Development and application of a weighted change score to evaluate interventions for vasomotor symptoms in patients with breast cancer using regression trees: a cohort study.

PURPOSE: Vasomotor symptoms (VMS) are common among individuals with breast cancer (BC) and poorly managed symptoms are associated with reduced quality of life, treatment discontinuation, and poorer breast cancer outcomes. Direct comparisons among therapies are limited, as prior studies evaluating VMS interventions have utilized heterogeneous change measures which may not fully assess the perceived impact of change in VMS severity. METHODS: We performed a prospective study where BC patients chose one of four categories of interventions to manage VMS. Change in VMS severity at 6 weeks was assessed using the validated Hot Flush Rating Scale (HFRS). A novel weighted change score integrating baseline symptom severity and directionality of change was computed to maximize the correlation between the change score and a perceived treatment effectiveness score. Variables influencing change in VMS severity were included in a regression tree to model factors influencing the weighted change score. RESULTS: 100 baseline and follow-up questionnaires assessing VMS were completed by 88 patients. Correlations between treatment effectiveness and VMS outcomes strengthened following adjustment for baseline symptoms. Patients with low VMS severity at baseline did not perceive change in treatment effectiveness. Intervention category was predictive of change in HFRS at 6 weeks. CONCLUSION: Baseline symptom severity and the directionality of change (improvement or deterioration of symptoms) influenced the perception of clinically meaningful change in VMS severity. Future interventional studies utilizing the weighted change score should target moderate-high baseline severity patients.

2020 ASCO, 2023 NCCN, 2023 MASCC/ESMO, and 2019 CCO: a comparison of antiemetic guidelines for the treatment of chemotherapy-induced nausea and vomiting in cancer patients.

Chemotherapy-induced nausea and vomiting (CINV) is a common toxicity that may impair the quality of life of patients with various malignancies ranging from early to end stages. In light of frequent changes to the guidelines for optimal management of CINV, we undertook this narrative review to compare the most recent guidelines published by ASCO (2020), NCCN (2023), MASCC/ESMO (2023), and CCO (2019). The processes undertaken by each organization to evaluate existing literature were also described. Although ASCO, NCCN, MASCC/ESMO, and CCO guidelines for the treatment and prevention of CINV share many fundamental similarities, the literature surrounding low and minimal emetic risk regimens is lacking. Current data regarding adherence to these guidelines is poor and warrants further investigation to improve care.

The REthinking Clinical Trials Program Retreat 2023: Creating Partnerships to Optimize Quality Cancer Care.

Patients, families, healthcare providers and funders face multiple comparable treatment options without knowing which provides the best quality of care. As a step towards improving this, the REthinking Clinical Trials (REaCT) pragmatic trials program started in 2014 to break down many of the traditional barriers to performing clinical trials. However, until other innovative methodologies become widely used, the impact of this program will remain limited. These innovations include the incorporation of near equivalence analyses and the incorporation of artificial intelligence (AI) into clinical trial design. Near equivalence analyses allow for the comparison of different treatments (drug and non-drug) using quality of life, toxicity, cost-effectiveness, and pharmacokinetic/pharmacodynamic data. AI offers unique opportunities to maximize the information gleaned from clinical trials, reduces sample size estimates, and can potentially "rescue" poorly accruing trials. On 2 May 2023, the first REaCT international symposium took place to connect clinicians and scientists, set goals and identify future avenues for investigator-led clinical trials. Here, we summarize the topics presented at this meeting to promote sharing and support other similarly motivated groups to learn and share their experiences.

Diagnosis, isolation and description of a novel amnoonvirus recovered from diseased fancy guppies, Poecilia reticulata.

