Browse Articles

Erratum: All-Oral Combination of Revumenib, Decitabine, and Venetoclax for Relapsed or Refractory AML (SAVE)

Reply to: Prostate-Specific Membrane Antigen Positron Emission Tomography and Radiometabolic Therapies in Metastatic Castration-Resistant Prostate Cancer

Erratum: Risk Prognostication After Hypomethylating Agents Combined With Venetoclax in AML: The PRISM Risk Model

Phase II Randomized Trial of Radium-223 Dichloride and Cabozantinib in Patients With Renal Cell Carcinoma With Bone Metastases: RADICAL (Alliance A031801)

PURPOSE Bone metastases (BM) occur in approximately 30% of patients with metastatic renal cell carcinoma (mRCC) and are associated with poor survival and symptomatic skeletal events (SSEs). Radium-223, an alpha-emitting bone-seeking radioisotope, and cabozantinib, a tyrosine kinase inhibitor, have demonstrated activity in BM. RADICAL (Alliance A031801; ClinicalTrials.gov identifier: NCT04071223 ) evaluated cabozantinib ± radium-223 in mRCC with BM. METHODS This phase II trial enrolled patients with mRCC of any histology with ≥1 BM. Patients were randomly assigned 1:1 to cabozantinib ± radium-223, stratified by osteoclast-targeted therapy (OTT), prior therapy, opioid use, and International mRCC Database Consortium (IMDC) risk. The primary end point was SSE-free survival (SSE-FS). Secondary end points included safety, objective response rate (ORR), progression-free survival, and overall survival (OS). A target of 124 evaluable patients was planned, with a prespecified interim futility analysis at 50% of expected SSE-FS events; the trial would stop if the stratified hazard ratio (sHR) > 1.0. RESULTS The prespecified interim futility analysis was conducted after 90 patients were enrolled and crossed the futility boundary, leading to closure at 98 patients. The final analysis included all 98 patients. Median age was 63 years, 82.7% had clear cell histology, and 79.6% were using an OTT. IMDC risk was favorable (18.4%), intermediate (67.3%), and poor (14.3%). Median follow-up was 13.1 months. Median SSE-FS for cabozantinib with radium-223 versus cabozantinib was 16.7 versus 17.6 months (sHR, 1.46 [90% CI, 0.86 to 2.51]). Median OS was 28.3 versus 19.7 months (sHR, 1.40 [95% CI, 0.70 to 2.79]). ORR was 19.4% versus 25.0% ( P = .78). Grade ≥3 adverse events were similar across arms (69.6% v 75.5%). CONCLUSION Radium-223 did not improve SSE-FS when added to cabozantinib. The combination demonstrated a manageable safety profile.

End of Methotrexate for CNS Prophylaxis in Diffuse Large B-Cell Lymphoma

Moderate Hypofractionation for Regional Node Irradiation Is Safe and Effective

Taking Responsibility

This essay is about how caring for my complicated father with amyotrophic lateral sclerosis (ALS) unexpectedly shaped how I approached my work as a gynecologic oncologist.

High-Dose Methotrexate as CNS Prophylaxis in Ultra High-Risk Large B-Cell Lymphoma: An International Multicenter Analysis

PURPOSE In large B-cell lymphoma (LBCL), use of high-dose methotrexate (HD-MTX) to prevent CNS relapse (so-called CNS prophylaxis) remains controversial. International guidelines continue to recommend HD-MTX in patients deemed ultra high risk (UHR) because of a lack of robust data specific to these subgroups. This study was designed to examine the impact of HD-MTX specifically in UHR patients. METHODS Data from two previous retrospective analyses were combined to produce a cohort of UHR patients (≥1 of the following criteria: CNS international prognostic index score 5-6; testicular, renal/adrenal, or breast involvement; ≥3 extranodal sites), treated with or without HD-MTX. The primary outcome was CNS relapse rate (isolated or concurrent with systemic relapse) measured from diagnosis with additional landmark analysis of all responding patients with no progression event at 6 months. RESULTS Analyses were performed on 1,923 patients meeting UHR criteria. No significant difference in 3-year CNS relapse rate was observed between no HD-MTX (n = 1,051) versus HD-MTX patients (n = 872), including in multivariable analyses adjusting for baseline characteristics (3-year rate, 9.3% v 8.1%; adjusted hazard ratio [HR], 1.13 [95% CI, 0.82 to 1.57]). Analyses restricted to isolated CNS relapse also confirmed no difference (5.9% v 5.7%; adjusted HR, 1.03 [95% CI, 0.69 to 1.53]). In the landmark analysis (no HD-MTX n = 782, HD-MTX n = 773), no difference in 3-year CNS relapse was observed (6.7% v 6.6%, adjusted HR, 0.95 [95% CI, 0.62 to 1.44]). CONCLUSION To our knowledge, this is the largest international comparative data set of patients with LBCL with UHR features showing no significant reduction in CNS relapse with HD-MTX in all UHR or in any individual subgroup. Despite inherent limitations of retrospective analyses, the data strongly support previous studies in suggesting HD-MTX prophylaxis has no meaningful benefit for most patients.

