Myeloma and macroglobulinemia: what are the criteria for diagnosis?

Monoclonal gammopathy of undetermined significance (MGUS) is much more common than either multiple myeloma or Waldenstr?m's macroglobulinemia. Since individuals with MGUS do not need treatment but only monitoring, it is important to distinguish this group from those with progressive plasma cell disorders. Criteria for diagnosis of myeloma and macroglobulinemia and laboratory pitfalls related to meeting these criteria are discussed. The importance of using the serum protein electrophoretic pattern in determining the magnitude of the monoclonal immunoglobulin component and the need for accurate quantification and characterization of urine protein are emphasized. Uniform definitions and consensus on diagnostic standards are becoming increasingly necessary if more effective and less toxic therapeutic approaches for patients with myeloma and macroglobulinemia are to be applied in an optimal manner.     

Three-dimensional conformal radiation therapy: what are the costs and benefits?

Increased attention is being focused on the cost of various medical treatments as limited societal resources are recognized. Three-dimensional conformal radiation therapy is a sophisticated technique that allows high doses of radiation to be focused safely on a target. This technique is more expensive to implement and deliver compared with conventional radiation techniques. A consensus, however, is emerging after reviewing the data that shows three-dimensional conformal radiation therapy to be cost-effective when the clinical benefit is most apparent. More data, sophisticated analyses, and follow-up are necessary before more definitive conclusions can be made.     

The early diagnosis of pancreatic cancer and diabetes: what’s the relationship?

Pancreatic cancer (PC) has a dismal prognosis as cancer-specific symptoms occur only at an advanced stage. If the cancer is to be discovered early, it will have to be done in asymptomatic individuals. Since the incidence of PC is low, screening for asymptomatic cancer in the general population will not be feasible. Screening will have to be restricted to subjects at high risk for PC. The proportion of PC patients who also have hyperglycemia or diabetes has previously been under appreciated; new data show that up to 80% are either hyperglycemic or diabetic and this can be evident in the pre-symptomatic phase. Diabetes improves following PC resection suggesting that diabetes is caused by the cancer. Conversely, older subjects with new-onset diabetes have an approximately eight fold higher risk of having PC compared to the general population. Recognition of new-onset diabetes as an early manifestation of PC could lead to diagnosis of asymptomatic, early stage PC. However, primary type 2 diabetes is common and PC is relatively uncommon in the general population and the two forms of diabetes are clinically indistinguishable. The success of the strategy to use new-onset hyperglycemia and diabetes as a screening tool to identify subjects with a high likelihood of having asymptomatic PC will depend largely on our ability to differentiate PC-associated diabetes from the more common type 2 diabetes using a (serologic) biomarker.     

Exosomes in metastasis of colorectal cancers: Friends or foes?

Colorectal cancer (CRC), the third most common type of cancer worldwide, threaten human health and quality of life. With multidisciplinary, including surgery, chemotherapy and/or radiotherapy, patients with an early diagnosis of CRC can have a good prognosis. However, metastasis in CRC patients is the main risk factor causing cancer-related death. To elucidate the underlying molecular mechanisms of CRC metastasis is the difficult and research focus on the investigation of the CRC mechanism. On the other hand, the tumor microenvironment (TME) has been confirmed as having an essential role in the tumorigenesis and metastasis of malignancies, including CRCs. Among the different factors in the TME, exosomes as extracellular vesicles, function as bridges in the communication between cancer cells and different components of the TME to promote the progression and metastasis of CRC. MicroRNAs packaged in exosomes can be derived from different sources and transported into the TME to perform oncogenic or tumor-suppressor roles accordingly. This article focuses on CRC exosomes and illustrates their role in regulating the metastasis of CRC, especially through the packaging of miRNAs, to evoke exosomes as novel biomarkers for their impact on the metastasis of CRC progression.     

How close are we to customizing chemotherapy in early non-small cell lung cancer?

