Wiley: Cancer Medicine: Table of Contents

Lenalidomide Plus Dexamethasone as FIRST‐Line Therapy in Transplant‐Ineligible Patients With Multiple Myeloma: Final Results of the Prospective, Non‐Interventional Study FIRST‐NIS and Comparison With the FIRST Pivotal Phase III Clinical Trial

Thu, 02 Apr 2026 20:04:10 -0700

ABSTRACT

Objectives

Lenalidomide and low-dose dexamethasone (Rd) is a standard regimen for transplant-ineligible (TIE) patients with newly diagnosed multiple myeloma (NDMM), for whom a multi-drug treatment regimen is not considered appropriate. While Rd has been intensively investigated in clinical trials, prospective real-world data are still scarce.

Patients and Methods

The prospective, multicenter, non-interventional study FIRST-NIS (NTC02537808) investigated the effectiveness, safety, and quality of life (QoL) of Rd in a German real-world setting. G8-Geriatric assessment was used to assess patients' impairment status. Patients were treated according to the physician's discretion. Data were analyzed descriptively; no formal hypothesis was tested.

Results

Between 2015 and 2018, 168 patients with TIE NDMM were included, median age was 77.7 years. With a median follow-up of 64.2 months, median progression-free survival (PFS) in the real-world setting was 22.9 months [95% CI 19.3, 28.1], median overall survival (OS) 58.1 months [95% CI 45.7, 71.7]. Patients ≤ 75 years and non-impaired patients showed a more favorable PFS and OS, and Rd was a feasible treatment option in most patients with renal impairment. QoL was maintained during Rd treatment. No new safety signals emerged.

Conclusions

The results of the FIRST-NIS support Rd as an effective and safe frontline treatment option for patients with TIE NDMM, irrespective of age, with similar clinical outcomes in the real world compared to the pivotal trial.

Trial Registration

ClinicalTrials.gov identifier: NCT02537808

Communication Processes and Priorities in Medical Aid in Dying Conversations: A Cross‐Sectional Qualitative Study of Multidisciplinary Cancer Clinicians

Thu, 02 Apr 2026 19:23:52 -0700

ABSTRACT

Background

Medical aid in dying (MAiD) is a practice that enables eligible individuals with a terminal, life-limiting illness to end their lives in a self-directed way. Multidisciplinary care teams play a vital role in facilitating discussions and patient decision making about MAiD in cancer care settings. However, little is known about how multidisciplinary care teams navigate MAiD discussions to provide effective, person-centered care.

Objectives

To identify the communication priorities and processes that cancer care clinicians believe are most critical for multidisciplinary care teams when discussing MAiD with patients who have cancer.

Design

Cross-sectional online survey.

Setting/Subjects

Multidisciplinary clinicians who participated in a communication training program supported by the National Cancer Institute (N = 160) responded to five open-ended survey questions about communication considerations when working with a hypothetical patient with glioblastoma considering MAiD. Participants were presented with a case scenario and invited to describe how they would communicate with that patient as a member of a multidisciplinary team. A thematic analysis of responses using an iterative, inductive approach was conducted until saturation was reached.

Results

Four themes were identified as communication priorities and processes critical for multidisciplinary teams when discussing MAiD with cancer patients: (1) addressing complexity of MAiD in GBM; (2) thorough palliative care assessment; (3) strategies for clinicians and healthcare systems to optimize MAiD discussions; and (4) person-centered care that de-stigmatizes MAiD.

Conclusions

Findings underscore the distinct complexity of MAiD discussions in oncology and highlight the need for tailored, person-centered approaches that go beyond standard end-of-life communication.

Regrowth Patterns in Glioblastoma—Survival and Predictors

Thu, 02 Apr 2026 19:20:06 -0700

Multiple glioblastoma relapse patterns were associated with patients' progression-free and overall survival, even when other known prognostic factors were taken into account. Treatment with Tumor Treating Fields was associated with prolonged progression-free survival and predictive for a higher frequency of non-local recurrence patterns after subtotal tumor resection, most likely due to improved local control.

ABSTRACT

Glioblastomas (GBM) can recur in different ways. While local recurrence is most common, some GBM recur at distant sites or simultaneously at multiple sites. However, the consequences of different regrowth patterns for the clinical course and the factors that might influence regrowth patterns or different modalities of recurrence remain unclear. We wondered (1) whether a more accurate analysis of regrowth patterns helps to detect subgroups of GBM patients, (2) if evaluation of relapse patterns correlates with differences in survival, and (4) whether we can identify predictors for distinct regrowth patterns. Therefore, we retrospectively collected demographic data, as well as tumor- and patient-characteristics, from 251 patients treated at two institutions and characterized their recurrence patterns by analyzing Magnetic Resonance Imaging data. We observed distinct differences in patients' overall and progression-free survival with respect to multicentric and multifocal recurrences, further supporting the hypothesis that these recurrences develop differently. Several tumor relapse patterns were associated with patients' progression-free and overall survival (e.g., unifocal local and multicentric recurrences; p < 0.05), even when other known prognostic factors were taken into account. TTFields were associated with prolonged progression-free survival (mPFS 7.2 months vs. 4.8 months, p = 0.03). They were predictive of a higher frequency of non-local recurrence patterns (OR 0.16, p = 0.02) and longer time to development of a local recurrence after subtotal tumor resection (mPFS 11.1 months vs. 5.2 months; p = 0.01). This can be interpreted as a sign of improved local control.

