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Background Cancer-related fatigue is one of the most common and persistent issues experienced by cancer patients. Cancer-related fatigue is a distinct form of fatigue that is subjective, long-lasting and unalleviated by rest or sleep. Studies have shown that almost all cancer patients experience severe fatigue that disrupts the quality of life and physical function, but cancer-related fatigue remains under-addressed in clinical care, and only about half of all patients receive treatment. Methods To increase the awareness of cancer-related fatigue and improve current management, the Taiwan Society of Cancer Palliative Medicine and the Taiwan Oncology Nursing Society convened a consensus committee to develop recommendations for the screening, assessment and treatment of cancer-related fatigue. Results Thirteen consensus recommendations were subsequently developed based on the best available evidence and the clinical experience of committee members. Conclusions These recommendations are expected to facilitate the standardization of cancer-related fatigue management across Taiwan and may also serve as a reference for other clinicians.

Intratumoral HER2 expression

Changes in tumor size relative to Week 6 lapatinib concentrations (ng/mL).

Figure Legends for Supplementary Figures

Waterfall plot of maximum tumor shrinkage from baseline including (or with evaluable) unconfirmed response.

RECIST response by intatumoral median gene expression

Background Cancer-related fatigue (CRF) is an emerging clinical issue, although its prevalence and impact on quality of life (QOL) in cancer patients in Taiwan remain unclear. The present nationwide cross-sectional study was conducted to provide a thorough overview of the prevalence, related factors and impact of CRF in Taiwan. Methods In this multi-center survey, data were collected using the International Classification of Diseases 10th Revision (ICD-10) Fatigue evaluation, Brief Fatigue Inventory–Taiwan (BFI-T), the Chinese version of the Symptom Distressed Scale and a fatigue experience survey. Logistic regression was used to determine the correlations between fatigue characteristics and the factors studied. Results A total of 1207 cancer patients were recruited from 23 hospitals in Taiwan. Fatigue was the most distressing symptom in Taiwanese cancer patients. The distress score was higher if CRF was diagnosed using ICD-10 compared with BFI-T. Rest and nutritional supplementation were the most common non-pharmacological treatments; blood transfusion was the most common pharmacological treatment. There were 45% of patients reported not receiving a timely intervention for fatigue. Conclusions Fatigue is the most bothersome symptom reported by Taiwanese cancer patients. Caregivers should be aware of the impact of CRF on QOL in cancer patients, constantly measure the severity of fatigue and provide appropriate interventions., Depending on the questionnaire used, the prevalence of fatigue in cancer patients in Taiwan ranges from 23.4 to 71.9%. Fatigue is the most bothersome symptom reported by cancer patients.

We evaluated the analytical and clinical performance of a novel circulating tumor cell (CTC)-based blood test for determination of programmed death ligand 1 (PD-L1) protein expression status in real time in treatment-naïve non-small cell lung cancer (NSCLC) patients. CTCs were detected in 86% of patients with NSCLC (I-IV) at the time of diagnosis, with a 67% PD-L1 positivity rate (≥ 1 PDL + CTC). Among 33 NSCLC patients with PD-L1 results available via both tissue immunohistochemistry (IHC) and CTC assays, 78.9% were positive according to both methods. The CTC test identified an additional ten cases that were positive for PD-L1 expression but that tested negative via IHC analysis. Detection of higher PD-L1 expression on CTCs compared to that in the corresponding tissue was concordant with data obtained using other platforms in previously treated patients. The concordance in PD-L1 expression between tissue and CTCs was approximately 57%, which is higher than that reported by others. In summary, evaluation of PD-L1 protein expression status on CTCs isolated from NSCLC patients is feasible. PD-L1 expression status on CTCs can be determined serially during the disease course, thus overcoming the myriad challenges associated with tissue analysis.

Aim To evaluate the prevalence of pain in cancer outpatients in Taiwan and to investigate the impact of pain on quality of life (QoL) and patient satisfaction. Results were compared to those of a similarly designed study conducted in 2008 to identify trends. Methods Adult patients with cancer treated as outpatients in hospitals throughout Taiwan were recruited. Pain intensity and the extent to which pain interfered with QoL were self-reported using a modified version of the Brief Pain Inventory. Patients also indicated their level of satisfaction with their physician, as well as with their pain control. Results A total of 2652 patients were enrolled from 16 sites. Of these, 1167 (44.0%) patients reported experiencing pain during the previous week. Prevalence and severity of pain were highest in patients with progressive disease. A higher pain severity score was significantly associated with greater interference in both physical and psychological functions. Overall, 86.0% of all participants expressed satisfaction with their physician and 84.8% were satisfied with their pain control; satisfaction rates were associated with pain severity. Compared with the findings from the 2008 study, pain prevalence was notably lower and patient satisfaction was significantly greater in the current study. Conclusions Prevalence and severity of pain were associated with disease stage. Pain interference on QoL correlated significantly with pain severity. Treatment of pain in cancer patients in Taiwan seems to have improved from 2008 to 2014, possibly attributable to new cancer pain treatment guidelines and the wider availability of novel analgesic therapies.

Poor adherence to analgesic drugs is one of the most common barriers to adequate pain management. This prospective, cross-sectional, patient-oriented observational study aimed to explore the adherence rate, clinical factors, and impact of adherence to analgesic drugs on the quality of life (QoL) among cancer outpatients in Taiwan. Eight hundred ninety-seven consecutive adult outpatients with cancer who had reported tumor pain and received regular analgesic drug treatment were enrolled from 16 medical centers across Taiwan. The Brief Pain Inventory was used to assess pain intensity and QoL. Morisky’s four-item medication adherence scale was used to assess adherence to analgesic drugs. Clinical factors possibly associated with good adherence to analgesic drugs were analyzed using multivariate logistic regression analyses. Of the 897 patients, 26.9% met criteria for the good, 35.5% for the moderate, and 37.6% for the poor adherence groups. The good adherence group had significantly better QoL outcomes than the moderate and poor adherence groups (all p

AIM Pain assessment and management have been important criteria in hospital accreditation in Taiwan since 2007. We used a Taiwanese health insurance database to determine factors influencing patterns of strong opioid use in cancer patients in their final 12 months of life. METHODS Data from patients with cancer in Taiwan outpatient clinics with cancer-related deaths between 2008 and 2011 were included in the analysis. Strong opioid prescription data from the last 12 months of each patient's life, as well as patient, physician, and hospital characteristics, were collected from the National Health Insurance Research Database. RESULTS Among 162 679 patients, more were male (63.6%) than female (36.4%) and almost half (49.3%) were ≥70 years old. Most (44.9%) patients had gastrointestinal cancer. More than one-third (35.4%) of patients were prescribed strong opioids during the 12 months before death, and more than half (53.2%) of those prescribed opioids received them in the 3 months before death. Median duration of strong opioid use was 81 days before death. Patients with head/neck cancer (52.8%) or who were treated in hematology and oncology departments (45.8%) were most likely, and patients with gastrointestinal cancer (hazard ratio = 0.65; 95% confidence interval, 0.64-0.67) or treated in gastroenterology departments (hazard ratio = 0.88; 95% confidence interval, 0.84-0.93) were least likely to be prescribed strong opioids. CONCLUSION Strong opioid prescriptions varied among patients with different cancer diagnoses and physicians. Information from this study can guide efforts to improve patient and physician education about cancer pain management.