Hypo- Versus Standard Fractionated Locoregional Radiotherapy of Patients With High-Risk Breast Cancer in the Randomized Phase III Trial: The Danish Breast Cancer Group Skagen Trial 1

PURPOSE Adjuvant radiotherapy for node-positive breast cancer (BC) using 50Gy/25fx has been Danish Breast Cancer Group (DBCG) standard. Hypofractionated radiotherapy based on 40Gy/15fx has been increasingly used; however, it is less frequently for locoregional therapy because of concern over more morbidity. DBCG Skagen trial 1 hypothesized that 40Gy/15fx did not cause more lymphedema than 50Gy/25fx 3 years after radiotherapy without compromising the pattern of failure. METHODS Skagen trial 1 is a phase III, noninferiority trial randomly assigning high-risk BC patients with an indication for locoregional radiotherapy to standard 50Gy/25fx versus experimental 40Gy/15fx. The primary end point was arm lymphedema; assuming a 3-year incidence with 50Gy/25fx of 10%, noninferiority was predefined to maximum 5% excess incidence with 40Gy/15fx. Accrual continued until 3-year estimates were reported in 1,012 patients. RESULTS Between 2015 and 2021, 2,963 patients consented from 17 centers; the intention-to-treat cohort comprised 2,908 patients: 1,444 had 50Gy (50%), and 1,464 had 40Gy (50%). The median age was 57 years (range, 23-86). At a median follow-up of 4.1 years (IQR, 3.0-5.0), the 3-year rates of lymphedema were 9.4% (50Gy) versus 8.0% (40Gy), odds ratio 0.84 (95% CI, 0.62 to 1.14), and P = .27, thus within the +5-percentage-point noninferiority margin. The median follow-up for cancer outcomes was 5.25 years (IQR, 4.26 to 6.96). Within 8 years, the hazard ratio for locoregional recurrence was 0.96 (95% CI, 0.62 to 1.51), that for distant recurrence was 1.10 (95% CI, 0.89 to 1.37), that for BC mortality was 1.25 (95% CI, 0.93 to 1.66), and that for all-cause mortality was 1.08 (95% CI, 0.85 to 1.36), thus all with no differences by random assignment. CONCLUSION 40Gy/15fx for locoregional radiotherapy of BC did not result in more lymphedema compared with 50Gy/25fx. There were no differences in locoregional or distant recurrences, breast cancer mortality, nor all-cause mortality between the random assignment arms.

Watch and Wait for Rectal Cancer: A Risky Gamble or a Safe Strategy for Patients With a Near-Complete Response?

Pathologic Complete Response (pCR) Rate and Predictors of Response to Taxane, Trastuzumab, and Pertuzumab in HER2‑Positive Breast Cancer: Secondary Analyses of EA1181/CompassHER2 pCR

