Nivolumab in Advanced Hepatocellular Carcinoma: Safety Profile and Select Treatment-Related Adverse Events From the CheckMate 040 Study.

BACKGROUND: CheckMate 040 assessed the efficacy and safety of nivolumab in patients with advanced hepatocellular carcinoma (HCC). Understanding the safety profile of nivolumab is needed to support the management of treatment-related adverse events (TRAEs). This analysis assessed the safety of nivolumab monotherapy in the phase I/II, open-label CheckMate 040 study. MATERIALS AND METHODS: Select TRAEs (sTRAEs; TRAEs with potential immunologic etiology requiring more frequent monitoring) occurring between first dose and 30 days after last dose were analyzed in patients in the dose-escalation and -expansion phases. Time to onset (TTO), time to resolution (TTR), and recurrence of sTRAEs were assessed, and the outcome of treatment with immune-modulating medication (IMM) was evaluated. RESULTS: The analysis included 262 patients. The most common sTRAE was skin (35.5%), followed by gastrointestinal (14.5%) and hepatic (14.1%) events; the majority were grade 1/2, with 10.7% of patients experiencing grade 3/4 events. One patient had grade 5 pneumonitis. Median (range) TTO ranged from 3.6 (0.1-59.9) weeks for skin sTRAEs to 47.6 (47.1-48.0) weeks for renal sTRAEs. Overall, 68% of sTRAEs resolved, with median (range) TTR ranging from 3.7 (0.1-123.3+) weeks for gastrointestinal sTRAEs to 28.4 (0.1-79.1) weeks for endocrine sTRAEs. Most gastrointestinal and all hepatic events resolved with treatment in accordance with established toxicity management algorithms. In 57 patients (40%), sTRAEs were managed with IMM. Reoccurrence of sTRAEs was uncommon following rechallenge with nivolumab. CONCLUSION: Nivolumab demonstrated a manageable safety profile in this analysis of patients with advanced HCC. A majority of sTRAEs resolved with treatment. IMPLICATIONS FOR PRACTICE: Nivolumab is a viable treatment option for patients with previously treated advanced hepatocellular carcinoma as it has demonstrated durable tumor responses and promising survival. Nivolumab has a manageable safety profile. The most common select treatment-related adverse events (sTRAEs) in this analysis were skin related (35%). Gastrointestinal and hepatic sTRAEs were observed in approximately 14% of patients. The majority of sTRAEs resolved (68%). Safety events are easier to manage if addressed early. Patient education on signs and symptoms to watch out for and the importance of early reporting and consultation should be emphasized.

The association of liver function and quality of life of patients with liver cancer.

BACKGROUND: Quality of life (QOL) assessments with the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, QLQ-HCC18, C30 and HCC18 index scores have been shown to be prognostic factors for overall survival (OS) in patients with hepatocellular carcinoma (HCC), independent of disease stage and liver function. Liver function parameters (including bilirubin, albumin, international normalized ratio [INR], Child-Pugh class, ALBI grade, MELD, alkaline phosphatase [ALP]-to-platelet ratio, albumin-to-ALP ratio) have also been found to be independent prognostic factors for OS in HCC patients. There has been scanty data on whether QOL and baseline liver function per se are correlated in HCC patients. This study investigates the correlations between baseline QOL data and liver function variables in HCC patients. METHODS: From 2007 to 2011, 517 patients were enrolled. Baseline QOL was assessed at diagnosis using the EORTC QLQ-C30 and QLQ-HCC18; thereafter C30 and HCC18 index scores were derived. Clinical and laboratory data were collected. For liver function assessment, Child-Pugh class, ALBI grade, MELD, ALP-to-platelet ratio and albumin-to-ALP ratio were derived. Correlation analyses were performed between QOL and liver function data. RESULTS: Complete QOL data were available in 472 HCC patients. After adjusting for clinical variables, significant correlations were found between QOL (QLQ-C30 and QLQ-HCC18) and dichotomized liver function variables (including Child-Pugh class, ALBI grade and the presence of ascites). It was demonstrated that QOL had significant and potentially clinically important correlations with continuous liver function variables (albumin, bilirubin, ALP and albumin-to-ALP ratio), with the highest Spearman's rank correlation coefficient (rho) exceeding 0.4. HCC18 and C30 index scores were also significantly correlated with these liver function variables. HCC18 index score, which had rho up to 0.37, generally performed better than C30 index score, which had rho up to 0.33. CONCLUSIONS: In HCC patients, baseline QOL assessment (using EORTC QLQ-C30, QLQ-HCC18, C30 index-score or HCC18 index-score) is significantly correlated with liver function. Based on the findings of this study, future trials are warranted to assess whether treatment to enhance liver function could improve HCC patients' QOL.

Status of inflammation in relation to health related quality of life in hepatocellular carcinoma patients.