The guppy, Poecilia reticulata, is one of the most common cultured ornamental fish species, and a popular pet fish highly desired by hobbyists worldwide due to its availability of many brilliantly coloured fish of many varieties. The susceptibility of guppies to diseases presents a remarkable concern for both breeders and hobbyists. In this study, we report the emergence of disease in fancy guppies caused by a previously uncharacterized virus in the USA. This virus was isolated from moribund guppies in two separate outbreaks in California and Alabama, from December 2021 to June 2023. The infected guppies presented with acute morbidity and mortality shortly after shipping, displaying nonspecific clinical signs and gross changes including lethargy, anorexia, swimming at the water surface, gill pallor, mild to moderate coelomic distension and occasional skin lesions including protruding scales, skin ulcers and hyperaemia. Histological changes in affected fish were mild and nonspecific; however, liver and testes from moribund fish were positive for Tilapia lake virus (TiLV), the single described member in the family Amnoonviridae, using immunohistochemistry and in situ hybridization, although the latter was weak. A virus was successfully recovered following tissue inoculation on epithelioma papulosum cyprini and snakehead fish cell lines. Whole genome sequencing and phylogenetic analyses revealed nucleotide and amino acid homologies from 78.3%-91.2%, and 78.2%-97.7%, respectively, when comparing the guppy virus genomes to TiLV isolates. Based on the criteria outlined herein, we propose the classification of this new virus, fancy tailed guppy virus (FTGV), as a member of the family Amnoonviridae, with the name Tilapinevirus poikilos (from the Greek 'poikilos', meaning of many colours; various sorts, akin to 'poecilia').

Surveillance for Acute Flaccid Myelitis - United States, 2018-2022.

Acute flaccid myelitis (AFM) is a serious neurologic condition primarily affecting children; AFM can cause acute respiratory failure and permanent paralysis. AFM is a rare but known complication of various viral infections, particularly those of enteroviruses (EVs). Increases in AFM cases during 2014, 2016, and 2018 were associated with EV-D68 infection. This report examines trends in confirmed AFM cases during 2018-2022 and patients' clinical and laboratory characteristics. The number of AFM cases was low during 2019-2022 (28-47 cases per year); the number of cases remained low in 2022 despite evidence of increased EV-D68 circulation in the United States. Compared with cases during the most recent peak year (2018), fewer cases during 2019-2021 had upper limb involvement, prodromal respiratory or febrile illness, or cerebrospinal fluid pleocytosis, and more were associated with lower limb involvement. It is unclear why EV-D68 circulation in 2022 was not associated with an increase in AFM cases or when the next increase in AFM cases will occur. Nonetheless, clinicians should continue to suspect AFM in any child with acute flaccid limb weakness, especially those with a recent respiratory or febrile illness.

The COVID-19 pandemic and its effects on follow-up of patients with early breast cancer: A patient survey.

PURPOSE: Despite limited evidence supporting its effectiveness, most guidelines recommend long-term, routinely scheduled in-person surveillance of patients with early breast cancer (EBC). The COVID-19 pandemic led to increased use of virtual care. This survey evaluated patient perspectives on follow-up care. METHODS: Patients with EBC undergoing surveillance were surveyed about follow-up protocols, perceptions, and interest in clinical trials assessing different follow-up strategies. RESULTS: Of 402 approached patients 270 completed the survey (response rate 67%). Median age 62.5 years (range 25-86) and median time since breast cancer diagnosis was 3.8 years (range < 1-33 years). Most (n = 148/244, 60%) were followed by more than one provider. Routine follow-ups with breast examination were mostly conducted by medical/radiation oncologists every 6 months (n = 110/236, 46%) or annually (n = 106/236, 44%). Participants felt routine follow-up was useful to monitor for recurrence, manage side effects of cancer treatment and to provide support/reassurance. Most participants felt regular follow-up care would detect recurrent cancer earlier (n = 214/255, 96%) and increase survival (n = 218/249, 88%). The COVID-19 pandemic reduced the number of in-person visits for 54% of patients (n = 63/117). Patients were concerned this reduction of in-person visits would lead to later detection of both local (n = 29/63, 46%) and distant recurrences (n = 25/63, 40%). While many felt their medical and radiation oncologists were the most suited to provide follow-up care, 55% felt comfortable having their primary care provider (PCP) conduct surveillance. When presented with a scenario where follow-up has no effect on earlier detection or survival, 70% of patients still wanted routine in-person follow-up for reassurance (63%) with the goal of earlier recurrence detection (56%). CONCLUSIONS: Despite limited evidence of effectiveness of routine in-person assessment, patients continue to place importance on regularly scheduled in-person follow-up.

