Thu, 21 May 2026 20:48:45 -0700

ABSTRACT

Background

The EORTC QLQ-C30 (QLQ-C30) is the most widely used cancer-specific patient-reported outcome questionnaire in adult clinical trials, but its suitability for adolescents who have distinct developmental needs is unclear. Adolescents with cancer are often underrepresented in clinical trials, and efforts are underway to improve their participation by lowering the age of entry. This study evaluated the QLQ-C30's acceptability, reliability, validity and delivery preferences in adolescents with cancer across different languages and cultural backgrounds.

Materials and Methods

Adolescents aged 12–17 years, undergoing or having completed cancer treatment for curative or palliative intent, completed the QLQ-C30 alongside the PedsQL Cancer Teen questionnaire and shared their feedback on relevance, ease of completion and preferred mode of administration (paper or electronic). Socio-demographic and clinical data were recorded.

Results

Two hundred adolescents (mean age 14.5 years, standard deviation (SD) 1.6 years; 51.5% male) representing different cultures participated. The QLQ-C30 required a mean 12 min to complete and was described as acceptable and easy to complete. Psychometric testing confirmed the QLQ-C30 subscale structure with acceptable-to-good internal consistency (Cronbach's α 0.70–0.84), as well as good convergent and discriminant validity with PedsQL subscales. Comparisons of scores according to treatment intent and performance status demonstrated some support for known-group validity. Over half (57%) adolescents preferred paper completion of questionnaires.

Conclusions

This study is the first to systematically evaluate the QLQ-C30 in adolescents and establishes its acceptability and validity in this population, confirming it as a measure of choice for clinical trials involving adolescents and enabling robust life course-based outcome assessment.

Safety, Tolerability, and Pharmacokinetics of Mirvetuximab Soravtansine in Chinese Patients With Folate Receptor α‐Positive Advanced Ovarian Cancer

Thu, 21 May 2026 03:10:27 -0700

ABSTRACT

Background

Prognostic Value and Therapeutic Implications of MRI‐Based Negative Lymph Nodes in Nasopharyngeal Carcinoma

Thu, 21 May 2026 01:26:26 -0700

ABSTRACT

Background

This study aimed to evaluate the prognostic significance of negative lymph nodes (LNnegs) identified by magnetic resonance imaging (MRI) and treatment implications in patients with N0 locoregionally advanced NPC.

Methods

This retrospective cohort study included 753 patients with T3–4N0M0 NPC receiving concurrent chemoradiotherapy (CCRT) with or without induction chemotherapy (IC) at two independent hospitals. Pre-treatment and post-radiotherapy MRI scans were performed. Recursive partitioning analysis (RPA) stratified patients by radiological LNneg features. Cox regression and Kaplan–Meier analysis were performed with overall survival (OS) as the primary endpoint.

Results

Neck LNneg levels and the short-axial diameter (SD) of the largest cervical LNneg were identified as significant factors associated with OS through Cox analysis (all p ≤ 0.009). Incorporating these two factors, RPA categorized patients into RPA-I (n = 177; ≥ 4 LNneg levels and SD decreased by > 40%) and RPA-II (n = 576; < 4 LNneg levels, or ≥ 4 levels and SD decreased by ≤ 40%). The 5-year OS in RPA-I was significantly better than in RPA-II (98.3% vs. 89.5%; hazard ratio [HR]: 0.16; 95% confidence interval [CI]: 0.05–0.50; p < 0.001), validated after propensity score matching (n = 177 vs. 177; HR: 0.20; 95% CI: 0.06–0.70; p = 0.005). The OS advantage of RPA-I was significantly influenced by the cumulative cisplatin dose during CCRT (≥ 200 mg/m², p < 0.001; < 200 mg/m², p = 0.660), but was independent of IC (all p ≥ 0.040).

Conclusions

Dispersed LNnegs with a considerable decrease in the SD of the largest cervical LNneg in T3–4N0M0 NPC indicated a low OS risk and potential benefit from a cumulative cisplatin dose of ≥ 200 mg/m² in CCRT.

Multicenter Real‐World Evaluation of Neoadjuvant Carboplatin in Triple‐Negative Breast Cancer

Thu, 21 May 2026 01:21:11 -0700

ABSTRACT

Background

The role of carboplatin in neoadjuvant chemotherapy for triple-negative breast cancer (TNBC) remains controversial, particularly in settings where access to immunotherapy is limited. This study evaluated the real-world impact of adding carboplatin to neoadjuvant chemotherapy on pathological complete response (pCR) and survival outcomes in patients with TNBC.

Methods

This retrospective multicenter study included patients with nonmetastatic TNBC treated with neoadjuvant anthracycline- and taxane-based chemotherapy between 2018 and 2023 at three oncology centers in Turkey. Patients were grouped according to receipt of platinum-containing therapy. Survival outcomes were estimated using the Kaplan–Meier method and compared with the log-rank test. Cox regression analyses were performed to evaluate factors associated with survival. Propensity score matching was also performed as a supportive analysis.

Results

A total of 142 patients were included, of whom 45 (32.2%) received platinum-containing neoadjuvant chemotherapy. Overall, 80 patients (56.3%) achieved pCR. The pCR rate was significantly higher in the platinum group than in the non-platinum group (68.9% vs. 50.5%, p = 0.031). After a median follow-up of 57 months, 24 deaths and 33 DFS events were observed. Median OS and DFS were not reached. The 60-month OS rate was 96.0% in the platinum group and 73.9% in the non-platinum group (log-rank p = 0.027), whereas the 60-month DFS rates were 86.1% and 67.6%, respectively (log-rank p = 0.139). Patients who achieved pCR had significantly better OS and DFS than those with residual disease. In the propensity score-matched cohort, non-platinum treatment remained associated with inferior OS and DFS.

Conclusions

In this multicenter real-world cohort, carboplatin was associated with a higher pCR rate and numerically favorable survival outcomes. These findings may be clinically relevant where immunotherapy is not readily accessible but should be considered hypothesis-generating and require prospective validation.

Feasibility Study of Trifluridine/Tipiracil and Zolbetuximab as Third‐ or Later‐Line Chemotherapy for CLDN18.2‐Positive and HER2‐Negative Gastric or Gastroesophageal Junction Adenocarcinoma: A Study Protocol

Wed, 20 May 2026 23:34:38 -0700

ABSTRACT

Zolbetuximab is an anti-claudin18.2 (CLDN18.2) antibody, and the addition of zolbetuximab in combination with fluoropyrimidine and oxaliplatin as a first-line treatment for CLDN18.2-positive and HER2-negative gastric or gastroesophageal junction adenocarcinoma has been shown to improve survival. However, the efficacy and safety of the combination of zolbetuximab with combinations other than fluoropyrimidine and oxaliplatin have not been elucidated. The objective of the present study is to evaluate the feasibility of combination treatment with trifluridine/tipiracil (FTD/TPI), which is effective as a third- or later-line treatment, and zolbetuximab. In this study, 32 patients with CLDN18.2-positive and HER2-negative unresectable or recurrent gastric or gastroesophageal junction adenocarcinoma who received two or more lines of chemotherapy will be recruited. The patients will receive FTD/TPI (35 mg/m² twice daily on days 1–5 and days 8–12 every 4 weeks) plus zolbetuximab (an initial dose of 800 mg/m² or 400 mg/m² depending on prior zolbetuximab exposure, followed by 400 mg/m² every 3 weeks). The primary endpoint is treatment-emergent events leading to the discontinuation of zolbetuximab. The secondary endpoints are the time to treatment failure, progression-free survival, overall survival, response rate, incidence of adverse events, and incidence of Grade 3 or higher adverse events. The results will be used to evaluate the feasibility of the treatment and are expected to be used to evaluate whether future trials can be conducted.

Insurance Network Status and 1‐Year Health Care Utilization and Outpatient Costs Among Commercially Insured Patients With Newly Diagnosed and Non‐Definitively Treated Prostate Cancer, 2010–2021

Wed, 20 May 2026 21:34:37 -0700

ABSTRACT

Introduction

Cancer care in the U.S. exceeds $200B, with patients paying over $16B out-of-pocket. We examined whether insurance network status (in-network [IN] vs. out-of-network [OON]) at prostate cancer diagnosis was associated with subsequent OON care use and patient spending within 1 year of diagnosis.

Methods

Using the MarketScan database (2010–2021), we identified patients aged 40–64 with a new outpatient prostate cancer diagnosis. Patients who received definitive local treatment (radical prostatectomy or radiotherapy) were excluded. The exposure was network status at diagnosis. Outcomes were the proportion of OON claims and patient spending for prostate cancer-related care and/or non-definitive treatments during 1 year of follow-up. Results were stratified by insurance type.

Results

Among 67,271 patients, 5% were diagnosed OON. Compared with IN diagnosis, OON diagnosis was associated with greater OON follow-up claims (aIRR 29.0, 95% CI 25.0, 33.5), lower odds of prostate cancer-related spending (aOR 0.55, 95% CI 0.49, 0.61), and lower outpatient costs (% difference = −8.6, 95% CI −13.4, −3.6). In stratified analyses, patients with HMO (aOR 0.54, 95% CI 0.44, 0.67) and PPO (aOR 0.47, 95% CI 0.41, 0.54) plans had lower odds of any spending. Patients with HMO (% difference = −22.3, 95% CI −30.9, −12.5) and CDHP (% difference = −26.5, 95% CI −43.6, −4.3) plans had lower costs.

Conclusions

OON diagnosis was associated with continued OON care. Some patients diagnosed OON had lower liability, likely reflecting differences in plan design and adjudicated claims. Claims-based estimates may underestimate the financial impact of OON non-definitive prostate cancer care.

Current Knowledge of Immune Checkpoint Inhibitor‐Induced Thrombocytopenia: Epidemiology, Mechanisms, and Management

Youran Dai, Wenhui Yang, Zexing Sun, Linfeng Wu, Keding Shao, Dijiong Wu — Wed, 20 May 2026 21:11:52 -0700

ABSTRACT

Immune checkpoint inhibitors (ICIs) have been widely adopted in the treatment of malignant tumors, and their durable antitumor effects have revolutionized cancer therapy. Immune checkpoint inhibitor-induced thrombocytopenia (ICIIT) represents a rare but potentially severe or even fatal hematologic toxicity associated with immunotherapy. Therefore, it is imperative for healthcare professionals to recognize this potential adverse event and to understand its identification and management. However, the pathophysiological mechanisms underlying ICIIT remain incompletely understood, and both its diagnosis and treatment pose significant challenges. This review summarizes current knowledge on the epidemiology, prognosis, diagnosis, pathogenesis, and clinical management strategies of ICIIT. The findings of this review may serve as critical evidence to aid clinicians in the recognition and treatment of ICIIT and to inform future research efforts. Subsequent studies should aim to identify predictive biomarkers and develop novel therapeutic approaches to improve patient outcomes.

Pertuzumab Vs. Pyrotinib in Combination With Trastuzumab and Taxanes for First‐Line Treatment of HER2+ MBC: A Multicenter Real‐World Study

Wed, 20 May 2026 20:49:51 -0700

ABSTRACT

Background

Taxanes combined with trastuzumab plus either pertuzumab (THP) or pyrotinib (THPy) are standard first-line treatments for HER2-positive metastatic breast cancer (HER2+ MBC). Nevertheless, direct comparative evidence remains insufficient. This study compared the efficacy and safety of THP vs. THPy for HER2+ MBC.

Methods

The multicenter retrospective study comprised patients treated in first-line with either THP or THPy from January 2018 to March 2025. Confounding factors were adjusted using 1:1 propensity score matching (PSM) and multivariable Cox regression. Progression-free survival (PFS) was the primary endpoint, with clinical benefit rate (CBR), objective response rate (ORR), and safety as secondary endpoints.

