scholarly journals Clinical Effectiveness of Neoadjuvant Chemotherapy in Gastric Carcinoma and Exploration of Perioperative Imaging Assessment Parameters

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Jiajun Lai ◽  
Junsheng Li ◽  
Xianwei Mo
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Gastric Carcinoma ◽  
Tumor Regression ◽  
Clinical Effectiveness ◽  
Clinical Staging ◽  
Tumor Regression Grade ◽  
Clinical Value ◽  
Advanced Gastric Carcinoma ◽  
Before And After ◽  
Assessment Approach

Background and Aims. Due to the difficulty in clinical staging, a simple and feasible perioperative assessment approach for guiding personalized neoadjuvant chemotherapy (NAC) is lacking. We investigated the clinical value of NAC in advanced gastric carcinoma (GC) and the concordance between perioperative imaging and postoperative pathological assessments. Methods. This study included 62 patients with advanced GC who received NAC between January 2012 and December 2018. The preoperative and postoperative T stages, postoperative pathological tumor regression grade (TRG), and changes in computed tomography (CT) values after NAC were assessed. Follow-ups were conducted to obtain the median survival time (MST), and Kaplan–Meier survival curves were plotted. Results. The T stages significantly differed between before and after NAC ( p = 0.001 ). The MST of patients in the TRG0 group was significantly different from that of patients in the TRG1+2 and TRG3 groups ( p = 0.223 ). The percentages of positive lymph nodes were 0%, 24.17%, and 27.64% in the TRG0, TRG1+2, and TRG3 groups, respectively. TRG was correlated with changes in CT values before and after NAC, and the extent of change was associated with patient prognosis. Conclusions. Perioperative imaging can be used to assess the short-term effectiveness of NAC for patients with GC.

scholarly journals Genomic Analysis of Response to Neoadjuvant Chemotherapy in Esophageal Adenocarcinoma

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3394
Author(s):  
Fereshteh Izadi ◽  
Benjamin Sharpe ◽  
Stella Breininger ◽  
Maria Secrier ◽  
Jane Gibson ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Esophageal Adenocarcinoma ◽  
Copy Number ◽  
Tumor Regression ◽  
Locally Advanced ◽  
Genomic Analysis ◽  
Tumor Regression Grade ◽  
Comparative Genomic ◽  
Mutation Burden ◽  
Response To Neoadjuvant Chemotherapy

Neoadjuvant therapy followed by surgery is the standard of care for locally advanced esophageal adenocarcinoma (EAC). Unfortunately, response to neoadjuvant chemotherapy (NAC) is poor (20–37%), as is the overall survival benefit at five years (9%). The EAC genome is complex and heterogeneous between patients, and it is not yet understood whether specific mutational patterns may result in chemotherapy sensitivity or resistance. To identify associations between genomic events and response to NAC in EAC, a comparative genomic analysis was performed in 65 patients with extensive clinical and pathological annotation using whole-genome sequencing (WGS). We defined response using Mandard Tumor Regression Grade (TRG), with responders classified as TRG1–2 (n = 27) and non-responders classified as TRG4–5 (n =38). 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 in non-responders (282 vs. 136/patient, p < 0.001). We identified copy number variants unique to each group in our cohort, 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 note, NAV3 mutations were exclusively present in the non-responder group with a frequency of 22%. Thus, lower mutation burden, higher chromosomal instability and specific copy number alterations are associated with resistance to NAC.

scholarly journals Impact of neoadjuvant chemotherapy with PELF-protocoll versus surgery alone in the treatment of advanced gastric carcinoma

BMC Surgery ◽  
2014 ◽  
Vol 14 (1) ◽  
Author(s):  
Catharina Ruf ◽  
Oliver Thomusch ◽  
Matthias Goos ◽  
Frank Makowiec ◽  
Gerald Illerhaus ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Gastric Carcinoma ◽  
Advanced Gastric Carcinoma

scholarly journals Body Composition Changes in Gastric Cancer Patients during Preoperative FLOT Therapy: Preliminary Results of an Italian Cohort Study

