Pancreatic ductal adenocarcinoma (PDAC) ranks among the deadliest malignancies, with only 13% of patients surviving five years after diagnosis. This poor prognosis stems from late detection, treatment resistance, spatial and phenotypic heterogeneity, and a highly immunosuppressive tumor microenvironment. Unlike immunogenic cancers, PDAC is an immunologically 'cold' tumor, marked by minimal immune cell infiltration, defective antigen-presentation machinery, and stromal barriers. While immune checkpoint blockade (ICB) has shown success against various cancers, it has proven largely ineffective when used alone in PDAC. However, emerging research has identified promising new approaches, including neoantigen-targeted vaccines, stromal modulation, and combination therapies such as ICB with chemotherapy, cytokine blockade, and kinase inhibitors. The development of personalized immunotherapy approaches is being refined by predictive biomarkers that assess factors such as T cell infiltration levels, antigen-presenting capacity, and the spatial immune cell landscape. Here, we review the immune landscape of PDAC, current and emerging immunotherapeutic strategies, and highlight the critical role of biomarkers and immune profiling in appropriately categorizing patients. Collectively, these insights provide a foundation for designing rational combination therapies to transform PDAC into a cancer that is more immunologically responsive and amenable to therapy.

Patients with idiopathic inflammatory myopathies (IIM) are at increased risk of malignancy, particularly around disease onset, but practical tools for risk stratification of cancer-associated myositis (CAM) remain limited. We aimed to characterise CAM in Japanese patients with IIM and develop a clinically applicable risk-stratification model.

We conducted a multicentre retrospective study using the Japanese MYKO cohort, including patients diagnosed with IIM between 2001 and 2024. CAM was defined as malignancy diagnosed within ±3 years of IIM onset. Baseline demographic, clinical, laboratory, and autoantibody variables were compared between patients with and without CAM. Standardised incidence ratios (SIRs) were calculated using age-, sex-, and calendar year-specific cancer incidence rates from the Japanese general population. Random forest analysis and logistic regression were used to derive a CAM risk-stratification model. Overall survival and stage-specific survival were assessed using Kaplan-Meier analysis.

Among 364 patients with IIM, 42 (11.4%) had CAM. Most CAM cases occurred close to IIM onset, with 30 of 42 cases diagnosed within ±1 year. Compared with the general Japanese population, malignancy risk was increased within ±3 years of IIM onset (SIR 2.54, 95% CI 1.81-3.47) and was highest during the first year after onset (SIR 8.66, 95% CI 5.55-12.88). CAM was associated with older age at onset, male sex, smoking history, family history of malignancy, dermatomyositis subtype, dysphagia, elevated C-reactive protein (CRP) and anti-TIF1γ antibody positivity. Anti-TIF1γ positivity was the strongest predictor in random forest analysis. A five-factor model including anti-TIF1γ antibody positivity, elevated CRP, dermatomyositis subtype, older age at IIM onset, and family history of malignancy showed good discriminative performance (AUC 0.86; sensitivity 92.5%; specificity 65.1%). Five-year survival was lower in patients with CAM than in those without CAM (73.6% vs 94.6%) and was better in patients with early-stage than advanced-stage cancer (100% vs 44.0%).

In this multicentre Japanese IIM cohort, malignancies in patients with CAM were diagnosed mainly around IIM onset. A machine learning-derived five-factor model identified patients at increased risk of CAM. An earlier-stage cancer at diagnosis was associated with better survival, highlighting the clinical importance of timely cancer detection.

In papillary thyroid carcinoma (PTC) patients with suspected Hashimoto's thyroiditis (HT) indicated by elevated preoperative thyroglobulin antibodies (TgAb) and thyroid peroxidase antibodies (TPOAb), reactive lymphadenopathy can mimic metastatic disease on imaging. This overlap complicates preoperative cervical lymph node assessment and may lead to either unnecessary dissection or missed metastases. We aimed to develop and validate separate nomograms to predict central lymph node metastasis (CLNM) and lateral lymph node metastasis (LLNM) in PTC patients with concurrent HT.

We retrospectively enrolled 660 PTC patients with preoperatively confirmed HT who underwent thyroid surgery in Ward A of Ningbo No. 2 Hospital (training cohort). Independent predictors of CLNM and LLNM were identified using univariate analyses followed by multivariable logistic regression, and two nomograms were constructed. An independent cohort of 459 patients from Ward B served as an external validation set. Model discrimination, calibration, and clinical utility were assessed using the area under the receiver operating characteristic curve (AUC), calibration plots, and decision curve analysis (DCA), respectively.

For CLNM, age, calcification, capsular status, and maximum tumor diameter (MTD) were independent predictors. For LLNM, tumor margins, capsular status, and MTD were independent predictors. In the training cohort, the CLNM nomogram achieved an AUC of 0.760 and the LLNM nomogram an AUC of 0.864. Both models showed good calibration and favorable net benefit on DCA. External validation confirmed stable performance (AUC 0.726 for CLNM; 0.832 for LLNM).

