Surveillance active du cancer de la prostate [Active surveillance in prostate cancer].

Active surveillance in prostate cancer The spread of PSA in the screening of prostate cancer has almost doubled the incidence of this disease in the last twenty years. An improved understanding of the natural history of this cancer allows for risk stratification of the disease and to better predict insignificant prostate cancer. Active surveillance has recently been proposed as a new option to delay or avoid a radical treatment for patients with low-risk disease. The principle, results and future perspectives of this treatment modality are discussed in this review.

Sclérodermie et risques oncologiques [Systemic sclerosis and cancer]

The combination of skin induration with clinical features such as dyspnea, facial telangiectasia, digital infarctions and/or dysphagia supports the diagnosis of systemic sclerosis. The oesophageal dysmotility is associated with symptoms which may delay the diagnosis of gastro-oesophageal cancer. Herein we report a case of long standing systemic sclerosis with heartburn and dysphagia symptoms which were monitored closely. Unfortunately, these symptoms delayed the diagnosis of gastric adenocarcinoma. This case prompted us to review the evidence of the association of cancer and systemic sclerosis and if any oncologic evaluation is required during the follow-up of patients affected with systemic sclerosis.

Choline-PET in prostate cancer management: The point of view of the radiation oncologist.

Among PET radiotracers, FDG seems to be quite accepted as an accurate oncology diagnostic tool, frequently helpful also in the evaluation of treatment response and in radiation therapy treatment planning for several cancer sites. To the contrary, the reliability of Choline as a tracer for prostate cancer (PC) still remains an object of debate for clinicians, including radiation oncologists. This review focuses on the available data about the potential impact of Choline-PET in the daily clinical practice of radiation oncologists managing PC patients. In summary, routine Choline-PET is not indicated for initial local T staging, but it seems better than conventional imaging for nodal staging and for all patients with suspected metastases. In these settings, Choline-PET showed the potential to change patient management. A critical limit remains spatial resolution, limiting the accuracy and reliability for small lesions. After a PSA rise, the problem of the trigger PSA value remains crucial. Indeed, the overall detection rate of Choline-PET is significantly increased when the trigger PSA, or the doubling time, increases, but higher PSA levels are often a sign of metastatic spread, a contraindication for potentially curable local treatments such as radiation therapy. Even if several published data seem to be promising, the current role of PET in treatment planning in PC patients to be irradiated still remains under investigation. Based on available literature data, all these issues are addressed and discussed in this review.

Rapid evolution of cancer/testis genes on the X chromosome.

BACKGROUND: Cancer/testis (CT) genes are normally expressed only in germ cells, but can be activated in the cancer state. This unusual property, together with the finding that many CT proteins elicit an antigenic response in cancer patients, has established a role for this class of genes as targets in immunotherapy regimes. Many families of CT genes have been identified in the human genome, but their biological function for the most part remains unclear. While it has been shown that some CT genes are under diversifying selection, this question has not been addressed before for the class as a whole. RESULTS: To shed more light on this interesting group of genes, we exploited the generation of a draft chimpanzee (Pan troglodytes) genomic sequence to examine CT genes in an organism that is closely related to human, and generated a high-quality, manually curated set of human:chimpanzee CT gene alignments. We find that the chimpanzee genome contains homologues to most of the human CT families, and that the genes are located on the same chromosome and at a similar copy number to those in human. Comparison of putative human:chimpanzee orthologues indicates that CT genes located on chromosome X are diverging faster and are undergoing stronger diversifying selection than those on the autosomes or than a set of control genes on either chromosome X or autosomes. CONCLUSION: Given their high level of diversifying selection, we suggest that CT genes are primarily responsible for the observed rapid evolution of protein-coding genes on the X chromosome.

