Impact of Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography on Therapeutic Decisions and Radiotherapy Planning in Head and Neck Squamous Carcinoma: A Retrospective Study of 46 Patients.

BACKGROUND Positron emission tomography/computed tomography (PET/CT) using fluorodeoxyglucose (FDG) is essential in oncology for precise tumor delineation. This study evaluated FDG PET/CT's impact on therapeutic decisions in head and neck cancer, comparing metabolic tumor volumes (MTV) measured by different methods with radiotherapy targets, crucial for treatment planning and patient outcomes. MATERIAL AND METHODS We retrospectively analyzed 46 patients with histologically confirmed head and neck cancer who underwent FDG PET/CT examination before radiotherapy. The mean age was 62 years (46-78 years). Then, we calculated MTV of the primary tumor or local recurrence using a local threshold of 41% of the standard uptake volume (SUV) corrected for lean body mass (SULmax) of the lesion and absolute threshold of SUV 2.5. Descriptive analysis of the recruited patients was assessed based on the clinical database (Medsol). RESULTS The study included 45 patients with squamous carcinoma and 1 with sarcoid cell carcinoma. PET/CT examination led to therapeutic decision changes in 11 cases. No significant difference was found in median values of Gross Tumor Volume (GTV) and MTV absolute (p=0.130). However, significant differences were observed in MTV local, MTV absolute, and GTV median values (p<0.001), with both MTVs showing significant correlation with GTV (p<0.01), especially MTV absolute (r=0.886). CONCLUSIONS FDG PET/CT examination prior to radiotherapy significantly influences therapeutic decisions in head and neck cancer patients. Based on our findings, the absolute threshold method (SUV: 2.5) appears to be an effective approach for calculating MTV for radiotherapy planning purposes.

Influence of Oncotherapy and Clinical Parameters on Survival of Glioblastoma Patients: A Single Center Experience.

BACKGROUND: Routine administration of temozolomide (TMZ) in the treatment protocol of glioblastoma in the last few years resulted in improving survival parameters of these patients but efficacy of supplementary bevacizumab (BVC) monotherapy has not been evidently proven. In this study, the effectiveness of different postoperative therapy for glioblastoma patients treated in our institute was evaluated. In addition, the prognostic value of clinical parameters on survival was also analyzed. METHODS: Accordance of clinical parameters (age, gender, tumor localization, size, side, Karnofsky performance score, and extension of tumor removal), postoperative treatment (radiotherapy [RT], RT + TMZ, RT + TMZ + BVC), and survival data were tested by 104 patients operated on glioblastoma in the Department of Neurosurgery, University of Debrecen between 2002 and 2012. RESULTS: Concurrent chemo-RT resulted in significant longer overall survival (OS) than RT alone (PRTvs.RT + TMZ = 0.0219) and BVC treatment after progression during TMZ also elongated survival significantly (PRT vs. RT + TMZ + BVC < 0.0001; PRT + TMZvs.RT + TMZ + BVC = 0.0022), respectively. Clinical parameters showed no significant influence on OS in comparison with different methods of postoperative oncotherapy. CONCLUSIONS: Both TMZ and BVC had a beneficial effect on glioblastoma patients' survival, but tested clinical parameters showed no evident accordance with final outcome. Although neurosurgery has an indispensable role in resecting space occupying tumors and providing good postoperative performance score patients for oncotherapy, the survival of glioblastoma patients depends rather on radio- and chemo-sensitivity than tested clinical parameters.

Combined Treatment of MCF-7 Cells with AICAR and Methotrexate, Arrests Cell Cycle and Reverses Warburg Metabolism through AMP-Activated Protein Kinase (AMPK) and FOXO1.

Cancer cells are characterized by metabolic alterations, namely, depressed mitochondrial oxidation, enhanced glycolysis and pentose phosphate shunt flux to support rapid cell growth, which is called the Warburg effect. In our study we assessed the metabolic consequences of a joint treatment of MCF-7 breast cancer cells with AICAR, an inducer of AMP-activated kinase (AMPK) jointly with methotrexate (MTX), a folate-analog antimetabolite that blunts de novo nucleotide synthesis. MCF7 cells, a model of breast cancer cells, were resistant to the individual application of AICAR or MTX, however combined treatment of AICAR and MTX reduced cell proliferation. Prolonged joint application of AICAR and MTX induced AMPK and consequently enhanced mitochondrial oxidation and reduced the rate of glycolysis. These metabolic changes suggest an anti-Warburg rearrangement of metabolism that led to the block of the G1/S and the G2/M transition slowing down cell cycle. The slowdown of cell proliferation was abolished when mitotropic transcription factors, PGC-1α, PGC-1ß or FOXO1 were silenced. In human breast cancers higher expression of AMPKα and FOXO1 extended survival. AICAR and MTX exerts similar additive antiproliferative effect on other breast cancer cell lines, such as SKBR and 4T1 cells, too. Our data not only underline the importance of Warburg metabolism in breast cancer cells but nominate the AICAR+MTX combination as a potential cytostatic regime blunting Warburg metabolism. Furthermore, we suggest the targeting of AMPK and FOXO1 to combat breast cancer.

[The role of extracellular matrix components in the invasion of intracranial malignancies]. / Az extracelluláris mátrix komponensek tumorinvázióban betöltött szerepe intrakraniális daganatokban.

The usual local recurrence of primary brain tumors is mainly due to the infiltration of adjacent brain parenchyma by the glioma cells. This invasive feature of the tumors makes total surgical excision impossible and also decreases the efficacy of focal radiotherapy. Interestingly, intracerebral metastases originating from many anaplastic tumors of other organs perform very moderate peritumoral infiltration, therefore radical resection can be routinely achieved and focal irradiation, even stereotactic radiotherapy, provides good tumor control. Differences in the effectiveness of treatment between the two tumor types derive from the remarkably different extent of peritumoral infiltration. Thus significant molecular biological research has been dealing with the infiltrative activity of various brain tumors and many attempts were made to develop anti-invasive drugs for oncotherapy. This review summarizes the results of these studies, describing cellular and molecular events of brain tumor invasion and according potential oncotherapeutic possibilities.