Epithelioid fibrous histiocytoma (EFH) is a benign fibrohistiocytic neoplasm characterized by morphologic heterogeneity and recurrent anaplastic lymphoma kinase (ALK) gene rearrangements. We present a rare case of EFH located on the lateral neck of a 56-year-old male patient, demonstrating a predominantly spindle cell morphology. Immunohistochemical analysis revealed granular cytoplasmic positivity for ALK, along with expression of CD68, CD4, epithelial membrane antigen, caldesmon, and smooth muscle actin. Next-generation sequencing confirmed the presence of a rare PPFIBP1-ALK fusion. The presented case highlights a predominantly spindle cell variant of EFH and suggests inclusion within the recently described myxoid spindle cell EFH spectrum, which encompasses the superficial ALK-rearranged myxoid spindle cell neoplasms (SAMS).

Given the variable pathological complete response (pCR) rate of neoadjuvant chemotherapy (NAC) in patients with breast cancer, identifying predictive markers is crucial. This study evaluated the predictive accuracy of three machine learning-based models: (1) radiomics using MRI features; (2) genomics based on DNA microarray data; and (3) radiogenomics integrating both MRI and microarray data to predict pCR after NAC across all breast cancer subtypes. This study aimed to determine which model provides the most precise non-invasive prediction by utilizing a consistent dataset and analytical pipeline.

In this retrospective study, 112 patients with breast cancer who underwent DNA microarray analysis and dynamic contrast-enhanced MRI before receiving NAC at a single institution between July 2006 and November 2016 were classified into pCR (N = 21) and non-pCR (N = 91) groups. The prediction accuracy of pCR after NAC was evaluated for three models using repeated stratified nested cross-validation (CV). Model performance was assessed by the area under the receiver operating characteristic curve (ROC-AUC), and statistical significance was tested using DeLong's test.

Among the 112 patients, the radiogenomics model yielded an AUC of 0.607 (95% confidence interval (CI): 0.438-0.758), outperforming both the radiomics (AUC 0.563, 95% CI: 0.410-0.718) and the genomics (AUC 0.559, 95% CI: 0.379-0.722) models. However, this improvement was not statistically significant (p>0.05).

Machine learning-based radiogenomics, which combines MRI features and DNA microarray data, improved the accuracy of pCR prediction after NAC, although the improvement was not statistically significant. These findings suggest the potential utility of radiogenomics as a non-invasive tool to support treatment decision-making in patients undergoing NAC.

Over the last decade, the development of innovative cancer treatments has accelerated and has been associated with improved mortality trends; however, local regulatory approval times are extensive. This study estimated the clinical and economic impact of delays in the approval of innovative therapies for the treatment of advanced lung cancer in men in five Latin American countries.

Using public data, we estimated the relationship between available innovative therapies (AIT) and age-specific mortality rate (ASMR) for Argentina, Brazil, Chile, Colombia, and Mexico through a regression model. Based on the difference between the number of FDA-approved therapies and the number approved by each local agency, we calculated the avoidable deaths (ADs) if innovation had been available. We estimated the Years of Life Lost (YLLs) using the life expectancy, the median age of death, and the ADs. Productivity loss (PL) was calculated using each country's retirement age and yearly Gross Domestic Product per capita (GDPc) in 2022 constant USD.

Total ADs, YLLs, and PL were 8694, 114,477, and USD 439,179,876, respectively. Argentina had the highest impact of AIT on ASMR. Brazil's results showed a high clinical and economic impact, primarily due to its large population. Chile's high GDPc led to high PL. Colombia and Mexico showed a high clinical impact, suggesting a benefit of early approval. Differences in availability and approval times have increased with the number of FDA-approved therapies, yet local time gaps have recently increased.