Profiling Ten RHO GTPases in Myeloid Malignancies Reveals Distinct Expression Patterns and Prognostic Associations

Thu, 02 Apr 2026 19:00:37 -0700

Expression of RHO GTPases in myeloid malignancies. Gene expression analysis of ten RHO GTPases revealed RHOBTB2, RND2, and RHOQ as differently expressed in patients with MDS and/or AML. RHOBTB2 was identified as a promising prognostic indicator. BM, bone marrow. MDS, myelodysplastic neoplasm. AML, acute myeloid leukemia.

ABSTRACT

The RHO GTPase family regulates cytoskeleton-dependent processes, including proliferation and migration. Although their dysregulation is well described in solid tumors, little is known about their role in hematologic malignancies. We investigated the expression of ten RHO GTPase genes in bone marrow samples from patients with acute myeloid leukemia (AML) and myelodysplastic neoplasms (MDS) and analyzed TCGA AML data for prognostic associations. RHOBTB2, RND2, and RHOQ were differentially expressed compared with healthy controls. RHOBTB2 was elevated in both MDS and AML and associated with inferior overall and disease-free survival, including in intermediate-risk AML. Our findings reveal distinct dysregulation patterns of RHO GTPases in myeloid malignancies and confirm RHOBTB2 as a candidate prognostic marker in AML with a potential oncogenic role. These data support further investigation into the functional roles of RHO GTPases in leukemogenesis and their utility as emerging biomarkers in hematologic cancers.

PSAT1 Promotes NSCLC Progression via the De Novo Serine Synthesis Pathway and Represents a Therapeutic Vulnerability

Xijia Zhou, Min Zhao, Yingshu Cao, Xiangyu Zhou, Ke Wang — Thu, 02 Apr 2026 04:00:27 -0700

ABSTRACT

Background

Non-small cell lung cancer (NSCLC) is a malignant tumor characterized by high morbidity and mortality, as well as metabolic reprogramming. Enhanced serine synthesis plays a crucial role in the aberrant metabolism of NSCLC. Among the three key enzymes involved in serine synthesis, phosphoserine aminotransferase 1 (PSAT1) requires further investigation to elucidate its regulatory mechanisms in NSCLC.

Methods

In this study, we employed bioinformatics analysis, immunohistochemistry, CCK-8 assay, colony formation assay, flow cytometry assay, isotope tracing technique, WB analysis, and nude mouse xenograft models to validate the expression and function of PSAT1 in NSCLC.

Results

Our results demonstrated that PSAT1 was significantly upregulated in NSCLC cells and contributed to promoting cell proliferation, inhibiting apoptosis, and attenuating the efficacy of gefitinib treatment. Moreover, knockdown of PSAT1 led to inhibition of the de novo serine synthesis pathway (SSP), elevation of reactive oxygen species (ROS) levels, and activation of the mitochondrial apoptotic pathway. Notably, combined knockdown of PSAT1 with exogenous serine intake inhibition synergistically suppressed NSCLC progression.

Conclusion

Collectively, our findings highlight that PSAT1 serves as a biomarker for metabolic reprogramming in NSCLC and exhibits a close association with disease development and treatment.

The Role of Gut Microbiota and Their Derived Metabolites in Chemotherapy‐Induced Nausea and Vomiting in Ovarian Cancer

Shuiling Zu, Xiaoyan Yu, Jihong Song, Yu Xiao, Huan Yi, Hong Li — Thu, 02 Apr 2026 03:56:33 -0700

ABSTRACT

Objective

This study aimed to investigate the relationship between gut microbiota and chemotherapy-induced nausea and vomiting (CINV) in patients with ovarian cancer undergoing platinum-based chemotherapy (carboplatin or cisplatin combined with paclitaxel).

Methods

Clinical data and fecal samples were collected from patients with ovarian cancer after admission but prior to the initiation of their first chemotherapy cycle. Patients were divided into the CINV (n = 25) and non-CINV (n = 25) groups on the basis of symptoms occurring after chemotherapy. No additional samples were collected during chemotherapy. Integrated metagenomic sequencing and untargeted metabolomic profiling identified CINV-associated microbial taxa and metabolites. Additionally, fecal microbiota transplantation (FMT) in SD rats validated causal links between gut dysbiosis and CINV pathogenesis.