Results

A total of 411 patients were enrolled (THP: 148; THPy: 263). After matching, 139 pairs formed. Before PSM, patients in the THPy group experienced a longer median PFS than those in the THP group (23.6 vs. 19.3 months, HR = 0.72, 95% CI: 0.53–0.97, p = 0.031). After PSM, THPy still provided a PFS benefit (23.6 vs. 17.3 months, HR = 0.68, 95% CI: 0.48–0.97, p = 0.033), with an adjusted HR of 0.44 (95% CI 0.30–0.66, p < 0.001). Before PSM, the THPy group had a lower ORR than the THP group (69.2% vs. 81.1%, p = 0.009), but after PSM, this disparity in ORR was no longer significant (74.1% vs. 79.9%, p = 0.254), and CBR remained comparable between the two groups throughout. THPy showed potential PFS benefit in the subgroup with de novo stage IV disease and liver metastasis. Gastrointestinal toxicities were more common in the THPy group, with diarrhea being the most prominent (any grade: 76.1%; grade ≥ 3: 22.7%).

Conclusions

THPy may provide PFS benefit over THP in HER2+ MBC, with suggestive advantages in patients with de novo stage IV disease and liver metastasis. A higher frequency of diarrhea and other gastrointestinal toxicities was observed in the THPy regimen.

Paediatric and Adult Solid Tumours Exhibiting NTRK Gene Fusions in Australia, 2020–2044: A Population‐Based Statistical Modelling Study

A Novel Strategy to Produce CAR‐γδ T Cells via Site‐Directed Gene Integration by a Combination of CRISPR/Cas9 and AAV

Mon, 18 May 2026 00:00:00 -0700

ABSTRACT

Chimeric antigen receptor (CAR)-αβ T cells are commonly employed in tumor therapy but hindered by some limitations. γδ T cells are promising substrates for CAR therapy for their major histocompatibility complex (MHC)-unrestricted recognition manner and innate immune function. Here, we established a novel method for generating CAR-γδ T cells. We utilized the clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) (CRISPR/Cas9) method to interrupt the TCR delta chain constant region (TRDC) sequence, followed by the site-directed insertion of the CAR sequence into the TRDC locus via homologous complementation mediated by adeno-associated virus (AAV) gene delivery. We optimized electroporation parameters for Cas9/ribonucleoproteins (RNP) delivery and infection conditions for CAR-gene carrying AAV in γδ T cells. These optimizations facilitated efficient TCR knockout and site-directed CAR insertion, ultimately yielding functional CAR-γδ T cells. In vitro experiments demonstrated that these newly prepared CAR-γδ T cells could stimulate cytokine production, kill tumor cells as well as exhibit robust proliferative potential and memory-like phenotype. These state-of-the-art CAR-γδ T cells could reduce tumor burden and extend the survival period of tumor-bearing mice.

Type 2 Diabetes, Glycemic Traits and Overall Cancer Risk: A Large‐Scale Prospective Cohort Study

Sun, 17 May 2026 21:29:35 -0700

ABSTRACT

Background

Evidence concerning the associations of T2D and glycemic traits with overall cancer risk and their combined effect with genetic susceptibility remains inconsistent and unexplored.

Methods

This large-scale prospective cohort study included 475,637 eligible participants from the UK Biobank. We identified 25,887 participants with T2D by clinical data, baseline self-report data, and biochemistry data. HbA1c and random blood glucose were measured at baseline. The associations of T2D, HbA1c, and random blood glucose with the risk of overall cancer and 20 site-specific cancers, stratified by gender, were evaluated by the Cox regression models. We calculated the cancer site-specific polygenic risk scores (PRS) to define genetic risk for each cancer and evaluated the joint effects of genetic risk and T2D on cancer risk. Additive and multiplicative interaction models were established to assess the gene-T2D interaction.

Results

During a median follow-up of 10.95 years, 41,650 incident cancer cases were observed, including 21,957 males and 19,693 females. For all cancers combined, a higher risk was found in females with T2D (HR: 1.20, 95% CI: 1.13–1.28) or high HbA1c levels (≥ 48 mmol/mol) (HR: 1.20, 95% CI: 1.10–1.31). Among site-specific cancers, individuals with T2D or high glycemic traits had a higher risk of pancreatic, bladder, kidney, colorectal, gastric, lung and endometrial cancer. In contrast, we observed inverse associations of T2D and glycemic traits with prostate cancer. Additive interactions between high PRS and T2D were observed in pancreatic cancer risk (with relative excess risk of interaction (RERI) of 2.39 (95% CI: 0.34 to 4.72) and 4.41 (95% CI: 1.09 to 8.62), in males and females respectively), and in prostate cancer risk (with RERI of −0.94 (95% CI: −1.51 to −0.37) in males).

Conclusions

Our study suggests that T2D and high glycemic traits are associated with a higher risk of multiple malignant cancers, particularly in females.

Integrated Molecular Risk Stratification and Measurable Residual Disease‐Guided Consolidation Improve Outcomes in Pediatric Non‐Down Syndrome Acute Megakaryoblastic Leukemia

Sun, 17 May 2026 20:49:42 -0700

This multicenter study demonstrates that integrating molecular risk stratification with MRD-guided consolidation improves outcomes in pediatric non-DS-AMKL. Specifically, HSCT in the first complete remission provides a significant survival advantage over chemotherapy for patients with high-risk genetics or suboptimal induction response.

ABSTRACT

Management of pediatric acute megakaryoblastic leukemia (AMKL) without Down syndrome (non-DS-AMKL) remains challenging due to suboptimal induction responses and poor survival. This study assessed the efficacy of fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin (FLAG-IDA) in non-DS-AMKL and evaluated the role of risk-adapted consolidation strategies, including hematopoietic stem cell transplantation (HSCT) during first complete remission (CR1), guided by genetic profiles and measurable residual disease (MRD) dynamics. In this multicenter retrospective study from China, we analyzed 58 non-DS-AMKL patients treated with FLAG-IDA (n = 50) or daunorubicin, cytarabine, etoposide (DAE) (n = 8) induction, followed by risk-adapted consolidation. FLAG-IDA demonstrated CR rates comparable to those with DAE (first-course: 70.0% vs. 87.5%, p = 0.423; cumulative: 82.0% vs. 87.5%, p = 1.000). Compared with other AML subtypes, non-DS-AMKL showed inferior 5-year overall survival (OS) (61.7% vs. 78.2%, p = 0.001) and event-free survival (EFS) (58.5% vs. 68.8%, p = 0.045), attributable to a higher relapse rate (34.8% vs. 19.5%, p = 0.002). High-risk genetics predicted worse outcomes. HSCT in CR1 significantly improved survival for high-risk or poor responders. CR with MRD negativity after second induction predicted superior OS and EFS (p < 0.001). Risk-adapted HSCT and MRD-guided stratification are critical for non-DS-AMKL management.

Efficacy of Neoadjuvant Immunochemotherapy in Pulmonary Lymphoepithelioma Carcinoma Compared With Lung Squamous Cell Carcinoma and Adenocarcinoma: A Retrospective Cohort Study

Fri, 15 May 2026 23:11:51 -0700

ABSTRACT

Objective

Immunotherapy has emerged as a promising treatment for patients with pulmonary lymphoepithelioma carcinoma (PLEC). This study aimed to evaluate the efficacy and safety of neoadjuvant immunochemotherapy in patients with PLEC.

Methods

Clinical stage IB-III patients with PLEC who underwent neoadjuvant immunochemotherapy followed by radical surgery were retrospectively collected from two centers. For comparative analysis, 83 lung squamous cell carcinoma (LUSC) and 82 lung adenocarcinoma (LUAD) patients receiving the same neoadjuvant regimen were retrospectively enrolled. Pathological response and survival outcomes were compared between PLEC and the other cohorts. To minimize selection bias and potential confounding factors, the data were analyzed using inverse probability of treatment weighting (IPTW).

Results

Among 40 patients with PLEC, 23 (57.5%) were female, with a mean age of 50.2 years. Major pathological response (MPR) was identified in 18 patients (45.0%) and pathological complete response (pCR) was achieved in 8 patients (20.0%). The median event-free survival (EFS) was 24.8 months, with 1-year and 2-year EFS rates of 92.3% and 76.6%. Following IPTW adjustment, both pathological response and survival outcomes were comparable among the three cohorts. No statistically significant differences were observed between PLEC and LUSC patients in terms of MPR (45.0% vs. 66.3%, p = 0.306), pCR (20.0% vs. 47.0%, p = 0.228), or EFS (median: 24.8 vs. 28.5 months, p = 0.983). Similarly, PLEC demonstrated comparable MPR, pCR, and EFS to the LUAD cohort (MPR: 45.0% vs. 41.5%, p = 0.646; pCR: 20.0% vs. 25.6%, p = 0.978; median EFS: 24.8 vs. 22.5 months, p = 0.623).

Conclusion

Neoadjuvant immunochemotherapy demonstrates favorable efficacy and safety in patients with PLEC in this retrospective two-center cohort. In adjusted analyses, EFS did not significantly differ from that observed in matched LUSC or LUAD patients, suggesting that this approach may be a reasonable option for selected PLEC patients.

A Real‐World Experience of Prognostic Factors of Survival Outcomes in a Taiwanese Population With Unresectable Hepatocellular Carcinoma Treated With First‐Line Lenvatinib

Fri, 15 May 2026 23:08:55 -0700

ABSTRACT

Introduction

Lenvatinib is approved as a first-line treatment for unresectable hepatocellular carcinoma (HCC), but real-world outcomes may vary due to patient heterogeneity. This study aimed to evaluate the real-world efficacy of lenvatinib in Taiwanese patients and to identify prognostic factors influencing outcomes.

Methods

This retrospective cohort study included 111 patients with unresectable HCC treated with the first-line lenvatinib between February 2020 and April 2023 at Taichung Veterans General Hospital. All patients were Child-Pugh class A and had at least one measurable lesion per mRECIST. Radiological tumor response, overall survival (OS), and progression-free survival (PFS) were recorded and analyzed.

Results

The ORR and DCR were 36% and 81% respectively. The median OS of all patients was 17 months, and PFS was 10 months. Patients with ALBI grade 1 (HR 0.45, 95% CI 0.24–0.84, p = 0.011) and receiving combined locoregional therapy (LRT) (HR 0.38, 95% CI 0.20–0.79, p = 0.003) had significantly longer OS. AFP ≤ 400 ng/mL was associated with longer PFS (HR 0.35, 95% CI 0.35–0.94, p = 0.028).

Conclusion

Lenvatinib is effective in real-world treatment of unresectable HCC, especially when combined with LRT. ALBI grade 1 and AFP ≤ 400 ng/mL are favorable prognostic indicators for survival and disease control. These findings support personalized treatment strategies and warrant further prospective validation.

DEC1 Deficiency Attenuates Breast Cancer‐Induced Osteolytic Destruction by Suppression of Cancer‐Associated Fibroblast Differentiation

Zhiyi Qiang, Ying Huo, Lan Lin, Kaiao Chen, Wei Liu, Jian Yang — Fri, 15 May 2026 22:20:42 -0700

Schematic diagram of the mechanism by which DEC1 deficiency attenuates breast cancer-induced osteolytic destruction through suppression of cancer-associated fibroblast differentiation.

ABSTRACT

Background

Cancer-associated fibroblasts (CAFs) in the bone microenvironment play a key role in breast cancer (BC) osteolytic bone metastases. Differentiated embryo-chondrocyte expressed gene 1 (DEC1) has been implicated as a potential therapeutic target in CAFs. Here, we investigate the role of DEC1 within the bone microenvironment during BC cell-induced bone destruction.

