Cancer[JOURNAL]
Sun
200 papers
First-line CDK4/6 inhibitors fail to improve overall survival in advanced breast cancer.
Lawrence L
Cancer · 2026 Jun · PMID 42316758 · Publisher ↗
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No RFS benefit found from adding vibostolimab to pembrolizumab in patients with high-risk melanoma: Adding the anti-TIGIT antibody vibostolimab to adjuvant pembrolizumab failed to improve recurrence-free survival and increased toxicity.
Lawrence L
Cancer · 2026 Jun · PMID 42316576 · Publisher ↗
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Immunohistochemical breast cancer subtypes in Palestinian Women: an 18-year multicenter retrospective analysis.
Salhi I, Maqboul H, Jallad F … +4 more , Jaradat H, Bannoura S, El-Krunz D, Karmi B
BMC Cancer · 2026 Jun · PMID 42316123 · Full text
OBJECTIVE: To describe the demographic, geographic, and immunohistochemical (IHC) subtype distribution of breast cancer in a large multi-center Palestinian cohort, and to examine temporal trends in subtype frequency over...
OBJECTIVE: To describe the demographic, geographic, and immunohistochemical (IHC) subtype distribution of breast cancer in a large multi-center Palestinian cohort, and to examine temporal trends in subtype frequency over an 18-year period. METHODS: A retrospective descriptive analysis of 2,323 consecutive female breast cancer patients diagnosed at 27 pathology service centers across 11 Palestinian governorates between August 2008 and May 2026. Estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67 status were abstracted from the immunohistochemistry reports. Patients with complete ER, PR, and HER2 data were classified into four molecular surrogate subtypes: Luminal A-like (HR+/HER2-), Luminal B HER2+ (HR+/HER2+), HER2-enriched (HR-/HER2+), and triple-negative (HR-/HER2-). RESULTS: The cohort was geographically broad, with the highest proportions of specimens contributed from Nablus (51.5%) and Ramallah & Al-Bireh (20.9%) governorates. Mean age at diagnosis was 52.8 years (SD 13.2; range 19-98). Among patients with reported IHC results, ER positivity was 67.4% (1,352/2,005), PR positivity was 63.4% (1,166/1,840), and HER2 positivity was 21.4% (425/1,985). Of the 1,628 patients with complete triple-marker data, Luminal A-like tumors comprised the majority (60.7%, n = 988), followed by triple-negative (17.6%, n = 286), Luminal B HER2+ (11.9%, n = 193), and HER2-enriched (9.9%, n = 161). HER2-enriched tumors occurred in younger patients (mean age 48.8 years) than the other subtypes. CONCLUSION: Palestinian breast cancer is dominated by hormone-receptor-positive disease, but the combined HER2-positive fraction (21.8%) and triple-negative fraction (17.6%) together account for nearly two-fifths of cases - a higher burden of aggressive subtypes than is reported in most Western series. These findings underline the importance of universal IHC testing and targeted therapy access in Palestinian breast cancer care.
Impact of precision oncology research in pediatric poor prognosis cancer: patient, parent and healthcare provider perspectives.
McCloskey N, Mahon P, Rassekh SR … +5 more , Hetherington K, Regier DA, Wakefield CE, Pollard S, Deyell RJ
BMC Cancer · 2026 Jun · PMID 42316091 · Full text
BACKGROUND: Comprehensive genomic analyses are increasingly accessible to children, adolescents and young adults (AYAs) with poor prognosis cancers. Challenges and successes of pediatric precision oncology studies from t...
BACKGROUND: Comprehensive genomic analyses are increasingly accessible to children, adolescents and young adults (AYAs) with poor prognosis cancers. Challenges and successes of pediatric precision oncology studies from the perspectives of AYA patients, parents and healthcare providers (HCPs) are poorly described. METHODS: Between March 2021 and May 2023, we interviewed AYA patients (12-21 years), parents and HCPs who participated in pediatric precision oncology studies for poor prognosis cancers in British Columbia. Interviews followed an investigator-developed semi-structured topic guide. Data were coded inductively and deductively by one qualitative researcher and one trainee, supported by two additional team members. Analytic themes were established using qualitative thematic analysis. RESULTS: We interviewed 9 AYAs, 10 parents, and 17 HCPs. We identified five analytic themes: importance of clear communication of study information between patients, families and multidisciplinary HCPs; a need to support disclosure, understanding and clinical integration of research results; barriers to accessing innovative therapy and mitigation strategies; approaches to managing parent, patient and HCP hopes and expectations; personal challenges and stressors related to participation. CONCLUSIONS: We highlight unmet needs and offer practical considerations for integrating precision oncology into clinical practice. Considerations include educating and supporting oncologists through genomics results disclosure, increasing engagement with multidisciplinary HCPs, streamlining access to study information and results, coordinating efforts to clinically validate results and access therapies, and establishing real-world outcome data to inform clinical decision-making. Implementation of these strategies will optimize care for patients and families who are navigating poor prognosis cancers.
Screening of cytochrome CYP26A1 expression in different bone tumors.
Al-Zu'bi B, Alshammari FOFO, AlQaisi R … +5 more , Al-Abadleh AA, Satari AO, Al-Sarayreh S, Al-Saraireh YM, Hareedy MS
BMC Cancer · 2026 Jun · PMID 42316073 · Full text
BACKGROUND: Cytochrome P450 26A1 (CYP26A1) is a retinoic acid metabolizing enzyme which is overexpressed in many cancers. However, its expression in bone tumors has not been characterized. METHODS: Immunohistochemistry w...