PURPOSE EA1181 (ClinicalTrials.gov identifier: NCT04266249 ) is a single-arm trial evaluating neoadjuvant taxane, trastuzumab, and pertuzumab (THP) in patients with clinical stage II/IIIa human epidermal growth factor receptor 2 (HER2)–positive breast cancer. This report focuses on the secondary end points of pathologic complete response (pCR) rates and associated factors. The primary end point—3-year recurrence-free survival among patients achieving a pCR (ypT0/Tis, ypN0)—will be reported when data mature. METHODS Patients received four cycles of trastuzumab and pertuzumab (HP) with either once per week paclitaxel (12 weeks) or docetaxel (every 3 weeks for four cycles), followed by surgery. Clinicopathologic characteristics were assessed in all patients. The HER2DX pCR score was determined using diagnostic biopsy samples in a representative subset. Logistic regression models identified factors associated with pCR. RESULTS A total of 2,175 patients were enrolled (781 HER2+/estrogen receptor‑negative [ER–]; 1,394 HER2+/ER+). Of 2,141 patients who initiated THP, the overall pCR rate was 43.8%: 63.7% in HER2+/ER– and 32.4% in HER2+/ER+ tumors. Higher pCR rates were observed in tumors that were ER-negative or low ER expressing, progesterone receptor-negative or low expressing, HER2 immunohistochemistry (IHC) 3+, and in patients treated with once per week paclitaxel. T3 disease was associated with a lower pCR rate in HER2+/ER– tumors; otherwise, tumor (T) and nodal (N) stage did not significantly affect pCR. Among 569 patients assessed for HER2DX pCR scores, a high score was independently associated with higher pCR rates, after adjustment for clinicopathologic variables. CONCLUSION Neoadjuvant THP achieved pCR in nearly two-thirds of patients with HER2+/ER– and one third with HER2+/ER+ breast cancer. Low hormone receptor expression, HER2 IHC 3+ status, once per week paclitaxel use, and a high HER2DX pCR score were independent predictors of pCR. These findings should help optimize risk stratification and treatment personalization for patients with HER2-positive breast cancer.

Reply to: Adjuvant Carboplatin for Early-Stage, Triple-Negative Breast Cancer: Taxane and Patient Selection

Erratum: High-Dose Methotrexate as CNS Prophylaxis in Ultra High-Risk Large B-Cell Lymphoma: An International Multicenter Analysis

Amivantamab in Recurrent/Metastatic Head and Neck Squamous Cell Cancer After Checkpoint Inhibitor and Chemotherapy: Pivotal Results From the Phase Ib/II OrigAMI-4 Study

Single-agent paclitaxel or cetuximab after immune checkpoint inhibitor (ICI) and chemotherapy demonstrated objective response rates (ORRs) of 21%-24% in recurrent/metastatic (R/M) head/neck squamous cell cancer (HNSCC). Epidermal growth factor receptor (EGFR) and MET are overexpressed in R/M HNSCC. Amivantamab, an EGFR-MET bispecific antibody, may be a rational treatment. Cohort 1 of OrigAMI-4 (ClinicalTrials.gov identifier: NCT06385080 ) evaluated subcutaneous amivantamab administered every 3 weeks in participants with non-human papillomavirus R/M HNSCC after PD-(L)1 inhibitor and platinum-based chemotherapy. Prior anti-EGFR therapy and p16-positive oropharyngeal cancer were exclusionary. The primary end point was RECIST v1.1 ORR. Secondary end points included duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. In 102 participants, blinded independent central review‑assessed ORR was 42% (95% CI, 32 to 52); the complete response rate was 15%. Median DoR was not reached (NR; 95% CI, 6.9 to NR); 56% of responses lasted ≥6 months. Investigator-assessed ORR was 47% (95% CI, 37 to 57). At a median follow-up of 11.8 months (range, 1.1-21.9), median PFS and OS were 6.8 months (95% CI, 5.2 to 8.3) and 12.5 months (95% CI, 10.2 to 16.8), respectively. Adverse events were consistent with previous experience with no new safety signals. Treatment-related discontinuations were low (8%). Amivantamab demonstrated greater antitumor activity in participants previously exposed to ICI and chemotherapy than has been reported for paclitaxel or cetuximab.

Adjuvant Chemotherapy ± Chemoradiotherapy for Adenocarcinoma of the Pancreatic Head: Results of the Radiotherapy Random Assignment of NRG Oncology/RTOG 0848

