Trends in the Management and Outcomes of Neuroendocrine Liver Metastases: A Three-decade, Multi-centre Observational Cohort Study.

Objective: To describe the evolution of management strategies for neuroendocrine liver metastases (NE LM) and trends in patient outcomes over the preceding 3 decades.

Summary Background Data: Liver metastases are common in neuroendocrine neoplasms and impair prognosis. A broad therapeutic armamentarium has evolved over recent decades but there remains uncertainty regarding optimal treatment selection and sequencing.

Pancreatic Adenocarcinoma: Long-Term Outcomes of Adjuvant Therapy in the ESPAC4 Phase III Trial.

Purpose: The ESPAC4 trial showed that adjuvant chemotherapy with gemcitabine plus capecitabine (GemCap) produced longer overall survival (OS) than gemcitabine monotherapy. Subsequently, the PRODIGE24-CCTG PA.6 trial showed even longer survival for modified fluorouracil, folinic acid, irinotecan, and oxaliplatin (mFOLFIRINOX) than gemcitabine but had more restrictive eligibility criteria.

Molecular profiling of BRAF-V600E-mutant metastatic colorectal cancer in the phase 3 BEACON CRC trial.

The BEACON CRC study demonstrated that encorafenib (Enco)+cetuximab (Cetux)±binimetinib (Bini) significantly improved overall survival (OS) versus Cetux + chemotherapy in previously treated patients with BRAF-V600E-mutant mCRC, providing the basis for the approval of the Enco+Cetux regimen in the United States and the European Union. A greater understanding of biomarkers predictive of response to Enco+Cetux±Bini treatment is of clinical relevance. In this prespecified, exploratory biomarker analysis of the BEACON CRC study, we characterize genomic and transcriptomic correlates of clinical outcomes and acquired resistance mechanisms through integrated clinical and molecular analysis, including whole-exome and -transcriptome tissue sequencing and circulating tumor DNA genomic profiling.

A plain language summary of the results from the phase 2b HERIZON-BTC-01 study of zanidatamab in participants with HER2-amplified biliary tract cancer.

What Is This Summary About?: Researchers wanted to study whether the research drug zanidatamab could help people with a type of cancer called biliary tract cancer. In some people, biliary tract cancer cells make extra copies of a gene called HER2 (also called ERBB2). This is known as being HER2-amplified.

Standard or high dose chemoradiotherapy, with or without the protease inhibitor nelfinavir, in patients with locally advanced pancreatic cancer: The phase 1/randomised phase 2 SCALOP-2 trial.

Background: The multi-centre two-stage SCALOP-2 trial (ISRCTN50083238) assessed whether dose escalation of consolidative chemoradiotherapy (CRT) or concurrent sensitization using the protease inhibitor nelfinavir improve outcomes in locally advanced pancreatic cancer (LAPC) following four cycles of gemcitabine/nab-paclitaxel.

Methods: In stage 1, the maximum tolerated dose (MTD) of nelfinavir concurrent with standard-dose CRT (50.4 Gy in 28 fractions) was identified from a cohort of 27 patients.

Multidisciplinary Delphi Consensus on Safety of Combining Transarterial Radioembolization with Yttrium-90 Microspheres with Systemic Anticancer Agents for the Treatment of Liver Malignancy.

Purpose: To provide guidance, via multidisciplinary consensus statements, on the safety interactions between systemic anticancer agents (such as radiosensitizing chemotherapy, immunotherapy, targeted therapy, and peptide receptor radionuclide therapy) and transarterial radioembolization (TARE) with yttrium-90 (Y)-labeled microspheres in the treatment of primary and metastatic liver malignancies.

Materials And Methods: A literature search identified 59 references that informed 26 statements on the safety of Y TARE combined with systemic therapies. Modified Delphi method was used to develop consensus on statements through online anonymous surveys of the 12 panel members representing the fields of interventional radiology, medical oncology, surgical oncology, hepatology, and pharmacy, focusing on hepatocellular carcinoma (HCC), metastatic colorectal cancer (mCRC), neuroendocrine tumors, metastatic breast cancer, and intrahepatic cholangiocarcinoma.

Prescription-based cost analysis of medicines for cardiovascular risk factors at Indian Council of Medical Research-Rational Use of Medicine Centre Hospitals of India.

