Publications by authors named "Hans Prenen"

116 Publications

Safety, pharmacokinetics, and efficacy of budigalimab with rovalpituzumab tesirine in patients with small cell lung cancer.

Cancer Treat Res Commun 2021 25;28:100405. Epub 2021 May 25.

Cancer Care Center, Blacktown Hospital, Sydney, NSW, Australia. Electronic address:

Background: Agents targeting programmed cell death protein 1 (PD-1) have been approved as monotherapy for patients with small cell lung cancer (SCLC). In preclinical models, the combined targeting of PD-1 and delta-like protein 3 resulted in enhanced antitumor activity. Herein, we report results from the expansion arm of study NCT03000257 evaluating the combination of the anti-PD-1 antibody budigalimab and the targeted antibody-drug conjugate rovalpituzumab tesirine (Rova-T) in patients with previously treated SCLC.

Materials And Methods: This expansion arm of a multicenter, open-label, multi-arm, first-in-human phase 1 clinical trial enrolled adult patients with progressive SCLC. The primary objective was to assess safety and tolerability. Patients received budigalimab 375 mg via intravenous infusion every 3 weeks, and Rova-T was administered as a dose of 0.3 mg/kg intravenously, on day 1 of the first and third 3-week cycle.

Results: As of October 2019, 31 patients with SCLC were enrolled and treated with budigalimab plus Rova-T. The combination was tolerated, with the most common treatment-emergent adverse events (in >30%) being pleural effusion, fatigue, and cough. The overall response rate was 24.1%, with one confirmed complete response and six confirmed partial responses. The overall response rate in patients with high delta-like protein 3 expression was similar (21.1%). The median progression-free survival was 3.48 months.

Conclusion: Combination therapy with budigalimab and Rova-T had promising efficacy and appeared to be tolerated in patients with SCLC. Although Rova-T development has been discontinued, development of budigalimab combined with other anticancer agents is ongoing.

Clinical Trial Registration Number: NCT03000257 Statement on originality of the work The manuscript represents original work and has not been submitted for publication elsewhere nor previously published. Statement of prior presentation Data from this study were previously presented at the European Society for Medical Oncology (ESMO) Congress 2019.
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http://dx.doi.org/10.1016/j.ctarc.2021.100405DOI Listing
May 2021

The impact of hepatic and renal function on panitumumab exposures in patients with metastatic RAS wild-type colorectal cancer.

Cancer Chemother Pharmacol 2021 Oct 2;88(4):665-672. Epub 2021 Jul 2.

Clinical Pharmacology, Modeling and Simulation, Amgen Inc, 1120 Veterans Boulevard, South San Francisco, CA, 94080, USA.

Purpose: Panitumumab is a human monoclonal antibody targeting the epidermal growth factor receptor for the treatment of wild-type RAS metastatic colorectal cancer (mCRC). Currently, no dedicated clinical studies have evaluated the effect of organ impairment on the pharmacokinetics of panitumumab. Here, we present data from late phase studies of panitumumab in patients with mCRC and analyses of the effect of hepatic or renal impairment on the exposure of panitumumab.

Methods: From three multicenter, open-label, phase 2 and phase 3 studies, 349 and 351 patients were included in hepatic and renal function subgroup analyses, respectively. Patients who received IV panitumumab and serum exposures were compared to patients with varying degrees of hepatic and renal organ dysfunction.

Results: The C and C values for patients with mild (n = 119) and moderate (n = 4) hepatic impairment were within the range of serum concentrations of panitumumab for the normal hepatic function subgroup. The distributions of serum concentration of panitumumab in patients with mild (n = 85) or moderate (n = 19) renal impairment were similar to the serum concentrations of panitumumab in the normal renal function subgroup. Population pharmacokinetic modeling and covariate analysis results were also consistent with lack of any significant effect of renal or hepatic impairment on the pharmacokinetics of panitumumab. Additionally, real-world evidence from case studies of patients with mCRC and severe hepatic or renal impairment, which is a rare patient population to study, indicated lack of clinically relevant differences in exposure of panitumumab compared with patients with mCRC and normal hepatic or renal function.

Conclusions: Mild-to-moderate hepatic or renal dysfunction had no clinically meaningful impact on the pharmacokinetics of panitumumab in patients with mCRC. No dose adjustments for panitumumab are warranted in patients with mCRC with mild-to-moderate hepatic or renal dysfunction.

Trial Registration: ClinicalTrials.gov; NCT00083616, NCT00089635, NCT00113763.
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http://dx.doi.org/10.1007/s00280-021-04319-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8367910PMC
October 2021

Macrophage miR-210 induction and metabolic reprogramming in response to pathogen interaction boost life-threatening inflammation.

Sci Adv 2021 May 7;7(19). Epub 2021 May 7.

Laboratory of Tumor Inflammation and Angiogenesis, CCB, VIB, Leuven, Belgium.

Unbalanced immune responses to pathogens can be life-threatening although the underlying regulatory mechanisms remain unknown. Here, we show a hypoxia-inducible factor 1α-dependent microRNA (miR)-210 up-regulation in monocytes and macrophages upon pathogen interaction. MiR-210 knockout in the hematopoietic lineage or in monocytes/macrophages mitigated the symptoms of endotoxemia, bacteremia, sepsis, and parasitosis, limiting the cytokine storm, organ damage/dysfunction, pathogen spreading, and lethality. Similarly, pharmacologic miR-210 inhibition improved the survival of septic mice. Mechanistically, miR-210 induction in activated macrophages supported a switch toward a proinflammatory state by lessening mitochondria respiration in favor of glycolysis, partly achieved by downmodulating the iron-sulfur cluster assembly enzyme ISCU. In humans, augmented miR-210 levels in circulating monocytes correlated with the incidence of sepsis, while serum levels of monocyte/macrophage-derived miR-210 were associated with sepsis mortality. Together, our data identify miR-210 as a fine-tuning regulator of macrophage metabolism and inflammatory responses, suggesting miR-210-based therapeutic and diagnostic strategies.
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http://dx.doi.org/10.1126/sciadv.abf0466DOI Listing
May 2021

Oral paclitaxel with encequidar compared to intravenous paclitaxel in patients with advanced cancer: A randomised crossover pharmacokinetic study.

