Search Results (63)

Background/Objectives: To analyze the parent-perceived quality of life (QoL) in children with cerebral palsy (CP) and to study the relationship between sociodemographic and clinical factors and this perception, under the perspective of the International Classification of Functioning, Disability and Health (ICF). Methods: A cross-sectional study was conducted with 95 participants (ages 5–19 years) with CP. Participants’ parents were asked about sociodemographic and clinical characteristics and compiled Cerebral Palsy Quality of Life (CP-QoL) and Pediatric Disability Inventory-Computer Adaptive Test (PEDI-CAT). Participants were assessed and classified into the following functional domains: gross motor function (GMFM-88, GMFCS), manual ability (MACS), eating and drinking abilities (EDACS), and communication function (CFCS). Correlations between CP-QoL domains and variables were investigated using Spearman’s correlation coefficient and multivariate predictive models were used to investigate the variables predicting CP-QoL scores for each domain. Results: A total of 95 children with a mean age of 12.4 ± 3.5 years (range 5–19 years) were included. Participants demonstrated moderate-high GMFM-88 level (228.8 ± 44.7) and high functional performance across PEDI-CAT domains: Activity (57.2 ± 5.1), Mobility (63.1 ± 5.6), and Social/Cognitive (70.2 ± 4.3). Parent-perceived QoL was significantly higher when children did not require AFOs, botulinum toxin, or recent hospitalizations, and lower among children who attended physical therapy >2 h/week. Moderate correlations were consistently found between the ‘Feelings about Functioning’ domain and functional variables, being positive for GMFM-88 and all PEDI-CAT domains, and negative for GMFCS, MACS, EDACS and CFCS. That domain of CP-QoL was best explained by the regression model (R² = 0.619, p < 0.001), with the combination of three variables: GMFM-88, PEDI-CAT Activity and PEDI-CAT Social/Cognitive. Among them, PEDI-CAT Activity was the strongest predictor (β = 0.1436). Conclusions: In children with CP, to enhance family well-being, interventions should prioritize social participation and carefully balance the intensity and frequency of therapy against family burden and daily life demands, as QoL is primarily driven by manual ability and functional performance. Full article

Background/Objectives: Comprehensive genomic profiling (CGP) is a cornerstone of personalized oncology. However, large-scale, systematic data on the somatic mutation spectrum in Russian cancer patients are scarce. This study aimed to characterize the genomic landscape and assess the potential for matched therapy in a Russian cohort of patients with solid tumors. Methods: This retrospective study included 204 patients with various solid tumors. CGP was performed using the FoundationOne^®CDx (FFPE tissue) and FoundationOne^®Liquid CDx (cfDNA) platforms. The analysis assessed single-nucleotide variants, indels, copy number alterations, gene fusions, tumor mutational burden (TMB), microsatellite instability (MSI), and PD-L1 expression. Results: The most frequently mutated genes were TP53 (61.5%) and KRAS. The median TMB was 4.0 mut/Mb and was significantly lower in stage IV tumors. Significant co-occurrence was observed between KRAS and TP53 mutations, as well as between APC and KRAS mutations, which were particularly characteristic of colorectal cancer. KRAS mutations were associated with higher combined positive score (CPS) values in cases with lung cancer. Based on the CGP results, 44% of patients had findings that supported the use of an approved matched targeted therapy or immunotherapy for their tumor type. An additional 36% of patients had alterations indicating potential benefit from off-label targeted therapy. Conclusions: This study reveals the distinct genomic characteristics of solid tumors in a Russian cohort and confirms the high clinical utility of CGP for identifying actionable targets. Implementing CGP early in the diagnostic process is a necessary step towards realizing personalized treatment strategies for cancer patients. Full article

