bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlation between irAEs and treatment efficacy of anti-PD-1 single agent in patients with recurrent/metastatic head and neck squamous cell carcinoma: A monocentric real-world observational study.
Authors: Gottardi Chiara , Anile Giuseppe , Micheletto Ilaria , Krengli Marco , Carobbio Andrea Luigi Camillo , El Khouzai Badr , Taboni Stefano , Pretto Greta , Guarneri Valentina , Ghi Maria Grazia 
Published: June 2024

6029 Background: Immune-related adverse events (irAEs) are associated with efficacy of ICIs-based treatment in various cancer types. The aim of this retrospective study was to assess the relationship between irAEs and outcomes in patients with recurrent/metastatic Head and Neck squamous cell carcinoma (R/M-HNSCC) treated with immune checkpoint inhibitors (ICIs) monotherapy. Methods: We retrospectively reviewed data from patients with R/M HNSCC treated with ICIs single-agent between January 2018 and June 2023 at the Istituto Oncologico Veneto of Padua. Common Terminology Criteria for Adverse Events v.5.0 was used to assess irAEs evaluation. Patients were stratified into irAEs (any grade) and non-irAEs groups. Overall survival (OS) and progression free survival (PFS) were assessed using the Kaplan-Meier method. Univariate and multivariate Cox-regression were used to compare survival outcomes. The chi-square test was used to assess the association between irAEs and objective responses (ORR). Results: A total of 89 patients were eligible for the analysis. Patients with platinum-refractory disease received nivolumab (64 patients, 72%). All the 25 patients (28%) with platinum-sensitive disease were PD-L1 positive (CPS≥1) and received pembrolizumab as first line treatment for R/M disease. Median follow-up was 8.7 months. IrAEs (any grade) were observed in 60 patients (67%), including 9 patients (10%) with grade ≥3 AEs. The most common irAEs were endocrinopathies (35%), skin events (15%), hepatic events (13%), diarrhea/colitis (10%) and lipase/amylase elevation (10%). The ORR was higher in the irAEs group than in the non-irAEs group (19.5% vs 2%, p=0.017). PFS and OS were also significantly longer in the irAEs group: median PFS was 3.9 months vs 2.1 months (HR 0.48 95% CI 0.30-0.77; p=0.003) and median OS was 12.5 months vs 4.3 months (HR 0.36 95% CI 0.21-0.60; p=0.000). The statistically significant benefit for both PFS and OS was confirmed at the multivariate analysis (Table1). Patients who experienced endocrine-related irAEs (p=0.004), diarrhea/colitis (p=0.040) and lipase/amylase increase (p=0.005) had significantly longer OS than those without the corresponding toxicity. A positive trend was observed for skin toxicity (p=0.051). Conclusions: The occurrence of irAEs was a predictor of response and survival outcomes in patients with R/M HNSCC treated with ICIs single-agent.[Table: see text]
Significance of imaging-detected extranodal extension (iENE) in locally advanced head and neck squamous cell carcinoma (LASCCHN) treated with induction chemotherapy followed by chemoradiotherapy.