Although surgery is the only potentially curative treatment for early-stage non-small cell lung cancer (NSCLC), 5-year survival rates range from 77% for stage IA tumors to 23% in stage IIIA disease. Adjuvant chemotherapy has recently been established as a standard of care for resected stage II-III NSCLC, on the basis of large-scale clinical trials employing third-generation platinum-based regimens. As the overall absolute 5-year survival benefit from this approach does not exceed 5% and potential long-term complications are an issue of concern, the aim of customized adjuvant systemic treatment is to optimize the toxicity/benefit ratio, so that low-risk individuals are spared from unnecessary intervention, while avoiding undertreatment of high-risk patients, including those with stage I disease. Therefore, the application of reliable prognostic and predictive biomarkers would enable to identify appropriate patients for the most effective treatment.This is an overview of the data available on the most promising clinicopathological and molecular biomarkers that could affect adjuvant and neoadjuvant chemotherapy decisions for operable NSCLC in routine practice. Among the numerous candidate molecular biomarkers, only few gene-expression profiling signatures provide clinically relevant information warranting further validation. On the other hand, real-time quantitative polymerase-chain reaction strategy involving relatively small number of genes offers a practical alternative, with high cross-platform performance. Although data extrapolation from the metastatic setting should be cautious, the concept of personalized, pharmacogenomics-guided chemotherapy for early NSCLC seems feasible, and is currently being evaluated in randomized phase 2 and 3 trials. The mRNA and/or protein expression levels of excision repair cross-complementation group 1, ribonucleotide reductase M1 and breast cancer susceptibility gene 1 are among the most potential biomarkers for early disease, with stage-independent prognostic and predictive values, the clinical utility of which is being validated prospectively. Inter-assay discordance in determining the biomarker status and association with clinical outcomes is noteworthing.     

Disclosing the cancer diagnosis: what contributes to patient satisfaction?

BACKGROUND: Despite the growing attention to the how, when and where of disclosing a cancer diagnosis, not all patients are satisfied with how the news is broken to them. As in German-speaking countries there is a lack of empirical studies on this subject, this analysis was conducted to determine how the cancer diagnosis was given in a German sample, and how satisfied the patients are with the disclosure experience. PATIENTS AND METHODS: 162 outpatients received a self-report questionnaire focusing on their experiences with physician-patient communication when the diagnosis was disclosed. RESULTS: Guidelines had been respected in most cases. 17% of patients were dissatisfied with the diagnosis disclosure. They reported a significantly shorter duration of the interaction, lack of privacy, deficits in understanding the information, and less emotional support by the physician. CONCLUSION: Adherence to guidelines of diagnosis disclosure in the German sample was fairly high. Respecting both informational and emotional needs is essential for patient satisfaction and can be taught in communication training.     

Promoter methylation of genes in bronchial lavages: a marker for early diagnosis of primary and relapsing non-small cell lung cancer?

A prospective screening program, including CT, autofluorescent bronchoscopy, biopsies and bronchial lavage (BL) collection, was initiated with the specific goal of identifying biomarkers for the early detection of non-small cell lung cancer. We report and discuss the results of p16, DAPK, MGMT, FHIT and APC methylation analysis in the 126 first patients: 77 at high risk of cancer and 49 followed up after primary cancer resection. Positive results were found in 49% of BLs, 53% in current smokers and 43% in former smokers. In presence of peripheral tumours, only 38% of BLs were abnormal versus 73% in presence of central tumours, 50% in presence of preneoplasic lesions and 47% in absence of lesions. FHIT methylation was an early event, observed in one-third of the BLs from patients with or without lesions as well as in tumours. APC methylation was a late event observed in 33% of tumours but rarely in BLs. p16 was methylated in 17% of BLs but in 48% of tumours; DAPK in 15% of BL and 22% of tumours. MGMT methylation was rare. Among patients followed up after cancer surgery, 14 were in remission with normalised BL, whereas three had positive BLs and relapsed with a central tumour. Thus, gene methylation in BL might help to detect central tumours but a CT is crucial for peripheral cancer detection.     

