Prognostic Impact of Microscopic Tumor Involved Resection Margin in Advanced Gastric Cancer Patients after Gastric Resection

Background

The prognosis of patients with positive surgical resection margins is dismal in gastric cancer. However, the influence of positive margin itself on prognosis is still uncertain, especially in advanced gastric cancer (AGC). The aims of the present study were to evaluate the prognostic impact of microscopic tumor involved resection margins in stage III–IV AGC after gastric resection in comparison with other well-known factors.

Methods

Among 1,536 consecutive gastric cancer patients who received intentional curative resection for stage III–IV AGC between April 2001 and December 2011 at the National Cancer Center, 35 patients (2.28 %) had positive resection margins on their final histology. A comparison of clinicopathologic characteristics, recurrence pattern, overall survival (OS), and disease-free survival (DFS) was made between positive margin (PM) patients and negative margin (NM) patients.

Results

Among the 35 PM patients, 15 (42.9 %) had proximal involved margins, 21 (60.0 %) had distal involved margins, and one (2.9 %) had both involved margins. Twenty-eight PM patients (80.0 %) were stage III, and 7 (20.0 %) were stage IV. Recurrence was significantly higher in PM than NM (63.6 % vs. 39.7 %, respectively; p = 0.005). The OS and DFS rates were significantly lower in the PM group than in the NM group (14.9 vs. 36.3 months, p < 0.001 and 11.6 vs. 27.1 months, p = 0.005, respectively). The presence of PM was an independent risk factor for both OS and DFS.

Conclusions

The presence of PM is an independent risk factor for OS and DFS. Considering the prognostic impact of PM, a sufficient resection margin should be ensured when determining the resection line in gastrectomy with curative intent. The reoperation to secure clear resection margins should be considered as a treatment of choice in the case of PM.     

Self-expandable metallic stent placement for malignant obstruction in patients with locally recurrent gastric cancer

Background  

Self-expandable metallic stents (SEMSs) provide effective palliation for inoperable malignant gastric outlet obstruction (GOO). The objective of this study was to evaluate the effectiveness of SEMSs in patients with recurrent gastric cancer after radical gastrectomy.     

A phase II study of perioperative S-1 combined with weekly docetaxel in patients with locally advanced gastric carcinoma: clinical outcomes and clinicopathological and pharmacogenetic predictors for survival

Gastric Cancer - We conducted a phase II study to evaluate the efficacy and safety of perioperative S-1 plus docetaxel in locally advanced gastric cancer (LAGC) and to investigate the association...     

Helicobacter pylori Seropositivity Is Associated with Gastric Cancer Regardless of Tumor Subtype in Korea

Background/Aims

To evaluate the association between Helicobacter pylori (H. pylori) infection and gastric cancer (GC) according to tumor subtype in Korea.

Methods

H. pylori status was determined serologically using the enzyme-linked immunosorbent assay. In total, 2,819 patients with GC and 562 healthy controls were studied. A logistic regression method was used after adjusting for possible confounders.

Results

The prevalence of H. pylori infection was significantly higher in the GC patients (84.7%) than in the controls (66.7%) (odds ratio [OR], 3.13; 95% confidence interval [CI], 2.46-3.97). The adjusted OR was significantly higher in H. pylori-infected patients aged <60 years (OR, 4.69; 95% CI, 3.44-6.38) than in those aged ≥60 years (OR, 1.48; 95% CI, 0.88-2.46; p<0.001). Subgroup analyses revealed no differences in seroprevalence between early gastric cancer (84.8%; OR, 3.01; 95% CI, 2.27-4.01) and advanced gastric cancer (84.6%; OR, 2.94; 95% CI, 2.24-3.85), cardia cancer (83.8%; OR, 2.98; 95% CI, 2.16-4.02) and noncardia cancer (84.8%; OR, 3.17; 95% CI, 2.48-4.04), and differentiated carcinoma (82.7%; OR, 2.99; 95% CI, 2.21-4.04) and undifferentiated carcinoma (86.8%; OR, 3.05; 95% CI, 2.32-4.00).

Conclusions

The seroprevalence of H. pylori was higher in GC patients than in healthy controls, especially in younger patients. H. pylori infection is associated with GC, regardless of the tumor location, stage, or differentiation.     

Predictive factors for the efficacy of cetuximab plus chemotherapy as salvage therapy in metastatic gastric cancer patients

Purpose

We performed a retrospective study to evaluate the efficacy of cetuximab plus chemotherapy in metastatic gastric cancer (MGC) patients previously treated with chemotherapy and to investigate potential predictors of treatment efficacy in those patients.

Methods

Thirty-two patients with MGC were included in this study. Cetuximab was delivered, often combined with irinotecan-based chemotherapy. Thirty patients were analyzed for K-ras mutations via direct sequencing of the tumor DNA.

