Przerzuty raka prostaty do mózgu (art. w j.ang.)

Przerzuty raka prostaty do mózgu (art. w j.ang.)

Nieprzeczytany postautor: zosia bluszcz » 12 kwie 2019, 11:01

Ponizej trzy interesujące artykuly dotyczące przerzutow raka prostaty do mozgu.
Do tej pory raczej rzadkie, obecnie coraz częsciej spotykane. Hipoteza jest taka, ze dzięki nowym terapiom pacjenci mCRPC zyją dluzej, a co za tym idzie, przerzuty mają wiecej czasu na ujawnienie sie (upowszechnienie MRI umozliwa potwierdzenie diagnozy).
Niestety, nowe leki nie przekraczają bariery krew - mózg (BBB = Blood-Brain Barrier). Nadzieje są pokladane w pochodnej Docetaxelu - Cabazitaxelu (Jevtana) - patrz artykul #3

Z analizy przypadkow omawianych w pierwszym artykule wynika, ze przerzuty do mozgu pojawiają sie czesciej u pacjentow z przrzutami do kosci, pluc i wątroby.
Autorzy podkreslaja, ze nie ma typowego obrazu przerzutow CaP do mozgu, i ze 1/3 pacjentow z ich kohorty miala przynajmniej 1 przerzut do mozgu (BM = Brain Metastasis) typu krwotocznego.

Brain Metastases from Prostate Cancer: An 11-Year Analysis in the MRI Era with Emphasis on Imaging Characteristics, Incidence, and Prognosis

One-third (7/21) of the patients we investigated had at least one hemorrhagic brain metastasis from prostate cancer, similar to more classically hemorrhagic metastases from melanoma, renal cell carcinoma, breast cancer, thyroid cancer, and choriocarcinoma.

Brain metastasis originating in prostate cancer is a rare phenomenon that frequently occurs in the setting of disseminated bone and soft tissue disease. Prostate cancer metastases to the brain have a highly variable MRI appearance and cannot be readily differentiated from metastases originating from other primary sites based on conventional imaging alone.
Our findings suggest that prostate cancer patients without osseous and/or lymph node metastases are highly unlikely to have brain lesions and that patients with Gleason scores below 6 are at lower risk than those with a score of 6 or above.
Although limited by the small number of patients, our study indicates that patients with nonadenocarcinoma prostate cancer subtypes are more likely to develop brain metastases than patients with adenocarcinoma.
Increased suspicion may be warranted when these patients present with neurological symptoms and further studies are warranted to assess the cost effectiveness of screening these patients for early detection. Additional work is also necessary to identify specific molecular features of the disease or treatment that may be associated with brain metastases.

Brain Metastases From Prostate Cancer

Brain metastases from prostate cancer (PC) seem to be more frequent than in the past, possibly because advances in the treatment of patients with castration-resistant PC have prolonged their survival. Furthermore, docetaxel (the drug of choice for the first-line treatment of castration-resistant PC) cannot cross the blood–brain barrier and control metastatic foci. However, this problem may be overcome by new active drugs such as cabazitaxel.

Future Perspective
The hypothesis that the improved overall survival associated with the introduction of docetaxel into clinical practice has 'unmasked' BMs that would otherwise have remained clinically silent needs to be supported by more robust clinical evidence.
Nevertheless, it is clear that the newly available drugs for CRPC are changing the natural history of the disease by allowing conditions that favor BM development.
Drugs such as cabazitaxel that are able to cross the BBB and concentrate in the brain open up a therapeutic scenario in which the development of BMs can be fought by simultaneously acting against the primary tumor and hitting lesions beyond the BBB. If cabazitaxel proves to be superior to docetaxel in first-line treatment, it could reduce the risk of BM development.
The other drugs that have improved survival in CRPC patients have not yet shown clear evidence of brain accumulation but, by contributing to prolong disease control, could reveal more frequent BM development in PC patients, particularly if they prove to be efficacious in hormone-sensitive patients and delay progression to castration resistance.

It can therefore be hypothesized that the number of long-term PC survivors will increase in the future as a result of both delayed castration resistance and longer survival during this stage of the disease.
Consequently, the opportunity of observing BMs could increase, and physicians should become aware of this by using instrumental staging to detect BMs at the time of the early occurrence of central symptoms in all PC patients.

Furthermore, future trials for PC (mainly in CRPC) patients should incorporate routine central imaging assessment into the study procedures to ensure an early detection of BMs in asymptomatic

Cabazitaxel in castration resistant prostate cancer with brain metastases: 3 case reports

Prostate cancer is the most common non-cutaneous malignancy for men. The skeleton is the most common metastatic site but, following an improvement in survival, metastases in uncommon sites are being found more frequently in clinical practice, especially brain metastases. Despite the new drugs now available for metastatic castration resistant prostate cancer, no clinical evidence exists about their effectiveness on brain metastases. We describe the clinical history of 3 patients treated with cabazitaxel plus whole brain radiotherapy. These case reports demonstrate that cabazitaxel is highly active and well tolerated in brain metastases.

Core tip:
Due to the improvement in terms of survival, the incidence of brain metastases (BMs) has increased in patients with metastatic castration resistant prostatic cancer (mCRPC). Despite the large number of treatments now available, the prognosis of patients with BMs is still poor. First, we demonstrate the efficacy of cabazitaxel on brain mestastases in three CRPC patients and then show its profile of tolerability in combination with whole brain radiotherapy.

Prostate cancer (PC) is the most common non-cutaneous malignancy for men, with an estimated number of new cases of 241740 in 2013 in the United States[1]. Nevertheless, PC is not the leading cause of death in the male population due to its ability to rarely metastasize to organs other than bones[2].

Although the skeleton remains the most common metastatic site, the availability of new active drugs for metastatic castration resistant prostatic cancer (mCRPC) has changed the natural history of this disease, leading to a considerable improvement in survival so that metastases in previously considered uncommon sites are now found more frequently[3].

Brain is the site of metastases in almost 12% of cases with a poor prognosis at their appearance[4].

Despite an increased incidence of BMs, the impact of new drugs for mCRPC on this metastatic site remains poorly understood. First of all, patients with BMs are not routinely enrolled in phase III clinical trials and there are no prospective and ad-hoc studies in this particular setting. Actually, there is only preclinical data showing that cabazitaxel is able to pass the brain-blood barrier (BBB)[5] but no evidence about its efficacy in humans.

Otherwise, there is also little data concerning the role of radiation therapy on the treatment of BMs from PC which seems to have only a palliative intent[6]. Here, we describe three case reports of brain metastases in CRPC patients who were treated with cabazitaxel plus whole brain radiotherapy.
zosia bluszcz
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