bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pembrolizumab plus nab-paclitaxel and platinum as first-line treatment in patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC): A prospective, single-arm, open-label, phase 2 study.
Authors: Gui Lin , Chen Xinrui , Xie Zucheng , He Xiaohui , Yang Jianliang , Liu Peng , Qin Yan , Shi Yuankai 
Published: June 2024

6023 Background: Based on KN-048, pembrolizumab combined with PF regimen has become the first-line standard treatment for R/M HNSCC. KN-B10 confirmed pembrolizumab combined with carboplatin and paclitaxel has a promising effect with manageable safety. This study aims to supplement the efficacy and safety data of pembrolizumab combined with nab-paclitaxel and platinum in the Chinese population. Methods: Untreated R/M HNSCC patients were treated with pembrolizumab 200mg, nab-paclitaxel 260mg/m2, plus cisplatin 75 mg/m2 or carboplatin AUC 5 (only if patients have cisplatin contraindications) on day 1 every 21 days for up to six cycles, followed by pembrolizumab maintenance therapy until progression or intolerable toxicity or completion of 35 cycles. Efficacy was evaluated according to RECIST 1.1, and survival analysis was performed using the Kaplan-Meier method. Adverse events were assessed using the CTCAE 5.0. The primary endpoint was ORR. Secondary endpoints include safety, DCR, OS, and PFS. High-resolution sequencing based on probe capture was performed on eligible patients. Results: Between Sep 15, 2020, and Nov 8, 2023, 67 R/M HNSCC patients were enrolled. Baseline characteristics are shown in the table. The median follow-up time was 12.7 months at the data cut-off date of January 8th, 2023, the ORR was 62.7%, and the DCR was 88.1%. The median PFS and OS were 11.6 months and 18.7 months, respectively. The median DOR was 14.7 months. The most common TRAEs of grade ≥3 were leukopenia (22.4%) and neutropenia (28.4%). Grade≥3 immune-related AEs were pneumonitis (1.5%), hepatitis (1.5%), and enteritis (1.5%). Of the 35 patients with sequencing results, the most common alterations were the TP53 mutation (86%), CDKN2A mutation (22%), FGF19 (26%), FGF4 (20%), FGF3 (20%), and CCND1 (20%) amplification. FGF19, FGF4, FGF3, and CCND1 amplification were associated with poor ORR, and CDKN2A mutation was associated with poor OS. Conclusions: Pembrolizumab combined with nab-paclitaxel and platinum shows encouraging antitumor activity accompanied by a manageable safety profile in untreated R/M HNSCC patients in China. CDKN2A mutation was a potential independent prognostic factors for this patient population. Clinical trial information: NCT04857164 . [Table: see text]
The role and mechanism of circadian clock gene BMAL1 in the proliferation and metastasis of nasopharyngeal carcinoma by inhibition TGF-β1/Smads pathway.
Authors: Chaofen Zhao , Jin Feng , Liu Lina , He Qianyong , Chen Yue , Shang Kai , Li Xiaomei , Xu Xinyu , Luo Xunyan 
Published: June 2024

6027 Background: To explore the molecular mechanism of biological clock gene BMAL1 inhibiting the proliferation and metastasis of nasopharyngeal carcinoma(NPC). Methods: 1. IHC detected the expression of BMAL1 in 41 cases of nasopharyngeal chronic inflammatory tissue and 71 cases of NPCtissue. PCR and Western blot measured the expression levels of BMAL1 in NP69 in NPC cells and human immortalized nasopharyngeal epithelial cells, respectively. 2. To detect the effect of BMAL1 on the proliferation capacity of NPCcells in vitro and in vivo; Scratch healing and Transwell invasion migration experiments detected the effect of BMAL1 on the invasion and migration ability of NPCcells in vitro. Fluorescence in vivo imaging and HE staining to determine the transfer of nude mouse tail intravenous injection model. PCR and Western blot detect the effect of BMAL1 on the expression of EMT-related markers at the transcriptional and protein levels in NPC cells. 3. A series of molecular biological means such as bioinformatics technology, ChIP experiment, double luciferase reporter gene experiment, immunofluorescence colocalization experiment and Co-IP were used to verify its mechanism. Results: 1. The expression of BMAL1 in NPCtissues and cells is reduced. The expression of BMAL1 in NPC tissues was associated with the M stage of nasopharyngeal carcinoma patients (p=0.006). 2. Overexpression of BMAL1 can inhibit the proliferation, invasion and migration ability of nasopharyngeal cancer cells, while knocking down BMAL1 is the opposite. Overexpression of BMAL1 inhibits EMT of NPCcells. 