Histopathologic Tumor Regression Grade Research Articles

Evaluating Treatment Response in GEJ Adenocarcinoma: The Role of Pretherapeutic and Posttherapeutic Iodine Mapping.

Neoadjuvant therapy regimens have significantly improved the prognosis of GEJ (gastroesophageal junction) cancer; however, there are a significant percentage of patients who benefit from earlier resection or adapted therapy regimens, and the true response rate can only be determined histopathologically. Methods that allow preoperative assessment of response are lacking. The purpose of this retrospective study is to assess the potential of pretherapeutic and posttherapeutic spectral CT iodine density (IoD) in predicting histopathological response to neoadjuvant chemotherapy in patients diagnosed with adenocarcinoma of the GEJ. In this retrospective cohort study, a total of 62 patients with GEJ carcinoma were studied. Patients received a multiphasic CT scan at diagnosis and preoperatively. Iodine-density maps were generated based on spectral CT data. All tumors were histopathologically analyzed, and the tumor regression grade (TRG) according to Becker et al ( Cancer . 2003;98:1521-1530) was determined. Two experienced radiologists blindly placed 5 defined ROIs in the tumor region of highest density, and the maximum value was used for further analysis. Iodine density was normalized to the aortic iodine uptake. In addition, tumor response was assessed according to standard RECIST measurement. After assessing interrater reliability, the correlation of IoD values with treatment response and with histopathologic TRG was evaluated. The normalized ΔIoD (IoD at diagnosis - IoD after neoadjuvant treatment) and the normalized IoD after neoadjuvant treatment correlated significantly with the TRG. For the detection of responders and nonresponders, the receiver operating characteristic (ROC) curve for normalized ΔIoD yielded the highest area under the curve of 0.95 and achieved a sensitivity and specificity of 92.3% and 92.1%, respectively. Iodine density after neoadjuvant treatment achieved an area under the curve of 0.88 and a sensitivity and specificity of 86.8% and 84.6%, respectively (cutoff, 0.266). Iodine density at diagnosis and RECIST did not provide information to distinguish responders from nonresponders. Using the cutoff value for IoD after neoadjuvant treatment, a reliable classification of responders and nonresponders was achieved for both readers in a test set of 11 patients. Intraclass correlation coefficient revealed excellent interrater reliability (intraclass correlation coefficient, >0.9). Lastly, using the cutoff value for normalized ΔIoD as a definition for treatment response, a significantly longer survival of responders was shown. Changes in IoD after neoadjuvant treatment of GEJ cancer may be a potential surrogate for therapy response.

The effectiveness of neoadjuvant chemoradiotherapy in oesophageal adenocarcinoma with presence of extracellular mucin, signet-ring cells, and/or poorly cohesive cells.

Oesophageal adenocarcinomas may show different histopathological patterns, including excessive acellular mucin pools, signet-ring cells (SRCs), and poorly cohesive cells (PCCs). These components have been suggested to correlate with poor outcomes after neoadjuvant chemoradiotherapy (nCRT), which might influence patient management. However, these factors have not been studied independently of each other with adjustment for tumour differentiation grade (i.e. the presence of well-formed glands), which is a possible confounder. We studied the pre- and post-treatment presence of extracellular mucin, SRCs, and/or PCCs in relation to pathological response and prognosis after nCRT in patients with oesophageal or oesophagogastric junction adenocarcinoma. A total of 325 patients were retrospectively identified from institutional databases of two university hospitals. All patients were scheduled for ChemoRadiotherapy for Oesophageal cancer followed by Surgery Study (CROSS) nCRT and oesophagectomy between 2001 and 2019. Percentages of well-formed glands, extracellular mucin, SRCs, and PCCs were scored in pre-treatment biopsies and post-treatment resection specimens. The association between histopathological factors (≥1 and >10%) and tumour regression grade 3-4 (i.e. >10% residual tumour), overall survival, and disease-free survival (DFS) was evaluated, adjusted for tumour differentiation grade amongst other clinicopathological variables. In pre-treatment biopsies, ≥1% extracellular mucin was present in 66 of 325 patients (20%); ≥1% SRCs in 43 of 325 (13%), and ≥1% PCCs in 126 of 325 (39%). We show that pre-treatment histopathological factors were unrelated to tumour regression grade. Pre-treatment presence of >10% PCCs was associated with lower DFS (hazard ratio [HR] 1.73, 95% CI 1.19-2.53). Patients with post-treatment presence of ≥1% SRCs had higher risk of death (HR 1.81, 95% CI 1.10-2.99). In conclusion, pre-treatment presence of extracellular mucin, SRCs, and/or PCCs is unrelated to pathological response. The presence of these factors should not be an argument to refrain from CROSS. At least 10% PCCs pre-treatment and any SRCs post-treatment, irrespective of the tumour differentiation grade, seem indicative of inferior prognosis, but require further validation in larger cohorts.

