This open-label phase III trial assessed a chemotherapy-free regimen for recurrent/metastatic triple-negative breast cancer (TNBC). Patients were 1:1 randomized to benmelstobart plus anlotinib or nab-paclitaxel monotherapy, stratified by prior taxane exposure, liver and brain metastases. Planned enrollment was 322, yet recruitment was prematurely stopped by COVID-19, leaving only 147 randomized participants (75 experimental, 72 control). All efficacy analyses are exploratory and require cautious interpretation. The primary endpoint, IRC-assessed progression-free survival (PFS), was not met. Investigator-assessed median PFS reached 7.85 months for the combination vs. 5.55 months for nab-paclitaxel (HR = 0.70, 95%CI 0.46–1.06, P = 0.1687). Median overall survival (OS) was 35.81 vs. 21.03 months (HR = 0.78, 95%CI 0.49–1.24, P = 0.2625). Grade ≥3 treatment-related adverse events affected 58.7% of combination patients and 36.6% of monotherapy patients. This regimen failed to deliver statistically superior clinical benefits over nab-paclitaxel, only showing a non-significant favorable trend. Further trials are warranted to validate this observation. Trial ID: NCT04405505, registered May 24, 2020 on ClinicalTrials.gov.

6048 Background: Oral squamous cell carcinoma (OSCC) is one of the most common malignant tumors of the head and neck. Stage IVB OSCC had long been considered unresectable with extremely poor prognosis, and mainstream guidelines encourage exploring new therapies via clinical trials. This study aimed to evaluate the efficacy and safety of adebrelimab plus cisplatin/docetaxel as neoadjuvant therapy for stage IVB OSCC (NCT06277791). Methods: IVB OSCC patients aged 18–75 years were enrolled and received 2 cycles of neoadjuvant immunochemotherapy (adebrelimab 1200 mg + cisplatin 75 mg/m²/docetaxel 75 mg/m², q3w). Three weeks after neoadjuvant treatment, patients underwent extended primary tumor resection and radical neck dissection, followed by adjuvant radiotherapy/chemoradiotherapy. The primary endpoint was pathological response rate (pCR+MPR); secondary endpoints included radiographic response, R0 resection rate, and safety. Results: 28 patients were enrolled between June 2023 and January 2026. The mean age was 47.8 years, with a male predominance (25, 89.3%). Primary tumors were mainly located in the buccal mucosa (14, 50.0%) and tongue (10, 35.7%). Smoking, alcohol consumption, and betel nut chewing histories were noted in 75.0%, 42.9%, and 64.3% of patients, respectively. Most had an ECOG performance status of 1 (75.0%). 8 cases (28.6%) were classified as cT4b and 20 cases (71.4%) as cN3b at baseline. Three patients (10.7%) were excluded from efficacy analysis due to insufficient data. In the evaluable population (n=25), no complete response (CR) was observed; 8 (28.6%) achieved partial response (PR), 14 (50.0%) stable disease (SD), and 3 (10.7%) progressive disease (PD), with an overall objective response rate (ORR) of 32.0% (8/25). Subgroup ORRs were 33.3% (2/6) for cT4b and 31.6% (6/19) for cN3b. Pathological assessment was available for 25 patients: based on the combined pathological assessment of the primary tumor and lymph nodes, 15 (60.0%) achieved MPR, 1 (4.0%) pCR, resulting in a 64.0% pathological response rate. For subgroups, the pathological response rate was 50.0% in 6 evaluable cT4b (2 MPR, 1 pCR) and 68.4% in 19 evaluable cN3b (13 MPR, no pCR). The R0 resection rate was 100% among 25 surgical patients. Treatment-related adverse events (TRAEs) were mostly grade 1–2. Grade 3 TRAEs occurred in 2 cases (7.2%), with no grade 4/5 events. At data cutoff (median follow-up: 12.0 months), 3 deaths occurred. The estimated 1-year OS rate was 87.9%, with subgroup rates of 89.1% for cN3b (median follow-up: 12.0 months) and 87.5% for cT4b (median follow-up: 19.4 months). Conclusions: Neoadjuvant adebrelimab combined with chemotherapy achieves a high pathological response rate in stage IVB OSCC, with manageable adverse events and favorable safety. Clinical trial information: NCT06277791 .

