Search

// Cho-Hao Lee 1 , Chin Lin 2, 3 , Chieh-Yung Wang 4 , Tzu-Chuan Huang 1 , Yi-Ying Wu 1 , Wu-Chien Chien 2 and Jia-Hong Chen 1, 5 1 Division of Hematology and Oncology Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China 2 School of Public Health, National Defense Medical Center, Taipei, Taiwan, Republic of China 3 Department of Research and Development, National Defense Medical Center, Taipei, Taiwan, Republic of China 4 Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China 5 Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, Republic of China Correspondence to: Jia-Hong Chen, email: ndmc_tw.tw@yahoo.com.tw Keywords: overweight; small-cell lung cancer; prognostic factor; body mass index Received: September 29, 2017 Accepted: March 05, 2018 Published: May 15, 2018 ABSTRACT Numerous evidence has indicated that excess weight is associated with an increased risk of mortality in patients in several cancer types including breast, colorectal, pancreatic, endometrial, and prostate cancer However, with respect to non-small cell lung cancer and upper aero-digestive cancer, evidence suggests that low body mass index (BMI) may increase the risk of mortality of these cancers, but a definitive link between premorbid BMI and overall survival in small cell lung cancer patients has yet to be fully explored. To investigate this possibility, we conducted a retro-spective of 173 small-cell lung cancer patients. Multivariate Cox analysis indicated that pretreatment overweight (BM I ≥ 23) was an independent prognostic factor for overall survival (OS) (Hazard ratio, = 0.58, 95% CI = 0.39–0.87, p = 0.008). In addition, meta-regression revealed that per-formance status (≤ 2) marginally interacted with increased BMI ( p = 0.068). However, subgroup analysis showed that patients with a BMI ≥ 23 and performance status ≤ 2 had the best OS (Hazard ratio: 0.31, 95% CI: 0.16–0.61, p = 0.001). Premorbid BMI and performance status level are easy to measure and may provide physicians an additional measurement to predict a small-cell lung cancer patient’s survival. The data from the present study indicates that a, further large scale prospective study is warranted to better assess the association of pretreatment BMI and OS in small-cell lung cancer.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the effectiveness and safety of maintenance therapy in individuals with chronic lymphocytic leukaemia (CLL).

Most chronic lymphocytic leukemia patients experience a relapse or become refractory to treatment with conventional chemotherapeutic agents. The network meta-analysis assesses the relative efficacy of novel targeted agents for the treatment of a relapse or refractory chronic lymphocytic leukemia. A systematic literature search included seven phase III randomized controlled trials, including a total of 2512 patients treated with nine regimens. Data were extracted and evidence synthesized using network meta-analysis. All novel targeted therapies were significantly more effective than ofatumumab and demonstrated promising prolongation of progression free survival (PFS), with a hazard ratio (HR) ranging from 0.10 to 0.52. Two novel targeted agent regimens, venetoclax plus rituximab and ibrutinib monotherapy, resulted in greater overall survival (HR, 0.335 and 0.361, respectively). Venetoclax plus rituximab and ibrutinib monotherapy were most favorable based on (1) HR for PFS compared with ofatumumab (Ibrutinib: HR, 0.10, 95% CI, 0.07&ndash, 0.14, Venetoclax plus rituximab: HR, 0.10, 95% CI, 0.05&ndash, 0.21) and SUCRA value (probability of being best) (Ibrutinib SUCRA, 0.92, Venetoclax rituximab SUCRA, 0.90) (2) HR for overall survival compared with ofatumumab (Ibrutinib: HR, 0.361, 95% CI, 0.208&ndash, 0.627, Venetoclax rituximab: HR, 0.335, 95% CI, 0.112&ndash, 0.997) and SUCRA value (Ibrutinib SUCRA, 0.84, Venetoclax rituximab SUCRA, 0.85) Both treatments reduced the risk of progression or death by 90% versus conventional ofatumumab. Both ibrutinib monotherapy and venetoclax rituximab have a high probability of being the most effective treatments for a relapse or refractory chronic lymphocytic leukemia with respect to long-term progression-free survival and overall survival.

