Kupčinskaitė, Rita

Introduction: Pancreatic ductal adenocarcinoma (PDAC) remains a challenge in oncology with an overall survival rate remaining about 10%. Sur -gery and adjuvant chemotherapy stands as only curative treatment options. Only a minority of patients are diagnosed with resectable disease.While traditional diagnostic modalities show limitations in detecting and monitoring pancreatic cancer, liquid biopsies is a relatively new, non-invasive and promising diagnostic method for early detection, molecular profiling, and observation.Despite previous published or ongoing research projects and studies, liquid biopsies and specifically cell-free DNA (cfDNA) alterations role in management of pancreatic cancer remains unverified.Aims & Methods: The aim of our study was to evaluate the diagnostic value of liquid biopsies and alterations in cfDNA levels in patients with pancreatic cancer. This study was approved by the Kaunas Regional Bio-ethics Committee (Approval ID: BE-2-31). Patients with newly diagnosed and histologically confirmed pancreatic cancer and patients with chronic pancreatitis, admitted to the Department of Surgery at Lithuanian University of Health Sciences Hospital, Kaunas Clinics, between September 2022 and December 2023, and healthy volunteers (control group) were includ-ed. Blood samples were obtained from the patients before any treatment procedures commenced. cfDNA was extracted from the collected blood using the QI Amp Circulating Nucleic Acid Kit (Qiagen).The concentration and quality of the extracted cfDNA were determined using the Qubit™ 1X dsDNA High Sensitivity (HS) and Broad Range (BR) Assay Kits (ThermoFisher Scientific, Inc., Waltham, MA, USA). Mann-Whitney U-test and Kruskal-Wallis H-test were used to determine the differences in quantitative traits between the comparison groups, with results being presented in median (min – max). The predictive capability (diagnostic performance) of cfDNA to distinguish PDAC and chronic pancreatitis/healthy controls was investigated by means of the area under the ROC(Receiver-Operating Characteristics) curve (AUC). Results: Sixty-five patients were included (47 patients with PDAC, 10 patients with chronic pancreatitis and 8 healthy controls). Levels of cfDNA were statistically significantly higher in PDAC patients (46.5 (4 - 768) ng/ml) compared to patients with chronic pancreatitis (23.4 (8.56 - 138.4) ng/ml) (p = 0.032) and healthy controls (19.75 (17.6 - 22.8) ng/ml) (p < 0.001).The cfDNA cut-off value distinguishing PDAC from chronic pancreatitis and healthy controls were determined to be 23,65 ng/ml (AUC = 0.716)and 22.9 ng/ml (AUC = 0.915), respectively. There were no differences in cfDNA levels concerning tumor localization, size, differentiation, spread,or survival rates (all p > 0.05).Conclusion: Liquid biopsies and cfDNA level alterations offer promising opportunities for distinguishing pancreatic cancer from benign inflammatory diseases, such as chronic pancreatitis. However, additional experiments and studies are necessary for more comprehensive validation and clinical use.

Background & objectives: PD-L1 is tested as predictive marker optimizing immunotherapy strategy in advanced oncologic cases. PD-L1 combined positive scoring (CPS) in correlation with gastric carcinoma patient survival remains unclear. Aim is to optimize PD-L1 CPS application in stomach carcinoma excised before HIPEC. Methods: Immunohistochemical reactions against PD-L1 (clone 22C3) were performed for 15 selected gastric carcinoma cases excised before HIPEC, scanning them with „Pannoramic Viewer (3D Histech)“. CPS was calculated from digital morphometric data (fve annotated 304 558 μm2 microscopic felds per sample) in digital microimaging software. Disease free, overall, and long-term survival were evaluated. Mann-Whitney, Kruskal-Wallis’s tests, Kaplan-Meier method were applied (p<0.05). Results: PD-L1 CPS median of 3.05 (interquartile range-12.40) was calculated in gastric carcinoma excised before HIPEC procedure. PD-L1 CPS was signifcantly lower in gastric carcinoma of difuse type vs mixed/intestinal type according to Lauren classifcation (median-1.09, interquartile range-4.60 vs median-12.40, interquartile range-17.17, correspondingly; U=44.00, p=0.019). Medians of PD-L1 CPS were similar among diferent clinical stages of gastric carcinoma (H=3.63, p=0.163). Patients with higher than median CPS score and higher then median number of PD-L1+ immune cells had a longer disease free (10 vs 22 months, p<0.05) and overall survival (17 vs 26 months, p<0.05). There was no diference in number of long survivors (>3 years) in diferent PD-L1 expression groups (p>0.05). Conclusion: A signifcant lower PD-L1 CPS in gastric carcinoma of difuse type according to Lauren classifcation identifed during study may contribute to revealing yet unknown PD-L1 role in microenvironmental processes of difuse gastric carcinoma. Also, patients with high PD-L1 CPS score and high number of PD-L1 positive immune cells demonstrate signifcantly longer disease free and overall survival suggesting that these parameters can be applied as an additional diagnostic marker for selecting patients to undergo prophylactic and/or curative HIPEC in gastric carcinoma.

