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Restriction of mouth opening (RMO) is a common manifestation of head and neck cancer (HNC) and a poor prognostic factor following concurrent chemoradiotherapy (CCRT) of patients. This study aimed to explore whether the Mallampati score, a visual assessment of the distance from the tongue base to the roof of the mouth, can be used as a surrogate for RMO in predicting treatment outcomes in patients with HNC undergoing CCRT.A total of 461 consecutive patients who received definitive CCRT for the treatment of locally advanced HNC between August 2016 and December 2017 at Chang Gung Memorial Hospital in Taiwan (Linkou, Keelung, and Kaohsiung branches) were enrolled in this prospective study. Patients were allocated by the pre-treatment Mallampati score of 1 or 2 (n=24) vs. 3 or 4 (n=207) to compare treatment compliance and treatment-related complications.Patients in the Mallampati score of 3 or 4 group had a higher prevalence of betel quid chewing, oral cavity and oropharynx cancers, advanced tumor stage, poorer performance status, and were more likely to receive platinum monotherapy during CCRT. Patients in the Mallampati score of 3 or 4 group had a 2.08-fold (p=0.002) hazard ratio (HR) for overall survival compared to those in the score of 1 or 2 group in the univariate analysis, the difference remained significant in multivariate analysis (adjusted HR=1.61; 95% CI=1.02-2.61; p=0.047). Patients in the Mallampati score 3 or 4 group had a 2.36-fold (95% CI=1.07-5.19; p=0.033) increased likelihood of incomplete chemotherapy, 2.44-fold (95% CI=1.17-5.06; p=0.017) increased likelihood of incomplete radiotherapy, and 1.84-fold (95% CI=1.18-2.87; p=0.007) risk of unexpected hospitalization compared to those with a Mallampati score of 1 or 2 in multivariate analysis.Patients with HNC with higher pre-treatment Mallampati scores had poorer survival outcomes and were at a higher risk of treatment incompletion and treatment-related toxicities when undergoing CCRT. Our results support the utility of Mallampati score as a surrogate for measuring RMO to predict survival outcomes, treatment compliance, and safety profiles in patients with HNC undergoing CCRT.

BACKGROUND/AIM The clinical significance of frailty status on treatment outcome in patients with esophageal cancer (EC) has been seldom explored. This study aimed to evaluate the impact of pretreatment frailty on treatment-related toxicity and survival outcome in patients with EC undergoing concurrent chemoradiotherapy (CCRT). PATIENTS AND METHODS Patients aged ≥20 years and with newly diagnosed locally advanced EC receiving neoadjuvant radiotherapy and concurrent chemotherapy with weekly administration of carboplatin and paclitaxel for 5 weeks were prospectively enrolled. A pretreatment frailty assessment was performed within 7 days before CCRT initiation. The primary endpoint was treatment-related toxicity and complications of CCRT while the secondary endpoint was overall survival. RESULTS A total of 87 patients were enrolled, 41 (47%) and 46 (53%) of whom were allocated in the frail and fit group, respectively. Frail patients had a significantly higher incidence of having at least one severe hematological adverse event (63.4% vs. 19.6%, p

Adding protein-bound polysaccharide K (PSK) to adjuvant chemotherapy with mitomycin and fluorouracil after gastrectomy for gastric cancer was demonstrated to improve survival in a previous study in Japan. However, the efficacy of PSK outside Japan and in combination with other adjuvant chemotherapeutic agents remains unclear. The aims of this study were to evaluate the efficacy of PSK. We conducted a population-based historical cohort study using the National Health Insurance Research Database of Taiwan. We performed sensitivity analysis with propensity score matching to control for possible confounders. Patients who used PSK (PSK group) were matched at a 1:4 ratio to those who had never used PSK (control group) after adjusting for covariates including sex, age, urbanization, income and comorbidities. The primary outcome was overall survival. Multivariate hazard ratios from competing risk analysis were calculated by adjusting for demographic data and all confounding factors. From 1999 to 2008, we identified 10,617 patients with gastric cancer received gastrectomy and adjuvant chemotherapy. 1295 patients used PSK (PSK group) and 5180 patients never used PSK (control group) were analyzed after propensity score matching. The median overall survival was 6.49 years (95% confidence interval [CI] 5.22-7.63) in the PSK group and 3.59 years (95% CI 3.38-3.80) in the control group. After adjusting for age, sex, urbanization, income, and comorbidities, adding PSK to adjuvant chemotherapy was the most significant prognostic factor for improved survival (hazard ratio 0.76, P.0001). Adjuvant chemotherapy combined with PSK significantly prolonged overall survival in gastric cancer patients after gastrectomy.