PURPOSE: Both Inflammation and health-related quality of life (HRQoL) are independent prognosticators in HCC patients. We hypothesized that inflammation can cause impairment in HRQoL and investigated the correlation between inflammatory status and HRQoL in HCC patients. METHODS: Clinical, laboratory and HRQoL (using EORTC QLQ-C30, QLQ-HCC18, C30 and HCC18 index-scores) data were prospectively collected from HCC patients at diagnosis. Correlation analyses were performed between HRQoL and inflammation-based markers including C-reactive protein (CRP), CRP/albumin ratio (CRP/alb), Glasgow Prognostic Score (GPS), Inflammation-Based Index (IBI) and Prognostic Index (PI). RESULTS: Among 445 HCC patients, higher inflammatory states were significantly correlated with worse HRQoL. For CRP and CRP/alb ratio, the HRQoL factors with higher correlations included C30 and HCC18 index-scores, certain QLQ-C30 domains and items ('physical functioning', 'role functioning', 'fatigue', 'pain', 'appetite loss') and QLQ-HCC18 items ('fatigue', 'body image', 'nutrition' and 'abdominal swelling'), where the Pearson's correlation coefficients were up to 0.416. Multivariate analyses indicated that worse HRQoL factors were significantly correlated with worse scores in GPS, IBI and PI. CONCLUSION: In HCC patients, inflammatory status correlates with HRQoL at presentation. In particular, relatively stronger correlations with CRP-based markers have been observed in HRQoL scales that assess constitutional symptoms (QLQ-C30 'physical functioning', 'role functioning', 'fatigue', 'appetite loss' and QLQ-HCC18 'fatigue' and 'nutrition') and tumor burden (QLQ-C30 'pain' and QLQ-HCC18 'abdominal swelling' and 'body image'). Future studies are warranted to evaluate whether intervention that reduces inflammation could improve HRQoL in HCC patients.

A phase 2 study of the efficacy and biomarker on the combination of transarterial chemoembolization and axitinib in the treatment of inoperable hepatocellular carcinoma.

BACKGROUND: A surge of vascular endothelial growth factor (VEGF) after transarterial chemoembolization (TACE) may contribute to tumor progression. Axitinib is a potent antiangiogenic agent with main activity against VEGF receptors 1 to 3. To the authors' knowledge, its role in combination with TACE for the treatment of patients with inoperable hepatocellular carcinoma (HCC) is unclear. METHODS: A phase 2 clinical trial (ClinicalTrials.gov identifier NCT01352728) was conducted to evaluate the combination treatment. Patients with inoperable HCC who were potential candidates for TACE initiated treatment with axitinib at a dose of 5 mg twice daily and were evaluated for the need for TACE every 8 weeks. Axitinib was withheld 24 hours before TACE, and resumed 24 hours afterward when fulfilling predefined criteria. Radiologic assessment was conducted every 8 weeks. The primary endpoint was the 2-year overall survival (OS) rate. RESULTS: A total of 50 patients were recruited from March 2011 to April 2014. The mean age of the patients was 61.8 years, and 46 patients (92%) had hepatitis B infection. The Barcelona Clinic Liver Cancer stage B/C percentage was 76% (38 cases)/24% (12 cases). The 2-year OS rate was 43.7%, and the median OS was 18.8 months in the intention-to-treat population. Among the evaluable population (44 patients), 40.9% (18 patients) and 27.3% (12 patients) achieved complete and partial responses, respectively. Common grade 3 or above axitinib-related complications included hand-foot skin reaction (14%) and hypertension (24%). The presence of hypertension during treatment was found to be an independent prognosticator (hazard ratio, 0.563; P = .0073) suggestive of a contributory role of axitinib to efficacy. CONCLUSIONS: The combination of axitinib and TACE was potentially efficacious for patients with inoperable HCC with a high radiologic response rate. Cancer 2017;123:3977-85. © 2017 American Cancer Society.

Prognostic values of EORTC QLQ-C30 and QLQ-HCC18 index-scores in patients with hepatocellular carcinoma - clinical application of health-related quality-of-life data.