Extracellular volume fraction determined by equilibrium contrast-enhanced CT for the prediction of the pathological complete response to neoadjuvant chemoradiotherapy for locally advanced rectal cancer.

To determine the extracellular volume (ECV) fraction derived from equilibrium contrast-enhanced CT for predicting pathological complete response (pCR) after neoadjuvant chemoradiotherapy (NCRT) in locally advanced rectal cancer (LARC). The ECV fraction before NCRT (ECVpre) and/or ECV after NCRT (ECVpost) of rectal tumors was assessed, and ECVΔ was calculated as ECVpost - ECVpre. The histopathologic tumor regression grading (TRG) was assessed. pCR (TRG 0 grade) was defined as the absence of viable tumor cells in the primary tumor and lymph nodes. Demographic and clinicopathological characteristics and ECV fraction were compared between the pCR and non-pCR groups. A mixed model was constructed by logistic regression. The performance for predicting pCR was assessed with the area under the receiver-operator curve (AUC). The AUCs of the different methods were compared by the method proposed by DeLong et al. RESULTS: Seventy-five patients were included; 17 achieved pCR, and 58 achieved non-pCR. The ECVpost (17.05 ± 2.36% vs. 29.94 ± 1.20%; p < 0.001) and ECVΔ (- 17.01 ± 3.01% vs. 0.44 ± 1.45%; p < 0.001) values in the pCR group were significantly lower than those in the non-pCR group. The mixed model that combined ECVpost with ECVΔ achieved an AUC of 0.92 (95% confidence interval (CI) = 0.81-0.98), which was higher than that of ECVpost (AUC, 0.91 (95% CI = 0.80-0.97); p = 0.60) or ECVΔ (AUC, 0.90 (95% CI = 0.79-0.97); p = 0.61). ECVpost and ECVΔ determined by using equilibrium contrast-enhanced CT were useful in distinguishing between pCR and non-pCR patients with LARC who received NCRT. • ECVpost and ECVΔ (ECVpost - ECVpre) differed significantly between the non-pCR and pCR groups. • ECVpre cannot be used to predict the efficacy of neoadjuvant chemoradiotherapy. • ECVpost combined with ECVΔ had the best performance with an AUC of 0.92 for predicting pCR after NCRT in LARC.

The predictive value of tumor volume reduction ratio on three-dimensional endorectal ultrasound for tumor response to chemoradiotherapy for locally advanced rectal cancer.

BackgroundPreoperative chemoradiotherapy remains part of the standard treatment for patients with locally advanced rectal cancer. Subsequent treatment individualization requires accurate prediction of tumor response to chemoradiotherapy. Three-dimensional endorectal ultrasound (3D-ERUS) can automatically capture and store the images of the rectal wall and rectal cancer with high resolution. In this study, we aimed to assess the correlation and predictive value between tumor volume changes measured on 3D-ERUS and the histopathological tumor response after chemoradiotherapy for patients with locally advanced rectal cancer.MethodsA total of 54 patients with locally advanced rectal cancer who underwent chemoradiotherapy and had complete 3D-ERUS data pre-and post-chemoradiotherapy were enrolled in the study. The tumor volume pre-and post-chemoradiotherapy was measured manually on 3D-ERUS, and the tumor volume reduction ratio was calculated. The histopathological tumor regression grade (TRG) was used to assess tumor response. The differences in volumetry parameters were compared between groups with varying tumor response. The diagnostic efficacy of the tumor volume reduction ratio was evaluated by the receiver operating characteristic (ROC) curve.ResultsThe mean age of all patients was 55.19±12.46 years. The relative proportions of TRG 0–3 were 29.6% (16/54), 16.6% (9/54), 50% (27/54), and 3.8% (2/54), respectively. The median tumor volumes post-chemoradiotherapy in good responders (TRG 0–1, median tumor volume =3.26 cm3) and the complete response group (TRG 0, median tumor volume =2.61 cm3) were smaller than those in poor responders (TRG 2–3, median tumor volume =5.43 cm3) and the partial response group (TRG 1–3, median tumor volume =4.00 cm3), while tumor volume reduction ratios were higher than those of poor responders (79.32% vs. 59.67%) and the partial response group (82.22% vs. 61.64%), with significant differences (all P values <0.05). The ROC curves showed that the cut-off values of the tumor volume reduction ratio to predict good responders and complete response were 67.77% and 72.02%, respectively. The corresponding areas under the curve in the prediction of good responders and complete response were 0.830 and 0.829, respectively.ConclusionsThe tumor volume reduction ratio measured on 3D-ERUS might be a helpful indicator for tumor response in patients with locally advanced rectal cancer.

