PURPOSE:Patients with recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) have limited therapeutic options after failing platinum and anti-PD-1/PD-L1 therapy. We investigated the efficacy and safety of an epidermal growth factor receptor (EGFR)-directed antibody-drug conjugate (ADC) becotatug vedotin (BV) combined with a PD-1 inhibitor pucotenlimab in this setting of patients. MATERIALS AND METHODS:Magic-C001 (ClinicalTrials.gov identifier: NCT05688605) is an ongoing, open-label, multicohort, dose escalation (phase I) and expansion (phase II) study in patients with EGFR-positive solid tumors. Eligible patients received pucotenlimab 3.0 mg/kg and BV at 1.8-2.3 mg/kg (phase I) or 2.0 mg/kg (phase II for NPC) once every 3 weeks. The primary end point for phase II was objective response rate (ORR). Secondary end points included duration of response (DoR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS:Among 31 patients with NPC at the recommended phase II dose (RP2D) from phase I and II who had received anti-PD-1/PD-L1 and platinum-based therapy, the confirmed ORR was 71.0% (95% CI, 52.0 to 85.8); DCR was 93.5% (95% CI, 78.6 to 99.2). The median DoR and PFS were 14.0 months (95% CI, 5.7 to not estimated) and 12.0 months (95% CI, 6.8 to 15.4), respectively. Median OS was not mature. Most common treatment-related adverse events (TRAEs) were pruritus (71.9%), hypoesthesia (65.6%), anemia (59.4%), and rash (56.3%). TRAEs of ≥grade 3 occurred in 40.6% of patients. No TRAEs led to death. CONCLUSION:To our knowledge, we report the first trial combining an ADC with immunotherapy for platinum and anti-PD-1/PD-L1-resistant NPC. BV plus pucotenlimab yielded a notable ORR with exceptionally durable responses and substantially prolonged PFS, alongside manageable toxicities. This regimen may offer a promising anti-PD-1 rechallenge strategy in this population, which is being confirmed in an ongoing, multicenter, randomized controlled, phase III study.

BACKGROUND:Nasopharyngeal carcinoma (NPC) is strongly associated with Epstein-Barr virus (EBV) infection. The gut microbiome can influence outcomes of viral infections but the potential links among the gut microbiome, EBV infection and NPC remain unclear. OBJECTIVE:To characterise gut microbiome alterations in EBV-associated NPC, evaluate microbiome-based diagnostic performance (alone and in combination with EBV markers), and explore associations between microbial features, EBV DNA burden, prognosis and the tumour microenvironment. DESIGN:We conducted a large-scale shotgun metagenomic study including 516 patients with EBV-associated NPC and 263 healthy controls. Microbiome dysbiosis, functional pathways and associations with plasma EBV DNA were assessed. Species-level markers were used to build a random forest classifier for NPC diagnosis, and performance was evaluated alone and in combination with EBV-specific markers. Survival analyses were performed to identify microbial features associated with NPC-related mortality and relationships with an immune-suppressive tumour microenvironment were explored. RESULTS:NPC was characterised by gut microbiome dysbiosis, including depletion of short-chain fatty acid-producing species and reduced butanoate metabolism, which were significantly associated with plasma EBV DNA. A random forest classifier based on species-level markers distinguished NPC from controls with an area under the curve (AUC) of 0.917; performance improved to an AUC of 0.984 when combined with EBV-specific markers. Specific microbial species were associated with NPC-related mortality and prognostic microbial features were linked to an immune-suppressive tumour microenvironment. CONCLUSION:EBV-associated NPC is associated with distinct gut microbiome and functional alterations that correlate with plasma EBV DNA. Microbial markers show strong diagnostic potential, particularly when integrated with EBV-specific markers, and prognostic microbial features may be linked to an immune-suppressive tumour microenvironment, supporting a potential role of the gut microbiome in NPC tumourigenesis.

