Clinical trials

Axillary ultrasound scan (AUS) is routinely employed in the UK for preoperative axillary staging and can diagnose approximately 50 - 80% of node positive patients when combined with percutaneous needle biopsy techniques (either core-biopsy or fine-needle aspiration cytology). It is recognised that nodal burden is generally higher in clinically node negative patients with abnormal nodes on AUS and confirmed on needle-biopsy to be histologically positive than patients diagnosed as node positive on sentinel node biopsy (SNB). However, up to 40% of biopsy-proven node positive patients are found to have fewer than 3 involved nodes on subsequent axillary lymph node dissection (ALND) and are potential candidates for less extensive axillary surgery with axillary radiotherapy (ART) rather than ALND. The total number of abnormal nodes on ultrasound is a key predictor of overall nodal tumour burden. The AMAROS and OTOASOR trials randomised patients with up to 2 positive sentinel nodes to either ALND or ART. These trials were conducted around the turn of the millennium and before routine use of AUS and therefore would have included a significant number of patients who were radiologically node positive (cN1). Likewise, the ACOSOG Z0011 trial that randomised a similar group of patients to either ALND or observation only, did not incorporate routine AUS and would have included some (radiological) cN1 patients. These trials revealed no adverse impact on disease-free or overall survival from omission of completion ALND. Targeted axillary dissection (TAD) was introduced a few years ago to reduce the false negative rate of SNB following neoadjuvant chemotherapy (NACT) and has been standardised as part of the ongoing ATNEC trial \[ClinicalTrials.govNCT04109079\]. This technique for axillary staging after NACT is increasingly being adopted in the UK and elsewhere. TAD is technically more straightforward and less challenging in patients undergoing primary surgery with no concerns about clip migration consequent to nodal shrinkage as part of treatment response to NACT. Furthermore, the risk of under-treating the axilla is offset by the protocol: if no disease is identified in the targeted nodes (false-negative case), then patients proceed to ALND, thereby ensuring adequate treatment. Unlike TAD following NACT, the presence of viable tumour within the sampled nodes is mandatory and finding fibrosis is irrelevant except as a response to nodal biopsy per se. Current ASCO guidelines support both SNB and TAD as staging options for patients with ultrasound-detected, biopsy-confirmed nodal disease. The Edinburgh randomised trials comparing four-node sampling with ALND demonstrated significantly lower arm morbidity with node sampling, supporting TAD as a less morbid appropriate alternative in this patient population. The UK-ANZ POSNOC trial randomised 1,900 patients with \<3 macrometastases to either no further axillary treatment or additional axillary treatment. The study included cN1 patients with biopsy-confirmed nodal metastases who underwent sentinel node biopsy or TAD. Patients with \<3 macrometastases on final histology were randomised to receive no further axillary treatment or proceed with additional axillary treatment (ALND or ART). POSNOC trial will answer whether further axillary treatment provides any benefit in patients with low volume nodal disease on SNB or TAD. Notably, patients with biopsy-confirmed metastases and \<3 macrometastases on SNB/TAD are biologically and clinically similar to patients with normal AUS who are later found to have low-volume disease on SNB. Clinical decision-making and patient outcomes are driven by tumour biology and overall disease burden rather than the method of nodal disease detection. Furthermore, AUS sensitivity is operator dependent and whether FNA or core biopsy was used to sample the node. A patient considered node negative on AUS by one radiologist may be diagnosed with core biopsy confirmed nodal metastases with another radiologist. Pending the results of POSNOC trial, patients with less than 3 macrometastases are generally advised further axillary treatment, and ART is preferred over ALND to reduce the risk of lymphoedema. NodeSMART is a prospective audit collecting data on patients undergoing TAD in the primary surgery setting. Its goal is to audit surgical outcomes and benchmark them against - a) Comparing technical outcomes with those from sentinel node biopsy in the primary surgery setting and TAD performed after neoadjuvant chemotherapy. b) Assessing rates of arm lymphoedema and disease progression relative to findings from the AMAROS and Z11 trials, and the POSNOC trial once results are available. The term "Targeted Axillary Dissection" is somewhat misleading in this context, as the marked (biopsied) node is removed alongside sentinel nodes - not in isolation. NodeSMART therefore refers to the procedure more accurately as Targeted Sentinel Node Biopsy (TSNB).

