TPS6125 Background: Nasopharyngeal carcinoma (NPC) is a prevalent malignancy in Southeast Asia and Southern China. Around 10% of pts have distant metastasis at initial diagnosis, and ~30% of those initially without metastasis will develop distant metastasis after radical treatment. These recurrent/metastatic (R/M) NPC pts have poor prognosis with a 5-year survival rate of only 20–30%. The RATIONALE-309 study established tislelizumab plus GP as a standard first-line therapy for R/M NPC, but most pts still experience disease progression in 2 years. Furthermore, in real-world clinical practice, a lot of pts are either platinum-intolerant or platinum-refractory recurrent, underscoring the urgent need for novel treatments. Recent studies suggest that first-line treatment regimens incorporating capecitabine may provide longer progression-free survival (PFS) compared to the GP regimen with a more favorable safety profile. Additionally, a retrospective study demonstrated that tislelizumab plus GX achieved notable tumor responses and PFS benefits in R/M NPC pts who have relapsed immunotherapy. Methods: This is a prospective, multicenter, randomized, controlled Phase III trial evaluating the efficacy and safety of tislelizumab + GX vs. tislelizumab + GP as first-line therapy in R/M NPC. 266 pts will be randomly assigned to the experimental or the control group. The experimental group will receive tislelizumab plus GX (gemcitabine 1g/m² D1,8 + capecitabine 1000 mg/m² BID D1-14) for 4–6 cycles, followed by tislelizumab plus capecitabine maintenance. The control group will receive tislelizumab plus GP (gemcitabine 1 g/m² D1,8 + cisplatin 80mg/m² D1) for 4–6 cycles, followed by tislelizumab monotherapy. Treatment will continue until disease progression or intolerable toxicity. The primary endpoint is PFS. Secondary endpoints include objective response rate, duration of response, overall survival, etc. Adverse events will be monitored and graded according to NCI CTCAE v5.0. Patient enrollment began in December 2023 across 10 centers in China, with 168 pts enrolled by December 2025. Clinical trial information: NCT06177301 .

Purpose. To investigate how annotation consistency influences deep learning-based auto-contouring performance for organs-at-risk (OARs) in nasopharyngeal cancer radiotherapy.Methods. We evaluated CT scans from 1,301 nasopharyngeal carcinoma patients: 65 contoured by Physician A, 76 by Physician B, and 1,160 by heterogeneous multi-physician teams. Three cohorts (50 samples each for Physicians A/B; 1,000 for multi-physician) with standardized U-Net training protocols generated Models A, B, and C. Model C underwent physician-specific fine-tuning. Performance was quantified via Dice similarity coefficients (DSC) against ground-truth contours across 14 critical OARs.Results. Each model achieved peak accuracy on physician-matched test data. Critically, small-consistency models (A/B) outperformed large-heterogeneous Model C on target cohorts (Model A: 0.777 versus Model C's 0.743 on Test A; Model B: 0.806 versus 0.765 on Test B). Physician-specific fine-tuning closed institutional data gaps, boosting Model C's DSC to 0.795 (+7.08% versus original) on Test A and 0.814 (+6.32%) on Test B-surpassing both original Model C and dedicated small-data models (Model A: +2.39%; Model B: +0.97%).Conclusion. Annotation consistency supersedes dataset scale as the primary performance driver for OAR auto-contouring. Small high-consistency datasets enable optimal native model accuracy, whereas fine-tuning large pre-trained models with targeted physician data closes domain adaptation gaps and delivers state-of-the-art segmentation, advancing precision radiotherapy for head and neck oncology.​.