Our study shows the substantial clinical and economic impact of delays in approving innovative therapies, underscoring the potential of improving regulatory processes to increase the availability of lung cancer treatments. Accelerating the introduction of innovative therapies for advanced lung cancer in Latin America represents a significant opportunity to enhance survival rates, instilling hope and optimism while also avoiding substantial PL.

This study was conducted as a research partnership between Roche and CTIC. No funding was received. Authors participated in the study design, data collection, data analysis, interpretation, and writing of the report.

Background: Heterogenized sphingolipid metabolism (SM) drives osteosarcoma tumorigenesis and its tumor-promoting microenvironment. State-of-the-art bioinformatic tools, such as machine learning, are essential for dissecting the prognostic value of SM by investigating its molecular and cellular mechanisms. Methods: A tailored machine learning pipeline was established by integrating Cox regression, 5-fold cross-validation, Elastic Net, eXtreme Gradient Boosting (XGBoost), and Bayesian optimization (for hyperparameters tuning) to foster an SM Elastic Net-XGBoost (SNEX) prognostic model, interpreted by the Shapley additive explanations (SHAP) algorithm. The alterations in molecular pathways and immune microenvironment-driven unfavorable prognosis of SNEX-identified high-risk osteosarcoma were further investigated. The SNEX predicted results have also been clinically and experimentally validated. Results: We identified 22 critical SM prognostic genes for Bayesian-optimized SNEX. This model provided outstanding estimates of the prognoses of osteosarcoma patients (C-index of 1.000). Its robustness was confirmed in the independent test set with a high area under the curve (AUC) of 0.875 at 1 year, 0.930 at 3 years, and 0.930 at 5 years. SNEX also significantly outperformed all previous genetic prognostic signatures with a significantly higher net benefit of decision curves and higher AUCs. ACTA2 was the most pivotal gene critical to the negative prediction of SNEX, while BNIP3 was for positive prediction. Mechanistically, SNEX-identified high-risk osteosarcoma suffered unfavorable prognoses due to dysregulation of many critical metabolic/inflammatory/immune biologic processes and immunosuppressive microenvironment, with reduced infiltration of 14 types of immune cells (macrophages, CD8+ T cells, NK cells, etc.). Notably, SNEX highlighted TERT as the most remarkable SM prognostic gene. Clinical osteosarcomas with high expression of TERT exhibited more significant malignant characteristics than others, as evidenced by their higher proliferation efficiency. In addition, all the experiments in vitro and in vivo validated that inhibiting TERT abundance reduces the proliferation, invasion, and migration capabilities of osteosarcoma cells. Conclusions: This study is a first-hand report employing a tailored machine-learning pipeline for dissecting the prognostic value and roles of SM in osteosarcoma. The present study fostered a SNEX for risk-stratification with outstanding accuracy and offered deep insights into SM-mediated pathways and microenvironment dysregulation in osteosarcoma.

Brain metastases occur in 40% of advanced NSCLC patients, with poorer prognosis in squamous subtypes. Immune checkpoint inhibitors (ICIs) combined with chemotherapy have revolutionized treatment, yet data on the systematic treatment of stage IV squamous non-small cell lung cancer with surgery remain limited. A 59-year-old male smoker presented with stage cT4N2M1b IVA squamous NSCLC and a solitary brain metastasis. Next-generation sequencing revealed programmed cell death ligand 1 (PD-L1) high expression (TPS=75%) and TMB-High (28.49 Mut/Mb) without driver mutations. After pembrolizumab plus platinum-based chemotherapy induced conversion therapy for 3 cycles, the brain lesion achieved pathological complete response (pCR) following resection, while the primary lung tumor showed major pathological response (MPR) post-surgery. Postoperative adjuvant chemoimmunotherapy and 2-year pembrolizumab maintenance were administered. Serial circulating tumor DNA (ctDNA) monitoring remained negative, with no recurrence observed over 50 months. This is the first reported case of long-term survival (PFS >50 months) in a PD-L1-high/TMB-High squamous NSCLC patient with brain metastasis treated with immunotherapy-based multimodal therapy. Our findings suggest that biomarker-guided strategies integrating systemic therapy, surgery, and MRD monitoring may enable curative potential in select advanced NSCLC patients. Further studies are warranted to validate this "sandwich" approach (drug-surgery-drug) and optimize treatment duration.

