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Clinical utility of tumour mutational burden on efficacy of immune checkpoint inhibitors in malignant solid tumours: protocol for a systematic review and meta-analysis

Por: Xiang · X. · Li · Y. · Yang · X. · Guo · W. · Zhou · P.
Introduction

A major development in solid malignancy treatment is the application of immune checkpoint inhibitors (ICIs), which have produced durable responses and increased survival rates. However, the therapeutic effect of ICIs has great heterogeneity in patients with cancer. We propose a systematic review to evaluate the predictive value of tumour mutation burden (TMB) on efficacy of ICIs.

Methods and analysis

A systematic literature search will be conducted in the PubMed, OVID, Web of Science, Embase and Cochrane Central Register of Controlled Trials Library databases up to 31 May 2022. We will compare the efficacy of ICIs between TMB high group and TMB low group in terms of the HRs of overall survival (OS) and progression-free survival (PFS), and the OR of the objective response rate/overall response rate (ORR). The HRs of PFS and OS, and the OR of ORR, will be measured by an inverse variance weighted fixed effects model (I2≤50%) or a DerSimonian-Laird random effects model (I2>50%). In addition, subgroup analysis, sensitivity analysis, heterogeneity analysis and publication bias will be conducted. We plan to conduct a subgroup analysis on age, sex, area, number of patients (high/low TMB), cancer type, tumour size, stage, line of therapy, TMB sequencing method, type of immunotherapy and follow-up period.

Ethics and dissemination

Ethical approval and informed consent are not needed, as the study will be a literature review and will not involve direct contact with patients or alterations to patient care. This systematic review is anticipated to be finished in December 2023, and the results will be published in a peer-reviewed journal.

PROSPERO registration number

CRD42021262480.

Factors affecting the implementation of guideline-based prophylactic antiemetic therapy for chemotherapy-induced nausea and vomiting in Japan: a protocol for a hospital-based qualitative study

Por: Yaguchi-Saito · A. · Kaji · Y. · Matsuoka · A. · Okuyama · A. · Fujimori · M. · Saito · J. · Odawara · M. · Otsuki · A. · Uchitomi · Y. · Zenda · S. · Shimazu · T.
Introduction

Chemotherapy-induced nausea and vomiting (CINV) decrease patients’ quality of life and negatively impact treatment outcomes. Although standard prophylactic antiemetic therapy for acute CINV recommended by guidelines is effective, poor guideline implementation is a worldwide problem. In Japan, prophylactic antiemetic therapy is relatively well implemented for chemotherapy associated with high emetogenic risk, while implementation gaps are observed for that with low emetogenic risk.

Although most reports on factors influencing appropriate antiemetic prescription focus on physicians’ attitudes and behaviours, a more comprehensive exploration is needed since chemotherapy is expected to involve pharmacists, nurses and eventually hospital directors. The purpose of this qualitative study is to comprehensively explore the factors that influence the implementation of appropriate prophylactic antiemetic procedures at cancer care hospitals in Japan.

Methods and analysis

This study is a hospital-based qualitative study using semistructured individual interviews. The target population will be hospital directors, and chiefs (including proxies) of departments of oncology and/or chemotherapy, pharmacy and nursing, working in the hospitals, selected by purposive sampling. We will obtain information on antiemetics in chemotherapy regimens, antiemetic routine use and awareness of guidelines using prequestionnaires. Interviews will then be conducted online using an interview guide. The Consolidated Framework for Implementation Research will be used to collect and analyse the interview data. We will also create new codes inductively, as required. In addition, we will refer to the aggregate results of the Quality Indicator survey to determine the implementation of recommended antiemetic prescriptions for each hospital and discuss the relationship with influencing factors.

Ethics and dissemination

This study has been approved by the National Cancer Centre Ethics Approval Committee (approval number: 2020-305). The study findings will be disseminated via peer-reviewed journal publications and presentations to academics, policy-makers, and clinicians at scientific conferences.

RECIST 1.1 versus mRECIST for assessment of tumour response to molecular targeted therapies and disease outcomes in patients with hepatocellular carcinoma: a systematic review and meta-analysis

Por: Yu · H. · Bai · Y. · Xie · X. · Feng · Y. · Yang · Y. · Zhu · Q.
Objectives

Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1) and modified RECIST (mRECIST) are commonly used to assess tumour response. Which one is better to evaluate efficacy after molecular targeted therapies in hepatocellular carcinoma (HCC) patients is still controversial. A systemic review was performed to compare the objective response rate (ORR) and disease control rate (DCR) and a meta-analysis was conducted to compare the correlation between objective response and overall survival (OS).

Design

Systematic review and meta-analysis using the Grading of Recommendations Assessment, Development and Evaluation approach.

Data sources

EMBASE, PubMed, Web of Science and Cochrane Library were searched through 31 December 2021.

Eligibility criteria

We included studies assessing the efficacy of molecular targeted therapy for HCC according to both RECIST 1.1 and mRECIST.