Background: Nivolumab plus chemotherapy has shown significant benefits in advanced gastric cancer (AGC) patients with PD-L1 combined positive score (CPS) 5 or higher. However, real-world data on its efficacy across different PD-L1 expression levels are limited. Methods: We conducted a retrospective analysis of 143 AGC patients treated with first-line nivolumab plus chemotherapy. Patients were stratified by PD-L1 CPS. Progression-free survival (PFS), overall survival (OS), and clinical factors affecting outcomes were evaluated. Results: Among 143 patients, 87 (60.8%) were classified as PD-L1 CPS < 5 and 56 (39.2%) as CPS ≥ 5. The PD-L1 ≥ 5 group had a higher proportion of dMMR and TMB-high. Notably, patients in the PD-L1 < 5 group also derived a PFS benefit from chemotherapy plus nivolumab, achieving a median PFS of 6.8 months, although outcomes were further enhanced in the PD-L1 ≥ 5 group with statistical significance (10.0 months; HR 0.56, p = 0.004). Although the PD-L1 ≥ 5 group showed a higher median OS compared with the PD-L1 < 5 group (26.2 vs. 18.8 months), the difference was not statistically significant (p = 0.234). Exploratory analyses demonstrated a stepwise trend toward improved survival with increasing PD-L1 cutoffs, with the most pronounced benefit observed in the PD-L1 ≥ 25 subgroup (PFS HR 0.28, p = 0.012; OS HR 0.21, p = 0.031). Conclusions: This real-world study suggests that nivolumab plus chemotherapy may benefit AGC patients across various PD-L1 expression levels, with trends favoring higher expression. These findings warrant further investigation in larger real-world studies to optimize patient selection and treatment strategies. Full article

Advanced gastric/gastroesophageal junction (G/GEJ) adenocarcinoma remains a common and deadly form of cancer. Advances in G/GEJ cancer treatment have improved survival outcomes with the claudin-18.2 (CLDN18.2)-targeted agent, zolbetuximab, and immune checkpoint inhibitors (ICIs) targeting the PD-1 receptor. This article offers an evidence-informed opinion on considerations when selecting between these first-line treatments for G/GEJ adenocarcinoma in patients with HER2-negative disease that expresses CLDN18.2 and/or PD-L1, including the reliability of biomarker scoring and interpretation, overall survival (OS) rates, toxicity profiles, and logistical practicalities. Evidence from Phase III trials for zolbetuximab and ICIs suggest similar OS benefits of 14–18 months compared to chemotherapy alone, but there appears to be a gradient of benefit for ICIs with increasing PD-L1 combined positive score (CPS). There is high inter-observer variability in CPS scoring, particularly at lower thresholds. Zolbetuximab is associated with high rates of nausea and vomiting during the initial infusion, whereas ICIs are associated with risk of later-onset immune-related toxicities that can be fatal in rare cases. In considering the available evidence, our opinion is that zolbetuximab is a reasonable option for initial targeted treatment in HER2-/CLDN18.2-positive advanced G/GEJ when PD-L1 CPS score is <10 based on the reliability of biomarker testing, comparable OS, and avoidance of potentially irreversible ICI-induced immune toxicity. Full article

Programmed death-ligand 1 (PD-L1) biomarker testing in gastric cancer is required to identify patients suitable for immunotherapy. However, the PD-L1 testing landscape is complex, with various PD-L1 tests available and multiple algorithms that combine tumor and immune cell staining. To provide guidance on the best practices for PD-L1 testing in gastric cancer, we reviewed the literature and incorporated our extensive experience using the PD-L1 IHC PharmDx 22C3 and 28-8 assays and scoring with the combined positive score (CPS) algorithm. This review summarizes inter-reader agreement and PD-L1 assay concordance studies in gastric cancer, highlights practical challenges and pitfalls encountered in our own laboratory, and proposes solutions to address them. Accurate and consistent interpretation of PD-L1 CPS in gastric cancer is challenging, but can be improved with training, experience, and close attention to interpretation guidelines. Techniques are available that can optimize the automated staining of PharmDx PD-L1 assays using the Autostainer Link 48 to ensure consistent staining performance. The PD-L1 IHC PharmDx 22C3 and PD-L1 IHC PharmDx 28-8 assays show high concordance when used according to manufacturers’ guidelines. Full article

