BMC Cancer[JOURNAL]
Sun
200 papers
Genomic landscape of triple-negative breast cancer in South Asian populations: a systematic review.
Bhattacharyya S, Thomas JV, Prasad A … +4 more , Deep A, Bhuvan FNU, Ramachandiran S, Garanayak RK
BMC Cancer · 2026 Jul · PMID 42402565 · Full text
Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype defined by the absence of estrogen receptor, progesterone receptor, and HER2 expression, and is associated with limited targeted treatment optio...
Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype defined by the absence of estrogen receptor, progesterone receptor, and HER2 expression, and is associated with limited targeted treatment options and poor clinical outcomes. Although major genomic studies have characterized TNBC in Western populations, the genomic landscape of TNBC in South Asian populations remains insufficiently understood despite a relatively high disease burden in this region. We conducted a systematic review following PRISMA 2020 guidance to synthesize available genomic evidence on TNBC in South Asian cohorts. Studies reporting genomic alterations in TNBC patients from South Asia were identified through searches of PubMed, Scopus, Web of Science, and ProQuest, supplemented by citation tracking and a ClinicalTrials.gov search. Eight studies from India and Pakistan met the eligibility criteria. Because the evidence base was sparse and clinically and methodologically heterogeneous, and because the number of studies reporting extractable denominators for any single biomarker did not reach our pre-specified threshold for pooling, data were synthesized descriptively rather than by meta-analysis. Across the included studies, recurrent alterations were reported in key tumor-suppressor and DNA-repair genes, particularly BRCA1, BRCA2, and TP53. Germline BRCA1 alterations were reported at a relatively high frequency in several cohorts, most notably in Pakistani TNBC patients, suggesting a contribution of hereditary DNA-repair defects to TNBC pathogenesis in this population. These findings highlight the importance of population-specific genomic analyses and support the growing role of DNA-repair-directed therapies and biomarker-driven precision oncology strategies in TNBC management. We additionally propose, as recommendations for future work, a two-tier framework for ancestry classification and a tiered scheme for harmonizing homologous recombination deficiency (HRD) reporting.
Psychometric and structural properties of Traditional Chinese version of postoperative oral dysfunction-10 in patients with oral cancer undergoing facial free flap reconstruction surgery.
Hsu WC, Yu WP, Han HM … +2 more , Kao HK, Chiu HY
BMC Cancer · 2026 Jul · PMID 42402562 · Full text
PURPOSE: Dysphagia is a frequent complication in oral cancer patients after free-flap reconstruction. Although the Postoperative Oral Dysfunction-10 (POD-10) is widely used to assess swallowing dysfunction, no validated...
PURPOSE: Dysphagia is a frequent complication in oral cancer patients after free-flap reconstruction. Although the Postoperative Oral Dysfunction-10 (POD-10) is widely used to assess swallowing dysfunction, no validated Traditional Chinese version exists for Mandarin-speaking Taiwanese patients. This study aimed to translate the POD-10 into Traditional Chinese (TC-POD-10) and evaluate its reliability and validity in Mandarin-speaking Taiwanese patients with oral cancer undergoing free-flap reconstruction. METHODS: A cross-sectional study was conducted with 100 oral cancer patients post free-flap surgery in a medical center. Internal consistency was tested using Cronbach's alpha. Construct validity was evaluated through exploratory factor analysis (EFA). Criterion validity was assessed by correlating TC-POD-10 with the Chinese Functional Oral Intake Scale (FOIS). Known-group validity was tested using Eating Assessment Tool-10 (EAT-10) scores to distinguish between patients with and without dysphagia. Diagnostic accuracy was determined using the area under the receiver operating characteristic curve (AUC). RESULTS: The TC-POD-10 demonstrated excellent internal consistency (α = 0.94) and strong correlation with FOIS (r = -0.89, p < 0.001). Patients with dysphagia had significantly higher TC-POD-10 scores (14.6 vs. 10.0, p < 0.001). EFA revealed a single-factor model explaining 65.6% of variance. The tool showed high accuracy (AUC = 0.92), with sensitivity of 89% and specificity of 96% at a cutoff score of 15. CONCLUSION: The TC-POD-10 is a reliable and valid instrument for assessing dysphagia in Taiwanese oral cancer patients. Its strong psychometric performance supports its clinical use for evaluating and managing swallowing dysfunction.
Ethyl caffeate reprograms tumor-associated macrophages to enhance CD8 T-cell immunity in colorectal cancer.
Bao Z, Gao J, Cheng X … +3 more , Yang W, Ma X, Ji R
BMC Cancer · 2026 Jul · PMID 42402561 · Full text
BACKGROUND: The colorectal cancer (CRC) tumor microenvironment contains diverse myeloid populations that critically regulate antitumor immunity and therapeutic response. Tumor-associated macrophages are key regulators of...
BACKGROUND: The colorectal cancer (CRC) tumor microenvironment contains diverse myeloid populations that critically regulate antitumor immunity and therapeutic response. Tumor-associated macrophages are key regulators of macrophage-T-cell crosstalk within the CRC microenvironment. This study aimed to investigate the antitumor effects of Ethyl caffeate (EC) and determine whether EC modulates macrophage-associated immune remodeling in CRC. METHODS: Public single-cell RNA sequencing data from CRC tissues were analyzed to characterize myeloid infiltration, macrophage heterogeneity, Cell-cell communication, pseudotime trajectories, and macrophage-associated prognostic signatures. RAW264.7 cells and bone marrow-derived macrophages (BMDMs) were used to evaluate the effects of EC on macrophage viability and polarization in vitro. An immunogenic syngeneic MC38 CRC model was established in C57BL/6 mice to assess the antitumor activity of EC. Flow cytometry was used to quantify tumor infiltrating macrophages, CD86⁺ M1-like macrophages, CD8⁺ T cells, Granzyme B expression, and PD-1 expression. Clodronate liposome-mediated macrophage depletion was performed to determine whether the antitumor effect of EC was macrophage dependent. RESULTS: Single-cell analysis revealed extensive myeloid infiltration and marked TAM heterogeneity in CRC. State-specific analyses identified CXCL9/CXCL10 IFN-responsive TAMs as a transitional immune activating population closely associated with CXCL10-CD8 T-cell immune signatures. Macrophage-derived gene signatures were associated with overall survival in the TCGA-COAD/READ cohort. EC showed limited cytotoxicity at 30 and 60 µM and promoted macrophage polarization toward an M1-like antitumor phenotype in RAW264.7 cells and BMDMs. In the immunogenic MC38 syngeneic CRC model, EC treatment significantly suppressed tumor growth, reducing tumor volume by 31.3% ± 10.0% at 25 mg/kg and 46.6% ± 13.5% at 50 mg/kg. EC increased CD86⁺ inflammatory macrophage-associated activation, enhanced CD8⁺ T-cell infiltration, increased Granzyme B expression, and reduced PD-1 expression on tumor infiltrating CD8⁺ T cells, suggesting enhanced CD8⁺ T-cell cytotoxic activation. Macrophage depletion largely attenuated the antitumor effect of EC. CONCLUSIONS: EC suppresses colorectal tumor growth at least partly through macrophage-dependent immune remodeling. These findings identify EC as a potential macrophage-reprogramming compound that enhances CD8⁺ T-cell antitumor immunity in CRC.