Duration of Enterovirus D68 RNA Shedding in the Upper Respiratory Tract and Transmission among Household Contacts, Colorado, USA.

Enterovirus D68 (EV-D68) causes cyclical outbreaks of respiratory disease and acute flaccid myelitis. EV-D68 is primarily transmitted through the respiratory route, but the duration of shedding in the respiratory tract is unknown. We prospectively enrolled 9 hospitalized children with EV-D68 respiratory infection and 16 household contacts to determine EV-D68 RNA shedding dynamics in the upper respiratory tract through serial midturbinate specimen collections and daily symptom diaries. Five (31.3%) household contacts, including 3 adults, were EV-D68-positive. The median duration of EV-D68 RNA shedding in the upper respiratory tract was 12 (range 7-15) days from symptom onset. The most common symptoms were nasal congestion (100%), cough (92.9%), difficulty breathing (78.6%), and wheezing (57.1%). The median illness duration was 20 (range 11-24) days. Understanding the duration of RNA shedding can inform the expected rate and timing of EV-D68 detection in associated acute flaccid myelitis cases and help guide public health measures.

A Multi-Centre Randomized Study Comparing Two Standard of Care Chemotherapy Regimens for Lower-Risk HER2-Positive Breast Cancer.

BACKGROUND: Neither paclitaxel plus trastuzumab (P-H) nor docetaxel-cyclophosphamide plus trastuzumab (TC-H) have been prospectively compared in HER2-positive early-stage breast cancer (EBC). A randomized trial was performed to assess the feasibility of a larger study. METHODS: Lower-risk HER2-positive EBC patients were randomized to either P-H or TC-H treatment arms. The co-primary feasibility outcomes were: ≥75% patient acceptability rate, active trial participation of ≥50% of medical oncologists, ≥75% and ≥90% treatment completion, and receipt rate of planned cycles of chemotherapy, respectively. SECONDARY OUTCOMES: Febrile neutropenia (FN) rate, treatment-related hospitalizations, health-related quality of life (HR-QoL) questionnaires. Analyses were performed by per protocol and intention-to-treat. RESULTS: Between May 2019 and March 2021, 49 of 52 patients agreed to study participation (94% acceptability rate). Fifteen (65%) of 23 medical oncologists approached patients. Rates of FN were higher (8.3% vs. 0%) in the TC-H vs. P-H arm. Median (IQR) changes in scores from baseline in FACT-Taxane Trial Outcome Index at 24 weeks were -4 (-10, -1) vs. -6.5 (-15, -2) for TC-H and P-H arms, respectively. CONCLUSIONS: A randomized trial comparing P-H and TC-H was feasible. Expansion to a larger trial would be feasible to explore patient-reported outcomes of these adjuvant HER2 chemotherapy regimens.

Patients' attitudes and preferences toward delayed disease progression in the absence of improved survival.

BACKGROUND: Cancer patients' attitudes toward progression-free survival (PFS) gains offered by treatment are not well understood, particularly in the absence of overall survival (OS) gains. The objectives were to describe patients' willingness to accept treatment that offers PFS gains without OS gains, to compare these findings with treatments offering OS gains, and to qualitatively summarize patients' reasons for their preferences. METHODS: A multicenter, cross-sectional, convergent mixed-methods study design recruited patients who had received at least 3 months of systemic therapy for incurable solid tumors. A treatment trade-off exercise determined the gains in imaging PFS that patients require to prefer additional systemic treatment for a scenario of a newly diagnosed, asymptomatic, incurable abdominal tumor. A qualitative, descriptive, thematic analysis explored factors influencing patients' decisions, and a narrative method integrated the quantitative and qualitative findings. RESULTS: In total, 100 patients participated (63% were older than 60 years of age). If additional treatment with added toxicity offered no OS advantage, 17% would prefer it for no PFS benefit; 26% for some PFS benefit (range, 3-9 months), whereas 51% would decline it regardless of PFS benefit. Similarly, 71% preferred additional treatment offering a 6-month OS advantage dependent on described toxicity levels (P = .03). A spectrum of reasons for these preferences reflected the complexity of participants' attitudes and values. CONCLUSIONS: Prolongation of time to progression was not universally valued. Most patients did not prefer treatments that negatively affect quality of life for PFS gains alone. Implications for individual decision making, policy, and trials research are discussed.