Results

Bacteroides caccae, Corynebacteriales, and Corynebacterium were significantly enriched in the CINV group. KEGG enrichment revealed upregulated pathways in CINV, including focal adhesion, lysosome function, and eukaryotic cellular communities. Metabolomic analysis identified 19 significantly increased metabolites in the fecal samples of CINV patients versus 10 in non-CINV controls. KEGG enrichment revealed that the pentose phosphate pathway, glutathione metabolism, and lipoic acid metabolism were significantly implicated in CINV pathogenesis. Multi-omics integration revealed Bacteroides sp. A1C1 strongly correlated with hesperetin, arbutin, orciprenaline, and myristolic acid. In rats, cisplatin-induced CINV models showed higher kaolin consumption versus controls (p < 0.05). FMT from non-CINV donors reduced kaolin consumption in cisplatin-treated rats (p < 0.05). The expression of 5-HT3R, NK1R, and NK2R in the medulla oblongata and colon was significantly increased in the cisplatin model group (p < 0.05) and partially reversed by non-CINV FMT (p < 0.05).

Conclusions

Gut microbiota dysbiosis directly contributes to CINV pathogenesis. Bacteroides sp. A1C1 and its putatively identified metabolites (hesperetin, arbutin, orciprenaline, and myristolic acid) represent potential diagnostic biomarkers for CINV.

Immune‐Related Adverse Events in Bladder Cancer Patients Treated With Immune Checkpoint Inhibitors: Insights From a FAERS Disproportionality Analysis

Pooja Gokhale, Lorenzo Villa Zapata — Thu, 02 Apr 2026 03:50:48 -0700

ABSTRACT

Introduction

Immune checkpoint inhibitors (ICIs) are an important treatment option in bladder cancer, but clinical trials have demonstrated that they are associated with immune-related adverse events (irAEs), such as rash, hypothyroidism, hyperthyroidism, and others. This study aimed to evaluate real-world evidence of these irAEs using the FDA Adverse Event Reporting System (FAERS).

Methods

We analyzed FAERS data through December 2024 to identify irAEs associated with atezolizumab, pembrolizumab, avelumab, and nivolumab in patients with bladder cancer. A case/non-case pharmacovigilance analysis was conducted to assess the association between ICI monotherapy and specific irAEs, including rash, pruritus, hypothyroidism, hyperthyroidism, colitis, nephritis, myocarditis, pneumonitis, and myositis.

Results

A total of 365 unique irAE reports were identified. Significant safety signals were observed for hyperthyroidism with atezolizumab (PRR: 3.51 [95% CI: 1.07–11.45]; ROR: 3.53 [95% CI: 1.07–11.61]; IC: 1.10 [95% CI: 0.33–1.87]), rash with pembrolizumab (PRR: 2.11 [95% CI: 1.17–3.80]; ROR: 2.14 [95% CI: 1.18–3.90]; IC: 0.44 [95% CI: 0.17–0.71]), and myositis with avelumab (PRR: 5.30 [95% CI: 1.35–20.82]; ROR: 5.47 [95% CI: 1.34–22.29]; IC: 1.95 [95% CI: 0.65–3.25]). While not reaching the threshold for statistical significance, nephritis with atezolizumab did not meet predefined signal detection criteria and should only be considered as hypothesis-generating. A similar borderline pattern was observed for hypothyroidism with avelumab.

Conclusion

The occurrence of irAEs varies by ICI agent among bladder cancer patients. These findings underscore the importance of post-marketing surveillance in identifying real-world safety signals. Proactive management and patient education are essential to mitigate irAEs and preserve quality of life.

Exercise Preferences, Barriers, Motivators, Facilitators, and Perceived Benefits in Adults With Brain Tumours—A Systematic Review

Tue, 31 Mar 2026 18:14:51 -0700

ABSTRACT

Introduction

Adults with brain tumours face a poor prognosis, and physical and mental impairments reduce quality of life. Exercise can improve outcomes for this population; however, uptake and adherence remain low. Understanding exercise preferences, barriers, motivators, facilitators, and perceived benefits is crucial to optimising engagement.

Methods

A systematic search of Embase, MEDLINE, Scopus, CINAHL Complete, and the Nursing and Allied Health Database (2015–2025) was conducted. Studies were eligible if they included adults (≥ 18 years) with brain tumours and reported original qualitative or quantitative data. Screening, data extraction, and quality appraisal (Mixed Methods Appraisal Tool, 2018 version) were performed by two authors, with discrepancies resolved by a third. Data were synthesised narratively due to heterogeneity.

Results

Seven studies involving 163 participants were included, with mean ages of 48–63.5 years and 44.8% males. Most studies included individuals diagnosed with glioblastoma, glioma, or oligodendroglioma. Exercise preferences were reported in 5/7 studies. Participants preferred flexible, individualised exercise programs with varied delivery modes and session durations. Walking was the most commonly preferred activity in 2/7 studies (48%–56% of participants); 1/7 study reported 65% chose multiple activities, including cycling, swimming, and running. Barriers were identified in 5/7 studies, including symptom burden, cognitive impairment, treatment-related side effects, and psychological and external factors. Facilitators and motivators were reported in 3/7 studies and included support from carers and healthcare providers, structural enablers, and intrinsic motivations. Perceived benefits were identified in 5/7 studies, including improved physical function, energy, quality of life, well-being, self-efficacy, and social engagement.

Conclusions

Exercise interventions for adults with brain tumours should be flexible, individualised, and supported by carers and healthcare providers. Moderate aerobic training is preferred, while resistance training remains underexplored. Addressing barriers and providing structured support may enhance uptake and adherence. Further research is needed to establish optimal program characteristics across disease stages.

