Prospective Multicenter Interventional Study of Surgical Resection for Liver Metastasis from Gastric Cancer: R0 Resection Rate, and Operative Morbidity and Mortality

Objective: The aim of this study was to compare the clinical efficacy of neoadjuvant chemoradiotherapy (NACRT) combined with postoperative adjuvant XELOX (Oxaliplatin +Capecitabine) chemotherapy and postoperative adjuvant chemotherapy (ACT) with XELOX for local advanced gastric cancer (LAGC). Methods: In this prospectively randomized trial, we investigated the effect of NACRT combined with postoperative ACT for LAGC. 60 patients were randomly divided into NACRT group and ACT group, with 30 patients in each group. Patients in NACRT group were given three-dimensional conformal radiotherapy (45 Gy/1.8 Gy/f) accompanied by synchronous XELOX of two cycles, followed by surgery, and then postoperative adjuvant XELOX chemotherapy of four cycles was performed. Patients in ACT group received surgery in advance, and then XELOX chemotherapy of six cycles was given. Results: The objective response rate of NACRT was 76.7%. The overall incidence of postoperative complications in NACRT group was not significantly different from that in ACT group (23.1% vs 30.0%, p = 0.560). The 1 year, 2 years, and 3 years progression-free survival (PFS）and overall survival (OS) in NACRT and ACT groups were 80.0% vs 56.7%, 73.3% vs 46.7%, 60.0% vs 33.3%, and 86.7% vs 80.0%, 76.7% vs 66.7%, 63.3% vs 50.0%, respectively. Patients in NACRT group showed a significantly higher R0 resection rate (84.6% vs 56.7%, p = 0.029),lower loco-regional recurrence rate (36.7% vs 11.5%, p = 0.039), longer PFS (p = 0.019) and freedom from locoregional progression(FFLP) (p = 0.004) than patients in ACT group, while there was no difference in OS (p = 0.215) and in toxicity incidence (p > 0.05). Conclusions: NACRT combined with postoperative adjuvant XELOX chemotherapy can improve R0 resection rate, reduce loco-regional recurrence, prolong PFS and FFLP without increasing the incidence of postoperative complications in patients with LAGC. Advances in knowledge: Compared with postoperative adjuvant chemotherapy, locally advanced gastric cancer patients may benefit from neoadjuvant chemoradiotherapy, and toxicity associated with chemoradiotherapy was tolerant and manageable.

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Neoadjuvant Chemotherapy Compared With Surgery Alone for Locally Advanced Cancer of the Stomach and Cardia: European Organisation for Research and Treatment of Cancer Randomized Trial 40954

Journal of Clinical Oncology ◽

10.1200/jco.2009.26.6114 ◽

2010 ◽

Vol 28 (35) ◽

pp. 5210-5218 ◽

Cited By ~ 356

Author(s):

Christoph Schuhmacher ◽

Stephan Gretschel ◽

Florian Lordick ◽

Peter Reichardt ◽

Werner Hohenberger ◽

...

Keyword(s):

Gastric Cancer ◽

Lymph Node ◽

Neoadjuvant Chemotherapy ◽

Preoperative Chemotherapy ◽

Survival Benefit ◽

Locally Advanced ◽

Postoperative Chemotherapy ◽

Phase Iii ◽

R0 Resection ◽

Resection Rate

PurposePatients with locally advanced gastric cancer benefit from combined pre- and postoperative chemotherapy, although fewer than 50% could receive postoperative chemotherapy. We examined the value of purely preoperative chemotherapy in a phase III trial with strict preoperative staging and surgical resection guidelines.Patients and MethodsPatients with locally advanced adenocarcinoma of the stomach or esophagogastric junction (AEG II and III) were randomly assigned to preoperative chemotherapy followed by surgery or to surgery alone. To detect with 80% power an improvement in median survival from 17 months with surgery alone to 24 months with neoadjuvant, 282 events were required.ResultsThis trial was stopped for poor accrual after 144 patients were randomly assigned (72:72); 52.8% patients had tumors located in the proximal third of the stomach, including AEG type II and III. The International Union Against Cancer R0 resection rate was 81.9% after neoadjuvant chemotherapy as compared with 66.7% with surgery alone (P = .036). The surgery-only group had more lymph node metastases than the neoadjuvant group (76.5% v 61.4%; P = .018). Postoperative complications were more frequent in the neoadjuvant arm (27.1% v 16.2%; P = .09). After a median follow-up of 4.4 years and 67 deaths, a survival benefit could not be shown (hazard ratio, 0.84; 95% CI, 0.52 to 1.35; P = .466).ConclusionThis trial showed a significantly increased R0 resection rate but failed to demonstrate a survival benefit. Possible explanations are low statistical power, a high rate of proximal gastric cancer including AEG and/or a better outcome than expected after radical surgery alone due to the high quality of surgery with resections of regional lymph nodes outside the perigastic area (celiac trunc, hepatic ligament, lymph node at a. lienalis; D2).

