In the past decade, several successful clinical trials provided new therapeutic agents approved for advanced gastric cancer (AGC). This study evaluated whether these practice-changing results actually altered the clinical practice.

We retrospectively reviewed medical records of treatment-naive AGC patients who received combination chemotherapy of fluoropyrimidine and platinum between 2007 and 2018 and divided them into three groups: Groups A (2007-10), B (2011-14), and C (2015-2018), respectively. We compared the clinicopathological features, treatment details, and clinical outcomes among the three groups.

In total, 1004 consecutive patients were enrolled (A; n = 254, B; n = 300, and C; n = 450). The number of patients with poor performance status, older age, esophagogastric junction adenocarcinoma, and primary tumor increased during the study period. All groups had similar median overall survival (OS); ~16 months) without any statistical difference but steady prolongation of survival was observed in the adjusted with imbalance prognostic factors among groups (B/A; hazard ratio, HR 0.82, 95% C.I 0.68-0.98, C/A; HR 0.72, 95% CI 0.60-0.86); OS of HER2-positive AGC patients was clearly improved (HER2-positive vs HER2-negative in Group B, HR 0.80, 95% CI 0.60-1.06; Group C, HR 0.68, 95% CI 0.51-0.90) but that of diffuse-type AGC patients remained dismal.

The increasing availability of chemotherapy options potentially contributed to improved survival of AGC patients, but expanded chemotherapeutic indications made the survival benefit inconspicuous in the whole population. Future therapeutic development for the AGC subset not adequately receiving benefit from previous clinical trials is warranted.

• Adenocarcinoma
• Antineoplastic Combined Chemotherapy Protocols/therapeutic use
• Esophageal Neoplasms/drug therapy
• Humans
• Neoplasm Recurrence, Local/drug therapy
• Retrospective Studies
• Stomach Neoplasms/pathology

The Japan Clinical Oncology Group (JCOG) prognostic index, consisting of performance status, primary tumor resected, number of metastases, and serum alkaline phosphatase, has been one of the robust prognostic indices for patients with advanced gastric cancer on the basis of which clinical trials have stratified prognosis. Only a few studies, however, have utilized the JCOG prognostic index in daily practice.

We conducted a retrospective study on patients with advanced gastric cancer who received first-line platinum-containing chemotherapy at a single institute between 2011 and 2017. Prognostic factors were evaluated using a Cox proportional regression model.

A total of 608 patients were enrolled. Multivariate analysis showed that performance status ≥1, presence or absence of primary tumor, serum alkaline phosphatase, neutrophil-to-lymphocyte ratio ≥4, and diffuse-type histology were significantly associated with worse prognosis, whereas the number of metastases was not. Although the original prognostic index could not adequately stratify patients into three risk groups, the modified index (good: 0 and 1, moderate: 2 and 3, poor: 4-6), which was established by incorporating diffuse-type histology and high neutrophil-to-lymphocyte ratio, demonstrated excellent stratification. The median overall survival of the good (n = 315), moderate (n = 243), and poor (n = 54) risk groups was 20.5, 13.5, and 10.2 months, respectively. Hazard ratios (HRs) were 1.69 [95% confidence interval (CI), 1.40-2.04; good versus moderate] and 1.52 (95% CI, 1.11-2.08; moderate versus poor). This novel index also demonstrated a statistically significant stratification of survival after progression following first-line chemotherapy (good versus moderate: HR, 1.41; 95% CI, 1.16-1.70; moderate versus poor: HR, 2.00; 95% CI, 1.45-2.74).

The modified JCOG prognostic index showed excellent stratification of overall survival in real-world patients, which could also help determine the need for treatment changes throughout the continuum of chemotherapy.

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The applicability of the JCOG prognostic index in daily practice was investigated for advanced gastric cancer (AGC).

• diffuse type
• gastric or gastroesophageal junction cancer
• neutrophil-to-lymphocyte ratio
• postprogression survival
• prognostic factor

• SEER Program
• distant metastasis
• nomogram
• superficial gastric cancer

Many large-sample prospective randomized clinical trials investigating advanced gastric cancer (AGC) have confirmed the survival advantages of first-line, second-line, or third-line chemotherapy compared with their respective control groups. However, due to the ethical concerns of prospective clinical trials, it is impossible to conduct a randomized comparative study of patients who do not receive chemotherapy and those who receive a second-line or above chemotherapy. Few research reports have addressed the relationship between the number of chemotherapy lines and overall survival (OS) in patients with AGC. In the present study, we analyzed the impact of the number of chemotherapy lines on OS in AGC patients using real-world data.

