Efficacy and tolerability of ramucirumab monotherapy or in combination with paclitaxel in gastric cancer patients from the Expanded Access Program Cohort by the Korean Cancer Study Group (KCSG)

Background

Ramucirumab improves survival in gastric cancer patients. The efficacy and safety of ramucirumab outside of a clinical trial were evaluated using an expanded access program (EAP).

Methods

Advanced gastric cancer patients treated with ramucirumab in combination with paclitaxel or with ramucirumab monotherapy in a Korean EAP were evaluated. Baseline characteristics were assessed for progression-free survival (PFS) and overall survival (OS), and adverse events were evaluated according to the treatment regimen.

Results

Of 265 patients, 228 received ramucirumab plus paclitaxel, and 37 received ramucirumab monotherapy. Grade 3 or 4 neutropenia was more common with ramucirumab plus paclitaxel than with ramucirumab monotherapy (46.7 vs. 8.1%). Gastrointestinal (GI) perforation developed in seven patients (3.1%) in the ramucirumab plus paclitaxel group. The overall response and disease control rates were 16.6 and 66.3% in the ramucirumab plus paclitaxel group, and 5.4 and 37.8% in the ramucirumab monotherapy group, respectively. PFS and OS were 3.8 and 8.6 months in the ramucirumab plus paclitaxel group, and 1.8 and 6.4 months in the ramucirumab monotherapy group, respectively. In multivariate analysis, alkaline phosphatase, albumin, and neutrophil-to-lymphocyte ratio (NLR) were the independent prognostic factors for PFS, while albumin, NLR, number of metastatic sites, and large amount of ascites were independent prognostic factors for OS.

Conclusion

In the Korean EAP cohort, ramucirumab showed similar efficacy to the results of the previous trials for gastric cancer. However, the level of GI perforation was slightly increased in the ramucirumab plus paclitaxel group.

     

Poor prognosis in Epstein–Barr virus-negative gastric cancer with lymphoid stroma is associated with immune phenotype

Background

Gastric cancer with lymphoid stroma (GCLS) is pathologically characterized by poorly developed tubular structures with a prominent lymphocytic infiltration. Its clinical and prognostic features differ in patients positive and negative for Epstein–Barr virus (EBV) infection. This study analyzed the expression of programmed cell death-1 (PD-1), programmed cell death ligand-1 (PD-L1), and the density of tumor-infiltrating lymphocytes (TILs) including CD3+ and CD8+ T cells, as well as their prognostic significance in patients with GCLS.

Methods

The study included 58 patients with GCLS (29 EBV+ and 29 EBV?) who underwent curative resection. Expression of CD3, CD8, PD-1, and PD-L1 in tumor cells and TILs was analyzed using a quantitative multispectral imaging system (Opal?), with these results validated by immuno-histochemical assays for PD-L1 on whole slide sections.

Results

The proportion of tumors overexpressing PD-L1 (31.0 vs. 0%, P = 0.002), TIL density (4548 vs. 2631/mm², P < 0.001), and intra-tumoral CD8+ T-cell density (2650 vs. 1060/mm², P < 0.001) were significantly higher in EBV+ than in EBV? GCLS. In addition, CD8+/CD3+ T-cell ratio was higher in EBV+ than in EBV? GCLS (55.3 vs. 35.8%, P < 0.001). Lower TIL density, defined as < 1350/mm², was a significant negative factor of survival.

Conclusions

Despite histopathological similarity, quantitative multispectral imaging revealed differences in the tumor immune micro-environment between EBV+ and EBV? GCLS, indicating that the underlying pathogenesis differs in these two disease entities. TIL density may be a prognostic marker in patients with GCLS.

     

Complete metabolic response (CMR) in positron emission tomography–computed tomography (PET‐CT) scans may have prognostic significance in patients with marginal zone lymphomas (MZL)

Although clinical use of positron emission tomography–computed tomography (PET‐CT) scans is well established in aggressive lymphomas, its prognostic value in marginal zone lymphoma (MZL) remains yet unclear. Hence, we investigated potential role of PET‐CT in predicting MZL patients' outcomes following systemic chemotherapy. A total of 32 patients with MZL who received first‐line chemotherapy were included in the analysis. They all underwent pretreatment, interim, and posttreatment PET‐CT scans. The primary objective was to evaluate the role of complete metabolic response (CMR) in posttreatment PET‐CT scans in predicting progression‐free survival (PFS). Compared with non‐CMR group, 5‐year PFS rate was significantly higher in patients who achieved CMR in posttreatment PET‐CT (54.2% vs 0.0%, P = .003) and also in patients gaining CMR in interim PET‐CT scans (62.5% vs 15.6%, P = .026). Interestingly, early CMR group, who achieved and maintained CMR in both interim and posttreatment PET‐CT scans, showed significantly higher 5‐year PFS than those with delayed or never CMR group (62.5% vs 37.5% vs 0%, P = .008). Therefore, interim and/or posttreatment CMR can be prognostic at least in these subsets of patients with MZL treated with chemotherapy.     