Authors: Onaga Ryutaro , Enokida Tomohiro , Hiyama Takashi , Tanaka Nobukazu , Hoshi Yuta , Tanaka Hideki , Fujisawa Takao , Okano Susumu , Kuno Hirofumi , Tahara Makoto 
Published: June 2024

6034 Background: Extranodal extension (ENE) of nodal metastasis is a significant prognostic factor in p16-negative SCCHN and is classified as N3b by the AJCC 8th edition. Therefore, pretreatment determination of ENE has significant clinical implications in SCCHN, and iENE has just recently been proposed. We previously discussed association with pathological ENE and iENE (Jpn J Radiol. 2020;38(6):489-506.). However, the role of iENE in non-surgical sequential therapy remains unclear. Methods: We retrospectively reviewed patients with LASCCHN originating from the oropharynx, hypopharynx, and larynx who received enhanced computed tomography (CT), then treated with induction chemotherapy (IC) with paclitaxel, carboplatin, and cetuximab followed by chemoradiotherapy (CRT) from 2013 to 2022 in our hospital. Two radiologists specializing in head and neck cancer blindly annotated the status of iENE in baseline CT images by the previously reported criteria (Oral Oncol. 2022;125:105716.). Multivariate analysis variables for event-free survival (EFS) and overall survival (OS) included the presence or absence of iENE, a response to IC, clinical T-category, performance status, smoking status, etc. Results: In the 88 patients, 67 (76.1%) had iENE and 21 (23.9%) did not at baseline. In the former and latter group, stage II/III/IV were 10.4%/26.9%/62.7% and 0%/28.6%/71.4%, HPV-positive were 37.3% and 28.6%, respectively. With the median follow-up of 37.4 months (range: 6.7-108.8), the former had significantly shorter EFS (3-y EFS: 41.9% vs. 75.6%, hazard ratio [HR]; 2.9 (1.2-7.4), p-value; 0.02) and OS (3-y OS: 72.8% vs. 100%, HR; Inf (0.01-Inf), p-value=0.003). Multivariate analysis identified the presence of iENE (HR for EFS: 2.80, 95%CI: 0.97-8.05, HR for OS: 2.93, 95%CI: 1.01-8.44) and unresponsiveness to IC (HR for EFS: 2.47, 95%CI: 1.31-4.68, HR for OS: 2.87, 95%CI: 1.13-7.26) as mutually independent unfavorable prognostic factors for both EFS and OS. Furthermore, classification based on the two factors could identify the population with a worse prognosis (Table). Conclusions: In the sequential therapy of IC followed by CRT, the current study revealed for the first time that subjects with an iENE at baseline, together with an unsatisfactory response to IC would require special attention, such as more intensified post-treatment follow-up as well as additional therapeutic interventions to improve their prognosis. [Table: see text]
Trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2-expressing head and neck tumors: Outcomes from DESTINY-PanTumor02 (DP-02).
Authors: Meric-Bernstam Funda , Kim Seung Tae , Parinyanitikul Napa , Moreno Alberto , Lin Chia-Chi , Gornastolev Dmitry , Chindaprasirt Jarin , Lugowska Iwona A. , Stroyakovskiy Daniil , Jassem Jacek , Harrison Michelle L. , Ostwal Vikas S. , Michelini Flavia , Jung Lindsey , Kuptsova-Clarkson Nataliya , Puvvada Soham D. , Gan Hui Kong 
Published: June 2024

6037 Background: In DP-02, T-DXd demonstrated an objective response rate (ORR) by investigator (INV) of 37.1% (95% CI 31.3, 43.2) and clinically meaningful survival outcomes in 267 pretreated pts with HER2-expressing tumors. In this post-hoc analysis, we report outcomes and characterize those with an objective response (OR) in a subset of pts with head and neck cancers (previously included in the ‘other tumor’ cohort), most of which were salivary gland tumors. Methods: This open-label, Phase 2 study (NCT04482309) evaluated T-DXd (5.4 mg/kg Q3W) in pts with HER2-expressing (immunohistochemistry [IHC] 3+/2+ by local or central testing) locally advanced/metastatic disease after ≥1 systemic treatment or without treatment options. The primary endpoint was confirmed ORR by INV. Secondary endpoints included duration of response (DOR), progression-free survival (PFS), disease control rate (DCR), and safety. Exploratory endpoints included efficacy outcomes by HER2 expression. Results: At data cutoff (June 2023), 24 pts with head and neck tumors (n=19 salivary gland, n=3 squamous cell carcinoma [SCC], n=1 adenoid cystic carcinoma, n=1 lacrimal gland) had received treatment (median [m] follow up: 20.8 months [range: 4.7–31.6]). Of these pts, 15 (62.5%) had received ≥2 prior treatment regimens. 10/24 pts (41.7%; 95% CI 22.1, 63.4; n=8 salivary gland, n=1 SCC, n=1 lacrimal gland) had a confirmed OR by INV; 9 responders had received prior radiation therapy, and 4 had known PD-L1 immune cell status ≥1%. The Table shows efficacy outcomes in all pts and by HER2 expression (central testing). Grade (G) ≥3 drug-related adverse events occurred in 10/24 (41.7%) pts. Adjudicated drug-related interstitial lung disease / pneumonitis occurred in 3/24 (12.5%) pts (n=1 G1; n=1 G2; n=1 G5). Conclusions: T-DXd showed clinically meaningful benefit in pretreated pts with head and neck tumors. Responses were observed across HER2 expression levels. Safety was consistent with the known profile. These data support T-DXd as a potential treatment for pretreated pts with HER2-expressing head and neck tumors. Clinical trial information: NCT04482309 . [Table: see text]
A phase II study of nivolumab in patients with recurrent or metastatic carcinosarcomas.