Data extraction and synthesis

Two investigators extracted data independently. The consistency between RECIST 1.1 vs mRECIST is measured by the k coefficient. HRs with corresponding 95% CIs were used for meta-analysis.

Results

23 studies comprising 2574 patients were included in systematic review. The ORR according to mRECIST is higher than RECIST1.1 (15.9% vs 7.8%, p=0.0004) calculated from 7 studies including 566 patients, however, the RECIST1.1 could not distinguish the OS well (HR 0.68, 95% CI 0.44 to 1.05, p=0.08). Subgroup analusis by type of treatment was conducted.

Conclusions

mRECIST may be more accurate than RECIST 1.1 in assessing ORR after molecular targeted therapies in HCC patients and can better assess the prognosis. However, the performance of both criteria in assessing disease progression is identical.

PROSPERO registration number

CRD42020200895.

Ethics approval

Ethics approval is not required in this meta-analysis.

Web-based mindfulness and skills-based distress reduction for patients with cancer: study protocol of the multicentre, randomised, controlled confirmatory intervention trial Reduct

Por: Bäuerle · A. · Martus · P. · Erim · Y. · Schug · C. · Heinen · J. · Krakowczyk · J. B. · Steinbach · J. · Damerau · M. · Bethge · W. · Dinkel · A. · Dries · S. · Mehnert-Theuerkauf · A. · Neumann · A. · Schadendorf · D. · Tewes · M. · Wiltink · J. · Wünsch · A. · Zipfel · S. · Graf · J.
Introduction

Many patients with cancer experience severe psychological distress, but as a result of various barriers, few of them receive psycho-oncological support. E-mental health interventions try to overcome some of these barriers and the limitation of healthcare offers, enabling patients with cancer to better cope with psychological distress. In the proposed trial, we aim to assess the efficacy and cost-effectiveness of the manualised e-mental health intervention Make It Training- Mindfulness-Based and Skills-Based Distress Reduction in Oncology. Make It Training is a self-guided and web-based psycho-oncological intervention, which includes elements of cognitive behavioural therapy, mindfulness-based stress reduction and acceptance and commitment therapy. The training supports the patients over a period of 4 months. We expect the Make It Training to be superior to treatment as usual optimised (TAU-O) in terms of reducing distress after completing the intervention (T1, primary endpoint).

Methods and analysis

The study comprises a multicentre, prospective, randomised controlled confirmatory interventional trial with two parallel arms. The proposed trial incorporates four distinct measurement time points: the baseline assessment before randomisation, a post-treatment assessment and 3 and 6 month follow-up assessments. We will include patients who have received a cancer diagnosis in the past 12 months, are in a curative treatment setting, are 18–65 years old, have given informed consent and experience high perceived psychological distress (Hospital Anxiety and Depression Scale ≥13) for at least 1 week. Patients will be randomised into two groups (Make It vs TAU-O). The aim is to allocate 600 patients with cancer and include 556 into the intention to treat analysis. The primary endpoint, distress, will be analysed using a baseline-adjusted ANCOVA for distress measurement once the intervention (T1) has been completed, with study arm as a binary factor, baseline as continuous measurement and study centre as an additional categorical covariate.

Ethics and dissemination

The Ethics Committee of the Medical Faculty Essen has approved the study (21-10076-BO). Results will be published in peer-reviewed journals, conference presentations, the project website, and among self-help organisations.

Trial registration number

German Clinical Trial Register (DRKS); DRKS-ID: DRKS00025213.

Factors that influence clinical trial participation by patients with cancer in Australia: a scoping review protocol

Por: You · K. H. · Lwin · Z. · Ahern · E. · Wyld · D. · Roberts · N.
Introduction

Clinical trials are the backbone of research. It is well recognised that patient participation in clinical trials can be influenced by a myriad of factors such as access to a clinical trial, restrictive trial eligibility criteria and perceptions held by patients or physicians about clinical trials. Australia is a key stakeholder in the global clinical trials sphere. This scoping review protocol aims to identify and map the current literature describing factors that influence clinical trial participation of patients with cancer, in Australia.

Methods and analyses

The Joanna Briggs Institute (JBI) methodology for scoping reviews will be used to conduct this review. Four electronic databases will be systematically searched for relevant published literature on this topic, as a collaborative process involving the lead investigator and a health science librarian. We will hand search of citations and reference lists of the included papers, and a grey literature search through Google scholar, Grey Literature Report, Web of Science Conference Proceedings. All published papers pertaining to patients diagnosed with solid organ or haematological malignancies will be included. Studies which did not involve patients from Australia will also be excluded. A customised data extraction tool will be pilot tested and refined, and subsequently two independent reviewers will perform data screening and extraction. Results will be collated and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for scoping reviews: PRISMA-Scoping Reviews. Quantitative data will be presented using descriptive statistics. Qualitative data will be synthesised using thematic analyses. This scoping review does not require ethical approval as the methodology focuses on analysing information from available published data.

Ethics and dissemination

Results will be disseminated to relevant stakeholders including consumers, clinicians, professional organisations and policy-makers through peer-reviewed publications and national and international conferences.

