BMC Cancer[JOURNAL]
Sun
200 papers
First-in-human evidence of multidrug resistance reversal in solid tumors: a cohort analysis of carbon nanoparticles‑Fe(II) complex trials.
Xie P, Huang Y, Wang Y … +8 more , Shi H, Chen Y, Gou Z, Lai L, Dang Q, Wu X, Yang ST, Tang X
BMC Cancer · 2026 Jun · PMID 42249319 · Full text
BACKGROUND: Multidrug resistance (MDR) is a major barrier to treat relapsed solid tumors. Carbon nanoparticles‑Fe(II) complex (CNSI-Fe) is composed of carbon nanoparticles and Fe²⁺ ions, which directly deliver Fe into tu...
BACKGROUND: Multidrug resistance (MDR) is a major barrier to treat relapsed solid tumors. Carbon nanoparticles‑Fe(II) complex (CNSI-Fe) is composed of carbon nanoparticles and Fe²⁺ ions, which directly deliver Fe into tumor cells to induce ferroptosis. In this cohort analysis from a Phase I trial, we aim to evaluate the safety, imaging response, survival outcomes, and potential restoration of sensitivity to systemic therapies. METHODS: Nineteen patients in a Phase I study (NCT06048367) received the intratumoral injection of CNSI-Fe. The primary outcomes were safety and tolerability; secondary outcomes included radiographic response assessed by revised RECIST v1.1, tumor biology evaluated by necrosis and tumor growth rate (TGR), and long-term survival. All patients were followed after withdrawal from the study therapy. RESULTS: CNSI-Fe demonstrated an acceptable safety profile. CNSI-Fe consistently induced marked central necrosis on imaging despite minimal revised RECIST v1.1 shrinkage. Four patients (4/19, 21.1%) with heavily pretreated, progressive disease (ovarian serous carcinoma, pancreatic adenocarcinoma, myoepithelioma-like tumor of the vulvar region, and thyroid carcinoma) achieved long-term survival for 28.9-36.2 months post CNSI-Fe injection, accompanied by restored response to chemotherapies or targeted agents to which they were previously resistant (e.g., resensitization-restored sensitivity, hypersensitization-enhanced sensitivity). These four patients (4/19, 21.1%) demonstrated renewed sensitivity to subsequent systemic therapies (e.g., paclitaxel, carboplatin, bevacizumab, irinotecan liposome, and lenvatinib). CONCLUSIONS: This case series provides preliminary clinical evidence that CNSI-Fe could weaken MDR and resensitize solid tumors to systemic therapy. These findings warrant biomarker-integrated expansion cohorts and Phase II trials of CNSI-Fe-based combinations with radiotherapy, chemotherapy, targeted therapy, and immunotherapy. TRIAL REGISTRATION: The clinical data were derived from a completed prospective, single-arm, dose-escalation first-in-human trial (The Center for Drug Evaluation of the National Medical Products Administration, Registration No.: CTR20222235, Approval date: September 1, 2022; ClinicalTrials.gov Identifier: NCT06048367, First submitted date: August 24, 2023; RRID: SCR_002309).
Communication barriers in aftercare: a qualitative study of allogeneic stem cell transplant patients.
Wilhelm E, Tavori G, Bernardi C … +3 more , Ram R, Wolff D, Herrmann A
BMC Cancer · 2026 Jun · PMID 42243800 · Full text
BACKGROUND: Effective communication between patients and healthcare providers is a crucial component in aftercare after allogeneic hematopoietic stem cell transplantation (alloHSCT). Despite significant advances, unmet p...
BACKGROUND: Effective communication between patients and healthcare providers is a crucial component in aftercare after allogeneic hematopoietic stem cell transplantation (alloHSCT). Despite significant advances, unmet physical and psychological needs due to communication failures persist. OBJECTIVE: We performed a multicenter cross-sectional study assessing domains not communicated and underlying causes to identify and comprehend communication gaps in alloHSCT aftercare. STUDY DESIGN: Semi-structured in-depth interviews were conducted with patients after alloHSCT at the transplant centres Regensburg and Tel Aviv. Framework analysis was used to examine the qualitative data. RESULTS: The study recruited 47 patients with a median age of 57 years. A number of communication barriers were identified including (i): being overwhelmed during consultation preventing receiving and conveying information which interfered with early self-detection of chronic graft-versus-host disease; (ii) discrepancy in labelling psychosocial symptom load (e.g., psychological distress in part caused by war (Israel), cognitive impairment, adherence) being frequently neither recognized nor addressed due to discordance on who is considered responsible for bringing-up symptoms and issues considered as taboos, such as sexual health (iii) non-functioning chains of communication leading to loss of information. Other themes included strategies to compensate for communication deficits, i.e. (iv): buffering information gaps through social network and nurses. Finally, guidance and suggestions for communication and aftercare from the patient's view were provided. CONCLUSION: Our qualitative study highlights significant communication gaps experienced by patients undergoing alloHSCT. The findings advocate for better communication training for healthcare professionals, improvement of the informed consent process and the development of prompt sheets for patients and checklists for physicians.
Simultaneous activation and late-stage inhibition of autophagy induces autophagy-dependent cell death in leukemia.
Chua YW, Chow SC
BMC Cancer · 2026 Jun · PMID 42243772 · Full text
BACKGROUND: Resistance to apoptosis is a major challenge in cancer therapy, especially in relapsed or refractory leukemia. Autophagy, a conserved lysosomal degradation pathway, plays a complex dual role: it can promote t...