e23537 Background: Radiation-induced sarcoma of the head and neck (RISHN) is a rare but devastating late toxicity of curative radiotherapy (RT). We conducted a single-center cohort study to analyze the clinicopathological characteristics, management, survival, and hemorrhagic risk of RISHN and to identify associated prognostic factors and effective clinical treatments. Methods: We conducted a retrospective analysis of 25 pathologically confirmed RISHN patients treated at Fudan University Shanghai Cancer Center (January 2019 to December 2025), constituting the largest single-institution case series to date. The clinical data include diagnostic age, RT dose, latency, RISHN site, histological subtype, stage, first symptoms and treatment. The survival analysis was estimated by the Kaplan–Meier method. Results: The median age at RISHN diagnosis was 47 years and the median latency was 10.7 months. The most common primary tumor was nasopharyngeal carcinoma (NPC, 21 cases, 84.0%), receiving RT doses ≥66 Gy. RISHN arose chiefly in paranasal sinuses and nasopharynx. Bleeding and nasal congestion were most common presenting symptoms. The Median follow-up time was 24.2 months. The major histological subtypes of RISHN included post-radiation sarcoma (11 cases), undifferentiated sarcoma (4 cases) and osteosarcoma (4 cases). Surgery was the cornerstone of initial management and gross total resection (GTR) was achieved in 11 patients. However, the median EFS was only 10.4 months with the 1-year EFS rate of 41.1%. GTR conferred a significant EFS benefit over nonGTR (incomplete resection or systemic therapy alone), with median EFS times of 12.9 versus 6.9 months (p=0.03; HR=0.34). The median OS was 28.3 months and a numerical advantage in median OS was observed for GTR group (36.9 months) over nonGTR group (20.0 months) (p=0.17, HR=0.40). In 18 patients receiving first-line systemic therapy, the disease control rate (DCR) was 83.4% and the median PFS was 7.7 months. Exploratorily, patients who received immunotherapy had numerically longer PFS (12.7 vs 6.0 months, p=0.53, HR=0.66) and OS (48.9 vs 28.3 months, p=0.99, HR=1.01) than those who did not. Hemorrhage was a notable clinical manifestation especially in anlotinib-treated RISHN patients, whereas none of six patients undergoing prophylactic carotid embolization experienced significant bleeding subsequently. Conclusions: RISHN had a poor prognosis. GTR was an independent prognosis predictor of RISHN, while the EFS was unsatisfactory. Systemic therapy offers an important treatment option. First-line treatment with immunotherapy may improve survival outcomes in RISHN patients. Hemorrhage mitigation, particularly careful use of anti-angiogenic therapy and selective prophylactic endovascular intervention, should be integrated into multidisciplinary care.

Advanced salivary gland carcinoma (SGC) lacking both human epidermal growth factor receptor 2 (HER2) and androgen receptor (AR) expression has limited treatment options. In this single-center, phase II trial, patients with recurrent/metastatic HER2-negative/AR-negative SGC received SHR-A1921, a TROP-2-directed antibody-drug conjugate, every 3 weeks until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) per RECIST v1.1; secondary endpoints included progression-free survival (PFS), safety, and exploratory analyses of baseline TROP-2 expression by immunohistochemistry. As of August 1, 2025, 17 patients were treated and 15 were evaluable for efficacy, including 10 with non-adenoid cystic carcinoma (non-ACC) and 5 with adenoid cystic carcinoma (ACC). In non-ACC SGC, confirmed ORR was 20.0%, disease control rate was 80.0%, and clinical benefit rate was 60.0%. All patients with ACC achieved stable disease, with median PFS of 15.4 months. Treatment-related adverse events were manageable; oral mucositis was most common. No grade 4-5 treatment-related adverse events or treatment-related serious adverse events occurred; one patient discontinued treatment due to toxicity. Baseline TROP-2 expression was heterogeneous, with numerically higher H-scores in responders but no significant association with PFS. SHR-A1921 showed preliminary activity in non-ACC SGC and disease stabilization in ACC, supporting further evaluation in stratified cohorts. Trial registration: ClinicalTrials.gov, NCT05924256. Registered on June 29, 2023.

