Efficacy and safety of prostate radiotherapy in de novo metastatic castration-sensitive prostate cancer (PEACE-1): a multicentre, open-label, randomised, phase 3 study with a 2 × 2 factorial design.

Background: The 2 × 2 PEACE-1 study showed that combining androgen-deprivation therapy with docetaxel and abiraterone improved overall and radiographic progression-free survival in patients with de novo metastatic castration-sensitive prostate cancer. We aimed to examine the efficacy and safety of adding radiotherapy in this population.

Methods: We conducted an open-label, randomised, controlled, phase 3 trial with a 2 × 2 factorial design (PEACE-1) at 77 hospitals across Europe.

Treatment Classification by Intent in Oncology-The Need for Meaningful Definitions: Curative, Palliative and Potentially Life-Prolonging.

Background: Realistic cancer treatment goals should be used by health care professionals and communicated to patients, families, and the public. The current nomenclature on this subject is outdated and has not been changed since the advent of modern oncology in the middle of the 20th century.

Methods: Based on the literature we propose a three-tier system composed of curative, palliative, and potentially life-prolonging (PLP) therapies, instead of the current two-tier system of only curative and palliative treatment.

Serum Calcium Level at Diagnosis Can Predict Lethal Prostate Cancer Relapse.

: The most important prognostic factors in curatively treated prostate cancer are T and N stage, histology, grade group and initial PSA. A recent study found that men with blood calcium levels at the high end of the normal range are over two-and-a-half times more likely to develop fatal prostate cancer than those with lower calcium levels. However, there is limited evidence regarding the prognostic value of calcium levels at the time of prostate cancer diagnosis.

Real-World Patterns and Decision Drivers of Radiotherapy for Lung Cancer Patients in Romania: RADIO-NET Study Results.

Radiotherapy (RT) plays a crucial role in all stages of lung cancer. Data on recent real-world RT patterns and main drivers of RT decisions in lung cancer in Romania is scarce; we aimed to address these knowledge gaps through this physician-led medical chart review in 16 RT centers across the country. Consecutive patients with lung cancer receiving RT as part of their disease management between May-October 2019 (pre-COVID-19 pandemic) were included.

Reverse and Forward Electron Flow-Induced HO Formation Is Decreased in α-Ketoglutarate Dehydrogenase (α-KGDH) Subunit (E2 or E3) Heterozygote Knock Out Animals.

α-ketoglutarate dehydrogenase complex (KGDHc), or 2-oxoglutarate dehydrogenase complex (OGDHc) is a rate-limiting enzyme in the tricarboxylic acid cycle, that has been identified in neurodegenerative diseases such as in Alzheimer's disease. The aim of the present study was to establish the role of the KGDHc and its subunits in the bioenergetics and reactive oxygen species (ROS) homeostasis of brain mitochondria. To study the bioenergetic profile of KGDHc, genetically modified mouse strains were used having a heterozygous knock out (KO) either in the dihydrolipoyl succinyltransferase (DLST) or in the dihydrolipoyl dehydrogenase (DLD) subunit.

Final Safety and Health-Related Quality of LIfe Results of the Phase 2/3 Act.In.Sarc Study With Preoperative NBTXR3 Plus Radiation Therapy Versus Radiation Therapy in Locally Advanced Soft-Tissue Sarcoma.

Purpose: Act.In.Sarc (NCT02379845) demonstrated that the first-in-class radioenhancer NBTXR3, activated by preoperative radiation therapy (RT), doubled the rate of pathologic complete response after resection compared with preoperative RT alone in adult patients with locally advanced soft tissue sarcoma of the extremity or trunk wall (16.

Abiraterone plus prednisone added to androgen deprivation therapy and docetaxel in de novo metastatic castration-sensitive prostate cancer (PEACE-1): a multicentre, open-label, randomised, phase 3 study with a 2 × 2 factorial design.

Background: Current standard of care for metastatic castration-sensitive prostate cancer supplements androgen deprivation therapy with either docetaxel, second-generation hormonal therapy, or radiotherapy. We aimed to evaluate the efficacy and safety of abiraterone plus prednisone, with or without radiotherapy, in addition to standard of care.

Methods: We conducted an open-label, randomised, phase 3 study with a 2 × 2 factorial design (PEACE-1) at 77 hospitals across Belgium, France, Ireland, Italy, Romania, Spain, and Switzerland.

Difficulties in diagnosing anorectal melanoma: A case report and review of the literature.

Background: Anorectal melanoma is a tumour that is difficult to identify due to its rarity and variability of presentation. Insufficient data published in the literature do not allow for diagnostic and treatment guidelines to be established. Anorectal melanoma has the worst prognosis among mucosal melanomas and is frequently misdiagnosed by standard identification methods.

