scholarly journals A retrospective comparison of outcome and toxicity of preoperative image-guided intensity-modulated radiotherapy versus conventional pelvic radiotherapy for locally advanced rectal carcinoma

2016 ◽  
Vol 58 (2) ◽  
pp. 247-259 ◽  
Author(s):  
Chun-Ming Huang ◽  
Ming-Yii Huang ◽  
Hsiang-Lin Tsai ◽  
Ching-Wen Huang ◽  
Cheng-Jen Ma ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Tumor Regression ◽  
Locally Advanced ◽  
Survival Rates ◽  
Pathologic Complete Response ◽  
Intensity Modulated Radiotherapy ◽  
Treatment Modalities ◽  
Tumor Regression Grade ◽  
Image Guided ◽  
Intensity Modulated

Abstract The aim of the study was to compare clinical outcomes and toxicity between 3D conformal radiotherapy (3DCRT) and image-guided intensity-modulated radiotherapy (IG-IMRT) administered through helical tomotherapy in locally advanced rectal cancer (LARC) patients receiving preoperative chemoradiotherapy. We reviewed 144 patients with Stage II–III rectal cancer receiving preoperative fluoropyrimidine-based chemoradiotherapy followed by radical resection. Tumor responses following chemoradiotherapy were evaluated using the Dworak tumor regression grade (TRG). Of the 144 patients, 45 received IG-IMRT and 99 received 3DCRT. A significant reduction in Grade 3 or 4 acute gastrointestinal toxicity (IG-IMRT, 6.7%; 3DCRT, 15.1%; P = 0.039) was observed by IG-IMRT. The pathologic complete response (pCR) rate did not differ between the IG-IMRT and the 3DCRT group (17.8% vs 15.1%, P = 0.52). Patients in the IG-IMRT group had the trend of favorable tumor regressions (TRG 3 or 4) compared with those in the 3DCRT group (66.7% vs 43.5%, P = 0.071). The median follow-up was 53 months (range, 18–95 months) in the 3DCRT group and 43 months (range, 17–69 months) in the IG-IMRT group. Four-year overall, disease-free, and local failure–free survival rates of the IG-IMRT and 3DCRT groups were 81.6% and 67.9% (P = 0.12), 53.8% and 51.8% (P = 0.51), and 88% and 75.1% (P = 0.031), respectively. LARC patients treated with preoperative IG-IMRT achieved lower acute gastrointestinal adverse effects and a higher local control rate than those treated with 3DCRT, but there was no prominent difference in distant metastasis rate and overall survival between two treatment modalities.

scholarly journals Evaluating treatment response to neoadjuvant chemoradiotherapy in rectal cancer using various MRI-based radiomics models

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zhihui Li ◽  
Xiaolu Ma ◽  
Fu Shen ◽  
Haidi Lu ◽  
Yuwei Xia ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Treatment Response ◽  
Nearest Neighbor ◽  
Tumor Regression ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Neoadjuvant Chemoradiotherapy ◽  
Principal Component ◽  
Tumor Regression Grade ◽  
K Nearest Neighbor

Abstract Background To validate and compare various MRI-based radiomics models to evaluate treatment response to neoadjuvant chemoradiotherapy (nCRT) of rectal cancer. Methods A total of 80 patients with locally advanced rectal cancer (LARC) who underwent surgical resection after nCRT were enrolled retrospectively. Rectal MR images were scanned pre- and post-nCRT. The radiomics features were extracted from T2-weighted images, then reduced separately by least absolute shrinkage and selection operator (LASSO) and principal component analysis (PCA). Four classifiers of Logistic Regression, Random Forest (RF), Decision Tree and K-nearest neighbor (KNN) models were constructed to assess the tumor regression grade (TRG) and pathologic complete response (pCR), respectively. The diagnostic performances of models were determined with leave-one-out cross-validation by generating receiver operating characteristic curves and decision curve analysis. Results Three features related to the TRG and 11 features related to the pCR were obtained by LASSO. Top five principal components representing a cumulative contribution of 80% to overall features were selected by PCA. For TRG, the area under the curve (AUC) of RF model was 0.943 for LASSO and 0.930 for PCA, higher than other models (P < 0.05 for both). As for pCR, the AUCs of KNN for LASSO and PCA were 0.945 and 0.712, higher than other models (P < 0.05 for both). The DCA showed that LASSO algorithm was clinically superior to PCA. Conclusion MRI-based radiomics models demonstrated good performance for evaluating the treatment response of LARC after nCRT and LASSO algorithm yielded more clinical benefit.

