Histopathologic Tumor Regression Research Articles

Whole transcriptome analysis to reveal epithelial-mesenchymal transition after neoadjuvant therapy with or without additional anti-EGFR treatment: Subgroup analysis of esophageal squamous cell carcinomas of the SAKK 75/08 and the EORTC AIO POWER study.

4071 Background: In localized disease of esophageal squamous cell cancer (ESCC), a trend in higher pathological response rates and longer time to treatment failure was seen by addition of anti-EGFR treatment to radio-chemotherapy (RCTX) compared to RCTX alone (SAKK 75/08 trial and others). On the contrary, the effect of anti-EGFR treatment to chemotherapy (CTX) remains unclear as no survival benefit was detected within advanced patients (EORTC-AIO-POWER study). Since perfect discrimination and selection of subgroups with highest benefit for anti-EGFR treatment (AB) is missing, we investigated the predictive values of whole transcriptomic gene expression analysis (WTGE) applied on biopsy tissue. Methods: 50 pretherapeutic formalin fixed paraffin embedded specimens of ESCC patients from SAKK 75/08 study were analyzed for the effect of RCTX with and without anti-EGFR AB. As well as 26 historic controls of primary resected tumor stage equally distributed ESCC were analyzed. For the advanced setting, we analyzed 28 additional pretherapeutic biopsies and compared groups from CTX to CTX plus AB. The HTG EdgeSeq method was used for NGS-based WTGE. Response to treatment was assessed by histopathological tumor regression in localized disease and clinical courses. Response to treatment in the advanced tumor setting was assessed to the clinical course of stable disease and partial response versus non-responders. Results: Firstly, NGS-based WTGE failed to show significant differences in expression patterns between responding and non-responding ESCC patients, irrespective of treatment protocols and EGFR AB in the localized as well in advanced disease setting. Secondly however, comparison between pre-treatment biopsies and posttreatment residual tumor tissues detected 781 genes that were upregulated and 623 that were downregulated with gene sets associated with muscle processes and epithelial-mesenchymal transition (EMT) in the localized disease. EMT genes were also enriched in residual tumors after neoadjuvant RCTX compared to primary resection in an independent control cohort. Additionally performed immunohistochemical studies showed lower numbers of ZEB-1 positive ESCC in an independent collection of tumors treated by neoadjuvant RCTX compared to primary resection. Conclusions: Our Whole transcriptomic gene expression analyses suggest that EMT is involved in responses to neoadjuvant protocols including EGFR targeting therapies. Targeting EMT may be a molecular pathway to increase complete responses after neoadjuvant RCTX in ESCC.

Benzimidazole-oxindole hybrids as multi-kinase inhibitors targeting melanoma

In the current study, a series of benzimidazole-oxindole conjugates 8a-t were designed and synthesized as type II multi-kinase inhibitors. They exhibited moderate to potent inhibitory activity against BRAFWT up to 99.61 % at 10 µM. Notably, compounds 8e, 8k, 8n and 8s demonstrated the most promising activity, with 99.44 to 99.61 % inhibition. Further evaluation revealed that 8e, 8k, 8n and 8s exhibit moderate to potent inhibitory effects on the kinases BRAFV600E, VEGFR-2, and FGFR-1. Additionally, compounds 8a-t were screened for their cytotoxicity by the NCI, and several compounds showed significant growth inhibition in diverse cancer cell lines. Compound 8e stood out with a GI50 range of 1.23 – 3.38 µM on melanoma cell lines. Encouraged by its efficacy, it was further investigated for its antitumor activity and mechanism of action, using sorafenib as a reference standard. The hybrid compound 8e exhibited potent cellular-level suppression of BRAFWT, VEGFR-2, and FGFR-1 in A375 cell line, surpassing the effects of sorafenib. In vivo studies demonstrate that 8e significantly inhibits the growth of B16F10 tumors in mice, leading to increased survival rates and histopathological tumor regression. Furthermore, 8e reduces angiogenesis markers, mRNA expression levels of VEGFR-2 and FGFR-1, and production of growth factors. It also downregulated Notch1 protein expression and decreased TGF-β1 production. Molecular docking simulations suggest that 8e binds as a promising type II kinase inhibitor in the target kinases interacting with the key regions in their kinase domain.

