Feasibility study of a multimodal prehabilitation programme in women receiving neoadjuvant therapy for breast cancer in a major cancer hospital: a protocol.

INTRODUCTION: Neoadjuvant therapy has become a standard treatment for patients with stage II/III HER2 positive and triple negative breast cancer, and in well-selected patients with locally advanced and borderline resectable high risk, luminal B breast cancer. Side effects of neoadjuvant therapy, such as fatigue, cardiotoxicity, neurotoxicity, anxiety, insomnia, vasomotor symptoms, gastrointestinal disturbance as well as a raft of immune-related adverse events, may impact treatment tolerance, long-term outcomes, and quality of life. Providing early supportive care prior to surgery (typically termed 'prehabilitation') may mitigate these side effects and improve quality of life.During our codesign of the intervention, consumers and healthcare professionals expressed desire for a programme that 'packaged' care, was easy to access, and was embedded in their care pathway. We hypothesise that a multimodal supportive care programme including exercise and complementary therapies, underpinned by behavioural change theory will improve self-efficacy, quality of life, readiness for surgery and any additional treatment for women with breast cancer. We seek to explore cardiometabolic, residual cancer burden and surgical outcomes, along with chemotherapy completion (relative dose intensity). This article describes the protocol for a feasibility study of a multimodal prehabilitation programme. METHODS AND ANALYSIS: This is a prospective, mixed-method, feasibility study of a multi-modal programme in a hospital setting for 20-30 women with breast cancer receiving neoadjuvant therapy. Primary outcomes are recruitment rate, retention rate, adherence and acceptability. Secondary outcomes include patient reported outcome measures (PROMs), surgical outcomes, length of stay, satisfaction with surgery, chemotherapy completion rates, changes in metabolic markers and adverse events. Interviews and focus groups to understand the experience with prehabilitation and different factors that may affect feasibility of the intervention . The output of this study will be a codesigned, evidence-informed intervention assessed for feasibility and acceptability by women with breast cancer and the healthcare professionals that care for them. ETHICS AND DISSEMINATION: The study received ethics approval from the St Vincents Hospital HREC (HREC/2021/ETH12198). Trial results will be communicated to participants, healthcare professionals, and the public via publication and conferences. TRIAL REGISTRATION NUMBER: ACTRN12622000584730.

Accurate isolation and detection of circulating tumor cells using enrichment-free multiparametric high resolution imaging.

Introduction: The reliable and accurate detection of rare circulating tumor cells (CTCs) from cancer patient blood samples promises advantages in both research and clinical applications. Numerous CTC detection methods have been explored that rely on either the physical properties of CTCs such as density, size, charge, and/or their antigen expression profiles. Multiple factors can influence CTC recovery including blood processing method and time to processing. This study aimed to examine the accuracy and sensitivity of an enrichment-free method of isolating leukocytes (AccuCyte® system) followed by immunofluorescence staining and high-resolution imaging (CyteFinder® instrument) to detect CTCs. Method: Healthy human blood samples, spiked with cancer cells from cancer cell lines, as well as blood samples obtained from 4 subjects diagnosed with cancer (2 pancreatic, 1 thyroid, and 1 small cell lung) were processed using the AccuCyte-CyteFinder system to assess recovery rate, accuracy, and reliability over a range of processing times. Results: The AccuCyte-CyteFinder system was highly accurate (95.0%) at identifying cancer cells in spiked-in samples (in 7.5 mL of blood), even at low spiked-in numbers of 5 cells with high sensitivity (90%). The AccuCyte-CyteFinder recovery rate (90.9%) was significantly higher compared to recovery rates obtained by density gradient centrifugation (20.0%) and red blood cell lysis (52.0%). Reliable and comparable recovery was observed in spiked-in samples and in clinical blood samples processed up to 72 hours post-collection. Reviewer analysis of images from spiked-in and clinical samples resulted in high concordance (R-squared value of 0.998 and 0.984 respectively). Discussion: The AccuCyte-CyteFinder system is as an accurate, sensitive, and clinically practical method to detect and enumerate cancer cells. This system addresses some of the practical logistical challenges in incorporating CTCs as part of routine clinical care. This could facilitate the clinical use of CTCs in guiding precision, personalized medicine.

