Rudžianskas, Viktoras

Objectives: The aim of this study was to assess the impact of polymorphisms in cytokine genes on pain severity and pain treatment with palliative radiotherapy.

Introduction Squamous cell carcinoma is the most common malignant cancer of the larynx [1], and it is also more common in males [2, 3]. The main treatment goal for early-stage disease (T1-T2N0M0) is to achieve cancer control and to preserve the function of adjacent sites. Early-stage laryngeal cancer is either treated with radiation therapy or surgery, depending on factors such as cancer type, tumor location, patient health status, and personal preference [4]. Case Presentation 76 y.o. male presented with a two-month history of progressive hoarseness. Laryngoscopy revealed thickening of the right vocal cord. Biopsy confirmed a well-differentiated squamous cell carcinoma (G1). Contrast-enhanced CT of the neck showed 1.1 x 0.6 x 0.7 cm infiltrative lesion. The tumor was staged as cT2N0M0 (II). Following a multidisciplinary team discussion, stereotactic body radiotherapy using MR-LINAC was selected. Total dose of 42.5 Gy was delivered in five fractions. Treatment was well tolerated. Only transient voice hoarseness was observed. Three-month follow up imaging showed marked tumor regression, indicating a favorable treatment response. Discussion The main advantage of MR-LINAC technology is integrated real time MRI imaging compared to the older LINAC technology, which uses CT imaging [5]. MRI provides a more detailed view of soft tissue. Furthermore, MRI allows monitoring of tumor and surrounding organ movement, anatomical changes (e.g., due to breathing or digestion), and real-time treatment adjustments. These advantages allow reduction of the radiation dose to healthy tissue and planning a narrower margin around the tumor area [6]. For example, the patient received 42.5 Gy in five fractions, whereas using conventional LINAC technology, the patient would have received 63 Gy in 28 fractions. Conclusions This case illustrates the use of MR-LINAC–guided hypofractionated radiotherapy in a patient with early-stage laryngeal cancer. Although the total physical dose was lower, the biological effect was maintained through the use of larger per-fraction doses. Treatment was completed over a shorter course, which may be advantageous for patient convenience, while achieving favorable short-term tumor control and preservation of laryngeal function.

Background and Objectives Laryngeal cancer is among the most common malignancies of the upper respiratory tract, with early-stage (T1,T2) cases typically treated by surgery or radiotherapy (RT), achieving comparable overall survival rates. Nowadays intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) techniques are used for laryngeal cancer treatment irradiating a whole larynx volume. New technologies, such as magnetic resonance based linear accelerator (MR-linac), led to reduce the target volume and treatment time. This study aims to explore the clinical and dosimetric feasibility of stereotactic ablative radiotherapy (SABR) guided by MR-linac technology (SMART) as an alternative for early-stage laryngeal cancer. Material (patients) and research method used Two complementary investigations were performed. The first compared standard fractionated RT (63 Gy/28 fr.) to MR-Linac-based SABR (42.5 Gy/5 fr.) in 32 patients, evaluating safety, treatment duration, toxicity, and precision. The second focused on validating dosimetric accuracy using individualized 3D-printed phantoms filled with radiation-sensitive gels and assessed treatment plans through gamma analysis. Findings/results in sufficient details to support conclusions Results demonstrated that SMART enables more precise dose delivery, reduces treatment time and irradiated volume (up to 15%), and preserves laryngeal function. Dosimetric analysis showed high concordance between planned and delivered doses, with gamma passing rates above 95%. Conclusions and recommendations In conclusion, MR-Linac-guided SMART appears to be a safe, efficient, and innovative approach for early-stage laryngeal cancer treatment, with promising implications for clinical implementation and patient quality of life. However, challenges remain in target volume definition and further accuracy enhancement, highlighting the potential role of machine learning in future personalization.