BACKGROUND: Cytochrome P450 26A1 (CYP26A1) is a retinoic acid metabolizing enzyme which is overexpressed in many cancers. However, its expression in bone tumors has not been characterized. METHODS: Immunohistochemistry was used to evaluate CYP26A1 expression in a human bone disease spectrum comprising duplicated cores of 95 cases of benign, intermediate and malignant bone tumors alongside normal bone samples. STRING database was utilized to perform CYP26A1 protein-protein interaction and functional enrichment analyses. RESULTS: CYP26A1 staining was not identified in the normal bone samples analyzed. Collectively, CYP26A1 was expressed in 31.6% (30/95) of bone tumors, with cytoplasmic localization, while no immunoreactivity was detected in normal tissues. Compared with benign (18.8%) and malignant tumors (27.1%), intermediate bone tumors expressed CYP26A1 significantly more frequently (66.7%). This difference in expression between tumor categories was statistically confirmed (p < 0.05, Cramér's V = 0.382). Among intermediate tumors, CYP26A1 was detected with high frequency and weak staining intensity in giant cell tumors (GCTs, 14/20 cases), with immunoreactivity localized mainly in osteoblast-like and osteocyte-like stromal cells. Malignant bone tumors predominantly showed focal or an absence of CYP26A1 immunoreactivity. However, strong CYP26A1 immunoreactivity was displayed in the limited chordoma and adamantinoma cases examined, while osteosarcoma and Ewing sarcoma displayed no immunoreactivity in general. Interestingly, functional enrichment analysis confirmed the established association of CYP26A1 with retinoid metabolic pathways. CONCLUSIONS: CYP26A1 expression was most frequent in giant cell tumors of bone. While also detected in a subset of other bone tumors, expression was limited or absent in most benign and malignant lesions, and entirely absent in normal bone tissue. These findings provide novel descriptive insight into CYP26A1 distribution and support further investigation into its role in retinoid-related pathways in bone tumor biology.
Real-world evidence for the impact of circadian clock on the benefit from immune checkpoint inhibitors in solid tumors.
Soyfer EM, Lee BJ, Qavi AJ … +3 more , Masri S, Fleischman AG, Dayyani F
BMC Cancer · 2026 Jun · PMID 42316066 · Full text
BACKGROUND: The circadian clock regulates tumor-immune interactions in a time-of-day-dependent manner, yet whether this translates to a clinically meaningful benefit across diverse solid tumors in real-world populations...
BACKGROUND: The circadian clock regulates tumor-immune interactions in a time-of-day-dependent manner, yet whether this translates to a clinically meaningful benefit across diverse solid tumors in real-world populations remains unclear. METHODS: We retrospectively analyzed 969 patients receiving anti-PD-1 or anti-PD-L1 therapy at UCI Health between 2018 and 2022. Patients were classified as early (before 12 PM) or late (12 PM or after) based on infusion time. The primary outcome was disease control rate (DCR), defined as complete response (CR), partial response (PR), or stable disease (SD) per RECIST criteria. Unadjusted comparisons used the Pearson chi-square test. Multivariable logistic regression adjusting for disease stage, age, and ethnicity was performed in 806 patients with complete covariate data. Propensity score-matched analyses and sensitivity analyses using alternative exposure definitions were conducted. RESULTS: Early infusion was associated with significantly higher DCR compared with late infusion (49% vs. 40%, p = 0.007). This association persisted after multivariable adjustment (adjusted OR 1.18, 95% CI 1.02-1.38, p = 0.024). The effect was directionally consistent across subgroups defined by sex, age, stage, and ICI agent. In ethnicity-stratified analyses, the association was significant among non-Hispanic patients (adjusted OR 1.18, 95% CI 1.02-1.39) but was indeterminate among Hispanic patients due to limited sample size (adjusted OR 1.18, 95% CI 0.84-1.65); the ethnicity-by-TOD interaction term was non-significant (p = 0.958). Sensitivity analyses using alternative exposure definitions and propensity score matching yielded consistent results. CONCLUSIONS: In a large, heterogeneous real-world cohort spanning multiple tumor types and a diverse patient population, early ICI administration was independently associated with higher DCR. These findings support a chronotherapeutic effect of ICI timing and underscore DCR as a sensitive endpoint for its detection. Prospective validation across tumor types and demographic subgroups is warranted.
Effect of immunonutrition on surgery outcomes in cancer patients: evidence from an umbrella review on interventional and observational meta-analyses.
Mardani H, Riazi Khameneh U, Jafari A … +13 more , Dolati S, Baziar N, Amirpour M, Zamanian G, Zamani O, Zavareh MAT, Akbari ME, Akbari A, Alamdari NM, Javid Z, Rahmani J, Ardehali SH, Shadnoush M
BMC Cancer · 2026 Jun · PMID 42316063 · Full text
BACKGROUND: Malnutrition is highly prevalent in cancer patients, leading to increased post-surgical complications. This umbrella review of meta-analyses aims to investigate the effect of immunonutrition on surgery outcom...