The combination of anti-PD-L1 and paclitaxel (PTX) is a standard-of-care regimen for triple-negative breast cancer (TNBC). However, TNBC is classified as a ″cold″ tumor characterized by low immunogenicity, hypoxia, and the aberrant activation of signal transducer and activator of transcription 3 (STAT3), which greatly reduces the efficacy of immune checkpoint blockades (ICBs). This project aims to construct an albumin-based nanomedicine coloaded with atovaquone (ATO) and PTX for targeted tumor delivery, thereby enhancing the therapeutic efficacy of ICBs. The nanomedicine exhibits optimal particle size, exceptional stability, excellent biocompatibility, and a high drug encapsulation efficiency. Among these, ATO enhances PTX-induced immunogenic cell death by alleviating tumor hypoxia, thereby increasing tumor immunogenicity. Furthermore, ATO reduces STAT3 phosphorylation, modulating the immunosuppressive tumor microenvironment. The combination of nanomedicine with ICBs synergistically transforms TNBC from an immunologically ″cold″ to a ″hot″ tumor. This transformative approach significantly enhances the therapeutic efficacy of combination chemotherapy, leading to potent suppression of primary tumors while concurrently preventing postoperative recurrence and pulmonary metastases. This project has the potential to introduce innovative strategies and methodologies aimed at overcoming the limited efficacy of PTX combined with ICBs in the treatment of TNBC.

PURPOSE:We previously reported that reduced-dose (60 Gy) radiation was associated with favorable survival outcomes and limited toxicities in patients with low-risk stage III nasopharyngeal carcinoma (NPC) sensitive to induction chemotherapy (IC). However, the consistency of long-term outcomes remains unclear. METHODS AND MATERIALS:This 5-year follow-up secondary analysis of a single-arm phase II trial enrolled patients with nonkeratinizing stage III NPC with pretreatment Epstein-Barr virus (EBV) DNA <4000 copies/mL. All 215 eligible patients received 2 cycles of IC. After IC, 116 patients achieved complete response/partial response and undetectable EBV DNA, and they were assigned to receive intensity-modulated radiation therapy (IMRT) at 60 Gy in 30 fractions. The remaining 99 patients were assigned to receive standard IMRT at 70 Gy in 33 fractions. The primary endpoint was progression-free survival. RESULTS:At a median follow-up of 68.1 months, the 5-year progression-free survival was 90.5% (95% CI, 85.3%-96.0%) in the 60 Gy cohort and 79.8% (72.3%-88.1%) in the 70 Gy cohort, whereas the 5-year overall survival was 96.6% (93.3%-99.9%) and 94.9% (90.7%-99.4%), respectively. The 5-year locoregional relapse-free survival was 93.1% in the 60 Gy cohort and 82.8% in the 70 Gy cohort; the 5-year distant metastasis-free survival was 93.1% in the 60 Gy cohort and 89.9% in the 70 Gy cohort. No grade 3-4 late toxicity was observed in the 60 Gy group. In the 70 Gy cohort, 10.1% of patients experienced grade 3-4 late toxicities, with dry mouth and deafness/otitis being the most frequently reported. CONCLUSIONS:Long-term analysis showed that in patients with low-risk stage III NPC selected by EBV DNA and IC response, reduced-dose IMRT (60 Gy) achieved favorable survival outcomes with limited late toxicities.

6013 Background: The docetaxel, cisplatin, and 5-fluorouracil (TPF) regimen is the standard induction therapy regimen for locoregionally advanced nasopharyngeal carcinoma (LANPC). However, it is associated with poor patient compliance and notable side effects. This phase 3 trial aimed to compare the efficacy and safety of induction chemotherapy with nab-paclitaxel plus cisplatin (nab-TP) with those of the TPF regimen in patients with LANPC. Methods: In this multicenter, noninferiority, open-label, randomized controlled trial, treatment-naive patients with LANPC were recruited from 5 hospitals in China and were randomly assigned to receive two cycles of nab-TP (nab-paclitaxel 260 mg/m², cisplatin 80 mg/m²) or TPF (docetaxel 60 mg/m², cisplatin 60 mg/m², 5-FU 3 g/m²), followed by concurrent chemoradiotherapy. The primary endpoint was the 3-year failure-free survival (FFS) rate (non-inferiority margin 10%) in the intention-to-treat population. Secondary endpoints included overall survival, treatment response, safety, and patient-reported outcomes. This trial is registered with chictr.org.cn (ChiCTR1800019922) and is now completed. Based on previous studies, we hypothesized that the 3-year FFS (approximately 80%) is the same between the TPF regimen and the nab-TP regimen for patients with LANPC. We specify a clinically acceptable noninferiority margin of 10%. The dropout rate in both arms was set at 4% per year. Accordingly, a minimum of 506 participants was needed to achieve 80% statistical power with a one-sided type I error of 2·5%. Results: Between January 22, 2019 and March 24, 2023, 515 patients (71·8% male; median age: 45 years (IQR 37–51)) were randomized: 259 to the nab-TP group and 256 to the TPF group. Compared with the TPF group, the nab-TP group had significantly better treatment compliance. With a median follow-up of 55·2 months, the 3-year FFS rate in the intention-to-treat population was 86·7% (95% confidence interval (CI): 82·6–90·9) in the nab-TP group and 88·2% (95% CI: 84·2–92·1) in the TPF group. The difference in the 3-year FFS between groups was -1·4% (95% CI: -7·2 to 4·3)(P non-inferiority = 0·0018). Compared with the TPF group, the nab-TP group had significantly lower incidences of grade 1+ leucopenia (34·0% vs. 62·6%, P < 0·0001), neutropenia (20·3% vs. 48·8%, P < 0·0001), electrolyte disturbances (86·3% vs. 96·5%, P < 0·0001), and diarrhea (28·5% vs. 39·0%, P = 0·012), whereas the nab-TP group had a higher incidence of nausea (91·0% vs. 85·4%, P =0·047). No treatment-related death was documented. Conclusions: In LANPC, nab-TP was non-inferior to TPF in terms of 3-year FFS rate and was associated with a significantly better safety and tolerability profile, supporting its use as a viable therapeutic alternative. Clinical trial information: ChiCTR1800019922.