Invasive bilateral breast cancer and high grade serous ovarian cancer with BRCA1-germline mutation and brainstem metastasis under PARP inhibitors.

For breast cancer patients, BRCA gene mutations are predictive of a good response to chemotherapy, but are hampered by a high risk of bilateral and synchronous or metachronous ovarian cancer. Novel therapies such as PARP-inhibitors have proven effective for BRCA1/2 mutated ovarian cancer. We present the case of a 50-year-old woman, initially diagnosed with bilateral luminal B breast cancer with BRCA1 mutation.

Microwave ablation in the treatment of liver tumors. A better tool or simply more power?

It has been a long time since tumor ablation was first tested in patients with liver cancer, especially hepatocellular carcinoma. Since than it has become a first line treatment modality for hepatocellular carcinoma. Over the years, the indications of thermal ablation have expanded to colorectal cancer liver metastases and intrahepatic cholangiocarcinoma as well.

Local staging of prostate cancer with multiparametric-MRI: accuracy and inter-reader agreement.

Background: The accuracy of prostate cancer local staging at the time of diagnosis directly influences patient prognosis and treatment.

Aim: To evaluate the diagnostic performance and interobserver variability of mp-MRI in local staging of prostate cancer, using the histopathologic findings at prostatectomy as the reference standard.

Methods: Fifty patients (mean age 64.

The in vivo modulatory effects of Cornus mas extract on photodynamic therapy in experimental tumors.

Background: Photodynamic therapy (PDT) is a treatment of cancer due to its ability to induce cell death, oxidative stress and acute inflammatory reaction in targeted sites. To optimize the effect of PDT the addition of some compounds with supplementary cytotoxic effect on tumor cells was tried.

Methods: The study was performed on 35 Wistar male albino rats with Walker 256 carcinosarcoma.

Real-Time Contrast-Enhanced-Guided Biopsy Compared with Conventional Ultrasound-Guided Biopsy in the Diagnosis of Hepatic Tumors on a Background of Advanced Chronic Liver Disease: A Prospective, Randomized, Clinical Trial.

We aimed to compare contrast-enhanced-guided liver biopsy (CEUSLB) and ultrasound-guided liver biopsy (USLB) in the diagnosis of focal liver lesions (FLLs) developed on a background of advanced chronic liver disease (ACLD). Between 2011 and 2019, patients diagnosed with liver tumors on a background of ACLD were evaluated for inclusion in the study. Patients were randomly assigned to the CEUSLB or USLB group.

High dose vs low dose irradiation of the subventricular zone in patients with glioblastoma-a systematic review and meta-analysis.

Purpose: The published data indicate that the irradiation of the subventricular zone (SVZ) might play a role in the treatment of patients with glioblastoma (GBM). We aimed to determine whether radiation treatment doses (high vs low) applied to the SVZ can lead to an increase in progression free survival (PFS) and overall survival (OS).

Patients And Methods: We undertook a systematic review and meta-analysis according to the PICOS research criteria of patients with glioblastoma which received high doses compared to low doses in order to determine if they have a better survival in observational and experimental studies.

NBTXR3, a first-in-class radioenhancer hafnium oxide nanoparticle, plus radiotherapy versus radiotherapy alone in patients with locally advanced soft-tissue sarcoma (Act.In.Sarc): a multicentre, phase 2-3, randomised, controlled trial.

Background: Pathological complete response to preoperative treatment in adults with soft-tissue sarcoma can be achieved in only a few patients receiving radiotherapy. This phase 2-3 trial evaluated the safety and efficacy of the hafnium oxide (HfO) nanoparticle NBTXR3 activated by radiotherapy versus radiotherapy alone as a pre-operative treatment in patients with locally advanced soft-tissue sarcoma.

Methods: Act.

Mind the Gap Between Scientific Literature Recommendations and Effective Implementation. Is There Still a Role for Surgery in the Treatment of Locally Advanced Cervical Carcinoma?

According to evidence accumulated in the last years, many cancer centers recommend a treatment plan based solely on chemo-radiotherapy and exclude surgery from the treatment options in locally advanced cervical cancer (LACC). In Romania, surgery was at the forefront of therapeutic options. Nevertheless, current data shows that in fact, a large number of patients are still referred to surgery in various stages of diagnosis and treatment.

SChitosan-capped gold nanoparticles impair radioresistant glioblastoma stem-like cells.

Purpose: Glioblastoma is a rapidly evolving lethal disease mainly due to its highly chemo- and radioresistant glioblastoma stem cells (GSCs). Herein, we tested if chitosan-capped gold nanoparticles (Chit-GNPs) may overcome the limitations of drug concentrations by increased cell internalization in GSCs and if such GNPs could enhance the response to irradiation.

