Jančiauskienė, Rasa

Background and Objectives Electroporation is a method that applies controlled electrical pulses to enhance the permeability of the cell membrane, thereby enabling improved intracellular delivery of therapeutic agents or inducing direct cytotoxic effects. Checkpoint inhibitor therapy, a form of immunotherapy, targets inhibitory signaling pathways exploited by cancer cells to evade immune detection, thereby restoring and amplifying the host’s antitumor immune response. Recent studies suggest that combining electroporation-based therapies with immunotherapy may further enhance antitumor efficacy [1]. This study aims to determine whether a multimodal treatment strategy provides greater tumor control than single-modality interventions. Specifically, we investigated the therapeutic efficacy of combining cytotoxic drugs (Cisplatin or Oxaliplatin) with electroporation and checkpoint inhibitor therapy in the treatment of tumors in mouse models. Results Experiments were performed using the 4T1 murine breast cancer cell line (ATCC). Cells were cultured in RPMI medium (Sigma-Aldrich, St. Louis, MO, USA) supplemented with 1% penicillin–streptomycin and 10% fetal bovine serum. Experimental scheme Eight- to twelve-week-old female BALB/c mice were used in this study. Tumors were induced by a single 100 μL subcutaneous injection of 4T1 cells (20 × 10⁶ cells/mL), resulting in one tumor per mouse. Tumors were allowed to develop until they reached a volume of approximately 150–500 mm³, after which treatment was initiated (~10 days post-injection), depending on tumor growth rate. Mice were assigned to experimental groups based on tumor volume to ensure balanced distribution across groups. A total of ten groups were included: untreated control (CTRL) (n = 8), Oxaliplatin (Ox) (n = 8), Ox + EP (n = 8), Cisplatin (Cis) (n = 8), Cis + EP (n = 8), EP (n = 8), checkpoint inhibitor therapy (Nivolumab, Ch.P) (n = 8), Ch.P + EP (n = 4), Ch.P + EP + Ox (n = 8), and Ch.P + EP + Cis (n = 8). Prior to treatment, the tumor-bearing area was shaved and depilated. Mice were anesthetized with ketamine (80 mg/kg) and xylazine (7.5 mg/kg, i.p.) to ensure adequate sedation during procedures. Electroporation Electroporation was performed using a BTX T820 electroporator (Harvard Apparatus, San Diego, CA, USA). Reversible electroporation (EP) was applied to groups 3, 5, 6, 8, 9, and 10 using the following parameters: 1.5 kV/cm × 8 pulses, 99 µs, 1 Hz. Treatment with drugs Cisplatin (88 μL, 1 mg/mL) was administered as a single dose via the tail vein (groups 4, 5, and 10). Oxaliplatin (33 μL, 5 mg/mL) was administered in the same manner (groups 2, 3, and 9). As a checkpoint inhibitor therapy, Nivolumab (200 μg) was administered intraperitoneally (i.p.) every two days for a total of four injections (groups 7, 8, 9 and 10). Evaluation of tumor sizes Tumors were measured every 2 days, starting on day 1 (the day of treatment) and continuing until day 19. Tumor dimensions were determined using a digital caliper. Tumor volume (mm³) was calculated according to the formula: V = (π × l × w × h) / 6, where l denotes length, w width, and h height of the tumor [2]. Tumor growth analysis revealed time-dependent differences between treatment groups. In the early phase (days 2–6), statistically significant reductions in tumor volume compared to CTRL (Dunnett test, p < 0.05) were observed in the Cis + EP, EP, and Ch.P + EP + Cis groups, indicating an early therapeutic response. Due to technical limitations (insufficient reliable measurements), the Ch.P + EP group was excluded from comparative analysis. By the intermediate phase (day 10), the Ch.P + EP + Cis combination demonstrated the strongest and most consistent antitumor effect, achieving nearly a 2-fold reduction in tumor volume compared to CTRL. A strong but less consistent effect was also observed in the Ch.P + EP + Ox + Cis group. In the late phase, these groups maintained approximately 2.0–2.2-fold lower tumor volumes compared to control; however, differences were not statistically significant, likely due to increased variability. EP alone also showed a consistent ~2-fold inhibitory effect. Notably, the addition of Oxaliplatin, a chemotherapeutic agent with reported immunomodulatory properties, appeared to reduce treatment efficacy in combination regimens (~1.2–1.3-fold reduction), suggesting a potential antagonistic interaction. These findings indicate that while electroporation enhances checkpoint inhibitor therapy, certain drug combinations may attenuate this effect and require further investigation. Conclusions and Recommendations Ch.P + EP demonstrated the strongest antitumor effect, achieving ~2-fold tumor reduction compared to control, while the addition of Oxaliplatin reduced efficacy, suggesting a potential antagonistic interaction. Further studies are needed to clarify underlying mechanisms and optimize combination strategies.

