MRI predictive factors for tumor response in rectal cancer following neoadjuvant chemoradiation therapy--implications for induction chemotherapy?

Clinical and magnetic resonance imaging (MRI) characteristics at baseline and following chemoradiation therapy (CRT) most strongly associated with histopathologic response were investigated and survival outcomes evaluated in accordance with imaging and pathological response. Responders were defined as mrT3c/d-4 downstaged to ypT0-2 on pathology or low at risk mrT2 downstaged to ypT1 or T0. Multivariate logistic regression of baseline and posttreatment MRI: T, N, extramural venous invasion (EMVI), circumferential resection margin, craniocaudal length <5 cm, and MRI tumor height ≤5 cm were used to identify independent predictor(s) for response. An association between induction chemotherapy and EMVI status was analyzed. Survival outcomes for pathologic and MRI responders and nonresponders were analyzed. Two hundred eighty-one patients were eligible; 114 (41%) patients were pathology responders. Baseline MRI negative EMVI (odds ratio 2.94, P=.007), tumor height ≤5 cm (OR 1.96, P=.02), and mrEMVI status change (positive to negative) following CRT (OR 3.09, P<.001) were the only predictors for response. There was a strong association detected between induction chemotherapy and ymrEMVI status change after CRT (OR 9.0, P<.003). ymrT0-2 gave a positive predictive value of 80% and OR of 9.1 for ypT0-2. ymrN stage accuracy of ypN stage was 75%. Three-year disease-free survival for pathology and MRI responders were similar at 80% and 79% and significantly better than poor responders. Tumor height and mrEMVI status are more important than baseline size and stage of the tumor as predictors of response to CRT. Both MRI- and pathologic-defined responders have significantly improved survival. "Good response" to CRT in locally advanced rectal cancer with ypT0-2 carries significantly better 3-year overall survival and disease-free survival. Use of induction chemotherapy for improving mrEMVI status and knowledge of MRI predictive factors could be taken into account in the pursuit of individualized neoadjuvant treatments for patients with rectal cancer.

Yu SK ，Tait D ，Chau I ，Brown G ... -  《-》

The prognostic significance of postchemoradiotherapy high-resolution MRI and histopathology detected extramural venous invasion in rectal cancer.

Chand M ，Evans J ，Swift RI ，Tekkis PP ，West NP ，Stamp G ，Heald RJ ，Brown G ... -  《-》

Magnetic resonance imaging in rectal cancer downstaged using neoadjuvant chemoradiation: accuracy of prediction of tumour stage and circumferential resection margin status.

Kulkarni T ，Gollins S ，Maw A ，Hobson P ，Byrne R ，Widdowson D ... -  《-》

Adjuvant chemotherapy may improve disease-free survival in patients with rectal cancer positive for MRI-detected extramural venous invasion following chemoradiation.

MRI-detected extramural venous invasion (mrEMVI) is a poor prognostic factor in rectal cancer. Preoperative chemoradiotherapy (CRT) can cause regression in the severity of EMVI and subsequently improve survival whereas mrEMVI persisting after CRT confers an increased risk of recurrence. The effect of adjuvant chemotherapy (AC) following CRT on survival in rectal cancer remains unclear. The aim of this study was to determine whether there is a survival advantage for AC given to patients with mrEMVI persisting after CRT. A prospective analysis was conducted of consecutive patients with locally advanced rectal cancer between 2006 and 2013. All patients underwent CRT followed by surgery. AC was given to selected patients based on the presence of specific 'high-risk' features. Comparison was made between patients offered AC with observation alone. The primary outcome was 3-year disease-free survival (DFS). Of 631 patients, 227 (36.0%) demonstrated persistent mrEMVI following CRT. Patients were grouped on the basis of AC or observation and were matched for age, performance status and final histopathological staging. Three-year DFS in the AC group was 74.6% compared with 53.7% in the observation only group. AC had a survival benefit on multivariate analysis (hazard ratio 0.458; 95% CI: 0.271-0.775, P = 0.004). Patients with persistent mrEMVI following CRT who receive AC may have a decreased risk of recurrence and an improved 3-year DFS compared with patients not receiving AC, irrespective of age and performance status.

Chand M ，Rasheed S ，Heald R ，Swift I ，West N ，Rao S ，Tekkis P ，Brown G ... -  《-》

Diffusion-weighted MRI and MR- volumetry--in the evaluation of tumor response after preoperative chemoradiotherapy in patients with locally advanced rectal cancer.

To determine the diagnostic performance of diffusion-weighted MRI and MR volumetry for the assessment of tumor response after preoperative chemoradiotherapy (CRT) in patients with locally advanced rectal cancer. Forty-three patients with rectal cancer who underwent preoperative CRT were prospectively examined for the study. This prospective study was approved by our institutional review board. DW- and high resolution T2-weighted imaging were performed before and after therapy. Two different diffusion gradients (b = 0 and b = 600, then separately b = 0 and b = 1000) were applied. The mean tumor volume and mean ADC values were measured before and after therapy. To evaluate the responders and nonresponders to neoadjuvant CRT, two criteria, ypT stage determined in the pathologic examination after treatment and histopathologic tumor regression grade (Ryan), were used as reference standards. The patients with a lower ypT stage than T stage in the first MRI before neoadjuvant CRT were evaluated as the responder group, while the patients with a higher or the same ypT stage relative to the first MRI T stage were evaluated as the nonresponder group. According to Ryan tumor regression grade, grade 1 was evaluated as the responders, whereas grades 2 and 3 were evaluated as the nonresponder group. The percentage ADC increase and percentage tumor volume regression were compared between the responders and nonresponders using two reference standards: T downstaging and tumor regression grade (TRG). Before CRT, the mean tumor ADC in the responder group was significantly lower than that in the nonresponder group (p < 0.001). At the end of CRT, the mean percentage of tumor ADC change in the responder group was significantly higher than that in the nonresponder group. The percentage tumor volume regression of the responders was significantly higher than that of the nonresponders (p = 0.001). The cut-off ADC value for discriminating between the responders and nonresponders after treatment was determined to be (b = 600) 1.03 × 10(-3)mm(2)/s and the sensitivity, 71%; specificity, 79%; accuracy, 74%; positive predictive value, 81%; negative predictive value, 68% respectively. The cut-off value for discriminating between the responders and the nonresponders after treatment was determined for b = 1000 as 1.20 × 10(-3)mm(2)/s and the sensitivity, 42%; specificity, 84%; accuracy, 60%; positive predictive value, 77%; negative predictive value, 53%. The increase in the mean tumor ADC and percentage tumor volume regression in patients with rectal cancer treated with preoperative CRT was correlated with good response. DW MR imaging is a promising non-invasive technique that can help predict and monitor early therapeutic response in patients with rectal cancer who undergo CRT.

Birlik B ，Obuz F ，Elibol FD ，Celik AO ，Sokmen S ，Terzi C ，Sagol O ，Sarioglu S ，Gorken I ，Oztop I ... -  《-》