Surveillance and outcomes after curative resection for gastroesophageal adenocarcinoma (GEAC).

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 162-162
Author(s):  
Di Maria Jiang ◽  
Chihiro Suzuki ◽  
Osvaldo Espin-Garcia ◽  
Melania Pintilie ◽  
Charles Henry Lim ◽  
...  

162 Background: Although commonly performed, the benefit of routine surveillance testing (SvT) following curative resection of GEAC is undefined. We aimed to determine frequency of successful salvage therapy (SST) in patients (pts) with relapsed GEAC who were surveyed post curative therapy. Methods: Between 2011 and 2016, 210 consecutive pts with locally advanced GEAC underwent curative surgery and subsequent surveillance at Princess Margaret Cancer Center. SST was defined as any potentially curative therapy for recurrence which resulted in post-recurrence survival (PRS) two years without further relapse. Time-to-event outcomes were analyzed using Kaplan-Meier and Cox regression methods. Results: Median age was 64.1 years. Esophageal (14%), gastroesophageal junction (41%), and gastric adenocarcinomas (45%) were included. Pts received surgery alone (29%), surgery with perioperative chemotherapy (26%) or perioperative chemoradiation (45%) as primary curative therapy. At median follow-up of 33.6 months (m, range 6.0-122.4), 3- and 5-year overall survival (OS) rates were 68% (95% CI 61-75%) and 59% (95% CI 51-68%) respectively. SvT modalities included imaging (69%), endoscopy (19%), tumor markers (4%), and clinical visits only (9%). Recurrences occurred in 95 (45%) pts, 51% were surveillance-detected (SvDR), and 47% were non-SvDR. Types of recurrences included locoregional only (4%), distant (87%) or both (9%). Salvage therapy was attempted in 14 pts (7%) with SvDR and 1 with non-SvDR. In four pts with SvDR (1.9%) salvage therapy was successful with chemoradiation or surgery perioperative chemotherapy, six were unsuccessful, and 5 had immature follow-up. Compared with pts with non-SvDR, pts with SvDR had longer median OS (34.8 vs. 24.0m, p=0.03) and PRS (14.4 vs. 4.8m, p < 0.001), and similar time-to-relapse (15.6 vs. 12.0m, p = 0.67). Palliative chemotherapy was administered in 25 pts with SvDR and 18 pts with non-SvDR with similar median duration (3.5m vs. 3.3m, p=0.64). Conclusions: Following curative therapy, 96% of relapses were distant. SvT enabled SST in only 1.9% of pts, and did not extend duration of palliative chemotherapy. These data do not support the use of routine SvT in resected GEAC.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15579-e15579
Author(s):  
Di Maria Jiang ◽  
Chihiro Suzuki ◽  
Osvaldo Espin-Garcia ◽  
Charles Henry Lim ◽  
Lucy Xiaolu Ma ◽  
...  