Non-linear association between body mass index and port-related thrombosis in breast cancer patients: a retrospective cohort study.
Chen Y, Wang D, Li L … +4 more , Lin T, Lin X, Du X, Lian W
BMC Cancer · 2026 Jul · PMID 42401902 · Full text
BACKGROUND: The association between body mass index (BMI) and the risk of catheter-related thrombosis in breast cancer patients remains unclear, particularly regarding potential non-linear relationships and clinically re...
BACKGROUND: The association between body mass index (BMI) and the risk of catheter-related thrombosis in breast cancer patients remains unclear, particularly regarding potential non-linear relationships and clinically relevant thresholds. This study aimed to investigate the impact of BMI on the risk of port-related thrombosis and to characterize its dose-response pattern. METHODS: This retrospective cohort study included 1,247 breast cancer patients who underwent totally implantable venous access port (TIVAP) implantation at a single center between January 2019 and September 2025. Restricted cubic spline (RCS) analysis was performed to explore the non-linear association between BMI and thrombosis risk and to identify a potential threshold. Based on the RCS results, patients were categorized into two groups (BMI ≤ 23 vs. > 23 kg/m²). Logistic regression analyses were conducted to identify independent risk factors, and Kaplan-Meier analysis was used to evaluate thrombosis-free survival. RESULTS: RCS analysis revealed a non-linear association between BMI and the risk of port-related thrombosis, with a threshold at approximately 23 kg/m², beyond which the risk increased progressively. The incidence of thrombosis was significantly higher in patients with BMI > 23 kg/m² compared with those with BMI ≤ 23 kg/m² (9.30% vs. 5.58%, P = 0.013). In multivariate logistic regression analysis, BMI > 23 kg/m² remained an independent risk factor for thrombosis (OR = 1.58, 95% CI: 1.02-2.47, P = 0.042), while hypertension was also associated with increased risk (OR = 2.53, 95% CI: 1.37-4.66, P = 0.003), and HER2-positive status was associated with a lower risk of thrombosis (OR = 0.58, 95% CI: 0.36-0.93, P = 0.024). Kaplan-Meier analysis showed that patients with higher BMI had significantly lower thrombosis-free survival, with early curve separation and a progressively widening difference over time. CONCLUSIONS: Elevated BMI is significantly associated with an increased risk of port-related thrombosis in breast cancer patients, with a non-linear dose-response relationship and a threshold effect at approximately 23 kg/m². These findings suggest that BMI may serve as a clinically useful marker for risk stratification and highlight the importance of tailored thromboprophylaxis strategies in high-risk patients.
Anesthetic-chemotherapy interplay in osteosarcoma: preliminary investigations with in vitro models.
Gürler Balta M, Erden Tayhan S, Bilgin S … +3 more , Kölükçü V, Şahin AT, Genç A
BMC Cancer · 2026 Jul · PMID 42401870 · Full text
BACKGROUND: The primary objective of this study is to evaluate whether anesthetic agents modulate the apoptotic activity and migration-inhibitory effects of chemotherapeutic agents, thereby informing the optimization of...
BACKGROUND: The primary objective of this study is to evaluate whether anesthetic agents modulate the apoptotic activity and migration-inhibitory effects of chemotherapeutic agents, thereby informing the optimization of perioperative management strategies in oncologic interventions. METHODS: SAOS-2 cells were treated with varying concentrations of thiopental, ketamine, and doxorubicin. Cell viability was assessed via MTT assay to determine IC₅₀ values. Thiopental exhibited greater antiproliferative activity than ketamine and was selected for further study. Its interaction with doxorubicin was analyzed using the Chou-Talalay method, yielding a combination index (CI) of 0.92608 at Fa = 0.5, indicating moderate synergism. The combination treatment also led to reduced IC₅₀ values. Cell migration was evaluated using a scratch wound healing assay. Gene expression changes related to apoptosis and metastasis were analyzed using qRT-PCR. In silico molecular docking simulations were performed to provide mechanistic insights into the observed biological effects. RESULTS: Thiopental and doxorubicin exhibited dose-dependent cytotoxicity, with the combination showing enhanced antiproliferative activity. Co-treatment reduced IC₅₀ values and suppressed SAOS-2 cell migration more effectively than either drug alone. Gene expression analysis revealed increased pro-apoptotic markers and decreased Bcl-2 expression. Metastasis-associated genes were significantly downregulated, despite upregulation of hypoxia-responsive genes. Molecular docking analyses identified interactions of thiopental and doxorubicin with HSP70, HSP90, and CYP450, providing complementary information for the interpretation of the observed cellular responses. CONCLUSION: The findings suggest that thiopental may influence the cellular response to doxorubicin in osteosarcoma through treatment-associated modulation of apoptosis- and migration-related molecular responses. The observed moderate synergistic interaction and dose-reduction potential warrant further investigation in more clinically relevant experimental models.
LAR/NMLR stratify mortality risk before and after checkpoint inhibitor pneumonitis in NSCLC: multi-state and time-dependent analyses.