Background: Chronic pain (CP) is one of the biggest burdens for health systems across the globe. It frequently presents in conjunction with comorbidities and considerable challenges for the maintenance of homeostasis and well-being. The lack of long-term effective treatments requires further attention and innovative approaches from the health care community. The present observational study aims to prove the feasibility of a breathing protocol focused on long exhalations (LEx) as a complementary treatment for CP populations. Methods: Eighteen CP patients (nine men and nine women) were selected for this observational pilot study. The inclusion criteria were having pain for more than 3 months, not having any previous experience with breathing exercises and not having a clinical diagnosis for the condition suffered. In addition to the usual physiotherapy care, the participants were trained in breathing techniques and the effects of LEx. Before each appointment, the Numeric Pain Rating Scale (NPRS), Pain Catastrophising Scale (PCS) and exhalatory times were registered. The data analysis consisted of a repeated measures ANOVA and a Pearson Correlation Coefficient. Results: A total of 18 participants completed the breath intervention and the assessments. All participants improved their exhalation times by 4.78 s (SD = 3.19) or 64% (F = 45.62, p < 0.001) and their pain scores: NPRS by 2.55 units (SD = 2.2) or 47% (F = 34.19, p < 0.001); and PCS by 11.34 units (SD = 16.05) or 33% (F = 24.05, p < 0.001). There was a moderate positive correlation (r = 0.49, p = 0.05) between exhalation times and NPRS. Conclusions: Breathing techniques focused on LEx in combination with the usual physiotherapy care are a feasible pain management protocol to reduce subjective pain perception and pain catastrophizing scores. Long-term studies with bigger samples might benefit from the inclusion of accurate and reproducible measures for exhalation times. Full article

Background and Objectives: To evaluate the prognostic value of the Clinical–Pathologic Stage–Estrogen receptor status and Grade (CPS+EG) staging system, which combines clinical staging, pathological staging, oestrogen receptor (ER) status, and tumour grade in predicting survival outcomes in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer receiving neoadjuvant therapy (NACT). Materials and Methods: A retrospective review was performed on 245 female breast cancer patients who received anti-HER2 therapy alongside NACT at the Medical Oncology Department of Kartal Dr Lütfi Kırdar City Hospital, University of Health Sciences, from April 2012 to June 2024. The CPS+EG score was calculated using the MD Anderson Cancer Centre neoadjuvant treatment response calculator. Patients were categorised into two groups based on their CPS+EG score < 3 and ≥3. The primary outcomes assessed were disease-free survival (DFS) and overall survival (OS). Kaplan–Meier and log-rank tests were utilised for time-to-event analysis; Cox regression was used for multivariate analysis. A significance level of ≤0.05 was considered. Results: The median age of the patient cohort was 51 years (range: 27–82 years). Among these patients, 183 (74.6%) had a CPS+EG score less than 3, while 62 (25.3%) exhibited a score of 3 or higher. The median follow-up duration was 37.6 months. The pathological complete response (pCR) rate across the entire cohort was 51.8%. Specifically, the pCR rate was 56.3% in the group with CPS+EG scores below 3, and 38.7% in those with scores of 3 or higher (p = 0.017). Patients with CPS+EG scores less than 3 demonstrated superior overall survival (OS), which reached statistical significance in univariate analysis. Multivariate analysis identified the CPS+EG score as an independent prognostic factor for both overall survival and disease-free survival (DFS), with hazard ratios of 0.048 (95% CI: 0.004–0.577, p = 0.017) and 0.35 (95% CI: 0.14–0.86, p = 0.023), respectively. Conclusions: The CPS+EG score is an independent and practical prognostic marker, particularly for overall survival, in patients with HER2-positive breast cancer who have received neoadjuvant therapy. Patients with a CPS+EG score < 3 have higher pCR rates and survival rates. When used in conjunction with pCR, it can improve risk categorisation and contribute to the individualisation of adjuvant strategies in the post-neoadjuvant period. Due to its ease of calculation and lack of additional costs, this score can be instrumental in clinical practice for identifying high-risk patients. Our findings support the integration of the CPS+EG score into routine clinical decision-making processes, although prospective validation studies are necessary. Full article