Patients with myeloproliferative neoplasms (MPNs) are characterized by systemic inflammation. With the indolent nature of the diseases, second cancers (SCs) have emerged as a challenging issue in afflicted patients. Epidemiological studies have confirmed the excessive risk of SCs in MPNs, but little is known about their molecular basis. To explore further, we used whole exome sequencing to explore the genetic changes in the granulocytes of 26 paired MPN patients with or without SC. We noticed that MPN–SC patients harbor genomic variants of distinct genes, among which a unique pattern of co-occurrence or mutual exclusiveness could be identified. We also found that mutated genes in MPN–SC samples were enriched in immune-related pathways and inflammatory networks, an observation further supported by their increased plasma levels of TGF-β and IL-23. Noteworthily, variants of KRT6A, a gene capable of mediating tumor-associate macrophage activity, were more commonly detected in MPN–SC patients. Analysis through OncodriveCLUST disclosed that KRT6A replaces JAK2V617F as the more prominent disease driver in MPN–SC, whereas a major mutation in this gene (KRT6A c.745T>C) in our patients is linked to human carcinoma and predicted to be pathogenic in COSMIC database. Overall, we demonstrate that inflammation could be indispensable in MPN–SC pathogenesis.

Purpose This study aimed to identify vulnerable patients with head and neck cancer undergoing concurrent chemoradiation therapy (CCRT) who are susceptible to higher treatment-related adverse effects and have poorer treatment tolerance. This study also aimed to determine whether comprehensive geriatric assessment, developed in the geriatric population, can predict vulnerability to treatment-related adverse events and survival even in nongeriatric patients with head and neck cancer, as well as the prevalence of vulnerability and its effect on toxicities and survival among these patients. Methods and Materials This prospective cohort study examined 461 patients with primary head and neck cancer who underwent definitive CCRT during 2016 to 2017 at 3 medical centers across Taiwan. Vulnerability is defined as susceptibility to cancer- and treatment-related adverse events that result in poor treatment tolerance and unexpected emergent medical needs, such as hospitalization and emergency room visits. Vulnerability was assessed as impairment with ≥2 dimensions on comprehensive geriatric assessment, 7 days before CCRT. The association of vulnerability with treatment-related adverse events and survival was analyzed. Results The prevalence of vulnerability was 22.2%, 27.3%, 30.2%, and 27.9% among patients aged 20 to 34, 35 to 49, 50 to 64, and >65 years, respectively. Survival was poorer in vulnerable patients than in nonvulnerable patients (hazard ratio, 1.97; 95% confidence interval, 1.26-3.07; P = .003). Vulnerable patients showed a higher tendency toward CCRT incompletion (19.5% vs 6.1%, P Conclusions Vulnerability, which is an urgent concern when it presents among patients with head and neck cancer, was independently associated with poorer survival and severe treatment-related complications. Vulnerability assessment should be routinely evaluated in all patients with primary head and neck cancer who are undergoing definitive CCRT, not only in such patients who are geriatric.

Mutations that lead to constitutive activation of key regulators in cellular processes are one of the most important drivers behind vigorous growth of cancer cells, and are thus prime targets in cancer treatment. BRAF V600E mutation transduces strong growth and survival signals for cancer cells, and is widely present in various types of cancers including lung cancer. A combination of BRAF inhibitor (dabrafenib) and MEK inhibitor (trametinib) has recently been approved and significantly improved the survival of patients with advanced NSCLC harboring BRAF V600E/K mutation. To improve the detection of BRAF V600E/K mutation and investigate the incidence and clinicopathological features of the mutation in lung cancer patients of southern Taiwan, a highly sensitive and specific real-time quantitative PCR (RT-qPCR) method, able to detect single-digit copies of mutant DNA, was established and compared with BRAF V600E-specific immunohistochemistry. Results showed that the BRAF V600E mutation was present at low frequency (0.65%, 2/306) in the studied patient group, and the detection sensitivity and specificity of the new RT-qPCR and V600E-specific immunohistochemistry both reached 100% and 97.6%, respectively. Screening the BRAF V600E/K mutation with the RT-qPCR and V600E-specific immunohistochemistry simultaneously could help improve detection accuracy.

Nutritional counseling is frequently overlooked in cancer patients with normal nutritional status. This study aimed to evaluate the impact of nutritional counseling in head and neck cancer (HNC) patients with normal nutritional status prior to concurrent chemoradiotherapy (CCRT). A total of 243 patients with pretreatment normal nutritional status and locally advanced HNC receiving concurrent chemoradiotherapy (CCRT) at three medical centers were enrolled. All patients were retrospectively allocated into the early (≤ 2 weeks, n = 105, 43.2%), late (> 2 weeks, n = 102, 42.0%), and no nutritional counseling groups (n = 36, 14.8%) according to the time interval between the date of CCRT initiation and the first date of nutritional counseling for comparison. The 1-year overall survival rates were 95.0%, 87.5%, and 81.3% in the early, late, and no nutritional counseling groups (p = 0.035), respectively. The median body weight changes at end of CCRT were − 4.8% (range, − 13.3 to 8.7%), − 5.6% (range, − 21.9 to 5.6%), and − 8.6% (range, − 20.3 to 2.4%) in patients in the early, late, and no nutritional counseling groups, respectively. The early termination of chemotherapy rates and the incompletion rates of planned radiotherapy were 1.9% and 1.9%, 2.9%, and 2.0%, 13.9%, and 19.4% in patients in the early, late, and no nutritional counseling groups, respectively. Our findings strongly suggest that while some HNC patients may have pretreatment normal nutritional status, early nutritional counseling is nevertheless essential for the improvement of treatment tolerance and survival outcome.