Although cancer patients were satisfied with their physicians, treatment of cancer pain was still suboptimal. Guidelines should be revised to improve pain assessment and control in patients with cancer., Background We have limited knowledge about cancer patients’ pain control satisfaction in outpatient departments in Taiwan and doctors’ practice of adjusting analgesics according to their pain status. This survey examined pain management and satisfaction among cancer outpatients with pain and obtained information on their quality of life and treatment management for different pain intensities. Methods The Short version of the Brief Pain Inventory was used as the outcome questionnaire. Participants comprised 2075 patients with different cancers and disease statuses at 14 oncological outpatient departments, of which 1051 reported pain within the week prior to testing. The impact of pain management on physical and psychological functioning, and satisfaction with doctors were evaluated. Information about doctors’ prescriptions was collected. Logistic regression analyses were conducted to evaluate whether the interference scale performed identically in the different analgesic ladders. Results Pain was significantly linked to disease status and affected patients’ physical and psychiatric functioning. Almost 100% of patients were satisfied with their pain control, but more than 70% of doctors did not change analgesics based on patients’ current pain status. The results show that although patients were satisfied with their physicians, treatment of cancer pain was still suboptimal. Conclusion Pain assessment and treatment need to be more thorough and management guidelines should be revised to improve pain control in patients with cancer.

Background Falls and fall-related injuries are important indicators for quality of nursing care in institutions. Few studies have been conducted specifically on this topic for hospitalized patients with cancer in Taiwan. Purpose The aims of this study were to understand falls and levels of injury; to identify associations among fall-related injuries, demographics, and causes of falling; and to predict fall-related injuries in hospitalized patients with cancer. Methods A retrospective survey design was used. Data were retrieved from the Taiwan Patient-Safety Reporting system query fall incidences for persons hospitalized with cancer at a medical center in northern Taiwan from 2010 to 2012. Data were encoded and analyzed with descriptive statistics, the chi-square test, and multiple stepwise logistic regression analysis using IBM SPSS Statistics version 18.0. Results One hundred fifty-six (85%) of the 184 hospitalized patients with cancer had fall-related injuries. Falling tended to be more frequent in men without a history of falls and more prevalentat night. The results of regression analysis showed that the variables being with companions at the time of a fall (OR = 5.411, 95% CI [1.619, 18.081]), lower limb weakness (OR = 0.284, 95% CI [0.097, 0.832]), postural hypotension (OR = 0.101, 95% CI [0.014, 0.733]), total score of fall risk factors (OR = 1.688, 95% CI [1.071, 2.660]), and a fall occurring at the bedside (OR = 3.493, 95% CI [1.119, 10.903]) were all positively associated with fall-related injuries, with a Nagelkerke R of 42.8%. Conclusions/implications for practice The risk factors for falls that affect hospitalized patients with cancer are complex. Nursing staff must evaluate the risk factors and treatment methods for each patient and facilitate fall prevention measures to achieve safety-centered quality of care. This study provides an example for nursing staff when assessing factors associated with falls and working to reduce fall-related injuries among patients with cancer.

// Yi-Hao Chiang 1, 2, * , Yu-Cheng Chang 1, 2, 3 * , Huan-Chau Lin 1, 2 , Ling Huang 2 , Chun-Chia Cheng 1, 2 , Wei-Ting Wang 1 , Hung-I Cheng 4 , Nai-Wen Su 1, 2, 3 , Caleb Gon-Shen Chen 1, 2, 3, 5 , Johnson Lin 1, 2 , Yi-Fang Chang 1, 2, 3 , Ming-Chih Chang 1, 2, 3 , Ruey-Kuen Hsieh 1, 2 , Wen-Chien Chou 6, 7 , Ken-Hong Lim 1, 2, 3, 8 and Yuan-Yeh Kuo 8 1 Division of Hematology and Oncology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan 2 Laboratory of Good Clinical Research Center, Department of Medical Research, MacKay Memorial Hospital, New Taipei City, Taiwan 3 Department of Medicine, MacKay Medical College, New Taipei City, Taiwan 4 Division of Hematology and Oncology, Department of Internal Medicine, MacKay Memorial Hospital, Hsinchu, Taiwan 5 Institute of Molecular and Cellular Biology, National Tsing-Hua University, Hsinchu, Taiwan 6 Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan 7 Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan 8 Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan * Co-first authors, these authors contributed equally to this work Correspondence to: Ken-Hong Lim, email: khlim@mmh.org.tw Yuan-Yeh Kuo, email: yykuo@ntu.edu.tw Keywords: JAK2, TERT, myeloproliferative neoplasms, single nucleotide polymorphism Received: September 16, 2016 Accepted: June 09, 2017 Published: July 12, 2017 ABSTRACT Germline variations at JAK2 , TERT , HBS1L - MYB and MECOM have been found to associate with myeloproliferative neoplasms (MPNs) in European populations. Whether these germline variations are associated with MPNs in Taiwanese population is obscure. Here we aimed to evaluate the association of five germline variations ( JAK2 46/1 haplotype tagged by rs12343867, JAK2 intron 8 rs12339666, TERT rs2736100, HBS1L - MYB rs9376092 and MECOM rs2201862) and the risk of MPNs in Taiwanese population. A total of 178 MPN patients (109 essential thrombocythemia, 54 polycythemia vera and 15 primary myelofibrosis) were enrolled into this study. The information of 17033 control subjects was obtained from Taiwan Biobank database. The JAK2 46/1 haplotype, JAK2 rs12339666 and TERT rs2736100 were significantly associated with Taiwanese MPNs ( P = 3.6x10 -19 , 1.9x10 -19 and 3.1x10 -6 , respectively), and JAK2 V617F -positive MPNs (n=121) ( P = 5.6x10 -21 , 4.4x10 -21 and 8.6x10 -7 , respectively). In JAK2 V617F -negative cases (n=55), only the JAK2 46/1 haplotype and JAK2 rs12339666 remained statistically significant ( P = 0.009 and 0.007, respectively). When stratified by disease subtypes, the JAK2 46/1 haplotype and JAK2 rs12339666 were significantly associated with all three MPN subtypes, but TERT rs2736100 was only associated with essential thrombocythemia and polycythemia vera. We did not find any association of these five SNPs with CALR mutations in our cohort. Furthermore, the risk alleles of MECOM rs2201862 and HBS1L - MYB rs9376092 were demonstrated to be negatively associated with the risk of developing polycythemia vera. In conclusion, germline variations at JAK2 (both the 46/1 haplotype and rs12339666) and TERT rs2736100 were associated with MPNs in Taiwanese population.

