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Objectives: Patient safety incidents can impact not only patients and families but also healthcare providers, who may experience negative emotions and symptoms, such as anxiety, guilt, stress, and loss of confidence. To identify and support these "second victims," a screening tool called the Second Victim Experience and Support Tool (SVEST) has been developed. This scoping review aims to map our current knowledge of the SVEST in terms of its scope of use, validation and limitations., Study Design: Scoping review., Methods: In accordance with the framework outlined by Arksey and O'Malley and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for Scoping Reviews, we conducted a literature search in MEDLINE, CINAHL, Cochrane Library, SCOPUS, Embase and PsycINFO databases from database inception up till 1 March 2023., Results: A total of 31 studies were reviewed. The SVEST has been cross-culturally adapted from English into other languages. The SVEST has been successfully used in different contexts and with various healthcare professionals, including doctors, nurses, allied health professionals, midwives and pharmacists. The tool has been used to assess the impact of second victim experiences and the effectiveness of support interventions in addressing the phenomenon. Validity assessment of translated versions of SVEST in the reviewed studies revealed good content validity in most cases, although some studies did not report clear values for scale-level Content Validity Index. On the whole, SVEST is generally a reliable and valid tool, although further refinements and modifications may improve its validity and reliability., Conclusions: The review highlights the significance of SVEST as a crucial resource for healthcare providers and organisations that prioritise well-being and safety in health care. It also underscores the importance of recognising the needs of second victims and offering them appropriate interventions to manage the aftermath of adverse events., (Copyright © 2023 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Background: Pembrolizumab previously demonstrated robust antitumor activity and manageable safety in a phase Ib study of patients with heavily pretreated, PD-L1-positive, recurrent or metastatic nasopharyngeal carcinoma (NPC). The phase III KEYNOTE-122 study was conducted to further evaluate pembrolizumab versus chemotherapy in patients with platinum-pretreated, recurrent and/or metastatic NPC. Final analysis results are presented., Patients and Methods: KEYNOTE-122 was an open-label, randomized study conducted at 29 sites, globally. Participants with platinum-pretreated recurrent and/or metastatic NPC were randomly assigned (1:1) to pembrolizumab or chemotherapy with capecitabine, gemcitabine, or docetaxel. Randomization was stratified by liver metastasis (present versus absent). The primary end point was overall survival (OS), analyzed in the intention-to-treat population using the stratified log-rank test (superiority threshold, one-sided P = 0.0187). Safety was assessed in the as-treated population., Results: Between May 5, 2016, and May 28, 2018, 233 participants were randomly assigned to treatment (pembrolizumab, n = 117; chemotherapy, n = 116); Most participants (86.7%) received study treatment in the second-line or later setting. Median time from randomization to data cutoff (November 30, 2020) was 45.1 months (interquartile range, 39.0-48.8). Median OS was 17.2 months (95% confidence interval [CI], 11.7-22.9) with pembrolizumab and 15.3 months (95% CI, 10.9-18.1) with chemotherapy (hazard ratio, 0.90 [95% CI, 0.67-1.19; P = 0.2262]). Grade 3-5 treatment-related adverse events occurred in 12 of 116 participants (10.3%) with pembrolizumab and 49 of 112 participants (43.8%) with chemotherapy. Three treatment-related deaths occurred: 1 participant (0.9%) with pembrolizumab (pneumonitis) and 2 (1.8%) with chemotherapy (pneumonia, intracranial hemorrhage)., Conclusion: Pembrolizumab did not significantly improve OS compared with chemotherapy in participants with platinum-pretreated recurrent and/or metastatic NPC but did have manageable safety and a lower incidence of treatment-related adverse events., Clinical Trial Registry: ClinicalTrials.gov, NCT02611960., (Copyright © 2022. Published by Elsevier Ltd.)