Br J Clin Pharmacol 2021 May 7. Epub 2021 May 7.

Auckland District Health Board, Auckland, New Zealand.

Aims: Paclitaxel is a widely used anti-neoplastic agent but has low oral bioavailability due to gut extrusion by P-glycoprotein (P-gp). Oral paclitaxel could be more convenient, less resource intensive, and more tolerable than intravenous administration. Encequidar (HM30181A) is a novel, minimally absorbed gut-specific P-gp inhibitor. We tested whether administration of oral paclitaxel with encequidar (oPac+E) achieved comparable AUC to intravenous paclitaxel (IVP) 80 mg/m .

Methods: We conducted a multi-centre randomised crossover study with two treatment periods. Patients (pts) with advanced cancer received either oral paclitaxel 615 mg/m divided over 3 days and encequidar 15 mg orally 1 hour prior, followed by IVP 80 mg/m , or the reverse sequence. PK blood samples were taken up to Day 9 for oPac+E and Day 5 for IVP.

Results: Forty-two patients were enrolled; 35 completed both treatment periods. AUC was 5033.5 ± 1401.1 ng.h/mL for oPac+E and 5595.9 ± 1264.1 ng.h/mL with IVP. The geometric mean ratio (GMR) for AUC was 89.50% (90% CI 83.89-95.50). Mean absolute bioavailability of oPac+E was 12% (CV% = 23%). PK parameters did not change meaningfully after 4 weeks administration of oPac+E in an extension study. G3 treatment-emergent adverse events occurred in seven (18%) pts with oPac+E and two (5%) with IVP. Seventy-five per cent of patients preferred oPac+E over IVP.

Conclusions: GMR for AUC was within the predefined acceptable range of 80-125% for demonstrating equivalence. oPac+E is tolerable and there is no evidence of P-gp induction with repeat administration. With further study, oPac+E could be an alternative to IVP.
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http://dx.doi.org/10.1111/bcp.14886DOI Listing
May 2021

A Phase I Study of an IDO-1 Inhibitor (LY3381916) as Monotherapy and in Combination With an Anti-PD-L1 Antibody (LY3300054) in Patients With Advanced Cancer.

J Immunother 2021 09;44(7):264-275

Sarah Cannon Research Institute Tennessee Oncology, Nashville, TN.

LY3381916 is an orally available, highly selective, potent inhibitor of indoleamine 2,3-dioxygenase 1. This study explored the safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity of LY3381916 monotherapy and in combination with a programmed death-ligand 1 (PD-L1) inhibitor (LY3300054) in patients with advanced solid tumors. During dose escalation, patients received escalating doses of LY3381916 at 60-600 mg once daily (qd) and 240 mg twice daily in monotherapy (n=21) and in combination with PD-L1 inhibitor at 700 mg every 2 weeks (n=21). A modified toxicity probability interval method was used to guide dose escalation. Dose-limiting toxicities occurred in 3 patients; 1 at LY3381916 240 mg twice daily (alanine aminotransferase/aspartate aminotransferase increase and systemic inflammatory response syndrome) and 2 at LY3381916 240 mg qd in combination with PD-L1 inhibitor (fatigue and immune-related hepatitis). LY3381916, at the recommended phase II dose, 240 mg qd, in combination with PD-L1 inhibitor, produced maximal inhibition of indoleamine 2,3-dioxygenase 1 activity in plasma and tumor tissue, and led to an increase of CD8 T cells in tumor tissue. In the combination dose expansion cohorts, 14 triple-negative breast cancer and 4 non-small cell lung cancer patients were enrolled. Treatment-related liver toxicity (grade ≥2 alanine aminotransferase/aspartate aminotransferase increase or immune-related hepatitis) was the most prominent adverse event in triple-negative breast cancer patients (n=5, 35.7%). Best response was stable disease. These preliminary data suggest an alternative dose level of LY3381916 is needed for the combination with PD-L1 inhibitor. The combination clinical activity was limited in this study.
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http://dx.doi.org/10.1097/CJI.0000000000000368DOI Listing
September 2021

Immunoglobin G/total antibody testing for SARS-CoV-2: A prospective cohort study of ambulatory patients and health care workers in two Belgian oncology units comparing three commercial tests.

Eur J Cancer 2021 05 27;148:328-339. Epub 2021 Feb 27.

Multidisciplinary Oncologic Centre Antwerp (MOCA), Antwerp University Hospital, Wilrijkstraat 10, Edegem, B-2650, Belgium; Center for Oncological Research (CORE), Integrated Personalised and Precision Oncology Network (IPPON), University of Antwerp, Universiteitsplein 1, Wilrijk, B-2610, Belgium.

Background: Coronavirus disease (COVID-19) is interfering heavily with the screening, diagnosis and treatment of cancer patients. Better knowledge of the seroprevalence and immune response after Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in this population is important to manage them safely during the pandemic.

Methods: 922 cancer patients, 100 non-cancer patients and 94 health care workers (HCW) attending the Multidisciplinary Oncology Unit of Antwerp University Hospital from 24th of March 2020 till 31st of May 2020, and the Oncology Unit of AZ Maria Middelares Hospital, Ghent, from 13th of April 2020 till 31st of May 2020 participated in the study. The Alinity® (A; Abbott) and Liaison® (D; DiaSorin) commercially available assays were used to measure SARS-CoV-2 IgG, while total SARS-CoV-2 Ig was measured by Elecsys® (R; Roche).