Authors: Kim Miso , Hong Jung Yong , Kim Min Hwan , Jung Minkyu , Kim Gun Min , Kim Kyoo Hyun , Yun Kum-Hee , Shin Su-Jin , Lee Young Han , Park Jiwoo , Lee Jeeyun , Kim Hyo Song 
Published: June 2024

6041 Background: We aimed to determine the activity of anti-PD-1 inhibitor, nivolumab in metastatic and/or recurrent carcinosarcoma. Methods: In this phase 2 trial, eligible patients had histologically confirmed metastatic and/or recurrent carcinosarcoma, measurable disease, 1-3 prior chemotherapy, and adequate renal/hepatic/hematologic function. In this single arm phase 2 trial, treatment consisted of nivolumab 3 mg/kg every 2 weeks. Primary outcome was progression free rate (PFR) at 6 months and secondary outcomes included overall response rate, progression-free survival (PFS), overall survival, and safety. Results: Between July 2020 and Nov 2023, 28 patients enrolled and received trial treatment. As of the time of data cut-off (Feb 1, 2024), 4 remains on treatment. Of the 28 patients evaluable, 4 (14.3%) achieved confirmed partial response, and 9 (32.1%) had stable disease, yielding and disease control rate of 46.4%. The median PFS was 2.6 months. The pre-specified primary endpoint was met with 6-months PFR of 30.8%. The common-treatment related adverse events included urticaria (5 [17.9%]), dyspepsia (4 [14.3%]), elevated aspartate aminotransferase (3 [10.7%]), and anemia (3 [10.7%]). The genomic analysis will be available at the meeting. Conclusions: Nivolumab demonstrated promising efficacy with favourable toxicity profile in metastatic/recurrent carcinosarcoma. Clinical trial information: NCT05224999 .
Associations of ctDNA clearance and pathological response after neoadjuvant treatment in patients with locally advanced oral cancer.
Authors: Zhong Lai-ping , Zhou Zhi-hang , Huang Ying-ying , Zhang Yi-yi , Lu Yi , Li Bing , Wang Jing , Zhao Tong-chao , Ju Wu-tong , Zhu Dong-wang 
Published: June 2024

6043 Background: Neoadjuvant treatment (NAT) has improved clinical outcomes in some patients with locally advanced oral squamous cell carcinoma (LAOSCC). Effective biomarkers assessing the treatment response is still lacking. Previous studies have posed the potential of circulating tumor DNA (ctDNA) in monitoring treatment response, but the underlying mechanisms behind non-shedding in tumors remain unclear. Methods: 29 LAOSCC patients received NAT followed by surgery were enrolled. Seven (24.1%), 9 (31%), and 13 (44.8%) patients received NAT of apatinib+camrelizumab, TPF chemoagents, and toripalimab+paclitaxel+cisplatin, respectively. Tumor tissues before NAT underwent whole exome sequencing and whole transcriptome resequencing. Blood samples at pre-NAT (T0), mid-NAT (T1), before surgery (T2) and after surgery (T3) were analyzed using a tumor-informed, personalized NGS assay. Multi-omics analysis, including ctDNA status, was performed with patients' clinical features and outcomes. Results: Among the 29 patients received NAT, the MPR rate was 55.2% (16/29), and the pCR rate was 27.6% (8/29). At baseline(T0), ctDNA was detectable in 25/29 (86.2%) patients, which decreased over time (T1: 77.8%; T2: 51.7%; T3: 6.9%). Persistent ctDNA at T2 indicates a higher rate of residual disease after NAT (100% non-pCR) compared to ctDNA-negative patients (42.8% non-pCR; p = 0.0047). All patients achieving pCR at T2 were ctDNA-negative (n=8, 100%) including 2 non-shedders. The PPV and NPV for predicting pCR by ctDNA clearance at T2 were 57.1% (8/14) and 100% (15/15), respectively. ARSF, CFAP47, or HAUS8 mutations at baseline were associated with significantly higher pCR rates (p<0.05). Four non-shedders with undetectable ctDNA at T0 were significantly enriched in patients with negative lymph nodes, lower clinical T stage, and high CPS score. The non-shedders had significantly lower tumor mutational burden (TMB), higher stromal score and cancer-associated fibroblast (CAF) (p<0.05). Spatial transcriptome analysis further supports that MHC-II pathway-related genes were significantly up-regulated in the non-shedders. The enhancing communication intensity between CAFs, endothelial cells and T cells might provide an anti-cancer immune microenvironment for non-shedders. Conclusions: Our results indicate that the clearance of ctDNA clearance at T2 was associated with an improved pCR rate. Furthermore, our findings shed light on the factors that prevent ctDNA release from oral squamous cell carcinoma.[Table: see text]
Tislelizumab plus neoadjuvant chemotherapy and concurrent chemoradiotherapy versus neoadjuvant chemotherapy and concurrent chemoradiotherapy in local advanced nasopharyngeal carcinoma.