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.

Buprenorphine is one of the strongest opioids used for the relief of cancer pain. This study aims to evaluate the real-world clinical experiences of transdermal buprenorphine used in moderate to severe cancer pain in the Asian population.This is an open-labeled, multicenter, 4-week observational study. Stable cancer pain patients who decided to switch the previous opioid to transdermal buprenorphine will be enrolled in this study. The safety and effectiveness were observed and collected. Pain assessment was performed using a numerical rating scale by the investigators and the Brief Pain Inventory Short Form (BPI-SF) by the patient. The safety profiles included concomitant medications and adverse events (AEs).A total of 83 patients were enrolled in this study. The global pain scores in the BPI, as well as the four individual pain parameters (worst, least, average, and right now), showed a continued decrease (p .05) from week 2 to week 4. Significant improvements were observed in normal work activities, relations with other people, sleep, enjoyment of life, and global BPI pain interference score on week 4. Pain assessments conducted by investigators demonstrated significant, continuous improvements during the study periods. In addition, transdermal buprenorphine demonstrated good safety/tolerability with limited drug-related AEs in the Asian population with cancer pain.This study demonstrated that transdermal buprenorphine in the Asian population has good safety profiles and continued improvements in pain relief, sleep, and pain interferences. Transdermal buprenorphine can be an effective and convenient option as a transdermal opioid for patients with moderate to severe cancer pain in Taiwan. (NCT Number: NCT04315831).

Background We previously developed a robust prognostic model (GS model) to predict the survival outcome of patients with advanced pancreatic cancer (APC) receiving palliative chemotherapy with gemcitabine plus S‐1 (GS). This study aimed to validate the application of the GS model in APC patients receiving chemotherapy other than the GS regimen. Patients and methods We retrospectively analyzed 727 APC patients who received first‐line palliative chemotherapy other than the GS regimen between 2010 and 2016 at four institutions in Taiwan. The patients were categorized into three prognostic groups based on the GS model for comparisons of survival outcome, best tumor response, and in‐group survival differences with monotherapy or combination therapy. Results The median survival times for the good, intermediate, and poor prognostic groups were 13.4, 8.4, and 4.6 months, respectively. The hazard ratios for the comparisons of intermediate and poor to good prognostic groups were 1.51 (95% confidence interval [CI]), 1.22‐1.88, P, This study provided validation of the previously developed gemcitabine + S‐1 model in predicting the survival outcome of advanced pancreatic cancer patients receiving first‐line palliative chemotherapy.

Evasion of immune surveillance is a significant factor in head and neck squamous cell carcinoma (HNSCC) carcinogenesis. IL-6 signaling is a critical mechanism for the induction of dysfunctional immune responses. In the present study, we examined the role of IL-6 in the prognosis of HNSCC regarding the immunosuppressive tumor microenvironment. We retrospectively analyzed the clinical outcomes of HNSCC patients and examined its correlation with the levels of IL-6 in tumors and circulating myeloid-derived suppressor cells (MDSCs) in peripheral blood. Furthermore, the relationships between IL and 6, programmed death ligand (PD-L1) expression, and immune response were examined in vitro and in vivo. Our data revealed that IL-6 overexpression was associated with the increased risk of developing disease failure and poor prognosis for HNSCC. The immunoreactivity of IL-6 in HNSCC specimens was positively linked to the staining of PD-L1 and the level of circulating MDSCs. By cellular and animal experiments, there were augmented radiation-induced increases in the expression of PD-L1 and the activation of MDSCs noted in IL-6-positive tumors. When IL-6 signaling was inhibited, the levels of PD-L1 and MDSC recruitment were significantly down-regulated. Furthermore, the neutrophil-to-lymphocyte ratio (NLR) was positively correlated with the levels of IL-6 and PD-L1 in tumor, and circulating MDSCs. In conclusion, IL-6 is a significant predictor of treatment outcome in HNSCC patients, and plays an important role in the induction of immunosuppressive tumor microenvironment mediated by increased MDSCs and PD-L1 expression. Furthermore, IL-6 combined with NLR can assist the clinician to make an informed decision regarding treatment options.

