The lancet oncology
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The lancet oncology · Jul 2017
ReviewFrom class waivers to precision medicine in paediatric oncology.
New drugs are crucially needed for children with cancer. The European Paediatric Regulation facilitates paediatric class waivers for drugs developed for diseases only occurring in adults. In this Review, we retrospectively searched oncology drugs that were class waivered between June, 2012, and June, 2015. 147 oncology class waivers were confirmed for 89 drugs. ⋯ Two (2%) class-waivered drugs were considered not relevant and 16 (18%) required further data. In light of these results, we propose five initiatives: an aggregated database of paediatric biological tumour drug targets; molecular profiling of all paediatric tumours at diagnosis and relapse; a joint academic-pharmaceutical industry preclinical platform to help analyse the activity of new drugs (Innovative Therapy for Children with Cancer Paediatric Preclinical Proof-of-Concept Platform); paediatric strategy forums; and the suppression of article 11b of the European Paediatric Regulation, which allows product-specific waivers on the grounds that the associated condition does not occur in children. These initiatives and a mechanism of action-based approach to drug development will accelerate the delivery of new therapeutic drugs for front-line therapy for those children who have unmet medical needs.
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Targeted radionuclide therapy (TRT) is a branch of cancer medicine concerned with the use of radioisotopes, radiolabelled molecules, nanoparticles, or microparticles that either naturally accumulate in or are designed to target tumours. TRT combines the specificity of molecular and sometimes physical targeting with the potent cytotoxicity of ionising radiation. Targeting vectors for TRT include antibodies, antibody fragments, proteins, peptides, and small molecules. ⋯ Use of TRT is increasing with the adoption into practice of radium-223 dichloride for the treatment of bone metastases and with the ongoing clinical development of, among others, 177Lu-dodecanetetraacetic acid tyrosine-3-octreotate (DOTATATE) for the treatment of neuroendocrine tumours and 90Y-microspheres for the treatment of hepatic tumours. The increasing use of TRT raises the question of how best to integrate TRT into multimodality protocols. Achievements in this area and the future prospects of TRT are evaluated in this Review.
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The lancet oncology · Jul 2017
ReviewMethods to reduce postoperative surgical site infections after head and neck oncology surgery.
Head and neck cancer surgery is often a complex multi-step procedure that includes major resections, vascularised tissue reconstruction, and extensive neck dissection. The upper aerodigestive tract mucosal lining is often disrupted during surgery, which requires the management of a clean-contaminated field and the need to reconstruct the mucosal lining. With bacterial contamination, surgical site infections (SSI) are a serious complication that can result in delayed wound healing, wound breakdown, fistula formation, and compromised tissue reconstruction. ⋯ In this Review, we outline the data supporting perioperative antibiotic prophylaxis for clean-contaminated surgeries, which suggest that clindamycin is an inadequate prophylactic antibiotic therapy in the reduction of SSI, and that prolonged antibiotic courses have no established benefit. For salvage laryngectomy after radiotherapy with or without chemotherapy, reconstruction with vascularised tissue reduces the frequency and severity of pharyngocutaneous fistula formation. These evidence-based recommendations have been shown to reduce the chance of SSI after head and neck surgery.
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The lancet oncology · Jul 2017
ReviewRadiotherapy in patients with HIV: current issues and review of the literature.
Although the introduction of highly active antiretroviral therapy has radically improved the life expectancy of patients with HIV, HIV positivity is still considered a major barrier to oncological treatment for patients with cancer because of their worse prognosis and increased susceptibility to toxic effects compared with patients who are immunocompetent. The use of radiotherapy with or without chemotherapy, immunotherapy, or molecular targeted therapy is the standard of care for several cancers. ⋯ In this Review, we discuss the role of radiotherapy, with or without chemotherapy or new drugs, in the treatment of cancer in patients with HIV, with a focus on the efficacy and tolerability of this approach on the basis of available evidence. Moreover, we analyse and discuss the biological basis of interactions between HIV and radiotherapy, evidence from preclinical studies, and immunomodulation by radiotherapy in the HIV setting.
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The lancet oncology · Jul 2017
Previous radiotherapy and the clinical activity and toxicity of pembrolizumab in the treatment of non-small-cell lung cancer: a secondary analysis of the KEYNOTE-001 phase 1 trial.
Preclinical studies have found radiotherapy enhances antitumour immune responses. We aimed to assess disease control and pulmonary toxicity in patients who previously received radiotherapy for non-small-cell lung cancer (NSCLC) before receiving pembrolizumab. ⋯ US National Institutes of Health.