Results: In the overall study population IgG/total SARS-CoV-2 antibodies were found in respectively 32/998 (3.2%), 68/1020 (6.7%), 37/1010 (3.7%) and of individuals using the A, D or R test. Forty-six out of 618 (7.4%) persons had a positive SARS-CoV-2 polymerase chain reaction (RT-PCR) test. Seroprevalence in cancer patients (A:2.2%, D:6.2%, R:3.0%), did not significantly differ from that in non-cancer patients (A:1.1%, D:5.6%, R:0.0%), but was lower than the HCW (A:13%, D:12%, R:12%; respectively Fisher's exact test p = 0.00001, p = 0.046, p = 0.0004). A positive SARS-CoV-2 RT-PCR was found in 6.8% of the cancer patients, 2.3% of the non-cancer patients and 28.1% of the HCW (Fisher's exact test p = 0.0004). Correlation between absolute values of the different Ig tests was poor in the cancer population. Dichotomising a positive versus negative test result, the A and R test correlated well (kappa 0.82 p McNemar test = 0.344), while A and D and R and D did not (respectively kappa 0.49 and 0.57; result significantly different p McNemar test = <0.0001 for both). The rate of seroconversion (>75%) and median absolute antibody levels (A: 7.0 versus 4.7; D 74.0 versus 26.6, R: 16.34 versus 7.32; all >P Mann Whitney U test = 0.28) in cancer patients and HCW with a positive RT-PCR at least 7 days earlier did not show any differences. However, none (N = 0/4) of the patients with hematological tumours had seroconversion and absolute antibody levels remained much lower compared to patients with solid tumours (R: 0.1 versus 37.6, p 0.003; D 4.1 versus 158, p 0.008) or HCW (all p < 0.0001).

Conclusion: HCW were at high risk of being infected by SARS-CoV-2 during the first wave of the pandemic. Seroprevalence in cancer patients was low in the study period. Although Ig immune response in cancer patients with solid tumours does not differ from healthy volunteers, patients with hematological tumours have a very poor humoral immune response. This has to be taken into account in future vaccination programmes in this population. SARS-CoV-2 antibody tests have divergent results and seem to have little added value in the management of cancer patients.
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http://dx.doi.org/10.1016/j.ejca.2021.02.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914028PMC
May 2021

The Role of Neoadjuvant Chemotherapy in Locally Advanced Colon Cancer.

Cancer Manag Res 2021 17;13:2567-2579. Epub 2021 Mar 17.

Medical Oncology, Monash Medical Centre, Clayton, Melbourne, VIC, Australia.

Neoadjuvant systemic therapy has many potential advantages over up-front surgery, including tumor downstaging, early treatment of micrometastatic disease, and providing an in vivo test of tumor biology. Due to these advantages, neoadjuvant therapy is becoming the standard of care for an increasing number of tumor types. Currently, colon cancer patients are still routinely treated with up-front surgery, and neoadjuvant systemic therapy is not yet standard. Limitations to widespread use of neoadjuvant therapy have included inaccurate radiological staging, concerns about tumor progression while undergoing preoperative treatment rendering a patient incurable, and a lack of randomized data demonstrating benefit. However, there is great interest in neoadjuvant chemotherapy, and a number of trials are under way. Early follow up of the first phase III trial of neoadjuvant chemotherapy for colon cancer demonstrated tumor downstaging and suggested an improvement in disease-free survival with neoadjuvant chemotherapy, and it is hoped that this will translate into longer-term overall survival benefit. Clinicians should closely watch this developing field, consider the option of neoadjuvant chemotherapy for colon cancer patients, and actively seek out opportunities for their patients to participate in ongoing clinical trials to further inform this field in future.
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http://dx.doi.org/10.2147/CMAR.S262870DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982559PMC
March 2021

Cancer-Associated Fibroblasts as a Common Orchestrator of Therapy Resistance in Lung and Pancreatic Cancer.

Cancers (Basel) 2021 Feb 27;13(5). Epub 2021 Feb 27.

Center for Oncological Research (CORE), Integrated Personalized and Precision Oncology Network (IPPON), University of Antwerp, B2610 Antwerp, Belgium.

Cancer arises from mutations accruing within cancer cells, but the tumor microenvironment (TME) is believed to be a major, often neglected, factor involved in therapy resistance and disease progression. Cancer-associated fibroblasts (CAFs) are prominent and key components of the TME in most types of solid tumors. Extensive research over the past decade revealed their ability to modulate cancer metastasis, angiogenesis, tumor mechanics, immunosuppression, and drug access through synthesis and remodeling of the extracellular matrix and production of growth factors. Thus, they are considered to impede the response to current clinical cancer therapies. Therefore, targeting CAFs to counteract these protumorigenic effects, and overcome the resistance to current therapeutic options, is an appealing and emerging strategy. In this review, we discuss how CAFs affect prognosis and response to clinical therapy and provide an overview of novel therapies involving CAF-targeting agents in lung and pancreatic cancer.
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http://dx.doi.org/10.3390/cancers13050987DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956441PMC
February 2021

RNA Based Approaches to Profile Oncogenic Pathways From Low Quantity Samples to Drive Precision Oncology Strategies.

Front Genet 2020 5;11:598118. Epub 2021 Feb 5.

University of California, San Diego, La Jolla, CA, United States.

Precision treatment of cancer requires knowledge on active tumor driving signal transduction pathways to select the optimal effective targeted treatment. Currently only a subset of patients derive clinical benefit from mutation based targeted treatment, due to intrinsic and acquired drug resistance mechanisms. Phenotypic assays to identify the tumor driving pathway based on protein analysis are difficult to multiplex on routine pathology samples. In contrast, the transcriptome contains information on signaling pathway activity and can complement genomic analyses. Here we present the validation and clinical application of a new knowledge-based mRNA-based diagnostic assay platform (OncoSignal) for measuring activity of relevant signaling pathways simultaneously and quantitatively with high resolution in tissue samples and circulating tumor cells, specifically with very small specimen quantities. The approach uses mRNA levels of a pathway's direct target genes, selected based on literature for multiple proof points, and used as evidence that a pathway is functionally activated. Using these validated target genes, a Bayesian network model has been built and calibrated on mRNA measurements of samples with known pathway status, which is used next to calculate a pathway activity score on individual test samples. Translation to RT-qPCR assays enables broad clinical diagnostic applications, including small analytes. A large number of cancer samples have been analyzed across a variety of cancer histologies and benchmarked across normal controls. Assays have been used to characterize cell types in the cancer cell microenvironment, including immune cells in which activated and immunotolerant states can be distinguished. Results support the expectation that the assays provide information on cancer driving signaling pathways which is difficult to derive from next generation DNA sequencing analysis. Current clinical oncology applications have been complementary to genomic mutation analysis to improve precision medicine: (1) prediction of response and resistance to various therapies, especially targeted therapy and immunotherapy; (2) assessment and monitoring of therapy efficacy; (3) prediction of invasive cancer cell behavior and prognosis; (4) measurement of circulating tumor cells. Preclinical oncology applications lie in a better understanding of cancer behavior across cancer types, and in development of a pathophysiology-based cancer classification for development of novel therapies and precision medicine.
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http://dx.doi.org/10.3389/fgene.2020.598118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893109PMC
February 2021

The tele-transition of toxicity management in routine oncology care during the severe acute respiratory syndrome (SARS-CoV-2) pandemic.

