Preliminary analysis of total neoadjuvant therapy for patients with locally advanced gastric (G) and gastroesophageal (GE) adenocarcinoma.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 393-393
Author(s):  
Eric Roeland ◽  
Katie Kanter ◽  
Jennifer Yon-Li Wo ◽  
Madeleine Fish ◽  
Ryan David Nipp ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Neoadjuvant Therapy ◽  
Progressive Disease ◽  
Small Sample Size ◽  
Locally Advanced ◽  
Concurrent Chemotherapy ◽  
Small Sample ◽  
Completion Rates ◽  
Chi Squared ◽  
Total Neoadjuvant Therapy

393 Background: Nearly half of patients with G/GE cancer do not receive or complete post-operative chemotherapy and/or chemoradiation (CRT). Total neoadjuvant therapy (TNT) is as an emerging alternate treatment strategy. We have previously reported a 28% pCR with FOLFIRINOX followed by CRT. However, TNT outcomes with FLOT or FOLFOX followed by CRT are lacking. Methods: We retrospectively analyzed patients after resection of locally advanced G/GE after receiving TNT. Patient received neoadjuvant FOLFOX or FLOT x 8 cycles, CRT (G 45 Gy, GE 50.4 Gy) with concurrent chemotherapy (5FU, carboplatin/paclitaxel). The primary aim was to explore TNT completion rates. Secondary aims included pCR and toxicity. We performed descriptive statistics, t-test, chi-squared, and Fisher’s exact tests as appropriate. Results: From 12/2015 to 8/2019, 57.1% (40/70) completed TNT and resection (15.7% active treatment, 15.7% progressive disease, 11% treated elsewhere). Median age was 66.0 (range:27-79) and 73% male. Tumor locations included 57.5% G, 30.0% GE, and 12.5% overlapping. Neoadjuvant chemotherapy included FLOT 22.5% (n = 9) or FOLFOX 77.5% (n = 31). Overall we found a 25% pCR without significant differences between type of neoadjuvant chemotherapy. Conclusions: TNT followed by resection is feasible with acceptable rates of treatment completion and toxicity. Notable limitations include the retrospective analysis, small sample size, and heterogenous treatment. The pCR rate is promising and warrants further prospective study to optimize TNT approaches. [Table: see text]

scholarly journals O29: PREDICTING RESPONSE TO NEOADJUVANT THERAPY IN OESOPHAGEAL ADENOCARCINOMA PRE-TREATMENT BIOPSIES

2021 ◽  
Vol 108 (Supplement_1) ◽  
Author(s):  
M Lloyd ◽  
F Izadi ◽  
S Rahman ◽  
R Walker ◽  
A Hayden ◽  
...  
Keyword(s):  
Pilot Study ◽  
Neoadjuvant Therapy ◽  
Small Sample Size ◽  
Expression Profiles ◽  
Locally Advanced ◽  
Small Sample ◽  
Oesophageal Adenocarcinoma ◽  
Tumour Regression ◽  
Precision Therapy ◽  
Pre Treatment

Abstract Aims We currently cannot predict which patients with locally advanced oesophageal adenocarcinoma will be amongst the 15-20% to gain a clinically important response to neoadjuvant therapy (NAT). This pilot study aimed to identify differentially expressed genes from oesophageal adenocarcinoma pre-treatment biopsies between responders and non-responders to NAT and develop methodology for predicting response. Method Response to NAT was assessed pathologically using Tumour Regression Grading (TRG). Pre-treatment formalin-fixed paraffin embedded samples were analysed with two nuclease protection assays (EdgeSeq, HTG = Oncology Biomarker Panel (OBP) and Precision Immuno-Oncology Panel (PIP)). Sequencing was performed on the NextSeq500 (Illumina). Result Whilst there was no difference in pre-treatment characteristics, responders (TRG1-2, n=26) had significantly better post-treatment pathology and overall survival than non-responders (TRG4-5, n=30). Genes up-regulated in responders were involved in regulating cell cycling, whereas genes up-regulated in non-responders were involved in cytokine signalling and the immune response. Neuronal artificial network models could predict response to NAT with overall accuracy of 73% and 68% for the OBP and PIP, respectively, which is promising considering the small sample size. As no model will be 100% accurate, we developed a model that could take patient's views into consideration with an adjustable probability threshold for classification. Conclusion This pilot study informs a biologically sound hypothesis for the basis of response to NAT and suggests prediction from pre-treatment biopsies may be possible using EdgeSeq. We now aim to validate these results in a larger study to inform a bespoke classifier of response to enable delivery of precision therapy. Take-home message In oesophageal adenocarcinoma, responders and non-responders to neoadjuvant therapy have different expression profiles. Through using EdgeSeq in larger studies, we may be able to predict which patients will respond to treatment, allowing for delivery of precision therapy.