SHR-A1811, an antibody‒drug conjugate consisting of the anti-HER2 antibody trastuzumab conjugated via a cleavable linker to a topoisomerase I inhibitor payload, demonstrated substantial antitumor activity in patients with heavily treated HER2-expressing or mutated advanced solid tumors. The main analysis was reported, and this is a long-term follow-up of the HORIZON-X trial (NCT04446260). This global, multicenter, first-in-human, phase 1 trial enrolled patients aged ≥ 18 years with unresectable, advanced, or metastatic HER2-expressing or mutated solid tumors refractory or intolerant to standard therapies across 38 hospitals. SHR-A1811 was administered intravenously at doses ranging from 1.0 to 8.0 mg/kg every three weeks. The primary endpoints included dose-limiting toxicity, safety, and the recommended phase 2 dose. From September 7, 2020, to June 4, 2024, 396 patients with a median of three prior treatment regimens (IQR 2-5) received SHR-A1811. As of March 12, 2025, the median follow-up was 17.1 months for HER2-positive breast cancer, 10.6 months for HER2-low expressing breast cancer, and 4.3 to 8.2 months in non-breast cancers. The safety profile remained consistent with that of previous reports. Grade 3 or higher treatment-related adverse events occurred in 261 patients (65.9%), and any grade interstitial lung disease was observed in 10 patients (2.5%). The median progression-free survival was 25.0 months (95% CI 17.2-33.6) for HER2-positive breast cancer, 11.0 months (95% CI 8.2-13.8) for HER2-low expressing breast cancer, and 3.5 to 17.2 months for non-breast tumors. This final analysis further confirmed the long-term efficacy and favorable safety profile of SHR-A1811 among heavily prior-treated advanced solid tumors, reinforcing its potential as an effective HER2-targeted therapy.

Importance Approximately 70% of patients with breast cancer (BC) have hormone receptor–positive, human epidermal growth factor receptor 2 ( ERBB2 ; formerly HER2 )–negative disease. Objective To evaluate the efficacy and safety of fovinaciclib plus an aromatase inhibitor as first-line treatment for hormone receptor–positive, ERBB2 -negative advanced BC. Design, Setting, and Participants This double-blind, phase 3 randomized clinical trial enrolled patients from March 2, 2022, to June 28, 2023, from 63 centers in China. Eligible patients were adult women with hormone receptor–positive, ERBB2 -negative advanced BC and no history of systemic therapy for advanced disease. The data cutoff date was June 25, 2024. Data were analyzed from September to October 2024. Intervention Patients were randomized (1:1) to receive fovinaciclib, 200 mg (orally once daily on days 1 to 21), or placebo plus letrozole, 2.5 mg, or anastrozole, 1 mg (orally once daily on days 1 to 28), in 28-day cycles. Premenopausal or perimenopausal patients also received goserelin, 3.6 mg (subcutaneously on day 1). Main Outcomes and Measures The primary end point was progression-free survival (PFS) per blinded independent central review (BICR). Secondary end points included other efficacy end points and safety. Exploratory end points included overall survival (OS) and quality of life. Results Of 417 randomized female patients, the median (range) age was 57.0 (32-84) years. A total of 208 were randomized to the fovinaciclib arm and 209 to the placebo arm. At prespecified interim analysis (median [range] follow-up, 16.6 [0.3-27.8] months), a significantly prolonged median PFS was observed with fovinaciclib compared with placebo (not reached vs 20.2 months [95% CI, 16.4 months to not evaluable]; hazard ratio, 0.55; 95% CI, 0.38-0.77; 1-sided P < .001) per BICR assessments. Consistent PFS benefit was observed in most patient subgroups. Fovinaciclib was also favored across secondary efficacy end points. OS data were immature, with only 40 events (9.6%). The most common treatment-emergent adverse events were hematologic toxic effects, none of which led to serious adverse events or study drug discontinuation. Incidence of discontinuation due to treatment-emergent adverse events was only 1.4% in both arms (3 of 208 receiving fovinaciclib and 3 of 209 receiving placebo). Longitudinal changes in global health status, function domains, and symptom domains of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 were similar between the 2 arms. Conclusions and Relevance In this randomized clinical trial, adding fovinaciclib to first-line aromatase inhibitor conferred significant and clinically meaningful PFS benefit and consistent improvements in other efficacy outcomes, along with manageable safety and unaffected quality of life. Trial Registration ClinicalTrials.gov Identifier: NCT05439499

