Chordoma: update on disease, epidemiology, biology and medical therapies

Assessment of the change in tumour burden is an important feature of the clinical evaluation of cancer therapeutics: both tumour shrinkage (objective response) and disease progression are useful endpoints in clinical trials. Since RECIST was published in 2000, many investigators, cooperative groups, industry and government authorities have adopted these criteria in the assessment of treatment outcomes. However, a number of questions and issues have arisen which have led to the development of a revised RECIST guideline (version 1.1). Evidence for changes, summarised in separate papers in this special issue, has come from assessment of a large data warehouse (>6500 patients), simulation studies and literature reviews. HIGHLIGHTS OF REVISED RECIST 1.1: Major changes include: Number of lesions to be assessed: based on evidence from numerous trial databases merged into a data warehouse for analysis purposes, the number of lesions required to assess tumour burden for response determination has been reduced from a maximum of 10 to a maximum of five total (and from five to two per organ, maximum). Assessment of pathological lymph nodes is now incorporated: nodes with a short axis of 15 mm are considered measurable and assessable as target lesions. The short axis measurement should be included in the sum of lesions in calculation of tumour response. Nodes that shrink to <10mm short axis are considered normal. Confirmation of response is required for trials with response primary endpoint but is no longer required in randomised studies since the control arm serves as appropriate means of interpretation of data. Disease progression is clarified in several aspects: in addition to the previous definition of progression in target disease of 20% increase in sum, a 5mm absolute increase is now required as well to guard against over calling PD when the total sum is very small. Furthermore, there is guidance offered on what constitutes 'unequivocal progression' of non-measurable/non-target disease, a source of confusion in the original RECIST guideline. Finally, a section on detection of new lesions, including the interpretation of FDG-PET scan assessment is included. Imaging guidance: the revised RECIST includes a new imaging appendix with updated recommendations on the optimal anatomical assessment of lesions. A key question considered by the RECIST Working Group in developing RECIST 1.1 was whether it was appropriate to move from anatomic unidimensional assessment of tumour burden to either volumetric anatomical assessment or to functional assessment with PET or MRI. It was concluded that, at present, there is not sufficient standardisation or evidence to abandon anatomical assessment of tumour burden. The only exception to this is in the use of FDG-PET imaging as an adjunct to determination of progression. As is detailed in the final paper in this special issue, the use of these promising newer approaches requires appropriate clinical validation studies.

Sarcomas are a heterogeneous group of malignant neoplasms arising from mesenchymal cells which encompass dozens of histological types and can occur in virtually any anatomic site. They form one of the principal groups of rare cancers in Europe as defined in the RARECARE project. We analysed 45,568 incident cases diagnosed during 1995-2002 and registered by 76 population-based cancer registries. Total crude incidence was 5.6 per 100,000 per year with an estimated 27,908 new cases per year in the EU27 countries, of which 84% were soft tissue sarcomas and 14% were bone sarcomas. Gastrointestinal stromal tumours (GIST) were only widely recognised as an entity in the late 1990s and consequently were under-registered. Their true incidence is believed to be about 1.5 per 100,000. Age-standardised incidence of soft tissue sarcomas ranged from 3.3 per 100,000 in Eastern Europe to 4.7 per 100,000 in Northern Europe. About 280,000 persons were estimated to be alive at the beginning of 2003 with a past diagnosis of sarcoma, of which 83% were soft tissue sarcomas and 16% were bone sarcomas. Five-year relative survival for 2000-2002 by the period was 58% for soft tissue sarcomas and 62% for bone sarcomas. The diversity and rarity of sarcomas combined with the quite large number of people affected by them mean that they provide a classic example of the importance of networking in diagnosis, therapy and research for rare cancers. Copyright © 2012 Elsevier Ltd. All rights reserved.

Enhancer of zeste homologue 2 (EZH2), the catalytic subunit of Polycomb repressive complex 2 (PRC2), has attracted broad research attention in the past few years because of its involvement in the development and maintenance of many types of cancer and the use of specific EZH2 inhibitors in clinical trials. Several observations show that PRC2 can have both oncogenic and tumour-suppressive functions. We propose that these apparently opposing roles of PRC2 in cancer are a consequence of the molecular function of the complex in maintaining, rather than specifying, the transcriptional repression state of its several thousand target genes.