BACKGROUND: Malnutrition is highly prevalent in cancer patients, leading to increased post-surgical complications. This umbrella review of meta-analyses aims to investigate the effect of immunonutrition on surgery outcomes in Cancer patients. METHODS: MEDLINE/PubMed, SCOPUS, and WOS databases were investigated from their inception until Sep 2025. Meta-analysis investigating the impact of immunonutrition (or its components) on overall complications, infectious complications, non-infectious complications, mortality, surgical-site infections, anastomotic leak, and length of hospital stay in patients with cancer. Pooled effect sizes and CIs were calculated using a random-effects model. RESULTS: Fifty-four studies were included in the umbrella review. The pooled results showed RR = 0.79; 95%CI: 0.70-0.88; I2 = 39.5% for postoperative overall complications, RR = 0.61; 95%CI: 0.58-0.65; I2 = 47.3% for infectious complications, RR = 0.88; 95%CI: 0.82-0.94; I2 = 0% for non-infectious complications, HR = 0.86; 95%CI: 0.74-0.99; I2 = 0% for mortality, RR = 0.66; 95%CI: 0.59-0.74; I2 = 6.5% for surgical-site infection, RR = 0.69; 95%CI: 0.62-0.77; I2 = 0% for anastomotic leak, and WMD=-1.75 days; 95%CI: -2.09,-1.41; I2 = 90.3% for length of hospital stay in immunonutrition intervention compared to control groups. Subgroup analysis by time of intervention showed that postoperative intervention is more effective in reducing overall complications (RR = 0.69; 95%CI:0.54-0.89) and the length of hospital stay (2.26 days, P = 0.001) compared to preoperative or perioperative intervention. CONCLUSION: Cancer patients undergoing surgery may benefit from immunonutrition. Postoperative intervention is more effective than pre-or perioperative intervention.
Beyond oncogenesis: the unexplored benefits of viruses in cancer immunity.
Wang XW, Day CP, Koonin EV
Nat Rev Cancer · 2026 Jun · PMID 42315907 · Publisher ↗
The connections between viruses and cancer have historically been studied in the context of viral oncogenesis. For decades, tumour virology has focused on oncogenic viruses such as hepatitis B virus, hepatitis C virus, h...
The connections between viruses and cancer have historically been studied in the context of viral oncogenesis. For decades, tumour virology has focused on oncogenic viruses such as hepatitis B virus, hepatitis C virus, human papillomavirus, Epstein-Barr virus, human T cell leukaemia virus type 1, Kaposi sarcoma-associated herpesvirus and Merkel cell polyomavirus, elucidating their oncogenic mechanisms, which include mutagenesis, chronic inflammation and immune evasion. However, the human virome is vast and complex, and this oncogenesis-centred view has overshadowed the possibility that certain viral exposures enhance antitumour immunity. Through millions of years of coevolution with animal hosts, the virome, consisting of diverse bacteriophages and eukaryotic viruses, including endogenous retroviruses, appear to have evolved strategies for coexistence that shape immune development and potentiate host surveillance pathways capable of recognizing and eliminating cancer cells. Non-oncogenic viruses can prime innate and adaptive immune responses, mimic tumour antigens and modulate the expression of immune checkpoints, as exemplified by the association of the enterovirus and rhinovirus CE1 epitope with protective liver cancer immunity. Moreover, endogenous retroviruses, naturally occurring oncolytic viruses and microbiome-associated phages may act as allies in cancer control. This Review explores the emerging evidence for viral anticancer immunity, its underlying mechanisms, and implications for a virome-guided framework for cancer prevention including new approaches to risk assessment, immune-based therapeutics and applications in low-resource settings.
Hepatorenal protective and antitumor effects of astaxanthin-loaded chitosan nanoparticles against ehrlich ascites carcinoma in mice through antioxidant, anti-inflammatory, and apoptotic pathway modulation.
Alfawaz MS, Elmorsy EM, Al Doghaither HA … +5 more , Al-Ghafari AB, Mansour AA, Alshammari AN, Fawzy MS, Elghareeb MM
BMC Cancer · 2026 Jun · PMID 42310631 · Full text
BACKGROUND: Ehrlich ascites carcinoma (EAC) is an aggressive experimental tumor model associated with severe oxidative stress, inflammation, and hepatorenal injury. Astaxanthin (ASX), a potent natural antioxidant caroten...
BACKGROUND: Ehrlich ascites carcinoma (EAC) is an aggressive experimental tumor model associated with severe oxidative stress, inflammation, and hepatorenal injury. Astaxanthin (ASX), a potent natural antioxidant carotenoid, has demonstrated anticancer and cytoprotective properties; however, its therapeutic application is limited by poor bioavailability and stability. Therefore, this study investigated the anticancer and hepatorenal protective effects of astaxanthin-loaded chitosan nanoparticles (ASX-CNPs) compared with free ASX in EAC-bearing mice. METHODS: Ninety female Swiss albino mice were randomly allocated into six groups: control, ASX, ASX-CNPs, EAC, EAC + ASX, and EAC + ASX-CNPs. Tumor progression, survival rate, oxidative stress biomarkers, inflammatory mediators, apoptotic markers, and histopathological alterations in hepatic and renal tissues were evaluated. Antioxidant parameters included SOD, CAT, GPx, GSH, TAC, and TBARS. Inflammatory and apoptotic signaling pathways were assessed through measurement of COX-2, TNF-α, IFN-γ, IL-1β, Bcl-2, Bax, and caspase-3 expression levels. RESULTS: ASX-CNPs markedly suppressed tumor progression and improved survival compared with free ASX. Treatment with ASX-CNPs significantly downregulated Bcl-2 expression while upregulating Bax and caspase-3, indicating enhanced apoptotic activity. Antioxidant defenses were significantly restored, as evidenced by increased SOD, CAT, GPx, GSH, and TAC levels, alongside reduced TBARS. Inflammatory responses were attenuated through decreased COX-2 activity and reduced TNF-α, IFN-γ, and IL-1β levels. Histopathological examination confirmed substantial protection against EAC-induced hepatic and renal damage. Overall, ASX-CNPs demonstrated greater therapeutic efficacy than free ASX across biochemical, molecular, and histopathological assessments. CONCLUSIONS: ASX-loaded chitosan nanoparticles exerted potent anticancer, antioxidant, anti-inflammatory, and hepatorenal protective effects in EAC-bearing mice. The enhanced efficacy of ASX-CNPs relative to free ASX is likely attributable to improved bioavailability and targeted modulation of oxidative stress, inflammatory, and apoptotic pathways, supporting their potential as a promising nanotherapeutic strategy for cancer-associated organ injury.
