scholarly journals PATHOLOGICAL COMPLETE RESPONSE TO NEOADJUVANT CHEMORADIOTHERAPY IN PATIENTS WITH LOCALLY ADVANCED GASTRIC CANCER

2020 ◽  
Vol 19 (3) ◽  
pp. 38-46
Author(s):  
V. Yu. Skoropad ◽  
D. D. Kudriavtsev ◽  
L. N. Titova ◽  
S. A. Moserov ◽  
T. A. Agababyan ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Tumor Regression ◽  
Locally Advanced ◽  
Survival Rates ◽  
Neoadjuvant Chemoradiotherapy ◽  
Complete Response ◽  
Pathological Response ◽  
Locally Advanced Gastric Cancer ◽  
Long Term Treatment

The impact of pathological complete response (pCR) on long-term treatment outcomes was analyzed in patients with locally advanced gastric cancer, who received prolonged neoadjuvant chemoradiotherapy.Material and Methods. The study included 45 patients with locally advanced gastric cancer. Neoadjuvant hyperfractionated accelerated radiotherapy at a total dose of 45 Gy was given concurrently with capecitabine and oxaliplatin chemotherapy. There were more men than women. The median age of the patients was 62 years. Tumors were most commonly located in the upper (46 %) and middle (38 %) thirds of the stomach. Low-grade adenocarcinoma and signet-ring cell carcinoma were the most common (65 %). According to a comprehensive examination, including CT and laparoscopy, tumors which invaded the subserous layer of the stomach wall were diagnosed in 17 (37.8 %) patients, and tumors which penetrated the serous layer or surrounding structures were found in 28 (62.2 %) patients. Regional lymph node metastases were detected in 38 (84.4 %) cases.Results. The absolute majority of patients underwent gastrectomy (43 patients, 96 %). Grade IaIb pathological response occurred in almost half of the patients (45.4 % of cases). Peritoneal metastases were found to be the most common mode of cancer dissemination; they were mostly observed in patients with poorly differentiated gastric cancer. Multivariate analysis revealed no effect of any of the factors characterizing the patient, tumor and completeness of treatment on the pathological response grade. However, a correlation between the clinical and morphological assessments of tumor regression was observed. In cases with complete or partial responses of the primary tumor and regional lymph nodes to chemoradiotherapy, 1aIb grades of pathological response were more frequently observed. It was also demonstrated a direct correlation between the pathological response grade and pathomorphological stage of the tumor (yp), as well as ypT and ypN categories. Analysis of long-term treatment outcomes showed that the overall and relapse-free 5-year survival rates were significantly higher in patients with 1a and Ib grades of pathological response. The overall 3-year survival rates were 70 ± 10 % and 41 ± 11 %, respectively (p=0.003). Multivariate analysis using the Cox regression model confirmed a statistically significant independent effect of the pathological response grade on the overall survival (p=0.015).Conclusion. Grade IaIb pathological response was observed in almost half of the patients, who received neoadjuvant chemoradiotherapy for locally advanced gastric cancer. No clinical and morphological factors influencing the pathological response grade were found. A correlation between the clinical and morphological assessments of tumor regression was observed. Patients with Ia-Ib pathological response had significantly higher overall and disease-free survival rates. 

scholarly journals Neoadjuvant Docetaxel, Oxaliplatin, Leucovorin, and 5-Fluorouracil (FLOT) Versus S-1 plus Oxaliplatin (SOX) for Patients with Locally Advanced Gastric Cancer

2020 ◽  
Author(s):  
Birendra Kumar Sah ◽  
Benyan Zhang ◽  
Huan Zhang ◽  
Jian Li ◽  
Fei Yuan ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Advanced Gastric Cancer ◽  
Tumor Regression ◽  
Locally Advanced ◽  
Pathological Response ◽  
Clinicopathological Parameters ◽  
Regression Grading ◽  
Locally Advanced Gastric Cancer ◽  
Significant Difference