Methods

In vivo, a BC bone metastasis mouse model by intratibially injecting 4 T1 cells into DEC1^+/+ and DEC1^−/− mice was used to explore the effects of DEC1 deficiency in the bone microenvironment on BC osteolytic bone destruction. Bone mesenchymal stromal cells (BMSCs) isolated from DEC1^+/+ and DEC1^−/− mice were induced to differentiate into CAFs, as in vitro model to explore the roles and underlying mechanisms.

Results

DEC1 deficiency markedly attenuated BC-induced osteolytic destruction. Notably, DEC1^+/+-4 T1 mice exhibited a higher abundance of CAF biomarker-positive cells in the bone microenvironment compared to DEC1^−/−-4 T1 mice. Mechanistically, tumor-conditioned medium (TCM) and IL-6 were found to promote the differentiation of BMSCs into CAFs through activation of the JAK2/STAT3 pathway, whereas DEC1 deletion suppressed this process by inhibiting JAK2/STAT3 signaling. Furthermore, DEC1 deficiency reduced RANKL secretion, thereby limiting osteoclastogenesis, and decreased PAI-1 levels, which contributed to remodeling of the tumor microenvironment and suppression of BC cell migration.

Conclusion

Our findings demonstrate that DEC1 deficiency in the bone microenvironment critically restrains BC cell-induced bone destruction through inhibition of CAF differentiation.

Investigating Associations Between Psychological Distress and Changes in Peripheral Blood Monocytes in Patients With CLL/SLL Managed With Active Surveillance

Fri, 15 May 2026 22:04:55 -0700

Among asymptomatic patients with CLL/SLL managed with active surveillance, psychological distress was associated with a lower percentage of intermediate monocytes and a greater percentage of classical monocytes. This is one of the first studies to observe that psychological distress is associated with differential patterns of monocyte distribution in untreated patients with CLL/SLL.

ABSTRACT

Asymptomatic patients with a new diagnosis of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) are commonly managed by active surveillance as per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria; however, many patients report elevated distress during surveillance. Psychological distress may have biologic implications given that natural killer [NK] cells, T cells, and monocytes are not only sensitive to distress, but also critical in controlling disease progression. Therefore, the objective of this study was to explore associations of distress with immune biomarkers in patients with CLL/SLL being managed by active surveillance. We enrolled 76 participants and assessed perceived stress, anxiety, and depressive symptoms at study entry and every 6 months for up to 2 years during active surveillance. Blood samples were collected at the same time points to assess biomarkers on T cell, NK cell, and monocyte subsets. In multivariable regression analyses, higher levels of perceived stress and anxiety were significantly associated with lower percentages of intermediate monocytes (IM); anxiety was also significantly associated with higher percentages of classical monocytes (CM). In longitudinal analyses, higher stress and anxiety were significantly associated with higher percentages of CM at 12 months. This is one of the first studies to observe that psychological distress is associated with differential patterns of monocyte distribution in patients with CLL/SLL managed with active surveillance.

Germline Pathogenic Variants in HER2‐Positive Breast Cancer: Spectrum and Clinical Implications in a High‐Risk Chinese Cohort

Fri, 15 May 2026 21:44:41 -0700

ABSTRACT

Objective

Hereditary cancer risk assessment has predominantly focused on HER2-negative breast cancer (BC), with limited characterization of germline pathogenic variants (GPVs) in HER2-positive disease. This study aimed to delineate the prevalence, clinicopathological correlates, and clinical implications of GPVs in a cohort of HER2-positive BC patients.

Methods

We retrospectively reviewed BC patients who had undergone genetic testing at the Sun Yat-sen University Cancer Center from 2014 to 2024. GPV profiles, clinicopathological features, and survival outcomes were compared between HER2-positive and HER2-negative patients, with additional stratified analysis in HER2-positive GPV carriers.

Results

Among 1692 BC patients, 1,499 patients met NCCN high-risk criteria. In multigene panel testing, GPVs were identified in 18.1% (52/288) of HER2-positive BC and 22.4% (269/1,201) of HER2-negative BC patients. HER2-positive GPV carriers exhibited distinct molecular profiles, with higher frequencies of BRCA2 (23/52, 44.2%) and TP53 (14/52, 26.9%) mutations and a lower BRCA1 prevalence (6/52, 11.5%) compared to HER2-negative carriers (BRCA2: 106/269, 37.9%; TP53: 9/269, 3.3%; BRCA1: 117/269, 43.5%). Clinically, HER2-positive carriers were diagnosed at a younger median age, had higher hormone receptor (HR) positivity, and less frequently reported a family history of BRCA-related cancers. GPVs were not associated with increased locoregional recurrence or distant metastasis in HER2-positive BC but significantly elevated the risk of contralateral BC and other secondary primary cancers—a risk particularly pronounced in TP53 carriers.

Conclusions

HER2-positive BC patients harbored a distinct GPV spectrum compared to HER2-negative patients. While GPVs did not worsen primary BC-specific outcomes, they conferred a significantly increased risk of second primary cancers, underscoring the clinical utility of multigene panel testing for comprehensive risk stratification and long-term management in this population.

Study Limitations

This retrospective, single-center study comprised a clinically enriched high-risk cohort, which may limit the generalizability of prevalence estimates. The extended inclusion period and evolving classification standards, despite reannotation, represent inherent methodological constraints.

Association of Visceral Obesity Indices With Survival Among Cancer Survivors: Evidence From Two Nationally Population‐Based Cohort Study

Qiang Li, Yao Wang, Qingchun Liu, Wei Zhang — Fri, 15 May 2026 21:21:31 -0700

ABSTRACT

Background

Obesity is critical for cancer prognosis, but the impact of visceral obesity indices on survival in cancer survivors remains unclear. This study explored associations between six visceral obesity indices, BMI, and overall survival using two large population-based cohorts of cancer survivors.

Methods

A retrospective cohort study was conducted using data from the 2001 to 2018 National Health and Nutrition Examination Survey (NHANES) and China Health and Retirement Longitudinal Study (CHARLS). Visceral obesity was assessed by a body shape index (ABSI), conicity index (ConI), visceral adiposity index (VAI), Chinese visceral adiposity index (CVAI), metabolic score for visceral fat (METS-VF), and lipid accumulation product (LAP). Kaplan–Meier curves, multivariable Cox regression, restricted cubic splines (RCS), mediation analysis, subgroup, and sensitivity analyses were employed.

Results

The study included 1783 NHANES survivors (weighted population: 8,556,033; weighted median follow-up 85 months) and 162 CHARLS patients (weighted population: 5,631,233; weighted median follow-up 37 months). Only ABSI was significantly associated with increased all-cause mortality risk in both cohorts (p < 0.05). In NHANES, individuals in the highest ABSI level had 80% increased mortality risk compared to the lowest level (adjusted HR 1.80; p for trend = 0.004), consistent with CHARLS. RCS showed a linear ABSI-mortality relationship. Mediation analyses indicated that neutrophil mediated 16.77% proportion of the ABSI-mortality association in NHANES. Subgroup analyses and sensitivity analyses further confirmed these findings.

Conclusion

Compared to other indices, ABSI may be a valuable, potentially independent predictor of survival in cancer survivors, highlighting its value for clinical assessment to identify high-risk individuals and guide targeted interventions.

Sequential Use of Systemic Therapy With Locoregional Therapy for Hepatocellular Carcinoma in Japan: Analyses of Real‐World Data Based on a Health Claims Database

Fri, 15 May 2026 21:11:36 -0700

This study examined how patients with hepatocellular carcinoma, a type of liver cancer often suitable for locoregional therapy, were treated at hospitals in Japan between 2020 and 2022. Our findings highlight the need for clear strategies to evaluate and establish appropriate combination therapies for patients with hepatocellular carcinoma.

ABSTRACT

Aim

The treatment of hepatocellular carcinoma (HCC) in Japan is driven by locoregional therapies (LRTs). However, the treatment landscape in the era of systemic targeted therapies and immunotherapies is not well understood. We investigated the real-world treatment patterns of combined LRT and systemic therapy in Japan.

Methods

We performed analyses of the Medical Data Vision (MDV) database using data for patients with a recorded diagnosis of HCC and at least one record of a first LRT (January 1, 2020–December 31, 2022; hepatectomy, transarterial chemoembolization [TACE], radiation therapy [RT], ablation, or hepatic arterial infusion chemotherapy [HAIC]) after the record of HCC diagnosis. We examined the use of preceding systemic therapy (PSysT), maintenance treatment (MT), and next treatments.

Results

Among 15,285 patients, hepatectomy, TACE, RT, ablation, and HAIC were performed in 4506, 6389, 991, 3351, and 48 patients, respectively. Few patients received PSysT, including lenvatinib (by LRT: 0.93%–12.50%) and atezolizumab + bevacizumab (by LRT: 0.29%–4.94%). Only TACE with PSysT increased slightly during the study period. MT was infrequent. Cumulative incidence of next treatment at 6 months varied by type of first LRT, ranging from 6.61% following hepatectomy to 45.06% following HAIC.

Conclusion

LRT alone remained the standard approach for treating HCC in Japan in 2020–2022. The type and duration of therapies used before or after first LRT varied, suggesting a lack of standardized protocols. A clear strategy is needed to evaluate and establish appropriate LRT-based combination therapies for HCC, considering the unmet medical needs identified in this study.

EXPRESSION OF CONCERN: Overexpression of TNKS1BP1 in Lung Cancers and Its Involvement in Homologous Recombination Pathway of DNA Double‐Strand Breaks

Fri, 15 May 2026 20:42:07 -0700

Cancer Medicine, Volume 15, Issue 5, May 2026.

Mass Spectrometry‐Driven Proteomic Biomarkers for Serum‐Based Detection of Pancreatic Ductal Adenocarcinoma and Intraductal Papillary Mucinous Neoplasm‐Associated Invasive Carcinoma

HyunGyo Jung, Namyoung Park, Jaihwan Kim, Min‐Jung Kang — Thu, 14 May 2026 23:25:45 -0700

LC-MS/MS-based serum profiling of 60 discovery samples has been achieved for pancreatic cancer biomarkers (IPMC and PDAC). ANOVA, ROC Analysis and Permutation Importance were applied for feature selection. 6-Protein panel (CALR, FCN1, MBL2, SPP1, TAGLN2, and VWF) was validated using PRM analysis of 40 samples from independent cohort. AUROC of this panel showed 0.962 and 0.856 for IPMC and PDAC, respectively.

ABSTRACT

Background

Pancreatic cancer remains a highly lethal malignancy due to late diagnosis and the lack of effective non-invasive biomarkers for detection, further complicated by biological heterogeneity, including intraductal papillary mucinous neoplasm (IPMN) and IPMN-associated invasive carcinoma (IPMC).

Methods

Serum samples from a discovery cohort (n = 60), including patients with IPMN, IPMC, and pancreatic ductal adenocarcinoma (PDAC), were analyzed using LC–MS/MS-based serum proteomic profiling to identify candidate biomarkers. Feature selection was performed using ANOVA, receiver operating characteristic analysis, and permutation feature importance. The selected markers were further evaluated in an independent validation cohort (n = 40).

Results

In the discovery cohort, the model demonstrated robust performance, with leave-one-out cross-validation AUROC values ranging from 0.814 to 1.000 across classifications of healthy controls and disease groups (IPMN, IPMC, and PDAC). In the independent validation cohort, the six-marker panel (CALR, FCN1, MBL2, SPP1, TAGLN2, and VWF) achieved an AUROC of 0.962 with a specificity of 95.0% for distinguishing healthy controls from IPMC, and an AUROC of 0.856 with a specificity of 90.0% for healthy controls vs. PDAC.

Conclusions

These findings demonstrate the robustness and clinical potential of the six-protein panel as a non-invasive diagnostic tool for pancreatic cancer.