Br J Cancer 2021 04 9;124(8):1366-1372. Epub 2021 Feb 9.

Department of Oncology, Antwerp University Hospital Antwerp, Antwerp, Belgium.

Background: Telehealth modalities were introduced during the SARS-CoV-2 pandemic to assure continuation of cancer care and maintain social distance.

Methods: This is a retrospective cohort analysis of our telehealth expansion programme. We adapted two existing patient-reported outcome (PRO) telemonitoring tools that register and (self-)manage toxicities to therapy, while screening for SARS-CoV-2-related symptoms. Outpatients from a tertiary cancer centre were enrolled. The adapted PRO interface allowed for uniform registration of SARS-CoV-2-related symptoms and effective triage of patients at home where we also implemented systematic throat washings, when available.

Results: Three hundred and sixty patients registered to the telemonitoring systems from March 13 to May 15, 2020. Four prespecified SARS-CoV-2 alarms resulted in three patients with positive PCR testing. Other Covid-19 symptoms (fever 5× and cough 2×) led to pretreatment triage resulting in 1 seroconversion after initial negative testing. One of the 477 throat washings proved positive.

Conclusions: The rapid adoption of an amended PRO (self-)registrations and toxicity management system was feasible and coordinated screening for Covid-19. Continued clinical cancer care was maintained, with significant decreased waiting time. The systemic screening with throat washings offered no real improvement.
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http://dx.doi.org/10.1038/s41416-020-01235-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039036PMC
April 2021

Neoadjuvant Therapy for Locally Advanced Rectal Cancer: Recent Advances and Ongoing Challenges.

Clin Colorectal Cancer 2021 03 5;20(1):29-41. Epub 2021 Jan 5.

Medical Oncology, Monash Medical Centre, Clayton, Australia; School of Clinical Sciences, Monash University, Clayton, Australia.

Locally advanced rectal cancer has a rising global incidence. Over the last 4 decades, advances first in surgery and later in radiotherapy and chemoradiotherapy have improved outcomes, particularly with regard to local recurrence. Unfortunately, distant metastases remain a significant problem. In clinical trials of patients with stage II and III disease, distant relapse occurs in 25% to 30% of patients regardless of the treatment approach. Recent phase 3 trials have therefore focused on intensification of systemic therapy for localized disease, with an aim of reducing the distant relapse rate. Early results of trials of total neoadjuvant therapy with combination systemic therapy provided in the neoadjuvant setting are promising; for the first time, a significant improvement in the rate of distant relapse has been noted. Longer-term follow-up is eagerly awaited. On the other hand, trimodal therapy with chemotherapy, radiotherapy, and surgery is toxic. Several trials are currently assessing the feasibility of a watch-and-wait approach, omitting surgery in those with complete response to neoadjuvant treatment, in an attempt to reduce the burden of treatment on patients. The future for rectal cancer patients is likely to be highly personalized, with more intense approaches for high-risk patients and omission of unnecessary therapy for those whose disease responds well to initial treatment. Biomarkers such as circulating tumor DNA will help to more accurately stratify patients into risk groups. Improvements in survival and quality of life are expected as the results of ongoing research become available throughout the next decade.
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http://dx.doi.org/10.1016/j.clcc.2020.12.005DOI Listing
March 2021

Dihydropyrimidine dehydrogenase deficiency in patients with severe toxicity after 5-fluorouracil: a retrospective single-center study.

Ann Gastroenterol 2021 12;34(1):68-72. Epub 2020 Oct 12.

Department of Oncology, University Hospital Antwerp, Edegem, Belgium (Hans Prenen).

Background: 5-Fluorouracil (5-FU) is an agent frequently used in the treatment of solid cancers. A deficiency in the enzyme that catabolizes 5-FU leads to severe toxicity. The gene responsible for this enzyme is , located on chromosome 1q22. The most prevalent alteration described is , which leads to a splicing defect and thus skipping of the translation of an entire exon. The objectives of this retrospective study were to describe the frequencies of gene mutations in a Belgian population and to correlate them with the grade of toxicity.

Methods: This was a retrospective, single-center study conducted at the University Hospitals Leuven, by reviewing a database of patients screened for gene mutations between May 2009 and June 2015 after prolonged grade 3-4 toxicity. Polymerase chain reaction sequencing of exons 2, 6, 10, 11, 13, 18, 19 and 22, and pyrosequencing of exon 14 were performed by an in-house laboratory.

Results: Of the 80 patients screened, 65 were heterozygous or compound heterozygous for and 3 had a homozygous mutation. The most prevalent mutation in our population was .

Conclusions: Despite previous reports, in our small retrospective study the most prevalent variation in patients with severe adverse events was . As this variant has previously been reported to be benign, we suggest that screening for dihydropyrimidine dehydrogenase deficiency should be extended across multiple exons of the gene.
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http://dx.doi.org/10.20524/aog.2020.0551DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774667PMC
October 2020

Is Bodyweight-Based Dosing Truly Better Than Flat Dosing for Panitumumab? [Response to Letter].

Clin Pharmacol 2020 9;12:189-190. Epub 2020 Dec 9.

Clinical Pharmacology, Modeling & Simulation, Amgen Inc., South San Francisco, CA, USA.

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http://dx.doi.org/10.2147/CPAA.S289793DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7734040PMC
December 2020

Patient-derived organoids as individual patient models for chemoradiation response prediction in gastrointestinal malignancies.

Crit Rev Oncol Hematol 2021 Jan 28;157:103190. Epub 2020 Nov 28.