Evaluation of the Swedish adjustable gastric band VC (SAGB-VC) in an Australian population: early results.

BACKGROUND: The Swedish adjustable gastric band VC (SAGB-VC) has been in use in Australia since 2007. We evaluated its efficacy and safety. METHODS: We retrospectively analyzed the prospective clinical data of patients who received the implant between November 2007 and June 2009 at 3 Australian bariatric centres. RESULTS: In all, 1176 patients (mean age 45.9 [standard deviation (SD) 12.3] yr, mean body mass index 43.4 [SD 7.6]) received the SAGB-VC. At a mean follow-up of 11 (SD 3) months, weight reduced by a mean of 18.4 (SD 11.1) kg with an excess weight loss of 37.8% (SD 19.9%). Body mass index decreased (from mean 43.4 [SD 7.7] to mean 36.7 [SD 6.5], p < 0.001). Type 2 diabetes (T2DM) was reported in 167 patients and hypertension in 373. Improvement occurred in 73.5% of patients with T2DM and 31% with hypertension, with patient-reported reduction or cessation of medication. Metabolic syndrome indices improved during follow-up: high-density lipoprotein cholesterol (mean 1.3 [SD 0.3] v. mean 1.4 [SD 0.3] mmol/L, p < 0.001), triglycerides (mean 1.6 [SD 0.8] v. mean 1.3 [SD 0.7] mmol/L, p < 0.001), waist circumference (men 141 [SD 103] to 121 [SD 15] cm, women 117 [SD 14] to 105 [SD 14] cm, both p < 0.001), C-reactive protein (90.5 [SD 75.2] v. 53.3 [SD 61.9] nmol/L, p < 0.001). The complication rate was 4.2%. CONCLUSION: The SAGB-VC is safe and effective for treating obesity and its comorbidities. The results are reproducible in separate Australian centres and consistent with published literature.

Improvement in comorbid illness after placement of the Swedish Adjustable Gastric Band.

BACKGROUND: Obesity and its related comorbid illnesses have become a national health priority. We report comorbidity and quality of life (QoL) data after weight loss with gastric banding using the Swedish Adjustable Gastric Band (SAGB). METHODS: Data were collected prospectively for 838 consecutive morbidly obese patients who underwent laparoscopic adjustable gastric banding (LAGB) between January 2001 and July 2007. Patients were followed-up by a multidisciplinary team consisting of a surgeon, physician, dietician, and exercise consultant, all of whom were involved in the evaluation of clinical outcomes. Continuous data were reported as mean +/- SD; categorical data were reported as number and percentage. Patients served as their own controls. RESULTS: Respective preoperative mean age, weight, and body mass index (BMI) were 44 years (range 16-76), 122 kg (range 86-240), and 44 kg/m2 (range 35-86), respectively. SAGB implantation was accomplished by the pars flaccida technique with no conversion to an open procedure. Mature follow-up data were available for 35% of patients at 24 months and 21% at 36 months. In the total cohort of 838 patients, BMI (mean +/- SD) decreased to 32 +/- 5 kg/m2 and 32 +/- 7 kg/m2 at 24 months and 36 months, respectively. Percentage excess weight loss (%EWL) (mean +/- SD) was 32% +/- 14% (n = 506), 47% +/- 15% (n = 461), 52% +/- 16% (n = 291), and 54% +/- 23% (n = 175) at 6, 12, 24, and 36 months, respectively (P < .001). There were 545 patients identified with comorbid illness at >6-month follow-up. After a median follow-up of 13 months (range 6-36 months), resolution and/or improvement of comorbidities was as follows: type 2 diabetes mellitus, 79%; metabolic syndrome, 78%; hypertension, 67%; dyslipidemia, 66%; gastroesophageal reflux, 66%; asthma, 57%; arthritis/joint pain, 70%; polycystic ovarian syndrome, 48%; and depression, 57%. There was a significant improvement in QoL (as measured by the Short Form-36 Health Survey [SF-36]), bringing patients' QoL to a level consistent with that of community norms in all 8 domain scores. Of 342 patients surveyed with the Beck Depression Inventory (BDI-II), a statistically significant improvement in depressive mood was also observed (P < .001). CONCLUSION: Weight loss achieved by use of the SAGB provides a dramatic reduction in many serious comorbid illnesses as well as improvement in the psychosocial wellbeing of morbidly obese patients.