Objective Studies have rarely explored the efficacy of S‐1 in treating advanced pancreatic cancer outside Japan. This study compared the survival outcomes of patients with advanced pancreatic cancer treated with S‐1 with the survival outcomes of those without S‐1 treatment before and after S‐1 reimbursement was introduced in Taiwan in June of 2014. Method We retrospectively analyzed 838 patients with locally advanced or metastatic pancreatic cancer who underwent palliative chemotherapy from 2010 to 2016 at 4 institutes in Taiwan. For survival analysis, patients were categorized into two groups according to whether they received S‐1 treatment as palliative chemotherapy after diagnosis: (a) S‐1‐treated (n = 335) and (b) non‐S‐1‐treated (n = 503) groups. Results The median overall survival was longer in the S‐1‐treated group than in the non‐S‐1‐treated group (10.7 vs 6.0 mo, P

Mutations that lead to constitutive activation of key regulators in cellular processes are one of the most important drivers behind vigorous growth of cancer cells, and are thus prime targets in cancer treatment. BRAF V600E mutation transduces strong growth and survival signals for cancer cells, and is widely present in various types of cancers including lung cancer. A combination of BRAF inhibitor (dabrafenib) and MEK inhibitor (trametinib) has recently been approved and significantly improved the survival of patients with advanced NSCLC harboring BRAF V600E/K mutation. To improve the detection of BRAF V600E/K mutation and investigate the incidence and clinicopathological features of the mutation in lung cancer patients of southern Taiwan, a highly sensitive and specific real-time quantitative PCR (RT-qPCR) method, able to detect single-digit copies of mutant DNA, was established and compared with BRAF V600E-specific immunohistochemistry. Results showed that the BRAF V600E mutation was present at low frequency (0.65%, 2/306) in the studied patient group, and the detection sensitivity and specificity of the new RT-qPCR and V600E-specific immunohistochemistry both reached 100% and 97.6%, respectively. Screening the BRAF V600E/K mutation with the RT-qPCR and V600E-specific immunohistochemistry simultaneously could help improve detection accuracy.

Concurrent chemoradiotherapy (CCRT) treatment incompletion is a known negative prognosticator for patients with head and neck cancer (HNC). Malnutrition is a common phenomenon which leads to treatment interruption in patients with HNC. We aimed to compare the performance of three nutritional tools in predicting treatment incompletion in patients with HNC undergoing definitive CCRT. Three nutritional assessment tools, Mini Nutritional Assessment-Short Form (MNA-SF), Malnutritional Universal Screening Tool (MUST), and Nutritional Risk Screening 2002 (NRS-2002), were prospectively assessed prior to CCRT for HNC patients. Patients were stratified into either normal nutrition or malnourished groups using different nutrition tools. Treatment incompletion and treatment-related toxicities associated with CCRT were recorded. A total of 461 patients were included in the study; malnourished rates ranged from 31.0 to 51.0%. The CCRT incompletion rates were 4.9–6.3% and 14.5–18.2% for normal nutrition patients and malnourished patients, respectively. The tools had significant correlations with each other (Pearson correlation 0.801–0.837, p

BACKGROUND Thrombocytopenia is a common extrahepatic manifestation in chronic liver disease. However, there have been rare studies of impacts of risk for hepatitis C virus-associated thrombocytopenia (HCV-TP) and hepatitis B virus-associated thrombocytopenia (HBV-TP). The aim of this study is to evaluate different impacts of risk factors for HCV-TP and HBV-TP. MATERIAL AND METHODS We retrospectively collected 1803 HCV patients and 1652 HBV patients to examine the risk factors for time to moderate and severe thrombocytopenia (platelet counts

4088 Background: In the randomized, double-blind, phase 3 KEYNOTE-394 trial (NCT03062358), pembro + BSC vs PBO + BSC as 2L therapy significantly reduced the risk of death by 21% (HR 0.79, 95% CI 0.63-0.99, P= 0.0180), prolonged PFS (HR 0.74, 95% CI 0.60-0.92, P= 0.0032), and improved ORR (estimated difference 11.4%, 95% CI 6.7-16.0, P= 0.00004) with a manageable safety profile in pts in Asia with advanced HCC and progression on or intolerance to sorafenib or oxaliplatin-based chemotherapy. Here we present the results of prespecified exploratory HRQoL analyses. Methods: EORTC QLQ-C30 and EuroQol-5D3L (EQ5D-3L) questionnaires were administered at baseline (BL); wks 3, 6, 9, 12, 18; every 9 wks thereafter up to 1 yr or end of treatment; at treatment discontinuation, and at the 30-day safety follow-up visit. Pts who received ≥1 dose of study treatment and completed ≥1 HRQoL assessment were included in the analyses. Least squares mean (LSM) score changes from BL to wk 12 were compared using a constrained longitudinal data analysis model, including treatment by study visit interaction and stratification factors as covariates. Kaplan-Meier method was used to estimate time to deterioration (TTD) (time to 1st onset of ≥10-point decline from BL/confirmed by a 2nd adjacent ≥10-point decline from BL) for EORTC QLQ-C30 global health status (GHS)/QoL. Stratified Cox proportional hazards model was used to assess the magnitude of the treatment difference (HR) between treatment arms in TTD with nominal, one-sided P value calculated. Results: The HRQoL population included 450 pts (298 pembro; 152 PBO). HRQoL compliance rate at wk 12 was 95.7% for pembro for both questionnaires and 94.4% for EORTC QLQ-C30 and 95.3% for EQ5D-3L for PBO. There was a statistically significant difference in LSM for change from BL to wk 12, between the two arms for the QLQ-C30 GHS/QoL score and EQ-5D VAS score, with more decline observed in the PBO arm. Difference in LSM for QLQ-C30 GHS/QoL score between pembro (-3.97; 95% CI, -6.38, -1.56) and PBO (-8.40; 95% CI, -11.71, -5.10) arms was 4.43 (95% CI, 0.47, 8.40; P= 0.0142). Difference in LSM for EQ-5D VAS score between pembro (-2.74; 95% CI, -4.51, -0.96) and PBO (-6.94; 95% CI, -9.40, -4.48) arms was 4.20 (95% CI, 1.21, 7.19; P= 0.0030). GHS/QOL mean scores generally remained stable over time in pembro arm. TTD in EORTC QLQ-C30 GHS/QoL score was similar between arms (HR, 0.85; 95% CI, 0.58, 1.25; P= 0.1993). Conclusions: Over 12 wks, pts treated with PBO + BSC showed more decline in HRQoL than those receiving pembro + BSC. Combined with the efficacy and safety results from KEYNOTE-394, as well as other global 2L trials with pembro, including KEYNOTE-240 and KEYNOTE-224, our data support the benefit of pembro as 2L therapy for pts with advanced HCC. Clinical trial information: NCT03062358.