YpN0 in Patients With Definitive cN-positive Status After Preoperative Treatment Is a Prognostic Factor in Esophageal Cancer

Histopathological tumor regression grade is applied not to lymph nodes but primary tumors modified by preoperative treatments. This study focused on patients whose pathological examination at the time of surgery showed no residual tumor after chemo(radio)therapy in the primary lesion (ypT0) or lymph nodes (ypN0). A total of 87 patients with clinical stage II/III thoracic esophageal cancer underwent esophagectomy following preoperative treatments to evaluate significances between pathological response and clinical outcomes; 51 patients with clinically definitive lymph node metastasis (cN+) were analyzed as a subgroup. ypT0 rates were 20.7% and 23.5%, and ypN0 rates were 47.1% and 27.5% in the whole cohort and in the cN+ subgroup, respectively. Disease-free survival, from surgery to relapse or death, was significantly influenced by ypN status (p=0.035) but not by ypT status in the 51 patients with definitive cN+ disease. Preoperative chemoradiation was an independent favorable factor for achievement of ypN0 in the 51 patients (odds ratio=0.09; p=0.007). ypN status was a predictive factor for DFS in patients treated with docetaxel plus low-dose 5-fluorouracil and cisplatin combined chemotherapy, superior to ypT status, especially in patients with definitive cN+ disease.

Correlation between MRI morphological response patterns and histopathological tumor regression after neoadjuvant endocrine therapy in locally advanced breast cancer: a randomized phase II trial

PurposeTo correlate MRI morphological response patterns with histopathological tumor regression grading system based on tumor cellularity in locally advanced breast cancer (LABC)-treated neoadjuvant with third-generation aromatase inhibitors.MethodsFifty postmenopausal patients with ER-positive/HER-2-negative LABC treated with neoadjuvant letrozole and exemestane given sequentially in an intra-patient cross-over regimen for at least 4 months with MRI response monitoring at baseline as well as after at least 2 and 4 months on treatment. The MRI morphological response pattern was classified into 6 categories: 0/complete imaging response; I/concentric shrinkage; II/fragmentation; III/diffuse; IV/stable; and V/progressive. Histopathological tumor regression was assessed based on the recommendations from The Royal College of Pathologists regarding tumor cellularity.ResultsFollowing 2 and 4 months with therapy, the most common MRI pattern was pattern II (24/50 and 21/50, respectively). After 4 months on therapy, the most common histopathological tumor regression grade was grade 3 (21/50). After 4 months an increasing correlation is observed between MRI patterns and histopathology. The overall correlation, between the largest tumor diameter obtained from MRI and histopathology, was moderate and positive (r = 0.50, P-value = 2e-04). Among them, the correlation was highest in type IV (r = 0.53).ConclusionThe type II MRI pattern “fragmentation” was more frequent in the histopathological responder group; and types I and IV in the non-responder group. Type II pattern showed the best endocrine responsiveness and a relatively moderate correlation between sizes obtained from MRI and histology, whereas type IV pattern indicated endocrine resistance but the strongest correlation between MRI and histology.

Organ Sparing for Locally Advanced Rectal Cancer after Neoadjuvant Treatment Followed by Electrochemotherapy.