Objectives: This study aimed to study the public's sentiments on the current monkeypox outbreaks via an unsupervised machine learning analysis of social media posts., Study Design: This was an exploratory analysis of tweets sentiments., Methods: We extracted original tweets containing the terms 'monkeypox', 'monkey pox' or 'monkey_pox' and posted them in the English language from 6 May 2022 (first case detected in the United Kingdom) to 23 July 2022 (when World Health Organization declared Monkeypox to be a global health emergency). Retweets and duplicate tweets were excluded from study. Bidirectional Encoder Representations from Transformers (BERT) Named Entity Recognition. This was followed by topic modelling (specifically BERTopic) and manual thematic analysis by the study team, with independent reviews of the topic labels and themes., Results: Based on topic modelling and thematic analysis of a total of 352,182 Twitter posts, we derived five topics clustered into three major themes related to the public discourse on the ongoing outbreaks. These include concerns of safety, stigmatisation of minority communities, and a general lack of faith in public institutions. The public sentiments underscore growing (and existing) partisanship, personal health worries in relation to the evolving situation, as well as concerns of the media's portrayal of lesbian, gay, bisexual, transgender and queer and minority communities, which might further stigmatise these groups., Conclusions: Monkeypox is an emerging infectious disease of public concern. Our study has highlighted important societal issues, including misinformation, political mistrust and anti-gay stigma that should be sensitively considered when designing public health policies to contain the ongoing outbreaks., (Copyright © 2022 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of renal cell carcinoma was published in 2019 with an update planned for 2021. It was therefore decided by both the ESMO and the Singapore Society of Oncology (SSO) to convene a special, virtual guidelines meeting in May 2021 to adapt the ESMO 2019 guidelines to take into account the ethnic differences associated with the treatment of renal cell carcinomas in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with renal cell carcinoma representing the oncological societies of China (CSCO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence and was independent of the current treatment practices and drug access restrictions in the different Asian countries. The latter were discussed when appropriate., Competing Interests: Disclosure RK declares institutional payments from Pfizer, Merck Sharp & Dohme (MSD), Bristol Myers Squibb (BMS), Eisai, Amgen, Astellas, Johnson & Johnson (J&J), Novartis and Merck, support for meeting attendance or travel from Pfizer, MSD, BMS, Eisai, Amgen, Astellas, J&J, Novartis and Merck. CP declares consulting fees from AstraZeneca, BMS, Eisai, EUSA Pharma, Ipsen, Merck, MSD, Novartis and Pfizer, payment or honoraria from Angelini Pharma, AstraZeneca, BMS, Eisai, EUSA Pharma, General Electric, Ipsen, Janssen, Merck, MSD, Novartis and Pfizer, support for attending meetings and/or travel from Roche. AW declares personal fees from MS, MSD, Pfizer, EISAI and IPSEN, participation on a data safety monitoring or advisory board for BMS, MSD, Pfizer, EISAI, IPSEN. TP declares research funding from Merck Serono, MSD, Roche, BMS, AstraZeneca, Astellas, Novartis, J&J, Seattle Genetics, Pfizer, Exelixis and Eisai, honoraria from Merck Serono, MSD, Roche, BMS, AstraZeneca, Astellas, Novartis, J&J, Seattle Genetics, Pfizer, Exelixis and Eisai. QSN declares support for attending meetings and/or travel from BMS, Boehringer Ingelheim, MSD and Astellas, participation on a data safety monitoring or advisory board for MSD and Boehringer Ingelheim. MSc declares honoraria from BMS, MSD, Merck, Roche, Pfizer, EUSA, EISAI, EXELIXIS and Ipsen, consulting fees from BMS, MSD, Merck, Roche, Pfizer, EUSA, EISAI, EXELIXIS and Ipsen, support for attending meetings and/or travel from BMS, Roche, Pfizer and Ipsen, participation on a data or safety monitoring board for BMS, MSD, Merck, Roche, Pfizer, EUSA, EISAI, EXELIXIS and Ipsen. YM declares payments or honoraria from BMS, MSD and Takeda, participation on an advisory board for Chugai Pharmaceutical and Takeda, local PI, institutional, financial interest from MSD. JL declares grants or contracts from Pfizer, Ipsen, BMS, MSD, Merck, Roche, AstraZeneca, Seattle Genetics, participation on a data safety monitoring or advisory board from Pfizer Korea, Astella Korea, BMS, Merck, MSD, AstraZeneca, stocks or stock