Cancer du sein chez la jeune femme: traitements adjuvants et désir de grossesse [Breast cancer in young women: adjuvant therapy and fertility]

Prognosis of breast cancer women has been dramatically improved by the adjuvant therapies. As the vast majority of patients are cured, the importance of long-term quality of life is growing. The question of the maternity is an essential concern for the young women who have to receive chemotherapy or several years of endocrine therapy. This problem is often underestimated and may lead to emotional distress, depression or anxiety. A regional multidisciplinary working group was set up in order to offer optimal information about fertility and cancer as to propose specific therapeutic reproduction options, when applicable. Specificity of the young patients' breast cancer, the treatment approaches and their impact on fertility are discussed in this paper.

Cost-effectiveness of low-molecular-weight heparin for secondary prophylaxis of cancer-related venous thromboembolism.

Although extended secondary prophylaxis with low-molecular-weight heparin was recently shown to be more effective than warfarin for cancer-related venous thromboembolism, its cost-effectiveness compared to traditional prophylaxis with warfarin is uncertain. We built a decision analytic model to evaluate the clinical and economic outcomes of a 6-month course of low-molecular-weight heparin or warfarin therapy in 65-year-old patients with cancer-related venous thromboembolism. We used probability estimates and utilities reported in the literature and published cost data. Using a US societal perspective, we compared strategies based on quality-adjusted life-years (QALYs) and lifetime costs. The incremental cost-effectiveness ratio of low-molecular-weight heparin compared with warfarin was 149,865 dollars/QALY. Low-molecular-weight heparin yielded a quality-adjusted life expectancy of 1.097 QALYs at the cost of 15,329 dollars. Overall, 46% (7108 dollars) of the total costs associated with low-molecular-weight heparin were attributable to pharmacy costs. Although the low-molecular-weigh heparin strategy achieved a higher incremental quality-adjusted life expectancy than the warfarin strategy (difference of 0.051 QALYs), this clinical benefit was offset by a substantial cost increment of 7,609 dollars. Cost-effectiveness results were sensitive to variation of the early mortality risks associated with low-molecular-weight heparin and warfarin and the pharmacy costs for low-molecular-weight heparin. Based on the best available evidence, secondary prophylaxis with low-molecular-weight heparin is more effective than warfarin for cancer-related venous thromboembolism. However, because of the substantial pharmacy costs of extended low-molecular-weight heparin prophylaxis in the US, this treatment is relatively expensive compared with warfarin.

Cancers de l'adulte jeune [Overview on cancer in young adults]

To make a diagnostic of cancer in a young adult (15-30 years of age) has important physical, psychological and social implications. The most frequent cancers seen at this age are cancer of the thyroid, testicular germ cell tumours, 'melanoma, Hodgkin's lymphoma, non-Hodgkin lymphoma, leukaemia, cerebral tumours and sarcomas. Even if the prognostic of most of these cancers is excellent, treatments are difficult and often associated with long-term side effects. A multidisciplinary approach of these patients is essential. A long-term follow-up by a general practicioner or an oncologist is indispensable.

Superior outcome of women with stage I/II cutaneous melanoma: pooled analysis of four European Organisation for Research and Treatment of Cancer phase III trials.

PURPOSE: Several studies observed a female advantage in the prognosis of cutaneous melanoma, for which behavioral factors or an underlying biologic mechanism might be responsible. Using complete and reliable follow-up data from four phase III trials of the European Organisation for Research and Treatment of Cancer (EORTC) Melanoma Group, we explored the female advantage across multiple end points and in relation to other important prognostic indicators. PATIENTS AND METHODS: Patients diagnosed with localized melanoma were included in EORTC adjuvant treatment trials 18832, 18871, 18952, and 18961 and randomly assigned during the period of 1984 to 2005. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% CIs for women compared with men, adjusted for age, Breslow thickness, body site, ulceration, performed lymph node dissection, and treatment. RESULTS: A total of 2,672 patients with stage I/II melanoma were included. Women had a highly consistent and independent advantage in overall survival (adjusted HR, 0.70; 95% CI, 0.59 to 0.83), disease-specific survival (adjusted HR, 0.74; 95% CI, 0.62 to 0.88), time to lymph node metastasis (adjusted HR, 0.70; 95% CI, 0.51 to 0.96), and time to distant metastasis (adjusted HR, 0.69; 95% CI, 0.59 to 0.81). Subgroup analysis showed that the female advantage was consistent across all prognostic subgroups (with the possible exception of head and neck melanomas) and in pre- and postmenopausal age groups. CONCLUSION: Women have a consistent and independent relative advantage in all aspects of the progression of localized melanoma of approximately 30%, most likely caused by an underlying biologic sex difference.