A narrative review from gut to lungs: non-small cell lung cancer and the gastrointestinal microbiome.

Background and Objective: The gut microbiome has emerged as an important gateway to improving therapeutic outcomes in lung cancer, especially for immunotherapy. Our objective is to review the impact of the bidirectional relationship between the gut microbiome, lung cancer, and the immune system, and to identify areas of future research. Methods: We conducted a search on PubMed, EMBASE, and ClinicalTrials.gov using the search terms non-small cell lung cancer (NSCLC), gut microbiome, and microbiota until July 11, 2022. The authors screened resulting studies independently. Results were synthesized and presented descriptively. Key Content and Findings: Sixty original published studies were identified from PubMed (n=24) and EMBASE (n=36), respectively. Twenty-five ongoing clinical studies were identified on ClinicalTrials.gov. Gut microbiota has been shown to influence tumorigenesis and modulate tumor immunity via local and neurohormonal mechanisms depending on the microbiome ecosystem that populates the gastrointestinal tract. Probiotics, antibiotics, and proton pump inhibitors (PPIs), amongst other medications, can impact gut microbiome health, leading either to improved or worsened therapeutic outcomes with immunotherapy. Most clinical studies assess the impact of the gut microbiome, but emerging data suggest microbiome composition in other host sites may be important. Conclusions: A strong relationship exists between gut microbiome, oncogenesis, and anticancer immunity. Although the underlying mechanisms are poorly understood, immunotherapy outcomes seem to depend on host-related factors such as gut microbiome alpha diversity, relative abundance of microbial genera/taxa, and extrinsic factors such as prior or concurrent exposure to probiotics, antibiotics, and other microbiome-modifying drugs.

Temozolomide Chronotherapy in Glioma: A Systematic Review.

Outcomes for patients with high-grade glioma remain poor. Temozolomide (TMZ) is the only drug approved for first-line treatment of glioblastoma multiforme, the most aggressive form of glioma. Chronotherapy highlights the potential benefit of timed TMZ administration. This is based on pre-clinical studies of enhanced TMZ-induced glioma cytotoxicity dependent on circadian, oscillating expression of key genes involved in apoptosis, DNA damage repair, and cell-cycle mediated cell death. The current systematic review's primary aim was to evaluate the efficacy and toxicity of TMZ chronotherapy. A systemic review of literature following PRISMA guidelines looking at clinical outcomes on TMZ chronotherapy on gliomas was performed. The search in the English language included three databases (PubMed, EMBASE, and Cochrane) and five conferences from 1946 to April 2022. Two independent reviewers undertook screening, data extraction, and risk-of-bias assessment. A descriptive analysis was conducted due to limited data. Of the 269 articles screened, two unique studies were eligible and underwent abstraction for survival and toxicity findings. Both studies-one a retrospective cohort study (n = 166) and the other a prospective randomized feasibility study (n = 35)-were conducted by the same academic group and suggested a trend for improved overall survival, but possibly increased toxicity when TMZ was administered in the morning (vs. evening). There was limited evidence suggesting possible therapeutic value from administering TMZ in the morning, which may be consistent with the pre-clinical observations of the importance of the timing of TMZ administration in vitro. Larger, pragmatic, prospective randomized controlled trials are needed to ascertain the value of TMZ chronotherapy to provide optimized and equitable care for this population.