Zhang Q, Xu Y, Liu J … +1 more , Wang Y
BMC Cancer · 2026 Jul · PMID 42401858 · Full text
BACKGROUND: Checkpoint inhibitor pneumonitis (CIP) is a clinically important immune-related adverse event in non-small cell lung cancer (NSCLC), but its time-varying occurrence complicates prognostic assessment. OBJECTIV...
BACKGROUND: Checkpoint inhibitor pneumonitis (CIP) is a clinically important immune-related adverse event in non-small cell lung cancer (NSCLC), but its time-varying occurrence complicates prognostic assessment. OBJECTIVE: This study evaluated whether baseline lactate dehydrogenase-to-albumin ratio (LAR) and neutrophil-monocyte-to-lymphocyte ratio (NMLR) were associated with CIP onset and mortality risk before and after CIP. METHODS: This retrospective cohort included adults with advanced or recurrent NSCLC treated with immune checkpoint inhibitors (ICIs) at Zhongshan Hospital (Xiamen), Fudan University, between 2021 and 2024. CIP incidence was estimated using cumulative incidence functions with death without prior CIP as a competing event. Transition-specific associations were evaluated using an illness-death multi-state model: CIP-free at-risk state after ICI initiation (state 0), post-CIP state (state 1), and death as the absorbing state (state 2). Overall survival (OS) was assessed using a time-dependent Cox model with CIP modeled as a time-varying exposure. Restricted cubic splines (RCS), calibration analyses, penalized sensitivity analyses, and benchmark comparisons with the lung immune prognostic index (LIPI) were performed. RESULTS: Among 202 patients, 24 developed CIP and 119 died during follow-up. In parsimonious transition-specific Cox models, cause-specific hazard ratios (csHRs) showed that zLAR and zNMLR were not associated with CIP onset, but were associated with death without prior CIP (0→2: zLAR csHR 1.22, 95% CI 1.00-1.50; zNMLR csHR 1.28, 95% CI 1.09-1.51) and death after CIP (1→2: zLAR csHR 2.47, 95% CI 0.93-6.57; zNMLR csHR 3.14, 95% CI 1.32-7.45). In the time-dependent Cox model, CIP was not significantly associated with mortality, whereas zLAR (HR 1.25, 95% CI 1.01-1.55) and zNMLR (HR 1.25, 95% CI 1.01-1.54) remained prognostic. Adding zLAR and zNMLR to the clinical base model increased the C-index from 0.623 to 0.682. The dual-outcome risk map showed partial separation between predicted CIP and death risks. CONCLUSION: Baseline LAR and NMLR were associated with mortality risk rather than the occurrence of CIP in ICI-treated NSCLC patients. These simple blood-based indices may help identify patients who require closer survival-oriented monitoring, while CIP risk should be assessed together with clinical pulmonary factors.
Machine learning-driven development of a novel unfolded protein response-related gene signature for predicting lung adenocarcinoma patient prognosis.
Jiao R, Wu C, Zhang T … +4 more , Yan H, He W, Wang Z, Yan X
BMC Cancer · 2026 Jul · PMID 42401850 · Full text
Lung adenocarcinoma (LUAD) is the most common lung cancer histological subtype. Although the unfolded protein response (UPR) has been linked to various human diseases, its role in LUAD remains unclear. To identify UPR-re...
Lung adenocarcinoma (LUAD) is the most common lung cancer histological subtype. Although the unfolded protein response (UPR) has been linked to various human diseases, its role in LUAD remains unclear. To identify UPR-related genes, we applied various methods, including weighted gene co-expression network analysis, differential expression analysis, and multivariate Cox regression. Ten machine learning algorithms were used to construct a UPR-related signature (UPRRS), which was validated using multiple public LUAD datasets. The UPRRS was integrated into a nomogram used in clinical practice for prognosis prediction. We also evaluated predicted drug sensitivity patterns across different risk subgroups. We identified 33 UPR-associated hub genes. A UPRRS was developed through systematic evaluation of 101 machine-learning combinations, exhibiting stable prognostic performance across multiple cohorts. Integration of the UPRRS into a nomogram facilitated the construction of a quantitative prognostic model. Significant differences in biological processes and tumor microenvironment immune cell infiltration were observed between the high- and low-risk UPRRS groups. All five UPRRS genes (ALDH2, FKBP4, KLF4, LAIR1, SIDT2) were validated at the protein level in LUAD cell lines, and FKBP4 was further confirmed by IHC in clinical tissues. Functional experiments showed that FKBP4 knockdown inhibited proliferation, migration, and invasion of A549 and H1975 cells, supporting a potential role for FKBP4 in LUAD progression. Our UPRRS provides a promising tool for prognostic stratification and may offer additional insights into tumor immune microenvironment characterization and therapeutic response prediction in LUAD.
Intensity-modulated radiotherapy alone versus concurrent chemoradiotherapy ± induction chemotherapy in older patients with low-risk stage II or T3N0M0 nasopharyngeal carcinoma.
Liao ZW, Xu Q, Sun XS … +11 more , Lin C, Cai HT, Hu L, Wang Q, Zhang YB, Chen XL, Zhang LJ, Lin XD, Tian YH, Yu HW, Wen YF
BMC Cancer · 2026 Jul · PMID 42401810 · Full text
BACKGROUND: The optimal treatment strategy for older patients with low-risk stage II or T3N0M0 nasopharyngeal carcinoma (NPC) remains undefined. This multicenter retrospective study compared the long-term outcomes and to...