e15579 Background: Although commonly performed, evidence supporting routine surveillance testing (SvT) in patients (pts) with resected GEAC is lacking. We evaluated patterns of relapse, frequency of salvage therapy and outcomes among pts with resected GEAC who underwent surveillance. Methods: Between 2011 and 2016, 210 consecutive pts with GEAC followed at Princess Margaret Cancer Center after resection were reviewed. SvT was any investigation performed in the absence of pt-reported symptoms, abnormal physical exam findings, or bloodwork. Relapse patterns were classified as locoregional (LRR; surgical anastomosis/gastroesophageal lumen/regional nodes) or distant (DR; beyond locoregional). Time-to-relapse (TTR) and overall survival (OS) were calculated from initial diagnosis, post recurrence survival (PRS) from initial relapse. Results: Median age was 64.1 years. Esophageal (14%), gastroesophageal junction (40%), and gastric adenocarcinomas (45%) were treated with surgery alone (29%), surgery plus perioperative chemotherapy (26%) or surgery plus chemoradiation (45%). SvT included imaging (71%), endoscopy (19%), tumor markers (6%), and clinical visits alone (9%). After median follow-up of 38.3 months (mo) (range 5.6-122.3), 3- and 5-year OS rates were 68% (95% confidence interval (CI) 62-75%) and 56% (95% CI 49-64%) respectively. Among 97 relapses (46%), 51 were detected by SvT, 45 by symptoms. Relapse patterns included LRR alone (4%), DR alone (86%) and both (10%). The majority of relapses (93%) occurred within 3 years. Pts with SvT-detected relapse had similar median TTR (16.2 vs 13.3 mo, p = 0.40) but longer PRS (16.5 vs 4.6 mo, p < 0.001) and OS (36.2 vs 23.7 mo, p = 0.004) than pts with symptomatic relapse. Salvage therapy in 4 pts (2%) resulted in post recurrence disease-free survival ≥2 years. Duration of palliative chemotherapy was similar between 28 pts with SvT-detected relapse and 18 pts with symptomatic relapses (3.9 vs 3.3 mo, p = 0.64). Conclusions: Following curative resection, 96% of relapses were distant. Routine SvT rarely enabled successful salvage therapy and did not extend duration of palliative chemotherapy. Longer OS in SvT-detected relapses was not due to earlier disease detection. These findings do not support routine SvT in pts with resected GEAC.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4046-4046
Author(s):  
Thierry Alcindor ◽  
Touhid Opu ◽  
Arielle Elkrief ◽  
Farzin Khosrow-Khavar ◽  
Carmen L. Mueller ◽  
...  

4046 Background: Perioperative chemotherapy improves cure rate in locally advanced gastroesophageal adenocarcinoma (GEA), and immune checkpoint inhibitors are active at the metastatic stage. This trial tests the hypothesis that the addition of avelumab to perioperative chemotherapy will increase the major pathologic response (MPR) rate in comparison with historical controls. Methods: Phase II study of avelumab + chemotherapy (docetaxel, cisplatin and 5-FU or mDCF) given every 2 weeks for 4 cycles before and after surgery. Main inclusion criteria: GEA, cT3 and/or cN+, M0, WHO PS 0-1. Main exclusion criteria: use of immunosuppressants, serious autoimmune disease, daily intake >10 mg prednisone. Staging studies: CT, PET-CT, endoscopic ultrasound, diagnostic laparoscopy. Surgical resection: D2 lymphadenectomy, en-bloc esophagectomy for type I/II gastroesophageal junction (GEJ) tumors. Aim of the study: MPR as defined as tumor regression grades 0-1 (modified Ryan scheme); as per hypothesis, this experimental regimen will result in a 20% rate of MPR, compared with 7% with chemotherapy alone. Simon 2-stage design: if less than 2 MPR are seen in the first 16 patients, the study will be closed. The study hypothesis cannot be rejected if at least 6 MPR are seen in the first 50 patients. All adverse effects are prospectively recorded per CTCAE guidelines in patients who have received at least one treatment cycle. Survival rates are calculated with Kaplan-Meier method. Preliminary results are presented since the study has met its primary endpoint. Results: Feb 2018-Feb 2020: 28 patients enrolled (25 M/3 F, age 45-78). Location: GEJ (23), stomach (5). Staging: cT3 (25), cT4 (1), cN+ (20). Biomarkers expression: mismatch repair (MMR) protein loss (3/28); PD-L1(clone 73-10) expression in 1% (TPS) or more of tumor cells seen in 12/28 samples, and >10% in 6 patients. Grade 3 toxicity: stomatitis (2/28); nausea (2/28); vomiting (1/28); diarrhea (1/28); hypothyroidism (1/28); arthralgia (3/28); neutropenia (1/28). Grade 4 toxicity: pneumonia (1/28); neutropenia (2/28). Postoperative 30-day mortality: 0%. One patient was excluded from efficacy analyses for M1 staging; 27 patients underwent surgery, 26 with R0 (96%). Six cases (22%) show MPR: 3 grade 0 (11%) and 3 grade 1 (11%) tumor regressions. No correlation was seen between MMR proteins or PD-L1 expression and tumor regression. With a median follow-up of 1.5 years (range 0.4-2.5), the disease-free survival rate is projected to be 0.92 (95% CI 0.83-1.00) at 12 months and 0.77 (95% CI 0.58-1.00) at 24 months. Conclusions: The combination of mDCF chemotherapy with Avelumab demonstrates a promising safety and activity profile. Ongoing laboratory investigations are underway to correlate our findings with tumor molecular features before exposure to treatment. Clinical trial information: NCT03288350.


