The introduction of immune checkpoint inhibitor (ICI) based therapies has significantly improved the prognosis of patients with unresectable hepatocellular carcinoma (HCC). However, the variable treatment response and the uncertain benefit in patients with advanced liver cirrhosis emphasise the urgent need for prognostic and predictive biomarkers guiding patient selection. The soluble urokinase plasminogen activator receptor (suPAR) is strongly associated with inflammation, liver cirrhosis and various types of cancer. In this study, we investigated suPAR as a potential novel biomarker in patients with unresectable HCC.

This multicenter retrospective study, conducted at three German tertiary care centers, included 90 patients with unresectable HCC and suPAR measurements prior to and during atezolizumab/bevacizumab therapy. Patients with liver cirrhosis without HCC (n = 235) and non-cirrhotic patients with other gastrointestinal tumours (n = 155) were selected as control cohorts.

Median suPAR levels were significantly higher in patients with liver cirrhosis compared to non-cirrhotic cancer patients. A strong association with parameters of liver function, but not with HCC characteristics, was observed. In patients with HCC receiving atezolizumab/bevacizumab, suPAR was the most accurate independent predictor of hepatic decompensation and overall survival (OS). In addition, suPAR was able to stratify the risk of hepatic decompensation within the different Child-Pugh classes.

SuPAR represents a promising novel biomarker in patients with HCC treated with ICI-based therapies and bears the potential to guide the selection of antitumoral systemic therapies in patients with advanced liver cirrhosis.

This systematic review and meta-analysis evaluated the effectiveness and the safety of transarterial radioembolization using Holmium-166 microspheres (Ho-166-TARE) for the treatment of primary and secondary liver tumors. The aim of the study was to offer a detailed analysis of clinical outcomes and the potential benefits of this innovative therapy.

The study was conducted according to the PRISMA 2020 guidelines. The systematic search was performed in five databases in November 2023 and updated in June 2024. All 16 eligible studies were original research that evaluated Ho-166-TARE. The endpoints analyzed were disease control rate (DCR), overall survival (OS), progression-free survival (PFS), clinical and laboratory adverse events, healthy-liver- and tumor-liver-absorbed doses. The risk of bias was assessed using the MINORS checklist.

The pooled overall disease control rate (DCR) was 72% (95% CI, 46-89%); by mRECIST, it was 93% (95% CI, 71-99%); and by RECIST 1.1, it was 54% (95% CI, 22-83%) at 3-month follow-up. Overall survival (OS) at 3, 6, 12, and 30 months was 98%, 89%, 74%, and 39%, respectively. Severe clinical adverse events were minimal, although some patients showed elevated GGT levels and lymphocytopenia. Tumor-absorbed doses were nearly three times higher than those in healthy liver tissue.

These findings suggest that Ho-166-TARE is a safe and effective locoregional treatment option for liver tumors, especially in cases where systemic therapy alone is insufficient or surgical resection is not feasible. Further studies are needed to investigate tumor-specific response, optimize dosimetry strategies, and establish standardized protocols for long-term outcome assessment.

This study aimed to evaluate the efficacy of durvalumab + tremelimumab (Dur + Tre) in real-world clinical practice, characterize "stable disease (SD)," and identify SD responders (SD-R) who benefit from Dur + Tre treatment.

This multicenter observational study included 212 patients with unresectable hepatocellular carcinoma (u-HCC) treated with Dur + Tre between March 2023 and November 2024. The patients were categorized into 95 first-line and 117 later-line cases, respectively. Sequential cutoff points for depth of response (DOR) and progression-free survival (PFS) were tested to identify subgroups with survival outcomes comparable to those of responders.

Disease control rate (DCR) and PFS were significantly better in the first-line setting for both response evaluation criteria in solid tumors (RECIST) and modified RECIST (mRECIST) criteria. Patients who achieved PFS of ≥84 days or RECIST DOR of ≤-10% were classified as SD-R, as they had long-term survival outcomes similar to those with PR or CR. Furthermore, the CR + PR + SD-R group had significantly better survival outcomes than the other groups (p < 0.01), and multivariate analysis confirmed that SD-R was an independent prognostic factor with the strongest impact on survival outcomes (hazard ratio = 0.11).

In real-world clinical practice, Dur + Tre is highly effective as a first-line treatment for u-HCC. Additionally, patients with SD who met the SD-R criteria (PFS ≥84 days or RECIST DOR ≤-10%) showed survival outcomes comparable to those of patients with PR or CR. These findings may help identify patients who are most likely to benefit from treatment and improve their prognoses.

Immunotherapy has transformed rectal cancer treatment but poses risks of immune-related adverse events (irAEs), particularly in elderly patients who exhibit immunosenescence and inflammaging. This study compares the incidence and severity of irAEs in elderly and young rectal cancer patients receiving immunotherapy and identifies predictive biomarkers for these events.

We retrospectively analyzed 405 rectal cancer patients treated with immunotherapy from January 2015 to December 2023. Patients were categorized into younger (< 60 years) and older (≥ 60 years) groups. Incidence and severity of irAEs were assessed using the Common Terminology Criteria for Adverse Events (CTCAE) standards. Blood samples were analyzed for hematological and immunological markers.

The older group displayed a significantly higher incidence of irAEs at 48.65% compared to 32.11% in the younger group (P = 0.003). Severity varied, with 69.72% of younger patients experiencing irAEs of grade ≤ 2 versus 51.69% in the older group (P = 0.001). Notably, higher absolute lymphocyte count (ALC), interleukin-6 (IL-6), and C-reactive protein (CRP) levels were associated with increased irAEs (P = 0.002, P = 0.001, P = 0.007, respectively). The multivariate analysis identified ALC, IL-6, CRP, B and T Lymphocyte Attenuator, Human Granulocyte-macrophage Colony Stimulating Factor, Programmed Death-1 and Programmed Death-Ligand 1 as significant predictors of irAEs, with ALC showing an odds ratio (OR) of 9.700 (P = 0.001) and IL-6 an OR of 58.961 (P < 0.001). Furthermore, the platelet-to-lymphocyte ratio (PLR) inversely correlated with irAEs (P = 0.013).