Adhésion thérapeutique aux traitements oncologiques oraux et prise en charge interdisciplinaire [Therapeutic adherence to oral cancer therapy and interdisciplinary management].

Medication adherence is a well-known risk factor in internal medicine. However in oncology this dimension is emerging due to the increasing number of oral formulations. First results in the oral oncology literature suggest that patients' ability to cope with medical prescription decreases with time. This might preclude patients from reaching clinical outcomes. Factors impacting on medication adherence to oral oncology treatments have not been yet extensively described neither strategies to address them and support patient's needs. Oncologists and pharmacists in our University outpatient settings performed a pilot study which aimed at measuring and facilitating adherence to oral oncology treatments and at understanding determinants of patient's adherence. The ultimate purpose of such a patient-centered and interdisciplinary collaboration would be to promote patient self-management and complement the standard medical follow-up.

Systematic identification of genomic markers of drug sensitivity in cancer cells.

Clinical responses to anticancer therapies are often restricted to a subset of patients. In some cases, mutated cancer genes are potent biomarkers for responses to targeted agents. Here, to uncover new biomarkers of sensitivity and resistance to cancer therapeutics, we screened a panel of several hundred cancer cell lines--which represent much of the tissue-type and genetic diversity of human cancers--with 130 drugs under clinical and preclinical investigation. In aggregate, we found that mutated cancer genes were associated with cellular response to most currently available cancer drugs. Classic oncogene addiction paradigms were modified by additional tissue-specific or expression biomarkers, and some frequently mutated genes were associated with sensitivity to a broad range of therapeutic agents. Unexpected relationships were revealed, including the marked sensitivity of Ewing's sarcoma cells harbouring the EWS (also known as EWSR1)-FLI1 gene translocation to poly(ADP-ribose) polymerase (PARP) inhibitors. By linking drug activity to the functional complexity of cancer genomes, systematic pharmacogenomic profiling in cancer cell lines provides a powerful biomarker discovery platform to guide rational cancer therapeutic strategies.

Clinical benefit of fulvestrant in postmenopausal women with advanced breast cancer and primary or acquired resistance to aromatase inhibitors: final results of phase II Swiss Group for Clinical Cancer Research Trial (SAKK 21/00).

BACKGROUND: The aim of this study was to evaluate the efficacy and tolerability of fulvestrant, an estrogen receptor antagonist, in postmenopausal women with hormone-responsive tumors progressing after aromatase inhibitor (AI) treatment. PATIENTS AND METHODS: This is a phase II, open, multicenter, noncomparative study. Two patient groups were prospectively considered: group A (n=70) with AI-responsive disease and group B (n=20) with AI-resistant disease. Fulvestrant 250 mg was administered as intramuscular injection every 28 (+/-3) days. RESULTS: All patients were pretreated with AI and 84% also with tamoxifen or toremifene; 67% had bone metastases and 45% liver metastases. Fulvestrant administration was well tolerated and yielded a clinical benefit (CB; defined as objective response or stable disease [SD] for >or=24 weeks) in 28% (90% confidence interval [CI] 19% to 39%) of patients in group A and 37% (90% CI 19% to 58%) of patients in group B. Median time to progression (TTP) was 3.6 (95% CI 3.0 to 4.8) months in group A and 3.4 (95% CI 2.5 to 6.7) months in group B. CONCLUSIONS: Overall, 30% of patients who had progressed following prior AI treatment gained CB with fulvestrant, thereby delaying indication to start chemotherapy. Prior response to an AI did not appear to be predictive for benefit with fulvestrant.