LBA6005 Background: Induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) is the current standard treatment for locoregionally advanced nasopharyngeal carcinoma (LA-NPC); however, patients with a suboptimal response to IC remain at high risk of disease progression. Although adjuvant capecitabine has demonstrated efficacy in high-risk LA-NPC, whether intensifying adjuvant therapy by adding sintilimab, a highly selective, fully humanized monoclonal PD-1 inhibitor to capecitabine, can further improve survival outcomes remains unclear. Methods: This open-label, randomized, phase 2 trial enrolled patients aged 18–70 years with untreated, non-keratinising, stage II–IVA LA-NPC according to the eighth edition of the American Joint Committee on Cancer classification system with suboptimal response to IC, defined as detectable EBV DNA and/or stable or progressive disease after platinum-based IC. After CCRT, all patients were randomly assigned (1:1) to receive either adjuvant sintilimab plus capecitabine or capecitabine alone. Sintilimab (200 mg intravenously) was administered on days 1 and 14 after randomization as a lead-in phase, and then every 3 weeks starting 28 days after CCRT, combined with capecitabine (1000 mg/m² twice daily, days 1–14) for eight cycles; the control group received capecitabine alone on the same schedule starting 28 days after CCRT for eight cycles. The primary endpoint was 2-year progression-free survival (PFS) in the intention-to-treat population. Safety was assessed in all participants who received at least one dose of the assigned treatment. The study was registered at ClinicalTrials.gov (NCT05201859), and patients are under follow-up. Results: One hundred fifty patients were randomised (76 to sintilimab–capecitabine group; 74 to capecitabine group). At a median follow-up of 41 (IQR 35-44) months, the 2-year PFS was 88.2 % in the sintilimab–capecitabine group and 87.8% in the capecitabine group (stratified HR 0.85; 90% CI 0.43–1.70; p=0.77). Grade 3-4 adverse events were reported in 25 (34%) patients in the sintilimab–capecitabine group and in 22 (31%) patients in the capecitabine group; hand-foot syndrome was the most common adverse event in both groups (8% vs. 10%). Immune-related grade 3 myocarditis were occurred in 2 (3%) patients in the sintilimab–capecitabine group. No treatment-related deaths occurred. Conclusion: In patients with LA-NPC who had a suboptimal response to IC, intensification of adjuvant therapy with the addition of sintilimab to capecitabine did not result in a significant improvement in progression-free survival. Future studies are warranted to focus on biomarker-driven patient selection and optimization of immunotherapy sequencing with conventional treatments. Clinical trial information: NCT05201859 .