BACKGROUND: Resistance to apoptosis is a major challenge in cancer therapy, especially in relapsed or refractory leukemia. Autophagy, a conserved lysosomal degradation pathway, plays a complex dual role: it can promote tumor survival under stress, yet its excessive activation can trigger autophagy-dependent cell death (ACD). This paradox has inspired a novel therapeutic strategy that simultaneously activates and inhibits specific stages of autophagy to push cells toward death. However, the molecular mechanisms underlying this approach remain poorly understood, particularly in non-solid tumors like leukemia. METHODS: This study investigated the effects of simultaneous autophagy activation and stage-specific inhibition on cell death in human Jurkat E6.1 leukemic T cells. Cells were treated with rapamycin (RAPA) to induce autophagy, combined with either chloroquine (CQ) to block late-stage degradation or 3-methyladenine (3-MA) to inhibit early-stage autophagosome formation. Cell viability was measured by MTS assay, while autophagy flux was evaluated using a combination of MDC staining, mCherry-eGFP-LC3 fluorescence imaging and Western blot analysis for LC3. To delineate the mode of cell death, we accessed apoptosis via caspase-3 cleavage and employed pharmacological inhibitors of apoptosis (z-VAD-FMK) and necrosis (Necrostatin-1). RESULTS: Simultaneous autophagy induction with RAPA and late-stage inhibition with CQ (RAPA + CQ) triggered massive autophagosome accumulation and significantly enhanced cell death. In contrast, early-stage inhibition with 3-MA (RAPA + 3-MA) prevented autophagic vesicle formation and abrogated the cytotoxic effect. Importantly, this cell death occurred independently of both apoptosis and necroptosis, suggesting a direct result of excessive and unprocessed autophagosomes, consistent with ACD. CONCLUSION: In conclusion, our findings demonstrate that trapping cells in a state of high autophagic flux through simultaneous induction and late stage inhibition, is a potent strategy to trigger non-apoptotic cell death in leukemia. This approach represents a promising therapeutic strategy to overcome apoptosis-resistant leukemia.
Expression patterns of GPX4 and LINC00618 across disease phases in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL): an exploratory study.
Shayanmanesh M, Ahmadi SE, Faranoush M … +4 more , Safa M, Nourbakhsh SM, Jaafarian AS, Amini A
BMC Cancer · 2026 Jun · PMID 42243765 · Full text
BACKGROUND: Acute lymphoblastic leukemia (ALL) remains a significant challenge in pediatric malignancies, particularly in cases of relapse and treatment resistance. This study aimed to investigate the expression patterns...
BACKGROUND: Acute lymphoblastic leukemia (ALL) remains a significant challenge in pediatric malignancies, particularly in cases of relapse and treatment resistance. This study aimed to investigate the expression patterns of ferroptosis-related genes, GPX4 and LINC00618, across different disease phases in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL). METHODS: This case-control study analyzed 82 samples from pediatric BCP-ALL patients comprising 14 new cases, 29 in remission, and 17 relapsed cases alongside 22 healthy controls. Expression levels of GPX4 and LINC00618 were evaluated using quantitative real-time PCR. The relationship between gene expression and clinical parameters was assessed. Statistical analyses were performed employing parametric or nonparametric tests. RESULTS: GPX4 expression was significantly elevated in ALL patients compared to controls (p < 0.01), with notably higher levels in new cases (p < 0.01) and relapsed patients (p < 0.05). Similarly, LINC00618 exhibited significant upregulation in ALL patients (p < 0.05), particularly in new cases (p < 0.01) and relapsed patients (p < 0.05). Both genes demonstrated reduced expression during the remission. External validation using the GSE13159 dataset demonstrated a consistent direction of increased GPX4 expression in ALL samples compared to controls. CONCLUSIONS: Our findings suggest phase-associated expression patterns of GPX4 and LINC00618 in pediatric BCP-ALL. The consistent direction of GPX4 expression observed in external validation supports its potential relevance in leukemic biology. These results provide a basis for further studies to clarify the role of ferroptosis-related pathways in disease progression and therapeutic response.
The expression status and clinical value of TIM-3 in intrahepatic cholangiocarcinoma.
Yin Z, Li J, Liu L … +3 more , Zhang L, Zhang W, Ma B
BMC Cancer · 2026 Jun · PMID 42243754 · Full text
BACKGROUND: T cell immunoglobulin and mucin-domain containing protein 3 (TIM-3) is an immune checkpoint that plays a crucial role in immune exhaustion. High expression of TIM-3 has been implicated in exerting immunosuppr...
BACKGROUND: T cell immunoglobulin and mucin-domain containing protein 3 (TIM-3) is an immune checkpoint that plays a crucial role in immune exhaustion. High expression of TIM-3 has been implicated in exerting immunosuppression across a variety of malignant tumors. Elucidating the expression profile of TIM-3 and its prognostic impact may hold great significance for the therapeutic management of intrahepatic cholangiocarcinoma (ICC). METHODS: We analyzed 117 ICC patients using immunohistochemical staining for TIM-3 and other immune checkpoints to examined their expression and immune cell infiltration in ICC tissue samples. Furthermore, the correlation of checkpoint expression with clinical characteristics and prognosis were analyzed. RESULTS: High expression of TIM-3 in tumor cells was observed in 61 patients (52.1%) and was significantly correlated with poorer tumor differentiation (P = 0.019). Survival analysis showed that high TIM-3 expression in tumor cells was a prognostic factor for disease-free survival (DFS) and overall survival (OS) in univariate analysis, and an independent risk predictor for DFS in multivariate analysis (P = 0.048, HR = 1.589, 95%CI = 1.004-2.515). Furthermore, TIM-3 expression in ICC tissues was significantly correlated with CD4⁺ and CD8⁺ tumor-infiltrating lymphocytes (both P < 0.005). CONCLUSION: Patients with high TIM-3 expression in tumor cells had shorter DFS and OS, which could serve as a valuable biomarker for predicting the inflammatory status and prognosis of ICC. Targeting TIM-3 may represent a promising therapeutic strategy for ICC.
Prognostic value of CA125, HE4, ROMA, and CPH-I in advanced epithelial ovarian cancer.
Zhao M, Huang F, Yang T … +4 more , Zhang D, Man S, Sun Z, Xie B
BMC Cancer · 2026 Jun · PMID 42243732 · Full text
BACKGROUND: Optimal cytoreductive surgery and platinum sensitivity are critical prognostic factors in advanced epithelial ovarian cancer (EOC). However, the preoperative value of routinely available serum biomarkers in p...