Background/Objectives: The combination of anti-programmed death-1 (PD-1) inhibitors and chemotherapy is the standard first-line treatment for unresectable or metastatic esophageal squamous cell carcinoma (ESCC). However, real-world data remain limited, particularly regarding prognostic biomarkers. Methods: This multi-institutional retrospective study analyzed patients with metastatic or unresectable ESCC who received first-line pembrolizumab or nivolumab plus fluoropyrimidine and platinum-based chemotherapy. Treatment regimens mirrored those in KEYNOTE-590 and CheckMate 648. Efficacy, safety, and prognostic factors were assessed. Prognostic factors were identified using multivariable Cox regression, and a point-based risk scoring system was developed. Results: Among 87 patients, the objective response rate was 48.3%, and the disease control rate was 77.0%. Median progression-free survival (PFS) was 5.6 months (95% CI, 4.5–8.7), and the median overall survival (OS) was 13.1 months (95% CI, 10.6–not reached). Grade 3–4 treatment-related adverse events occurred in 51.7% of patients. Eastern Cooperative Oncology Group (ECOG) performance status ≥ 2, elevated C-reactive protein, and lower programmed death-ligand 1 (PD-L1) combined positive score (CPS) were independently associated with worse PFS and OS. A prognostic risk score ranging from 0 to 5 based on these factors stratified patients into four prognostic groups with distinct survival outcomes. Median PFS ranged from not reached in the low-risk group to 2.1 months in the high-risk group. Stratifying PD-L1 CPS into three levels (<10, 10–49, ≥50) revealed a graded association between CPS and treatment outcomes, supporting the need for more nuanced PD-L1 evaluation beyond binary classification. Conclusions: First-line anti-PD-1 therapy combined with chemotherapy demonstrated favorable real-world outcomes in ESCC. The proposed prognostic scoring system may help personalize treatment strategies. Full article

Backgrounds: Programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) is a critical predictive biomarker for immune checkpoint inhibitor (ICI) therapy in triple-negative breast cancer (TNBC). However, prolonged storage of formalin-fixed paraffin-embedded (FFPE) tissue may reduce antigenicity, potentially leading to false-negative results. False-negative results may lead to the inappropriate selection of ICI therapy. We investigated the effect of FFPE storage duration on PD-L1 immunoreactivity. Methods: We retrospectively analyzed 63 TNBC cases with PD-L1 testing using the 22C3 pharmDx assay at diagnosis and repeated IHC on the same FFPE blocks after varying storage durations (<1, 1–2, 2–3, ≥3 years). PD-L1 positivity was defined as Combined Positive Score (CPS) ≥ 10. Associations with clinicopathologic features, pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC), and survival were evaluated. Results: At diagnosis, 41 patients (65.1%) were PD-L1–positive. In the PD-L1–positive group, decreased staining was observed in 0%, 11%, 13%, and 50% of cases for <1, 1–2, 2–3, and ≥3 years of storage, respectively (p = 0.015). PD-L1 positivity correlated with higher Ki67 and nuclear grade. pCR was achieved in 33% of PD-L1–positive vs. 0% of PD-L1–negative NAC patients (p = 0.0527). Survival analysis showed a non-significant trend toward shorter recurrence-free and overall survival in PD-L1–positive patients. Conclusions: Prolonged FFPE storage, particularly beyond three years, significantly reduces PD-L1 immunoreactivity. Testing on recent specimens is recommended to avoid false-negative results that may impact ICI eligibility. Full article

Gastric cancer remains a major global health burden, with limited response rates to current immunotherapies targeting the programmed death-ligand 1 (PD-1/PD-L1) axis. Recent studies have identified sialic acid-binding immunoglobulin-like lectin 15 (SIGLEC-15) as a novel immune checkpoint molecule that may drive immune evasion through PD-L1–independent pathways. This study aimed to evaluate the expression patterns of SIGLEC-15 and PD-L1 in gastric adenocarcinoma and to investigate their associations with clinicopathological features and patient outcomes. We retrospectively analyzed 133 consecutive cases of gastric adenocarcinoma with complete clinicopathologic and follow-up data. Immunohistochemical staining was performed on formalin-fixed tumor samples; SIGLEC-15 expression on tumor cells was quantified by H-score (high expression defined as ≥110) and PD-L1 status by combined positive score (CPS, positive if ≥1). High SIGLEC-15 expression correlated with multiple adverse pathological features, including lymphatic (p = 0.003), venous (p = 0.030), and perineural invasion (p = 0.010), and was associated with significantly poorer 3-year overall survival (hazard ratio = 3.36, p < 0.001). While SIGLEC-15 and PD-L1 expression were not mutually exclusive, an inverse relationship was generally observed. Patients with dual positivity (SIGLEC-15 high/PD-L1 CPS ≥ 1) showed the lowest 36-month survival (32%), compared to 56% in the dual-negative group (SIGLEC-15 low/PD-L1 CPS < 1). These results highlight the clinical relevance of SIGLEC-15 as an independent marker of tumor aggressiveness and poor prognosis in gastric adenocarcinoma. Moreover, stratification based on combined SIGLEC-15 and PD-L1 CPS expression revealed that patients co-expressing high levels of both markers experienced the poorest survival outcomes. These findings suggest that the dual assessment of SIGLEC-15 and PD-L1 may enhance prognostic accuracy and support immunotherapeutic decision-making in gastric cancer. Full article

