The lancet oncology
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The lancet oncology · Oct 2020
ReviewTotal marrow and total lymphoid irradiation in bone marrow transplantation for acute leukaemia.
The use of total body irradiation as part of conditioning regimens for acute leukaemia is progressively declining because of concerns of late toxic effects and the introduction of radiation-free regimens. Total marrow irradiation and total marrow and lymphoid irradiation represent more targeted forms of radiotherapy compared with total body irradiation that have the potential to decrease toxicity and escalate the dose to the bone marrow for high-risk patients. ⋯ The exact role of total marrow irradiation or total marrow and lymphoid irradiation in new conditioning regimens seems dependent on its technological implementation, aiming to make the whole procedure less time consuming, more streamlined, and easier to integrate into the clinical workflow. We also foresee a role for computer-assisted planning, as a way to improve planning and delivery and to incorporate total marrow irradiation and total marrow and lymphoid irradiation in multi-centric phase 2-3 trials.
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The lancet oncology · Oct 2020
ReviewDemystifying the estimand framework: a case study using patient-reported outcomes in oncology.
Patient-reported outcome (PRO) measures describe how a patient feels or functions and are increasingly being used in benefit-risk assessments in the development of cancer drugs. However, PRO research objectives are often ill-defined in clinical cancer trials, which can lead to misleading conclusions about patient experiences. The estimand framework is a structured approach to aligning a clinical trial objective with the study design, including endpoints and analysis. ⋯ We apply the estimand framework to a hypothetical trial for breast cancer, using physical function to develop specific PRO research objectives. This Policy Review is not an endorsement of a specific study design or outcome; rather, it is meant to show the application of principles of the estimand framework to research study design and add to ongoing discussion. Use of the estimand framework to review medical products and label PROs in oncology can improve communication between stakeholders and ultimately provide a clearer interpretation of patient experience in the development of oncological drugs.
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The lancet oncology · Sep 2020
ReviewTurning up the heat on non-immunoreactive tumours: opportunities for clinical development.
Notable advances have been achieved in the treatment of cancer since the advent of immunotherapy, and immune checkpoint inhibitors have shown clinical benefit across a wide variety of tumour types. Nevertheless, most patients still progress on these treatments, highlighting the importance of unravelling the underlying mechanisms of primary resistance to immunotherapy. ⋯ In this Review, we discuss preclinical data that serves as the basis for ongoing immunotherapy clinical trials for the treatment of non-immunoreactive tumours, as well as reviewing clinical and translational data where available. We explain how improving our understanding of the underlying mechanisms of primary resistance to immunotherapy will help elucidate an increasingly granular view of the tumour microenvironment cellular composition, functional status, and cellular localisation, with the goal of further therapy refinement.
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The lancet oncology · Sep 2020
ReviewDevelopment of paediatric non-stage prognosticator guidelines for population-based cancer registries and updates to the 2014 Toronto Paediatric Cancer Stage Guidelines.
Population-based cancer registries (PBCRs) generate measures of cancer incidence and survival that are essential for cancer surveillance, research, and cancer control strategies. In 2014, the Toronto Paediatric Cancer Stage Guidelines were developed to standardise how PBCRs collect data on the stage at diagnosis for childhood cancer cases. These guidelines have been implemented in multiple jurisdictions worldwide to facilitate international comparative studies of incidence and outcome. ⋯ With the use of these principles, recommendations were made on which NSPs should be collected for the major malignancies in children. The 2014 Toronto Stage Guidelines were also reviewed and updated where necessary. Wide adoption of the resultant Paediatric NSP Guidelines and updated Toronto Stage Guidelines will enhance the harmonisation and use of childhood cancer data provided by PBCRs.
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The lancet oncology · Sep 2020
ReviewMolecular profiling of neuroendocrine tumours to predict response and toxicity to peptide receptor radionuclide therapy.
Peptide receptor radionuclide therapy (PRRT) is a type of radiotherapy that targets peptide receptors and is typically used for neuroendocrine tumours (NETs). Some of the key challenges in its use are the prediction of efficacy and toxicity, patient selection, and response optimisation. In this Review, we assess current knowledge on the molecular profile of NETs and the strategies and tools used to predict, monitor, and assess the toxicity of PRRT. ⋯ No molecular markers exist that can predict the toxicity of PRRT. Candidate molecular targets include seven single nucleotide polymorphisms (SNPs) that are susceptible to radiation. Transcriptomic evaluations of blood and a combination of gene expression and specific SNPs, assessed by machine learning with algorithms that are tumour-specific, might yield molecular tools to enhance the efficacy and safety of PRRT.