OBJECTIVE:This study aimed to evaluate overall survival (OS), identify independent prognostic factors, and characterize prognostic heterogeneity across clinical subgroups in a large single-center Chinese cohort of patients with oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS:We retrospectively reviewed 2983 primary OSCC patients undergoing radical surgery between June 2012 and December 2023. OS was analyzed using Kaplan-Meier methods and Cox proportional hazards models. Subgroup analyses were performed according to gender, age, and anatomical site. RESULTS:The 1-, 3-, and 5-year OS rates were 92.0%, 79.6%, and 74.4%, respectively. Multivariate analysis identified age, alcohol consumption, time to presentation (TTP), perineural invasion (PNI), histological grade, pathologic tumor stage (pT stage), and pathologic lymph node stage (pN stage) as independent prognostic factors. Among these, pN stage showed the strongest association with survival, with a stepwise increase in risk from N1 (HR 1.60, 95% CI 1.31-1.96) to N2 (HR 2.34, 95% CI 1.97-2.78; both P < 0.001). Although the prognostic determinants varied across subgroups, pN stage remained a consistent independent predictor across nearly all subgroups defined by gender, age, and anatomical site. CONCLUSIONS:In this large Chinese OSCC cohort, pN stage was the most robust and consistent prognostic determinant across clinical subgroups, underscoring its central role in risk stratification and supporting more individualized prognostic assessment.

BACKGROUND:Radioresistance is fundamental to glioma progression and poor prognosis. Understanding its underlying mechanisms and identifying novel therapeutic targets through elucidating key molecules in glioma radiosensitivity pathways are therefore of significant clinical importance. METHODS:Radiosensitivity-related genes were identified based on radiotherapy response, glioma stemness, and prognosis. A predictive signature was constructed using Lasso-Cox regression and validated via clinicopathological, functional enrichment, immune infiltration, and correlation analyses. GPX8 expression and prognostic significance were assessed by tissue microarray. In vitro functional and radiobiological assays, complemented by in vivo subcutaneous xenograft models using BALB/c nude mice (treated with or without radiotherapy), evaluated the role of GPX8 in regulating malignant progression and radiosensitivity in glioma. RESULTS:The radiosensitivity-related signature demonstrated significant potential in predicting glioma malignancy and prognosis, serving as an indicator of the mesenchymal subtype and contributing to the maintenance of an immunosuppressive microenvironment. GPX8 was overexpressed in high-grade gliomas and correlated with recurrence and poor survival. Knockdown of GPX8 suppressed the malignant biological behaviors of glioma cells. Radiation upregulated GPX8 expression while GPX8 knockdown significantly enhanced the cytotoxicity of radiation and induced apoptosis by promoting oxidative stress and DNA damage. Suppression of GPX8 effectively potentiated radiosensitivity in murine xenograft models and reduced intratumoral infiltration of tumor-associated macrophages. CONCLUSIONS:The radiosensitivity-related signature serves as a significant predictor for assessing glioma malignancy and prognosis. GPX8 acts as a key regulator of malignant phenotypes and radiosensitivity in glioma, positioning it as a promising therapeutic target to counteract both malignant progression and radioresistance.

The clinical benefit of extending tumor treating fields (TTFields) beyond concurrent chemoradiotherapy (CRT) for newly diagnosed glioblastoma (ndGBM) is unclear. This multi-institutional retrospective study compared patients who continued TTFields into adjuvant temozolomide (CRT-TT, n = 68) versus those who discontinued after CRT (CRT-T, n = 32). With a median follow-up of 36.9 months, median progression-free survival (mPFS) did not significantly differ between the groups (12.8 vs. 12.5 months; hazard ratio [HR] 0.95, 95% confidence interval [CI] 0.57-1.59; p = 0.853) nor did median overall survival (mOS) (20.6 vs. 16.6 months; HR 0.73, 95% CI 0.43-1.27; p = 0.267). Additionally, continuing TTFields into the adjuvant phase did not increase scalp toxicity. Although a numerically longer OS was seen in the CRT-TT group, the lack of statistical significance may reflect limited power and non-randomized allocation. These findings underscore the need for further investigation.