6086 Background: This phase II study evaluated the efficacy and larynx-preservation potential of induction chemotherapy combined with the toripalimab in patients with locally advanced laryngeal and hypopharyngeal squamous cell carcinoma (LA-L/HPSCC). Primary and 1-year survival outcomes were previously reported; here we present the 3-year follow-up results. Methods: This is a single-arm phase II study. Patients with histopathologic confirmed, resectable LA-L/HPSCC and ECOG PS 0-1 were eligible. Three cycles of induction chemotherapy (paclitaxel 175mg/m 2 d1, cisplatin 25mg/m 2 d1-3) combined with toripalimab (240mg d0) were administered. Response assessment was performed after induction chemoimmunotherapy using RECIST 1.1 criteria. Patients with CR/PR of primary tumor received concurrent chemoradiation, followed by maintenance therapy of toripalimab. Otherwise, patients were referred to surgery, followed by adjuvant (chemo)radiation, and maintenance therapy of toripalimab. The primary endpoint is larynx-preservation rate at three months post-radiation. Secondary endpoints included overall survival (OS), progression-free survival (PFS), larynx preservation rate, and larynx-preservation survival (LPS), etc. Results: Twenty-seven patients were enrolled. Most cases exhibited stage IV disease (81.5%), with T4 representing 37.0%. Five patients underwent pretreatment tracheostomy. The date of data cut-off was Jan 23, 2026. With a median follow-up of 36.4 [95%CI: 33.4-39.4] months, 3-year OS rate, PFS rate, larynx preservation rate and LPS rate was 73.5%, 61.1%, 84.3% and 73.6%, respectively. Excluding patients with pretreatment tracheostomy, these rates improved to 86.4%, 70.8%, 90.2% and 81.1%. The 3-year larynx preservation rate for T2/3 and T4 disease was 92.9% and 70.0%, respectively ( p =0.081). All patients with preserved larynx at last follow-up maintained functional laryngeal status, free from tracheostomy or feeding tube dependence. Conclusions: Induction toripalimab combined with chemotherapy provided promising and durable larynx preservation rate in this cohort of extensively LA-L/HPSCC. Clinical trial information: NCT04995120 . Comparison of patients enrollment and survival among pivotal clinical trials. Study Phase Clinical Stage Larynx preservation rate at 3 year Progression-free rate at 3 year GORTEC 2000-01 III Stage III, IVHypopharynx 54.0%, larynx 46.0% 70.1% for TPF and 57.5% for PF 58% for TPF and 44% for PF Subgroup analysis ofTAX324 II Stage III 26.5%Stage IV 73.5%,Hypopharynx 46.4%, larynx l 64.5% Not available 43% for TPF and 29% for PF This study II Stage III 18.5%Stage IVa 33.3%Stage IVb 48.1%Hypopharynx 66.7%, larynx 33.3% 84.3% for whole cohort and 90.2% when excluding patients with pretreatment tracheostomy 61.1% for whole cohort and 70.8% when excluding patients with pretreatment tracheostomy

Background To explore the prognostic value of early Epstein-Barr Virus DNA response in locoregionally advanced nasopharyngeal carcinoma (LA-NPC). Methods Patients with stage III to IVA nonkeratinizing NPC were enrolled who received induction chemotherapy (IC) with gemcitabine and cisplatin, followed by definitive radiotherapy (RT) or concurrent chemoradiotherapy (CCRT). Plasma EBV DNA levels were assessed within one week prior to the initiation of the first IC cycle and within three days before subsequent cycles. Results A total of 273 patients were enrolled from August 12, 2020, to September 21, 2023. The C-index for EBV DNA post-C1 level to predict disease progression were 0.68, 0.7, 0.68 at 1, 2, 3 years, and 0.47, 0.62, 0.5 for baseline EBV DNA level. Patients with EBV DNA post-C1 levels ≥450 copies/ml demonstrated a worse PFS compared to those with EBV DNA post-C1 levels <450 copies/ml (2-year PFS: 74.7% [95% CI, 64.9 to 84.5] vs. 92.6% [95% CI, 88.48 to 96.7], p < 0.001). Multivariable analyses identified only EBV DNA post-C1 and the overall TNM stage as independent prognostic factors for PFS. Among patients with EBV DNA post-C1 < 450 copies/ml, IC + RT yielded comparable outcome to IC + RTcombined in terms of two-year PFS (93.5% [95% CI, 88.01 to 98.98] vs. 91.8% [95% CI, 85.92 to 97.68], p = 0.616), with reduced treatment-related toxicity. Conclusions EBV DNA post-C1 serves as an early prognostic biomarker for patient risk stratification. The utilization of EBV DNA post-C1 for personalized treatment warrants further validation through additional studies.