Concurrent chemoradiation and brachytherapy alone or in combination with nelfinavir in locally advanced cervical cancer (NELCER): study protocol for a phase III trial

Por: Chopra · S. · Goda · J. S. · Mittal · P. · Mulani · J. · Pant · S. · Pai · V. · Kannan · S. · Deodhar · K. · Krishnamurthy · M. N. · Menon · S. · Charnalia · M. · Shah · S. · Rangarajan · V. · Gota · V. · Naidu · L. · Sawant · S. · Thakkar · P. · Popat · P. · Ghosh · J. · Rath · S. · Gulia · S.
Introduction

In locally advanced cervical cancer, nodal, local and distant relapse continue to be significant patterns of relapse. Therefore, strategies to improve the efficacy of chemoradiation are desirable such as biological pathway modifiers and immunomodulating agents. This trial will investigate the impact of nelfinavir, a protease inhibitor that targets the protein kinase B (AKT) pathway on disease-free survival (DFS).

Methods and analysis

Radiosensitising effect of nelfinavir in locally advanced carcinoma of cervix is a single-centre, open-label, parallel-group, 1:1 randomised phase-III study. Patients aged over 18 years with a diagnosis of carcinoma cervix stage III are eligible for the study. After consenting, patients will undergo randomisation to chemoradiation and brachytherapy arm or nelfinavir with chemoradiation and brachytherapy arm. The primary aim of the study is to compare the difference in 3-year DFS between the two arms. Secondary aims are locoregional control, overall survival, toxicity and quality of life between the two arms. Pharmacokinetics of nelfinavir and its impact on tumour AKT, programmed cell death ligand 1, cluster of differentiation 4, cluster of differentiation 8 and natural killer 1.1 expression will be investigated. The overall sample size of 348 with 1 planned interim analysis achieves 80% power at a 0.05 significance level to detect a HR of 0.66 when the proportion surviving in the control arm is 0.65. The planned study duration is 8 years.

Ethics and dissemination

The trial is approved by the Institutional Ethics Committee-I of Tata Memorial Hospital, Mumbai (reference number: IEC/0317/1543/001) and will be monitored by the data safety monitoring committee. The study results will be disseminated via peer-reviewed scientific journals, and conference presentations. Study participants will be accrued after obtaining written informed consent from them. The confidentiality and privacy of study participants will be maintained.

Trial registration number

The trial is registered with Clinical Trials Registry-India (CTRI/2017/08/009265) and ClinicalTrials.gov (NCT03256916).

Evaluation of the psychometric properties of patient-reported and clinician-reported outcome measures of chemotherapy-induced peripheral neuropathy: a COSMIN systematic review protocol

Por: Berube-Mercier · P. · Tapp · D. · Cimon · M.-E. · Li · T. · Park · S. B. · Bouhelier · E. · McGarragle · K. · Robichaud · L.-A. · Gewandter · J. S. · Bouchard · M. · Gauthier · L. R.
Introduction

Chemotherapy-induced peripheral neuropathy (CIPN) is a poorly understood side effect of many antineoplastic agents. Patients may experience sensory, motor and autonomic symptoms, negatively impacting quality of life. A gold-standard assessment methodology has yet to be determined, limiting efforts to identify effective agents to prevent or treat CIPN.

Methods and analysis

This is a protocol of a systematic review of psychometric analyses of CIPN Clinician Reported Outcome Measures (ClinROM) and Patient-Reported Outcome Measures (PROM) among adults receiving, or who had previously received chemotherapy for cancer. The COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) quality ratings will be compared across studies and across ClinROMs and PROMs. Studies reporting psychometric proprieties of CIPN ClinROMs and/or PROMs among adults aged ≥18 years will be eligible for inclusion, with no restriction on language or year of publication. MEDLINE, Embase, CINAHL and APA PsycINFO databases will be searched from inception to 31 December 2021. Study characteristics, measurement properties of the ClinROMs and/or PROMs and the CIPN definitions will be extracted. The Synthesis Without Meta-analysis guideline will be used to guide data synthesis. The COSMIN Risk of Bias checklist will be used by two independent raters to assess methodological quality. Subgroup analyses by age, chemotherapy type, and study timing in relation to the delivery of chemotherapy will be carried out where data are available. An adapted version of Outcome Measures in Rheumatology filter 2.1 will be used to provide a best-evidence synthesis of CIPN ClinROMs and PROMs and to recommend a CIPN assessment tool for clinical and research settings.

Ethics and dissemination

Ethical approval is not necessary to be obtained for this systematic review protocol. Results will be disseminated to clinicians and policy-makers by publication in a peer-reviewed journal and by presenting at relevant conferences.

PROSPERO registration number

CRD42021278168.