Simple SummaryThis is a Phase II randomized controlled trial conducted with the aim of investigating whether the use of Electrochemotherapy after neoadjuvant therapy (ECT) and before surgery in patients with major clinical response allows for a more conservative surgical approach in patients with Locally Advanced Rectal Cancer (LARC) in comparison with the control group that will not receive ECT. The treatment response, in both the control arm and in the treatment arm, will be assessed using the histopathological tumor regression grade on tissue specimens after local excision.Background: Currently, 45–55% of rectal cancer patients receive preoperative chemo- radio-therapy for Locally Advanced Rectal Cancer (LARC). The idea of our study is to use Electrochemotherapy (ECT) before surgery, in patients with major clinical response after neoadjuvant therapy, to allow for a more conservative surgical approach. Objective: To evaluate the increase of the complete response rate after neoadjuvant treatment in LARC and to spare organ function due to total mesorectal excision (TME). Patients and Methods: This is a Phase II randomized controlled trial enrolling 70 patients that will be developed in two stages. In the first step, 28 patients will be enrolled: 14 of these will receive ECT for four weeks after neo-adjuvant treatment and then local excision (treatment group) and 14 patients will receive neo-adjuvant treatment and then local excision (control group). If an increase of response rate is observed in the first stage, and/or feasibility/safety is demonstrated, the second stage of the trial will be performed, enrolling an additional 42 patients. The treatment response. in both the control arm and the treatment arm, will be assessed using the histopathological tumor regression grade on tissue specimens after local excision.

Association of visual and quantitative heterogeneity of 18F-FDG PET images with treatment response in locally advanced rectal cancer: A feasibility study.

Background and purposeFew tools are available to predict tumor response to treatment. This retrospective study assesses visual and automatic heterogeneity from 18F-FDG PET images as predictors of response in locally advanced rectal cancer.MethodsThis study included 37 LARC patients who underwent an 18F-FDG PET before their neoadjuvant therapy. One expert segmented the tumor from the PET images. Blinded to the patient´s outcome, two experts established by consensus a visual score for tumor heterogeneity. Metabolic and texture parameters were extracted from the tumor area. Multivariate binary logistic regression with cross-validation was used to estimate the clinical relevance of these features. Area under the ROC Curve (AUC) of each model was evaluated. Histopathological tumor regression grade was the ground-truth.ResultsStandard metabolic parameters could discriminate 50.1% of responders (AUC = 0.685). Visual heterogeneity classification showed correct assessment of the response in 75.4% of the sample (AUC = 0.759). Automatic quantitative evaluation of heterogeneity achieved a similar predictive capacity (73.1%, AUC = 0.815).ConclusionA response prediction model in LARC based on tumor heterogeneity (assessed either visually or with automatic texture measurement) shows that texture features may complement the information provided by the metabolic parameters and increase prediction accuracy.

Tumor regression grading after neoadjuvant treatment of esophageal and gastroesophageal junction adenocarcinoma: results of an international Delphi consensus survey

Complete histopathologic tumor regression after neoadjuvant treatment is a well-known prognostic factor for survival among patients with adenocarcinomas of the esophagus and gastroesophageal junction. The aim of this international Delphi survey was to reach a consensus regarding the most useful tumor regression grading (TRG) system that could represent an international standard for histopathologic TRG grading of gastroesophageal carcinomas. Fifteen pathologists with special interest in esophageal and gastric pathology participated in the online survey. The initial questionnaire contained of 43 statements that addressed the following topics: (1) specimen processing, (2) gross examination, (3) cross sectioning, (4) staining, (5) Barrett's esophagus, (6) TRG systems, and (7) TRG in lymph node (LN). Participants rated the items using a 5-point Likert style scale and were encouraged to write comments for each statement. The expert panel recommended a 4-tiered TRG system for assessing the primary tumor: grade 1: No residual tumor (complete histopathologic tumor regression), grade 2: less than 10% residual tumor (near-complete regression), grade 3: 10%-50% residual tumor (partial regression), grade 4: greater than 50% residual tumor (minimal/no regression), combined with a 3-tiered system for grading therapeutic response in metastatic LNs: grade a: no residual tumor (complete histopathologic TRG), grade b: partial regression (tumor cells and regression), grade c: no regression (no sign of tumor response). This TRG grading system can be recommended as an international standard for histopathologic TRGgrading in esophageal and gastroesophageal junction adenocarcinoma.

