Independent Positive Prognostic Factor Research Articles

Prognosis versus Actual Outcomes in Stereotactic Radiosurgery of Brain Metastases: Reliability of Common Prognostic Parameters and Indices.

This study aims to evaluate the clinical outcome of stereotactic radiosurgery as the sole treatment for brain metastases and to assess prognostic factors influencing survival. A total of 108 consecutive patients with 213 metastases were retrospectively analyzed. Treatment was determined with close-meshed MRI follow-up. Various prognostic factors were assessed, and several prognostic indices were compared regarding their reliability to estimate overall survival. Median overall survival was 15 months; one-year overall survival was 50.5%. Both one- and two-year local controls were 90.9%. The rate of new metastases after SRS was 49.1%. Multivariate analysis of prognostic factors revealed that the presence of extracranial metastases, male sex, lower KPI, and progressive extracranial disease were significant risk factors for decreased survival. Of all evaluated prognostic indices, the Basic Score for Brain Metastases (BSBMs) showed the best correlation with overall survival. A substantial survival advantage was found for female patients after SRS when compared to male patients (18 versus 9 months, p = 0.003). SRS of brain metastasis is a safe and effective treatment option when frequent monitoring for new metastases with MRI is performed. Common prognostic scores lack reliable estimation of survival times. Female sex should be considered as an additional independent positive prognostic factor influencing survival.

Abstract 1053: The Influence of PD1 and TIM3 Expression on CD4+CD103+ and CD8+CD103+ Cells in Glioblastoma Progression

Abstract Glioblastoma (GB), IDH-wildtype, is the most common and aggressive high-grade primary malignant brain tumor with extremely poor outcome. Although the use of immune checkpoint inhibitors (ICIs) in GB has shown disappointing results, the identification of a small subgroup of responders underpins the role of the intratumoral immune contexture, in particular tumour-infiltrating lymphocytes (TILs), in determining disease outcome. This study aims to define the features of TIL subpopulations correlating with GB prognosis, and to establish in parallel the predictive roles of peripheral T cell subsets. A single cohort observational study, including patients undergoing GB resection and standard therapeutic and follow-up approaches in Neuro-Oncology, was conducted. Of the 45 patients, histologically confirmed WHO grade 4, 26 had MGMT promoter methylation (60.0%), 24 were male (53.3%) and the median age of young patients (≤63 years) vs elderly patients (>63 years) was 57 vs 71, respectively. Predictors of OS were KPS (≥70 vs <70: 14.7 vs 7.5 months, p=0.0007) and GTR (GTR vs non-GRT: 15 vs 9 months, p=0.004) whereas patients with methylated MGMT promoter had non-significant longer median OS compared to those with unmethylated promoter (14.5 vs 10.5 months). Patients were characterized for the expression of lineage, differentiation, memory, activation, and inhibition markers on intratumoral and peripheral CD4+ and CD8+ T cell subpopulations, and the correlation of an array of CD4+ and CD8+ T cell subsets with OS or PFS was evaluated by multiparametric flow cytometry and uni/multivariate analyses. Intratumoral immune infiltrate was positively associated with CD8+CD103+ tissue-resident memory T cells (Trm), and in particular with CD8+CD103+ Trm expressing PD1 and TIM3 rather than CD4+ Trm. Low CD8+CD103+PD1+ Trm resulted significantly associated with better OS and PFS (p=0.02 and 0.0031, respectively) and even higher significant was the correlation with better OS and PFS of low CD8+CD103+TIM3+ Trm (p=0.0002 and 0.0033, respectively) and CD8+CD103+PD1+TIM3+ Trm (p<0.0001, both). On multivariate analysis, low CD8+CD103+PD1+TIM3+ Trm and KPS ≥70 were confirmed to be the most predictive independent factors associated with longer OS (hazard ratios - HR [95%CI]: 0.14 [0.04 - 0.52] p˂0.001, 0.39 [0.16 - 0.96] p=0.04, respectively). Moreover, CD8+CD103+ Trm subpopulations resulted age-related predictors for GB survival. Consistent with this finding, in vitro PD1 and TIM3 blockade released the capability of intratumoral T cells to produce the effector cytokines IFN-γ and TNF-α, and the cytotoxic factor GrzB. Conversely, T cells expressing PD1 and TIM3 of peripheral blood did not show any prognostic significance. In conclusion, low frequency of Trm expressing PD1 or TIM3 or both markers defined TIL subsets as independent positive prognostic factors for patient survival. Citation Format: Lucia Gabriele, Giulia Romagnoli, Quintino Giorgio D'Alessandris, Imerio Capone, Andrea Tavilla, Irene Canini, Caterina Lapenta, Mariachiara Buccarelli, Martina Giordano, Valentina Tirelli, Massimo Sanchez, Alessandra Fragale, Stefano Giannetti, Rina Di Bonaventura, Liverana Lauretti, Mauro Biffoni, Lucia Ricci-Vitiani, Roberto Pallini. The Influence of PD1 and TIM3 Expression on CD4+CD103+ and CD8+CD103+ Cells in Glioblastoma Progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1053.