Hepatitis C virus-associated immune thrombocytopenia (HCV-ITP) has been assumed to be one of secondary ITP and associated with antiplatelet antibodies. This study was to clarify the antibody profile in HCV-ITP compared with primary ITP. We enrolled 55 HCV-ITP, 30 primary ITP, 11

Nutritional counseling is frequently overlooked in cancer patients with normal nutritional status. This study aimed to evaluate the impact of nutritional counseling in head and neck cancer (HNC) patients with normal nutritional status prior to concurrent chemoradiotherapy (CCRT).A total of 243 patients with pretreatment normal nutritional status and locally advanced HNC receiving concurrent chemoradiotherapy (CCRT) at three medical centers were enrolled. All patients were retrospectively allocated into the early (≤ 2 weeks, n = 105, 43.2%), late (2 weeks, n = 102, 42.0%), and no nutritional counseling groups (n = 36, 14.8%) according to the time interval between the date of CCRT initiation and the first date of nutritional counseling for comparison.The 1-year overall survival rates were 95.0%, 87.5%, and 81.3% in the early, late, and no nutritional counseling groups (p = 0.035), respectively. The median body weight changes at end of CCRT were - 4.8% (range, - 13.3 to 8.7%), - 5.6% (range, - 21.9 to 5.6%), and - 8.6% (range, - 20.3 to 2.4%) in patients in the early, late, and no nutritional counseling groups, respectively. The early termination of chemotherapy rates and the incompletion rates of planned radiotherapy were 1.9% and 1.9%, 2.9%, and 2.0%, 13.9%, and 19.4% in patients in the early, late, and no nutritional counseling groups, respectively.Our findings strongly suggest that while some HNC patients may have pretreatment normal nutritional status, early nutritional counseling is nevertheless essential for the improvement of treatment tolerance and survival outcome.

Background/purpose Ropeginterferon alpha-2b (Ropeg) is a novel pegylated interferon-alpha recently approved for the treatment of polycythemia vera (PV) in Europe. However, other than data from clinical trials, little is known about this agent in real world practice. Methods A compassionate use program employing Ropeg for treating patients with unmet medical need was initiated in Taiwan in 2017. Herein, we collected clinical data and assessed the safety as well as efficacy of Ropeg in nine patients treated in this program. Results Collectively, among evaluable patients, both the molecular response and complete blood count remission rates were 62.5%. Most therapy-related side effects were mild, and there was no treatment discontinuation attributable to intolerable adverse events. The agent also showed efficacy in symptom amelioration and spleen size reduction. Although no specific patterns of cytokine level alteration could be identified, significantly attenuated plasma levels of inflammation markers were observed in one particular patient who happened to have normalized spleen size and most remarkable reduction in JAK2 mutant allele burden, indicating all-around improvement in every aspect of this case. Furthermore, plasma hepcidin levels increased in two-thirds of PV patients, illustrating the potential of Ropeg to restore normal regulation of erythropoiesis. Using RNA sequencing on pre- and post-treatment samples from one patient, we demonstrated altered expression of genes participating in IFN response, inflammation, apoptosis, and cellular differentiation. Conclusion Conclusively, observed signs of efficacy and safety in our real-world experience prove Ropeg as a promising option for the treatment of MPN.