2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 336-336
Author(s):  
Angela Lamarca ◽  
Mairead Geraldine McNamara ◽  
Richard Hubner ◽  
Juan W. Valle

336 Background: The potential role of ctDNA to identify residual disease after potentially curative resection has been suggested in some malignancies; its role in resected pancreatico(P)-biliary(B) malignancies is unknown. Methods: Patients diagnosed with PB malignancies underwent molecular profiling (ctDNA) using FoundationMedicine Liquid (72 cancer-related genes) following potentially curative resection. Baseline patient characteristics and molecular profiling outcomes, including mutant allele frequency (MAF) for pathological alterations were extracted. Primary objective: prevalence of ctDNA identification and its correlation with recurrence (relapse-free survival (RFS) and relapse rate). Results: Total of 11 individuals had ctDNA analysed following potentially curative resection for PB malignancies: 8 B (4 extra-hepatic cholangiocarcinoma (eCCA), 2 ampulla, 1 intrahepatic cholangiocarcinoma (iCCA), 1 gallbladder cancer (GBC)) and 3 P. Baseline characteristics: 6 female (54.55%), median age 71.59 years (range 39.98-81.19). Most were pT2 (45.45%), pN0 (54.55%) and R0 (63.64%). Following surgery, 6 patients were started on adjuvant chemotherapy; at the end of follow-up (data cut-off 25/6/2020; median follow-up 11.15 months (range 5.45-13.52); 5 relapsed (45.45%) and 2 died (18.18%). Estimated median RFS was 11.43 months (95% CI 2.28-not reached); median overall survival was not reached. No sample failed ctDNA analysis; presence of ctDNA was identified in 3/11 (27.27%) of the samples; 2 and 1 samples had 2 and 1 pathological alterations identified, respectively: ALK fusion (1 sample; GBC), TP53 mutation (2 samples; eCCA and GBC), CHEK2 mutation (1 sample; pancreas), IDH2 mutation (1 sample; eCCA). Mean maximum MAF was 1.47 (2 in biliary; 0.43 in pancreas). Variants of unknown significance were identified in 72.73% of the samples (87.5% in B; 33.33% in P; p-value 0.152). None of the baseline characteristics explored correlated with presence of ctDNA. There was a trend towards increased relapse risk in the patients with ctDNA present following potentially curative surgery; Cox regression for RFS [HR 2.64 (95% CI 0.36-19.31); median RFS 11.44 months (95% CI 2.28-not reached) vs 10.87 (95% CI 2.21-not reached)]; relapse rate 37.5% (ctDNA absent) vs 66.67% (ctDNA present); statistical significance was not reached (p-value 0.340 and p-value 0.545, respectively). Conclusions: This pilot study demonstrates the feasibility of testing for ctDNA following potentially curative resection in PB malignancies. Presence of ctDNA may be associated with increased relapse risk; further studies are required to increase sample size and assess clinical implications.


2019 ◽  
Vol 81 (03) ◽  
pp. 287-294 ◽  
Author(s):  
Adam R. Wolfe ◽  
Dukagjin Blakaj ◽  
Nyall London ◽  
Adriana Blakaj ◽  
Brett Klamer ◽  
...  

