risk of Metastases?

BackgroundAdrenal incidentalomas (AIs) are regularly discovered on staging computed tomography (CT) of patients with colorectal cancer (CRC). Although CRC is considered unlikely to metastasize to the adrenal gland, it is not known how often an AI appears to be a CRC metastasis. This causes a diagnostic dilemma for many patients with newly diagnosed CRC. This study aimed primarily to describe the incidence of AIs and adrenal metastases in CRC patients.MethodsA single-center cohort of 475 consecutive patients with newly diagnosed CRC was defined. Retrospectively, all radiology reports and multidisciplinary team meeting reports were assessed for the presence of adrenal abnormalities. All AIs shown on staging CT were reevaluated for the purpose of this study, and the sizes of these adrenal glands were determined. Based on the CT reevaluation, follow-up imaging, and clinical follow-up assessment, conclusions on the presence or absence of adrenal metastases were drawn.ResultsThe incidence of AIs in this CRC patient cohort was 10.5% (50/475). In 96% (48/50) of the patients with AIs, adrenal metastases could be ruled out. No solitary adrenal metastases were encountered. In two patients who had widespread systemic disease without curative treatment options, the AIs were considered to be adrenal metastases (cohort incidence, 0.4%).ConclusionThis is the first study to report on adrenal incidentalomas in CRC patients. In newly diagnosed CRC patients without disseminated disease, AIs can be considered benign, and no additional imaging is indicated to rule out adrenal metastases in this group.