3. There are 5 BMAL1 binding sites in the TGF-β1promoter region, and BMAL1 can directly bind to the TGF-β1promoter region, which can inhibit the transcriptional activity of TGF-β1. Overexpression of BMAL1 inhibits TGF-β1/Smads pathway activity. Under the induction of recombinant human TGF-β1, the proliferation ability of NPC cells was enhanced, the activity of TGF-β1/Smads signaling pathway was enhanced, and nasopharyngeal cancer cells underwent EMT, and cell invasion and migration capacity increased. After overexpression of BMAL1, TGF-β1 no longer promotes TGF-β1/Smads signaling pathway activity, EMT is inhibited, and cell invasion and migration ability is weakened. BMAL1 combined with TGF-β1 has certain diagnostic value in predicting whether nasopharyngeal carcinoma metastasis. Conclusions: BMAL1 expression is downregulated in nasopharyngeal carcinoma, and its expression level is related to the development and metastasis of nasopharyngeal carcinoma. BMAL1 can inhibit the proliferation, epithelial-mesenchymal transformation and invasion and metastasis ability of NPC cells, and its mechanism is related to the inhibition of TGF-β1/Smads signaling pathway activity. It is speculated that it may become a new prognostic marker and therapeutic target for nasopharyngeal carcinoma.
Impact of immune-related adverse events (irAE) onset on disease response and survival in patients (pts) with head-neck cancer treated with immune check point inhibitors (ICI).
Authors: Patel Reema , Elghawy Omar , Barsouk Adam , Kaur Varinder 
Published: June 2024

6028 Background: ICI or combination chemo-immunotherapy are the mainstay of therapy for metastatic head-neck squamous cell carcinoma (mHNSCC) due to durable responses in certain pts. irAEs have emerged as a new challenge in the management of these pts. Some studies suggest a positive correlation between irAE onset and ICI efficacy in other cancers, however, whether such an association exists in HNSCC remains incompletely explored. Methods: We performed a retrospective, single-center cohort study of pts ≥ 18 years of age, with histologically confirmed mHNSCC who received ≥ 1 dose of ICIs at the University of Virginia Comprehensive Cancer Center, VA, USA between 2013-2022. Demographics, disease and treatment characteristics, and clinical outcomes related to irAEs and ICI re-challenge were analyzed. IrAEs were graded using CTCAE v4.0 criteria by chart review. Independent sample t-tests and chi-square analyses were used for univariate comparisons. Median PFS and OS from ICI therapy initiation were estimated using Kaplan-Meier methodology and censored at date of last follow up. P-values <0.05 were considered statistically significant. Results: Of 1979 pts who received ICI, 110 had mHNSCC (72.7% male; 84.5% White) with a median age of 62.4 years. ICI type included pembrolizumab or nivolumab in 109 pts, and nivolumab/ipilimumab in one pt. 53 (48%) pts experienced any grade irAE and 12 pts (11%) experienced >1 irAE. The most common irAEs were hypothyroidism (30.4%), dermatitis (14.3%), and hepatitis (10.7%). CTCAE ≥G3 irAEs were seen in 22.6% pts (n=12). These included hepatitis (n=3), colitis (n=3), hypothyroidism (n=1), arthritis (n=1), pneumonitis (n=1), adrenal insufficiency (n=1), vasculitis (n=1), and cardiomyopathy (n=1). Men (62% vs 37%, p= 0.015) and pts with prior radiation therapy (83% vs 17%, p=0.047) were more likely to experience irAEs. Treatment interruption/discontinuation occurred in 43% pts with irAEs. Topical/supportive therapy was required in 52.8%, and 35.8% required systemic corticosteroids, with more than half experiencing complete irAE resolution. A statistically significant association was observed between irAE onset and objective response rate (68% vs 39%, p= 0.009). 12 pts underwent ICI re-challenge, resulting in partial response in 3 (25%), stable disease in 4 (33.3%) and progressive disease in 3 (25%) pts. There was no statistically significant difference in PFS (4.9 vs 9.7 months, p = 0.731) or OS (30.5 vs 21 months, p = 0.159) in irAE vs non-irAE groups, respectively. Conclusions: irAEs onset was associated with improved best response to ICI therapy in mHNSCC. Although OS was numerically superior in the irAE group, it did not meet statistical significance. ICI re-challenge is feasible in select pts, however further studies are needed to evaluate long term benefit of ICI re-challenge.