Hepatic angiosarcoma is a rare condition that has been associated with exposure to colloidal solutions of thorium dioxide, vinyl chloride, arsenic and radiation. Therapeutic guidelines have not been definitively established due to the small number of cases of this disease. The present study reviewed 28 cases of hepatic angiosarcoma from studies that had been published between January 2000 and December 2012, in addition to 6 cases diagnosed at Tri-Service General Hospital (Taipei, Taiwan). Clinical staging was based on American Joint Committee on Cancer staging system for soft tissue sarcoma (2014). With a mean follow-up of 27.5 months (range, 0.27–102 months), 18% (6/34) of the patients survived. The 1-, 3- and 5-year survival rates were 68.0±9.3, 42.1±10.2 and 32.7±9.8% for patients with stage I disease (mean follow-up, 32.7 months), whilst the 1- and 3-year survival rates were 33.3±15.7 and 22.2±13.9% for patients with stage IV disease (mean follow-up, 13.0 months). Determining an appropriate therapeutic strategy for this patient group is necessary. New studies encompassing larger patient populations are required in order to analyze and define standard prognostic parameters and to standardize a treatment approach for this extremely rare neoplasm.

Transposable element (TE) derived sequences comprise more than half of the human genome, and their presence has been documented to alter gene expression in a number of different ways, including the generation of alternatively spliced transcript isoforms. Alternative splicing has been associated with tumorigenesis for a number of different cancers. The objective of this study was to broadly characterize the role of human TEs in generating alternatively spliced transcript isoforms in cancer. To do so, we screened for the presence of TE-derived sequences co-located with alternative splice sites that are differentially utilized in normal versus cancer tissues. We analyzed a comprehensive set of alternative splice variants characterized for 614 matched normal-tumor tissue pairs across 13 cancer types, resulting in the discovery of 4,820 TE-generated alternative splice events distributed among 723 cancer-associated genes. SINEs (Alu) and LINEs (L1) were found to contribute the majority of TE-generated alternative splice sites in cancer genes. A number of cancer-associated genes - including MYH11, WHSC1, and CANT1 - were shown to have overexpressed TE-derived isoforms across a range of cancer types. TE-derived isoforms were also linked to cancer-specific fusion transcripts, suggesting a novel mechanism for the generation of transcriptome diversity via trans-splicing mediated by dispersed TE repeats. Citation Format: Evan A. Clayton, Lavanya Rishishwar, Tzu-Chuan Huang, Saurabh Gulati, Dongjo Ban, John F. McDonald, I. King Jordan. An atlas of transposable element derived alternative splicing in cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2115.

BACKGROUND Recently, many endocrine therapies have become available for hormone receptor-positive, human epidermal growth factor receptor 2-negative, pretreated, advanced breast cancer. Direct comparisons of these novel treatments to assess their added value, however, are lacking METHODS:: Our aim was to synthesize available evidence to compare all current endocrine treatments for hormone receptor-positive / human epidermal growth factor receptor 2-negative advanced breast cancer. We performed a systematic review to identify available randomized controlled trial evidence. We searched Embase, MEDLINE, and the Cochrane Central Register of Controlled Clinical Trials. Two trials presented at international oncology congresses (American Society of Clinical Oncology [ASCO]) were added to include the most recent evidence. A frequent network meta-analysis was used, and the surface under cumulative ranking area (SUCRA) was calculated to determine the best treatment RESULTS:: In total, 32 trials and 12,726 patients were identified, including 27 arms. Compared with fulvestrant 500 mg alone, novel target inhibitors combined with fulvestrant or exemestane had significantly prolonged progression-free survival with hazard ratios ranging from 0.62 to 0.82. Fulvestrant 500 mg plus palbociclib 125 mg and exemestane 25 mg plus entinostat 5 mg similarly extended progression-free survival (hazard ratio: 0.64 and 0.62 with SUCRA values of 91% and 92%, respectively). The exemestane 25 mg plus everolimus 10 mg combination had the best clinical benefit rate (risk ratio: 1.84, SUCRA: 91%) and overall response rate (risk ratio: 6.05, SUCRA: 97%) CONCLUSIONS:: On the basis of this analysis, the 2 combinations of exemestane plus everolimus and fulvestrant plus palbociclib were the best treatment options.

BCR-ABL tyrosine-kinase inhibitors are the first-line therapy for the majority of patients with chronic myelogenous leukemia (CML). Up to 20% of patients who have imatinib-treated CML in blast crisis (BC) experience a relapse in the central nervous system (CNS) due to the poor penetration of the drug by the blood-brain barrier. The present case reports a successful experience of using dasatinib-based combination therapy to treat a 22-year-old female who presented with initial symptoms of intermittent fever and easy bruising under the diagnosis of CML in BC. Although the patient eventually succumbed to profound sepsis, the CNS involvement was treated successfully using dasatinib-based combination therapy (cranial radiation and de-escalated intrathecal chemotherapy). This case demonstrates that dasatinib may be a viable option for those who are not medically fit for or are otherwise unwilling to receive high-dose chemotherapy. It appears that dose intensity is essential for optimal efficacy and should be maintained at 150 mg daily as far as possible.

