Mária Godény

Neoadjuvant Immunotherapy of Oral Squamous Cell Carcinoma Modulates Intratumoral CD4/CD8 Ratio and Tumor Microenvironment: A Multicenter Phase II Clinical Trial

PURPOSE To investigate the clinicopathologic effects of local neoadjuvant Leukocyte Interleukin Injection (LI) regimen in oral squamous cell carcinoma (OSCC) patients. Treatment regimen included LI 800 IU/d as interleukin-2 (IL-2), administered half peritumorally and half perilymphatically five times per week for 3 weeks; low-dose cyclophosphamide; indomethacin; zinc; and multivitamins. PATIENTS AND METHODS Thirty-nine patients diagnosed with T2-3N0-2M0 OSCC participated in the pathology portion of this phase II multicenter study (19 LI-treated patients and 20 historical controls). Clinical responses were determined by imaging. Paraffin-embedded tumor samples were obtained at surgery for all patients. Surgery for the LI-treated group was performed between days 14 and 54 after the end of treatment. Histologic evaluation, pathologic staging, necrosis, and American Joint Committee on Cancer grading were performed from hematoxylin and eosin sections. Immunohistochemistry and morphometry determined cellular infiltrate. RESULTS Two pathologically complete, two major (> 50%), and four minor responses (> 30% but < 50%) resulted from LI treatment (overall response rate, 42%). Histopathology showed that the intratumoral CD4+:CD8+ ratio was low (< 1) in patients not treated with LI (controls). An increase in tumor-infiltrating CD4+ and a decrease of CD8+ T cells was observed in LI-treated patients, leading to a significantly (P < .05) higher intratumoral CD4+:CD8+ ratio (> 2.5). This was paralleled by dendritic cell transition from tumor surface toward stromal interface (P < .05), with macrophage decrease and neutrophil accumulation, multifocal microscopic necrosis, and significant (P < .05) increase in tumor stroma of LI-treated patients compared with controls. CONCLUSION LI-treated OSCC patients were characterized by a markedly altered composition of tumor-infiltrating mononuclear cells, increased CD4+:CD8+ ratio, and increased tumor stroma to epithelial ratio, all of which were distinct from controls.

Radiation myelopathy with partial functional recovery: PET evidence of long-term increased metabolic activity of the spinal cord

Postoperative telecobalt irradiation was performed with a biologically effective extrapolated response dose of 165 Gy2 delivered to the spinal cord of a papillary thyroid cancer patient. Incomplete cervical transection developed, followed by a gradual functional improvement, which is still continuing 8 years after radiotherapy. Between the 6th and 8th years of the clinical course, positron emission tomography investigations demonstrated an increased 18F-deoxyglucose accumulation and (15)O-butanol perfusion, but negligible 11C-methionine uptake in the irradiated spinal cord segment. We suggest that the increased metabolism and perfusion, and the lack of detectable protein synthesis may be related to the increased energy demands of action potential conduction, due to the higher than normal density of sodium channels along demyelinated axons displaying restored conduction.

Revealing cancer initiating cells in metastatic melanomas by harnessing the host′s anti tumor humoral immune mechanisms

Results Cell cultures grew out of the great majority of the starter metastatic tissue specimen and cancer initiating cells could be sorted (BD FACSAvia Sorter) by colocalized unique sialilated glycosphingolipids and anti CD20 binding capacity. Characteristic growth pattern, spheroid forming, CSC markers like CD133, Nestin, ABCB5, CD20 and unique GD3 gangliosides were found. Patients′ sera and selected patients′ Epstein Barr Virus transformed cell supernatants in bulk or after limiting dilution cloning were tested for cancer binding by ELISA and immunofluorescence. Our novel tumor infiltrating B cell antibody phage display technique and DNA sequence cluster analysis (Vector NTI Advance 11, Bioedit 7.0, ClustalX2.0.11) resulted in some antibody fragments, belonging to representative tumor binding antibody variable region subgroups, with defined silalilated glycosphingolipid specificity.

FDG PET imaging in hereditary thyroid cancer

AIM To report the role of different imaging methods in staging individuals with multiple endocrine neoplasia 2A (MEN2A) or familial medullary thyroid carcinoma (FMTC). MATERIAL AND METHODS Fourteen newly diagnosed gene carriers underwent cervical ultrasound scanning (US), cervical and mediastinal CT, MRI and whole-body meta-[131I]iodobenzylguanidine (MIBG) scintigraphy and [18F]fluorodeoxyglucose (FDG) PET scanning. RESULTS US identified seven true primary cancer. CT and MRI located only tumors > or =5 mm in diameter. MIBG scintigraphy and FDG PET could not identify MTC foci within the thyroid. Whole-body FDG PET identified two true-positive and one false-positive lymph node metastases. MIBG scintigraphy did not identify lymph node metastases. Total thyroidectomy was performed in 12 cases, and subtotal thyroidectomy in two subjects. CONCLUSIONS Whole-body FDG PET and cervical US help stage individuals carrying mutant genes verifying MEN2A or FMTC.