MRI T2-weighted sequences-based texture analysis (TA) as a predictor of response to neoadjuvant chemo-radiotherapy (nCRT) in patients with locally advanced rectal cancer (LARC).

To determine whether MRI T2-weighted sequences-based texture analysis (TA) can predict histopathological tumor regression grade (TRG) in patients with locally advanced rectal cancer (LARC) undergoing neoadjuvant chemo-radiotherapy (nCRT). Data on patients undergoing curative-intent surgery for LARC were collected. Patients with a complete pathological response, or TRG1 according to Mandard's system were classified as responders, while patients with TRG ≥ 2 were classified as non-responders. Tumor TA was performed on each patient's paraxial T2w MRI in both pre- and post-nCRT scans, in order to extract histograms, gray-level co-occurrence matrix (GLCM) and run-length matrix (RLM) texture parameters. For features that showed a significant difference between the two groups, a receiver operating characteristic (ROC) curve was drawn. Overall, 62 patients with LARC, treated with nCRT and resective surgery at our institution between 2013 and 2019 were identified. Only post-nCRT GLCM maximum probability showed a significant difference between the two groups (2909 ± 4479 in responders vs. 6515 ± 8990 in non- responders; p = 0.039); at the ROC curve, Youden index showed a sensitivity of 14% and a specificity of 100% for this parameter. MRI T2-weighted sequences-based TA was not effective in predicting pathological complete response to nCRT in patients with LARC. Further studies are needed to thoroughly investigate the potential of MRI TA in this setting.

Using positron-emission tomography-computed tomography for predicting radiotherapy-induced tumor regression in carcinoma esophagus in an Indian population.

Carcinoma esophagus is a common malignancy of the Indian subcontinent. The role of positron-emission tomography–computed tomography (PET-CT) in the assessment of response to radiotherapy has been widely studied and accepted. However, its precise use as a predictive tool for actual histopathological response to radiotherapy needs further evaluation, especially in an Indian population. The aim of this study was to identify a quantum of metabolic response on PET-CT that can also predict for a good pathological response. Forty-four patients of carcinoma esophagus treated with neoadjuvant chemoradiotherapy followed by surgery were included in the study. All patients underwent a PET-CT before starting treatment as well as at 4–6 weeks after completion of radiotherapy. The percentage change in pre and posttreatment maximum standardized uptake value (SUVmax) value (ΔSUV%) of the primary tumor was correlated against histopathological tumor regression grade (TRG) as per the Mandard's system. Seventy-five percent of the patients with a significant metabolic response, i.e., a ΔSUV% of 60% or more, also had a good pathological response to treatment. Thus, by considering a ΔSUV% of 60%, we could predict for a good pathological response (TRG of 1 or 2) to chemoradiotherapy in our patient set with a sensitivity of 95.45% and a specificity of 72.72%.

Pathological Tumor Regression Grade Classifications in Gastrointestinal Cancers: Role on Patients' Prognosis.

Preoperative chemotherapy or combined radiotherapy and chemotherapy (CRT), followed by surgery, represents the standard approach for locally advanced esophageal, gastric, and rectal carcinomas. To adequately evaluate the effects of neoadjuvant CRT in the resection specimens, several histopathologic tumor regression grade (TRG) scoring systems have been introduced into clinical practice. The primary goal of these TRG systems relies on a correct prognostic stratification of patients in the attempt to help clinical decision-making and influence surgical strategies, postoperative adjuvant therapies, and surveillance intensity. However, most TRG systems suffer from poor reproducibility and low interobserver concordance rates. Many efforts have been made in the identification of alternative, robust, simple, and universally accepted TRG scoring systems, which would help in the comparison of different treatment strategies and in the standardization of multimodal therapies. The aim of this review is to analyze the most commonly used TRG systems in gastrointestinal cancers highlighting their pitfalls and usefulness, depending on the tumor type.

Value of High-Resolution DWI in Combination With Texture Analysis for the Evaluation of Tumor Response After Preoperative Chemoradiotherapy for Locally Advanced Rectal Cancer.