PurposeIn a retrospective cohort study, we report the current epidemiology of patients with multiple myeloma (MM) and analyze the real-world clinical outcomes of bortezomib-based therapy.Materials and methodsThis retrospective study was mainly designed to evaluate the characteristics, treatment outcomes, and prognostic factors of patients with MM who received bortezomib-based therapy. We identified 5,726 patients in Taiwan with MM newly diagnosed between 2007 and 2015. Confidential data from the National Health Insurance Research Database (NHIRD) was used under strict guidelines, as it was made available in an electronic format for research purposes. In addition, we analyzed 96 patients who have been diagnosed with MM and were treated at the Tri-Service General Hospital (TSGH) between January 1, 2002, and December 31, 2018.ResultsPatients receiving first-line treatment with bortezomib had longer overall survival (OS) compared to those who received non-first-line treatment (pConclusionsBortezomib as a first-line treatment extended the OS in four-year mortality tracking and lowered the mortality risk according to the NHIRD analysis. In the TSGH analysis, the results indicated that the initial conditions of patients with MM have a lower influence on the OS and PFS after bortezomib-based therapy was administered.

Malignant bowel obstruction (MBO) is a disease with a poor prognosis, particularly in patients with advanced bowel or gynecological cancers. Multimodality teatments may be used to relieve the symptoms in patients with MBO; however, there is currently no consensus regarding the optimal treatment and no strong evidence supporting the efficacy of any treatment in improving the quality of life (QOL) and prolonging survival. We conducted a search through our medical center database of cancer registries for MBO cases between January, 1995 and December, 2008 and analyzed the clinicopathological characteristics and association between treatments and prognosis or QOL. The primary type of cancer causing MBO was found to be adenocarcinoma of colon. The overall survival time was found to be significantly higher among patients presenting with MBO as the initial symptom and improved QOL was achieved in patients who received surgical treatment. The mean survival time and the functional status of colorectal cancer patients receiving targeted therapy and chemotherapy were more satisfactory compared with those receiving surgery alone or conservative treatment. Furthermore, for end-stage cancer patients with MBO, hospice care was effective in reducing pain scores and relieving the symptoms of the disease.

There are numerous causes of lower back pain. In the oncological setting, spine metastasis from a solid tumor is the most common. However, hematological disorders should also be taken into consideration. The current study presents a case of chronic myelomonocytic leukemia with the initial presentation of chronic lower back pain, followed by symptoms that included urinary retention, stool incontinence and left gum swelling, in a patient who was eventually diagnosed with granulocytic sarcoma (GS) over the sacral region. GS is a rare presentation of a tumor consisting of extramedullary leukemic infiltrations, which develop at different sites and cause different symptoms. Prompt and correct diagnosis of this type of disease may be crucial to improve the survival outcome by the early initiation of adequate treatment.

Objective Trastuzumab-containing treatment regimens have been shown to improve survival outcomes in HER2-positive breast cancer (BC). It is much easier to infuse a fixed one-vial dose to every patient on a regular schedule in the general clinical setting. The aims of this study were evaluating the efficacy of a 440 mg fixed-dose of trastuzumab administered on a monthly infusion schedule, and the risk factors for cardiac events. Patients and methods We retrospectively reviewed data from 300 HER2-positive BC patients in our institute: 208 were early-stage BC patients undergoing adjuvant trastuzumab treatment, and 92 were metastatic BC patients treated with trastuzumab infusions until disease progression. There were 181 patients receiving regular trastuzumab infusions every 3 weeks (Q3W; 8 mg/kg loading dose followed by 6 mg/kg every 3 weeks), and the other 119 patients were treated monthly with a fixed 440 mg dose (QM; fixed 440 mg every 4 weeks). Results The medians of progression-free survival (PFS) and overall survival (OS) in the adjuvant setting were not reached in both treatment groups. In the metastatic setting, there was no significant difference between groups in PFS or OS. The median time to significant cardiovascular (CV) dysfunction was 4.54 months. The incidence of congestive heart failure requiring medication in our cohort was 3.4%. Conclusion In our study, we found that fixed-dose monthly trastuzumab was feasible and effective. In addition, the CV risk was not higher with the fixed-dose protocol. This treatment modality could lower the cost and was easier to implement in clinical practice. Larger prospective randomized studies with longer-term follow up are needed to confirm our results.