Melanoma Brain Metastasis, Prognostic Factors, and Survival Outcomes After First Metastatic Line Therapy: A Monocentric Retrospective Study

Thu, 14 May 2026 22:55:11 -0700

ABSTRACT

Brain metastases (BMs) are a major cause of mortality in patients with melanoma. We conducted a retrospective observational study to identify prognostic factors for BM development and to evaluate the impact of first-line systemic therapy on BM occurrence and survival outcomes in patients with advanced melanoma. A total of 258 patients with unresectable Stage III or IV melanoma without BM at diagnosis were included and followed for BM occurrence. During a median follow-up of 8.7 years (95% CI, 7.0–10.6), 100 patients (38.8%) developed BM. Patients who developed BM were younger (median age 60.5 vs. 66 years; p = 0.008) and more frequently harbored a BRAF V600E/K mutation (51.4% vs. 48.6%; p < 0.001) compared with patients without BM, whereas ulceration status was similar between groups (p = 0.525). A mitotic rate ≥ 1 was more frequently observed in patients with BM (67.7% vs. 31.3%; p = 0.044). In multivariable logistic regression analyses, a high mitotic rate (≥ 6/mm²), BRAF V600 mutation, and AJCC stage IV M1b disease were independently associated with an increased risk of BM. The effect of first-line systemic therapy on BM was further assessed using Fine–Gray competing-risk models and cause-specific Cox models with a 12-week landmark analysis. Compared with combination immune checkpoint inhibitors (ICIs), first-line chemotherapy was independently associated with a markedly higher risk of BM, whereas targeted therapy showed a strong but non-significant association. Tumor-related factors, including AJCC stage IV M1b disease, high mitotic rate, and BRAF V600 mutation, remained independently associated with BM across competing-risk and cause-specific analyses. In cause-specific Cox models, chemotherapy, advanced disease stage, high mitotic rate, and BRAF V600 mutation were associated with poorer BM-free survival. In our study, the BRAF V600 mutation appears to be an independent and strong prognostic factor for BM, regardless of systemic treatment received in the metastatic setting. First-line combination ICIs significantly reduce the risk of BM and improve survival outcomes.

Prognostic Factors in Oropharyngeal Cancer Treated With Definitive Chemoradiotherapy

Wed, 13 May 2026 22:45:39 -0700

We studied 630 OPSCC patients treated with chemoradiotherapy in our institute. There was a low incidence of HPV-associated OPSCC in our cohort. Tobacco remains the main etiological factor in our cohort. HPV status by p16 IHC, T stage, RT technique, and RT doses were independent prognostic factors for OPSCC patients.

ABSTRACT

Objectives

HPV-negative oropharyngeal squamous cell cancer (OPSCC) is associated with poor clinical outcomes. The main objective of this study was to evaluate prognostic factors of OPSCC treated with definitive chemoradiotherapy (CTRT).

Materials and Methods

Consecutive patients of OPSCC treated with definitive CTRT in a tertiary care center from January 2013 to December 2017 were analysed retrospectively. Kaplan–Meier method was used for survival analysis, Log-rank test was used for univariate analysis (UVA), and Cox regression method was used for multivariate analysis (MVA).

Results

Out of 630 eligible patients, 543 (86.1%) had locally advanced stage according to AJCC 7^th edition. HPV status was known for 500 patients, of which 55 (11%) tested p16 positive, reflecting a predominantly HPV-negative cohort. Chemo-radiotherapy was offered to 447 (71%) patients. Intensity-modulated-radiotherapy (IMRT) technique was used for 163 (25.9%) patients. On UVA KPS ≤ 80 (p = 0.001), p16 negative tumours (p < 0.001), T3-T4 stage (p < 0.001), advanced group stage (AJCC 8^th ed.) (p < 0.001), conventional RT technique (p < 0.001), RT dose < 66 Gy EQD2 (p < 0.001) and residual disease after treatment (p < 0.001) were associated with poor Locoregional control (LRC) rates. On MVA p16 negative tumours (HR 3.1 [95% CI 1.8–5.3]), T3-T4 stage (HR 1.6 [95% CI 1.2–2.2]), conventional RT technique (HR 1.6 [95% CI 1.5–2.3]), RT dose < 66 Gy EQD2 (HR 2.2 [95% CI 1.5–3.4]) were independent prognostic factors for poor LRC. These variables were also significant for local control, disease-free free and overall survival.

Conclusion

In this predominantly HPV-negative OPSCC cohort, HPV status, T stage, RT technique, and RT doses > 66 Gy were independent prognostic factors for all outcomes.

Exploring Resistance to ETS Targeting Agents in Diffuse Large B‐Cell Lymphoma

Wed, 13 May 2026 22:26:04 -0700

This study provides the first systematic characterization of resistance to ETS inhibition in diffuse large B-cell lymphoma (DLBCL). Using TK216-resistant models, we reveal heterogeneous escape mechanisms, including MDR1 upregulation, transcriptional reprogramming, and cytoskeletal remodeling, each associated with distinct mutational signatures. Importantly, pharmacologic profiling identified vulnerabilities to BCL2, MCL1, and XPO1 inhibitors, highlighting rational strategies to overcome resistance. These findings extend the translational potential of ETS targeting in lymphoma and establish a framework for biomarker-guided combination therapies in future clinical development.

ABSTRACT

Diffuse large B-cell lymphoma (DLBCL) remains a challenging disease with limited therapeutic options beyond standard immunochemotherapy. ETS transcription factors, including SPIB and SPI1, are implicated in lymphoma pathogenesis and can be targeted by the small molecule TK216, which disrupts ETS–DHX9 interactions. To explore mechanisms of resistance, we generated stable TK216–resistant clones from the ABC-DLBCL line U2932. Resistant clones exhibited a 4–5-fold increase in IC₅₀ values and lost the ability to undergo G2–M arrest upon treatment. Transcriptomic and mutational analyses revealed three resistance patterns: (i) MDR1/ABCB1 overexpression, leading to multidrug efflux; (ii) Cluster A, enriched for proliferation, Wnt, and transcriptional programs, with mutations in ESR2, USP24, and SFSWAP; and (iii) Cluster B, characterized by actin/microtubule remodeling, altered metabolism, and mutations in SRSF11 and PATJ. Pharmacologic screening revealed an increased sensitivity of resistant cells to BCL2, MCL1, and XPO1 inhibitors, while also showing reduced sensitivity to aurora kinase and microtubule-targeting agents. Venetoclax and selinexor retained activity in resistant models, supporting their potential for rational combinations with TK216. These findings demonstrate that multiple, heterogeneous mechanisms drive resistance to ETS inhibition in DLBCL, highlighting therapeutic strategies to overcome it.

Racial, Ethnic, and Neighborhood Disparities in Acute Kidney Injury in Pediatric Acute Leukemia

Wed, 13 May 2026 22:25:26 -0700

This multicenter retrospective cohort study describes racial, ethnic, and neighborhood disparities in acute kidney injury in pediatric patients with acute lymphoblastic/acute myeloid leukemia using electronic health record data. Racial and ethnic disparities were present after controlling for clinical factors.

ABSTRACT

Introduction

We sought to identify racial/ethnic and neighborhood disparities in acute kidney injury (AKI) in children with acute lymphoblastic or myeloid leukemia (ALL, AML).

Methods

Electronic health record data were retrospectively collected from patients treated for de novo pediatric ALL or AML in the multicenter Leukemia Electronic Abstraction of Records Network. AKI was defined by modified Kidney Disease Improving Global Outcomes criteria. Neighborhood-level resources were defined by the Child Opportunity Level (COL). Prevalence ratios (PRs) for AKI at diagnosis by race/ethnicity and COL were calculated using modified Poisson regression. Cox regression was used to calculate hazard ratios (HRs) of first AKI after initiation of chemotherapy (i.e., “during therapy”).

Results

Of 952 ALL patients, Non-Hispanic Black (NHB) ALL patients had significantly increased prevalence of AKI at leukemia diagnosis compared to Non-Hispanic White (NHW) patients in the adjusted model (PR 1.50); there were no significant differences by COL. During ALL therapy overall, NHB patients did not have any significant differences in hazard of AKI by race/ethnicity or COL in adjusted models. Among 168 AML patients, there were no significant differences in AKI at diagnosis by race/ethnicity or COL in AML. During AML therapy overall, NHB patients had significantly higher risk of AKI in both unadjusted (HR 1.95) and adjusted (HR 2.68) models, but no differences by COL.

Conclusion

NHB patients with ALL had increased risk of AKI at the time of leukemia diagnosis, and NHB patients with AML had significantly increased risk of AKI during therapy. Further studies to identify drivers and interventions that mitigate AKI risk are warranted.

RELB Overexpression Induced by DNA Hypomethylation Contributes to Perioperative Immunotherapy Resistance in Resectable Esophageal Squamous Cell Carcinoma by Modulating the mregDC‐Treg Axis

Visualized Clinical‐Radiomics Model Based on Non‐Contrast Computed Tomography for Predicting Efficacy of Surufatinib in Hepatic Metastases of Neuroendocrine Neoplasms

Miaomiao Feng, Man Zhao, Xiaoling Duan, Jiaojiao Hou, Qi Wang, Fei Yin — Tue, 12 May 2026 20:30:28 -0700

NCCT radiomics for surufatinib efficacy prediction in HM-NENs.

ABSTRACT

Background

Hepatic metastatic neuroendocrine neoplasms (HM-NENs) have few treatment biomarkers and low survival rates. We created a clinical-radiomics fusion model based on non-contrast computed tomography (NCCT) to predict Surufatinib efficacy in HM-NENs. We presented it as a nomogram, meeting unmet requirements in precision medicine.

Methods

This retrospective study included 76 HM-NEN patients (131 hepatic metastases) treated with Surufatinib. Regions of interest (ROI) were manually segmented, and the best response to Surufatinib was decided based on Modified Response Evaluation Criteria in Solid Tumor (mRECIST). Radiomics features were extracted from the pretreatment NCCT. The Least Absolute Shrinkage and Selection Operator (LASSO) was used to select radiomics features and calculate a Radiomics score (Radscore). Multivariable logistic regression analysis was utilized to create the clinical-radiomics fusion model, which included clinical characteristics and Radscore and was displayed as a nomogram. The area under the receiver operating characteristic curve (ROC) was used to assess model performance, and internal validation was done using the bootstrap resampling approach.

Results

After multivariate logistic regression analysis, the Radscore, the diameter of hepatic metastasis, the number of hepatic metastases, and extrahepatic metastasis were included as predictors in the final model. The area under the curve (AUC) of the clinical-radiomics fusion model to predict the response of Surufatinib of HM-NENs was 0.926 (95% confidence interval [CI]: 0.881–0.971). The AUC verified by bootstrap was 0.926 (95% CI: 0.880–0.966), indicating a good performance of the fusion model.

Conclusion

The clinical-radiomics fusion model can effectively identify patients with HM-NENs sensitive to Surufatinib therapy. The nomogram provides clinicians with a convenient and dependable tool for decision-making.

Time Trends in the Prevalence of Hospital‐Diagnosed Chronic Diseases Among Stage I‐IV Colorectal Cancer Patients in Denmark (2002–2021): A Population‐Based Cross‐Sectional Study

Jannik Wheler, Henrik Toft Sørensen, Rune Erichsen, Deirdre P. Cronin‐Fenton — Tue, 12 May 2026 20:18:23 -0700

The prevalence of chronic diseases among colorectal cancer patients has increased markedly since 2002, rising from 36% to 51%, with more patients now presenting with chronic diseases than without at diagnosis. Metabolic diseases showed the most pronounced increase over time, whereas the prevalence of cardiopulmonary diseases among patients with one or more chronic diseases decreased.