Cumulative incidence and prognostic factors for leukemic transformation in chronic myelomonocytic leukemia: a competing risk analysis.
Huang J, Zheng C, Liu Y … +2 more , Li C, Xin X
BMC Cancer · 2026 Jun · PMID 42310629 · Full text
BACKGROUND: Leukemic transformation represents a pivotal event in the natural history of chronic myelomonocytic leukemia (CMML), yet conventional survival analysis may yield biased estimates by treating non-transformatio...
BACKGROUND: Leukemic transformation represents a pivotal event in the natural history of chronic myelomonocytic leukemia (CMML), yet conventional survival analysis may yield biased estimates by treating non-transformation deaths as censored observations. We hypothesised that competing risk methodology would provide more accurate transformation estimates and could alter the interpretation of treatment-associated effects compared with traditional approaches. METHODS: We retrospectively analysed 102 patients with CMML diagnosed and treated at Ganzhou People's Hospital between January 2014 and November 2025. Cumulative incidence functions (CIF) were estimated using the Aalen-Johansen method with death without transformation as the competing event. Fine-Gray subdistribution hazard models identified independent predictors, with parallel Cox regression for methodological comparison. Treatments were classified by primary modality at baseline (HMA, chemotherapy, best supportive care (BSC), allo-HSCT) and entered as a stratification covariate rather than as a randomised exposure. RESULTS: During follow-up, 54 patients (52.9%) developed acute myeloid leukemia and 7 (6.9%) died without transformation. The 12-, 24-, and 36-month CIF were 46.9%, 63.4%, and 73.8%, respectively, whereas 1 - Kaplan-Meier estimates were 49.2%, 67.2%, and 78.4% (4.9-6.2% relative overestimation). Baseline treatment strategy was associated with transformation risk: compared with HMA, BSC showed a higher subdistribution hazard (SHR 4.77, 95% CI 1.86-12.22, P = 0.001) and chemotherapy SHR 2.16 (1.04-4.48, P = 0.039), with allo-HSCT not significantly associated (SHR 0.52, P = 0.261); these associations should be interpreted as exploratory given non-random allocation and small subgroup sizes (allo-HSCT n = 13, BSC n = 22). Intermediate and high-risk karyotypes independently predicted transformation (SHR 3.09 and 2.98, both P < 0.05). Within the NGS-tested subgroup, SETBP1 (SHR 3.09, P = 0.009) and TP53 (SHR 3.66, P = 0.009) mutations marked small subsets at very high transformation risk. For allo-HSCT, Cox regression yielded a significant protective effect (HR 0.31, P = 0.026) that became non-significant in the Fine-Gray model, illustrating how cause-specific analysis can overstate the isolated anti-transformation effect of a treatment that simultaneously reduces mortality. CONCLUSIONS: This study shows how competing-risk analysis complements standard Kaplan-Meier estimates of overall and progression-free survival when the cumulative incidence of a specific event, leukaemic transformation, is the quantity of interest. Although the modest, single-centre sample and non-randomised treatment allocation preclude definitive treatment recommendations, cytogenetic risk was the strongest disease-related prognostic factor, and molecular profiling provided additional risk discrimination within the NGS-tested subgroup. Cumulative incidence functions should therefore be reported routinely alongside Kaplan-Meier estimates in CMML and other myeloid neoplasms with non-negligible competing mortality.
Ablative ultra-hypofractionated radiotherapy with surgical GI exclusion as a "functional spacer" for pancreatic cancer: a phase I safety and feasibility study.
Di Y, Xia T, Wang Y … +1 more , Ren G
BMC Cancer · 2026 Jun · PMID 42310617 · Full text
OBJECTIVES: The therapeutic window for radiotherapy in locally advanced pancreatic cancer (LAPC) is severely constrained by the anatomical proximity of the duodenum. We hypothesized that radiation-induced gastrointestina...
OBJECTIVES: The therapeutic window for radiotherapy in locally advanced pancreatic cancer (LAPC) is severely constrained by the anatomical proximity of the duodenum. We hypothesized that radiation-induced gastrointestinal (GI) injury is exacerbated by physiological digestion, and that surgically bypassing the irradiated duodenum would provide a biological "functional spacer." We aimed to evaluate the safety and clinical feasibility of ablative ultra-hypofractionated radiotherapy (UHRT) followed directly by elective GI exclusion surgery. METHODS: In this prospective Phase I protocol, 10 patients with LAPC received ablative UHRT using Helical Tomotherapy at a prescribed dose of 40-60 Gy in 5 fractions. A prophylactic GI exclusion surgery (gastric truncation and GI bypass) was strictly scheduled within 7 days post-radiotherapy to place the high-dose irradiated duodenal segment into physiological quiescence. The primary endpoint was treatment safety assessed via CTCAE v4.02 and technical feasibility. RESULTS: All participants provided written informed consent and successfully completed the combined radiotherapeutic and surgical protocol. After a median follow-up of 12 months, no Grade 4-5 toxicities, bleeding, or gastrointestinal perforations were recorded. Only one patient (10%) experienced Grade 3 GI toxicity (abdominal pain). The Objective Response Rate (ORR) was 50%, with a 1-year overall survival rate of 60%. Furthermore, 70% of symptomatic patients achieved significant cancer-related pain relief. CONCLUSIONS: Preliminary results suggest that the integration of ablative UHRT with an immediate prophylactic surgical GI bypass is a feasible and safe protocol. This "functional spacer" concept potentially mitigates the duodenal dose-limiting bottleneck, allowing the practical delivery of biologically ablative radiation doses in LAPC without catastrophic GI consequences. However, larger multi-center trials are warranted for further validation. TRIAL REGISTRATION: Not prospectively registered. At the time of study initiation in 2015, this investigator-initiated, single-center exploratory Phase I safety and technical feasibility study was reviewed and approved by the Institutional Ethics Committee of Air Force Medical Center, PLA, and public trial registration was not requested by the committee. The study was not designed as a randomized comparative efficacy trial, but rather as a pilot evaluation of the safety and feasibility of an individualized combined radiotherapy-surgical strategy. The protocol was approved by the Institutional Ethics Committee of Air Force Medical Center, PLA (Approval No. 2015-118-S01) on 12 March 2015.