Introduction: Nonsmall cell lung cancer (NSCLC) is the leading cause of cancer-related deaths in many countries. Brain metastases (BM) from NSCLC are poor prognosis, with a median survival of 6 months following whole-brain radiotherapy. NSCLC patients harboring activating epidermal growth factor receptor (EGFR) mutations have generally responded to afatinib with good objective response rate, progression-free survival (PFS), and overall survival (OS), and platinum-double chemotherapy. These findings demonstrate the potential effectiveness of afatinib for the treatment of EGFR-positive with BM. The aim of this retrospective study is to present data on the prognostic effect of afatinib versus gefitinib in an unselected population with newly diagnosed NSCLC with BM collected. Patients and Methods: Data were obtained from our electronic database from 48 patients with newly diagnosed EGFR mutative NSCLC with BM and treated from January 2007 to December 2017, in which data on EGFR mutation was all available at the time of diagnosis. Results: Thirteen of forty-eight were treated with afatinib, and the other was treated with gefitinib. There were seven Exon 19 deletion and six were Exon 21 mutation ([p.Leu858Arg, (c.2573T>G)]:4; [p.Leu861Gln, (c.2582T>A)]:2). There was 18 Exon 19 deletion, and 16 were Exon 21 mutation ([p.Leu858Arg, (c.2573T>G)]:16) and the other one was Exon 18 mutation [p.Gly719Ser (c.2155G>A)]. There was no significant difference between two groups included PFS (afatinib: 12.0 months vs. gefitinib: 10.1 months, P = 0.766) and OS (afatinib: 20.6 months vs. gefitinib: 14.5 months, P = 0.362). Conclusion: From the K–M survival curve evaluation, neither the PFS nor OS have the statistical significance between gefitinib and afatinib. We provided a real-world data to compare the efficacy of EGFR-TKI in NSCLC. Due to relative small sample size, we urged large clinical trial to provide more precise results.

The National Comprehensive Cancer Network (NCCN) International Prognostic Index (IPI) is an enhanced prognostic tool that has identified some specific extranodal sites as a poor prognostic factor. We retrospectively analyzed 148 Taiwanese patients with newly diagnosed diffuse large B-cell lymphoma receiving rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP)-like regimens from January 2001 to December 2010 at the Tri-Service General Hospital. In univarate analysis, ≥ 2 extranodal involved sites had no significant prognostic relevance (p = 0.108), although extranodal involvement of the lung/pleura, liver, lower urinary tract or bone marrow was a statistically significant poor prognostic factor (p < 0.001). In multivariate analysis, specific extranodal sites had a stronger predictive value for poor prognosis (relative risk 3.654, 95% confidence interval 1.514-8.815, p = 0.004) compared with the number of extranodal sites involved. This finding suggests that specific extranodal involved sites have prognostic value in the R era.

EW02, a polysaccharide-enriched crude extract from black soybean, has been shown to assist hematopoiesis in chemotherapy-treated animals. The present study aimed to clarify the safety, quality of life (QOL) and efficacy for myelopoiesis of EW02 administration in early breast cancer (EBC) patients receiving adjuvant chemotherapy. A total of 60 eligible EBC patients were enrolled in a randomized, double-blinded trial, 40 of whom were prescribed 700 mg oral EW02 three times daily for 15 days in chemotherapy cycle (C)2. The remainder were prescribed a placebo. All subjects took EW02 in C3 for 15 days. Blood samples were collected at different time-points for determining the blood cell count, and the serum level of granulocyte colony-stimulating factor (G-CSF) and interleukin (IL)-6. All patients tolerated EW02 well without severe side-effects. QOL evaluation showed that only the score of one questionnaire section (QLQ-C30) was significantly increased at C1 day (D)8 to C2D8 when the EW02 and placebo groups were compared (P=0.045). No significant myelopoiesis recovery, and no incremental change in IL-6 and G-CSF levels were found in C2. Subgroup analysis showed a slightly lower decrease in absolute neutrophil count (ANC) in the EW02 patients who underwent Adriamycin + cyclophosphamide treatment compared with the placebo group. Although EW02 failed to show efficacy for myelopoiesis in the present study, EW02 was still well tolerated in EBC patients who underwent adjuvant chemotherapy.