scholarly journals Radiotherapy Scheme Effect on PD-L1 Expression for Locally Advanced Rectal Cancer

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 2071
Author(s):  
Jihane Boustani ◽  
Valentin Derangère ◽  
Aurélie Bertaut ◽  
Olivier Adotevi ◽  
Véronique Morgand ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Tumor Regression ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Tumor Regression Grade ◽  
The Impact

In locally advanced rectal cancer, radiotherapy (RT) followed by surgery have improved locoregional control, but distant recurrences remain frequent. Although checkpoint inhibitors have demonstrated objective response in several cancers, the clinical benefit of PD-1/PD-L1 blockade remains uncertain in rectal cancer. We collected data from biopsies and surgical specimens in 74 patients. The main objective was to evaluate the impact of neoadjuvant RT and fractionation on PD-L1 expression. Secondary objectives were to study the relation between PD-L1 expression and tumor regression grade (TRG), progression-free survival (PFS), overall survival (OS), and CD8 TILs infiltration. Median rates of cells expressing PD-L1 pre- and post-RT were 0.15 (range, 0–17) and 0.5 (range, 0–27.5), respectively (p = 0.0005). There was no effect of RT fractionation on PD-L1+ cell rates. We found no relation between CD8+ TILs infiltration and PD-L1 expression and no difference between high-PD-L1 or low-PD-L1 expression and TRG. High-to-high PD-L1 expression profile had none significant higher OS and PFS compared to all other groups (p = 0.06). Median OS and PFS were higher in biopsies with >0.08 PD-L1+ cells. High-to-high PD-L1 profile and ypT0-2 were significantly associated with higher OS and PFS. This study did not show the differential induction of PD-L1 expression according to fractionation.

scholarly journals 474 GENOMIC ANALYSIS OF RESPONSE TO NEOADJUVANT CHEMOTHERAPY IN ESOPHAGEAL ADENOCARCINOMA

2020 ◽  
Vol 33 (Supplement_1) ◽  
Author(s):  
F Izadi ◽  
G Devonshire ◽  
R Walker ◽  
M Lloyd ◽  
J Gibson ◽  
...  
Keyword(s):  
Dna Damage ◽  
Neoadjuvant Chemotherapy ◽  
Esophageal Adenocarcinoma ◽  
Tumor Regression ◽  
Locally Advanced ◽  
Chemotherapy Resistance ◽  
Treatment Modalities ◽  
Tumor Regression Grade ◽  
Driver Genes ◽  
The Impact

Abstract   In the UK, neoadjuvant chemotherapy (NAC) for locally advanced esophageal adenocarcinoma (EAC) is the standard of care. Unfortunately, response to NAC, following surgery is often low (&lt;30%) and survival benefit at 2 years is only 5.1%. The EAC genome is complex and heterogeneous between patients, where specific mutagenic processes and mutations may result in chemotherapy resistance. Here we report preliminary results from whole-genome sequencing (WGS) of 48 patients who were subsequently treated with NAC. Methods We defined response as Mandard Tumor Regression Grade (TRG) 1-2 (n = 15) and non-response as TRG4-5 (n = 33). WGS of 50x coverage and calling of genomic events (Strelka2, SCAT/GISTIC) was performed according to Frankell Nat Genet 2019 with modifications, to differentiate driver from passenger mutations (dNdScv, oncodriveCLUST), determine variant allele frequencies (VAF; copy number-adjusted) and mutation signatures (NMF R-package). Following stringent variant QC (Phred score ≥ 30), filtering (VAF &gt;0.02) and annotation (ANNOVAR, cancer census/helper, the 77 known EAC drivers and false positive genes) and visualisation in maftools, we evaluated the data for associations between genomic events and response to NAC. Results COSMIC mutation signatures 2 (TRG1-2; Cosθ = 0.89) and 6 (TRG4-5; Cosθ = 0.82) were enriched, suggesting defective mismatch repair in non-responders. Using 5,193 high-confidence non-silent mutations (TRG1-2,n = 1969; TRG4-5, n = 3224), we identified 39 mutated driver genes (Figure-1) with a median of 2.9(0-5) (TRG1-2) and 2.7(0-9) (TRG4-5) driver events/patient. Shared dysregulated pathways, included DNA-damage (TP53), cell cycle (CDKN2A), TGF-β (SMAD4) and chromatin regulation (ARID1A). There was no difference in the prognostic of SMAD4 and GATA4 genes. Interestingly, NAV3 mutations were only present in non-responders (21%,7/33); and in responders TP53 incidence was higher (93% vs. 58%) with a concomitant reduction in clonal cell fraction (0.25 vs. 0.39;Wilcoxon, p &lt; 0.0001). Conclusion The data suggest that specific genomic events, such as NAV3 mutation and the intra-tumoral heterogeneity of mutated DNA-damage response genes may offer additional predictive value. Ongoing work includes analysis of the impact of non-coding variation on response. While our analysis is limited by sample size and requires validation in additional cohorts, it demonstrates the potential of genomic sequencing to identify NAC response biomarkers and may guide alternative or novel treatment modalities for chemo-resistant tumours.