Results

Patients were heavily pretreated with a median number of three previous lines of palliative chemotherapy (56% of the patients were refractory to all of the following drugs: fluoropyrimidines, cisplatin, irinotecan, oxaliplatin, and docetaxel) and 53% of the patients displayed poor performance status. Of 28 response-assessable patients, the overall response rate to cetuximab plus chemotherapy was 3.6% [95% confidence interval (CI) 0–10.5%] and the disease control rate was 28.6%. The median progression-free survival (PFS) was 1.7 months (95% CI 1.3–2.1 months), and the median overall survival (OS) was 3.2 months (95% CI 1.4–5.0 months). Multivariate analyses revealed that skin rash and performance status were significantly associated with PFS and OS. The presence of a K-ras mutation (13.3%) was not associated with either PFS or OS.

Conclusion

Our study suggests that MGC patients with good performance status and skin rash benefit most from salvage cetuximab combined with chemotherapy, even in heavily pretreated status.     

Phase I clinical and pharmacokinetic/pharmacogenetic study of a triplet regimen of S-1/irinotecan/oxaliplatin in patients with metastatic colorectal or gastric cancer

Purpose

We conducted a phase I study of S-1 combined with irinotecan and oxaliplatin (TIROX) to determine the maximum-tolerated dose (MTD) and recommended dose (RD) and to assess its safety, pharmacokinetics, pharmacogenetics, and preliminary efficacy in patients with metastatic colorectal cancer (MCRC) or metastatic gastric cancer (MGC).

Methods

Patients received escalating doses of S-1 (30–40 mg/m² b.i.d.) orally on days 1–14, an escalating dose of intravenous irinotecan (120–150 mg/m²) on day 1, and a fixed dose of intravenous oxaliplatin (85 mg/m²) on day 1 every 3 weeks.

Results

Twenty-three patients (10 MCRC, 13 MGC; 13 chemonaive, 10 previously treated for metastatic disease) were treated across six dose levels. Because only one patient experienced a dose-limiting toxicity of grade 3 anorexia at the highest dose level (S-1 40 mg/m² b.i.d., irinotecan 150 mg/m², and oxaliplatin 85 mg/m²) (n = 8), the MTD was not obtained, and this level was established as the RD. With a median of 10 cycles per patient, the most common grade 3 or 4 adverse events included neutropenia (43 %), diarrhea (13 %), and nausea (13 %). In 22 efficacy-evaluable patients, the objective tumor response rate was 59.1 % (75 % for both MCRC and MGC in the first-line setting) and the disease control rate was 100 %. The exploratory pharmacokinetic/pharmacogenetic study showed that CYP2A6 variants (*4, *7, *9) are associated with a lower metabolic ratio of S-1 (exposure ratio of 5-fluorouracil to tegafur).

Conclusions

The new triplet TIROX regimen has shown promising antitumor activity and a favorable toxicity profile in patients with MCRC and MGC.     

Clinical characteristics and treatment outcomes of gastric cancer patients with isolated para-aortic lymph node involvement

Background

Although gastric cancer with isolated para-aortic lymph node (PAN) involvement is considered an advanced disease, the clinical characteristics of it have not been comprehensively elucidated.

Patients and methods

We reviewed the medical records of 1,277 patients received palliative chemotherapy with advanced gastric cancer according to metastatic sites: PAN-only metastasis, single organ metastasis other than PAN, and multiple organ metastasis. Time to other organ metastasis (TTOM) was determined only in PAN-only metastasis group as the time interval between initial diagnosis of recurrence or de novo metastasis and confirming distant metastasis beyond PAN area.

Results

The median overall survival (OS) of patients with PAN-only metastasis was significantly longer than that of patients with single organ metastasis other than PAN or multiple organ metastasis (13.8?months vs. 11.4?months vs. 8.4?months; P?<?0.001). In the PAN-only metastasis group, patients with recurrent diseases showed longer TTOM beyond the PAN area (10.7 vs. 7.7?months; P?=?0.037) and OS (23.8 vs. 12.8?months; P?=?0.010) than those with de novo metastatic disease and it was validated by multivariate analysis.

Conclusion

Patients with isolated PAN metastasis showed an excellent prognosis compared with patients with metastasis at other sites and it was primarily evident in patients with recurrent PAN metastasis.     

Clinical Outcomes and Prognostic Factors of Metastatic Gastric Carcinoma Patients Who Experience Gastrointestinal Perforation During Palliative Chemotherapy

Background  

We conducted the current study to investigate the clinical outcomes of metastatic gastric carcinoma (MGC) patients who experienced gastrointestinal (GI) perforation during palliative chemotherapy and to examine the prognostic factors associated with survival after perforation.