Attila Marcell Szasz

Ten percent of patients with breast cancer, and probably somewhat more in patients with ovarian cancer, have inherited germline DNA mutations in the breast and ovarian cancer genes BRCA1 and BRCA2. In the remaining cases, the disease is caused by acquired somatic genetic and epigenetic alterations. Targeted therapeutic agents, such as poly ADP-ribose polymerases (PARP) inhibitors (PARPi), have emerged in treating cancers associated with germline BRCA mutations since 2014. The first PARPi was FDA-approved initially for ovarian cancer patients with germline BRCA mutations. Deleterious variants in the BRCA1/BRCA2 genes and homologous recombination deficiency status have been strong predictors of response to PARPi in a few solid tumors since then. However, the relevance of somatic BRCA mutations is less clear. Somatic BRCA-mutated tumors might also respond to this new class of therapeutics. Although the related literature is often controversial, recently published case reports and/or randomized studies demonstrated the effectiveness of PARPi in treating patients with somatic BRCA mutations. The aim of this review is to summarize the predictive role of somatic BRCA mutations and to provide further assistance for clinicians with the identification of patients who could potentially benefit from PARPi.

The mEHT method uses tissues’ thermal and bioelectromagnetic heterogeneity for the selective mechanisms. The success of the therapy for advanced, relapsed, and metastatic aggressive tumors can only be demonstrated by measuring survival time and quality of life (QoL). The complication is that mEHT-treated patients cannot be curatively treated any longer with “gold standards”, where the permanent progression of the disease, the refractory, relapsing situation, the organ failure, the worsening of blood counts, etc., block them. Collecting a cohort of these patients is frequently impossible. Only an intent-to-treat (ITT) patient group was available. Due to the above limitations, many studies have single-arm data collection. The Phase III trial of advanced cervix tumors subgrouping of HIV-negative and -positive patients showed the stable efficacy of mEHT in all patients’ subgroups. The single-arm represents lower-level evidence, which can be improved by comparing the survival data of various studies from different institutes. The Kaplan–Meier probability comparison had no significant differences, so pooled data were compared to other methods. Following this approach, we demonstrate the feasibility and superiority of mEHT in the cases of glioblastoma multiform, pancreas carcinomas, lung tumors, and colorectal tumors.