Machine learning -- based diffractive imaging with subwavelength resolution

Far-field characterization of small objects is severely constrained by the diffraction limit. Existing tools achieving sub-diffraction resolution often utilize point-by-point image reconstruction via scanning or labelling. Here, we present a new imaging technique capable of fast and accurate characterization of two-dimensional structures with at least wavelength/25 resolution, based on a single far-field intensity measurement. Experimentally, we realized this technique resolving the smallest-available to us 180-nm-scale features with 532-nm laser light. A comprehensive analysis of machine learning algorithms was performed to gain insight into the learning process and to understand the flow of subwavelength information through the system. Image parameterization, suitable for diffractive configurations and highly tolerant to random noise was developed. The proposed technique can be applied to new characterization tools with high spatial resolution, fast data acquisition, and artificial intelligence, such as high-speed nanoscale metrology and quality control, and can be further developed to high-resolution spectroscop

Zoledronic acid significantly improves pain scores and quality of life in breast cancer patients with bone metastases: a randomised, crossover study of community vs hospital bisphosphonate administration

Patients with bone metastases from breast cancer often experience substantial skeletal complications – including debilitating bone pain – which negatively affect quality of life. Zoledronic acid (4 mg) has been demonstrated to reduce significantly the risk of skeletal complications in these patients and is administered via a short, 15-min infusion every 3 weeks, allowing the possibility for home administration. This study compared the efficacy and safety of zoledronic acid administered in the community setting vs the hospital setting in breast cancer patients with ⩾1 bone metastasis receiving hormonal therapy. After a lead-in phase of three infusions of 4 mg zoledronic acid in the hospital setting, 101 patients were randomized to receive three open-label infusions in the community or hospital setting, followed by three infusions in the opposite venue (a total of nine infusions). The Brief Pain Inventory (BPI) and the European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire 30 (EORTC QLQ-C30) were used to assess potential benefits of zoledronic acid therapy. At study end, analysis of the BPI showed significant reductions in worst pain (P=0.008) and average pain in the last 7 days (P=0.039), and interference with general activity (P=0.012). In each case, there were significantly greater improvements in pain scores after treatment in the community setting compared with the hospital crossover setting for worst pain (P=0.021), average pain (P=0.003), and interference with general activity (P=0.001). Overall global health status showed a significant median improvement of 8.3% (P=0.013) at study end. Physical, emotional, and social functioning also showed significant overall improvement (P=0.013, 0.005, and 0.043, respectively). Furthermore, physical, role, and social functioning showed significantly greater improvements after treatment in the community setting compared with the hospital crossover setting (P=0.018, 0.001, and 0.026, respectively). There was no difference between hospital and community administration in renal or other toxicity, with zoledronic acid being well tolerated in both treatment settings. These data confirm the safety and quality-of-life benefits of zoledronic acid in breast cancer patients with bone metastases, particularly when administered in the community setting

The treatment of nephrotic syndrome caused by primary (light chain) amyloid with vincristine, doxorubicin and dexamethasone.

Three out of four patients with primary (light chain) amyloid nephrotic syndrome treated with vincristine, doxorubicin and dexamethasone (VAD) induction obtained a partial response and are alive in continuing remission at 4.1, 6.5 and 9.3 years. These preliminary results are of considerable interest and suggest that prospective evaluation of this regimen is warranted in patients with this condition

Adjuvant trastuzumab duration trials in HER2 positive breast cancer - what results would be practice-changing? Persephone investigator questionnaire prior to primary endpoint results.

Trastuzumab Duration questionnaire. The questionnaire that was completed by the oncologists. (PDF 476 kb

Predictors of early relapse in postmenopausal women with hormone receptor-positive breast cancer in the BIG 1-98 trial

Background: Aromatase inhibitors are considered standard adjuvant endocrine treatment of postmenopausal women with hormone receptor-positive breast cancer, but it remains uncertain whether aromatase inhibitors should be given upfront or sequentially with tamoxifen. Awaiting results from ongoing randomized trials, we examined prognostic factors of an early relapse among patients in the BIG 1-98 trial to aid in treatment choices. Patients and methods: Analyses included all 7707 eligible patients treated on BIG 1-98. The median follow-up was 2 years, and the primary end point was breast cancer relapse. Cox proportional hazards regression was used to identify prognostic factors. Results: Two hundred and eighty-five patients (3.7%) had an early relapse (3.1% on letrozole, 4.4% on tamoxifen). Predictive factors for early relapse were node positivity (P < 0.001), absence of both receptors being positive (P < 0.001), high tumor grade (P < 0.001), HER-2 overexpression/amplification (P < 0.001), large tumor size (P = 0.001), treatment with tamoxifen (P = 0.002), and vascular invasion (P = 0.02). There were no significant interactions between treatment and the covariates, though letrozole appeared to provide a greater than average reduction in the risk of early relapse in patients with many involved lymph nodes, large tumors, and vascular invasion present. Conclusion: Upfront letrozole resulted in significantly fewer early relapses than tamoxifen, even after adjusting for significant prognostic factor