// Ken-Hong Lim 1,2,3,4 , Caleb Gon-Shen Chen 2,3,4,5 , Yu-Cheng Chang 2,3,4 , Yi-Hao Chiang 2,3 , Chen-Wei Kao 3 , Wei-Ting Wang 3 , Chiao-Yi Chang 3 , Ling Huang 3 , Ching-Sung Lin 3 , Chun-Chia Cheng 3 , Hung-I Cheng 6 , Nai-Wen Su 2,3,4 , Johnson Lin 2 , Yi-Fang Chang 2,3,4 , Ming-Chih Chang 2,3,4 , Ruey-Kuen Hsieh 2,3 , Huan-Chau Lin 2,3 and Yuan-Yeh Kuo 1 1 Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan 2 Department of Internal Medicine, Division of Hematology and Oncology, MacKay Memorial Hospital, Taipei, Taiwan 3 Department of Medical Research, Laboratory of Good Clinical Research Center, MacKay Memorial Hospital, Tamsui District, New Taipei City, Taiwan 4 Department of Medicine, MacKay Medical College, New Taipei City, Taiwan 5 Institute of Molecular and Cellular Biology, National Tsing-Hua University, Hsinchu, Taiwan 6 Department of Internal Medicine, Division of Hematology and Oncology, MacKay Memorial Hospital, Hsinchu, Taiwan Correspondence to: Ken-Hong Lim, email: // Huan-Chau Lin, email: // Yuan-Yeh Kuo, email: // Keywords : B cell, CALR, essential thrombocythemia, immune Received : January 06, 2017 Accepted : February 28, 2017 Published : March 18, 2017 Abstract Essential thrombocythemia (ET) is a BCL-ABL1 -negative myeloproliferative neoplasm. We have reported that increased activated B cells can facilitate platelet production mediated by cytokines regardless JAK2 mutational status in ET. Recently, calreticulin ( CALR ) mutations were discovered in ~30% JAK2 / MPL- unmutated ET and primary myelofibrosis. Here we sought to screen for CALR mutations and to evaluate B cell immune profiles in a cohort of adult Taiwanese ET patients. B cell populations, granulocytes/monocytes membrane-bound B cell-activating factor (mBAFF) levels, B cells toll-like receptor 4 (TLR4) expression and intracellular levels of interleukin (IL)-1β/IL-6 and the expression of CD69, CD80, and CD86 were quantified by flow cytometry. Serum BAFF concentration was measured by ELISA. 48 healthy adults were used for comparison. 19 (35.2%) of 54 ET patients harbored 8 types of CALR exon 9 mutations including 4 (7.4%) patients with concomitant JAK2 V617F mutations. Compared to JAK2 V617F mutation, CALR mutations correlated with younger age at diagnosis ( p =0.04), higher platelet count ( p =0.004), lower hemoglobin level ( p =0.013) and lower leukocyte count ( p =0.013). Multivariate analysis adjusted for age, sex, follow-up period and hematological parameters confirmed that increased activated B cells were universally present in JAK2 -mutated, CALR -mutated and triple-negative ET patients when compared to healthy adults. JAK2 - and CALR -mutated ET have significantly higher fraction of B cells with TLR4 expression when compared to triple-negative ET ( p =0.019 and 0.02, respectively). CALR -mutated ET had significantly higher number of CD69-positive activated B cells when compared to triple-negative ET ( p =0.035). In conclusion, increased B cell activation is present in ET patients across different mutational subgroups.

Summary Background Evidence indicates apoptosis deregulation is associated with aging. We correlated expression of cIAP-2, a member of the inhibitor of apoptosis protein family, with survival and age in patients with resected squamous cell carcinoma of head and neck (SCCHN). Methods Immunohistochemical (IHC) staining for cIAP-2 and other markers were performed using tissue microarrays from 103 resected SCCHN patients. Expression was grouped according to IHC scores (0–3) and statistical association with clinical–pathological factors was determined. Results High expression of cIAP-2 was found to be increased in patients aged 60 or greater. High expression of cIAP-2 and an age ≥60 were significantly associated with worse survival in univariate analysis, but only an age ≥60, and not cIAP-2 expression, was prognostic in multivariate analysis. Conclusion High expression of cIAP-2 was found more frequently in elderly SCCHN patients but was not independently associated with survival after adjusting other clinical–pathologic factors.

An exploratory phase II biomarker-embedded trial (LPT109747; NCT00526669) designed to determine the association of lapatinib-induced fluoropyrimidine gene changes with efficacy of lapatinib plus capecitabine as first-line treatment for advanced gastric cancer or gastroesophageal junction adenocarcinoma independent of tumor HER2 status. Tumor biopsies obtained before and after 7-day lapatinib (1,250 mg) to analyze changes in gene expression, followed by a 14-day course of capecitabine (1,000 mg/m2 twice daily, 14/21 days) plus lapatinib 1,250 mg daily. Blood samples were acquired for pharmacokinetic analysis. Primary clinical objectives were response rate (RR) and 5-month progression-free survival (PFS). Secondary objectives were overall survival (OS), PFS, time to response, duration of response, toxicity, and identification of associations between lapatinib pharmacokinetics and biomarker endpoints. Primary biomarker objectives were modulation of 5-FU-pathway genes by lapatinib, effects of germline SNPs on treatment outcome, and trough steady-state plasma lapatinib concentrations. Sixty-eight patients were enrolled; (75% gastric cancer, 25% gastroesophageal junction). Twelve patients (17.9%) had confirmed partial response, 31 (46.3%) had stable disease, and 16 (23.9%) had progressive disease. Median PFS and OS were 3.3 and 6.3 months, respectively. Frequent adverse events included diarrhea (45%), decreased appetite (39%), nausea (36%), and fatigue (36%). Lapatinib induced no changes in gene expression from baseline and no significant associations were found for SNPs analyzed. Elevated baseline HER3 mRNA expression was associated with a higher RR (33% vs. 0%; P = 0.008). Lapatinib plus capecitabine was well tolerated, demonstrating modest antitumor activity in patients with advanced gastric cancer. The association of elevated HER3 and RR warrants further investigation as an important player for HER-targeted regimens in combination with capecitabine. Mol Cancer Ther; 15(9); 2251–8. ©2016 AACR.