Purpose/Objective: Laryngeal cancer is the one of the most common upper respiratory tract cancer with 40 025 new cases and 19 728 deaths in Europe in 2020 [1]. The overall survival rate for patients undergoing surgery is around 80% and 90% for RT [2]. Laryngeal preservation has been evaluated only in few clinical trials [3]. The aim of this study is to develop an innovative stereotactic ablative magnetic resonance image-guided radiotherapy (SMART) treatment method, clinical parameters and results of individualized phantom dosimetry measurements and apply it for early stage laryngeal cancer treatment in MRI-LINAC modality. Main objectives are to evaluate clinical and dosimetric parameters of early-stage laryngeal cancer patients, to introduce phantom-based dose verification method, including development and fabrication of individualized 3D printed phantom which enables dose mapping functions due to application of specially developed [4] radiationsensitive gels and to evaluate the feasibility of SMART method for the clinical laryngeal cancer treatment. Material/Methods: Diagnostic images of patients were acquired using CT (LightSpeed RT16), MRI (Siemens Magnetom Avanto 1.5T), and PET/CT facility. Six patients were treated using the adaptive radiotherapy modality Electa Unity, 1.5T MRI and patient treatment plans were prepared and analyzed using TPS Monaco. Gafchromic films and volumetric gel dosimetry were used for dose plans verification. Data of patients treated in Trilogy and Truebeam linacs and dose plans prepared by TPS Eclipse 15.5™ (Varian Medical Systems) were analyzed. For 3D printout was used ZORTRAX M300 printer. Special 3D printing materials were used. Dosimetric gels were prepared, irradiated and dosimetric characteristics investigated. Results: All TP were generated with 42.5Gy (8.5Gy/fr) in five fractions. MRI-CT individualized phantom was created based on patient DICOM images [1fig] and filled with dose gels. 3D printed components, dosimetric gel and in target center positioned radiochromic films were irradiated with one fraction dose and compared with planned in TPS. It was estimated phantom components and dose gel densities similarity to patient's tissues in Hounsfield units (HU). All structures met requirements: phantom (plastic/bone) 187HU, target 152HU, gelatin 10-15HU. Gamma passing rate was 95.7% to radiochromic films, 96.8% to dosimetric gels. During TP comparison (Eclipse/Monaco) was found that using SMART treatment method is possible to reduce treatment volume at least 15%. Conclusion: SMART treatment integration into clinical practice could improve access to services for cancer patients, shorten the duration of treatment, preserve laryngeal function, and protect organs at risk.

Pasaulyje kasmet nustatoma daugiau nei 180 000 naujų gerklų vėžio atvejų ir apie 100 000 mirties atvejų. Jungtinėse Amerikos Valstijose per metus diagnozuojama apie 12 400 naujų gerklų karcinomos atvejų ir aprašoma apie 3800 mirčių nuo šios ligos [1], Gerklų vėžys yra antra dažniausia galvos ir kaklo srities onkologinė liga. Tai yra vienuolikta dažniausia vėžinė liga vyrų populiacijoje, tačiau gerokai rečiau nustatoma moterims. Pagal įvairius literatūros duomenis sergamumo gerklų vėžiu vyrų ir moterų santykis yra 11 :1 [2]. Daugiausia pacientų, sergančių gerklų karcinoma, nustatoma 60-70 metų grupėje. Didelę reikšmę gerklų vėžiui atsirasti turi rūkymas ir alkoholinių gėrimų vartojimas. Rūkantys asmenys turi 6,5 karto didesnę tikimybę susirgti gerklų vėžiu. Prie rizikos veiksnių taip pat priskiriama darbas su naftos perdirbimo ir deginimo produktais, gastroezofaginis refliuksas, žmogaus papilomos virusas. Pagal naujausius prieinamus nacionalinio vėžio registro duomenis kiekvienais metais 100 000 gyventojų tenka 6,6 naujų gerklų vėžio atvejų, penkerių metų realiatyvus išgyvenamumas - 69 proc., o 60 proc. pacientų kreipiasi jau esant įsisenėjusiai (III-IV stadijų) ligai [3, 4], Todėl ypač svarbu gerinti gerklų vėžio diagnostikų. Svarbu atsiminti, jog žmogus, kuris skundžiasi ilgiau nei 3 savaites nepraeinančiu užkimimu, privalo būti konsultuojamas gydytojo otorinolaringologo.