Active surveillance of chemotherapy-related symptom burden in ambulatory cancer patients via the implementation of electronic patient-reported outcomes and sensor-enabled vital signs capture: protocol for a decentralised feasibility pilot study

Por: Offodile · A. C. · DiBrito · S. R. · Finder · J. P. · Shete · S. · Jain · S. · Delgado · D. A. · Miller · C. J. · Davidson · E. · Overman · M. J. · Peterson · S. K.
Introduction

Remote patient monitoring (RPM) has emerged as a potential avenue for optimising the management of symptoms in patients undergoing chemotherapy. However, RPM is a complex, multilevel intervention with technology, workflow, contextual and patient experience components. The purpose of this pilot study is to determine the feasibility of RPM protocol implementation with respect to decentralised recruitment, patient retention, adherence to reporting recommendations, RPM platform usability and patient experience in ambulatory cancer patients at high risk for chemotherapy-related symptoms.

Methods and analysis

This protocol describes a single-arm decentralised feasibility pilot study of technology-enhanced outpatient symptom management system in patients with gastrointestinal and thoracic cancer receiving chemotherapy and cancer care at a single site (MD Anderson Cancer Center, Houston Texas). An anticipated total of 25 patients will be recruited prior to the initiation of chemotherapy and provided with a set of validated questionnaires at enrollment and after our 1-month feasibility pilot trial period. Our intervention entails the self-reporting of symptoms and vital signs via a HIPAA-compliant, secure tablet interface that also enables (1) the provision of self-care materials to patients, (2) generation of threshold alerts to a dedicated call-centre and (3) videoconferencing. Vital sign information (heart rate, blood pressure, pulse, oxygen saturation, weight and temperature) will be captured via Bluetooth-enabled biometric monitoring devices which are integrated with the tablet interface. Protocolised triage and management of symptoms will occur in response to the alerts. Feasibility and acceptability metrics will characterise our recruitment process, protocol adherence, patient retention and usability of the RPM platform. We will also document the perceived effectiveness of our intervention by patients.

Ethics and dissemination

This study has been granted approval by the institutional review board of MD Anderson Cancer Center. We anticipate dissemination of our pilot and subsequent effectiveness trial results via presentations at national conferences and peer-reviewed publications in the relevant medical journals. Our results will also be made available to cancer survivors, their caregivers and hospital administration.

Trial registration number

NCI202107464.

Precision medicine for liver tumours with quantitative MRI and whole genome sequencing (Precision1 trial): study protocol for observational cohort study

Por: Welsh · F. K. · Connell · J. J. · Kelly · M. · Gooding · S. · Banerjee · R. · Rees · M.
Introduction

Radiogenomic analysis of patients being considered for liver resection is seldom performed in the clinic despite recent evidence indicating that quantitative MRI could improve posthepatectomy outcomes. Meanwhile, the increasingly accessible results from whole genome sequencing reporting on clinically actionable genetic biomarkers are yet to be fully integrated into the clinical care pathway.

Methods and analysis

A prospective observational cohort study of up to 200 participants is planned, recruiting adults with primary or secondary liver cancer being considered for liver resection at Hampshire Hospitals NHS Foundation Trust. The data will be evaluated to address the primary endpoint to calculate the proportion of participants in which the results from whole genome sequencing would have resulted in a change in clinical management. Participants will be offered an additional non-invasive quantitative MRI scan prior to the operation and the impact of the imaging results on treatment decision-making will be evaluated.

Ethics and dissemination

This study was reviewed by the NHS Health Research Authority and given favourable opinion by the Brighton and Sussex Research Ethics Committee (REC reference: 20/PR/0222). Research findings will be discussed with a patient and public involvement and engagement group, presented at relevant scientific conferences and published in open access journals.

Trial registration number

NCT04597710

Evaluation of tyrosine kinase inhibitors combined with antiprogrammed cell death protein 1 antibody in tyrosine kinase inhibitor-responsive patients with microsatellite stable/proficient mismatch repair metastatic colorectal adenocarcinoma: protocol for o

Por: Dong · Q. · Diao · Y. · Sun · X. · Zhou · Y. · Ran · J. · Zhang · J.
Introduction

The prognosis of patients with advanced metastatic colorectal adenocarcinoma (mCRC) after multiple-line therapy remains poor due to the high tumour load, high level of malignancy and strong drug resistance. The application of programmed cell death protein 1 (PD-1) blockade alone for patients with microsatellite stable/proficient mismatch repair (MSS/pMMR) mCRC is ineffective. PD-1 blockade combined with antiangiogenic therapy has synergistic effects and has initially shown therapeutic effects. The aim of this trial is to explore the efficiency and safety of tyrosine kinase inhibitors (TKIs) combined with PD-1 blockade therapy in patients with mCRC with MSS/pMMR.

Methods and analysis

The screening phase of the trial will involve administering one cycle of TKIs (fruquintinib or regorafenib). Patients will be divided into three arms—arm A (obvious response to TKIs), arm B (general response to TKIs) and arm C (poor response to TKIs)—according to their response to TKIs, as determined by significant changes in imaging findings. Patients in arm A will then receive TKIs in combination with anti-PD-1 antibody, patients in arm C will withdraw from the study, and those in arm B will continue to take TKIs for another one further cycle. Next, patients with obvious response to TKIs will be reallocated to arm A, those with general response to TKIs will stay in arm B and will continue to take TKIs, and patients with poor response to TKIs will withdraw from the study. Administration of arm A or arm B will last until disease progression or intolerable toxicity. Anti-PD-1 antibody can be administered for up to 2 years. This trial will provide necessary data to improve the prognosis of patients with MSS/pMMR mCRC.