The prognostic significance of body mass index (BMI) in elderly acute myeloid leukemia (AML) patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) remains controversial.

This retrospective study analyzed 142 AML patients aged ≥50 years receiving allo-HCT (2013-2022), stratified by Chinese BMI criteria: low BMI (<24 kg/m², n = 83) vs. high BMI (≥24 kg/m², n = 59).

The median pre-transplant BMI was 23.63 (IQR, 22.07-25.78) kg/m². Multivariate analysis identified BMI <24 kg/m² as an independent risk factor for inferior OS (HR=1.80, p=0.037) and GRFS (HR=2.00, p = 0.003). Although BMI did not correlate with relapse, long-term non-relapse mortality (NRM), or the incidence of acute and chronic graft versus host disease (GVHD), the one-year NRM was significantly higher in the low BMI group compared to the high BMI group (p = 0.006). Subgroup analysis revealed that high-risk patients [not complete remission (NR) or CR but minimal residual disease (MRD)-positive) with low BMI had markedly reduced 3-year OS (20.87% vs. 57.69%, p=0.006), whereas no difference was observed in low-risk (CR/MRD-negative) patients.

Pre-transplant BMI independently predicts inferior survival in older adults with AML undergoing allo-HCT. These findings highlight the need for BMI-guided nutritional interventions, especially for high-risk older patients.

Background: The efficacy of HLX02, a trastuzumab biosimilar, in combination with chemotherapy for treating metastatic breast cancer (BC) has been established as equivalent to the reference Herceptin. This study aimed to assess the treatment response of HLX02-based neoadjuvant therapy in HER2-positive BC, with a focus on HR-positive versus HR-negative subgroups. Additionally, we investigated the potential role of a CDK4/6 inhibitor in combination with anti-HER2 therapy. Methods: This retrospective study included HER2-positive BC patients who received HLX02-based neoadjuvant therapy followed by curative surgery at Anhui Provincial Cancer Hospital between March 2021 and August 2023. Pathological complete response (pCR) rates were analyzed, and subgroup analyses evaluated predictors of pCR. In vitro experiments using BT-474 and MCF-7 cell lines assessed the effects of combining CDK4/6 inhibitors with anti-HER2 therapy on cell viability and apoptosis. Results: The study included 67 patients with a median age of 53 years. The overall pCR rate was 53.73%, with higher pCR rates observed in HR-negative patients compared to HR-positive patients (63.89% vs. 41.94%). Dual HER2 blockade with HLX02 and pertuzumab was associated with a numerically improved pCR rate (62.16%). ER expression significantly increased post-treatment, potentially indicating treatment resistance mechanisms. In vitro, the combination of CDK4/6 inhibitors with anti-HER2 therapy significantly reduced cell viability and promoted apoptosis in HR-positive, HER2-positive cell lines. Conclusion: HLX02 demonstrates real-world efficacy as part of neoadjuvant therapy for HER2-positive BC, especially in HR-negative patients. The lower pCR rate in HR-positive patients highlights the need for additional strategies. Combining CDK4/6 inhibitors with anti-HER2 therapy presents a promising approach for HR-positive HER2-positive patients, warranting further clinical validation.

Existing research has shown that long non-coding RNA (lncRNA) MAGI2 antisense RNA3 (MAGI2-AS3) expression is significantly decreased in breast cancer tissues and can inhibit breast cancer progression. However, the relationship between MAGI2-AS3 expression levels in peripheral blood mononuclear cells (PBMCs) and breast cancer remains unclear. This study aimed to explore the clinical significance of MAGI2-AS3 expression in PBMCs for diagnosing breast cancer and predicting patient prognosis.

Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect MAGI2-AS3 expression in PBMCs from healthy donors and breast cancer patients. The chi-square test analyzed the associations between MAGI2-AS3 expression and breast cancer clinicopathological parameters. The Kaplan-Meier method evaluated the impact of MAGI2-AS3 on patients' overall survival (OS), and receiver operating characteristic (ROC) analysis assessed its diagnostic accuracy for breast cancer.

MAGI2-AS3 expression was significantly downregulated in breast cancer patients' PBMCs compared to the control group. Its expression decreased with the advancement of tumor-node-metastasis (TNM) stage and elevation of pathological grade, and was remarkably lower in patients with distant metastasis (DM). Low MAGI2-AS3 expression in PBMCs was correlated with shorter OS. ROC curve analysis showed that MAGI2-AS3 in PBMCs had good diagnostic accuracy.

MAGI2-AS3 expression in breast cancer patients' PBMCs is reduced and negatively correlated with patient outcomes. Thus, it has the potential to be a valuable biomarker for breast cancer diagnosis and prognostic evaluation.

Ovarian endometriosis cysts are associated with infertility, and recent research increasingly focuses on improving pregnancy outcomes. Traditional Chinese medicine (TCM) has long been used for gynecological issues, yet the impact of staged TCM administration on pregnancy outcomes and Endometriosis Fertility Index (EFI) scores in infertile patients remains underexplored.

This study aims to evaluate the effects of staged TCM administration on pregnancy outcomes and EFI scores in patients with ovarian endometriosis cysts.

A retrospective analysis of 150 infertile patients treated with staged TCM administration was conducted. Patients received Formula I before ovulation and Formula II post-ovulation, with the cohort split into pregnancy (n=91) and non-pregnancy groups (n=49). All patients underwent laparoscopic surgery prior to TCM treatment. Logistic regression and ROC analysis were used to assess pregnancy predictors.

Significant differences in age, infertility type, infertility duration, r-AFS stage, cyst diameter, and EFI score (P<0.05) were found. Age, secondary infertility, infertility duration (≥3 years), advanced r-AFS stage, cyst diameter (≥3cm), and EFI score (<7) were key risk factors. The EFI score's AUC for predicting pregnancy was 0.731 (95%CI, 0.617-0.844), with 72.58% sensitivity and 75.83% specificity. No significant difference in follow-up duration was observed between the groups.

Age, secondary infertility, infertility duration (≥ 3 years), r-AFS stage (stages III and IV), cyst diameter (≥ 3cm), and EFI score (< 7) were identified as risk factors for infertility in patients with ovarian endometriosis following a two-phase staged oral administration of traditional Chinese medicine. Among these factors, the EFI score can serve as a crucial evaluation index for postoperative pregnancy, assessing the likelihood of pregnancy and predicting patient prognosis.

We report a case of a 58-year-old male patient with an extrapleural solitary fibrous tumor (SFT) arising in the soft tissues surrounding the right elbow joint, which is a highly unusual anatomical location. The lesion exhibited slow, progressive growth over the years and was associated with intermittent neurological symptoms. Surgical excision was performed due to tumor growth and progressive neurological deficits to relieve discomfort and prevent further neural damage. Imaging demonstrated a well-circumscribed soft tissue mass, and complete surgical excision was undertaken. Histopathological evaluation revealed a well-circumscribed, encapsulated tumor measuring 5×4.8×3.5 cm with fibrous areas. Immunohistochemical staining showed strong positivity for Cluster of Differentiation (CD)34 and CD99, consistent with the diagnosis of SFT. This case highlights the necessity of including SFT in the differential diagnosis of slow-growing soft tissue masses in various, often atypical locations. Taking into account the potential for local recurrence and malignant transformation, long-term surveillance after resection is recommended, even in histologically benign cases.