H3K27-altered diffuse midline glioma (DMG) is a highly malignant pediatric central nervous system (CNS) tumor with an extremely poor prognosis. Extraneural metastases are rare, and systemic dissemination accompanied by pleural effusion is even more uncommon, with limited clinical evidence reported to date. We report an 8-year-old female with brainstem-origin H3K27-altered DMG who achieved 2-year local control of the primary lesion after radical radiotherapy. The lesion first metastasized to the spinal epidural space, followed by widespread systemic dissemination characterized by bilateral pleural effusion and extensive lymphadenopathy. Pathological and genetic testing confirmed the metastatic lesions were consistent with the primary DMG, with H3F3A p.K28M missense mutation identified. This case challenges the conventional understanding of limited metastatic potential of H3K27-altered DMG, suggesting prolonged survival may facilitate systemic spread, with lymphatic drainage as a hypothesized dissemination pathway that lacks direct pathological validation. The unique metastatic pattern provides new insights into the biological behavior of this tumor. This case enriches the clinical spectrum of H3K27-altered DMG, highlighting the necessity of long-term systemic surveillance for long-surviving patients and further investigation of systemic anti-tumor therapies; the hypothesized lymphatic metastatic route requires additional pathological verification in future cohorts.

BACKGROUND:Trastuzumab brengitecan (T-Bren; BL-M07D1) is a HER2-directed antibody-drug conjugate (ADC) comprising a monoclonal antibody, a cathepsin B-cleavable linker, and a potent topoisomerase I inhibitor payload (Ed-04). We aimed to evaluate the safety, tolerability, pharmacokinetics, and preliminary antitumour activity of T-Bren in patients with advanced breast cancer and other solid tumours. METHODS:This phase 1 dose escalation and expansion study enrolled patients with inoperable locally advanced or metastatic breast cancer or other solid tumours pretreated with systemic therapy. Patients received intravenous T-Bren at doses ranging from 1.0 mg/kg on days 1 and 8 every 3 weeks (D1D8 Q3W) (accelerated titration), to 2.6 mg/kg, 3.2 mg/kg, 3.8 mg/kg, 4.4 mg/kg, 5.0 mg/kg, 5.6 mg/kg, 6.2 mg/kg on day 1 every 3 weeks (D1Q3W) (i3+3 design). Primary objectives were to assess dose-limiting toxicity/maximum tolerated dose (DLT/MTD), and establish the recommended phase 2 dose (RP2D). FINDINGS:Overall, 253 patients were treated: DLTs occurred in two patients treated at 6.2 mg/kg Q3W, including grade 4 neutropenia with myelosuppression and grade 3 thrombocytopaenia in one patient, and grade 4 febrile neutropenia in another. In patients with breast cancer, ORR was 81.5% (66/81) in HER2-positive subgroup, 69.5% (57/82) in hormone receptor-positive/HER2-low disease, and 58.3% (14/24) in hormone receptor-negative/HER2-low disease. Median PFS was 18.2 months, 14.0 months, and 7.2 months in the HER2-positive, HR-positive/HER2-negative, and HR-negative/HER2-negative subgroups, respectively. INTERPRETATION:T-Bren demonstrated a manageable safety profile and clinically meaningful antitumour activity across a broad spectrum of HER2 expression in advanced breast cancer. The 4.4 mg/kg every three weeks regimen was established as the RP2D in breast cancer. FUNDING:This study was funded by the sponsor Baili-Bio (Chengdu) Pharmaceutical Co., Ltd.

Nasopharyngeal carcinoma (NPC) is a geographically prevalent malignant mucosal tumor endemic to southern China and Southeast Asia. Radiotherapy constitutes the core curative treatment for NPC, often combined with chemotherapy or targeted therapy in clinical practice. Hearing loss is a common radiotherapy-related complication caused by radiation damage to middle ear structures, inner ear cells and auditory nerves, with a variable incidence affected by treatment protocols and patient characteristics. Such auditory dysfunction negatively impacts patients' cognition, emotion and quality of life. However, systematic summaries of subjective evaluation tools and targeted non-surgical rehabilitation strategies for radiotherapy-induced hearing impairment remain insufficient. Accordingly, this review aims to elaborate on the classification, multidimensional clinical impacts, subjective assessment scales, and non-surgical interventions of radiotherapy-related hearing loss, so as to provide evidence-based references for clinical rehabilitation of NPC survivors.