Objectives: India has taken several initiatives to provide health care to its population while keeping the related expenditure minimum. Since cardiovascular diseases are the most prevalent chronic conditions, in the present study, we aimed to analyze the difference in prices of medicines prescribed for three cardiovascular risk factors, based on (a) listed and not listed in the National List of Essential Medicines (NLEM) and (b) generic and branded drugs.

Materials And Methods: Outpatient prescriptions for diabetes mellitus, hypertension, and dyslipidemia were retrospectively analyzed from 12 tertiary centers.

Strategies to improve antibiotic access and a way forward for lower middle-income countries.

Antibiotics have substantially improved life expectancy in past decades through direct control or prevention of infections. However, emerging antibiotic resistance and lack of access to effective antibiotics have significantly increased the death toll from infectious diseases, making it one of the biggest threats to global health. Addressing the antibiotic crisis to meet future needs require considerable investment in both research and development along with ensuring a viable marketplace to encourage innovation.

Management of Small Bowel Neuroendocrine Tumours: 10 Years' Experience at a Tertiary Referral Centre.

Background: Neuroendocrine tumours (NET) arising from the small bowel are clinically challenging and are often diagnosed at advanced stages. Disease control with surgery alone can be demanding. Multimodal treatment concepts integrating surgery and non-surgical modalities could be of benefit.

Optimal maintenance strategy following FOLFOX plus anti-EGFR induction therapy in patients with RAS wild type metastatic colorectal cancer: An individual patient data pooled analysis of randomised clinical trials.

Background: Anti-EGFR antibodies plus doublet chemotherapy is the standard of care in RAS/BRAF wild-type metastatic colorectal cancer (mCRC). No phase-3 level of evidence is available to guide treatment de-escalation after anti-EGFR-based first-line. Several randomised clinical trials investigated de-intensification strategies with 5-fluorouracil/leucovorin (5-FU/LV) and/or anti-EGFR.

Zanidatamab for HER2-amplified, unresectable, locally advanced or metastatic biliary tract cancer (HERIZON-BTC-01): a multicentre, single-arm, phase 2b study.

Background: HER2 is overexpressed or amplified in a subset of biliary tract cancer. Zanidatamab, a bispecific antibody targeting two distinct HER2 epitopes, exhibited tolerability and preliminary anti-tumour activity in HER2-expressing or HER2 (also known as ERBB2)-amplified treatment-refractory biliary tract cancer.

Methods: HERIZON-BTC-01 is a global, multicentre, single-arm, phase 2b trial of zanidatamab in patients with HER2-amplified, unresectable, locally advanced, or metastatic biliary tract cancer with disease progression on previous gemcitabine-based therapy, recruited at 32 clinical trial sites in nine countries in North America, South America, Asia, and Europe.

The management of hepatocellular carcinoma. Current expert opinion and recommendations derived from the 24th ESMO/World Congress on Gastrointestinal Cancer, Barcelona, 2022.

This article summarises expert discussion on the management of patients with hepatocellular carcinoma (HCC), which took place during the 24th World Gastrointestinal Cancer Congress (WGICC) in Barcelona, July 2022. A multidisciplinary approach is mandatory to ensure an optimal diagnosis and staging of HCC, planning of curative and therapeutic options, including surgical, embolisation, ablative strategies, or systemic therapy. Furthermore, in many patients with HCC, underlying liver cirrhosis represents a challenge and influences the therapeutic options.

European expert panel consensus on the clinical management of BRAF-mutant metastatic colorectal cancer.

Metastatic colorectal cancer (mCRC) is a heterogenous disease caused by various genetic alterations. The BRAF mutation occurs in approximately 8-12% of patients and is characterised by an aggressive clinical course and poor prognosis. Here we review the current knowledge on BRAF-mutant mCRC and provide a series of consensus statements on its clinical management.

Landscape of Push Funding in Antibiotic Research: Current Status and Way Forward.

The growing need for effective antibiotics is attributed to the intrinsic ability of bacteria to develop survival mechanisms. The speed at which pathogens develop resistance is at par or even faster than the discovery of newer agents. Due to the enormous cost of developing an antibiotic and poor return on investment, big pharmaceutical companies are stepping out of the antibiotic research field, and the world is now heading towards the silent pandemic of antibiotic resistance.

Adverse Events Associated with Encorafenib Plus Cetuximab in Patients with BRAFV600E-mutant Metastatic Colorectal Cancer: An in-depth Analysis of the BEACON CRC Study.