Trial registration number

NCT04483219; Pre-results.

Development and validation of multivariable machine learning algorithms to predict risk of cancer in symptomatic patients referred urgently from primary care: a diagnostic accuracy study

Por: Savage · R. · Messenger · M. · Neal · R. D. · Ferguson · R. · Johnston · C. · Lloyd · K. L. · Neal · M. D. · Sansom · N. · Selby · P. · Sharma · N. · Shinkins · B. · Skinner · J. R. · Tully · G. · Duffy · S. · Hall · G.
Objectives

To develop and validate tests to assess the risk of any cancer for patients referred to the NHS Urgent Suspected Cancer (2-week wait, 2WW) clinical pathways.

Setting

Primary and secondary care, one participating regional centre.

Participants

Retrospective analysis of data from 371 799 consecutive 2WW referrals in the Leeds region from 2011 to 2019. The development cohort was composed of 224 669 consecutive patients with an urgent suspected cancer referral in Leeds between January 2011 and December 2016. The diagnostic algorithms developed were then externally validated on a similar consecutive sample of 147 130 patients (between January 2017 and December 2019). All such patients over the age of 18 with a minimum set of blood counts and biochemistry measurements available were included in the cohort.

Primary and secondary outcome measures

sensitivity, specificity, negative predictive value, positive predictive value, Receiver Operating Characteristic (ROC) curve Area Under Curve (AUC), calibration curves

Results

We present results for two clinical use-cases. In use-case 1, the algorithms identify 20% of patients who do not have cancer and may not need an urgent 2WW referral. In use-case 2, they identify 90% of cancer cases with a high probability of cancer that could be prioritised for review.

Conclusions

Combining a panel of widely available blood markers produces effective blood tests for cancer for NHS 2WW patients. The tests are affordable, and can be deployed rapidly to any NHS pathology laboratory with no additional hardware requirements.

Primary care and cancer: an analysis of the impact and inequalities of the COVID-19 pandemic on patient pathways

Por: Watt · T. · Sullivan · R. · Aggarwal · A.
Objectives

We explore the routes to cancer diagnosis to further undertanding of the inequality in the reduction in detection of new cancers since the start of the pandemic. We use different data sets to assess stages in the cancer pathway: primary care data for primary care consultations, routine and urgent referrals and published analysis of cancer registry data for appointments and first treatments.

Setting

Primary and cancer care.

Participants

In this study we combine multiple data sets to perform a population-based cohort study on different areas of the cancer pathway. For primary care analysis, we use a random sample of 5 00 000 patients from the Clinical Practice Research Datalink. Postreferral we perform a secondary data analysis on the Cancer Wait Times data and the National Cancer Registry Analysis Service COVID-19 data equity pack.

Outcome measures

Primary care: consultation, urgent cancer referral and routine referral rates, then appointments following an urgent cancer referral, and first treatments for new cancer, for all and by quintile of patient’s local area index of multiple deprivation.

Results

Primary care contacts and urgent cancer referrals in England fell by 11.6% (95% CI 11.4% to 11.7%) and 20.2% (95% CI 18.1% to 22.3%) respectively between the start of the first non-pharmaceutical intervention in March 2020 and the end of January 2021, while routine referrals had not recovered to prepandemic levels. Reductions in first treatments for newly diagnosed cancers are down 16.3% (95% CI 15.9% to 16.6%). The reduction in the number of 2-week wait referrals and first treatments for all cancer has been largest for those living in poorer areas, despite having a smaller reduction in primary care contact.

Conclusions

Our results further evidence the strain on primary care and the presence of the inverse care law, and the dire need to address the inequalities so sharply brought into focus by the pandemic. We need to address the disconnect between the importance we place on the role of primary care and the resources we devote to it.

Coeliac plexus radiosurgery for pain management in patients with advanced cancer : study protocol for a phase II clinical trial

Por: Jacobson · G. · Fluss · R. · Dany-BenShushan · A. · Golan · T. · Meron · T. · Zimmermann · C. · Dawson · L. A. · Barry · A. · Miszczyk · M. · Buckstein · M. · Diaz Pardo · D. · Aguiar · A. · Hammer · L. · Dicker · A. P. · Ben-Ailan · M. · Morag · O. · Hausner · D. · Symon · Z. · Lawrence
Introduction

Pancreatic cancer is characterised by severe mid-back and epigastric pain caused by tumour invasion of the coeliac nerve plexus. This pain is often poorly managed with standard treatments. This clinical trial investigates a novel approach in which high-dose radiation (radiosurgery) is targeted to the retroperitoneal coeliac plexus nerve bundle. Preliminary results from a single institution pilot trial are promising: pain relief is substantial and side effects minimal. The goals of this study are to validate these findings in an international multisetting, and investigate the impact on quality of life and functional status among patients with terminal cancer.

