Current Strategy of Chemotherapy for Bone Tumors

Despite the rarity of primary bone tumors, osteosarcoma and Ewing sarcoma are the most common primary malignant bone tumors in children and adolescents. Multiagent chemotherapy regimens for neoadjuvant and adjuvant treatment remarkably improved the survival outcome for patients with osteosarcoma and Ewing sarcoma, therefore, most patients are now limb-salvage candidates. However, survival rate reached a plateau for last decades and is still unsatisfactory in the metastatic and relapse setting. Therefore, as seen in denosumab in giant cell tumor, further clinical trials based on molecular mechanism are warranted. This article reviews the current state of the art of systemic chemotherapy by focusing on the clinical heterogeneity of each subtype.ope

Clinicopathological implications of EpCAM expression in adenocarcinoma of the lung

BACKGROUND: The frequency of epithelial cell adhesion molecule (EpCAM) expression was investigated in non-small cell lung cancer (NSCLC) cells and human tissues, and its clinicopathological significance in adenocarcinoma of the lung was evaluated. MATERIALS AND METHODS: EpCAM expression was analysed by reverse transcription-polymerase chain reaction (RT-PCR) and flow cytometry in human NSCLC cells. EpCAM protein expression was evaluated in 234 adenocarcinoma tissues using immunohistochemistry. RESULTS: A high expression level of EpCAM was observed in human NSCLC cells by flow cytometry and RT-PCR. EpCAM overexpression was detected in 120/234 (51.3%) surgically resected adenocarcinoma tissues. EpCAM overexpression occurred significantly more frequently in adenocarcinoma than in bronchioloalveolar carcinoma (p=0.02). The overall survival did not differ significantly between EpCAM-overexpressing and EpCAM-negative patients (p=0.40). CONCLUSION: These findings suggest EpCAM plays a role in the carcinogenesis of adenocarcinoma of the lung and might provide a promising molecule for targeted therapy in NSCLC.ope

Clinical analysis of patients with skeletal metastasis of lung cancer

BACKGROUND: Many factors influence bone metastases of lung cancer, and several studies report about survival of skeletal metastasis. However, few studies have focused on identifying the prognostic factors for skeletal metastasis of lung cancer, especially following orthopedic surgery. We conducted a retrospective analysis of the clinical characteristics of skeletal metastasis from lung cancer and discuss the prognostic factors. METHODS: We performed a medical record review of 202 patients who were diagnosed with skeletal metastasis from lung cancer. Adenocarcinoma was found in 116 patients (57.4%), squamous cell carcinoma in 29 (14.4%), small-cell lung cancer (SCLC) in 37 (18.7%), and large-cell carcinoma and other types of cancer in 20 patients (9.9%). Orthopedic surgery for skeletal metastasis was performed in 41 patients (20.3%). RESULTS: Lung cancer survival was 12.1 months. After diagnosis of lung cancer, skeletal metastasis was found at a mean of 2.5 months, and skeletal metastasis survival was 9.8 months. Lung cancer survival in patients younger than 60 years was 13.8 months, and lung cancer survival in patients 60 years or older was 10.8 months (p = 0.009). Skeletal metastasis survival in patients younger than 60 years was 11.0 months, and skeletal metastasis survival in patients 60 years or older was 8.8 months (p = 0.002). Mean skeletal metastasis survival with surgery was 12.6 months and without surgery was 9.1 months (p < 0.000). In the multivariate analysis of lung cancer survival, age under 60 years [HR (95% CI) 1.549 (1.122-2.139), p = 0.008], non-small cell lung cancer pathology type [HR (95% CI) 1.711 (1.157-2.532), p = 0.008], chemotherapy for skeletal metastasis [HR (95% CI) 8.064 (3.981-16.332), p < 0.000], and radiation therapy for skeletal metastasis [HR (95% CI) 1.791 (1.170-2.742), p = 0.007] were significant, independent, good prognostic factors. In the multivariate analysis of skeletal metastasis survival, age under 60 years [HR (95% CI) 1.549 (1.124-2.134), p = 0.007], non-small cell lung cancer pathology type [HR (95% CI) 2.045 (1.373-3.047), p < 0.000], chemotherapy for skeletal metastasis [HR (95% CI) 7.121 (3.542-14.317), p < 0.000], and orthopedic surgical treatment for skeletal metastasis [HR (95% CI) 1.710 (1.148-2.547), p = 0.008] were significant, independent, good prognostic factors. CONCLUSIONS: Patients who survived longer were less than 60 years old, received chemotherapy as treatment for skeletal metastasis, had NSCLC rather than SCLC, and underwent orthopedic surgery for skeletal metastasis.ope

Mass-forming ischemic colitis that mimics colon cancer

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Retrospective analysis of palliative chemotherapy for the patients with bladder adenocarcinoma: Korean Cancer Study Group Genitourinary and Gynecology Cancer Committee.