PURPOSE To assess whether adding fluoropyrimidine sensitized radiotherapy (CXRT) to adjuvant chemotherapy improves overall survival (OS) after curative intent resection of the pancreatic head. METHODS This was a multicenter, randomized phase III, two step trial. Step 1: gemcitabine versus gemcitabine + erlotinib (previously reported). Step 2: random assignment to sixth chemotherapy cycle ± CXRT after five cycles of step 1 chemotherapy without progression. Outcomes of step 2 random assignment are reported here. Assuming 17 months median OS (chemotherapy alone), the sample size was 354 patients (hazard ratio [HR], 0.76, 80% power, one-sided α = .05, 316 OS events). OS/disease-free survival (DFS) were estimated by Kaplan-Meier and arms compared using the log-rank test. RESULTS A total of 354 patients (median age 63, 55% male, 56% performance status, 1) were randomly assigned to chemotherapy (174) or chemotherapy + CXRT (180). Univariable median and 5-year OS (90% CIs) were 2.6 years (2.1-3.1) and 23.1% (17.7-28.6) for chemotherapy alone, and 2.3 years (2.0-2.6) and 27.9% (22.2-33.6) for chemotherapy + CXRT. The OS primary end point was not met (HR, 0.96 [90% CI, 0.79 to 1.18]; one-sided P = .38, two-sided P = .77). Chemotherapy + CXRT was associated with a trend for improved DFS (univariably; HR, 0.82 [95% CI, 0.65 to 1.03]; P = .089), without increase in grade 4/5 toxicities. However, grade 3 toxicity increased (38% v 19%, P < .001). Significantly, treatment by nodal status interactions showed that CXRT improved OS ( P = .0063) and DFS ( P = .014) in node-negative patients. CONCLUSION Overall, the addition of adjuvant CXRT to adjuvant gemcitabine did not statistically significantly improve OS, DFS, or increase grade 4/5 toxicity. For node-negative patients, CXRT improved OS and DFS. These results, if confirmed in studies with current or future systemic therapies, would support the use of adjuvant/neoadjuvant CXRT for node-negative patients.

Virtual Sustained Tobacco Treatment for Patients With Cancer: A Randomized Controlled Trial (ECOG-ACRIN: EAQ171CD) Within the National Cancer Institute Community Oncology Research Program

PURPOSE Persistent smoking among patients diagnosed with cancer is associated with adverse clinical outcomes, yet tobacco treatment has not been integrated into community oncology settings. We conducted a trial of a virtual sustained tobacco treatment intervention across community oncology settings nationwide. METHODS This randomized controlled trial compared the effectiveness of sustained telehealth counseling plus medication (virtual sustained treatment [VST]) to referral to the National Cancer Institute (NCI) quitline (enhanced usual care [EUC]) in assisting patients recently diagnosed with cancer to quit smoking. The VST group received up to 11 synchronous telehealth sessions (four weekly, four biweekly, three monthly) of motivational counseling and up to 12 weeks of free nicotine replacement therapy (NRT). RESULTS From August 2019 to December 2022, 306 English- and Spanish-speaking patients were randomly assigned from 37 NCI Community Oncology Research Program community sites. Participants were 70.9% female; 86.3% was White; the median age was 57 years; and 45.4% had non–smoking-related tumors. A total of 221 of 302 (73.2%) smoked within 30 minutes of waking. Six-month, 7-day point abstinence rates were 28.4% (42 of 148) in the VST group versus 14.7% (21 of 143) in the EUC group; there were no significant treatment moderators. A total of 80.8% (126 of 156) of VST participants engaged in counseling, and 85.7% (108 of 126) were dispensed NRT. Participants who completed >8 sessions versus <5 sessions were more likely to quit; P = .005. VST participants were almost four times more likely to report guideline-concordant smoking cessation medication use. Continuous abstinence and significant reduction rates at 6 months were higher in the VST group. The incremental cost per quit was $7,724 in US dollars. CONCLUSION Among recently diagnosed patients, sustained remotely delivered telehealth counseling and free NRT were well utilized and nearly doubled 6-month quit rates compared with EUC. Findings support the benefit of adopting sustained tobacco treatment within community oncology care settings nationwide.

Review of Inorganic Separator Engineering for Next‐Generation Lithium–Sulfur Batteries: Compromise or Cornerstone?

ABSTRACT Lithium–sulfur (Li–S) batteries are promising next‐generation energy‐storage systems, but their practical application remains limited by polysulfide shuttling, sluggish redox kinetics, and interfacial instability. Separator engineering offers an effective route to regulate sulfur chemistry. This review summarizes metal compound‐based separators as active interfacial architectures that promote polysulfide adsorption and catalytic conversion while regulating ion and electron transport. To evaluate diverse separator systems, we propose a Practical Relevance Index (PRI)‐guided framework that integrates intrinsic electrochemical improvements with system‐level constraints. A localized figure of merit is further introduced to interpret performance trends without direct cross‐study ranking. Recent advances in metal oxides, sulfides, nitrides, carbides, and MXene‐based separators are discussed, with emphasis on heterostructures, defect engineering, electronic‐structure regulation, and atomic‐scale design. Particular attention is given to constraint‐aware strategies that connect interfacial chemistry with practical energy density. Finally, major challenges and future directions are outlined, including reaction‐pathway regulation, operando characterization, system integration, and scalable manufacturing. This review provides a unified framework for designing practical, high‐energy‐density Li–S batteries.