BACKGROUND: Optimal cytoreductive surgery and platinum sensitivity are critical prognostic factors in advanced epithelial ovarian cancer (EOC). However, the preoperative value of routinely available serum biomarkers in predicting surgical outcomes, platinum resistance, and disease progression remains unclear. METHODS: This retrospective study included patients with benign ovarian tumors (n = 80), early-stage EOC (n = 84), and advanced EOC (n = 97) treated between January 2018 and June 2024. Serum cancer antigen 125 (CA125) and human epididymis protein 4 (HE4) levels were measured before initial treatment, and the Risk of Ovarian Malignancy Algorithm (ROMA) and Copenhagen Index (CPH-I) values were calculated. Predictive performance for surgical outcomes, platinum resistance, and recurrence in advanced EOC was evaluated using receiver operating characteristic analysis, and progression-free survival was analyzed using Kaplan-Meier methods. RESULTS: Serum CA125, HE4, ROMA, and CPH-I levels progressively increased from the benign ovarian tumor group to the early-stage and advanced-stage EOC groups (P < 0.001). In advanced EOC, significantly higher biomarker levels were observed in patients with suboptimal cytoreduction and disease recurrence (P < 0.05). ROC analysis showed moderate discriminatory ability of all four biomarkers for suboptimal cytoreduction, platinum resistance, and recurrence (P < 0.05). ROMA and CPH-I showed relatively higher AUC values for predicting suboptimal cytoreduction, with AUCs of 0.807 and 0.800, respectively. Kaplan-Meier analysis showed that elevated CA125, HE4, ROMA, and CPH-I levels were significantly associated with shorter progression-free survival (P < 0.005). Multivariable Cox regression analyses further demonstrated that CA125, HE4, ROMA, and CPH-I remained independently associated with unfavorable progression-free survival after adjustment for clinicopathological confounders. CONCLUSIONS: Elevated serum CA125, HE4, ROMA, and CPH-I are associated with unfavorable surgical outcomes, platinum resistance, and poor prognosis in advanced EOC. ROMA and CPH-I, in particular, may serve as valuable adjunctive tools for preoperative prediction of cytoreductive surgery outcomes, while all four biomarkers contribute to risk stratification for platinum sensitivity and disease progression. These findings support the potential role of combined serum biomarker assessment in guiding individualized treatment strategies for patients with advanced EOC.
Adjuvant pressurized intraperitoneal aerosol chemotherapy (PIPAC) in suboptimally cytoreduced advanced ovarian cancer: a randomized phase II trial (PIPAC-OVA).
Dzasokhov AS, Khomyakov VM, Turiev AV … +4 more , Astashov VL, Kostin AA, Gunyakov SO, Andreeva MA
BMC Cancer · 2026 Jun · PMID 42243730 · Full text
PURPOSE: Patients with advanced epithelial ovarian cancer (EOC) who undergo suboptimal primary cytoreductive surgery (PCS) have poor outcomes with standard platinum-taxane chemotherapy. This randomized controlled trial e...
PURPOSE: Patients with advanced epithelial ovarian cancer (EOC) who undergo suboptimal primary cytoreductive surgery (PCS) have poor outcomes with standard platinum-taxane chemotherapy. This randomized controlled trial evaluated whether adding adjuvant Pressurized Intraperitoneal Aerosol Chemotherapy with low-dose cisplatin and doxorubicin (PIPAC C/D) to first-line systemic therapy improves survival in this high-risk population. METHODS: In this single-center, open-label trial, patients with advanced EOC and residual disease > 1 cm after PCS were randomly assigned (1:1) to receive six cycles of carboplatin/paclitaxel alone (control arm) or the same chemotherapy plus three adjuvant PIPAC C/D procedures (intervention arm). No patient received neoadjuvant chemotherapy. The primary endpoint was progression-free survival (PFS) from PCS. Secondary end points included overall survival (OS), CA-125 response, peritoneal disease control assessed macroscopically and histologically, and safety. TRIAL REGISTRATION: ISRCTN15843444. RESULTS: A total of 186 patients were randomized. After excluding four after definitive histology, 182 comprised the mITT population (control, n = 91; PIPAC, n = 91). Median PFS was significantly longer with PIPAC (19.7 vs 12.5 months; HR, 0.31; 95% CI, 0.23-0.42; P < 0.001), as was OS (46.2 vs 38.1 months; HR, 0.48; 95% CI, 0.32-0.72; P < 0.001). In the PIPAC group, complete macroscopic regression occurred in 98.8% (83/84 treated patients), complete pathological regression in 85.7%, and ascites control in 98.8%. Treatment was well tolerated with no increase in grade 3-4 toxicity and minimal procedure-related morbidity. CONCLUSION: In patients with suboptimally debulked advanced EOC, the addition of adjuvant PIPAC C/D to first-line chemotherapy significantly improved PFS and OS while maintaining a favorable safety profile. These findings support further evaluation of PIPAC C/D as a component of primary treatment in this high-risk subgroup in confirmatory phase III trials.
Complex structural variations functionally inactivate the telomerase chaperone TCAB1 in osteosarcoma.
Keegan J, Sorbello S, Mori J … +4 more , Muratani S, Leshchiner I, Heaphy CM, Flynn RL
BMC Cancer · 2026 Jun · PMID 42243724 · Full text
Activation of the alternative lengthening of telomeres (ALT) pathway accounts for cellular immortalization in 75% of pediatric osteosarcoma. ALT does not rely on a single enzyme but instead, catalyzes telomere elongation...
Activation of the alternative lengthening of telomeres (ALT) pathway accounts for cellular immortalization in 75% of pediatric osteosarcoma. ALT does not rely on a single enzyme but instead, catalyzes telomere elongation via homologous recombination. There has been steady progress in defining the mechanisms that regulate the ALT pathway. However, the spectrum of genetic mutations that underlie activation of ALT remains unclear. Osteosarcomas, like many cancers, frequently harbor inactivating mutations in the tumor suppressor gene TP53. However, instead of single nucleotide variants that lead to expression of mutant TP53 protein, osteosarcoma tumors often acquire unique structural variants (SVs) within the first intron of the TP53 gene leading to complete gene inactivation. TP53 is located on chromosome 17p13.1 in a head-to-head orientation and partially overlapping with the gene WRAP53 (WD repeat containing antisense to TP53). WRAP53, also known as TCAB1, is an RNA chaperone that is an essential component of the telomerase holoenzyme. TCAB1 functions to facilitate trafficking of the telomerase RNA (hTR) within the nucleus to ensure assembly and localization of the telomerase enzyme to telomere ends to promote telomere elongation. Loss of TCAB1 function abolishes telomerase activity, driving progressive telomere attrition. Here, using whole-genome sequencing of osteosarcoma samples we identified SVs within the TP53 gene that not only compromise TP53, but also inactivate TCAB1. These TCAB1 SVs were prevalent in approximately 40% of ALT positive osteosarcoma tumors suggesting that functional inactivation of the telomerase holoenzyme is an early and previously unrecognized event contributing to the activation of the ALT pathway.
Antiviral therapy and hidden predictors of postoperative outcomes in hepatocellular carcinoma.