The purpose of this study is to investigate the prevalence of pain, pain management, and impact of recent pain on daily functioning in patients with head and neck cancer (HNC) and patients with other cancers. This multi-center survey was conducted by using Brief Pain Inventory questionnaire to evaluate pain status and its impact on daily functioning. A total of 3289 patients were analyzed including 708 HNC patients and 2581 patients with other cancers. The overall pain prevalence was 69.17%. A higher percentage of HNC patients had recent pain (60.59 vs. 44.01%, P

Objective To investigate the prevalence of pain in cancer patients at different disease statuses, the impact of pain on physical and psychiatric functions of patients and the satisfaction of pain control of patients at outpatient clinic department in Taiwan. Methods Short form of the Brief Pain Inventory was used as the outcome questionnaire. Unselected patients of different cancers and different disease statuses at outpatient clinic department were included. The impacts of their current pain control on physical function, psychiatric function and the satisfaction of doctors were evaluated. Logistic regression analyses were performed to evaluate whether the interference scale performed identically in the different analgesic ladders. The dependent variables were satisfaction toward physician and treatment. Results A total of 14 sites enrolled 2075 patients in the study. One thousand and fifty-one patients reported pain within the last 1 week. In patients whose diseases deteriorated, >60% of them need analgesics for pain control. Pain influenced physical and psychiatric functions of patients, especially in the deteriorated status. More than 80% of patients were satisfied about current pain control, satisfaction rate related to disease status, pain intensities and treatments for pain. Conclusion Our study found that different cancers at different statuses had pain at variable severity. Pain can influence physical and psychological functions significantly. More than 75% of subjects reported satisfaction over physician and pain management in outpatient clinic department patients with cancer pain in Taiwan.

Background Somatic CALR exon 9 mutations have recently been identified in patients with JAK2/MPL-unmutated myeloproliferative neoplasm, and have become an important clonal marker for the diagnosis of essential thrombocythemia (ET) and primary myelofibrosis. In the present study, we sought to use high-resolution melting analysis (HRMA) as a screening method for the detection of CALR mutations. Methods 32 JAK2/MPL-unmutated ET patients were retrospectively enrolled and 8 healthy adults were used as wild-type control. CALR exon 9 mutation was independently screened by HRMA with the CFX Connect real-time system and Sanger sequencing. TA-cloning was used to detect CALR exon 9 mutations in patients suspected to have low mutant allele burden. Results The maximal sensitivity of HRMA in identifying both CALR type 1 and type 2 mutants from patients' genomic DNA was 2.5%. Twenty-two samples were found to have distinct melting curves from wild-type. The presence of CALR mutations in 16 of these 22 samples was confirmed by Sanger sequencing, while the other 6 samples were wild-type by sequencing. After TA-cloning, CALR mutations were detected in 5 of 6 patients from 1 (6%) of 16 clones to 1 (2%) of 50 clones. Therefore, HRMA identified CALR mutations in 21 (65.6%) of 32 ET patients compared to 16 (50%) patients by Sanger sequencing, with a false positive rate of 3% and no false negative. Conclusion The HRMA developed in our system is a rapid and sensitive technique for the detection of CALR exon 9 mutations.

Background Breast and cervical cancer are the most common cancers affecting women. The symptom distresses experienced by cancer survivors are critical factors influencing their quality of life (QOL). This study investigated the QOL of breast and cervical cancer survivors, their physical, psychological and social conditions. Methods The participants were older than 20 years, had been diagnosed with breast or cervical cancer for more than 2 years, and had completed their cancer treatment. The survey incorporated the QOL questionnaires developed by the European Organization of Research and Treatment for Cancer and a self-designed questionnaire. Results The mean age at diagnosis was 48.89 ± 8.53 years for the breast cancer survivors and 49.00 ± 10.30 years for the cervical cancer survivors. The corresponding QOL scores were 75.33 ± 20.25 and 75.56 ± 17.93. The factors influencing QOL of breast cancer survivors were household income, number of comorbidities, stage of cancer, type of cancer treatment and duration of illness, whereas the factor related to QOL of cervical cancer survivors was only household income. Conclusions The QOL of the two groups was similar. Healthcare providers should demonstrate greater concern toward breast and cervical cancer survivors.

Mutations in JAK2, MPL and CALR genes have been identified in the majority of myeloproliferative neoplasm (MPN) patients, and patients negative for these three mutations are the so-called triple-negative (TN) MPN. In this study, we examined the mutational profiles of 16 triple-negative MPN patients including 7 essential thrombocythemia (ET), 1 primary myelofibrosis and 8 polycythemia vera (PV). Targeted next-generation sequencing was performed using the ACTOnco Comprehensive Cancer Panel (Ion AmpliSeq Comprehensive Cancer Panel, Life Technologies) to target all coding exons of 409 cancer-related genes. Overall, 30 nonsynonymous somatic mutations were detected in 12 (75%) patients with a range of 1-5 mutations per sample. Notably, one ET patient was found to have JAK2V617F and KITP551L mutations at very low allele frequency. One MPLP70L and 1 MPLM602T mutations were identified each in 1 ET and 1 PV, respectively. Other recurrent mutations were also identified including KMT2C, KMT2D, IRS2, SYNE1, PDE4DIP, SETD2, ATM, TNFAIP3 and CCND2. In addition, germline mutations were also found in some cancer-related genes. Copy number changes were rare in this cohort of TN MPNs. In conclusion, both somatic and germline mutations can be detected in TN MPN patients.

Some patients experience nausea and/or vomiting (NV) before receipt of chemotherapy. Our objective was to evaluate the impact of prior chemotherapy-induced NV (CINV) on the incidence of anticipatory NV in later cycles.This multicenter, prospective non-interventional study enrolled chemotherapy-naïve adults scheduled to receive highly or moderately emetogenic chemotherapy (HEC/MEC) for cancer in six Asia Pacific countries, excluding those with emesis within 24 h before cycle 1 chemotherapy. On day 1 before chemotherapy, patients answered four questions regarding emesis in the past 24 h, nausea, expectation of post-chemotherapy nausea, and anxiety in the past 24 h, the latter three scored from 0-10 (none-maximum). Multivariate logistic regression was used to assess the impact of prior CINV on anticipatory NV in cycles 2 and 3.Five hundred ninety-eight patients (59% female) were evaluable in cycle 2 (49% HEC, 51% MEC). The incidence of anticipatory emesis was low before cycles 2 and 3 (1.5-2.3%). The incidence of clinically significant anticipatory nausea (score of ≥3) was 4.8, 7.9, and 8.3% before cycles 1, 2, and 3, respectively, with adjusted odds ratio (OR), 3.95 (95% confidence interval (CI), 2.23-7.00; p 0.001) for patients with clinically significant nausea in prior cycles, compared with none. The adjusted ORs for other anticipatory NV endpoints ranged from 4.54-4.74 for patients with prior CINV. The occurrence of clinically significant anxiety in the prior cycle also resulted in a significantly increased likelihood of anticipatory nausea.These findings highlight the importance of preventing CINV in cycle 1 to reduce anticipatory NV in subsequent cycles.