Introduction and Aim Glioblastoma (IDH-wildtype) is the most aggressive primary brain tumor in adults, with a median overall survival of 12–15 months. Only around 5% of patients survive beyond five years, and extreme long-term survivors living 10 or more years represent less than 1% of all cases. The biological and clinical factors that allow some patients to achieve such outcomes remain largely unknown. We report four patients with histologically confirmed IDH-wildtype glioblastoma diagnosed between the ages of 42 and 46, all of whom achieved 17-18 years of progression-free survival, aiming to contribute to the understanding of biological heterogeneity in this disease. Case report We retrospectively reviewed four patients treated at our institution from 2007 to 2008. Three patients were female and one male; age at diagnosis ranged from 42 to 46 years (median 44 years). Histology included glioblastoma multiforme cases and one glioblastoma with rhabdoid differentiation. All patients underwent surgical resection followed by concurrent chemoradiotherapy with temozolomide (75 mg/m² for 42 days) and adjuvant temozolomide (female, age 42: 5 cycles; female, age 46: 6 cycles; male, age 43: 3 cycles, female with rhabdoid differentiation, age 45: 6 cycles). MGMT promoter methylation status was unavailable due to archival tissue limitations. All patients achieved 17-18 years of progression-free survival with no radiological evidence of recurrence on long-term follow-up imaging, and all remain alive at current ages of 59-65 years. Discussion All four patients were a relatively young at diagnosis, which is a recognised favourable prognostic factor in glioblastoma. Younger patients typically have better performance status, tolerate treatment better, and more likely to undergo gross total resection. However, younger age alone is unlikely to explain survival of this magnitude, as most patients in this age group still have a median survival of approximately 15 months. One particularly notable case is the patient with rhabdoid glioblastoma, a subtype associated with early leptomeningeal dissemination and very poor prognosis. Reported median survival is under 18 weeks, and a previously documented maximum of 9 months, with only rare cases exceeding several months, making this prolonged disease-free survival highly unusual. Due to the age of the histological material, it was not possible to perform additional molecular tests. The absence of MGMT promoter methylation data is an important limitation. MGMT methylation has been reported in a high proportion (95%) of long- term glioblastoma survivors in some series, and its absence is generally associated with poorer outcomes. However, recent registry data suggest that a subset of long-term survivors - particularly those without recurrence - may harbour MGMT-unmethylated tumours at a surprisingly high rate, suggesting they may represent a biologically distinct glioblastoma subtype. This challenges the assumption that MGMT methylation is a prerequisite for exceptional outcomes. Additionally, long-term survival in IDHwildtype glioblastoma has been associated with reduced expression of genes such as CHI3L1, SERPING1, and IGFBP2, although their clinical significance remains uncertain. Conclusions This case series suggests that very long-term, progression-free survival is possible in IDH-wildtype glioblastoma, including the rhabdoid variant, which is typically associated with poor prognosis. Standard prognostic markers available in our cohort do not adequately explain these outcomes, pointing to the likely presence of additional biological factors not captured by routine diagnostics. Comprehensive molecular profiling, including MGMT promoter methylation, TERT promoter mutation, and immune microenvironment characterisation, may help identify mechanisms underlying guide more individualised treatment strategies.

