Nat. Rev. Clin. Oncol. doi: /nrclinonc

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Nat. Rev. Clin. Oncol. doi: /nrclinonc

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Nat. Rev. Clin. Oncol. doi: /nrclinonc

Figure 2 Underreporting by physicians of specific treatment-associated symptoms by physicians in the TORCH trial Figure 2 | Underreporting by physicians.

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Nat. Rev. Clin. Oncol. doi: /nrclinonc

Figure 3 Response after appearance of a new lesion

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Figure 2 Multiscale modelling in oncology

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EULAR Lupus Nephritis Trials Network Study Group 2017

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Nat. Rev. Clin. Oncol. doi: /nrclinonc

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Figure 1 Underreporting of treatment-related toxicities by physicians, relative to patients with either advanced-stage lung cancer, or early-stage breast.

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Nat. Rev. Clin. Oncol. doi: /nrclinonc

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Nat. Rev. Clin. Oncol. doi: /nrclinonc

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Nat. Rev. Clin. Oncol. doi: /nrclinonc

Nat. Rev. Clin. Oncol. doi: /nrclinonc

Figure 1 Therapeutic targeting of the B-cell receptor (BCR)

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Nat. Rev. Clin. Oncol. doi: /nrclinonc

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Nat. Rev. Clin. Oncol. doi: /nrclinonc

Theis Lange and Shanmei Liao

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Nat. Rev. Clin. Oncol. doi:10.1038/nrclinonc.2017.59 Figure 1 Proposed three-stage (Ensign) design of early phase clinical trials in children Figure 1 | Proposed three-stage (Ensign) design of early phase clinical trials in children. The aim of this design is to evaluate therapeutic agents by assessing toxicity and antitumour activity (>30% and never <10% at any stage). Expansion cohorts are defined by molecular characteristics or disease entities. Patients in the dose-confirmation study can be included in the expansion cohort if they received the recommended phase II dose (RP2D) for paediatric patients. A molecularly targeted agent (MTA) or immunotherapeutic agent without serious, dose-related toxicities and a wide therapeutic index has a starting dose of 100% of body surface area (BSA)-corrected RP2D for adults. By contrast, an MTA or immunotherapeutic agent with serious, dose-related toxicities and a narrow therapeutic index has a starting dose of 80% of BSA-corrected RP2D for adults. Dose-escalation is performed using a Bayesian logistic regression model (BLRM) or continuous reassessment method (CRM). Moreno, L. et al. (2017) Early phase clinical trials of anticancer agents in children and adolescents — an ITCC perspective Nat. Rev. Clin. Oncol. doi:10.1038/nrclinonc.2017.59