This study collected the medical records of patients with AGC diagnosed at Shandong Cancer Hospital from December 2007 to December 2017. According to the treatment received, AGC patients were divided into groups that did not receive chemotherapy, those who received only 1 line, 2 lines, or 3 lines and above. Kaplan–Meier analysis was used to assess patient survival.

A total of 596 AGC patients were included in this study. The following patients were enrolled: 0 lines (did not receive chemotherapy), 77 (12.9%); 1 line, 235 (39.4%) patients; 2 lines, 185 (31.1%) patients; and ≥3 lines 99 (16.6%) patients. OS was significantly correlated with the number of chemotherapy lines (P<0.001), with a median OS from diagnosis of 3.3, 8.6, 15.6, and 21.0 months for patients receiving 0, 1, 2, ≥3 lines of chemotherapy, respectively.

This study showed that the more chemotherapy lines AGC patients received, the longer the OS. This study not only confirmed the impact of chemotherapy lines on OS but it also supplements the results of prospective clinical trials that cannot be completed due to the ethical implications.

• advanced gastric cancer
• number of chemotherapy lines
• overall survival
• real world data

• Lauren subtype
• chemotherapy
• gastric cancer
• meta-analysis
• survival

• Gastric cancer
• Prognostic factor
• RECIST
• Tumor marker

• Antibodies, Monoclonal, Humanized/administration & dosage
• Antineoplastic Combined Chemotherapy Protocols/therapeutic use
• Biomarkers, Tumor/analysis
• Humans
• Nivolumab/administration & dosage
• Paclitaxel/administration & dosage
• Practice Guidelines as Topic
• Prognosis
• Stomach Neoplasms/drug therapy
• Stomach Neoplasms/pathology
• Treatment Outcome
• Ramucirumab

• Controlled drug delivery
• Gastric cancer
• Imaging
• Nanoparticles
• Nanotherapeutics

The present study investigated the prognosis value of preoperative fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in patients with local advanced gastric cancer (LAGC).

In total, 144 patients [median age 63 (range: 48−80) years old] with LAGC underwent¹⁸F-FDG PET/CT prior to any treatment. The maximum standardized uptake values (SUV_max), mean standardized uptake values (SUV_mean), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) of the primary lesion were measured on PET/CT and correlated with clinicopathological features and survival.

Significant differences in SUV_mean, SUV_max, MTV and TLG were found according to Lauren’s classification, histologic grade and T category (P<0.05). During the 26.5-month follow-up, 51 (35.4%) patients died and 70 (48.6%) exhibited disease progression. The optimal thresholds of MTV and TLG were 15.1 cm³ and 47.3 cm³, respectively. The 3-year progression-free survival (PFS) and overall survival (OS) for patients with high TLG values were 30% and 38% compared to 38% and 47% for low TLG values, respectively (P<0.05). Univariate and multifactor analyses demonstrated that lymph node metastasis and T stage were independent prognostic factors for PFS; T stage, histologic grade and TLG were independent prognostic factors for OS (P<0.05). Molecular markers had no relationship with patient’s outcomes.

Metabolic activity of primary gastric tumors from ¹⁸F-FDG PET/CT is a prognostic factor in patients with LAGC.

• 18F-FDG PET/CT
• Gastric cancer
• metabolic parameters
• prognosis

Gastric cancer (GC) is the third most common cancer-related cause of death worldwide. In locally advanced tumors, neoadjuvant chemotherapy has recently been introduced in most international Western guidelines. For metastatic and unresectable disease, there is still debate regarding correct management and the role of surgery. The standard approach for stage IV GC is palliative chemotherapy. Over the last decade, an increasing number of M1 patients who responded to palliative regimens of induction chemotherapy have been subsequently undergone surgery with curative intent. The objective of the present review is to analyze the literature regarding this approach, known as “conversion surgery”, which has become one of the most commonly adopted therapeutic options. It is defined as a treatment aiming at an R0 resection after chemotherapy in initially unresectable tumors. The 13 retrospective studies analyzed, with a total of 411 patients treated with conversion therapy, clearly show that even if standardization of unresectable and metastatic criteria, post-chemotherapy resectability evaluation and timing of surgery has not yet been established, an R0 surgery after induction chemotherapy with partial or complete response seems to offer superior survival results than chemotherapy alone. Additional larger sample-size randomized control trials are needed to identify subgroups of well-stratified patients who could benefit from this multimodal approach.