BACKGROUND: The optimal treatment strategy for older patients with low-risk stage II or T3N0M0 nasopharyngeal carcinoma (NPC) remains undefined. This multicenter retrospective study compared the long-term outcomes and toxicities of intensity-modulated radiotherapy (IMRT) alone versus concurrent chemoradiotherapy with or without induction chemotherapy (CCRT ± IC) in this population, and explored the underlying tumor microenvironment (TME) characteristics. METHODS: A total of 1,265 older patients aged ≥ 60 years with low-risk NPC, defined as stage II or T3N0M0 disease without adverse features including lymph node diameter ≥ 3 cm, extranodal extension, or EBV DNA ≥ 4000 copies/mL, were enrolled from three centers between 2010 and 2022. Propensity score matching (PSM) was used to balance baseline characteristics between treatment groups. Survival outcomes and toxicities were compared. Additionally, a deep learning-based Hover-Net model was applied to analyze immune cell infiltration in hematoxylin and eosin-stained sections from a subset of patients to investigate TME differences between risk groups. RESULTS: After PSM, IMRT alone demonstrated comparable survival outcomes to CCRT ± IC across all cohorts. In the training cohort, the 5-year cancer-specific survival rate was 91.4% in both groups (HR 1.07; P = 0.87), with consistent findings for progression-free survival, locoregional relapse-free survival, and distant metastasis-free survival. These results were validated in two external cohorts. However, CCRT ± IC led to significantly higher acute grade 3/4 hematologic and gastrointestinal toxicities. Hover-Net analysis revealed that the low-risk group exhibited significantly higher lymphocyte infiltration in the TME compared with the high-risk group (P < 0.05), suggesting a potential biological basis for the favorable outcomes observed with IMRT alone. CONCLUSIONS: For older patients with low-risk stage II or T3N0M0 NPC, IMRT alone achieves survival outcomes equivalent to CCRT ± IC with significantly fewer acute toxicities. The enriched lymphocyte infiltration in the low-risk TME provides a biological rationale for this chemotherapy-sparing approach, supporting IMRT alone as a preferred toxicity-de-escalation strategy.
Plexin A2 regulated the metastasis in breast cancer through MCM7.
Xiang C, Chen X, Mo F … +5 more , Zhong Z, Wang Q, Kong D, Deng J, Hong M
BMC Cancer · 2026 Jul · PMID 42399903 · Full text
Breast cancer is a malignant tumour that affects women's health. In clinical practice, breast cancer is mainly treated by surgery, radiation, and drugs, but the risk of metastasis and recurrence is high, and metastasis i...
Breast cancer is a malignant tumour that affects women's health. In clinical practice, breast cancer is mainly treated by surgery, radiation, and drugs, but the risk of metastasis and recurrence is high, and metastasis is inextricably linked to the transcription and regulation of many molecule. In this manuscript, we first found 27 highly expressed genes and 58 lower expressed genes related to metastasis, then Plexin A2 was found highly expressed in the tissues from metastasis breast cancer and exerted as promote role in cell proliferation, migration, and invasion of MDA-MB-231. Also, CoIP-MS was used to detect the proteins which bind with Plexin A2 and differential expressed in highly metastasis MDA-MB-231 and 9 proteins were selected in highly invasion MDA-MB-231. Plexin A2 was found bind with MCM7 in a binding set of S45 through a phosphoserine/threonine binding group in highly metastasis MDA-MB-231. Moreover, Plexin A2 and MCM7 was found involved in cell proliferation, apoptosis inhibition, migration, and invasion of MDA-MB-231. In conclusion, Plexin A2 bind with MCM7 in a binding set of S45 through a phosphoserine/threonine binding group, Plexin A2 and MCM7 was involved in cell proliferation, apoptosis inhibition, migration, and invasion of MDA-MB-231. These results showed that Plexin A2 can be considered as a promising biomarker in breast cancer metastasis.
Spatial profiling of tissue-resident memory T cells reveals stromal IL-15 niches and a paradoxical CD103⁺ phenotype predicting survival in oral squamous cell carcinoma.
Ali A, Bari MF, Arshad S … +4 more , Wahid M, Safdar J, Anwar K, Farooqui WA
BMC Cancer · 2026 Jul · PMID 42399859 · Full text
Oral squamous cell carcinoma (OSCC) is a major malignancy in South Asia, driven by betel nut/tobacco use, with 5-year survival near 50-60% and frequent recurrences reflecting its aggressive biology. Although tissue resid...
Oral squamous cell carcinoma (OSCC) is a major malignancy in South Asia, driven by betel nut/tobacco use, with 5-year survival near 50-60% and frequent recurrences reflecting its aggressive biology. Although tissue resident memory (TRM) T cells mediate innate immunity, their spatial organization and associated regulatory role of cytokine, interleukin-15 (IL-15) in the OSCC tissues and their microenvironment remain unclear.This study aimed to map CD4⁺ and CD8⁺ T lymphocytes, and TRM markers (CD103, CD49a, CD69) across tumor and stromal compartments, to assess the regulatory role of IL-15 and CD103 associated epithelial E-cadherin interactions and build a multivariate prognostic model.Method Eighty OSCC cases confirmed by histopathological examination. Formalin-fixed, paraffin-embedded tumor tissues (~ 1 g) from surgical resections underwent immunohistochemistry. Whole-slide digital imaging (×40) quantified CD4⁺ and CD8⁺ T lymphocytes, and TRM markers across tumor and stromal fields. Staining intensity and percent scores were generated as a composite score (0-3). Inter-observer reliability (Kendall's τ ≥ 0.7) was verified. Associations were tested using χ²/Fisher's exact, while survival was analyzed by Kaplan-Meier and Cox regression (HR, 95% CI).Results Immune and epithelial marker expression varied significantly across tumor and stromal compartments (p < 0.001). Advanced tumor stage predicted poor survival (p = 0.044). Retained E-cadherin correlated with improved survival (p = 0.027), while CD49a expression was associated with adverse outcomes (p = 0.006). Multivariate Cox regression identified CD103 (Adj.HR 2.02, 95% CI 1.03-3.96) and E-cadherin (Adj.HR 3.01, 95% CI 1.25-7.23) as independent adverse predictors, whereas stromal CD8 (HR 0.35, 95% CI 0.14-0.99) and CD49a (HR 0.37, 95% CI 0.14-0.98) were protective. High IL-15 expression showed a positive association with CD103 TRM T cell infiltration, particularly within the stromal compartment, although the association did not reach statistical significance (p = 0.076).Conclusion The spatial interplay among IL-15 expression, CD103⁺ immune infiltration, and the localization of TRM-associated markers suggests the presence of an integrated immune-epithelial axis associated with OSCC progression and may provide prognostic and therapeutic insights.
Epidemiological trends of non-small cell lung cancer and systemic treatment rates as part of initial therapeutic strategy from 2016 to 2020 in Greece: results of the epidemiological part of INFINITY study.