Ashraf N, Hong Q, Guo Z … +1 more , Li K
BMC Cancer · 2026 Jun · PMID 42243721 · Full text
BACKGROUND: Hepatocellular carcinoma (HCC) is a global health burden and hepatitis B virus (HBV) infection is a common cause. Antiviral therapy has the possibility to reduce the incidence of HCC, and recurrence of HCC af...
BACKGROUND: Hepatocellular carcinoma (HCC) is a global health burden and hepatitis B virus (HBV) infection is a common cause. Antiviral therapy has the possibility to reduce the incidence of HCC, and recurrence of HCC after surgical resection. METHODS: A total of 410 HCC patients had hepatectomy at Zhongnan hospital of Wuhan University. Categorization of these patients was done on the basis of HBV antiviral therapy. Recurrence-free survival (RFS) and the overall survival (OS) rates were assessed during follow-up period. Tumor necrosis percentage, recovery of liver functions, and tumor-related characteristics were also examined in these patients. Statistical analyses were conducted using Kaplan-Meier survival curves and Cox regression models. RESULTS: After applying strict selection criteria, only 93 patients formed the observation group. These patients had comparatively smaller tumor size ≤5 cm(76.3% vs. 45.1%) and less tumor necrosis (30.1% vs. 54.6%). OS (p = 0.035) and RFS (p = 0.034) was also improved in the observation group. However, antiviral therapy did not show any significant effect on OS (p = 0.188) and RFS (p = 0.527) after a multivariate adjustment. Microvascular invasion of more than 5 foci (OS HR = 2.96; RFS HR = 1.97), poor differentiation (RFS HR = 2.70), and stage C versus 0 of BCLC (OS HR = 3.75; RFS HR = 4.40) were independent adverse prognostic factors. Kaplan-Meier analysis indicated that tumour necrosis was associated with overall survival (OS) and recurrence-free survival (RFS), and this finding was validated in sensitivity analyses. CONCLUSION: While antiviral therapy correlated with improved tumor pathology and univariate survival outcomes, it was not an independent prognostic factor after adjustment. Tumor necrosis independently predicted worse OS and RFS. Prognosis was primarily driven by microvascular invasion, poor differentiation, and advanced BCLC stage, suggesting antiviral benefits may operate indirectly through tumor biology modulation.
Carbon ion radiotherapy for unresectable primary or recurrent soft tissue sarcomas: long-term outcomes based on the local effect model.
Li P, Li Y, Bao C … +3 more , Cai X, Wang Z, Zhang Q
BMC Cancer · 2026 Jun · PMID 42243703 · Full text
BACKGROUND: The application of carbon ion radiotherapy (CIRT) for unresectable primary or recurrent soft tissue sarcoma (STS) remains controversial and existing data are limited. We herein present our institutional exper...
BACKGROUND: The application of carbon ion radiotherapy (CIRT) for unresectable primary or recurrent soft tissue sarcoma (STS) remains controversial and existing data are limited. We herein present our institutional experience with CIRT for unresectable primary or recurrent STS. METHODS: We retrospectively evaluated the outcomes of CIRT in unresectable primary or recurrent STS patients at our center. We assessed the 4-and 5-year local control (LC), overall survival (OS), distant metastasis free survival (DMFS), progression free survival (PFS), as well as acute and late toxicities. Additionally, we analyzed the prognostic factors associated with the treatment outcomes. RESULTS: Between June 2015 and August 2022, 48 consecutive patients with unresectable primary (n = 8, 16.7%) or recurrent (n = 40, 83.3%) STS were treated with CIRT. The most common tumor sites were the retroperitoneum and pelvis (75.0%). The predominant histological subtypes included liposarcoma (20.8%), leiomyosarcoma (10.4%), synovial sarcoma (8.3%) and undifferentiated pleomorphic sarcoma (8.3%). Nine patients (18.8%) had a history of prior in-field radiotherapy. The median follow-up duration was 48.6 months. The 4-year LC, OS, DMFS, and PFS rates were 65.8%, 59.7%, 50.3%, and 36.7%, respectively. The 5-year LC, OS, DMFS, and PFS rates were 60.3%, 54.7%, 44.0%, and 28.0%, respectively. The median survival time was 67.3 months. Late toxicities included grade 3 dermatitis (n = 2, 4.2%), grade 3 decreased joint range of motion (n = 1, 2.1%), and grade 3 peripheral neuropathy (n = 1, 2.1%). Patients who received a higher prescribed dose (biologically effective dose, BED ≥ 129 Gy) exhibited significantly better LC (p = 0.010) and PFS (p = 0.004) compared to those who received a lower prescribed dose. A pre-CIRT neutrophil-to-lymphocyte ratio (NLR) ≥ 3 was significantly associated with inferior DMFS (p = 0.020). CONCLUSIONS: For select patients with unresectable primary or recurrent STS, CIRT represents a potentially effective and well-tolerated treatment option, though it requires careful evaluation of neural risks-particularly for lesions adjacent to critical nerve structures.
Factors influencing the impact of financial toxicity on the quality of life of breast cancer patients after mastectomies.
Ma X, Liu X, Ren J … +2 more , Wang M, Yang L
BMC Cancer · 2026 Jun · PMID 42243699 · Full text
BACKGROUND: This study aims to explore the relationship between financial toxicity (FT), fear of cancer recurrence (FCR), quality of life (QOL), and illness perception (IP) in breast cancer patients undergoing chemothera...
BACKGROUND: This study aims to explore the relationship between financial toxicity (FT), fear of cancer recurrence (FCR), quality of life (QOL), and illness perception (IP) in breast cancer patients undergoing chemotherapy after a mastectomy, to provide new ideas and directions for improving their quality of life. METHODS: A total of 305 breast cancer patients who received chemotherapy after a mastectomy were included in this study using the convenience sampling method. FT, FCR, IP, and QOL were cross-sectionally investigated using the General Information Questionnaire, Comprehensive Score for Financial Toxicity, Simplified Fear of Disease Progression Questionnaire, Functional Assessment of Cancer Therapy-General, and Brief Illness Perception Questionnaire. Data were analyzed using SPSS 26.0. RESULTS: Place of residence, employment status, household income per month, personal monthly income, age, literacy, and healthcare payment method, radiotherapy and surgical approach were found to affect the QOL of patients. QOL and FT scores were significantly correlated. FCR could mediate the effect of FT on QOL, and IP played a moderating role in the relationship between FT and QOL. CONCLUSIONS: The relationships between FT, FCR, IP, and QOL aligned with the findings of the stress response model. FT directly affects QOL and also further affects it via FCR, while IP modulates the effect of FT on the QOL, offering new insights for clinical staff tasked with choosing measures to improve the quality of life of patients.