BACKGROUND: Health-related quality-of-life (HRQOL) assessment with EORTC QLQ-C30 was prognostic for overall survival (OS) in patients with advance-stage hepatocellular carcinoma (HCC), but no data existed for early-stage patients. The HCC-specific QLQ-HCC18 has not been evaluated for prognostic value in HCC patients. Utilization of raw HRQOL data in clinical setting has been impractical and non-meaningful. Therefore we developed index scores of QLQ-C30 and QLQ-HCC18 in an attempt to enable clinical utilization of these HRQOL measurements. This study investigates the prognostic significance of QLQ-C30, QLQ-HCC18 and C30/HCC18 index-scores in patients with newly diagnosed HCC which encompasses all stages. METHODS: From 2007-2011, 517 patients were prospectively recruited. HRQOL was assessed at diagnosis using QLQ-C30 and QLQ-HCC18; C30 and HCC18 index-scores were calculated from raw HRQOL data. Cox regression was performed using continuous, dichotomized QLQ-C30 and QLQ-HCC18 variables, or index-scores, together with clinical factors to identify independent factors for OS. Various multivariate models were validated with c-index and bootstrapping for 1000 replications. RESULTS: Four hundred and seventy two patients had complete HRQOL data. Their median OS was 8.6 months. In multivariate analysis, independent prognostic HRQOL variables for OS were QLQ-C30 pain (HR 1.346 [1.092-1.661], p = 0.0055), QLQ-C30 physical functioning (HR 0.652 [0.495-0.860], p = 0.0024); QLQ-HCC18 pain (HR 1.382 [1.089-1.754], p = 0.0077) and QLQ-HCC18 fatigue (HR 1.441 [1.132-1.833], p = 0.0030). C30 index-score (HR 2.143 [1.616-2.841], p < 0.0001) and HCC18 index-score (HR 1.957 [1.411-2.715], p < 0.0001) were highly significant factors for OS. The median OS of patients with C30 index-score of 0-20, 21-40, 41-60, 61-100 were 16.4, 7.3, 3.1, 1.8 months respectively (p < 0.0001); while for HCC18 index-score: 16.4, 6.0, 2.8, 1.8 months respectively (p < 0.0001). All the multivariate models were validated, with mean optimism <0.01. The bootstrap validated c-index was 0.78. CONCLUSIONS: QLQ-C30 and QLQ-HCC18 were prognostic for OS in patients with newly diagnosed HCC irrespective of stage. Both C30 and HCC18 index-scores were highly significant prognostic factors for OS in newly diagnosed HCC patients. Index-scoring provides an effective way to summarize, analyze and interpret raw HRQOL data, and renders QLQ-C30 and QLQ-HCC18 meaningful and communicable in clinical practice. Index-scores could potentially serve as a standardized tool for future HRQOL research.

Profiles of lipids, blood pressure and weight changes among premenopausal Chinese breast cancer patients after adjuvant chemotherapy.

BACKGROUND: Adjuvant chemotherapy improves outcome of patients with early breast cancer. However, chemotherapy may be associated with long term toxicities. In this retrospective cohort study, the objectives were to determine body weight, body mass index (BMI), blood pressure and fasting lipids levels of young premenopausal Chinese breast cancer patients after adjuvant chemotherapy. Potential factors associated with these parameters were identified. METHODS: Eligibility criteria include premenopausal Chinese patients who were diagnosed to have stage I-III breast cancer within 3-10 years, age < 45 and having received adjuvant chemotherapy at the time of breast cancer diagnosis. Information at initial breast cancer diagnosis were retrieved from patients' medical records and include age at diagnosis, tumor characteristics, anti-cancer treatments, blood pressure and body weight and height. At study entry, all patients had additional background demographics collected, as well as blood pressure, body weight and fasting serum lipid profiles measured. Incidence of chemotherapy-related amenorrhoea (CRA) and menopause were determined. Factors associated with weight gain, hypertension and dyslipidaemias were analyzed. RESULTS: Two hundred and eighty patients were studied. The median age at breast cancer diagnosis was 41 years (range: 24-45). The median time from breast cancer diagnosis to study entry was 5.0 years. The median age at study entry was 46.5 years (range: 28-54). 91.1% developed CRA; 48.9% had become menopausal and 10% were peri-menopausal. Between initial breast cancer diagnosis and the time of study entry, the median weight gain was 1.8 kg; 63.2% gained weight by >2%; 52.1% were overweight/obese; 30.7% had hypertension. Abnormal total-cholesterol and LDL-cholesterol occurred in 34.3% and 56.1% respectively. On multivariate analyses, older age was associated with reduced risk while occurrence of CRA and having received taxane-containing regimens were associated with increased risk of weight gain. Oestrogen-receptor positivity was associated with reduced risk while overweight/obese statuses were associated with increased risk of hypertension. Use of tamoxifen was associated with reduced risk of abnormal LDL-cholesterol. Weight gain, overweight/obese, older age, progression to post/peri-menopausal status at study entry, having received corticosteroid premedication before adjuvant chemotherapy and having received taxane-containing adjuvant chemotherapy were associated with increased risk of dyslipidaemias. CONCLUSION: Among young premenopausal Chinese breast cancer patients who had received adjuvant chemotherapy, the current study has revealed that although there was only a median weight gain of 1.8 kg, there was a nearly 60% increase in abnormal BMI. Further, a significant proportion of patients were detected to have hypertension and dyslipidaemias. Interventional studies with lifestyle modifications are warranted.

Phase I/II study of temsirolimus for patients with unresectable Hepatocellular Carcinoma (HCC)- a correlative study to explore potential biomarkers for response.