Methods and analysis

A single-arm prospective phase II clinical trial. Eligible patients are required to have severe coeliac pain of at least five on the 11-point BPI average pain scale and Eastern Cooperative Oncology Group performance status of two or better. Non-pancreatic cancers invading the coeliac plexus are also eligible. The intervention involves irradiating the coeliac plexus using a single fraction of 25 Gy. The primary endpoint is the complete or partial pain response at 3 weeks. Secondary endpoints include pain at 6 weeks, analgesic use, hope, qualitative of life, caregiver burden and functional outcomes, all measured using validated instruments. The protocol is expected to open at a number of cancer centres across the globe, and a quality assurance programme is included. The protocol requires that 90 evaluable patients" be accrued, based upon the assumption that a third of patients are non-evaluable (e.g. due to death prior to 3-weeks post-treatment assessment, or spontaneous improvement of pain pre-treatment), it is estimated that a total of 120 patients will need to be accrued. Supported by Gateway for Cancer Research and the Israel Cancer Association.

Ethics and dissemination

Ethic approval for this study has been obtained at eight academic medical centres located across the Middle East, North America and Europe. Results will be disseminated through conference presentations and peer-reviewed publications.

Trial registration number

NCT03323489.

Non-operative management after chemoradiotherapy plus consolidation or sandwich (induction with bevacizumab and consolidation) chemotherapy in patients with locally advanced rectal cancer: a multicentre, randomised phase II trial (NOMINATE trial)

Por: Akiyoshi · T. · Shinozaki · E. · Taguchi · S. · Chino · A. · Hiratsuka · M. · Tominaga · T. · Nonaka · T. · Toda · S. · Matoba · S. · Matsui · S. · Okabayashi · K. · Mukai · T. · Hiyoshi · Y. · Yamaguchi · T. · Nagasaki · T. · Yamaguchi · K. · Ueno · M. · Kuroyanagi · H. · Fukunaga · Y. · Is
Introduction

Total mesorectal excision (TME) and postoperative adjuvant chemotherapy following neoadjuvant chemoradiotherapy (CRT) is the standard treatment for locally advanced rectal cancer (LARC). However, neoadjuvant CRT has no recognised impact on reducing distant recurrence, and patients suffer from a long-lasting impairment in quality of life (QOL) associated with TME. Total neoadjuvant therapy (TNT) is an alternative approach that could reduce distant metastases and increase the proportion of patients who could safely undergo non-operative management (NOM). This study is designed to compare two TNT regimens in the context of NOM for selecting a more optimal regimen for patients with LARC.

Methods and analysis

NOMINATE trial is a prospective, multicentre, randomised phase II selection design study. Patients must have clinical stage II or III (T3-T4Nany) LARC with distal location (≤5 cm from the anal verge or for those who are candidates for abdominoperineal resection or intersphincteric resection). Patients will be randomised to either arm A consisting of CRT (50.4 Gy with capecitabine) followed by consolidation chemotherapy (six cycles of CapeOx), or arm B consisting of induction chemotherapy (three cycles of CapeOx plus bevacizumab) followed by CRT and consolidation chemotherapy (three cycles of CapeOx). In the case of clinical complete response (cCR) or near cCR, patients will progress to NOM. Response assessment involves a combination of digital rectal examination, endoscopy and MRI. The primary endpoint is the proportion of patients achieving pathological CR or cCR≥2 years, defined as the absence of local regrowth within 2 years after the start of NOM among eligible patients. Secondary endpoints include the cCR rate, near cCR rate, rate of NOM, overall survival, distant metastasis-free survival, locoregional failure-free survival, time to disease-related treatment failure, TME-free survival, permanent stoma-free survival, safety of the treatment, completion rate of the treatment and QOL. Allowing for a drop-out rate of 10%, 66 patients (33 per arm) from five institutions will be accrued.

Ethics and dissemination

The study protocol was approved by Wakayama Medical University Certified Review Board in December 2020. Trial results will be published in peer-reviewed international journals and on the jRCT website.

Trial registration number

jRCTs051200121

Efficacy of virtual reality-based interventions for patients with breast cancer symptom and rehabilitation management: a systematic review and meta-analysis

Por: Zhang · H. · Xu · H. · Zhang · Z.-x. · Zhang · Q.
Objectives

To determine the effectiveness of virtual reality (VR)-based intervention on the symptoms and rehabilitation management in patients with breast cancer.

Design

Systematic review and meta-analysis.

Study selection

We included all eligible randomised controlled trials and quasi-experimental studies (published in English and Chinese).

Participants

Patients with breast cancer (≥18 years) undergoing cancer treatment.

Interventions

Any intervention administered to improve the symptoms and rehabilitation of patients with breast cancer. The control group was given conventional care.

Outcomes

All outcomes were as follows: pain, fatigue, anxiety, depressive symptoms, cognitive function, and range of motion of upper limb in patients with breast cancer.