Older rectal cancer patients receiving immunotherapy were at increased risk for both greater incidence and severity of irAEs. Specific biomarkers, such as ALC and IL-6, were associated with a heightened risk of these events.

To retrospectively analyze the safety and efficacy of intra-arterial chemoperfusion (IAC) for symptomatic patients with recurrent or post-therapeutic progressive primary malignant brain tumors in regard to safety, survival and therapy response as a palliative treatment.

Thirty-nine patients (24 men, 15 women; mean age: 52) who were treated by IAC in 181 sessions (mean: 4.6 sessions/patient) were enrolled and evaluated in this study. Out of total 39 patients with primary malignant brain tumor, 27 (69 %) were diagnosed with glioblastoma. The overall survival (OS) was calculated using the Kaplan-Meier method. Therapy response was determined according to RECIST 1.1.

All IAC treatments were performed without major adverse events or treatment-related deaths. The median OS time was 10.3 months (95 %CI: 0.6 - 19.9). The median PFS time was 5.9 months (95 %CI: 3.6 - 8.3). The rate of partial response was 10.8 % (4/37) and stable disease was achieved in 56.8 % (21/37) of patients. Progressive disease was observed in 32.4 % of cases (12/37). There were no cases of complete response. In two cases RECIST could not be analyzed due to loss of radiological follow-up.

This study could show that IAC may serve as a safe palliative strategy for symptomatic patients with recurrent or post-therapeutic progressive primary malignant brain tumors.

To assess the oncologic outcomes in patients with oral squamous cell carcinoma (SCC) who underwent treatment with radiotherapy (RT) or chemoradiation therapy (CRT) following neoadjuvant immunochemotherapy and surgery.

Data from patients who underwent neoadjuvant immunochemotherapy, surgery, and adjuvant therapy were collected prospectively and analyzed retrospectively. The primary outcomes assessed were 3-year overall survival and locoregional control. Secondary endpoints included the objective response rate (ORR), rates of pathologic complete response (pCR) and major pathologic response (MPR), as well as safety.

A total of 137 patients were included in the analysis. Neoadjuvant therapy yielded an ORR of 81.7%, with pCR and MPR achieved in 47 and 73 patients, respectively. Grade III and IV adverse events were rare, comprising only 1.6% of all events. The addition of adjuvant chemotherapy to RT did not show a significant reduction in the risk of locoregional recurrence. However, with regards to overall survival, the hazard ratios were 0.85 (95% CI: 0.73-0.96) for the MPR group and 0.66 (95% CI: 0.37-0.89) for the pCR group, both significantly higher than that in patients with incomplete pathologic response. The addition of adjuvant chemotherapy to RT was associated with a 5% reduction in the risk of mortality (95% CI: 1%-14%), the protective effect of CRT was the most obvious in patients with MPR.

Neoadjuvant immunochemotherapy demonstrated high safety and efficacy in oral SCC. CRT was superior to RT in terms of overall survival especially in patients with MPR when administered following neoadjuvant immunochemotherapy and surgery.

IMBrave 150 established atezolizumab and bevacizumab as the new standard for advanced hepatocellular carcinoma (HCC) treatment. However, the trial reported significant adverse events leading to bevacizumab dose interruptions or discontinuations. This retrospective, real-world analysis evaluated the effect of reduced bevacizumab dose intensity on clinical outcomes in 354 patients receiving first-line combination immunotherapy for advanced HCC. To minimize immortal time bias, only those on therapy for over 3 months were included. Of 219 patients included in the landmark analysis, 52 received a reduced dose intensity of bevacizumab. The median relative dose intensity (RDTI) of bevacizumab was 75% (range 9.1-96.9%). There was no significant difference in progression-free survival (11.2 vs. 14.8 months, p = 0.5) or overall survival (20.4 vs. 26.8 months, p = 0.1) between those receiving 100% vs. reduced RDTI. Exploratory analysis showed that even doses under 75% had no survival impact. Treatment-related grade 3/4 adverse events occurred more frequently with RDTI (30.7% vs. 15.5%). Reduced bevacizumab doses do not impact survival.

Lung neuroendocrine neoplasms (NENs) represent about 20% of all lung cancers. Few therapeutic options are available for atypical carcinoids (ACs). Single-agent temozolomide (TEM) is active in lung NENs, but whether the addition of capecitabine (CAPTEM) is associated with improved outcomes, is unknown. We sought to investigate the TEM-based therapies (TEM or CAPTEM) in patients with advanced AC.

This was a retrospective analysis of prospectively collected data from patients with AC of the lung referred to our institution from January 2003 to January 2023 who have received chemotherapy with either TEM or CAPTEM as any line treatment. Primary endpoint was progression free survival (PFS), secondary endpoints included overall response rate (ORR) and overall survival (OS).

In this study we included 31 patients with advanced AC. Median Ki-67 was 14.4% (3-30). CAPTEM in 17 patients (54.8%), while TEM was administered in 14 patients (45.2%). Overall, ORR was 39% (N = 12/31, all partial responses), while median PFS and OS were 57.4 months (95%CI: 43.2-71.7) and 24.4 months (95% confidence interval [95%CI]: 14.7-34.1). Median PFS was 33.9 months (15.6-52.1) in the CAPTEM group, while it was 15.5 (7.3-23.8) in the TEM group (p = 0.047). When adjusting for potential confounding factors, treatment with TEM vs CAPTEM retained its independent association with an increased risk of progression (HR: 4.01 [95%CI: 1.18-13.68]; p = 0.027).

Treatment with CAPTEM is associated with longer PFS than TEM alone in patients with AC. Prospective studies with larger sample size are needed to validate this finding.

The BALAD model, a scoring system for staging hepatocellular carcinoma (HCC), is based on five serum markers: bilirubin, albumin, lens culinaris agglutinin-reactive alpha-fetoprotein [AFP], AFP, and des-gamma-carboxy prothrombin. It has shown good ability to predict survival in patients with HCC irrespective of stage and treatment, a high BALAD value being associated with a poor prognosis. However, its prognostic significance is unclear in patients with advanced unresectable HCC (uHCC) who undergo systemic therapies. We assessed the prognostic ability of BALAD in this subpopulation.