BACKGROUND: The oncogenic PI3K/Akt/mTOR pathway is frequently activated in HCC. Data on the mTOR inhibitor, temsirolimus, is limited in HCC patients with concomitant chronic liver disease. The objectives of this study were: (1) In phase I, to determine DLTs and MTD of temsirolimus in HCC patients with chronic liver disease; (2) In phase II, to assess activity of temsirolimus in HCC, and (3) to explore potential biomarkers for response. METHODS: Major eligibility criteria included histologically confirmed advanced HCC and adequate organ function. In Phase I part of the study, temsirolimus was given weekly in 3-weekly cycle; dose levels were 20 mg (level 1), 25 mg (level 2) and 30 mg (level 3). The MTD was used in the subsequent phase II part; the primary endpoint was PFS and secondary endpoints were response and OS. In addition, exploratory analysis was conducted on pre-treatment tumour tissues to determine stathmin, pS6, pMTOR or p-AKT expressions as potential biomarkers for response. Overall survival and PFS were calculated using the Kaplan-Meier method. Reassessment CT scans were done every 6 weeks. All adverse events were reported using CTCAE v3. RESULTS: The Phase I part consisted of 19 patients, 2 of 6 patients at level 3 experienced DLT; dose level 2 was determined to be the MTD. The phase II part consisted of 36 patients. Amongst 35 assessable patients, there were 1 PR, 20 SD and 14 PD. Overall, the median PFS was 2.83 months (95% C.I. 1.63-5.24). The median OS was 8.89 months (95% C.I. 5.89-13.30). Grade ≥ 3 that occurred in > 10% of patients included thrombocytopenia (4) and hyponatraemia (4). Exploratory analysis revealed that disease stabilization (defined as CR + PR + SD > 12 weeks) in tumours having high and low pMTOR H-scores to be 70% and 29% respectively (OR 5.667, 95% CI 1.129-28.454, p = 0.035). CONCLUSIONS: In HCC patients with chronic liver disease, the MTD of temsirolimus was 25 mg weekly in a 3-week cycle. The targeted PFS endpoint was not reached. However, further studies to identify appropriate patient subgroup are warranted. TRIAL REGISTRATION: This study has been registered in ClinicalTrials.gov (Id: NCT00321594) on 1 December 2010.

Applicability of BALAD score in prognostication of hepatitis B-related hepatocellular carcinoma.

BACKGROUND AND AIMS: The BALAD score is developed to provide an objective determination of prognosis for hepatocellular carcinoma (HCC) by incorporating five serum markers, namely albumin, bilirubin, alpha-fetoprotein (AFP), agglutinin-reactive alpha-fetoprotein (AFP-L3), and des-γ-carboxy prothrombin. We aim to study the applicability of BALAD score and prognostication of the three tumor markers in hepatitis B virus-related HCC. METHODS: Patients with newly diagnosed HCC were prospectively enrolled. All of the baseline characteristics and serum albumin and bilirubin level were documented at baseline. The levels of the three tumor markers (AFP, AFP-L3, and des-γ-carboxy prothrombin) were determined in archival serum samples. Patients were followed up for survivals according to local practice. The prognostic performances of the three markers and BALAD score were studied in association with overall survival (OS). RESULTS: A total of 198 patients with hepatitis B-related HCC were recruited. AFP and AFP-L3 levels were independent prognostic factors. The number of elevated tumor markers was also predictive of worse OS. BALAD score could stratify the cohort into different patient groups with distinct median OS. The median OS of BALAD score of 0, 1, 2, 3, and 4 was not reached, 26.6, 8.3, 2.6, and 1.9 months, respectively (P < 0.0001). BALAD score could further stratify outcomes in each Barcelona Clinic Liver Cancer (BCLC) subgroup. In particular, BALAD score of 3-4 had median OS of 2.6 months only in BCLC stage C patients. CONCLUSION: BALAD score is applicable in the population of hepatitis B virus-related HCC. The combined use of BALAD score and BCLC staging system could help identify more suitable candidates for clinical trial.

A 10-year prospective audit of LASIK outcomes for myopia in 37,932 eyes at a single institution in Asia.

PURPOSE: This study evaluates the efficacy, predictability and safety of LASIK surgery as a treatment for myopia performed as part of a large-scale, prospective clinical audit spanning 10 years in an Asian study population and to evaluate the outcomes and trends. DESIGN: Prospective, nonrandomized, single-center, multisurgeon study. PARTICIPANTS: We included 37,932 eyes of 19,753 patients that underwent myopic LASIK at the Singapore National Eye Centre between 1998 and 2007. METHODS: All eyes underwent LASIK as a treatment for myopia. Pre- and postoperative refractions, uncorrected visual acuity (UCVA), and best-corrected visual acuity (BCVA) were documented. MAIN OUTCOMES MEASURES: Safety, efficacy, refractive predictability, treatment trends, retreatment rates, and complications for mild, moderate, and high myopia according to spherical equivalence (SE) of less than -5.00 diopters (D), -5.00 D or more to less than -10.0 D, and -10.00 D or more, respectively. RESULTS: Patients' median age was 32 years (mean, 33.0+/-7.9 years); there were 6832 males (34.6%) and 12,921 females included. Patients were predominantly ethnic Chinese (90.5%). Mean follow-up time was 68.8 days. The mean spherical error corrected was -5.90+/-2.57 D (median, -5.625 D), and outcomes were categorized into low, moderate, or high myopia. The UCVA achieving > or =20/40 has been consistently above 90% since 2000, with 72.8% achieving > or =20/20. More than 93.0% of eyes achieved within +/-1.00 D target in the last 4 years. An improvement in safety was observed since the start of the study, with the best outcomes observed in 2007; loss of 1 and 2 Snellen line BCVA postoperatively was 2.4% and 0.1%, respectively. The overall retreatment rate was 3.8%; 91% of retreated eyes achieved UCVA of > or =20/30. Between 1998 and 2007, there was a significant improvement in postoperative UCVA and BCVA (P<0.001). CONCLUSIONS: Myopic LASIK performed in Asian eyes within a comprehensive LASIK clinical program with appropriate clinical audit governance can be safe and effective, with high refractive predictability. Improvements in the nomograms to prevent undercorrection and to compensate for myopic regression have led to better efficacy after LASIK, with an increasing percentage of patients achieving 20/15 visual acuity postoperatively.