Methods: Chitosan was used for Chit-GNP synthesis as a reducing and stabilizing agent.

Reduction of 2-methoxy-1,4-naphtoquinone by mitochondrially-localized Nqo1 yielding NAD supports substrate-level phosphorylation during respiratory inhibition.

Provision of NAD for oxidative decarboxylation of alpha-ketoglutarate to succinyl-CoA by the ketoglutarate dehydrogenase complex (KGDHC) is critical for maintained operation of succinyl-CoA ligase yielding high-energy phosphates, a process known as mitochondrial substrate-level phosphorylation (mSLP). We have shown previously that when NADH oxidation by complex I is inhibited by rotenone or anoxia, mitochondrial diaphorases yield NAD, provided that suitable quinones are present (Kiss G et al., FASEB J 2014, 28:1682).

Lactate - A new frontier in the immunology and therapy of prostate cancer.

Prostate cancer, one of the most common male malignancies with an increasing incidence in the recent years, requires the development of new methods of treatment. One of the most debated subjects is the tumor-associated macrophages (TAM). Although, the pathophysiological mechanisms are still a subject of intense research, TAM acts as procarcinogenic factors.

Phase III Study Comparing a Reduced Dose of Cabazitaxel (20 mg/m) and the Currently Approved Dose (25 mg/m) in Postdocetaxel Patients With Metastatic Castration-Resistant Prostate Cancer-PROSELICA.

Purpose Cabazitaxel 25 mg/m (C25) significantly improved overall survival (OS) versus mitoxantrone ( P < .001) in postdocetaxel patients with metastatic castration-resistant prostate cancer (mCRPC) in the phase III TROPIC study. The phase III PROSELICA study ( ClinicalTrials.

Catabolism of GABA, succinic semialdehyde or gamma-hydroxybutyrate through the GABA shunt impair mitochondrial substrate-level phosphorylation.

GABA is catabolized in the mitochondrial matrix through the GABA shunt, encompassing transamination to succinic semialdehyde followed by oxidation to succinate by the concerted actions of GABA transaminase (GABA-T) and succinic semialdehyde dehydrogenase (SSADH), respectively. Gamma-hydroxybutyrate (GHB) is a neurotransmitter and a psychoactive drug that could enter the citric acid cycle through transhydrogenation with α-ketoglutarate to succinic semialdehyde and d-hydroxyglutarate, a reaction catalyzed by hydroxyacid-oxoacid transhydrogenase (HOT). Here, we tested the hypothesis that the elevation in matrix succinate concentration caused by exogenous addition of GABA, succinic semialdehyde or GHB shifts the equilibrium of the reversible reaction catalyzed by succinate-CoA ligase towards ATP (or GTP) hydrolysis, effectively negating substrate-level phosphorylation (SLP).

The total and mitochondrial lipidome of Artemia franciscana encysted embryos.

Encysted embryos (cysts) of the crustacean Artemia franciscana exhibit enormous tolerance to adverse conditions encompassing high doses of radiation, years of anoxia, desiccation and extreme salinity. So far, several mechanisms have been proposed to contribute to this extremophilia, however, none were sought in the lipid profile of the cysts. Here in, we used high resolution shotgun lipidomics suited for detailed quantitation and analysis of lipids in uncharacterized biological membranes and samples and assembled the total, mitochondrial and mitoplastic lipidome of Artemia franciscana cysts.

Two transgenic mouse models for β-subunit components of succinate-CoA ligase yielding pleiotropic metabolic alterations.

Succinate-CoA ligase (SUCL) is a heterodimer enzyme composed of Suclg1 α-subunit and a substrate-specific Sucla2 or Suclg2 β-subunit yielding ATP or GTP, respectively. In humans, the deficiency of this enzyme leads to encephalomyopathy with or without methylmalonyl aciduria, in addition to resulting in mitochondrial DNA depletion. We generated mice lacking either one Sucla2 or Suclg2 allele.

Nanoparticles for Targeting Intratumoral Hypoxia: Exploiting a Potential Weakness of Glioblastoma.

Extensive hypoxic regions are the daunting hallmark of glioblastoma, as they host aggressive stem-like cells, hinder drug delivery and shield cancer cells from the effects of radiotherapy. Nanotechnology could address most of these issues, as it employs nanoparticles (NPs) carrying drugs that selectively accumulate and achieve controlled drug release in tumor tissues. Methods overcoming the stiff interstitium and scarce vascularity within hypoxic zones include the incorporation of collagenases to degrade the collagen-rich tumor extracellular matrix, the use of multistage systems that progressively reduce NP size or of NP-loaded cells that display inherent hypoxia-targeting abilities.