• Metastatic gastric cancer
• Gastric cancer
• Conversion surgery
• R0 resection
• Stage IV gastric cancer
• Palliative chemotherapy
• Unresectable gastric cancer

• Cisplatin
• Elderly patients
• Gastric cancer
• Propensity score matching method (3-5 words)
• S-1

This meta-analysis was performed to evaluate the efficacy and safety of apatinib in patients with advanced gastric cancer (AGC).

After evaluating the inclusion and exclusion criteria, the data of eligible randomized clinical trials (RCTs) were extracted. Outcomes including objective response rate (ORR), disease control rate (DCR), and adverse events (AEs) were analyzed in the meta-analysis.

Data of 1,069 patients from 13 RCTs were statistically analyzed. Pooled odds ratio (OR) for ORR and DCR was found to be 0.46 (95% confidence interval [CI]: 0.33, 0.64; P<0.00001) and 0.23 (95% CI: 0.15, 0.36; P<0.00001), respectively. Compared with placebo, apatinib showed statistical significance in AEs at any grade, including leucopenia, neutropenia, thrombocytopenia, diarrhea, hypertension, proteinuria, hand-foot syndrome, and fatigue (all P<0.05).

The results of our meta-analysis revealed that apatinib shows short-term efficacy over no-apatinib regimens or placebo regardless of its use as first- or second-line chemotherapy or for further treatment in patients with AGC accompanied with apparent AEs of any grade.

• adverse events
• disease control rate
• objective response rate

• Chemotherapy
• Gastric cancer
• Irinotecan
• Paclitaxel
• Ramucirumab

• Gastric cancer (GC)
• Lauren classification
• diffuse histology
• meta-analysis
• prognostic factor

• Cisplatin
• Irinotecan
• Paclitaxel
• Pharmacokinetics

• S-1
• fluorouracil
• gastric cancer
• heterogeneity
• irinotecan plus cisplatin

• Adjuvant surgery
• Chemotherapy
• Conversion therapy
• Gastric cancer
• Stage IV gastric cancer

AIM: To evaluate the timing of chemotherapy in gastric cancer by comparing survival outcomes in treatment groups.

METHODS: Patients with surgically resected gastric adenocarcinoma from 1988 to 2006 were identified from the Los Angeles County Cancer Surveillance Program. To evaluate the population most likely to receive and/or benefit from adjunct chemotherapy, inclusion criteria consisted of Stage II or III gastric cancer patients > 18 years of age who underwent curative-intent surgical resection. Patients were categorized into three groups according to the receipt of chemotherapy: (1) no chemotherapy; (2) preoperative chemotherapy; or (3) postoperative chemotherapy. Clinical and pathologic characteristics were compared across the different treatment arms.

RESULTS: Of 1518 patients with surgically resected gastric cancer, 327 (21.5%) received perioperative chemotherapy. The majority of these 327 patients were male (68%) with a mean age of 61.5 years; and they were significantly younger than non-chemotherapy patients (mean age, 70.7; P < 0.001). Most patients had tumors frequently located in the distal stomach (34.5%). Preoperative chemotherapy was administered to 11.3% of patients (n = 37) and postoperative therapy to 88.7% of patients (n = 290). An overall survival benefit according to timing of chemotherapy was not observed on univariate or multivariate analysis. Similar results were observed with stage-specific survival analyses (5-year overall survival: Stage II, 25% vs 30%, respectively; Stage III, 14% vs 11%, respectively). Therefore, our results do not identify a survival advantage for specific timing of chemotherapy in locally advanced gastric cancer.

CONCLUSION: This study supports the implementation of a randomized trial comparing the timing of perioperative therapy in patients with locally advanced gastric cancer.

• Chemotherapy
• Gastric cancer
• Adjunct therapy
• Postoperative therapy
• Preoperative therapy
• Timing

• P30 CA033572 NCI NIH HHS