Publications by authors named "Eva Segelov"

74 Publications

The experiences, attitudes and understanding of research amongst medical students at an Australian medical school.

BMC Med Educ 2021 May 10;21(1):267. Epub 2021 May 10.

School of Clinical Sciences, Monash University, Melbourne, Australia.

Background: Research engagement plays an integral role in developing clinicians that practice effective, evidence-based medicine. Research participation by clinicians, however, is declining. Given the link between research during medical school and future research output, promotion of medical student research is one avenue by which this shortage can be addressed. Student research attitudes and participation in Australia are not well-documented in the literature. This study therefore aims to investigate research practices, motivators, and barriers amongst Australian medical students in order to determine whether there is a need for further integration of research within Australian medical school curriculums.

Methods: A cross-sectional study design was used to explore research experience and attitudes, as well as the enablers and barriers to research amongst students enrolled in all years of the five-year medical course at Monash University. A questionnaire was created by combining questions from several surveys on medical student research and comprised Likert scales, multiple choice options and free-text responses assessing research experience, attitudes, motivators, and barriers.

Results: Seven hundred and four respondents (69.4% female; survey response rate 36.7%) reported variable research experience and interest. Less than half of the cohort (n = 296; 44.9%) had contributed to a research project. Increasing employability for specialty training programs was the primary motivating factor (n = 345; 51.9%) for pursuing research, with only 20.5% (n = 136) citing an interest in academia as a motivator. Time constraints (n = 460; 65.3%) and uncertainty surrounding how to find research opportunities (n = 449; 63.8%) were the most common barriers to research.

Conclusions: Medical students at Monash University are interested in but have limited experience with research. Students are, however, primarily motivated by the prospect of increasing employability for specialist training; medical schools should therefore focus on encouraging intrinsic motivation for pursuing research. Greater integration of research education and opportunities within medical school curricula may also be required to provide students with the skills necessary to both pursue research and practice evidence-based medicine.
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http://dx.doi.org/10.1186/s12909-021-02713-9DOI Listing
May 2021

Whole blood expression as a prognostic biomarker in metastatic hormone-sensitive and castration-resistant prostate cancer.

Transl Androl Urol 2021 Apr;10(4):1688-1699

Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, Australia.

Background: As potent systemic therapies transition earlier in the prostate cancer disease course, molecular biomarkers are needed to guide optimal treatment selection for metastatic hormone-sensitive prostate cancer (mHSPC). The value of whole blood RNA to detect candidate biomarkers in mHSPC remains largely undefined.

Methods: In this cohort study, we used a previously optimised whole blood reverse transcription polymerase chain reaction assay to assess the prognostic utility [measured by seven-month undetectable prostate-specific antigen (PSA) and time to castration-resistance (TTCR)] of eight prostate cancer-associated gene transcripts in 43 mHSPC patients. Transcripts with statistically significant associations (P<0.05) were further investigated in a metastatic castration-resistant prostate cancer (mCRPC) cohort (n=119) receiving contemporary systemic therapy, exploring associations with PSA >50% response (PSA), progression-free survival (PFS) and overall survival (OS). Clinical outcomes were prospectively collected in a protected digital database. Kaplan-Meier estimates and multivariable Cox proportional-hazards models assessed associations between gene transcripts and clinical outcomes (mHSPC covariates: disease volume, docetaxel use and haemoglobin level; mCRPC covariates: prior exposure to chemotherapy or ARPIs, haemoglobin, performance status and presence of visceral disease). Follow-up was performed monthly during ARPI treatment, three-weekly during taxane chemotherapy, and three-monthly during androgen deprivation therapy (ADT) monotherapy. Serial PSA measurements were performed before each follow-up visit and repeat imaging was at the discretion of the investigator.

Results: Detection of circulating Grainyhead-like 2 () transcript was associated with poor outcomes in mHSPC and mCRPC patients. Detectable expression in mHSPC was associated with a lower rate of seven-month undetectable PSA levels (25% 65%, P=0.059), and independently associated with shorter TTCR (HR 7.3, 95% CI: 1.5-36, P=0.01). In the mCRPC cohort, expression predicted significantly lower PSA response rates (46% 69%, P=0.01), and was independently associated with shorter PFS (HR 3.1, 95% CI: 1.8-5.2, P<0.001) and OS (HR 2.9, 95% CI: 1.6-5.1, P<0.001). Associations were most apparent in patients receiving ARPIs.

