What's in a word? Defining "gene therapy medicines".

Gene therapy medicinal products (GTMPs) have emerged as a transformative class of medicines. Defining what a certain class of medicines encompasses, and what it does not, is key, with ample implications and consequential regulatory requirements. In April 2023, the European Commission proposed new pharmaceutical legislation safeguarding the public health within the European Union with a new, broader definition of GTMP, including genome editing medicines and nucleic acids of either source, regulating, replacing, or adding a genetic sequence that mediates its effect by transcription or translation.

Content validation of the National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy Lymphoma Symptom Index-18 (NFLymSI-18) in indolent B-cell non-Hodgkin's lymphoma.

Background: The NFLymSI-18 is a patient-reported outcome measure comprised of the highest priority symptoms, emotional concerns, treatment side effects, and other concerns identified by lymphoma patients and oncologists. This study assessed the content validity of the NFLymSI-18 for patients with indolent B-cell non-Hodgkin's lymphoma (iNHL), with a focus on the Disease-Related Symptoms Physical (DRS-P) subscale.

Methods: Patients with a confirmed iNHL diagnosis who had received one or more lines of treatment were recruited during clinic visits.

Prognosis and oncogenomic profiling of patients with tropomyosin receptor kinase fusion cancer in the 100,000 genomes project.

Introduction: Neurotrophic tyrosine receptor kinase (NTRK) gene fusions are oncogenic drivers in various tumor types. Limited data exist on the overall survival (OS) of patients with tumors with NTRK gene fusions and on the co-occurrence of NTRK fusions with other oncogenic drivers.

Materials And Methods: This retrospective study included patients enrolled in the Genomics England 100,000 Genomes Project who had linked clinical data from UK databases.

Indirect Treatment Comparison of Larotrectinib versus Entrectinib in Treating Patients with TRK Gene Fusion Cancers.

Information regarding the comparative efficacy of first-generation receptor tyrosine kinase inhibitors is limited. This matching-adjusted indirect comparison (MAIC) evaluated differences in efficacy and safety across larotrectinib and entrectinib trials. Data from clinical trials for larotrectinib (LOXO-TRK-14001 (NCT02122913), SCOUT (NCT02637687), and NAVIGATE (NCT02576431)) and entrectinib (ALKA-372-001 (EudraCT 2012-000148-88), STARTRK-1 (NCT02097810), and STARTRK-2 (NCT02568267)) were used.

TRK Fusion Cancer: Patient Characteristics and Survival Analysis in the Real-World Setting.

Background: Neurotrophic tyrosine receptor kinase (NTRK) gene fusions are oncogenic drivers in various tumor types. While NTRK gene fusions are predictive of benefit from tropomyosin receptor kinase inhibitors regardless of tumor type, the prognostic significance of NTRK gene fusions in a pan-tumor setting remains unclear.

Objective: This study evaluated the characteristics and prognosis of tropomyosin receptor kinase fusion cancer in the real-world setting.

Quality of Life in Adult and Pediatric Patients with Tropomyosin Receptor Kinase Fusion Cancer Receiving Larotrectinib.

Neurotrophic tyrosine receptor kinase (NTRK) gene fusions lead to chimeric tropomyosin receptor kinase (TRK) fusion proteins, which act as primary oncogenic drivers in diverse tumor types in adults and children. Larotrectinib, a highly selective and central nervous system-active TRK inhibitor, has shown high objective response rates, durable disease control, and a favorable safety profile in patients with TRK fusion cancer. The impact of larotrectinib on health-related quality of life (HRQoL) was evaluated in adult and pediatric patients in two phase I/II clinical trials (NAVIGATE; NCT02576431 and SCOUT; NCT02637687).

A systematic review and meta-analysis of neurotrophic tyrosine receptor kinase gene fusion frequencies in solid tumors.

Introduction: The research objective was to systematically review evidence on neurotrophic tyrosine receptor kinase () gene fusion frequency in solid tumors.

Methods: Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic literature review (SLR) was conducted of studies published from January 1987 to 2 January 2020. Selected studies were appraised for use in meta-analysis, with frequency reported as a point estimate with confidence intervals, to estimate gene fusion tumor incidence and prevalence.

Larotrectinib versus Prior Therapies in Tropomyosin Receptor Kinase Fusion Cancer: An Intra-Patient Comparative Analysis.

Randomized controlled basket trials investigating drugs targeting a rare molecular alteration are challenging. Using patients as their own control overcomes some of these challenges. Growth modulation index (GMI) is the ratio of progression-free survival (PFS) on the current therapy to time to progression (TTP) on the last prior line of therapy; GMI ≥ 1.