Three-Year Outcomes of Simultaneous Accelerated Corneal Crosslinking and Femto-LASIK for the Treatment of High Myopia in Asian Eyes.

PURPOSE: To determine the long-term visual outcomes of simultaneous femtosecond laser-assisted laser in situ keratomileusis (femto-LASIK) and accelerated cross-linking (CXL) [LASIK Xtra] for the treatment of high myopia. PATIENTS AND METHODS: All 163 consecutive eyes of 85 patients who underwent LASIK Xtra for the treatment of high myopia and/or myopic astigmatism (spherical equivalent ≥ -6.00 D) in Singapore National Eye Centre from the years 2013 to 2017 were included in this retrospective case series. Post-operative follow-up was up to 3 years. RESULTS: Of the 163 eyes, 67 were followed up for 1 year (mean 12.9 months), 69 for 2 years (mean 24.0 months) and 43 for 3 years (mean 36.4 months). Overall mean follow-up was 22.8 months (9-46 months). The mean pre-operative spherical equivalent (SE) was -8.60 ± 1.47 D [range: -11.75 to -4.75] (n = 163) and mean attempted correction SE was -8.84 ± 1.41 D [range: -11.88 to -5.25]. Most eyes (>95%) maintained an uncorrected distance visual acuity of 6/12 or better over 3 years. Visual outcomes were predictable with ≥95% of eyes achieving a SE correction within ± 1D of attempted correction over 3 years. There was a mild regression in SE refraction over 3 years with a mean of -0.10 ± 0.45 D three years post-operatively (p = 0.03). The safety index was >1.05 at 3 years follow-up. There were no significant post-operative complications though 24 eyes had mild haze and 2 eyes had grade 1 diffuse lamellar keratitis that resolved within 1 month. CONCLUSION: Our 3-year LASIK Xtra results show favorable safety, efficacy, predictability and stability outcomes in Asian patients with high myopia.

Bone Health in Premenopausal Chinese Patients after Adjuvant Chemotherapy for Early Breast Cancer.

BACKGROUND: In this cohort study, the objectives were to determine bone mineral density (BMD) and potential associated factors for bone health among young premenopausal patients after adjuvant chemotherapy. METHODS: Eligibility criteria included premenopausal Chinese aged <45 years who had received adjuvant chemotherapy. At study entry, background demographics and menstrual history were collected; BMD was measured. Factors associated with reduced BMD and fracture risk were analyzed. RESULTS: A total of 271 patients entered the study. The median time from breast cancer diagnosis to study entry was 5.0 years. The median ages at breast cancer diagnosis and at study entry were 41 and 47 years, respectively. The median BMDs for femoral neck (FN) and lumbar spine (LS) were 0.72 and 0.91 g/cm2, respectively; 40.2% had abnormal Z-scores (defined as ≤-1) and 50.2% had osteopenia/osteoporosis of either FN or LS. On multivariate analyses, factors that were identified to have a positive association with bone health (higher BMD) included higher family income (OR [95% CI] for LS = 1.573 [1.091-2.268]), taller stature (OR for LS = 2.975 [1.723-5.137]), and higher BMI (OR for FN = 2.156 [1.599-2.907]), while negatively associated factors included longer interval since last adjuvant treatment (OR for LS: 0.435 [0.250-0.757]), peri-/postmenopausal status at study entry (OR for LS = 0.443 [0.255-0.768]; OR for FN = 0.353 [0.205-0.609]), and having received adjuvant tamoxifen (OR for FN = 0.452 [0.243-0.841]). CONCLUSION: About 5 years after breast cancer diagnosis and adjuvant chemotherapy, >50% of premenopausal patients who had received adjuvant chemotherapy were detected to have osteopenia/osteoporosis and 40% had abnormal Z-scores for FN/LS.

TOP2A overexpression in hepatocellular carcinoma correlates with early age onset, shorter patients survival and chemoresistance.

Genomic gain represents an important mechanism in the activation of proto-oncogenes. In many instances, induced oncogenes hold clinical implications both as prognostic markers and targets for therapeutic design. In hepatocellular carcinoma (HCC), although chromosomal gains are common, information on underlying oncogenes induced remains minimal. Here, we examined 7 causal sites of HCC for overexpressed genes by array-based transcriptional mapping. In 22 HCC cell lines and early passages of cultures studied, clusters of up-regulated genes were indicated, where TOP2A expression ranked the highest. Distinct TOP2A transcriptions were confirmed in an independent series of HCC tumors relative to adjacent non-tumoral liver (p=0.0018). By tissue microarray analysis of 172 HCC, we found TOP2A expressions correlated with advance histological grading (p<0.001), microvascular invasion (p=0.004) and an early age onset of the malignancy (

Correlations of health-related quality of life with serum inflammatory indicators IL-8 and mIBI in patients with hepatocellular carcinoma.

