scholarly journals P-OGC29 Pathological response profiles of FLOT and ECX neoadjuvant chemotherapy in oesophageal adenocarcinoma

2021 ◽  
Vol 108 (Supplement_9) ◽  
Author(s):  
William Knight ◽  
Arion Pepas ◽  
Melody Lee ◽  
Larysa Hlukha ◽  
Andrew Jackson ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Primary Tumour ◽  
Neoadjuvant Treatment ◽  
Tumour Response ◽  
Oesophageal Adenocarcinoma ◽  
Tumour Regression ◽  
Tumour Regression Grade ◽  
Node Negative ◽  
Treatment Regimens ◽  
Nodal Upstaging

Abstract Background 70% of patients undergoing neo-adjuvant ECX chemotherapy for adenocarcinoma of the oesophagus, show little to know response in their primary tumour (Mandard 4,5). However, among these patients, those who have a complete nodal response (cN+ to ypN0) have equivalent survival to those with Mandard 1,2,3 tumours. FLOT chemotherapy has shown a survival advantage to ECX, however, rates of primary tumour response and nodal response are yet to be the focus of published study. Methods Retrospective cohort study comparing patients undergoing ECX and FLOT neoadjuvant chemotherapy between 2014 and 2021. Pathological outcomes were examined including, Mandard tumour regression grade (1-5), complete nodal response (cN+ to ypN0), clinically node negative nodal progression (cN0 to ypN+).   Results 226 patients had data available for analysis (193 ECX and 33 FLOT). 27% (52/193) of patients receiving ECX showed a response in the primary tumour (Mandard 1,2,3) compared to 63% (21/33) with patients undergoing FLOT (p < 0.001). Complete nodal response rates were 25% in ECX patients and 21% FLOT patients (p = 0.556). Clinically node negative nodal upstaging (cN0 to pN+) was higher among FLOT patients 30% (13/33) than ECX patients 12% (24/193) (p < 0.001). Conclusions FLOT chemotherapy confers improved primary tumour response. However, these findings were not echoed in locoregional nodal responses. Survival advantages with FLOT may result from improved responses in primary tumour and not improved systemic coverage. More data will be needed to explore this and over-come the confounding effect of staging inaccuracies. However, understanding systemic and loco-regional responses of different chemotherapy regimens will be needed to tailor future neoadjuvant treatment regimens.

646 PREDICTING RESPONSE TO NEOADJUVANT CHEMOTHERAPY IN PATIENTS WITH OESOPHAGEAL ADENOCARCINOMA

2021 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Rebecca Bott ◽  
Gincy George ◽  
Ricardo McEwen ◽  
Janine Zylstra ◽  
William Knight ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Surgical Resection ◽  
Tumour Response ◽  
Oesophageal Adenocarcinoma ◽  
Tumour Regression ◽  
Multivariable Logistic Regression Analysis ◽  
Chemotherapy Response ◽  
Roc Curve Analysis ◽  
Tumour Regression Grade ◽  
Dysphagia Score

Abstract   Neoadjuvant chemotherapy is often used prior to surgical resection for oesophageal adenocarcinoma but remains ineffective in a high proportion of patients. The histological Mandard tumour regression grade is used to determine chemoresponse but is not available at the time of treatment decision-making. The aim of this study was to identify factors that predict chemotherapy response prior to surgery. Methods A prospectively collected database of patients undergoing surgical resection for oesophageal adenocarcinoma from a high-volume UK institution was used. Patients were subcategorised using pathological tumour response into ‘responders’ (Mandard grade 1–3) and ‘non-responders’ (Mandard grade 4&5). Multivariable logistic regression analysis was performed to calculate crude and adjusted odds ratios (OR) with 95% confidence intervals (CI) for responder status adjusting for a variety of parameters. Receiver-operator curves (ROC) were calculated. Results Among 315 patients included, 102 (32%) were responders and 213 (68%) non-responders. A decrease in radiological tumour volume (OR 1.92 95%CI 1.02–3.62; p = 0.05), a ‘partial response’ RECIST score (OR 7.16 95%CI 1.49–34.36; p = 0.01), a clinically improved dysphagia score (OR 2.79 95%CI 1.05–7.04; p = 0.04) and lymphovascular invasion (OR 0.06 95%CI 0.02–0.13; p = 0.000) influenced responder status. ROC curve analysis for responder status utilising all available parameters had an area under the curve (AUC) of 0.86. Conclusion This study has highlighted the potential for using pre-defined factors to identify those patients who have responded to neoadjuvant chemotherapy, prior to surgical resection, potentially facilitating a more individualised therapeutic approach.