Intermediate Levels of Pre-Existing Protective Antibody Allow Priming of Protective T Cell Immunity against Influenza.

Overcoming interfering impacts of pre-existing immunity to generate universally protective influenza A virus (IAV)-specific T cell immunity through vaccination is a high priority. In this study, we passively transfer varied amounts of H1N1-IAV-specific immune serum before H1N1-IAV infection to determine how different levels of pre-existing Ab influence the generation and protective potential of heterosubtypic T cell responses in a murine model. Surprisingly, IAV nucleoprotein-specific CD4 and CD8 T cell responses are readily detected in infected recipients of IAV-specific immune serum regardless of the amount transferred. When compared with responses in control groups and recipients of low and intermediate levels of convalescent serum, nucleoprotein-specific T cell responses in recipients of high levels of IAV-specific serum, which prevent overt weight loss and reduce peak viral titers in the lungs, are, however, markedly reduced. Although detectable at priming, this response recalls poorly and is unable to mediate protection against a lethal heterotypic (H3N2) virus challenge at later memory time points. A similar failure to generate protective heterosubtypic T cell immunity during IAV priming is seen in offspring of IAV-primed mothers that naturally receive high titers of IAV-specific Ab through maternal transfer. Our findings support that priming of protective heterosubtypic T cell responses can occur in the presence of intermediate levels of pre-existing Ab. These results have high relevance to vaccine approaches aiming to incorporate and evaluate cellular and humoral immunity towards IAV and other viral pathogens against which T cells can protect against variants escaping Ab-mediated protection.

Nearly Complete Genome Sequences of Type 2 Sabin-Like Polioviruses from Northern Nigerian Poliovirus Surveillance, 2016 to 2018.

We sequenced 109 type 2 Sabin-like poliovirus isolates that had been collected from acute flaccid paralysis patients or healthy children in Nigeria. Understanding the genetic makeup of these viruses may contribute to polio eradication efforts.

Wastewater Testing and Detection of Poliovirus Type 2 Genetically Linked to Virus Isolated from a Paralytic Polio Case - New York, March 9-October 11, 2022.

In July 2022, a case of paralytic poliomyelitis resulting from infection with vaccine-derived poliovirus (VDPV) type 2 (VDPV2)§ was confirmed in an unvaccinated adult resident of Rockland County, New York (1). As of August 10, 2022, poliovirus type 2 (PV2)¶ genetically linked to this VDPV2 had been detected in wastewater** in Rockland County and neighboring Orange County (1). This report describes the results of additional poliovirus testing of wastewater samples collected during March 9-October 11, 2022, and tested as of October 20, 2022, from 48 sewersheds (the community area served by a wastewater collection system) serving parts of Rockland County and 12 surrounding counties. Among 1,076 wastewater samples collected, 89 (8.3%) from 10 sewersheds tested positive for PV2. As part of a broad epidemiologic investigation, wastewater testing can provide information about where poliovirus might be circulating in a community in which a paralytic case has been identified; however, the most important public health actions for preventing paralytic poliomyelitis in the United States remain ongoing case detection through national acute flaccid myelitis (AFM) surveillance†† and improving vaccination coverage in undervaccinated communities. Although most persons in the United States are sufficiently immunized, unvaccinated or undervaccinated persons living or working in Kings, Orange, Queens, Rockland, or Sullivan counties, New York should complete the polio vaccination series as soon as possible.

Public Health Response to a Case of Paralytic Poliomyelitis in an Unvaccinated Person and Detection of Poliovirus in Wastewater - New York, June-August 2022.

