scholarly journals Pathological Complete Response After a Single Dose of Anti-PD-1 Therapy in Combination with Chemotherapy as a First-Line Setting in an Unresectable Locally Advanced Gastric Cancer with PD-L1 Positive and Microsatellite Instability

2020 ◽  
Vol Volume 13 ◽  
pp. 1751-1756
Author(s):  
Hailong Jin ◽  
Peijie Li ◽  
Chenyu Mao ◽  
Kankai Zhu ◽  
Hai Chen ◽  
...  
2020 ◽  
Vol 13 (2) ◽  
pp. 716-720
Author(s):  
Masato Kondo ◽  
Shogo Nishino ◽  
Daisuke Yamashita ◽  
Satoshi Kaihara

The prognosis of locally advanced gastric cancer is poor even if radical gastrectomy with D2 lymphadenectomy is followed by adjuvant chemotherapy. Hence, neoadjuvant chemotherapy is performed to try to improve the prognosis, as it can significantly downstage the tumor and safely improve the R0 resection rate of patients. Herein, we report a case of locally advanced gastric cancer with pancreatic invasion and gastric outlet obstruction that showed a pathological complete response after neoadjuvant chemotherapy with S-1 and oxaliplatin (SOX). A 74-year-old man presented to our hospital with abdominal pain and pyloric stenosis. CT images revealed a cStage IVb, cT4b tumor in the pancreas, cN1, cM0. Therefore, we performed laparoscopic gastrojejunostomy, and the patient’s oral intake improved after surgery; we then administered neoadjuvant chemotherapy with SOX on postoperative day 18, without any surgical complications. After 3 courses of neoadjuvant chemotherapy, the patient underwent radical distal gastrectomy, thereby avoiding pancreatoduodenectomy. Histopathological examination of the resected sample revealed no residual cancer cells, indicating a pathological complete response. No recurrence has occurred for 1 year after surgery. Thus, neoadjuvant chemotherapy with SOX can help in tumor downstaging and may be a multipotent option for the treatment of locally advanced gastric cancer, such as cases with the invasion of other organs; this treatment can result in improved curability and avoid overinvasive surgery.


2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 205-205
Author(s):  
Daisuke Takahari ◽  
Manabu Ohashi ◽  
Atsuo Takashima ◽  
Takuro Mizukami ◽  
Naoki Ishizuka ◽  
...  

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.


2016 ◽  
Vol 3 (1) ◽  
pp. 19-22
Author(s):  
Mohamed Mesmoudi ◽  
Tarik Mahfoud ◽  
Samir Ahid ◽  
Nabil Ismaili ◽  
Saber Boutayeb ◽  
...  

Background: The goal of this study is to determine the efficacy and toxicity of a non-platinum based chemotherapy combination using irinotecan associated to bolus 5-FU as first line treatment in advanced gastric cancer. Materiel and methods: Retrospective analysis of a population of patients treated for metastatic and locally advanced gastric cancer with irinotecan and 5-FU as upfront chemotherapy. Results: Thirteen patients were enrolled. The median age was 56 years. Seven patients were males and six were of females. Ten patients had a metastatic disease and three patients had a locally advanced disease. Patients received a total number of 43 cycles of chemotherapy. Overall response rate was 38,4%, median time to progression (TTP) was 3 months, and median overall survival was 4 months. Three patients (23,1%) presented grade 3 /4 neutropenia complicated with an infectious episode with fever in two cases, three patients (23,1%) required blood transfusion for a grade 4 anemia, and one patient (7,6%) was hospitalized for a severe episode of diarrhea. Conclusion: Three weekly irinotecan and bolus 5-FU is an interesting combination as first line treatment of advanced gastric cancer; designed clinical trials are needed to confirm the activity of this combination.


2020 ◽  
Vol 19 (3) ◽  
pp. 38-46
Author(s):  
V. Yu. Skoropad ◽  
D. D. Kudriavtsev ◽  
L. N. Titova ◽  
S. A. Moserov ◽  
T. A. Agababyan ◽  
...  

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. 


2021 ◽  
Vol 10 ◽  
Author(s):  
Jia Wei ◽  
Xiaofeng Lu ◽  
Qin Liu ◽  
Lin Li ◽  
Song Liu ◽  
...  

Programmed death 1(PD-1) blockade has shown promising efficacy in advanced gastric cancer. Here, we performed a retrospective analysis of three patients with locally advanced gastric cancer who received adjuvant PD-1 plus chemoradiotherapy as neoadjuvant treatment. Neoadjuvant sintilimab plus concurrent chemoradiotherapy had an acceptable side-effect profile. All three patients underwent surgical gastrectomy after a median of 3.9 months. A major pathological response occurred in two resected tumors and a pathologic complete response was observed in one patient. Our results suggest that PD-1 blockade combined with chemoradiotherapy is a promising strategy as a neoadjuvant therapy in patients with unresectable locally advanced gastric cancer.


2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 71-71 ◽  
Author(s):  
Nils Glenjen ◽  
Katrin Hammerling ◽  
Ingunn Hatlevoll ◽  
Rune Småland ◽  
Petra Weber Hauge ◽  
...  

71 Background: The Norwegian Gastrointestinal Cancer Group (NGICG) conducted a phase II randomized study comparing the efficacy and safety of FLOX and FLIRI as first line treatment in metastatic or locally advanced gastric cancer. At progression or unacceptable drug related toxicity, a crossover to the other treatment arm should be done, if second line chemotherapy was indicated. Methods: 66 patients from 6 treatment centers in Norway were randomized to FLOX (oxaliplatin 85 mg/m2 on day 1, bolus 5-FU 500 mg/m2 and FA 60 mg/m2 on day 1 and 2, or FLIRI (irinotecan 180 mg/m2 on day 1, bolus 5-FU 500 mg/m2 and FA 60 mg/m2 on day 1 and 2). Both treatments were repeated every second week. The primary endpoint was response rate (RR) and time to progression (TTP). Secondary endpoints were overall survival (OS) and safety data. Results: At the present time data from 63 patients are available for analysis. First-line treatment: FLOX (n = 32) versus (v.) FLIRI (n = 31): Complete response (CR) n = 0 in both arms, partial response (PR) n = 16 v. 9, stable disease (SD) n = 12 v. 13, progressive disease (PD) n = 3 v. 6, not assessable for evaluation n = 1 v. 3 patients. RR was 50 % in the FLOX arm v. 29 % in the FLIRI arm, p = not significant (n.s), Pearson Chi-Square test. Median TTP was 5 months (95 % CI 2.2-7.8) v. 4 months (95 % CI 2.2-5.8), p = n.s, median OS was 11 months (95 % CI 9.2-12.8 ) v. 10 months (95 % CI 5.7-14.3), p = n.s, Log Rank test. Patient characteristics were well balanced. Febrile neutropenia was present among 10 % of the patients in the FLOX arm versus 7 % in the FLIRI arm. Second line treatment: 30 patients received second line treatment with FLOX or FLIRI. Data regarding RR, TTP, OS and safety will be updated in December 2011. Conclusions: The FLOX and FLIRI regimens are well tolerated among patients with locally advanced and metastatic gastric cancer. As first line treatment the FLOX regime had a higher RR of 50% v. 29% for the FLIRI regime, longer TTP; 5 v. 4 months and longer OS 11 v. 10 months, but the difference did not reach statistical significance.


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