Self-perceived burden and quality of life in patients with radiation-induced brain injury after radiotherapy for nasopharyngeal carcinoma: a cross-sectional study on the mediating role of stigma and the moderating role of sleep quality.
Ye Y, Song R, Zhao F … +1 more , Chen L
BMC Cancer · 2026 Jun · PMID 42310606 · Full text
BACKGROUND: Although self-perceived burden (SPB), stigma and sleep quality are associated with quality of life (QoL) in patients with radiation-induced brain injury (RBI) after radiotherapy for nasopharyngeal carcinoma (...
BACKGROUND: Although self-perceived burden (SPB), stigma and sleep quality are associated with quality of life (QoL) in patients with radiation-induced brain injury (RBI) after radiotherapy for nasopharyngeal carcinoma (NPC), little is known about the mechanism underlying the relationship among these variables. The aim of this study was to examine the relationship among SPB, stigma, and QoL, and further explore how sleep quality may moderate the effect of stigma. METHODS: This cross-sectional study investigated 150 NPC patients with RBI who were recruited from an affiliated hospital of the university in Guangzhou, China. The participants completed several questionnaires, including a socio-demographic characteristics questionnaire, the Chinese version of the Self-Perceived Burden Scale (SPBS), the Social Impact Scale (SIS), the World Health Organization Quality of Life Instrument Short Form (WHOQOL-BREF), and the Pittsburgh Sleep Quality Index (PSQI). The mediation analysis and moderated mediation analysis were conducted using PROCESS macro Model 4 and Model 58 in SPSS 28, respectively. RESULTS: The results of mediation analysis showed that stigma had a significant indirect effect between self-perceived burden and quality of life (effect = -0.152, 95% CI = -0.223 to -0.032), and the direct effect of self-perceived burden on quality of life was not statistically significant (effect = -0.083, 95% CI = -0.300 to 0.134). In the moderated mediation analysis, the indirect effect of self-perceived burden on quality of life as mediated by stigma was apparent only among patients with poorer sleep quality (higher PSQI scores; effect = -0.115, 95% CI = -0.246 to -0.021). CONCLUSIONS: The findings suggest that stigma may function as a mechanism through which self-perceived burden is associated with quality of life in NPC patients with RBI, especially when patients suffer low sleep quality. Healthcare providers should pay attention to sleep quality and consider developing a supportive care intervention to improve patients' quality of life by incorporating effective strategies to reduce self-perceived burden and stigma for this population.
Molecular characteristics and clinicopathology of CTNNB1-mutated endometrial cancer: Implications for fertility-sparing management in young women.
Li WQ, Wu HX, Li HB … +3 more , Shuai GN, Zhang Q, Shen Y
BMC Cancer · 2026 Jun · PMID 42310566 · Full text
BACKGROUND: The incidence rate of endometrial cancer (EC) is increasing among young women who require fertility preservation. The identification of molecular biomarkers can improve clinical outcomes in these patients. Th...
BACKGROUND: The incidence rate of endometrial cancer (EC) is increasing among young women who require fertility preservation. The identification of molecular biomarkers can improve clinical outcomes in these patients. This study evaluated the role of CTNNB1 mutations in EC and whether the CTNNB1 gene can serve as a molecular marker in fertility-sparing management. METHODS: Retrospective cohorts of patients with pathologically confirmed EC were included in the study. The molecular landscape and TCGA-based molecular classification were analyzed through targeted next-generation sequencing and immunohistochemistry. The clinicopathological and molecular characteristics of CTNNB1-mutated and CTNNB1-wild-type patients were assessed. For young patient who received fertility-sparing treatment (FST), the responses to progestin treatment were evaluated. RESULTS: CTNNB1 mutations were significantly more common in the age group ≤ 40 years than in the age group > 40 years, indicating that CTNNB1 had a significant role in young patients with EC seeking fertility preservation. Most cases carrying CTNNB1 mutations were in the no specific molecular profile group. The most frequent CTNNB1 hotspot mutations were Ser37Phe on exon3 (16.13%). Moreover, CTNNB1 mutations were significantly associated with higher rates of endometrioid EC (p = 0.0001) and earlier stages (FIGO I or II) than the absence of mutations (p = 0.0457). Nonetheless, there were no significant differences in other pathological risk factors between the mutant and wild-type groups. The immunohistochemical expression of β-catenin can be used as a surrogate for CTNNB1 mutation status; nonetheless, specificity was associated with the frequency of CTNNB1 mutations. Patients with CTNNB1 mutations showed poor response to progestin treatment, possibly because of the reduced expression of progesterone receptors since the nuclear expression of β-catenin in the endometrium was negatively correlated with progesterone receptor expression. CONCLUSIONS: CTNNB1 status in EC can help predict the response to fertility-sparing treatment, allowing early stratification and risk assignment.