ABSTRACT

Introduction

As the population ages, the prevalence of chronic diseases is increasing. We evaluated trends in the prevalence of hospital-diagnosed chronic diseases in newly diagnosed colorectal cancer (CRC) patients.

Methods

This manuscript focuses on the design and implementation of 2 real-world screening programs conducted in Ghana and India. These programs were developed to align with the operational realities and resource constraints of each setting, prioritizing approaches that are both sustainable and scalable for long-term cancer control. These integrated programs in Ghana and India showcased how linking screening, diagnosis, treatment, and follow-up can strengthen secondary prevention of breast and cervical cancers, and the results and lessons learned may hopefully continue to serve as a platform to scale efforts to meet demand, raise awareness, and decrease the burden in other low- and middle-income countries.

ABSTRACT

Introduction

Cervical and breast cancer are the leading causes of women's cancer mortality in Ghana and India. Using an integrated, scalable approach of screening, diagnosis, and treatment, 2 real-world programs were independently designed and conducted in Ghana and India. Each program was adapted to the local healthcare infrastructure to increase screening and management of breast and cervical cancers.

Methods

Government, healthcare, industry, non-governmental organization, and community leader partnerships in Ghana and India created a comprehensive patient engagement framework. Cascade training in cervical and breast cancer for healthcare workers, cancer awareness community outreach, screening, and follow-up for women were instituted. Patient navigators and accredited social health activists supported patients throughout the program. Human papillomavirus (HPV) DNA testing and HPV DNA self-sample collection were introduced.

Results

In the Bekwai municipality of Ghana, 20 facilities participated in the screening program. Sixteen trainers and 70 providers were trained. Of 5730 women screened for breast cancer; 100% of 113 with confirmed breast abnormalities had diagnostic services and treatment if necessary. For cervical cancer screening, 4997 women provided samples (80% self-collected); 811 were HPV-positive, 609 (75%) returned for further assessment, and of those, 100% were treated. In Amethi, India, 19 facilities participated. Forty trainers and providers were trained. Collectively, 4505 women were screened for breast cancer; 28/123 with abnormalities (23%) were referred for further management. Of 10,141 women who provided cervical samples (75% self-collected), 370 were HPV-positive, and 193/370 women (52%) returned for treatment or referral to tertiary centers.

Conclusions

Establishing multiple-stakeholder partnerships resulted in cervical and breast cancer screening programs that were successfully implemented into routine clinical service in diverse environments and resulted in large numbers of women receiving cancer screening and treatment.

Full‐Length Transcriptome Profiles Reveal the Molecular Function of Oncogene HNRNPA2B1 in Triple‐Negative Breast Cancer

Lina Yi, Yongtao Li, Jianghua Ou — Sun, 10 May 2026 20:36:32 -0700

ABSTRACT

Triple negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer with the worst prognosis. Heterogeneous nuclear ribonucleoprotein A2/B1 (HNRNPA2B1), a member of the RNA-binding protein (RBP) hnRNPs family, is aberrantly expressed in various human cancers, serving as a marker of poor prognosis and acting as an oncogene. However, its expression, biological function, and molecular mechanism in TNBC remain unclear. In this study, we examined the expression of HNRNPA2B1 in one normal mammary epithelial cell line (MCF10A) and four TNBC cell lines (HS 578 T, BT-20, MDA-MB-468, and MDA-MB-231). We conducted in vitro and in vivo knockdown experiments to compare the growth ability, gene expression profiles, and alternative splicing patterns of TNBC cells with HNRNPA2B1 knockdown to those of control cells. Our results demonstrated that HNRNPA2B1 is overexpressed in triple-negative breast cancer tissues and cell lines. Knockdown of HNRNPA2B1 significantly inhibited proliferation and metastasis while promoting apoptosis in TNBC cells. Mechanistically, HNRNPA2B1 knockdown broadly impacted the expression and alternative splicing of genes associated with cell migration, proliferation, and apoptosis. Using Nanopore long-read sequencing, we further revealed that HNRNPA2B1 regulates gene expression in TNBC cells through the modulation of alternative polyadenylation. These findings highlight the critical role of HNRNPA2B1 in TNBC progression, providing new insights into its mechanisms and potential therapeutic applications.

Metronomic Capecitabine Triggers Ferroptosis in Hepatocellular Carcinoma Cells Through Inhibition of TYMS

Sun, 10 May 2026 20:29:55 -0700

In the syngeneic tumor mouse model, capecitabine inhibits TYMS by metabolizing to 5-fluorouracil in vivo, which leads to the activation of intracellular NOX. The massive release of ROS leads to the accumulation of ferrous ions in mitochondria, and the imbalance of intracellular oxidative stress and the accumulation of ferrous ions cause ferroptosis of liver cancer cells.

ABSTRACT

Objective

Capecitabine (CAP) is an orally administered prodrug of fluorouracil, predominantly utilized in the treatment of solid tumors. Triggering tumor ferroptosis is an important mechanism for the treatment of hepatocellular carcinoma (HCC). However, the potential of CAP to induce ferroptosis in HCC, along with the underlying mechanisms, remains unknown.

Methods

In this study, a subcutaneous HCC model was constructed using the syngeneic Hepa1-6 cell line in C57BL/6 mice, followed by treatment with metronomic CAP (mCAP). The anti-tumor effects of mCAP were evaluated by monitoring tumor volume, performing pathological staining, and evaluating tumor oxidative stress levels. In vitro, various thymidylate synthase (TYMS) inhibitors were used to treat both mouse and human HCC cell lines. Furthermore, TYMS-overexpressing plasmids were transfected into mouse and human HCC cell lines to directly investigate their impact on intracellular oxidative stress. Intracellular oxidative stress and ferroptosis-related markers were detected using flow cytometry, transmission electron microscopy, and Western blotting.

Results

5-FU, an active metabolite of CAP, as well as TYMS-specific inhibitors, suppressed the proliferation of Hepa1-6 and HepG2 cells. These treatments promoted p67^phox expression, activated nicotinamide adenine dinucleotide phosphate hydrogen oxidase (NOX), induced reactive oxygen species production, and increased ferrous ion accumulation. Electron microscopy revealed mitochondrial alterations characteristic of ferroptosis. Raltitrexed, another TYMS inhibitor, also induced ferroptosis in hepatocellular carcinoma cells. In vivo, the anti-tumor effect of mCAP was antagonized by co-treatment with an NOX inhibitor.

Conclusion

CAP targets TYMS to induce ferroptosis by activating NOX, thereby inhibiting HCC progression.

Outcomes Among MM Patients Receiving Early Intervention for MRD Progression Following Autologous Stem Cell Transplantation

Xiaozhe Li, Meilan Chen, Lifen Kuang, Junru Liu, Beihui Huang, Juan Li — Sun, 10 May 2026 20:15:56 -0700

1. Some patients experience MRD progression (MRD-P) before clinical or biochemical progression (PD), highlighting the value of MRD monitoring for the early detection of relapse. 2. Early intervention upon MRD progression in multiple myeloma patients was associated with improved survival outcomes and higher rates of MRD re-negativity. Despite significant limitations, such as the small sample size, nonrandomized design, and unmeasured confounders, these findings provide preliminary data to inform the design of future prospective randomized trials.

ABSTRACT

Minimal residual disease (MRD) testing is essential for evaluating treatment response among multiple myeloma (MM) patients. Many patients experience MRD progression (MRD-P) before they meet the criteria for clinical or biochemical progression (PD), thus raising questions about the timing of treatment. In this retrospective study, the effect of early intervention (EI) on prognosis was investigated among 42 newly diagnosed MM patients who developed MRD-P after initial treatment with autologous stem cell transplantation. In the EI group (n = 9), treatment was modified at the onset of MRD-P; in the PD group (n = 33), treatment was delayed until disease progression occurred. At a median follow-up of 25 months, compared with the PD group, the EI group demonstrated a longer time to progression (median 34.8 months vs. 6.6 months, p = 0.029), superior overall survival (median not reached vs. 41.0 months, p = 0.034), and significantly higher MRD re-negativity rates (median 12.6 months vs. 75.9 months, p < 0.001). Multivariate analysis revealed that early intervention was significantly associated with improved MRD re-negativity (HR = 0.07; p = 0.001). This hypothesis-generating retrospective study demonstrated that early intervention at MRD-P onset was associated with improved survival outcomes and higher rates of MRD re-negativity in this cohort. Despite significant limitations, such as the small sample size, nonrandomized design, and unmeasured confounders, these findings provide preliminary data to inform the design of future prospective randomized trials.

Temporal Trends of Colorectal Cancer Burden in India: A Nationwide and State‐Level Analysis

Rupayan Kundu, Nivedita Sarkar, Rishabh Kundu, Arjun Chatterjee — Sun, 10 May 2026 17:15:24 -0700

ABSTRACT

Introduction

Colorectal cancer (CRC) ranks third among cancers globally, posing a significant public health issue. This study aimed to analyze CRC incidence, mortality, and risk factors across India from 1990 to 2021 using data from the Global Burden of Disease (GBD) 2021 study.

Methods

We utilized GBD 2021 data, analyzing age-standardized incidence rates (ASIR), age-standardized death rates (ASDR), and annual percentage changes (APC) for CRC across India's 31 states. Statistical modeling, including two sample t-tests, was done.

Results

In 2021, India reported 69,409 CRC cases (ASIR: 5.69 per 100,000) and 54,018 deaths (ASDR: 4.60 per 100,000). Both ASIR and ASDR showed increases from 1990 to 2021, highest in adults aged 85+, although these trends were not statistically significant. Mizoram reported the highest incidence rate. Behavioral risks accounted for the largest proportion of CRC deaths (38.85% [95% UI: 24.71–50.32]), particularly diets low in milk (19.16% [95% UI: 5.28–30.72]). High BMI contributed to 4.17% of CRC deaths and showed the highest increase from 1990 to 2021 (+127.47%).

Conclusion

The rising incidence and mortality of CRC in India highlight the need for targeted public health interventions emphasizing dietary changes, improved screening, and healthcare infrastructure.

Enhancing Postoperative Decision‐Making in Esophageal Cancer: Clinical Perspectives and Future Research Needs

Huazhen Wu, Jia Liao, Lishan Hu, Siwen Li — Sun, 10 May 2026 00:00:00 -0700

Cancer Medicine, Volume 15, Issue 5, May 2026.

Reply to “Enhancing Postoperative Decision‐Making in Esophageal Cancer: Clinical Perspectives and Future Research Needs”

Yizhou Huang, Maohui Chen, Chun Chen, Bin Zheng — Sun, 10 May 2026 00:00:00 -0700

Cancer Medicine, Volume 15, Issue 5, May 2026.

The RESILIENT Study: A Retrospective, Descriptive, Correlational Investigation of Correlates of Oral Endocrine Therapy Adherence in Older Women With Breast Cancer

Fri, 08 May 2026 22:06:31 -0700

ABSTRACT

Background

Immunotherapy and Breast Reconstruction: Opportunities, Challenges, and Future Directions

Results

The overall pathogen detection rate of mNGS was 64.29% (9/14), with corresponding diagnostic sensitivity, specificity, false-negative rate and false-positive rate of 90.00%, 25.00%, 10.00% and 75.00%, respectively. Among 13 paired sputum specimens, mNGS exhibited a numerically higher pathogen detection rate (61.54%, 8/13) than conventional diagnostic assays (38.46%, 5/13). McNemar's paired chi-square test demonstrated no statistically significant difference between the two detection methods (p = 0.37), and Kappa concordance analysis generated a coefficient of 0.27 (p = 0.23), suggesting poor inter-method consistency. Compared with conventional tests, mNGS detected additional pathogens in 8 specimens and identified a greater number of pathogens in 9/14 (64%) samples. Moreover, mNGS results led to diagnostic revisions and subsequent antimicrobial therapy adjustments in 64% (9/14) of enrolled patients. Additionally, mNGS detected antibiotic resistance genes in five patients, which provided guidance for antibiotic selection.