Significance of Early Proton Beam Therapy Initiation in Achieving Complete Response in Pediatric Medulloblastoma: A Retrospective Study

Tue, 31 Mar 2026 18:09:33 -0700

ABSTRACT

Introduction

Proton beam therapy (PBT) has proven to be highly effective in treating pediatric medulloblastoma, offering both excellent therapeutic outcomes and reduced side effects. However, factors influencing tumor response following PBT remain poorly defined, including the optimal interval time between surgery and PBT initiation (ISP).

Methods

This retrospective study analyzed data from 52 patients with postoperative residual medulloblastoma treated with PBT, focusing on the correlation between tumor response and ISP, as well as other variables associated with achieving complete response (CR).

Results

The median follow-up period was 12.5 months (5.3–20.3 months). Treatment response was assessable in all patients, with 26 (50.00%) patients in CR, 15 (28.85%) patients in partial response (PR), and 11 (21.15%) patients with stable disease (SD). Patients who initiated PBT within 31 days post-surgery had a markedly higher CR rate (74.07%), while those with longer ISPs were more likely to exhibit PR (32.00%) or SD (44.00%). An improved tumor response was significantly associated with a shorter ISP (30.15 ± 5.31 days, p < 0.001). Univariate logistic regression identified Chang staging M3 (Odds ratio [OR] = 0.103, p = 0.046), residual tumor size > 1.5 cm (OR = 0.278, p = 0.043), and longer ISP (OR = 0.906, p = 0.013)—particularly beyond 31 days (OR = 0.111, p = 0.001)—as factors associated with a lower likelihood of CR. Multivariate analysis further confirmed that ISP was the only independent factor correlated with CR (OR = 0.884, p = 0.009).

Conclusion

This study highlights that the timely initiation of PBT following surgery, particularly within 31 days, is associated with improved CR in pediatric medulloblastoma. Our findings suggest that a shorter interval between surgery and PBT initiation may be an important factor influencing early treatment response, providing preliminary evidence to support earlier postoperative PBT delivery.

A Disproportionality Analysis of Immune Checkpoint Inhibitors in Combination With Platinum‐Based Agents Using the FDA Adverse Event Reporting System Database

Mon, 30 Mar 2026 20:01:06 -0700

ABSTRACT

Objective

Immune checkpoint inhibitors (ICIs) combined with platinum-based compounds are commonly used in the treatment of certain malignant tumors. This study aims to analyze adverse events (AEs) associated with the combination therapy of ICIs and platinum-based compounds by using the FAERS database.

Methods

This study retrieved relevant adverse event (AE) data from the FAERS database (2008–2024) and conducted a retrospective analysis of the collected AEs. Multiple disproportionality analysis algorithms were employed, including the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS).

Results

Analysis of 28,585 reports identified 27 significant SOC-level signals, strongest for hematological (ROR = 6.3), endocrine (ROR = 14.3), and hepatobiliary disorders (ROR = 4.49). Key PTs included malignant neoplasm progression (ROR = 16), febrile neutropenia (ROR = 15.31), and myocarditis (ROR = 16.3). 45.5% of AEs occurred within 1 month (median onset: 38 days). Combination therapy showed lower rates vs. monotherapy for malignancy progression and nephrotoxicity, but higher neurotoxicity (628 neuropathy cases).

Conclusion

The combination exhibits distinct early-onset toxicities (early-onset hematological/endocrine/hepatic) and novel risks (neuropathy/myocarditis/leukemia), necessitating enhanced initial monitoring and subgroup-specific management.

Nationwide Incidence, Treatment Pattern, and Prognosis of Primary CNS Lymphoma in Taiwan, 2012–2020: A Retrospective Cohort Study

Fei‐Yuan Hsiao, Hung‐Yu Lin, Ho‐Min Chen, Wan‐Hsuan Hsu, Bor‐Sheng Ko — Sun, 29 Mar 2026 21:25:07 -0700

Using data from the Taiwan Cancer Registry, the Taiwan National Health Insurance Research Database, and the Taiwan National Death Registry, this nationwide real-world study examined the epidemiology, treatment patterns, prognosis, medical costs, and adverse events associated with primary central nervous system lymphoma (PCNSL) in Taiwan over a nine-year period (2012–2020).

ABSTRACT

Background

Primary central nervous system lymphoma (PCNSL) is a rare but devastating form of non-Hodgkin lymphoma with persistently poor outcomes despite treatment advances. This nationwide population-based study evaluated real-world epidemiology, treatment patterns, and survival outcomes in Asian PCNSL patients.

Methods

Patients with newly diagnosed PCNSL (2012–2020) were identified from the Taiwan Cancer Registry Database and linked with the National Health Insurance Research Database. Incidence, treatment patterns, survival outcomes, healthcare costs, and adverse events were analyzed for identified PCNSL patients. Specifically, median survival times (MSTs), with 95% confidence intervals (CIs), were estimated using the Kaplan–Meier method.

