Living systematic review to assess the analgesic undertreatment in cancer patients.

Background And Aims: This living and systematic review aimed to provide an updated summary of the available evidence on pain undertreatment prevalence in patients with cancer; correlations with some potential determinants and confounders were also carried out.

Materials And Methods: We updated a systematic review published on 2014, including observational and experimental studies reporting the use of the pain management index (PMI) in adults with cancer and pain, from 2014 to 2020. We conducted searches in PubMed/MEDLINE, Embase, and Google Scholar.

European Society for Radiotherapy and Oncology Advisory Committee in Radiation Oncology Practice consensus recommendations on patient selection and dose and fractionation for external beam radiotherapy in early breast cancer.

High-quality randomised clinical trials testing moderately fractionated breast radiotherapy have clearly shown that local control and survival is at least as effective as with 2 Gy daily fractions with similar or reduced normal tissue toxicity. Fewer treatment visits are welcomed by patients and their families, and reduced fractions produce substantial savings for health-care systems. Implementation of hypofractionation, however, has moved at a slow pace.

Personalized (N-of-1) Trials for Patient-Centered Treatments of Multimorbidity.

Treatment of patients who suffer from concurrent health conditions is not well served by (1) evidence-based clinical guidelines that mainly specify treatment of single conditions and (2) conventional randomized controlled trials (RCTs) that identify treatments as safe and effective on . Clinical decision-making based on the average patient effect may be inappropriate for treatment of those with multimorbidity who experience burdens and obstacles that may be unique to their personal situation. We describe how the personalized (N-of-1) trials can be integrated with an automatic platform and virtual/remote technologies to improve patient-centered care for those living with multimorbidity.

Impact of Duration of Neoadjuvant Aromatase Inhibitors on Molecular Expression Profiles in Estrogen Receptor-positive Breast Cancers.

Purpose: Aromatase inhibitor (AI) treatment is the standard of care for postmenopausal women with primary estrogen receptor-positive breast cancer. The impact of duration of neoadjuvant endocrine therapy (NET) on molecular characteristics is still unknown. We evaluated and compared changes of gene expression profiles under short-term (2-week) versus longer-term neoadjuvant AIs.

Ponatinib with fludarabine, cytarabine, idarubicin, and granulocyte colony-stimulating factor chemotherapy for patients with blast-phase chronic myeloid leukaemia (MATCHPOINT): a single-arm, multicentre, phase 1/2 trial.

Background: Outcomes for patients with blast-phase chronic myeloid leukaemia are poor. Long-term survival depends on reaching a second chronic phase, followed by allogeneic haematopoietic stem-cell transplantation (HSCT). We investigated whether the novel combination of the tyrosine-kinase inhibitor ponatinib with fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin (FLAG-IDA) could improve response and optimise allogeneic HSCT outcomes in patients with blast-phase chronic myeloid leukaemia.

Implementation of platform trials in the COVID-19 pandemic: A rapid review.

Motivation: Platform designs - master protocols that allow for new treatment arms to be added over time - have gained considerable attention in recent years. Between 2001 and 2019, 16 platform trials were initiated globally. The COVID-19 pandemic seems to have provided a new motivation for these designs.

Trends in patient-reported outcome use in early phase dose-finding oncology trials - an analysis of ClinicalTrials.gov.

Background: Patient-reported adverse events (AEs) may be a useful adjunct to clinician-assessed AEs for assessing tolerability in early phase, dose-finding oncology trials (DFOTs). We reviewed DFOTs on ClinicalTrials.gov to describe trends in patient-reported outcome (PRO) use.

VinCaP: a phase II trial of vinflunine in locally advanced and metastatic squamous carcinoma of the penis.

Background: We investigated the first-line activity of vinflunine in patients with penis cancer. Cisplatin-based combinations are commonly used, but survival is not prolonged; many patients are unfit for such treatment or experience toxicity that outweighs clinical benefit.

Methods: Twenty-five patients with inoperable squamous carcinoma of the penis were recruited to a single-arm, Fleming-A'Hern exact phase II trial.

