Diffusion Tensor Imaging for Assessment of Response to Neoadjuvant Chemotherapy in Patients With Breast Cancer.

In this study, the prognostic significance of tumor metrics derived from diffusion tensor imaging (DTI) was evaluated in patients with locally advanced breast cancer undergoing neoadjuvant therapy. DTI and contrast-enhanced magnetic resonance imaging were acquired at 1.5 T in 34 patients before treatment and after 3 cycles of taxane-based therapy (early treatment). Tumor fractional anisotropy (FA), principal eigenvalues (λ1, λ2, and λ3), and apparent diffusion coefficient (ADC) were estimated for tumor regions of interest drawn on DTI data. The association between DTI metrics and final tumor volume change was evaluated with Spearman rank correlation. DTI metrics were investigated as predictors of pathological complete response (pCR) by calculating the area under the receiver operating characteristic curve (AUC). Early changes in tumor FA and ADC significantly correlated with final tumor volume change post therapy (ρ = -0.38, P = .03 and ρ = -0.71, P < .001, respectively). Pretreatment tumor ADC was significantly lower in the pCR than in the non-pCR group (P = .04). At early treatment, patients with pCR had significantly higher percent changes of tumor λ1, λ2, λ3, and ADC than those without pCR. The AUCs for early percent changes in tumor FA and ADC were 0.60 and 0.83, respectively. The early percent changes in tumor eigenvalues and ADC were the strongest DTI-derived predictors of pCR. Although early percent change in tumor FA had a weak association with pCR, the significant correlation with final tumor volume change suggests that this metric changes with therapy and may merit further evaluation

Initial experience of dedicated breast PET imaging of ER+ breast cancers using [F-18]fluoroestradiol.

Dedicated breast positron emission tomography (dbPET) is an emerging technology with high sensitivity and spatial resolution that enables detection of sub-centimeter lesions and depiction of intratumoral heterogeneity. In this study, we report our initial experience with dbPET using [F-18]fluoroestradiol (FES) in assessing ER+ primary breast cancers. Six patients with >90% ER+ and HER2- breast cancers were imaged with dbPET and breast MRI. Two patients had ILC, three had IDC, and one had an unknown primary tumor. One ILC patient was treated with letrozole, and another patient with IDC was treated with neoadjuvant chemotherapy without endocrine treatment. In this small cohort, we observed FES uptake in ER+ primary breast tumors with specificity to ER demonstrated in a case with tamoxifen blockade. FES uptake in ILC had a diffused pattern compared to the distinct circumscribed pattern in IDC. In evaluating treatment response, the reduction of SUVmax was observed with residual disease in an ILC patient treated with letrozole, and an IDC patient treated with chemotherapy. Future study is critical to understand the change in FES SUVmax after endocrine therapy and to consider other tracer uptake metrics with SUVmax to describe ER-rich breast cancer. Limitations include variations of FES uptake in different ER+ breast cancer diseases and exclusion of posterior tissues and axillary regions. However, FES-dbPET has a high potential for clinical utility, especially in measuring response to neoadjuvant endocrine treatment. Further development to improve the field of view and studies with a larger cohort of ER+ breast cancer patients are warranted

Effect of Longitudinal Variation in Tumor Volume Estimation for MRI-guided Personalization of Breast Cancer Neoadjuvant Treatment

Purpose To investigate the impact of longitudinal variation in functional tumor volume (FTV) underestimation and overestimation in predicting pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC). Materials and Methods Women with breast cancer who were enrolled in the prospective I-SPY 2 TRIAL (Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging and Molecular Analysis 2) from May 2010 to November 2016 were eligible for this retrospective analysis. Participants underwent four MRI examinations during NAC treatment. FTV was calculated based on automated segmentation. Baseline FTV before treatment (FTV0) and the percentage of FTV change at early treatment and inter-regimen time points relative to baseline (∆FTV1 and ∆FTV2, respectively) were classified into high-standard or standard groups based on visual assessment of FTV under- and overestimation. Logistic regression models predicting pCR using single predictors (FTV0, ∆FTV1, and ∆FTV2) and multiple predictors (all three) were developed using bootstrap resampling with out-of-sample data evaluation with the area under the receiver operating characteristic curve (AUC) independently in each group. Results This study included 432 women (mean age, 49.0 years ± 10.6 [SD]). In the FTV0 model, the high-standard and standard groups showed similar AUCs (0.61 vs 0.62). The high-standard group had a higher estimated AUC compared with the standard group in the ∆FTV1 (0.74 vs 0.63), ∆FTV2 (0.79 vs 0.62), and multiple predictor models (0.85 vs 0.64), with a statistically significant difference for the latter two models