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 960
Author(s):  
Emanuele Rinninella ◽  
Antonia Strippoli ◽  
Marco Cintoni ◽  
Pauline Raoul ◽  
Raffaella Vivolo ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Body Composition ◽  
Tumor Regression ◽  
Evaluation Criteria ◽  
Tumor Regression Grade ◽  
Skeletal Muscle Index ◽  
Before And After ◽  
Gastric Cancer Patients ◽  
The Impact ◽  
Composition Changes

Background: The impact of the new chemotherapy, fluorouracil plus leucovorin, oxaliplatin, and docetaxel (FLOT) on body composition in gastric cancer (GC) patients remains unknown. We assessed body composition changes of GC patients receiving the FLOT regimen and their impact on treatment outcomes. Methods: Preoperative pre- and post-FLOT computed tomography (CT) scans of advanced GC patients were studied. Lumbar skeletal muscle index (SMI) and adipose indices were calculated before and after FLOT. Results: A total of 26 patients were identified between April 2019 and January 2020. Nineteen patients were sarcopenic at diagnosis. The mean BMI decreased (from 24.4 ± 3.7 to 22.6 ± 3.1; p < 0.0001) as well as the SMI (from 48.74 ± 9.76 to 46.52 ± 9.98; p = 0.009) and visceral adipose index (VAI) (from 49.04 ± 31.06 to 41.99 ± 23.91; p = 0.004) during preoperative FLOT therapy. BMI, SMI, and VAI variations were not associated with toxicity, Response Evaluation Criteria in Solid Tumors (RECIST), response, delay and completion of perioperative FLOT chemotherapy, and the execution of gastrectomy; a decrease of SMI ≥ 5% was associated with a higher Mandard tumor regression grade (p = 0.01). Conclusions: Almost three-quarters (73.1%) of GC patients were sarcopenic at diagnosis. Preoperative FLOT was associated with a further reduction in SMI, BMI, and VAI. These changes were not associated with short-term outcomes.

Neoadjuvant chemotherapy (NCT) in locally advanced gastric carcinoma (LAGC)

1993 ◽  
Vol 29 ◽  
pp. S107
Author(s):  
Ph Lasser ◽  
Ph Rougier ◽  
M Ducreux ◽  
M Mahjoubi ◽  
D Elias ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Gastric Carcinoma ◽  
Locally Advanced ◽  
Advanced Gastric Carcinoma

scholarly journals 474 GENOMIC ANALYSIS OF RESPONSE TO NEOADJUVANT CHEMOTHERAPY IN ESOPHAGEAL ADENOCARCINOMA

2020 ◽  
Vol 33 (Supplement_1) ◽  
Author(s):  
F Izadi ◽  
G Devonshire ◽  
R Walker ◽  
M Lloyd ◽  
J Gibson ◽  
...  
Keyword(s):  
Dna Damage ◽  
Neoadjuvant Chemotherapy ◽  
Esophageal Adenocarcinoma ◽  
Tumor Regression ◽  
Locally Advanced ◽  
Chemotherapy Resistance ◽  
Treatment Modalities ◽  
Tumor Regression Grade ◽  
Driver Genes ◽  
The Impact