Glucuronide prodrug strategies may enhance target specificity and reduce the toxicity of PARP inhibitors, but no clinical evaluation has been performed. We evaluated TSL-1502, a novel glucuronide prodrug of a PARP inhibitor, in a randomized, open-label, phase 2 study at 28 sites in China (NCT05420779). Eligible patients were women aged 18-75 years with HER2-negative locally advanced or metastatic breast cancer and germline BRCA mutations. Patients were assigned randomly (2:2:1) to receive TSL-1502 at 350 mg or 500 mg once daily or the investigator's choice of chemotherapy (eribulin, capecitabine, or vinorelbine) in 3-week cycles. Sixty-three patients were enrolled between August 18, 2022, and March 5, 2024. According to the Independent Review Committee assessment, the objective response rates were 36.0% (95% CI, 18.0-57.5) in the 350 mg group, 55.6% (95% CI, 35.3-74.5) in the 500 mg group, and 40.0% (95% CI, 12.2-73.8) in the chemotherapy group. The median progression-free survival times were 5.6 (95% CI, 4.0-8.2), 8.8 (95% CI, 5.7-not assessable [NA]), and 9.2 (95% CI, 1.38-NA) months, respectively, and the overall survival times were 17.4 months (95% CI, 9.1-NA), not reached (95% CI, 16.9-NA), and 19.8 months (95% CI, 9.2-NA), respectively. Grade ≥3 treatment-related adverse events occurred in 60.0%, 59.3%, and 80.0% of patients, with anemia most common in the TSL-1502 group and neutropenia most common with chemotherapy. No treatment-related deaths occurred. TSL-1502 at 500 mg showed promising antitumor activity and a manageable safety profile, supporting further clinical development.

Immunotherapy has revolutionized the treatment of malignant tumors and is now recognized as a first-line option for various cancers. In resectable locally advanced oral squamous cell carcinoma (OSCC), neoadjuvant immunotherapy has been integrated into clinical practice, representing significant progress. While neoadjuvant immunochemotherapy shows promising efficacy in this setting, several critical challenges remain unresolved. These include defining optimal endpoints and response evaluation methods, identifying and managing hyperprogression, determining surgical strategies for patients with significant tumor reduction, assessing the feasibility of de-escalating postoperative adjuvant therapy in those achieving pathological complete response, and managing immune-related adverse events. This consensus addresses these challenges by integrating current evidence with pressing clinical questions and incorporating multidisciplinary expert insights from the OSCC field. The objective is to establish a standardized, unified framework for evaluating and managing these complex issues in resectable locally advanced OSCC.