Background The prognostic relevance of extranodal extension (ENE) for salivary gland carcinoma (SGC) remains unclear. The present study is undertaken to investigate the predictive significance of pathological nodal parameters in surgically treated patients with nodal metastatic SGC. Methods This multicenter cohort included 114 patients with pathologically proven node-positive SGC between 2000 and 2014. Possible correlations of clinicopathological parameters and outcomes were examined. Results The median follow-up was 69 months (range, 11-173 months). The multivariate analysis identified metastatic node number (1-2 vs 3-6; 1-2 vs ≥7) as an independent predictor for regional control (P = 0.005; P = 0.02), locoregional control (P = 0.008; P = 0.04), distant metastasis-free survival (P = 0.17; P = 0.006), disease-free survival (P = 0.05; P = 0.002), and overall survival (P = 0.18; P = 0.009), whereas ENE was not associated with survival outcomes. Conclusions Metastatic node number, not ENE, is an independent node-related prognosticator for SGC. Integration of ENE into the American Joint Committee on Cancer 8th edition staging criteria may not improve prognostic performance.

BackgroundThe programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) axis plays a central role in suppressing antitumor immunity; axis dysregulation can be used by cancer cells to evade the immune system. Tislelizumab, an investigational monoclonal antibody with high affinity and binding specificity for PD-1, was engineered to minimize binding to FcγR on macrophages to limit antibody-dependent phagocytosis, a potential mechanism of resistance to anti-PD-1 therapy. The aim of this phase IA/IB study was to investigate the safety/tolerability, antitumor effects and optimal dose and schedule of tislelizumab in patients with advanced solid tumors.MethodsPatients (aged ≥18 years) enrolled in phase IA received intravenous tislelizumab 0.5, 2, 5 or 10 mg/kg every 2 weeks; 2 or 5 mg/kg administered every 2 weeks or every 3 weeks; or 200 mg every 3 weeks; patients in phase IB received 5 mg/kg every 3 weeks. Primary objectives were to assess tislelizumab’s safety/tolerability profile by adverse event (AE) monitoring and antitumor activity using RECIST V.1.1. PD-L1 expression was assessed retrospectively with the VENTANA PD-L1 (SP263) Assay.ResultsBetween May 2015 and October 2017, 451 patients (n=116, IA; n=335, IB) were enrolled. Fatigue (28%), nausea (25%) and decreased appetite (20%) were the most commonly reported AEs. Most AEs were grade 1–2 severity; anemia (4.9%) was the most common grade 3–4 AE. Treatment-related AEs led to discontinuation in 5.3% of patients. Grade 5 AEs were reported in 14 patients; 2 were considered related to tislelizumab. Pneumonitis (2%) and colitis (1%) were the most common serious tislelizumab-related AEs. As of May 2019, 18% of patients achieved a confirmed objective response in phase IA and 12% in phase IB; median follow-up duration was 13.6 and 7.6 months, respectively. Pharmacokinetics, safety and antitumor activity obtained from both phase IA and IB determined the tislelizumab recommended dose; ultimately, tislelizumab 200 mg intravenous every 3 weeks was the dose and schedule recommended to be taken into subsequent clinical trials.ConclusionsTislelizumab monotherapy demonstrated an acceptable safety/tolerability profile. Durable responses were observed in heavily pretreated patients with advanced solid tumors, supporting the evaluation of tislelizumab 200 mg every 3 weeks, as monotherapy and in combination therapy, for the treatment of solid tumors and hematological malignancies.Trial registration numberNCT02407990.

No gold standard of nutritional assessment is established among patients with head and neck cancer (HNC) receiving concurrent chemoradiotherapy (CCRT). This study aimed to evaluate the clinical significance of pre-treatment nutritional status using the Mini Nutritional Assessment-short form (MNA-SF) among HNC patients receiving CCRT. A total of 461 consecutive patients with newly diagnosed HNC treated with definitive CCRT at three medical institutes were prospectively enrolled. Nutritional status was assessed using MNA-SF within 7 days before CCRT initiation. Patients were classified as having normal nutrition, at risk of malnutrition, and malnourished groups according to MNA-SF for comparison. The 1-year overall survival rates were 89.8%, 76.8%, and 67.7% in the normal nutrition, at risk of malnutrition, and malnourished groups, respectively. Patients with normal nutrition had significantly lower rates of uncompleted radiotherapy and chemotherapy (4.5% and 4.1%, respectively) compared with patients at risk for malnutrition (14.1% and 11.5%, respectively) and those malnourished (11.1% and 11.1%, respectively). Patients with normal nutrition had significantly lower treatment-related complication rates regarding emergency room visits, hospital admission, and need for tubal feeding than those with at risk of malnutrition and malnourished. Patients with normal nutrition had significantly fewer severe hematologic toxicities (p = 0.044) and severe non-hematologic toxicities (p = 0.012) of CCRT than those malnourished. Pre-CCRT nutritional status identifies HNC patients vulnerable to treatment interruption and treatment complications. We suggest that nutritional assessment with MNA-SF should be incorporated in pre-CCRT evaluation for all HNC patients.