Abstract   In the UK, neoadjuvant chemotherapy (NAC) for locally advanced esophageal adenocarcinoma (EAC) is the standard of care. Unfortunately, response to NAC, following surgery is often low (&lt;30%) and survival benefit at 2 years is only 5.1%. The EAC genome is complex and heterogeneous between patients, where specific mutagenic processes and mutations may result in chemotherapy resistance. Here we report preliminary results from whole-genome sequencing (WGS) of 48 patients who were subsequently treated with NAC. Methods We defined response as Mandard Tumor Regression Grade (TRG) 1-2 (n = 15) and non-response as TRG4-5 (n = 33). WGS of 50x coverage and calling of genomic events (Strelka2, SCAT/GISTIC) was performed according to Frankell Nat Genet 2019 with modifications, to differentiate driver from passenger mutations (dNdScv, oncodriveCLUST), determine variant allele frequencies (VAF; copy number-adjusted) and mutation signatures (NMF R-package). Following stringent variant QC (Phred score ≥ 30), filtering (VAF &gt;0.02) and annotation (ANNOVAR, cancer census/helper, the 77 known EAC drivers and false positive genes) and visualisation in maftools, we evaluated the data for associations between genomic events and response to NAC. Results COSMIC mutation signatures 2 (TRG1-2; Cosθ = 0.89) and 6 (TRG4-5; Cosθ = 0.82) were enriched, suggesting defective mismatch repair in non-responders. Using 5,193 high-confidence non-silent mutations (TRG1-2,n = 1969; TRG4-5, n = 3224), we identified 39 mutated driver genes (Figure-1) with a median of 2.9(0-5) (TRG1-2) and 2.7(0-9) (TRG4-5) driver events/patient. Shared dysregulated pathways, included DNA-damage (TP53), cell cycle (CDKN2A), TGF-β (SMAD4) and chromatin regulation (ARID1A). There was no difference in the prognostic of SMAD4 and GATA4 genes. Interestingly, NAV3 mutations were only present in non-responders (21%,7/33); and in responders TP53 incidence was higher (93% vs. 58%) with a concomitant reduction in clonal cell fraction (0.25 vs. 0.39;Wilcoxon, p &lt; 0.0001). Conclusion The data suggest that specific genomic events, such as NAV3 mutation and the intra-tumoral heterogeneity of mutated DNA-damage response genes may offer additional predictive value. Ongoing work includes analysis of the impact of non-coding variation on response. While our analysis is limited by sample size and requires validation in additional cohorts, it demonstrates the potential of genomic sequencing to identify NAC response biomarkers and may guide alternative or novel treatment modalities for chemo-resistant tumours.

S-1 plus oxaliplatin compared with fluorouracil/leucovorin/oxaliplatin as neoadjuvant chemotherapy for locally advanced gastric carcinoma.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 147-147
Author(s):  
Jiren Yu ◽  
Yijun Wu ◽  
Yuan Gao ◽  
Qianyun Shen ◽  
Qing Zhang ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Gastric Carcinoma ◽  
Clinical Response ◽  
Response Rate ◽  
Locally Advanced ◽  
Preoperative Staging ◽  
Complete Response ◽  
Clinical Response Rate ◽  
R0 Resection ◽  
Advanced Gastric Carcinoma

147 Background: Perioperative chemotherapy could improve the prognosis compared with surgery alone. This study is to compare the efficacy and safety of S-1 and oxaliplatin (SOX) with fluorouracil, leucovorin and oxaliplatin (FOLFOX) as neoadjuvant chemotherapy for locally advanced gastric carcinoma. Methods: Patients with histologically confirmed locally advanced gastric carcinoma were enrolled and divided into two groups. Preoperative staging and response evaluation was achieved mainly by gastroscopy and abdominal computer tomography. Neoajuvant chemotherapy consisted of 2-6 cycles of S-1 80mg/m2 (2-week administration and 1-week rest) plus oxaliplatin 130mg/m2 on Day1 in SOX group, or 2 h infusion of 130mg/m2 oxaliplatin plus 2h infusion of 400 mg/m2 leucovorin, followed by infusion of 400 mg/m2 5-fluorouracil on Day 1 and 46 h 2.4 g/m2 bolus in FOLFOX group. The clinical response was evaluated after 2 cycles of chemotherapy, and surgery was attempted. Results: From 2009.9 to 2011.5, 88 patients were enrolled in this study(56 in SOX and 32 in FOLFOX). The clinical response rate was significant higher in the SOX compared with FOLFOX (54.7% vs. 31.2%, p=0.03). 68 patients received surgery(45 in SOX and 23 in FOLFOX), R0 resection rate was similar in both group (SOX: 93.3% vs. FOLFOX: 82.6%, p=0.22). Pathological complete response was observed in 3 patients in SOX group. All enrolled patients were evaluated for the adverse events (AE). The most common non-hematological AE was nausea (57.1% in SOX and 50% in FOLFOX) and vomiting (41.1% in SOX and 40.6% in FOLFOX). The major hematological AE included thrombocytopenia (37.5% in SOX and 21.9% in FOLFOX), neutropenia (33.9% in SOX and 53.1% in FOLFOX) and leukocytopenia (32.1% in SOX and 40.6% in FOLFOX). Conclusions: SOX had higher response rate and acceptable toxicity compared with FOLFOX as neoadjuvant chemotherapy.