The aim of this study is to assess whether, omitting further axillary treatment (ALND and ART) for patients with early stage breast cancer and axillary nodal metastases on needle biopsy, who after NACT have no residual cancer in the lymph nodes on sentinel node biopsy, is non-inferior to axillary treatment in terms of disease free survival (DFS) and results in reduced risk of lymphoedema at 5 years.

When a person's kidneys are not working properly, they need a life-saving treatment called haemodialysis three times a week to filter the waste and extra fluids from the blood. 25 000 adults in the United Kingdom are currently having haemodialysis and unfortunately more than two-thirds of these people experience problems with thinking and memory, which may lead to dementia. These problems tend to worsen more rapidly than people who are not on haemodialysis. This decline in brain function can make it harder for people to do everyday tasks, increase their reliance on others, and lower their overall quality of life. It also raises the chances of needing hospital care and can shorten their lifespan. One reason for this decline in thinking and memory could be the dialysis treatment itself. Research has shown that blood flow to the brain can drop during dialysis. If this happens regularly, it can harm the brain over time. Earlier studies found that cooling the dialysis fluid slightly (to 0.5°C below body temperature) helped people tolerate dialysis better and showed less brain damage on magnetic imaging brain scans (MRI) after a year, compared to those who had haemodialysis without cooling the dialysis fluid. However, the investigators still don't know if this brain protection translates into better thinking and memory for people on haemodialysis. This study will see if cooling the dialysis fluid helps preserve thinking and memory function. The investigators will invite participants at three hospitals with haemodialysis centres to take part. Those who agree will be randomly assigned to either standard dialysis or cooled dialysis. The investigators will assess participants' thinking and memory functions using special tests at the start of the study and again after a year. By comparing the results from both groups, the investigators hope to see if the cooled dialysis really helps protect brain.

Who can participate? Any adults over the age of 18 who have received a kidney transplant at the research centre are eligible for recruitment within the first month after transplant What does the study involve? The study involves observing and gathering data to understand how the health of people who receive a kidney transplant changes over the first year. In particular the investigators are interested in the risk factors for heart disease and stroke, and how these change over the first year of transplant. The investigators are also interested in multiple health conditions, and how these impact patients after transplant. There are no interventions but there will be measurements of diagnoses, risk factors for heart disease and stroke, and assessments of physical fitness Blood pressure, BMI, routine blood tests as well as assessing muscle and fat changes, how fit patients are and what new health conditions they have. What are the possible benefits and risks of participating? There is no active treatment or intervention, so there are no risks of benefits compared to normal care. Where is the study run from? University Hospitals of Derby and Burton NHS trust, at the Royal Derby hospital Renal Department. When is the study starting and how long is it expected to run for? The study is expected to start 1/9/2025 and run for 2 years. Who is funding the study? The only costs of the study are funding for the staff member running the study, who is funded by the NIHR as an academic research fellow Who is the main contact? Dr Samuel Strain, [email protected]

In this feasibility study, 60 women undergoing reconstruction will be randomly allocated to receive biological or synthetic mesh and followed for 6 months. The findings will tell us if patients and surgeons are comfortable with not being able to choose which mesh is used for the operation. In the larger surgical study, the investigators plan to measure patients' satisfaction with the reconstruction, patients' quality of life, complications from the operation and costs over 5 years.

The aim of the research study is to look at a new type of MRI scanning that can measure the amount of sodium in different parts of the body. Sodium (or 'salt') levels are very important in maintaining health, and high levels lead to high blood pressure. This is very important to patients with kidney disease, as the kidney is the main organ that regulates the amount of sodium in the body. It is possible to measure blood sodium levels, but this does not tell us how much sodium is present in other areas of the body. Previously, it has not been possible measure this. Sodium MRI (Na-MRI) is a new type of MRI scanning that can directly measure sodium in other parts of body such as skin, muscles, kidneys, and brain. The investigators believe that this will help to guide treatment in patients with kidney disease who are on haemodialysis, research studies are needed to prove the benefits.