Importance Induction chemotherapy (IC) plus concurrent chemoradiotherapy (CCRT) has been a standard treatment for locoregionally advanced nasopharyngeal carcinoma (LA-NPC) but with high acute toxic effects in CCRT phase. Whether CCRT can be safely replaced by radiation therapy with adjuvant chemotherapy (AC) is unknown. Objective To assess if sequential chemoradiotherapy (SCRT; IC, followed by radiotherapy alone, followed by AC) is noninferior to IC plus CCRT for LA-NPC in terms of efficacy, with less acute toxic effects. Design, Setting, and Participants This multicenter, open-label, phase 3 noninferiority randomized clinical trial was conducted from January 2018 to September 2021 in 6 centers in China. Patients aged 18 to 65 years with newly diagnosed stage III/IVA NPC were enrolled. The data cutoff date was June 30, 2024. Interventions Patients were randomly assigned 1:1 to receive 2 cycles of IC with a gemcitabine and cisplatin (GP) regimen (gemcitabine, 1000 mg/m(2), on days 1 and 8 plus cisplatin, 25 mg/m(2), on days 1, 2, and 3, repeated every 3 weeks) plus radiotherapy alone, followed by 2 cycles of AC with a GP regimen (SCRT group) or 2 cycles IC (GP regimen) followed by radiotherapy concurrent with weekly cisplatin, 30 mg/m(2) (IC plus CCRT group). Main Outcomes and Measures The primary end points were 3-year failure-free survival (FFS) with a noninferiority margin of 10% (hazard ratio [HR] less than 1.6) and the incidence of grade 3 or higher acute mucositis during radiotherapy. The secondary end points included overall survival, locoregional FFS, distant FFS, response rate, and toxic effects. Results Of 420 enrolled patients, 107 (25.5%) were women, and the median (IQR) age was 48 (41-54) years. A total of 210 patients were randomized to the SCRT group and 210 to the IC plus CCRT group. The median (IQR) follow-up time was 50 (40-61) months. In the intention-to-treat population, 3-year FFS was 83.7% (95% CI, 78.6-88.8) vs 79.5% (95% CI, 74.0-85.0) in the SCRT group vs the IC plus CCRT group, respectively (HR, 0.77; 95% CI, 0.50-1.19; P = .24), with the upper bound of the 95% CI less than 1.6. Identical outcomes were reported in the per-protocol population. Compared with the IC plus CCRT group, the SCRT group had significantly lower incidences of grade 3 or higher acute nonhematological toxic effects (acute mucositis, 61 [29.0%] vs 88 [41.9%], respectively; P < .001; nausea, 20 [9.5%] vs 38[18.1%], respectively; P = .01; vomiting, 8 [3.8%] vs 20 [9.5%], respectively; P = .02). No differences were observed in late toxic effects. Conclusions and Relevance Results from this noninferiority randomized clinical trial suggest that SCRT is noninferior to IC plus CCRT in terms of 3-year FFS in LA-NPC, with less severe acute nonhematological toxic effects.