Conclusions: Detectable circulating was a negative prognostic biomarker in our mHSPC and mCRPC cohorts. These data support further investigation of as a candidate prognostic biomarker in metastatic prostate cancer, in addition to expanding efforts to better understand a putative role in therapeutic resistance to AR targeted therapies.
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http://dx.doi.org/10.21037/tau-20-1444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100842PMC
April 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.

Background And Purpose: 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) 80mg/m .

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

Key Results: 42 pts 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 7 (18%) pts with oPac+E and 2 (5%) with IVP. 75% of pts preferred oPac+E over IVP.

Conclusion And Implications: 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

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

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

Clin Colorectal Cancer 2021 Mar 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

Management of Asymptomatic Sporadic Nonfunctioning Pancreatic Neuroendocrine Neoplasms (ASPEN) ≤2 cm: Study Protocol for a Prospective Observational Study.

Front Med (Lausanne) 2020 23;7:598438. Epub 2020 Dec 23.

National NET Centre and ENETS Centre of Excellence, St Vincent's University Hospital, Dublin, Ireland.

The optimal treatment for small, asymptomatic, nonfunctioning pancreatic neuroendocrine neoplasms (NF-PanNEN) is still controversial. European Neuroendocrine Tumor Society (ENETS) guidelines recommend a watchful strategy for asymptomatic NF-PanNEN <2 cm of diameter. Several retrospective series demonstrated that a non-operative management is safe and feasible, but no prospective studies are available. Aim of the ASPEN study is to evaluate the optimal management of asymptomatic NF-PanNEN ≤2 cm comparing active surveillance and surgery. ASPEN is a prospective international observational multicentric cohort study supported by ENETS. The study is registered in ClinicalTrials.gov with the identification code NCT03084770. Based on the incidence of NF-PanNEN the number of expected patients to be enrolled in the ASPEN study is 1,000 during the study period (2017-2022). Primary endpoint is disease/progression-free survival, defined as the time from study enrolment to the first evidence of progression (active surveillance group) or recurrence of disease (surgery group) or death from disease. Inclusion criteria are: age >18 years, the presence of asymptomatic sporadic NF-PanNEN ≤2 cm proven by a positive fine-needle aspiration (FNA) or by the presence of a measurable nodule on high-quality imaging techniques that is positive at Gallium DOTATOC-PET scan. The ASPEN study is designed to investigate if an active surveillance of asymptomatic NF-PanNEN ≤2 cm is safe as compared to surgical approach.
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http://dx.doi.org/10.3389/fmed.2020.598438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785972PMC
December 2020

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

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

Towards new models of cancer care in Australia: lessons from Victoria's response to the COVID-19 pandemic.

Intern Med J 2020 Oct 20;50(10):1282-1285. Epub 2020 Sep 20.

Department of Oncology, Monash University and Monash Health, Melbourne, Victoria, Australia.

In response to the COVID-19 pandemic, the Department of Health and Human Services Victoria (DHHS), the Monash Partners Comprehensive Cancer Consortium (MPCCC) and Victorian Comprehensive Cancer Centre (VCCC) pooled their combined infrastructure to establish the Victorian COVID-19 Cancer Network (VCCN) backed by a Taskforce of expert members. In a few short months, this state-wide clinical network implemented a number of new models of care including clinics to manage acutely presenting cancer patients away from emergency departments, chemotherapy in the home, telehealth models and addressing sustainability of clinical trials.
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http://dx.doi.org/10.1111/imj.15012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7537092PMC
October 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

Australian experience of peptide receptor radionuclide therapy in lung neuroendocrine tumours.

Oncotarget 2020 Jul 7;11(27):2636-2646. Epub 2020 Jul 7.

Department of Medical Oncology, Monash Health, Melbourne, Australia.

Background: Peptide receptor radionuclide therapy (PRRT) is an approved treatment modality for gastroenteropancreatic neuroendocrine tumours (GEP NETs), Although Phase III randomised clinical trial data is not available for NETs of other site of origin, in practice, PRRT is used more widely in clinical practice, based on its mechanism of targeting the somatostatin receptor. Use of PRRT for lung (bronchial) NET, specifically typical and atypical carcinoid (TC, AC), has been reported only in small retrospective case series. This multicentre study adds to the evidence regarding utility of PRRT for lung NETs.