scholarly journals O-OGC06 Genomic analysis of response to neoadjuvant chemotherapy in oesophageal adenocarcinoma

2021 ◽  
Vol 108 (Supplement_9) ◽  
Author(s):  
Stella Breininger ◽  
Fereshteh Izadi ◽  
Benjamin Sharpe ◽  
Maria Secrier ◽  
Jane Gibson ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Locally Advanced ◽  
Genomic Analysis ◽  
Standard Of Care ◽  
Response Prediction ◽  
Oesophageal Adenocarcinoma ◽  
Comparative Genomic ◽  
Tumour Regression ◽  
Tumour Regression Grade ◽  
Almost All

Abstract Background Oesophageal adenocarcinoma (OAC) is the ninth most common cancer worldwide, with an estimated mortality of over 500,000 deaths yearly. Neoadjuvant chemotherapy (NAC) followed by surgery is the standard of care (SOC) for locally advanced OAC. Although almost all patients receive chemotherapy as SOC, fewer than 20% obtain a clinically meaningful response and benefit before surgery. The OAC genome is complex and heterogeneous between patients, and it is not yet understood whether specific mutational patterns may result in chemotherapy sensitivity or resistance. Methods To identify associations between genomic events and response to NAC in OAC, a comparative genomic analysis was performed in 65 patients using whole-genome sequencing.  We defined response to NAC using Mandard Tumour Regression Grade (TRG), with responders classified as TRG1-2 (n = 27) and non-responders classified as TRG4-5 (n = 38). Results We report a higher non-synonymous mutation burden in responders (median 2.08/Mb vs 1.70/Mb, P = 0.036) and elevated copy number variation (CNV) in non-responders (282 vs 136/patient, P<0.001). We identified CNVs unique to each group, with cell cycle (CDKN2A, CCND1), c-Myc (MYC), RTK/PIK3 (KRAS, EGFR) and gastrointestinal differentiation (GATA6) pathway genes being specifically altered in non-responders. Of particular interest was the identification of the Neuron Navigator-3 (NAV3), a known tumour suppressor downstream of EGFR, which was mutated exclusively in non-responders with a frequency of 22%. Conclusions Our work characterises genetic features and mutations that are uniquely associated with response to NAC. We envision a treatment pipeline that incorporates driver mutation profiling in OAC, combining response prediction with targeted therapies to enhance response to NAC and improve survival outcomes.

Propensity score regression analysis of esophageal cancer treatment with surgery alone or neoadjuvant chemotherapy.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 405-405
Author(s):  
Wyn Griffith Lewis ◽  
Arfon GMT Powell ◽  
Adam Christian
Keyword(s):  
Regression Analysis ◽  
Neoadjuvant Chemotherapy ◽  
Propensity Score ◽  
Positive Margin ◽  
Primary Outcome Measure ◽  
Oesophageal Adenocarcinoma ◽  
Tumour Regression ◽  
Poor Responders ◽  
Tumour Regression Grade ◽  
Cancer Network