Immunotherapy treatment with checkpoint inhibitors (ICIs) has led to a breakthrough in the treatment of oncological diseases. Despite its clinical effectiveness, this treatment differs from others, such as cytotoxic chemotherapy, in that it causes immune-related adverse events. This type of toxicity can affect any organ or organ system of the body. We present a literature review and a rare clinical case from our clinical practice, in which a patient with metastatic clear cell renal carcinoma was treated with a single dose of dual checkpoint blockade (cytotoxic T-lymphocyte-4 (CTLA-4) and programmed death-1 (PD-1)) and simultaneously diagnosed with colitis, hepatitis, and nephritis. After early immunosuppressive treatment with the glucocorticoids, complete organ function recovery was achieved. The follow-up revealed a sustained complete response lasting more than a year.

Background: Pancreatic cancer remains an aggressive and highly lethal disease, exhibiting an overall 5-year survival rate of merely 10%, among the lowest compared to other oncological conditions. The absence of early and effective diagnostic tools hampers the management of pancreatic cancer (PC) patients, leading to compromised quality of life and treatment outcomes. Liquid biopsies, a relatively novel diagnostic method, enable non-invasive sampling of tumor materials. Specific genetic information, particularly changes in circulating free DNA (cfDNA) levels, is believed to forecast poorer tumor differentiation, a more aggressive disease course, faster relapse, and potential use as an early cancer diagnostic marker or for evaluating treatment efficacy. Methods: This study was approved by the Kaunas Regional Bioethics Committee (Approval ID: BE-2-31). Patients with newly diagnosed and histologically confirmed PC, without prior treatment and patients with chronic pancreatitis (control group), admitted to the Department of Surgery at Lithuanian University of Health Sciences Hospital, Kaunas Clinics, between September 2022 and November 2023 were included in this study. Blood samples were obtained from the patients before any treatment procedures commenced. cfDNA was extracted from the collected blood using the QIAmp Circulating Nucleic Acid Kit (Qiagen). The concentration and quality of the extracted cfDNA were determined using the Qubit™ 1X dsDNA High Sensitivity (HS) and Broad Range (BR) Assay Kits (ThermoFisher Scientific, Inc., Waltham, MA, USA). Results: Throughout the study period, 55 patients were included (47 with PC and 8 with chronic pancreatitis). cfDNA levels exhibited significant elevation in PC patients compared to those with chronic pancreatitis (p = 0.037; median (minimum – maximum): 46.5 ng/ml (4 – 768) vs 21.9 ng/ml (8.56 – 138.4) accordingly). The determined cut-off value for cfDNA levels distinguishing PC from chronic pancreatitis was 23.65 ng/ml (Area Under the Curve (AUC) = 0.73, sensitivity = 0.851, specificity = 0.625. Nevertheless, no distinctions in cfDNA levels were noted concerning tumor localization, size, differentiation, spread, or survival rates. Conclusions: Liquid biopsies and alterations in cfDNA levels could aid in distinguishing pancreatic cancer from benign inflammatory diseases like chronic pancreatitis. Nonetheless, further studies and experiments are necessary for comprehensive validation.

Introduction Pancreatic cancer (PC) remains one of the leading causes of cancer related mortality with 5-year survival estimating about 10%. The absence of effective early diagnostic tools impedes patient management, leading to compromised outcomes and quality of life. Liquid biopsies, a novel diagnostic method, enable non-invasive tumor material sampling. Genetic information, especially alterations in circulating free DNA (cfDNA) levels, is believed to predict poorer tumor differentiation, aggressive disease progression and potential use as an early diagnostic marker or treatment efficacy evaluator.

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.

Genes carrying high-penetrance germline mutations may also be associated with cancer susceptibility through common low-penetrance genetic variants. To increase the knowledge on genetic pancreatic ductal adenocarcinoma (PDAC) aetiology, the common genetic variability of PDAC familial genes was analysed in this study. We conducted a multi-phase study analysing 7,745 single nucleotide polymorphisms (SNPs) from 29 genes reported to harbour a high-penetrance PDAC-associated mutation in at least one published study. To assess the effect of the SNPs on PDAC risk, a total of 14,666 PDAC cases and 221,897 controls across five different studies were analysed. The T allele of the rs1412832 polymorphism, that is situated in the CDKN2B-AS1/ANRIL, showed a genome-wide significant association with increased risk of developing PDAC (OR=1.11, 95%CI=1.07-1.15, P=5.25×10(-9) ). CDKN2B-AS1/ANRIL is a long non-coding RNA, situated in 9p21.3, and regulates many target genes, among which CDKN2A (p16) that frequently shows deleterious somatic and germline mutations and deregulation in PDAC. Our results strongly support the role of the genetic variability of the 9p21.3 region in PDAC aetiopathogenesis and highlight the importance of secondary analysis as a tool for discovering new risk loci in complex human diseases. This article is protected by copyright. All rights reserved.