Materials And Methods: A retrospective chart review of patients with TC and AC who received Lu-dotatate PRRT between January 2002 and June 2019 in six hospitals across Australia was undertaken. Data regarding demographics, efficacy and toxicity was evaluated at each site by the treating clinician.

Results: Forty-eight patients (32 AC, 15 TC, 1 unclassified) received a median of four Lu-dotatate treatments. There was a median of one prior line of systemic treatment (range: 0-3). The response rate to Lu-dotatate was 33%, with a median overall survival of 49 months (range of 3-91), at a median follow up of 33 months. This compares favourably with GEP NET. Overall toxicity was recorded as modest.

Conclusions: Lu-dotatate PRRT in patients with lung NETs is used in real world practice, where it appears well-tolerated with some efficacy. Further evidence could be obtained through a global prospective clinical or registry trial.
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http://dx.doi.org/10.18632/oncotarget.27659DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7343632PMC
July 2020

Commonwealth Neuroendocrine Tumour Research Collaboration and the North American Neuroendocrine Tumor Society Guidelines for the Diagnosis and Management of Patients With Lung Neuroendocrine Tumors: An International Collaborative Endorsement and Update of the 2015 European Neuroendocrine Tumor Society Expert Consensus Guidelines.

J Thorac Oncol 2020 10 11;15(10):1577-1598. Epub 2020 Jul 11.

Department of Oncology, Monash Health, Monash University, Melbourne, Victoria, Australia.

Lung neuroendocrine tumors (LNETs) are uncommon cancers, and there is a paucity of randomized evidence to guide practice. As a result, current guidelines from different neuroendocrine tumor societies vary considerably. There is a need to update and harmonize global consensus guidelines. This article reports the best practice guidelines produced by a collaboration between the Commonwealth Neuroendocrine Tumour Research Collaboration and the North American Neuroendocrine Tumor Society. We performed a formal endorsement and updating process of the 2015 European Neuroendocrine Tumor Society expert consensus article on LNET. A systematic review from January 2013 to October 2017 was conducted to procure the most recent evidence. The stepwise endorsement process involved experts from all major subspecialties, patients, and advocates. Guided by discussion of the most recent evidence, each statement from the European Neuroendocrine Tumor Society was either endorsed, modified, or removed. New consensus statements were added if appropriate. The search yielded 1109 new publications, of which 230 met the inclusion criteria. A total of 12 statements were endorsed, 22 statements were modified or updated, one was removed, and two were added. Critical answered questions for each topic in LNET were identified. Through the consensus process, guidelines for the management of patients with local and metastatic neuroendocrine tumors have been updated to include both recent evidence and practice changes relating to technological and definitional advances. The guidelines provide clear, evidence-based statements aimed at harmonizing the global approach to patients with LNETs, on the basis of the principles of person-centered and LNET-specific care. The importance of LNET-directed research and person-centered care throughout the diagnosis, treatment, and follow-up journey is emphasized along with directions for future collaborative research.
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http://dx.doi.org/10.1016/j.jtho.2020.06.021DOI Listing
October 2020

International Rare Cancers Initiative Multicenter Randomized Phase II Trial of Cisplatin and Fluorouracil Versus Carboplatin and Paclitaxel in Advanced Anal Cancer: InterAAct.

J Clin Oncol 2020 08 12;38(22):2510-2518. Epub 2020 Jun 12.

Royal Marsden Hospital, London, United Kingdom.

Purpose: To compare cisplatin plus fluorouracil (FU) versus carboplatin plus paclitaxel in chemotherapy-naïve advanced anal cancer to establish the optimal regimen.

Patients And Methods: Patients who had not received systemic therapy for advanced anal cancer were randomly assigned 1:1 to intravenous cisplatin 60 mg/m (day 1) plus FU 1,000 mg/m (days 1-4) every 21 days or carboplatin (area under the curve, 5; day 1) plus paclitaxel 80 mg/m (days 1, 8, and 15) every 28 days for 24 weeks, until disease progression, intolerable toxicity, or withdrawal of consent. Primary end point was objective response rate (ORR). Primary and secondary end points were assessed in a hierarchic model to compare the regimens and pick the winner.