Hypofractionated stereotactic re-irradiation for progressive glioblastoma: twelve years’ experience of a single center

PurposeWe aimed to evaluate the prognostic factors and the role of stereotactic radiotherapy (SRT) as a re-irradiation technique in the management of progressive glioblastoma.MethodsThe records of 77 previously irradiated glioblastoma patients who progressed and received second course hypofractionated SRT (1–5 fractions) between 2009 and 2022 in our department were evaluated retrospectively. Statistical Package for the Social Sciences (SPSS) version 23.0 (IBM, Armonk, NY, USA) was utilized for all statistical analyses.ResultsThe median time to progression from the end of initial radiotherapy was 14 months (range, 6–68 months). The most common SRT schedule was 30 Gy (range, 18–50 Gy) in 5 fractions (range, 1–5 fractions). The median follow-up after SRT was 9 months (range, 3–80 months). One-year overall (OS) and progression-free survival (PFS) rates after SRT were 46% and 35%, respectively. Re-irradiation dose and the presence of pseudoprogression were both significant independent positive prognostic factors for both OS (p = 0.009 and p = 0.04, respectively) and PFS (p = 0.008 and p = 0.04, respectively). For PFS, progression-free interval > 14 months was also a prognostic factor (p = 0.04). The treatment was well tolerated without significant acute toxicity. During follow-up, radiation necrosis was observed in 17 patients (22%), and 14 (82%) of them were asymptomatic.ConclusionHypofractionated SRT is an effective treatment approach for patients with progressive glioblastoma. Younger patients who progressed later than 14 months, received higher SRT doses, and experienced pseudoprogression following SRT had improved survival rates.

Correlation between functional drainage and survival in malignant biliary obstruction after percutaneous biliary drainage

PurposeMalignant biliary obstruction (MBO) is common in patients with advanced malignant tumors, leading to poor prognosis and hindering antitumor therapy. The purpose of our study was to assess the survival outcomes for patients under therapy after percutaneous transhepatic biliary drainage (PTBD) and identify prognostic factors associated with survival in patients with MBO. MethodsFrom July 2010 to February 2021, 269 patients with MBO secondary to malignant tumor were divided into two groups (functional success and non-functional success). Survival time and prognostic factors were analyzed by Kaplan–Meier curves and the Cox model. ResultsThe overall median survival time after PTBD was 4.6 months (95 % IC:3.9–5.3). The 3- and 6-month survival rates were 68.0 % and 38.7 %, respectively. The median survival improved from 3.2 months to 8.4 months when the procedure achieved functional success. Multivariate analysis demonstrated that functionally successful drainage and antitumor treatment after PTBD were independent positive prognostic factors, but the total bilirubin after drainage and tumor size were independent negative predictive values. ConclusionsFunctionally successful drainage could prolong survival time in patients with malignant biliary obstruction. Palliative care after drainage can prolong patient survival and improve their quality of life.

High Infiltration of CD163-Positive Macrophages in Intratumor Compartment Predicts Poor Prognosis in Patients With Upper Urinary Tract Urothelial Carcinoma and Radical Nephroureterectomy.

To investigate the prognostic value of CD68- and CD163-positive macrophages in patients with upper urinary tract urothelial carcinoma (UTUC). This retrospective study enrolled 50 patients (34 men and 16 women) with UTUC who received radical nephroureterectomy (RNU). We evaluated the expression of CD68 and CD163 in the intratumor compartment by immunohistochemistry. The Kaplan-Meier method and Cox proportional hazards regression model were used to evaluate overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS), and bladder recurrence-free survival (BRFS). High infiltration of CD163-positive macrophages in patients with UTUC was significantly correlated with worse OS, CSS, and RFS (P < .05 for all). Multivariate analysis showed that high infiltration of CD163-positive macrophages was an independent negative prognostic factor of OS and CSS in patients with UTUC who received RNU. Lymphovascular invasion was an independent negative prognostic factor of RFS, and high infiltration of CD68-positive macrophages was an independent positive prognostic factor of BRFS. This study indicated that high infiltration of CD163-positive macrophages in the intratumor compartment might be a useful prognostic marker for survival in patients with UTUC who receive RNU. Further, high infiltration of CD68-positive macrophages in the intratumoral compartment might be a useful prognostic marker for bladder recurrence in these patients.