Breast Multiparametric MRI for Prediction of Neoadjuvant Chemotherapy Response in Breast Cancer: The BMMR2 Challenge

Purpose To describe the design, conduct, and results of the Breast Multiparametric MRI for prediction of neoadjuvant chemotherapy Response (BMMR2) challenge. Materials and Methods The BMMR2 computational challenge opened on May 28, 2021, and closed on December 21, 2021. The goal of the challenge was to identify image-based markers derived from multiparametric breast MRI, including diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE) MRI, along with clinical data for predicting pathologic complete response (pCR) following neoadjuvant treatment. Data included 573 breast MRI studies from 191 women (mean age [±SD], 48.9 years ± 10.56) in the I-SPY 2/American College of Radiology Imaging Network (ACRIN) 6698 trial (ClinicalTrials.gov: NCT01042379). The challenge cohort was split into training (60%) and test (40%) sets, with teams blinded to test set pCR outcomes. Prediction performance was evaluated by area under the receiver operating characteristic curve (AUC) and compared with the benchmark established from the ACRIN 6698 primary analysis. Results Eight teams submitted final predictions. Entries from three teams had point estimators of AUC that were higher than the benchmark performance (AUC, 0.782 [95% CI: 0.670, 0.893], with AUCs of 0.803 [95% CI: 0.702, 0.904], 0.838 [95% CI: 0.748, 0.928], and 0.840 [95% CI: 0.748, 0.932]). A variety of approaches were used, ranging from extraction of individual features to deep learning and artificial intelligence methods, incorporating DCE and DWI alone or in combination. Conclusion The BMMR2 challenge identified several models with high predictive performance, which may further expand the value of multiparametric breast MRI as an early marker of treatment response. Clinical trial registration no. NCT0104237

Fuzzy clustering with spatial-temporal information

Clustering geographical units based on a set of quantitative features observed at several time occasions requires to deal with the complexity of both space and time information. In particular, one should consider (1) the spatial nature of the units to be clustered, (2) the characteristics of the space of multivariate time trajectories, and (3) the uncertainty related to the assignment of a geographical unit to a given cluster on the basis of the above com- plex features. This paper discusses a novel spatially constrained multivariate time series clustering for units characterised by different levels of spatial proximity. In particular, the Fuzzy Partitioning Around Medoids algorithm with Dynamic Time Warping dissimilarity measure and spatial penalization terms is applied to classify multivariate Spatial-Temporal series. The clustering method has been theoretically presented and discussed using both simulated and real data, highlighting its main features. In particular, the capability of embedding different levels of proximity among units, and the ability of considering time series with different length

Predicting breast cancer response to neoadjuvant treatment using multi-feature MRI: results from the I-SPY 2 TRIAL.

Dynamic contrast-enhanced (DCE) MRI provides both morphological and functional information regarding breast tumor response to neoadjuvant chemotherapy (NAC). The purpose of this retrospective study is to test if prediction models combining multiple MRI features outperform models with single features. Four features were quantitatively calculated in each MRI exam: functional tumor volume, longest diameter, sphericity, and contralateral background parenchymal enhancement. Logistic regression analysis was used to study the relationship between MRI variables and pathologic complete response (pCR). Predictive performance was estimated using the area under the receiver operating characteristic curve (AUC). The full cohort was stratified by hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status (positive or negative). A total of 384 patients (median age: 49 y/o) were included. Results showed analysis with combined features achieved higher AUCs than analysis with any feature alone. AUCs estimated for the combined versus highest AUCs among single features were 0.81 (95% confidence interval [CI]: 0.76, 0.86) versus 0.79 (95% CI: 0.73, 0.85) in the full cohort, 0.83 (95% CI: 0.77, 0.92) versus 0.73 (95% CI: 0.61, 0.84) in HR-positive/HER2-negative, 0.88 (95% CI: 0.79, 0.97) versus 0.78 (95% CI: 0.63, 0.89) in HR-positive/HER2-positive, 0.83 (95% CI not available) versus 0.75 (95% CI: 0.46, 0.81) in HR-negative/HER2-positive, and 0.82 (95% CI: 0.74, 0.91) versus 0.75 (95% CI: 0.64, 0.83) in triple negatives. Multi-feature MRI analysis improved pCR prediction over analysis of any individual feature that we examined. Additionally, the improvements in prediction were more notable when analysis was conducted according to cancer subtype