Results: We conducted an international multicenter randomized phase II study in 60 centers between December 2013 and November 2017. Median follow-up was 28.6 months. A total of 91 patients were randomly assigned: 46 to cisplatin plus FU and 45 to carboplatin plus paclitaxel. ORR was 57% (95% CI, 39.4% to 73.7%) for cisplatin plus FU versus 59% (95% CI, 42.1% to 74.4%) for carboplatin plus paclitaxel. More serious adverse events were noted in the cisplatin plus FU arm (62%) compared with the carboplatin plus paclitaxel arm (36%; = .016). Median progression-free survival was 5.7 months (95% CI, 3.3 to 9.0 months) for cisplatin plus FU compared with 8.1 months (95% CI, 6.6 to 8.8 months) for carboplatin plus paclitaxel. Median overall survival was 12.3 months for cisplatin plus FU (95% CI, 9.2 to 17.7 months) compared with 20 months (95% CI, 12.7 months to not reached) for carboplatin plus paclitaxel (hazard ratio, 2.00; 95% CI, 1.15 to 3.47; = .014).

Conclusion: This is the first international randomized trial to our knowledge conducted in chemotherapy-naïve advanced anal cancer. Although there was no difference in ORR, the association with clinically relevant reduced toxicity and a trend toward longer survival suggest that carboplatin plus paclitaxel should be considered as a new standard of care.
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http://dx.doi.org/10.1200/JCO.19.03266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7406334PMC
August 2020

AMTRA: a multicentered experience of a web-based monitoring and tailored toxicity management system for cancer patients.

Support Care Cancer 2021 Feb 9;29(2):859-867. Epub 2020 Jun 9.

Department of Oncology, Multidisciplinary Oncological Center Antwerp, MOCA, University Hospital Antwerp, Wilrijkstraat 10, 2650, Edegem, Belgium.

Background: Technology-based interventions are increasingly being introduced in routine clinical cancer care. There is a need for reliable systems to monitor treatment-related toxicity in a standardized manner. Such electronic tools bridge the gap in providing quality home-based monitoring.

Methods: From July 2017 to December 2017, we performed a multicentered, non-randomized prospective cohort analysis with patients who were receiving routine chemotherapy for various solid tumors, using a web-based patient-reported toxicity registration, management, and intervention system called AMTRA (ambulatory Monitoring of cancer Therapy using an interactive Application) linked to the homecare nursing organization Remedus®. Twelve common toxicities plus pain and two biometrics could be registered daily or more frequently as required. These were processed centrally to generate tailored advice for lesser symptoms or a phone call from a dedicated nurse in case of severe or prolonged toxicity. A compliance tool to monitor oral therapies was incorporated in the system.

Results: One hundred sixty-eight patients (92%) were enrolled, with 31,514 registrations analyzed. One hundred eight patients reported severe toxicity (> 1461 registrations), resulting in 102 clinical interventions ranging from self-management advice, supplemental consultations to hospitalizations. Compliance to oral chemotherapy was high using AMTRA with a median of 98.7% (95 confidence interval (CI) [93.5-100.0%]). Seventy-nine percent of patients stated that the availability of AMTRA self-reports was useful in communication with the care provider, while 75% felt more in control while managing their treatment.

Conclusions: The application of an interactive PRO-system in routine symptom management of cancer patients allowed standardized documentation of toxicities and recorded a high compliance with oral treatment. It allows for rapid interaction for toxicities and cancer-related symptoms experienced at home.
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http://dx.doi.org/10.1007/s00520-020-05550-6DOI Listing
February 2021

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

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

Anti-cancer therapy made easier: a 25-year update.

Intern Med J 2021 Apr;51(4):473-480

Department of Oncology, Monash Health, Melbourne, Victoria, Australia.

In 1993, the Internal Medicine Journal published 'Chemotherapy made easier', outlining developments in supportive care of patients undergoing chemotherapy. This described the contemporary state of anti-emetics, colony stimulating factors, cardiac toxicity, neurotoxicity, development of drug analogues and venous access devices. Twenty-five years later, we update the measures that improve the tolerability of the plethora of new anti-cancer therapies, which have extended well beyond traditional chemotherapy agents to include immunotherapy and targeted therapies. Optimisation of supportive care is paramount to allow safe delivery with the least possible impact on quality of life of these new treatments, many of which have resulted dramatically improved outcomes across multiple cancer types. This state of the art update summarises advances in supportive care therapies relating to improving the patient experience during and after anti-cancer treatment, including new anti-emetics, hair preservation techniques, bone marrow support and improved venous access devices; the ongoing challenge of neurotoxicity; and the advent of multidisciplinary sub-specialised fields such as cardio-oncology and oncofertility. Supportive care medications for immuno-oncology therapies is a new section; these highly effective (although not universally so) agents were a mere illusion in 1993.
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http://dx.doi.org/10.1111/imj.14878DOI Listing
April 2021

Management of early-stage gastro-esophageal cancers: expert perspectives from the Australasian Gastrointestinal Trials Group (AGITG) with invited international faculty.