Background: The BRAF inhibitor encorafenib in combination with cetuximab was recently approved for patients with BRAF-mutated (BRAFmut) metastatic colorectal cancer (mCRC). Approval was based on positive results from the phase 3 BEACON CRC study in BRAFmut mCRC patients who had progressed after 1-2 previous regimens. This analysis provides a detailed examination of the adverse events (AEs) of interest (AEIs) with encorafenib+cetuximab in the BEACON study to aid gastrointestinal oncologists, given the limited experience with this combination.

Erratum: Jiedu Sangen Decoction Reverses Epithelial-to-mesenchymal Transition and Inhibits Invasion and Metastasis of Colon Cancer via AKT/GSK-3β Signaling Pathway: Erratum.

[This corrects the article DOI: 10.7150/jca.32873.

Drug development process and COVID-19 pandemic: Flourishing era of outsourcing.

Traditional drug development is a tedious process with involvement of enormous cost and a high attrition rate. Outsourcing drug development services to contract research organizations (CROs) has become an important strategy for cost and risk reduction, capacity building, and data generation. The therapeutic and operational expertise of these CROs has allowed pharmaceutical industry to reduce in-house infrastructure as well as research capacity.

Immediate surgery compared with short-course neoadjuvant gemcitabine plus capecitabine, FOLFIRINOX, or chemoradiotherapy in patients with borderline resectable pancreatic cancer (ESPAC5): a four-arm, multicentre, randomised, phase 2 trial.

Background: Patients with borderline resectable pancreatic ductal adenocarcinoma have relatively low resection rates and poor survival despite the use of adjuvant chemotherapy. The aim of our study was to establish the feasibility and efficacy of three different types of short-course neoadjuvant therapy compared with immediate surgery.

Methods: ESPAC5 (formerly known as ESPAC-5f) was a multicentre, open label, randomised controlled trial done in 16 pancreatic centres in two countries (UK and Germany).

[Corrigendum] Resveratrol inhibits the invasion and metastasis of colon cancer through reversal of epithelial‑mesenchymal transition via the AKT/GSK‑3β/Snail signaling pathway.

Subsequently to the publication of the above article, an interested reader drew to the authors' attention that the Nc‑control and si‑AKT1‑control data panels featured in Fig. 4A for the SW480 Transwell assay experiments on p. 2788 appeared to contain overlapping data, such that the data, which were intended to show the results from experiments performed under different experimental conditions, may have been derived from the same original source.

Is antibody-drug conjugate a rising star for clinical treatment of solid tumors? A systematic review and meta-analysis.

Antibody-drug conjugates (ADCs) show significant advantages in cancer treatment due to their high selectivity and anti-tumor activity, but the efficacy and safety of the treatment of solid tumors are unknown. We searched research databases, major conference proceedings and trial registries for randomized controlled trials (RCTs). Then, we selected qualified studies and extracted dates.

Establishing a colorectal cancer research database from routinely collected health data: the process and potential from a pilot study.

Objective: Colorectal cancer is a common cause of death and morbidity. A significant amount of data are routinely collected during patient treatment, but they are not generally available for research. The National Institute for Health Research Health Informatics Collaborative in the UK is developing infrastructure to enable routinely collected data to be used for collaborative, cross-centre research.

Spend less to achieve more: Economic analysis of intermittent versus continuous cetuximab in KRAS wild-type patients with metastatic colorectal cancer.

Background: In 2014, the COIN-B clinical trial demonstrated that intermittent cetuximab (IC) was a safe alternative to continuous cetuximab (CC), with less cytotoxic chemotherapy, in first-line treatment for KRAS wild-type metastatic colorectal cancer (mCRC). Cetuximab has been available for this indication in England since 2015, but treatment breaks beyond 6 weeks were prohibited, despite real-world evidence that therapy de-escalation maintains equivalent disease control, but with superior Quality-of-Life (QoL). We performed health economic analyses of IC versus CC and used this evidence to help underpin policy change and guide clinical practice through reduction in unnecessary treatment for mCRC patients.

Quality of life with encorafenib plus cetuximab with or without binimetinib treatment in patients with BRAF V600E-mutant metastatic colorectal cancer: patient-reported outcomes from BEACON CRC.

Background: In the BEACON CRC study (NCT02928224), encorafenib plus cetuximab with binimetinib {9.3 versus 5.9 months; hazard ratio (HR) [95% confidence interval (CI)]: 0.