Background: SHR-A1811, an anti-HER2 ADC comprising trastuzumab, a cleavable linker, and the topoisomerase I inhibitor payload SHR169265, has shown substantial tumor response and a manageable safety profile in heavily treated multiple solid tumors with HER2 expression or mutations (Yao. et al., JCO, 2024). Here we present for the first time the progression-free survival (PFS) analysis results of SHR-A1811 and updated safety results, including an additional 1-year of follow-up and an expanded cohort from 307 to 391 patients. Methods: Patients eligible for this study had HER2-expressing or mutated unresectable, advanced, or metastatic solid tumors and were refractory or intolerant to standard therapies. SHR-A1811 was administered intravenously at doses ranging from 1.0 to 8.0 mg/kg every 3 weeks. Primary endpoints included dose-limiting toxicity, safety, and the recommended phase 2 dose. Results: Between Sep 7, 2020 and Jan 12, 2024, 391 patients received SHR-A1811 treatment, including 136 HER2-positive breast cancers, 110 HER2 low-expressing breast cancers, 42 biliary tract cancers, 39 urothelial carcinomas, 22 gynecological cancers, 14 colorectal cancers (CRC), 13 gastric or gastro-esophageal junction adenocarcinomas (GC/GEJ), 4 non-small cell lung cancers (NSCLC), and 11 other types of solid tumor. These patients had undergone a median of 3 (IQR 2–5) prior treatment regimens for metastatic disease. Of these, 261 (66.8%) had an ECOG performance status of 1, 196 (50.1%) had liver metastasis, and 186 (47.6%) had lung metastasis. As of data cutoff (Feb 29, 2024), the median follow-up for HER2-positive breast cancer, HER2-low breast cancer, and non-breast tumor was 13.4, 9.5, and 6.3 months (mo), respectively. The adverse events remained consistent with previous findings in terms of frequency, severity, and specificity. No new safety signals were identified. Grade ≥3 treatment-related adverse events (TRAEs) were reported in 247 patients (63.2%) and 26 patients (6.6%) discontinued treatment due to TRAEs. Incidence of interstitial lung disease was limited, occurring in only 10 patients (2.6%), predominantly at grade 1–2. Of the patients whose tumor responses were evaluable, the confirmed objective response rate (ORR) was 79.1% (95% CI 71.2–85.6) in HER2-positive breast cancer, 62.0% (95% CI 52.2–71.2) in HER2-low breast cancer, and 40.0% (95% CI 31.5–49.0) in non-breast tumor. Responses were durable, with median duration of response (DoR) of 23.6 mo (95% CI 15.6–NE), 12.2 mo (95% CI 7.3–NE), and 15.2 mo (95% CI 9.9–20.9), respectively. Median PFS was 20.0 mo (95% CI 15.1–NE) in HER2-positive breast cancer, 11.0 mo (95% CI 8.2–13.7) in HER2-low breast cancer, and ranged 3.4–8.5 mo in various non-breast tumor types. In breast cancer patients with liver metastasis, the median DoR and PFS (HER2-positive: not reached for DoR, 20.0 mo for PFS; HER2-low: 10.8 mo for DoR, 10.9 mo for PFS) were consistent with the total breast cancer population. Similarly, for breast cancer patients with visceral metastasis, the median DoR and PFS (HER2-positive: 23.7 mo for DoR, 21.9 mo for PFS; HER2-low: 9.9 mo for DoR, 9.8 mo for PFS) also aligned with the overall breast cancer population. Additionally, patients with HER2-positive non-breast tumors showed a trend of better efficacy compared to the overall non-breast tumor cohort in terms of ORR (45.1%), DoR (median 15.2 mo), and PFS (median 7.9 mo). Conclusions: This updated analysis reaffirms the manageable safety profile and promising efficacy of SHR-A1811 in heavily pretreated multiple solid tumors with HER2 expression or mutations. Pivotal study results are highly expected in HER2-positive breast cancer, HER2-low breast cancer, CRC, GC/GEJ, and NSCLC. Citation Format: Herui Yao, Min Yan, Zhongsheng Tong, Xinhong Wu, Yongmei Yin, Min-Hee Ryu, John J. Park, Tao Dai, Yiming Zhao, Jee Hyun Kim, Shouman Wang, Yahua Zhong, Mark Voskoboynik, Jian Zhang, Andreas Kaubisch, Caigang Liu, Yu Chen, Seock-Ah Im, Lingying Wu, Yingbin Liu, Vinod Ganju, Minal Barve, Hui Li, Guangyu Yao, Lequn Bao, Kaijing Zhao, Yu Shen, Shangyi Rong, Xiaoyu Zhu, Erwei Song. Efficacy and safety of SHR-A1811, an anti-HER2 antibody-drug conjugate (ADC), in 391 heavily pretreated multiple solid tumors with HER2-expression or mutations: a global, multi-center, first-in-human, phase 1 study [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr PS8-08.