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A Long Surviving Case of Gastric Cancer with Liver Metastasis and Portal Vein Thrombus Successfully Treated by Surgical Resection after S-1 and CDDP Chemotherapy

The Japanese Journal of Gastroenterological Surgery ◽

10.5833/jjgs.2014.0065 ◽

2015 ◽

Vol 48 (4) ◽

pp. 297-305 ◽

Cited By ~ 4

Author(s):

Hiroto Nishino ◽

Ben Sasaki ◽

Yoshito Asao ◽

Hiroaki Furuyama ◽

Tsunehiro Yoshimura

Keyword(s):

Gastric Cancer ◽

Liver Metastasis ◽

Portal Vein ◽

Surgical Resection ◽

Portal Vein Thrombus

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Apatinib combined with SOX neoadjuvant therapy for locally advanced gastric cancer: A multicenter, single-armed, prospective study.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.367 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 367-367

Author(s):

Jian-Xian Lin ◽

Changming Huang

Keyword(s):

Gastric Cancer ◽

Prospective Study ◽

Neoadjuvant Therapy ◽

Advanced Gastric Cancer ◽

Locally Advanced ◽

Gastric Surgery ◽

R0 Resection ◽

Resection Rate ◽

Locally Advanced Gastric Cancer ◽

Tumor Response Evaluation

367 Background: Molecular targeted therapy has made great progress in the treatment of gastric cancer. In some previous studies, apatinib, an oral small molecular of VEGFR-2 TKI, had been confirmed can improve OS and PFS with an acceptable safety profile in patients with advanced gastric cancer refractory to two or more lines of prior chemotherapy. However, there is limited evidence about the safety and feasibility of apatinib combined with SOX regimen as neoadjuvant therapy for locally advanced gastric cancer (AGC). Methods: This is a multicenter, single-armed, prospective study. Patients with AGC (cT2-4N+M0) without prior anti-cancer strategies were included. Patients were received 2 to 5 cycles (21 days a cycle) of neoadjuvant therapy using S-1 (po, 40-60 mg bid, day1-day14), oxaliplatin (iv, 130 mg/m2, day1), and apatinib (po, 500 mg qd). Apatinib was prohibited in the last cycle. The operation should be performed 2 to 4 weeks later of the neoadjuvant therapy. The primary endpoint was R0 resection rate. The secondary endpoint included safety, ORR, and DCR. Results: A total of 56 patients from 10 centers in China were recruited. There were 43 males and 13 females. The median age was 63.04 years (range 41-75 years). There were 43 patients with tumor response evaluation, 29 patients (67.4%) had partial response (PR), 12 patients (27.9%) had stable disease (SD), and 2 patient (4.6%) had progressive disease (PD). The ORR and DCR were 67.4% (29/43) and 95.3% (41/43), respectively. 36 patients received gastric surgery, the R0 resection rate was 97.2%, 3 patients had postoperative complication: one had intestinal obstruction and 2 had pneumonia (all Clavien-Dindo classification less than grade II). 46 patients were included for safety analysis. The incidence of adverse events (AEs) and grade 3/4 AEs were 84.8% (39/46) and 17.4% (8/46), respectively. The most common AEs were neutropenia (40%), low platelet count (40%), leucopenia (32.6%), vomit (13%). Conclusions: This prospective study shows that neoadjuvant therapy using apatinib plus SOX brings clinical benefit to AGC with a high disease control rate and tolerable adverse reactions. Clinical trial information: NCT 03192735.

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Prognostic Value of Lymph Node Ratio in Patients Receiving Combined Surgical Resection for Gastric Cancer Liver Metastasis

Medicine ◽

10.1097/md.0000000000003395 ◽

2016 ◽

Vol 95 (16) ◽

pp. e3395 ◽

Cited By ~ 3

Author(s):

Mu-Xing Li ◽

Zheng-Xiong Jin ◽

Jian-Guo Zhou ◽

Jian-Ming Ying ◽

Zhi-Yong Liang ◽

...