OBJECTIVE. The purpose of this study is to determine the performance of the apparent diffusion coefficient (ADC) value calculated from high-resolution DWI using readout-segmented echo-planar imaging (rs-EPI) and to assess the texture parameters of T2-weighted MR images in identifying pathologic complete response (pCR) after patients with locally advanced rectal cancer (LARC) undergo preoperative chemoradiotherapy (CRT). MATERIALS AND METHODS. A total of 76 patients with LARC who underwent preoperative CRT and subsequent surgery were enrolled in the study retrospectively. All patients underwent post-CRT MRI, which included acquisition of a DWI sequence with use of the rs-EPI technique. The histopathologic tumor regression grade was the reference standard. Patients were subdivided into pCR and non-pCR groups. Two radiologists independently drew whole-tumor ROIs on DW images and T2-weighted MR images to calculate the mean ADC value and first-order texture parameters. RESULTS. Interobserver agreement was good to excellent (intraclass correlation coefficient [ICC], 0.79-0.993) for imaging analysis. Calculated from high-resolution DWI, the mean post-CRT ADC value was significantly higher in the pCR group (p < 0.001). The pCR group also showed lower uniformity (p < 0.001) of the T2-weighted image. The mean ADC value and uniformity were significantly correlated with the tumor regression grade. The mean ADC value was a good indicator for differentiating pCR from absence of pCR (ROC AUC value, 0.912). Uniformity (ROC AUC value, 0.776) showed a moderate ability to identify pCR. Combining the mean ADC value and uniformity yielded an ROC AUC value comparable to that of the mean ADC value (p = 0.125). CONCLUSION. Mean post-CRT ADC values calculated from high-resolution DWI using rs-EPI could effectively select for patients with LARC who have a pCR after preoperative CRT. First-order texture parameters of T2-weighted MR images could also identify patients with pCR by reflecting tumor heterogeneity, even though they could not significantly improve the diagnostic performance.

479 - Independent multicenter validation of the prognostic significance of histopathologic tumor regression grade after neoadjuvant chemotherapy in bladder cancer

479 - Independent multicenter validation of the prognostic significance of histopathologic tumor regression grade after neoadjuvant chemotherapy in bladder cancer

Histopathologic tumor regression grading in patients with gastric carcinoma submitted to neoadjuvant treatment: results of a Delphi survey

Studies investigating the histopathologic response of gastric carcinoma to neoadjuvant treatment have used a variety of different tumor regression grading systems. The aim of this Delphi survey was to review the available systems and reach consensus on a potential international standard. An international e-mail-based Delphi survey involving 6 expert pathologists was undertaken between January and October 2017. A questionnaire consisting of 72 items was formed after reviewing the 5 available systems. Rating of the items was done on a symmetric 4-point Likert-type scale, and feedback was provided between rounds. A total of 4 rounds were required to reach consensus on 97% of the items covering the topics: (1) specimen processing, (2) gross examination, (3) cross sectioning/method of sampling, (4) staining, (5) immunohistochemistry, (6) assessment of tumor regression in response to neoadjuvant therapy, (7) tumor regression grading, (8) assessment of regression of nodal metastases, and (9) role of histologic tumor type. Through the outcome of this comprehensive Delphi study, a group of experts is proposing a 4-tiered system for the grading of regression of the primary tumor, combined with a 3-tiered system for lymph node metastases. Grade 1 represents complete response, grade 2 contains less than 10% residual tumor (subtotal regression), grade 3 contains 10% to 50% residual tumor (partial regression), and grade 4 contains greater than 50% residual tumor (minimal/no regression). The addition of "a", "b", or "c" indicates complete, partial, or no response of lymph node metastases. It is recommended to use this grading system irrespective of histologic subtype.