Background: The treatment of multiple myeloma (MM) has changed dramatically due to the introduction of novel agents in the last decade. However, the treatment of patients who had been treated with two or more previously lines of therapy remains challenging. Monoclonal antibodies against CD38 are a suitable option in disease progression. Immunotherapies are under clinical investigations and not available in multiple countries. The allogeneic stem cell transplantation (SCT) still remains the option to treat selected patients. Crossmatching by flow cytometry (FCXM) and complement–dependent lymphocytotoxicity (CDCXM) are used to identify the alloimmune pre-transplant risk which is associated with worse allograft outcome. Methods: We report the first case of Isatuximab interference of allogeneic crossmatch assessment causing false-positive results in heavily pre-treated patient with multiple myeloma. Results: 42-year-old male diagnosed with MM in 2018. Diagnose was based on positive serum kappa/lambda free light chain (FLC) ratio of 0.02 (kappa 5.91 mg/l; lambda 310 mg/l), monoclonal protein on serum protein electrophoresis and IgG lambda positive immunofixation. Bone marrow biopsy revealed infiltration of 15 % of plasma cells. On fluorescence in situ hybridization any specific genetic aberrations were not detected. The patient was treated with 4 courses of VTD (Bortezomib, Thalidomide, Dexamethasone) and tandem autologous SCT was done. The complete remission continued 20 months. After the first relapse the patient was treated with KRD (Carfilzomib, Lenalidomide and Dexamethasone). During the treatment the multiple plasmacytomas in bones and organs were detected and treatment was switched to PACE (Cisplatin, Doxorubicin, Cyclophosphamide, Etoposide). After two courses the disease progression was revealed and treatment with Isa-Pom-Dex regiment (Isatuximab, Pomalidomide, Dexamethasone) was started in named patient program. After four courses of Isa-Pom-Dex the partial remission was achieved. After consolidation with salvage autologous SCT, allogenic matched related donor SCT were performed. Patient received conditioning regiment of Fludarabine and 8 Gy TBI. Pre-transplant crossmatching was done using two techniques. CDCXM was done between donor T and B lymphocytes and recipient sera with and without dithiothreitol (DTT) and ¼ dilutions, according to guidelines of the American Society for Histocompatibility and Immunogenetics. FCXM was done on a BD FACSLyric flow cytometer using FACSuite software (BD Biosciences, San Jose, CA, USA). Median channel shift (MCS) was used for results evaluation. A cutoff value for positive FCXM assay was defined as more than 2 SD. Unexpected results were obtained – CDCXM was negative but FCXM was positive with T and B cells. We hypothesized that FCXM results were falsely positive. Subsequently, antibodies against HLA (antiHLA) were tested by Luminex (Luminex, Austin, TX) using singleantigen bead ® xMAP® technology (LIFECODES LSA Class I and Class II kits, Immucor Inc., USA). The results revealed the absence of either anti-HLA class I or anti-HLA class II antibodies. Conclusions: Isatuximab is a chimeric humanized IgG1 monoclonal antibody which binds the CD38. CD38 is present on plasma cells and expressed on T and B lymphocytes, and can contribute to variability in FCXM results. The false-positive results of FCXM assessment after treatment with Isatuximab can be caused by anti-CD38 monoclonal antibodies binding to donor cell surface CD38.

Pasaulyje tarp vėžinių susirgimų galvos ir aklo vėžys sudaro apie 5-6 proc. ir yra šeštoje vietoje pagal paplitimą. [...].