BACKGROUND:Recent clinical trials have suggested that incorporating immunotherapy into the treatment of locoregionally advanced nasopharyngeal carcinoma (LA-NPC) may improve survival outcomes. However, for patients who experience disease progression despite immunotherapy, the clinical value of immunotherapy rechallenge as a first-line treatment for recurrent or metastatic disease remains unclear. METHODS:In this real-world study, patients with LA-NPC who received immunotherapy during the initial treatment and subsequently experienced disease progression were retrospectively analyzed. All patients received first-line treatment with or without immunotherapy rechallenge after progression. The primary endpoint was progression-free survival after the first relapse (PFS-r). FINDINGS:From a total of 24,183 consecutive patients screened between 2018 and 2023, 160 met the eligibility criteria and were included, with 117 receiving immunotherapy rechallenge and 43 receiving non-immunotherapy treatment after progression. The median follow-up time was 39.3 months (interquartile range, 26.0-48.4). After inverse probability of treatment weighting adjustment, immunotherapy rechallenge did not confer a significant survival advantage in the overall cohort (2-year PFS-r, 40.8% vs. 26.2%; hazard ratio [HR] = 0.677, 95% confidence interval [CI] 0.419-1.094, p = 0.111). Subgroup analyses showed that, in patients with an immunotherapy-free interval >1 year, immunotherapy rechallenge was associated with a significantly improved prognosis (2-year PFS-r, 65.4% vs. 15.5%; HR = 0.210, 95% CI 0.093-0.474, p < 0.001). CONCLUSIONS:Immunotherapy rechallenge may not provide a significant survival benefit following initial immunotherapy failure in LA-NPC, except in patients with an immunotherapy-free interval exceeding 1 year. FUNDING:National Natural Science Foundation of China and Science and Technology Program of Guangzhou.

232 Background: To evaluate the efficacy and safety of stereotactic body radiation therapy (SBRT) combined with gemcitibine plus cisplatin (GP) chemotherapy and PD-1 inhibitor in patients with oligometastatic nasopharyngeal carcinoma (NPC), registered on clincialtrials.gov (NCT05524168). Methods: Main eligibility criteria included diagnosed as oligometastasis NPC (≤5 lesions), and have ≥1 measurable lesion meeting the RECIST 1.1 criteria. Patients firstly receive SBRT for oligometastatic lesions (6-8Gy/fraction × 3-5 fractions), then receive GP+PD-1 inhibitor for 4-6 cycles followed by PD-1 inhibitor maintenance for 1 year. For patients with primary metastasis, the primary lesion and regional metastatic lymph nodes are given radiotherapy (RT) after completing 4-6 cycles of GP+PD-1 inhibitor. The primary endpoint was the 1-year progression-free survival (PFS) rate. Results: Between Nov 2022 to Jun 2025, 41 oligometastasis NPC patients were recruited (Table 1). 23 patients were primary metastases, and 17 had distant metastasis (DM) after receiving chemo-radiotherapy, and 1 had regional relapse and DM. All patients finished SBRT for metastatic lesions followed by GP+PD-1, and 23 patients with primary metastasis also received RT for primary lesions after 6 cycles of GP+PD-1. Then 17 received ≥1 year PD-1 maintenance, 3 discontinued for PD, 1 requested to withdraw, and 20 still under PD-1 maintenance. With the median follow-up time of 17.3 (IQR, 12.9-21.8) months, all these metastatic lesions receiving SBRT controlled well; 7 patients had disease progression, including 1 regional relapse, 4 DM, and 2 loco-regional relapse and DM, and all these lesions were newly developed metastatic lesions except one regional relapse which didn’t receive SBRT. The primary endpoint 1-year PFS rate was 92.2% (95%CI, 77.6-97.4%), and the secondary survival endpoints 1-year OS, DMFS and LRRFS rate were 100.0% (95%CI, 100-100%), 92.2% (95%CI, 77.6-97.4%), and 97.5% (95%CI, 83.5-99.6%), respectively. The best objective response rate (ORR) and disease control rate (DCR) before starting PD-1 maintenance were 92.7% and 100%, with 27 got complete response, 11 got partial response and 3 got stable disease. The median value of EBV DNA copies pretreatment was 743 (IQR, 151.5-5331.0) copies/ml, then decreased to 0 (IQR, 0-0) copies/ml post 6 cycles of GP+PD-1. No grade 5 therapeutic toxicity was observed in this trial. Conclusions: Patients with oligometastatic NPC who receive SBRT for metastatic lesions combined with GP and PD-1 inhibitor could achieve good therapeutic effects with acceptable toxicities. Clinical trial information: NCT05524168 . Basic information. Characteristic N (%) Median age (IQR), year 48 (39-54) Sex Female 13 (31.7) Male 28 (68.3) ECOG, points 0 4 (9.8) 1 37 (90.2) Number of metastases lesions 1-2 33 (80.5) 3-4 8 (19.5) Number of metastases organs 1 31 (75.6) 2 10 (24.4)

