Preoperative Capecitabine, Oxaliplatin, and Irinotecan in Resectable Gastric or Gastroesophageal Junction Cancer: Pathological Response as Primary Endpoint and FDG-PET Predictions

Oncology ◽  
2017 ◽  
Vol 93 (5) ◽  
pp. 279-286 ◽  
Author(s):  
Rosa Berenato ◽  
Federica Morano ◽  
Filippo Pietrantonio ◽  
Christian Cotsoglou ◽  
Marta Caporale ◽  
...  
2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 184-184
Author(s):  
Prianka Singh ◽  
Joseph Gricar ◽  
deMauri S Mackie ◽  
Hong Xiao ◽  
Marc DeCongelio ◽  
...  

184 Background: Global neoadjuvant and adjuvant treatment patterns among patients with resected Esophageal Cancer (EC) and Gastroesophageal Junction cancer (GEJC) remain unclear. This study describes real-world treatment patterns and outcomes for patients receiving surgery for Stage II or III EC or GEJC. Methods: Physicians in North America (US, Canada), Asia (China, Japan, Taiwan), and Europe (UK, France, Germany, Italy, Spain) provided clinical and treatment data in this retrospective, non-interventional chart review conducted from April-June 2020. Included patients were adults (Japan ≥20 years; elsewhere, ≥18 years), who underwent resection of Stage II or III EC or GEJC between October 2017 and October 2018 and were followed until death, loss to follow up, or end of data collection. Results: Physicians (N = 609) provided data on 1693 patients of mean age of 62.4 years, who received surgery for Stage II or III esophageal squamous cell carcinoma (ESCC) (33.3%), esophageal adenocarcinoma (EAC) (31.5%), or GEJC (35.2%) and were followed a mean (median) of 17.7 (17) months (to death or end of study period). At diagnosis, 85.6% of patients had performance status of 0/1. The majority of patients received an R0 resection (overall, 70.6%; ESCC, 76.6%, EAC, 67.4%, GEJC, 68.0%; p < 0.05); of these, 32.0% had a complete pathological response and 64.1% had a partial pathological response. Neoadjuvant therapy use differed among the treatment groups (ESCC 56.5%; EAC, 65.9%; GEJC, 62.6%, p < 0.05), as did adjuvant therapy (ESCC: 39.8%; EAC, 40.3%; GEJC, 44.5%; p = 0.023). Recurrence rate following surgery did not differ between groups for any recurrence (overall, 21.0%; ESCC 18.5%, EAC 23.6%, GEJC 21.1%); for local or regional recurrence (overall, 11.6%; ESCC, 10.3%; EAC, 12.7%; GEJC, 11.7%); or for metastatic recurrence (overall, 9.5%; ESCC, 8.2%; EAC, 10.9%; GEJC, 9.4%). The median time to local or regional recurrence (for those who progressed during the reporting period) was 8 months from date of initial surgery (overall, 8 mo; ESCC, 8 mo; EAC, 7 mo; GEJC, 8.5 mo; p > 0.05). The frequency of 1L systemic therapy for advanced disease at the time of survey completion was 16.1% overall and differed among patients with ESCC (14.6%); EAC (17.8%); and GEJC (15.9%); p > 0.05. Conclusions: This large multi-country real world data study shows that over half of all patients received neoadjuvant therapy, and over a third received adjuvant treatment. The high unmet need in this population is evident from the post-resection recurrence rate of 21.1% at median 8 months and the high proportion of patients who went on to require advanced disease treatment.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4018-4018 ◽  
Author(s):  
Sylvie Lorenzen ◽  
Michael Quante ◽  
Isabel Rauscher ◽  
Julia Slotta-Huspenina ◽  
Karl Friedrich Becker ◽  
...  

