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 Propensity score regression analysis of oesophageal adenocarcinoma treatment with surgery alone or neoadjuvant chemotherapy

BJS Open ◽  
2020 ◽  
Vol 4 (4) ◽  
pp. 593-600
Author(s):  
A. G. M. T. Powell ◽  
A. Karran ◽  
P. Blake ◽  
A. Christian ◽  
S. A. Roberts ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Neoadjuvant Chemotherapy ◽  
Propensity Score ◽  
Oesophageal Adenocarcinoma

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&lt;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.

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 &lt; 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 &lt; 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.

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.

Tumour regression grade (TRG) analyses in patients with resectable gastro-oesophageal adenocarcinomas treated with platinum-based neoadjuvant chemotherapy

2009 ◽  
Vol 55 (4) ◽  
pp. 399-406 ◽  
Author(s):  
Khaleel R Fareed ◽  
Mohammad Ilyas ◽  
Philip V Kaye ◽  
Irshad N Soomro ◽  
Dileep N Lobo ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Tumour Regression ◽  
Tumour Regression Grade ◽  
Regression Grade

scholarly journals Postoperative survival following perioperative MAGIC versus neoadjuvant OE02-type chemotherapy in oesophageal adenocarcinoma

2017 ◽  
Vol 99 (5) ◽  
pp. 378-384 ◽  
Author(s):  
AM Reece-Smith ◽  
JH Saunders ◽  
IN Soomro ◽  
CR Bowman ◽  
JP Duffy ◽  
...  
Keyword(s):  
Oesophageal Cancer ◽  
Subgroup Analysis ◽  
Oesophageal Adenocarcinoma ◽  
Tumour Regression ◽  
Anatomical Site ◽  
Tumour Regression Grade ◽  
Kaplan Meier ◽  
Lower Stage ◽  
Time Period ◽  
Early Cohort

The optimal management of resectable oesophageal adenocarcinoma is controversial, with many centres using neoadjuvant chemotherapy following the Medical Research Council (MRC) oesophageal working group (OE02) trial and the MRC Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial. The more intensive MAGIC regimen is used primarily in gastric cancer but some also use it for oesophageal cancer. A database of cancer resections (2001–2013) provided information on survival of patients following either OE02 or MAGIC-type treatment. The data were compared using Kaplan–Meier analysis. Straight-to-surgery patients were also reviewed and divided into an ‘early’ cohort (2001–2006, OE02 era) and a ‘late’ cohort (2006–2013, MAGIC era) to estimate changes in survival over time. Subgroup analysis was performed for responders (tumour regression grade [TRG] 1–3) versus non-responders (TRG 4 and 5) and for anatomical site (gastro-oesophageal junction [GOJ] vs oesophagus). An OE02 regimen was used for 97 patients and 275 received a MAGIC regimen. Those in the MAGIC group were of a similar age to those undergoing OE02 chemotherapy but the proportion of oesophageal cancers was higher among MAGIC patients than among those receiving OE02 treatment. MAGIC patients had a significantly lower stage following chemotherapy than OE02 patients and a higher median overall survival although TRG was similar. On subgroup analysis, this survival benefit was maintained for GOJ and oesophageal cancer patients as well as non-responders. Analysis of responders showed no difference between regimens. ‘Late’ group straight-to-surgery patients were significantly older than those in the ‘early’ group. Survival, however, was not significantly different for these two cohorts. Although the original MAGIC trial comprised few oesophageal cancer cases, our patients had better survival with MAGIC than with OE02 chemotherapy in all anatomical subgroups, even though there was no significant change in operative survival over the time period in which these patients were treated. The use of the MAGIC regimen should therefore be encouraged in cases of operable oesophagogastric adenocarcinoma.

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

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