BACKGROUND/AIMS: Because of rarity, role of chemotherapy of bladder adenocarcinoma are still unidentified. Therefore, we performed a retrospective analysis of the clinical features and chemotherapy outcomes of bladder adenocarcinoma. METHODS: Eligible patients for this retrospective analysis were initially diagnosed with bladder adenocarcinoma and presented with a clinically no other primary site of origin. The collected data included age, gender, performance status, stage, hemoglobin, albumin, initial date of diagnosis, treatment modality utilized, response to treatment, presence of relapse, last status of patient, and last date of follow-up. RESULTS: We retrospectively reviewed 29 patients, who were treated with chemotherapy for bladder adenocarcinoma at 10 Korean medical institutions from 2004 to 2014. The median age of patients was 58 years (range, 17 to 78) and 51.7% of the patients were female. Urachal adenocarcinoma was identified in 15 patients. Of 27 symptomatic patients, 22 experienced gross hematuria. Twelve patients were treated with 5-f luorouracil based chemotherapy, five were gemcitabine based, three were taxane and others. Thirteen of them achieved complete response (10.3%) or partial response (34.5%). Median progression-free survival (PFS) and overall survival (OS) for all patients were 10.6 months (95% confidence interval [CI], 9.5 to 11.6) and 24.5 months (95% CI, 1.2 to 47.8), respectively. The cases of urachal adenocarcinoma exhibited worse tendency in PFS and OS (p = 0.024 and p = 0.046, respectively). CONCLUSIONS: Even though bladder adenocarcinoma had been observed moderate effectiveness to chemotherapy, bladder adenocarcinoma is a highly aggressive form of bladder cancer. PFS and OS were short especially in urachal carcinoma.ope

Phase I dose-escalation study of the c-Met tyrosine kinase inhibitor SAR125844 in Asian patients with advanced solid tumors, including patients with MET-amplified gastric cancer

SAR125844 is a potent and selective inhibitor of the c-Met kinase receptor. This was an open-label, phase I, multicenter, dose-escalation, and dose-expansion trial of SAR125844 in Asian patients with solid tumors, a subgroup of whom had gastric cancer and MET amplification (NCT01657214). SAR125844 was administered by intravenous infusion (260-570 mg/m2) on days 1, 8, 15, and 22 of each 28-day cycle. Objectives were to determine the maximum tolerated dose (MTD) and to evaluate SAR125844 safety and pharmacokinetic profile. Antitumor activity was also assessed. Of 38 patients enrolled (median age 64.0 years), 22 had gastric cancer, including 14 with MET amplification. In the dose-escalation cohort (N = 19; unselected population, including three patients with MET-amplification [two with gastric cancer and one with lung cancer]), the MTD was not reached, and the recommended dose was established at 570 mg/m2. Most frequent treatment-emergent adverse events (AEs) were nausea (36.8%), vomiting (34.2%), decreased appetite (28.9%), and fatigue or asthenia, constipation, and abdominal pains (each 21.1%); none appeared to be dose-dependent. Grade ≥ 3 AEs were observed in 39.5% of patients and considered drug-related in 7.9%. SAR125844 exposure increased slightly more than expected by dose proportionality; dose had no significant effect on clearance. No objective responses were observed in the dose-escalation cohort, with seven patients (three gastric cancer, two colorectal cancer, one breast cancer, and one with cancer of unknown primary origin) having stable disease. Modest antitumor activity was observed at 570 mg/m2 in the dose-expansion cohort, comprising patients with MET-amplified tumors (N = 19). Two gastric cancer patients had partial responses, seven patients had stable disease (six gastric cancer and one kidney cancer), and 10 patients had progressive disease. Single-agent SAR125844 administered up to 570 mg/m2 has acceptable tolerability and modest antitumor activity in patients with MET-amplified gastric cancer.ope

Recommendations for the Use of Next-Generation Sequencing and the Molecular Tumor Board for Patients with Advanced Cancer: A Report from KSMO and KCSG Precision Medicine Networking Group

Next-generation sequencing (NGS) is becoming essential in the fields of precision oncology. With implementation of NGS in daily clinic, the needs for continued education, facilitated interpretation of NGS results and optimal treatment delivery based on NGS results have been addressed. Molecular tumor board (MTB) is multidisciplinary approach to keep pace with the growing knowledge of complex molecular alterations in patients with advanced solid cancer. Although guidelines for NGS use and MTB have been developed in western countries, there is limitation for reflection of Korea's public health environment and daily clinical practice. These recommendations provide a critical guidance from NGS panel testing to final treatment decision based on MTB discussion.ope

A phase I/Ib study of OTSGC-A24 combined peptide vaccine in advanced gastric cancer