Combination of AST to ALT and neutrophils to lymphocytes ratios as predictors of locally advanced disease in patients with bladder cancer subjected to radical cystectomy: Results from a single-institutional series

2021 ◽  
pp. 039156032110351
Author(s):  
Alessandro Uleri ◽  
Rodolfo Hurle ◽  
Roberto Contieri ◽  
Pietro Diana ◽  
Nicolòmaria Buffi ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Radical Cystectomy ◽  
Advanced Disease ◽  
Independent Predictor ◽  
Small Sample Size ◽  
Statistical Significance ◽  
Locally Advanced ◽  
Small Sample ◽  
Locally Advanced Disease ◽  
Increased Risk

Background: Bladder cancer (BC) staging is challenging. There is an important need for available and affordable predictors to assess, in combination with imaging, the presence of locally-advanced disease. Objective: To determine the role of the De Ritis ratio (DRR) and neutrophils to lymphocytes ratio (NLR) in the prediction of locally-advanced disease defined as the presence of extravescical extension (pT ⩾ 3) and/or lymph node metastases (LNM) in patients with BC treated with radical cystectomy (RC). Methods: We retrospectively analyzed clinical and pathological data of 139 consecutive patients who underwent RC at our institution. Logistic regression models (LRMs) were fitted to test the above-mentioned outcomes. Results: A total of 139 consecutive patients underwent RC at our institution. Eighty-six (61.9%) patients had a locally-advanced disease. NLR (2.53 and 3.07; p = 0.005) and DRR (1 and 1.17; p = 0.01) were significantly higher in patients with locally-advanced disease as compared to organ-confined disease. In multivariable LRMs, an increasing DRR was an independent predictor of locally-advanced disease (OR = 3.91; 95% CI: 1.282–11.916; p = 0.017). Similarly, an increasing NLR was independently related to presence of locally-advanced disease (OR = 1.28; 95% CI: 1.027–1.591; p = 0.028). In univariate LRMs, patients with DRR > 1.21 had a higher risk of locally advanced disease (OR = 2.83; 95% CI: 1.312–6.128; p = 0.008). Similarly, in patients with NLR > 3.47 there was an increased risk of locally advanced disease (OR = 3.02; 95% CI: 1.374–6.651; p = 0.006). In multivariable LRMs, a DRR > 1.21 was an independent predictor of locally advanced disease (OR = 2.66; 95% CI: 1.12–6.35; p = 0.027). Similarly, an NLR > 3.47 was independently related to presence of locally advanced disease (OR = 2.24; 95% CI: 0.95–5.25; p = 0.065). No other covariates such as gender, BMI, neoadjuvant chemotherapy or diabetes reached statistical significance. The AUC of the multivariate LRM to assess the risk of locally advanced disease was 0.707 (95% CI: 0.623–0.795). Limitations include the retrospective nature of the study and the relatively small sample size.

scholarly journals Pre-operative/Neoadjuvant Therapy and Vascular Debranching Followed by Resection for Locally Advanced Pancreatic Cancer (PREVADER): Clinical Feasibility Trial

2021 ◽  
Vol 8 ◽  
Author(s):  
Ulrich Ronellenfitsch ◽  
Christoph W. Michalski ◽  
Patrick Michl ◽  
Sebastian Krug ◽  
Joerg Ukkat ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Sample Size ◽  
Neoadjuvant Therapy ◽  
Locally Advanced ◽  
Tumor Resection ◽  
Phase Iii ◽  
Feasibility Trial ◽  
Arterial Reconstruction ◽  
Visceral Arteries

Introduction: Pancreatic cancer continues to have a poor outcome. Many patients are diagnosed with advanced disease, and in a considerable proportion, abutment or invasion of visceral arteries is present. Moreover, some patients have anatomical variations or stenosis of major visceral arteries requiring arterial reconstruction upon pancreatic cancer resection to avoid organ ischemia. Simultaneous arterial reconstruction during resection is associated with relevant morbidity and mortality. This trial evaluates the approach of visceral debranching, that is, arterial reconstruction, prior to neoadjuvant chemotherapy and tumor resection in patients with locally advanced, unresectable pancreatic cancer.Methods and Analysis: The trial includes patients with locally advanced, non-metastatic pancreatic cancer with arterial abutment or invasion (deemed primarily unresectable), variations in vascular anatomy, or stenosis of visceral arteries. The participants undergo visceral debranching, followed by current standard neoadjuvant chemotherapy (mFOLFIRINOX, gemcitabine–nab-paclitaxel, or other) and potential subsequent tumor resection. The primary outcome is feasibility, measured as the proportion of patients who start neoadjuvant therapy within 6 weeks of visceral debranching. The trial has an exact single-stage design. The proportion below which the treatment is considered ineffective is set at 0.7 (H0). The proportion above which the treatment warrants further exploration in a phase III trial is set at 0.9 (H1). With a power (1-beta) of 0.8 and a type 1 mistake (alpha) of 0.05, the required sample size is 28 patients. Feasibility of the approach will be assumed if 24 of the enrolled 28 patients proceed to neoadjuvant chemotherapy within 6 weeks from visceral debranching.Discussion: This trial evaluates a new treatment sequence, that is, visceral debranching followed by chemotherapy and resection, for pancreatic cancer with invasion or abutment of visceral arteries. The primary objective of the trial is to evaluate feasibility. Trial results will allow for estimating treatment effects and calculating the sample size of a randomized controlled trial, in which the approach will be tested if the feasibility endpoint is met.Clinical Trial Registration:clinicaltrials.gov, identifier: NCT04136769.

