The development and first results of a health-related outcomes set in familial hypercholesterolemia (FH) patients: Knowledge is health

Background and aims: Familial hypercholesterolemia (FH) is the most common hereditary lipid disorder requiring l

Quality assessment of estrogen receptor and progesterone receptor testing in breast cancer using a tissue microarray-based approach

Assessing hormone receptor status is an essential part of the breast cancer diagnosis, as this biomarker greatly predicts response to hormonal treatment strategies. As such, hormone receptor testing laboratories are strongly encouraged to participate in external quality control schemes to achieve optimization of their immunohistochemical assays. Nine Dutch pathology departments provided tissue blocks containing invasive breast cancers which were all previously tested for estrogen receptor and/or progesterone receptor expression during routine practice. From these tissue blocks

Mondklachten: bijwerkingen van nieuwe, doelgerichte kankertherapieën

Het aantal nieuwe, ‘doelgerichte’middelen voor de behandeling van kanker breidt zich snel uit en deze middelen nemen een steeds prominentere plaats in bij de behandeling van verschillende soorten kanker. Patiënten wordenmeestal ambulant en gedurende een langere periode (maanden tot jaren) behandeld. Ook de tandarts-algemeen practicus zal deze patiënten in de stoel krijgen. Veel van dezemiddelen gevenmondklachten. De prevalentie verschilt sterk permiddel en varieert van 0 tot 52%. Patiënten kunnen hinderlijke gevoeligheid en ulceraties van de orale slijmvliezen ontwikkelen, de sensibiliteit van gebitselementen is soms verhoogd en veelvuldig doen zich klachten over een droge mond en smaakveranderingen voor. Dit kan leiden tot het noodgedwongen aanpassen van de dosis, het onderbreken of het definitief beëindigen van de oncologische therapie. Tevens zijn er bijwerkingen die relevant zijn wanneer invasieve tandheelkundige ingrepen gepland zijn. Zo hebben angiogeneseremmers een effect op de bloedingsneiging en de wondgenezing. Ook is er casuïstiek van kaakbotnecrose ten gevolge van dezemiddelen beschreven. Dit artikel beoogt de tandarts te informeren over de orale bijwerkingen van een aantal doelgerichte kankertherapieën en aanwijzingen te geven voor de praktijk

Limited human epidermal growth factor receptor 2 discordance in metastatic breast cancer patients treated with trastuzumab, a population based study

Background Accurate assessment of the human epidermal growth factor receptor 2 (HER2) in breast cancer is essential for proper treatment decisions. HER2 positivity confirmation rates in breast cancer trials by central testing pathology laboratories were reported to be approximately 85%. The aim of our study was to assess in a population based sample concordance of HER2 status in metastatic breast cancer (MBC) patients locally tested HER2 positive and treated with trastuzumab. Moreover cost-effectiveness of in situ hybridisation (ISH) in patients with an immunohistochemical score 3+ (IHC3+) was explored. Methods MBC patients treated between 2005 and 2009 with trastuzumab-based therapy in North East Netherlands were identified by a survey of hospital pharmacies. Primary tumour samples were retested centrally for HER2 status using 1 immunohistochemical (IHC) method and two methods using ISH on tissue micro-arrays. Potential discordant patients were retested on whole tumour slides. HER2 positivity was defined as: (1) ISH amplification (according to American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) clinical practice Guideline Update) and (2) when ISH failed an IHC score of 3+. Cost-effectiveness was estimated using potential ISH and treatment costs. Results HER2 status could be retested in 174 of 194 (90%) patients. The HER2 concordance rate was 87%. The 21 discordant patients were in the 67% due to primary HER2 testing with only IHC. Overall survival of HER2 discordant and concordant patients was not significantly different (18 versus 25 months, p = 0.131). Structural ISH in the case of IHC3+ has an estimated potential saving of €87,710 per 100 patients. Conclusion HER2 concordance in a population based study is comparable to those described in selected populations. Discordance is mostly due to testing with only IHC. ISH in the case of IHC3+ is cost-effectiv

Oral adverse events associated with tyrosine kinase and mammalian target of rapamycin inhibitors in renal cell carcinoma: a structured literature review

Background. Oral adverse events (OAEs) associated with multitargeted tyrosine kinase inhibitors (TKIs) and mammalian target of rapamycin inhibitors (mTORIs) are underestimated but frequent and novel presentations of mucosal manifestations. Because optimal antitumor activity requires maintaining the optimal dose, it is essential to avoid unintended treatment delays or interruptions. Methods. We review the reported prevalence and appearance of OAEs with TKIs and mTORIs and the current oral assessment tools commonly used in clinical trials. We discuss the correlations between OAEs and hand-foot skin reaction (HFSR) and rash. Results. The reported prevalence of oral mucositis/stomatitis of any grade is 4% for pazopanib, 28% for sorafenib, 38% for sunitinib, 41% for temsirolimus, and 44% for everolimus. Oral lesions associated with these agents have been reported to more closely resemble aphthous stomatitis than OM caused by conventional agents. In addition, these agents may result in symptoms such as oral mucosal pain, dysgeusia, and dysphagia, in the absence of clinical lesions. Because of these factors, OAEs secondary to targeted agents may be underreported. In addition, a correlation between OAEs and HFSR was identified. Conclusions. OAEs caused by TKIs and mTORIs may represent dose-limiting toxicities, especially considering the fact that even low grades of OAEs may be troubling to the patient. We discuss how these novel AEs can be assessed because current mucositis assessment tools have limitations. Prospective studies investigating the pathogenesis, risk factors, and management of OAEs are needed in order to minimize the impact on patient's health-related quality of life