scholarly journals Successful Conversion Surgery for Stage IV Gastric Cancer after Nivolumab Monotherapy as Third-Line Chemotherapy

2021 ◽  
pp. 562-567
Author(s):  
Hayato Watanabe ◽  
Hirohito Fujikawa ◽  
Keisuke Komori ◽  
Kazuki Kano ◽  
Kosuke Takahashi ◽  
...  

There are few reports of conversion surgery (CS) after nivolumab monotherapy because it is considered as a third-line standard chemotherapy for unresectable or recurrent gastric cancer. Here, we report a rare case of stage IV gastric cancer effectively treated with CS after nivolumab monotherapy as a third-line chemotherapy. A 73-year-old man was referred to our hospital with loss of appetite and abdominal discomfort. Stage IV gastric cancer with liver metastasis was diagnosed via upper gastrointestinal endoscopy and CT. Twelve courses of capecitabine, cisplatin, and trastuzumab were administered as the first-line treatment, 25 courses of paclitaxel plus ramucirumab as the second-line treatment, and 31 courses of nivolumab monotherapy as the third-line treatment. After 31 courses of nivolumab monotherapy, CT showed that the primary tumor shrank with no liver metastasis or ascites. Diagnostic laparoscopy was performed with no peritoneal dissemination (P0), and the peritoneal lavage cytology was negative (CY0). CS was performed with total gastrectomy and D2 lymph node dissection (R0 resection). The pathological diagnosis was U, Ant-Less, Type 2, 70 × 63 mm, poorly differentiated adenocarcinoma (ypT3N0M0 ypStage IIA). R0 resection was performed, and the histological response was grade 1a. The patient did not show recurrence for 9 months after CS.

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Koichi Hayano ◽  
Hiroki Watanabe ◽  
Takahiro Ryuzaki ◽  
Naoto Sawada ◽  
Gaku Ohira ◽  
...  

Abstract Background Since the ToGA trial, trastuzumab-based chemotherapy is the standard treatment for HER2 positive stage IV gastric cancer. However, it is not yet clear whether surgical resection after trastuzumab-based chemotherapy (conversion surgery) can improve survival of HER2 positive stage IV gastric cancer. The purpose of this study is to evaluate the prognostic benefit of conversion surgery in HER2 positive stage IV gastric cancer patients. Case presentation We retrospectively investigated the medical records of the patients with HER2 positive (IHC3(+) or IHC2(+)/FISH(+)) stage IV gastric cancer treated with trastuzumab-based chemotherapy as the first line treatment. Overall survival (OS) was compared between patients with conversion surgery and without. Eleven HER2 positive stage IV gastric cancer patients treated with trastuzumab-based chemotherapy as the first line treatment were evaluated. Response rate was 63.6%, and 6 of 11 patients could receive conversion surgery. R0 resection was achieved in four patients. In Kaplan–Meier analysis, patients who received conversion surgery showed significantly better OS than those without surgery (3-year survival rate, 66.7% vs. 20%, P = 0.03). The median OS of patients who achieved R0 resection is 51.8 months. Conclusions Conversion surgery might have a survival benefit for HER2 positive stage IV gastric cancer patients. If curative surgery is technically possible, conversion surgery could be a treatment option for HER2 positive stage IV gastric cancer.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16041-e16041
Author(s):  
Qiang Xue ◽  
Baogui Wang ◽  
Xiaona Wang ◽  
Xuewei Ding ◽  
Yong Liu ◽  
...  