Blood circulating C228T TERT gene promoter mutation is an independent factor for the prognosis of HBV-related hepatocellular carcinoma.
Quang Trung P, Chau P, Quang Huy D … +5 more , Xuan Hoan N, Reboud J, Linh Toan N, Huu Song L, Tat Trung N
BMC Cancer · 2026 Jun · PMID 42237300 · Full text
BACKGROUND: Telomerase reverse transcriptase (TERT) promoter mutations are among the most common noncoding genetic lesions in various cancers, including hepatocellular carcinoma (HCC). The clinical and pathological impli...
BACKGROUND: Telomerase reverse transcriptase (TERT) promoter mutations are among the most common noncoding genetic lesions in various cancers, including hepatocellular carcinoma (HCC). The clinical and pathological implications of hepatitis B virus (HBV)-related HCC patients carrying promoter mutations are only partially resolved. METHODS: A nested real-time PCR assay was optimized to detect C228T TERT gene promoter mutation (C228T) from plasma samples with a detection limit of 0.1%. The established assay was used to investigate the association of the C228T with the clinical presentation of HBV-related HCC patients. RESULTS: The C228T was detected only in the HCC group (n = 40/159, 25.2%), not in the other control groups (n = 0/160). The mutation rate was significantly higher in HCC patients with low albumin concentration, increased direct bilirubin, abdominal lymphadenopathy, and portal vein thrombosis, compared with HCC patients without these factors (p < 0.05); the mutation rate also increased progressively with more advanced stages (p < 0.05) and was significantly associated with shorter overall survival (OS). CONCLUSION: The C228T is associated with advanced stages, poorer liver function, and shorter overall survival; hence, it could be used as a novel biomarker for the prognosis of HBV-related HCC patients.
Impact of RUNX1 mutations at distinct sites on the clinical characteristics and prognosis of patients with acute myeloid leukemia.
Huang Y, Long Z, Zhang Y … +5 more , Cheng J, Sun J, Jiang L, Fu H, Jiang X
BMC Cancer · 2026 Jun · PMID 42237268 · Full text
BACKGROUND: Acute myeloid leukemia (AML) patients with Runt-related transcription factor 1 (RUNX1) mutations are categorized into the adverse-risk group with poor prognosis. However, the impact of RUNX1 mutations at dist...
BACKGROUND: Acute myeloid leukemia (AML) patients with Runt-related transcription factor 1 (RUNX1) mutations are categorized into the adverse-risk group with poor prognosis. However, the impact of RUNX1 mutations at distinct sites on clinical characteristics, chemosensitivity, and prognosis in AML remains incompletely defined. This study aims to elucidate this impact thereby furnishing robust evidence to refine precision therapeutic strategies for individuals harboring RUNX1-mutant AML. METHODS: In this study, 92 AML patients harboring RUNX1 mutation, were enrolled and stratified into five groups based on mutation location: RHD domain, TAD domain, ID domain, outside domain, and biallelic mutations. Baseline demographics, complete-remission (CR) rate and minimal residual disease (MRD) negativity rates after chemotherapy, as well as 2-year overall survival (OS) and event-free survival (EFS) were systematically compared. RESULTS: Biallelic-mutant patients exhibited the lowest CR rate, the highest 2-year relapse rate, and the poorest 2-year OS and EFS. Cox regression analysis identified single-site mutation as an independent favorable prognostic factor. Among patients harboring single-site RUNX1 mutation, ID-domain mutations group achieved the highest two-cycle CR and MRD negativity rates, whereas TAD-domain mutants displayed the lowest MRD-negativity rate. CONCLUSIONS: Collectively, these findings indicate that the specific locus of RUNX1 mutation modulates chemotherapy efficacy and outcome, providing critical insights for precision therapy in RUNX1mutant AML. TRIAL REGISTRATION: This study has been approved by the Ethics Committee of Nanfang Hospital, Southern Medical University (Approval Number: NFEC-2025-505), and it has been reviewed and approved by the Chinese Clinical Trial Registry (Registration number: ChiCTR2500111148) and registered in the National Medical Research Information Filing Information System of China.
Investigating the expression of CTLA-4 and CD28 genes as immune regulators in patients with colorectal polyps.
Etesami M, Forouzesh F, Hooshmand A … +3 more , Niasar MS, Moghadam PK, Nazemalhosseini-Mojarad E
BMC Cancer · 2026 Jun · PMID 42237250 · Full text
BACKGROUND: Colorectal cancer (CRC) develops through a multistep process originating from precancerous polyps. Elucidating the mechanisms that regulate immune homeostasis in precancerous lesions and in the systemic circu...
BACKGROUND: Colorectal cancer (CRC) develops through a multistep process originating from precancerous polyps. Elucidating the mechanisms that regulate immune homeostasis in precancerous lesions and in the systemic circulation prior to malignant transformation is of critical importance. This study aimed to evaluate alterations in the expression levels of the CTLA-4 and CD28 genes in patients with hyperplastic and adenomatous colorectal polyps. METHODS: Peripheral blood samples were collected from 40 patients diagnosed with adenomatous or hyperplastic colorectal polyps and 30 healthy controls. The relative expression levels of CTLA-4 and CD28 were quantified using real-time quantitative PCR (qRT-PCR). Transcriptomic data for microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) were retrieved from the TCGA-COAD database. Differential expression analysis was performed using the edgeR package, with thresholds set at a false discovery rate (FDR) < 0.05 and |log2 fold change (FC)| > 1.5. Subsequently, miRNA-mRNA and lncRNA-miRNA interactions were integrated to construct a lncRNA-miRNA-mRNA regulatory network. Immune cell infiltration analysis was conducted using the TIMER platform to evaluate the association between gene expression levels and immune cell infiltration in colon adenocarcinoma (COAD). RESULTS: The results demonstrated that CTLA-4 and CD28 expression levels were upregulated in patients with colorectal polyps, although the magnitude of upregulation varied between polyp subtypes. Receiver operating characteristic (ROC) curve analysis yielded area under the curve (AUC) values of 0.66 and 0.54 for CTLA-4 and CD28, respectively. A significant positive correlation was observed between CTLA-4 and CD28 expression levels. In COAD tissues, 245 differentially expressed miRNAs and 868 differentially expressed lncRNAs were identified from the TCGA dataset. Construction of the lncRNA-miRNA-mRNA network identified KCNQ1OT1 as a hub lncRNA, potentially regulating CD28 and CTLA-4 indirectly through interactions with multiple miRNAs. Furthermore, TIMER analysis revealed significant associations between CD28 and CTLA-4 expression and the infiltration of immune cells, including neutrophils, macrophages, CD8⁺ T cells, and CD4⁺ T cells, within the COAD cohort. CONCLUSIONS: Our findings indicate that CTLA-4 and CD28 are upregulated in patients with colorectal polyps and exhibit a positive correlation in expression. The regulatory network analysis highlights KCNQ1OT1 as a potential upstream modulator of these genes via miRNA-mediated mechanisms. Moreover, the strong association between CTLA-4 and CD28 expression and immune cell infiltration underscores their potential role in immune dysregulation during the early stages of colorectal tumorigenesis. Collectively, these findings suggest that CTLA-4 and CD28 may contribute to polyp progression through modulation of the immune microenvironment.