Preventing and managing chemotherapy-induced nausea and vomiting (CINV) remain important goals. The objective of the Pan Australasian chemotherapy-induced emesis burden of illness (PrACTICE) study was to describe the incidence of CINV after highly or moderately emetogenic chemotherapy (HEC or MEC) for cancer in current clinical practice in Australia and five Asian countries (China, India, Singapore, South Korea, and Taiwan). This prospective, observational study of CINV was conducted at 31 sites in these six countries from August 2011 through September 2012 and enrolled male and female adult patients (≥18 years of age) naive to HEC and MEC who were scheduled to receive at least two cycles of single-day chemotherapy. The primary effectiveness endpoint was complete response, defined as no vomiting or use of rescue therapy, during chemotherapy cycle 1 in the overall phase (0–120 h), acute phase (0–24 h), and delayed phase (>24–120 h). Study outcomes were analyzed descriptively. Primary outcomes, CINV incidence, and treatment patterns (chemotherapy, CINV prophylaxis, rescue medication prescription, and rescue medication use) were assessed by phase (overall, acute, delayed), by cycle (as appropriate), within and across countries, and by level of chemotherapy emetogenicity (HEC vs MEC). The impact of CINV in cycle 1 on CINV in cycle 2 was analyzed for all patients with evaluable data for cycle 2. No site-specific analyses were performed. The remainder of this special series of papers reports on the results of this study.

Objective Adequate knowledge of prognosis is a prerequisite for planning appropriate end-of-life (EOL) care. However, questions remain about whether the association between prognostic understanding and EOL-care intensity reflects terminally ill cancer patients' preferences for EOL care. This study investigated the associations between accurate prognostic understanding and EOL-care preferences, and identified correlates of accurate prognostic understanding. Methods A cross-sectional survey of 2452 terminally ill cancer patients from 23 hospitals throughout Taiwan. Results Nearly half the participants (49.80%) accurately understood their prognosis. These patients were significantly more likely to prefer comfort-oriented care as their goal for EOL care, but less likely to prefer life-prolonging treatments. Accurately understanding prognosis decreased the likelihood of preferring intensive care unit care, cardiac pulmonary resuscitation, cardiac massage, intubation, and mechanical ventilation support, but increased preference for hospice care. Participants were significantly more likely to accurately understand their prognosis if they were male, younger, better educated, with a stronger preference for physicians to disclose their prognosis to them, and receiving care at a hospital accredited as a medical center and in northwest Taiwan. The likelihood of accurate prognostic understanding was lower for patients recently (≤12 months) diagnosed with cancers with better prognosis and hematologic malignancies than for lung cancer patients. Conclusions Accurately understanding prognosis is associated with fewer preferences for life-sustaining treatments and is correlated with both patient and institutional characteristics. Interventions should be developed to improve accurate prognostic understanding, thus facilitating informed EOL-care decisions that may limit the use of aggressive interventions. Copyright © 2014 John Wiley & Sons, Ltd.

Objective This postmarketing surveillance study evaluated the safety and efficacy of cetuximab therapy in patients with epidermal growth factor receptor (EGFR)-expressing metastatic colorectal cancer (mCRC) in Taiwan. Methods Patients with EGFR-expressing mCRC who had failed prior irinotecan-based chemotherapy and were receiving cetuximab therapy were monitored for treatment efficacy and safety from the time of first infusion until 28 days after the last infusion regardless of the reasons fordiscontinuation. The study followed 269 patients for approximately 2years. Results No unexpected adverse events associated with cetuximab therapy were reported, and most events were grade 1 or 2. The most common drug-related adverse events of any grade were rash (21.6%) and dermatitis acneiform (4.8%). Reported grade 3/4 events were rash (4.5%), dermatitis acneiform (0.4%), and diarrhea (0.4%). Cetuximab treatment for patients receiving second-/third-line (177 patients) or above therapy (92 patients) was associated with a median progression-free survival time of 3.37 and 3.90 months, respectively, and a median overall survival time of 17.6 and 21.1 months, respectively. The response rates for the second-/third-line treatment and fourth-line or above cetuximab treatment groups were similar (21.5% vs 17.4%; P = 0.428). Conclusion Cetuximab showed no unexpected safety findings and was efficacious in treating patients with EGFR-expressing mCRC in community practice in Taiwan.

Summary Background Essential thrombocythemia (ET) is classified as a chronic myeloproliferative neoplasm. JAK2 V617F mutation is found in about 50–60% patients with ET. We aim to determine the prevalence of JAK2 V617F mutation and its association with phenotype in adult Taiwanese patients with ET. Methods In this combined retrospective and prospective study, adult ET patients, at least 18 years of age, were enrolled between November 2007 and September 2011. Genomic DNA was extracted from unsorted bone marrow and/or peripheral blood samples for the detection of JAK2 V617F mutation by allele-specific polymerase chain reaction. The clinical and laboratory characteristics of all patients at the time of diagnosis or referral were determined retrospectively by chart review. Results A total of 82 patients were enrolled, and JAK2 V617F mutation was detected in 55 patients (67.1%). JAK2 V617F mutation was significantly more prevalent in old patients (36.4% vs. 14.8%, p =0.044), and associated with higher hemoglobin level (median 13.7 vs. 12.8g/dL p =0.012) and higher white blood cell count at diagnosis (12.1×10 3 vs. 8.8×10 3 /μL p =0.015). ET patients with the mutation also tend to have lower platelet count (median 902×10 3 vs. 1078×10 3 /μL p =0.051). In a binary logistic regression model, only higher hemoglobin concentration was significantly associated with JAK2 V617F mutational status (odds ratio 1.2 95% confidence interval 1.0–1.5; p =0.047). Conclusion JAK2 V617F mutation in Taiwanese adult patients with ET has a high prevalence of 67.1% and is associated with old age, higher hemoglobin level, and higher leukocyte count.

Context Undertreatment of cancer pain among outpatient cancer patients needs to be addressed to enhance care and improve patients' quality of life (QoL). Objectives This prospective, cross-sectional, patient-focused study aimed to explore the prevalence of pain and undertreatment of cancer pain in outpatients in Taiwan. Methods A total of 2652 non-selected outpatients with cancer and aged 20 years or older from 16 medical centers across Taiwan were included in this survey. All patients completed a questionnaire based on the Brief Pain Inventory. Pain management index (PMI) was used to evaluate the adequacy of pain management. Possible clinical variables of patients with positive PMI were examined by univariate and multivariate logistic regressions. Results A total of 1659 (62.6%) outpatients had experienced some degree of pain; among these, 32.4% had negative PMI. Patients with a negative PMI score had significantly poor outcomes of QoL and a significantly higher tendency toward dissatisfaction with pain control by the physician and with the prescribed analgesic drugs. Female gender, primary tumor from breast, non–cancer-related cause of pain, and hospital locations from north Taiwan were independent variables that predicated patients with undertreatment of cancer pain. Most importantly, a forward trend of undertreatment of pain among patients who presented with lower prevalent rate of pain was observed. Conclusion One-third of Taiwanese outpatients experienced pain because of undertreatment. Awareness of the prevalence of undertreatment of cancer pain and identification of the vulnerable subjects may assist in enhancing patient care and improving patient's QoL.