On July 18, 2022, the New York State Department of Health (NYSDOH) notified CDC of detection of poliovirus type 2 in stool specimens from an unvaccinated immunocompetent young adult from Rockland County, New York, who was experiencing acute flaccid weakness. The patient initially experienced fever, neck stiffness, gastrointestinal symptoms, and limb weakness. The patient was hospitalized with possible acute flaccid myelitis (AFM). Vaccine-derived poliovirus type 2 (VDPV2) was detected in stool specimens obtained on days 11 and 12 after initial symptom onset. To date, related Sabin-like type 2 polioviruses have been detected in wastewater* in the patient's county of residence and in neighboring Orange County up to 25 days before (from samples originally collected for SARS-CoV-2 wastewater monitoring) and 41 days after the patient's symptom onset. The last U.S. case of polio caused by wild poliovirus occurred in 1979, and the World Health Organization Region of the Americas was declared polio-free in 1994. This report describes the second identification of community transmission of poliovirus in the United States since 1979; the previous instance, in 2005, was a type 1 VDPV (1). The occurrence of this case, combined with the identification of poliovirus in wastewater in neighboring Orange County, underscores the importance of maintaining high vaccination coverage to prevent paralytic polio in persons of all ages.

Association of anticoagulant use with clinical outcomes from crizotinib in ALK- and ROS1-rearranged advanced non-small cell lung cancers: A retrospective analysis of PROFILE 1001.

BACKGROUND: ROS1- and ALK-rearranged advanced NSCLCs are associated with increased thromboembolic risk. We hypothesized that a prothrombotic phenotype offers an evolutionary advantage to subsets of these cancers. The impact of this phenotype could alter outcomes from targeted therapy. METHODS: In a retrospective analysis of ROS1- and ALK-rearranged NSCLCs treated with crizotinib in a phase 1 trial, we compared progression-free survival (PFS) and objective response rate (ORR) based on the history of anticoagulation use (a possible surrogate of thromboembolism) at baseline (within 90 days before study enrollment) or within 90 days of study treatment. RESULTS: Twelve out of 53 (22.6%) ROS1- and 39 out of 153 (25.5%) ALK-rearranged NSCLCs received anticoagulation before or during the trial. Most ROS1 and ALK patients on anticoagulation received low-molecular-weight heparin (75% and 64.1%, respectively). In the ROS1-rearranged group, the median PFS (95% CI) values were 5.1 (4.4-14.4) and 29.0 (16.5-48.8) months, and the ORR values were 41.7% (95% CI: 15.2 to 72.3) and 80.5% (95% CI: 65.1 to 91.2) among those with and without anticoagulation treatment, respectively. In the ALK-rearranged group, the median PFS (95% CI) was 7.1 (5.4-7.7) and 12.0 (9.4-18.3) months, and the ORR was 41% (95% CI: 25.6 to 57.9) and 74.3% (95% CI: 65.3 to 82.1) among those with and without anticoagulation, respectively. CONCLUSIONS: Anticoagulation (as a potential surrogate of a prothrombotic subset) in ROS1- and ALK-rearranged NSCLCs may be associated with a lower PFS and ORR to crizotinib. CLINICALTRIAL: gov: NCT00585195.

VPipe: an Automated Bioinformatics Platform for Assembly and Management of Viral Next-Generation Sequencing Data.

Next-generation sequencing (NGS) is a powerful tool for detecting and investigating viral pathogens; however, analysis and management of the enormous amounts of data generated from these technologies remains a challenge. Here, we present VPipe (the Viral NGS Analysis Pipeline and Data Management System), an automated bioinformatics pipeline optimized for whole-genome assembly of viral sequences and identification of diverse species. VPipe automates the data quality control, assembly, and contig identification steps typically performed when analyzing NGS data. Users access the pipeline through a secure web-based portal, which provides an easy-to-use interface with advanced search capabilities for reviewing results. In addition, VPipe provides a centralized system for storing and analyzing NGS data, eliminating common bottlenecks in bioinformatics analyses for public health laboratories with limited on-site computational infrastructure. The performance of VPipe was validated through the analysis of publicly available NGS data sets for viral pathogens, generating high-quality assemblies for 12 data sets. VPipe also generated assemblies with greater contiguity than similar pipelines for 41 human respiratory syncytial virus isolates and 23 SARS-CoV-2 specimens. IMPORTANCE Computational infrastructure and bioinformatics analysis are bottlenecks in the application of NGS to viral pathogens. As of September 2021, VPipe has been used by the U.S. Centers for Disease Control and Prevention (CDC) and 12 state public health laboratories to characterize >17,500 and 1,500 clinical specimens and isolates, respectively. VPipe automates genome assembly for a wide range of viruses, including high-consequence pathogens such as SARS-CoV-2. Such automated functionality expedites public health responses to viral outbreaks and pathogen surveillance.