1104 Background: Recurrent or metastatic triple-negative breast cancer (TNBC) represents an aggressive malignancy with unfavorable prognoses. Benmelstobart (TQB2450) is a humanized monoclonal antibody targeting PD-L1, and anlotinib (ALTN) is an anti-angiogenic oral multi-target tyrosine kinase inhibitor. Herein, we present the findings of a randomized, open-label, phase 3 study comparing the combination of benmelstobart plus ALTN with nab-paclitaxel as first-line treatments for patients (pts) with recurrent or metastatic TNBC. Methods: In this phase 3 trial, patients with previously untreated stage IV or recurrent/metastatic TNBC were randomly allocated in a 1:1 ratio. One group received 1200 mg of intravenous benmelstobart on day 1, along with 12 mg of oral ALTN from days 1 to 14, following a 3-week cycle. The other group was administered 100 mg/m² of intravenous nab-paclitaxel on days 1, 8, and 15 within a 4-week cycle. Randomization was stratified based on whether patients had received neoadjuvant or adjuvant taxane therapy and the presence or absence of liver or brain metastases at baseline. The primary endpoint was progression-free survival (PFS), evaluated by the blinded independent central review by RECIST version 1.1. Results: The initial plan was to enroll 332 pts in this trial. However, due to the COVID-19 pandemic, the enrollment process was delayed, and recruitment was terminated in January 2023. Eventually, 147 pts were randomized (with a median follow-up of 14 months), among whom 75 were assigned to the benmelstobart plus ALTN group and 72 to the nab-paclitaxel group. In the intention-to-treat analysis, as assessed by the investigators, the median PFS was 7.85 months for the benmelstobart plus ALTN combination, in contrast to 5.55 months for nab-paclitaxel (hazard ratio, 0.70; 95% confidence interval, 0.46 to 1.06; P = 0.1687). The median overall survival was 35.81 months for study group and 21.03 months for control group (hazard ratio, 0.78; 95% confidence interval, 0.49 to 1.24; P = 0.2625). Grade ≥3 drug-related adverse events occurred in 56.5% of the patients in the study group and 36.6% in the control group. The most prevalent grade ≥3 adverse events in the study group were hypertension (28.0%) and hypertriglyceridemia (13.3%). Conclusions: The combination of benmelstobart plus ALNT might extend both progression-free survival and overall survival in the first-line treatment of patients with recurrent or metastatic TNBC. The adverse events were in line with the previously established safety profiles of each individual agent. (Funded by Chia Tai Tianqing Pharmaceutical Group Co., Ltd. ClinicalTrials.gov number, NCT04405505). Clinical trial information: NCT04405505 .

Purpose: Radiation-induced lymphopenia (RIL) correlates with poor prognoses in solid tumors. This study aimed to investigate the post–radiation therapy (RT) longitudinal lymphocyte changes and the impact of different RT techniques on RIL in breast cancer patients. Methods and Materials: We prospectively assessed 607 breast cancer patients who received hypofractionated postmastectomy RT in 8 hospitals. Radiation therapy techniques included integrated photon-based intensity modulated technique (integrated RT) and a combination of photon irradiation of supraclavicular nodes and electron irradiation of the chest wall and/or the internal mammary node (hybrid RT). Peripheral lymphocyte counts (PLC) were determined before RT, weekly during RT, at 1 and 2 weeks, 3 and 6 months post–RT, and then every 6 months. The primary outcome was the nadir PLC during RT, for which associated factors were analyzed. Univariate, multivariable linear regression and propensity score matching analyses were performed to evaluate the effect of different RT techniques on nadir PLC. Results: During RT, 121 (19.9%) patients had grade ≥3 RIL with a nadir PLC of 0.75 ± 0.33 × 109/L. The PLC started to recover at 1 week and reached pre–RT levels 1 year after RT and higher than pre–RT levels 2 years later. Multivariate analysis identified young age, low body mass index, radiation therapy targets involving multiple regions, integrated RT, and low pre–radiation therapy PLC as independent risk factors for nadir PLC (P < .005). The PLC at each time point during and after radiation therapy was lower in patients receiving integrated RT than in those receiving hybrid RT (P < .05). Before and after propensity score matching, integrated RT was significantly associated with lower nadir PLC after adjusting for radiation therapy targets and age (P < .001). Conclusions: Breast cancer patients had prolonged lymphopenia post–RT. Integrated RT increased the risk of RIL and adversely affected recovery. Therefore, an appropriate RT technique should be considered to minimize RIL.