In a multicenter cohort of 1,510 patients with advanced uHCC treated with first-line systemic therapies, the baseline BALAD score was calculated on the basis of pretreatment serum levels. Overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and disease control rate (DCR) were calculated and related to the BALAD score.

In all, 502 patients were treated with sorafenib, 435 with lenvatinib, and 573 with atezolizumab plus bevacizumab. Irrespective of treatment regimen, OS, PFS, ORR, and DCR were all independently negatively correlated with the BALAD score. The beneficial effects of specific systemic therapy regimens differed according to the BALAD score.

The BALAD score had good prognostic ability for predicting OS and PFS in patients with advanced uHCC who underwent systemic therapies and was associated with treatment response. Application of the BALAD score offers increased precision in the prediction of outcome both for individual patients and for specific subgroups of patients with HCC.

Breast cancer is one of the most prevalent cancers and has emerged as a major global challenge. Circulating tumor DNA (ctDNA), a liquid biopsy method, overcomes the accessibility limitations of tissue-based testing and is widely used for monitoring minimal residual disease and molecular relapse, predicting prognosis, evaluating the response of neoadjuvant therapy, and optimizing treatment decisions in non-metastatic breast cancer. However, the application of ctDNA still faces many challenges. Here, we survey the clinical applications of ctDNA in non-metastatic breast cancer and discuss the significant biological and technical challenges of utilizing ctDNA. Importantly, we investigate potential avenues for addressing the challenges. In addition, emerging technologies, including fragmentomics detection, methylation sequencing, and long-read sequencing, have clinical potential and could be a future direction. Proper utilization of machine learning facilitates the identification of meaningful patterns from complex fragment and methylation profiles of ctDNA. There is still a lack of clinical trials focused on the subsets of ctDNA (e.g., circulating mitochondrial DNA), ctDNA-inferred drug-resistant clonal evolution, tumor heterogeneity, and ctDNA-guided clinical decision-making in non-metastatic breast cancer. Due to regional differences in the number of registered clinical trials, it is essential to enhance communication and foster global collaboration to advance the field.

In cancer therapy, enhancing therapeutic indices and patient compliance has been a central focus in recent drug delivery technology development. However, achieving a delicate balance between improving anti-tumor efficacy and minimizing toxicity to normal tissues remains a significant challenge. With the advent of smart on-demand drug release strategies, new opportunities have emerged. These strategies represent a promising approach to drug delivery, enabling precise control over the release of therapeutic agents in a programmed and spatiotemporal manner. Recent studies have focused on designing delivery systems capable of releasing multiple therapeutic agents sequentially, while achieving spatial resolution in vivo. Smart on-demand drug release strategies have demonstrated considerable potential in tumor combination therapy for achieving precision drug delivery and controlled release by responding to specific physiological signals or external physical stimuli in the tumor microenvironment. These strategies not only improve tumor targeting and reduce toxicity to healthy tissues but also enable sequential release in combination therapy, allowing multiple drugs to be released in a specific spatiotemporal order to enhance synergistic treatment effects. In this paper, we systematically reviewed the current research progress of smart on-demand drug release drug delivery strategies in anti-tumor combination therapy. We highlighted representative integrated drug delivery systems and discussed the challenges associated with their clinical application. Additionally, potential future research directions are proposed to further advance this promising field.

Liposomal irinotecan + fluorouracil/leucovorin (nal-IRI + 5FU/LV) is commonly used as a second- or later-line treatment for pancreatic ductal adenocarcinoma (PDAC) and offers survival benefits. However, its efficacy and safety in patients previously treated with FOLFIRINOX, which includes irinotecan, remain unclear. We evaluated the efficacy and safety of nal-IRI + 5FU/LV in patients with unresectable PDAC who received previous FOLFIRINOX therapy and those who did not.

This retrospective observational study included 42 patients with PDAC who were treated with nal-IRI + 5FU/LV (October 2020-November 2023). Patients were grouped based on prior FOLFIRINOX treatment.

The progression-free survival (PFS) in patients who previously received modified FOLFIRINOX (mFFX) therapy was shorter than that in patients who did not (2.5 vs. 3.5 months, P = 0.07). When patients with greater than- and less than the cut-off value of irinotecan-free interval (IFI) were classified into the long and short IFI groups, respectively, PFS was significantly longer in the long-IFI group than that in the short IFI group (4.0 vs. 2.1 months, P = 0.01). Moreover, the C-reactive protein/albumin ratio (CAR) was also a significant predictor of PFS (P = 0.03). Furthermore, both factors were found to be independent factors influencing PFS in the univariate Cox regression analysis (P = 0.02 and P = 0.04).

Nal-IRI + 5FU/LV therapy may be a safe and effective option as a second- or later-line treatment, particularly for patients who have not previously received mFFX therapy. For patients who received prior mFFX exposure, a longer IFI and lower CAR may indicate greater potential benefit, thus aiding in more personalized treatment approaches.

Background and Objectives: Conversion surgery for liver metastatic colorectal cancer (mCRC) has been associated with prolonged survival. This study aimed to evaluate the efficacy and safety of integrating biological therapies with fluorouracil-based induction chemotherapy in patients with isolated liver mCRC who subsequently underwent curative resection of both the primary tumor and liver metastases. Materials and Methods: This multicenter, retrospective study, conducted by the Turkish Oncology Group (TOG), included 116 patients from 11 tertiary centers who underwent conversion surgery following induction chemotherapy between 2009 and 2024. Results: The median age was 57 years, with 62% male patients. The median follow-up period was 55.3 months. The median progression-free survival (PFS) and overall survival (OS) were 21.1 and 53.7 months, respectively. No significant differences in PFS or OS were observed based on biological therapy use or tumor localization. Among patients with RAS/RAF wild-type tumors, PFS and OS were comparable between those receiving Anti-EGFR and Anti-VEGF therapy. In RAS/RAF mutant tumors, the addition of Anti-VEGF therapy did not confer a survival benefit. Factors associated with shorter PFS included advanced tumor stage (ypT3-T4), lymph node metastasis, and multiple metastases, while shorter OS was linked to advanced tumor stage and lack of objective response. Conclusions: Surgical resection plays a pivotal role in improving survival outcomes in patients with potentially resectable liver mCRC. Optimizing induction chemotherapy regimens may enhance conversion rates and prolong long-term survival. Further studies are needed to refine treatment selection based on tumor localization, mutation status, and molecular biomarkers.