Results

Among 820 PCNSL patients (median age 65 [IQR 56–74] years; 53.5% male; 94.4% DLBCL subtype), age-standardized incidence was 0.39 per 100,000 person-years (2012–2020) with male predominance (0.44 vs. 0.34) and elderly burden (1.62 in ≥ 75 years vs. 0.28 in < 65 years). Despite 89.5% receiving induction therapy within median 24 days, outcomes remained poor: median survival 1.85 (95% CI 1.53–2.27) years, with 1-, 2-, and 3-year survival rates of 61.5%, 48.3%, and 40.2%, respectively. All-cause survival deteriorated markedly with age—median survival of 5.71, 3.29, 2.32, 0.97, and 0.69 years for ages < 50, 50–59, 60–69, 70–79, and ≥ 80 years, respectively. MTX-based chemotherapy with rituximab adoption increased (22.2% to 55.3%), achieving superior survival (3.44 years) versus WBRT alone (1.24 years). However, 46.2% developed relapsed/refractory disease at median 156 (89–339) days. Consolidation therapy was administered in 52.5% at median 53 days post-induction. Infection (87.9%), nausea/vomiting (81.1%), and neutropenia (54.4%) dominated adverse events, with first-year costs averaging $35,472 (SD $20,816) USD.

Conclusion

PCNSL demonstrates persistently poor prognosis, with elderly patients experiencing disproportionately worse outcomes. High relapse rates, substantial treatment-related adverse events, and considerable healthcare burden underscore the urgent need for novel therapeutic approaches.

Molecular Characterization and Its Clinical Application of GNAS Variants in Intramuscular Myxoma

Sun, 29 Mar 2026 21:17:51 -0700

This graphical abstract illustrates the workflow of fragment signal analysis for detecting GNAS codon 201 variants, combining PNA clamping PCR, restriction digestion, and capillary electrophoresis to differentiate wild-type and variant alleles.

ABSTRACT

Background

Intramuscular myxoma (IM) is a benign tumor that harbors GNAS missense variants. Distinguishing IM from low-grade myxofibrosarcoma (LGMFS) is challenging due to similarities in imaging and histological features. While molecular analysis aids differentiation, the low number of tumor cells available for DNA extraction necessitates highly accurate detection methods for variant identification. The aim of this study was to delineate molecular characteristics using next-generation sequencing (NGS) and to propose an optimal screening method in a clinical setting to differentiate IM from LGMFS.

Materials

Ten IM cases and nine LGMFS cases with extractable DNA from FFPE samples were recruited.

Results

A custom NGS panel-based analysis for GNAS revealed R201C/R201H variants in resected samples of eight cases with IM and in none of the eight cases, excluding one with insufficient sample quality, with LGMFS, and in biopsy samples of both available cases with IM. Additionally, various sequence alterations were detected irrespective of the clinical status (IM, LGMFS, and normal tissue) or sample conditions (resected, biopsy, and relapsed). The detection rate of GNAS-positive IM using other methods (PCR-direct sequencing, fragment signal analysis using restriction digestion and capillary electrophoresis after PCR combined with peptide nucleic acid (PNA) clamping, and PCR-direct sequencing combined with PNA clamping) was calculated as 0.42, 0.83, and 0.75, respectively, while the detection rate for GNAS-negative LGMFS was 1.

Conclusion

These findings suggest that fragment signal analysis is a reasonable diagnostic approach for differentiating IM from LGMFS. However, it is important to recognize that the absence of GNAS R201C/R201H variants does not rule out IM.

Post‐Neoadjuvant Chemotherapy Axillary Ultrasound in cN+ Breast Cancer: Can It Reliably Support de‐Escalation of Axillary Surgery?

Fri, 27 Mar 2026 04:13:35 -0700

ABSTRACT

Background

Neoadjuvant chemotherapy (NAC) in up to 40%–60% of node-positive (cN+) breast cancer patients allows nodal pathological complete response, particularly in Her2+ and triple-negative subtypes. Accurate post-NAC axillary restaging is therefore critical to identify candidates for surgical de-escalation. Axillary ultrasound (AUS) remains the most widely used tool, but prior studies report highly variable performance, with false-negative rates approaching 25%, raising concerns about its reliability as a standalone guide.

Methods

We retrospectively evaluated 413 patients with biopsy-proven cN+ breast cancer treated with NAC (2000–2024). All underwent AUS before surgery. AUS results (ycN0 vs. ycN+) were compared with final pathology (ypN0 vs. ypN+). Diagnostic performance was assessed, and predictors of false-negative AUS were identified using logistic regression.

Results

AUS classified 51.6% of patients as ycN0, whereas only 45% achieved nodal pathologic complete response. Overall, AUS demonstrated 68% sensitivity, 76% specificity, 72% accuracy, positive predictive value 78%, and negative predictive value 66%. Performance differed by subtype: accuracy was highest in ER-/Her2 tumors (75%), but markedly lower in Her2+ (69%) and lobular carcinoma (67%). On multivariate analysis, absence of breast clinical complete response (OR 2.38, 95% CI [1.14–4.93]) independently predicted false-negative AUS findings.