Agelaki S, Demiri S, Kotsakis A … +18 more , Mauri D, Mountzios G, Christopoulou A, Christodoulou C, Goumas G, Bafaloukos D, Koumarianou A, Korantzis I, Boukovinas I, Linardou H, Kosmidis P, Zagouri F, Ramfidis V, Emmanouilides C, Desiniotis A, Dimitriadis I, Iliopoulou E, Syrigos KN
BMC Cancer · 2026 Jul · PMID 42399856 · Full text
BACKGROUND: In view of the shifting standard of care for non-small cell lung cancer (NSCLC), we aimed to capture the evolution of the epidemiological and systemic treatment (ST) landscape in Greece. METHODS: This non-int...
BACKGROUND: In view of the shifting standard of care for non-small cell lung cancer (NSCLC), we aimed to capture the evolution of the epidemiological and systemic treatment (ST) landscape in Greece. METHODS: This non-interventional, single-country, multicenter, retrospective study, collected high-level aggregate data for adult patients who were newly diagnosed with histologically/cytologically confirmed Stage I-IV NSCLC between 01-Jan-2016 and 31-Dec-2020 (index period) at leading oncology clinics across the country. RESULTS: Overall, 10,644 patients were newly diagnosed with NSCLC during the entire 5-year index period at the 18 participating sites (63.8% of the patients inside Attica; 51.0% at public academic institutions). An increasing trend in NSCLC diagnoses was observed throughout the index period, with the largest rise seen from n = 1765 in 2016 to n = 2013 in 2017 which was driven by an abrupt increase in Stage IV diagnoses, and the lowest from n = 2332 in 2019 to n = 2373 in 2020. Over the index period, 5.9%, 10.3%, 23.4% and 60.4% of all cases were Stage I, II, III, and IV, respectively. Of the Stage I and II patients, 41.3% and 73.3% were treated with ST, respectively, which mostly comprised of chemotherapy, with negligible variations through the years. Most of the Stage III and IV patients received ST (85.9% and 88.4%, respectively) with respective overall chemotherapy rates of 82.6% and 63.8% which remained relatively constant over the examined years, and immunotherapy utilisation rates of 29.6% and 31.3% which exhibited gradual and substantial increases (reaching 43.5% and 55.0% in 2020). Among Stage IV patients, 6.6% and 4.8% were treated with targeted and investigational therapies, respectively, accounting for the majority of NSCLC patients treated with such therapies (88.4% and 86.6%). Institutional variations were noticed in temporal trends of NSCLC diagnoses, stage distribution, and ST rates. CONCLUSION: The number of new NSCLC cases continues to rise with more than half still presenting with metastatic disease. Albeit certain medical practice variations, the observed remarkable increases in immunotherapy use are aligned with immune checkpoint inhibitor approvals and their incorporation into European and national clinical practice guidelines.
Multi-level stakeholder perspectives on barriers and facilitators to engaging older adult cancer survivors in mental health treatment.
Saracino RM, Park EY, Jutagir DR … +5 more , Walsh LE, Gilliland J, Demirjian C, McConnell K, Nelson CJ
BMC Cancer · 2026 Jul · PMID 42399839 · Full text
BACKGROUND: The current study sought to identify the barriers to and facilitators of connecting older adult cancer survivors (OACS) to mental health treatment in cancer survivorship and to better understand the opportuni...
BACKGROUND: The current study sought to identify the barriers to and facilitators of connecting older adult cancer survivors (OACS) to mental health treatment in cancer survivorship and to better understand the opportunities to improve the likelihood that OACS receive appropriate services in survivorship. METHODS: Four virtual focus groups with 22 stakeholders (i.e., OACS, social workers, and APPs) were conducted. A semi-structured focus group guide queried participants about their experiences of referring and connecting to mental health services during cancer survivorship with a focus on barriers and facilitators. Thematic content analysis guided the generation and interpretation of major and minor study themes from the focus groups. RESULTS: OACS were 56% female [n = 5; mean age = 74 (range: 66-85)]. Providers were 92% female (n = 12) and 69% (n = 9) had been working in oncology for over ten years. Three major conceptual themes were identified: (1) Care pathway characteristics (i.e., limited referral resources and knowledge); (2) Patient-level characteristics (i.e., motivation, stigma); (3) Perspectives on telehealth (i.e., overall increased access to care but may present challenges for some OACS). These overarching themes included sub-themes of barriers and facilitators to connecting OACS to mental health services. CONCLUSIONS: OACS remain disconnected from mental health services and providers struggle to overcome systemic barriers to getting survivors the care they need. Given the standard of care to screen for depression in cancer survivorship, OACS will continue to be identified as depressed with no clear recourse for intervention. Therefore, future research on how to mitigate barriers and improve existing care pathways to connect OACS to mental health treatment is warranted.
Preliminary study on the mechanism of OPN up-regulating PD-L1 to induce CD8 + T cell exhaustion in synovial sarcoma.
Zhuo H, Li X, Xue Z … +4 more , An W, Meng L, Jia W, Wang N
BMC Cancer · 2026 Jul · PMID 42399829 · Full text
BACKGROUND: Synovial sarcoma (SS) is a rare and highly malignant soft tissue sarcoma. The efficacy of existing therapies is limited, and new strategies are urgently needed. Osteopontin (OPN) promotes disease progression...
BACKGROUND: Synovial sarcoma (SS) is a rare and highly malignant soft tissue sarcoma. The efficacy of existing therapies is limited, and new strategies are urgently needed. Osteopontin (OPN) promotes disease progression by regulating tumor-immune cell interaction and immunosuppressive microenvironment, which is a potential therapeutic target. The aim of this study was to investigate the role of OPN in SS immune regulation and tumor progression. METHODS: A stable cell line with OPN knockdown was constructed using lentiviral transduction. RNA-seq and bioinformatics analysis were used to predict the correlation between OPN and immunity. Flow cytometry and ELISA were used to detect the changes in the number and function of CD8 + T cells. EDU, CCK-8 and Transwell chamber experiments were used to detect the proliferation, invasion and migration ability of SS. The protein interaction between OPN and PD-L1 was detected by molecular docking and Co-IP. The expression of PD-L1 was detected by Western blot and flow cytometry. The expression levels of OPN, PD-L1 and CD8 were detected by immunohistochemistry. To predict the correlation of OPN, PD-L1 and CD8 in sarcoma tissues and their clinical prognostic significance. RESULTS: RNA-seq analysis revealed that OPN-associated differentially expressed genes were significantly enriched in immune response-related biological processes. Bioinformatics analysis demonstrated that OPN expression in sarcoma was associated with immune responses and T-cell activation, and was negatively correlated with immune cell infiltration. OPN induced CD8⁺ T-cell exhaustion, thereby promoting immune evasion and facilitating the proliferation, invasion, and migration of synovial sarcoma (SS) cells. Molecular docking and co-immunoprecipitation assays confirmed a direct protein-protein interaction between OPN and PD-L1, and knockdown of OPN resulted in a significant reduction in PD-L1 expression. In SS tissues, OPN was highly expressed, whereas PD-L1 and CD8 were expressed at low levels and exhibited a positive correlation. Furthermore, bioinformatics analysis showed that PD-L1 expression was positively correlated with CD8 expression in sarcoma, and low CD8 expression was associated with poor prognosis. CONCLUSIONS: We preliminarily propose that OPN promotes immune evasion in synovial sarcoma (SS) by regulating PD-L1 expression and subsequently inducing CD8⁺ T-cell exhaustion. This mechanism suggests that OPN may serve as a novel immunotherapeutic target and provides new insights into the development of immunotherapy strategies for SS.