Datopotamab–deruxtecan plus durvalumab in early-stage breast cancer: the sequential multiple assignment randomized I-SPY2.2 phase 2 trial

Sequential adaptive trial designs can help accomplish the goals of personalized medicine, optimizing outcomes and avoiding unnecessary toxicity. Here we describe the results of incorporating a promising antibody-drug conjugate, datopotamab-deruxtecan (Dato-DXd) in combination with programmed cell death-ligand 1 inhibitor, durvalumab, as the first sequence of therapy in the I-SPY2.2 phase 2 neoadjuvant sequential multiple assignment randomization trial for high-risk stage 2/3 breast cancer. The trial includes three blocks of treatment, with initial randomization to different experimental agent(s) (block A), followed by a taxane-based regimen tailored to tumor subtype (block B), followed by doxorubicin-cyclophosphamide (block C). Subtype-specific algorithms based on magnetic resonance imaging volume change and core biopsy guide treatment redirection after each block, including the option of early surgical resection in patients predicted to have a high likelihood of pathologic complete response, which is the primary endpoint assessed when resection occurs. There are two primary efficacy analyses: after block A and across all blocks for six prespecified HER2-negative subtypes (defined by hormone receptor status and/or response-predictive subtypes). In total, 106 patients were treated with Dato-DXd/durvalumab in block A. In the immune-positive subtype, Dato-DXd/durvalumab exceeded the prespecified threshold for success (graduated) after block A; and across all blocks, pathologic complete response rates were equivalent to the rate expected for the standard of care (79%), but 54% achieved that result after Dato-DXd/durvalumab alone (block A) and 92% without doxorubicin-cyclophosphamide (after blocks A + B). The treatment strategy across all blocks graduated in the hormone-negative/immune-negative subtype. No new toxicities were observed. Stomatitis was the most common side effect in block A. No patients receiving block A treatment alone had adrenal insufficiency. Dato-DXd/durvalumab is a promising therapy combination that can eliminate standard chemotherapy in many patients, particularly the immune-positive subtype.ClinicalTrials.gov registration: NCT01042379