6003 Background: Although two- and three-cycle induction chemotherapy are both widely utilized and confer significant survival benefits in locoregionally advanced nasopharyngeal carcinoma, direct comparative evidence remains lacking. Furthermore, given the cumulative treatment-related toxicity, economic burden, and potential delays in the initiation of radiotherapy, the optimal number of induction chemotherapy cycles remains undefined. Methods: We conducted a phase 3, open-label, multicenter, randomized controlled noninferiority trial in an endemic area. Patients with previously untreated, stage III-IVB (except T3-4N0, AJCC 8 th edition) nasopharyngeal carcinoma, aged 18-70 years without severe comorbidities were enrolled. Eligible patients were randomly assigned to receive two cycles or three cycles induction chemotherapy followed by concurrent chemoradiotherapy in a 1:1 ratio. The primary endpoint was failure-free survival (FFS) and the noninferiority margin was defined as an 8% absolute between-group difference, with an 80% statistical power and a one-sided α of 0.025. The secondary endpoints included overall survival, distant metastasis-free survival, locoregional relapse-free survival, and toxicity, , among others. Results: Among 654 eligible patients, 327 were allocated to each group (two-cycle vs three-cycle). Two groups were well-balanced in all prognostic factors. After a median follow-up of 34.3 months, intention-to-treat analysis showed that estimated 3-year FFS was 85.4% (95% CI 80.9-89.9) in the two-cycle group and 86.7% (95% CI 82.4-91.0) in the three-cycle group, with a difference of -1.3% (95% CI, -7.54% to 4.94%; hazard ratio 1.11, 95% CI 0.72-1.71; P = 0.0031 for noninferiority). Similar result was found in the per-protocol analysis: estimated 3-year FFS for two-cycle group and three-cycle group was 86.5% (95% CI 82.0-91.0) and 87.0% (95% CI 82.7-91.3), respectively, with a difference of -0.5% (95% CI, -6.74% to 5.74%; hazard ratio 1.10, 95% CI 0.69-1.75; P = 0.0014 for noninferiority). No differences were observed between groups in terms of overall survival and the cumulative incidences of locoregional relapse and distant metastasis. Patients in the three-cycle group developed significantly more grade 3-4 adverse events such as neutropenia (three-cycle group 34.3% vs two-cycle group 24.8%), leukopenia (32.7% vs 24.5%) and vomiting (15.9% vs 10.4%). No patients died from treatment-related causes. Conclusions: Two-cycle induction chemotherapy followed by concurrent chemoradiotherapy provides comparable disease control and survival, with less toxicity, compared to three-cycle counterpart in locoregionally advanced nasopharyngeal carcinoma. Clinical trial information: ChiCTR1800018417 .

Induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) is the standard treatment for locoregionally advanced nasopharyngeal carcinoma (LA-NPC); however, patients with a suboptimal response to IC, defined as detectable Epstein-Barr virus DNA and/or stable or progressive disease after IC, remain at high risk of treatment failure. Here we report an open-label, randomised, phase 2 trial evaluating whether adding nimotuzumab, a humanised anti-epidermal growth factor receptor antibody, to CCRT improves outcomes in this high-risk population. A total of 246 patients with untreated, non-keratinising, stage II-IVA LA-NPC were randomly assigned (1:1) to receive CCRT with or without nimotuzumab. The primary endpoint was 2-year progression-free survival (PFS); secondary endpoints included overall survival, distant metastasis-free survival, locoregional relapse-free survival, short-term response rate, and safety. At a median follow-up of 47 months, the 2-year PFS was 81.0% (90% confidence interval [CI], 74.3-86.1) in the nimotuzumab plus CCRT group and 80.8% (90% CI, 74.2-85.7) in the CCRT-alone group (hazard ratio, 0.93 [90% CI, 0.63-1.37]; p = 0.70). Survival outcomes were similar between groups, while low-grade rash occurred more frequently with nimotuzumab. These findings indicate that adding nimotuzumab to CCRT does not improve survival in patients with LA-NPC with a suboptimal response to IC, underscoring the need for predictive biomarkers and alternative therapeutic strategies. Trial registration: NCT04223024.