Treatment patterns and outcomes in older adults with castration-resistant prostate cancer: Analysis of an Australian real-world cohort

IntroductionProstate cancer (PC) is the second commonest malignancy and fifth leading cause of cancer death in men worldwide. Older men are more likely to develop PC but are underrepresented in pivotal clinical trials, leading to challenges in treatment selection in the real-world setting. We aimed to examine treatment patterns and outcomes in older Australians with metastatic castration-resistant prostate cancer (mCRPC). Materials and MethodsWe identified 753 men with mCRPC within the electronic CRPC Australian Database (ePAD). Clinical data were analysed retrospectively to assess outcomes including time to treatment failure (TTF), overall survival (OS), PSA doubling time (PSADT), PSA50 response rate, and pre-defined adverse events of special interest (AESIs). Descriptive statistics were used to report baseline characteristics, stratified by age groups (<75y, 75-85y and >85y). Groups were compared using Kruskal-Wallis and Chi-square analyses. Time-to-event analyses were performed using Kaplan-Meier methods and compared through log-rank tests. Cox proportional hazards univariate and multivariate analyses were performed to evaluate the influence of variables on OS. ResultsFifty-seven percent of men were aged <75y, 31% 75-85y, and 12% >85y. Patients ≥75y more frequently received only one line of systemic therapy (40% of <75y vs 66% 75-85y vs 68% >85y; P < 0.01). With increasing age, patients were more likely to receive androgen receptor signalling inhibitors (ARSIs) as initial therapy (42% of <75y vs 70% of 75-85y vs 84% of >85y; p < 0.01). PSA50 response rates or TTF did not significantly differ between age groups for chemotherapy or ARSIs. Patients >85y receiving enzalutamide had poorer OS but this was not an independent prognostic variable on multivariate analysis (hazard ratio [HR] 0.93(0.09–9.35); p = 0.95). PSADT >3 months was an independent positive prognostic factor for patients receiving any systemic therapy. Older patients who received docetaxel were more likely to experience AESIs (18% in <75y vs 37% 75-85y vs 33% >85y, p = 0.038) and to stop treatment as a result (21% in <75y vs 39% in 75-85y; p = 0.011). DiscussionIn our mCRPC cohort, older men received fewer lines of systemic therapy and were more likely to cease docetaxel due to adverse events. However, treatment outcomes were similar in most subgroups, highlighting the importance of individualised assessment regardless of age.

The impact of concurrent bacterial lung infection on immunotherapy in patients with non-small cell lung cancer: a retrospective cohort study.

To find out how bacterial lung infections (BLI) affect the effectiveness of therapy and the rate of pneumonia caused by pneumonia related to checkpoint inhibitors (CIP) in patients with non-small cell lung cancer (NSCLC) who are getting immunotherapy with checkpoint inhibitors (ICIs). 507 NSCLC patients who received at least two ICI treatments between June 2020 and December 2022 at the Affiliated Hospital of Kunming University of Science and Technology(AHKUST) were included in a retrospective cohort study. Based on whether there was a concurrent BLI diagnosis from high-resolution CT scans of the chest, the patients were divided into two groups: 238 in the NSCLC with BLI group (NSCLC-BLI group), and 269 in the NSCLC alone group. The collected therapeutic outcome measures included the objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and the incidence rate of CIP. We analyzed the effect of BLI on the therapeutic efficacy of ICI treatment and the incidence rate of CIP in NSCLC patients.Inclusion criteria based on NSCLC patients staged I to IV according to the 8th edition of the International Association for Lung Cancer Research (IASLC). The NSCLC-BLI group showed superior ORR to the NSCLC group when treated with ICIs. Multifactorial logistic regression and Cox analyses, adjusted for confounders, identified BLI as an independent positive prognostic factor for ORR (HR=0.482, 95%CI: 0.391-0.550; P<0.001) and PFS (HR=0.619; 95%CI: 0.551-0.771; P<0.001). No correlation between BLI and OS was found. Out of 26 cases of CIP, 12 were in the NSCLC-BLI group and 14 in the NSCLC group, with no significant difference in incidence (P=0.145). NSCLC patients with BLI receiving ICI treatment show superior ORR and PFS compared to NSCLC alone without an increased CIP risk, positioning BLI as a predictive factor for improved outcomes in NSCLC patients receiving ICIs. However, the study has limitations including its retrospective nature and lacking data on BLI bacteria types and levels, which could influence therapy outcomes.

