Research Appraisals
Evidence-based critical appraisals of the latest medical research, systematically evaluated using Oxford CEBM methodology.
Showing 8 appraisals
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
HER2CLIMB-05: A Phase III Study of Tucatinib Versus Placebo in Combination With Trastuzumab and Pertuzumab as First-Line Maintenance Therapy for HER2+ Metastatic Breast Cancer
PURPOSE: The HER2CLIMB-05 study (ClinicalTrials.gov identifier: NCT05132582) is investigating the efficacy and safety of adding tucatinib to trastuzumab and pertuzumab as first-line (1L) maintenance therapy in patients with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC). METHODS: Patients with centrally confirmed HER2+ MBC without evidence of progression post induction therapy and no or asymptomatic brain metastases (BM) were enrolled. Patients were randomly assigned 1:1 to tucatinib (300 mg) or placebo twice a day combined with trastuzumab/pertuzumab. The primary end point is investigator-assessed progression-free survival (PFS); secondary end points include overall survival (OS), PFS per blinded independent central review, CNS-PFS, and safety. RESULTS: Between March 2022 and July 2024, 654 patients were randomly assigned to tucatinib (n = 326) and placebo (n = 328) arms. All patients were female (median age, 54 years), 69.3% had de novo MBC, 52.6% were hormone receptor-positive, and 12.4% had presence/history of baseline BM. In this primary analysis, PFS was statistically significantly improved with addition of tucatinib versus placebo (hazard ratio, 0.641 [95% CI, 0.514 to 0.799]; P < .0001; median PFS: 24.9 v 16.3 months); a PFS benefit was seen regardless of the presence/absence of BM or hormone receptor status. OS data remain immature. The most common treatment-emergent adverse events (TEAEs) in the tucatinib arm were diarrhea (72.7%), nausea (33.1%), and elevated liver enzymes (ALT: 28.2%; AST: 25.8%), of which 6.1%, 0.9%, 13.5%, and 7.1%, respectively, were grade ≥3. In the tucatinib arm, 13.5% discontinued tucatinib because of TEAEs. CONCLUSION: Tucatinib addition to trastuzumab and pertuzumab demonstrated improvement in PFS with no new safety signals identified and may be an option for 1L maintenance therapy in patients with HER2+ MBC.
12 June 2026
Read appraisal →Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer
Effectiveness of eHealth interventions in long-term follow-up care for breast and gynecological cancer survivors: a systematic review
PURPOSE: As survival rates for breast and gynecological cancers improve, many survivors experience persistent long-term challenges, including fatigue, psychological distress, and reduced health-related quality of life (HRQoL). eHealth interventions may offer a scalable and accessible approach to support survivorship care. This systematic review aimed to evaluate the effectiveness of eHealth interventions in long-term follow-up care for breast and gynecological cancer survivors. METHODS: A systematic literature search was conducted across six databases (PubMed, PsycINFO, Web of Science, Cochrane Library, MedRxiv, and PsyArXiv) for studies published between January 2010 and February 2026. Eligible studies included adult breast or gynecological cancer survivors and evaluated eHealth interventions in follow-up care compared with usual care. Outcomes included outcomes such as burden of treatment, HRQoL, self-management, hospital readmissions, complications, infections, fatigue, or malnutrition. Data were extracted, synthesized narratively, and methodological quality was assessed using established risk-of-bias tools. RESULTS: A total of 41 studies were included, predominantly involving breast cancer survivors, with very limited representation of gynecological cancer populations. Overall, methodological quality ranged from low to moderate, with higher risk of bias observed in nonrandomized studies. eHealth interventions were associated with small to moderate improvements in fatigue, anxiety, depression, HRQoL, and treatment adherence, particularly among breast cancer survivors. However, effect sizes were generally smaller in studies with lower risk of bias. Evidence for gynecological cancer survivors was scarce and inconclusive, with only one study exclusively focusing on this population. Long-term outcomes were rarely assessed, and no studies evaluated the defined outcomes infections, malnutrition and unplanned hospital admissions. CONCLUSIONS: eHealth interventions show potential to support long-term survivorship care, particularly in improving psychological outcomes and quality of life among breast cancer survivors. However, the overall evidence base is limited by methodological heterogeneity, short follow-up periods, and the underrepresentation of gynecological cancer populations. Further high-quality, long-term, and cancer-specific research is needed to better establish the effectiveness and generalizability of these interventions in survivorship care. IMPLICATIONS FOR CANCER SURVIVORS: As survivorship care needs continue to increase, eHealth interventions may contribute to more accessible, scalable, and patient-centered models of follow-up care. However, their long-term effectiveness and applicability across diverse cancer populations remain unclear. More rigorous, long-term, and cancer-specific research is required to better define their role in survivorship care.