Introduction and aim Sarcomas are rare malignancies of mesenchymal origin, with an annual incidence of 5–7 cases per 100,000 (1,2). Osteosarcoma (OS) is the most common primary malignant bone tumor, representing around 20% of all primary bone cancers (3). However, craniofacial (skull and jaw) localization is exceptionally rare and accounts for less than 10% of all cases (4). In contrast to conventional osteosarcoma, typically affecting adolescents and young adults, craniofacial OS more often occurs in older patients (4). Clinically, these tumors present as a firm, enlarging mass in the facial or cranial region and might cause symptoms such pain, facial asymmetry, neurologic signs or dental issues (5). Standard treatment of high-grade OS consists of perioperative chemotherapy (ChT) and surgery aiming R0 resection. Treatment should be planned and delivered by a specialized sarcoma multidisciplinary team (MDT) (6). As the anatomical complexity of the skull poses significant challenges for surgical management, achieving wide margins is often unfeasible (4). In such cases, postoperative radiotherapy may be considered (7). Despite optimal treatment, craniofacial OS carries a significant risk of local recurrence up to in 30–40%of the cases. Five-year overall survival in localized disease is 60-70% (7). Notably, these tumors demonstrate lower rates of pulmonary metastases compared to appendicular OS, possibly due to higher rates of local relapse influencing its prognosis (4). We present a case of an adult patient with OS of the skull to highlight its diagnostic and therapeutic complexity and the importance of personalized management in a specialized sarcoma center. Case report A 42-year-old man presented at the Sarcoma Center, Hospital of LUHS Kaunas Clinics, with a progressively enlarging lump on his forehead and intense headache. MRI revealed a 4.4 × 2.8 × 5.0 cm tumor mass occupying the frontal sinuses, with intracranial and extracranial extension. Biopsy confirmed the diagnosis of high-grade osteosarcoma. No evidence of distant metastasis was found. As the patient was deemed fit for ChT and given the importance of a shrinkage to achieve clear margins neoadjuvant MAP ChT was started. However, after the first cycle of metotrexate, the patient developed severe acute kidney injury. Methotrexate and cisplatin were excluded in favor of carboplatin and doxorubicin. After two cycles of ChT MRI showed initial dimensional and tissue response and considering the good tolerability the MDT decided to proceed with two more cycles to improve the quality of surgery. R0 surgery including reconstruction with cement cranioplasty followed, with excellent cosmetic and functional outcome. Due to clear margins and the risk of postoperative complications, adjuvant radiotherapy was not administered. The patient completed two further cycles of postoperative ChT. After a-1-year followup, the patient remains free from disease. Discussion Craniofacial OS are rare and present unique management challenges due to the complex anatomy of the skull and proximity to vital structures (4). In this case, the involvement of both intracranial and extracranial compartments required careful coordination between oncology, radiology, surgery, and supportive care. Since management in a specialized sarcoma center is crucial to coordinate care across disciplines and to provide individualized treatment planning (6) treatment decisions were made through repeated multidisciplinary team (MDT) discussions at a dedicated sarcoma center, enabling timely adaptation of the therapeutic plan based on toxicity and response. The initial use of MAP ChT was guided by the need to achieve maximal tumor shrinkage to allow radical resection. However, the onset of methotrexate-induced nephrotoxicity necessitated a regimen change. Response evaluation after two cycles of carboplatin-doxorubicin showed favorable changes in both size and imaging characteristics (e.g., mineralization, reduced enhancement), which informed the MDT decision to prolong neoadjuvant treatment. This highlights the critical role of dynamic response assessment in guiding the number of ChT cycles and improving resectability. Achieving R0 margins was essential to omit radiotherapy and avoid additional morbidity, which can be significant in such a delicate and functionally critical craniofacial region (7). This case reveals the value of specialized sarcoma center care, where individualized treatment, case-by-case MDT decision-making, and response guided therapy are fundamental for optimal outcomes. Conclusions Management of all sarcomas, including skull OS should be conducted in a specialized sarcoma center to ensure expert, multidisciplinary care. Treatment must be tailored case-by-case, balancing oncologic goals with patient-specific factors and therapy tolerability