Previous radiotherapy improves treatment responses and causes a trend toward longer time to progression among patients with immune checkpoint inhibitor-related adverse events

BackgroundImmune-related adverse events (irAEs) are frequently encountered by patients during immune checkpoint inhibitor (ICI) treatment and are associated with better treatment outcomes. The sequencing of radiotherapy (RT) and ICIs is widely used in current clinical practice, but its effect on survival has remained unclear.MethodsIn a real-world multicenter study including 521 patients who received ICI treatment for metastatic or locally advanced cancer, RT schedules and timing, irAEs, time to progression, overall survival, and treatment responses were retrospectively reviewed.ResultsPatients who received previous RT and developed irAE (RT +/AE +) had the best overall response rate (ORR 44.0%). The ORR was 40.1% in the RT −/AE + group, 26.7% in the RT −/AE − group and 18.3% in the RT + /AE − group (p < 0.001). There was a significantly longer time to progression (TTP) in the RT + /AE + group compared to the RT −/AE − and RT + /AE − groups (log rank p = 0.001 and p < 0.001, respectively), but the trend toward longer TTP in the RT + /AE + group did not reach statistical significance in pairwise comparison to that in the RT −/AE + group. Preceding RT timing and intent had no statistically significant effect on TTP. In a multivariate model, ECOG = 0 and occurrence of irAEs remained independent positive prognostic factors for TTP (HR 0.737; 95% CI 0.582–0.935; p = 0.012, and HR 0.620; 95% CI 0.499–0.769; p < 0.001, respectively).ConclusionsBetter ORR and a trend toward longer TTP were demonstrated for patients with RT preceding ICI treatment and development of irAEs, which suggests that RT may boost the therapeutic effect of immunotherapy in patients with metastatic cancers.

The Relationship of CCL5 and CCR1 Variants with Response Rate and Survival Taking into Account Thalidomide/Bortezomib Treatment in Patients with Multiple Myeloma.

(1) Background: Chemokines and chemokine receptors play an important role in tumor development. The aim of this study was to check the significance of CCL5 and CCR1 variants with response rate, survival, and the level of regulated on activation, normal T cells expressed and secreted (RANTES/CCL5) in multiple myeloma (MM) patients; (2) Methods: Genomic DNA from 101 newly diagnosed MM patients and 100 healthy blood donors were analyzed by Real-time PCR method (for CCL5 and CCR1 genotyping). In a subgroup of 70 MM patients, serum samples were collected to determine the level of RANTES; (3) Results: multivariate Cox regression showed increased risk of disease relapse or progression (HR = 4.77; p = 0.01) in MM patients with CG + CC genotypes of CCL5 rs2280788. In contrast, CT + TT genotypes of CCL5 rs2107538 were associated withdecreased risk of death (HR = 0.18; p = 0.028) and disease relapse or progression (HR = 0.26; p = 0.01). In MM patients with major genotypes of rs2280789, rs2280788, and rs2107538, higher survival rates were observed in response to treatment with thalidomide and bortezomib. Statistically significant lower RANTES levels were seen in minor genotypes and heterozygotes of CCL5 and CCR1 variants; (4) Conclusions: Major genotypes of CCL5 variants may be independent positive prognostic factors in MM.

Abstract P6-04-15: AI-based prediction of tertiary lymphoid structures and lymphocyte immune infiltration in breast carcinomas