Galvos ir kaklo navikai yra heterogeniška navikų grupė, kurių lokalizacija gali būti nuo kaukolės pamato iki raktikaulių. Šiose anatominėse srityse daug kritinių organų, svarbių juslėms, išvaizdai, kvėpavimui, bendravimui ir valgymui. Tiek šalutinės reakcijos, tiek gydomosios dozės paskyrimas į naviką ir patologinius limfmazgius priklauso nuo radioterapijos kokybės. Pastaraisiais dešimtmečiais spindulinės terapijos kokybė, atsižvelgiant į naujas vaizdavimo, planavimo ir paskyrimo galimybes, labai pagerėjo. Norint visapusiškai išnaudoti naujų technologijų privalumus vis svarbesnis darosi tikslus taikinių ir kritinių organų apibrėžimas. Siekiant sumažinti skirtumus tarp gydytojų ir radioterapijos skyrių specialistų sampratos apibrėžiant taikinio tūrį ir kritinius organus buvo sudarytos galvos ir kaklo navikų sritinių limfmazgių lygmenų nustatymo gairės ir kritinių organų apibrėžimo gairės. Įvairiose publikacijose autoriai pateikia skirtingus kritinių organų dozės ir tūrio vertinimo kriterijus. Dėl šių skirtumų, naudojant skirtingus apibrėžimo protokolus, neįmanoma palyginti skirtingų studijų rezultatų tarpusavyje, todėl siūloma, kad tiek kasdienėje klinikinėje praktikoje, tiek daugiainstituciniuose klinikiniuose tyrimuose būtų vadovaujamasi bendromis kritinių organų apibrėžimo bei dozės ir tūrio vertinimo gairėmis. Siekiant užtikrinti aukštą radioterapijos kokybę, būtina vadovautis rekomendacijomis, kurias pateikia pasaulinės radioterapijos organizacijos: AIRO (Italijos onkologų ir radioterapeutų asociacija), CACA (Galvos ir kaklo vėžio komitetas, Nosiaryklės vėžio komitetas, Kinijos kovos su vėžiu asociacija), DAHANCA (Danijos galvos ir kaklo vėžio grupė), EORTC (Europos vėžio tyrimų ir gydymo organizacija), GORTEC (Prancūzijos galvos ir kaklo radioterapinės onkologijos grupė), IAG-KHT (Vokietijos multidisciplininė galvos ir kaklo navikų grupė), RTOG (JAV spindulinio gydymo tyrimus koordinuojančioji grupė), TROG (Tran-Tasmanijos radioterapinės onkologijos grupė) ir kitos. Mokomoji knyga skirta gydytojams onkologams-radioterapeutams, gydytojams onkologams-chemoterapeutams, gydytojams otorinolaringologams, gydytojams veido žandikaulių chirurgams bei šių specialybių gydytojams rezidentams ir medicinos studentams.

Background and Objectives: To our knowledge, this is the first study that investigated the prognostic value of radiomics features extracted from not only staging 18F-fluorodeoxyglucose positron emission tomography (FDG PET/CT) images, but also post-induction chemotherapy (ICT) PET/CT images. This study aimed to construct a training model based on radiomics features obtained from PET/CT in a cohort of patients with locally advanced head and neck squamous cell carcinoma treated with ICT, to predict locoregional recurrence, development of distant metastases, and the overall survival, and to extract the most significant radiomics features, which were included in the final model. Materials and Methods: This retrospective study analyzed data of 55 patients. All patients underwent PET/CT at the initial staging and after ICT. Along the classical set of 13 parameters, the original 52 parameters were extracted from each PET/CT study and an additional 52 parameters were generated as a difference between radiomics parameters before and after the ICT. Five machine learning algorithms were tested. Results: The Random Forest algorithm demonstrated the best performance (R2 0.963–0.998) in the majority of datasets. The strongest correlation in the classical dataset was between the time to disease progression and time to death (r = 0.89). Another strong correlation (r ≥ 0.8) was between higher-order texture indices GLRLM_GLNU, GLRLM_SZLGE, and GLRLM_ZLNU and standard PET parameters MTV, TLG, and SUVmax. Patients with a higher numerical expression of GLCM_ContrastVariance, extracted from the delta dataset, had a longer survival and longer time until progression (p = 0.001). Good correlations were observed between Discretized_SUVstd or Discretized_SUVSkewness and time until progression (p = 0.007). Conclusions: Radiomics features extracted from the delta dataset produced the most robust data. Most of the parameters had a positive impact on the prediction of the overall survival and the time until progression. The strongest single parameter was GLCM_ContrastVariance. Discretized_SUVstd or Discretized_SUVSkewness demonstrated a strong correlation with the time until progression.

Background and Objectives This is the first study to explore the prognostic value of radiomics features extracted from both pre- and post-induction chemotherapy (ICT) PET/CT imaging for patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC). The study aimed to identify the most significant prognostic radiomics biomarkers for locoregional recurrence free survival (LRFS), based on a machine learning model. [...].