Correlated expression of MYBL2 and CCL5 defines an immunosuppressive microenvironment and predicts poor prognosis in intrahepatic cholangiocarcinoma.
Ren J, Xu S, He X … +2 more , Ye H, Li W
BMC Cancer · 2026 Jun · PMID 42310565 · Full text
BACKGROUND: The tumor immune microenvironment critically influences progression and therapeutic response in intrahepatic cholangiocarcinoma (ICC). MYBL2 drives tumor aggressiveness, while CCL5 regulates immune-cell recru...
BACKGROUND: The tumor immune microenvironment critically influences progression and therapeutic response in intrahepatic cholangiocarcinoma (ICC). MYBL2 drives tumor aggressiveness, while CCL5 regulates immune-cell recruitment; however, their combined impact on immune composition and PD-1 therapy response remains undefined. METHODS: Tumor specimens from 127 ICC patients were assessed by immunohistochemistry and whole-slide digital quantification. MYBL2 and CCL5 expression were classified into four combinatorial phenotypes. Associations with immune-cell infiltration, survival, and treatment response were evaluated using correlation analysis, Kaplan-Meier curves, Cox regression, and PD-1 interaction analyses. Seventy patients received adjuvant PD-1 therapy. RESULTS: MYBL2 and CCL5 expression were positively correlated (r = 0.38, p < 0.001). Higher CCL5 levels were associated with increased CD163⁺ TAM density (r = 0.31, p < 0.001) and a reduced CD8/CD163 ratio, indicating an immunosuppressive microenvironment. The MYBL2-CCL5 classification provided clear prognostic discrimination, with the Double-High subgroup showing the shortest OS and PFS. Among PD-1-treated patients, treatment benefit varied markedly across phenotypes: the Double-Low group achieved the greatest survival advantage, whereas the Double-High group showed minimal response, reflecting primary resistance. In multivariable analysis, Double-Low remained strongly protective compared with Double-High. CONCLUSION: The MYBL2-CCL5 co-expression phenotype identifies an immunosuppressive, TAM-dominant microenvironment and serves as a dual biomarker for both prognosis and PD-1 treatment sensitivity in ICC. This immunologic classification offers a practical framework for postoperative risk stratification and personalized immunotherapy decision-making.
Efficacy of a structured rehabilitation program for patients with terminal cancer: A multicenter randomized controlled trial.
Nishiyama N, Matsuda Y, Fujiwara N … +28 more , Narita K, Oyamada S, Ariyoshi K, Hosono Y, Kushi K, Ichimaru K, Yabuki R, Kaneishi K, Abe K, Fujihara T, Kono Y, Suzuki K, Kinoshita T, Sasara T, Nakajima M, Mawatari H, Sugawara H, Nobutani K, Shindoh Y, Kobayashi K, Yamaguchi T, Iwaki R, Kitazoe Y, Kanai Y, Ueno J, Fukumi T, Ishii R, Nakajima N
Cancer · 2026 Jun · PMID 42304645 · Full text
BACKGROUND: Maintaining activities of daily living is of great importance for patients who have cancer, and dependency is associated with psychological distress. However, evidence for rehabilitation remains scarce in thi...
BACKGROUND: Maintaining activities of daily living is of great importance for patients who have cancer, and dependency is associated with psychological distress. However, evidence for rehabilitation remains scarce in this setting. The objective of this study was to evaluate the efficacy of a structured rehabilitation program for maintaining activities of daily living among patients with terminal cancer. METHODS: This multicenter randomized controlled trial across 19 Japanese inpatient hospices/palliative care units enrolled patients who had terminal cancer with an Eastern Cooperative Oncology Group performance status of 2-3, a life expectancy ≥3 weeks, and no severe symptoms. Participants were randomly assigned (1:1, stratified by performance status and site) to either a 3-week structured rehabilitation program that incorporated key elements of rehabilitation for patients with terminal cancer or usual unstructured rehabilitation. The primary outcome was a change in the total modified Barthel Index from baseline to day 22. Secondary outcomes included the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 15-Palliative Care score and safety. RESULTS: Between July 8, 2019, and February 20, 2024, 130 patients were randomized (59 to the intervention group, 71 to the control group; 56 patients [43.0%] were women). The primary analysis included 77 participants who had complete data available. The mean change in total modified Barthel Index was -1.31 (95% confidence interval [CI], -10.89, 8.08) in the intervention group and -15.51 (95% CI, -24.02, -7.01) in the control group. The between-group difference was 14.21 (95% CI, 1.77, 26.64; p = .026), exceeding the minimally clinically important difference (9.25). Patient-reported physical functioning on the European for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 15-Palliative Care instrument was also significantly higher in the intervention group than in the control group. No serious harms occurred. CONCLUSIONS: Structured rehabilitation maintained activities of daily living better than unstructured rehabilitation in patients with terminal cancer, supporting its integration into routine care even in the last stage of cancer.
Trajectory and predictors of cancer- and treatment-related fatigue (CRF) in adolescent and young adult cancer patients: a prospective, longitudinal study.
Chan A, Chan D, Agrawal P … +5 more , Beppu LL, Kober K, Ng DQ, Sayer M, Trudeau J
BMC Cancer · 2026 Jun · PMID 42304319 · Full text
BACKGROUND: Although cancer- and treatment-related fatigue (CRF) is well recognized as a clinically important and distressing symptom among adolescent and young adult cancer (AYAC) patients, the understanding of the unde...