Conclusions

AUS following NAC provides only moderate accuracy, with a clinically relevant risk in patients lacking breast response. AUS alone should not determine omission of axillary surgery. A multimodal, biology-informed strategy combining AUS with other imaging techniques is needed to safely guide axillary de-escalation and minimize both overtreatment and undertreatment.

Health Insurance as a Mediator of Neighborhood Deprivation and Pediatric Cancer Survival: An Analysis of State Cancer Registry Data

Fri, 27 Mar 2026 04:06:59 -0700

ABSTRACT

Introduction

To develop interventions to reduce neighborhood-level disparities in pediatric cancer outcomes, it is necessary to understand their underlying mechanisms. It has been suggested that individual-level health insurance is a mediator of neighborhood deprivation and pediatric cancer survival.

Methods

This study was a population-based longitudinal study of children with cancer from 2000 to 2020 in the Iowa Cancer Registry and Louisiana Tumor Registry. Neighborhood deprivation was measured using the Area Deprivation Index. Log-binomial regression models were used to identify predictors of health insurance status at diagnosis. Cox regression models were used to assess the association between health insurance status at diagnosis and cancer-specific survival. Causal mediation analyses were conducted to investigate whether health insurance status serves as a mediator of the relationship between neighborhood deprivation and survival.

Results

The study included 5782 children with cancer: 2069 in Iowa and 3723 in Louisiana. Children in more deprived neighborhoods, non-White children, and children in Louisiana were more likely to have non-private insurance. Compared with children with private insurance, those with non-private insurance had a 32% higher hazard of cancer death (aHR = 1.32, 95% CI: 1.13–1.55). Insurance status was observed to mediate the association between ADI and cancer-specific survival, mediating 7.33%–14.59% of the estimated association.

Conclusion

While individual-level health insurance status was a mediator of neighborhood-level disparities in pediatric cancer survival, it did not explain a large proportion of the observed disparities. This suggests that structural and systemic factors, beyond just individual insurance coverage, may play a significant role in shaping pediatric cancer outcomes.

Influence of Gut Microbiota on Response to Immune Check Point Inhibitors in MASLD Patients With HCC: Unraveling the Connection

Fri, 27 Mar 2026 04:06:58 -0700

ABSTRACT

Immune checkpoint inhibitors (ICIs) have emerged as a promising treatment for various cancers, including advanced hepatocellular carcinoma (HCC). However, a significant proportion of patients with HCC, particularly those with metabolic dysfunction-associated liver disease (MASLD), exhibit resistance to ICI therapy. Studies have revealed that the presence of specific gut bacteria, such as Akkermansia, Bifidobacterium, and Lachnoclostridium, is associated with improved outcomes with ICI-treated HCC patients. Conversely, the overgrowth of bacteria like Enterobacteriaceae is linked to resistance to therapy. This review investigates the role of gut microbiota in shaping immune checkpoint inhibitor responses in MASLD-related hepatocellular carcinoma, focusing on how dysbiosis may contribute to ICI resistance and exploring microbiome modulation strategies, such as fecal microbiota transplantation and probiotics, aiming to optimize therapeutic outcomes.

Efficacy and Safety of Envafolimab Combined With Capecitabine and Lenvatinib as Postoperative Adjuvant Therapy in Resected Biliary Tract Cancer With High‐Risk Recurrence Factors: A Phase II Single‐Center Prospective Study

Fri, 27 Mar 2026 04:02:15 -0700

A phase II single-center prospective study evaluating envafolimab combined with capecitabine and lenvatinib as postoperative adjuvant therapy in resected biliary tract cancer with high-risk recurrence factors. The regimen demonstrated encouraging efficacy (median DFS 15.6 months; 1-year DFS 68.3%; 1-year OS 91.4%) and manageable safety, with no treatment-related deaths. Elevated CA19-9 was associated with early recurrence.

ABSTRACT

Background

Biliary tract cancer (BTC) is an aggressive malignancy characterized by a high recurrence rate and poor postoperative prognosis, despite advances in adjuvant therapy. This phase II study evaluated the efficacy and safety of a novel adjuvant regimen combining envafolimab, lenvatinib, and capecitabine in patients with BTC at high risk of recurrence following R0 resection.

Methods

This single-center, open-label, single-arm phase II trial enrolled patients with high-risk recurrence factors after curative resection. Patients received envafolimab (400 mg subcutaneously once every 3 weeks), Lenvatinib (8 mg orally once daily), and capecitabine (1000 mg/m² orally twice daily, 2 weeks on/1 week off, continued without cycle limitation). The primary endpoint was disease-free survival (DFS); secondary endpoints included overall survival (OS) and safety.

Results

28 of 30 screened patients were included in the final analysis. The median DFS was 15.63 months, and the 1-year DFS rate was 68.3%. Median OS was not reached but 1-year OS was 91.4%. Treatment-related adverse events (TRAEs) occurred in 17 patients, with grade 3/4 TRAEs observed in eight patients. No treatment-related deaths were reported. Exploratory analysis suggested that baseline CA19-9 levels were significantly associated with early recurrence.