Background and Objectives Cancer remains a major public health challenge and one of the leading causes of death worldwide [1]. In Lithuania, cancer accounted for 18.4% of all deaths in 2022, highlighting the urgent need for new treatment strategies. Despite advances in diagnostics and therapy, many cancers are still difficult to treat due to tumor heterogeneity and drug resistance [2]. Electrochemotherapy (ECT) has emerged as a promising option for local tumor control, especially in patients with superficial tumors or those unfit for systemic treatments [3]. ECT combines low-dose chemotherapy with electroporation—short, high-voltage pulses that temporarily increase cell membrane permeability [4]—enhancing drug uptake and boosting the cytotoxicity of agents like bleomycin up to 100-fold [5]. Clinically, ECT improves local control, reduces pain and bleeding, and enhances patient quality of life [6]. Material In Vitro Bleomycin Electrotransfer: CHO (non-cancerous) and 4T1 (murine breast cancer) cell lines were cultured in RPMI medium supplemented with 10% fetal bovine serum. Cells were harvested, resuspended in low-conductivity buffer, and exposed to a single square-wave electric pulse (100 µs) at varying field strengths (1000–1800 V/cm) in the presence of bleomycin at concentrations ranging from 0 to 20 nM. Post-treatment viability was determined using colony formation assays, quantified via ImageJ software [7] . In Vivo Electrochemotherapy: BALB/c mice (8–12 weeks old) were injected subcutaneously with 4T1 cells to induce tumor growth. Once tumors reached measurable size, mice received intravenous bleomycin (470 µM), followed by eight pulses of electroporation (1500 V/cm, 100 µs, 1 Hz) 10 minutes later. Tumor volumes were monitored daily for 11 days using caliper measurements, and response to therapy was assessed. Clinical Case Report: A 68-year-old male diagnosed with amelanotic melanoma in late 2021 experienced disease progression despite multiple systemic treatments, including pembrolizumab, chemotherapy (dacarbazine, carboplatin/paclitaxel), interferon, and others. By April 2024, the patient presented with painful, bleeding cutaneous and nodal metastases in the right groin and leg. ECT was performed using intravenous bleomycin (15 mg/m²) and electric pulses under general anesthesia, aiming for symptomatic relief. Results In Vitro Findings: CHO cells displayed significant sensitivity to bleomycin electrotransfer, with ~80% reduction in viability at 1000 V/cm. In contrast, 4T1 cells were more resistant, requiring stronger electric fields and higher bleomycin concentrations to achieve comparable cytotoxicity. At 20 nM bleomycin and 1400 V/cm, 4T1 viability dropped to 6.5%. These findings indicate that drug resistance, rather than membrane permeability, was the primary determinant of response in 4T1 cells. In Vivo Efficacy: Tumor regression in treated mice began on day 2 post-treatment and reached statistical significance by day 4. By day 11, 43% of tumors had completely regressed, and the remaining tumors exhibited partial response. No adverse effects were observed, demonstrating the safety and effectiveness of the therapy. Clinical Outcome: At 3 weeks post-ECT, partial regression of skin metastases and reduced bleeding were observed. By 7 weeks, lesions had significantly healed with granulation tissue formation. The patient reported decreased pain, better mobility, and no systemic side effects, confirming ECT as a tolerable and beneficial intervention. Conclusions and Recommendations The results of this study demonstrate that bleomycin electrotransfer is an efficient means of inducing cancer cell death in both in vitro and in vivo models. CHO and 4T1 cells responded differently to treatment, largely due to intrinsic sensitivity to bleomycin. This underlines the importance of optimizing drug concentration and electroporation parameters for each tumor type. In mice, ECT significantly reduced tumor volume and induced complete remission in nearly half of treated animals. Clinically, ECT provided meaningful symptom relief and local disease control for a heavily pre-treated patient with metastatic melanoma. These findings collectively support the potential of ECT as a complementary or palliative option in the oncology setting. Electrochemotherapy with bleomycin demonstrates high effectiveness across experimental and clinical settings. It provides a viable, well-tolerated palliative treatment for patients with cutaneous metastatic melanoma who have exhausted conventional therapies. Its ability to deliver local tumor control and symptom relief makes it a valuable addition to the current therapeutic arsenal.