Purpose: GFH018 is a novel TGFβRI inhibitor, which has been shown to potentiate the antitumor effect of anti-PD-1/PD-L1 blockade. This study aimed to evaluate the safety and efficacy of GFH018 plus toripalimab in recurrent/metastatic (R/M) NPC patients. Patients & Methods: This phase Ib/II study included patients with R/M NPC who had failed at least one prior line of standard therapy. Patients received GFH018 (40 or 80 mg) BID for 14 days on/14 days off, combined with toripalimab (3 mg/kg) intravenously every two weeks on a 28-day cycle. Treatment continued until disease progression or intolerable toxicity. The primary endpoint was the objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), duration of response (DoR), and safety. Results: Forty-six patients were were accrued. The ORR was 26.1% (90% CI: 15.8–38.8%), and the disease control rate (DCR) was 43.5% (90% CI: 31.0–56.6%). The median PFS was 2.0 months (90% CI: 1.8–8.9), and the median DoR was 7.6 months (90% CI: 5.6–not reached). In patients without prior immune checkpoint inhibitor (ICI) treatment, the ORR was 40% (90% CI: 23.6–58.3%), and the DCR was 60% (90% CI: 41.7–76.4%). The median PFS was 9.0 months (90% CI: 1.9–not reached), and the median DoR was not reached. High parenchymal CD8+ T cell density correlated with better PFS in these patients. Conclusions: The combination of GFH018 and toripalimab showed a manageable toxicity profile and durable antitumor activity in R/M NPC patients, especially those without prior ICI exposure.

6040 Background: The PRANCIS model has been shown to be robust for identifying patients with recurrent nasopharyngeal carcinoma (rNPC) who are at high risk of treatment-related adverse events from re-irradiation (reRT). Here, we investigate the efficacy of combination doublet gemcitabine-cisplatin (GP) and PD-1 inhibitor (Toripalimab) to down-classify PRANCIS high risk (>252) to low-risk post-3 cycles of treatment, and the survival outcomes of these patients. For patients who converted to low-risk, reRT may be considered (NCT03930498). Methods: Eligibility criteria included diagnosed as local ± regional recurrence after ≥1 year of radical treatment, not suitable for surgery, histologic or clinically diagnosis of NPC, stage rII-IVa (AJCC/UICC 8th), PRANCIS model > 252 points. All patients received 3 cycles of GP + PD-1 inhibitor, then received reRT (GTV, 60-66Gy, 1.8-2.0Gy/f) plus PD-1 inhibitor if got CR/PR (reRT group), or received another 3 cycles of GP+PD-1 inhibitor if got SD (no reRT group), finally all got 4 cycles of PD-1 inhibitor maintenance. Primary end point was 2-year overall survival (OS). Results: Between Mar 2020 to Nov 2023, 68 high-risk patients were recruited (Table 1). After 3 cycles of GP + PD-1 inhibitor, 44 (64.7%) patients got PR (34 down-classify to low-risk and 10 still high-risk) and received full-course reRT, 22 (32.4%) got SD (all high-risk) and kept receiving GP + PD-1 inhibitor, and 2 (2.9%) could not be evaluated due to 1 died of COVID-19 and 1 withdrew after 2 cycles of treatment. 56 (82.4%) patients finished the scheduled treatment, and 12 discontinued chemo-immunotherapy. With a median follow-up time of 32.7 months, the 2-year OS of whole cohort was 67.2%, and 73.8% vs 51.2% ( P = 0.019) in reRT group vs no reRT group. The 2-year progression-free survival (PFS) of whole cohort was 47.9%, and 61.0% vs 24.3% ( P < 0.0001) in reRT group vs no reRT group. The most common ≥grade 3 toxicities included neutropenia (30.9%), lymphopenia (22.1%), and xerostomia (16.2%). The incidences of grade 3 nasopharyngeal necrosis was 5.9%. Two (2.9%) patients died of massive nasal bleeding. Conclusions: Induction chemo-immunotherapy offered the chance of reRT for high-risk rNPC patients and improved their overall survival with acceptable toxicities. Clinical trial information: NCT03930498 . Basic information. Variables Whole cohort reRT group no reRT group Age † , year 52.0 (43.0 - 58.0) 54.5 (42.8 - 58.8) 47.0 (43.0 - 54.8) Sex Male 51 (75.0) 30 (68.2) 21 (87.5) Female 17 (25.0) 14 (31.8) 3 (12.5) rT stage T3 36 (52.9) 28 (63.6) 8 (33.3) T4 32 (47.1) 16 (36.4) 16 (66.7) rN stage N0 36 (52.9) 25 (56.8) 11 (45.8) N1-3 32 (47.1) 19 (43.2) 13 (54.2) rTNM stage III 35 (51.5) 27 (61.4) 8 (33.3) IVa 33 (48.5) 17 (38.6) 16 (66.7) pre-treatment EBV DNA, copy/ml 0 23 (33.8) 14 (31.8) 9 (37.5) >0 41 (60.2) 27 (61.4) 14 (58.3) Missing 4 (5.9) 3 (6.8) 1 (4.2) PRANCIS model † , points 295.3 (264.1 - 321.8) 270.8 (258.1 - 340.5) 309.2 (297.5 - 319.4) † median (IQR).