Outcomes of hypofractionated stereotactic radiotherapy for brain metastases: do we treat patients or lesions?
Figen M, Kirli Bolukbas M, Soydemir GP … +1 more , Kocak Uzel E
BMC Cancer · 2026 Jun · PMID 42237247 · Full text
BACKGROUND: Hypofractionated stereotactic radiotherapy (HFSRT) is increasingly preferred over whole-brain radiotherapy (WBRT) for patients with limited brain metastases, aiming to balance durable local control with neuro...
BACKGROUND: Hypofractionated stereotactic radiotherapy (HFSRT) is increasingly preferred over whole-brain radiotherapy (WBRT) for patients with limited brain metastases, aiming to balance durable local control with neurocognitive preservation, and it can be applied both to intact tumors and in the postoperative period. The objective of this study was to retrospectively evaluate the clinical and dosimetric outcomes of stereotactic radiosurgery (SRS) in patients with brain metastases, treated either in the intact tumor setting or postoperatively. METHODS: We retrospectively reviewed a total of 70 lesions in 58 consecutive adults (KPS ≥ 70) treated with linear accelerator-based (LINAC-based) image-guided HFSRT between January 2021 and August 2024 for either intact metastases (i-HFSRT) or postoperative resection cavities (r-HFSRT). Standard prescriptions were 30 Gy/5 fractions (alternate-day delivery); 25 Gy/5 fractions was used at physician's discretion (large volume, prior WBRT, proximity to organs at risk). For the evaluation of overall survival, patients were stratified according to extracranial disease status (present vs. absent), timing of brain metastases presentation, and receipt of systemic therapies with central nervous system penetration (yes vs. no). Outcomes included local control (LC), distant brain progression (DBP), leptomeningeal disease (LMD), radiation necrosis (RN), and overall survival (OS). The volumes of brain parenchyma receiving 24 Gy (V24 Gy) and 30 Gy (V30 Gy) were evaluated. RESULTS: Fifty-eight patients were included (median age 55; 55.2% male); 40 lesions (57.1%) received i-HFSRT and 30 (42.9%) r-HFSRT. Lung (50%) and breast (24%) cancer were the most common primaries. Median follow-up was 13 months (range 4-38). Overall survival was significantly prolonged in patients who received systemic therapies with central nervous system penetration compared to those who did not. Local failure occurred in 4 lesions (5.7%) 2 in i-HFSRT group, 2 in r-HFSRT group. DBP occurred in 23 (39.7%) patients 12 in i-HFSRT group, 11 in r-HFSRT group. LMD developed in 3 patients (5.2%), all in the r-HFSRT cohort at a median of 7 months. RN occurred in 5 lesions (7.1%): 4 i-HFSRT, 1 r-HFSRT. None of these outcomes differed significantly between groups. Median OS was 18 months (95% CI, 9.6-26.4). Despite statistically significant larger GTV/PTV volumes and higher V24/V30 in r-HFSRT, RN did not increase versus i-HFSRT. CONCLUSIONS: Five-fraction LINAC-based HFSRT (25-30 Gy) was effective in both groups, with necrosis more frequent in the intact group and leptomeningeal dissemination confined to the operated group, though not statistically significant, emphasizing that, in this patient population with limited overall survival, surgery should be reserved for appropriately selected patients to avoid treatment-related time toxicity.
External validation of predictive models for high-grade cervical lesions in Thai women undergoing colposcopy: a retrospective external validation study.
Eidbur A, Atjimakul T
BMC Cancer · 2026 Jun · PMID 42237140 · Full text
BACKGROUND: Predictive models for high-grade cervical lesions (CIN2+/HSIL) have been developed in various populations; however, their generalizability across different healthcare settings is uncertain. External validatio...
BACKGROUND: Predictive models for high-grade cervical lesions (CIN2+/HSIL) have been developed in various populations; however, their generalizability across different healthcare settings is uncertain. External validation in specific populations is required before clinical implementation. METHODS: This retrospective external validation study included Thai women who underwent colposcopy between 2022 and 2024 at a tertiary referral center. The primary outcome was histologically confirmed CIN2+/HSIL. Two previously published predictive models were applied without any modifications. Model performance was evaluated in terms of discrimination using the area under the receiver operating characteristic curve (AUROC), calibration using calibration plots, calibration metrics, Brier scores, and clinical utility using decision curve analysis. RESULTS: A total of 536 women were included, of whom 28.7% were diagnosed with CIN2+/HSIL. Despite differences in demographic characteristics, HPV genotype distribution, cytological findings, and colposcopic features compared to the original development cohorts, both models demonstrated good performance in the Thai population. The Xue model demonstrated good discrimination, with an AUROC of 0.82 (95% CI: 0.77-0.86), whereas the Sheng model demonstrated good discrimination, with an AUROC of 0.80 (95% CI: 0.77-0.85). Both models showed acceptable calibration. The Xue model had a calibration-in-the-large of 0.03 (95% CI: -0.22 to 0.28) and a calibration slope of 0.77 (95% CI: 0.64-0.91), indicating mild overfitting that may benefit from recalibration. The Sheng model showed good calibration, with a slope of 0.88 (95% CI: 0.68-1.08) and a calibration-in-the-large of 0.17 (95% CI: -0.05 to 0.38). Brier scores were 0.148 and 0.163, respectively. Decision curve analysis demonstrated a positive net clinical benefit across clinically relevant threshold probabilities. At the original model-specific predefined probability thresholds, the Xue model achieved a sensitivity of 56.5% and specificity of 93.7%, whereas the Sheng model achieved a sensitivity of 93.5% and specificity of 34.3%, demonstrating a marked trade-off that highlights the importance of threshold selection. CONCLUSIONS: Both predictive models showed good external validity and clinical utility in Thai patients undergoing colposcopy. These findings support individualized risk stratification in women with abnormal screening results to guide clinical decisions.
