1. Immune infiltration, effector T-cell enrichment, and functional context for prediction of pathologic complete response to neoadjuvant chemotherapy in breast cancerAna Demšar, Klara Geršak, Barbara Gazić, Tanja Blagus, Katja Goričar, Gregor Jezernik, Vita Dolžan, Cvetka Grašič-Kuhar, 2026, izvirni znanstveni članek Povzetek: Tumor-infiltrating lymphocytes (TILs) are an established predictor of pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) in breast cancer. However, TILs primarily reflect the extent of immune infiltration and provide limited insight into immune functional state. We investigated whether integrating measures of immune infiltration (TILs), effector T-cell presence (CD8), and functional context (immune checkpoint components) may improve prediction of pCR beyond TILs alone. Pretreatment tumor biopsies from 166 patients with early breast cancer treated with standard NACT were assessed for stromal TILs and mRNA expression of CD8, PD-1, LAG-3, and TIM-3. Associations with pCR were evaluated using univariate and multivariable logistic regression, and composite immune phenotypes were constructed to capture functional immune states. In univariate analyses, higher TILs, CD8, PD-1, and LAG-3 were associated with pCR (all p < 0.05), whereas TIM-3 was not (p = 0.801). In multivariable models, TILs remained independently associated with pCR when adjusted for checkpoint markers, but this association was attenuated when CD8 was included, consistent with the strong biological correlation between TILs and CD8, and neither CD8 nor checkpoint markers retained independent significance. PD-1 and LAG-3 expression strongly correlated with CD8 and moderately correlated with TILs, indicating that checkpoint expression predominantly reflects an immune effector-engaged tumor microenvironment. Composite immune phenotypes based on CD8/PD-1 co-expression identified distinct immune functional states, with CD8-high/PD-1-high tumors demonstrating the highest pCR rates. Hierarchical modeling showed modest improvements in discrimination with sequential addition of immune variables to clinical predictors, with the integrative CD8/PD-1 model achieving the highest discrimination within the cohort (AUC = 0.849), although the magnitude of improvement beyond TIL assessment alone was limited. In conclusion, immune infiltration, effector T-cell presence, and functional immune context represent complementary dimensions for pCR prediction following NACT in breast cancer. However, TILs remain the most robust and clinically feasible immune biomarker.
Ključne besede: PD-1 immune checkpoint, breast cancer, immune microenvironment, neoadjuvant chemotherapy
Objavljeno v DiRROS: 20.04.2026; Ogledov: 354; Prenosov: 260
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2. Integrating chronic inflammation and hypoxia : the potential role of HIF-1α in tumor behavior and therapy response in high-grade serous ovarian cancerSara Polajžer, David Lukanović, Erik Škof, Borut Kobal, Katarina Černe, 2026, izvirni znanstveni članek Povzetek: High-grade serous ovarian carcinoma (HGSOC) is marked by late diagnosis and chemoresistance, partly driven by chronic inflammation and hypoxia in the tumor microenvironment. Hypoxia-inducible factor 1-alpha (HIF-1a) is a key regulator of these processes; however, its spatial distribution, interaction with inflammation, and effect on chemotherapy response in HGSOC remain unclear. This retrospective study included 28 advanced HGSOC patients treated with neoadjuvant chemotherapy (NACT). Samples were collected at primary surgery (PS) (ovarian and peritoneal tissue, plasma, ascites) and post-NACT at interval debulking surgery (IDS) (omentum, peritoneal tissue, plasma). HIF-1a mRNA expression varied by site, with higher levels in omental and peritoneal tissues compared to ovarian tissue. Plasma and ascites concentrations were significantly correlated, although the mean ascites concentration was lower. Elevated HIF-1a concentration in ascites and plasma at baseline correlated with ESR (erythrocyte sedimentation rate) >30 mm/h, which was also correlated with BRCA mutation status. No correlation was found between HIF-1a and CRP (C-reactive protein) levels. Higher HIF-1a concentrations in ascites and plasma were linked to poor chemotherapy response (CRS1) at IDS. No significant changes in plasma HIF-1a, ESR, or peritoneal HIF-1a mRNA expression were observed before and after chemotherapy. Increased peritoneal HIF-1a at baseline showed a trend toward shorter progression-free survival. These findings suggest that HIF-1a may reflect hypoxia-inflammation crosstalk associated with chemoresistance and progression in HGSOC. The hypoxic-inflammatory microenvironment appears to persist despite chemotherapy and could contribute to ongoing disease activity. However, these observations require validation in independent cohorts before any prognostic or predictive implications can be considered.