Benefits and challenges of adding BKM120 to a BI-3406 plus trametinib combination therapy.
Schulz B, Leitner E, Rabierad M … +6 more , Khan MI, Ehlers L, Escobar HM, Jaster R, Vollmar B, Zechner D
BMC Cancer · 2026 Jul · PMID 42399819 · Full text
BACKGROUND: Achieving a balance between efficacy and side effects is essential for the success of new combinatorial cancer therapies. This study investigated the impact of adding BKM120, a PI3K inhibitor, to a dual regim...
BACKGROUND: Achieving a balance between efficacy and side effects is essential for the success of new combinatorial cancer therapies. This study investigated the impact of adding BKM120, a PI3K inhibitor, to a dual regimen consisting of BI-3406, a KRAS/SOS1 inhibitor, and trametinib, a MEK inhibitor. METHODS: The therapeutic effects of these drug combinations were evaluated in the pancreatic cancer cell line 6606PDA using both monolayer and three-dimensional cultures. Additionally, their efficacy and potential side effects were assessed in vivo using a syngeneic orthotopic mouse model of pancreatic cancer. RESULTS: In vitro studies demonstrated that the addition of BKM120 to BI-3406 and trametinib significantly reduced cell viability in both monolayer and three-dimensional cultures. However, in a syngeneic pancreatic cancer mouse model, the triple therapy failed to significantly improve survival outcome compared to the dual therapy. Tumor weights were unaffected in female mice, while a minor, non-significant reduction was observed in male mice. This was accompanied by a slight, non-significant decrease in cancer cell proliferation. In the triple therapy group, Cdkn2a expression in tumors, a marker for senescence, remained largely unchanged. However, PD-L1 was significantly reduced in males, and CD8 T-cell infiltration was notably enhanced in females. Importantly, the triple therapy demonstrated several concerning drawbacks. It significantly increased lung metastases in female mice, reduced lymphocyte and erythrocyte counts, and elevated C-peptide concentrations in both sexes. Furthermore, behavioral analysis indicated a significant decline in burrowing and nesting activities among female mice during specific experimental phases. CONCLUSION: The addition of BKM120 to the combination of BI-3406 and trametinib provides minimal therapeutic benefit while introducing significant adverse effects, underscoring the need for caution when considering clinical applications.
Radiomics-based intratumoral heterogeneity subtypes in IDH wild-type glioblastoma with pathomic and transcriptomic association analyses: a multicenter study.
Duan X, Niu W, Li X … +5 more , Li Z, Liang Q, Yang X, Tan Y, Zhang H
BMC Cancer · 2026 Jul · PMID 42399813 · Full text
BACKGROUND: IDH wild-type glioblastoma (IDH-wt GBM) exhibits substantial intratumoral heterogeneity, which contributes to treatment resistance, disease recurrence, and variable clinical outcomes. This study aimed to iden...
BACKGROUND: IDH wild-type glioblastoma (IDH-wt GBM) exhibits substantial intratumoral heterogeneity, which contributes to treatment resistance, disease recurrence, and variable clinical outcomes. This study aimed to identify radiomics-based intratumoral heterogeneity (RITH) subtypes in IDH-wt GBM and to assess their prognostic relevance, associated pathomic differences, and transcriptomic associations. METHODS: We enrolled 333 patients with IDH-wt GBM across three cohorts. Radiomic features were extracted from CE-T1 and T2-FLAIR images, and partitioning around medoids (PAM) clustering was applied to identify RITH subtypes. Survival analyses included Kaplan-Meier analysis, log-rank tests, and univariable and multivariable Cox proportional hazards regression. Pathomic features extracted via CellProfiler were used to construct the PathScore to assess RITH subtype-associated pathomic differences. RNA-seq data from Cohort 3 were used for exploratory transcriptomic analysis, including candidate differentially expressed gene (DEG) identification, protein-protein interaction (PPI) network construction, and enrichment analysis. RESULTS: PAM clustering identified two RITH subtypes with significantly different overall survival (OS). The High RITH subtype was associated with shorter OS and remained independently associated with worse OS after adjustment for age, sex, hospital, MGMT promoter methylation status, and treatment category. The PathScore differed significantly between RITH subtypes, indicating associated histopathological differences. Exploratory transcriptomic analysis identified eleven candidate hub genes (CCL4, IL6, CSF2, HGF, IFNG, SERPINE1, CCR2, CXCR3, CXCL13, CCL20, and IL1B). Enrichment analyses suggested that these candidate hub genes were mainly associated with immune-inflammatory processes and pathways. CONCLUSIONS: The High RITH subtype was associated with poorer survival and showed corresponding pathomic and exploratory transcriptomic associations. These findings suggest that RITH subtypes may serve as non-invasive imaging phenotypes linked to prognosis and biological heterogeneity in IDH-wt GBM.
A predictive model for pathological complete response in neoadjuvant-treated breast cancer: integrating pretreatment clinicopathologic and contrast-enhanced ultrasound characteristics via interpretable machine learning.