Keyword(s):

Gastric Cancer ◽

Lymph Node ◽

Liver Metastasis ◽

Surgical Resection ◽

Prognostic Value ◽

Lymph Node Ratio ◽

Node Ratio

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Long-term outcomes after surgical resection for gastric cancer liver metastasis: an analysis of 64 macroscopically complete resections

Langenbeck s Archives of Surgery ◽

10.1007/s00423-012-0959-z ◽

2012 ◽

Vol 397 (6) ◽

pp. 951-957 ◽

Cited By ~ 81

Author(s):

Nobuyuki Takemura ◽

Akio Saiura ◽

Rintaro Koga ◽

Junichi Arita ◽

Ryuji Yoshioka ◽

...

Keyword(s):

Gastric Cancer ◽

Liver Metastasis ◽

Surgical Resection ◽

Long Term Outcomes

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Prognostic value of duodenal invasion length in patients with gastric cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.4_suppl.24 ◽

2011 ◽

Vol 29 (4_suppl) ◽

pp. 24-24

Author(s):

N. Oshima ◽

M. Tokunaga ◽

Y. Tanizawa ◽

E. Bando ◽

T. Kawamura ◽

...

Keyword(s):

Gastric Cancer ◽

Survival Rate ◽

Cancer Patients ◽

Curative Resection ◽

R0 Resection ◽

Resection Rate ◽

Direct Invasion ◽

Curative Operation ◽

Duodenal Invasion ◽

Gastric Cancer Patients

24 Background: Duodenal invasion (DI) has been considered as a poor prognostic factor of gastric cancer patients. Not all the patients would be able to undergo curative operation. Neoadjuvant chemotherapy (NAC) may improve the rate of curative operation of these patients. In this study, we investigated whether the length of duodenal invasion preoperative diagnosis can be one of factor to decide indication of NAC. Methods: A total of 118 gastric cancer patients with clinically evident DI, who underwent laparotomy at our center, were enrolled in this study. 42 patients with DI length 20 mm or longer were categorized into long invasion group (LI), 76 patients with DI length shorter than 20 mm were categorized into short invasion group (SI). Clinicopathologic features, rate of direct invasion and lymph nodes involvement, R0 resection, and survival rate were compared between two groups. Results: Resection rate was significantly different between two groups: SI group (85.5%; 65/76), LI group (69.0%; 29/42). Direct invasion to adjacent organs was significantly more frequently observed in LI group (21%; 6/29) than SI group (4 %; 3/65, p = 0.02). In LI group, pancreas invasion was observed in all patients except for one patient. Multivariate analysis to predict the adjacent organ invasion revealed that CT diagnosis (p = 0.005) and invasion length (p = 0.01) were selected as risk factors of direct invasion to adjacent organs. There was no significant difference of nodal involvement between LI group (83%; 24/29) and SI group (83%; 54/65 p = 0.99). The 5-year survival rate was 19% in LI group and 43% in SI group (p = 0.23). The number of patients who underwent R0 resection was more frequently in SI group (75.4%; 49/65) than SI group (69.1%; 16/29). The factors of R1 or R2 resection were metastasis of peritoneum or direct invasion to adjacent organs. Conclusions: In patients with long duodenal invasion, direct invasion to the pancreas was more frequently observed, and resulted in low curative resection rate and poor survival. Preoperative chemotherapy may improve the curative resection rate and survival in these patients. Prospective study is warranted to evaluate the efficacy of NAC for these patients. No significant financial relationships to disclose.

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A phase II study of panitumumab with FOLFOX or FOLFIRI as first-line chemotherapy for KRAS-wild type metastatic colorectal cancer: The PaFF-J study.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.4_suppl.722 ◽

2017 ◽

Vol 35 (4_suppl) ◽

pp. 722-722 ◽

Cited By ~ 1

Author(s):

Eiji Shinozaki ◽

Megumi Ishiguro ◽

Eiji Nakatani ◽

Tatsuro Yamaguchi ◽

Masato Nakamura ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Surgical Resection ◽