scholarly journals Immunohistochemical Markers as Predictors of Histopathologic Response and Prognosis in Rectal Cancer Treated with Preoperative Adjuvant Therapy: State of the Art

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Alessandro Del Gobbo ◽  
Stefano Ferrero
Keyword(s):  
Rectal Cancer ◽  
State Of The Art ◽  
Tumor Regression ◽  
Dihydropyrimidine Dehydrogenase ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Response To Therapy ◽  
Tumor Regression Grade ◽  
Immunohistochemical Markers ◽  
Rectal Cancers

We explain the state of the art of the immunohistochemical markers of response in rectal cancers treated with neoadjuvant medical therapies and its implication with prognosis. Neoadjuvant chemoradiotherapy is widely used to improve the outcome of patients with locally advanced rectal cancer, and the evaluation of the effects of medical therapy is to date based on histomorphological examination by applying four grading systems of response to therapy (tumor regression grade (TRG)). The need to identify immunohistochemical markers that could ensure a better assessment of response and possibly provide additional prognostic information has emerged. We identified p53, p27kip1, Ki67, matrix metalloprotease-9, survivin, Ki67 proliferative index, CD133, COX2, CD44v6, thymidylate synthase, thymidine phosphorylase, and dihydropyrimidine dehydrogenase as the most common markers studied in literature to date, and we explained their prognostic potential and their implications in the evaluation of the response to preoperative therapies in rectal cancers.

Is there any significant difference between tumor regression grade systems of rectal cancer?

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3583-3583
Author(s):  
Atthaphorn Trakarnsanga ◽  
Mithat Gonen ◽  
Jinru Shia ◽  
Garrett Michael Nash ◽  
Larissa K. F. Temple ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Tumor Regression ◽  
Combined Modality Therapy ◽  
Clinical Stage ◽  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
Cancer Center ◽  
Tumor Regression Grade ◽  
Significant Difference ◽  
Regression Grade

3583 Background: Tumor regression grade (TRG) is a measure of histopathologic response of rectal cancer to preoperative chemoradiation (CRT) and correlates with outcomes. Several TRG systems have been reported including Mandard (5, 3 tier), Dowrak/Rodel (5, 3 tier), Memorial Sloan Kettering Cancer Center (MSKCC), and American Joint Committee of Cancer (AJCC). The purpose of this study is to compare the different TRG systems and determine which one(s) best predict recurrence and survival. Methods: Review of prospective maintained database from 1998 to 2007 identified 563 patients with locally advanced rectal cancer (T3/4 and/or N1) and treated with long-course CRT followed by total mesorectal excision. TRG was determined by measuring proportion of tumor mass replaced by fibrosis. Patients were then classified into the various TRG schemes which were compared by analyzing association with recurrence and survival using concordance index (CI) and reclassification index. CI is a measure that summarizes the predictive strength of a marker. Computing and contrasting CI across several markers is a way of selecting the best prognostic marker. Results: 75% of patients were noted to have clinical stage III disease by endorectal ultrasound or rectal MRI. Following resection with median follow-up of 39.3 months, 2% developed local recurrence and 17% developed distant metastasis. The median interval time between completion of CRT and surgery is 48 days. 20% demonstarted complete pathological response. CI of the 3 tier Mandard, 3 tier Dowrak/Rodel, MSKCC and AJCC are 0.665, 0.653, 0.683, and 0.694, respectively (higher number indicates better prediction). The AJCC was significantly more accurate in predicting recurrence than the 3- tier Mandard (p=0.002), and Dowrak/Rodel (p=0.006). AJCC had a higher CI than MSKCC although it did not reach significance (p=0.068). Comparing the 3 tier systems, MSKCC was most accurate and correctly reclassified 17 % and 23 % of the patients Mandard and Dowrak/Rodel systems, respectively. Conclusions: TRG predicts recurrence and survival following combined modality therapy for rectal cancer. The TRG system that recently was proposed in the 7thAJCC staging is currently the most accurate predictor.

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