Department of Abdominal Surgery, Antwerp University Hospital, Wilrijkstraat 10, 2650 Edegem, Belgium; Antwerp Surgical Training, Anatomy and Research Centre (ASTRAC), University of Antwerp, Campus Drie Eiken, Building T, Universiteitsplein 1, 2610, Wilrijk, Antwerp, Belgium. Electronic address:

Chemoradiotherapy (CRT) is an important treatment modality for specific gastrointestinal (GI) cancers, as it has been shown to improve clinical outcomes. Recent developments in the neoadjuvant setting such as wait-and-see strategies for rectal as well as for esophageal cancers have even proven that CRT might be an effective organ-sparing treatment. However, due to molecular heterogeneity, only a subset of patients will show a complete response to CRT, which addresses the need for an individualized treatment approach. In recent years, the demand for more physiologically relevant predictive in vitro models has fostered the development of patient-derived tumor organoids. In this review, we describe the current treatment options for patients with GI cancers who are treated with (neo)adjuvant CRT. Furthermore, we provide an in-depth discussion of the organoid technology in the context of predicting CRT response for GI cancers as well as possible challenges for clinical implementation.
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http://dx.doi.org/10.1016/j.critrevonc.2020.103190DOI Listing
January 2021

Germline variation in the insulin-like growth factor pathway and risk of Barrett's esophagus and esophageal adenocarcinoma.

Carcinogenesis 2021 04;42(3):369-377

Department of Medicine, Institute of Clinical Science, Royal Victoria Hospital, Belfast, UK.

Genome-wide association studies (GWAS) of esophageal adenocarcinoma (EAC) and its precursor, Barrett's esophagus (BE), have uncovered significant genetic components of risk, but most heritability remains unexplained. Targeted assessment of genetic variation in biologically relevant pathways using novel analytical approaches may identify missed susceptibility signals. Central obesity, a key BE/EAC risk factor, is linked to systemic inflammation, altered hormonal signaling and insulin-like growth factor (IGF) axis dysfunction. Here, we assessed IGF-related genetic variation and risk of BE and EAC. Principal component analysis was employed to evaluate pathway-level and gene-level associations with BE/EAC, using genotypes for 270 single-nucleotide polymorphisms (SNPs) in or near 12 IGF-related genes, ascertained from 3295 BE cases, 2515 EAC cases and 3207 controls in the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) GWAS. Gene-level signals were assessed using Multi-marker Analysis of GenoMic Annotation (MAGMA) and SNP summary statistics from BEACON and an expanded GWAS meta-analysis (6167 BE cases, 4112 EAC cases, 17 159 controls). Global variation in the IGF pathway was associated with risk of BE (P = 0.0015). Gene-level associations with BE were observed for GHR (growth hormone receptor; P = 0.00046, false discovery rate q = 0.0056) and IGF1R (IGF1 receptor; P = 0.0090, q = 0.0542). These gene-level signals remained significant at q < 0.1 when assessed using data from the largest available BE/EAC GWAS meta-analysis. No significant associations were observed for EAC. This study represents the most comprehensive evaluation to date of inherited genetic variation in the IGF pathway and BE/EAC risk, providing novel evidence that variation in two genes encoding cell-surface receptors, GHR and IGF1R, may influence risk of BE.
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http://dx.doi.org/10.1093/carcin/bgaa132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8052954PMC
April 2021

An update on the use of immunotherapy in patients with colorectal cancer.

Expert Rev Gastroenterol Hepatol 2021 Mar 9;15(3):291-304. Epub 2020 Nov 9.

Medical Oncology, Monash Medical Centre , Clayton, Australia.

: Colorectal cancer (CRC) is the third most common malignancy worldwide, with recent trends demonstrating increasing incidence amongst younger patients. Despite multiple treatment options, metastatic disease remains incurable. A new therapeutic strategy to harness the host immune system, specifically with immune checkpoint inhibitors, now has reported results from a number of clinical trials. : This review will discuss in detail microsatellite instability (MSI) and other biomarkers for response to immunotherapy, summarize the pivotal clinical trials of immune checkpoint inhibitors in early-stage and metastatic MSI colorectal cancer, explore strategies to induce treatment responses in MSS CRC and highlight the emerging treatments and novel immune-based therapies under investigation. : Immunotherapy is now a standard of care for the proportion of CRC patients with MSI. While overall survival data are still awaited, the promise of profound and durable responses is highly anticipated. The lack of efficacy in MSS CRC is disappointing and strategies to convert these 'cold' tumors are needed. Further elucidation of optimal use of treatment sequences, combinations and novel agents will improve outcomes.
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http://dx.doi.org/10.1080/17474124.2021.1845141DOI Listing
March 2021

The CIREL Cohort: A Prospective Controlled Registry Studying the Real-Life Use of Irinotecan-Loaded Chemoembolisation in Colorectal Cancer Liver Metastases: Interim Analysis.

Cardiovasc Intervent Radiol 2021 Jan 24;44(1):50-62. Epub 2020 Sep 24.

Assistance Publique Hôpitaux de Paris, Service d'hepatogastroentérologie et d'oncologie digestive, Hôpital Européen Georges Pompidou, Université Paris Descartes, Sorbonne Paris-Cité, 20 Rue Leblanc, 75015, Paris, France.

Purpose: Transarterial chemoembolisation (TACE) using irinotecan-eluting beads is an additional treatment option for colorectal cancer liver metastases (CRLM) patients that are not eligible for curative treatment approaches. This interim analysis focuses on feasibility of the planned statistical analysis regarding data distribution and completeness, treatment intention, safety and health-related quality of life (HRQOL) of the first 50 patients prospectively enrolled in the CIrse REgistry for LifePearl™ microspheres (CIREL), an observational multicentre study conducted across Europe.

Methods: In total, 50 patients ≥ 18 years diagnosed with CRLM and decided to be treated with irinotecan-eluting LifePearl™ microspheres TACE (LP-irinotecan TACE) by a multidisciplinary tumour board. There were no further inclusion or exclusion criteria. The primary endpoint is the categorisation of treatment intention, and secondary endpoints presented in this interim analysis are safety, treatment considerations and HRQOL.

Results: LP-irinotecan TACE was conducted in 42% of patients as salvage therapy, 20% as an intensification treatment, 16% as a first-line treatment, 14% a consolidation treatment and 8% combination treatment with ablation with curative intent. Grade 3 and 4 adverse events were reported by 4% of patients during procedure and by 10% within 30 days. While 38% reported a worse, 62% reported a stable or better global health score, and 54% of patients with worse global health score were treated as salvage therapy patients.