Locally advanced gastric cancer: total iodine uptake to predict the response of primary lesion to neoadjuvant chemotherapy

PurposePathologic response to neoadjuvant chemotherapy is a prognostic factor in many cancer types. However, the existing evaluative criteria are deficient. We sought to prospectively evaluate the total iodine uptake derived from dual-energy computed tomography (DECT) in predicting treatment efficacy and progression-free survival (PFS) time in gastric cancer after neoadjuvant chemotherapy.MethodsFrom October 2012 to December 2015, 44 patients with locally advanced gastric cancer were examined with DECT 1 week before and three cycles after neoadjuvant chemotherapy. The percentage changes in tumor area (%ΔS), diameter (%ΔD), and density (%ΔHU) were calculated to evaluate the WHO, RESCIST, and Choi criteria. The percentage changes in tumor volume (%ΔV) and total iodine uptake of portal phase (%ΔTIU-p) were also calculated to determine cut-off values by ROC curves. The correlation between the different criteria and histopathologic tumor regression grade (Becker score) or PFS were statistically analyzed.ResultsForty-four patients were divided into responders and non-responders according to 43.34% volume reduction (P = 0.002) and 63.87% (P = 0.002) TIU-p reduction, respectively. The %ΔTIU-p showed strong (r = 0.602, P = 0.000) and %ΔV showed moderate (r = 0.416, P = 0.005), while the WHO (r = 0.075, P = 0.627), RECIST (r = 0.270, P = 0.077) and Choi criteria (r = 0.238, P = 0.120) showed no correlation with the Becker score. The differences in PFS time between the responder and non-responder groups were significant according to %ΔTIU-p and Choi criteria (P = 0.001 and P = 0.013, respectively).ConclusionsThe TIU-p can help predict pathological regression in advanced gastric cancer patients after neoadjuvant chemotherapy. In addition, the %ΔTIU-p could be one of the potentially valuable predictive parameters of the PFS time.

DW-MRI and DCE-MRI are of complementary value in predicting pathologic response to neoadjuvant chemoradiotherapy for esophageal cancer

Purpose To explore the potential benefit and complementary value of a multiparametric approach using diffusion-weighted (DW-) and dynamic contrast-enhanced (DCE-) magnetic resonance imaging (MRI) for prediction of response to neoadjuvant chemoradiotherapy (nCRT) in esophageal cancer. Material and methods Forty-five patients underwent both DW-MRI and DCE-MRI prior to nCRT (pre), during nCRT (week 2–3) (per) and after completion of nCRT, but prior to esophagectomy (post). Subsequently, histopathologic tumor regression grade (TRG) was assessed. Tumor apparent diffusion coefficient (ADC) and area-under-the-concentration time curve (AUC) were calculated for DW-MRI and DCE-MRI, respectively. The ability of these parameters to predict pathologic complete response (pCR, TRG1) or good response (GR, TRG ≤ 2) to nCRT was assessed. Furthermore the complementary value of DW-MRI and DCE-MRI was investigated. Results GR was found in 22 (49%) patients, of which 10 (22%) patients showed pCR. For DW-MRI, the 75th percentile (P75) ΔADCpost-pre was most predictive for GR (c-index = 0.75). For DCE-MRI, P90 ΔAUCper-pre was most predictive for pCR (c-index = 0.79). Multivariable logistic regression analyses showed complementary value when combining DW-MRI and DCE-MRI for pCR prediction (c-index = 0.89). Conclusions Both DW-MRI and DCE-MRI are promising in predicting response to nCRT in esophageal cancer. Combining both modalities provides complementary information, resulting in a higher predictive value.

MR Imaging with Apparent Diffusion Coefficient Histogram Analysis: Evaluation of Locally Advanced Rectal Cancer after Chemotherapy and Radiation Therapy.

Purpose To determine response to neoadjuvant chemotherapy and radiation therapy in patients with locally advanced rectal cancer (LARC) by using magnetic resonance (MR) apparent diffusion coefficient (ADC) histogram analysis. Materials and Methods Ninety-two patients with LARC underwent MR imaging with rectal barium before and after chemotherapy and radiation therapy (CRT). Rectal expansion with barium expanded the lumen, provided similar imaging geometry before and after CRT, and eliminated fecal matter, air, and residual fluid. T2-weighted images, the percentage change in ADC, and ADC histogram skewness and kurtosis were assessed. The histopathologic tumor regression grade (TRG) ranged from 1a (66%-99% residual tumor cells) to 3 (no residual cells). The Wilcoxon signed-rank test, the Spearman correlation test, multivariable linear regression, and one-way analysis of variance were used to determine post- and pretreatment differences and correlations between tumor size and ADC. Results Of the 92 patients, 16 (17.4%) had TRG 3, 27 (29.3%) had TRG 2b, 24 (26.1%) had TRG 2a, 14 (15.2%) had TRG 1b, and 11 (12%) had TRG 1a. Post-CRT skewness (regression coefficient = 10.9, P = .06) and percentage ADC change (regression coefficient = -0.18, P = .03) were associated with the percentage of residual tumor. Post-CRT skewness and percentage ADC change, respectively, showed negative and positive correlation with histopathologic TRG (post-CRT skewness: P = .024; percentage ADC change: P = .001). Conclusion In patients with LARC, post-CRT skewness of the ADC histogram and percentage change in ADC were useful for predicting a favorable response to neoadjuvant CRT. © RSNA, 2018 Online supplemental material is available for this article.