Pre-medication protocols for the prevention of paclitaxel-induced infusion related reactions: a systematic review and meta-analysis.

BACKGROUND: Prophylaxis against infusion-related reactions (IRR) from paclitaxel with steroids and antihistamines is a standard of care due to high rates of IRR. This systematic review and meta-analysis aimed to comprehensively summarize the evidence behind various prophylaxis strategies. METHODS: EMBASE, MEDLINE, PubMed, and the Cochrane Register of Controlled Trials were searched (1946 to May 14, 2021). The primary outcomes were Grade 3/4 IRR and any-grade IRR. Secondary outcomes included treatment delay or discontinuation and adverse events secondary to pre-medications. RESULTS: Of the 1285 unique citations, 26 studies were selected: 11 studies for quantitative analysis and 15 studies for qualitative analysis. Studies included randomized controlled trials and observational studies (n = 25-281). There was a non-significant benefit in favour of oral steroids starting 12 h prior to paclitaxel administration versus intravenous steroids immediately prior to paclitaxel administration for grade 3/4 IRRs, with a risk difference (RD) of 2% [95%CI 0 to 5%], any-grade IRR with a RD of 4% [95%CI: -1% to 9%] and treatment discontinuation with a RD of 1% [95%CI -1% to 2%]. For de-escalation strategies, a point-estimate for any-grade IRR was 0.44% [95% CI, 0 to 0.02, p = 0.98] and for grade 3/4 IRR was 3.1% (95% CI, 0.02 to 0.07, p = 0.11). CONCLUSION: Although studies have high risk of bias and risk, differences between steroid routes of administration were small, there was a non-significant trend in favour of oral steroids. De-escalation strategies after two previous successful paclitaxel infusions have an overall low incidence rate of severe IRR and warrant further prospective clinical trials. Insufficient evidence remains to recommend for or against other interventions for the prevention of paclitaxel IRR.

Symptomatic skeletal-related events in patients receiving longer term bone-modifying agents for bone metastases from breast and castration resistant prostate cancers.

BACKGROUND: The effect of longer-term use of bone-modifying agent (BMA) on symptomatic skeletal event (SSE) rates in patients with bone metastases remains unclear. This retrospective study of a cohort of patients in a randomized controlled trial evaluated SSEs in patients receiving BMAs at a single cancer center. METHODS: Data from patients with metastatic breast and castration-resistant prostate cancer (CRPC) were interrogated to evaluate the effects of longer-term use of BMAs on incidence, type, and risk factors for SSEs. RESULTS: Of 162 patients, 109 (67%) had breast cancer (BC) and 53 (33%) CRPC. Median age at diagnosis of bone metastases was 61.9 years (range 27.5-97.2) for BC patients and 72.1 (range 37.0-92.2) for CRPC patients. Median duration of BMA use was 2.3 years (range 0.1-9.9 years) for BC and 3.8 years (range 1.5-9.4) for CRPC patients. The initial BMAs in BC patients were pamidronate (46.8%), denosumab (31.2%), and zoledronate (22%). All CRPC patients received denosumab. During follow-up, 59% of BC and 75% of CRPC patients had at least one SSE. The number of patients experiencing ≥ 1 SSE per year was higher in the first year after bone metastasis diagnosis (63/162; 38.9%) compared with that in the second (26/149; 17.5%) and third years (30/123; 24.4%). Neither age, visceral disease, multiple bone metastases, nor biological markers for BC had a significant impact on time to first SSE. CONCLUSIONS: The risk for SSEs was greatest in the first year after diagnosis of bone metastasis. Studies evaluating de-escalation and even stopping of BMAs with longer-term use may therefore be warranted.