Identifying patients at high risk of recurrence by rebound of plasma Epstein-Barr virus DNA in nasopharyngeal carcinoma.
Authors: Zhang Qixian , Zhou Xin , Xu Tingting , Shen Chunying , Qian Wei , Zhu Lin , Ying Hongmei , He Xiayun , Hu Chaosu , Lu Xueguan 
Published: June 2024

6030 Background: About 10-30% of patients with nasopharyngeal carcinoma (NPC) would develop disease recurrence following treatment. The optimal method to screen patients needing early medical intervention remains to be studied. We investigated the potential cut-off values of plasma EBV DNA in identifying patients at high risk of recurrence. Methods: From 2012 to 2020, 950 patients with detectable pre-treatment plasma EBV DNA and undetectable EBV DNA within 3 months after treatment were retrospectively reviewed. Survival outcomes of patients with different plasma EBV DNA rebound patterns were analyzed. The diagnostic performance of different cut-off values was evaluated in patients with ≥ 2 positive tests. Results: The number of patients with continuous negative plasma EBV DNA, only 1 positive test, and ≥ 2 positive tests during post-treatment surveillance were 747, 89, and 114, respectively. Patients with ≥ 2 positive plasma EBV DNA tests had worse PFS, LRRFS, and DMFS when compared with the ones with negative tests ( P < 0.001, P < 0.001, and P < 0.001) and only 1 positive test ( P < 0.001, P < 0.001, and P < 0.001). Superior PFS was observed for patients with negative tests compared to patients with only 1 positive test ( P = 0.006). Of 56 patients with more than 50 copies/ml plasma EBV DNA in both tests, 48 developed recurrences within 4 years. The sensitivity, specificity, PPV, and NPV of this cut-off for recurrence prediction were 35.8%, 99.0%, 85.7%, and 90.4, respectively. Then, the whole population was divided into the low-risk group (≤ 1 positive test), the intermediate-risk group (≥ 2 positive tests and at least one test had < 50 copies/ml) and the high-risk group (≥ 2 positive tests and both tests had ≥ 50 copies/ml). The PFS of the high-risk group was worse than that of the low-risk group ( P < 0.001) and the intermediate-risk group ( P < 0.001). The PFS of the high-risk patients with and without capecitabine or tegafur/gimeracil/oteracil before clinical confirmed relapse were 59.3% and 15.0% ( P = 0.004). Conclusions: NPC patients with ≥ 2 positive tests and ≥ 50 copies/ml in both tests during follow-up were at high risk of relapse. Early medical intervention could bring survival benefits to this cohort.
Long-term outcomes of anlotinib and penpulimab combined with chemotherapy in the treatment of patients with metastatic nasopharyngeal carcinoma that failed definitive platinum-based chemoradiotherapy.
Authors: Huang Shuang , Chen Xiaozhong , Qu Song , Qu Shenhong , Han Yaqian , Yang Kunyu 
Published: June 2024

6040 Background: The median progression-free survival (mPFS) of anti-PD-1 monoclonal antibody (mAb) plus gemcitabine (G) and cisplatin (C) in the first-line treatment of metastatic nasopharyngeal carcinoma (M NPC) is still limited in about 10 ~12 months. The tolerance is also unfavorable, especially for patients (pts) who had undergone platinum-based chemoradiotherapy (CRT) previously. We performed a phase 2 study to explore the potency of replacing cisplatin with anloinib (A), a multi-kinase inhibitor in combined with penpulimab (P), a novel anti-PD-1 mAb as the first-line treatment of M NPC for pts with prior explosure of platinum-based CRT. Here we report the updated long term outcomes of this study. Methods: This is a prospective, three cohorts, single-arm study. Eligible pts were aged 18 ~ 75 years old, diagnosed with NPC and developed metastasis after platinum-based CRT. Pts who were diagnosed as having M NPC at the first visit or experienced treatment failure within 6 months after definitive CRT or adjuvant therapy were excluded. Pts were randomized to receive G + A + P (cohort GAP), G + C + A + P (cohort GCAP) or G+C+P (cohort GCP). Gemcitabine (1000mg/m2, d1, d8) and cisplatin (80mg/m2, d1) were given intravenously for 4 to 6 cycles, 3 weeks per cycle. Penpulimab (200mg, d1) and anlotinib (10mg, qd, d1-14) were given intravenously and orally respectively until disease progression, or unacceptable toxicities. The primary endpoint was objective response rate (ORR). Results: 21 pts were randomized to three cohorts in lead-in phase while only cohort GAP was selected into expansion phase to enrolled another 7 pts. Finally, totally 28 pts were enrolled and received study treatment. The data cutoff date was December 1, 2023. The median follow-up was 20.2 month (95% CI: 17.0, 23.4). The results were summered in the table below. In cohort GAP, the confirmed ORR was 92.3% (95% CI: 64.0%, 99.8%) and the mPFS was still not reached (95% CI: NE, NE). The most common Grade 3 treatment-related adverse event (TRAE) was neutrophil count decreased (3 pts). Only one patient occurred Grade 4 TRAE (neutrophil count decreased) and no treatment-related death was observed. Conclusions: The long term outcomes of this phase 2 study preliminarily disclosed the advantage of the treatment regimen including gemcitabine, anlotinib and penpulimab as the first-line treatment of M NPC, especially for pts who had exposed to platinum-based chemotherapy. The further study with more sample size is warranted. Clinical trial information: NCT04736810 . [Table: see text]
Efficacy from the phase 1 study of FID-007, a novel nanoparticle paclitaxel formulation, in patients with head and neck squamous cell carcinoma.