Despite increasing utilization of CAR T-cell therapy, data are lacking regarding long term follow up and risk of infectious complications after the early period following CAR T-cell infusion. In this study, we sought to compare epidemiology and risk factors for early (≤ 3 months) and late (3 months to 1 year) infections. Data were retrospectively collected at six time points: pre-CAR T, day of infusion, and at 3, 6, 9, and 12 months post CAR-T infusion for all consecutive adult patients treated at our institution. In this cohort, the cumulative incidence of any infection was 73.2% in the first year. Bridging therapy, CRS, neurotoxicity and steroid use were identified as contributing risk factors for early bacterial infections. After 3 months, community acquired respiratory infections were common. We characterize bacterial, viral and fungal pathogens based on time elapsed after CAR T-cell infusion.

Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality worldwide. ALK gene rearrangement has been identified in 3 % to 5 % of the patients with NSCLC. Thanks to the advancements in second-generation sequencing technology, an increasing number of novel fusion partners have been identified. In our research, we discovered a rare ALK fusion, TTC7A-ALK, in a patient with advanced lung adenocarcinoma using targeted next-generation sequencing (NGS). After being diagnosed with advanced lung adenocarcinoma with TTC7A-ALK fusion, the patient received crizotinib treatment and achieved a progression-free survival of 29 months. Additonanlly, we conducted further functional analyses on this fusion protein to assess its oncogenic potential. Similar to EML4-ALK, the TTC7A-ALK fusion protein can promote the growth of Ba/F3 cells under IL-3-independent conditions in vitro. In vivo studies demonstrate that the TTC7A-ALK fusion protein could enhance the tumorigenesis of NIH3T3 cells in nude mice, which can be suppressed by crizotinib. Mechanistic studies indicated that the ectopic expression of TTC7A-ALK in 293T cells led to the hyperactivation of downstream MAPK and PI3K/Akt pathways, which can be inhibited by crizotinib. Furthermore, upon tumor progression, the patient transitioned to alectinib, which provided rapid symptom relief and controlled the majority of lesions. Conclusionly, we identified and validated TTC7A-ALK as a oncogenic fusion in NSCLC. The patient demonstrated a significant clinical benefit from sequential treatment with crizotinib and alectinib, highlighting TTC7A-ALK as a novel therapeutic target for ALK inhibitors. These findings extend the spectrum of actionable ALK fusions and promote the inclusion of rare fusion detection in clinical diagnostic processes and treatment strategies.

Structured reporting enhances comparability, readability, and content detail. Large language models (LLMs) could convert free text into structured data without disrupting radiologists' reporting workflow. This study evaluated an on-premise, privacy-preserving LLM for automatically structuring free-text radiology reports.

We developed an approach to controlling the LLM output, ensuring the validity and completeness of structured reports produced by a locally hosted Llama-2-70B-chat model. A dataset with de-identified narrative chest radiograph (CXR) reports was compiled retrospectively. It included 202 English reports from a publicly available MIMIC-CXR dataset and 197 German reports from our university hospital. Senior radiologist prepared a detailed, fully structured reporting template with 48 question-answer pairs. All reports were independently structured by the LLM and two human readers. Bayesian inference (Markov chain Monte Carlo sampling) was used to estimate the distributions of Matthews correlation coefficient (MCC), with [-0.05, 0.05] as the region of practical equivalence (ROPE).

The LLM generated valid structured reports in all cases, achieving an average MCC of 0.75 (94% HDI: 0.70-0.80) and F1 score of 0.70 (0.70-0.80) for English, and 0.66 (0.62-0.70) and 0.68 (0.64-0.72) for German reports, respectively. The MCC differences between LLM and humans were within ROPE for both languages: 0.01 (-0.05 to 0.07), 0.01 (-0.05 to 0.07) for English, and -0.01 (-0.07 to 0.05), 0.00 (-0.06 to 0.06) for German, indicating approximately comparable performance.

Locally hosted, open-source LLMs can automatically structure free-text radiology reports with approximately human accuracy. However, the understanding of semantics varied across languages and imaging findings.

Question Why has structured reporting not been widely adopted in radiology despite clear benefits and how can we improve this? Findings A locally hosted large language model successfully structured narrative reports, showing variation between languages and findings. Critical relevance Structured reporting provides many benefits, but its integration into the clinical routine is limited. Automating the extraction of structured information from radiology reports enables the capture of structured data while allowing the radiologist to maintain their reporting workflow.

Whether patients with advanced non-small cell lung cancer (NSCLC) who experience progressive disease (PD) after the initial immunotherapy treatment benefit from subsequent immunotherapy remains unclear. In this study, we aimed to identify predictive factors and develop a nomogram to predict successful immunotherapy rechallenge for such patients with NSCLC to guide clinical treatment and improve prognosis.

Between January 2019 and December 2022, 352 patients with advanced NSCLC who received immunotherapy rechallenge after experiencing PD were divided into the training (n=246) and validation (n=106) cohorts. Clinicopathological factors and radiomics features were included in the univariate and multivariate analyses, with significant predictive factors being used to develop the nomogram.

Univariate and multivariate analyses showed that time from the initial immunotherapy to PD occurrence (duration), clinical N stage, liver metastasis, treatment after PD following the first immunotherapy (post-PD treatment), and radiomics features were independent predictive factors for progression-free survival (PFS). In addition, age, duration, clinical N stage, post-PD treatment, and radiomics were independent predictive factors for overall survival (OS). Accordingly, these predictive factors were used to develop a nomogram. The area under the curves (AUCs) of the nomogram for predicting 6-, 12-, and 18-month PFS and 12-, 18-, and 24-month OS were 0.731, 0.809, 0.878, 0.742, 0.782, and 0.868, respectively, in the training cohorts, whereas the corresponding values in the validation cohort were 0.672, 0.774, 0.826, 0.833, 0.705, and 0.762. This indicated good discrimination.