Crop Updates 2006 - Lupins and Pulses

This session covers sixty six papers from different authors: 2005 LUPIN AND PULSE INDUSTRY HIGHLIGHTS 1. Lupin Peter White, Department of Agriculture 2. Pulses Mark Seymour, Department of Agriculture 3. Monthly rainfall at experimental sites in 2005 4. Acknowledgements Amelia McLarty EDITOR 5. Contributors 6. Background Peter White, Department of Agriculture 2005 REGIONAL ROUNDUP 7. Northern agricultural region Wayne Parker, Department of Agriculture 8. Central agricultural region Ian Pritchard and Bob French, Department of Agriculture 9. Great southern and lakes Rodger Beermier, Department of Agriculture 10. South east region Mark Seymour, Department of Agriculture LUPIN AND PULSE PRODUCTION AGRONOMY AND GENETIC IMPROVEMENT 11. Lupin Peter White, Department of Agriculture 12. Narrow-leafed lupin breeding Bevan Buirchell, Department of Agriculture 13. Progress in the development of pearl lupin (Lupinus mutabilis) for Australian agriculture, Mark Sweetingham1,2, Jon Clements1, Geoff Thomas2, Roger Jones1, Sofia Sipsas1, John Quealy2, Leigh Smith1 and Gordon Francis1 1CLIMA, The University of Western Australia 2Department of Agriculture 14. Molecular genetic markers and lupin breeding, Huaan Yang, Jeffrey Boersma, Bevan Buirchell, Department of Agriculture 15. Construction of a genetic linkage map using MFLP, and identification of molecular markers linked to domestication genes in narrow-leafed lupin (Lupinus augustiflolius L) Jeffrey Boersma1,2, Margaret Pallotta3, Bevan Buirchell1, Chengdao Li1, Krishnapillai Sivasithamparam2 and Huaan Yang1 1Department of Agriculture, 2The University of Western Australia, 3Australian Centre for Plant Functional Genomics, South Australia 16. The first gene-based map of narrow-leafed lupin – location of domestication genes and conserved synteny with Medicago truncatula, M. Nelson1, H. Phan2, S. Ellwood2, P. Moolhuijzen3, M. Bellgard3, J. Hane2, A. Williams2, J. Fos‑Nyarko4, B. Wolko5, M. Książkiewicz5, M. Cakir4, M. Jones4, M. Scobie4, C. O’Lone1, S.J. Barker1, R. Oliver2, and W. Cowling1 1School of Plant Biology, The University of Western Australia, 2Australian Centre for Necrotrophic Fungal Pathogens, Murdoch University, 3Centre for Bioinformatics and Biological Computing, Murdoch University, 4School of Biological Sciences and Biotechnology, SABC, Murdoch University,5Institute of Plant Genetics, Polish Academy of Sciences, Poznań, Poland 17. How does lupin optimum density change row spacing? Bob French and Laurie Maiolo, Department of Agriculture 18. Wide row spacing and seeding rate of lupins with conventional and precision seeding machines Martin Harries, Jo Walker and Murray Blyth, Department of Agriculture 19. Influence of row spacing and plant density on lupin competition with annual ryegrass, Martin Harries, Jo Walker and Murray Blyth, Department of Agriculture 20. Effect of timing and speed of inter-row cultivation on lupins, Martin Harries, Jo Walker and Steve Cosh, Department of Agriculture 21. The interaction of atrazine herbicide rate and row spacing on lupin seedling survival, Martin Harries and Jo Walker Department of Agriculture 22. The banding of herbicides on lupin row crops, Martin Harries, Jo Walker and Murray Blyth, Department of Agriculture 23. Large plot testing of herbicide tolerance of new lupin lines, Wayne Parker, Department of Agriculture 24. Effect of seed source and simazine rate of seedling emergence and growth, Peter White and Greg Shea, Department of Agriculture 25. The effect of lupin row spacing and seeding rate on a following wheat crop, Martin Harries, Jo Walker and Dirranie Kirby, Department of Agriculture 26. Response of crop lupin species to row spacing, Leigh Smith1, Kedar Adhikari1, Jon Clements2 and Patrizia Guantini3, 1Department of Agriculture, 2CLIMA, The University of Western Australia, 3University of Florence, Italy 27. Response of Lupinus mutabilis to lime application and over watering, Peter White, Leigh Smith and Mark Sweetingham, Department of Agriculture 28. Impact of anthracnose on yield of Andromeda lupins, Geoff Thomas, Kedar Adhikari and Katie Bell, Department of Agriculture 29. Survey of lupin root health (in major production areas), Geoff Thomas, Ken Adcock, Katie Bell, Ciara Beard and Anne Smith, Department of Agriculture 30. Development of a generic forecasting and decision support system for diseases in the Western Australian wheatbelt, Tim Maling1, Art Diggle1,2, Debbie Thackray1, Kadambot Siddique1 and Roger Jones1,2 1CLIMA, The University of Western Australia, 2Department of Agriculture 31.Tanjil mutants highly tolerant to metribuzin, Ping Si1, Mark Sweetingham1,2, Bevan Buirchell1,2 and Huaan Yang l,2 1CLIMA, The University of Western Australia, 2Department of Agriculture 32. Precipitation pH vs. yield and functional properties of lupin protein isolate, Vijay Jayasena1, Hui Jun Chih1 and Ken Dods2 1Curtin University of Technology, 2Chemistry Centre 33. Lupin protein isolation with the use of salts, Vijay Jayasena1, Florence Kartawinata1,Ranil Coorey1 and Ken Dods2 1Curtin University of Technology, 2Chemistry Centre 34. Field pea, Mark Seymour, Department of Agriculture 35. Breeding highlights Kerry Regan1,2, Tanveer Khan1,2, Stuart Morgan1 and Phillip Chambers1 1Department of Agriculture, 2CLIMA, The University of Western Australia 36. Variety evaluation, Kerry Regan1,2, Tanveer Khan1,2, Jenny