Conclusions

The adjuvant combination of envafolimab, lenvatinib, and capecitabine demonstrates promising efficacy and a manageable safety profile in high-risk BTC patients after R0 resection. However, these findings still require validation in larger, multicenter, randomized controlled trials.

Enhancing Quality of Life in Head and Neck Cancer: A Scoping Review on the Role of Physical Prehabilitation

Fri, 27 Mar 2026 03:41:56 -0700

ABSTRACT

Background/Aim

Head and neck cancer presents a significant challenge for patients. Beyond the direct impact of the disease, chemotherapy and radiotherapy, while essential for cancer control, can further compromise patients' quality of life (QoL) and emotional well-being, while also introducing additional complications. These treatments may exacerbate existing cancer-related symptoms and contribute to malnutrition. This review aimed to identify and evaluate physical prehabilitation interventions implemented before or during radiotherapy/chemotherapy treatments to determine their impact on the QoL of patients with head and neck cancer.

Methods

This scoping review was structured according to the framework proposed by the Joanna Briggs Institute (JBI) and reported following the Preferred Reporting Items for Scoping Reviews (PRISMA-ScR) guidelines.

Results

Eight studies were included, encompassing a total sample of 819 subjects (397 in experimental groups). The interventions identified included exercises and stretching to prevent mobility issues and trismus, home-based training programs with periodic supervision, comprehensive programs with supervised physiotherapy sessions, jaw mobility exercises, dysphagia therapy, oral exercises, and preventive rehabilitation. A positive association was found between prehabilitation interventions and improved QoL in patients. Customizing interventions based on patient characteristics and treatment modalities was shown to enhance the effectiveness of these programs.

Conclusions

Prehabilitation interventions represent a holistic and functional approach to improving patient outcomes and QoL. Further research is needed to refine these approaches and optimize the overall QoL of head and neck cancer survivors.

Standardizing the Clinical Approach to Cancer Therapy‐Related Cardiac Dysfunction: Applying Cardio‐Oncology Guidelines as a Practical Tool for Hematology and Oncology Providers

Fri, 27 Mar 2026 03:25:18 -0700

ABSTRACT

Introduction and Methods

Cancer therapy–related cardiac dysfunction (CTRCD) is a well established and potentially life-threatening complication of contemporary oncologic treatment. Although comprehensive cardio-oncology guidelines have been developed, their integration into routine hematology and oncology practice remains inconsistent. This consensus statement, developed by a multidisciplinary panel of cardio-oncology experts, aims to provide practical, case-based guidance to help oncology providers recognize, assess, and manage CTRCD across a spectrum of malignancies and cardiovascular presentations.

Clinical Scenarios and Discussion

We present representative clinical scenarios that illustrate real-world challenges in cardio-oncology and apply evidence-based recommendations from current guidelines, including those from the European Society of Cardiology (ESC) and the International Cardio-Oncology Society (ICOS)—to support informed decision-making. Key areas of focus include baseline cardiovascular risk stratification prior to initiating potentially cardiotoxic therapies, with an emphasis on biomarker and imaging surveillance strategies tailored to individual risk profiles. Also, this document outlines the application of guideline-directed medical therapy (GDMT) for cancer patients with heart failure.

Conclusion

By offering a structured, user-friendly framework, this document seeks to bridge the implementation gap between oncology and cardiology disciplines. Our goal is to equip oncology providers with accessible tools that facilitate early recognition, consistent surveillance, and timely referral, thereby preserving cancer treatment intensity while minimizing cardiovascular morbidity.

Initial Site of Metastasis Influences Prognosis in Pancreatic Ductal Adenocarcinoma

Thu, 26 Mar 2026 22:21:20 -0700

ABSTRACT

Introduction

Metastatic pancreatic ductal adenocarcinoma (mPDAC) is a highly aggressive malignancy. Prior studies suggest that the initial site of metastasis may impact prognosis. This study investigates whether overall survival in mPDAC patients differs between patients first presenting with lung metastases versus those presenting with liver metastases.

Methods

This retrospective analysis utilized the multi-institutional TriNetX database, identifying patients with histologically diagnosed PDAC who initially presented with either liver or lung metastases. Demographic, histologic, and outcome data were collected and analyzed. Patients were matched 1:1 using a nearest neighbor propensity score (PS) algorithm, and Kaplan–Meier survival analyses were performed. Cox regression was also used to further validate the results of the PS matching.

Results

A total of 6256 patients were identified, including 5390 patients presenting with liver and 866 patients presenting with lung metastases at diagnosis. The mean age was 66.6 ± 10.5, the male-to-female ratio was 54%:46%, the mean carbohydrate-antigen (CA) 19-9 level was 1309 ± 2078 ng/mL, the mean carcinoembryonic-antigen (CEA) level was 117 ± 1044 U/mL. Propensity score matching yielded 848 matched pairs. Median survival from time of metastatic diagnosis was significantly longer for patients with lung metastases compared to liver (377 vs. 195 days, p < 0.0001). Cox regression identified several factors associated with increased risk of death: older age, obesity, malnutrition, and elevated CEA or CA 19-9. Additionally, initial lung metastases were associated with decreased risk of death (HR = 0.61, p < 0.0001).