27 May 2026
Read appraisal →PloS one
An exploratory dosimetric and treatment-time analysis of tangent-arc and continuous semi-arc VMAT in deep inspiration breath-hold radiotherapy for stage I left-sided breast cancer
BACKGROUND: The use of the deep inspiration breath-hold (DIBH) technique reduces cardiac and lung radiation exposure during left breast cancer radiotherapy. However, the optimal beam delivery technique and the effects of patient adaptation during DIBH remain incompletely understood. OBJECTIVE: In this study, the dosimetric differences between continuous semi-arc and tangent-arc plans in stage I left-sided breast cancer patients using DIBH were compared, and the treatment session duration was descriptively analyzed to characterize treatment-time trends during routine DIBH delivery. METHODS: Twenty patients treated at our hospital from 01/05/2022-31/05/2023 were retrospectively selected from the institutional database for exploratory dosimetric analysis. Two radiotherapy plans were created on the basis of each patient's computed tomography (CT) images. Dosimetric parameters for the planning target volume (PTV) and organs at risk (OARs), and beam-on and total treatment times, were compared. RESULTS: The conformity index (CI) for the PTV was significantly better with the continuous semi-arc plan (P < 0.05), whereas the other PTV parameters did not significantly differ between the plans (P > 0.05). The doses and beam-on time for all OARs (except the left ventricle) were significantly lower for the tangent-arc plan (P < 0.05). Treatment time tended to stabilize across fractions, with a significant difference between the 15th and 16th sessions (P < 0.05). CONCLUSION: With the tangent-arc plan, the beam-on time and radiation exposure to OARs were observed to be lower, while adequate PTV coverage was maintained in patients with stage I left-sided breast cancer using DIBH. Treatment times tended to stabilize with increasing treatment fractions. This observation suggests gradual patient adaptation during routine DIBH rather than a predefined training effect. Given the exploratory nature of these findings and the limited sample size from a single institution, these findings should be interpreted with caution and warrant further investigation in larger, multicenter studies.
11 May 2026
Read appraisal →The British journal of radiology
Automatic segmentation of clinical target volume for radiation therapy in breast-conserving patients and exploration of clinical factors influential to its performance
OBJECTIVES: To develop and validate a deep learning model for whole breast clinical target volume (CTV) contouring and evaluate clinical features affecting its performance. METHODS: Five datasets with 857 patients from a single center were used. Dataset 1 (n = 300) trained and tested the model. Dataset 2 (n = 10) evaluated contouring time and dosimetric parameters. Datasets 3 (n = 20) and 4 (n = 10) were for clinical evaluation. Dataset 5 (n = 517) identified clinical factors influencing auto-contouring accuracy. Model performance was assessed using Dice Similarity Coefficient (DSC) and 95th percentile Hausdorff Distance (HD95). RESULTS: The median DSC and HD95 for left- and right-sided models in Dataset 1 were 0.941, 1.75 mm and 0.937, 2.47 mm, respectively. In Dataset 2, both auto-contouring and auto-contouring with manual corrections were significantly faster than manual contouring (P = .005 for both), while still achieving clinically acceptable dosimetric results. In Dataset 3, two physicians rated automatic and manual contours as equivalent (P = .214, P = .075), while the other rated auto-contouring higher (P < .001). In Dataset 4, the auto-contouring model outperformed 1/5 physicians by DSC (P = .009) and 3/5 by HD95 (P = .015, P = .007, P = .017). In Dataset 5, peripheral tumor-bed and low-density breast tissue were associated with lower DSC (P < .001 for both) and higher HD95 (P < .001 for both). Cases without unfavorable factors performed better than those with (P < .001 for both). CONCLUSIONS: The proposed model demonstrated acceptable accuracy, consistency, and efficiency in breast CTV contouring. Peripheral tumor-bed and low-density breast tissue reduced auto-contouring performance. ADVANCES IN KNOWLEDGE: The characteristics of challenging cases in whole breast CTV auto-contouring should be identified.