Phase Ii ◽

R0 Resection ◽

Strong Impact ◽

Tumor Shrinkage ◽

Wild Type ◽

Resection Rate ◽

Line Chemotherapy

722 Background: For the patients with unresectable metastatic colorectal cancer (mCRC), response to the1st line chemotherapy has strong impact on their prognosis. Shrinkage of tumors may result in conversion to surgical resection and, concurrently, improved their survival. We conducted a multicenter phase II trial to investigate the efficacy and safety of panitumumab (Pmab) with chemotherapy as the 1st line treatment in Japanese patients with mCRC. Methods: Patients with no prior chemotherapy for unresectable, KRAS wild type mCRC, 20-80 years, and PS 0-1 were arbitrarily received either FOLFOX + Pmab or FOLFIRI + Pmab. Patients were evaluated every 8 weeks until progression. The primary endpoint was overall response rate (ORR), the secondary endpoints were progression-free survival (PFS), overall survival (OS), disease control rate (DCR), R0 resection rate, and safety. Results: A total of 162 patients (140 with FOLFOX + Pmab and 22 with FOLFIRI + Pmab) were analyzed. Median follow-up was 28.2 months, median age at enrollment was 64.5 years, and 17.9% of the patients was recurrent disease. Number of target organ was 1 in 35.2%, 2 in 40.7%, and ≥ 3 in 24.1% of the subjects. Median administered cycle was 7, and median treatment duration was 16 weeks. ORR was 51.2% (95%CI: 43.3-59.2), and DCR was 82.1% (95%CI: 75.3-87.7). ≥ 30% tumor shrinkage (PR-in) was observed in 115 patients (71.0%). Median time to PR-in and maximum shrinkage was 10 and 16 weeks, respectively. Surgical resection was done in 66 patients (40.7%), of which R0 was in 43 patients; R0 resection rate was 26.5% (95%CI: 19.9-34.0). Median PFS and OS was 9.2 (95%CI: 7.2-11.4) and 33.8 months (95%CI: 29.4-43.1), respectively. ≥ Grade 3 adverse events with > 5% incidence were neutropenia (31.8%), stomatitis (10.5%), rash acneiform (9.9%), paronychia (9.3%), anorexia (8.6%), and diarrhea (6.2%). Conclusions: In our study, OS was favorable with high R0 resection rate, whereas ORR, DCR, PFS and toxicities were similar to those in previously reported studies. Because the maximum tumor shrinkage was observed around 16 weeks, optimal timing for considering conversion surgery might be 16 weeks from the start of treatment. Clinical trial information: UMIN000004991.

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Early results of the randomized, multicenter, controlled evaluation of S-1 and oxaliplatin as neoadjuvant chemotherapy for Chinese advanced gastric cancer patients (RESONANCE Trial).

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.280 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 280-280 ◽

Cited By ~ 1

Author(s):

Xinxin Wang ◽

Shuo Li ◽

Tianyu Xie ◽

Yixun Lu ◽

Xin Guo ◽

...

Keyword(s):

Gastric Cancer ◽

Clinical Trials ◽

Neoadjuvant Chemotherapy ◽

Neoadjuvant Therapy ◽

R0 Resection ◽

Perioperative Chemotherapy ◽

Resection Rate ◽

Early Results ◽

Lymph Nodes Dissection ◽

Gastric Cancer Patients

280 Background: Perioperative chemotherapy brings potential benefits to growing patients with gastric cancer based on several clinical trials including MAGIC, ACTS-GC, CLASSIC and INT-0116. However, the effect of neoadjuvant therapy before D2 gastrectomy remains pending. According to phase II clinical trials, SOX regimen as neoadjuvant chemotherapy is associated with increased rate of D2 lymph nodes dissection and R0 resection. We hypothesize that SOX regimen can improve survival of patients with gastric cancer. Methods: Through CT, EUS and laparoscopic exploration, patients with gastric cancer on the stage IIA-IIIC were included in the study and divided into 2 groups randomly. Patients in neoadjuvant group received 2-4 cycles of SOX before surgery and 4-6 cycles after surgery, while patients in no neoadjuvant group received 8 cycles after surgery. The primary endpoint was 3-y DFS and the secondary endpoint were 5-y OS, ORR, D2/R0 resection rate and side effect. Results: A total of 772 patients were enrolled in the study between September 2012 and July 2019. After neoadjuvant therapy, the downstaging was found in neoadjuvant group (261/386, 67.6%). The pathological efficiency rate and pCR rate of neoadjuvant group were 67.8% and 23.6% respectively. The R0 resection rate in neoadjuvant group was significantly higher than that in adjuvant group(73.1% vs 58.1%, p < 0.05). There was no difference in terms of surgical time, blood loss, postoperative complications and hospital stay. Conclusions: SOX makes increased rate of R0 resection, acceptable adverse effect and no impression on surgeries, which suggest that perioperative chemotherapy using SOX can prolong median survival time, DFS and OS. Clinical trial information: NCT01583361.

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