4018 Background: We evaluated a PET-guided treatment stratification for improvement in obtaining negative surgical margins (R0) in resectable gastroesophageal junction (GEJ) adenocarcinoma. According to sequential 18F-FDG PET, only 40–50% of patients (pts) respond to neoadjuvant chemotherapy (CTX). Early PET non-responders (P-NR) after induction CTX might benefit from changing to chemoradiation (CRT). Methods: 75 pts with resectable GEJ adenocarcinomas were enrolled in this interventional, prospective, non-randomized multicenter trial. Pts underwent baseline 18F-FDG PET scan followed by 1 cycle of CTX (physicians’ choice, e.g. EOX, XP, mFOLFOX6). PET was repeated at day 14-21 and responders (P-R), defined as ≥ 35% decrease in SUVmax from baseline, continued with CTX. P-NR switched to CRT (41.4 Gy/23 fractions with weekly carboplatin/paclitaxel). Pts underwent surgery 4-6 weeks post-CTX/CRT. Primary objective was an improvement of R0 resection rates in P-NR above a proportion of 70% based on results from the MUNICON1/2 trials. Secondary endpoints include disease-free survival (DFS), overall survival (OS), measured from randomization to death from any cause, and translational endpoints. Results: Between 12/2014 and 07/ 2018 160 pts with resectable GEJ adenocarcinomas were prospectively screened with PET in three German university centers. Overall, 85 pts (53%) could not be included due to previously undetectable metastases (40/25%), no or too low FDG uptake of the primary tumor (21/13%), other reasons (24/15%). 75 eligible pts were enrolled in the study and 69 were evaluable. Based on PET criteria, 47 (68%) and 22 (32%) were P-R and P-NR, respectively. R0 resection rates were 94% (44/47) for P-R and 91% (20/22) for P-NR. Pathologic complete remission (pCR; < 10% vital tumor cells), was 33% (15/46) in P-R and 55% (12/22) in P-NR. With a median follow-up time of 19 months (mo), estimated 18 mo DFS was 71%/61% for P-R/P-NR, respectively. Observed median 18 mo OS was 95% for P-R and 75% for P-NR. Conclusions: Alternative CRT for GEJ adenocarcinoma improved R0- and pCR rates among pts who were P-NR after induction CTX. PET response was prognostic for a prolonged OS and DFS. Clinical trial information: 2014-000860-16.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1129-1129
Author(s):  
Yanina Dockx ◽  
Manon Thirza Huizing ◽  
Tim Van Den Wyngaert ◽  
Sevilay Altintas ◽  
Ivan Huyghe ◽  
...  

1129 Background: Use of FDG-PET in the early evaluation of NACT for NPBC is currently under investigation. The aim of this study is to assess FDG-PET in NPBC pts receiving NACT in order to identify a subset of pts that can be spared axillary lymph node dissection (ALND) in case of response. Methods: All pts (period 2009-2011) had [cT2 (≥3cm)-T4, pN1-3], and no prior BC treatment. All pts received 8 cycles (cy) of NACT +/- trastuzumab. FDG-PET was performed at baseline and after 2 cy. After NACT, mastectomy with SLN and ALND was peformed. As primary endpoint, the change in maximum standardized uptake value (SUVmax) in the primary tumor (PT) and ALNs was compared with pathological response (Jonckheere-Terpstra test). Logistic regression was used to determine the predictive value of a 50% reduction in SUVmax on pathological response and SLN status. Results: Forty-one pts were evaluable for the primary endpoint and 31 pts had successful SN procedures. The median age was 49.8 years (range 27-75). Overall, 9.8% (4/41; 95% CI 2.7 – 23.1) of pts had progressive disease (PD), 7.3% (3/41 ; 95% CI 1.5 – 19.9 ) stable disease (SD), 53.7% (22/41; 95% CI 37.4 – 69.3) partial response (PR), and 21.9% (9/41; 95% CI 10.6 – 37.6) a complete pathological response (pCR). A linear trend existed between pCR and higher decreases in SUVmax of the PT site (p=0.008), but not with lymph node SUVmax (p=0.294). The odds of achieving a pCR, increased significantly when SUVmax of the PT decreased with >50% (OR 10.7; 95% CI 1.2 - 98.0; p=0.03), but not lymph node SUVmax (OR 4.75; 95% CI 0.82 - 27.5; p=0.08). Achieving a true negative SLN status was more likely with >50% reductions in PT SUVmax (OR 41.2; 95% CI 4.0 - 421.9; p= 0.002). A reduction of >50% in nodal SUVmax was not predictive of negative SLN status (OR 3.33; 95% CI 0.66 - 16.8; p=0.1). Conclusions: Early changes in PT metabolism imaged with FDG-PET after only 2 cy of NACT is a promising biomarker in the management of the axilla in NPBC. Molecular imaging of PT biology and to a lesser extent of axillary lymph nodes using FDG-PET warrants further study.


Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 400 ◽  
Author(s):  
Seiichiro Mitani ◽  
Hisato Kawakami

Trastuzumab, a monoclonal antibody to human epidermal growth factor receptor 2 (HER2), has improved survival in patients with HER2-positive advanced gastric or gastroesophageal junction cancer (AGC). The inevitable development of resistance to trastuzumab remains a problem, however, with several treatment strategies that have proven effective in breast cancer having failed to show clinical benefit in AGC. In this review, we summarize the mechanisms underlying resistance to HER2-targeted therapy and outline past and current challenges in the treatment of HER2-positive AGC refractory to trastuzumab. We further describe novel agents such as HER2 antibody–drug conjugates that are under development and have shown promising antitumor activity in early studies.


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