Garlinge1 and Rod Hunter1 1Department of Agriculture, 2CLIMA, The University of Western Australia 37. Days to flowering of field pea varieties throughout WA Mark Seymour1, Ian Pritchard1, Rodger Beermier1, Pam Burgess1 and Dr Eric Armstrong2 Department of Agriculture, 2NSW Department of Primary Industries, Wagga Wagga 38. Semi-leafless field peas yield more, with less ryegrass seed set, in narrow rows, Glen Riethmuller, Department of Agriculture 39. Swathing, stripping and other innovative ways to harvest field peas, Mark Seymour, Ian Pritchard, Rodger Beermier and Pam Burgess, Department of Agriculture 40. Pulse demonstrations, Ian Pritchard, Wayne Parker, Greg Shea, Department of Agriculture 41. Field pea extension – focus on field peas 2005, Ian Pritchard, Department of Agriculture 42. Field pea blackspot disease in 2005: Prediction versus reality, Moin Salam, Jean Galloway, Pip Payne, Bill MacLeod and Art Diggle, Department of Agriculture 43. Pea seed-borne mosaic virus in pulses: Screening for seed quality defects and virus resistance, Rohan Prince, Brenda Coutts and Roger Jones, Department of Agriculture, and CLIMA, The University of Western Australia 44. Yield losses from sowing field peas infected with pea seed-borne mosaic virus, Rohan Prince, Brenda Coutts and Roger Jones, Department of Agriculture, and CLIMA, The University of Western Australia 45. Desi chickpea, Wayne Parker, Department of Agriculture 46. Breeding highlights, Tanveer Khan 1,2, Pooran Gaur3, Kadambot Siddique2, Heather Clarke2, Stuart Morgan1and Alan Harris1, 1Department of Agriculture2CLIMA, The University of Western Australia, 3International Crop Research Institute for Semi Arid Tropics (ICRISAT), India 47. National chickpea improvement program, Kerry Regan1, Ted Knights2 and Kristy Hobson3,1Department of Agriculture, 2Agriculture New South Wales 3Department of Primary Industries, Victoria 48. Chickpea breeding lines in CVT exhibit excellent ascochyta blight resistance, Tanveer Khan1,2, Alan Harris1, Stuart Morgan1 and Kerry Regan1,2, 1Department of Agriculture, 2CLIMA, The University of Western Australia 49. Variety evaluation, Kerry Regan1,2, Tanveer Khan1,2, Jenny Garlinge2 and Rod Hunter2, 1CLIMA, The University of Western Australia 2Department of Agriculture 50. Desi chickpeas for the wheatbelt, Wayne Parker and Ian Pritchard, Department of Agriculture 51. Large scale demonstration of new chickpea varieties, Wayne Parker, MurrayBlyth, Steve Cosh, Dirranie Kirby and Chris Matthews, Department of Agriculture 52. Ascochyta management with new chickpeas, Martin Harries, Bill MacLeod, Murray Blyth and Jo Walker, Department of Agriculture 53. Management of ascochyta blight in improved chickpea varieties, Bill MacLeod1, Colin Hanbury2, Pip Payne1, Martin Harries1, Murray Blyth1, Tanveer Khan1,2, Kadambot Siddique2, 1Department of Agriculture, 2CLIMA, The University of Western Australia 54. Botrytis grey mould of chickpea, Bill MacLeod, Department of Agriculture 55. Kabuli chickpea, Kerry Regan, Department of Agriculture, and CLIMA, The University of Western Australia 56. New ascochyta blight resistant, high quality kabuli chickpea varieties, Kerry Regan1,2, Kadambot Siddique2, Tim Pope2 and Mike Baker1, 1Department of Agriculture, 2CLIMA, The University of Western Australia 57. Crop production and disease management of Almaz and Nafice, Kerry Regan and Bill MacLeod, Department of Agriculture, and CLIMA, The University of Western Australia 58. Faba bean,Mark Seymour, Department of Agriculture 59. Germplasm evaluation – faba bean, Mark Seymour1, Tim Pope2, Peter White1, Martin Harries1, Murray Blyth1, Rodger Beermier1, Pam Burgess1 and Leanne Young1,1Department of Agriculture, 2CLIMA, The University of Western Australia 60. Factors affecting seed coat colour of faba bean during storage, Syed Muhammad Nasar-Abbas1, Julie Plummer1, Kadambot Siddique2, Peter White 3, D. Harris4 and Ken Dods4.1The University of Western Australia, 2CLIMA, The University of Western Australia, 3Department of Agriculture, 4Chemistry Centre 61. Lentil,Kerry Regan, Department of Agriculture, and CLIMA, The University of Western Australia 62. Variety and germplasm evaluation, Kerry Regan1,2, Tim Pope2, Leanne Young1, Phill Chambers1, Alan Harris1, Wayne Parker1 and Michael Materne3, 1Department of Agriculture 2CLIMA, The University of Western Australia, 3Department of Primary Industries, Victoria Pulse species 63. Land suitability for production of different crop species in Western Australia, Peter White, Dennis van Gool, and Mike Baker, Department of Agriculture 64. Genomic synteny in legumes: Application to crop breeding, Huyen Phan1, Simon Ellwood1, J. Hane1, Angela Williams1, R. Ford2, S. Thomas3 and Richard Oliver1,1Australian Centre of Necrotrophic Plant Pathogens, Murdoch University 2BioMarka, School of Agriculture and Food Systems, ILFR, University of Melbourne 3NSW Department of Primary Industries 65. ALOSCA – Development of a dry flow legume seed inoculant, Rory Coffey and Chris Poole, ALOSCA Technologies Pty Ltd 66. Genetic dissection of resistance to fungal necrotrophs in Medicago truncatula, Simon Ellwood1, Theo Pfaff1, Judith Lichtenzveig12, Lars Kamphuis1, Nola D\u27Souza1, Angela Williams1, Emma Groves1, Karam Singh2 and Richard Oliver1 1Australian Centre of Necrotrophic Plant Pathogens, Murdoch University, 2CSIRO Plant Industry APPENDIX I: LIST OF COMMON ACRONYM