Induction chemotherapy (IC) plus concurrent chemoradiotherapy (CCRT) has been a standard treatment for locoregionally advanced nasopharyngeal carcinoma (LA-NPC) but with high acute toxic effects in CCRT phase. Whether CCRT can be safely replaced by radiation therapy with adjuvant chemotherapy (AC) is unknown. To assess if sequential chemoradiotherapy (SCRT; IC, followed by radiotherapy alone, followed by AC) is noninferior to IC plus CCRT for LA-NPC in terms of efficacy, with less acute toxic effects. This multicenter, open-label, phase 3 noninferiority randomized clinical trial was conducted from January 2018 to September 2021 in 6 centers in China. Patients aged 18 to 65 years with newly diagnosed stage III/IVA NPC were enrolled. The data cutoff date was June 30, 2024. Patients were randomly assigned 1:1 to receive 2 cycles of IC with a gemcitabine and cisplatin (GP) regimen (gemcitabine, 1000 mg/m2, on days 1 and 8 plus cisplatin, 25 mg/m2, on days 1, 2, and 3, repeated every 3 weeks) plus radiotherapy alone, followed by 2 cycles of AC with a GP regimen (SCRT group) or 2 cycles IC (GP regimen) followed by radiotherapy concurrent with weekly cisplatin, 30 mg/m2 (IC plus CCRT group). The primary end points were 3-year failure-free survival (FFS) with a noninferiority margin of 10% (hazard ratio [HR] less than 1.6) and the incidence of grade 3 or higher acute mucositis during radiotherapy. The secondary end points included overall survival, locoregional FFS, distant FFS, response rate, and toxic effects. Of 420 enrolled patients, 107 (25.5%) were women, and the median (IQR) age was 48 (41-54) years. A total of 210 patients were randomized to the SCRT group and 210 to the IC plus CCRT group. The median (IQR) follow-up time was 50 (40-61) months. In the intention-to-treat population, 3-year FFS was 83.7% (95% CI, 78.6-88.8) vs 79.5% (95% CI, 74.0-85.0) in the SCRT group vs the IC plus CCRT group, respectively (HR, 0.77; 95% CI, 0.50-1.19; P = .24), with the upper bound of the 95% CI less than 1.6. Identical outcomes were reported in the per-protocol population. Compared with the IC plus CCRT group, the SCRT group had significantly lower incidences of grade 3 or higher acute nonhematological toxic effects (acute mucositis, 61 [29.0%] vs 88 [41.9%], respectively; P < .001; nausea, 20 [9.5%] vs 38[18.1%], respectively; P = .01; vomiting, 8 [3.8%] vs 20 [9.5%], respectively; P = .02). No differences were observed in late toxic effects. Results from this noninferiority randomized clinical trial suggest that SCRT is noninferior to IC plus CCRT in terms of 3-year FFS in LA-NPC, with less severe acute nonhematological toxic effects. ClinicalTrials.gov Identifier: NCT03366415

This study aims to evaluate the efficacy and toxicity of the two induction chemotherapy (IC) regimens (TPF: docetaxel, cisplatin and 5-fluorouracil, and PF: cisplatin and 5-fluorouracil) combined with radiotherapy in young and middle aged patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC). A retrospective analysis was conducted on 329 cases with stage III-IVA nasopharyngeal carcinoma from September 2005 to February 2017. Of the 329 cases, 253 cases underwent TPF (docetaxel: 60 mg/m2 on day 1, cisplatin: 25 mg/m2 on days 1–3, 5-fluorouracil: 500 mg/m2 on days 1–5, intravenous 120-h infusion), while 76 cases received the PF regimen (cisplatin: 25 mg/m2 on days 1–3, 5-fluorouracil: 500 mg/m2 on days 1–5, intravenous 120-h infusion) every 3 weeks. Radiotherapy was administered after IC with or without concurrent chemotherapy. The survival rates were assessed by Kaplan–Meier analysis, and the survival curves were compared using a log‑rank test. The 5-year and 8-year overall survival (OS) rates of the PF group and TPF group were 80.1