Authors: Chow Lydia D. , Hsu Robert , Nieva Jorge J. , Umayam Rebecca , Smith Bryant Angela , Tsao-Wei Denice , Hsieh Ming , Yin Ray , El-Khoueiry Anthony B. , Thomas Jacob Stephen 
Published: June 2024

6042 Background: Patients with recurrent or metastatic squamous-cell carcinoma of the head and neck (HNSCC) have limited treatment options after progression on first-line immunotherapy with or without platinum-based chemotherapy. Taxanes in this setting have historically demonstrated response rates around 14-27%. FID-007 (FID) consists of paclitaxel encapsulated in a polyethyloxazoline (PEOX) polymer excipient designed to enhance PK, biodistribution, and tolerability. This allows the drug to remain in solution until it can enter a cancer cell and preferentially delivers paclitaxel to the tumor through the leaky hyperpermeable vasculature. Preclinically, FID was more effective at lower or comparable taxane doses, including nab-paclitaxel. In the phase I study of FID, we determined 125 mg/m2 as the recommended phase 2 dose. Here we present updated safety and efficacy data with emphasis on pts with HNSCC. Methods: The study evaluated the safety, PK, and preliminary efficacy of FID in pts with advanced solid tumors. The primary objective is to determine the MTD and RP2D. Pts received FID in doses between 15mg/m2 and 160mg/m2 using a 3+3 dose escalation. FID was given IV on Days 1, 8, and 15 of a 28-day cycle. Eligibility included ECOG 0-2, adequate organ function, and < 3 prior lines of cytotoxic therapy. Results: 46 patients were enrolled, of which 9 had HNSCC (2 nasopharynx, 2 sinonasal, 3 oropharynx, 1 oral cavity, and 1 occult primary). Median age (range) was 60 (53-75). ECOG PS was 1 in all HNSCC pts. Median number of prior therapies was 3 (1-5) and all had received prior immune checkpoint inhibitor. All grade treatment related adverse events (TRAEs) in ≥ 25% of pts included rash (72%), alopecia (52%), leukopenia (46%), pruritus (43%), neutropenia (41%), anemia (37%), fatigue (37%), nausea (28%), and anorexia (28%). Grade 3/4 TRAEs occurring in >1 pt were maculopapular rash (35%), neutropenia (20%), leukopenia (20%), anemia (17%), lymphopenia (7%), and febrile neutropenia (4%). No pts experienced > grade 2 peripheral sensory neuropathy; 20% experienced grade 1-2. Across all solid tumors, the overall response rate (ORR) was 17%. In patients with HNSCC, 5 (56%) had a partial response, 2 (22%) had stable disease, and 2 (22%) had PD. Three out of 5 HNSCC patients previously treated with a taxane achieved a partial response. Median duration of treatment was 4 months (1-15). Conclusions: FID demonstrates preliminary evidence of anti-tumor activity in heavily pre-treated HNSCC pts across different primary tumor sites, with an ORR 56%, including those with prior taxane exposure. A phase 2 study of FID with cetuximab in pts with HNSCC is planned to begin enrollment in 2024. Clinical trial information: NCT03537690 .
Characterizing the impact of sarcopenia on treatment response and survival in previously treated recurrent or metastatic nasopharyngeal carcinoma: Insights from a secondary analysis of the KL-A167 randomized trial.