We developed and externally validated two practical nomograms based on readily available preoperative clinical and ultrasonographic features to estimate CLNM and LLNM risk in PTC patients with concurrent HT. These tools may support preoperative risk stratification and help tailor the extent of neck dissection.

Iparomlimab and tuvonralimab (QL1706) is a MabPair product consisting of PD-1 and CTLA-4 monoclonal antibodies. This single-arm, multicenter, phase 2 study assessed the safety and efficacy of first-line QL1706 plus etoposide and carboplatin (EC) for extensive-stage small cell lung cancer (ES-SCLC).

Patients with ES-SCLC received QL1706 plus EC every 3 weeks for 4-6 cycles, followed by QL1706 maintenance therapy until disease progression. Primary endpoint was safety.

Among 40 patients enrolled, all patients experienced at least one treatment-related adverse event (TRAE). Most TRAEs were hematologic toxicities. Nine patients (22.5%) experienced immune-related adverse events, mostly grade 1-2, with a median time from treatment to the first irAE of 3.1 months (range 0.1-11.0) with a median duration of the irAEs of 1.3 months (range 0.1-10.7). Grade 3 irAEs occurred in 2 (5.0%) patients, one case each for rash and vomiting. No TRAEs leading to death or treatment discontinuation occurred. In 38 patients evaluable for efficacy, the confirmed objective response rate was 92.1% (95% confidence interval [CI] 78.6-98.3). Median progression-free survival (PFS) and overall survival (OS) were 6.0 months (95% CI 5.4-8.3) and 15.8 months (95% CI 11.4-20.0), respectively. In exploratory analyses, the median OS was 20.5 months (95% CI 11.4-not evaluable) in patients with a good lung immune prognostic index status and 19.7 months (95% CI 11.4-22.5) in patients with a combined positive score <1.

QL1706 plus EC was well-tolerated and showed promising anti-tumor activity and survival benefit in first-line treatment for ES-SCLC, and warranted further validation in larger scale phase 3 studies.

Hematologic neoplasms remain a growing global burden, with relapse, resistance, and limited treatment options persisting. Bispecific antibodies (BsAbs) offer a novel multi-antigen targeting strategy. This systematic review assesses their efficacy and safety, offering an in-depth appraisal of their therapeutic potential and the unmet medical needs.

We conducted this systematic review following the PRISMA 2020 guidelines. Articles published up to 20 June 2026 were searched across PubMed, Scopus, Web of Science, and Embase. Efficacy outcomes such as measurable residual disease (MRD), overall response rate (ORR), complete response (CR), overall survival (OS), and progression-free survival (PFS), as well as safety outcomes such as severe adverse events (SAEs), grade ≥3 adverse events (≥3 AEs), hematologic and non-hematologic toxicities were systematically evaluated.

Thirty-six studies evaluating nineteen different BsAbs were included. Blinatumomab (CD3-CD19) remains the most extensively studied bispecific antibody in relapsed or refractory B-cell precursor acute lymphoblastic leukemia (R/R BCP-ALL). CD3-CD20 BsAbs (Glofitamab, Epcoritamab) demonstrated durability in non-Hodgkin lymphoma (NHL). In multiple myeloma (MM), BCMA- and GPRC5D-targeting BsAbs achieved MRD negativity and deep responses including very good partial response (VGPR) and stringent complete response (sCR). BsAbs in acute myeloid leukemia (AML) and Hodgkin/T-cell lymphoma (HL/TCL) remained early-phase with limited efficacy and no approvals to date. Cytokine release syndrome (CRS) and neurotoxicity were the dominant toxicities of CD3-engaging agents (neurologic events >50% in several Blinatumomab studies). Teclistamab (CD3-BCMA) and Talquetamab (CD3-GPRC5D) were associated with frequent CRS, with neurotoxicity also reported. However, hematologic toxicity and infections remain major challenges in multiple myeloma treatment.

BsAbs demonstrate established clinical activity in BCP-ALL, B-cell NHL, and MM but remain under investigation in AML, HL, and T-cell lymphoma. CRS, neurotoxicity, cytopenias, and infections remain key safety considerations. Further studies should optimize treatment strategies and evaluate emerging targets and non-CD3-engaging bispecific antibodies.The protocol was prospectively registered in PROSPERO (CRD42023467556).

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023467556.