405 Background: The aim of this study was to examine the outcomes of oesophageal adenocarcinoma (OC) treatment with either surgery alone (S), or with neoadjuvant chemotherapy (NAC) followed by surgery (NACS), by means of propensity score (PS) regression analysis, in order to examine whether the benefits reported in the MRC OE02 trial were reproducible in UK cancer network clinical practice. Methods: Consecutive patients undergoing potentially curative treatment for OC in a regional cancer network were studied. Multiple regression models, including PS were developed to account for confounding factors and the primary outcome measure was disease-free (DFS) and overall survival (OS). Results: A cohort of 440 patients was included in a regression analysis controlling for confounders (176 S, 264 NACS). NACS was associated with positive margin status (NACS vs. S, 42.4% vs. 26.7%, p<0.05), poor 5-year DFS (32.1% vs. 56.9, p<0.001), and poor 5-year OS (27.5% vs. 47.3%, p<0.001). On regression adjustment based on propensity scores, NACS was not associated with DFS (p=0.220) or OS (p=0.431). Mandard tumour regression grade (TRG) was significantly associated with DFS (hazard ratio (HR) 0.21,95% CI 0.07-0.70) and OS (HR 0.27 (95% CI 0.13-0.59). Five-year DFS and OS related to TRG was 63.6 and 61.5% vs. 8.0 and 8.6% (p<0.001) for good and poor responders respectively. Conclusions: Prescribing NAC to all OC patients risks delay in effective treatment of patients who are relatively chemo-resistant, given the variabilityin pathological response. Identifying OC patients who derive the most NAC benefit should be the focus.

scholarly journals O4 Neural network image capture to predict response of oesophageal adenocarcinoma to neoadjuvant therapy

2021 ◽  
Vol 108 (Supplement_5) ◽  
Author(s):  
S Rahman ◽  
J Early ◽  
B Sharpe ◽  
M Lloyd ◽  
B Grace ◽  
...  
Keyword(s):  
Neural Network ◽  
High Resolution ◽  
Neoadjuvant Therapy ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Oesophageal Adenocarcinoma ◽  
Tumour Regression ◽  
Tumour Regression Grade ◽  
Pre Treatment ◽  
Diagnostic Biopsies

Abstract Introduction Locally advanced oesophageal adenocarcinoma is typically treated with neoadjuvant chemotherapy (NACT) or chemoradiotherapy (NACRT) followed by surgery. Significant benefit to neoadjuvant treatment however is confined to a minority of patients (&lt;25%) and there are no reliable means of establishing prior to treatment in whom this benefit will occur. In this study, we assessed the utility of features extracted from high-resolution digital microscopy of pre-treatment biopsies in predicting response to neoadjuvant therapy in a machine-learning based modelling framework. Method A total of 102 cases were included in the study. Pre-treatment clinical information, including TNM staging, was obtained, along with diagnostic biopsies. Diagnostic biopsies were converted into high-resolution whole slide-images and features extracted using a pre-trained convolutional neural network (Xception). Elastic net regression models were then trained and validated with bootstrapping with 1000 resampled datasets. The response was considered according to Mandard tumour regression grade (TRG). Result There were 45 (44.1%) responders (TRG1-2) and 57 (57%) non-responders (TRG3-5) in the dataset. 34 patients (33.3%) received NACT and 68 (66.7%) received NACRT. A model trained with RNA-seq data achieved fair performance only in predicting response (AUC 0.598 95% CI 0.593–0.603), which was far exceeded by use of segmented diagnostic biopsy images (AUC 0.872 95% CI 0.869–0.875), which also produced well calibrated predictions of risk. Conclusion Despite using a small dataset, impressive performance in classifying response to neoadjuvant treatment can be achieved, particularly using automated image classification. Further study to refine the methodology is required before expansion to clinical settings. Take-home Message Response to neoadjuvant treatment for oesophageal cancer can be predicted from diagnostic biopsies

Predicting axillary response to neoadjuvant chemotherapy: the role of diffusion weighted imaging

2021 ◽  
Author(s):  
Lucia Graña-López ◽  
Tania Pérez-Ramos ◽  
Fiz Andrés Maciñeira ◽  
Ángeles Villares ◽  
Manuel Vázquez-Caruncho
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Diffusion Weighted Imaging ◽  
Primary Tumour ◽  
Pathologic Complete Response ◽  
Tumour Response ◽  
Complete Response ◽  
Adc Value ◽  
Diffusion Weighted ◽  
Adc Values ◽  
Response To Neoadjuvant Chemotherapy