AbstractBackgroundDespite growing trends of neoadjuvant chemotherapy for advanced gastric cancer, there is still no consensus of optimal regimens between East and West countries. Neoadjuvant chemotherapy with docetaxel, oxaliplatin, fluorouracil, and Leucovorin (FLOT) regimen has shown promising results in terms of pathological response and survival rate. However, S-1 plus oxaliplatin (SOX) is a more favorable chemotherapy regimen in Eastern countries. We conducted this study to evaluate the safety and efficacy of both regimens, and to explore a suitable regimen for Chinese patients.MethodsPatients with locally advanced gastric cancer(LAGC) were 1:1 randomly assigned to receive either 4 cycles of FLOT or 3 cycles of SOX regimen before curative gastrectomy. The primary endpoint was the comparison of complete or sub-total tumor regression grading (TRG1a+ TRG1b) in the primary tumor.ResultsAltogether 74 cases enrolled between August 2018 and March 2020. All 74 randomly assigned cases were considered as intention-to-treat (ITT) population, and the 55 patients who completed the planned chemotherapy plus surgery were considered as per protocol (PP) population. There was no significant difference in pre-treatment clinicopathological parameters between the FLOT and SOX group(p>0.05). There was no significant difference in adverse effects or postoperative morbidity and mortality between two groups (p>0.05). Similarly, there was no significant difference in the proportion of tumor regression grading between the FLOT and SOX group(p>0.05). In the ITT population, complete or sub-total TRG was 20.0 % in FLOT versus 32.4 % in the SOX group (p>0.05).ConclusionsOur study demonstrates that FLOT and SOX regimens are similarly effective for locally advanced gastric cancer patients in terms of clinical downstaging and pathological response. Both regimens were well-tolerated in this study. A large scale phase 3 randomized controlled trial is necessary to validate this result.

Feasibility study of TAS-118 plus oxaliplatin as perioperative chemotherapy for patients with locally advanced gastric cancer (APOLLO-11).

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 205-205
Author(s):  
Daisuke Takahari ◽  
Manabu Ohashi ◽  
Atsuo Takashima ◽  
Takuro Mizukami ◽  
Naoki Ishizuka ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Locally Advanced ◽  
Dose Intensity ◽  
Complete Response ◽  
Free Survival ◽  
D2 Gastrectomy ◽  
Locally Advanced Gastric Cancer ◽  
Grade 3