Gastric banding for the treatment of type 2 diabetes mellitus in morbidly obese.

BACKGROUND: To assess the efficacy of the Swedish adjustable gastric band in the treatment of type 2 diabetes mellitus (T2DM), impaired glucose tolerance (IGT), and the metabolic syndrome (MS) in the morbidly obese. METHODS: We identified all patients with T2DM, IGT, or the MS at surgery from our database of 905 consecutive patients who had undergone placement of the Swedish adjustable gastric band between January 2001 and April 2007. The patients were followed up by our multidisciplinary team, and their T2DM was managed by their treating primary care physician and/or endocrinologist. RESULTS: A total of 682 patients had >6 months of follow-up. Of these, 78 patients had T2DM, 64 had IGT, and 100 had the MS. At a median follow-up of 12.5 months, patients with T2DM had a mean +/- SD excess weight loss of 38% +/- 15%. This was associated with hemoglobin A1c and fasting blood sugar levels decreasing from 8.0% +/- 1.7% to 6.1% +/- 1.0% (P <.0001) and from 9.6 +/- 3.4 mmol/L to 5.7 +/- 1.5 mmol/L (P <.0001), respectively. Remission and/or improvement in patients with T2DM was judged by the complete cessation and/or reduction in medication and normalization of laboratory values. This occurred in 81% of those taking oral hypoglycemic agents. Of the patients taking a combination of oral hypoglycemic agents and insulin, 43% ceased and/or reduced their oral hypoglycemic agents, and 93% ceased and/or reduced their insulin requirements. Of those on insulin only, 75% ceased and/or reduced their insulin. No patient with IGT developed diabetes or progressed to require medications. Remission and/or improvement in the MS occurred in 88% of patients. Remission of T2DM was dependent on both the magnitude of excess weight loss (P = .008) and the duration of the pre-existing T2DM. Using binary logistic regression analysis, a duration of T2DM of <5 years before surgery was 6.5 times more likely to lead to resolution of T2DM after the weight loss (P = .004). CONCLUSION: Weight loss after Swedish adjustable gastric band placement is an effective treatment of T2DM in morbidly obese patients, with early intervention offering the greatest chance of remission. It might even prevent the occurrence of T2DM in patients with IGT.

Rapid significant weight loss and regional lipid deposition: Implications for insulin sensitivity.

AIM: To compare regional lipid deposition and insulin sensitivity after differing weight loss strategies: very low calorie diet (VLCD) and laparoscopic adjustable gastric banding (LAGB). METHOD: Thirty-nine obese women underwent anthropometry, proton magnetic resonance (MR) spectroscopy for assessment of liver fat (LFAT) and MR imaging for visceral (VAT) and subcutaneous abdominal fat volume (SAT) determination. Fasting blood was taken for insulin, glucose and free fatty acid (FFA) analysis. Measurements were repeated after 6-weeks Optifast VLCD (n = 14) or 3 months after LAGB (n = 25). RESULTS: Similar, significant (p < 0.001) weight loss occurred after VLCD (8%) and LAGB (9%). Both interventions induced significant (p < 0.001) and similar reductions in body mass index (BMI) and waist circumference, and in SAT and VAT (VLCD p < 0.05, LAGB p < 0.001). LFAT fell only after VLCD (p < 0.05). Plasma FFA only fell after LAGB (p < 0.05). Homeostasis model assessment (HOMA-R) improved only following VLCD (p < 0.05). No relations were detected between the changes in LFAT, VAT and SAT. The change in LFAT related to the change in HOMA-R in both interventions combined (r = 0.410, p = 0.013) and in the VLCD group (r = 0.660, p = 0.020). There was no change in relative dietary fat intake after LAGB (p = 0.11). CONCLUSION: Caloric and fat restriction for 6 weeks (VLCD) reduces weight, SAT, VAT, LFAT and HOMA-R. Less severe caloric restriction for 12 weeks (LAGB) causes significant loss of weight, VAT and SAT but no detectable change in LFAT and HOMA-R. Following weight loss, a change in LFAT is related more to changes in insulin sensitivity or dietary fat than to abdominal adiposity loss.