5 May 2026
Read appraisal →Radiology. Artificial intelligence
Radiopathomic Graph Deep Learning for Multiscale Spatial-Contextual Modeling of Intratumoral Heterogeneity to Predict Breast Cancer Response to Neoadjuvant Therapy
Purpose To develop an explainable radiopathomic graph deep learning (RPGDL) system for multiscale spatial-contextual modeling of intratumoral heterogeneity and evaluate its performance for the prediction of pathologic complete response (pCR) to neoadjuvant therapy in breast cancer. Materials and Methods The RPGDL system was developed from dual-center retrospective analysis of patients with biopsy-proven invasive breast cancer (May 2018-August 2024). For each tumor, individual radiomic and pathomic graphs were generated from pretherapeutic MRI and hematoxylin-eosin-stained biopsy slide images, respectively. These graphs were then processed by three distinct graph neural networks (GNNs): radiomic, pathomic, and radiopathomic. GNN performance was assessed with the area under the receiver operating characteristic curve (AUC), net reclassification index (NRI), and integrated discrimination improvement (IDI). A multifaceted approach was used to explain the GNNs' predictions. Results The training set included 582 (mean age, 52 years ± 9 [SD]) patients and the external test set 468 (50 years ± 10) patients from centers 1 and 2, respectively. The radiomic GNN achieved AUCs of 0.89 (95% CI: 0.85, 0.93) in the training set and 0.84 (95% CI: 0.80, 0.89) in the external test set; the pathomic GNN achieved AUCs of 0.87 (95% CI: 0.83, 0.91) in the training set and 0.83 (95% CI: 0.78, 0.88) in the external test set, with no significant difference between them (P > .05). The radiopathomic GNN outperformed both single-modality GNNs (training set: AUC, 0.95 [95% CI: 0.92, 0.98]; external test set: AUC, 0.91 [95% CI: 0.87, 0.94]; P < .05; NRI and IDI confirmed). Pathomic graphs dominated probability increases for pCR predictions, while radiomic graphs drove probability decreases for non-pCR predictions. Multifaceted analyses verified GNNs' explainability. Conclusion The developed RPGDL system enabled multiscale spatial-contextual intratumoral heterogeneity modeling for high-performance, explainable prediction of pCR to neoadjuvant therapy in breast cancer. Keywords: Dynamic Contrast-enhanced MRI, Breast, Tumor Response, Radiology-Pathology Integration, Prognosis, Principal Component Analysis, Perception, Supervised Learning, Reconstruction Algorithm Supplemental material is available for this article. © RSNA, 2026.
4 May 2026
Read appraisal →Journal of clinical oncology : official journal of the American Society of Clinical Oncology
VIKTORIA-1 Trial of Gedatolisib Plus Fulvestrant With or Without Palbociclib in Hormone Receptor-Positive/HER2-/PIK3CA Wild-Type Advanced Breast Cancer
PURPOSE: Gedatolisib potently targets all four class I PI3K isoforms and mTORC1 and mTORC2 to comprehensively block the PI3K/AKT/mTOR pathway and has shown compelling activity in early clinical trials with palbociclib and fulvestrant. METHODS: This phase III randomized trial (VIKTORIA-1; ClinicalTrials.gov identifier: NCT05501886) evaluated the efficacy of gedatolisib-based therapy, comparing gedatolisib, palbociclib, and fulvestrant (gedatolisib triplet) and gedatolisib plus fulvestrant (gedatolisib doublet) with fulvestrant monotherapy in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HER2-), PIK3CA wild-type (WT) advanced breast cancer. Eligible patients had disease progression during or after CDK4/6 inhibitor and aromatase inhibitor treatment. Comparison of progression-free survival as assessed by blinded independent central review for gedatolisib triplet versus fulvestrant and gedatolisib doublet versus fulvestrant was the primary objective. RESULTS: A total of 392 patients were randomly assigned 1:1:1. The median study follow-up was 10.1 months. The median progression-free survival was 9.3 months in the gedatolisib-triplet group, 2.0 months in the fulvestrant group (hazard ratio [HR] for progression or death, 0.24 [95% CI, 0.17 to 0.35]; P < .001), and 7.4 months in the gedatolisib-doublet group (HR, 0.33 [95% CI, 0.24 to 0.48]; P < .001 v fulvestrant). Grade ≥3 treatment-related adverse events (TRAEs) reported in the gedatolisib-triplet and gedatolisib-doublet groups, respectively, included neutropenia (62.3%, 0.8%), stomatitis (19.2%, 12.3%), rash (4.6%, 5.4%), hyperglycemia (2.3%, 2.3%), and diarrhea (1.5%, 0.8%). Study treatment discontinuation because of TRAEs was reported in 2.3% (triplet) and 3.1% (doublet) of patients. CONCLUSION: The addition of gedatolisib to fulvestrant, with or without palbociclib, significantly reduced the risk of disease progression or death in patients with hormone receptor-positive/HER2-, PIK3CA WT advanced breast cancer.