options from Myovant Sciences, Amgen, J&J and Merck. FC declares payment for educational events from Eisai and Pfizer, receipt of equipment for a patient sampling programme from Pfizer. Y-SP declares honoraria and consulting fees from MSD, Roche, Merck, Ipsen, BMS/ONO, Novartis, Pfizer, Astellas, Janssen and GlaxoSmithKline (GSK), support for attending meetings and/or travel from Ipsen, BMS/ONO, Novartis, Pfizer, Astellas and Janssen. MSa declares research grants from Roche and MSD, payments or honoraria from MSD, Novartis, Roche, Pfizer, Eisai, Novartis, AstraZeneca, Amgen and Ipsen, receipt of equipment/materials for a compassionate programme for drugs/drug samples from Pfizer, AstraZeneca, Novartis, Ipsen, Eisai and MSD. HL declares payment or honoraria from MSD, Amgen, Astellas and IPSEN, participation on a data safety monitoring or advisory board for MSD and Astellas. HK declares payment or honoraria from BMS, MSD, Merck Biopharma, Takeda and Pfizer. GSB (deceased). GC declares institutional grants from Merck, consulting fees from BMS, Pfizer, MSD, AstraZeneca, Daichii Sankyo, Lilly, Novartis and Seattle Genetics, payment or honoraria from AstraZeneca, Roche and Daichii Sankyo. SC declares consulting fees from BMS, AstraZeneca, MSD, Roche and Servier, payment or honoraria from BMS, AstraZeneca, Roche, Ipsen, MSD Eisai and Bayer, consulting fees from BMS, AstraZeneca, MSD, Roche and Servier and stock or stock options in BMS and Agenus Oncology. SP declares fees for consultancy/advisory roles from AbbVie, Amgen, AstraZeneca, Bayer, Beigene, Biocartis, Boehringer Ingelheim, BMS, Clovis, Daiichi Sankyo, Debiopharm, ecancer, Eli Lilly, Elsevier, Foundation Medicine, Illumina, Imedex, Incyte, Janssen, Medscape, MSD, Merck Serono, Merrimack, Novartis, Pharma Mar, Phosplatin Therapeutics, PER, Pfizer, PRIME, Regeneron, Roche/Genentech, RTP, Sanofi, Seattle Genetics, Takeda, speaker roles for AstraZeneca, Boehringer Ingelheim, BMS, ecancer, Eli Lilly, Illumina, Imedex, Medscape, MSD, Novartis, PER, Pfizer, Prime, Roche/Genentech, RTP, Sanofi, Takeda and the receipt of grants/research support: (Sub) investigator in trials (institutional financial support for trials) sponsored by Amgen, AstraZeneca, Biodesix, Boehringer Ingelheim, BMS, Clovis, GSK, Illumina, Lilly, MSD, Merck Serono, Mirati, Novartis, and Pfizer, Phosplatin Therapeutics, Roche/Genentech. TY declares institutional grants or contracts from Taiho Pharmaceuticals, Sumitomo Dainippon, Ono Pharmaceuticals, Chugai Pharmaceuticals, Amgen, Parexel International, MSD, Daiichi Sankyo, and Sanofi. All other authors have declared no conflicts of interest. See also ICMJE forms., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of squamous cell carcinoma (SCC) of the oral cavity, larynx, oropharynx and hypopharynx was published in 2020. It was therefore decided by both the ESMO and the Korean Society of Medical Oncology (KSMO) to convene a special, virtual guidelines meeting in July 2021 to adapt the ESMO 2020 guidelines to consider the potential ethnic differences associated with the treatment of SCCs of the head and neck (SCCHN) in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with SCCHN (excluding nasopharyngeal carcinomas) representing the oncological societies of Korea (KSMO), China (CSCO), India (ISMPO), Japan (JSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence and was independent of the current treatment practices and drug access restrictions in the different Asian countries. The latter was discussed when appropriate. This manuscript provides a series of expert recommendations (Clinical Practice Guidelines) which can be used to provide guidance to health care providers and clinicians for the optimisation of the diagnosis, treatment and management of patients with SCC of the oral cavity, larynx, oropharynx and hypopharynx across Asia., Competing Interests: Disclosure BK declares grants or contracts from Merck Sharp & Dohme (MSD) Oncology, Ono Pharmaceutical and AstraZeneca, consulting fees from AstraZeneca, MSD Oncology, ABL Bio, Genexine, Cellid, Handok, Celid, Trial Informatics and CBS Bio, payment or honoraria from MSD Oncology and Merck. J-PM declares consulting fees/honoraria from Pfizer, Roche, AstraZeneca, Bayer, Innate, Merck Serono, Boehringer, Bristol Myers Squibb (BMS), Novartis, Janssen, Incyte, Cue Biopharma, ALX Oncology, iTEOS, TheRNA and NEKTAR, support for attending meetings and/or travel from Amgen, Pfizer and MSD and participation at a Safety or Advisory Board for PsiOxus. LL declares institutional grants or contracts from AstraZeneca, BMS, Boehringer Ingelheim, Celgene International, Eisai, Exelixis