Homologous recombination deficiency in ovarian cancer: a review of its epidemiology and management.

Ovarian cancer patients with homologous recombination deficiencies exhibit specific clinical behaviors, and improved responses to treatments, such as platinum-based chemotherapy and poly (ADP-ribose) polymerase (PARP) inhibitors, have been observed. Germline mutations in the BRCA 1/2 genes are the most well-known mechanisms of homologous recombination deficiency. However, other mechanisms, such as germline and somatic mutations in other homologous recombination genes and epigenetic modifications, have also been implicated in homologous recombination deficiency. The epidemiology and implications of these other mechanisms need to be better understood to improve the treatment strategies for these patients. Furthermore, an evaluation of various diagnostic tests to investigate homologous recombination deficiency is essential. Comprehension of the role of homologous recombination deficiency in ovarian cancer also allows the development of therapeutic combinations that can improve the efficacy of treatment. In this review, we discuss the epidemiology and management of homologous recombination deficiency in ovarian cancer patients.

Cystic brain metastases in ALK-rearranged non-small cell lung cancer.

The central nervous system (CNS) is a common site of disease progression in patients with non-small-cell lung cancer (NSCLC) with anaplastic lymphoma kinase (ALK)-rearrangement treated with crizotinib. Cystic brain metastases (CBM) have been recently identified as one possible variant of this disease. An illustrative case report is presented along with a literature review performed in order to track relevant papers about CBM in ALK-rearranged NSCLC, including possible pathophysiology, differential diagnosis and treatment options for this condition. Three case reports have been published describing six ALK-rearranged NSCLC patients presenting with CBM, all of which were under treatment with crizotinib by the time of CBM diagnosis. Treatment with CNS-penetrating tyrosine kinase inhibitors (TKIs) resulted in CNS disease control in three of the six cases reported either as single therapy or in combination with radiation therapy (RT). Investigation of differential diagnoses of CBM might be necessary, which include inflammatory and demyelinating disorders, primary brain tumours and infectious diseases, especially neurocysticercosis that might mimic CBM images. Treatment options include RT, CNS-penetrating TKIs and invasive procedures, such as stereotactic drainage. Thus, CBM are associated with ALK-rearranged NSCLC, particularly in patients who use crizotinib and should prompt investigation of differential diagnosis. CNS-penetrating TKIs are effective in the control of solid brain metastases and also seem to be active in CBM as single therapy or in combination with RT.

Homologous recombination deficiency in ovarian cancer: a review of its epidemiology and management

Ovarian cancer patients with homologous recombination deficiencies exhibit specific clinical behaviors, and improved responses to treatments, such as platinum-based chemotherapy and poly (ADP-ribose) polymerase (PARP) inhibitors, have been observed. Germline mutations in the BRCA 1/2 genes are the most well-known mechanisms of homologous recombination deficiency. However, other mechanisms, such as germline and somatic mutations in other homologous recombination genes and epigenetic modifications, have also been implicated in homologous recombination deficiency. The epidemiology and implications of these other mechanisms need to be better understood to improve the treatment strategies for these patients. Furthermore, an evaluation of various diagnostic tests to investigate homologous recombination deficiency is essential. Comprehension of the role of homologous recombination deficiency in ovarian cancer also allows the development of therapeutic combinations that can improve the efficacy of treatment. In this review, we discuss the epidemiology and management of homologous recombination deficiency in ovarian cancer patients.