Abstract Introduction Tertiary lymphoid structures (TLSs) and tumor-infiltrating lymphocytes (TILs) in breast carcinomas are prognostic for survival and predictive of certain therapy responses. The presence of TLSs and TILs are identified by manual pathological examination; however, this method often lacks reproducibility, limiting its use in routine clinical practice. Here, we demonstrate that morphological evaluation of whole slide images (WSIs) using an artificial intelligence (AI)-based analytic workflow comprised of convolutional neural network (CNN) deep learning models that accurately and reproducibly characterizes TILs, measured as the lymphocyte immune-infiltrated area (LIIA), and TLSs in the tumor microenvironment (TME) of breast carcinomas. Methods We collected a cohort of 445 TCGA breast cancer H&amp;E WSIs, including clinical and sequencing data, and divided this cohort into luminal invasive lobular carcinoma (ILC) (n = 192), HER2-enriched (n = 110), and basal-like (n = 143) molecular subtypes. After 55 samples were excluded due to artifacts or incomplete clinical annotation, a total of 390 samples were analyzed. A combination of CNN-based deep learning models was used to detect and classify the tumor area, TLSs present in the TME, TLS density (number of TLS per mm2 of tumor), and lymphocyte-rich regions. The LIIA was calculated as the area of the stromal and TIL components of the TME. Validation was performed by manually annotating 10 random WSIs from the dataset. Spatial model predictions of the tumor and TLSs were combined to identify TLS locations. Each model’s predictions were verified by univariate (Kaplan-Meier) and multivariate (Cox regression) survival analyses, and the log-rank test was used to calculate overall survival. Additionally, the relationship between TLSs and LIIAs with CD274 expression (PD-L1) and a high tumor mutational burden (TMB &amp;gt; 10) was analyzed. Statistical analyses included Spearman’s rank correlation and Mann-Whitney tests. Results TLS were detected in 53% (n = 207) of the samples, with a mean density of 26.02 TLS/mm2 (Q3 = 5.53 TLS/mm2). TLS density was higher in basal-like subtype samples compared to luminal and HER2-enriched subtypes. While LIIA and TMB-high samples exhibited a significant relationship (p = 0.00001), no significant association was found between TME and TLS quantities or density. PD-L1 gene expression exhibited weak to moderate correlations with predicted LIIA in basal-like (r = 0.38, p = 0.00001) and HER2-enriched subtypes (r = 0.38, p = 0.0001). The luminal subtype had no significant correlation between PD-L1 expression and predicted LIIA. As a result, LIIA and TLS were characterized as positive prognostic factors for the basal-like subtype. After adjusting for age, stage, and grade, the LIIA and TLS density were found to be significant independent positive prognostic overall survival factors for the basal-like subtype (LIIA HR: 0.02, p = 0.003; TLS-high group HR: 0.09, p = 0.002). For the HER2-enriched subtype, TLS density was also a significant predictor (HR: 0.05, p = 0.035), while LIIA was not a statistically significant prognostic factor (HR: 0.0002, p = 0.08). Associations were not observed between the TLSs and LIIA between the ILC subtypes and survival outcomes. The same result was observed for univariate analyses. Conclusion The developed analytic pipeline accurately identified the presence of LIIA and TLS on H&amp;E slides, demonstrating the potential of CNN for automated characterization of the breast cancer TME. AI-based TLS and LIIA quantification can be a robust tool for pathology processes, offering additional information to help in clinical decision-making. This approach can be used to detect features of immune morphology biomarkers in other cancer types. Citation Format: Vladimir Kushnarev, Daniil Dymov, Nadezhda Lukashevich, Lev Popyvanov, Anna Belozerova, Diana Shamsutdinova, Aida Akaeva, Yury Popov, Svetlana Khorkova, Ivan Valiev, Anastasia Zotova, Jessica H. Brown, Anna Love, Alexander Bagaev, Ekaterina Postovalova, Nathan Fowler. AI-based prediction of tertiary lymphoid structures and lymphocyte immune infiltration in breast carcinomas [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-04-15.

Prognostic Factors in Pseudomyxoma Peritonei with Emphasis on the Predictive Role of Peritoneal Cancer Index and Tumor Markers

Pseudomyxoma peritonei (PMP) is a rare peritoneal condition where mucus-secreting tumorous cells progressively produce a thick, gelatin-like substance. The prognosis of patients with PMP is determined by the degree of cellularity within the mucin (low-grade (LAMN) vs. high-grade (HAMN) histologic features) and by the extent of the disease. Prognostic relevance of tumor markers CA19-9 and CEA, gender, Peritoneal Cancer Index (PCI), and completeness of cytoreduction (CC) after cytoreductive surgery were evaluated on 193 consecutive PMP patients, based on a retrospective analysis of prospectively gathered data from a German tertial referral center. We demonstrated that low PCI, CC0 status, low-grade histology, and female gender were independent positive prognostic factors for both overall survival (OS) and progression-free survival (PFS). Furthermore, LAMN patients with achieved CC0 status show significantly better OS and PFS compared to those with CC1 status (p = 0.0353 and p = 0.0026 respectively). In contrast, the duration and drug of hyperthermic intraperitoneal chemotherapy (HIPEC) were not prognostic in any comparison. Increased CA19-9 and CEA levels were significantly associated with HAMN cases, but also predicted recurrence in patients with low-grade histologies. Our study confirmed the prognostic role of tumor markers and emphasized the importance of CC status and PCI in a large cohort of PMP- and LAMN patients.

The Rates of Breastfeeding in Baby-Friendly Hospitals in Greece: A Nationwide Survey.

Exclusive breastfeeding (EBF) remains the cornerstone of infant nutrition for the first six months of life, presenting multiple short and long term benefits. The purpose of this study is the demonstration of EBF rates of infants born in baby-friendly hospitals (BFH) and the factors that positively influence EBF. The study was conducted in all four of the BFH that exist in Greece, between 2020 and 2022. The study sample consisted of 1200 mothers, taken from the 7101 that delivered at those hospitals during the time of the study. A questionnaire was used that included questions to evaluate the infant's nutrition after birth, after exiting the maternity hospital and during the 2nd, 4th and 6th month of age. The WHO guidelines on EBF and breastfeeding (BF), as well as the "Infant and Young Child Feeding" indicators, were used. The EBF rate within 1 h after birth was 71.3%, which gradually declined to 21.2% in the 6th month. The respective rate of BF was 94.5% and declined to 66.1%. The logistic regression revealed that attending antenatal breastfeeding courses, vaginal delivery, full-term pregnancies and the mothers' advanced education level constitute independent positive prognostic factors for increased EBF rates. The results of the first national study on BFH are presented. Despite the improvement of EBF rates in Greece, compared to the latest available data from 2018, reinforcement of EBF promotion measures is required in order to approach the WHO's targets by 2025.