Objective: The aim of this study is to investigate whether the primary tumour response to neoadjuvant chemotherapy (NAC), based on the increase in the ADC-values (apparent diffusion coefficient) within the breast lesion, could help to predict axillary complete response. Methods: We retrospectively included 74 patients who were treated with NAC followed by surgery at Lucus Augusti Hospital between January 2015 and September 2020. Simple logistic regression was used to evaluate the factors associated with axillary pathological complete response, including the changes in breast tumour ADC-values due to the treatment. Results: Axillary complete response was correlated with negative oestrogen receptor status, Her2 positivity and response of primary tumour. It was achieved in 31% of the patients. In addition, the increase in the tumour ADC-values with NAC was higher for responders. Among the tumours that demonstrated an increase in ADC-value >0.92 ×10−3 mm2/s, 42.8% (15/35) showed axillary complete response. Eight (20.5%) breast cancers with an increase in ADC below the cut-off value were found to have no metastatic nodes after treatment (p = 0.038). Conclusion: Our results suggest that the performance of models predicting axillary response to NAC can be improved by adding the tumour response determined also using diffusion-weighted imaging. Advances in knowledge: For the fist time, we investigate the relation between tumour response to NAC, assessed using diffusion-weighted imaging, and axillary pathologic complete response.

scholarly journals Neoadjuvant Therapy in Pancreatic Cancer: An Emerging Strategy

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Alessandro Bittoni ◽  
Matteo Santoni ◽  
Andrea Lanese ◽  
Chiara Pellei ◽  
Kalliopi Andrikou ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Case Series ◽  
Tumour Response ◽  
Tumour Regression ◽  
Resectable Pancreatic Cancer ◽  
Borderline Resectable ◽  
Future Directions ◽  
Tumour Implantation

Pancreatic adenocarcinoma (PDAC) is the fourth leading cause of cancer deaths among men and women, being responsible for 6% of all cancer-related deaths. Surgical resection offers the only chance of cure, but only 15 to 20 percent of cases are potentially resectable at presentation. In recent years, increasing evidences support the use of neoadjuvant strategies in pancreatic cancer in patients with resectable pancreatic cancer as well as in patients with borderline resectable or locally advanced PDAC in order to allow early treatment of micrometastatic disease, tumour regression, and reduced risk of peritoneal tumour implantation during surgery. Furthermore, neoadjuvant treatment allows evaluation of tumour response and increases patient’s compliance. However, most evidences in this setting come from retrospective analysis or small case series and in many studies chemotherapy or chemoradiation therapies used were suboptimal. Currently, prospective randomized trials using the most active chemotherapy regimens available are trying to define the real benefit of neoadjuvant strategies compared to conventional adjuvant strategies. In this review, the authors examined available data on neoadjuvant treatment in patients with resectable pancreatic cancer as well as in patients with borderline resectable or locally advanced PDAC and the future directions in this peculiar setting.

scholarly journals The Prognostic Value of the Lymph Node in Oesophageal Adenocarcinoma; Incorporating Clinicopathological and Immunological Profiling

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4005
Author(s):  
Noel E. Donlon ◽  
Maria Davern ◽  
Andrew Sheppard ◽  
Robert Power ◽  
Fiona O’Connell ◽  
...  
Keyword(s):  
Lymph Node ◽  
Prognostic Value ◽  
Response Rates ◽  
Tumour Microenvironment ◽  
Oesophageal Adenocarcinoma ◽  
Standards Of Care ◽  
Immune Checkpoints ◽  
Tumour Regression ◽  
Tumour Regression Grade ◽  
Radio Therapy

Response rates to the current gold standards of care for treating oesophageal adenocarcinoma (OAC) remain modest with 15–25% of patients achieving meaningful pathological responses, highlighting the need for novel therapeutic strategies. This study consists of immune, angiogenic, and inflammatory profiling of the tumour microenvironment (TME) and lymph node microenvironment (LNME) in OAC. The prognostic value of nodal involvement and clinicopathological features was compared using a retrospective cohort of OAC patients (n = 702). The expression of inhibitory immune checkpoints by T cells infiltrating tumour-draining lymph nodes (TDLNs) and tumour tissue post-chemo(radio)therapy at surgical resection was assessed by flow cytometry. Nodal metastases is of equal prognostic importance to clinical tumour stage and tumour regression grade (TRG) in OAC. The TME exhibited a greater immuno-suppressive phenotype than the LNME. Our data suggests that blockade of these checkpoints may have a therapeutic rationale for boosting response rates in OAC.