Ključne besede: body fluids, chronic inflammation, HIF-1a, high-grade serous ovarian carcinoma, neoadjuvant chemotherapy, tumor tissue
Objavljeno v DiRROS: 26.03.2026; Ogledov: 319; Prenosov: 228
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3. Preoperative serum CA-125 level as a predictor for the extent of cytoreduction in patients with advanced stage epithelial ovarian cancerSebastjan Merlo, Nikola Bešić, Eva Drmota, Nina Kovačević, 2021, izvirni znanstveni članek Povzetek: Background. Ovarian cancer is the seventh most common cancer in women worldwide and the eighth most common cause of cancer death. Due to the lack of effective early detection strategies and the unspecific onset of symptoms, it is diagnosed at an advanced stage in 75% of cases. The cancer antigen (CA) 125 is used as a prognostic marker and its level is elevated in more than 85% of women with advanced stages of epithelial ovarian cancer (EOC). The standard treatment is primary debulking surgery (PDS) followed by adjuvant chemotherapy (ACT), but the later approach is neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS). Several studies have been conducted to find out whether preoperative CA-125 serum levels influence treatment choice, surgical resection and survival outcome. The aim of our study was to analyse experience of single institution as Cancer comprehensive center with preoperative usefulness of CA-125. Patients and methods. At the Institute of Oncology Ljubljana a retrospective analysis of 253 women with stage FIGO IIIC and IV ovarian cancer was conducted. Women were divided into two groups based on their primary treatment. The first group was the NACT group (215 women) and the second the PDS group (38 women). The differences in patient characteristics were compared using the Chi-square test and ANOVA and the Kaplan-Meier method was used for calculating progression-free survival (PFS) and overall survival (OS). Results. The median serum CA-125 level was higher in the NACT group than in the PDS group, 972 IU/ml and 499 IU/ ml, respectively. The PFS in the NACT group was 8 months (95% CI 6.4%9.5) and 18 months (95% CI 12.5%23.4) in the PDS group. The median OS was lower in the NACT group than in the PDS group, 25 months (95% CI 20.6%29.5) and 46 months (95% CI 32.9%62.1), respectively. Conclusions. Preoperative CA-125 cut off value of 500 IU/ml is a promising threshold to predict a successful PDS.
Ključne besede: ovarian cancer, tumour marker, neoadjuvant chemotherapy, CA-125
Objavljeno v DiRROS: 22.07.2024; Ogledov: 1350; Prenosov: 450
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4. Induction chemotherapy, chemoradiotherapy and consolidation chemotherapy in preoperative treatment of rectal cancer : long-term results of phase II OIGIT-01 TrialDanijela Golo, Jasna But-Hadžić, Franc Anderluh, Erik Brecelj, Ibrahim Edhemović, Ana Jeromen, Mirko Omejc, Irena Oblak, Ajra Šečerov Ermenc, Vaneja Velenik, 2018, izvirni znanstveni članek Povzetek: The purpose of the study was to improve treatment efficacy for locally advanced rectal cancer (LARC) by shifting half of adjuvant chemotherapy preoperatively to one induction and two consolidation cycles. Patients and methods Between October 2011 and April 2013, 66 patients with LARC were treated with one induction chemotherapy cycle followed by chemoradiotherapy (CRT), two consolidation cycles, surgery and three adjuvant capecitabine cycles. Radiation doses were 50.4 Gy for T2-3 and 54 Gy for T4 tumours in 1.8 Gy daily fraction. The doses of concomitant and neo/adjuvant capecitabine were 825 mg/m2/12h and 1250mg/m2/12h, respectively. The primary endpoint was pathologic complete response (pCR). Results Forty-three (65.1%) patients were treated according to protocol. The compliance rates for induction, consolidation, and adjuvant chemotherapy were 98.5%, 93.8% and 87.3%, respectively. CRT was completed by 65/66 patients, with G % 3 non-hematologic toxicity at 13.6%. The rate of pCR (17.5%) was not increased, but N and the total-down staging rates were 77.7% and 79.3%, respectively. In a median follow-up of 55 months, we recorded one local relapse (LR) (1.6%). The 5-year disease-free survival (DFS) and overall survival (OS) rates were 64.0% (95% CI 63.89%64.11) and 69.5% (95% CI 69.39%69.61), respectively. Conclusions In LARC preoperative treatment intensification with capecitabine before and after radiotherapy is well tolerated, with a high compliance rate and acceptable toxicity. Though it does not improve the local effect, it achieves a high LR rate, DFS, and OS.
