Survival benefit of conversion therapy after intensive chemotherapy for unresectable metastatic gastric cancer: A propensity score-matched analysis.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 354-354
Author(s):  
Hiroyuki Ohnuma ◽  
Yasushi Sato ◽  
Ginji Omori ◽  
Naoki Onoyama ◽  
Saki Ameda ◽  
...  

354 Background: The significance of conversion therapy (CT), whereby patients (pts) with unresectable disease respond to chemotherapy and subsequently receive surgery with curative intent (adjuvant surgery: AS), has been specifically established for metastatic colorectal cancer. However, such a strategy for advanced or recurrent gastric cancer (AGC) remains controversial. This study aims to clarify the clinical significance of CT for AGC. Methods: In this retrospective multi-institution observational study, we analyzed 168 AGC pts who received chemotherapy consisting of docetaxel, cisplatin or oxaliplatin, and S-1 ± trastuzumab between 2003 and 2019. We divided pts into two groups: those who underwent CT (group CT) or chemotherapy only (group C). Propensity score analysis with 1:1 matching minimized confounding bias when comparing efficacy and safety between groups. Results: A tumor response to chemotherapy was observed in 82.4% of all cases, while 34.5% (58/168) underwent AS. Fifty-one of the 58 pts underwent an R0 resection, and 79.3% were deemed histological responders. After matching, 44 pairs of C and CT pts were selected; significant differences in baseline characteristics were not observed. Incidences of adverse events during chemotherapy were similar between groups, with neutropenia and febrile neutropenia as common grade 3–4 events. Compared with group C, group CT had a significantly better median overall survival (OS) (15.5 vs. 46.0 months; hazard ratio [HR] 0.32; 95% confidence interval [CI] 0.18–0.58; p < .001), and a prolonged progression-free survival (6.5 vs.22.6 months; HR 0.33; 95% CI 0.19–0.56; p < .001). Subgroup analysis of OS showed a favorable trend for CT for almost all parameters. In a multivariate analysis, ECOG performance status (HR 0.10; 95% CI 0.03–0.31) and AS (HR 0.20; 95% CI 0.10–0.40) correlated with favorable OS. In the CT group, pathological response was an independent prognostic factor (HR 0.16; 95% CI 0.06–0.39). Conclusions: CT was associated with better outcomes in AGC pts, even after baseline adjustment. Our data warrants further large-scale studies to establish a conversion therapeutic strategy.

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yusuke Sakimura ◽  
Noriyuki Inaki ◽  
Toshikatsu Tsuji ◽  
Shinichi Kadoya ◽  
Hiroyuki Bando

Abstract Omentectomy is conducted for advanced gastric cancer (AGC) patients as radical surgery without an adequate discussion of the effect. This study was conducted to reveal the impact of omentum-preserving gastrectomy on postoperative outcomes. AGC patients with cT3 and 4 disease who underwent total or distal gastrectomy with R0 resection were identified retrospectively. They were divided into the omentum-preserved group (OPG) and the omentum-resected group (ORG) and matched with propensity score matching with multiple imputation for missing values. Three-year overall survival (OS) and 3-year relapse-free survival (RFS) were compared, and the first recurrence site and complications were analysed. The numbers of eligible patients were 94 in the OPG and 144 in the ORG, and after matching, the number was 73 in each group. No significant difference was found in the 3-year OS rate (OPG: 78.9 vs. ORG: 78.9, P = 0.54) or the 3-year RFS rate (OPG: 77.8 vs. ORG: 68.2, P = 0.24). The proportions of peritoneal carcinomatosis and peritoneal dissemination as the first recurrence site and the rate and severity of complications were similar in the two groups. Omentectomy is not required for radical gastrectomy for AGC.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3540-3540 ◽  
Author(s):  
Shota Fukuoka ◽  
Toshikazu Moriwaki ◽  
Hiroya Taniguchi ◽  
Atsuo Takashima ◽  
Yosuke Kumekawa ◽  
...  