Ionizing radiation (IR) and chemotherapy, often employing cisplatin (CIS), are widely used cancer treatment modalities. However, despite their effectiveness, these treatments often cause undesirable side effects due to high drug doses and systemic administration. This study aimed to evaluate the combined effects of IR, CIS, and electroporation (EP) on the viability of Chinese hamster ovary (CHO) cells in vitro. The goal was to determine if combination therapy, utilizing EP for CIS delivery into cells, could reduce the required CIS concentration and thus mitigate side effects while maintaining effective anti-cancer activity. Initially, the efficacy of individual treatments was assessed. Statistically significant CHO cell death was observed starting at an IR dose of 3 Gy, reducing viability to 80%. Increasing the dose to 10 Gy decreased cell viability to 1%. EP was effective from a field strength of 3500 V/cm, reducing viability to 87%, with a maximum field of 4000 V/cm resulting in 58% viability. CIS, without EP, significantly reduced cell viability only at higher concentrations – from 50 µg/ml (85% viability) and 100 µg/ml (76% viability). Subsequent experiments analyzed the effects of combined treatments. The combination of IR and EP did not produce a synergistic effect, with cell death primarily dependent on the IR dose. In contrast, the combination of CIS and EP demonstrated a pronounced synergistic effect. At low CIS concentrations (5 µg/ml) and an EP field of 1500-2500 V/cm, cell viability decreased to ~30%, and at 3000-4000 V/cm to <10%. The combined effect of IR and CIS also resulted in synergistic cell death, particularly at an IR dose of 3 Gy and a CIS concentration of >1 µg/ml, where viability decreased to <10%. Finally, the combination of all three modalities – IR, EP, and CIS – exhibited the most pronounced synergistic effect. Even at low doses of IR (1 Gy), EP (1000 V/cm), and CIS (10 µg/ml), cell viability decreased to 37%, compared to >92% with individual treatments. Increasing the CIS concentration further enhanced cell death. In conclusion, the results of this study demonstrate that combined IR, EP, and CIS therapy exhibits significant anti-cancer potential, allowing for a reduction in CIS concentration and potentially minimizing side effects.

Health networking is in principle a formidable instrument to address many challenges posed by cancer, one of the two most common and most lethal non-communicable chronic diseases. The European Union (EU)'s Beating Cancer Plan foresaw the addition of new health networks to the four already existing European Reference Networks on rare cancers: the Network of Comprehensive Cancer Centres and several networks of expertise (NoEs), which will be shortly deployed on items as complex and poor-prognosis cancers, palliative care, survivorship, personalised primary and secondary prevention, omic technologies, hi-tech medical resources, and cancers in adolescents and young adults. The community of experts of the EU Joint Action, due to build such NoEs, has drafted this 'green paper', incorporating 13 open questions, in an effort to foster discussion on some open questions about health networking on cancer in the EU. These affect highly diverse issues such as the following: how gaps in research into the instrument of health networking may be filled; which items lend themselves more to health networking in the EU; what degree of cooperation and harmonisation should be required of EU member states to best exploit health networking and give rise to European networks of national/regional networks; how the idea of subsidiarity may be best interpreted to support health networking in the context of EU treaties, which basically do not include health; how health networks should be funded and with what degree of cooperation between the EU and national levels; whether EU health networks should be shaped as legal entities or could give rise to secondary legal entities, also with a view to fundraising; how health networks should be best shaped to advance cancer research and how the EU regulatory system should be updated to exploit such impulse to health networks, in view of the EU General Data Protection Regulation and the new EU Health Data Space; how artificial intelligence can be exploited today within health networks and to what extent it will be able to overcome challenges such as the current lack of interoperability of electronic health records and the language barrier across the EU; and how health networks should involve patients and their groups, with regard to their formal role within EU health networks as well as their ability to have a say in items such as production of clinical practice guidelines, the design of investigator-driven clinical trials, EU regulatory decisions on medicines and devices, health service data governance, and identification of unmet needs.