We developed and validated a predictive nomogram based on clinicopathological factors and radiomics features for the prognosis of patients with advanced NSCLC who received immunotherapy rechallenge following PD after the first immunotherapy. The nomogram showed strong predictive utility and can be a suitable tool for such patients with advanced NSCLC.

Prognostic prediction plays a pivotal role in guiding personalized treatment for patients with locoregionally advanced nasopharyngeal carcinoma (LANPC). However, few studies have investigated the incremental value of functional MRI to the conventional MRI-based radiomic models. Here, we aimed to develop a radiomic model including functional MRI to predict the prognosis of LANPC patients.

One hundred and twenty-six patients (training dataset, n = 88; validation dataset, n = 38) with LANPC were retrospectively included. Radiomic features were extracted from T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), contrast-enhanced T1WI (cT1WI), and diffusion-weighted imaging (DWI). Pearson correlation analysis and recursive feature elimination or Relief were used for identifying features associated with progression-free survival (PFS). Five machine learning algorithms with cross-validation were compared to develop the optimal single-layer and fusion radiomic models. Clinical and combined models were developed via multivariate Cox regression model.

The clinical model based on TNM stage achieved a C-index of 0.544 in the validation dataset. The fusion radiomic model, incorporating DWI-, T1WI-, and cT1WI-derived imaging features, yielded the highest C-index of 0.788, outperforming DWI-based (C-index = 0.739), T1WI-based (C-index = 0.734), cT1WI-based (C-index = 0.722), and T1WI plus cT1WI-based models (C-index = 0.747) in predicting PFS. The fusion radiomic model yielded the C-index of 0.786 and 0.690 in predicting distant metastasis-free survival and overall survival, respectively. However, the addition of TNM stage to the fusion radiomic model could not improve the predictive power.

The fusion radiomic model demonstrates favorable performance in predicting survival outcomes in LANPC patients, surpassing TNM staging alone. Integration of DWI-derived features into conventional MRI radiomic models could enhance predictive accuracy.

Advanced esophageal cancer presents significant treatment challenges, especially after immunochemotherapy failure. This study evaluates the efficacy of further treatment with combination chemotherapy versus combination immunotherapy crossover in terms of tumor regression, quality of life, and identifies factors influencing treatment outcomes.

In a retrospective case-control study, clinical data from 293 patients with advanced esophageal cancer treated at Shanxi Province Cancer Hospital between February 2021 and February 2023 were analyzed. Patients excluded from radical resection due to failure of first-line immunotherapy were divided into two groups: 95 received combination chemotherapy with Irinotecan and Tigio (S-1, Tegafur/Gimeracil/Oteracil Potassium), and 198 underwent Anlotinib targeted therapy combined with immunotherapy crossover. Treatment efficacy was assessed using tumor regression grading (TRG), and quality of life was evaluated using EORTC QLQ-C30 and QLQ-OES18 scales. Potential factors affecting treatment efficacy were examined using multivariate logistic regression analysis.

Baseline characteristics, including age, gender, body mass index (BMI), and history of smoking and alcohol consumption, were comparable between the two groups. TRG showed no significant differences in distribution, with objective response rates of 40% in the Irinotecan/S-1 group and 44.44% in the combined immunotherapy crossover group (P = 0.472). However, quality of life measures indicated superior outcomes from immunotherapy crossover in physical (P = 0.024), emotional (P = 0.002), and general health scores (P = 0.003). Factors negatively impacting treatment success included male gender, smoking, alcohol consumption history, and certain tumor locations. Elevated CEA levels positively correlated with treatment efficacy. Logistic regression analysis identified male gender (OR, 2.109; P = 0.021), smoking (OR, 2.575; P = 0.003), alcohol consumption (OR, 1.995; P = 0.043), and CEA levels (OR, 0.742; P = 0.017) as significant predictors of treatment efficacy.

Immunotherapy combined with targeted therapy and chemotherapy alone showed comparable efficacy in tumor regression. However, immunotherapy combined with targeted therapy improved certain aspects of quality of life. Factors such as gender, lifestyle habits, and CEA levels can significantly influence treatment outcomes.

Immune checkpoint blockade (ICB)-based immunotherapy has significantly improved survival in advanced melanoma. However, many patients exhibit resistance to these therapies. This study examines the impact of BTLA promoter methylation on its expression, immune cell infiltration, and clinical outcomes, evaluating its potential as a prognostic and predictive biomarker for immunotherapy response.

We analyzed methylation and gene expression data from public datasets (The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO)) and an in-house cohort of melanoma patients treated with ICB therapy at the First Affiliated Hospital of Zhengzhou University. We developed a quantitative methylation-specific PCR (qMSP) assay to measure methylation levels of the cg24157392 and cg03995631 CpG sites, and a targeted bisulfite sequencing assay was used to validate the accuracy of qMSP. We measured BTLA protein expression using multiplex immunofluorescence and immunohistochemical staining methods. Pearson correlation, survival analysis, and immune cell infiltration estimation were conducted to explore the associations between BTLA promoter methylation, mRNA and protein expression, clinical outcomes, and immune characteristics.

Hypomethylation at CpG sites cg24157392 and cg03995631 in the BTLA promoter were significantly associated with higher BTLA mRNA and protein expression. In the TCGA dataset, low methylation at these sites predicted longer overall survival and was validated in an independent cohort of 50 stage III/IV melanoma patients, with an area under the curve of 0.94 for predicting 5-year survival. Furthermore, BTLA promoter hypomethylation correlated with higher infiltration of immune cells, such as CD8+T cells, CD4+T cells, B cells, and macrophages. Additionally, low methylation at cg24157392 and cg03995631, as quantified by the qMSP assay, was significantly associated with better progression-free survival in patients treated with immune checkpoint inhibitors. These findings were further validated using GEO datasets.

BTLA promoter hypomethylation serves as a significant biomarker for favorable prognosis and enhanced response to ICB therapy in melanoma. The developed qMSP assays for cg24157392 and cg03995631 accurately quantified methylation levels and demonstrated their potential for clinical application in patient stratification and personalized immunotherapy.

Tarlatamab, a novel bispecific T-cell engager, has demonstrated unprecedented efficacy in patients with small cell lung cancer. However, there is no known mechanism of resistance to tarlatamab. This study suggests that a transcriptional expression shift might be associated with acquired resistance to tarlatamab.