Data sources

We searched PubMed, Embase, CENTRAL and SinoMed, four electronic databases, covering the database establishment period to January 2022.

Review methods

Two reviewers independently extracted content and data consistent with the prespecified framework and assessed risk bias. Random-effects meta-analysis was used to pool data across trials. Meta-analysis was performed using Review Manager V.5.4.

Results

A total of eight studies met the eligibility criteria and were included in this study. The combined effect size showed that VR was positive for improving patients’ anxiety(standard mean differenc (SMD)=–2.07, 95% CI= (–3.81 to –0.34), I2=95%) and abduction of upper limbs (MD=15.54, 95% CI= (12.79 to 18.29), I2=0%), but fatigue (SMD=–0.92, 95% CI= (–4.47 to 2.62), I2=99%) was not. Qualitative analysis showed VR improved patients' depressive symptoms, pain and cognitive function.

Conclusions

VR technology has a good effect on symptoms and rehabilitation management of patients with breast cancer, but the quality of evidence is low, and the sample size is small. To date, there are few intervention studies, therefore, giving precise recommendation or conclusion is difficult. We have a favourable view of this, and more clinical studies are needed in the future to improve the credibility of the results.

Decision regret regarding treatments among women with early-stage breast cancer: a systematic review protocol

Por: Liu · J. · Hunter · S. · Zhu · J. · Lee · R. L.-T. · Chan · S. W.-C.
Introduction

Women with early-stage breast cancer (EBC) are commonly required to make treatment decisions. Decision regret regarding treatments is an adverse outcome that negatively affects women’s psychological well-being and quality of life. A systematic review will be conducted to synthesise evidence about decision regret among women regarding treatments for EBC. The study will focus on levels of decision regret, what is regretted, and the factors associated with decision regret.

Methods and analysis

A systematic review will be conducted following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols 2015 checklist. Electronic databases, including CINAHL Complete, Embase, PubMed, Medline and Web of Science, will be searched for relevant articles published from 2000 to 2021. The reference lists of eligible studies will also be manually searched. All types of quantitative, qualitative and mixed-methods studies that report on decision regret regarding treatments among women with EBC will be included. The primary outcome of this review will be women’s levels of decision regret regarding breast cancer treatments. The secondary outcomes will include the content of their regrets, and the factors contributing to decision regret. The methodological quality of the studies will be assessed using the Joanna Briggs Institute appraisal tools. Meta-analysis and thematic synthesis approaches will be used to synthesise quantitative and qualitative data, respectively. A convergent parallel approach will be used to integrate quantitative and qualitative findings.

Ethics and dissemination

Ethical approval is not required for this systematic review. The findings of this work will be disseminated at international conferences and peer-reviewed journals. The findings of this systematic review will inform the development of decision interventions to improve the decision outcomes of breast cancer treatments.

PROSPERO registration number

CRD42021260041.

Effectiveness and safety of weekly therapy versus 3-weekly therapy of paclitaxel plus carboplatin in women with ovarian cancer: a protocol of systematic review and meta-analysis

Por: Qiu · W. · Fu · Y. · Dang · Y. · Cai · B. · Tuo · S. · Mao · B. · Lin · R. · Liu · Q. · Li · Y.
Introduction

Network meta-analyses have confirmed that paclitaxel plus carboplatin could improve progression-free survival (PFS) and overall survival (OS) compared with platinum alone. However, detailed implementation schedule (weekly or 3-weekly therapy) was not specified in clinical practice guidelines. Evidence from studies is also inconsistent. We will conduct a systematic review and meta-analysis to evaluate the benefits and harms of weekly therapy and 3-weekly therapy of paclitaxel combined with carboplatin in women with ovarian cancer.

Methods

We will search PubMed, EMBASE and the Cochrane Library databases to include relevant randomised controlled trials comparing weekly therapy versus 3-weekly therapy of paclitaxel combined with carboplatin for women with ovarian cancer. Random-effects model will be used to pool data for patient-reported outcomes including survival rate, OS, PFS and adverse events. Grading of Recommendation, Assessment, Development and Evaluation approach will be used to rate the quality of evidence.

Ethics and dissemination

This systematic review and meta-analysis will be based on published data and does not therefore require specific ethical approval or consent for participation. The results will be published in a peer-reviewed journal.

OSF registration number

10.17605/OSF.IO/GJUMA.

Histopathological profile of cervical biopsies in northern Malawi: a retrospective cross-sectional study

Por: Kaseka · P. U. · Kayira · A. · Chimbatata · C. S. · Chisale · M. R. O. · Kamudumuli · P. · Wu · T.-S. J. · Mbakaya · B. C. · Sinyiza · F. W.
Objectives

According to the WHO (2014), cervical cancer is the second most common cancer in women globally. More than 85% of the global cervical cancer morbidity and mortality occur in low-income and middle-income countries and the highest risk region is in Eastern and Southern Africa. Malawi has the highest age-standardised rate of cervical cancer in the world. This study was carried out to determine the histopathological profile of cervical biopsies in a public tertiary hospital in Mzuzu, northern region of Malawi.