6006 Background: Salivary gland cancer (SGC) is a rare and heterogeneous malignancy with limited treatment options in advanced stages. Overexpression of human epidermal growth factor receptor 2 (HER2) is linked to aggressive histological subtypes and poor prognosis in SGC, making HER2 a promising target for precision therapy. This study evaluates the efficacy and safety of SHR-A1811, a HER2-targeted antibody-drug conjugate (HER2-ADC), in patients with advanced SGC through a molecular subtype-guided approach (NCT05924256). Methods: Patients with advanced SGC were stratified into four arms based on genetic subtypes. This analysis focuses on Arm 1 (HER2 overexpression: IHC 3+ or IHC 2+/ISH+) and Arm 4 (HER2-low: IHC 1+ or IHC 2+/ISH-). In Arm 1, patients received SHR-A1811 at 4.8 mg/kg IV on Day 1 of a 21-day cycle. In Arm 4, patients received 4.8 mg/kg or 5.6 mg/kg (if tolerated). The study followed Simon’s two-stage design, with the primary endpoint of objective response rate (ORR) per RECIST v1.1. Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Results: As of January 1, 2025, 33 patients were enrolled (baseline characteristics in Table 1). In Arm 1 (21 evaluable patients), the ORR was 85.7%, and the DCR was 100%. In Arm 4 (10 evaluable patients), the ORR was 30.0%, and the DCR was 100%. After a median follow-up of 9.9 months (range: 1.2–16.6) for Arm 1 and 6.0 months (range: 4.7–9.2) for Arm 4, neither median OS nor PFS was reached. Only one patient in Arm 4 experienced disease progression. Treatment-related adverse events (TRAEs) occurred in 32 patients (97%). The most common grade 3/4 TRAEs included neutropenia (36%), leukopenia (15%), anemia (12%), and lymphopenia (12%). Two patients (6%) experienced treatment-related serious adverse events (SAEs), and one patient (3%) developed grade 1 interstitial lung disease. No patient discontinued treatment due to TRAEs, and no treatment-related deaths were reported. Conclusions: SHR-A1811 demonstrated promising efficacy in both HER2-positive and HER2-low advanced salivary gland cancers, achieving high ORRs and DCRs with an acceptable toxicity profile. Clinical trial information: NCT05924256 . Baseline characteristics. Arm 1（N=23） Arm 4（N=10） Age (years), Median (range) 58 (26-75) 56 (36-66) Male : Female 16:7 8:2 HER2 status, n (%) IHC 3+, 19 (83)IHC 2+/ISH+, 4(17) IHC 1+, 8(80)IHC 2+/ISH-, 2(20) Histology Salivary duct carcinoma, n (%) 12 (52) 1 (10) Carcinoma ex pleomorphic adenoma, n (%) 3 (13) 2 (20) Adenoid cystic carcinoma, n (%) 0 2 (20) Others, n (%) 8 (35) 5 (50) Prior treated for patients, n (%) 16 (70) 9(90) Prior systemic therapy lines, Median (range) 0 (0-3) 1 (0-7) Anti-HER2 treatment, n (%) 5 (22) 0

Objectives: We aimed to investigate the long-term survival benefit of PET/CT compared with the routine examination (chest CT, abdominal enhanced CT and emission computed tomography (ECT)) for locally advanced nasopharyngeal carcinoma (NPC) before treatment. Methods: From June 8th 2005 to August 10th 2017, 507 histologically diagnosed NPC patients with the 8th AJCC/UICC staging criteria III-IVA were enrolled in this study. Among them, patients underwent chest CT, abdominal enhanced CT and bone emission CT (control group), or replaced by positron emission tomography-CT (PET-CT group) to check for distant metastases. Results: The numbers of patients in the control and PET-CT group were 344 (67.9%) and 163 (32.1%), respectively. With the median follow-up of 72 months, a total of 127 (25.0%) patients died. The 5-year and 8-year overall survival (OS) rates of the control and PET-CT group were 81.1% and 86.9%, 70.8% and 74.6% (P=0.087), respectively. Patients with T1-3, III stage and TPF showed improved 5-year and 8-year OS rates compared with T4, IVA stage and PF patients (P=0.001, P=0.000 and P=0.009). Patients with initially PET-CT-based staged showed improved 5-year and 8-year distant control (DC) compared with the control group (90.6% vs. 83.3% and 90.6% vs. 81.0%, P=0.013). There was no significant difference in local control (LC) and regional control (RC), between the control and PET-CT group. Conclusions: Patients with initially PET-CT-based staged showed improved long-term DC compared with the control group. Initially PET-CT-based staged is recommended routinely in locoregionally advanced NPC.