Circulating tumour DNA (ctDNA) represents an increasingly important biomarker for the screening, diagnosis and management of patients in clinical practice in advanced/metastatic disease across multiple cancer types. In this context, ctDNA-based comprehensive genomic profiling is now available for patient management decisions, and several ctDNA-based companion diagnostic assays have been approved by regulatory agencies. However, although the assessment of ctDNA levels in Phase II-III drug development is now gathering momentum, it remains somewhat surprisingly limited in the early Phase I phases in light of the potential opportunities provided by such analysis. In this perspective review, we investigate the potential and hurdles of applying ctDNA testing for the inclusion and monitoring of patients in phase 1 clinical trials. This will enable more informed decisions regarding patient inclusion, dose optimization, and proof-of-mechanism of drug biological activity and molecular response, thereby supporting the evolving oncology drug development paradigm. Furthermore, we will highlight the use of cost-efficient, agnostic genome-wide techniques (such as low-pass whole genome sequencing and fragmentomics) and methylation-based methods to facilitate a more systematic integration of ctDNA in early clinical trial settings.

Cyclin-dependent kinase inhibitor 2A/2B (CDKN2A/2B) deletions are frequently identified in patients with biliary tract cancer; however, standard treatment options for this genetic alteration are lacking. Here, we present the case of a 64-year-old woman diagnosed with intrahepatic cholangiocarcinoma and hilar lymph node metastasis who underwent radical surgery. Postoperative pathology confirmed moderately differentiated adenocarcinoma. The tumor recurred during the second cycle of adjuvant chemotherapy following surgery, and the metastatic sites included the cranial region, right lung, and right adrenal gland. Genetic analysis revealed a CDKN2A/2B deletion, indicating palbociclib sensitivity. Subsequently, the patient received palbociclib plus lenvatinib as systemic therapy, along with stereotactic radiotherapy for the intracranial lesion. Notably, the right pulmonary metastasis significantly regressed after 12 months of treatment, with the complete disappearance of the intracranial tumor. However, the disease progressed at 32.2 months, with significant enlargement of the right adrenal gland metastasis and new metastasis in the right lung. The progression-free survival and overall survival were 32.2 months and 34.4 months, respectively. In conclusion, our case demonstrates that palbociclib plus lenvatinib is a promising chemotherapy-free second-line treatment for intrahepatic cholangiocarcinoma with a CDKN2A/2B deletion.

Gallbladder cancer (GBC) is a refractory primary cancer. Some GBC patients are prone to recurrence even after surgical resection. In such cases, chemotherapy is the most common non-surgical treatment. The emergence of programmed cell death protein 1 (PD-1) inhibitors and targeted therapy have provided an additional option for those suffering from advanced tumors.

This was a retrospective study involving patients with advanced GBC treated at the Shanghai Eastern Hepatobiliary Surgery Hospital between June 2019 and June 2022. The patients who received a PD-1 inhibitor (tislelizumab) with chemotherapy or with lenvatinib were retrospectively analyzed. The Response Evaluation Criteria in Solid Tumors (RECIST 1.1) was used as the efficacy evaluation standard. The overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and tumor marker CA199 were evaluated.

This study involved 61 patients with advanced GBC. Of these, 32 patients received tislelizumab and GS (gemcitabine and TS-1) chemotherapy, whereas 29 patients received tislelizumab and lenvatinib. For the Tislelizumab plus GS chemotherapy group, the median OS and PFS were 19.64 ± 11.81 (95% CI: 16.47-25.20) and 15.44 ± 13.42 (95% CI: 12.08-22.25) months, respectively. For the lenvatinib group, the OS and PFS were 13.06 ± 9.41 (95% CI: 9.72-16.63) and 10.34 ± 10.03 (95% CI: 6.56-14.13) months, respectively. The ORR and DCR were 59.38% and 81.3%, respectively, for the Tislelizumab plus GS chemotherapy group, which were significantly longer than those for the Tislelizumab plus Lenvatinib group. Treatment-related adverse events were similar between the groups.

Tislelizumab combined with GS chemotherapy provides a safe and more efficient treatment option for advanced GBC patients.

Novel combinations are required to overcome resistance to immune checkpoint inhibitors in proficient mismatch repair (pMMR) or microsatellite-stable (MSS) metastatic colorectal cancer (mCRC). We aimed to determine whether vorbipiprant, a prostaglandin E2 receptor EP4 subtype antagonist, can convert immune-resistant mCRC into a tumor responsive to anti-PD-1 inhibition.

This phase Ib/IIa prospective, open-label, single-arm trial followed a 3 + 3 dose-escalation and dose-optimization design. A total of 28 patients with chemorefractory pMMR/MSS mCRC were given dose-escalated oral vorbipiprant (30, 90, or 180 mg twice daily), along with biweekly intravenous balstilimab (3 mg/kg), an anti-PD-1 antibody. The primary endpoints included safety and the disease control rate (DCR). Secondary endpoints were the overall response rate, duration of response, progression-free survival, and overall survival.

No dose-limiting toxicities were observed. Of the 28 patients, seven (25%) experienced serious adverse events, but only one was attributed to vorbipiprant and one to balstilimab. The trial achieved a DCR of 50% observed across the entire cohort. In the subgroup of patients with liver metastases (n = 12), the DCR was 25%. The overall response rate was 11%, with three patients showing a partial response (median duration of response, 7.4 months). The median progression-free survival was 2.6 months, and the median overall survival was 14.2 months. Translational exploratory analyses suggested that vorbipiprant may boost response to anti-PD-1 in patients with immunogenic tumors.

The combination of vorbipiprant and a PD-1 inhibitor (balstilimab) yielded sufficient activity in refractory pMMR/MSS mCRC, which is worthy of confirmation in future clinical trials in biomarker-enriched populations.