Setting

A public tertiary hospital in Mzuzu, northern region of Malawi.

Participants

This was a retrospective study of all cervical biopsy specimen reports received in a public tertiary hospital in northern Malawi over a period of 5 years from July 2013 to June 2018. Demographic, clinical and diagnostic data were obtained from original histopathology reports.

Results

A total of 500 cervical biopsy reports were reviewed during the study period. The mean age of the patients was 41.99±12.5. Age ranged from 15 to 80 years. Cervicitis accounted for 46.0% (n=162) of the total non-malignant lesions seen, followed by cervical intraepithelial neoplasm, at 24.4% (n=86) and endocervical polyp, at 20.5% (n=72). Squamous cell carcinoma (SCC) accounted for 15.6% (n=78) of the total cervical biopsies studied and 85.7% of all total malignant lesions. Adenocarcinoma and undifferentiated carcinoma were 8.8% and 4.4%, respectively of the total malignant diagnosis. All patients with malignant lesions had HIV.

Conclusion

Our study shows that cervicitis and SCC were most common among non-malignant and malignant cervical biopsies, respectively. Since the frequency of cervical cancer is high, there is a need to have well detailed national policies to be put in place to increase detection of preinvasive lesions in order to reduce the prevalence of cervical cancer.

Prediction models for venous thromboembolism in ambulatory adults with pancreatic and gastro-oesophageal cancer: protocol for systematic review and meta-analysis

Por: Zaheer · A. · Naumovski · N. · Toohey · K. · Niyonsenga · T. · Yip · D. · Brown · N. · Mortazavi · R.
Introduction

Venous thromboembolism (VTE) is a common complication of cancer. Pancreatic and gastro-oesophageal cancers are among malignancies that have the highest rates of VTE occurrence. VTE can increase cancer-related morbidity and mortality and disrupt cancer treatment. The risk of VTE can be managed with measures such as using anticoagulant drugs, although the risk of bleeding may be an impeding factor. Therefore, a VTE risk assessment should be performed before the start of anticoagulation in individual patients. Several prediction models have been published, but most of them have low sensitivity and unknown clinical applicability in pancreatic or gastro-oesphageal cancers. We intend to do this systematic review to identify all applicable published predictive models and compare their performance in those types of cancer.

Methods and analysis

All studies in which a prediction model for VTE have been developed, validated or compared using adult ambulatory patients with pancreatic or gastro-oesphageal cancers will be identified and the reported predictive performance indicators will be extracted. Full text peer-reviewed journal articles of observational or experimental studies published in English will be included. Five databases (Medline, EMBASE, Web of Science, CINAHL and Cochrane) will be searched. Two reviewers will independently undertake each of the phases of screening, data extraction and risk of bias assessment. The quality of the selected studies will be assessed using Prediction model Risk Of Bias Assessment Tool. The results from the review will be used for a narrative information synthesis, and if the same models have been validated in multiple studies, meta-analyses will be done to pool the predictive performance measures.

Ethics and dissemination

There is no need for ethics approval because the review will use previously peer-reviewed articles. The results will be published.

PROSPERO registration number

CRD42021253887.

Disease progression in osteosarcoma: a multistate model for the EURAMOS-1 (European and American Osteosarcoma Study) randomised clinical trial

Por: Hazewinkel · A.-D. · Lancia · C. · Anninga · J. · van de Sande · M. · Whelan · J. · Gelderblom · H. · Fiocco · M.
Objectives

Investigating the effect of prognostic factors in a multistate framework on survival in a large population of patients with osteosarcoma. Of interest is how prognostic factors affect different disease stages after surgery, with stages of local recurrence (LR), new metastatic disease (NM), LR+NM, secondary malignancy, a second NM, and death.

Design

An open-label, international, phase 3 randomised controlled trial.

Setting

325 sites in 17 countries.

Participants

The subset of 1631 metastases-free patients from 1965 patients with high-grade resectable osteosarcoma, from the European and American Osteosarcoma Study.

Main outcome measures

The effect of prognostic factors on different disease stages, expressed as HRs; predictions of disease progression on an individual patient basis, according to patient-specific characteristics and history of intermediate events.

Results

Of 1631 patients, 526 experienced an intermediate event, and 305 died by the end of follow-up. An axial tumour site substantially increased the risk of LR after surgery (HR=10.84, 95% CI 8.46 to 13.86) and death after LR (HR=11.54, 95% CI 6.11 to 21.8). A poor histological increased the risk of NM (HR=5.81, 95% CI 5.31 to 6.36), which sharply declined after 3 years since surgery. Young patients (18 had a decreased risk of death after event (eg, for death after LR: HR=2.40, 95% CI 1.52 to 3.90; HR=0.35, 95% CI 0.21 to 0.56, respectively).

Conclusions

Our findings suggest that patients with axial tumours should be monitored for LR and patients with poor histological response for NM, and that for young patients (

Trial registration number

NCT00134030.

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