Germline variations at JAK2, TERT, HBS1L-MYB and MECOM have been found to associate with myeloproliferative neoplasms (MPNs) in European populations. Whether these germline variations are associated with MPNs in Taiwanese population is obscure. Here we aimed to evaluate the association of five germline variations (JAK2 46/1 haplotype tagged by rs12343867, JAK2 intron 8 rs12339666, TERT rs2736100, HBS1L-MYB rs9376092 and MECOM rs2201862) and the risk of MPNs in Taiwanese population. A total of 178 MPN patients (109 essential thrombocythemia, 54 polycythemia vera and 15 primary myelofibrosis) were enrolled into this study. The information of 17033 control subjects was obtained from Taiwan Biobank database. The JAK2 46/1 haplotype, JAK2 rs12339666 and TERT rs2736100 were significantly associated with Taiwanese MPNs (P = 3.6×10-19, 1.9×10-19 and 3.1×10-6, respectively), and JAK2V617F-positive MPNs (n=121) (P = 5.6×10-21, 4.4×10-21 and 8.6×10-7, respectively). In JAK2V617F-negative cases (n=55), only the JAK2 46/1 haplotype and JAK2 rs12339666 remained statistically significant (P= 0.009 and 0.007, respectively). When stratified by disease subtypes, the JAK2 46/1 haplotype and JAK2 rs12339666 were significantly associated with all three MPN subtypes, but TERT rs2736100 was only associated with essential thrombocythemia and polycythemia vera. We did not find any association of these five SNPs with CALR mutations in our cohort. Furthermore, the risk alleles of MECOM rs2201862 and HBS1L-MYB rs9376092 were demonstrated to be negatively associated with the risk of developing polycythemia vera. In conclusion, germline variations at JAK2 (both the 46/1 haplotype and rs12339666) and TERT rs2736100 were associated with MPNs in Taiwanese population.

Background: Afatinib has demonstrated clinical benefit in patients with non-small-cell lung cancer progressing after treatment with erlotinib/gefitinib. This phase III trial prospectively assessed whether continued irreversible ErbB-family blockade with afatinib plus paclitaxel has superior outcomes versus switching to chemotherapy alone in patients acquiring resistance to erlotinib/gefitinib and afatinib monotherapy. Patients and methods: Patients with relapsed/refractory disease following ≥ 1 line of chemotherapy, and whose tumors had progressed following initial disease control (≥ 12 weeks) with erlotinib/gefitinib and thereafter afatinib (50 mg/day), were randomized 2:1 to receive afatinib plus paclitaxel (40 mg/day; 80 mg/m2/week) or investigator's choice of single-agent chemotherapy. The primary end point was progression-free survival (PFS). Other end points included objective response rate (ORR), overall survival (OS), safety and patient-reported outcomes. Results: Two hundred and two patients with progressive disease following clinical benefit from afatinib were randomized to afatinib plus paclitaxel (n ≥ 134) or single-agent chemotherapy (n ≥ 68). PFS (median 5.6 versus 2.8 months, hazard ratio 0.60, P ≥ 0.003) and ORR (32.1% versus 13.2%, P ≥ 0.005) significantly improved with afatinib plus paclitaxel. There was no difference in OS. Global health status/quality of life was maintained with afatinib plus paclitaxel over the entire treatment period. The median treatment duration was 133 and 51 days with afatinib plus paclitaxel and single-agent chemotherapy, respectively; 48.5% of patients receiving afatinib plus paclitaxel and 30.0% of patients receiving single-agent chemotherapy experienced drug-related grade 3/4 adverse events. Treatment-related adverse events were consistent with those previously reported with each agent. Conclusion: Afatinib plus paclitaxel improved PFS and ORR compared with single-agent chemotherapy in patients who acquired resistance to erlotinib/gefitinib and progressed on afatinib after initial benefit. LUX-Lung 5 is the first prospective trial to demonstrate the benefit of continued ErbB targeting post-progression, versus switching to single-agent chemotherapy. Trial registration number: NCT01085136 (clinicaltrials.gov).

Tumor type, dose level, DLT, best response and single nucleotide polymorphisms of UGT1A1*28 and UGT1A1*6. (DOCX 18Â kb)

Aims: The optimal maintenance therapy for patients with acute promyelocytic leukemia (APL) who achieved complete remission (CR) and complete consolidation chemotherapy is still controversial. Whether the use of arsenic trioxide (ATO) alone or along with all-trans retinoic acid (ATRA) improves overall survival (OS) or disease-free survival (DFS) is still debated. Methods: A retrospective reivew was conducted of 20 patients diagnosed with APL according to the French – American – British system. After achieving CR and receiving consolidation chemotherapy, nine patients were given maintenance therapy for 1 year (ATRA 45 mg/m2/day p.o., mercaptopurine 60 mg/m2/day p.o. and ATO 0.15 mg/kg/day × 5 days/week for six cycles in five patients; ATRA 45 mg/m2/d p.o. alternating with ATO 0.15 mg/kg/day × 5 days/week in 1 patient; ATRA only in three patients). Results: In all patients the rates of CR, 3-year OS and 5-year OS were 75, 71 and 57%, respectively. For patients treated with ATO maintenance, the rates were 100% for both 5-year OS and 5-year DFS. Four of six patients on ATO maintenance had grade 1 or grade 2 adverse events. Excluding the two patients who died from intracerebral hemorrhage within 4 days after diagnosis, these rates were 85, 82 and 78%, respectively. Conclusion: Upfront ATO maintenance therapy for one year is safe and appears to be effective, with the benefits restricted to patients with APL with t(15;17) translocation. Larger studies will be required to confirm this observation.

