Prognosis research strategy (PROGRESS) 4: Stratified medicine
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Abstract

In patients with a particular disease or health condition, stratified medicine seeks to identify those who will have the most clinical benefit or least harm from a specific treatment. In this article, the fourth in the PROGRESS series, the authors discuss why prognosis research should form a cornerstone of stratified medicine, especially in regard to the identification of factors that predict individual treatment response

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Rapid planetesimal formation in turbulent circumstellar discs

Anders Johansen, Jeffrey S. Oishi, Mordecai-Mark Mac Low … (2007)

The initial stages of planet formation in circumstellar gas discs proceed via dust grains that collide and build up larger and larger bodies (Safronov 1969). How this process continues from metre-sized boulders to kilometre-scale planetesimals is a major unsolved problem (Dominik et al. 2007): boulders stick together poorly (Benz 2000), and spiral into the protostar in a few hundred orbits due to a head wind from the slower rotating gas (Weidenschilling 1977). Gravitational collapse of the solid component has been suggested to overcome this barrier (Safronov 1969, Goldreich & Ward 1973, Youdin & Shu 2002). Even low levels of turbulence, however, inhibit sedimentation of solids to a sufficiently dense midplane layer (Weidenschilling & Cuzzi 1993, Dominik et al. 2007), but turbulence must be present to explain observed gas accretion in protostellar discs (Hartmann 1998). Here we report the discovery of efficient gravitational collapse of boulders in locally overdense regions in the midplane. The boulders concentrate initially in transient high pressures in the turbulent gas (Johansen, Klahr, & Henning 2006), and these concentrations are augmented a further order of magnitude by a streaming instability (Youdin & Goodman 2005, Johansen, Henning, & Klahr 2006, Johansen & Youdin 2007) driven by the relative flow of gas and solids. We find that gravitationally bound clusters form with masses comparable to dwarf planets and containing a distribution of boulder sizes. Gravitational collapse happens much faster than radial drift, offering a possible path to planetesimal formation in accreting circumstellar discs.

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Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma.

Tony Mok, Yi-Long Wu, Sumitra Thongprasert … (2009)

Previous, uncontrolled studies have suggested that first-line treatment with gefitinib would be efficacious in selected patients with non-small-cell lung cancer. In this phase 3, open-label study, we randomly assigned previously untreated patients in East Asia who had advanced pulmonary adenocarcinoma and who were nonsmokers or former light smokers to receive gefitinib (250 mg per day) (609 patients) or carboplatin (at a dose calculated to produce an area under the curve of 5 or 6 mg per milliliter per minute) plus paclitaxel (200 mg per square meter of body-surface area) (608 patients). The primary end point was progression-free survival. The 12-month rates of progression-free survival were 24.9% with gefitinib and 6.7% with carboplatin-paclitaxel. The study met its primary objective of showing the noninferiority of gefitinib and also showed its superiority, as compared with carboplatin-paclitaxel, with respect to progression-free survival in the intention-to-treat population (hazard ratio for progression or death, 0.74; 95% confidence interval [CI], 0.65 to 0.85; P<0.001). In the subgroup of 261 patients who were positive for the epidermal growth factor receptor gene (EGFR) mutation, progression-free survival was significantly longer among those who received gefitinib than among those who received carboplatin-paclitaxel (hazard ratio for progression or death, 0.48; 95% CI, 0.36 to 0.64; P<0.001), whereas in the subgroup of 176 patients who were negative for the mutation, progression-free survival was significantly longer among those who received carboplatin-paclitaxel (hazard ratio for progression or death with gefitinib, 2.85; 95% CI, 2.05 to 3.98; P<0.001). The most common adverse events were rash or acne (in 66.2% of patients) and diarrhea (46.6%) in the gefitinib group and neurotoxic effects (69.9%), neutropenia (67.1%), and alopecia (58.4%) in the carboplatin-paclitaxel group. Gefitinib is superior to carboplatin-paclitaxel as an initial treatment for pulmonary adenocarcinoma among nonsmokers or former light smokers in East Asia. The presence in the tumor of a mutation of the EGFR gene is a strong predictor of a better outcome with gefitinib. (ClinicalTrials.gov number, NCT00322452.) 2009 Massachusetts Medical Society

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The path to personalized medicine.

Margaret A Hamburg, Francis Collins (2010)

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Author and article information

Contributors

Aroon D Hingorani: Role: professor of genetic epidemiology

Daniëlle A van Windt: Role: professor in primary care epidemiology

Richard D Riley: Role: senior lecturer in medical statistics

Keith Abrams: Role: professor of medical statistics

Karel G M Moons: Role: professor of clinical epidemiology

Ewout W Steyerberg: Role: professor of medical decision making

Sara Schroter: Role: senior researcher

Willi Sauerbrei: Role: professor of medical biometry

Douglas G Altman: Role: professor of statistics in medicine

Harry Hemingway: Role: professor of clinical epidemiology

Journal

Journal ID (nlm-ta): BMJ

Journal ID (iso-abbrev): BMJ

Journal ID (publisher-id): bmj

Title: BMJ : British Medical Journal

Publisher: BMJ Publishing Group Ltd.

ISSN (Print): 0959-8138

ISSN (Electronic): 1756-1833

Publication date Collection: 2013

Publication date (Print): 2013

Publication date (Electronic): 5 February 2013

Volume: 346

Electronic Location Identifier: e5793

Affiliations

[1 ]Department of Epidemiology and Public Health, University College London, London WC1E 7HB, UK

[2 ]Arthritis Research UK Primary Care Centre, Primary Care Sciences, Keele University, Keele ST5 5BG, UK

[3 ]School of Health and Population Sciences, University of Birmingham, Birmingham B15 2TT, UK

[4 ]Centre for Biostatistics & Genetic Epidemiology, Department of Health Sciences, School of Medicine, University of Leicester, Leicester LE1 7RH, UK

[5 ]Julius Center for Health Sciences and Primary Care, UMC Utrecht, Utrecht, Netherlands

[6 ]Department of Public Health, Erasmus MC, 3000 CA Rotterdam, Rotterdam, Netherlands

[7 ]BMJ, BMA House, London WC1H 9JR, UK

[8 ]Institute of Medical Biometry and Informatics, University Medical Center Freiburg, 79104 Freiburg, Germany

[9 ]Centre for Statistics in Medicine, University of Oxford, Oxford OX2 6UD, UK

Author notes

Correspondence to: H Hemingway h.hemingway@ 123456ucl.ac.uk

Article

Publisher ID: hina004188

DOI: 10.1136/bmj.e5793

PMC ID: 3565686

PubMed ID: 23386361

SO-VID: 6dbe54d6-6298-4f98-b553-eb80c9d0db3c

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/2.0/ and http://creativecommons.org/licenses/by-nc/2.0/legalcode.

Prognosis research strategy (PROGRESS) 4: Stratified medicine research

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Abstract

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UCL: UN SDG 03 Good Health and Well-Being

Most cited references 53

Rapid planetesimal formation in turbulent circumstellar discs

Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma.

The path to personalized medicine.

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