Negative impact of intraoperative blood loss on long-term outcome after curative gastrectomy for advanced gastric cancer: exploratory analysis of the JCOG1001 phase III trial

86 Background: The number of reports investigating the impact of postoperative complications on long-term outcome following curative gastrectomy is limited and still remains unclear. The aim of this study is to clarify the effect of postoperative intra-abdominal infectious complications on overall survival (OS) and relapse-free survival (RFS) following curative gastrectomy. Methods: Three hundred and sixty-seven patients pts who underwent curative gastrectomy for gastric cancer between June 2003 and December 2004 at Shizuoka Cancer Center were included. Clinicopathological features and effects of postoperative intra-abdominal infectious complications on OS and RFS were investigated. In this study, postoperative intra-abdominal infectious complications were defined as Clavien-Dindo grade II or more severe pancreas fistula, anastomotic leak, or intra-abdominal abscess. Results: Median age was 63 years, male-female ratio was 2:1. Pathological stage was Stage I; 225 patients, stage II; 72 patients, stage III; 64 patients, and stage IV; 6 patients. Median observation periods of survivors were 71 months. Of 367 patients, 32 patients (8.7%) had intra-abdominal infectious complications. Overall 5-year survival rate was significantly better in patients without complications than in those with complications (86.1 vs 67.9%, P<0.001). The same trend was observed even after stratification by pathological stage (Stage II; 76.9 vs 66.7%, P=0.254, Stage III; 62.1 vs 40.9%, P=0.218) although each difference was not statistically significant. Relapse free 5-year survival rate was significantly better in patient without complications (85.0 vs 64.9%, P=0.002), and the same trend was also observed after stratification by pathological stage. Conclusions: Postoperative intra-abdominal infectious complications adversely affect overall and relapse free survival of patients following curative gastrectomy. Reduced incidence of infectious complications may be beneficial to improve long-term outcome of patients with gastric cancer.

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Long-term outcome of a randomized phase III trial exploring the significance of extensive intraoperative peritoneal lavage in addition to standard treatment for ≥ T3 resectable gastric cancer: CCOG 1102.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.4_suppl.1 ◽

2018 ◽

Vol 36 (4_suppl) ◽

pp. 1-1 ◽

Cited By ~ 2

Author(s):

Daishi Morimoto ◽

Kazunari Misawa ◽

Yoshinari Mochizuki ◽

Mitsuru Sakai ◽

Jin Teramoto ◽

...

Keyword(s):

Gastric Cancer ◽

Peritoneal Lavage ◽

Disease Free Survival ◽

Phase Iii ◽

Small Scale ◽

Clinicopathologic Characteristics ◽

Term Outcome ◽

Long Term Outcome ◽

Phase Iii Trial ◽

Significant Difference

1 Background: Extensive intraoperative peritoneal lavage (EIPL) for gastric cancer reportedly improved survival by physically removing and reducing intraperitoneal-free cancer cells in a small-scale randomized trial (Ann Surg 2009). To confirm this, we conducted a multicenter randomized Phase III trial. Methods: Eligibility criteria: (i) histologically confirmed primary gastric adenocarcinoma, (ii) clinically T3(SS), T4a(SE) or T4b(SI), (iii) clinically M0, and (iv) scheduled for total or distal gastrectomy. Patients were intraoperatively randomized to either the EIPL group or the non-EIPL group after confirming the ≥T3 status and resectability. In the EIPL group, peritoneal lavage was conducted at least 10 times using 1L of saline before the closure of the abdomen. In the non-EIPL group, the lavage was conducted with ≤3L of saline. The primary end-point was disease-free survival (DFS). To detect the difference of 15% in 3-year DFS with a both-sided alpha of 5% and 80% power, the planned sample size was 300 cases. This study was registered as UMIN000005907. Results: Between July 2011 and January 2014, 314 patients were registered from 15 institutions. After excluding the R1/R2 resection cases, 295 patients (145 in the EIPL group and 150 in the non-EIPL group) were analyzed. There were no significant differences between the groups in clinicopathologic characteristics. The median volume of saline for the peritoneal lavage was 10.0 L (10 - 12) for the EIPL group and 3.0 L (1 - 4) for the non-EIPL group. No difference was observed in the incidence of postoperative complications. The 3-year DFS was 63.9% in the EIPL group and 59.7% in the non-EIPL group (p = 0.25, Hazard ratio 0.81 [95% CI 0.57-1.16]). The overall survival rate of the EIPL group and non-EIPL group were 75.0%, 73.7% (3 years), and 62.5%, 57.1% (5 years), respectively (p = 0.65). In the subset analysis, no subgroup with significant difference in survival was identified. Conclusions: Although EIPL for advanced gastric cancer was safe and suggested some efficacy, the primary endpoint designed based on the previous small-scale trial was not met. Clinical trial information: 000005907.

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Thalidomide / Dexamethasone (TD) Vs. Bortezomib (Velcade)â/Thalidomide / Dexamethasone (VTD) Vs. VBMCP/VBAD/Velcadeâ as Induction Regimens Prior Autologous Stem Cell Transplantation (ASCT) in Multiple Myeloma (MM): Results of a Phase III PETHEMA/GEM Trial.

Blood ◽

10.1182/blood.v114.22.130.130 ◽

2009 ◽

Vol 114 (22) ◽

pp. 130-130 ◽

Cited By ~ 17

Author(s):

Laura Rosiñol ◽

Ma Teresa Cibeira ◽

Joaquin Martinez ◽

Maria Victoria Mateos ◽

Albert Oriol ◽

...