Purpose To evaluate the therapeutic efficacy of 3-month triplet induction chemotherapy (ICT) followed by concomitant chemoradiotherapy (CCRT) in patients with locally advanced pancreatic cancer (LAPC). Patients and Methods Chemonaive patients with measurable, histologically confirmed LAPC were eligible. The ICT consisted of biweekly gemcitabine (800 mg/m 2 ) infusion at a fixed dose rate (10 mg/m 2 /min), followed by 85 mg/m 2 oxaliplatin and 48-h infusion of 5-fluorouracil/leucovorin (3000/150 mg/m 2 ) for 6 cycles. Patients without disease progression 4 weeks after ICT would receive weekly 400 mg/m 2 gemcitabine and 5040 cGy radiation in 28 fractions. After CCRT, patients were subjected for surgical intervention and/or maintenance chemotherapy until progression or intolerable toxicity. Results Between December 2004 and August 2008, 50 patients were enrolled. The best responses after ICT were partial response (PR) in 9, stable disease in 26, and progressive disease or not evaluable in 15. Among the former 35 patients, 2 had disease progression before CCRT, and 3 declined to have CCRT. Of the 30 patients receiving CCRT, an additional 4 and 1 patient(s) achieved PR at the end of CCRT and during maintenance chemotherapy, respectively. On intent-to-treat analysis, the overall best response was PR in 14 patients and stable disease in 21. The overall response rate and disease control rate were 28% (95% confidence interval [CI], 16.2–42.5%) and 70% (95% CI, 44.4–99.2%), respectively. The median time to progression and overall survival of the intent-to-treat population was 9.3 (95% CI, 5.8–12.8) months and 14.5 (95% CI, 11.9–17.1) months, respectively. One- and two-year survival rates were 68% (95% CI, 55.1–80.9%) and 20.6% (95% CI, 8.7–32.5%), respectively. Neutropenia was the most common Grade 3–4 toxicity of both ICT and CCRT, with a frequency of 28% and 26.7%, respectively. Significant sensory neuropathy occurred in 9 patients (18%). Conclusion Three months of triplet ICT followed by gemcitabine-based CCRT is feasible, moderately active, and associated with encouraging survival in patients with LAPC.

Background: Essential thrombocythemia (ET) is a BCL-ABL1-negative myeloproliferative neoplasm characterized by increased number of mature megakaryocytes in the bone marrow and sustained thrombocytosis in the peripheral blood. ET is associated with an increased risk of hemorrhagic and thrombotic complications and leukemic transformation. In addition to somatic mutations, microRNA (miRNA) deregulation has been proposed to play roles in the molecular pathogenesis and disease phenotype in ET patients. The aims of this study were to investigate the plasma miRNA profiles in ET patients with those obtained from healthy adults (HA) and its correlation with clinical and prognostic features. Methods: ET patients seen at the MacKay Memorial Hospital were enrolled into this study. The clinical and laboratory characteristics at the time of diagnosis or referral were determined retrospectively by chart review. Total plasma miRNA was derived from bone marrow or peripheral blood in patients or HA. Mutational status of JAK2V617F,CALR and MPL were detected by Sanger sequencing and/or allele-specific PCR. Plasma miRNA profiling was carried out on PanelChip™ Analysis System (Quark Biosciences, Taiwan) using a customized miRNA panel including 165 miRNAs called mirSCAN™ PanCancer Chips 1 & 2. KEGG pathways that miRNAs were associated with were analyzed using DIANA TOOLS - mirPath v.3. Differentially expressed miRNAs were identified by student t-test (P < 0.05) and significantly affected miRNAs in ET were identified by a change in expression of two-fold or more compared to the expression in HA. Statistical analysis was performed using SPSS. Results: A total of 53 ET patients (median age at diagnosis 59 years; 60.4% females) were enrolled. Frequency of the 3 driver mutations was 64% for JAK2V617F, 15% CALR, 4% JAK2V617F and CALR co-mutations, and none for MPL. 17% of patients were classified as triple-negative. A total of 40 differentially expressed miRNAs were identified (Figure left axis) including 4 miRNAs (hsa-miR-940, hsa-miR-411-5p, hsa-miR-596 and hsa-miR-376c-3p) with higher expression levels. The putative target genes of these 40 differentially expressed miRNAs were enriched in signaling pathway including TGF-beta signaling pathway (p-value = 1.86E-12), Hippo signaling pathway (p-value = 1.84E-07), MAPK signaling pathway (p-value = 0.03), and FoxO signaling pathway (p-value < 0.001). According to the expression levels of these 40 miRNAs, samples were grouped into two clusters, i.e. low expression group and high expression group. ET patients with JAK2V617F were significantly associated with high expression of 40 miRNAs (n = 31 of 34, 91%) when compared with triple-negative ET patients (n = 5 of 9, 56%) (p = 0.03). ET patients with low expression of 40 miRNAs were significantly associated with acute leukemia transformation (n = 2 of 11, 18%) when compared with high expression group (n = 0 of 42, 0%) (p = 0.04). However, the expression levels of 40 miRNAs were not statistically correlated with other clinical features including hemogram, secondary solid cancer, myelofibrosis transformation, or thrombotic/hemorrhagic events. Conclusions: In this cohort of ET patients, distinct plasma miRNA profiles correlated with JAK2V617F mutation and leukemic transformation. Larger cohort is warranted to validate our findings. Figure Figure. Disclosures Chen: Quark Biosciences, Inc.: Employment. Kang:Quark Biosciences, Inc.: Employment. Huang:Quark Biosciences, Inc.: Employment. Lin:Quark Biosciences, Inc.: Employment. Wang:Quark Biosciences, Inc.: Employment.

Background: We performed an on-site cancer prevention educational program by oncologists focusing on all cancer types, and with emphasis on oral cancer. The program has been long-term supported by charity organizations of the Taiwan Total Cancer Care Foundation, and the Taiwan Cancer Total Care Information Society. Aim: To have a better understanding for cancer-related risk behaviors of our junior high school students in Taiwan, we performed a self-reported questionnaire survey before each educational activity. Methods: The questionnaire survey mainly focused on 3 cancer-related risk behaviors CBA [cigarette smoking (C), betel-nut chewing (B), alcohol drinking (A)], regarding the percentage of “frequent” CBA consumption, “ever-experience” of cancer-related risk behavior, starting time of risk behavior, sources of CBA, and existence of risk behavior among their parents/senior family members. Results: During 2016, 4,589 junior high school students received our on-site educational program whose questionnaires are valid for analysis. Among them, 4,097 and 492 students are from western and eastern towns. Taiwan is geographically divided by the high-altitude Central Mountains into western and eastern towns. Western towns are relatively more urban, while eastern towns are more rural in both industrial and economic development. Questionnaires from 7th, 8th, 9th grade of junior high school students represent 37.1%, 44.0%, and 18.9%. The average body mass index (BMI) is 20.68 and 21.47 in western and eastern towns, respectively. The average BMI of boy students between western & eastern towns shows statistically significant difference of 21.87 (eastern) and 21.01 (western), respectively ( P = 0.005, Pearson χ2), while the average BMI of girl students has only a trend to be higher in eastern towns (20.82) than that in western towns (20.30) ( P = 0.072). The percentage of “frequent” (daily, or 2-6 days per week) consumption of C, B, and A is 2.7%, 0.6%, and 1.3%, respectively. The percentage of “frequent” C consumption shows statistically significant higher in eastern (4.5%) than western (2.5%) towns ( P = 0.009), the percentage of “frequent” B consumption also shows statistically significant higher in eastern (1.6%) than western (0.5%) towns ( P = 0.003). However, the percentage of frequent A consumption has no significant difference between western (1.2%) & eastern (1.8%) towns ( P = 0.257). The percentage of “ever-experience” of A is significantly higher in eastern (5%) than western (3%) towns ( P = 0.001), while the percentage of ever-experience of C has no significant difference between eastern (9%) & western (7%) towns ( P = 0.257), the percentage of ever-experience of B also has no significant difference between eastern (16%) & western (15%) towns ( P = 0.751). Conclusion: Self-reported survey for junior high school students on cancer-related risk behaviors, CBA, revealed that frequent cigarette smoking (C) is the most prevalent (2.7%) one among CBA in Taiwan.

