The lancet oncology
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Primary brain tumours are heterogeneous in histology, genetics, and outcome. Although WHO's classification of tumours of the CNS has greatly helped to standardise diagnostic criteria worldwide, it does not consider the substantial progress that has been made in the molecular classification of many brain tumours. ⋯ However, these molecular approaches cannot yet predict patients' benefit from therapeutic interventions. Similarly, transcriptome-based classification of medulloblastoma has delineated four variants that might now be candidate diseases in which to explore novel targeted agents.
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The lancet oncology · Aug 2013
ReviewPrevention and management of treatment-induced pharyngo-oesophageal stricture.
Pharyngo-oesophageal stricture (PES) is a serious complication that occurs in up to a third of patients treated with external beam radiotherapy or combined chemoradiotherapy for head and neck cancer. This entity is under-reported and as a result, our understanding of the pathophysiology and prevention of this complication is restricted. ⋯ We discuss various treatment options, including swallowing exercises and manoeuvres, endoscopic dilatations, and for advanced cases, oesophageal reconstruction. Study of the subset of patients who develop this toxicity and early recognition and intervention of this pathological change in future trials will help to optimise treatment of these patients.
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The lancet oncology · Aug 2013
ReviewPredictors of recurrence for ductal carcinoma in situ after breast-conserving surgery.
Ductal carcinoma in situ (DCIS) constitutes a major public health problem, with up to half of screen-detected cancers representing pure forms of DCIS without evidence of invasion. A proportion of cases detected with routine screening would not have progressed to a life-threatening form of breast cancer during the patient's lifetime, and overdiagnosis of breast cancer is a cause for concern. Once DCIS has been detected, treatment is obligatory and present technologies do not allow accurate risk stratification such that intensity of treatment can be tailored to risk of recurrence and progression to invasive disease. ⋯ With increasing molecular characterisation of these preinvasive lesions, data will be available for how factors such as oestrogen receptor, progesterone receptor, HER2, and indicators of proliferative activity can provide additional information about both prognosis and benefit from adjuvant treatments such as radiotherapy and hormonal therapy. Low-risk patients are especially poorly defined in terms of need for adjuvant therapies, which can be associated with both short-term adverse sequelae and long-term effects (eg, cardiotoxicity) that can affect all-cause mortality. Optimum risk prediction in the future is likely to be achieved by integration of both conventional and molecular factors, which should be incorporated into a validated predictive model to help with clinical decision making.
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The lancet oncology · Aug 2013
ReviewInhibition of HSP90 molecular chaperones: moving into the clinic.
Heat shock protein 90 (HSP90) is a molecular chaperone that is crucial for the stability and function of many proteins essential for cell survival. Many oncogenes, including tyrosine kinases, transcription factors, and cell-cycle regulatory proteins, are client proteins of HSP90. ⋯ Here, we review the current status of HSP90 inhibitors in clinical development, including geldanamycin derivatives, resorcinol derivatives, purine analogues, and other synthetic inhibitors. We also discuss novel strategies and future perspectives on how to optimise the therapeutic potential of this exciting new class of drugs.