Biomarkers of Response and Resistance to Palbociclib Plus Letrozole in Patients With ER/HER2 Breast Cancer.

Purpose: To determine (i) the relationship between candidate biomarkers of the antiproliferative (Ki67) response to letrozole and palbociclib alone and combined in ER/HER2 breast cancer; and (ii) the pharmacodynamic effect of the agents on the biomarkers.

Experimental Design: 307 postmenopausal women with ER/HER2 primary breast cancer were randomly assigned to neoadjuvant treatment with letrozole for 14 weeks; letrozole for 2 weeks, then letrozole+palbociclib to 14 weeks; palbociclib for 2 weeks, then letrozole+palbociclib to 14 weeks; or letrozole+palbociclib for 14 weeks. Biopsies were taken at baseline, 2 and 14 weeks and surgery at varying times after stopping palbociclib.

Impact of the menstrual cycle on commercial prognostic gene signatures in oestrogen receptor-positive primary breast cancer.

Purpose: Changes occur in the expression of oestrogen-regulated and proliferation-associated genes in oestrogen receptor (ER)-positive breast tumours during the menstrual cycle. We investigated if Oncotype® DX recurrence score (RS), Prosigna® (ROR) and EndoPredict® (EP/EPclin) prognostic tests, which include some of these genes, vary according to the time in the menstrual cycle when they are measured.

Methods: Pairs of test scores were derived from 30 ER-positive/human epidermal growth factor receptor-2-negative tumours sampled at two different points of the menstrual cycle.

ATARI trial: ATR inhibitor in combination with olaparib in gynecological cancers with ARID1A loss or no loss (ENGOT/GYN1/NCRI).

Background: ARID1A (AT-rich interactive domain containing protein 1A) loss-of-function mutations have been reported in gynecological cancers, including rarer subtypes such as clear cell carcinoma. Preclinical studies indicate that mutant cancers display sensitivity to ATR inhibition while tumors without mutations may be sensitive to Ataxia telangiectasia and Rad3 related (ATR) inhibitors in combination with poly-ADP ribose polymerase (PARP) inhibitors.

Primary Objective: To determine whether the ATR inhibitor, ceralasertib, has clinical activity as a single agent and in combination with the PARP inhibitor, olaparib, in patients with ARID1A 'loss' and 'no loss' clear cell carcinomas and other relapsed gynecological cancers.

Best Practices for Spatial Profiling for Breast Cancer Research with the GeoMx Digital Spatial Profiler.

Breast cancer is a heterogenous disease with variability in tumor cells and in the surrounding tumor microenvironment (TME). Understanding the molecular diversity in breast cancer is critical for improving prediction of therapeutic response and prognostication. High-plex spatial profiling of tumors enables characterization of heterogeneity in the breast TME, which can holistically illuminate the biology of tumor growth, dissemination and, ultimately, response to therapy.

Hypofractionation: less is more?

One third of patients with bladder cancer present with muscle invasive bladder cancer (MIBC) which has a poor prognosis. International guidelines for the management of MIBC recommend radical cystectomy or bladder-preserving treatment based on radical radiotherapy with a form of radiosensitisation. In the UK, both conventional fractionation with 64 Gy in 32 fractions and hypofractionation with 55 Gy in 20 fractions are standard of care options with the choice varying between centres.

The Retail Outlet Health Kiosk Hypertension Trial (ROKHYT): Pilot Results.

Background: Blood pressure (BP) control was only 43.7% in the National Health and Nutrition Survey (NHANES) survey in 2017-2018. Scalable, nonclinic-based strategies to control BP are needed.

Patterns of Care, Tolerability, and Safety of the First Cohort of Patients Treated on a Novel High-Field MR-Linac Within the MOMENTUM Study: Initial Results From a Prospective Multi-Institutional Registry.