Real-world outcomes of second-line pembrolizumab in urothelial carcinoma: a multicenter analysis from the Campania Oncological Network (ROC).
Tambaro R, Calvanese G, Muto A … +20 more , Formisano L, Di Lorenzo G, Buonerba C, Bosso D, Sabbatino F, Coppola E, Di Napoli M, Rossetti S, Pisano C, Cecere SC, Passarelli A, Ventriglia J, Lobianco L, Limongello D, Perri E, Lamia M, D'Alessio C, Contieri R, Feroce F, Pignata S
BMC Cancer · 2026 Jun · PMID 42237111 · Full text
BACKGROUND: Platinum-based chemotherapy followed by second-line immunotherapy has been traditionally the standard of care for locally advanced or metastatic urothelial cancer (La/mUC). However, checkpoint inhibitors are...
BACKGROUND: Platinum-based chemotherapy followed by second-line immunotherapy has been traditionally the standard of care for locally advanced or metastatic urothelial cancer (La/mUC). However, checkpoint inhibitors are remarkably reshaping the therapeutic landscape for urothelial cancer. Despite these advances, La/mUC remains a highly lethal disease with poor prognosis and limited therapeutic response. Moreover, discrepancies between clinical trial populations and real-world patients often result in different outcomes and toxicity profiles. In this context, oncology networks have become critical in generating Real-World Data (RWD), which can be translated into Real-World Evidence (RWE) to support clinical decision-making in everyday practice. We retrospectively analysed La/mUC patients treated with second-line pembrolizumab within the Campania Oncological Network (Rete Oncologica Campana, ROC). PATIENTS AND METHODS: This multicenter retrospective study included adult patients (≥ 18 years) with histologically or cytologically confirmed La/mUC, who had previously received chemotherapy and were treated with Pembrolizumab (200 mg every three weeks) across six ROC centres. Primary endpoints were progression-free survival (PFS) and overall survival (OS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR) and safety. RESULTS: Between January 2021 and November 2023, 132 patients with La/mUC received at least one Pembrolizumab dose. The median age was 67 years (range 30-88), and most were male (73.5%). The majority had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 (20.5%) or 1 (62.1%). Histologically, 115 patients (87.1%) had pure urothelial carcinoma, while 17 (12.9%) had rare urothelial carcinoma subtypes, including squamous, sarcomatoid/carcinosarcoma, micropapillary or nested variants. At the time of initial diagnosis, 45 (34.1%) patients presented with metastatic disease (stage IV), and 72 (54.5%) had undergone radical cystectomy. Metastatic sites included lymph nodes 98 (74.2%), lung 51 (38.6%), bones 45 (34.1%), and liver 21 (15.9%). Liver metastases were more frequent in pure urothelial carcinoma (17.4% vs. 5.9%), while non-urothelial variants showed a higher incidence of peritoneal carcinomatosis (23.5% vs. 1.7%). After a median follow-up of 20 months (95% CI 12.7-32.6), 108 patients (81.8%) experienced disease progression or death. Median PFS was 3.75 months (95% CI: 3.4 to 4.7), while median OS was 7.3 months (95% CI: 6.05-9.33). The ORR was 13.5% (95% CI: 7.4% - 19.7%), DCR was 33.9% (95% CI: 25.6%-42.0%) (driven by a 20.4% stable disease rate). Among 17 patients with rare subtypes of urothelial carcinoma, the ORR was 23.5% (95% CI: 3.3% to 43.7%). Multivariate analysis revealed that metastatic disease at diagnosis (HR = 2.01, p = 0.02) and liver metastases (HR = 2.11, p = 0.02) were independently associated with increased mortality risk (Table 3B). Lymph node-only metastases had a significantly lower risk of disease progression (HR = 0.46, p = 0.004) and death (HR = 0.52, p = 0.02). (). Univariate analysis indicated that prior cystectomy was associated with improved PFS (HR = 0.67, p = 0.04) and OS (HR = 0.54, p = 0.003), suggesting its role as a favourable prognostic factor in this cohort [1] (Table 2 A and 2B). A total of 114 treatment-related AEs were reported, with 79.8% being grade 1-2 and 20.2% grade 3-4. The most common events were asthenia (20.0%), pruritus (10.0%), and myalgia (7.0%). No treatment-related deaths occurred. Pembrolizumab was discontinued in 7.6% of patients due to AEs. The safety profile was manageable; 7.6% of patients discontinued treatment due to AEs (predominantly drug-induced pneumonitis), and 1.5% required permanent corticosteroid replacement for immune-related adrenal insufficiency. CONCLUSIONS: This real-world analysis supports the clinical applicability of second-line Pembrolizumab in La/mUC, demonstrating efficacy and acceptable safety. Prognostic indicators, including metastatic sites and prior cystectomy, significantly impacted outcomes. These findings highlight the value of oncology networks in generating real-world evidence to refine treatment approaches.
Tumor immune microenvironment and epithelial-mesenchymal transition in recurrence of low-grade stage IA endometrial endometrioid carcinoma.
Hachisuga K, Katayama Y, Inomata Y … +9 more , Kawakami M, Maenohara S, Yagi H, Yasunaga M, Onoyama I, Asanoma K, Yahata H, Oda Y, Kato K
BMC Cancer · 2026 Jun · PMID 42231230 · Full text
BACKGROUND: Low-grade, low-stage endometrial carcinomas are generally associated with an excellent prognosis. However, some of these tumors recur, although the prognostic factors are largely unknown. Recently, reports ha...