Many patients with advanced solid tumors ultimately develop resistance to conventional therapies, with especially limited options for those experiencing rapid progression or poor performance status, highlighting the need for personalized immunotherapies capable of inducing durable responses. In this retrospective case series, we describe the clinical course and outcomes of five adults (4 male, 1 female; median age 51 years [range, 39-62]) with metastatic solid tumors who achieved complete and durable remission following doubly loaded autologous dendritic cell therapy after failure of standard treatments, such as immune checkpoint inhibition, radiation, surgery, or endocrine therapy. Five patients, including prostate adenocarcinoma (n=1), malignant melanoma (n=2), triple-negative breast cancer (n=1), and urothelial carcinoma (n=1), were treated between July 2022 and March 2025 at a single-site referral-based immunotherapy center (Immunocine Cancer Center). Over the course of six weeks, patients received three vaccines of approximately 5-7 million modified dendritic cells injected adjacent to the lymph node draining to the tumor site. Follow-up ranged from 6 to 28 months, where radiographic response, clinical performance status, and tumor and available clinical and biological biomarkers were assessed. All five patients achieved complete radiographic remission confirmed by PET/CT or histology, with sustained responses ranging from 6 to 28 months and ongoing in all cases, and no grade 3 or higher adverse events observed. These observations support further evaluation of doubly-loaded autologous dendritic cell therapy in larger, controlled studies.

Older patients (aged ≥ 75 years) with advanced non-small cell lung cancer (NSCLC) receiving immunotherapy represent a growing but understudied population, yet few tools incorporate multidimensional host factors that influence prognosis. We therefore developed and externally validated a real-world prognostic model using bedside-available clinical variables, and compared its performance against conventional indices.

This multicenter retrospective study included patients aged ≥ 75 years with advanced NSCLC receiving first-line immunotherapy. Cox regression analyses were performed to identify potential survival-associated host variables. A composite model, based on clinically relevant candidate variables identified through univariate screening, was developed using endpoint-specific L2-penalized Cox regression and internally validated with 1,000 bootstrap resamples. The final model was externally validated in two independent cohorts. Model performance was assessed using Harrell's C-index, inverse probability of censoring-weighted (IPCW) cumulative/dynamic area under the curve (AUC), calibration, decision curve analysis, and Kaplan-Meier survival analysis with log-rank tests. The model was formally compared with conventional indices using paired bootstrap analyses.

A total of 241 patients were included, with 115 in the development cohort and 126 in the pooled external validation cohort. We developed the CALI (Comorbidity-Advanced Lung Cancer Inflammation Index) model integrating comorbidity burden (hypertension, diabetes, chronic obstructive pulmonary disease), recent weight loss, and inflammatory-nutritional status represented by ALI. In the development cohort, 1- and 2-year AUCs were 0.587 and 0.712 for overall survival (OS), 0.584 and 0.708 for progression-free survival (PFS), with significant stratification for OS (P = 0.013) and PFS (P = 0.021). In the pooled validation cohort, 1- and 2-year AUCs were 0.561 and 0.806 for OS, 0.553 and 0.793 for PFS, also significant stratification for OS (P = 0.006) and PFS (P = 0.008). In paired comparisons, CALI showed modest but significant OS improvements over conventional indices, whereas PFS gains were less consistent.

CALI provided modest prognostic discrimination and risk stratification in older patients with advanced NSCLC receiving immunotherapy, with stronger and more consistent performance for OS than for PFS. The model offers a simple, bedside-applicable tool using routinely available clinical variables, and can be easily accessed via our online calculator (https://jccclv.github.io/CALI-calculator) for individualized risk stratification.

Granulocyte colony-stimulating factor (G-CSF) is routinely used to manage chemotherapy-induced neutropenia in patients receiving chemoimmunotherapy for advanced non-small cell lung cancer (NSCLC). However, its potential to promote immunosuppressive tumor-associated neutrophils (TANs) has raised theoretical concerns about compromising the efficacy of immune checkpoint inhibitors (ICIs). We aimed to evaluate the real-world association between G-CSF use and survival outcomes in this setting.

In this retrospective cohort study, we analyzed data from patients with unresectable, locally advanced or metastatic NSCLC who initiated first- or later-line chemoimmunotherapy at a tertiary academic center between 2018 and 2021. Multivariable Cox regression and inverse probability of treatment weighting (IPTW) were used to adjust for key prognostic confounders.

Among 120 enrolled patients, 57 (47.5%) received G-CSF during treatment. With a median follow-up of 22.6 months, the median progression-free survival (PFS) was 12.9 months in the G-CSF group versus 9.6 months in the non-G-CSF group (hazard ratio [HR] = 0.97, 95% CI: 0.60-1.58; P = 0.92). The median overall survival (OS) was 17.6 versus 15.3 months, respectively (HR = 0.99, 95% CI: 0.50-1.98; P = 0.99). In multivariable analysis, G-CSF administration was not independently associated with PFS (adjusted HR [aHR] = 1.08, 95% CI: 0.60-1.93; P = 0.80) or OS (aHR = 1.96, 95% CI: 0.80-4.78; P = 0.14). IPTW-adjusted analyses confirmed these null associations (PFS: HR = 1.30, P = 0.85; OS: HR = 1.00, P = 0.95).