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 micro metastases. A comparison of these 2 approaches was the aim of study. Objective To determine the differences in rates of pathologic complete response (pCR), mesorectal fascia (MRF) involvement, disease-free survival (2 year DFS) between patients receiving NIC vs standard CRT. Material and Method This is a prospective single institution clinical trial (ClinicalTrials.gov Identifier: NCT05378919). The study included patients with locally advanced stage II-III rectal cancer. Patients were randomized 1:1 for neoadjuvant concomitant chemoradiation or neoadjuvant intensified chemotherapy (FOLFOX4 regimen, a total of 8 cycles). 4-6 weeks after completion of treatment radiological examination was performed and the patients underwent surgery. For those from NIC arm who did not achieve MRF (neg.) additional concomitant chemoradiation was given before surgery. Results 85 patients (pts.) were included into the study and analyzed. The median follow-up of patients is 36 months (1-77 months). Both groups are well balanced: by age, sex, disease stage, MRF status. At baseline, MRF was involved in 21/42 patients (pts) (50%) in the NIC arm and in 25/43 pts (58%) in CRT arm. The pelvic MRI was performed after neoadjuvant treatment. Radiologically, MRF remained involved after initial treatment in 13/42 pts (31%) NIC group and 11/43 pts (26%) in the CRT group. Surgery was not performed in 5/42 pts. (12%) from NIC arm due to disease progression (1) or early deaths during neoadjuvant treatment (thromboembolism (2), stroke (1), covid-19 infection (1) and in 6/43 pts. (14%) in the CRT arm (1 pts. remained not resectable, 2 cases of disease progression, 3 refused surgery but one of them achieved a complete response). Additional neoadjuvant CRT was given to 7 / 42 pts. in the NIC arm. After this treatment, surgery was performed 6/7 pts. and R0 surgery was achieved. Surgery was not performed for only one pts due disease progression. [...].

1.1 Background Primary tumors of the pericardium are rare. Secondary or metastatic pericardial disease is much more common. Symptomatic pericarditis may be the first clinical manifestation of malignancy. The diagnosis is usually an incidental finding during imaging processing. Pericardiocentesis and percutaneous drainage of pericardial effusion (PE) are indicated in PE if neoplastic etiology is suspected. In this report, we describe the case of a patient presenting with nonspecific symptoms of PE and neoplastic disease. 1.2 Case presentation A 47 - year old man was admitted to the hospital with 2 years history of intermittent low - grade fever, non - productive cough, malaise, and dyspnea. Computed tomography (CT) scan was done allegedly to find the pulmonary embolism, but the CT scan disclosed multiple enlarged lymph nodes in mediastinal, intraperitoneal areas, and pericardial effusion. Pericardial effusion and neoplastic disease were diagnosed by lymph node biopsy and positron emission tomography/computed tomography (PET/CT), respectively. Treatment started with Alectinib and radiation therapy. However, after 10 months the progression of the disease was observed, so treatment changed to second-line drug Lorlatinib. In order to prevent pathological bone fractures, treatment changed to Denosumab. It resulted in the complete remission of PE. In 1 year and 6 months after diagnosis of the lung cancer was confirmed regarding the successful treatment, the patient is fully active, back to social life with no signs of dyspnea. 1.3 Conclusions The diversity of clinical manifestation (such as low - grade fever, non - productive cough, malaise, dyspnea, and PE) in such a potentially severe disease should alert the physician to prompt diagnosis and treatment of malignant process.

After radical treatment of head and neck cancer about 20–50% of patients are diagnosed with the locoregional recurrence during first two years. The main treatment for recurrent disease is salvage surgery, but in most cases, surgery is not feasible due to the high risk of complications and morbidity, and only 20% of patients are suitable for surgical salvage. Reirradiation is an effective treatment method with acceptable toxicity, but this treatment method is limited to normal tissue tolerance to a total dose. When chemotherapy is administered for recurrence, the response rate is up to 40%, so with the advancement of technical measures, after introduction of intensity‐modulated radiotherapy, fractionated stereotactic body radiation therapy, high‐dose‐rate brachytherapy, proton beam reirradiation, a reirradiation is increasingly more often used for head and neck cancer relapse treatment. In this chapter, we will discuss about reirradiation with curative intent using new different radiation techniques (intensity‐modulated radiotherapy (IMRT), stereotactic body radiation therapy (SBRT), high‐dose‐rate brachytherapy (HDR‐BRT) and proton beam reirradiation (PBRT) for previously irradiated head and neck cancer and present recommendations for retreatment of head and neck cancer relapse using reirradiation alone or with systemic chemotherapy/biologic therapy. 1. Introduction Despite the sophisticated methods of cancer diagnosis, more than 50% of cases are still diagnosed when the disease has reached III/IV stage. After radical treatment of head and neck cancer, about 20–50% of patients are diagnosed with the locoregional recurrence during first two years [1–3]. The main treatment for recurrent disease is salvage surgery, but in most cases, surgery is not feasible due to the high risk of complications and morbidity, and only 15–30% of patients are suitable for surgical salvage [4–8], and 5 [...].