205 Background:TAS-118 (S-1 and leucovorin) + oxaliplatin (L-OHP) improved overall survival (OS) compared to S-1 + cisplatin for patients (pts) with advanced gastric cancer (GC) (Kang, Lancet Oncol. 2020). This study investigated the feasibility of peri (pre and post)-operative (op) chemotherapy (chemo) with TAS-118 ± L-OHP in pts with locally advanced resectable GC. While it was reported that pre-op TAS-118 + L-OHP followed by D2 gastrectomy was well tolerated and showed promising efficay (Takahari, ASCO-GI. 2020), the recommended post-op chemo regimen, TAS-118 or TAS-118 + L-OHP, has yet to be determined. Methods:Eligible pts with GC of clinical T3-4N1-3M0 were enrolled. The protocol treatment consisted of pre-op chemo with 4 courses of TAS-118 (40-60 mg/body, orally, twice daily, 7 days) + L-OHP (85 mg/m2, intravenously, day 1) in a 2-week cycle, and gastrectomy with D2 lymphadenectomy, followed by post-op chemo with 12 courses of TAS-118 (step 1) and 8 courses of TAS-118 + L-OHP (step 2). Step 2 was started if the dose-limiting toxicity (DLT) occurred in < 6 of 10 pts in step 1. Up to 20 pts were included in the analysis of feasibility after a recommended regimen was determined. Results:Between December 2016 and February 2019, 45 pts were enrolled. The numbers of pts with cT3/4a and cN1/2/3 were 13/32 and 25/17/3, respectively. Excluding 14 pts (4 achieving pathological complete response, 4 not satisfying the criteria for post-op chemo, 3 physician judgement or pt withdrawal, 2 progressive disease, 1 adverse event [AE]), 31 pts (11/20 in step 1/2) received the post-op chemo. No DLT was observed in either step. The post-op chemo completion rate was 90.9% (95% CI, 63.6-99.5) in step 1 and 80.0% (95% CI, 59.9-92.9) in step 2. The median relative dose intensity of TAS-118 in step 1 was 83.3%, and those of TAS-118 and L-OHP in step 2 were 69.9% and 74.3%, respectively. One pt in step 2 discontinued post-op chemo due to AE. Grade ³ 3 AEs observed in ≥ 10% of pts were weight loss in both step 1 and step 2 (2 in each), and hypokalemia (n = 3) and neutropenia (n = 2) in step 2. At 1-year follow-up after the last pt was enrolled, recurrence-free survival and OS rates were 91.1% (95% CI, 78.0-96.6) and 100%, respectively at 12 months, and 69.1% (95% CI, 49.6-82.3) and 95.5% (95% CI, 71.9-99.3), respectively at 24 months. Conclusions:Taken together with the feasibility and efficacy of pre-op chemo, peri-op chemo with TAS-118 + L-OHP with D2 gastrectomy was well tolerated and showed promising efficacy. Clinical trial information: UMIN000024688.

Randomized trial of adjuvant chemotherapy with mitomycin plus ftorafur versus mitomycin alone in resected locally advanced gastric cancer.

1998 ◽  
Vol 16 (3) ◽  
pp. 1036-1039 ◽  
Author(s):  
J J Grau ◽  
J Estapé ◽  
J Fuster ◽  
X Filella ◽  
J Visa ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Adjuvant Chemotherapy ◽  
Advanced Gastric Cancer ◽  
Early Stage ◽  
Locally Advanced ◽  
Survival Rates ◽  
Group Versus ◽  
Node Negative ◽  
Treatment Groups ◽  
Locally Advanced Gastric Cancer

PURPOSE We performed a clinical trial to determine whether postoperative adjuvant chemotherapy with two drugs versus one drug could prolong survival. PATIENTS AND METHODS From 1985 to 1996, 85 patients with completely resected locally advanced gastric cancer were enrolled. The subjects were randomized into two treatment groups, as follows: mitomycin (MMC) 10 to 20 mg/m2 intravenously (i.v.) on day 1 every 6 weeks plus ftorafur (FT) 500 mg/m2/d for 36 consecutive days; or MMC alone, 10 to 20 mg/m2 i.v. every 6 weeks. All courses were repeated four times. RESULTS After a median follow-up duration of 62 months, the overall 5-year survival rates were 67% for the MMC-FT group versus 44% for the MMC group (P = .04). Subgroup analysis to compare survival curves using the method of Mantel-Cox showed survival rates significantly in favor of the MMC-FT group in the subsets of patients with node-negative disease (P = .01) and those whose disease was stage IB or II (P = .008). CONCLUSION Significantly better survival results were observed for MMC-FT versus MMC alone. Subset analysis suggest a strong benefit in patients with node-negative and early-stage resected gastric cancer.

scholarly journals ANALYSIS OF HEMATOLOGIC, HEPATIC AND PANCREATIC TOXICITY DURING NEOADJUVANT CHEMORADIOTHERAPY IN PATIENTS WITH LOCALLY ADVANCED GASTRIC CANCER

2018 ◽  
Vol 17 (3) ◽  
pp. 20-27 ◽  
Author(s):  
V. Yu. Skoropad ◽  
D. D. Kudryavtsev ◽  
E. N. Anikina ◽  
M. V. Poluaktova ◽  
L. N. Titova
Keyword(s):  
Gastric Cancer ◽  
Radiation Therapy ◽  
Advanced Gastric Cancer ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Subtotal Resection ◽  
Combined Modality Treatment ◽  
Symptomatic Therapy ◽  
Locally Advanced Gastric Cancer ◽  
Pancreatic Toxicity