Expert Rev Anticancer Ther 2020 04 12;20(4):305-324. Epub 2020 Apr 12.

Queen Elizabeth Hospital, University of Adelaide, Adelaide, Australia.

: A multimodal approach in operable early-stage oesophago-gastric (OG) cancer has evolved in the last decade, leading to improvement in overall outcomes.: A review of the published literature and conference abstracts was undertaken on the topic of optimal adjunctive chemotherapy or chemoradiotherapy in early-stage OG cancers. This review article focuses on the current evidence pertaining to neoadjuvant and perioperative strategies in curable OG cancers including the evolving landscape of immunotherapy and targeted drugs in this setting.: Adjunctive therapies in the form of preoperative chemo-radiotherapy (CRT) or chemotherapy and perioperative chemotherapy over surgery alone improve outcomes in patients with operable OG cancer. Although there are variations in practice around the world, a multi-disciplinary approach to patient care is of paramount importance. Immunotherapy and on treatment functional imaging are two examples of emerging strategies to improve the outcome for early-stage patients. A better understanding of the molecular biology of this disease may help overcome the problem of tumor heterogeneity and enable more rationally designed and targeted therapeutic interventions in the future.
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http://dx.doi.org/10.1080/14737140.2020.1746185DOI Listing
April 2020

Update on optimal treatment for metastatic colorectal cancer from the AGITG expert meeting: ESMO congress 2019.

Expert Rev Anticancer Ther 2020 04 6;20(4):251-270. Epub 2020 Apr 6.

Medical Oncology, The Queen Elizabeth Hospital, Woodville, Australia.

: Outcomes in metastatic colorectal cancer are improving, due to the tailoring of therapy enabled by better understanding of clinical behavior according to molecular subtype.: A review of the literature and recent conference presentations was undertaken on the topic of systemic treatment of metastatic colorectal cancer. This review summarizes expert discussion of the current evidence for therapies in metastatic colorectal cancer (mCRC) based on molecular subgrouping.: EGFR-targeted and VEGF-targeted antibodies are now routinely incorporated into treatment strategies for mCRC. EGFR-targeted antibodies are restricted to patients with extended wild-type profiles, with evidence that they should be further restricted to patients with left-sided tumors. Clinically distinct treatment pathways based on tumor and MMR status, are now clinically applicable. Evidence suggests therapy for additional subgroups will soon be defined; the most advanced being for patients with G12 C mutation and gene fusion defects.
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http://dx.doi.org/10.1080/14737140.2020.1744439DOI Listing
April 2020

Medical Oncologists' Perspectives on How the Results of the IDEA Collaboration Impact the Adjuvant Treatment of Stage III Colon Cancer.

Oncologist 2020 03 22;25(3):229-234. Epub 2019 Oct 22.

BC Cancer, Vancouver, British Columbia, Canada.

Background: The International Duration Evaluation of Adjuvant Chemotherapy (IDEA) collaboration aimed to evaluate whether 3 months of adjuvant chemotherapy are noninferior to 6 months. Our study objectives were to characterize medical oncologists' perspectives toward the results of the IDEA collaboration and to evaluate how IDEA impacted prescribing patterns of adjuvant FOLFOX and CAPOX in colon cancer.

Materials And Methods: A list of questions developed by four medical oncologists regarding IDEA results were formulated and distributed online to gastrointestinal medical oncologists globally. Descriptive statistics and chi-square tests were used to summarize information.

Results: Of 174 responses, 145 were complete and analyzed. Responses were obtained globally from South America (53%); the U.S. and Canada (28%); Europe, Australia, and New Zealand (12%); and Asia (7%). Most clinicians (98%) were aware of the IDEA study. Prior to IDEA, clinicians preferred FOLFOX over CAPOX (81% vs. 19%). Subsequent to IDEA, 55% of clinicians preferred CAPOX over FOLFOX (odds ratio, 5.0; 95% confidence interval, 3.0-8.5; p < .01 compared with pre-IDEA). Two thirds (68%) of responders tailored duration of adjuvant therapy based on risk stratification. Most oncologists (76%) were more willing to discontinue oxaliplatin early if toxicities develop after the results of IDEA. Half of responders (50%) found that IDEA increased their confidence in decision making for adjuvant treatment; 36% were unchanged, and 15% indicated decreased confidence. Less than half (48%) were comfortable communicating the study results and the concept of a noninferiority trial with patients.