SURG-08. COMBINED LOCAL TREATMENT OF BRAIN METASTASES: SURGERY AND POSTOPERATIVE STEREOTACTIC RADIOTHERAPY

Abstract INTRODUCTION Modern comprehensive local treatment of BM provides the possibility of adequate local control while maintaining a satisfactory quality of life. METHODS Patients after metastasectomy and postoperative radiotherapy treated between 2007-2020 were evaluated. Local control was assessed separately at the site of the operated MM (localPFS) and separately in other parts of the brain (distalPFS). RESULTS A total of 118 patients were enrolled (70 with WBRT), 54% were women, the median age was 60 years, the median performance status Karnofsky 80%. The most common primary tumor was lung carcinoma (39/118, 33%). Targeted stereotactic radiotherapy was significantly more often indicated in operations performed after 2016 (p &amp;lt; 0.001). In the period 2013-2019, gross total resection was achieved significantly more often (83 vs 64%; p = 0.061). The median follow-up is 49 months. The median overall survival (OS) is 9 months (6.2 - 12), the median localPFS 22 months (14 - unattainable), median distPFS 11 months (6.8 - 27 months), median extracranialPFS 11 months (5.9 - 15). Stratification of patients according to the prognostic index brainmetgpa.com led to significant separation of patients for OS (p = 0.00017). In a multivariate analysis, stereotactic radiotherapy was statistically significant positive prognostic factor for OS compared to WBRT (median OS 17 vs. 5.6 months, HR 0.59, p = 0.018) with no effect on localPFS. CONCLUSION Our results of comprehensive local treatment of BM are comparable with the results presented by important foreign studies from prestigious oncology centers. We described targeted stereotactic postoperative radiotherapy as an independent positive prognostic factor after brain metastasectomy. The study was supported by the programme project of the Ministry of Health of the Czech Republic with reg. no. NV18-03-00398, NV19-03-00501 and NV19-03-00559 and Supported by Ministry of Health, Czech Republic-conceptual development of research organization (FNBr, 65269705).

Outcomes and prognostic factors of cytoreductive surgery and perioperative intraperitoneal chemotherapy in high-volume peritoneal carcinomatosis

Background and objectives The management of patients with extensive appendiceal mucinous neoplasms and mesothelioma is controversial. Our aims were to analyze overall survival (OS), disease-free survival (DFS) and independent prognostic factors associated with high peritoneal cancer index (PCI) status in patients who underwent cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy (PIC). Methods A prospectively-maintained database for patients with appendiceal neoplasms and mesothelioma undergoing CRS/PIC from year 1996 to 2018 was retrospectively analyzed. Patients who achieved complete cytoreduction were stratified into limited (PCI < 30) and extensive (PCI ≥ 30) disease groups. Results 260 female and 235 male patients were identified. The 5-year survival for low-grade appendiceal mucinous neoplasms (LAMN) was significantly higher in the low PCI group (96.2% vs. 63.5%, p < 0.001). There was no difference in the OS across both groups in high-grade appendiceal mucinous neoplasms (HAMN) (63 vs. 69 months; p = 0.942) and mesothelioma (72 vs. 42 months; p = 0.058). Overall mortality was 2%. Grade III/IV complications were significantly higher in extensive disease (68% vs. 36.6%, p < 0.001). On multivariate analysis, use of EPIC and blood transfusion (>8 units) were independent positive and negative prognostic factors, respectively, associated with OS. Meanwhile, use of EPIC conferred benefit in DFS while increased blood transfusion (>8 units) and elevated preoperative CA125 were predictive of a poor DFS. Conclusion Long-term survivals following CRS/PIC are achievable with acceptable mortality and higher morbidity rates in extensive appendiceal mucinous neoplasms and mesothelioma. High PCI status does not preclude treatment with CRS/PIC.

Tumor-infiltrating lymphocytes predict survival in ≥ pT2 urothelial bladder cancer

Tumor-infiltrating lymphocytes (TILs) are associated with improved survival in several types of cancers, including genitourinary cancers. However, multiple different scoring methods used to assess TILs complicate the comparison of different studies and are not always suitable for daily practice. In 2014, the International TILs Working Group (ITWG) proposed a simple and robust assessment method for a more standardized evaluation of TILs. Here, we validated this system in muscle-invasive urinary bladder cancer (MIBC). Patient history and histologic specimens from 203 patients with MIBC were retrospectively analyzed. The stromal TIL (sTIL) score was determined using the ITWG system and 3 groups were defined according to the degree of stromal lymphocytic infiltration: low (0–10%), intermediate (10–55%) and high (55–100%). Associations between sTIL score, clinicopathological variables, tumor-specific survival (TSS), overall survival (OS), and disease-free survival (DFS) were analyzed. High stromal lymphocytic infiltration was associated with significantly higher OS, TSS and DFS when compared to low grade sTILs. The survival benefit remained statistically significant in multivariate analyses, confirming that sTILs are a strong independent positive prognostic factor in patients with MIBC. In summary, the degree of sTILs as defined by the ITWG robustly predicts survival in MIBC patients. Prospective studies with larger case numbers are needed to determine whether sTILs should be included in staging guidelines and how they could aid in therapeutic decision making.