Conclusions

Metagenomic next-generation sequencing (mNGS) showed potential value in pathogen detection, as it appeared to identify pathogens more rapidly and comprehensively than conventional methods. It may provide auxiliary support for the diagnosis and treatment of pneumonia in this vulnerable population.

Artesunate Induces G0/G1 Phase Arrest in Tumor Cells and Associates With Cyclin‐Dependent Kinase 4 (CDK4)

Xinyu Chi, Qicong Chen, Gang Wang, Honglin Luo, Shenhong Qu, Xiaosu Zou — Mon, 04 May 2026 22:03:04 -0700

ABSTRACT

Background

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide. Cyclin-dependent kinase 4 (CDK4) is a well-validated oncogenic driver in NSCLC, yet current CDK4 inhibitors—predominantly based on the aminopyrimidine scaffold—are limited by structural homogeneity and the rapid emergence of acquired resistance, underscoring the need for novel chemotypes.

Methods

We employed a HuProt human proteome microarray to screen for direct cellular targets of artesunate, an FDA-approved artemisinin derivative. Candidate interactions were validated by molecular docking, surface plasmon resonance (SPR), and in vitro kinase assays. Functional effects were assessed in A549 and H1299 NSCLC cell lines using flow cytometry and Western blotting.

Results

Artesunate was identified as a direct binder of CDK4, with molecular docking revealing a strong binding affinity (−7.069 kcal/mol). SPR analysis confirmed this interaction with a K _d of 488 μM, and in vitro kinase assays demonstrated potent inhibition of CDK4/Cyclin D3 activity (IC₅₀ = 0.2943 μM). Treatment with artesunate induced significant G0/G1 cell cycle arrest in both A549 and H1299 cells. This effect was mediated through inhibition of the CDK4–Rb–E2F axis, as evidenced by dose-dependent suppression of Rb phosphorylation at Ser780 and Ser795.

Conclusion

Our findings establish artesunate as a structurally distinct, non-aminopyrimidine CDK4 inhibitor with potent biochemical and cellular activity in NSCLC models. This work provides a promising therapeutic strategy to circumvent resistance associated with current CDK4 inhibitors and supports the repurposing of artesunate for CDK4-driven cancers.

The Immune Landscape of Acral Melanoma: From Basic to Clinical

Lihong Jiang, Zhaotian Zhang — Mon, 04 May 2026 22:00:27 -0700

ABSTRACT

Background

Acral melanoma (AM) is an aggressive melanoma subtype with poor prognosis and limited response to immune checkpoint inhibitors (ICIs). Despite increasing research efforts, the mechanisms underlying therapeutic resistance remain incompletely understood.

Aim

Tumor‐Immune‐On‐Chip to Evaluate Pathophysiological Feature of T Lymphocytes Expanded from Patient Tumors and Lymph Node Tissues

Sun, 03 May 2026 07:35:11 -0700

3D Tumor-Immune On-Chip reveals patient-derived tumor-infiltrating lymphocytes (TILs) exhibit superior infiltration and cytotoxicity against colorectal cancer spheroids compared to lymph node T cells, providing a platform to study patient-specific tumor-immune interactions for developing personalized cancer immunotherapies.

ABSTRACT

The infiltration and cytotoxicity of T lymphocytes are critical for cancer immunotherapy efficacy; however, the behavior of these immune cells has not been thoroughly investigated. Herein, a Tumor-Immune-On-Chip is established using cells acquired from the tissues of a patient with colorectal cancer to monitor T lymphocytes. Through the Tumor-Immune-On-Chip, the interaction between tumor spheroid and either T lymphocytes expanded from tumors (tumor-infiltrating lymphocytes; TILs) or lymph nodes (lymph node-derived lymphocytes; LN T cells) are investigated. Although initial 24-h analysis showed no statistical differences, extended 48-h observation revealed a significant deviation in T cell-mediated cell death signals between TILs and LN T cells. TILs demonstrated more potent cytotoxic effects than LN T cells after 48 h. The number of tumor-infiltrating CD3⁺ cells and cleaved caspase-3 expression levels were 4- and 2.1-fold higher, respectively, in TIL co-cultures compared to LN T cell co-cultures. Therefore, this proof-of-concept platform allows us to explore the patient-specific tumor-immune microenvironment, focusing on different types of T lymphocytes and establishing methodology for future clinical applications.

ClinicalTrial.gov identifier: NCT02589496

Age‐Associated Targetable Genomic Alterations and PD‐L1 Expression in 2509 Patients With Pulmonary Ground‐Glass Opacities

Sat, 02 May 2026 00:04:33 -0700

ABSTRACT

Aim

To investigate the landscape of targetable genomic alterations and programmed cell death ligand 1 (PD-L1) expression in pulmonary ground-glass opacities (GGOs) and their association with age.

Methods

A total of 2509 patients with GGOs were retrospectively analyzed. Tumor characteristics, PD-L1 expression, and prevalence of targetable alterations were compared across age groups.

Results

In GGOs, the mutation rates of EGFR (61.5%) and ERBB2 (12.0%) were relatively high, whereas those of KRAS (8.2%) and ALK rearrangements (2.3%) were relatively low. The patients exhibited a low tumor mutational burden (TMB), and PD-L1 expression was negative in 86.7% of cases. TMB, PD-L1 expression, and the mutation rates of EGFR, KRAS, and MET increased significantly with age, whereas the rates of ERBB2 mutations, ALK rearrangements, and RET rearrangements decreased significantly with age. Age was identified as an independent predictor for the above eight variables. The optimal age cutoff was determined to be 53 years. Compared with the younger age group (< 53 years), the older age group (≥ 53 years) showed a 31.6%, 130.4%, and 800.0% higher likelihood of harboring EGFR, KRAS, and MET mutations, respectively. Conversely, compared with the older age group, the younger age group showed a 289.1%, 94.1%, and 108.7% higher likelihood of harboring ERBB2 mutations, ALK rearrangements, and RET rearrangements, respectively.

Conclusions

GGOs exhibit a distinct genomic and PD-L1 profile with significant age-related heterogeneity, providing insights for age-stratified therapeutic strategies.

Differentiation of Fat‐Poor Renal Angiomyolipoma From Clear Cell Renal Cell Carcinoma: Diagnostic Performance of a Novel Type of Color Contrast Enhanced Ultrasound

Yiman Du, Xuyang Wang, Bo Jiang, Luda Song, Yukun Luo, Qiuyang Li — Fri, 01 May 2026 23:56:18 -0700

Our study confirms CPI can distinguish AML.wovf from ccRCC, potentially helping patients with AML.wovf avoid unnecessary surgery. These findings expand CPI's clinical utility, providing a promising tool for diagnosing renal tumors.

ABSTRACT

Background

The similar imaging characteristics of renal angiomyolipoma without visible fat (RAML.wvf) and clear cell renal cell carcinoma (ccRCC) are notable. Color Parameter Imaging (CPI) has emerged as an advanced contrast-enhanced ultrasound (CEUS) analysis tool that quantifies temporal perfusion dynamics.

Objective

Evaluate the diagnostic value of CPI in distinguishing AML.wovf from ccRCC.

Methods

In this prospective study, 88 patients (35 with AML and 53 with ccRCC) underwent CEUS and CPI. Junior and senior radiologists independently analyzed the CEUS and CPI images. Three diagnostic approaches were compared: (1) CPI alone, (2) CEUS alone, and (3) CEUS combined with CPI. The diagnostic sensitivity, specificity, accuracy, and receiver operating characteristic (ROC) curves of resident and staff radiologists were analyzed.

Results

The CPI features of ccRCC and AML.wovf analyzed by the junior and senior radiologist groups showed significant differences: the mosaic sign and the Cold sign (both p < 0.001) were more indicative of AML.wovf, whereas the Warm sign was more suggestive of ccRCC (both p < 0.05). The area under the curve (AUC) for the combined CEUS+CPI diagnosis in the junior radiologist group was higher than that for CEUS alone (p = 0.012). Regarding diagnostic confidence between the two radiologist groups, the proportion of uncertain cases in the CPI group was significantly lower than in the CEUS group for both the senior radiologist group and the junior radiologist group (both p < 0.05).

Conclusion

CPI technology can enhance the diagnostic performance of contrast-enhanced ultrasound in differentiating ccRCC from AML.wovf, particularly offering an advantage in improving the diagnostic accuracy of junior radiologists.

Different Immune Cells Modified With Chimeric Antigen Receptors Are Being Applied to Ovarian Cancer: Which Is the Most Effective?

Liying Wang, Yisen Cao, Yuan Ren, Yuhang Zhang, Liang Wang — Fri, 01 May 2026 23:49:54 -0700

ABSTRACT

Ovarian Cancer (OC), the deadliest gynecological malignancy, poses a major therapeutic challenge in advanced stages owing to its high recurrence rate and metastatic potential. In this regard, it is noteworthy that immunotherapy has recently gained significant attention in OC treatment, a phenomenon attributable to notable advances in over-the-counter Chimeric Antigen Receptor (CAR)-based cell therapy. At the heart of CAR-T Cell (CAR-T) immunotherapy is genetically modified CAR molecules that enable immune cells to target and recognize tumor antigens. Based on such strategies, CAR-T therapies have developed rapidly in hematological oncology and are gradually being extended to solid tumors. Despite their potential in OC treatment, several factors, including off-target effects attributable to the lack of Tumor-Specific Antigens (TSAs), as well as severe side effects such as tumor immune barriers, Cytokine Release Syndrome (CRS), and neurotoxicity, have been established to limit the clinical use of CAR-T therapies. Moreover, compared to CAR-T, CAR-Natural Killer (NK) and CAR-Macrophage (M) therapies have distinct advantages. The killing mechanism of NK cells integrates both CAR-dependent and non-dependent pathways, avoiding severe CRS and neurotoxicity. Furthermore, besides directly phagocytosing tumors due to its strong ability to infiltrate tumors, CAR-M therapy could also effectively improve the Immunosuppressive Microenvironment (IME) via immunomodulatory factor secretion to remodel M2-type Tumor-Associated Macrophages (TAMs) into the M1 phenotype with anti-tumor function. In this review, we systematically describe the research progress in CAR-T therapy for OC and compare the similarities and differences of three types of cellular therapies (CAR-T, CAR-NK, and CAR-M) regarding their mechanisms of action, clinical advantages, and technological bottlenecks. We hope that our findings will provide a theoretical basis for optimizing immunotherapeutic strategies for OC.

Trial Registration: ClinicalTrials.gov identifier: NCT03585764

Predicting Prognosis for Gastric Cancer Patients Receiving Neoadjuvant Treatment With Body Composition‐Based Deep Learning

Fri, 01 May 2026 23:40:25 -0700

ABSTRACT

Background

This study sought to develop an innovative body composition (BC)-based deep learning (DL) model to precisely evaluate survival in gastric cancer (GC) patients undergoing neoadjuvant treatment (NT).

Materials and Methods

This retrospective study included GC patients undergoing NT from two centers. CT images both pre-NT and post-NT were preprocessed, focusing on the automatic segmentation of subcutaneous fat, visceral fat, and skeletal muscle regions using TotalSegmentator. Delta Radiomics features were extracted using Pyradiomics. After feature fusion and selection, the optimal model is Naive Bayes (Rad model). A hybrid DL model was developed by combining ResNet18 and Transformer networks for feature extraction. The Clinic_Rad_DL model was constructed by combining clinical features, radiomic signatures, and DL signatures. The ExtraTree classifier was used for the Clinic_Rad_DL model, while a separate Cox regression model was developed for survival analysis using the same features.