To evaluate the efficacy, safety and pharmacokinetic profiles of S-1, which composed of tegafur (FT, a prodrug of 5-FU), 5-chloro-2,4-dihydroxypyridine and potassium oxonate (Oxo), in Taiwanese advanced gastric cancer (AGC) patients.Patients with chemo-naïve, histologically confirmed AGC were eligible. S-1 was given orally at dose of 40, 50 or 60 mg, twice daily for patients with body surface1.25, 1.25-1.5 and1.5 m(2), respectively, on day 1-28 every 42 days/cycle.Thirty-four patients were included. On intent-to-treat analysis, the overall response rate, median progression-free and overall survival were 35.3% [95% confidence interval (CI): 19.2-51.3%], 2.9 (95% CI: 2.4-5.8) months and 9.8 (95% CI: 6.1-NA) months, respectively. The most common grade 3-4 toxicities were anemia 23.5% and neutropenia 11.8%. There were two treatment-related mortality, which occurred in patients with suboptimal renal function underestimated by serum creatinine level at study entry. Single-dose pharmacokinetic study showed trend toward lower AUC(5-FU), and higher AUC(FT) and AUC(Oxo) comparing to most Western reports.The efficacy, toxicity and pharmacokinetic profiles of S-1 in current study are compatible with those from other Asian populations. Accurate renal function assessment and more closely monitoring is mandatory for S-1 therapy in patients with low body mass. Literature review suggests that, besides AUC(5-FU), AUC(Oxo) may also attribute to the difference in the compliance to S-1 between Asian and Caucasian populations.

Aim: We reviewed our experience with adult T-cell leukemia (ATL), describing the clinical manifestations and outcome in order to facilitate case recognition in the future. Methods: We retrospectively reviewed the charts of 17 patients with ATL diagnosed from January 1996 to September 2009 at Mackay Memorial Hospital, Taipei, Taiwan. Results: The overall survival of the whole study group was 138 days. The medial survival of the 10 patients who received chemotherapy is 204 days. The other six patients who did not receive any chemotherapy had a median survival of 28 days. The co-infection rate with HTLV-1 and HBV or HCV is 47% and 35% respectively. Conclusion: ATL in Taiwan is a rare malignant T-cell lymphoma with a very poor prognosis. Our series raised the interesting possibility of an association with chronic hepatitis B or C.

Introduction The availability of targeted and immunotherapies has provided NSCLC patients with more effective treatment options. However, this has resulted in an increase in the number and modality of tests required for treatment selection. Given 30-50% of advanced lung cancer patients have insufficient or unavailable tissue for comprehensive genomic profiling, there is a need for a non-invasive assay that can accurately detect all guideline-recommended markers for NSCLC treatment selection. To meet this need, we have developed a blood test that detects six classes of alterations (SNV, Indels, Rearrangements, CNA, Microsatellite Instability and PD-L1 expression) for therapy selection. Methods & Results Three tubes of blood from a routine blood draw were sent to our CLIA-certified and/or CAP accredited lab for analysis. PD-L1 expression was evaluated in circulating tumor cells (CTCs) utilizing two different assays; (i) Immunofluorescence (IF) antibody staining, (ii) mRNA qPCR. CTCs were captured on the CMxTM CTC Platform coated with lipid bilayer and antibodies to EpCAM. PD-L1 expression results were highly correlated between IF and qPCR assays in ten solid tumor cell lines (lung, breast, prostate and colorectal cancer) spiked into whole blood to mimic the actual patient CTC capture process. In an ongoing study on clinical samples from NSCLC patients (N=20), we observed greater than 90% concordance between tissue (IHC by 22C3 PD-L1 clone) and blood (CTC IF and mRNA assays). A proprietary Single Molecule Sequencing (SMSEQTM) NGS assay was performed on plasma in order to detect 5 classes of genomic alterations (SNV, Indels, Rearrangements, CNA, MSI) from ctDNA. This assay was validated in accordance with the latest ACMG and AMP guidelines to accurately detect variants at low mutant allele fraction (.1% for SNVs and Indels, 1% for rearrangements and 5 copies for CNA) with high sensitivity and specificity. MSI status was determined by assessing nucleotide repeat sequences in five standard markers (BAT-25, BAT-26, MONO-27, NR-21, NR-24), and was detectable down to a MAF of 1%. In an ongoing study on clinical samples from NSCLC patients (N=20), we observed high concordance of MSI status between tissue (immunohistochemistry for dMMR/MSI status) and blood (ctDNA SMSEQ assay). Conclusion Tissue insufficiency and procurement challenges are the primary reasons why ~90% of patients diagnosed with advanced NSCLC are not comprehensively tested per NCCN-guidelines in the community setting where most cancer is treated, leading to suboptimal treatment selection. An accurate blood test that detects all 6 NCCN-recommended markers for immunotherapy and targeted therapy selection has the potential to significantly improve adherence to NCCN testing guidelines and enable optimal treatment selection. Citation Format: Huangpin B. Hsieh, Jen-chia Wu, Feng-Ming Lin, Julian Lucas, Alex Atkins, Pratyush Gupta, Hung-Jen Shao, Yen-Lin Chen, Wen-Jie Huang, Chia-Hsun Hsieh, Ruey Kuen Hsieh, Kuo-Wei Chen, Ming-Hong Yen, Mana Javey, Shih-En Chang, Twinkal Marfatia, Drew Watson, Mahul Amin, Ashish Nimgaonkar, Oscar Segurado, Rui Mei. CTC and ctDNA profiling to detect 6 NCCN-guideline recommended classes of alterations for immunotherapy and targeted therapy selection using sample from a single blood draw [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3635.

e15107Background: PD-L1 expression on circulating tumor cells (CTCs) is an alternative to checkpoint inhibitor selection by IHC and it offers possibility for serial monitoring following chemotherap...