Exploring novel genetic and hematological predictors of response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer.

Introduction: The standard treatment for locally advanced rectal cancer (LARC) is neoadjuvant chemoradiotherapy (nCRT). To select patients who would benefit the most from nCRT, there is a need for predictive biomarkers. The aim of this study was to evaluate the role of clinical, pathological, radiological, inflammation-related genetic, and hematological parameters in the prediction of post-nCRT response. Materials and methods: In silico analysis of published transcriptomics datasets was conducted to identify candidate genes, whose expression will be measured using quantitative Real Time PCR (qRT-PCR) in pretreatment formaline-fixed paraffin-embedded (FFPE) samples. In this study, 75 patients with LARC were prospectively included between June 2020-January 2022. Patients were assessed for tumor response in week 8 post-nCRT with pelvic MRI scan and rigid proctoscopy. For patients with a clinical complete response (cCR) and initially distant located tumor no immediate surgery was suggested ("watch and wait" approach). The response after surgery was assessed using histopathological tumor regression grading (TRG) categories from postoperative specimens by Mandard. Responders (R) were defined as patients with cCR without operative treatment, and those with TRG 1 and TRG 2 postoperative categories. Non-responders (NR) were patients classified as TRG 3-5. Results: Responders group comprised 35 patients (46.6%) and NR group 53.4% of patients. Analysis of published transcriptomics data identified genes that could predict response to treatment and their significance was assessed in our cohort by qRT-PCR. When comparison was made in the subgroup of patients who were operated (TRG1 vs. TRG4), the expression of IDO1 was significantly deregulated (p < 0.05). Among hematological parameters between R and NR a significant difference in the response was detected for neutrophil-to-monocyte ratio (NMR), initial basophil, eosinophil and monocyte counts (p < 0.01). According to MRI findings, non-responders more often presented with extramural vascular invasion (p < 0.05). Conclusion: Based on logistic regression model, factors associated with favorable response to nCRT were tumor morphology and hematological parameters which can be easily and routinely derived from initial laboratory results (NMR, eosinophil, basophil and monocyte counts) in a minimally invasive manner. Using various metrics, an aggregated score of the initial eosinophil, basophil, and monocyte counts demonstrated the best predictive performance.

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.

Impact of Neoadjuvant Chemotherapy on SATB2 Expression in Colorectal Carcinomas: SATB2 Positivity is Preserved in Most Cases, but Down-Expressed in Effective Cases of Chemotherapy.

Special AT-rich sequence-binding protein 2 (SATB2) is a novel, diagnostically useful, and highly sensitive immunohistochemical marker for both primary and metastatic colorectal or appendiceal tumors. In the present study, we aimed to assess the impact of neoadjuvant chemotherapy on SATB2 expression in primary colorectal carcinomas and their corresponding liver metastases. Forty-four patients with colorectal carcinomas who received neoadjuvant chemotherapy were included. SATB2 expression in specimens of biopsy, resected primary colorectal carcinomas, and resected metastatic foci were examined by immunohistochemistry and compared to caudal-type homeobox transcription factor 2 (CDX2). Using a modified H-score, expressions were scored semiquantitatively for both staining intensity and tumor cell proportion with nuclear staining. SATB2 was positive in 43/44 cases (98%) in biopsy specimens, 42/44 cases (96%) in resected colorectal carcinomas with neoadjuvant chemotherapy, and 9/9 cases (100%) with liver metastases. However, these expressions were variably decreased, and the H-score was lower in resected colorectal carcinomas (158 ± 69) than in biopsy specimens (174 ± 60) (p < 0.01). The proportion of SATB2-positive area of colorectal carcinoma was 93% in metastatic foci, while the CDX2-positive area was 78%. When categorized by histopathological tumor regression, the most effective tumors of chemotherapy showed the lowest H-score in resected colorectal carcinomas among the three groups (p < 0.01). SATB2 is a useful marker for both primary colorectal carcinoma and corresponding liver metastases, even with neoadjuvant chemotherapy. However, caution should be exercised when performing needle biopsy for metastatic foci with neoadjuvant therapy because expressions could be decreased, especially in chemotherapy-effective cases, and show immunohistochemically negative results.

