Álvaro Pinto Marín

Role of anti-Her-2 therapy in bladder carcinoma

Bladder cancer, in its advanced stage, has very few therapeutic strategies with proven efficacy. Platinum-combination chemotherapy can be considered a standard for first-line therapy, but after progression there is no standard therapy, and the prognosis is very poor. The development of targeted therapies in the last few years has significantly changed the prognosis of a wide variety of tumors. In bladder cancer, there is no targeted therapy currently approved for its use in advanced disease. There is evidence that Her-2 amplification and/or overexpression is seen in bladder cancer, and may influence prognosis. Anti-Her-2 drugs, such as trastuzumab or lapatinib, are under investigation in urothelial neoplasms, but there is no phase III trial that has evaluated their use in bladder cancer. We review the published evidence about Her-2 determination, its influence on bladder carcinoma prognosis, the clinical development of anti-Her-2-targeted therapies, and the possible future research directions involving this pathway in bladder cancer.

Comparison of prognostic gene profiles using qRT-PCR in paraffin samples: a retrospective study in patients with early breast cancer.

Introduction Gene profiling may improve prognostic accuracy in patients with early breast cancer, but this technology is not widely available. We used commercial assays for qRT-PCR to assess the performance of the gene profiles included in the 70-Gene Signature, the Recurrence Score and the Two-Gene Ratio. Methods 153 patients with early breast cancer and a minimum follow-up of 5 years were included. All tumours were positive for hormonal receptors and 38% had positive lymph nodes; 64% of patients received adjuvant chemotherapy. RNA was extracted from formalin-fixed paraffin-embedded (FFPE) specimens using a specific kit. qRT-PCR amplifications were performed with TaqMan Gene Expression Assays products. We applied the three gene-expression-based models to our patient cohort to compare the predictions derived from these gene sets. Results After a median follow-up of 91 months, 22% of patients relapsed. The distant metastasis-free survival (DMFS) at 5 years was calculated for each profile. For the 70-Gene Signature, DMFS was 95% -good prognosis- versus 66% -poor prognosis. In the case of the Recurrence Score, DMFS was 98%, 81% and 69% for low, intermediate and high-risk groups, respectively. Finally, for the Two-Gene Ratio, DMFS was 86% versus 70%. The 70-Gene Signature and the Recurrence Score were highly informative in identifying patients with distant metastasis, even in multivariate analysis. Conclusion Commercially available assays for qRT-PCR can be used to assess the prognostic utility of previously published gene expression profiles in FFPE material from patients with early breast cancer. Our results, with the use of a different platform and with different material, confirm the robustness of the 70-Gene Signature and represent an independent test for the Recurrence Score, using different primer/probe sets.

Adjuvant chemotherapy for breast cancer and cognitive impairment.

Complaints of loss of memory and lack of concentration have been reported by long-term survivors of breast cancer. This mild cognitive impairment (MCI), also called “chemobrain” or “chemofog,” has been the subject of a number of studies in the last few years. This cognitive impairment, although usually mild, must be studied to define possible risk factors for its development, and for future research into a preventive or therapeutic treatment approach. Long-term survivors of breast cancer must be followed to detect possible treatment sequelae as soon as possible. Since the number of these long-term survivors has increased in the last years, in part because of more active adjuvant treatments, our knowledge about the long-term side effects of these therapies has also grown.

mTOR pathway inhibition in renal cell carcinoma

Renal cell carcinoma therapy has changed in a very significant way in the last few years. Up to 5 new agents have been developed, improving the results previously achieved with cytokine therapy. Bevacizumab, sorafenib, sunitinib, temsirolimus, and everolimus are now part of the therapeutic arsenal for this illness. Particularly, this has been the first tumoral type in which inhibition of mammalian target of rapamycin (mTOR) has proved its efficacy in phase III trials, either as first-line therapy for poor prognosis patients (temsirolimus, CCI-779) or as second-line therapy after failure of tyrosine-kinase inhibitors (everolimus, RAD001). In this paper, we review the basis for mTOR inhibition in RCC, and discuss the results of the trials involving temsirolimus and everolimus for the treatment of this disease.

Sedation in clinical oncology

The clinical status of terminal cancer patients is very complex and is affected by several severe symptoms, of extended duration, changing with time and of multifactorial origin. When there are no reasonable cancer treatments specifically able to modify the natural history of the disease, symptom control acquires priority and favours the possible better adaptation to the general inexorable deterioration related to the neoplasic progression.Despite the important advances in Palliative Medicine, symptoms are frequently observed that are intolerable for the patient and which do not respond to usual palliative measures. This situation, characterised by rapid deterioration of the patient, very often heralds, implicitly or explicitly, approaching death. The intolerable nature and being refractory to treatment indicates to the health-care team, on many occasions, the need for sedation of the patient.The requirement for sedation of the cancer patient is a situation that does not allow for an attitude of doubt regarding maintenance of the patient in unnecessary suffering for more than a reasonable time. Given the undoubted clinical difficulty in its indication, it is important to have explored at an earlier stage all usual treatments possible and the grade of response, commensurate with the patients values and desires.Sedation consists of the deliberate administration of drugs in minimum doses and combinations required not only to reduce the consciousness of the patients but also to achieve adequate alleviation of one or more refractory symptoms, and with the prior consent given by the patient explicitly, or implicitly or delegated.Sedation is accepted as ethically warranted when considering the imperative of palliation and its administration and, whenever contemplated, the arguments that justify them are clear recorded in the clinical history.It is not an easy decision for the physican since, traditionally, the training has been “for the fight to save life”. Nevertheless, it seems necessary to make some preparations regarding these problems that have a central affect on the clinical oncologist in his daily function.

Intra-abdominal desmoplastic small round cell tumour in a 39-year-old man

Desmoplastic small round cell tumor is a very rare neoplasm, that usually appears in children and young adolescents. There is no standard therapy, and responses to chemotherapy are infrequent. Surgery is still the main treatment for this disease. We report the case of a 39 year-old man and briefly summarize the evidence about this tumor.