e16041 Background: Chemotherapy and PD-1 inhibitor have shown significant clinical benefits in first-line treatment of GC, overall survival was still dismal. The surgical intervention with curative or life prolonging intention was evaluated as feasible for stage IV GC from clinical trials and retrospective cohorts. Our previous study of cytotoxic chemotherapy (S-1 & PTX) in combination with multi-targets anti-angiogenic TKIs illustrated increased response and R0 resection rate. Given the enhanced response from chemo, PD-1 and TKIs regimens, this trial was designed to assess the feasibility of surgical conversion from this combination in stage IV GC. Methods: This is a prospective, single-arm, single-center, phase II trial. Eligible criteria were treatment naïve, histopathologically confirmed stage IV (AJCC8th) and ECOG PS 0-1 GC adenocarcinoma. Pts were given with sintilimab (200mg, iv, d1) combined with Nab-PTX (w/o peritoneal spread: 260 mg/m2, iv, d1; w/ peritoneal spread: 180 mg/m2, iv, d1 and 80 mg/m2, ip, d1), S-1 (60mg, po, bid, d1-14), and apatinib (250mg, po, qd) every 3 wks. Tumor response was assessed every 2-4 cycles by radiologic imaging and MDT was employed to determine surgical feasibility. Safety run-in was employed in the first 3+3 pts by DLTs to determine the tolerability. The primary endpoint was ORR and R0 surgical conversion rate. Results: 42 pts were enrolled up to 2/2021. The median follow-up was 3.5m (range 0.7-11.3). The median age was 56 yrs (range 31-72), male was 47.6%, and PS 1 was 31.0%. The metastatic factors were characterized as No.16 lymph nodes 54.8% (23), liver 23.8% (10), peritoneum 40.5% (17), Krukenberg 2.4% (1), and extensive metastases (≥2 organs) 42.9% (18). No DLT occurred in initial 6 pts. Of 36 evaluable pts, ORR was 61.1% and DCR was 97.2%. Surgical conversion was currently identified in 18 pts with 94.4% (17) R0 resection, and the R0 surgical conversion rate was 47.2% (17/36). Median treatment cycle in converted pts was 4. 22.2% (4/18) pts achieved pathological complete response (TRG 0), and 27.8% (5/18) pts had major response (TRG 0-1). The most common AEs were grade 1-2, and 1 SAE of hemorrhage grade 4 occurred. No increase of anastomotic leakage, hemorrhage, and abdominal infection, and no surgery caused death and complication caused second operation occurred. The median postoperative length of stay was 9.5d (range 6-16). Conclusions: These preliminary results showed favorable tumor response and acceptable tolerability for potential surgical resection. Sintilimab, doublet chemotherapy, and apatinib might offer an opportunity of cure for stage IV gastric cancer. Trial ID: NCT04267549. Clinical trial information: NCT04267549. [Table: see text]


2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Satoshi Toyota ◽  
Hiroshi Naito ◽  
Saki Motoyoshi ◽  
Ryota Nakanishi ◽  
Eiji Oki ◽  
...  

Abstract Background Chemotherapy has been considered the main treatment for stage IV gastric cancer (GC). However, advances in chemotherapy have provided new clinical approaches, permitting conversion surgery with the aim of R0 resection after resolving unresectability issues. Case presentation A 70-year-old man with gastric cancer invading the pancreatic tail and spleen and with periaortic lymph-node enlargement was admitted to our hospital. After 24 courses of nivolumab as third-line chemotherapy, periaortic lymph-node enlargement was resolved, and conversion surgery was planned. Intraoperatively, we found no peritoneal metastasis, but the distal pancreas, splenic hilum, and transverse colon were adhered to the gastric body. Therefore, we performed D2 total gastrectomy with distal pancreatosplenectomy and partial transverse colectomy. The pathological diagnosis was type III moderately differentiated tubular adenocarcinoma (tub2) with signet ring cells, stage ypT1b (SM), ly0, and v0. The pathological proximal and distal tumor margins were negative. One lymph-node metastasis was observed (No. 4d; 1/23). Postoperatively, no recurrence was observed over 7 months, without adjuvant chemotherapy. Conclusions Nivolumab may allow R0 resection in patients with unresectable gastric cancer. Conversion surgery should be considered even after third-line nivolumab treatment.


Author(s):  
Yuji Toyota ◽  
Kunio Okamoto ◽  
Norimitsu Tanaka ◽  
Hugh Shunsuke Colvin ◽  
Yuta Takahashi ◽  
...  

2021 ◽  
Vol 41 (11) ◽  
pp. 5643-5649
Author(s):  
KEISHI OKUBO ◽  
TAKAAKI ARIGAMI ◽  
DAISUKE MATSUSHITA ◽  
YOSHIKAZU UENOSONO ◽  
SHIGEHIRO YANAGITA ◽  
...  

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 164-164
Author(s):  
Tsutomu Sato ◽  
Ken Nishimura ◽  
Norisuke Nakayama ◽  
Osamu Motohashi ◽  
Kenki Segami ◽  
...  