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.

P-OGC24 Comparison of the histopathological regression after neoadjuvant FLOT versus ECX in resectable gastroesophageal adenocarcinoma

Abstract Background Neoadjuvant chemotherapy is a key component in the treatment of resectable oesophagogastric cancer (OGC). Histopathological tumour regression is associated with a prognostic benefit in OGC. There is increased usage of the FLOT regimen as part of neoadjuvant chemotherapy (NAC) for these tumours. The initial phase 2 trial demonstrated complete pathological response (pCR) in 15% for FLOT versus 6% for ECX but there is no data outside a trial setting. The aim of this study was to evaluate the differences in pCR and the extent of downstaging between patients receiving FLOT versus ECX in the neoadjuvant setting. Methods Consecutive patients treated for OGC in a single, high-volume UK centre between 2018 and 2021 were identified from a contemporaneously maintained database. Patients underwent 3 cycles of ECX or 4 cycles of FLOT as part of NAC. Histopathological tumour regression was assessed by the Mandard classification. A comparison of T- and N stage migration between FLOT and ECX was performed. Major pCR was defined as TRG 1-2 based on the Mandard classification. Results The study included 162 patients. 6/84 (7.1%) patients receiving ECX and 5/78 (6.4%) patients receiving FLOT achieved a pCR (p = 0.853). 11/84 (13.1%) patients in the ECX group and 12/78 (15.4%) patients in the FLOT group achieved a major pCR (p = 0.677). With regards to stage migration by T-stage, 36 (42.9%) patients were downstaged and 6 patients (7.1%) were upstaged with ECX. Amongst FLOT patients, 42 (53.8%) were downstaged and 8 (10.3%) upstaged (p = 0.189). When comparing N-stage, 29 (34.5%) patients achieved downstaging and 28 (33.3%) were upstaged with ECX. 30 (38.5%) patients were downstaged and 20 (25.6%) were upstaged with FLOT (0.563). Conclusions There was no significant difference in pCR and stage migration rates between patients receiving neoadjuvant ECX and FLOT. pCR rates were lower than previously reported, and it is unclear if the difference in prognosis will translate comparable outcomes between patients receiving ECX versus FLOT.

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.

Association between gastrin-releasing peptide receptor expression as assessed with [68Ga]Ga-RM2 PET/CT and histopathological tumor regression after neoadjuvant chemotherapy in primary breast cancer

IntroductionThe gastrin-releasing peptide receptor is overexpressed in breast cancer (BC) tissue and can be visualized by positron emission tomography (PET) using the GRPR antagonist [68Ga]Ga-RM2. This study assessed tumor binding of RM2 before and after neoadjuvant chemotherapy (NAC) in primary BC with reference to residual tumor size in the resected specimen. Materials and methodsIn this retrospective study, five female patients with biopsy-confirmed estrogen receptor (ER)-positive primary BC (one with bilateral tumors) underwent [68Ga]Ga-RM2 PET/CT before and after NAC. PET/CT was acquired 1 h after injection of 143–224 MBq [68Ga]Ga-RM2. Time from pre-NAC PET to beginning of NAC was 23 ± 4.9 days, from end of NAC to post-NAC PET 18.7 ± 6.3 days, and from post-NAC PET to surgery 9.5 ± 10.8 days. In vivo tumor uptake of [68Ga]Ga-RM2 was assessed before and after NAC and correlated with histopathological response. ResultsAll tumors (6/6) showed strongly increased [68Ga]Ga-RM2 uptake compared to normal breast tissue on pre-NAC PET (mean SUVmax 13.2 ± 7.3; mean SUVpeak 9.4 ± 4.4). [68Ga]Ga-RM2 uptake was significantly reduced on post-NAC PET in all primary tumors (mean SUVmax 2.3 ± 0.8, −79 ± 11%; p = 0.0125; mean SUVpeak 1.6 ± 0.4, −79 ± 10%; p = 0.0096). Residual tumor size in resected specimens correlated well with SUVmax (r = 0.91, p = 0.0057) and SUVpeak (r = 0.88, p = 0.0196) on [68Ga]Ga-RM2 PET/CT after NAC. Conclusion and implications for patient careIn this pilot study, residual uptake of [68Ga]Ga-RM2 in ER-positive primary BC correlated well with residual vital tumor size after NAC. This suggests that [68Ga]Ga-RM2 PET/CT merits further investigation for response assessment to NAC in patients with ER-positive BC.