Authors: Luo Haiqing , He Jiaqi , Yi Guihua , Tang Haifeng , Yang Donghong , Li Haiwen , Yu Ying , Chen Zihong , Zhan Dechao 
Published: June 2024

6045 Background: Given the recent successes of immunotherapy in local advanced nasopharyngeal carcinoma (LA-NPC), maybe it is promising to achieve better response and improve the survival of LA-NPC if immunotherapy plus neoadjuvant and concurrent chemoradiotherapy (CCRT). Therefore, we retrospectively analysed the safety and efficacy of tislelizumab plus neoadjuvant chemotherapy and CCRT and neoadjuvant chemotherapy followed CCRT in the treatment of LA-NPC. Methods: A total of 90 patients with stage III-IVa NPC were enrolled between January 2020 and March 2021 at Affiliate Hospital of Guangdong Medical University. 43 patients were treated with tislelizumab plus TP (nab-paclitaxel 260mg/m2, cisplatin 80mg/m2, Q3W, 3 cycles) regimen followed tislelizumab plus CCRT as the combination therapy group (CG) and 47 patients were treated with TP regimen followed CCRT as the observation group (OG). Results: As of January 30th, 2024, the median follow-up time is 37.5 months. The median age was 42 years (range: 16–75 years). A total of 37 patients had stage III cancer and 53 had stage IVa , with 43 and 47 patients in OG and CG, respectively. The male–female ratio in the entire cohort was approximately 2.15:1. All reported parameters were balanced between the two groups with no statistical differences. The complete response rate (CRR) in CG after neoadjuvant therapy improved significantly (37.2% in CG vs 12.8% in OG). The ORR was 88.4% in CG and 70.2% in OG, respectively. The 3-year PFS was 93.75% in CG and 80% in OG. The incidence of acute treatment related adverse events in grades 3 or 4 was 70.2% and 65.6%, respectively. The most common grade 3-4 immune-related adverse events were hypothyroidism (7.0%) and hepatotoxicity (4.7%). No patients in CG had disease progression during treatment. Conclusions: Compared with regular treatment, tislelizumab plus neoadjuvant chemotherapy and concurrent chemoradiotherapy was feasible and well tolerated in LA-NPC patients. This trial is supportive of further prospective trials in LA-NPC.
The potential prognostic value of the head and neck advanced lung inflammation index (HN-ALI) for patients treated with immunotherapy.