BACKGROUND:Concurrent chemoradiotherapy (CCRT) followed by adjuvant chemotherapy (AC) is the standard treatment for locoregionally advanced nasopharyngeal carcinoma (LA-NPC). However, the optimal duration of oral AC remains poorly defined. METHODS:This study examined newly diagnosed patients between April 2017 and December 2020. The primary endpoint was overall survival (OS). Restricted cubic splines (RCS) and Kaplan-Meier method were used to evaluate the relationship between AC maintenance and survival. Inverse probability of treatment weighting (IPTW) was used to control for confounding factors. RESULTS:The RCS demonstrated an L-shaped association between oral AC maintenance and OS. The risk of mortality was relatively flat after 12 months. Patients with oral AC duration >186 days (defined by RCS) had a significantly better OS (HR 0.23 [95% CI 0.10-0.55], log-rank p < 0.001), with a higher 3-year OS rate (98.7% [95% CI 96.8-100.0] vs 88.3% [95% CI 82.5-94.5]). For patients with pretreatment Epstein-Barr virus (EBV) DNA level >4000 copies/mL, mortality risk decreased to 1 at 194 days of AC duration. CONCLUSIONS:The optimal duration of oral AC after CCRT was >186 days (6 months) for LA-NPC. And the maintenance beyond 12 months may not bring additional benefits.

Nasopharyngeal carcinoma (NPC) is often diagnosed at an advanced stage due to its hidden location, with 70–80

Importance:It remains uncertain which chemotherapy sequence is more effective for locoregionally advanced nasopharyngeal carcinoma. Objective:To compare the efficacy and safety of induction-concurrent with concurrent-adjuvant chemotherapy in high-risk N2 to N3 nasopharyngeal carcinoma. Design, Setting, and Participants:In this open-label, randomized, phase 3 clinical trial conducted at Sun Yat-sen University Cancer Center (China) from November 20, 2017, to March 19, 2021, patients aged 18 to 65 years with stage T1-4N2-3M0 and a pretreatment Epstein-Barr virus DNA level of 1500 or more copies/mL were enrolled. The data were analyzed from December 2024 to March 2025. Intervention:The patients were randomly assigned to receive 3 cycles of paclitaxel-cisplatin-fluorouracil induction chemotherapy followed by concurrent chemoradiotherapy or concurrent chemoradiotherapy followed by 3 cycles of cisplatin-fluorouracil adjuvant chemotherapy. Main Outcome and Measure:The primary end point was 3-year progression-free survival, assessed locally by the investigator and defined as the time from random assignment to documented local or regional relapse, distant metastasis, or death of any cause, whichever occurred first. Results:A total of 162 patients (median [IQR] age, 44 [34-53] years; 40 female individuals [24.7%]) were assigned to the induction-concurrent group and 162 (median [IQR] age, 45 [37-52] years; 36 female individuals [22.2%]) to the concurrent-adjuvant group. Regarding the data cutoff (October 8, 2024), the median (IQR) follow-up period was 60.4 (58.2-62.6) months. The 3-year progression-free survival rates were 73.5% (95% CI, 65.9%-79.6%) in the induction-concurrent group and 70.4% (95% CI, 62.7%-76.8%) in the concurrent-adjuvant group (stratified hazard ratio, 0.86; 95% CI, 0.58-1.27; P = .45). The most common short-term grade 3 or worse adverse events were leukopenia (53 of 160 [33.1%] in the induction-concurrent group vs 47 of 142 [33.1%] in the concurrent-adjuvant group), neutropenia (52 [32.5%] vs 32 [22.5%], respectively), and mucositis (47 [29.4%] vs 42 [29.6%], respectively). The most common grade 3 or worse late adverse event was auditory or hearing loss (10 [6.3%] vs 12 [8.5%], respectively). Two patients in the induction-concurrent group died of treatment-related toxic effects. No treatment-related death occurred in the concurrent-adjuvant group. Conclusions and Relevance:This randomized clinical trial found that induction-concurrent chemotherapy did not significantly improve progression-free survival compared with concurrent-adjuvant chemotherapy in high-risk N2 to N3 nasopharyngeal carcinoma. Both treatment strategies were effective, and clinicians should discuss with the patients about the potential risks and benefits of the induction chemotherapy or adjuvant chemotherapy to provide the most appropriate treatment for patients with high-risk features. Trial Registration:ClinicalTrials.gov Identifier: NCT03306121.