Ključne besede: rectal cancer, neoadjuvant chemotherapy, preoperative chemoradiotherapy
Objavljeno v DiRROS: 11.06.2024; Ogledov: 1617; Prenosov: 1009
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5. The role of neoadjuvant chemotherapy in patients with advanced (stage IIIC) epithelial ovarian cancerErik Škof, Sebastjan Merlo, Gašper Pilko, Borut Kobal, 2016, izvirni znanstveni članek Povzetek: Primary treatment of patients with advanced epithelial ovarian cancer consists of chemotherapy either before (neoadjuvant chemotherapy, NACT) or after primary surgery (adjuvant chemotherapy). The goal of primary treatment is no residual disease after surgery (R0 resection) what is associated with an improvement in survival of patients. There is, however, no evidence of survival benefits in patients with R0 resections after prior NACT. Methods. We retrospectively reviewed the records of patients who were treated with diagnosis of epithelial ovarian cancer at Institute of Oncology Ljubljana in the years 2005%2007. The differences in the rates of R0 resections, progression free survival (PFS), overall survival (OS) and in five-year and eight-year survival rates between patients treated with NACT and patients who had primary surgery were compared. Results. Overall 160 patients had stage IIIC epithelial ovarian cancer. Eighty patients had NACT and eighty patients had primary surgery. Patients in NACT group had higher rates of R0 resection (42% vs. 20%; p = 0.011) than patients after primary surgery. PFS was 14.1 months in NACT group and 17.7 months after primary surgery (p = 0.213). OS was 24.8 months in NACT group and 31.6 months after primary surgery (p = 0.012). In patients with R0 resections five-year and eight-year survival rates were 20.6% and 17.6% in NACT group compared to 62.5% and 62.5% after primary surgery (p < 0.0001), respectively. Conclusions. Despite higher rates of R0 resections achieved by NACT, survival of patients treated with NACT was inferior to survival of patients who underwent primary surgery. NACT should only be offered to patients with advanced epithelial cancer who are not candidates for primary surgery.
Ključne besede: ovarian cancer, advanced ovarian cancer, neoadjuvant chemotherapy, primary surgery
Objavljeno v DiRROS: 30.04.2024; Ogledov: 2024; Prenosov: 629
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6. Preoperative treatment with radiochemotherapy for locally advanced gastroesophageal junction cancer and unresectable locally advanced gastric cancerIvica Ratoša, Irena Oblak, Franc Anderluh, Vaneja Velenik, Jasna But-Hadžić, Ajra Šečerov Ermenc, Ana Jeromen, 2015, izvirni znanstveni članek Povzetek: To purpose of the study was to analyze the results of preoperative radiochemotherapy in patients with unresectable gastric or locoregionally advanced gastroesophageal junction (GEJ) cancer treated at a single institution. Between 1/2004 and 6/2012, 90 patients with locoregionally advanced GEJ or unresectable gastric cancer were treated with preoperative radiochemotherapy at the Institute of Oncology Ljubljana. Planned treatment schedule consisted of induction chemotherapy with 5-fluorouracil and cisplatin, followed by concomitant radiochemotherapy four weeks later. Three-dimensional conformal external beam radiotherapy was delivered by dual energy (6 and 15 MV) linear accelerator in 25 daily fractions of 1.8 Gy in 5 weeks with two additional cycles of chemotherapy repeated every 28 days. Surgery was performed 4-6 weeks after completing radiochemotherapy. Following the surgery, multidisciplinary advisory team reassessed patients for the need of adjuvant chemotherapy. The primary endpoints were histopathological R0 resection rate and pathological response rate. The secondary endpoints were toxicity of preoperative radiochemotherapy and survival. Treatment with preoperative radiochemotherapy was completed according to the protocol in 84 of 90 patients (93.3%). Twenty patients (22.2%) did not undergo the surgery because of the disease progression, serious comorbidity, poor performance status or still unresectable tumour. In 13 patients (14.4%) only exploration was performed because the tumour was assessed as unresectable or diffuse peritoneal carcinomatosis was established. Fifty-seven patients (63.4%) underwent surgery with the aim of complete removal of the tumour. Radical resection was achieved in 50 (55.6%) patients and the remaining seven (7.8%) patients underwent non-radical surgery (R1 in five and R2 in two patients). In this group of patients (n = 57), pathological complete response of tumour was achieved in five patients (5.6% of all treated patients or 8.8% of all operated patients). Down-staging was recorded in 49 patients (86%), in one patient (1.8%) the stage after radiochemotherapy was unchanged while in seven patients (12.3%) the pathological stage was higher than clinical, mainly due to higher pN stage. No death was recorded during preoperative radiochemotherapy. Most grade 3 and 4 toxicities were due to vomiting, nausea and bone marrow suppression (granulocytopenia). Twentysix (45.6%) patients died due to GEJ or gastric carcinoma, one died because of septic shock following the surgery and a reason for two deaths was unknown. Twenty-eight patients (49.1%) were disease free at the time of analysis, while 29 patients (50.9%) developed the recurrence, mostly as distant metastases. At two years, locoregional control, diseasefree survival, disease-specific survival and overall survival were 82.9%, 43.9%, 56.9% and 53.9%, respectively. Preoperative radiochemotherapy was feasible in our group of patients and had acceptable toxicity. Majority of patients achieved down-staging, allowing greater proportion of radical resections (R0), which are essential for patientsʼ cure.
Ključne besede: neoadjuvant radiochemotherapy, perioperative chemotherapy, chemotherapy, adenocarcinoma, carcinoma, surgery
Objavljeno v DiRROS: 23.04.2024; Ogledov: 1705; Prenosov: 532
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7. Neoadjuvant chemotherapy in 13 patients with locally advanced poorly differentiated thyroid carcinoma based on Turin proposal : a single institution experienceNikola Bešić, Marta Dremelj, Andreja A. Schwarzbartl-Pevec, Barbara Gazić, 2015, izvirni znanstveni članek Povzetek: There is a paradigm that chemotherapy is ineffective in thyroid carcinoma. The aim of our study was to find out whether neoadjuvant chemotherapy before thyroid surgery had an effect on the size of primary tumour in patients with poorly differentiated thyroid carcinoma (PDTC) based on Turin proposal. Patients and methods. Altogether, 13 patients (8 women, 5 men; median age 61 years) with PDTC based on Turin proposal were treated with neoadjuvant chemotherapy between 1986 and 2005. Tumour diameter was from 4.5 to 18 cm (median 9 cm). Regional and distant metastases were detected in 6 and 9 patients, respectively. Eight patients had pT4 tumour. Results. Altogether, 29 (range 1%5) cycles of chemotherapy were given. Tumour diameter decreased in all the patients and by more than 30% in 5 patients (= 38%). Two of these five patients had also preoperative external beam irradiation (EBRT). Total thyroidectomy, lobectomy and neck dissection were performed in 10, 3 and 5 cases, respectively. R0 and R1 resection was done in 5 and 8 cases, respectively. Eight patients had postoperative EBRT of the neck and upper mediastinum. The 5-year and 10-year cause-specific survival rates of patients were 66% and 20%, respectively. Conclusions. After neoadjuvant chemotherapy a partial tumour regression was observed in 38% of patients with PDTC based on Turin proposal.
Ključne besede: poorly differentiated thyroid carcinoma, neoadjuvant, chemotherapy, survival
Objavljeno v DiRROS: 22.04.2024; Ogledov: 1708; Prenosov: 777
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