Authors: Filippini Daria Maria , Carosi Francesca , Fermi Matteo , Trudu Lucia , Cabitza Eleonora , Napolitano Martina , Depenni Roberta , Nobili Elisabetta , Dominici Massimo , Molteni Gabriele , Bertolini Federica 
Published: June 2024

6052 Background: The ALI is recognized as a potential prognostic and predictive biomarker for patients (pts) treated with immune checkpoint inhibitors (ICIs) in non-small-cell lung cancer. In head and neck squamous cell carcinoma (HNSCC) its prognostic role has been acknowledged in locally advanced setting. We evaluated whether HN-ALI could provide similar value in pts with recurrent/metastatic (R/M) HNSCC undergoing treatment with ICIs. Methods: We conducted a multicentric observational retrospective study including R/M HNSCC pts treated with ICIs alone or in combination with chemotherapy from April 2016 to November 2023. The ALI was calculated as follows: BMI (kg/m2) × serum albumin (g/dL)/neutrophil-to-lymphocyte ratio (NLR). Using the bibliographic cut off value of 18, pts were divided into two groups: ALI < 18 (high inflammation) and ALI > 18 (low inflammation). The primary outcomes were overall survival (OS) and progression free survival (PFS), evaluated with the Kaplan-Meier estimator. Cox proportional hazard regression models were employed to perform multivariate analysis. Results: A total of 145 pts [105 males, median (m) age 66 years, 128 with ECOG PS < 1] were treated with ICIs (35% nivolumab, 64% pembrolizumab) across two Italian centers. Primary tumor sites were: oral cavity (35%), oropharynx (33%), larynx (14%), hypopharynx (7%), other (9%). ICIs were administered as single agents in 86 pts and in combination with chemotherapy in 59 pts. The HN-ALI was collected for 92 pts. The mPFS was 6 months (95%CI, 2.16-9.83) within the ALI group > 18 versus 1 month for the ALI group < 18 (95%CI, 0.26-1.73) (p< .001); analogously, the mOS was 17 months (95%CI, 11.63-22.36) versus 2 months (95%CI, 0.68-3.32) for the ALI group > 18 and < 18, respectively (p< .001). At the multivariate analysis, high ALI score represented an independent risk factor for better OS, also including ECOG PS and PD-L1 expression [HR 0.38; (95% CI,0.15 – 0.96), p= .042], while showing a trend towards longer disease progression [HR 0.52; (95% CI, 0.26 - 1.02), p= .058]. Conclusions: In our experience, ALI value >18 is associated with better prognosis in pts treated with ICIs alone and in combination with chemotherapy. Further analyses are warranted to validate the prognostic relevance of the ALI value in pts with HNSCC undergoing ICIs.
Features of HPV+ OPSCC predictive of recurrence identified by transcriptional profiling of a case-control cohort.
Authors: Basu Devraj , Sannigrahi Malay Kumar , Raghav Lovely , Sun Lova , Cohen Roger B. , Gimotty Phyllis A. , Jalaly Jalal , Pearson Alexander T. 
Published: June 2024

6055 Background: De-escalating therapy for HPV+ oropharyngeal cancers (OPSCCs) is hampered by poor ability to predict recurrence, and limited insight into the biologic traits predisposing to recurrence impedes personalizing therapy. We aimed to (1) define biologic features underlying therapy resistance by transcriptional profiling and (2) evaluate the features for prognostic utility. Methods: A single institution cohort of 851 HPV+ OPSCC patients undergoing transoral robotic surgery during 2007-2020 was used to identify 50 cases that recurred locoregionally in the adjuvant RT field (n=14) and/or at distant sites (n=43). As controls, we used 49 recurrence-free patients with long-term follow up and similar stage, smoking history, and adjuvant therapy. RNAseq of pretreatment tumors was used to compare individual gene expression and Hallmark/Kegg pathway activity between cases and controls using unpaired t-test (p<.05) and Gene Set Enrichment Analysis (p-adj<.05), respectively. Activity of the significant pathways was quantified in individual tumors using Gene Set Variation Analysis (GSVA), and a regression-based composite of GSVA scores was developed to distinguish cases from controls by ROC analysis. The composite score was used to test for stratification of recurrence free survival (RFS) in external cohorts using Youden Index and logrank test. Results: The21 Hallmark/Kegg pathways downregulated in cases indicated suppression of anti-tumor immunity, and the 20 upregulated ones revealed increased biosynthetic function and tumor cell proliferation. The 1472 upregulated mRNAs contained several components of the ATR-chk1 DNA repair pathway and trans-lesion synthesis polymerases, suggesting that mitigation of DNA replication stress enhanced tumor growth. The 958 downregulated mRNAs suggested reductions in the cytoplasmic dsDNA sensing and downstream NF-kB signals that lead to replication stress-driven anti-tumor immunity. Two GSVA scores were created to quantify the key tumor-intrinsic and immune suppressive features separately in each tumor. The scores correlated with each other (R=0.6, p<.001), and a regression-based combination of them distinguished cases from controls (AUC=.76, p<.001). This composite score also stratified RFS in three external cohorts: TCGA (n=52, p<0.001) and two single institution cohorts containing both surgical and nonsurgical cases (n=46, p=.002; n=81, p<0.001). Conclusions: HPV+ OPSCCs failing primary surgical therapy show evidence of reduced replication stress mediating tumor progression and low anti-tumor immunity. These features appear generalizable to heterogeneously treated external cohorts, where they predicted recurrence. Our results provide a new basis for creating transcriptomic predictors of treatment response and suggest targetable molecular mechanisms to overcome therapy resistance.