Results

A total of 356 patients (mean age, 59 ± 10 years; 264 males [74.2%]) were enrolled and divided into training, validation, and test sets in a 7:2:1 ratio. The DL model outperformed the Rad model. The Clinic_Rad_DL model outperformed both Rad model and DL model, with AUC of 0.915, 0.890, and 0.890 in training, validation, and test sets, respectively. The Cox proportional hazards model showed C-index of 0.806, 0.803, and 0.819, effectively stratifying patients into high- and low-risk groups with significant survival differences.

Conclusion

The study developed and validated a BC-based DL model to predict survival in GC patients undergoing NT, offering potential for personalized treatment strategies in clinical practice.

Efficacy of Fertility‐Sparing Treatment With Progestin Is Associated With Different Molecular Classification in Endometrial Carcinoma and Atypical Endometrial Hyperplasia

Xue‐Qian Qian, Hao‐Hui Fu, Xiao‐Yun Wan, Dong‐Xiao Hu, Yuan‐Ming Shen — Fri, 01 May 2026 22:35:26 -0700

Molecular profiles and outcomes of CR rate in 74 cases.

ABSTRACT

Objective

To investigate the impact of various molecular characteristics on the outcomes of fertility-preserving therapy in patients with endometrial cancer (EC) and atypical endometrial hyperplasia (AEH).

Methods

A total of 14 EC cases and 60 AEH cases were retrospectively analyzed at the Women's Hospital, Zhejiang University from January 2013 to October 2022.

Results

This study investigated the molecular profiles and outcomes of fertility preservation in 74 cases. The most prevalent molecular profile was NSMP type (63.9%), followed by p53abn type (21.3%) and MMRd type (14.8%). After 6 months of progesterone therapy, the cumulative CR rates were 100% for NSMP type, 83.3% for MMRd type, and 33.3% for p53abn type (p = 0.006). The CR rate in the p53abn group was significantly lower than in the other two groups (p = 0.006), with a notably higher recurrence rate (p = 0.006). ER and PR expression was significantly lower in the MMRd and p53abn groups (p = 0.002). A total of 26 pregnancies (42.6%) were observed. In the EC group, the pregnancy rate of p53abn was lower than that of the NSMP group (0% vs. 83.3%, p = 0.02). In the AEH group, pregnancy rates of p53abn and MMRd were not significantly different from the NSMP group (0% vs. 50%, p = 0.16; 33.3% vs. 50%, p = 0.20).

Conclusion

Molecular classification may serve as a predictive tool for the efficacy of fertility preservation therapy in patients with EC and AEH and was found to be particularly useful for identifying p53 mutants, which are associated with a high risk of recurrence, as well as MMRd types, which are known to lead to poor responses to progesterone treatment.

The Clinical Benefits of Nutritional Supplementation Across the Chemotherapy Journey in Cancer Patients: A Multicenter Prospective Cohort Study

Fri, 01 May 2026 22:21:38 -0700

Objective

There is inconsistent data on cancer risk in people with intellectual disability. Our primary objective was to compare the incidence of cancer in people with and without intellectual disability.

Methods and Analysis

A cohort study using linked population-based administrative and cancer registry data in New South Wales, Australia 2001–2018. We compared the incidence of cancer in people with intellectual disability and a comparator group without intellectual disability matched for age, sex and residential postcode. We also compared cancer incidence in people with Down syndrome and people with intellectual disability without Down syndrome. We used a flexible parametric survival model accounting for competing risks.

Results

People with intellectual disability had a slightly higher risk of developing any cancer (sub-hazard ratio, SHR 1.07 [95% CI 1.03 to 1.12]) compared to those without intellectual disability. An increased risk was evident in the 0–14 year (SHR 2.19, 95% CI 1.85 to 2.59) and 15–49 year (SHR 1.34, 95% CI 1.23 to 1.46) age groups, and a decreased risk was observed for those aged 50 years and above (SHR 0.93, 95% CI 0.88 to 0.98). People with intellectual disability had a higher risk of colorectal cancer (SHR 1.32, 95% CI 1.15 to 1.51) and a lower risk of prostate cancer (SHR 0.45, 95% CI 0.38 to 0.53) and melanoma (SHR 0.75, 95% CI 0.64 to 0.88). People with Down syndrome had a significantly higher risk of childhood cancer (SHR 7.94, 95% CI 5.72 to 11.04) compared to those with other intellectual disability, and a similar risk as an adult.

Conclusions

These findings underscore the need for targeted health promotion campaigns and, for adults, customised cancer screening programmes to improve access, acceptability and outcomes for people with intellectual disability.

Assessing the Impact of Specialist Palliative Care on Healthcare Utilisation at the End of Life Among Patients With Pancreatic Cancer: A Nationwide Register‐Based Cohort Study

Wed, 29 Apr 2026 22:54:15 -0700

ABSTRACT

Introduction

Advanced pancreatic cancer is often a rapidly progressing malignancy causing high symptom burden. The objective of this study was to assess the association of specialist palliative care (SPC) and its timing with healthcare resource utilisation at the end of life.

Methods

This nationwide retrospective study which covers the whole population of Finland included all 1199 patients who died of pancreatic cancer in 2019. Data were obtained from national registries. Patients were categorised into two groups based on the timing of their first contact with SPC: Group I (> 30 days before death), and Group II (≤ 30 days before death or no contact).

Results

Among 1199 patients, 438 (36%) had a SPC contact, and median time from the first contact to death was 51 days. Contact with a SPC occurred > 30 days before death for 22.5% of the patients (n = 270). Having an earlier contact with SPC (Group I) was significantly associated with fewer secondary care hospitalisations (25% vs. 56%, p < 0.001) and fewer emergency department (ED) contacts (50% vs. 61%, p < 0.001) during the last month of life. In addition, patients in Group I were more likely to receive hospital-at-home services (44% vs. 9%, p < 0.001) and to receive care in SPC wards (23% vs. 5%, p < 0.001). Most of the patients died in hospital (56% vs. 79%, p < 0.001), but death in SPC ward (22% vs. 5%, p < 0.001) or at home (19% vs. 13%, p < 0.014) was more likely for patients in Group I.

Conclusion

Lower secondary healthcare utilisation and ED contacts during the last month of life, and higher probability of dying in SPC ward or at home, were observed in patients who had an earlier SPC contact. Integration of SPC in time should be ensured for all patients with advanced pancreatic cancer.

Fruquintinib Plus TAS‐102 With or Without SBRT as Third‐ Or Later‐Line Therapy for Metastatic Colorectal Cancer: Preliminary Results From a Prospective Phase II Trial

Wed, 29 Apr 2026 21:46:53 -0700

ABSTRACT

Both fruquintinib and TAS-102 monotherapies are guideline-recommended for third-line treatment of metastatic colorectal cancer (mCRC). This study aimed to analyze the preliminary outcomes of fruquintinib combined with TAS-102, with or without stereotactic body radiation therapy (SBRT), as a third- or later-line therapy for mCRC. This prospective, two-arm, phase II study planned to enroll 66 patients with mCRC who were unresponsive to at least two prior lines of therapy. Patients were allocated to either the FTS (fruquintinib + TAS-102 + SBRT) or FT (fruquintinib + TAS-102) group. Eligible patients received fruquintinib (4 mg, qd, days 1–21) and TAS-102 (30 mg/m², bid, days 1–5; 15–19) orally every 4 weeks until disease progression or intolerable toxicity. The primary endpoint was progression-free survival (PFS, per RECIST 1.1); secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs, graded using CTCAE v5.0). By January 20, 2025, 40 patients were enrolled (FTS group, 11; FT group, 29), with a median follow-up of 8.48 months. In 20 (50%) patients, the number of metastatic organs was ≥ 3. However, the number of metastatic lesions was > 5 in 32 (80%) patients. For the 36 eligible patients, the ORR and DCR were 19.4% and 88.9%, respectively. The median PFS was 8.58 months; however, the median OS has not been attained. The most common treatment-related AE was decreased white blood cell count (92.5%); grade 3–4 AEs included decreased lymphocyte count (12.5%). No treatment-related death occurred. Fruquintinib combined with TAS-102, with or without SBRT, showed promising preliminary efficacy and acceptable safety as third- or later-line treatment of mCRC.

Integrated Molecular Profiling Improves Subtype Classification and Reveals Inherited Susceptibility in Medulloblastoma: Insights From a Real‐World Cohort

Jiwei Song, Tiantian Han, Siqi Chen, Dongsheng Chen, Ziying Liu — Wed, 29 Apr 2026 20:03:14 -0700

ABSTRACT

Background

Medulloblastoma (MB) is a heterogeneous pediatric brain tumor characterized by distinct molecular subtypes. Although genomics and transcriptomics have improved subtype classification and informed targeted therapies, the clinical utility of integrated molecular profiling in real-world settings remains incompletely defined.

Methods

Identification of Prognostic Risk Factors in Older Patients With Extensive‐Stage Small Cell Lung Cancer

Mon, 27 Apr 2026 09:05:14 -0700

The study corroborates the prognostic value of previously identified risk factors impacting progression-free survival (PFS) and overall survival (OS) in older patients with extensive-stage small cell lung cancer (ES-SCLC). The figure was created with Microsoft PowerPoint. mPFS, Median progression-free survival; mOS, Median overall survival; CI, Confidence interval; HR, Hazard ratio; CT, Chemotherapy; LDH, Lactate dehydrogenase; ProGRP, Pro-gastrin-releasing peptide.

ABSTRACT

Given the limited evidence on prognostic factors specifically for older patients with extensive-stage small cell lung cancer (ES-SCLC), a population with distinct clinical characteristics, this study aimed to validate whether previously reported prognostic indicators retain their predictive value in this vulnerable group. A retrospective analysis was conducted on data from 270 older ES-SCLC patients who received treatment at the Fourth Hospital of Hebei Medical University between December 2016 and June 2024. By the final follow-up date of October 15, 2024, 212 deaths had been recorded. The median progression-free survival (mPFS) was 6.7 months (95% confidence interval [CI] 6.0–7.4), and the median overall survival (mOS) was 13.1 months (95% CI 11.8–14.4). For PFS, univariate and multivariate Cox analyses identified first-line chemotherapy (CT) and old-old (≥ 75 years) as independent adverse prognostic factors. For OS, old-old, a positive smoking history, bone metastasis, and high-lactate dehydrogenase (> 250 U/L) were identified as significant adverse prognostic factors. Notably, high-pro-gastrin-releasing peptide (ProGRP) (> 69.2 pg/mL) was significantly associated with an increased risk of death during the follow-up period beyond 10 months (HR = 1.85, 95% CI 1.05–3.26, p = 0.032); conversely, no significant association was observed within the initial 10 months of follow-up (HR = 0.84, 95% CI 0.44–1.60, p = 0.604). In conclusion, these findings not only corroborate the prognostic value of previously identified risk factors in older patients with ES-SCLC but also demonstrate that the prognostic impact of ProGRP is distinctly time-dependent.

Efficacy of Hepatic Artery Infusion Chemotherapy Combined With Regorafenib and Sintilimab Versus Regorafenib Alone in MSS/pMMR Colorectal Cancer Liver Metastases After Second‐Line Treatment Failure

Mon, 27 Apr 2026 09:03:19 -0700

ABSTRACT

Background

Microsatellite stable/proficient mismatch repair (MSS/pMMR) colorectal cancer liver metastases (CRCLM) have limited treatment options after failure of second-line systemic therapies. Hepatic artery infusion chemotherapy (HAIC) combined with targeted therapy and immunotherapy may offer improved outcomes.

Methods

This retrospective single-center study compared the efficacy and safety of HAIC (oxaliplatin, 5-fluorouracil, leucovorin) combined with regorafenib and sintilimab (HAIC-R-S) versus regorafenib monotherapy in MSS/pMMR CRCLM patients refractory to ≥ 2 lines of systemic therapy. Propensity score matching was used to balance baseline characteristics, resulting in 45 matched pairs (n = 90). Survival outcomes, tumor response, and adverse events (AEs) were analyzed.