BACKGROUND: Although cancer- and treatment-related fatigue (CRF) is well recognized as a clinically important and distressing symptom among adolescent and young adult cancer (AYAC) patients, the understanding of the underlying mechanisms behind CRF in AYAC remains limited. We evaluated the trajectory and associated predictors of CRF among AYAC patients (Clinicaltrials.gov: NCT03476070, registered 03/23/2018). METHODS: Newly diagnosed AYAC (15-39 years old) and non-cancer controls (NC) recruited from National Cancer Centre Singapore completed clinical assessments and provided blood draws for inflammatory cytokine measurements every 3 months up to 12 months. Mixed-effects models were used to evaluate significant factors associated with fatigue (MFSI-SF Total score), with AYAC stratified by chemotherapy status (active chemotherapy vs. >30 days post-chemotherapy). RESULTS: Fifty AYAC and 105 NC participants were included, with nearly 1 in 3 AYAC participants reported clinically important CRF at some point. Measurements collected during active chemotherapy had a higher rate of clinically important CRF symptoms relative to samples collected post-chemotherapy and from non-cancer controls. Regression analyses evaluating significant influencers of fatigue scores demonstrated that active chemotherapy, female sex, worsened psychological distress scores, and increased IL-10 levels were associated with worse self-reported fatigue symptoms (all p < 0.05). CONCLUSION: Given the observed prevalence of clinically important CRF amongst AYAC within our study, our results further demonstrate that these patients are vulnerable to fatigue challenges. Identifying factors associated with these debilitating symptoms enables clinicians to better recognize at-risk patients and proactively address symptom burden.
Differential predictive value of inflammation- and coagulation-based composite biomarkers for venous thromboembolism and mortality in patients with NSCLC receiving immune checkpoint inhibitors.
Liu J, Wang L, Xia X … +4 more , Chen S, Yang D, Lu X, Xu Y
BMC Cancer · 2026 Jun · PMID 42304312 · Full text
BACKGROUND: Venous thromboembolism (VTE) is a clinically important complication in patients with non-small cell lung cancer (NSCLC) receiving immune checkpoint inhibitors (ICIs). Although inflammation and coagulation abn...
BACKGROUND: Venous thromboembolism (VTE) is a clinically important complication in patients with non-small cell lung cancer (NSCLC) receiving immune checkpoint inhibitors (ICIs). Although inflammation and coagulation abnormalities may contribute to both thrombosis and poor prognosis, it remains unclear whether routinely available composite biomarkers have similar or differential predictive value for VTE occurrence and all-cause mortality in this setting. METHODS: This single-center retrospective cohort included 206 patients with advanced NSCLC who received at least two cycles of ICI therapy between January 2020 and December 2024. Baseline clinical, treatment, laboratory, and conventional thrombosis risk score data were collected. The D-dimer-to-albumin ratio (DAR), platelet-to-hemoglobin ratio (PHR), and fibrinogen-to-prealbumin ratio (FPR) were analyzed as log2-transformed continuous variables. VTE was evaluated using cumulative incidence functions and Fine-Gray competing-risk models with death without prior VTE as a competing event. All-cause mortality was assessed using time-dependent Cox models, with incident VTE modeled as a time-dependent covariate. Exploratory transition-specific Cox models evaluated baseline-to-VTE, baseline-to-death without prior VTE, and VTE-to-death pathways. E-values and proportional hazards diagnostics were used for sensitivity assessment and model checking. RESULTS: During a median follow-up of 23.0 months, 29 patients (14.1%) developed VTE, 101 died without prior VTE, and 76 were censored. The median time to VTE was 5.0 months, and the 12-, 24-, and 36-month cumulative incidences were 9.2%, 13.7%, and 14.4%, respectively. Neither the Padua nor Khorana score effectively discriminated VTE risk. In Fine-Gray models, DAR was associated with VTE risk after full adjustment, with a subdistribution hazard ratio of 1.28 per doubling (95% confidence interval, 1.00-1.64; P = 0.048), whereas PHR and FPR were not. In time-dependent Cox models, PHR and FPR remained associated with all-cause mortality, whereas DAR and incident VTE did not. Transition-specific analyses suggested that DAR was more closely related to VTE occurrence, whereas PHR and FPR were more closely related to death without prior VTE. CONCLUSIONS: In patients with advanced NSCLC receiving ICIs, DAR, PHR, and FPR showed differential predictive patterns for VTE and all-cause mortality. These findings require validation in larger multicenter cohorts.
Comparative assessment of asparaginase activity, population pharmacokinetics, and safety of biosimilar native Escherichia coli and pegylated asparaginase in children with newly diagnosed acute lymphoblastic leukemia: a pharmacometrics-based randomized clinical trial.
Sethuramalingam S, Mohapatra S, Agarwal PK … +5 more , Kumar-M P, Hota D, Gopal J, Kulkarni A, Srinivasan A
BMC Cancer · 2026 Jun · PMID 42304309 · Full text
BACKGROUND: There is a paucity of data regarding the comparison of asparaginase activity, pharmacokinetics, pharmacodynamic outcomes, and safety of biosimilar native E.coli asparaginase (N-Asp) and biosimilar pegylated a...