Inc, Debiopharm International SA, Hoffman-La Roche Ltd., IRX Therapeutics Inc., Medpace Inc., Merck-Serono, MSD, Novartis, Pfizer, Roche Spa and Buran and receipt of honoraria or fees (for public speaking/teaching in medical meetings and/or for providing expert opinion in Advisory Boards) for AstraZeneca, Bayer, BMS, Eisai, MSD, Merck-Serono, Boehringer Ingelheim, Hoffman La Roche Ltd., Novartis, Roche, Debiopharm International SA, Sobi, Incyte Biosciences Italy SRL, Doxa Pharma, Amgen, Nanobiotics and GlaxoSmithKline (GSK). CB declares payment or honoraria from Merck KGaA, BMS and Roche. MT declares consulting fees from Ono Pharmaceuticals, MSD, BMS and Merck Biopharma, and honoraria from Eisai, Ono Pharmaceuticals, BMS and Merck Biopharma. MA declares consulting fees from MSD, AstraZeneca, Eli Lilly, DKSH, Eisai, Roche, Novartis and Merck, payment or honoraria from MSD, AstraZeneca, Eli Lilly, DKSH, Eisai, Roche, Novartis and Merck, support for attending meetings and/or travel from MSD, Roche, Elekta/Abex and AstraZeneca, and is the president of the Malaysian Oncological Society. MKA declares honoraria for presentations from Pfizer and Boehringer Ingelheim, sponsorship for meetings from AstraZeneca, Boehringer Ingelheim and DKSH. QSNg declares support for attending meetings and or travel from BMS, Boehringer Ingelheim, MSD and Astellas, and participation in Safety or Advisory Boards for MSD and Boehringer Ingelheim. WIWZ declares honoraria for lectures from Amgen Malaysia, DKSH Malaysia, Eisai Malaysia, Eli Lilly Malaysia, Ipsen Malaysia, MSD Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Merck Serono Malaysia, Pfizer Malaysia and Roche Malaysia, travel grants from Amgen Malaysia, Celgene Malaysia, Eisai Malaysia, Eli Lilly Malaysia, MSD Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and Roche Malaysia, participation on an Advisory Board for Celgene Malaysia, Roche Malaysia, Eli Lilly Malaysia, Eisai Malaysia and MSD Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and is a member of ASCO AP Regional Council and Greater Petaling Cancer City Challenge UICC. NK declares institutional grants or contracts from Ono Pharmaceutical, BMS, AstraZeneca, Pfizer, Chugai Pharmaceutical, Rakuten Medical, Bayer and Adlai Nortye, payment or honoraria from Ono Pharmaceutical, BMS, Merck Biopharma, MSD, Eisai and Bayer, participation on a Data Safety Monitoring Board or Advisory Board for Bayer and Adlai Nortye. GC declares institutional grants from Merck, consulting fees from BMS, Pfizer, MSD, AstraZeneca, Daichii Sankyo, Lilly, Novartis and Seattle Genetics, payment or honoraria from AstraZeneca, Roche and Daichii Sankyo. SP declares fees for consultancy/advisory roles from AbbVie, Amgen, AstraZeneca, Bayer, Beigene, Biocartis, Boehringer Ingelheim, BMS, Clovis, Daiichi Sankyo, Debiopharm, ecancer, Eli Lilly, Elsevier, Foundation Medicine, Illumina, Imedex, Incyte, Janssen, Medscape, MSD, Merck Serono, Merrimack, Novartis, PharmaMar, Phosplatin Therapeutics, PER, Pfizer, PRIME, Regeneron, Roche/Genentech, RTP, Sanofi, Seattle Genetics, Takeda, speaker roles for AstraZeneca, Boehringer Ingelheim, BMS, ecancer, Eli Lilly, Illumina, Imedex, Medscape, MSD, Novartis, PER, Pfizer, Prime, Roche/Genentech, RTP, Sanofi, Takeda and the receipt of grants/research support: (Sub) investigator in trials (institutional financial support for trials) sponsored by Amgen, AstraZeneca, Biodesix, Boehringer Ingelheim, BMS, Clovis, GSK, Illumina, Lilly, MSD, Merck Serono, Mirati, Novartis, and Pfizer, Phosplatin Therapeutics, Roche/Genentech. TWK declares institutional grants or contracts from Roche, and sanofi-aventis. TY declares institutional grants or contracts from Taiho Pharmaceutical, Sumitomo Dainippon, Ono Pharmaceutical, Chugai Pharmaceutical, Amgen, Parexel International, MSD, Daiichi-Sankyo and Sanofi. All other authors have declared no conflicts of interest., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Mechanisms explaining the link between psoriasis, a proinflammatory condition, and cardiovascular disease are not fully known. PCSK9 is predominantly expressed in hepatocytes as a critical regulator of lipid metabolism, and clinical trials targeting PCSK9 reduce cardiovascular disease. Independent of its role in lipid metabolism, PCSK9 levels associate with endothelial dysfunction and predict cardiovascular events. We used two separate human psoriasis cohorts and the K14-Rac1V12 -/+ murine model of psoriasis to investigate PCSK9 and cardiovascular risk in psoriasis. In both psoriasis cohorts (n = 88 and n = 20), PCSK9 levels were 20% and 13% higher than in age-, sex-, and