Purpose Olfactory neuroblastoma (ONB) is a rare head and neck cancer believed to be originated from neural crest cells of the olfactory membrane located in the roof of the nasal fossa. This study evaluates clinical outcomes and failure patterns in ONB patients of those patients treated with surgical resection at a high-volume tertiary cancer center. Methods and Materials Thirty-nine ONB patients who underwent surgical resection at our institution from 1996 to 2017 were retrospectively identified. Univariate, multivariate, and survival analysis were calculated using Cox regression analysis and Kaplan–Meier log-rank. Results Median follow-up time was 59 months (range: 5.2–236 months). The median overall survival (OS) and disease-free survival (DFS) for the entire cohort were 15 and 7.6 years, respectively. The 5-year cumulative OS and DFS were 83 and 72%, respectively. The 5-year OS for low Hyams grade (LHG) versus high Hyams grade (HHG) was 95 versus 61% (p = 0.041). LHG was found in 66% of the early Kadish stage patients compared with 28% in the advanced Kadish stage patients (p = 0.057). On multivariate analysis, HHG and positive node status predicted for worse OS and only HHG predicted for worse DFS. Of note, five patients (all Kadish stage A) who received surgical resection alone had no observed deaths or recurrences with a median follow-up of 44 months (range: 5–235 months). Conclusion In this retrospective cohort, patients with positive nodes or HHG have significantly worse clinical outcomes. Future studies should explore treatment intensification for HHG or positive nodes.


1990 ◽  
Vol 8 (7) ◽  
pp. 1231-1238 ◽  
Author(s):  
J A Ajani ◽  
J A Roth ◽  
B Ryan ◽  
M McMurtrey ◽  
T A Rich ◽  
...  

Thirty-five consecutive patients with resectable adenocarcinoma of the esophagus or gastroesophageal junction were treated with two preoperative and three or four postoperative chemotherapy courses consisting of etoposide, fluorouracil, and cisplatin (EFP) to evaluate the rate of curative resection, clinical and pathologic response, toxic effects, and survival. One hundred thirty-seven courses with a median number of five courses (range, one to six) were administered. Preoperative EFP resulted in 17 (49%) major responses, including six patients who did not have carcinoma cells in the repeat endoscopic biopsy specimens and cytologic brushings. Among 32 patients who had surgery, 25 (78%) had curative resection, one patient had a complete pathologic response, and one had microscopic carcinoma in the resected specimen. Six patients had microscopic carcinoma at the resection margins and received postoperative radiotherapy. At a median follow-up of 20 months, the projected survival of 35 patients is 23 months (range, 6 to 33+). Fifteen patients died of their carcinomas, and 15 patients were alive (median follow-up, 20+ months; range, 15+ to 33+ months) with no evidence of relapse. There were no deaths related to chemotherapy, surgery, or radiotherapy. EFP-induced toxic reactions were moderate. Our data suggest that multiple courses of EFP are feasible. Future strategies for this disease should consider prolonged chemotherapy with regimens that result frequently in pathologic complete responses.


BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Sylvie Lorenzen ◽  
Alexander Biederstädt ◽  
Ulrich Ronellenfitsch ◽  
Christoph Reißfelder ◽  
Stefan Mönig ◽  
...  