Gemcitabine/docetaxel (GD) versus gemcitabine/cisplatin (GC) in stage III/IV non-small cell lung cancer (NSCLC): Preliminary results

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17116-17116 ◽  
Author(s):  
M. Gamaz ◽  
T. Makhloufi ◽  
S. Taright ◽  
R. Baba-Ahmed ◽  
R. Amrane ◽  
...  
Keyword(s):  
Squamous Cell ◽  
Small Sample Size ◽  
Locally Advanced ◽  
Small Sample ◽  
Stage Iiib ◽  
Metastatic Nsclc ◽  
Randomized Phase Ii ◽  
Significant Toxicity ◽  
Baseline Characteristics ◽  
The Difference

17116 Background: This study was designed to compare the response rates and toxicities of the standard GC regimen versus GD, a non-platin regimen, in locally advanced and metastatic NSCLC. Methods: In both arms, gemcitabine 1250 mg/m2 was administered on days 1 and 8. In the GD arm, docetaxel 75 mg/m2 was given on day 8. In the GC arm, cisplatin 70 mg/m2 was given on day 1. Both regimens were repeated every 3 weeks. Results: From September 2004 to September 2005, 47 patients were enrolled In the GD arm (N = 25), the median age was 54.6 years (range, 45–70), and 22 (88.0%) were male. The majority of patients had either squamous cell (52.0%) or adenocarcinoma (44.0%), and stage IIIB disease (64.0%). In the GC arm (N = 22), the median age was 60.9 years (range, 42–74), and 20 (90.9%) were male. Most patients also had either squamous cell (50.0%) or adenocarcinoma (31.8%), and stage IIIB disease (59.1%). The difference in age between arms was significant (p = 0.046), but the differences in the remaining baseline characteristics and demographics were not significant. Toxicity and response results are in the table below. Conclusions: Overall response rate was numerically higher in the GC arm than the GD arm, but the difference was not significant because of the small sample size in each arm. The toxicity profile was significantly better in the GC arm for fatigue and nausea/vomiting. We think that GC regimen will remain the standard in treatment for advanced and metastatic NSCLC; however, we will confirm these findings in a randomized phase II study. [Table: see text] No significant financial relationships to disclose.

A phase Ib dose escalation, safety, and tolerability study of sonidegib in combination with gemcitabine in patients with locally advanced or metastatic pancreatic adenocarcinoma.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 371-371 ◽  
Author(s):  
Teresa Macarulla ◽  
Josep Tabernero ◽  
Daniel H. Palmer ◽  
Sunil Sharma ◽  
Kenneth H. Yu ◽  
...  
Keyword(s):  
Pancreatic Adenocarcinoma ◽  
Dose Escalation ◽  
Standard Dose ◽  
Small Sample Size ◽  
Objective Response ◽  
Locally Advanced ◽  
Small Sample ◽  
Moderate Activity ◽  
Current Standard ◽  
Grade 3

371 Background: Sonidegib (LDE225) is a potent, selective, and orally bioavailable inhibitor of smoothened receptor that demonstrated preclinical activity in combination with gemcitabine (GEM). Here, we present data from a phase 1b trial of sonidegib in combination with GEM in patients (pts) with pancreatic adenocarcinoma (PA). Methods: Pts with histologically or cytologically confirmed, locally advanced, or metastatic PA who had not been treated previously or had progressed despite prior chemotherapy (other than GEM) were included in the study. Dose escalation started with sonidegib 400 mg, once a day, in combination with GEM 1000 mg/m2 IV infusion on days 1, 8, and 15 of a 28-day cycle. Results: A total of 18 pts were enrolled (9 pts each the in dose escalation and dose expansion phases). Pts discontinued the study because of disease progression (n = 11, 61.1%), consent withdrawal (n = 3, 16.7%), administrative problems (n = 3, 16.7%), and grade 3 or 4 blood creatine kinase (CK) elevation (n = 1, 5.6%). Three of 9 pts in dose escalation phase experienced dose-limiting toxicities during the first 8 weeks including grade 3 mucositis (n = 1), grade 3 CK elevation (n = 1), and grade 3 aspartate aminotransferase elevation (n = 1). Drug-related adverse events (AEs) of all grades were reported in 14 pts (77.8%) and grade 3 or 4 AEs were reported in 10 pts (55.6%). The most commonly reported AEs were anemia and nausea. No pharmacokinetic (PK) interaction was observed. Based on considerations of the statistical model, clinical assessment of safety, tolerability, PK, and pharmacodynamic results, maximum-tolerated dose and recommended dose were established as 400 mg of sonidegib in combination with the fixed standard dose of GEM (1000 mg/m2).The objective response rate was 11.1% and the median progression-free survival (PFS) was 4.9 months. Conclusions: The combination of sonidegib and GEM was generally well tolerated with moderate activity. Although no formal comparison can be made due to small sample size of this study, this combination provided a median PFS comparable to the current standard of care without conferring any additional clinical benefit. Clinical trial information: NCT01487785.

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