cholesterol-matched controls, respectively (P < 0.05 for each comparison) and correlated with PASI (r = 0.43, P < 0.05). Despite no difference in hepatocyte expression, K14-Rac1V12 -/+ mice demonstrated skin-specific PCSK9 staining, which was confirmed in human psoriatic lesional skin. In patients with psoriasis, PCSK9 levels correlated with impaired endothelial vascular health (e.g., early atherosclerosis, β = 4.5, P < 0.01) and log converted coronary artery calcium score (β = 0.30, P = 0.01), which remained significant after adjustment for Framingham risk, body mass index, and active biologic use. Taken together, these findings suggest, independent of cholesterol, an association between circulating PCSK9 and early as well as advanced stages of atherosclerosis in psoriasis., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Treatment with sorafenib, although associated with inhibition of tumour growth and angiogenesis in in vivo studies, leads to up-regulation of pERK. The addition of MEK inhibition could potentially abrogate this effect and potentiate anti-tumour activity. This phase I study investigated the maximum tolerated dose (MTD), safety, tolerability, pharmacokinetics (PK) and biomarker correlates of selumetinib combined with sorafenib in patients with advanced hepatocellular carcinoma (HCC)., Methods: Patients with Child-Pugh (CP) score ≤7 were treated with 400 mg twice daily of sorafenib with escalating doses of selumetinib in a 3 + 3 study design. The dose-limiting toxicity (DLT) evaluation period was 28 days. PK of selumetinib was determined. Angiogenic effect was evaluated with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI)., Results: Twenty-seven patients of Asian ethnicity were enrolled. The MTD was selumetinib 75 mg daily with sorafenib 400 mg twice daily. DLT included grade 3 transaminitis, diarrhoea and fatigue. Most common treatment-related adverse events at MTD (all grades) were diarrhoea (85%), rash (59%), hypertension (44%), fatigue (30%), anorexia (22%) and hand-foot syndrome (22%). Four patients (15%) had PR and 13 (48%) had SD. PR or SD was observed for ≥6 months in seven patients. The median overall survival was 14.4 months. Selumetinib exposures in combination with sorafenib were comparable to other monotherapy studies. A reduction in permeability-surface area product noted in DCE-MRI with treatment correlated with worse survival outcomes., Conclusion: The MTD of selumetinib was 75 mg daily when combined with sorafenib 400 mg twice a day in CP ≤7 HCC. Acceptable adverse events and encouraging anti-tumour activity warrant further evaluation. DCE-MRI findings deserve prospective evaluation., Clinicaltrialsgov Identifier: NCT01029418., (© The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background and Aims: Psoriasis is a chronic inflammatory disorder associated with vascular inflammation, measured by 18-fluorodeoxyglucose positron emission tomography/computed tomography (18-FDG PET/CT), and an increased risk of myocardial infarction. Patients with psoriasis are also more likely to suffer from comorbid depression. Whether depression accelerates the development of subclinical atherosclerosis in psoriasis is unknown., Methods: Patients were selected from within a larger psoriasis cohort. Those who reported a history of depression (N = 36) on survey were matched by age and gender to patients who reported no history of psychiatric illness (N = 36). Target-to-background ratio from FDG PET/CT was used to assess aortic vascular inflammation and coronary CT angiography scans were analyzed to determine coronary plaque burden. Multivariable linear regression was performed to understand the effect of self-reported depression on vascular inflammation and coronary plaque burden after adjustment for Framingham risk (standardized β reported)., Results: In unadjusted analyses, vascular inflammation and coronary plaque burden were significantly increased in patients with self-reported depression as compared to patients with psoriasis alone. After adjustment for Framingham Risk Score, vascular inflammation (β = 0.26, p = 0.02), total plaque burden (β = 0.17, p = 0.03), and non-calcified burden (β = 0.17, p = 0.03) were associated with self-reported depression., Conclusions: Self-reported depression in psoriasis is associated with increased vascular inflammation and coronary plaque burden. Depression may play an important role in promoting subclinical atherosclerosis beyond traditional cardiovascular risk factors., Competing Interests: The authors confirm that there are no other potential conflicts of interest., (Published by Elsevier Ireland Ltd.)