BACKGROUND: There is a paucity of data regarding the comparison of asparaginase activity, pharmacokinetics, pharmacodynamic outcomes, and safety of biosimilar native E.coli asparaginase (N-Asp) and biosimilar pegylated asparaginase (P-Asp) used in India. METHODS: A randomized, open-labeled, population pharmacokinetic (PopPK) and pharmacodynamic trial comparing the N-Asp (10,000 IU/m) and P-Asp (1000 IU/m) administered intramuscularly in children with newly diagnosed acute lymphoblastic leukemia. The primary endpoint was asparaginase activity on day 33 of the induction phase of chemotherapy. Population pharmacokinetic modeling was done after the first dose in both groups, and the models were simulated to assess for the subtherapeutic trough concentrations. RESULTS: Fourteen patients were randomized to each arm. The asparaginase activity of 434[interquartile range(IQR) 259, 629] IU/L was observed in the P-Asp compared (p-0.04) to the N-Asp group 64[IQR 27, 184] IU/L on day 33 of the induction phase of chemotherapy. The anti-asparaginase antibody formation, minimal residual disease, and safety were comparable between both groups. The interindividual variability of the population parameters in the PopPK model was higher with N-Asp than P-Asp. The subtherapeutic trough levels of asparaginase were observed more in the N-Asp group (9/14 in N-Asp vs. 0/14 in P-Asp, p < 0.01). CONCLUSION: The asparaginase activity was higher with P-Asp at d33. P-Asp demonstrated less interindividual variability and a predictable kinetic profile, supporting its preferability over N-Asp for first-line management of ALL in the Indian pediatric population. While routine TDM for trough level monitoring may be less critical with P-Asp, TDM retains value to identify silent inactivation, differentiate hypersensitivity from infusion reactions, and confirm adequate activity in high-risk scenarios. In contrast, the higher variability of N-Asp strongly warrants the use of TDM. CLINICAL TRIAL REGISTRATION IDENTIFICATION: CTRI/2019/06/019520 registered on 04/June/2019.
Ultrasonographic characterization of malignant pleural effusion in a murine experimental model.
Mello AJ, Fortunato E, Pereira KR … +5 more , Silva CSR, Sales RKB, Nascimento SCR, Teixeira LR, Acencio MMP
BMC Cancer · 2026 Jun · PMID 42304274 · Full text
BACKGROUND: Malignant pleural effusion (MPE) is a common manifestation of advanced malignancies and is associated with high morbidity and poor prognosis. Thoracic ultrasound (TUS) has emerged as a sensitive, non-invasive...
BACKGROUND: Malignant pleural effusion (MPE) is a common manifestation of advanced malignancies and is associated with high morbidity and poor prognosis. Thoracic ultrasound (TUS) has emerged as a sensitive, non-invasive imaging modality for pleural evaluation; however, standardized ultrasonographic criteria for MPE in murine experimental model remains limited. The aim of this study was to describe and characterize the TUS findings of MPE in an experimental murine model. METHODS: MPE was induced in C57Bl/6 mice by intrapleural injection of Lewis lung carcinoma (LLC) cells. TUS examinations were performed longitudinally at predefined time points to assess pleural fluid depth, pleural line characteristics, pleural thickening, nodules, subpleural consolidations, lung parenchymal alterations, and ultrasound artifacts. Pleural fluid volume, cytology, and histological analyses were obtained after euthanasia and correlated with ultrasonographic findings. RESULTS: TUS detected early pleural changes as early as day 7, preceding large-volume effusion. Pleural fluid depth measured by TUS showed a strong correlation with pleural fluid volume obtained by direct puncture (R = 0.927, p < 0.001). Progressive pleural thickening and nodularity (R = 0.704 e p = 0.002) correlated with histopathological tumor involvement. CONCLUSION: TUS reliably characterizes and quantifies MPE progression in a murine model, closely reproducing human disease patterns. This experimental model supports translational research by enabling longitudinal and non-invasive assessment of biological and pathological processes over time, thereby allowing repeated evaluations within the same subject and significantly reducing the need for animal euthanasia at multiple experimental endpoints, while also providing a robust framework that may corroborate and facilitate future studies in related research fields.
Evolution of treatment patterns and survival outcomes in non-metastatic rectal cancer: a 15-year real-world single-center analysis.
Jang JY, Lim H, Ko J … +8 more , Lee JH, Kim Y, Chi SA, Yoo GS, Park HC, Kim N, Cho YB, Yu JI
BMC Cancer · 2026 Jun · PMID 42304266 · Full text
BACKGROUND: Treatment strategies for rectal adenocarcinoma have undergone substantial evolution, driven by advances in surgical techniques, radiotherapy, and systemic therapies. Nonetheless, longitudinal evidence on thei...
BACKGROUND: Treatment strategies for rectal adenocarcinoma have undergone substantial evolution, driven by advances in surgical techniques, radiotherapy, and systemic therapies. Nonetheless, longitudinal evidence on their real-world adoption and survival trends remains limited. This study investigated temporal trends in patient characteristics, treatment patterns, and outcomes over a 15-year period at a high-volume Korean tertiary center. METHODS: We retrospectively evaluated 6,314 patients with non-metastatic rectal adenocarcinoma who received curative-intent treatment between 2008 and 2022. The study period was divided into five consecutive 3-year intervals to facilitate temporal comparisons. RESULTS: The mean age at diagnosis was 59.4 years, and 62.0% of patients were male. The proportion of clinical T4 tumors increased substantially, from 7.0% to 28.0%, whereas well-differentiated histology declined over time. Minimally invasive surgery rose from 44.5% to 91.0%, driven by the growing adoption of robotic techniques. Neoadjuvant radiotherapy replaced adjuvant radiotherapy as the predominant approach, and capecitabine-based regimens became the most frequent systemic therapy. Across the entire cohort, the 5-year survival rate was 87.6%, with overall survival showing steady improvement across study periods. Relative to the general population, the standardized mortality ratio declined from 5.57 in Period 1 to 3.33 in Period 5, reflecting a measurable reduction in excess mortality. Among patients with locally advanced disease, the highest five-year survival rate was 88.4% in those treated with neoadjuvant therapy followed by surgery. CONCLUSIONS: These findings demonstrate substantial temporal changes in multidisciplinary rectal cancer management, with improved survival observed over time, supporting the continued refinement of multidisciplinary care strategies.
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