Conclusion: This interim analysis confirms in a prospective analysis the feasibility of the study, with an acceptable toxicity profile. More patients reported a stable or improved HRQOL than deterioration. Deterioration of HRQOL was seen especially in salvage therapy patients.

Trial Registration: NCT03086096.
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http://dx.doi.org/10.1007/s00270-020-02646-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7728640PMC
January 2021

LifePearl microspheres loaded with irinotecan in the treatment of Liver-dominant metastatic colorectal carcinoma: feasibility, safety and pharmacokinetic study.

Anticancer Drugs 2020 11;31(10):1084-1090

Department of Radiology, Minimal-Invasive Therapies and Nuclear Medicine, SLK Kliniken Heilbronn, Heilbronn, Germany.

To evaluate pharmacokinetic and safety profile of LifePearl microspheres loaded with irinotecan (LifePearl-IRI) in the treatment of liver-dominant, metastatic colorectal carcinoma (LM-CRC) by transarterial chemoembolization. In a prospective, multicentre pharmacokinetic study, 14 patients with LM-CRC progressing on at least one line of chemotherapy were treated with LifePearl-IRI. Six patients received unilobar treatment, treating one lobe per session with 100 mg of irinotecan every 2 weeks. Eight patients received bilobar treatment, treating two lobes per session with 100 mg of irinotecan each (200 mg in total), every 4 weeks. At 24 h, near complete plasma clearance occurred for both irinotecan and SN-38, regardless of the dose. Mean plasma Cmax(100 mg) was 254.50 ± 104.17 ng/mL for irinotecan and 46.72 ± 13.75 ng/mL for SN-38. Mean Cmax(200 mg) was 970.09 ± 353.75 ng/mL for irinotecan and 118.45 ± 25.11 ng/mL for SN-38. Significantly higher Cmax-iri(200 mg) than Cmax-iri (100 mg) supported rate-limiting irinotecan-to-SN-38 conversion. Adverse events during the first 30 days upon initial treatment were hypertension in 21.4%, abdominal pain in 14.3%, and increased transaminases and fever in 7.1% of patients. Four serious adverse events were noted: respiratory failure, constipation, necrotizing pancreatitis, and ischaemic cholecystitis. Chemoembolization with LifePearl-IRI is technically feasible and relatively well tolerated, with a good pharmacokinetic profile and minimal systemic exposure of both irinotecan and SN-38, after both unilobar and bilobar treatment with 100 or 200 mg, respectively.
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http://dx.doi.org/10.1097/CAD.0000000000000980DOI Listing
November 2020

High mortality of cancer patients in times of SARS-CoV-2: Do not generalize!

Eur J Cancer 2020 10 10;138:225-227. Epub 2020 Aug 10.

Multidisciplinary Oncologic Centre Antwerp (MOCA), Antwerp University Hospital, Wilrijkstraat 10, Edegem, B-2650, Belgium; Center for Oncological Research (CORE), Integrated Personalized and Precision Oncology Network (IPPON), University of Antwerp, Universiteitsplein 1, Wilrijk, B-2610, Belgium.

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http://dx.doi.org/10.1016/j.ejca.2020.07.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7416784PMC
October 2020

Dose Regimen Rationale for Panitumumab in Cancer Patients: To Be Based on Body Weight or Not.

Clin Pharmacol 2020 31;12:109-114. Epub 2020 Jul 31.

Clinical Pharmacology, Modeling & Simulation, Amgen Inc., South San Francisco, CA, USA.

Introduction: Body weight can affect exposure, safety and efficacy of antibody-based therapies; sometimes these effects may not be clinically relevant. Panitumumab is approved for wild-type metastatic colorectal cancer, using a body weight-based dosing regimen. Recently, a report cited fixed-dose usage of panitumumab, rather than approved body weight-based dosing. The current work evaluates optimal dosing regimen scientifically based on clinical data, modeling and simulation. Herein, we assessed the effect of fixed and body weight-based dosing on panitumumab pharmacokinetics to determine which approach resulted in the least interpatient pharmacokinetic variability.

Patients And Methods: From the Vectibix program, 352 patients enrolled in three studies were evaluated; they had received panitumumab (body weight-based dose: 6 mg/kg every 2 weeks) and had pharmacokinetic (maximum serum [C and trough [C] concentrations) and body weight data available. Additionally, concentration-time profiles at fixed (480 mg) and body weight-based doses (6 mg/kg) were simulated using a population pharmacokinetics model developed from 1200 patients.

Results: After administration of panitumumab 6 mg/kg, C and C increased with increasing body weight; the mean C and C for patients weighing <65 kg (lower quartile) were 23% and 30% lower, respectively, than for those weighing >88 kg (upper quartile). The simulated area under the concentration-time curve (AUC) data also indicated that overall panitumumab exposure increased with increasing body weight for the body weight-based regimen. When AUC was simulated for a fixed dose (480 mg), the opposite effect was observed. Over the range of body weights, interpatient variability in simulated AUC was lower for the weight-based dose (29%) than for the fixed dose (34%).

Conclusion: Results demonstrate that the weight-based dose (6 mg/kg) reduced variability in panitumumab exposure across the range of body weights compared with the fixed-dose approach, indicating that a body weight-based approach is the recommended patient dosing strategy.
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http://dx.doi.org/10.2147/CPAA.S262949DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7406372PMC
July 2020

Refractory Metastatic Colorectal Cancer: Current Challenges and Future Prospects.

Cancer Manag Res 2020 15;12:5819-5830. Epub 2020 Jul 15.

Department of Medical Oncology, Monash Medical Center, Clayton, Australia.

Despite advances, patients with metastatic colorectal cancer (mCRC) still have poor long-term survival. Identification of molecular subtypes is important to guide therapy through standard treatment pathways and holds promise for the development of new treatments. Following standard first- and second-line chemotherapy plus targeted agents, many patients retain a reasonable performance status, and thus are seeking further effective treatment to extend life and maintain symptom control. The challenge lies in selecting the most appropriate therapy in the third- and fourth-line settings, from a range of options including the relatively new oral agents TAS-102 and regorafenib, or rechallenge with previous chemotherapy or anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibodies (mAB). Beyond this, therapy consists of trials involving novel agents and new combinations of treatments with theoretical synergy and/or non-overlapping toxicity. There is a great focus on enhancing immunogenicity in mCRC, to reflect the impressive results of immunotherapy drugs in the small cohort with mismatch repair deficient (dMMR) mCRC. Rare molecular subtypes of mCRC are increasingly being identified, including -positive disease, fusions and others. Clinical trials exploring the efficacy of immunomodulatory and precision agents are plentiful and will hopefully yield clinically meaningful results that can be rapidly translated into routine care.
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http://dx.doi.org/10.2147/CMAR.S213236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7369412PMC
July 2020

SARS-CoV-2 and cancer: Are they really partners in crime?