Conclusion: IDEA appears to have shifted clinician preference from FOLFOX to CAPOX for adjuvant therapy, and most clinicians now use a risk-stratified approach in determining duration of adjuvant therapy. Patient education resources may facilitate better communication of IDEA results to patients.

Implications For Practice: This global survey illustrates that most gastrointestinal medical oncologists now use a risk-stratified approach for determining the duration of adjuvant chemotherapy for stage III colon cancer. Clinicians are five times more likely to choose CAPOX over FOLFOX after the International Duration Evaluation of Adjuvant Chemotherapy (IDEA) collaboration results.
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http://dx.doi.org/10.1634/theoncologist.2019-0553DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7066691PMC
March 2020

The prognostic role of inflammatory markers in patients with metastatic colorectal cancer treated with bevacizumab: A translational study [ASCENT].

PLoS One 2020 6;15(3):e0229900. Epub 2020 Mar 6.

Medical Oncology, Austin Health, Heidelberg, Australia.

Background: In spite of demonstrating prognostic and possibly predictive benefit in retrospective cohorts and meta-analyses of cancer populations, including colorectal cancer (CRC), prospective evaluation of the relationship between neutrophil to lymphocyte ratio (NLR) and treatment outcomes in previously untreated mCRC patients receiving bevacizumab-based therapy has not yet been performed.

Methods: An open-label, single arm, multi-centre study. Patients received first-line bevacizumab plus XELOX or mFOLFOX6 (Phase-A) and continued bevacizumab plus FOLFIRI beyond first progression (Phase-B). Analyses included the association of NLR with phase A progression free survival (PFS) and overall survival (OS). A sub-study investigated the safety in patients with the primary in situ tumor. An exploratory sub-study examined relationships of circulating proteomic markers with PFS.

Results: Phase-A enrolled 128 patients; median age was 64 years (range: 26-84), 70 (55%) were female, 71 (56%) were PS-0 and 51 (40%) had primary in situ tumor. Fifty-three (41%) patients entered Phase-B. The median baseline (b) NLR was 3.2 (range: 1.5-20.4) with 32 (25%) patients having bNLR > 5. The PFS hazard ratio (HR) by bNLR > 5 versus ≤ 5 was 1.4 (95% CI: 0.9-2.2; p = 0.101). The median PFS was 9.2 months (95% CI: 7.9-10.8) for Phase-A and 6.7 months (95% CI: 3.0-8.2) for Phase-B. The HR for OS based on bNLR > 5 versus ≤ 5 was 1.6 (95% CI: 1.0-2.7; p = 0.052). The median OS was 25 months (95% CI: 19.2-29.7) for the full analysis set and 14.9 months for Phase-B. Baseline levels of nine proteomic markers showed a relationship with PFS. Treatment related toxicities were consistent with what has previously been published. There were 4 (3%) instances of GI perforation, of which, 3 (6%) occurred in the primary in situ tumor group.

Conclusions: Results from this study are aligned with the previously reported trend towards worse PFS and OS in patients with higher bNLR.

Trial Registration: ClinicalTrials.gov: NCT01588990; posted May 1, 2012.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0229900PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7059922PMC
June 2020

Oncofertility as a Universal Right and a Global Oncology Priority.

JCO Glob Oncol 2020 03;6:314-316

Monash Health and Monash University, Clayton, Victoria, Australia.

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http://dx.doi.org/10.1200/GO.19.00337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7113082PMC
March 2020

The Economic Impact on Australian Patients with Neuroendocrine Tumours.

Patient 2020 06;13(3):363-373

School of Nursing and Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, Brisbane, QLD, 4059, Australia.

Background And Objective: Little is known about the economic burden to patients and families with neuroendocrine tumours (NETs) for medical out-of-pocket expenses and employment decisions. This study was performed to determine the extent and factors influencing the financial consequences of living with NETs and their effect on quality of life.