Transforming approaches to treating TRK fusion cancer: historical comparison of larotrectinib and histology-specific therapies.

Objective: The results from basket trials utilized to gain regulatory approval of tumor-agnostic therapies can be difficult to interpret without the context of a comparator arm. We describe the role and efficacy of histology-based treatments to provide a historical comparison with larotrectinib.

Methods: A systematic literature review (SLR) was conducted on the clinical outcomes of current histology-based standard of care treatments used in non-small cell lung cancer, colorectal cancer, thyroid cancer, gliomas, soft tissue sarcoma, salivary gland cancer, and infantile fibrosarcoma (7 of the 21 tumor histologies in the larotrectinib trials).

Follicular lymphoma treatment patterns between 2000 and 2014: a SEER-Medicare analysis of elderly patients.

Characterize follicular lymphoma (FL) treatment patterns among elderly patients using a dataset with longer follow-up time. Using the linked Surveillance, Epidemiology and End Results-Medicare data, we identified patients diagnosed with FL between 2000 and 2013 with claims data until 2014. We investigated the treatments received and assigned them to lines of treatment.

Patient-level Factors Associated With the Initial Management of Older Adults Diagnosed With Follicular Lymphoma: A Surveillance, Epidemiology, and End Results-Medicare Analysis.

Introduction: We evaluated patient-level factors associated with the initial management of older adults diagnosed with follicular lymphoma (FL).

Materials And Methods: Using linked Surveillance, Epidemiology, and End Results-Medicare (SEER-Medicare) data; we identified 11,500 beneficiaries aged ≥ 66 years, diagnosed with FL between 2000 and 2013. A logistic regression model was used to estimate adjusted odds ratios (AORs) for factors associated with the receipt of active treatment versus watchful waiting (WW) as an initial management strategy.

Survival benefit associated with treating follicular lymphoma in patients 80 years or older.

Objectives: To evaluate the overall survival benefit associated with follicular lymphoma (FL)-directed therapy among patients diagnosed with FL at 80+ years.

Patients And Methods: This retrospective cohort study utilized the linked Surveillance, Epidemiology and End Results-Medicare dataset to identify patients 80+ years, diagnosed with FL between 2000 and 2013. We identified FL-directed treatments based on published guidelines.

Does recall period matter? Comparing PROMIS physical function with no recall, 24-hr recall, and 7-day recall.

Purpose: To evaluate the influence of recall periods on the assessment of physical function, we compared, in cancer and general population samples, the standard administration of PROMIS Physical Function items without a recall period to administrations with 24-hour and 7-day recall periods.

Methods: We administered 31 items from the PROMIS Physical Function v2.0 item bank to 2400 respondents (n = 1001 with cancer; n = 1399 from the general population).

Development of a Joint Commission Disease-Specific Care Certification Program for Parkinson Disease in an Acute Care Hospital.

Background: Patients with Parkinson disease (PD) admitted to the hospital for any reason are at a higher risk of hospital-related complications. Frequent causes include delays in administering PD medications or use of contraindicated medications. The Joint Commission Disease-Specific Care (DSC) program has been used to establish a systematic approach to the care of specific inpatient populations.

Costs associated with follicular lymphoma among individuals diagnosed with non-Hodgkin lymphoma: a longitudinal analysis using SEER-Medicare data.

There is limited information on the cost burden associated with follicular lymphoma (FL) and how it compares to other non-Hodgkin lymphoma (NHL) subtypes. We examined the direct medical costs associated with FL and estimated the incremental 3-year cost of FL compared to other NHL subtypes. Using the linked Surveillance, Epidemiology and End Results-Medicare dataset, we identified 16,691 NHL patients aged 66 years or older who were diagnosed with NHL between 2007 and 2013.

Evaluation of the psychometric properties and minimally important difference of the MD Anderson Symptom Inventory for malignant pleural mesothelioma (MDASI-MPM).

Background: Symptom assessment requires psychometrically validated questionnaires that are easy to use, relevant to the disease, and quick to administer. The MD Anderson Symptom Inventory for malignant pleural mesothelioma (MDASI-MPM) was adapted from the general (core) MDASI to assess the severity of cancer-related and treatment-related symptoms specific to patients with this condition. The MDASI-MPM includes the 13 core MDASI symptoms, which are experienced by most cancer patients, and 6 MPM-specific items developed via qualitative interviewing, a method favored by the US Food and Drug Administration for instrument item generation and development.