Huang D, Chen Y, Chen W … +4 more , Wang Y, Lin W, Tang L, Liu X
BMC Cancer · 2026 Jul · PMID 42399808 · Full text
BACKGROUND: The ability to predict pathological complete response (pCR) prior to neoadjuvant therapy (NAT) would inform and facilitate tailored therapeutic regimens for patients with breast cancer. This study aimed to de...
BACKGROUND: The ability to predict pathological complete response (pCR) prior to neoadjuvant therapy (NAT) would inform and facilitate tailored therapeutic regimens for patients with breast cancer. This study aimed to develop and internally validate an interpretable machine-learning model for pretreatment pCR prediction using routinely available clinicopathologic variables, hematologic indices, and ultrasound (US)/contrast-enhanced ultrasound (CEUS) descriptors. METHODS: This retrospective analysis included 309 sequential breast cancer cases managed with neoadjuvant therapy followed by surgical intervention. Patients were randomly divided into training and testing cohorts at a ratio of 8:2 using stratified sampling according to pCR status. Feature selection was performed exclusively in the training cohort using least absolute shrinkage and selection operator (LASSO) regression. Five machine-learning classifiers, including CatBoost, LightGBM, XGBoost, SVM, and CART, were developed and evaluated. Model performance was assessed using the area under the receiver operating characteristic curve (AUC, with 95% CI), accuracy, specificity, sensitivity, precision, recall, F1-score, G-mean, Brier score, decision curve analysis (DCA) and calibration analysis. Shapley Additive Explanations (SHAP) were used for model interpretation. RESULTS: pCR was achieved in 29.8% (92/309) patients. LASSO regression selected eight predictors, including CEA, clinical T stage, ER, PR, HER2, Ki-67 index, Hyperechoic halo on US, and Range expansion on CEUS. In the testing cohort, CatBoost achieved an AUC of 0.8295 (95% CI: 0.7166-0.9231) and showed the highest overall accuracy (0.8065), specificity (0.8182), and precision (0.6364). CatBoost also demonstrated acceptable calibration, with a Brier score of 0.1595, and favorable net benefit across clinically relevant threshold probabilities. SHAP analysis identified HER2 status, CEA, clinical T stage, and hyperechoic halo as the leading contributors to the final model. CONCLUSIONS: An interpretable pretreatment CatBoost model showed good discrimination, acceptable calibration, and favorable clinical net benefit for predicting pCR after NAT in breast cancer. This approach may help support pretreatment risk stratification and inform multidisciplinary discussions.
Leveraging data-driven risk-adapted surveillance strategies after disease progression in locally advanced rectal cancer.
Qiu J, Ye Y, Yu Y … +5 more , Wang Z, Hong L, Shao L, Yang B, Wu J
BMC Cancer · 2026 Jul · PMID 42393631 · Full text
BACKGROUND: Post-progression survival (PPS) is a critical endpoint in oncology, yet predictors of PPS and data-driven strategies for post-progression management in locally advanced rectal cancer (LARC) remain undefined....
BACKGROUND: Post-progression survival (PPS) is a critical endpoint in oncology, yet predictors of PPS and data-driven strategies for post-progression management in locally advanced rectal cancer (LARC) remain undefined. This study aimed to identify prognostic factors for PPS, develop a predictive tool, and formulate risk-adapted surveillance strategies based on conditional survival to optimize long-term patient management. METHODS: The relationship between PPS and overall survival (OS) using spearman analysis. Independent predictors of PPS were identified through a combination of LASSO regression, machine learning approaches, and Cox regression, and a PPS prediction model was constructed. Model interpretability was elucidated using SHAP. Conditional PPS survival rates and annual recurrence risks were evaluated using Kaplan-Meier curve. Restricted cubic spline (RCS) analyses were employed to explore the association between a risk score and PPS. RESULTS: Among the cohort, 161 patients experienced disease progression. PPS was positively correlated with OS. Vascular tumor thrombus, perineural invasion, extramural venous invasion, body mass index, tumor size, and lymphocyte-to-monocyte ratio were identified as independent prognostic factors. The model achieved AUCs of 0.767, 0.801, and 0.802 at 1, 3, and 5 years, respectively, outperforming individual variables and TNM staging. The C-index of the model is 0.745. RCS analysis indicated a nonlinear relationship between higher risk score and worse PPS. After adjusting for other confounders, multi-model analysis demonstrated further supporting the positive association between risk score and adverse outcomes. Conditional survival analyses revealed that, across risk groups, longer PPS corresponded to higher survival probabilities and lower recurrence risks. Based on these findings, follow-up strategies should implement intensive surveillance for high-risk patients while adopting relatively streamlined monitoring for low-risk patients. CONCLUSION: This study provides the first integrated, data-driven framework for predicting PPS and personalizing surveillance in LARC. The validated nomogram and conditional survival-based strategies enable risk-adapted follow-up, supporting a shift from empirical to evidence-based management after disease progression.
Routine biomarkers map response probability in HER2-positive breast cancer treated with neoadjuvant chemotherapy and dual HER2 blockade.
Yang Z, Dai Y, Li Y … +9 more , Xia L, Li T, Chen X, Chi J, Yu Y, Lv X, Li J, Chen X, Cao X
BMC Cancer · 2026 Jul · PMID 42393615 · Full text
BACKGROUND: Pathologic complete response (pCR) after neoadjuvant chemotherapy and dual HER2 blockade is associated with improved outcomes in HER2-positive breast cancer, but treatment response remains heterogeneous. We a...