Purpose.We analyzed the frequency and severity of hematologic, hepatic and pancreatic toxicity during and after completion of neoadjuvant chemoradiotherapy in patients with gastric cancer.Material and methods. Phase II clinical trial was conducted to  evaluate the efficacy of the combined modality treatment including neoadjuvant chemoradiotherapy followed by D2  gastrectomy for patients with locally advanced gastric cancer. The  main inclusion criteria were: histologically verified gastric cancer,  cT3-4N0, cT2-4N1-3; M0. Before starting neoadjuvant therapy, all  patients underwent thoracic and abdominal CT and laparoscopy to  exclude peritoneal carcinomatosis. A total dose of radiation therapy  was 45 Gy (1 + 1.5 Gy/fraction/day with a 4–5 hour interval)  concurrently with the modified CAPOX chemotherapy regimen.  Gastrectomy or subtotal resection of the stomach was planned 4-6  weeks after the completion of chemoradiotherapy. The toxicity  assessment of neoadjuvant chemoradiotherapy was performed using the NCI CTC scale, version 3.0. The assessment of hematological, hepatic and pancreatic toxicities was done.Results.Among the toxicity during and after completion of  neoadjuvant chemoradiotherapy, thrombocytopenia, neutropenia and leukopenia (grade 1–2) were the most common, requiring no  additional symptomatic therapy. Radiation therapy was completed in  45 (98 %) patients. Chemotherapy was completed in 42 (91 %)  patients. The median time between the completion of  chemoradiotherapy and surgery was 44 days. Surgery following  chemoradiotherapy was performed in 100 % of patients, including R0 resection in 93 % of patients.Conclusion.Preoperative chemoradiotherapy was well tolerated by  patients, could be completed in most cases and did not prevent  subsequent surgical treatment.

scholarly journals THE ROLE OF ADJUVANT CHEMOTHERAPY IN THE TREATMENT OF LOCALLY ADVANCED GASTRIC CANCER

2021 ◽  
Vol 20 (1) ◽  
pp. 133-140
Author(s):  
A. A. Bobryshev ◽  
M. M. Davudov ◽  
M. N. Narimanov ◽  
S. B. Polycarpova ◽  
V. Y. Kirsanov ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Adjuvant Chemotherapy ◽  
Advanced Gastric Cancer ◽  
Treatment Options ◽  
Locally Advanced ◽  
Survival Rates ◽  
Literary Analysis ◽  
Cochrane Library ◽  
International Studies ◽  
Locally Advanced Gastric Cancer

The purpose of the study was a systemic literature review on data regarding the efficacy, safety and prospects for the use of adjuvant chemotherapy for locally advanced gastric cancer.Material and Methods. The study contained a thorough literary analysis of the results of international studies on the use of preoperative and postoperative chemotherapy for locally advanced gastric cancer. Relevant sources were searched in Medlin and Cochrane Library databases, and publications from 2001 to 2019 were included. Of all the studies analyzed, 28 were used to write the systematic review.Results. The increase in survival rates was mainly achieved due to the use of a multimodal approach to the treatment of gastric cancer. The effectiveness of this approach, which combined surgery with chemotherapy or chemoradiotherapy, was proven in several large clinical studies. However, despite the large number of treatment options for locally advanced gastric cancer, there is still no single standard for the management of patients with this disease. One of the treatment options successfully practiced in a number of leading countries is the use of adjuvant chemo/chemoradiation therapy.Conclusion. Analysis of the literature data of the last 18 years has shown the high relevance of studies on adjuvant chemotherapy for gastric cancer and the need to continue further study of this problem.

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