A theory and methodology to quantify knowledge

This article proposes quantitative answers to meta-scientific questions including 'how much knowledge is attained by a research field?', 'how rapidly is a field making progress?', 'what is the expected reproducibility of a result?', 'how much knowledge is lost from scientific bias and misconduct?', 'what do we mean by soft science?', and 'what demarcates a pseudoscience?'. Knowledge is suggested to be a system-specific property measured by K, a quantity determined by how much of the information contained in an explanandum is compressed by an explanans, which is composed of an information 'input' and a 'theory/methodology' conditioning factor. This approach is justified on three grounds: (i) K is derived from postulating that information is finite and knowledge is information compression; (ii) K is compatible and convertible to ordinary measures of effect size and algorithmic complexity; (iii) K is physically interpretable as a measure of entropic efficiency. Moreover, the K function has useful properties that support its potential as a measure of knowledge. Examples given to illustrate the possible uses of K include: the knowledge value of proving Fermat's last theorem; the accuracy of measurements of the mass of the electron; the half life of predictions of solar eclipses; the usefulness of evolutionary models of reproductive skew; the significance of gender differences in personality; the sources of irreproducibility in psychology; the impact of scientific misconduct and questionable research practices; the knowledge value of astrology. Furthermore, measures derived from K may complement ordinary meta-analysis and may give rise to a universal classification of sciences and pseudosciences. Simple and memorable mathematical formulae that summarize the theory's key results may find practical uses in meta-research, philosophy and research policy