Can TTMV clearance predict recurrence in HPV HNSCC?
Authors: Misiukiewicz Krzysztof , Worona Leslie Anne , Ramos Emily J , Bakst Richard Lorne , Sindhu Kunal K. , Westra William , Roof Scott , Genden Eric Michael , Posner Marshall R. 
Published: June 2024

6066 Background: Patients with locally advanced (LA) HPV HNSCC are treated with various types of induction chemotherapy (IC) followed by standard (sd) or reduced (rd) chemoradiation (CRT). Tumor tissue-modified viral HPV DNA (TTMV) pairs with PET-CT in predicting an early detection of treatment failure in HPV-related HNSCC. Mid-treatment TTMV assessment in HPV-related HNSCC can help identify patients who are eligible to receive a lower dose of IC and/or CRT or those who may require close follow-up. Methods: Patients with LA HPV+ HNSCC with high-risk features (radiographic ECE, T4 primary, >N2c) and <20 pack-year (py) smoking history were treated with IC followed by rdCRT (56 Gy); sdCRT (70 Gy) was used in non-responders. 16/23 received IC with TPF, 1/23 TP, and 6/23 TP-PD1, and all patients received carboplatin weekly with their CRT. Regeneron trial patients who received TP-Cemiplimab (PD1) IC followed by sdCRT are also continuing adjuvant Cemiplimab alone for 6 months (NCT05376553). PET-CT-confirmed residual, recurrent, or metastatic diseases were defined as treatment failures; TTMV + patients only if PET-CT confirmed. Results: 23 subjects treated with IC followed by CRT between 2/4/21-1/26/24, who had pre- and post-treatment TTMV were included in our analysis. The median pre-IC TTMV was 8082 (27 – 90770). The median follow-up time from treatment start was 21 months. 9/23 patients had full clearance TTMV after 1 cycle of IC defined as rapid responders (RR). 11/23 patients still had positive TTMV after 1st cycle of IC were defined as slow responders (SR). 1 patient had no TTMV done after 1 cycle of IC but was elevated after 2nd IC; he was defined as SR. 2 patients had a positive pre-IC TTMV, but no TTMV was drawn during IC to see if RR. 1 of 2 patients was TTMV negative prior to CRT, and 2/2 had a 1st post IC negative TTMV done 1 week after CRT started. They were both included in the analysis but defined as unknown response status. TTMV testing was done for all 23 subjects after CRT; all were negative. All subjects have TTMV testing done during their surveillance visits. Among 9/23 RR, none developed a failure. Among 12/23 SR, 3 patients developed a failure: 1/3 was TTMV+ but PET-, being followed with TTMV and PET-CT; and 2/3 were confirmed failures, TTMV+ and PET+; 1 locoregional, 1 metastatic. 2 patients were not known to be a SR or RR and had no recurrence. Among 23 patients, NPV of TTMV to detect failure was 100%, but PPV was 96% (1/23). Conclusions: IC followed in rapid clearance of TTMV in 39% of patients, and all remained disease-free. 3/11 (27%) with persistently elevated TTMV after cycle 1 relapsed as of this time point. This small study was not large enough to be practice-changing. However, this is significantly hypothesis-generating and should be tested in a larger trial to help identify patients for de-escalation (RR) or closer surveillance (SR).