3540 Background: It is unclear which drug of REG or TAS-102 should be used earlier for the patients with metastatic colorectal cancer (mCRC) who have access to both drugs. This study investigated the comparison of the efficacy between REG and TAS-102 in patients with refractory to standard chemotherapies. Methods: The clinical data of patients who were treated with REG or TAS-102 among these drugs naive mCRC patients between Jun 2014 and Sep 2015 were retrospectively delivered from 24 institutions of Japanese Society for Cancer of the Colon and Rectum (JSCCR). The primary endpoint was overall survival (OS). Propensity score (PS) was calculated with a logistic regression, in which using baseline parameters were included. Two methods, adjusted and matched analysis, to take propensity score were used. The clinical outcomes were evaluated with Kaplan-Meier method and Cox models based on PS adjustment and matching. Results: Total of 589 patients were enrolled and 550 patients (223 patients in the REG group and 327 patients in the TAS-102 group) met criteria for inclusion in the analysis. The results from PS adjusted analyses showed that OS was similar between the two groups (HR of TAS-102 to REG, 0.96; 95% confidence interval, 0.78–1.18). There were also no statistically significant differences between two groups for progression-free survival (HR 0.94) and time to ECOG Performance status≥2 (HR 1.00), expect for time to treatment failure (HR 0.81; P = 0.025). In the subgroup analysis, REG showed favorable survival compared with TAS-102 in the age of < 65 years patients and unfavorable survival in ≥65 years patients (P for interaction = 0.012). In the PS matched sample (174 patients in each group), the clinical outcomes were similar to the results of the PS adjusted analysis. Conclusions: Although REG and TAS-102 showed a similar efficacy in mCRC patients with refractory to standard chemotherapies, the choice of the drug by age might affect the survival. Supported by JSCCR. Clinical trial information: UMIN000020416


2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 53-53 ◽  
Author(s):  
Xiangdong Cheng ◽  
Zhiyuan Xu ◽  
Yian Du ◽  
Ping Hu ◽  
Guofa Yu ◽  
...  

53 Background: Occasionally, an initially unresectable gastric cancer (GC) can be converted to a resectable one by chemotherapy. Combination with inhibitors against VEGFR-2 can lead to a clinical improvement. We aimed to investigate the efficacy and safety of S1/paclitaxel chemotherapy plus apatinib, a novel inhibitor of VEGFR-2, in the conversion therapy of unresectable GC. Methods: This was a multicentre, single-arm, open-label, phase II design. Eligible patients (pts) were aged 20-70 years and had histologically proven unresectable, HER-2 negative, advanced GC with a single non-curable factor confined to either the liver (H1), peritoneum (P1), or para-aortic lymph nodes (16a1/b2). The ECOG performance status was 0-2. No prior radiotherapy, chemotherapy, target therapy or immunotherapy was allowed. Patients received 2 cycles of S1/paclitaxel chemotherapy (S1: 60 mg, oral, bid for 2 weeks followed by a drug-free interval of 1 week; paclitaxel: 150 mg/m2, iv, 3h, on day 1) plus apatinib (500 mg, oral, qd) and 1 cycle of S1/paclitaxel chemotherapy prior to radical surgery. Three cycles of adjuvant chemotherapy (S1 and apatinib) were given 4-6 weeks after surgery. Primary endpoint was R0 resection rate. Thirty-three pts were enrolled. Results: Among the 28 pts eligible for preoperative efficacy evaluation, 21 achieved partial response (PR), 5 had stable disease (SD), and 2 had progressive disease (PD), resulting in an overall response rate of 75.0% and a disease control rate of 92.9%. Of the 21 pts with PR, 3 refused consents for surgery and 18 achieved R0 resection. The incidence of adverse events (AEs) was 73.9%. The common hematologic AEs were neutropenia (60.9%), leukopenia (52.2%) and hemoglobin decrease (47.8%), and nonhematologic AEs included hyperbilirubinemia (56.5%), hand-foot syndrome (34.8%), oral mucositis (30.4%), fatigue (30.4%), proteinuria (21.7%) and hypocalcemia (21.7%). There was no severe surgery-related complication. Conclusions: Combination of apatinib with S1/paclitaxel chemotherapy shows clinical benefits in unresectable GC, with acceptable safety profile. Clinical trial information: NCT02529878.