Efficacy and safety of camrelizumab combined with FLOT versus FLOT alone as neoadjuvant therapy in patients with resectable locally advanced gastric and gastroesophageal junction adenocarcinoma who received D2 radical gastrectomy.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16020-e16020
Author(s):  
Ning Liu ◽  
Zimin Liu ◽  
Yanbing Zhou ◽  
Zhaojian Niu ◽  
Haitao Jiang ◽  
...  
Keyword(s):  
Neoadjuvant Therapy ◽  
Intraoperative Complications ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Tumour Regression ◽  
R0 Resection ◽  
Resection Rate ◽  
Tumour Regression Grade ◽  
Ecog Ps

e16020 Background: Docetaxel-based neoadjuvant chemotherapy has been suggested to be beneficial in patients with locally advanced gastric and gastro-oesophageal junction cancer (GC/GEJC). And immunotherapy also show promising treatment efficacy for advanced GC/GEJC. Here we compared the safety and efficacy of camrelizumab combined with chemotherapy versus chemotherapy alone as the neoadjuvant therapy for patients with resectable locally advanced GC/GEJC. Methods: Eligible patients diagnosed as resectable locally advanced GC/GEJC were randomized to receive neoadjuvant treatment, in arm A, the patients received FLOT alone (docetaxel 50 mg/m²; oxaliplatin 85 mg/m²; leucovorin 200 mg/m²; 5-FU 2600 mg/m², every 2 weeks), in arm B, the patients received FLOT combined with camrelizumab(camrelizumab 200mg intravenously every 3 weeks). Eligible patients underwent gastrectomy with D2 lymph node dissection. The primary end point of this trial was pCR rate and R0 resection rate, and the secondary end points were ORR,PFS, OS and safety profile. Results: From January 15 2020 to January 15 2021, 24 patients were recruited (11 patients in arm A and 13 patients in arm B). 19 patients had completed planned neoadjuvant treatment for 4 cycles (9 pts in the arm A, 10 ptsin the arm B). Two patients in the arm A were waiting for gastrectomy. This analysis was based on the 17 pts. In the arm A, the median age was 61 years (47-72 years) and a total of 5 males and 4 females, ECOG PS 0 (n = 1), ECOG PS 1 (n = 8). In the arm B, the median age was 63 years (57-71 years) and a total of 9 males and 1 females, all patients with ECOG PS 1. The R0 resection rate was high in arm B compared with arm A (10/10,100% vs. 5/7, 71.4%). No pCR were observed in the two arms. Tumour regression grade were as follows:TRG1 [arm A 0% (0/7), arm B 10% (1/10)], TRG2 [arm A 43% (3/7), arm B 60% (6/10)], TRG3 [arm A 29% (2/7), arm B 30% (3/10)].There was a significantly higher proportion of patients achieved a postoperative ypN0 in the arm B than arm A(60% vs 0%), which had preoperative clinical stage cT3-4N+M0. Postoperative pathologic staging was as follows: ypT1 [arm A 14% (1/7); armB 30% (3/10)]. ypT2 [armA 0% (0/7); armB 30% (3/10)]. ypT3 [arm A 29% (2/7); arm B 20% (2/10)]. ypT4 [armA 29% (2/7); armB 20% (2/10)]. Neither serious intraoperative complications nor immune-related adverse events were observed during perioperation. Treatment-related AEs neutropenia and leukopenia were manageable and there was no treatment-related death. Conclusions: Camrelizumab combined with FLOT showed promising efficacy as neoadjuvant treatment for patients with locally advanced gastric or GEJ adenocarcinoma, with low complications and acceptable toxicity. Clinical trial information: ChiCTR2000030610.

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