Background Aberrant MYC and BCL2 expression, cell of origin (COO), and National Comprehensive Cancer Network international prognostic index (NCCN-IPI) are commonly used for risk assessment and treatment decision in patients with diffuse large B-cell lymphoma (DLBCL). Although obesity has been shown to be of predictive value in DLBCL patients, it remains unclear whether it retains its prognostic relevance after those aforementioned novel factors being taken into consideration. Methods Patients with DLBCL were identified retrospectively in a single institute and data were collected through electronic databases and pharmacy records. Results Fifteen (17.6%) out of the 85 patients with DLBCL in our cohort were categorized as obese. They had lower platelet counts, were younger and more likely to harbor either BCL2- or MYC-overexpressing tumors. The NCCN-IPI scores, COO, and other clinical parameters were not significantly different between obese and non-obese patients. In spite that obesity adversely affected the treatment response to immunochemotherapy, multivariate analysis showed that only NCCN-IPI risk categories [hazard ratio (HR) 2.83 for high-intermediate or high-risk, versus low-intermediate or low-risk, P=0.034] and BCL2/MYC expressional status (HR 4.12 for BCL2high and/or MYChigh, versus both low expressors, P=0.004) independently predicted progression-free survival (PFS) outcome, whereas obesity lost its prognostic value in this regard (HR 1.81 for obese patients, P=0.242). Similarly, high-intermediate to high NCCN-IPI risk (HR 3.11, P=0.034) and increased expression in either BCL2 or MYC (HR 5.63, P=0.001) both portended an inferior overall survival (OS), but the presence of obesity did not affect the outcome (HR 1.65, P=0.352). Conclusions Our study has demonstrated that, for the first time, obesity increases the frequency of BCL2- or MYC-overexpressing tumors in patients with DLBCL.

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 Pazopanib is a multitargeted tyrosine kinase inhibitor used as a standard treatment for chemotherapy-refractory recurrent or metastatic soft tissue sarcoma. This study aimed to evaluate the efficacy and safety of pazopanib for treatment of metastatic soft tissue sarcoma in the Asian population. Methods Fifty patients with chemotherapy-refractory recurrent or metastatic soft tissue sarcoma, who had received pazopanib treatment between 2015 and 2016 were enrolled. We reviewed patients' clinical characteristics and studied survival outcomes following pazopanib treatment. Results Median follow-up was 5.7 months. Seven patients were still on pazopanib by the end of this study and the disease had progressed in the other 43 patients, leading to 23 deaths. We found that despite treatment more than half the patients experienced disease progression (56% vs 14% partial response and 30% stable disease). The median progression-free survival and overall survival was 3.1 and 11.0 months, respectively. Multivariate analysis identified good Eastern Cooperative Oncology Group performance status (0 or 1) and occurrence of hand-foot skin reaction as independent factors associated with better outcome. Hand-foot skin reaction was 32% in our cohort and the median onset time was 4 (1.00-8.29) weeks. It had dose-dependent effect by clinical observation. Conclusions Our study showed that the incidence rate of hand-foot skin reaction in Taiwan is higher than western population, and it is an independent predictive factor for better treatment outcomes.

Breast, ovarian, and uterine corpus cancers are common female cancers and categorized as hormone‐related diseases. Previous studies reported a unidirectional relationship for each cancer, but few studied the reciprocal association in the same cohort. A population‐based study was carried out in Taiwan to test the hypothesis that there are pairwise bidirectional associations among these cancers. Using the same cohort of 110,112 cases with primary female cancers including uterine corpus cancer (11,146 cases), ovarian cancer (12,139 cases), or breast cancer (86,827 cases) from the Taiwan Cancer Registry from 1979 to 2008, the pairwise risks of second cancer among uterine corpus, ovary, and breast cancer cases were evaluated by standardized incidence ratios (SIRs) and the corresponding 95% confidence intervals (CIs) to quantify the excess of second malignancies. A reciprocal relationship was found for these three female cancers, particularly most prominent between uterine and ovarian cancers, followed by breast and uterine cancers as well as breast and ovarian cancers. The overall risk of second cancers was highest within the first 5 years after the diagnosis of primary cancer. The bidirectional relationships suggest common risk factors among these three female cancers. This is the largest cohort study to focus on the bidirectional associations among hormone‐related cancers in Asian women, and these results could aid in the development of early prevention strategies and follow‐up surveillance programs.

Purpose: Being elevated body mass index (BMI) has been considered a poor prognostic factor in patients with cancer. However, studies about the impact of elevated BMI on the survival outcome after cancer surgery have conflicting results. This study aimed to evaluate the impact of BMI on long-term postoperative survival outcome in a large cohort of Asian population with solid cancers. Methods: A total of 33,551 patients who underwent curative-intent surgery for solid cancers between January 2007 and December 2012 at four hospitals in Taiwan were included. BMI was analyzed using univariate and multivariate regression analyses to determine its association with survival outcome. Results: With a median follow-up of 43.8 (range, 1-91) months, the rate of all-cause mortality was 21.7% (n=7264 patients), while that of cancer-related mortality was 13.4% (n=4499 patients). BMI was a significant prognostic factor in multivariate analysis for overall survival (OS) and cancer-specific survival (CSS). The adjusted hazard ratio (HR) per kg/m2 was 0.922 (95% confidence interval [CI], 0.916-0.929; P 35 kg/m2. Conclusions: This study showed that BMI was positively associated with survival outcome in patients with cancer who underwent radical surgery. BMI was an independent prognostic factor and can be used to risk stratify patients in Asians with solid cancers.