Purpose: High-field magnetic resonance-linear accelerators (MR-Linacs), linear accelerators combined with a diagnostic magnetic resonance imaging (MRI) scanner and online adaptive workflow, potentially give rise to novel online anatomic and response adaptive radiation therapy paradigms. The first high-field (1.5T) MR-Linac received regulatory approval in late 2018, and little is known about clinical use, patient tolerability of daily high-field MRI, and toxicity of treatments.

Effect of Celecoxib vs Placebo as Adjuvant Therapy on Disease-Free Survival Among Patients With Breast Cancer: The REACT Randomized Clinical Trial.

Importance: Patients with breast cancer remain at risk of relapse after adjuvant therapy. Celecoxib has shown antitumor effects in preclinical models of human breast cancer, but clinical evidence is lacking.

Objective: To evaluate the role of celecoxib as an addition to conventional therapy for women with ERBB2 (formerly HER2)-negative primary breast cancer.

Would the Recommended Dose Have Been Different Using Novel Dose-Finding Designs? Comparing Dose-Finding Designs in Published Trials.

Unlabelled: Simulation studies have shown that novel designs such as the continual reassessment method and the Bayesian optimal interval (BOIN) design outperform the 3 + 3 design by recommending the maximum tolerated dose (MTD) more often, using less patients, and allotting more patients to the MTD. However, it is not clear whether these novel designs would have yielded different results in the context of real-world dose-finding trials. This is a commonly mentioned reason for the continuous use of 3 + 3 designs for oncology trials, with investigators considering simulation studies not sufficiently convincing to warrant the additional design complexity of novel designs.

Postoperative hypoparathyroidism after completion thyroidectomy for well-differentiated thyroid cancer.

Objective: Thyroid surgery may lead to postoperative complications. The aim of this paper was to determine whether the rate of postoperative hypoparathyroidism (HPT) is influenced by whether surgery is staged.

Design: Single-institution retrospective observational study.

TRAFIC: statistical design and analysis plan for a pragmatic early phase 1/2 Bayesian adaptive dose escalation trial in rheumatoid arthritis.

Background: Adaptive model-based dose-finding designs have demonstrated advantages over traditional rule-based designs but have increased statistical complexity but uptake has been slow especially outside of cancer trials. TRAFIC is a multi-centre, early phase trial in rheumatoid arthritis incorporating a model-based design.

Methods: A Bayesian adaptive dose-finding phase I trial rolling into a single-arm, single-stage phase II trial.

KMDATA: a curated database of reconstructed individual patient-level data from 153 oncology clinical trials.

We created a database of reconstructed patient-level data from published clinical trials that includes multiple time-to-event outcomes such as overall survival and progression-free survival. Outcomes were extracted from Kaplan-Meier (KM) curves reported in 153 oncology Phase III clinical trial publications identified through a PubMed search of clinical trials in breast, lung, prostate and colorectal cancer, published between 2014 and 2016. For each trial that met our search criteria, we curated study-level information and digitized all reported KM curves with the software Digitizelt.

Can patient decision aids reduce decisional conflict in a de-escalation of breast radiotherapy clinical trial? The PRIMETIME Study Within a Trial implemented using a cluster stepped-wedge trial design.

Background: For patients with early breast cancer considered at very-low risk of local relapse, risks of radiotherapy may outweigh the benefits. Decisions regarding treatment omission can lead to patient uncertainty (decisional conflict), which may be lessened with patient decision aids (PDA). PRIMETIME (ISRCTN 41579286) is a UK-led biomarker-directed study evaluating omission of adjuvant radiotherapy in breast cancer; an embedded Study Within A Trial (SWAT) investigated whether PDA reduces decisional conflict using a cluster stepped-wedge trial design.

Beyond Lockdown: The Potential Side Effects of the SARS-CoV-2 Pandemic on Public Health.

Lockdowns to contain the spread of the SARS-CoV-2 have disrupted routines and behaviors, which could lead to a worsening of lifestyle and an increase in the burden of non-communicable diseases. This study aimed to describe the changes in physical activity, diet, alcohol drinking, and cigarette smoking during lockdown. A self-administered online survey addressing adults living in a province in northern Italy was advertised through websites and social media.