Background: The predictive value of muscle-related indicators in triple-negative breast cancer (TNBC) patients undergoing neoadjuvant chemotherapy (NAC) remains unclear. This study aimed to evaluate the association between the skeletal muscle density (SMD) and clinical variables related to the physical reserve with respect to its impact on the pathologic complete response (pCR). Methods: We retrospectively analyzed TNBC patients who underwent NAC at Seoul St. Mary’s Hospital, Catholic University of Korea, from March 2021 to March 2024, via receiving paclitaxel/carboplatin followed by doxorubicin/cyclophosphamide, with or without pembrolizumab. Muscle indices were assessed from CT measurements of the entire cross-sectional muscle area at the L3 level using commercial deep learning software (ClariMetabo version 1.03). Results: A total of 144 patients were included, where 102 received chemoimmunotherapy (NACIT) and 42 received chemotherapy alone (NACT). A higher SMD was significantly associated with a younger age, lower BMI, and fewer comorbidities. In the NACIT group, patients in the high-SMD group (n = 68) demonstrated a higher relative dose intensity (p = 0.003) and improved pCR rates (63.2% vs. 44.1%, p = 0.066) compared with the low-SMD group (n = 34). The multivariable regression analysis identified a higher SMD (per 5-unit increment: OR = 1.67, p = 0.003) and increased PD-L1 combined positive score (per 10-unit increment: OR = 1.38, p = 0.019) as independent predictors of a pCR. The event-free survival was significantly longer in the high-SMD group (p = 0.017) and among patients that achieved a pCR (p < 0.001). In the NACT group, the SMD was not associated with a pCR or survival. Conclusions: The CT-measured SMD reflected the physical reserve in the TNBC patients that received NAC. Alongside the CPS, SMD may serve as a predictive marker for NACIT efficacy. Full article

Background: Epstein–Barr virus-associated gastric cancer (EBVaGC) represents a distinct molecular subgroup with potential responsiveness to immunotherapy approved for programmed death-ligand 1 (PD-L1)-positive gastric cancer. This retrospective study aimed to assess the prevalence and association between EBVaGC and PD-L1 positivity among patients with gastric adenocarcinoma treated at a university hospital in Southern Thailand from January 2017 to October 2023. Methods: The EBV status of the patients and PD-L1 expression were determined using in situ hybridization and immunohistochemistry, respectively. Results: The prevalence of EBVaGC was 4.5% among 132 patients, whereas 9.1% of patients exhibited a PD-L1 combined positive score (CPS) of ≥1, with no significant association observed between them. EBVaGC was more prevalent in males, non-antral tumors, diffuse/mixed histologic subtypes, and poorly differentiated tumors. Median overall survival for patients with EBVaGC and PD-L1 CPS ≥ 1 was 9.48 and 14.19 months, respectively, compared with 10.32 and 9.79 months for those with non-EBVaGC (hazard ratio: 1.24; 95% CI: 0.50–3.04; p = 0.645) and PD-L1 CPS < 1 (hazard ratio: 0.82; 95% CI: 0.40–1.69; p = 0.590), respectively. Conclusions: Our findings revealed a low prevalence of EBVaGC and PD-L1 positivity in Thailand, with no significant association or survival impact observed. These findings highlight the regional variation in these biomarkers and support EBV as an independent biomarker from PD-L1. However, further research, particularly studies evaluating immunotherapy outcomes, is warranted to clarify the predictive and clinical significance of EBV in gastric cancer. Full article