Abstract Background Despite obvious advances over the last decades, locally advanced adenocarcinomas of the gastroesophageal junction (GEJ) still carry a dismal prognosis with overall 5-year survival rates of less than 50% even when using modern optimized treatment protocols such as perioperative chemotherapy based on the FLOT regimen or radiochemotherapy. Therefore the question remains whether neoadjuvant chemotherapy or neoadjuvant radiochemotherapy is eliciting the best results in patients with GEJ cancer. Hence, an adequately powered multicentre trial comparing both therapeutic strategies is clearly warranted. Methods The RACE trial is a an investigator initiated multicenter, prospective, randomized, stratified phase III clinical trial and seeks to investigate the role of preoperative induction chemotherapy (2 cycles of FLOT: 5-FU, leucovorin, oxaliplatin, docetaxel) with subsequent preoperative radiochemotherapy (oxaliplatin weekly, 5-FU plus concurrent fractioned radiotherapy to a dose of 45 Gy) compared to preoperative chemotherapy alone (4 cycles of FLOT), both followed by resection and postoperative completion of chemotherapy (4 cycles of FLOT), in the treatment of locally advanced, potentially resectable adenocarcinoma of the gastroesophageal junction. Patients with cT3–4, any N, M0 or cT2 N+, M0 adenocarcinoma of the GEJ are eligible for inclusion. The RACE trial aims to enrol 340 patients to be allocated to both treatment arms in a 1:1 ratio stratified by tumour site. The primary endpoint of the trial is progression-free survival assessed with follow-up of maximum 60 months. Secondary endpoints include overall survival, R0 resection rate, number of harvested lymph nodes, site of tumour relapse, perioperative morbidity and mortality, safety and toxicity and quality of life. Discussion The RACE trial compares induction chemotherapy with FLOT followed by preoperative oxaliplatin and 5-Fluorouracil-based chemoradiation versus preoperative chemotherapy with FLOT alone, both followed by surgery and postoperative completion of FLOT chemotherapy in the treatment of locally advanced, non-metastatic adenocarcinoma of the GEJ. The trial aims to show superiority of the combined chemotherapy/radiochemotherapy treatment, assessed by progression-free survival, over perioperative chemotherapy alone. Trial registration ClinicalTrials.gov; NCT04375605; Registered 4th May 2020;


2010 ◽  
Vol 28 (15_suppl) ◽  
pp. TPS200-TPS200
Author(s):  
E. C. Smyth ◽  
H. Schöder ◽  
D. G. Coit ◽  
V. E. Strong ◽  
M. F. Brennan ◽  
...  

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 124-124
Author(s):  
P. Cen ◽  
Y. Xing ◽  
C. J. Wray ◽  
M. B. Fallon ◽  
V. I. Machicao ◽  
...  

124 Background: Limited data is available for the role of multimodality management for gastric adenocarcinoma and its outcome in the community. Methods: We retrospectively reviewed the outcomes for 341 patients (pts) who were diagnosed with gastric cancer in a community-based health-care system, including 9 hospitals, from 2000 to 2009. Results: 148/341 pts had undergone surgery and were included in the analysis. Median age at diagnosis was 68 year (range: 32-96), 56% were male, 55% were Caucasian and 25% were black. The stage distribution was as follows: 27% (40 pts) localized, 61% (90 pts) locally advanced and 12% (18 pts) with distant metastasis. 98 pts (66%) received surgery alone, 22 pts (15%) received perioperative chemotherapy, and 28 pts (19%) received perioperative chemo-radiation. After a median follow-up time of 5.2 yrs, the median OS for the entire group was 1.9 years, and 88 deaths had occurred at the last follow up. By stage, the median OS was 7 yrs, 2.3 yrs, and 0.3 yrs for localized stage, regional stage, and metastatic disease, respectively. The 5-yr survival was significantly better in pts who received perioperative chemo-radiation (68%), compared to those who received with surgery alone (33%) or perioperative chemotherapy (0%) (p=0.002). The 5-yr survivals by stage and treatment are shown in the table. Conclusions: Perioperative chemo-radiation was associated with a significantly better OS compared to surgery alone. Trimodality therapy for gastric cancer appears to be underutilized in the community setting described here. The survival advantage of surgery plus chemoradiation compared to surgery plus chemotherapy remains controversial and should be investigated in clinical trials. [Table: see text] No significant financial relationships to disclose.