Quality of life in lung cancer: does disclosure of the diagnosis have an impact?

BACKGROUND: Quality of life (QOL) is an important component of evaluation in oncology. Usually, QOL is used in phase III studies to compare two treatments. The aim of this trial was to evaluate the impact of the disclosure of the diagnosis of cancer on QOL by using the European Organisation for Research and Treatment of Cancer core Quality of Life Questionnaire (EORTC QLQ)-C30 questionnaire and the supplemental lung cancer-specific module QLQ-LC13. PATIENTS AND METHODS: Patients hospitalised for exploration of an abnormal chest X-ray, with no previous history of cancer, a performance status < or =2, and able to fulfil the questionnaire were eligible. The patients answered the questionnaire two times: before (Q1) and after (Q2) the disclosure of the diagnosis. RESULTS: Seventy patients answered at Q1 and Q2. After the disclosure, some scores deteriorated: arm pain (P=0.009), physical functioning (P=0.01), role functioning (P=0.008), emotional functioning (P=0.0001) and social functioning (P=0.012), whereas the patients' own assessment of global QOL (item global QOL in functioning scales) did not show the same evolution. CONCLUSION: Disclosure of the diagnosis had an impact on social and emotional QOL. Patients with lung cancer need psychological support at the beginning of their disease.     

Improvement in survival of metastatic colorectal cancer: Are the benefits of clinical trials reproduced in population-based studies?

Aim of the StudyTo describe trends in survival of non-resectable metastatic colorectal cancer (MCRC) over a 34-year period in a French population-based registry taking into account major advances in medical therapy.Patients and Methods3804 patients with non-resectable metastatic colorectal cancer diagnosed between 1976 and 2009 were included. Three periods (1976–96, 1997–2004 and 2005–09) were considered.ResultsThe proportion of patients receiving chemotherapy dramatically increased from 19% to 57% between the first two periods, then increased steadily thereafter reaching 59% during the last period (p < 0.001). Median relative survival increased from 5.9 months during the 1976–96 period to 10.2 months during the 1997–2004 period but, despite the availability of targeted therapies, remained at 9.5 months during the 2005–09 period. During the last study period, less than 10% of elderly patients received targeted therapies compared to more than 40% for younger patients. Their median relative survival was 5.0 months compared to 15.6 months in younger patients.ConclusionThere was an improvement in survival in relation with the increased use of more effective medical treatment. However, at a population-based level, patients are not all treated equally and most of them, especially the elderly, do not benefit from the most up-to-date treatment options.     

Improving the early diagnosis of early nodular melanoma: can we do better?

Introduction: Cutaneous melanoma is the sixth most common malignant cancer in the USA. Among different subtypes of melanoma, nodular melanoma (NM) accounts about 14% of all cases but is responsible for more than 40% of melanoma deaths. Early diagnosis is the best method to improve melanoma prognosis. Unfortunately, early diagnosis of NM is particularly challenging given that patients often lack identifiable risk factors such as many moles or freckles. Moreover, early NM may mimic a range of benign skin lesions that are not routinely excised or biopsied in every day practice. For this reason, specific clinical and skin imaging clues have been proposed to improve early detection of NM.

Areas covered: The review discusses about the noninvasive tools to diagnose thin melanoma, particularly NM.

Expert commentary: Currently, dermatologists present a wide opportunity of diagnostic tools. Current data suggest that the early diagnosis of NM is a major challenge as the majority of early NM are symmetric, roundish, and lack specific pattern. Another promising strategy is based on recent data suggesting that artificial intelligence based on deep convolutional neural networking is able to outperform average dermatologist. Further research is necessary to validate the performance of this method in the real world and in the clinical setting.