Background: Gefitinib was demonstrated to be synergistic with cisplatin and radiotherapy (RT) in in vitro studies. Biomarkers predictive of response to gefitinib in squamous cell head and neck cancer is still lacking., Methods: Thirty-one patients with locally advanced and easily accessible primary tumor sites for biopsies were recruited. Gefitinib was started 3 weeks before the start of cisplatin/concurrent radiotherapy (CTRT) and continued during the CTRT phase and thereafter for 4 months as consolidation phase. Two baselines and a repeat tumor sample were taken after 2 weeks of gefitinib alone to study its impact on tumor gene expression. Epidermal growth factor receptor (EGFR) protein expression, FISH and mutational status, and matrix metallopeptidase 11 (MMP11) protein expression were correlated with response and survival outcome., Results: The overall response rate to gefitinib alone was 9.7%. The survival outcome is as follows: median disease free 1.3 years, median survival time 2.4 years, 3-year disease free 42.9%, and 3-year overall survival 48.4%. EGFR FISH, protein expression, and mutational status did not predict for response nor survival outcome of patients. Although MMP11 overexpression did not predict for response, it predicted significantly for a poorer survival outcome., Conclusions: Gefitinib can be combined safely with cisplatin/RT. More studies are needed to uncover predictive biomarkers of benefit to gefitinib.

Background: The vascular disrupting agent combretastatin-A4-phosphate (CA4P) demonstrated antitumour activity in preclinical studies when combined with radiation., Methods: Patients with non-small-cell lung cancer (NSCLC), prostate adenocarcinoma, and squamous cell carcinoma of the head and neck (SCCHN) received 27 Gy in 6 fractions treating twice weekly over 3 weeks, 55 Gy in 20 fractions over 4 weeks, and 66 Gy in 33 fractions over 6 weeks respectively. CA4P was escalated from 50 mg/m2 to 63 mg/m2. CA4P exposure was further increased from one to three to six doses. Patients with SCCHN received cetuximab in addition., Results: Thirty-nine patients received 121 doses of CA4P. Dose-limiting toxic effects (DLTs) of reversible ataxia and oculomotor nerve palsy occurred in two patients with prostate cancer receiving weekly CA4P at 63 mg/m2. DLT of cardiac ischaemia occurred in two patients with SCCHN at a weekly dose of 50 mg/m2 in combination with cetuximab. Three patients developed grade 3 hypertension. Responses were seen in 7 of 18 patients with NSCLC. At 3 years, 3 of 18 patients with prostate cancer had prostate-specific antigen relapse., Conclusions: Radiotherapy with CA4P appears well tolerated in most patients. The combination of CA4P, cetuximab, and radiotherapy needs further scrutiny before it can be recommended for clinical studies.

Composting is one of the waste disposal methods adopted for disposal of livestock waste in Hong Kong. The composting livestock waste normally undergoes 6-8 weeks fermentation, followed by 16-20 weeks maturation. The matured compost is sold as soil conditioner in the local market. In 2006, feedstock material and a time-series of compost samples were collected throughout the fermentation and maturation process from the Sha Ling Composting Plant in the New Territories. The feedstock material and compost samples were analyzed for contents of three unintentional persistent organic pollutants (POPs), i.e. dioxins/furans, dioxin-like PCBs and total PCBs. These POPs are unintentionally produced by-products of chemical industrial processes and combustion processes. Selected heavy metals were also analyzed, which served as conservative tracers to determine potential mass loss during the composting process. Levels of contamination by these POPs were found to be low in the matured compost for sale. The mean concentrations (lower-upper bound) of total dioxins/furans, total dioxin-like PCBs and total PCBs were 2.01-2.05 ng I-TEQ/kg dw, 0.04-0.05 ng WHO-TEQ/kg dw and 1.55-1.55 microg/kg dw, respectively. Progressively elevated levels of these POPs were observed in the compost samples during the fermentation process. Analysis of the congener profiles revealed that the heptaCDD and octaCDD were the main contributors to the observed increase in dioxin/furan content. The possible sources of dioxins/furans in the compost were discussed. The study results established a local dioxins/furans emission factor specific to the trade and provided a better estimate of the annual dioxins/furans emission for the livestock waste composting activity in Hong Kong.