Cancer Treat Rev 2020 Sep 11;89:102068. Epub 2020 Jul 11.

Multidisciplinary Oncologic Centre Antwerp (MOCA), Antwerp University Hospital, Wilrijkstraat 10, Edegem B-2650, Belgium; Center for Oncological Research (CORE), Integrated Personalized and Precision Oncology Network (IPPON), University of Antwerp, Universiteitsplein 1, Wilrijk B-2610, Belgium.

The outbreak of the SARS-CoV-2 pandemic has overwhelmed health care systems in many countries. The clinical presentation of the SARS-CoV-2 varies between a subclinical or flu-like syndrome to that of severe pneumonia with multi-organ failure and death. Initial reports have suggested that cancer patients may have a higher susceptibility to get infected by the SARS-CoV-2 virus but current evidence remains poor as it is biased by important confounders. Patients with ongoing or recent cancer treatment for advanced active disease, metastatic solid tumors and hematological malignancies are at higher risk of developing severe COVID-19 respiratory disease that requires hospitalization and have a poorer disease outcome compared to individuals without cancer. However it is not clear whether these are independent risk factors, or mainly driven by male gender, age, obesity, performance status, uncontrolled diabetes, cardiovascular disease and various other medical conditions. These often have a greater influence on the probability to die due to SARS-CoV-2 then cancer. Delayed diagnosis and suboptimal cancer management due to the pandemic results in disease upstaging and has considerable impact cancer on specific death rates. Surgery during the peak of the pandemic seems to increase mortality, but there is no convincing evidence that adjuvant systemic cancer therapy and radiotherapy are contraindicated, implicating that cancer treatment can be provided safely after individual risk/benefit assessment and some adaptive measures. Underlying immunosuppression, elevated cytokine levels, altered expression of the angiotensin converting enzyme (ACE-2) and TMPRSS2, and a prothrombotic status may fuel the effects of a SARS-CoV-2 in some cancer patients, but have the potential to be used as biomarkers for severe disease and therapeutic targets. The rapidly expanding literature on COVID-19 should be interpreted with care as it is often hampered by methodological and statistical flaws.
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http://dx.doi.org/10.1016/j.ctrv.2020.102068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351667PMC
September 2020

Characterization of Liver Metastases During Catheter-Directed Liver Interventions: A Comparison between Dual Phase Cone-Beam Computed Tomography and Conventional Contrast-Enhanced Computed Tomography.

J Belg Soc Radiol 2020 Jul 8;104(1):41. Epub 2020 Jul 8.

Department of Radiology, University Hospitals Leuven, BE.

Objectives: To compare the diagnostic performance of intra-arterial dual phase cone-beam computed tomography (DP-CBCT) with contrast-enhanced computed tomography (CE-CT) when characterizing tumor burden in patients with metastatic liver cancer.

Materials And Methods: This retrospective study included 29 patients with colorectal (n =10), breast (n = 9) and neuroendocrine (n = 10) liver metastases, referred for catheter-directed treatment. Tumor type, number, maximum size, and appearance were assessed. Paired-sample t-tests compared image quality, tumor numbers, and diameters between imaging modalities.

Results: Image quality was not different between DP-CBCT and CE-CT (p = 0.9). In 18 patients (62%) DP-CBCT and CE-CT showed diffuse, uncountable metastases in the liver. Of the remaining 11 patients, DP-CBCT identified two patients with diffuse tumors that appeared as a sum of 17 distinct metastases on CE-CT. In the remaining nine patients a total of 102 metastases were found using both DP-CBCT and CE-CT. Tumor detection accuracy was 98% in DP-CBCT and 67% in CE-CT (p = 0.025). Metastases were larger in diameter on DP-CBCT: colorectal: 57 +/- 9.5 mm versus 43 +/- 8.3 mm (p = 0.02); breast: 57 +/- 10 mm versus 43 +/- 8.5 mm (p = 0.03) and neuroendocrine: 56 +/- 6.3 mm versus 51 +/- 5.8 mm (p = 0.01). Rim enhancement appeared in 100% of patients with colorectal and 89% of patients with breast metastases on DP-CBCT, but was variable on CE-CT. Neuroendocrine tumors had variable rim enhancement within the same patient and across imaging modalities.

Conclusions: DP-CBCT of the liver may demonstrate larger metastatic tumor burden and lesion size with a variable contrast enhancement compared to CE-CT.
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http://dx.doi.org/10.5334/jbsr.2052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7350946PMC
July 2020

A multicentre, international, observational study on transarterial chemoembolisation in colorectal cancer liver metastases: Design and rationale of CIREL.

Dig Liver Dis 2020 08 30;52(8):857-861. Epub 2020 Jun 30.

Université Paris Descartes, Sorbonne Paris-Cité, Assistance Publique Hôpitaux de Paris, Service d'hepatogastroentérologie et d'oncologie digestive, Hôpital Européen Georges Pompidou, 20 Rue Leblanc, 75015 Paris, France.

Background: About 70-80% of patients with colorectal liver metastases appear as ineligible for a curative treatment approach. Transarterial chemoembolisation (TACE) using irinotecan-eluting beads has emerged as a promising treatment option in cases with irresectable liver metastases. Despite being in clinical practice for years, little is known about the treatment characteristics and outcomes when used as per routine hospital practice.

Methods: Patients with hepatic metastases from colorectal cancer origin, admitted to contributing centres to receive TACE with drug-eluting LifePearl® Microspheres loaded with irinotecan, as part of their standard care, will be consecutively added to the registry. Data will be collected until the end of study, loss to follow-up or death. Primary endpoint is the characterisation of the treatment usage at the selected sites in Europe. Secondary endpoints include outcome parameters, safety and toxicity, as well as quality of life.