Aim: Small-cell lung cancer (SCLC) is usually diagnosed as an advanced stage with a poor outcome. SCLC has limited response to immunotherapy due to the absence or lack of immune cell infiltration, so studying its tumor immune microenvironment (TIME) is essential. Methods: The study involved patients with extensive-stage small-cell lung cancer (ES-SCLC) diagnosed at the Guangdong Lung Cancer Institute between January 2018 and April 2022 who had received the atezolizumab/carboplatin/etoposide (ECT) treatment. We used multi-immunohistochemistry (mIHC) to assess the prognostic value of YAP1 and TIME in SCLC, with results confirmed using public data. Results: 15 patients with sufficient baseline biopsy samples were included in this study. The total population of YAP1-positive cells is inversely related to progression-free survival (PFS) and shows a potential negative correlation with overall survival (OS). CD56-positive cells are the primary components of TIME in SCLC tumor parenchyma and stroma. The total population and cell density of YAP1-positive cells are significantly positively correlated with CD4-positive cells. Furthermore, in the tumor parenchyma, both the proportion and the cell density of YAP1-positive cells are positively correlated with that of FOXP3-positive cells. The total population of CD56-positive cells showed a negative correlation trend with YAP1-positive cells but without significant difference. Conclusion: YAP1 has shown prognostic value in SCLC patients receiving ECT regimen treatment. The high expression level of YAP1 seems related to the inhibitory TIME. However, some prospective studies with larger populations are warranted.

Hepatocellular carcinoma (HCC) is a prevalent malignancy worldwide, with portal vein tumor thrombosis (PVTT) worsening its prognosis and complicating management. The combination of transarterial chemoembolization (TACE) and the targeted agent sorafenib has been proposed to improve treatment outcomes. This study investigates the prognostic factors influencing the effectiveness of this combined treatment in HCC patients with PVTT.

A retrospective cohort study was conducted on 299 patients diagnosed with HCC and PVTT who underwent TACE and sorafenib treatment between January 2018 and December 2022. Patients were categorized into good-prognosis (n = 197) and poor-prognosis (n = 102) groups based on Response Evaluation Criteria in Solid Tumors (RECIST) assessed four weeks post-treatment. Prognostic factors were analyzed using univariate and multivariate analyses to identify significant determinants affecting therapeutic outcomes.

Key prognostic factors included tumor number, differentiation, size, PVTT extent, Child-Pugh class, ECOG performance status, hospitalization duration, and AFP levels. Patients with a single tumor had better outcomes (OR 0.358, P = 0.002), whereas poor differentiation (OR 4.561, P = 0.005) and larger tumor size (OR 0.347, P < 0.001) were associated with worse prognosis. A higher Child-Pugh class (OR 0.563, P = 0.035) and better ECOG performance (OR 2.710, P = 0.025) improved prognosis, while prolonged hospitalization and elevated AFP levels were linked to poorer outcomes. ASA classification and HCC morphology did not significantly impact prognosis.

The prognosis of HCC with PVTT treated with TACE and sorafenib is significantly influenced by tumor characteristics, liver function, and overall patient health. Identifying these factors can aid in refining personalized treatment strategies to improve survival outcomes.

Pancreatic neuroendocrine tumors (PNETs) are the leading cause of death related to multiple endocrine neoplasia type 1 (MEN1). Previous studies have linked certain mutations in the MEN1 gene and loss of interactions with MENIN's functional partners to the mortality or aggressiveness of PNETs. This study aimed to evaluate the genotype-phenotype correlations of MEN1-related PNETs in Korean patients and to summarize the treatment outcomes comprehensively.

We retrospectively analyzed 72 patients diagnosed with MEN1 at a tertiary care center in Korea between January 2003 and September 2022. MEN1 mutations were analyzed using direct or next-generation sequencing.

Among 40 families with MEN1, 10 had exon 2 mutations, which were the most frequently observed. Of these, 50 (69.4 %) were diagnosed with PNETs; 20 underwent pancreatic resection. Patients with truncating mutations showed a significant difference in age-related penetrance of PNET (p = 0.029). No distinct genotype was associated with malignant transformation (lymph node or distant metastasis) in MEN1-related PNETs. In the subgroup Cox model, mutations in exons 3 or 10 showed significant differences in tumor progression in the observation group (adjusted hazard ratio: 8.164,(95 % CI: 1.648-40.436), p = 0.010, HR: 8.300, (95 % CI: 1.808-38.113), p = 0.007).

PNETs in Korean patients with MEN1 exhibit a stable prognosis. An individualized follow-up strategy may be necessary, particularly for young patients with truncating mutation in the MEN1 gene. In addition, those with mutations in exons 3 or 10 may require more active surveillance to decrease the risk of progression.

To investigate whether multiparametric quantitative diffusion weighted magnetic resonance imaging (DWI) can effectively predict the neoadjuvant therapy (NAT) response in borderline resectable pancreatic ductal adenocarcinoma (BRPC).

The clinicopathological data, including tumor size, location, and CA19-9 values, as well as DWI parameters(ADC, D, and f values) from 72 patients with BRPC, were analyzed. The differences and changes in these factors before and after NAT were compared to identify those most accurately reflect the response to NAT. ROC analysis was used to evaluate the diagnostic efficacy, and Kaplan-Meier survival analysis explored the relationship between DWI parameters and prognosis. Subgroup survival analysis to further identify populations potentially benefiting from NAT based on multiparametric DWI.

After-NAT, the response group showed significantly higher ADC and D values and lower f values compared to the non-response group. The ΔADC (OR: 12.24, P = 0.013) emerged as the most important independent factor for tumor response, demonstrating the highest diagnostic accuracy for NAT response with an AUC of 0.936. Kaplan-Meier showed the high ADC value group, high D value group and low f value group were associated with better prognosis after NAT; and the ΔADC ≥ 0 group, ΔD ≥ 0 group, and Δf < 0 group was significantly associated with better prognosis. In addition, subgroup analysis suggested two groups of patients might potentially benefit from NAT.

Multiparametric quantitative DWI may offer valuable insights into the efficacy and prognosis of NAT in BRPC. These findings have the potential to support the evaluation and decision-making process for patients undergoing NAT.

Pancreatic cancer involving the pancreas neck and body often invades the retroperitoneal vessels, making its radical resection challenging. Multimodal treatment strategies, including neoadjuvant therapy, surgery, and postoperative adjuvant therapy, are contributing to a paradigm shift in the treatment of pancreatic cancer. This strategy is also promising in the treatment of pancreatic neck-body cancer.