P213 PROGNOSTIC SIGNIFICANCE OF CHANGES IN LYMPH NODE MORPHOLOGY ON SURVIVAL IN ESOPHAGEAL CANCER AFTER NEOADJUVANT THERAPY: A SYSTEMATIC REVIEW AND META-ANALYSES

Abstract Aim To assess the prognostic significance of lymph node regression or downstaging following neoadjuvant therapy for esophageal cancer. Background and methods The prognostic value of histomorphologic regression in the primary esophageal cancer has been established, whilst the impact of lymph node response on survival still remains unclear. An electronic search was performed to identify articles evaluating lymph node regression or downstaging after neoadjuvant chemo- or chemoradiotherapy. Random effects meta-analyses were performed for regression and downstaging and primary outcome was the hazard ratio (HR) for overall mortality. Survival data were compared between patients with complete regression and those with partial or no response. Histopathological tumor regression in lymph nodes was defined by the absence of viable cells or degree of fibrosis. Furthermore, survival of patients with downstaged lymph nodes to N0 were compared to those with positive nodes following treatment. Results Eight articles were included, 4 of which assessed tumor regression (number of patients=789) and 4 assessing downstaging (number of patients=1937). Complete tumor regression (average rate of 30.0%) in the lymph nodes was associated with higher survival [HR= 0.63, 95% CI (confidence interval) = 0.43 – 0.92; p=0.017] (figure 1). Lymph nodes downstaging (average rate of 47.6%) had improved survival compared to node positivity (HR = 0.38, 95% CI = 0.29 – 0.50; p&lt;0.0001) (figure 2). Conclusion A prognostic benefit was seen in patients with good lymph node response to neoadjuvant therapy, suggesting this should be used as an important additional prognostic marker in staging and in comparative evaluation of different neoadjuvant regimes.

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.

Assessment of prognostic significance of unique tumor regression scoring system in advanced epithelial ovarian cancer patients treated with neoadjuvant chemotherapy followed by interval debulking surgery -Single tertiary care center experience

Aim and Objective: To assess the prognostic significance of pathological factors and the use of unique tumour regression scoring system over survival in advanced epithelial ovarian cancer patients treated with neoadjuvant chemotherapy (NAC) and Interval debulking surgery. Materials and Methods: We retrospectively investigated 135 patients from January 2011 to December 2017 received minimum of 3 cycles of NAC followed by interval debulking surgery (IDS) and their resected specimens were divided into 3 groups based on pathological tumour regression: Group 1: minimal response (residual disease with necrosis and fibrosis 50%) and Group 3: complete response (No residual disease). The clinico-pathological parameters and their prognostic influence over survival outcomes were assessed using Statistical Package for the Social Sciences (SPSS 21.0) software and a p value of Results: Histopathological tumour regression groups 1, 2 and 3 were significantly associated with histological grade, presence of residual disease in ovary with involvement of lymph node, omentum. DFS and overall survival were 42.0±8.0 and 47.1 ± 5.4 months respectively. The overall median survival in FIGO stage III patients was better than FIGO IV stage. Conclusion: This proposed 3 simple criterions of histopathological tumour regression has prognostic significance in association with clinical stage and amount of residual disease in resected specimen. This simplified unique tumour regression system may serve in the future as highly valuable prognostic tool, which needs further validation. Keywords: Advanced ovarian malignancy, Neoadjuvant chemotherapy, Interval debulking surgery, Tumour regression system.

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.