Combination therapy of chemotherapy and zolbetuximab demonstrated a significant survival benefit compared to chemotherapy alone in patients with human epidermal growth factor receptor 2 (HER2)-negative, claudin (CLDN) 18.2–positive metastatic gastric cancer (mGC). Consequently, it has been approved as a standard first-line therapy for these patients. Combination therapy of chemotherapy and immune checkpoint inhibitors (ICIs)—either nivolumab or pembrolizumab—is a standard first-line therapy for patients with HER2-negative mGCs that are positive for programmed death-ligand 1 (PD-L1) expression, as defined by a combined positive score (CPS). Although approximately 13–22% of CLDN-positive mGCs are also CPS-positive, optimal treatment for mGC patients expressing both CLDN and PD-L1 remains undetermined due to the absence of direct comparative studies between zolbetuximab and ICIs. Treatment selection under this condition has become a critical issue. In this review, we discuss the appropriate treatment selection for HER2-negative mGC patients who are double-positive for CLDN 18.2 and PD-L1 based on clinical data and differences in the mechanism of action and safety profile between zolbetuximab and ICI. Full article

Objective: To compare the efficacy and safety of immunotherapy combined with chemotherapy as the first-line treatment for advanced gastric cancer. Data Sources: Phase III randomised controlled trials were searched from PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials databases, and several international conference databases, from inception to 15 November 2024. Results: A total of eight eligible trials involved 7898 patients and eight treatments. The network meta-analysis showed that cadonilimab plus chemotherapy was the most superior treatment in improving overall survival (versus conventional chemotherapy, hazard ratio 0.62, 95% credible interval 0.50 to 0.78) and progression-free survival (0.53, 0.43 to 0.65), and consistency of results were observed in specific PD-L1 combined positive score groups. All immune checkpoint inhibitors combined with chemotherapy improved patient prognosis, but nivolumab plus chemotherapy may lead to an increase in grade 3 or higher adverse events (odds ratio 1.68, 95% credible interval 1.04 to 2.54), and the toxicity of cadonilimab plus chemotherapy was more likely to force patients to discontinue treatment. Conclusions: These results showed that cadonilimab plus chemotherapy had the best overall survival and progression-free survival benefits for advanced gastric cancer patients with HER-2 negative, and was preferentially recommended to patients with positive PD-L1 CPS. Full article

Background: Bladder cancer (BC) is a heterogeneous malignancy, and predicting response to immune checkpoint inhibitors (ICIs) remains a challenge. Herein, we investigate a high-risk bladder tumor, which developed during anti-BRAF/MEK therapy for a concurrent advanced BRAF-V600E-positive malignant melanoma (MM) and subsequently underwent complete spontaneous necrosis following Nivolumab immunotherapy, only to recur thereafter while still under the same treatment. This unique scenario provided an opportunity to investigate the roles of BRAF gene mutations in BC pathogenesis, respectively, of PD-L1 expression in immunotherapy response prediction. Methods: We retrospectively analyzed BC specimens obtained via transurethral resection at two critical time-points: prior to the complete spontaneous necrosis under Nivolumab (prenecrosis) and after tumor recurrence postnecrosis (postnecrosis). The BRAF gene mutation status was evaluated using quantitative polymerase chain reaction (qPCR). PD-L1 expression was assessed by immunohistochemistry (IHC), quantified using the combined positive score (CPS), and a cutoff of ≥10 for positivity. Results: Neither pre- nor postnecrosis BC samples harbored BRAF gene mutations. Prenecrosis PD-L1 expression (CPS = 5) indicated a minimal likelihood of response to immunotherapy. However, complete spontaneous necrosis occurred under Nivolumab, followed by recurrence with further reduced PD-L1 expression (CPS = 1). Conclusions: The complete BC regression challenges the conventional role of PD-L1 as a sole predictive biomarker for immunotherapy. This study also highlights the potential role of BRAF/MEK inhibitors in BC oncogenesis and underscores the need for alternative biomarkers, such as tumor mutation burden (TMB) and circulating tumor DNA (ctDNA), to guide treatment selection in BC better. Full article