Gimdos kaklelio vėžys yra plačiai paplitusi sveikatos problema. Nepaisant profilaktikos ir gydymo pažangos, jis ir toliau išlieka viena pagrindinių su vėžiu susijusio sergamumo ir mirtingumo priežasčių tarp moterų. Gimdos kaklelio vėžio patogenezė yra sudėtinga ir daugiaveiksnė, apimanti tiek aplinkos, tiek genetinius veiksnius. Nors pagrindinis etiologinis veiksnys yra didelės rizikos ŽPV infekcija, genetiniai variantai taip pat daro įtaką ligos eigai ir atsakui į gydymą. Tyrimo tikslias: įvertinti TLR4, RRP1B, SIPA1, SRSF1, HOTAIR ir MALAT1 germinacinių polimorfizmų reikšmę gimdos kaklelio vėžio prognozei. Tyrimo uždaviniai: nustatyti imuninio atsako moduliatoriaus TLR4 geno polimorfizmus ir įvertinti jų sąsajas su gimdos kaklelio vėžio progresavimu bei prognose; įvertinti metastazavimo procese dalyvaujančių RRP1B, SIPA1 ir SRSF1 genų variantų sąsajas su gimdos kaklelio vėžio eiga; analizuoti epigenetinių modifikatorių HOTAIR ir MALAT1 genų variantus ir ištirti jų ryšį su gimdos kaklelio vėžio progresavimu. Tyrimu siekta nustatyti naujus rizikos stratifikacijos biologi¬nius žymenis ir prisidėti prie tiksliosios medicinos metodų gimdos kaklelio vėžiui suvaldyti. Tyrimas suteikia naujų įžvalgų apie genetinius mechanizmus, lemiančius gimdos kaklelio vėžį, ir sudaro pagrindą būsimoms tikslinės medicinos priemonėms, kurios galėtų pagerinti profilaktiką, ankstyvą diagnozę ir individualizuotą gydymą gimdos kaklelio vėžio pacientėms. Išvados: nustatytas ryšys tarp TLR4 polimorfizmų ir gimdos kaklelio vėžio klinikinių patologinių ypatybių bei išgyve¬namumo: rs11536898 buvo susijęs su vėžio metasta¬zavimo rizika bei bendruo¬ju išgyvenamumu ir laiku be ligos progresavimo, o rs10759932 turėjo reikšmingos įtakos laikui be ligos progresavimo ir bendrajam išgyvenamu¬mui; RRP1B rs2838342 ir rs7276633 buvo susiję su naviko dydžiu, SIPA1 rs746429 – su naviko diferenciacija, o SRSF1 rs34592492 – su išgyvenamumo rodikliais; HOTAIR ir MALAT1 genų polimorfizmai nebuvo reikšmingi gimdos kaklelio vėžio fenotipui ir išgyvenamumui.

Background and Objectives: Seminoma is the most common solid malignant tumour in young men. Clear-cell kidney carcinoma is the most common malignancy of the genitourinary tract. However, the synchronous occurrence of both of these tumours is rare. Case presentation: We present the case of a 36-year-old patient who presented to a medical facility at the end of 2019 with an enlarged right testicle. A unilateral orchofuniculectomy was performed, and a mass measuring 30 cm was removed. During histological examination, testicular seminoma pT2, R0, was diagnosed. An abdominal computed tomography (CT) scan showed a 6.4 cm × 6.8 cm × 6.7 cm tumour in the right kidney and a metastatic-like lesion in the right adrenal gland. A right nephrectomy and an adrenalectomy and paraaortic and paracaval lymphadenectomies were performed. A histological evaluation confirmed the presence of clear-cell renal carcinoma pT2aR0 G2, adrenal hyperplasia, and seminoma metastases in the removed lymph node. Chemotherapy with a Bleomycin, Etoposide, and Cisplatin (BEP) regimen was carried out. Three years after the last cycle of chemotherapy, a follow-up CT scan showed metastases in the left kidney, the right ischium, and the right lung. A well-differentiated clear-cell carcinoma G1 of the left kidney and metastasis of clear-cell carcinoma G2 in the right ischium were confirmed after the biopsy, and no tumour lesions were found in the lung tissue specimen. Treatment with targeted therapy with Sunitinib was started because the risk was favourable according to the Heng criteria. Genetic testing was performed, and the following genes were analysed: VHL, BAP1, CHEK2, FH, MET, MUTYH, APC, and STK11. The testing did not reveal any pathogenic or potentially pathogenic mutations or sequence changes of unknown clinical significance in the genes analysed. Conclusions: According to the authors, the occurrence of synchronous primary tumours is linked to one’s genetic predisposition. DNA sequencing of tumour tissue could provide more information on the corresponding aetiopathogenesis.