BACKGROUND: Pathologic complete response (pCR) after neoadjuvant chemotherapy and dual HER2 blockade is associated with improved outcomes in HER2-positive breast cancer, but treatment response remains heterogeneous. We aimed to develop and externally validate an interpretable model based on routine clinicopathological biomarkers to predict pCR and identify clinically meaningful response states. METHODS: In this multicenter retrospective study, 1,082 patients with HER2-positive breast cancer treated with neoadjuvant chemotherapy and dual HER2 blockade at two Chinese centers were included for model development and internal validation. An independent cohort of 307 patients from a third center was used for external validation. Machine-learning models were developed using routinely available pretreatment clinicopathological variables. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC). Probability-landscape analyses were performed to characterize biomarker-defined response states associated with pCR. RESULTS: The final gradient boosting machine model achieved AUCs of 0.78 in internal testing and 0.70 in external validation. Probability-landscape analyses identified distinct response states with substantially different pCR probabilities. Low hormone receptor expression combined with HER2 immunohistochemistry (IHC) 3 + status defined a high-probability pCR state, whereas high hormone receptor expression, low Ki-67 expression, and HER2 IHC 2+/fluorescence in situ hybridization (FISH)-positive disease defined persistently low-probability states. Among baseline node-positive patients who achieved breast pCR, residual nodal disease was observed in only 6.1% of cases. CONCLUSIONS: Routine clinicopathological biomarkers can be integrated into an interpretable machine-learning model to predict pCR and enable scalable response probability mapping in HER2-positive breast cancer receiving neoadjuvant chemotherapy and dual HER2 blockade. This approach may facilitate individualized treatment selection and support future treatment-adaptation and surgical de-escalation strategies.
Beyond side effects: treatment-related adverse events are associated with improved survival outcomes in HCC patients on atezolizumab-bevacizumab therapy.
Xu XQ, Li WM, Shi LC … +7 more , Wang H, Li S, Huang C, You H, Jia JD, He YW, Kong YY
BMC Cancer · 2026 Jul · PMID 42393592 · Full text
BACKGROUND: Atezolizumab plus bevacizumab (Atez/Bev) is the first-line treatment for unresectable hepatocellular carcinoma (HCC). This study investigated the association of adverse events (AEs) with clinical outcomes by...
BACKGROUND: Atezolizumab plus bevacizumab (Atez/Bev) is the first-line treatment for unresectable hepatocellular carcinoma (HCC). This study investigated the association of adverse events (AEs) with clinical outcomes by treatment relation, organ systems, and severity. METHODS: This exploratory post hoc analysis included 435 HCC patients treated with Atez/Bev, 136 patients with sorafenib, and 58 patients with atezolizumab monotherapy from the IMbrave150 (NCT03434379) and GO30140 (NCT02715531) trials. Kaplan-Meier analysis was applied to estimate overall survival (OS) in patients treated with Atez/Bev for ≥ 3 months. RESULTS: Landmark analysis at 3 months restricted the OS analysis to 332 patients who completed ≥ 3 months of Atez/Bev. Among these patients, treatment-related renal/urinary, mild vascular, and skin/subcutaneous AEs were associated with improved OS compared with patients without the corresponding AE (mOS: not reached vs. 20.2 months, p < 0.001; not reached vs. 20.2 months, p < 0.001; and not reached vs. 22.8 months, p = 0.014, respectively). Experiencing one (HR = 0.56, 95% CI: 0.38, 0.81) or ≥ 2 types (HR = 0.20, 95% CI: 0.11, 0.37) of positively associated AEs demonstrated progressively improved OS. However, metabolism/nutrition, hepatobiliary, and grade 3 + gastrointestinal AEs were associated with poorer OS, with HRs at 1.58 (95% CI: 1.10, 2.26), 1.67 (95% CI: 1.08, 2.69) and 2.09 (95% CI: 1.28, 3.41), respectively. CONCLUSIONS: Atez/Bev-related renal/urinary, skin/subcutaneous, and mild vascular AEs were associated with favorable survival outcomes in HCC, whereas metabolism/nutrition, hepatobiliary, and severe gastrointestinal AEs were associated with poorer outcomes. These findings may help improve the interpretation of AEs during Atez/Bev treatment and inform individualized toxicity management.
Clinical outcomes of percutaneous cryoablation for pulmonary metastases of soft tissue and bone sarcomas under local anesthesia: a single-institution retrospective cohort study.
Aoki Y, Kaseda K, Nishida R … +13 more , Okubo Y, Masai K, Hishida T, Tamura M, Inoue M, Yashiro H, Nakatsuka S, Nakayama R, Yamauchi Y, Izumi Y, Kawamura M, Jinzaki M, Asakura K
BMC Cancer · 2026 Jul · PMID 42393581 · Full text
BACKGROUND: The management of pulmonary metastases of soft tissue and bone sarcomas is challenging due to their resistance to chemotherapy and radiotherapy. This study aimed to evaluate local tumor progression, overall s...
BACKGROUND: The management of pulmonary metastases of soft tissue and bone sarcomas is challenging due to their resistance to chemotherapy and radiotherapy. This study aimed to evaluate local tumor progression, overall survival (OS), and procedural safety after percutaneous cryoablation for pulmonary metastases of soft tissue and bone sarcomas. METHODS: This retrospective cohort study included 28 patients who underwent percutaneous cryoablation for 84 metastatic lung tumors of soft tissue and bone sarcomas during 53 sessions between July 2002 and December 2016. Percutaneous cryoablation was performed under local anesthesia using the CRYOcare system and computed tomography fluoroscopy. Procedural complications within 30 days were assessed using prospectively recorded clinical data and retrospectively graded according to the Common Terminology Criteria for Adverse Events version 5.0. The time to local progression of the treated tumors and overall survival were estimated using the Kaplan-Meier method. RESULTS: All cryoablation procedures were performed under local anesthesia. The median tumor diameter was 1.1 cm (range: 0.4-6.5 cm). Twelve tumors (14.3%) showed local tumor progression after initial cryoablation during the median follow-up duration of 16 months (range: 0-216 months). The primary efficacy rates were 88.8%, 79.1%, and 79.1% at 1, 3, and 5 years, respectively. After repeat cryoablation for four tumors with local progression, the assisted efficacy rates were 95.6%, 82.8%, and 77.9% at 1, 3, and 5 years, respectively. Three tumors in two patients had no local progression for more than 10 years. A tumor diameter of ≤ 2 cm was significantly associated with improved primary and assisted efficacy rates (P = 0.024 and P = 0.015, respectively). The median OS was 34 months (range, 2-155 months), and the OS rates were 75.0%, 52.8%, and 28.8% at 1, 3, and 5 years, respectively. Adverse events occurred in 31 sessions (58.5%); all were grade 1 or 2, and no grade ≥ 3 adverse events or 30-day mortality were observed. CONCLUSIONS: In this selected single-institution cohort of nonsurgical candidates with pulmonary metastases of soft tissue and bone sarcomas, percutaneous cryoablation was feasible and was associated with local tumor control and an acceptable safety profile.
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