PURPOSE: Health-related quality of life (HRQoL) is a significant prognostic factor for overall survival in hepatocellular carcinoma (HCC) patients, and this is independent of stage and liver function. Inflammation plays a significant role in HCC development and progression. It was hypothesized that the inflammatory status of HCC patients may affect their HRQoL. The relationship between HRQoL and inflammatory status was explored using indicators IL-8 level and modified inflammation-based index (mIBI, based on IL-8, C-reactive protein, and albumin). METHODS: From 2007-2011, HCC patients were enrolled prospectively. Baseline HRQoL assessment utilized the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ-HCC18; clinical and laboratory data were collected at diagnosis. Two summary indices, C30 and HCC18 index-scores, were calculated. Correlation analyses were performed between HRQoL and inflammatory markers. RESULTS: In the 445 patients studied, significant correlations were found between IL-8 levels and EORTC QLQ-C30, QLQ-HCC18, C30, and HCC18 index-scores. The strongest correlated factors were those reflective of constitutional symptoms, namely QLQ-C30 "appetite loss" (with Pearson's correlation coefficient, r=0.322, P<0.0001); QLQ-C30 "fatigue" (r=0.311, P<0.0001); QLQ-C30 "role functioning" (r=-0.305, P<0.0001); QLQ-HCC18 "nutrition" (r=0.317, P<0.0001); and QLQ-HCC18 "fatigue" (r=0.306, P<0.0001). In addition, moderate but significant correlations were also observed with HCC18 index score (r=0.321, P<0.0001), and C30 index score (r=0.306, P<0.0001). HRQoL factors were also significantly correlated with mIBI. CONCLUSION: Baseline HRQoL using the conventional assessments of EORTC QLQ-C30 and QLQ-HCC18, as well as C30 and HCC18 index-scores, significantly correlated with inflammatory indicators (IL-8 level and mIBI) in HCC patients. Among the strongest correlations were those between IL-8 level and the two index-scores, as well as HRQoL aspects that represent constitutional symptoms. When paralleled with molecular findings, traditional HRQoL assessment in HCC has gained a new level of understanding: pattern recognition within an HRQoL instrument could potentially identify patients with more severe inflammatory state.

Health Sciences Libraries Advancing Collaborative Clinical Research Data Management in Universities.

PURPOSE: Medical libraries need to actively review their service models and explore partnerships with other campus entities to provide better-coordinated clinical research management services to faculty and researchers. TRAIL (Translational Research and Information Lab), a five-partner initiative at the University of Washington (UW), explores how best to leverage existing expertise and space to deliver clinical research data management (CRDM) services and emerging technology support to clinical researchers at UW and collaborating institutions in the Pacific Northwest. METHODS: The initiative offers 14 services and a technology-enhanced innovation lab located in the Health Sciences Library (HSL) to support the University of Washington clinical and research enterprise. Sharing of staff and resources merges library and non-library workflows, better coordinating data and innovation services to clinical researchers. Librarians have adopted new roles in CRDM, such as providing user support and training for UW's Research Electronic Data Capture (REDCap) instance. RESULTS: TRAIL staff are quickly adapting to changing workflows and shared services, including teaching classes on tools used to manage clinical research data. Researcher interest in TRAIL has sparked new collaborative initiatives and service offerings. Marketing and promotion will be important for raising researchers' awareness of available services. CONCLUSIONS: Medical librarians are developing new skills by supporting and teaching CRDM. Clinical and data librarians better understand the information needs of clinical and translational researchers by being involved in the earlier stages of the research cycle and identifying technologies that can improve healthcare outcomes. At health sciences libraries, leveraging existing resources and bringing services together is central to how university medical librarians will operate in the future.

Simultaneous Accelerated Corneal Crosslinking and Laser In situ Keratomileusis for the Treatment of High Myopia in Asian Eyes.

