Heterogeneity in cancer guidelines: should we eradicate or tolerate?

Background: Heterogeneity in aspects of development, structure and context of oncology guidelines was not evaluated. We analysed and critically examined its implications. Materials and methods: Nine cancer clinical practice guidelines were selected on the basis of popularity among oncologists. The relevant Web sites and publications on three tumours were examined and characteristics grouped in the data domains: producing organisation, methodology, guideline structure and content, implementation and evaluation and scientific agreement. Results: ASCO, ESMO, NICE, SIGN, START, NHMRC, NCI, NCCN and CCO guidelines were examined. Development was initiated by stakeholders or authorised bodies, run by task forces with varying degrees of multidisciplinarity, with rare endorsement of external guidelines. Recommendation formulation was on the basis of evidence, shaped via interactive processes of expert review and public consultation-based modifications. Guidelines varied in comprehensiveness per tumour type, number, size, format, grading of evidence, update and legal issues. Orientation for clinic use or as reference document, end-users and binding or elective nature also varied. Standard dissemination strategies were used, though evaluation of adoption and of impact on health outcomes was implemented with considerable heterogeneity. Conclusions: Heterogeneity in development, structure, user and end points of guidelines is evident, though necessary in order to meet divergent demands. Crucial for their effectiveness are adherence to methodological standards, a clear definition of what the guideline intends to do for whom and a systematic evaluation of their impact on health car

Immunohistochemical Profile for Unknown Primary Adenocarcinoma

BACKGROUND: Development of tailored treatment based on immunohistochemical profiles (IPs) of tumors for cancers of unknown primary is needed. METHODOLOGY/PRINCIPAL FINDINGS: We developed an algorithm based on primary known adenocarcinoma for testing sensitivity and specificity. Formalin-fixed paraffin-embedded tissue samples from 71 patients of unfavorable subsets of unknown primary adenocarcinoma were obtained. We examined 15 molecular markers using the algorithm incorporating these IPs and classified the tumours into 9 subsets based on the primary tumour site. The sensitivity and specificity of this algorithm were 80.3% and 97.6%, respectively. Apparent primary sites were lung in 17 patients, digestive organs in 13, gynecological organs in 9, prostate in 7, liver or kidney in 6, breast in 4, urothelial organ in 2, biliary tract and pancreatic profile in none, and unclassified in 13. The response rate to chemotherapy was highest for the gynecological IPs. Patients with gynecological or lung cancer IPs had longer median progression-free survival than those with others: 11.2 months for gynecological IPs (p<0.001) and 6.8 months for lung IPs (p = 0.05). Lung, digestive, prostate, and gynecological profiles were associated with significantly longer median survival time than the other profiles. Multivariate analysis confirmed that the IPs were independent prognostic factors for survival. CONCLUSIONS/SIGNIFICANCE: The IPs identified in this study can be used to further stratify patient prognosis for unfavorable subsets of unknown primary adenocarcinoma

Cancers of unknown primary origin: current perspectives and future therapeutic strategies

It is widely accepted that systemic neoplastic spread is a late event in tumour progression. However, sometimes, rapidly invasive cancers are diagnosed because of appearance of metastatic lesions in absence of a clearly detectable primary mass. This kind of disease is referred to as cancer of unknown primary (CUP) origin and accounts for 3-5% of all cancer diagnosis. There is poor consensus on the extent of diagnostic and pathologic evaluations required for these enigmatic cases which still lack effective treatment. Although technology to predict the primary tumour site of origin is improving rapidly, the key issue is concerning the biology which drives early occult metastatic spreading. This review provides the state of the art about clinical and therapeutic management of this malignant syndrome; main interest is addressed to the most recent improvements in CUP molecular biology and pathology, which will lead to successful tailored therapeutic options

FDG PET/CT in carcinoma of unknown primary

Carcinoma of unknown primary (CUP) is a heterogeneous group of metastatic malignancies in which a primary tumor could not be detected despite thorough diagnostic evaluation. Because of its high sensitivity for the detection of lesions, combined 18F-fluoro-2-deoxyglucose positron emission tomography (FDG PET)/computed tomography (CT) may be an excellent alternative to CT alone and conventional magnetic resonance imaging in detecting the unknown primary tumor. This article will review the use, diagnostic performance, and utility of FDG PET/CT in CUP and will discuss challenges and future considerations in the diagnostic management of CUP