Adolescent and childhood nasopharyngeal carcinoma (NPC) is a rare malignancy with unique biological and genetic characteristics, often associated with Epstein-Barr virus (EBV). This CACA guideline provides an integrative approach to the management of adolescent and childhood NPC, focusing on biology, diagnosis, staging, and treatment strategies. The incidence of NPC is higher in adolescent boys and is more frequently diagnosed at an advanced stage in adolescent and childhood population compared to adults. However, adolescent and childhood NPC generally have a better prognosis. The primary treatment is radiotherapy (RT), with intensity-modulated radiation therapy (IMRT) being the preferred technique due to its reduced damage to normal tissues. Chemotherapy, particularly induction chemotherapy, plays a significant role, especially in locally advanced disease. Personalized treatment strategies, including adjusting RT dosage based on chemotherapy outcomes, may reduce long-term adverse effects. The role of adjuvant therapy post-RT remains unclear and requires further research. The main objective of this guideline is to standardize the clinical diagnosis and treatment process of adolescent and childhood nasopharyngeal carcinoma, with a multidisciplinary approach to optimize therapeutic outcomes and quality of life for this disease.

Metastasis is the main cause of treatment failure in nasopharyngeal carcinoma (NPC). Our previous study developed a transcriptomics-based gene signature (AK4, CPAMD8, DDAH1, and CRTR1) to predict metastasis in NPC and identify candidates that could benefit from induction chemotherapy (IC). Of these, adenylate kinase 4 (AK4) is a potent oncogene involved in the malignant progression of a variety of tumors. This study investigated the expression and mechanism of action of AK4, a member of the AK family of enzymes, in NPC. Quantitative real-time PCR, western blotting, and immunohistochemistry revealed that AK4 was upregulated in NPC and correlated with metastasis and chemoresistance. Stable ectopic overexpression of AK4 in NPC cell lines conferred resistance to taxol-induced apoptosis, promoted the migration, invasion, and EMT phenotype, and induced IL-1β secretion by activating the NLRP3 signaling pathway; knockdown of AK4 had the opposite effects. Mechanistically, AK4 co-localized with NNT, upregulated NLRP3 and IL-1β, and consequently altered NPC cell metastasis and chemoresistance. AK4 may play a role in the development of NPC and represent a potential therapeutic target.

BackgroundDrug-resistant Mycobacterium tuberculosis strains have challenged efforts to combat tuberculosis (TB), a major global killer. C-reactive protein (CRP) shows promise as a biomarker for TB screening, particularly in HIV-positive cases, with demonstrated sensitivity and specificity in meta-analyses.MethodsWe performed a meta-analysis to assess the accuracy of CRP for screening HIV-associated PTB in outpatients, combining the sensitivities and specificities of diagnostic tests. PubMed, Web of Science, and SCOPUS were searched for articles that were published until April 2024. Quality assessment was done using the QUADAS-2 scale, and analysis was conducted using the random-effect model in STATA 17.ResultsEighteen studies, primarily from Africa (2013-2023), were analysed from an initial pool of 1186. These studies included 5625 HIV patients, 1248 of whom had PTB coinfection. Using a CRP threshold of 10 mg/L, 17 studies (5109 patients) showed 84% sensitivity (95% CI: 72%-91%) and 67% specificity (95% CI: 52%-79%) with I2 = 84.91%. At 8 mg/L, nine studies (3631 patients) reported 77% sensitivity (95% CI: 65%-86%) and 81% specificity (95% CI: 69%-89%) with I2 = 86.75%.ConclusionsOur study showed that CRP may aid in screening for PTB in PLHIV but requires clinical assessment and additional tests. Its high sensitivity can rule out PTB, but low specificity necessitates further investigation.