Tumor-infiltrating OX40+ lymphocytes is an independent positive prognostic factor for patients with pancreatic ductal adenocarcinoma.

OX40 signaling pathway occupies a vital place in anti-tumor immunity; however, the role of tumor-infiltrating OX40+ lymphocytes in pancreatic ductal adenocarcinoma (PDAC) remains to be identified. A total of 325 sequential PDAC patients who received curative tumor resection between January 2014 and December 2016 were enrolled. Tissues of these patients were immunohistochemically assessed for tumor infiltration of CD4+ T cells, CD8+ cytotoxic T cells (CTLs), and OX40+ lymphocytes. The frequency of OX40+ tumor-infiltrating lymphocytes (TILs) was then analyzed to various clinicopathological features, densities of tumor infiltration of CD4+ T cells and CTLs, and survival analysis was conducted using Kaplan-Meier (KM) curves. The risk scores of associated markers were calculated by the Cox proportional-hazards model. Our results showed that higher OX40+ lymphocytes infiltration was significantly correlated with superior median overall survival (OS) (25.8 vs 13.4months, P < 0.001). Additionally, using univariate and multivariate Cox proportional hazards analyses, this study revealed that together with tumor differentiation, tumor size, serum CA199 levels, serum CA125 levels, and the infiltration of intratumoral CD8+ T cells. The abundance of OX40+ lymphocytes within the tumor was continued to be an independent predictor for OS (P = 0.023, HR = 0.713, 95% CI: 0.532-0.954). This study demonstrated that intratumoral infiltration by a high number of OX40+ lymphocytes is a novel biomarker for favorable prognosis in resected PDAC patients, which implies that OX40-agonist-based immunotherapy might be a potential target in PDAC patients.

Cerebral Circulation Time After Thrombectomy: A Potential Predictor of Outcome After Recanalization in Acute Stroke

BackgroundDespite successful recanalization, up to half of patients with acute ischemic stroke caused by large‐vessel occlusion treated with endovascular treatment (EVT) do not recover to functional independence. We aim to evaluate the role of cerebral circulation time (CCT) as outcome predictor after EVT.Methods and ResultsWe retrospectively enrolled consecutive patients with acute ischemic stroke–large‐vessel occlusion undergoing EVT. Three categories of CCT based on digital subtraction angiography were studied: CCT of the stroke side, CCT of the healthy side), and change of CCT of the stroke side versus CCT of the healthy side. Dramatic clinical recovery was defined as a 24‐hour National Institutes of Health Stroke Scale score ≤2 or ≥8 points drop. A modified Rankin Scale score ≤2 at 3 months was considered a favorable outcome. Logistic regression analysis was performed to evaluate the prediction of CCT on prognosis. One hundred patients were enrolled, of which 38 (38.0%) experienced a dramatic clinical recovery and 43 (43.0%) achieved a favorable outcome. Logistic regression analysis found that shorter change of CCT of the stroke side versus CCT of the healthy side and CCT of the stroke side were independent positive prognostic factors for dramatic clinical recovery (odds ratio [OR], 0.189; P=0.033; OR, 0.581; P=0.035) and favorable outcomes (OR, 0.142; P=0.020; OR, 0.581; P=0.046) after adjustment for potential confounders. A model including the change of CCT of the stroke side versus CCT of the healthy side also had significantly higher area under the curve values compared with the baseline model in patients with dramatic clinical recovery (0.780 versus 0.742) or favorable outcome (0.759 versus 0.713).ConclusionsTo our knowledge, this is the first report that CCT based on digital subtraction angiography data exhibits an independent predictive performance for clinical outcome in patients with acute ischemic stroke–large‐vessel occlusion after EVT. Given that this readily available CCT can provide alternative perfusion information during EVT, a prospective, multicenter trial is warranted.

Analysis of efficacy and safety of vismodegib therapy in patients with advanced basal cell carcinoma - real world multicenter cohort study.