Neoadjuvant chemotherapy for locally advanced colon cancer patients: Long-term results from a single institutional experience.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15598-e15598
Author(s):  
Lucia Ceniceros ◽  
Carlos Pastor ◽  
Carlos Sanchez-Justicia ◽  
Carolina Arean ◽  
Jorge Baixauli ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Tumor Regression ◽  
Locally Advanced ◽  
Haematological Toxicity ◽  
Median Number ◽  
Clinical Staging ◽  
Long Term Results ◽  
Long Term Outcome

e15598 Background: Neoadjuvant chemotherapy (NAC) is an emerging alternative in the management of patients with locally advanced colorectal cancer (LACRC), with promising results in terms of R0 resection rates, compliance, postoperative morbidity and a trend towards reduced risk of relapse. However, more mature data are required. We evaluated the long-term outcome of this strategy in our institution. Methods: We retrospectively analysed LACRC patients treated preoperatively with either biweekly FOLFOX or XELOX at standard doses as a follow-up of our previous experience with this neoadjuvant approach. Patients were identified from a prospectively collected tumor registry database from our institution. Clinical staging was based on colonoscopy and CT-scan. Only patients with radiological signs of lymph node involvement and/or extramural invasion > 5 mm were included. The uracil/dihidrouracil ratio was calculated at baseline as a surrogate marker of DPD deficiency. Pathological tumor regression was graded according to the MSKCC and toxicity with the NCI-CTCAE 4.0. Results: From February 2006 to November 2019 91 pts with MSS LACRC (M/F: 62/29; median age 66. Clinical stage; T3: 60.4%, T4: 37.4%, N+: 75.8%; Sideness: 82.4% left located were analysed. Preoperative chemo was FOLFOX in 46 pts and CAPOX in 45 pts. Median number of preoperative cycles was 4 (range 1-10). Side effects profile included G3-4 diarrhea (3.3%), G2 sensitive neuropathy (12.1%) and G2 neutropenia (4.4%). 9 pts had a treatment delay due to haematological toxicity. No progressive disease was noted during neoadjuvant chemotherapy. All patients underwent surgery, most of them (63.7%) by a laparoscopic approach. pCR was found in 11 pts (12.1%). Grade 3, 3+ and 4 tumor regression according to MSKCC score was reached in 50.5% of the patients (Median number of harvested nodes was 17 (range 7-51), with 75.8% being ypN0. Lymphovascular and perineural invasion were found in 7.7% and 6.6% of the patients, respectively. The median hospital stay was 7 days (3-36) and 13 pts develop any surgical complication. 37.4% received adjuvant treatment. After a median follow-up of 63 months, median progression-free (PFS) and overall survival (OS) have not been reached. 5-year actuarial PFS for right and left LACRC was 77 and 87%, respectively. Conclusions: Our data add to the growing evidence suggesting that NAC may play a meaningful role in LACRC patients

Preoperative (“Neoadjuvant”) Chemotherapy in Locally Advanced Gastric Carcinoma

1989 ◽  
pp. 161-168 ◽  
Author(s):  
H. Wilke ◽  
P. Preusser ◽  
U. Fink ◽  
W. Achterrath ◽  
H.-J. Meyer ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Gastric Carcinoma ◽  
Locally Advanced ◽  
Advanced Gastric Carcinoma
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