ABSTRACT
Metastatic prostate cancer remains an incurable lethal disease. Studies indicate that prostate cancer accumulates genomic changes during disease progression and displays the highest levels of chromosomal instability (CIN) across all types of metastatic tumours. CIN, which refers to ongoing chromosomal DNA gain or loss during mitosis, and derived aneuploidy, are known to be associated with increased tumour heterogeneity, metastasis and therapy resistance in many tumour types. Paradoxically, high CIN levels are also proposed to be detrimental to tumour cell survival, suggesting that cancer cells must develop adaptive mechanisms to ensure their survival. In the context of prostate cancer, studies indicate that CIN has a key role in disease progression and might also offer a therapeutic vulnerability that can be pharmacologically targeted. Thus, a comprehensive evaluation of the causes and consequences of CIN in prostate cancer, its contribution to aggressive advanced disease and a better understanding of the acquired CIN tolerance mechanisms can translate into new tumour classifications, biomarker development and therapeutic strategies.
Subject(s)
Chromosomal Instability , Prostatic Neoplasms , Humans , Male , Prostatic Neoplasms/genetics , Prostatic Neoplasms/pathology , Disease ProgressionABSTRACT
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Introduction. Whole brain irradiation (WBRT) remainsa recommended treatment for patients withbrain metastases from malignant melanoma interms of symptom palliation, especially when extracranialsystemic disease is present. Temozolomide(TMZ) has shown efficacy in the treatment ofmetastatic melanoma. The objective was to evaluatethe potential benefit in survival of two differentschedules of total dose and fractionation (20 Gy/5fractions vs 30 Gy/10 fractions) and further TMZbased chemotherapy.Materials and method. We have conducted a retrospectivestudy in a group of twenty-one patients(RTOG Recursive Partitioning Analysis class II) ofthe use of WBRT with 20 Gy/5 fractions (n = 11)and 30 Gy/10 fractions (n = 10). All patients receivedfurther TMZ based chemotherapy administered asa single chemotherapeutic agent or in combinationwith chemo-immunotherapy.Results. Prognostic variables such as: age, Karnofskyperformance status, extracranial metastases andnumber of brain metastases, were analyzed in bothgroups of treatment without statistically significantdifferences. The median survival time (MST) forWBRT 20 Gy group was 4 months (CI 95%: range 2-6 months) and for WBRT 30 Gy group was 4 months(CI 95%: range 0-7 months) without statistically significantdifferences ( Log rank p = 0.74). There wasone complete response and two partial responses.Conclusions. The results suggest that MST was notsignificantly affected by the total dose/fractionationschedule
Subject(s)
Male , Female , Adult , Aged , Middle Aged , Humans , Melanoma/pathology , Brain Neoplasms/radiotherapy , Antineoplastic Agents/therapeutic use , Radiotherapy Dosage , Neoplasm Metastasis/radiotherapy , Brain Neoplasms/secondaryABSTRACT
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