6030 Background: Pembrolizumab or cetuximab combined with platinum-based-chemo are standard first-line regimen for R/M HNSCC, but the efficacy is far from optimal. We conducted an open-label, single-arm, Simon' s two-stage, phase II study of camrelizumab (PD-1 monoclonal antibody) with cetuximab and cisplatin-based chemotherapy as first-line treatment in R/M HNSCC (NCT05673577). The outcomes from the 1 st stage showed promising efficacy. Methods: Eligible patients with R/M HNSCC not amenable to curative treatment were enrolled. Patients were treated with camrelizumab 200mg Q3W, cetuximab 400mg/m 2 loading dose followed by 250mg/m 2 weekly, cisplatin 75mg/m 2 Q3W, and nab-paclitaxel 125mg/m 2 on d1, d8 (21-day cycle), for up to 6 cycles. Maintenance therapy with camrelizumab 200mg Q2W, cetuximab 500mg/m 2 Q2W were given until intolerable toxicity or disease progression. Primary endpoint of this study is objective response rate (ORR). Secondary endpoints include progression-free survival (PFS), overall survival (OS), disease control rate (DCR), adverse events (AEs) (CTCAE v5.0) andmolecular biomarkers will be tested as exploratory endpoints. Results: Between April 2023 and September 2024, 41 patients were enrolled. The confirmed ORR per RECIST 1.1 was 90.0% (95% CI: 75.0-97.0), which met the prespecified criteria for the primary endpoint of ORR. The confirmed DCR was 100.0%. With the median follow-up duration of 14.5 months, the median PFS was 13.2 months (95% CI: 9.3-NR). The 1-year PFS rate was 54.6% (95% CI: 39.1-76.1). The median OS was not reached. The 1-year and 2-year OS rates were 88.4% (95% CI: 78.2-100.0) and 84.6% (95% CI: 72.8-98.3), respectively. The most common grade 3-4 AEs related to chemotherapy included neutropenia (16.7%), anemia (7.1%). Possible grade 3-4 targeted therapy-related AE was rash (7.1%). Additionally, 14.3% of the patients were administered anti-angiogenic medications to treat reactive cutaneous capillary endothelial proliferation mucositis that was specifically induced by camrelizumab. These AEs were manageable with dose modification. Conclusions: Camrelizumab combined with cetuximab and cisplatin-based chemotherapy showed encouraging efficacy and tolerability in the scenario of first-line R/M HNSCC. Further evaluation including a phase III study is warranted. Clinical trial information: NCT05673577 . Demographics and baseline characteristics. N=41 (100%) Age Median (range) 59 (34-72) Sex-n (%) Male/Female 36/5 (87.8% vs. 12.2%) HNSCC Primary site of disease Larynx 15 (36.5%) Oral Cavity 14 (34.1%) Oropharynx 4 (9.8%) HPV-pos 1 (25.0% of Oropharynx) HPV-neg 2 (50.0% of Oropharynx) unclear 1 (25.0% of Oropharynx) Hypopharynx 4 (9.8%) Others 4 (9.8%) Distant metastasis-n (%) 19 (46.3%) ECOG Performance Status-1 vs. 2 (%) 39 vs. 2 (95.1% vs. 4.9%)

6029 Background: Treatment for pre-treated patients (pts) with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) is an important unmet clinical need. Dual blockade of PD-L1 and TGF-β could reshape the tumor microenvironment. The aim of this study is to evaluate the efficacy and safety of retlirafusp alfa (SHR-1701, a bifunctional anti-PD-L1/TGF-βRII agent) plus nab-paclitaxel and carboplatin in platinum-refractory R/M HNSCC pts. Methods: Patients with R/M HNSCC who received ≥1 line of prior systemic anti-tumor therapy were included. Pts received retlirafusp alfa 30mg/kg, once every 3 weeks, combined with nab-paclitaxel (125mg/m 2 ) and carboplatin (AUC=1.5), on day 1 and day 8 of a 21-day cycle for up to six cycles, followed by retlirafusp alfa maintenance therapy. The primary endpoint was objective response rate (ORR). Secondary endpoints comprised progression free survival (PFS), overall survival (OS), disease control rate (DCR) and safety. Results: From September 5, 2023 to September 25, 2024, 12 eligible pts were enrolled. The median age was 60 (range: 35-72). Among these 12 patients, 11 (91.7%) had received prior immune checkpoint inhibitors (ICIs) and 8 (66.7%) had undergone at least two previous lines of treatment. The median follow-up was 5.45 (95%CI 3.93-6.97) months, and data cutoff was December 31, 2024. All the 12 pts had at least one post-baseline assessment, and 4 pts achieved partial response with a confirmed ORR of 33.33% (95%CI 13.81%-60.93%). Disease control was observed in 8 patients resulting in a DCR of 66.67% (95%CI 39.07%-86.19%). The median PFS was 4.21 (95%CI 0.59-7.83) months. The median OS was immature. Treatment-related adverse events (TRAEs) occurred in 11 (91.67%) pts, mainly grade 1-2. The most common TRAEs (≥30%) were anaemia (8/12, 66.67%), white blood cell count decreased (5/12, 41.67%), hypoalbuminaemia (5/12, 41.67%), haemoptysis (5/12, 41.67%) and epistaxis (4/12, 33.33%). Grade 3-4 TRAEs were observed in 4 (33.33%) pts, with more than 1 patient experiencing white blood cell count decreased (3/12, 25%), neutrophil count decreased (2/12, 16.67%) and anaemia (2/12, 16.67%). Conclusions: Even as most pts have progressed on ICIs before enrollment, retlirafusp alfa plus nab-paclitaxel and carboplatin demonstrated promising anti-tumor efficacy and manageable toxicities in pre-treated R/M HNSCC. Long-term efficacy needs to be confirmed by further follow-up. Clinical trial information: ChiCTR2300070675 .