Effects of symptom clusters and depression on the quality of life in patients with advanced lung cancer

People with advanced lung cancer experience later symptoms after treatment that is related to poorer psychosocial and quality of life (QOL) outcomes. The purpose of this study was to identify the effect of symptom clusters and depression on the QOL of patients with advanced lung cancer. A sample of 178 patients with advanced lung cancer at the National Cancer Center in Korea completed a demographic questionnaire, the M.D. Anderson Symptom Inventory–Lung Cancer, the Center for Epidemiological Studies Depression Scale, and the Functional Assessment of Cancer Therapy–General scale. The most frequently experienced symptom was fatigue, anguish was the most severe symptom‐associated distress, and 28.9% of participants were clinically depressed. Factor analysis was used to identify symptom clusters based on the severity of patients' symptom experiences. Three symptom clusters were identified: treatment‐associated, lung cancer and psychological symptom clusters. The regression model found a significant negative impact on QOL for depression and lung cancer symptom cluster. Age as the control variable was found to be significant impact on QOL. Therefore, psychological screening and appropriate intervention is an essential part of advanced cancer care. Both pharmacological and non‐pharmacological approaches for alleviating depression may help to improve the QOL of lung cancer patients.     

Supercritical carbon dioxide extraction of podophyllotoxin from Dysosma pleiantha roots

Supercritical fluid extraction (SFE) was utilized to extract podophyllotoxin from the roots of Dysosma pleiantha. The extraction was carried out in the temperature range of 40-80 degrees C and the pressure range of 13.6-34.0 MPa with supercritical carbon dioxide. However, podophyllotoxin was not sufficiently extracted by pure supercritical carbon dioxide. Methanol was used as modifier to enhance the extraction yield of podophyllotoxin. As a result, SFE produced a higher recovery of podophyllotoxin than conventional 95% ethanol extraction.     

Ginsenosides compound K and Rh2 inhibit tumor necrosis factor-α-induced activation of the NF-κB and JNK pathways in human astroglial cells

Ginsenosides, the main component of Panax ginseng, have been known for the anti-inflammatory and anti-proliferative activities. In this study, we investigated the molecular mechanisms responsible for the anti-inflammatory effects of ginsenosides on activated astroglial cells. Among 13 different ginsenosides, intestinal bacterial metabolites Rh₂ and compound K (C-K) showed a significant inhibitory effect on tumor necrosis factor-α (TNF-α)-induced expression of intercellular adhesion molecule-1 in human astroglial cells. Pretreatment with C-K or Rh₂ suppressed TNF-α-induced phosphorylation of IκBα kinase and the subsequent phosphorylation and degradation of IκBα. Additionally, the same treatment inhibited TNF-α-induced phosphorylation of MKK4 and the subsequent activation of the JNK-AP-1 pathway. The inhibitory effect of ginsenosides on TNF-α-induced activation of the NF-κB and JNK pathways was not observed in human monocytic U937 cells. These results collectively indicate that ginsenoside metabolites C-K and Rh₂ exert anti-inflammatory effects by the inhibition of both NF-κB and JNK pathways in a cell-specific manner.     

Cardiac tamponade due to a rupture of the coronary arteriovenous aneurysm--a case report.

We experienced an unusual case of cardiac tamponde caused by a rupture of the coronary arteriovenous aneurysm in a 54-year-old woman. The patient was suffered from sudden chest pain and syncope, and was initially managed by pericardiocentesis following an echocardiogram which revealed a massive pericardial effusion with signs of cardiac tamponade. She was referred to our hospital under the impression of aortic dissection with cardiac tamponade. She underwent an emergency operation and was found to have a 2 x 2 cm sized bleeding cystic mass protruding from the proximal anterior descending coronary artery. The aneurysm was excised and the openings connected with the coronary artery and right ventricular outflow tract were closed with sutures from the inside of aneurysm. Subsequent coronary arteriography supported the diagnosis.     

A small cell osteosarcoma on the calcaneus--a case report.

Small cell osteosarcoma is rare, representing 1-4% of all osteosarcomas. We experienced a case of small cell osteosarcoma in an 8-year-old girl on her calcaneus. Histologically, the tumor consists of small round cells that resemble those of Ewing''s sarcoma, and variable foci of lacy osteoid formation between tumor cells. The rare location, histologic characteristics and differential diagnostic points are discussed.     

Giant cell tumor of the scapula associated with secondary aneurysmal bone cyst

Giant cell tumors are distinctive neoplasms characterized by a profusion of multinucleate giant cells scattered throughout a stroma of mononuclear cells. Most giant cell tumors are found at the epiphyses of long bones, especially around the knee joint. Flat bone involvement is rare. However, a case of giant cell tumor with secondary aneurysmal bone cyst was encountered at the scapula of a 25-year-old man. Since the occurrence of a giant cell tumor with secondary aneurysmal bone cyst on flat bones (i.e., the scapula) is extremely rare, the above-mentioned case is worthy of reporting.