Methods: We undertook an online cross-sectional survey using a targeted approach and collected Australian Medicare claims data. Validated surveys measured health-related quality of life (EuroQol 5-dimension 5-level [EuroQol-5D-5L]) and financial toxicity (COmprehenSive Financial Toxicity [COST]), supplemented with questions on employment and retirement, insurance and out-of-pocket medical expenses. Generalised linear models were performed to assess determinants of quality of life and out-of-pocket expenses recorded by Medicare.

Results: The survey was answered by 204 patients with a mean age of 59 years who were diagnosed on average 5.2 years ago. Self-reported mean costs were 1698 Australian dollars ($A) (standard deviation [SD] $A2132) over 3 months (median $A877) and were highest for medical tests (mean $A376 [17% of total costs], SD $A722), travel-related expenses (mean $A289 [13%], SD $A559), and specialist visits (mean $A225 [10%], SD $A342) ($A1 = $US0.69). Imaging scans, surgery and travel expenses were the most common cost burdens reported by patients. Having private health insurance was the key determinant of higher out-of-pocket costs. Poorer quality of life was significantly associated with higher financial toxicity, not working due to cancer, nausea/diarrhoea, two or more co-morbidities and younger age.

Conclusions: Medical expenses are substantial for some patients with NETs. Quality of life is adversely affected for patients experiencing financial toxicity and avoiding early retirement is an important issue for supportive care services.
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http://dx.doi.org/10.1007/s40271-020-00412-zDOI Listing
June 2020

Cancer and Indigenous Populations: Time to End the Disparity.

JCO Glob Oncol 2020 02;6:80-82

Menzies School of Health Research, Darwin, Northern Territory, Australia.

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http://dx.doi.org/10.1200/JGO.19.00379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6998017PMC
February 2020

Circulating epigenetic biomarkers for detection of recurrent colorectal cancer.

Cancer 2020 04 7;126(7):1460-1469. Epub 2020 Jan 7.

Flinders Centre for Innovation in Cancer, Flinders University, Bedford Park, South Australia, Australia.

Background: The sensitive detection of recurrent colorectal cancer (CRC) by the measurement of circulating tumor DNA (ctDNA) might improve the chance of a cure. This study compared a quantitative methylated ctDNA test with carcinoembryonic antigen (CEA) in the setting of surveillance for recurrence.

Methods: Blood samples collected either during surveillance or within 12 months of the confirmation of recurrence were assayed for ctDNA (methylated branched-chain amino acid transaminase 1 [BCAT1]/Ikaros family zinc-finger 1 protein [IKZF1]) and CEA. The optimal ctDNA threshold was determined by receiver operating characteristic analysis, and the test performance for the detection of recurrence was compared with CEA (5 ng/mL threshold).

Results: The study cohort comprised 144 eligible patients and included 50 recurrence events. The sensitivity of the methylated ctDNA test for recurrence was 66.0% (95% confidence interval [CI], 57.1%-69.3%), which was significantly higher than the sensitivity of CEA (31.9%; 95% CI, 22.8%-36.6%; P < .001). The sensitivity for resectable recurrence (n = 20) was also higher (ctDNA, 60.0%; CEA, 20.0%; P = .01). The specificity did not differ between the tests (ctDNA, 97.9%; 95% CI, 93.2%-99.6%; CEA, 96.4%; 95% CI, 91.4%-99.0%). When adjustments were made for other predictors of the presence of recurrence, a positive ctDNA test was an independent predictor (odds ratio, 155.7; 95% CI, 17.9-1360.6; P < .001), whereas CEA was not (odds ratio, 2.5; 95% CI, 0.3-20.6; P = .407).

Conclusions: The quantitative ctDNA test showed superior sensitivity in comparison with CEA without a difference in the specificity for detecting recurrent CRC. Longitudinal studies are warranted to further assess the utility (specifically the survival benefit) of methylated BCAT1/IKZF1 ctDNA in the surveillance of patients with CRC.
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http://dx.doi.org/10.1002/cncr.32695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7155014PMC
April 2020

Is there a place for Ramucirumab after Sorafenib in patients with advanced HCC?

Hepatobiliary Surg Nutr 2019 Oct;8(5):546-548

Medical Oncology, Monash Health, Melbourne, Australia.

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http://dx.doi.org/10.21037/hbsn.2019.04.14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6791970PMC
October 2019

Consensus-Derived Quality Performance Indicators for Neuroendocrine Tumour Care.