Supplementary figures and legends

Purpose To establish and validate a delta-radiomics-based model for predicting progression-free survival (PFS) in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC) following induction chemotherapy (IC). Methods and Materials A total of 250 LA-NPC patients (training cohort: n = 145; validation cohort: n = 105) were enrolled. Radiomic features were extracted from MRI scans taken before and after IC, and changes in these features were calculated. Following feature selection, a delta-radiomics signature was constructed using LASSO-Cox regression analysis. A prognostic nomogram incorporating independent clinical indicators and the delta-radiomics signature was developed and assessed for calibration and discrimination. Risk stratification by the nomogram was evaluated using Kaplan-Meier methods. Results The delta-radiomics signature, consisting of 12 features, was independently associated with prognosis. The nomogram, integrating the delta-radiomics signature and clinical factors demonstrated excellent calibration and discrimination. The model achieved a Harrell’s concordance index (C-index) of 0.848 in the training cohort and 0.820 in the validation cohort. Risk stratification identified two groups with significantly different PFS rates. The three-year PFS for high-risk patients who received concurrent chemoradiotherapy (CCRT) or radiotherapy plus adjuvant chemotherapy (RT+AC) after IC was significantly higher than for those who received RT alone, reaching statistical significance. In contrast, for low-risk patients, the three-year PFS after IC was slightly higher for those who received CCRT or RT+AC compared to those who received RT alone; however, this difference did not reach statistical significance. Conclusions Our delta MRI-based radiomics model could be useful for predicting PFS and may guide subsequent treatment decisions after IC in LA-NPC.

Adverse effects during induction chemoimmunotherapy and adjuvant immunotherapy

Recurrence patterns and reasons for death (N=27)

Changes of quality of life at different timepoints

PURPOSE:To investigate whether a bounce in plasma Epstein-Barr virus (EBV) DNA during posttreatment surveillance of nasopharyngeal carcinoma (NPC) informs the risk of clinical recurrence and its implication for early therapeutic intervention. METHODS:950 non-disseminated NPC patients with completed remission in 3 months after treatment were retrospectively screened. Detectable EBV DNA with no evidence of clinical relapse during follow-up was deemed as DNA bounce. The diagnostic and prognostic performance of EBV DNA bounce was assessed for subsequent failures. RESULTS:Tumor recurrence occurred in 6.6 %, 10.1 % and 65.8 % in the group with persistently negative EBV DNA, single positive test and ≥ 2 positive tests, respectively. EBV DNA bounce over twice was associated with worse disease-free survival (DFS), locoregional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) than the other two groups. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy for the prediction of recurrence were 0.56, 0.95, 0.66, 0.93 and 0.90 using two positive tests, which were hence deemed as biological relapse. Serial cutoffs (EBV DNA 1 ≥ 40 copies/ml or EBV DNA 2 ≥100 copies/ml) further defined a high-risk subgroup with an eventual recurrence rate of 77.9 % and 3-year DFS of merely 20.5 %. Prophylactic medical intervention with capecitabine or S1 significantly improved the 3-year DFS when compared to those with observation. CONCLUSIONS:The earliest two positive tests of EBV DNA represent a biomarker of biological relapse that allows early detection of clinical recurrence in EBV-related NPC. For high-risk biological relapse, preemptive intervention provides potential survival benefits.