BackgroundBasal cell carcinoma (BCC) is the most frequent non‐melanoma skin cancer. The basis of treatment is surgical resection. The treatment of locally advanced and metastatic disease is currently based on sonidegb or vismodegib, small molecule inhibitors of the hedgehog signalling pathway.ObjectivesThe study aimed to retrospectively analyse the efficacy and safety of treatment with vismodegib in 108 patients with locally advanced or metastatic disease treated from August 1st, 2017 to December 31st, 2020. The primary objective was to evaluate the objective response rate (ORR), overall survival (OS) and progression‐free survival rates. The secondary aims of the study were the disease control rate, the incidence of adverse events (AEs) and the estimation of the factors that potentially impact the treatment outcome and patient survival.MethodsPatients treated in national drug programme were enrolled into this retrospective cohort study. Evaluation of the treatment efficacy was performed according to CT/MRI scans and by the response evaluation criteria in solid tumours (RECIST) 1.1. The safety evaluation was performed according to the Common Terminology Criteria for Adverse Events v. 5.0 (CTCAE) classification and severity assessment.ResultsThe median duration of treatment was 14 months (range 1–94 months). The median progression‐free survival reached 30.5 months (95% CI; 24.8–36.3), and the progression‐free survival rate after 6, 12 and 24‐months were 92%, 78% and 61%, respectively. The median overall survival was 41.5 months (95% CI; 31.6–51.3), and the overall survival rate after 1, 2 and 3 years accordingly 86%, 73% and 60%. The univariant and multivariant analysis indicated that the female gender is an independent positive prognostic factor of progression‐free survival.ConclusionsThe response to treatment is the prognostic factor for response maintenance and better overall survival. The therapy was well tolerated with the safety profile consistent in general with known from previous studies.

Correlation of EGFR mutation subtypes and survival in surgically treated brain metastasis from non-small-cell lung cancer

ObjectiveEpidermal growth factor receptor (EGFR) mutation is a positive prognostic factor for survival in patients with non–small-cell lung cancer (NSCLC). In such patients, brain metastasis signifies negative outcomes. Patients with NSCLC brain metastasis that may benefit from neurosurgery is under investigation. We aim to investigate the impact of different mutation loci in surgically treated NSCLC brain metastasis patients. MethodsThis retrospective cohort study included patients with NSCLC brain metastasis who underwent brain lesionectomy, followed by radiotherapy and chemotherapy or targeted therapy. Demographics and tumor characteristics were compared between the EGFR mutant type and wild type groups. Postoperative survival and risk factors were analyzed using log rank and Cox regression methods. ResultsOverall, 101 patients were included, with 57 belonging to the EGFR mutant type group and 44 to the EGFR wild type group. The median postoperative survival was 17 months for the entire cohort, with the duration being 19 and 14 months for EGFR mutant type and wild type patients (p = 0.013), respectively. Multivariate analysis revealed that exon 19 del (p = 0.02) and a high Karnofsky Performance Scale score (p < 0.01) were independent positive prognostic factors to predict survival. The timing of development of the brain metastasis or the location of the intracranial metastasis was not associated with EGFR mutations. ConclusionEGFR mutations are associated with better survival outcomes in patients with NSCLC brain metastasis suitable for surgical treatment. This advantage was attributed to patients having a specific mutation of exon 19 deletion.

Matrix Metalloproteinase 8 Expression in a Tumour Predicts a Favourable Prognosis in Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a significant cause of cancer-related death globally, and, despite improvements in diagnostics and treatment, survival remains poor. Matrix metalloproteinases (MMPs) are enzymes involved in stroma remodelling in inflammation and cancer. MMP-8 plays a varied prognostic role in cancers of the gastrointestinal tract. We examined the prognostic value of MMP-8 immunoexpression in tumour tissue and the amount of MMP-8-positive polymorphonuclear cells (PMNs) in PDAC and their association with immune responses using C-reactive protein (CRP) as a marker of systemic inflammation. Tumour samples from 141 PDAC patients undergoing surgery in 2002–2011 at the Department of Surgery, Helsinki University Hospital were stained immunohistochemically, for which we evaluated MMP-8 expression in cancer cells and the amount of MMP-8-positive PMNs. We assessed survival using the Kaplan–Meier analysis while uni- and multivariable analyses relied on the Cox proportional hazards model. A negative MMP-8 stain and elevated CRP level predicted a poor prognosis (hazard ratio [HR] = 6.95; 95% confidence interval (CI) 2.69–17.93; p < 0.001) compared to a positive stain and low CRP level (<10 mg/L). The absence of PMNs together with an elevated CRP level also predicted an unfavourable outcome (HR = 3.17; 95% CI 1.60–6.30; p = 0.001). MMP-8 expression in the tumour served as an independent positive prognostic factor (HR = 0.33; 95% CI 0.16–0.68; p = 0.003). Tumour MMP-8 expression and a low CRP level may predict a favourable outcome in PDAC with similar results for MMP-8-positive PMNs and low CRP levels. Tumoural MMP-8 expression represents an independent positive prognostic factor in PDAC.