21 Apr 2026
Read appraisal →Signal transduction and targeted therapy
HDAC inhibitor tucidinostat and metronomic capecitabine plus endocrine therapy for patients with HR-positive HER2-negative advanced breast cancer after CDK4/6 inhibitors treatment: clinical findings and exploratory circulating tumor cell and ctDNA biomarker analyses of a multicenter, phase 2 study (SYSUCC-020 trial)
Treatment options for patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC) that progresses after CDK4/6 inhibitor (CDK4/6i) continue to evolve, and no single regimen has been established as the preferred standard of care. We conducted a phase 2 trial (SYSUCC-020, NCT05411380) to investigate the efficacy and safety of a novel combination of tucidinostat and metronomic capecitabine (mCAP) with endocrine therapy (ET) in patients following progression on CDK4/6i. This trial adopted a Simon two-stage design: eligible patients received tucidinostat plus metronomic capecitabine together with either an aromatase inhibitor (Cohort 1) or fulvestrant (Cohort 2), selected according to prior ET. Seventy-two female patients were screened and sixty-six patients were included in the efficacy and safety analyses. The median follow-up was 13.88 months (Interquartile range, 8.67-20.67) and the objective response rate was 25.8%, with 17 partial responses. The median progression-free survival (PFS) was 5.39 months (95% CI, 4.07-7.69), namely 6.93 months (95% CI, 4.76-12.22) in Cohort 1 and 3.98 months (95% CI, 2.79-7.59) in Cohort 2. Most patients (93.9%) experienced at least one adverse event. In addition, exploratory analyses of biomarkers indicated that the baseline TP53 mutation status (Wild type vs. mutated, 7.64 months vs. 3.55 months) and circulating tumor cell (CTC) status (CTC-negative vs. CTC-positive, 7.59 months vs. 3.78 months) were associated with the median PFS. Our study demonstrated that tucidinostat combined with mCAP and ET is efficacious and well-tolerated in patients with HR-positive HER2-negative ABC previously treated with CDK4/6i.
17 Apr 2026
Read appraisal →Cancer
A phase 1 study of ASTX727 plus talazoparib in patients with triple-negative or hormone resistant/HER2-negative metastatic breast cancer
BACKGROUND: Poly(adenosine diphosphate ribose) polymerase (PARP) is recruited to DNA damage sites along with epigenetic factors such as DNA methyltransferase 1 (DNMT1). Inhibitors of DNMT modulate reactive oxygen species (ROS)-cyclic adenosine monophosphate (cAMP)/Protein Kinase A signaling and induce a "BRCAness phenotype" that further sensitizes cells to PARPi. In preclinical studies, combined DNMTi + PARPi therapy was effective in both triple-negative (TNBC) and hormone resistant (HRBC) models with intact BRCA. METHODS: The authors conducted a phase 1 study combining the oral DNMTi ASTX727 with the PARPi talazoparib in patients with previously treated TNBC or HRBC. Patients with deleterious mutations of BRCA were excluded. A classical 3+3 design guided dose escalation/de-escalation, and 28 days constituted each cycle. Serial peripheral blood mononuclear cells (PBMCs) were analyzed for changes in methylation using the Infinium Methylation EPIC BeadChip and LINE1 sequencing. RESULTS: Thirty-four evaluable patients were enrolled and treated in eight dose cohorts. Myelosuppression was common with grade >3 neutropenia in 42% and grade 3 anemia and thrombocytopenia in 13%. Dose-limiting toxicity was limited to neutropenia. Efficacy was assessed in 29 patients. There were no objective responses, six patients had stable disease persisting for >4 months in three patients. LINE1 demethylation ranged from ∼2%-10% and immune-specific CpGs (methylation in immune cells) changed 1%-5% at day 15. Methylation changes were not dose-dependent. CONCLUSIONS: ASTX727 plus talazoparib produces significant myelosuppression without other adverse events. Modest methylation changes in PBMCs were detected. There were no objective responses, but some heavily pretreated patients had stable disease for >4 months despite the attenuated doses.
15 Apr 2026
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