Results

The HAIC-R-S group showed significantly improved median progression-free survival (PFS) (6.5 vs. 3.4 months; p < 0.001) and overall survival (OS) (14.1 vs. 8.1 months; p < 0.001) compared to regorafenib alone. Objective response rate (ORR) (37.8% vs. 2.2%; p < 0.001) and disease control rate (71.1% vs. 42.2%; p = 0.006) were also superior. Grade ≥ 3 AEs were more frequent in the combination group (26.7% vs. 13.3%), primarily hematologic toxicities.

Conclusion

In this retrospective, hypothesis-generating study, HAIC (oxaliplatin, 5-fluorouracil, leucovorin) combined with regorafenib and sintilimab showed improved PFS, OS, and ORRs compared with regorafenib monotherapy in refractory MSS/pMMR CRCLM, albeit with increased hematologic toxicity. These findings require validation in prospective, multicenter randomized trials before clinical implementation.

Intratumoral Proton Density Fat Fraction Predicts the Outcome of HAIC Combined With PD‐1 Inhibitors in Advanced Hepatocellular Carcinoma

Mon, 27 Apr 2026 09:01:17 -0700

ABSTRACT

Background and Aims

This study aimed to explore the predictive value of intratumoral proton density fat fraction (PDFF) and the clinical efficacy of hepatic arterial infusion chemotherapy (HAIC) combined with anti-programmed cell death protein 1 (anti-PD-1) therapy in advanced hepatocellular carcinoma (HCC).

Methods

In this retrospective cohort study, patients with advanced HCC received FOLFOX-HAIC or HAIC combined with anti-PD-1 (camrelizumab). Progression-free survival (PFS) was evaluated as the time-to-event outcome, while therapeutic efficacy was assessed using tumor response rates. The Kaplan–Meier method and log-rank test were used to compare PFS. In the MRI-PDFF subset, receiver operating characteristic (ROC) analysis was used to determine the optimal PDFF cutoff for predicting nonresponse (SD or PD).

Results

Between September 2020 and August 2025, 103 patients were included, of whom 47 received HAIC monotherapy and 56 received HAIC combined with anti-PD-1 therapy. The HAIC-PD1 group demonstrated significantly longer PFS compared with the HAIC group (HR 0.423; 95% CI 0.218–0.818; p = 0.0085), and a higher objective response rate (ORR: 46.4% vs. 21.3%; p = 0.012). In the MRI-PDFF subset, baseline intratumoral PDFF was associated with treatment response. ROC analysis identified an optimal PDFF cutoff of 2.64% for predicting nonresponse (AUC 0.784; 95% CI 0.664–0.903). Patients with PDFF < 2.64% achieved a higher ORR and longer PFS compared with those with PDFF ≥ 2.64%. Longitudinal analyses showed treatment-dependent changes in PDFF after HAIC-PD1 therapy; however, ΔPDFF did not differ significantly between responders and nonresponders.

Conclusion

HAIC combined with anti-PD-1 therapy demonstrated superior efficacy compared with HAIC monotherapy in advanced HCC. Baseline intratumoral PDFF may serve as a promising imaging biomarker associated with treatment response in patients receiving HAIC-PD1 therapy. Its potential prognostic relevance for time-to-event outcomes requires further validation in prospective cohorts.

TYRO3, AXL, MERTK and Their Ligands in Brain Metastases From Colorectal Cancers

Mon, 27 Apr 2026 08:59:55 -0700

TYRO3, AXL, and MERTK are expressed in primary tumors and extra-cerebral and brain metastases from colorectal cancers. AXL, primarily expressed in endothelial cells, is the more conserved marker between primary tumor and brain metastasis. The Low AXL/High GAS6 ratio is of poor prognosis in metastatic colorectal cancer patients. AXL better stratifies patients when studied in brain metastasis than in primary tumors.

ABSTRACT

Introduction

TYRO3, AXL, and MERTK (TAM receptor tyrosine kinases) represent potential therapeutic targets in metastatic colorectal cancer. Pre-clinical and clinical data are needed to explore further how TAM receptors interact with the central nervous system, which could impact brain metastases from colorectal cancer (BM-CRC).

Methods

A multi-transcriptomic analysis reveals the “EREG/EGFR/CSF axis” as a key intercellular network in the tumor microenvironment that dictates anti-EGFR sensitivity in colorectal cancer.

ABSTRACT

Sidedness influences colorectal cancer (CRC) prognosis and treatment response, yet the mechanism dictating differential EGFR inhibitor (EGFRI) sensitivity is unclear. This study investigated the tumor microenvironment (TME) in relation to EGFRI eligibility―clinically defined by factors such as tumor sidedness (e.g., left-sided), RAS/BRAF wild-type status, and microsatellite stability (MSS)―using integrated single-cell RNA sequencing (scRNA-seq), with bulk RNA-seq and spatial transcriptomics validation. We found cancer cell features reflected EGFRI eligibility more strongly than sidedness. EGFRI eligible tumors exhibited high Epiregulin (EREG) expression by cancer cells. Cell interaction analysis revealed a specific “EREG/EGFR/CSF axis” in EGFRI eligible CRC: EREG derived from cancer cell stimulates EGFR-expressing non-myCAF subtypes of cancer-associated fibroblasts (CAFs), which signal via CSF to M1/M2-like Tumor-Associated Macrophages/Monocytes (TAM/TAMo), potentially promoting M2 polarization. Spatial analysis confirmed the proximity of these interacting cell populations and localized EGFR pathway activation near cancer cells specifically in eligible tumors. This study provides a TME-centric view of EGFRI eligibility, identifying a key intercellular communication network driving differential responses. These findings suggest TME features could offer more precise patient stratification than sidedness alone, potentially improving CRC therapeutic strategies.

Stanniocalcin 2‐Induced Autophagy Confers Resistance of Lung Cancer Cells to EGFR Inhibition via the ERK/Beclin 1 Signaling

Mon, 27 Apr 2026 07:53:15 -0700

ABSTRACT

Background

Trial Registration: PROSPERO registration number: CRD42021291665

Effect Size of Factors Influencing Colorectal Cancer Survivors' Quality of Life: A Systematic Review and Meta‐Analysis

Youran Lee, Eungyung Kim — Sun, 26 Apr 2026 21:09:18 -0700

ABSTRACT

Aims

An XGBoost‐Based Multicenter Model for Predicting HBV‐Related Hepatocellular Carcinoma: Development and Validation

Simultaneous Establishment of Autologous Colorectal Cancer and Mesothelial Stromal Cell Lines from Malignant Ascites Reveals a Mesothelial‐Stromal FGFR3 Axis as a Potential Vulnerability in Peritoneal Metastasis

Fri, 24 Apr 2026 21:29:39 -0700

ABSTRACT

Colorectal cancer (CRC) with peritoneal dissemination remains a major therapeutic challenge because of poor prognosis and limited treatment options. Experimental models that accurately recapitulate tumor–mesothelial interactions are scarce. Here, we report the establishment of a novel autologous paired model comprising a CRC cell line (OMUCR-1) and matched cancer-associated mesothelial cells (CAmeso), both simultaneously derived from the malignant ascites of the same patient. Lineage marker analysis using qPCR demonstrated that OMUCR-1 selectively expressed epithelial markers (EPCAM, KRT20), whereas CAmeso strongly expressed mesothelial-mesenchymal markers (ACTA2, MSLN) and lacked epithelial marker expression. These mutually exclusive expression patterns confirm that the two cell populations are phenotypically distinct and rule out cross-contamination. OMUCR-1 displayed strong tumorigenic capacity across multiple transplantation models. CAmeso enhanced CRC cell migration and invasion in vitro, and co-transplantation with OMUCR-1 resulted in larger tumors enriched with αSMA-positive stromal components. RNA sequencing of co-injected xenografts revealed increased expression of murine stromal Fgfr3. Treatment with the FGFR inhibitor BGJ398 reduced tumor growth and decreased stromal FGFR3-positive components, suggesting that stromal FGFR3 may represent a potential microenvironmental vulnerability in CRC with peritoneal dissemination. This autologous CRC-mesothelial system provides a physiologically relevant platform for dissecting tumor-stroma interactions in peritoneal metastasis and may advance stromal-targeted therapeutic strategies.

Mecapegfilgrastim for Prophylaxis of Immunochemotherapy‐Induced Neutropenia in Patients With Diffuse Large B‐Cell Lymphoma: A Multicenter Pilot Trial

Fri, 24 Apr 2026 10:30:07 -0700

ABSTRACT

Background

This study evaluated the efficacy and safety of mecapegfilgrastim for preventing immunochemotherapy-induced neutropenia in treatment-naive patients with diffuse large B-cell lymphoma (DLBCL).

Methods

In this open-label, multicenter exploratory trial, patients were randomized in a 2:1 ratio to receive mecapegfilgrastim or no prophylaxis. All participants received 4 cycles of R-CHOP or R-CHOP-like regimens. The primary endpoint was the incidence of grade ≥ 3 neutropenia during cycle 1.

Results

Between October 2021 and June 2024, 42 patients were enrolled (mecapegfilgrastim: n = 28; control: n = 14). Grade ≥ 3 neutropenia in cycle 1 occurred in 32.14% of the mecapegfilgrastim group versus 64.29% in the control group. Across all cycles, mecapegfilgrastim consistently reduced grade ≥ 3 neutropenia; nadir neutrophil counts were higher and the need for short-acting granulocyte colony-stimulating factor was lower in the mecapegfilgrastim group (all nominal p ≤ 0.05). No cases of febrile neutropenia occurred in the mecapegfilgrastim group, compared to one case in the control group. Objective response rates were 75.0% (95% CI: 55.1, 89.3) and 57.1% (95% CI: 28.9, 82.3), respectively (nominal p = 0.298). Mecapegfilgrastim reduced the incidence of grade ≥ 3 neutropenia regardless of treatment response. Grade ≥ 3 treatment-emergent adverse events (TEAEs) occurred in 42.9% of the mecapegfilgrastim group and 92.9% of controls; serious TEAEs were reported in 7.1% of patients in both groups.

Conclusions

Mecapegfilgrastim demonstrated a favorable safety profile and potential efficacy in reducing the incidence and severity of neutropenia in DLBCL patients receiving R-CHOP or R-CHOP-like regimens. These findings may support its prophylactic use in this population and warrant validation in larger trials.

Trial Registration

chictr.org.cn: ChiCTR2100048196. Registered on July 4, 2021

Modern Clinical Trials: Seamless Designs and Master Protocols

Thu, 23 Apr 2026 22:29:16 -0700

ABSTRACT

Background

Drug development is often inefficient, costly and lengthy, yet it is essential for evaluating the safety and efficacy of new interventions. Compared with other disease areas, this is particularly true for Phase II/III cancer clinical trials where many drug candidates fail to advance and reduced regulatory approvals are being seen. In response to these challenges, seamless clinical trials and master protocols have emerged to streamline the drug development process.

Methods

Seamless clinical trials, characterised by their ability to transition seamlessly from one phase to another, can lead to accelerating the development of promising therapies while Master protocols provide a framework for investigating multiple treatment options and patient subgroups within a single trial.

Results

We discuss the advantages of these methods through real trial examples and the principles that lead to their success while also acknowledging the associated regulatory considerations and challenges.

Conclusion

Seamless designs and master protocols have the potential to improve confirmatory clinical trials. In the disease area of cancer, this ultimately means that patients can receive life-saving treatments sooner.

Issue Information

Thu, 23 Apr 2026 22:23:20 -0700

Cancer Medicine, Volume 15, Issue 5, May 2026.