164 Background: Conversion surgery could be an option for stage IV gastric cancer when distant metastasis (M1) is disappeared by palliative chemotherapy, however, feasibility, safety and efficacy of surgery after long-term chemotherapy remains unclear. Methods: This retrospective study examined 21 gastric cancer patients who underwent curative conversion surgery between 2001 and 2013. Postoperative complications were evaluated according to the Clavien-Dindo classification. Overall survival (OS) was estimated by Kaplan-Meier method. Results: Median follow-up period (range) was 43.9 months (7.2-72.1 months). The number of M1 factors was one in 17 patients and two in 4, including metastases to non-regional lymph node in 11, peritoneum in 11, and liver in 3. The regimen of chemotherapy was S-1/CDDP in 11 patients, S-1/docetaxel/CDDP in 5, S-1/docetaxel in 2, 5FU/leucovorin/paclitaxel in 1, CPT/CDDP in 1, and S-1 monotherapy in 1. The median duration from initiation of chemotherapy to disappearance of M1 factor was 3.5 months and the median duration from initiation of chemotherapy to the operation was 7.5 months. A total of 19 patients (90.4%) underwent over D2 lymphadenectomy including modified D2 in 2 patients, D2 in 16, and D2 plus para-aortic nodal dissection in 3. M1 tumor was not resected except para-aortic nodal dissection in 3 patients. The median operation time and bleeding were 205 minutes and 228 ml, respectively. Grade 2/3/4 morbidities were observed in 5 patients (23.8%); 2 pancreatic fistula (grade 2), 2 abdominal abscess (grade 2 and 3), and 1 anastomotic leakage (grade 3). No mortality was observed. Pathological response of the primary tumor, defined as disappearance of more than two third of the tumor cells, was 66.7% including 19.0% of complete response. The overall survival (OS) after initiation of chemotherapy was 90.5% at 1-year, 85.7% at 2-year, and 75.9% at 3-year with median survival time (MST) of 52.9 months, while OS after surgery was 90.5% at 1 year, 76.2% at 2-year, and 64.5% at 3-year with MST of 40.9 months. Conclusions: Curative conversion gastrectomy for stage IV gastric cancer was feasible and safe. Considering excellent survival, conversion surgery has a value to be evaluated in prospective studies.


2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 78-78
Author(s):  
Tamotsu Sagawa ◽  
Yutaka Okagawa ◽  
Fumito Tamura ◽  
Tsuyoshi Hayashi ◽  
Koshi Fujikawa ◽  
...  

78 Background: Conversion surgery could be an option for unresectable stage IV gastric cancer when distant metastasis (M1) is disappeared by chemotherapy. However, the indication and the optimal timing of conversion surgery in stage IV gastric cancer remain unclear, even if metastatic lesions disappear with chemotherapy. Guideline of National Comprehensive Cancer Network also shows no principle after down-staging. Methods: This retrospective study examined 34 gastric cancer patients who underwent curative conversion surgery at our institute between 2005 and 2014. Clinicopathologic characteristics and patient outcomes were analyzed, with particular focus on the potential to select patients who might benefit from surgical resection. Results: The number of M1 factors was one in 31 patients and two in 3, including metastases to non-regional lymph node in 21, peritoneum in 8, liver in 5, and lung in 3. The regimen of chemotherapy was Docetaxel/CDDP/S-1 in 23 patients, Docetaxel/CDDP/S-1+Trastuzmab in 6, S-1/CDDP in 2, Docetaxel/S-1 in 1, CPT/CDDP in 1, and S-1 monotherapy in 1. The median duration from initiation of chemotherapy to the operation was 114 days (range 37-653 days). Total gastrectomy was performed in 27 patients and distal gastrectomy was performed in 7 patients. Complete resection with no residual tumor (R0) was achieved in 23 of 34 patients, microscopic residual tumor status (R1) in 10, and macroscopic residual tumor (R2) in 1. The 3-year overall survival (OS) rate among the patients who underwent conversion therapy was 58.0% with MST of 1190 days. Univariate analysis among the patents with conversion surgery identified intestinal differentiation, pathological response grade≧1b, R0 resection as significant prognostic factors. Patients operated on more than 91 days from initiation of chemotherapy had the 3-year survival rate of 68.2%, compared to 40.0% for patients operated on less than 90 days. Conclusions: Our data demonstrate the increased 3-year survival rate associated with delayed conversion surgery for stage IV gastric cancer. Delayed conversion surgery should be considered for patients, even if metastatic lesions disappear with chemotherapy.


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