Modification of existing patient-reported outcome measures: qualitative development of the MD Anderson Symptom Inventory for malignant pleural mesothelioma (MDASI-MPM).

Purpose: Malignant pleural mesothelioma (MPM) is an aggressive cancer of the lung pleura. The MD Anderson Symptom Inventory (MDASI) is a patient-reported outcome (PRO) measure of symptom burden, the combined impact of disease-related and treatment-related symptoms on functioning. Validated PRO measures may require modification for use in specific study populations.

Phase I studies of AZD1208, a proviral integration Moloney virus kinase inhibitor in solid and haematological cancers.

Background: Proviral integration Moloney virus (PIM) kinases (PIM1, 2 and 3) are overexpressed in several tumour types and contribute to oncogenesis. AZD1208 is a potent ATP-competitive PIM kinase inhibitor investigated in patients with recurrent or refractory acute myeloid leukaemia (AML) or advanced solid tumours.

Methods: Two dose-escalation studies were performed to evaluate the safety and tolerability, and to define the maximum tolerated dose (MTD), of AZD1208 in AML and solid tumours.

Prior knowledge transfer across transcriptional data sets and technologies using compositional statistics yields new mislabelled ovarian cell line.

Here, we describe gene expression compositional assignment (GECA), a powerful, yet simple method based on compositional statistics that can validate the transfer of prior knowledge, such as gene lists, into independent data sets, platforms and technologies. Transcriptional profiling has been used to derive gene lists that stratify patients into prognostic molecular subgroups and assess biomarker performance in the pre-clinical setting. Archived public data sets are an invaluable resource for subsequent in silico validation, though their use can lead to data integration issues.

The Hand-Foot Skin Reaction and Quality of Life Questionnaire: An Assessment Tool for Oncology.

Background: Skin toxicity (hand-foot syndrome/hand-foot skin reaction, HFS/R) related to antineoplastic therapy is a significant issue in oncology practice, with potentially large impacts on health-related quality of life (HRQL).

Materials And Methods: A patient-reported questionnaire, the hand-foot skin reaction and quality of life (HF-QoL) questionnaire was developed to measure the HFS/R symptoms associated with cancer therapeutic agents and their effect on daily activities. The validity and reliability of the HF-QoL questionnaire was tested in a randomized trial of capecitabine with sorafenib/placebo in 223 patients with locally advanced/metastatic breast cancer.

Variations in body weight, food intake and body composition after long-term high-fat diet feeding in C57BL/6J mice.

Objective: To investigate the variations in body weight, food intake, and body composition of both male and female C57BL/6J mice during a diet-induced obesity model with high-fat diet (HFD) feeding.

Methods: Mice were individually housed and fed ad libitum either a low-fat diet (LFD, 10% calories from fat; n = 15 male, n = 15 female) or HFD (45% calories from fat; n = 277 male, n = 278 female) from 8 to 43 weeks of age. Body weight, food intake, and body composition were routinely measured.

Vaccination with Gag, Vif, and Nef gene fragments affords partial control of viral replication after mucosal challenge with SIVmac239.

Unlabelled: Broadly targeted cellular immune responses are thought to be important for controlling replication of human and simian immunodeficiency viruses (HIV and SIV). However, eliciting such responses by vaccination is complicated by immunodominance, the preferential targeting of only a few of the many possible epitopes of a given antigen. This phenomenon may be due to the coexpression of dominant and subdominant epitopes by the same antigen-presenting cell and may be overcome by distributing these sequences among several different vaccine constructs.

Incidence of cetuximab-related infusion reactions in oncology patients treated at the University of North Carolina Cancer Hospital.

Purpose: The primary purpose of this study was to determine the rate of infusion reactions to cetuximab in oncology patients treated at the University of North Carolina Cancer Hospital. Secondarily, we sought to evaluate predictors of grade 3-4 hypersensitivity, including geography.

Methods: Data were collected by retrospective chart review for patients treated with cetuximab at the University of North Carolina Cancer Hospital between 15 November 2006 and 31 December 2010.

Psychometric evaluation of the Sinonasal Outcome Test-16 and activity impairment assessment in acute bacterial sinusitis.

Objective: To validate the Sinonasal Outcome Test-16 and Activity Impairment Assessment in patients with acute bacterial sinusitis.

Study Design: Data were used from a phase III clinical trial designed to evaluate the efficacy and safety of moxifloxacin 400 mg once daily for 5 consecutive days in the treatment of acute bacterial sinusitis. The psychometric properties and factor structure of the 2 measures were assessed.