Authors: Liu Zheran , Meng Dou , Li Huilin , Li Dong , Li Zhihui , Cai Lei , Zhou Jitao , Peng Xingchen 
Published: June 2024

6046 Background: The relationship between sarcopenia and adverse outcomes among patients with recurrent and metastatic nasopharyngeal carcinoma (R/M NPC) undergoing immunotherapy remains underexplored. This secondary analysis of the KL-A167 clinical trial data aims to elucidate the impact of sarcopenia on treatment efficacy and prognosis in this cohort, while also identifying potential mediating hematological biomarkers. Methods: A cohort of 148 patients enrolled in the KL-A167 clinical trial was analyzed. Logistic and Cox regression models were applied to assess the association between sarcopenia and treatment response, overall survival (OS), and progression-free survival (PFS), with adjustment for clinical prognostic factors. Counterfactual causal mediation analysis was conducted to identify hematological biomarkers potentially mediating the relationship between sarcopenia and prognosis in R/M NPC patients. Results: The presence of sarcopenia was significantly associated with reduced objective response rate (ORR: OR = 0.25, 95% CI = 0.08–0.81, p = 0.020) and disease control rate (DCR: OR = 0.23, 95% CI = 0.07–0.70, p = 0.010). Furthermore, sarcopenia was linked to inferior OS (HR = 2.07, 95% CI = 1.12–3.81, p = 0.020) and PFS (HR = 2.59, 95% CI = 1.48–4.54, p = 0.001). Notably, sarcopenia was characterized by elevated levels of neutrophil count, fibrinogen, and white blood cell count, alongside decreased creatine kinase levels. Fibrinogen emerged as the sole elevated biomarker significantly associated with both OS and PFS. Causal mediation analysis indicated that fibrinogen accounted for 23.5% of the association between sarcopenia and OS and 15.7% of PFS. Conclusions: Sarcopenia significantly correlates with poor treatment response and survival outcomes in patients with R/M NPC receiving immunotherapy. Targeting fibrinogen may offer a novel strategy to mitigate the negative impact of sarcopenia on patient survival.
Mapping the mental health correlates of head and neck cancer: A systemic review and meta-analysis.
Authors: Jiménez Labaig Pablo , Aymerich Claudia , Rullan Antonio , Llop Sandra , Brana Irene , Cacicedo Jon , Harrington Kevin Joseph , Catalan Ana 
Published: June 2024

6077 Background: Patients with head and neck cancer (HNC) present particularly high levels of mental health disorders. Yet the actual rate of relevant mental health symptoms and disorders, along with its determinants, remains unclear. Methods: A PRISMA/MOOSE-compliant systematic review and quantitative effects meta-analysis (PROSPERO: CRD42023441432) was conducted to determine the prevalence of depression, anxiety, distress, post-traumatic stress, insomnia and suicide among patients with HNC. MEDLINE, WebofScience, Cochrane Central Register, KCI-Korean Journal, SciELO, Russian Science Citation Index and Ovid/PsycINFO databases were searched from database inception to August 1, 2023. Secondary analyses were used to assess longitudinal trajectories of the samples over time. Results: 208 studies (n=713,527, median age 60.7; 25.5% female) were included. 19.5% patients reported depressive symptoms (95% confidence interval [CI]=17-21%), 17.8% anxiety symptoms (95%CI=14-21%), 34.3% distress (95%CI=29-39%), 17.7% post-traumatic symptoms (95%CI=6-41%) and 43.8% insomnia symptoms (95%CI=35-52%). Diagnostic criteria assessments revealed lower prevalence of disorders: 10.3% depression (95%CI=7-13%), 5.6% anxiety (95%CI=2-10%), 9.6% insomnia (95%CI=1-40%), and 1% post-traumatic stress (95%CI=0-84.5%). Pooled suicide incidence was 161.16 per 100,000 individuals per year (95%CI=82-239). A higher prevalence of anxiety was found in patients undergoing primary chemoradiation compared to surgery, and increased distress in smokers and advanced tumor staging. European samples exhibited lower prevalence of distress. Patients were more likely to be depressed after finishing radiation treatment. Conclusions: Patients with HNC exhibited a notable prevalence of mental health issues across various domains, where suicide emerged as a particular concern. There is a need for improved methods of assessment and intervention for these mental health concerns. Preventive interventions should be implemented before the start of radiation treatments. [Table: see text]