Conclusion

Initial presentation with lung metastases appears to be associated with improved survival outcomes as compared to initial presentation with liver metastases in patients with mPDAC.

Association Between Nasopharyngeal Carcinoma and Chinese Medicine Constitution: A Meta‐Analysis

Thu, 26 Mar 2026 21:59:36 -0700

ABSTRACT

Objective

To explore the distribution of Chinese medicine constitution (CMC) types across the spectrum of health states related to nasopharyngeal carcinoma (NPC) and provide evidence-based information for the prevention and treatment of NPC at different stages of the disease.

Methods

PubMed, Embase, Web of Science, and three major Chinese databases were searched to retrieve literature reporting the correlation between populations across related health states of NPC and CMC, using the same standardized classification since 2009. Three authors independently screened and evaluated the quality of the methodology. The main outcomes were the single proportion and the odds ratio (OR) of each constitution type across related health states of NPC, and the effect sizes were expressed as proportions or as ORs with 95% confidence intervals (CI). Sensitivity and subgroup analyses were performed to determine the sources of heterogeneity.

Results

Data of 1174 patients from 11 different studies were included in the present study. Qi-deficiency (QD), balanced, and Yang-deficiency constitutions accounted for 25.5% (95% CI: 19.0–32.0, p < 0.01), 16.1% (95% CI: 18.1–26.1), and 15.4% (95% CI: 9.5–21.4), respectively. The distribution across related health states of patients with NPC varied across different stages of the disease. QDC showed a significant association with both Epstein–Barr virus infection and NPC diagnosed status in the included populations compared with that in healthy controls.

Conclusion

QDC is a major factor associated with NPC across different health statuses. However, the cross-sectional nature of the available evidence highlights the need for more high-quality prospective cohort studies to clarify the temporal relationship and causal role of specific constitutions in NPC development.

A Butyrate Metabolism‐Related Gene Signature Predicts Prognosis, Immune Landscape, and Immunotherapy Efficacy in Breast Cancer

Thu, 26 Mar 2026 21:41:34 -0700

ABSTRACT

Emerging evidence highlights the critical role of metabolic pathways in breast cancer (BC) progression. Here, we developed a butyrate metabolism-specific gene (BMRG) signature to predict clinical outcomes and immunotherapy responses in BC, providing a novel pathway-focused prognostic tool. Using data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), we identified 102 butyrate metabolism-related differentially expressed genes (DEGs) through the intersection of DEGs, WGCNA-derived key module genes, and BMRGs. Univariate Cox followed by least absolute shrinkage and selection operator (LASSO) analysis identified nine genes to construct a prognostic signature, which served as an independent prognostic factor. Risk stratification revealed distinct immune microenvironment and mutation landscapes between subgroups, with risk scores strongly correlating with immune checkpoint expression. The signature exhibited robust prognostic performance, with AUC values for 3-, 5-, and 7-year overall survival ranging from 0.65–0.69 in TCGA and 0.57–0.77 in independent GEO cohorts. Protein–protein interaction analysis identified ACSL1 as a key hub gene, and functional validation confirmed that ACSL1 knockdown suppressed BC cell proliferation and migration. Our findings establish this novel nine-gene butyrate metabolism-specific signature as a promising prognostic biomarker and potential therapeutic target for BC, providing a metabolism-focused perspective for personalized BC management.

Umbrella Reviews Conducted in an Oncology Healthcare Context Focusing on Supportive Care, Systems, and Models of Care: A Review of Umbrella Reviews

İrem Koç, John Goodwin, Josephine Hegarty — Wed, 25 Mar 2026 22:09:48 -0700

ABSTRACT

Aims

Healthcare providers need access to evidence-based knowledge to deliver interventions effectively within clinical settings. This paper aims to provide an overview of umbrella reviews (URs) conducted in an oncology healthcare context. In this review, the oncology healthcare context relates to focusing on care delivery systems, supportive care, supportive care needs, and supportive care interventions, systems, and models of care for cancer survivorship care and support.

Methods

This overview followed the Preferred Reporting Items for Overviews of Reviews (PRIOR) statement. The literature search was performed in seven databases including PubMed, CINAHL, APA PsycArticles, APA PsycInfo, SocINDEX with Full Text, Embase, and Cochrane Database from 2012 to 2023. The search terms and eligibility criteria were organized around the PCC framework. The JBI Critical Appraisal Checklist for Systematic Reviews and Research Synthesis was used for quality assessment.

Results

Seventy-six umbrella reviews were included in this review. Only four reviews demonstrated low quality. Tables and bubble maps helped to outline the key findings of included URs. Recommendations to aid future studies and reviews were summarized into five overarching themes.

Conclusions

In conclusion, we outlined the range and gaps in topics covered, as well as the key features of umbrella reviews examining oncological supportive care systems and models of care over the past decade. Future research should address the multidimensional nature and complexity of clinical implementation and methodological concerns; consider underrepresented populations and be more targeted to inform policy development.

Issue Information

Wed, 25 Mar 2026 21:16:10 -0700

Cancer Medicine, Volume 15, Issue 4, April 2026.