To evaluate the feasibility and effectiveness of a multimodal strategy for the treatment of borderline/locally advanced pancreatic neck-body cancer.

From January 2019 to December 2021, we reviewed the demographic characteristics, neoadjuvant and adjuvant treatment data, intraoperative and postoperative variables, and follow-up outcomes of patients who underwent multimodal treatment for pancreatic neck-body cancer in a prospectively collected database of our hospital. This investigation was reported in line with the Preferred Reporting of Case Series in Surgery criteria.

A total of 11 patients with pancreatic neck-body cancer were included in this study, of whom 6 patients were borderline resectable and 5 were locally advanced. Through multidisciplinary team discussion, all patients received neoadjuvant therapy, of whom 8 (73%) patients achieved a partial response and 3 patients maintained stable disease. After multidisciplinary team reassessment, all patients underwent laparoscopic subtotal distal pancreatectomy and portal vein reconstruction and achieved R0 resection. Postoperatively, two patients (18%) developed ascites, and two patients (18%) developed pancreatic fistulae. The median length of stay of the patients was 11 days (range: 10-15 days). All patients received postoperative adjuvant therapy. During the follow-up, three patients experienced tumor recurrence, with a median disease-free survival time of 13.3 months and a median overall survival time of 20.5 months.

A multimodal treatment strategy combining neoadjuvant therapy, laparoscopic subtotal distal pancreatectomy, and adjuvant therapy is safe and feasible in patients with pancreatic neck-body cancer.

Bladder cancer is the 10th most common and 13th most deadly cancer worldwide, with urothelial carcinomas being the most common type. Distinguishing between non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC) is essential due to significant differences in management and prognosis. MRI may play an important diagnostic role in this setting. The Vesical Imaging Reporting and Data System (VI-RADS), a multiparametric MRI (mpMRI)-based consensus reporting platform, allows for standardized preoperative muscle invasion assessment in BCa with proven diagnostic accuracy. However, post-treatment assessment using VI-RADS is challenging because of anatomical changes, especially in the interpretation of the muscle layer. MRI techniques that provide tumor tissue physiological information, including diffusion-weighted (DW)- and dynamic contrast-enhanced (DCE)-MRI, combined with derived quantitative imaging biomarkers (QIBs), may potentially overcome the limitations of BCa evaluation when predominantly focusing on anatomic changes at MRI, particularly in the therapy response setting. Delta-radiomics, which encompasses the assessment of changes (Δ) in image features extracted from mpMRI data, has the potential to monitor treatment response. In comparison to the current Response Evaluation Criteria in Solid Tumors (RECIST), QIBs and mpMRI-based radiomics, in combination with artificial intelligence (AI)-based image analysis, may potentially allow for earlier identification of therapy-induced tumor changes. This review provides an update on the potential of QIBs and mpMRI-based radiomics and discusses the future applications of AI in BCa management, particularly in assessing treatment response. CRITICAL RELEVANCE STATEMENT: Incorporating mpMRI-based quantitative imaging biomarkers, radiomics, and artificial intelligence into bladder cancer management has the potential to enhance treatment response assessment and prognosis prediction. KEY POINTS: Quantitative imaging biomarkers (QIBs) from mpMRI and radiomics can outperform RECIST for bladder cancer treatments. AI improves mpMRI segmentation and enhances radiomics feature extraction effectively. Predictive models integrate imaging biomarkers and clinical data using AI tools. Multicenter studies with strict criteria validate radiomics and QIBs clinically. Consistent mpMRI and AI applications need reliable validation in clinical practice.

There are few studies on the efficacy of temozolomide (TMZ) in the treatment of Metastatic pheochromocytoma / paraganglioma (MPP) patients. And it remains unclear which MPP patients may benefit from TMZ treatment.

This was a prospective study. MPP patients were enrolled. Patients were treated with TMZ until disease progression or intolerable toxicities. The primary endpoints were disease control rate (DCR) and objective response rate (ORR). Secondary endpoints included biochemical response rate progression-free survival (PFS) and safety. We compared the difference between effective and ineffective groups, to explore which patients are more suitable for TMZ treatment.

62 patients with MPP were enrolled and tumor response were evaluated in 54 patients. The DCR was 83% (35/42), and the ORR was 24% (10/41) among the progressive patients. PFS was 25.2 ± 3.1 months. The most common adverse event was nausea (41/55). We found that 92.9% (13/14) of patients with MGMT methylation greater than 7% respond to treatment. For the patients with MGMT methylation less than 7%, Ki-67 index could be used to guide the use of TMZ in these patients. Among the patients with Ki-67 index less than 5%, 66% (8/12) patients showed respond to treatment, and only 33% (4/12) patients with Ki-67 index more than 5% showed respond to TMZ.

This study indicated that TMZ is a potential choice for the treatment of MPP with the high ability on disease control and well tolerability. We recommended to MGMT methylation analysis test and Ki-67 index to guide TMZ application.

Early indicators of metastatic cancer response to therapy are important for evaluating new drugs and stopping ineffective treatment. The RECIST guidelines based on repeat cancer imaging are widely adopted in clinical trials, are used to identify active regimens that may change practice, and contribute to regulatory approvals. However, these criteria do not provide insight before 6 to 12 weeks of treatment and typically require that patients have measurable disease. Recent data suggest that measuring on-treatment changes in the amount or proportion of ctDNA in peripheral blood plasma may accurately identify responding and nonresponding cancers at earlier time points. Over the past year, the RECIST working group has evaluated current evidence for plasma ctDNA kinetics as a treatment response biomarker in metastatic cancers and early endpoint in clinical trials to identify areas of focus for future research and validation. Here, we outline the requirement for large standardized trial datasets, greater scrutiny of optimal ctDNA collection time points and assay thresholds, and consideration of regulatory body guidelines and patient opinions. In particular, clinically meaningful changes in plasma ctDNA abundance are likely to differ by cancer type and therapy class and must be assessed before ctDNA can be considered a potential pan-cancer response evaluation biomarker. Despite the need for additional data, minimally invasive on-treatment ctDNA measurements hold promise to build upon existing response assessments such as RECIST and offer opportunities for developing novel early endpoints for modern clinical trials.