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is an emerging surgical procedure for peritoneal carcinomatosis (PC). CRS/HIPEC is a complicated treatment that requires multi-disciplinary teamwork (MDT), which may be lacking when establishing a CRS/HIPEC programme. Herein, we report our preliminary treatment outcomes with the early implementation of an MDT model for CRS/HIPEC.From April 2015 to December 2016, 45 patients with a diagnosis of PC who received CRS/HIPEC were reviewed retrospectively in a single institution in Taiwan.Among the 45 patients, CRS was mainly performed by laparotomy (n = 42), and only three patients with limited PC underwent laparoscopic CRS. The first 13 patients received treatment before the MDT had been established (group 1), and the other 32 patients were treated after the MDT had been established (group 2). The highest peri-HIPEC body temperature in group 2 was significantly lower than that in group 1 (36.8 °C vs. 37.5 °C, p 0.001). Overall, eight patients experienced major complications. The trend of a lower major complication rate was observed after the MDT model had been implemented (30.7% in group 1 vs. 12.4% in group 2, p = 0.202). Pre-CRS/HIPEC abdominal pain significantly increased the risk of post-operative major complications (p = 0.017).Our experience suggests that the early implementation of an MDT model when establishing a CRS/HIPEC programme at a single institution may result in a higher complete cytoreduction rate and lower major complication rate, and also shorten the learning curve of this complicated procedure.

Gastrointestinal stromal tumor (GIST) arises from the mesenchymal tissue of the gastrointestinal tract. It develops in the abdominal cavity and mostly the metastasis is limited to the liver and abdominal viscera. Metastasis beyond extra-abdominal site is rare in patients with GIST. Metastatic GIST to maxillary sinus is an extremely rare presentation and diagnostic challenge to clinicians. The treatment of metastatic GIST differs from squamous cell carcinoma of head and neck and tyrosine kinase inhibitor is the mainstay of therapy. We herein reported a case of 87-year-old lady diagnosed with recurrent GIST with metastasis to maxillary sinus and successfully treated with target therapy.

Hepatitis B virus (HBV) infection has been documented as a risk factor for non-Hodgkin lymphoma (NHL). However, there are few large cohort studies, and there is no report about the impact of HBV vaccination. We conducted this study to evaluate these issues. We used the nationwide cohort of the Taiwan National Health Insurance Research Database for 1997-2013. We compared the incidence and the risk of developing NHL and CD20+ aggressive lymphoma between HBV and non-HBV cohorts. The hazard ratios (HRs) were computed using Cox proportional hazards models. We matched these two large cohorts to reconfirm the data. We also compared the incidence of NHL between cohorts born before and after the inception of universal HBV vaccination. We found that HBV infection increased the risk for developing NHL and CD20+ aggressive lymphoma, with HRs of 4.14 and 5.52, with a higher incidence of 17.07 and 13.9 per 100 000 person-years, respectively, compared to the non-HBV cohort. The incidence of NHL in the cohort born in the era before universal HBV vaccination was higher with 1.85 per 100 000 person-years compared to 0.74 in the cohort born later aged younger than 20. Our study confirms that HBV confers a greater risk for developing NHL, especially CD20+ aggressive lymphoma. The impact of HBV vaccination is protective against lymphoma development in the teenagers in an endemic area, but longer follow-up is needed for older age.

BACKGROUND AND AIM Given that a wide variation in tumor response rates and survival times suggests heterogeneity among the patients with advanced pancreatic cancer (APC) who underwent second-line (L2) chemotherapy, it is a challenge in clinical practice to identify patients who will receive the most benefit from L2 treatment. METHODS We selected 183 APC patients who received L2 palliative chemotherapy between 2010 and 2016 from a medical center as the development cohort. A Cox proportional hazard model was used to identify the prognostic factors and construct the nomogram. An independent cohort of 166 patients from three other hospitals was selected for external validation. RESULTS The nomogram was based on eight independent prognostic factors from the multivariate Cox model: sex, Eastern Cooperative Oncology Group performance status, reason for first-line treatment discontinuation, duration of first-line treatment, neutrophil-to-lymphocyte ratio, tumor stage, body mass index, and serum carbohydrate antigen 19-9 levels at the beginning of L2 treatment. The model exhibited good discrimination ability, with a C-index of 0.733 (95% confidence interval, 0.681-0.785) and 0.724 (95% confidence interval, 0.661-0.787) in the development and validation cohorts, respectively. The calibration plots of the development and validation cohorts showed optimal agreement between model prediction and actual observation in predicting survival probability at 6 months, 1 year, and 2 years. CONCLUSIONS This study developed and externally validated a prognostic model that accurately predicts the survival outcome of APC patients before L2 palliative chemotherapy, which could assist in clinical decision-making, counseling for treatment, and most importantly, prognostic stratification of patients.