BACKGROUND: LASIK Xtra is a recently described technique which combines LASIK and accelerated corneal cross-linking(CXL) in the same setting. Its long-term outcome in Asians with high myopia is not well described. OBJECTIVES: To compare the efficacy, predictability and safety of LASIK Xtra with LASIK in patients with high myopia. METHOD: This is a retrospective study comparing 50 consecutive eyes undergoing LASIK Xtra for the correction of high myopia and/or myopic astigmatism (-6.63 to -15.50 D manifest spherical equivalent) with a matched control group of 50 eyes undergoing LASIK alone for correction of high myopia (-6.00 to -12.25 D manifest spherical equivalent). Mean follow-up was 5.7 months (range, 1.5-13.3 months) for LASIK Xtra and 3.6 months (range, 1.7-4.2 months) for LASIK only. Outcome measures included Uncorrected Distance Visual Acuity (UDVA), Corrected Distance Visual Acuity (CDVA), refraction and intraoperative and postoperative complications. RESULTS: At post-operative 3 months, all eyes achieved UDVA of 20/40 or better, and 80.0% of LASIK Xtra eyes achieved UDVA of 20/20 or better, compared to 66.0% of LASIK only eyes (p = 0.115). Efficacy indices were 0.99±0.17 for LASIK Xtra and 0.94±0.17 for LASIK only (p = 0.164). The proportion of eyes within ±0.50 D of attempted correction was 84% in the LASIK only group and 72% in the LASIK Xtra group at post-operative 3 months (p = 0.148). Safety indices were 1.11±0.19 and 1.11±0.18 in the LASIK Xtra and LASIK only groups, respectively (p = 0.735). CONCLUSION: LASIK Xtra achieved comparable safety, predictability and efficacy as LASIK in patients with high myopia. Good refractive stability was attained at 6-12 months. Further long term studies are required to determine whether simultaneous CXL is able to reduce postoperative LASIK keratectasia in high-risk individuals.

Quality of life of young Chinese breast cancer patients after adjuvant chemotherapy.

INTRODUCTION: Understanding of quality of life (QoL) of young Chinese breast cancer patients after adjuvant cytotoxic chemotherapy is limited. This study aims to assess the QoL of premenopausal Chinese breast cancer women after receiving adjuvant chemotherapy. PATIENTS AND METHODS: Eligibility criteria included stage I-III breast cancer, premenopausal and age ≤45 years at cancer diagnosis and having received adjuvant chemotherapy within 3-10 years before entry to the present study. Patients' background demographics at the time of breast cancer diagnosis, together with tumor characteristics and anticancer treatments, were collected. At the time of study entry, the menopausal status based on menstrual history, body mass index, and QoL (assessed using Functional Assessment of Cancer Therapy-Breast +4) were recorded. RESULTS: Two hundred and eighty patients were recruited. Ninety-five patients (33.9%) underwent breast-conserving surgery, and nearly all (98.6%) underwent axillary dissection. For adjuvant therapies, 249 patients (88.9%) received anthracycline-containing chemotherapy and 79 (28.2%) received taxane-containing chemotherapy, while 68 (24.3%) received both. One hundred and eighty six patients (66.4%) received adjuvant radiotherapy, and 214 (76.4%) received adjuvant tamoxifen. The median time from breast cancer diagnosis to study entry was 5.01 years. QoL assessment at study entry revealed that older patients had worse social well-being (SWB; mean scores for age ≤40, 41-45, 46-50 and >50 years were 22.0, 19.3, 19.1 and 18.1, respectively, P=0.0442). Patients who underwent axillary dissection had worse scores for breast cancer sub-scale (BCS; mean score 22.2 vs. 28.3, P=0.0212). Patients who underwent taxane-containing chemotherapy had worse scores for arm subscale (mean score 13.8 vs. 15.3, P=0.0053). CONCLUSION: At a median follow-up of 5 years post-diagnosis, patients who were younger had fewer disturbances in their SWB. Patients who had axillary dissection had worse BCS scores, while those who received taxane had worse scores for arm subscale. Further studies are warranted for breast-specific QoL to address the specific issues encountered by breast cancer patients.

An intensive surveillance program detected a high incidence of hepatocellular carcinoma among hepatitis B virus carriers with abnormal alpha-fetoprotein levels or abdominal ultrasonography results.

PURPOSE: To study the incidence and treatment outcomes of hepatocellular carcinoma (HCC) detected in an intensive surveillance program (ISP) of hepatitis B virus (HBV) carriers. PATIENTS AND METHODS: We screened 1,018 HBV carriers by serum alpha-fetoprotein (AFP) measurement and abdominal ultrasonography (AUS). Patients with an abnormal AFP level or AUS result were enrolled in an ISP that included Lipiodol computed tomography followed by AFP measurement/AUS every 3 months for 2 years and then every 6 months thereafter. The rest were on routine surveillance for 2 years. RESULTS: A total of 9,849 serum AFP measurements and 3,053 AUSs were performed. After a median follow-up of 4.12 years, we diagnosed 24 HCCs among 78 patients with abnormal screening test results at enrollment (group A); 23 HCCs among 93 patients with only abnormal surveillance test results during follow-up (group B); and nine HCCs among 847 patients with 2 years of normal surveillance (group C). Annual incidence of HCC in the ISP was 760.2 (95% CI, 538.4 to 1,073.7) per 100,000. Mean tumor sizes were 3.02, 2.91, and 4.82 cm in groups A, B, and C, respectively (P = .01). Tumor resection rate of the ISP was 36.2%, although another 29.8% of the patients were eligible for locoregional ablative therapy. CONCLUSION: This study illustrated that a high incidence of relatively small HCCs may be detected by using intensive surveillance of high-risk HBV carriers. However, the surgical resection rate was low, and we were not able to demonstrate clinical benefit with the early detection. Future surveillance studies should consider incorporation of therapy aimed at long-term control of small-sized tumors.

Liver resection after irinotecan, 5-fluorouracil, and folinic acid for patients with unresectable colorectal liver metastases: a multicenter phase II study by the Cancer Therapeutic Research Group.