Performance of diffusion-weighted magnetic resonance imaging at 3.0T for early assessment of tumor response in locally advanced rectal cancer treated with preoperative chemoradiation therapy.

The purpose of the article is to determine whether changes in apparent diffusion coefficient (ADC) values of locally advanced rectal cancer (LARC) obtained 2weeks after the beginning of chemoradiation therapy (CRT) allow to predict treatment response and whether correlate with tumor histopathologic response. Forty-three patients receiving CRT for LARC and 3.0T magnetic resonance imaging with diffusion-weighted sequences before treatment, 2weeks during, and 8weeks post the completion of CRT were included. ADC values were calculated at each time point and percentage of ADC changes at 2weeks (ΔADC during) and 8weeks (ΔADC post) were assessed. Data were correlated to surgical results and histopathologic tumor regression grade (TRG), according to Mandard's classification. ADC values and ΔADCs of complete responders (CR; TRG1) and non-complete responders (non-CR; TRG 2-5) were compared. Receiver-operating characteristic curve (ROC) analysis was used to assess diagnostic accuracy of ΔADC for differentiating CR from non-CR. The correlation with TRG was investigated using Spearman's rank test. ΔADC during and ΔADC post were significantly higher in CR (33.9% and 57%, respectively) compared to non-CR (13.5% and 2.2%, respectively) group (p=0.006 and p<0.001, respectively). ROC analysis revealed the following diagnostic performances: ΔADC during: AUC 0.78 (0.08), p=0.004, cut-off 20.6% (sensitivity 75% and specificity 76.5%); ΔADC post: AUC 0.94 (0.04), p≤0.001, cut-off 22% (sensitivity 95% and specificity 82.4%). Significant moderate and good negative correlation was found between ΔADC during and ΔADC post and TRG (r=-0.418, p=0.007; r=-694, p≤0.001, respectively). ΔADC at 2weeks after the beginning of CRT is a reliable tool to early assess treatment response.

Gastric Cancer Maximum Tumour Diameter Reduction Rate at CT Examination as a Radiological Index for Predicting Histopathological Regression after Neoadjuvant Treatment: A Multicentre GIRCG Study.

Aim To investigate the role of maximum tumour diameter (D-max) reduction rate at CT examination in predicting histopathological tumour regression grade (TRG according to the Becker grade), after neoadjuvant chemotherapy (NAC), in patients with resectable advanced gastric cancer (AGC). Materials and Methods Eighty-six patients (53 M, mean age 62.1 years) with resectable AGC (≥T3 or N+), treated with NAC and radical surgery, were enrolled from 5 centres of the Italian Research Group for Gastric Cancer (GIRCG). Staging and restaging CT and histological results were retrospectively reviewed. CT examinations were contrast enhanced, and the stomach was previously distended. The D-max was measured using 2D software and compared with Becker TRG. Statistical data were obtained using “R” software. Results The interobserver agreement was good/very good. Becker TRG was predicted by CT with a sensitivity and specificity, respectively, of 97.3% and 90.9% for Becker 1 (D-max reduction rate > 65.1%), 76.4% and 80% for Becker 3 (D-max reduction rate < 29.9%), and 70.8% and 83.9% for Becker 2. Correlation between radiological and histological D-max measurements was strongly confirmed by the correlation index (c.i.= 0.829). Conclusions D-max reduction rate in AGC patients may be helpful as a simple and reproducible radiological index in predicting TRG after NAC.