Incidence of cerebral metastases in patients treated with trastuzumab for metastatic breast cancer

Trastuzumab is an effective treatment for patients with metastatic breast cancer (MBC) that overexpresses HER-2. A high incidence of brain metastases (BM) has been noted in patients receiving trastuzumab. A retrospective chart review was conducted of 100 patients commencing trastuzumab for metastatic breast cancer from July 1999 to December 2002, at the Christie Hospital. Seven patients were excluded; five patients developed central nervous system metastases prior to starting trastuzumab, and inadequate data were available for two. Out of the remaining 93 patients, 23 (25%) have developed BM to date. In all, 46 patients have died, and of these 18 (39%) have been diagnosed with BM prior to death. Of the 23 patients developing BM, 18 (78%) were hormone receptor negative and 18 (78%) had visceral disease. Univariate analysis showed a significant association between the development of cerebral disease and both hormone receptor status and the presence of visceral disease. In conclusion, a high proportion of patients with MBC treated with trastuzumab develop symptomatic cerebral metastases. HER-2-positive breast cancer may have a predilection for the brain, or trastuzumab therapy may change the disease pattern by prolonging survival. New strategies to address this problem require investigation in this group of patients

Trastuzumab-associated cardiac events in the Persephone trial.

BACKGROUND: We report cardiac events in the Persephone trial which compares 6-12 months of adjuvant trastuzumab in women with confirmed HER2-positive, early-stage breast cancer. METHODS: Clinical cardiac events were defined as any of the following: symptoms and/or signs of congestive heart failure (CHF) and new or altered CHF medication. In addition, left ventricular ejection fraction (LVEF) was measured at baseline and then 3 monthly for 12 months. RESULTS: A total of 2500 patients, aged 22-82, were included: 1251 randomised to 12 months and 1249 to 6 months of trastuzumab treatment. A total of 93% (2335/2500) received anthracyclines, 49% of these (1136/2335) with taxanes. Cardiotoxicity delayed treatment in 6% of 12-month and 4% of 6-month patients (P=0.01), and stopped treatment early in 8% (96/1214) of 12-month and 4% (45/1216) of 6-month patients (P3 cycles of anthracycline was associated with higher risk of cardiac events only for 12-month patients (OR 1.41 (1.04-1.90)), and not for 6-month patients (OR 1.28 (0.91-1.79)). CONCLUSIONS: We demonstrate significantly fewer cardiac events from 6 months of adjuvant trastuzumab compared with that from 12 months. This cardiac signal adds importance to the question of the optimum duration of adjuvant trastuzumab treatment. If 6 months is proven to have non-inferior outcomes to 12 months treatment, these data would support 6 months as the standard of care.National Institute of Health Research Health Technology Assessment (NIHR HTA) Programme UK. Funding reference number - 06/303/98This is the author accepted manuscript. The final version is available from Nature Publishing Group via https://doi.org/10.1038/bjc.2016.35

Optimising the Duration of Adjuvant Trastuzumab in Early Breast Cancer in the UK.

Adjuvant trastuzumab for patients with HER2 positive early breast cancer demonstrated significant improvements in both disease-free and overall survival with 12 months treatment (1, 2), and this was NICE approved in the UK in 2006. When the FinHer trial demonstrated similar results with nine weeks trastuzumab (3), there was significant interest in whether shorter durations might be as effective. Additional benefits for patients could be less toxicity, fewer hospital visits and a more rapid return to normal life, with considerable societal benefits of reduced costs. PERSEPHONE was the pragmatic UK duration trial funded by the NIHR HTA, which showed that 6 months adjuvant trastuzumab was non-inferior to 12 months with 4-year disease-free survival rate of 89.4% compared with 89.8% respectively (non-inferiority p = 0.01) (4). Less toxicity was reported with 6 months particularly cardiac toxicity and there were cost savings over the first 2 years (5), which were maintained over an average patient’s lifetime when extrapolated using an economic model. After the publication of these results in June 2019, the Optimal Duration of Adjuvant Trastuzumab Working Group was convened, comprising a diverse, multi-disciplinary membership. There were representatives from the PERSEPHONE Trial Management Group including patient advocates, the NCRI Breast Group, the Association of Cancer Physicians (ACP), the Royal College of Radiologists (RCR), and the Independent Cancer Patients’ Voice (ICPV). By November 2019, both dual antibody treatment with trastuzumab and pertuzumab (https://www.nice.org.uk/guidance/ta569) and extended neratinib after single agent trastuzumab (https://www.nice.org.uk/guidance/ta612) had been approved by NICE only for those at high risk of recurrence. Therefore, single agent trastuzumab remained standard of care for those at lower risk of recurrence and recommendations were made for these patients.Funded by NIHR HTA