Conclusion And Aims: This multicentre, international, prospective observational study conducted in European centres plans to collect real-life data. This data will form an evidence-base from which conclusions can be drawn on how to improve patient selection and optimise treatment protocols when treating with TACE using irinotecan-eluting microspheres. Trial registration NCT03086096.
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http://dx.doi.org/10.1016/j.dld.2020.05.051DOI Listing
August 2020

Prescreening for COVID-19 in patients receiving cancer treatment using a patient-reported outcome platform.

ESMO Open 2020 06;5(3):e000817

Department of Medical Oncology, MOCA, University Hospital Antwerp (UZA), Antwerp, Belgium; Department of Molecular Imaging, Pathology, Radiotherapy & Oncology (MIPRO), Center for Oncological Research (CORE), Antwerp University, Antwerp, Belgium.

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http://dx.doi.org/10.1136/esmoopen-2020-000817DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7307523PMC
June 2020

A 2020 update of anal cancer: the increasing problem in women and expanding treatment landscape.

Expert Rev Gastroenterol Hepatol 2020 Aug 8;14(8):665-680. Epub 2020 Jun 8.

Medical Oncology, Monash Medical Centre , Clayton, Australia.

Introduction: Anal cancer is a rare malignancy with increasing incidence, notably in women. This disease is highly associated with HPV infection and its incidence and mortality are currently rising. Most patients present with localized disease which has a high survival after definitive treatment with chemoradiation. For patients who develop metastatic disease or present with this de novo, survival is poor.

Areas Covered: This review provides a summary of current literature on anal cancer. With a focus on women, this includes current epidemiological trends, role of HPV, and the current and future treatment landscape, including HPV vaccination and immunotherapy. Screening currently focusses on HIV-positive men, missing most female cases. In curative disease, trials are investigating treatment de-intensification in good prognostic groups. Immunotherapy is showing early promise in the advanced disease setting.

Expert Opinion: Similar to cervical cancer, anal cancer is strongly associated with HPV, and therefore, broader implementation of screening programs may reduce its incidence. HPV vaccination is expected to reduce the development of (pre)malignant anal lesions. The emergence of biomarkers will assist patient treatment selection, allowing optimal balance of treatment efficacy and morbidity. It is hoped that new treatment approaches, including immunotherapy, will improve outcomes. International collaboration is needed.
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http://dx.doi.org/10.1080/17474124.2020.1775583DOI Listing
August 2020

Transarterial chemoembolisation of colorectal liver metastases with irinotecan-loaded beads: What every interventional radiologist should know.

Eur J Radiol Open 2020 13;7:100236. Epub 2020 May 13.

SLK-Kliniken Heilbronn GmbH, Klinik für Radiologie, Minimal-invasive Therapien und Nuklearmedizin, Am Gesundbrunnen 20-26, 74078 Heilbronn, Germany.

The last decade has seen important developments in the treatment of metastatic colorectal cancer (mCRC). In this scenario, interventional locoregional treatments could play an expanding role offering safe and effective integrated options in the continuum-of-care offering curative as well as palliative approaches. Based on ESMO guidelines, the toolbox of ablative treatments also includes intra-arterial palliative options, like chemoembolization, that can be offered as an alternative option in patients failing the available chemotherapeutic regimens. However, to date, there is still a limited use of chemoembolization in clinical practice. Based on this background, a comprehensive review of the methodologic and technical considerations as well as clinical indications and future perspectives seems to be useful with the aim to demonstrate the field's value of the procedure, highlight their advantages, and ensure an increased role in treatment management of patients with colorectal liver metastases.
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http://dx.doi.org/10.1016/j.ejro.2020.100236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226646PMC
May 2020

Practical Considerations for Treating Patients With Cancer in the COVID-19 Pandemic.

JCO Oncol Pract 2020 08 13;16(8):467-482. Epub 2020 May 13.

Biosecurity Program, Kirby Institute, University of New South Wales, Sydney, New South Wales, Australia.

Cancer has become a prevalent disease, affecting millions of new patients globally each year. The COVID-19 pandemic is having far-reaching impacts around the world, causing substantial disruptions to health and health care systems that are likely to last for a prolonged period. Early data have suggested that having cancer is a significant risk factor for mortality from severe COVID-19. A diverse group of medical oncologists met to formulate detailed practical advice on systemic anticancer treatments during this crisis. In the context of broad principles, issues including risks of treatment, principles of prioritizing resources, treatment of elderly patients, and psychosocial impact are discussed. Detailed treatment advice and options are given at a tumor stream level. We must maintain care for patients with cancer as best we can and recognize that COVID-19 poses a significant competing risk for death that changes conventional treatment paradigms.
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http://dx.doi.org/10.1200/OP.20.00229DOI Listing
August 2020

Specialized Blood Collection Tubes for Liquid Biopsy: Improving the Pre-analytical Conditions.

Mol Diagn Ther 2020 02;24(1):113-124

Center for Oncological Research (CORE) Antwerp, University of Antwerp (UAntwerp), Universiteitsplein 1, 2610, Wilrijk, Belgium.

Introduction: The potential of circulating cell-free DNA (cfDNA) analysis as a liquid biopsy has led to the development of several specialized measuring tools. Interest in the (pre-)analytical conditions of the liquid biopsy workflow has increased over the past few years.

Methods: In this study, we performed a systematic review of the cfDNA stabilizing efficacy in standard EDTA and specialized blood collection tubes (BCTs), namely CellSave, Norgen, PAXgene, Roche, and Streck tubes, and compared the efficacy of the latter three BCTs in a situation resembling the clinical setting. Blood samples were collected from ten KRAS-mutated metastatic cancer patients and stored for 72 h. During this time, samples were shaken and kept at either 6 °C or at room temperature for 24 h to mimic transport.

Results: We demonstrated that while cfDNA levels in EDTA tubes are only stable for a couple of (≤ 6) hours, they could be sustained for at least 48-72 h in all three specialized BCTs, irrespective of temperature. This timespan enables a fast turnaround time, which is one of the advantages of liquid biopsy.

Conclusions: The choice between these specialized BCTs is less vital when they are processed correctly within a few days.
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http://dx.doi.org/10.1007/s40291-019-00442-wDOI Listing
February 2020
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