2021 ◽  
Author(s):  
Shaopeng Zhang ◽  
Song Wu ◽  
Yuan Kong ◽  
Wei Li

Abstract 【Objective】 To analyze the clinical efficacy of systemic chemotherapy combined with intraperitoneal hyperthermic perfusion in the treatment of locally invasive stage III gastric cancer and stage IV gastric cancer. 【Methods】 The clinical data of 191 patients with gastric cancer who received systemic chemotherapy combined with intraperitoneal hyperthermic perfusion from June 2010 to December 2018 were retrospectively analyzed. 【Results】 The unresectable factors in 191 patients with gastric cancer included peritoneum metastasis (106), local invasion (67), liver metastasis (25), lung metastasis (3), bone metastasis (4), adnexal metastasis (3) and adrenal metastasis (4). After conversion therapy, 191 patients were divided into finished conversion group and non-finished group. There were significant differences in T stage, M stage and tumor differentiation between the two groups. During the course of chemotherapy, 11 patients had grade 3 or 4 chemotherapy adverse reactions. The median survival was 36 months in the finished conversion group and 14 months in the non-finished group. The median survival of the 69 R0 resected patients was 38 months, which was higher than that of chemotherapy alone (14 months), best supportive care (13 months) and patients who completed chemotherapy without R0 resection (19 months). Univariate Cox survival analysis found that N stage, R0 resection, response to chemotherapy and unresectable factors were prognostic factors. Multivariate Cox survival analysis showed that N-stage, response to chemotherapy and unresectable factors were independent prognostic factors. 【 Conclusion 】 For unresectable gastric cancer patients, surgical treatment after chemotherapy can prolong survival. Radical surgical treatment after conversion therapy and chemotherapy response are important factors related to patient survival. Chemotherapy alone can prolong survival in primary unresectable gastric cancer, but with limited effect.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4627-4627
Author(s):  
D. J. Cohen ◽  
T. Ryan ◽  
E. Newman ◽  
S. Iqbal ◽  
M. Liu ◽  
...  

4627 Background: ChemoRT after surgery for locally advanced gastric cancer improves overall and relapse-free survival (OS and RFS) compared to observation (NEJM 2000,345:725–30). However, loco-regional recurrences (>50%) remain high and we hypothesized that adding IP FUDR would further improve outcome. Methods: Patients (pts) ECOG performance status (PS) 0–2, gastric/gastroesphogeal(GEJ) adenocarcinoma stage Ib-IV (M0) undergoing R0 resection were eligible, and had insertion of IP catheters at surgery. IP FUDR(3gm/dose/day) was given on protocol days 1, 2, 3 and 15, 16, 17 prior to 5-FU/LV and external beam RT (45Gy) as in cited study. Simon 2-stage optimum design was used to demonstrate safety. Endpoints also included were loco-regional recurrence and survival. Results: 28 pts with gastric/GEJ adenocarcinoma (25/3) were enrolled from 2002 to 2006 at 2 institutions: median age 59.5 years (range 39–81), M /F (21/7). R0 gastric resection was performed with dissection of median 22 (range 8–102) lymph nodes(LN’s). 22/28 pts were lymph node positive. Full dose IP FUDR was completed in 20/28 pts. 4 pts required dose reduction (1 for grade(gr) 2 hepatic enzyme elevation, 2 gr 2 neutropenia, 1 gr 4 neutropenia), 3 discontinued therapy (1 gr 3 abdominal pain, 1 GI abscess, and 1 bleeding arterial pseudoaneurysm). One pt received no IP treatment due to catheter failure. 24/28 pts completed chemoRT and had toxicity comparable to that previously reported in the Intergroup 0116 trial. At 26 month median follow up (range 2.8–43.4), of the 26 pts evaluable for response, 16 pts are NED, 6 alive with disease, 3 dead of disease, and 1 dead from other cause. 5 recurrences were intra-abdominal, 1 local, 2 distant, and 1 at multiple sites. At present analysis, the median RFS is 32.5 months. Conclusions: IP FUDR prior to chemoRT after R0 gastric cancer resection is well tolerated. A randomized study to test its role in reducing regional recurrence and improving outcome is warranted. (FDA Orphan Products grant# FD-R-2150–04) No significant financial relationships to disclose.


2021 ◽  
Vol 20 ◽  
pp. 153303382110363
Author(s):  
Xin Zhang ◽  
Hejing Huang ◽  
Dejun Yang ◽  
Peng Wang ◽  
Xin Huang ◽  
...  

Background: The optimal treatment for gastric cancer with peritoneal metastasis (GCPM) remains debatable. This study aimed to compare the efficacy and safety of neoadjuvant intraperitoneal and systemic chemotherapy (NIPS) versus neoadjuvant systemic chemotherapy (NSC) for GCPM. Methods: Patients of GCPM received neoadjuvant chemotherapy with docetaxel, oxaliplatin and S-1 between January 2011 and June 2019 were retrospectively evaluated. Propensity score matched (PSM) analysis was carried out to reduce the selection bias. Multivariate Cox regression model was applied to screen the prognostic factors. Results: After PSM processing, 71 patients in each group were matched among the 186 GCPM patients included. NIPS yielded a better ascites and cytology response to chemotherapy, higher conversion resection rate and R0 resection rate than NSC. The overall survival (OS) rate in NIPS group was better than that in NSC group. Multivariate analysis revealed that the P stage, ascites response, conversion surgery rate and R0 resection rate were independent prognostic factors. Subgroup analysis indicated that NIPS showed a survival benefit over NSC only in patients with cT3-4a, P1-2, whose cytology turned negative, and who received conversion surgery; while not in patients with cT4b, P0 or P3, whose cytology did not turn negative, or who did not receive conversion surgery. Conclusions: NIPS is a safe and feasible treatment for GCPM, which showed more benefit than NSC.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Honghu Wang ◽  
Hao Qi ◽  
Xiaofang Liu ◽  
Ziming Gao ◽  
Iko Hidasa ◽  
...  