Background: We conducted a phase I/Ib, open-label, single-arm trial to assess the safety, tolerability and optimal scheduling regimen of OTSGC-A24 cancer vaccine in patients with advanced gastric cancer. Methods: Patients with advanced gastric cancer with HLA-A*24:02 haplotype were included in this study. OTSGC-A24 was administered at 1 mg in 3-weekly (3w), 2-weekly (2w), and weekly (1w) cohorts to evaluate the safety, immunological response and schedule. Based on the highest specific cytotoxic T lymphocyte (CTL) induction rate at 4 weeks, using the ELISPOT test, cohorts were expanded to define the optimal dosing schedule for OTSGC-A24. Results: In this study, 24 advanced gastric cancer patients with HLA-A*24:02 haplotype were enrolled and treated in 3 cohorts (3w cohort: 3; 2w cohort: 11 and 1w cohort: 10 patients). The most common adverse events were decreased appetite (29%), diarrhea (21%), myalgia (25%). The most common treatment-related adverse event was injection site erythema (25%). No dose-limiting toxicities were observed in any cohort and OTSGC-A24 was well tolerated. Positive CTL responses after vaccination were observed in 15 patients (75%) at 4 weeks: 3w cohort (33%), 2w cohort (88%), 1w cohort (78%). At 12 weeks, 18 patients had responded (90%); 3w cohort (100%), 2w cohort (100%), 1w cohort (78%). The best radiological was stable disease (40%). Median progression free survival was 1.7 months (95% CI: 1.4 to 3.5) and median overall survival was 5.7 months (95% CI 3.8 to 8.6). Conclusions: OTSGC-A24 combined peptide cancer vaccine was well tolerated. Significant responses in CTL were observed and the recommended phase 2 dose is 1 mg OTSGC-A24 sub-cutaneous, every 2 weeks. Although no radiological response was observed, a respectable overall survival was achieved, consistent with other immunotherapy agents being investigated in gastric cancer. Trial registration: ClinicalTrials.gov Identifier: NCT01227772 , Date registered: 21 Oct 2010.ope

A Retrospective Analysis for Patients with HER2-Positive Gastric Cancer Who Were Treated with Trastuzumab-Based Chemotherapy: In the Perspectives of Ethnicity and Histology

PURPOSE: While the Trastuzumab for Gastric Cancer (ToGA) trial demonstrated the efficacy and safety of trastuzumab-based chemotherapy in HER2-positive metastatic gastric cancer, the overall survival (OS) benefit was not found in Asian and diffuse-type cancer patients. The aim of the study is to investigate predictive markers for trastuzumab-based chemotherapy. MATERIALS AND METHODS: Data of patients with HER2-positive gastric cancer treated with trastuzumab-based chemotherapy were analyzed retrospectively. RESULTS: A total of 168 Asian patients were included. The median age was 60 years (range, 27 to 85 years) and the male:female ratio was 118 (70.2%):50 (29.8%). Fourteen (8.3%), 63 (37.5%), 75 (44.6%), and 11 (6.5%) patients had well, moderately, poorly-differentiated tubular adenocarcinoma and signet ring cell carcinoma, respectively. With 14 complete responses and 73 partial responses, the response rate was 50.6%. The median progression-free survival (PFS) was 10.2 months (95% confidence interval [CI], 8.7 to 11.7), and the median OS was 18.5 months (95% CI, 16.4 to 50.6). Next, we investigated the effect of poorly-differentiated histology (PDH, poorly-differentiated tubular adenocarcinoma+signet ring cell carcinoma) on clinical outcomes. The median PFS (8.9 months vs. 11.5 months, p=0.16) was slightly inferior in PDH patients, and the median OS was significantly shorter in PDH patients (14.6 months vs. 19.0 months, p=0.025). CONCLUSION: While subset analysis of the ToGA trial demonstrated that trastuzumab-based chemotherapy may not be beneficial for Asians and patients with PDH, our data may suggest that even in Asian patients and patients with PDH, trastuzumab-based chemotherapy could be associated with improved clinical outcomes in patients with HER2-positive gastric cancer.ope

Clinical Features and Treatment of Collecting Duct Carcinoma of the Kidney from the Korean Cancer Study Group Genitourinary and Gynecology Cancer Committee

PURPOSE: Collecting duct carcinoma (CDC) of the kidney is an aggressive disease with a poor prognosis, accountings for less than 1% of all renal cancers. To date, no standard therapy for CDC has been established. The aim of this study is an investigation of clinicopathologic findings of CDC and correlation of the disease status with a prognosis. MATERIALS AND METHODS: From 1996 to 2009, 35 patients with CDC were treated at eight medical centers. The diagnosis of CDC was made based on nephrectomy in 27 cases and renal biopsy in eight cases. RESULTS: Median PFS and OS for all patients were 5.8 months (95% CI 3.5 to 9.2) and 54.4 months (95% CI 0 to 109.2), respectively. The OS of patients with Stages I-III was 69.9 months (95% CI 54.0 to 85.8), while that of patients with Stage IV was 8.6 months (95% CI 0 to 23.3), which showed a statistically significant difference (p=0.01). In addition, among patients with Stage IV, the OS of patients who received a palliative treatment (immunotherapy, chemotherapy, or targeted therapy) was 18.4 months, which was higher than the OS of patients without treatment of 4.5 months. CONCLUSION: CDC is a highly aggressive form of renal cell carcinoma. Despite most of the treatments, PFS and OS were short, however, there were some long-term survivors, therefore, conduct of additional research on the predictive markers of the several clinical, pathological differences and their treatments will be necessary.ope