Multiple myeloma (MM) is characterized by the neoplastic proliferation of monoclonal plasma cells in the bone marrow and results in complications. In Taiwan, melphalan and several novel agents are used to treat myeloma patients who are not candidate for hematopoietic stem cell transplant (HSCT). This retrospective study aimed to evaluate the characteristics, treatment outcome, and prognostic factors of MM patients who were ineligible for HSCT at our institution from October 2000 until November 2012. A total of 101 MM patients were reviewed. The median age was 71.0 years, and median overall survival (OS) was 22.0 months. Most of patients were diagnosed as IgG-type myeloma (55.4 %). The initial presentations included anemia (89.1 %), skeletal events (49.5 %), severe renal insufficiency (30.7 %), and hypercalcemia (28.7 %). With regard to the frontline therapy, thalidomide/steroid was the most common. Infection was the leading cause of death and adverse effects. Treatment with bortezomib, almost in the second- or third-line setting, was associated with longer median OS (35.5 months) and the median time to progression (TTP) (6.0 months). Bortezomib treatment, chemotherapy, International Staging System (ISS) stage I, and better performance status significantly correlated with survival benefit. In the bortezomib-treated subgroup, better treatment response caused excellent median OS (67.7 months) and also significantly delayed TTP. Therefore, this current analysis concluded a median OS of 22 months in myeloma patients ineligible for HSCT at our institution during the past 10 years. The use of bortezomib with better treatment response also achieved significantly better median OS and TTP.

Supplemental Digital Content is available in the text, The current retrospective study aimed to investigate the relationship between prognostic factors and overall survival (OS) in patients with advanced pancreatic head cancers who initially presented with obstructive jaundice. Furthermore, the impact of age and comorbidities on therapeutic strategies in such patients was evaluated. A total of 79 advanced pancreatic head cancer patients who were treated at our institution between January 2006 and November 2013 were reviewed. We analyzed OS risk factors including sex, age, laboratory characteristics, Eastern Cooperative Oncology Group performance status, Charlson Comorbidity Index Scores (CCIS), and therapeutic strategies using Cox proportional hazards regression models. There was no difference in the OS of patients according to the type biliary drainage procedure they underwent. Other related factors, such as better performance status, lower CCIS, and receiving chemotherapy significantly correlated with survival in multivariate analyses. There was a significant survival benefit in systemic chemotherapy compared to best supportive care (BSC) or local radiotherapy. However, no survival benefit was found in elderly patients (age >70 years) undergoing systemic therapy compared to younger patients, except in those elderly patients with CCIS ≤ 1. In advanced pancreatic head cancer patients with obstructive jaundice, systemic therapy and adequate biliary drainage were still the most effective procedures for improving OS in the general population. However, in elderly patients with relatively higher CCIS, BSC with adequate biliary drainage was palliative and no less effective than systemic/local therapies.

β-Blockers have been reported to exhibit potential anticancer effects in cancer cell lines and animal models. However, clinical studies have yielded inconsistent results regarding cancer outcomes and cancer risk when β-blockers were used. This study investigated the association between propranolol and cancer risk. Between January 1, 2000 and December 31, 2011, a patient cohort was extracted from the Longitudinal Health Insurance Database 2000, a subset of the Taiwan National Health Insurance Research Database. A propranolol cohort (propranolol usage >6 months) and nonpropranolol cohort were matched using a propensity score. Cox proportional hazard models were used to estimate the hazard ratio (HR) and 95% confidence intervals (CIs) of cancer associated with propranolol treatment. The study sample comprised 24,238 patients. After a 12-year follow-up period, the cumulative incidence for developing cancer was low in the propranolol cohort (HR: 0.75; 95% CI: 0.67–0.85; P

Background: Neoadjuvant chemoradiotherapy (NCRT) followed by total mesorectal excision is now recommended for patients with locally advanced rectal cancer (LARC). This retrospective study was aimed to analyze the treatment efficacy in LARC patients in a single institute. Materials and Methods: Rectal cancer patients with clinically T3, T4, or nodal positive (N1-2) diseases who received either NCRT or adjuvant chemoradiotherapy (ACRT) were retrospectively enrolled between 2007 and 2011. The treatment outcome and clinical characteristics of study population were compared. Results: There were 176 patients been enrolled with a mean age of 63.1 years. Totally, 123 (69.9%) patients received NCRT and 53 (30.1%) patients received ACRT, respectively. The median duration of follow-up was 43.3 months in NCRT group and 47.6 months in ACRT group. There was no significant difference about overall survival (OS), progression-free survival (PFS), and local relapse-free survival (LRFS) between two treatment groups. However, NCRT achieved pathological complete remission (pCR) of 27.6%. In addition, the patients with pathologically downstage after NCRT (the responders) had significantly better PFS (P < 0.0001), local RFS (P = 0.0468), and OS (P = 0.0045), compared with non-responder after NCRT. Oxaliplatin-based NCRT did not significantly increase treatment response, OS and PFS, compared with other regimens in our analysis (P = 0.29). Conclusions: In our cohort, NCRT achieved high pCR rate than those reported in previous literature. Although there was no significant improvement of OS, PFS, and LRFS in NCRT group, there was a significant improvement of LRFS, OS, and PFS in those responders after NCRT.