Dynamic Contrast-Enhanced MRI Parameters as Biomarkers in Assessing Head and Neck Lesions After Chemoradiotherapy Using a Wide-Bore 3 Tesla Scanner.

Pilot studies have shown promising results in characterizing head and neck tumors (HNT) using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), differentiating between malignant and benign lesions and evaluating changes in response to chemoradiotherapy (CRT). Our aim was to find DCE-MRI parameters, biomarkers in evaluating the post-CRT status. Two hundred and five patients with head and neck lesions were examined with DCE-MRI sequences. The time intensity curves (TIC) were extracted and processed to acquire time-to-peak (TTP), relative maximum enhancement (RME), relative wash-out (RWO), and two new parameters attack and decay. These parameters were analyzed using univariate tests in SPSS (Statistical Package for the Social Sciences, version 17, SPSS Inc. Chicago, USA) to identify parameters that could be used to infer tumor malignancy and post-CRT changes. Multiple parameters of curve characteristics were significantly different between malignant tumors after CRT (MACRT) and changes caused by CRT. The best-performing biomarkers were the attack and the decay. We also found multiple significant (p < 0.05) parameters for both the benign and malignant status as well as pre- and post-CRT status. Our large cohort of data supports the increasing role of DCE-MRI in HNT differentiation, particularly for the assessment of post-CRT status along with accurate morphological imaging.

[Quality assurance of fine-needle aspiration cytology of the organized mammography screening].

UNLABELLED The National Public Health Program has established the organized mammography screening in Hungary. AIM The aim of our study was to determine the quality assurance of breast aspiration cytology. METHOD Cytology results were rated to 5 categories (C1, C2, C3, C4 and C5). All cytology reports were compared with the final histology diagnosis. RESULTS 1361 women had aspiration cytology diagnosis performed from a total of 47718 mammography non-negative lesions. There were 805 (59.1%) benign and 187 (13.7%) malignant alterations. Sensitivity was 91%, specificity 88%, positive predictive value 96.6% and negative predictive value turned to be 71% (p<0.001). CONCLUSION The auditing values of fine needle aspiration cytology in our laboratory meet, or in certain aspects exceed the proposed minimum threshold values.

[The potential role of SPECT/CT in the preoperative detection of sentinel lymph nodes in breast cancer].

Regional lymph node status is the most important prognostic factor in breast cancer. Sentinel lymph node biopsy is the standard method of axillary staging in early breast cancer patients with clinically negative nodes. Preoperative lymphoscintigraphy might support refining biopsy findings by determining the number and location of sentinel lymph nodes. In aged or overweight patients, in the presence of atypical or extra-axillary lymphatic drainage, non-visualized lymph nodes, or sentinel lymph nodes close to the isotope injection site, detection could be aided by a new, hybrid imaging tool: the single-photon emission computed tomography combined with computed tomography (3D SPECT/CT). For the first time in Hungarian language, authors overview the literature: all 14 English-language articles on the implementation of 3D SPECT/CT in sentinel lymph node detection in breast cancer are included. It is concluded that 3D SPECT/CT increases the success rate and quality of preoperative sentinel node identification, and is capable of providing a more accurate staging of breast cancer patients in routine clinical practice.

Natural immunomodulator preimplantation factor PIF affected cancer growth in malignant melanomas

Background and objectives Malignant and trophoblastic cells share common features in terms of migration and invasion, while they represent striking differences also (1). Our results on immune mechanisms in pregnancy failure (2) and use of immunotherapeutics (3) fostered the present new approach: Pregnancy derived compounds for potential growth controlling effect in metastatic melanomas were studied. Methods

Minor tumor infiltrating B cells opened a door to reveal and eliminate cancer initiating cells in metastatic melanomas

Meeting abstracts The theory and investigations on cancer stem cells (CSCs) have received growing attention, as these cells are responsible for the failure of cancer therapeutic strategies and the return of cancer. A complex tumorimmunological study on primary and metastatic cancerous tissue

Anti-tumor antibody profile analysis to harness the potentials of B cells in melanomas and the natural humoral immune response

Meeting abstracts Natural humoral immune response and autoimmune mechanisms have great importance in keeping the balance of tumorimmunity, although it has not yet been fully understood. We aimed to reveal potential anti-tumor immune response by immunoglobulin (Ig) profile analysis of patients with