2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 158-158
Author(s):  
Jiajia Zhang ◽  
Jing Jin ◽  
Wang Xin

158 Background: To investigated the regional recurrence pattern of Siewert type II/III AGE patients after curative resection and refine the clinical target volume (CTV) delineation of radiotherapy. Methods: From 2009 to 2013, 78 patients who were histopathologically diagnosed with locally advanced AGE (T3/4 or any N+, Siewert II/III) after curative resection and confirmed of regional recurrence in follow-up CT images were retrospectively reviewed. First regional recurrence was recorded and one diagnostic radiologist with specialty of gastrointestinal tract investigated. Pattern of regional failure at each node station were analyzed. Reference CT images were obtained from a healthy volunteer. We then delineated the epicenters of recurrence sites at the equivalent location, based on the same vessels of reference CT images compared with the recurrence CT images on Pinnacle planning system. The combined contour of all recurrence sites was presented on a digitally reconstructed radiograph (DRR) image. Results: Most recurrence occurred within 2 years of follow-up (Median, 10.9 m). Of all, 35 (44.9%) patients had regional failure (RF) only; 24 (38%) had RF simultaneous with distant failure; 11 (14.1%) were locoregional, and 8 (10.3%) had concurrent distant and locoreginal failure. The most common recurrent node stations were No.16 (62.8%), No. 9 (32.1%), No. 11 (24.4%), No. 8 (17.9%), No. 7 (16.7%), No. 112 (12.8%), No. 4 (12.8%) and No. 12 (10.3%), respectively. 11 patients (14.1%) had recurrence at mediastinal lymph nodes. There was no significant difference of NF between Siewert type II and III AEG except for No. 9 (42.2% vs 18.2%, P = 0.027). The frequency and location of RF was shown by CT and digitally reconstructed radiograph (DRR) images. A three-dimensional (3D) atlas based on vessel delineation and distribution of RF was established. Conclusions: The most prevalent regional recurrence in Siewert type II/III AEG patients after curative resection was along the abdominal aorta, celiac artery and splenic artery. Our findings suggest a modified elective lymphatic target volume for IMRT contours in those patients.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4059-4059
Author(s):  
Shin Hye Yoo ◽  
Seo Young Kang ◽  
Gi Jeong Cheon ◽  
Do-Youn Oh ◽  
Yung-Jue Bang

4059 Background: Metabolic intratumoral heterogeneity (ITH) gives important information on treatment response and prognosis. However, temporal changes in metabolic ITH and their associations with treatment outcome have not been reported yet in gastric cancer (GC). We aimed to evaluate the early changes in metabolic ITH and their predictive roles in advanced GC patients receiving palliative chemotherapy. Methods: Unresectable locally advanced or metastatic GC patients were prospectively enrolled before the first-line palliative chemotherapy and underwent 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET-CT) at baseline (T1) and at the first response evaluation follow-up (T2). SUVs (Standardized uptake values), volumetric parameters, and textural features including entropyHisto and contrastGLCM were extracted from the primary gastric tumor at T1, T2, and ΔT (T2-T1) was evaluated. Associations of these parameters with treatment response, progression-free survival (PFS), and overall survival (OS) were analyzed. Results: 87 patients were analyzed. Of 86 evaluable patients, 44 obtained partial response, 33 stable disease, and 8 progressed. The objective response rate was 51.8% (95% confidence interval [CI], 40.7% to 62.7%). The median PFS and OS were 7.3 months (95% CI, 5.4 to 8.2 months) and 11.5 months (95% CI, 10.1 to 14.3 months), respectively. From T1 to T2, metabolic ITH was significantly reduced ( P < 0.01), and the degree of decrease was greater in responders than in non-responders ( P < 0.01). By multiple Cox regression analyses adjusted for clinical variables, low entropyHisto at T2 ( P= 0.001), larger decreases in coefficient of variance ( P= 0.003) and contrastGLCM ( P= 0.017) were associated with better PFS. Low SUVpeak at T2 ( P= 0.001), larger decreases in coefficient of variance ( P= 0.032) and being a responder were associated with better OS. Conclusions: Early reduction in metabolic ITH is useful to predict response to palliative chemotherapy, PFS and OS in advanced GC patients.


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