BACKGROUND: Low-grade, low-stage endometrial carcinomas are generally associated with an excellent prognosis. However, some of these tumors recur, although the prognostic factors are largely unknown. Recently, reports have described associations among tumor immune microenvironment (TIME), epithelial-mesenchymal transition (EMT), and circulating tumor cells (CTCs), factors that have also been reported to be associated with recurrence in endometrial carcinoma. Therefore, we conducted the present study to clarify the association between recurrence and TIME- and EMT-related factors in low-grade, low-stage endometrial carcinomas. METHODS: This study included 80 Japanese patients with low-grade, stage IA endometrial endometrioid carcinoma (20 in the recurrence group and 60 in the no-recurrence group). The institutional review board of Kyushu University approved this study (project number: 24101-00). The median follow-up was 94.5 months (range, 10-298). Immunohistochemistry was performed to evaluate regulatory T cells, marginal and intratumoral tumor-associated macrophages, and tumor cell expression of C-X-C motif chemokine ligand 12 (CXCL12) and Secreted Protein Acidic and Rich in Cysteine (SPARC). RESULTS: In 13 of the 20 recurrent cases, recurrence occurred distant from the primary site, at lung or lymph nodes. Immunohistochemistry revealed that the numbers of FoxP3-positive cells, and marginal and intratumoral CD68-positive cells in the recurrence group were significantly higher than in the no-recurrence group. In addition, tumor cell expression of CXCL12, a chemokine involved in macrophage recruitment, was significantly higher in the recurrence group. Similarly, tumor cell expression of SPARC, an EMT-associated protein, was also significantly higher in the recurrence group. These findings suggest that a tumor microenvironment permissive of tumor cell dissemination may be associated with recurrence. CONCLUSIONS: Recurrence in low-grade, stage IA endometrial carcinoma was associated with increased FoxP3-positive cells, increased marginal and intratumoral CD68-positive cells, and higher tumor cell expression of CXCL12 and SPARC. However, these findings suggesting a tumor microenvironment permissive of tumor cell dissemination should be interpreted as exploratory and hypothesis-generating, given that the involvement of CTCs was not directly evaluated in this study.
Circulating N6-methyladenosine RNA as a diagnostic and a stage-associated prognostic biomarker in colorectal cancer.
Lin YT, Chang AC, Chien CS … +4 more , Lin CC, Lan HY, Teng HW, Hwang WL
BMC Cancer · 2026 Jun · PMID 42231202 · Full text
BACKGROUND: Extracellular vesicle (EV)-based liquid biopsy is increasingly recognized as a promising strategy for cancer diagnosis and prognosis, as EVs carry abundant, stable biomolecular cargo. N6-methyladenosine (m6A)...
BACKGROUND: Extracellular vesicle (EV)-based liquid biopsy is increasingly recognized as a promising strategy for cancer diagnosis and prognosis, as EVs carry abundant, stable biomolecular cargo. N6-methyladenosine (m6A), the most prevalent modification in eukaryotic intracellular RNA, plays a critical role in regulating diverse cellular processes and has been implicated in tumor initiation and progression. However, the potential of EV-associated m6A-modified RNA (EV-m6A RNA) as a clinically useful biomarker for cancer detection remains unclear. METHODS: EV-RNA was isolated from tumor tissues and matched serum samples collected from 76 colorectal cancer (CRC) patients. Serum samples from 30 healthy donors were included as controls. Serum EVs were prepared using the ExoQuick™ precipitation reagent. EV-RNA was extracted using Trizol reagent, and EV-m6A RNA levels were quantified using an enzyme-linked immunosorbent assay (ELISA). RESULTS: Precipitation-enriched serum particles (PESPs) isolated from CRC patients and healthy donors were identified as CD9(+)/CD63(+)/ALIX(+) small particles, with a mean particle diameter of 60-70 nm. The ApoB expression was detectable in PESPs. The mean PESP concentration and PESP-RNA yield were significantly higher in CRC patients than in healthy controls (PESP concentration: 11 ± 8 × 10/mL vs. 5 ± 2 × 10/mL, p < 0.001; PESP-RNA yield: 57 ± 52 ng/µL vs. 22 ± 15 ng/µL, p < 0.001). Through m6A modification-specific ELISA quantification, receiver operating characteristic (ROC) curve analysis demonstrated good discriminatory performance of normalized PESP-m6A RNA levels for CRC detection (AUC, 0.8346; 95% CI, 0.7583-0.9110; p < 0.0001). PESP-m6A RNA levels were noted to be higher in late-stage (III/IV) CRC patients than in those with early-stage (I/II) disease (0.015 ± 0.001% vs. 0.009 ± 0.005%, p < 0.001) with no significant correlation with intratumoral METTL3 expression, a m6A writer. Increased PESP-m6A RNA abundance further predicted a worse overall survival (OS) in CRC patients (p = 0.0107; HR, 3.938), while m6A RNA levels in tumor tissues showed no significant prognostic value (p = 0.7765; HR, 1.153). CONCLUSION: These findings support circulating PESP-m6A RNA levels as a feasible and noninvasive biomarker for CRC diagnosis, with additional potential for liquid biopsy-based prognostication and longitudinal disease monitoring.
Breast cancer survival prediction using machine learning and multimodal data for personalized care plan.
Rady Raz N, Nafissi N, Babaee E … +1 more , Fadavi P
BMC Cancer · 2026 Jun · PMID 42226239 · Full text
This paper presents a time-stratified breast cancer survival analysis that incorporates tumor characteristics, disease stage, and patient features, using machine learning (ML) algorithms to support personalized care plan...
This paper presents a time-stratified breast cancer survival analysis that incorporates tumor characteristics, disease stage, and patient features, using machine learning (ML) algorithms to support personalized care planning. Considering nonlinear relationships between input data and the risk of death, as well as the dynamics of patient characteristics over time, we utilize 6 ML algorithms, including XGBoost, Logistic Regression, Random Forest, Decision Tree, AdaBoost, and Multilayer Perceptron, for less than 6 months, 6 months, 1-, 2-, 3-, 5-, and 10-year survival rates prediction. We utilize multimodal data from 3,476 breast cancer patients, comprising 43 features. XGBoost outperforms the rest, achieving an accuracy of over 90%. The top five predictors, using Shapley Additive exPlanations (SHAP), include DCIS, Ki-67, age, feeding, and lymph node grade. SHAP analysis indicated that lower values of DCIS and Ki-67, lower lymph node and tumor grade, less sentinel lymph node involvement, higher age, longer duration of breastfeeding, lower tumor size, medullary tumor type, PR+, ER+, less positive node, more pregnancy, DCIS pathology class, BCS surgery type for early-stage, lower tumor stage, no necrosis, HER2-, no family history, and no calcification are result in longer breast cancer survival. Furthermore, we validate the model's performance using 5-fold cross-validation (CV) and nested CV. We also evaluate model performance using accuracy, precision, F1 score, and recall. All results show the proposed method outperforms. This paper presents clinical, molecular, and demographic insights into survival analysis, utilizing explainable ML techniques to support personalized treatment decisions.
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