The main objectives of this study were to assess the use of irinotecan, 5-fluorouracil (5-FU), and leucovorin (FA) as neoadjuvant chemotherapy for patients with unresectable colorectal liver metastases and to determine the response rate and proportion of patients that could be down-staged to resectable tumors. Forty patients were treated with irinotecan (180 mg/m2 over 30 min) on d 1, FA (200 mg/m2 over 30 min) followed by 5-FU (400 mg/m2 bolus and continuous infusion of 600 mg/m2 over 22 h) on d 1 and 2 every 2 wk. The overall response rate was 55% (95% CI: 39.5-70.4%). The progression-free survival was 12.1 mo (95% CI: 11.4-14.8 mo). The median overall survival was 20 mo (95% CI: 17.7-26.6 mo). Four patients (10%) have undergone liver resection after a median of eight cycles. Those patients remained alive with a median follow up period of 33 mo. The principal grade 3-4 toxicity was neutropenia in 20 patients (50%). We conclude that the regimen of irinotecan/5-FU/FA was highly active in patients with colorectal cancer and liver metastases with limited toxicity. In a subgroup of patients with initial inoperable liver metastases, this regimen was able to down-stage the disease to an operable stage.

Vision-related quality of life and visual outcomes after small-incision lenticule extraction and laser in situ keratomileusis.

PURPOSE: To compare vision-related quality of life (VRQoL) scores and clinical outcomes between small-incision lenticule extraction and laser in situ keratomileusis (LASIK). SETTING: Singapore National Eye Centre, Singapore. DESIGN: Prospective study. METHODS: Patients had small-incision lenticule extraction using the Visumax 500 kHz femtosecond laser; or LASIK excimer ablation with the Wavelight Allegretto 400 Hz laser. Primary outcomes were 3-month predictability, efficacy, and safety. Secondary outcomes were intraoperative experience, visual symptoms, and VRQoL (validated Quality of Life Impact of Refractive Correction [QIRC] questionnaire) in 25 a subgroup of patients in each group. Following Rasch analysis, "Functional" and "Emotional," QIRC dimensions were analysed separately. RESULTS: At 3 months, predictability (82.5% versus 85.3%, ±0.5 diopters attempted correction, P =.453), safety index (1.13 ± 0.19 [SD] versus 1.07 ± 0.16, P = .158), and efficacy index (0.91 ± 0.21 versus 0.97 ± 0.19; P = .002) were found when comparing small-incision lenticule extraction (172 eyes) and LASIK (matched 688 eyes). Intraoperative experience between groups was not statistically different; visual fluctuations (P = .020) and episodes of visual blurring (P = .008) were greater after small-incision lenticule extraction than after LASIK at 1 month but not at 3 months. There was no difference in "functional" (66.7 ± 15.7 versus 55.3 ± 22.2, P = .064) and "emotional" (42.7 ± 23.2 versus 37.9 ± 23.8, P = .394) QIRC dimensions between the 2 groups (25 patients in each group) at 3 months. CONCLUSION: The study, 3-month predictability, safety, and VRQL scores were not statistically different between small-incision lenticule extraction and LASIK. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Chemotherapy-Related Amenorrhea and Menopause in Young Chinese Breast Cancer Patients: Analysis on Incidence, Risk Factors and Serum Hormone Profiles.

PURPOSE: In this prospective cross-sectional study on young premenopausal breast cancer patients, the objectives were to: determine the incidences of chemotherapy-related amenorrhea (CRA) and menopause (CRM); identify associated factors; and assess plasma levels of estradiol (E2) and follicular stimulating hormone (FSH) among patients who developed menopause. METHODS: Eligibility criteria include Chinese stage I-III breast cancer patients, premenopausal, age ≤45 at breast cancer diagnosis, having received adjuvant chemotherapy, within 3-10 years after breast cancer diagnosis. Detailed menstrual history prior to and after adjuvant treatment was taken at study entry. Patients' background demographics, tumor characteristics and anti-cancer treatments were collected. The rates of CRA and CRM were determined. Analysis was conducted to identify factors associated with CRM. For postmenopausal patients, levels of E2 and FSH were analyzed. RESULTS: 286 patients were recruited; the median time from breast cancer diagnosis to study entry was 5.0 years. 255 patients (91.1%) developed CRA. Of these, 66.7% regained menstruation. At the time of study entry, 137 (48.9%) had developed CRM, amongst whom 84 were age ≤45. On multivariate analysis, age was the only associated factor. Among patients with CRM, the median FSH was 41.0 IU/L; this was significantly lower in those who were taking tamoxifen compared to those who were not (20.1 vs. 59.7 IU/L, p<0.0001). The E2 level was <40 pmol/L; there was no difference between those who were still on tamoxifen or not. CONCLUSION: After adjuvant chemotherapy, the majority of young Chinese breast cancer patients developed CRA; ~50% developed CRM, with 61% at age ≤45. Age at diagnosis is the only factor associated with CRM. FSH level may be affected by tamoxifen intake.