In this real-world cohort, no statistically significant association between G-CSF use and survival outcomes was observed among patients with advanced NSCLC treated with chemoimmunotherapy. Further prospective studies are warranted to better define the potential risks and benefits of G-CSF in this setting, particularly regarding its long-term association with survival outcomes.

Accurate preoperative localization of parathyroid adenomas is essential for the success of minimally invasive parathyroidectomy. This study evaluated the detection rate of parathyroid hormone assay on fine-needle aspiration washout and in conventional and advanced imaging modalities modeling a hypothetical stepwise diagnostic approach for primary hyperparathyroidism.

We conducted a retrospective single-center study including 32 patients with primary hyperparathyroidism who underwent minimally invasive parathyroidectomy and preoperative parathyroid hormone assay on fine-needle aspiration washout. We used the PTH-FNA washout to serum PTH ratio as the cutoff: a value greater than 1 was considered indicative of positive localization, while a value equal to or less than 1 was considered negative. Preoperative localization procedures included ultrasonography, MIBI-Scan, and ¹⁸F-choline PET/CT. Results were compared with postoperative histology and biochemical outcome.

Parathyroid hormone assay on fine-needle aspiration washout was positive in 20 of 32 patients (62.5%, 95% CI 45.3-77.1%). Among washout-positive patients, 7 of 20 (35.0%) underwent surgery based on ultrasonography and washout findings alone, with histological confirmation of parathyroid adenoma in all cases. In the washout-positive subgroup in whom MIBI-Scan was also performed, scintigraphy was diagnostic in 7 of 13 cases (53.8%). In washout-negative patients, scintigraphy localized the lesion in 6 of 12 cases (50.0%). In patients with non-localizing washout and scintigraphy findings, ¹⁸F-choline PET/CT identified the lesion in all evaluated cases. In this retrospective series, a stepwise strategy based on ultrasonography combined with needle-aspiration washout as the first-line localization, followed by ¹⁸F-choline PET/CT in washout-negative cases, could have potentially avoided MIBI-scans in 25 out of 32 patients (78.1%; 95% CI 61.2-89.0%).

This retrospective, single-center, post-hoc reconstructed cohort study might suggest a stepwise approach for preoperative localization of parathyroid adenoma based on parathyroid hormone assay on fine-needle aspiration washout combined with ultrasonography as a useful first-line diagnostic technique and reserving ¹⁸F-choline PET/CT for non-localizing cases. It may reduce the use of additional imaging and radiation exposure. Larger prospective studies are needed to confirm these findings.

Prior studies examining the relationship between coronavirus disease 2019 (COVID-19) and thyroid cancer in general populations may be influenced by surveillance bias, complicating interpretation of their findings. To address this limitation, we evaluated the association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and incident thyroid cancer specifically among adults with pre-existing thyroid disease.

We used the TriNetX Global Collaborative Network to conduct a propensity score-matched cohort study of adults aged ≥18 years with thyroid disorders between 2020 and 2022. Patients with documented COVID-19 were compared with matched controls without recorded SARS-CoV-2 infection. A 24-month landmark design excluded cancers diagnosed during early post-infectious evaluation. The primary outcome was incident thyroid cancer, estimated using Cox proportional hazards models, and all-cause mortality was assessed as a secondary outcome. Follicular cysts of skin served as a negative-control outcome. E-values were calculated to assess the robustness of the observed association to potential unmeasured confounding. Sensitivity, subgroup, alternative landmark, hospitalization-based severity-stratified, competing-risk, and secondary generalizability analyses were performed.

After matching, 603,364 patients were included in each cohort. COVID-19 was associated with a higher risk of incident thyroid cancer (hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.49-1.75; E-value, 2.60). The association persisted across sensitivity analyses (HRs, 1.70-1.95), sex and age strata, baseline thyroid-disease subtypes, hospitalization status, and 1- to 3-year landmark analyses. Similar findings were observed in a secondary cohort of adults with type 2 diabetes and no prior thyroid disease (HR, 1.78; 95% CI, 1.53-2.07). All-cause mortality was higher in the COVID-19 cohort compared with controls (HR, 1.70; 95% CI, 1.66-1.73). The negative-control outcome showed no increase in cumulative incidence (risk ratio, 0.95) despite a modestly higher hazard (HR, 1.16; 95% CI, 1.13-1.19).

Among adults with pre-existing thyroid disease, COVID-19 was associated with a delayed increase in incident thyroid cancer. This association was not readily explained by measured healthcare utilization alone, but residual surveillance bias cannot be excluded. These findings represent an epidemiologic signal rather than proof of causation and do not support routine thyroid cancer screening based solely on prior COVID-19.