Keyword(s):

High Risk ◽

Induction Therapy ◽

High Risk Group ◽

Phase Iii ◽

Term Outcome ◽

Long Term Outcome ◽

Phase Iii Trial ◽

Grade 3

Abstract Abstract 130 In April 2006, the Spanish Myeloma Group (PETHEMA/GEM) activated a randomized phase III trial comparing TD vs. VTD vs. VBMCP/VBAD/Velcadeâ in patients 65 years-old or younger with newly diagnosed symptomatic MM, followed by ASCT with MEL-200. The primary end points were response rate after induction and after ASCT and time to progression. TD consisted of thalidomide 200 mg daily (escalating doses in the first cycle) and dexamethasone 40 mg on days 1–4 and 9–12 at 4-week intervals for 6 cycles. The VTD regimen was identical to TD plus Velcade 1.3 mg/m2 on days 1,4,8,11 of each cycle. Combination chemotherapy plus Velcadeâ consisted of 4 cycles of VBMCP/VBAD on an alternating basis followed by 2 cycles of Velcadeâ (1.3 mg/m2 on days 1,4,8, and 11 every 3 weeks). The duration of the induction therapy was 24 weeks in all arms. From April 6, 2006 to August 5, 2009 the 390 planned patients entered the study. As of December 31, 2008, 305 patients (median age: 57 yrs, M: 156, F:149; IgG. 181, IgA: 71, light chain: 43, others: 10) entered the study and are the basis of the current analysis. Fifty-six (18%) patients had soft-tissue extramedullary plasmacytomas (EMP) and the stage according to the ISS was I in 39%, II in 41 %, III in 19 % and unknown in 1%. The prognostic factors, including cytogenetics, was similar in the 3 arms. Fifty-five (18%) patients had high-risk cytogenetics (t(4;14), t(14;16) and/or 17p deletion). Two-hundred and ninety-nine patients (TD:103, VTD: 99 and VBMCP/VBAD/Velcade®: 97) were evaluable for response and toxicity to induction therapy. The ≥ PR rate was 64%, 82% and 75% with TD, VTD and VBMCP/VBAD/Velcade®, respectively (p=NS). The IF negative CR rate was significantly higher with VTD (29%) and with VBMCP/VBAD/Velcade® (25%) than with TD (14%) (p=0.009 and p=0.04, respectively). Progressive disease (PD) was significantly higher with TD than with VTD (21% vs. 8%, p=0.009). In the overall series, PD was significanty higher in patients with EMP (34% vs. 12%, p=0.0002) with a significanty higher PD rate for TD as compared with VTD (40% vs. 14%, p=0.05). In patients with poor cytogenetics the CR rate was significantly higher with VTD than with TD (42% vs. 5%, p=0.009). In this high-risk group the PD rate was higher with TD (37%) and with VBMCP/VBAD/Velcade® (23%) than with VTD (0%) (p=0.009 and p=0.04, respectively). The incidence of thrombotic events ≥ grade 3 was higher in the TD arm (9% vs. 1% vs. 3%, p=0.07 and p=0.01) while ≥3 peripheral neuropathy was higher with VTD (14% vs. 0% and 1%, p<0.0001 and p=0.0003). Treatment was discontinued due to toxicity in 11 patients (TD: 3, VTD: 6, VBMCP/VBAD/Velcade®:2). Eight patients died during induction period (TD:5, VTD: 2, VBMCP/VBAD/Velcade®: 1) One-hundred seventy-seven patients were evaluable for response after ASCT. The post-ASCT CR rate with TD, VTD and VBMCP/VBAD/Velcade® was 40%, 59% and 48%, respectively, being significantly higher with VTD than with TD (p=0.05). The estimated overall survival at 2 years is 82% with no significant differences among the 3 arms. TTP and PFS were significantly shorter with TD (p=0.05 and p=0.012, respectively). In summary, VTD results in a higher pre- and post-ASCT CR rate as well as in a lower PD rate than TD, particularly in patients with high-risk cytogenetics or with EMP. The TTP and PFS are shorter with TD. Intermediate results are observed with VBMCP/VBAD/Velcade®. Longer follow-up is needed to establish whether or not these results will translate into a significantly different long-term outcome. Updated data will be presented at the meeting. Disclosures: Rosiñol: Janssen-Cilag: Honoraria; Celgene: Honoraria. Off Label Use: Thalidomide and bortezomib are not yet approved in Spain. Cibeira:Jansse-Cilag: Honoraria; Celgene: Honoraria. Mateos:Janssen-Cilag: Honoraria; Celgene: Honoraria. Oriol:Janssen-Cilag: Honoraria; Celgene: Honoraria. García-Laraña:Janssen-Cilag: Honoraria; Celgene: Honoraria. de la Rubia:Janssen-Cilag: Honoraria; Celgene: Honoraria. Sureda:Janssen-Cilag: Honoraria; Celgene: Honoraria. Palomera:Janssen-Cilag: Honoraria; Celgene: Honoraria. Díaz-Mediavilla:Janssen-Cilag: Honoraria; Celgene: Honoraria. de Arriba:Janssen-Cilag: Honoraria; Celgene: Honoraria. Alegre:Janssen-Cilag: Honoraria; Celgene: Honoraria. Lahuerta:Janssen-Cilag: Honoraria; Celgene: Honoraria. San Miguel:Janssen-Cilag: Honoraria; Celgene: Honoraria. Blade:Janssen-Cilag: Honoraria; Celgene: Honoraria.

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