Background Standard therapy for locally advanced rectal cancer includes concurrent chemoradiotherapy (CRT) followed by surgery and adjuvant chemotherapy. An alternative strategy - neoadjuvant intensified chemotherapy (NIC) involves administration of neoadjuvant chemotherapy (FOLFOX4) before surgery plus concomitant chemoradiation (in those only who did not achieve MRF (neg.)) with the goal of delivering optimized systemic therapy to eradicate micrometastases. A comparison of these 2 approaches was the aim of study. Methods This is a prospective single institution clinical trial. The study included patients with locally advanced stage II-III rectal cancer. Patients were randomized 1:1 for neoadjuvant concomitant CRT or NIC (FOLFOX4 regimen, a total of 8 cycles). Results 142 patients (pts.) were included into the study. The median follow-up is 24 months. Both groups are well balanced. At baseline, MRF was involved in 40/65 pts. (62%) in the NIC arm and in 49/77 pts. (64%) in CRT arm (p=0.862). Radiologically, MRF remained involved after initial treatment in 17/40 pts (42.5%) NIC group and 22/49 pts. (44.9%) in the CRT group. Surgery was not performed in 11/65 pts. (16,9%) from NIC arm due to disease progression or early deaths during neoadjuvant treatment. In the CRT arm surgery was not performed in 15/77 pts. (19,5%). After surgery, circumferential resection margin (CRM) was involved in 2/44 pts. (5%) in NIC and in 1/55 pts. (2%). pCR was achieved in 3/44 pts (7%) NIC group and in 9/55 pts. (16%) CRT group (not sig). After treatment in NIC arm, a reduction in the tumor stage (evaluated by radiologist) was observed in 13/50 (26%) pts, and in pathologist’s report – in 27/44 pts (61%). In CRT arm, radiological downstaging was achieved in 28/69 pts. (41%) and pathologically in 39/55 (71%) ((not sig).). Three-year DFS was 86,4% and 92,7% in NIC and CRT groups, respectively (p = 0.6). Three-year overall survival (OS) did not differ statistically significantly between groups. Conclusions The preliminary findings of this ongoing prospective clinical trial did not show statistically significant difference in 3 year DFS and OS between neoadjuvant intensified chemotherapy and neoadjuvant concomitant chemoradiation arms but numerically chemoradiation arm was more benefitial.

Background and Objective Diagnostics and treatment of rectal cancer has changed dramatically over the past 20 years. Detailed radiological examination using MRI, surgical and radiotherapy innovations, neoadjuvant and adjuvant therapy have been implemented into the practice. Multidisciplinary team discussions on regular basis has started in the Hospital since 2013. Indeed, the wide application of screening programs is essential for early diagnosis of the disease – the pilot colorectal cancer screening in Kaunas region has started from 2009 and wide screening program was implemented in all the country since 2013. These innovations affect patients' life expectancy and quality. This is a retrospective analysis covering 20 years of single-institution clinical experience in the diagnostics and treatment of local rectal cancer. Material and Method Data on 924 patients which were treated for local (stage I-III) rectal cancer from 2004 till 2024 were retrospectively collected at the Hospital of Lithuanian University of Health Sciences (LUHS) Kauno klinikos. The period was divided into two decades (A, from 2004 till 2013, and B, from 2014 till March of 2024) to assess treatment progress. The groups were compared in terms of clinical characteristics and applied treatment. [...].