Results of the c-TRAK TN trial: a clinical trial utilising ctDNA mutation tracking to detect molecular residual disease and trigger intervention in patients with moderate- and high-risk early-stage triple-negative breast cancer.

BACKGROUND: Post-treatment detection of circulating tumour DNA (ctDNA) in early-stage triple-negative breast cancer (TNBC) patients predicts high risk of relapse. c-TRAK TN assessed the utility of prospective ctDNA surveillance in TNBC and the activity of pembrolizumab in patients with ctDNA detected [ctDNA positive (ctDNA+)]. PATIENTS AND METHODS: c-TRAK TN, a multicentre phase II trial, with integrated prospective ctDNA surveillance by digital PCR, enrolled patients with early-stage TNBC and residual disease following neoadjuvant chemotherapy, or stage II/III with adjuvant chemotherapy. ctDNA surveillance comprised three-monthly blood sampling to 12 months (18 months if samples were missed due to coronavirus disease), and ctDNA+ patients were randomised 2 : 1 to intervention : observation. ctDNA results were blinded unless patients were allocated to intervention, when staging scans were done and those free of recurrence were offered pembrolizumab. A protocol amendment (16 September 2020) closed the observation group; all subsequent ctDNA+ patients were allocated to intervention. Co-primary endpoints were (i) ctDNA detection rate and (ii) sustained ctDNA clearance rate on pembrolizumab (NCT03145961). RESULTS: Two hundred and eight patients registered between 30 January 2018 and 06 December 2019, 185 had tumour sequenced, 171 (92.4%) had trackable mutations, and 161 entered ctDNA surveillance. Rate of ctDNA detection by 12 months was 27.3% (44/161, 95% confidence interval 20.6% to 34.9%). Seven patients relapsed without prior ctDNA detection. Forty-five patients entered the therapeutic component (intervention n = 31; observation n = 14; one observation patient was re-allocated to intervention following protocol amendment). Of patients allocated to intervention, 72% (23/32) had metastases on staging at the time of ctDNA+, and 4 patients declined pembrolizumab. Of the five patients who commenced pembrolizumab, none achieved sustained ctDNA clearance. CONCLUSIONS: c-TRAK TN is the first prospective study to assess whether ctDNA assays have clinical utility in guiding therapy in TNBC. Patients had a high rate of metastatic disease on ctDNA detection. Findings have implications for future trial design, emphasising the importance of commencing ctDNA testing early, with more sensitive and/or frequent ctDNA testing regimes.

Assessment of structural chromosomal instability phenotypes as biomarkers of carboplatin response in triple negative breast cancer: the TNT trial.

BACKGROUND: In the TNT trial of triple negative breast cancer (NCT00532727), germline BRCA1/2 mutations were present in 28% of carboplatin responders. We assessed quantitative measures of structural chromosomal instability (CIN) to identify a wider patient subgroup within TNT with preferential benefit from carboplatin over docetaxel. PATIENTS AND METHODS: Copy number aberrations (CNAs) were established from 135 formalin-fixed paraffin-embedded primary carcinomas using Illumina OmniExpress SNP-arrays. Seven published [allelic imbalanced CNA (AiCNA); allelic balanced CNA (AbCNA); copy number neutral loss of heterozygosity (CnLOH); number of telomeric allelic imbalances (NtAI); BRCA1-like status; percentage of genome altered (PGA); homologous recombination deficiency (HRD) scores] and two novel [Shannon diversity index (SI); high-level amplifications (HLAMP)] CIN-measurements were derived. HLAMP was defined based on the presence of at least one of the top 5% amplified cytobands located on 1q, 8q and 10p. Continuous CIN-measurements were divided into tertiles. All nine CIN-measurements were used to analyse objective response rate (ORR) and progression-free survival (PFS). RESULTS: Patients with tumours without HLAMP had a numerically higher ORR and significantly longer PFS in the carboplatin (C) than in the docetaxel (D) arm [56% (C) versus 29% (D), PHLAMP,quiet = 0.085; PFS 6.1 months (C) versus 4.1 months (D), Pinteraction/HLAMP = 0.047]. In the carboplatin arm, patients with tumours showing intermediate telomeric NtAI and AiCNA had higher ORR [54% (C) versus 20% (D), PNtAI,intermediate = 0.03; 62% (C) versus 33% (D), PAiCNA,intermediate = 0.076]. Patients with high AiCNA and PGA had shorter PFS in the carboplatin arm [3.4 months (high) versus 5.7 months (low/intermediate); and 3.8 months (high) versus 5.6 months (low/intermediate), respectively; Pinteraction/AiCNA = 0.027, Padj.interaction/AiCNA = 0.125 and Pinteraction/PGA = 0.053, Padj.interaction/PGA = 0.176], whilst no difference was observed in the docetaxel arm. CONCLUSIONS: Patients with tumours lacking HLAMP and demonstrating intermediate CIN-measurements formed a subgroup benefitting from carboplatin relative to docetaxel treatment within the TNT trial. This suggests a complex and paradoxical relationship between the extent of genomic instability in primary tumours and treatment response in the metastatic setting.

With info systems, more may be less if needs aren't planned.

Updating the hospital's communications capability is becoming a concern of more and more boards with good reason: it allows the facility to make more informed decisions about competition, pricing, and other issues affecting survival. Discussed here are strategic planning concerns and the advantages and disadvantages of options concerning computer ownership and usage.

Keeping health promotion in the pink. Documentation can show how programs contribute to hospital goals.

Health promotion encompasses a wide range of services, including health information, health education, wellness, and employee health programs--important efforts, but hardly life-or-death matters. So with increased pressure to put programs to an institutional "worth" test, few health promotion programs make the grade, not because they fail, but because their managers do not know how to document and demonstrate their contributions to hospital goals. The tools that can be used to track program impact range from simple hand-written record keeping on file cards to more complicated and computer-supported systems of data gathering and analysis. It is a mistake to assume that only computer-based systems can yield meaningful information. In the documentation process it may be necessary to start small, but it is necessary to start. Sound management decisions depend on practical evidence that a program is helping a hospital's operations. When one hospital implemented an employee assistance program, program managers set out to document how the program saved the hospital money, improved the work environment, and improved quality of care. At another hospital, the manager of the inpatient cardiac rehabilitation program enlisted the assistance of the medical records department to document to the hospital that patients not in the program had longer lengths of stay than program participants.

The nurse shortage: how can we turn the exodus around?

The nurse shortage can be seen as a symptom of the problems caused by the unwillingness of most hospital power groups to share their control of both resources and decision making. Nurses will continue to leave hospital work if hospitals persist in ignoring nurses' pleas for a share of the rewards and power that should be commensurate with the enormous contributions they make to patient care.

Intimate partner violence: a health system's response--Part 2.

Part 1 of this two-part article (January-February 2001 issue) on a health care system's response to domestic violence (DV) described the process St. Joseph Mercy Health System (Ann Arbor, MI) followed to develop policies and procedures for identifying and intervening in DV cases among its patients. In Part 2, Continuum reports on the 2000 SSWLHC Conference presentation by the co-author of that article--Susan Kheder, MSW, ACSW, Program Director, Women's Health Services. Kheder explains how effectively implementing the new DV policy has depended on a long-term effort to foster cultural change among the professional staff and all system employees.