PURPOSE:Esophageal RV25 < 20 % and AV35 < 0.27 mL were reported as dose constraints predictive of grade ≥ 2 radiation esophagitis (RE) for breast cancer in our previous study. This prospective study aimed to validate the effectiveness of esophageal dose constraints and develop RE prediction models. METHODS:We enrolled 465 patients with breast cancer receiving 43.5 Gy in 15 fractions to the chest wall and nodal regions using IMRT/VMAT between January 2022 and February 2024. The esophagus was contoured from the cricoid cartilage level to the aortic arch's lower margin. RE was assessed weekly during radiotherapy and at weeks 1 and 2 and months 3 and 6 post-RT using CTCAE v3.0. Analyzed esophageal dosimetric parameters: total volume, mean/max dose, the relative and absolute volumes receiving at least 5-45 Gy by 5 Gy increments (RV5-RV45 and AV5-AV45). Predictive models incorporating tumor laterality, internal mammary nodal irradiation (IMNI), and RV25 or AV35 thresholds were developed. Discrimination (AUC) and calibration [Hosmer-Lemeshow (H-L) test] were evaluated, and risk stratification was performed using decision tree analysis. RESULTS:The grade 2 RE incidence (23.7 %) was considerably lower than in a previous report (40.9 %), and no grade ≥ 3 RE was observed. Both models performed well (RV25 model: AUC, 0.688, H-L, p = 0.974; AV35 model: AUC, 0.651, H-L, p = 0.776). Risk factors for RE included left-side tumor, IMNI, and RV25 ≥ 20 % or AV35 ≥ 0.27 mL. Patients with no risk factors were classified as low risk, those with one risk factor as intermediate risk, and those with ≥ 2 risk factors as high risk. The grade ≥ 2 RE incidence differed significantly across groups (RV25: 14.8 % vs. 24.7 % vs. 48.3 %; AV35: 14.7 % vs. 23.7 % vs. 45.4 %). CONCLUSION:Clinical validation confirmed the effectiveness of esophageal dose constraints and the predictive accuracy of the RV25 and AV35 models. Avoiding unnecessary IMNI and maintaining RV25 < 20 % and AV35 < 0.27 mL could reduce the risk for RE.

It is uncertain whether the combination of immunotherapy and radiotherapy can provide survival benefits for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). We retrospectively analyzed the impact of radiotherapy on the efficacy of immunotherapy and prognostic analysis in 113 patients with R/M HNSCC in our institution from 2018 to 2022. The Kaplan–Meier method was utilized for survival analysis, and Cox regression analysis was conducted to identify prognostic factors. The median follow-up time was 14.0 months. During immunotherapy, 37 patients received radiotherapy, targeting primary tumors, lymph nodes, metastasis in liver, lung, bone, and other sites. We found that the group receiving immunotherapy combined with radiotherapy had higher objective response rate (67.6

This study aimed to determine dosimetric and clinical predictors of radiation esophagitis (RE) in breast cancer patients undergoing conventional fractionated regional nodal irradiation (RNI). Eligible patients received radiotherapy (RT; 50 Gy in 25 fractions) to the chest wall, supraclavicular/infraclavicular fossa, level II axilla, and/or internal mammary chain. RE was graded weekly during RT and at weeks 1, 2 and months 3, 6 post-RT (CTCAE v3.0). The esophagus was contoured from the lower edge of cricoid cartilage to aortic arch. Esophageal parameters included mean dose (Dmean), maximum dose (Dmax), relative (RV5-RV45) and absolute volumes (AV5-AV45) receiving 5-45 Gy in 5-Gy increments. Univariate and multivariate analyses identified predictors of grade ≥2 RE. Among 541 prospectively enrolled patients (minimum 6 months follow-up), 271 (50.1%) had left-sided breast cancer. Grade 2 RE was 23.7% (128/541), with no grade ≥3 RE. Tumor laterality (p < .001) was the only clinical risk factor. Esophageal Dmean, Dmax, RV20-RV40, and AV20-AV35 were dosimetric parameters of grade ≥2 RE in univariate analysis. Multivariate analysis identified RV30 <9% (13.9% vs. 31.3%) and AV30 <1 mL (15.2% vs. 30.5%) as optimal dosimetric predictors. Therefore, RE is common in patients receiving RNI, with tumor laterality being the clinical risk factor. Limiting upper esophagus RV30 <9% and AV30 <1 mL may reduce RE risk.