J Clin Med 2019 Sep 12;8(9). Epub 2019 Sep 12.

Discipline of Oncology, Faculty of Medicine and Health Sciences, The University of Auckland, Auckland 1023, New Zealand.

Quality performance indicators (QPIs) are used to monitor the delivery of cancer care. Neuroendocrine tumours (NETs) are a family of individually uncommon cancers that derive from neuroendocrine cells or their precursors, and can occur in most organs. There are currently no QPIs available for NETs and their heterogeneity makes QPI development difficult. CommNETs is a collaboration between NET clinicians, researchers and advocates in Canada, Australia and New Zealand. We created QPIs for NETs using a three-step consensus process. First, a multidisciplinary team used the nominal group technique to create candidates ( = 133) which were then curated into appropriateness statements (62 statements, 44 sub-statements). A two-stage modified RAND/UCLA Delphi consensus process was conducted: an online survey rated the statement appropriateness then the top-ranked statements ( = 20) were assessed in a face-to-face meeting. Finally, 10 QPIs met consensus criteria; documentation of primary site, proliferative index, differentiation, tumour board review, use of a structured pathology report, presence of distant metastasis, 5- and 10-year disease-free and overall survival. These NET QPIs will be trialed as a method to monitor and improve care for people with NETs and to facilitate international comparison.
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http://dx.doi.org/10.3390/jcm8091455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6780732PMC
September 2019

Multifocal hepatic steatosis mimicking malignancy in two siblings.

JGH Open 2019 Aug 11;3(4):346-348. Epub 2019 Feb 11.

Department of Diagnostic Imaging St Vincent's Public Hospital Sydney New South Wales Australia.

Multifocal hepatic steatosis (MHS) is a rare subtype of hepatic steatosis which can pose a diagnostic challenge due to difficulty in distinguishing it from malignant disease. Steatotic nodules in MHS can vary in size from a few millimeters to several centimeters and may mimic hepatocellular carcinoma or metastases by both ultrasound and computed tomography assessment. Accurate detection of this abnormality is important and may prevent unnecessary investigation and biopsy, as well as anxiety for the patient. Here we present two cases of MHS occurring in adult siblings. The characteristic radiographic appearances of MHS will be described as well as tips provided for accurate detection. Given the rarity of this entity, the occurrence in two otherwise well adult siblings also raises the possibility of an inherited pathogenesis.
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http://dx.doi.org/10.1002/jgh3.12142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6684502PMC
August 2019

Physical Activity for Symptom Management in Women With Metastatic Breast Cancer: A Randomized Feasibility Trial on Physical Activity and Breast Metastases.

J Pain Symptom Manage 2019 12 30;58(6):929-939. Epub 2019 Jul 30.

Faculty of Health Sciences, The University of Sydney, Lidcombe, Australia. Electronic address:

Context: Physical activity for women with early-stage breast cancer is well recognized for managing cancer-related symptoms and improving quality of life. While typically excluded from interventions, women with metastatic breast cancer may also benefit from physical activity.

Objective: To 1) determine the safety and feasibility of a physical activity program for women with metastatic breast cancer and 2) explore the efficacy of the program.

Methods: Fourteen women with metastatic breast cancer were randomized to either a control group or an 8-week home-based physical activity intervention comprising twice weekly supervised resistance training and an unsupervized walking program.

Results: The recruitment rate was 93%. Adherence to the resistance and walking components of the program was 100% and 25%, respectively. No adverse events were reported. When mean change scores from baseline to postintervention were compared, trends in favor of the exercise group over the control group were observed for the Functional Assessment of Chronic Illness Therapy-Fatigue score (+5.6 ± 3.2 vs. -1.8 ± 3.9, respectively), VO (+1.6 ml/kg/minute ±1.8 mL/kg/minute vs. -0.2 mL/kg/minute ±0.1 mL/kg/minute, respectively) and six-minute walk test (+40 m ± 23 m vs. -46 m ± 56 m, respectively).

Conclusion: A partially supervised home-based physical activity program for women with metastatic breast cancer is feasible and safe. The dose of the resistance training component was well tolerated and achievable in this population. In contrast, adherence and compliance to the walking program were poor. Preliminary data suggest a physical activity program, comprising predominantly resistance training, may lead to improvements in physical capacity and may help women to live well with their disease.
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http://dx.doi.org/10.1016/j.jpainsymman.2019.07.022DOI Listing
December 2019