Vacuum‐Based Monolithically In Situ Integration of Quantum‐Confined CsPbBr ₃ Nanocrystals for Spectrally Stable Blue Electroluminescence

ABSTRACT Spectrally stable blue emission represents one of the most critical components of full‐color perovskite displays, which are highly attractive for display technologies. However, vapor‐deposited blue perovskite light‐emitting diodes have so far relied predominantly on Br/Cl mixed‐halide bandgap engineering, which is prone to halide migration and phase segregation under operation and therefore suffers from spectral instability. Here, we report spectrally stable vapor‐deposited, pure‐bromide blue perovskite light‐emitting diodes with spectrally stable emission achieved via a ligand‐buffered delayed nucleation (LBDN) strategy. In this method, p‐Br‐MBABr is co‐deposited as a kinetic buffer to create a ligand‐coordinated precursor state that suppresses immediate crystallization, delays nucleation, and confines subsequent crystal growth. As a result, we obtain quantum‐confined CsPbBr 3 nanocrystal films with tunable blue emission. Fully vapor‐deposited PeLEDs based on these films deliver spectrally stable pure‐blue electroluminescence. These results establish kinetic buffering as an effective route to quantum‐confined perovskites under vapor deposition and spectrally stable blue emitters for monolithically integrated full‐color perovskite displays.

Ultra‐broadband Epsilon‐Near‐Zero Ultrathin Metafilms Assembled by 2D Nanosheets Overcoming Size Limitation in Metamaterials

ABSTRACT Broadband epsilon‐near‐zero (ENZ) materials are crucial for 6G (sixth generation mobile networks) signal stability, biochemical sensor accuracy, and intelligent weapon systems. Here, the ultrathin ( d ∼10 µm) 2D metafilms achieving low‐frequency ultra‐broadband ENZ (10 kHz–1 MHz, d / λ ∼10 −10 ) are constructed via the self‐assembly of nanosheets (MXene and graphene oxide) and interface engineering. High‐resistance interfaces and wrinkles can block free carriers, suppressing long‐range plasma and Drude‐type negative dielectric response, while these carriers tend to accumulate locally at the interfaces and enhance Debye‐type positive dielectric response. These two pathways achieve the ultra‐broadband ENZ behavior via the synergistic cancellation effect between these two responses with comparable intensity and dispersion characteristics. The ENZ (|ε′|<1) with a 100‐fold ultrabroad bandwidth (10 kHz–1 MHz) is obtained, 10 kHz of ENZ also updates the low‐frequency limit of ENZ in materials. Besides, the thickness of 10 µm is achieved in metafilms, a smallest d / λ value (∼10 −10 ), overcoming the size limitation of ENZ media. The effectiveness of the ultra‐broadband ENZ is verified in electromagnetic tunneling devices, where metafilms can replace complex artificial arrays. This work establishes a new material‐genesis strategy for ultra‐broadband ENZ rather than artificial metamaterial arrays, easily applicable across the entire electromagnetic spectra.

Oxygen‐Vacancy Engineering of Na ₄ Fe ₃ (PO ₄ ) ₂ P ₂ O ₇ Enables Fast and Wide‐Temperature Sodium Storage

ABSTRACT The polyanionic cathode Na 4 Fe 3 (PO 4 ) 2 P 2 O 7 (NFPP) is regarded as a promising cathode for sodium‐ion batteries owing to its low cost, intrinsic safety, and robust framework stability. However, the strongly localized electronic structure and sluggish Na + transport kinetics impose coupled limitations on its rate capability and stability. Herein, we demonstrate a defect‐engineering strategy to activate coupled electronic‐ionic transport through the rational introduction of oxygen vacancies into NFPP. Combined experimental investigations and density functional theory calculations reveal that oxygen vacancies act as dual‐functional kinetic regulators by simultaneously reconstructing the local Fe–O electronic environment and facilitating Na + migration. The defect‐induced electronic redistribution narrows the bandgap and accelerates electron transport (over 7 times), while expanded Na + diffusion pathways and reduced migration energy barriers enable rapid ion diffusion (over 6 times). Consequently, the oxygen vacancy‐enriched NFPP cathode delivers exceptional cycling stability with 90.46% capacity retention after 7000 cycles at an ultra‐high rate of 20 C. This work establishes oxygen‐vacancy engineering as an effective strategy for coupled transport regulation in polyanionic cathodes and provides fundamental insights into defect‐mediated kinetic enhancement for advanced sodium‐ion batteries.