AbstractThe staging system of remnant gastric cancer (RGC) has not yet been established, with the current staging being based on the guidelines for primary gastric cancer. Often, surgeries for RGC fail to achieve the > 15 lymph nodes needed for TNM staging. Compared with the pN staging system, lymph node ratio (NR) may be more accurate for RGC staging and prognosis prediction. We retrospectively analyzed the data of 208 patients who underwent R0 gastrectomy with curative intent and who have ≤ 15 retrieved lymph nodes (RLNs) for RGC between 2000 and 2014. The patients were divided into four groups on the basis of the NR cutoffs: rN0: 0; rN1: > 0 and ≤ 1/6; rN2: > 1/6 and ≤ 1/2; and rN3: > 1/2. The 5-year overall survival (OS) rates for rN0, rN1, rN2, and rN3 were 84.3%, 64.7%, 31.5%, and 12.7%, respectively. Multivariable analyses revealed that tumor size (p = 0.005), lymphovascular invasion (p = 0.023), and NR (p < 0.001), but not pN stage (p = 0.682), were independent factors for OS. When the RLN count is ≤ 15, the NR is superior to pN as an important and independent prognostic index of RGC, thus predicting the prognosis of RGC patients more accurately.


Surgery ◽  
2019 ◽  
Vol 166 (3) ◽  
pp. 297-304 ◽  
Author(s):  
Cheng-Le Zhuang ◽  
Xian Shen ◽  
Yang-Yang Huang ◽  
Feng-Min Zhang ◽  
Xi-Yi Chen ◽  
...  

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16034-e16034
Author(s):  
Jin Li ◽  
Shukui Qin ◽  
Lu Wen ◽  
Junsheng Wang ◽  
Wenying Deng ◽  
...  

e16034 Background: Apatinib, a small molecule multi-target tyrosine kinase inhibitor with high selectivity for VEGFR-2, has been approved for the treatment of advanced gastric cancer or gastroesophageal adenocarcinoma in China by significantly improving progression-free survival (PFS) and overall survival (OS). Here, we report safety and efficacy data from an open-label, single-arm, multicenter, phase IV trial of apatinib as a third-line or later line treatment for advanced gastric cancer. Methods: Eligible patients had histologically or cytologically confirmed advanced gastric cancer or gastroesophageal junction adenocarcinoma; and an Eastern Cooperative Oncology Group (ECOG) performance status of 0–2; and adequate haematological and hepatic function; and failure of at least two lines of chemotherapy. Patients received oral apatinib until disease progression, death or unacceptable toxicity. The primary endpoint was safety, and secondary endpoints included PFS and OS. Results: The intention-to-treat population (ITT) included 2004 patients. At baseline, the median age was 59 (range, 19-85) years, ECOG performance status of 0/1/2 (%) was 15.4/68.8/15.1, and stage III/IV was 3.5/96.4; 98.8% had metastases, and among which metastatic foci≤2/ > 2 was 64.5/34.2 (%), respectively. 89.6% of the patients were given apatinib 500mg as the initial does and the median treatment duration was 56 days. After a median follow-up of 126.5 days, adverse events (AEs) occurred in 95.1% of the patients and 70.3% were grade ≥3. 87.9% of the patients experienced treatment-related AEs (TRAEs), of which 51% had grade ≥3, 12.3% and 16.8% reduced dose and discontinued the treatment, respectively. 57 (2.9%) TRAEs-related deaths were reported, mainly because of gastrointestinal bleeding (16 cases), upper gastrointestinal haemorrhage (7), cerebral haemorrhage (2), and gastric perforation (1). The incidence of TRAEs of special interest was 74.3%; 38.1% of patients developed grade≥3, mainly including hypertension (26.3%), bleeding (5.1%), proteinuria (4.5%), and hand-foot syndrome (3.1%). In an ITT population, median PFS was 2.7 months (95%CI 2.23-2.79) and median OS was 5.8 months (95% CI 5.42-6.11). Conclusions: This study confirms that apatinib has a well-established and manageable safety profile and survival benefit as third or later line therapy for patients with advanced gastric cancer or gastroesophageal junction adenocarcinoma. Clinical trial information: NCT02426034.


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