bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of molecular profiles of head and neck squamous cell carcinoma with heterogeneity across racial/ethnic groups in the United States.
Authors: Bhayani Mihir K , Jaeger Ellen B. , Al-Khudari Samer , Stenson Kerstin , Joshi Nikhil , Godden Jen , Stoppler Melissa Conrad , Jelinek Michael J. 
Published: June 2023

e18036 Background: Significant disparities exist across the head and neck cancer (HNC) care continuum in presentation, treatment, and survival. Along with demographic factors such as race or ethnicity, tumor-specific molecular signatures may play a role in these differences. In the United States, the current body of literature mainly highlights molecular contrasts between Black and White patients. Here, we further investigate the molecular profiles of Black and White patients with HNC and add to the literature by comparing additional racial/ethnic groups in a large, real-world cohort. Methods: De-identified records of patients with a primary diagnosis of HNC who underwent Tempus xT testing (Tempus Labs, Chicago, IL) were selected from the Tempus Database. Those with squamous cell histology and self-reported race were selected for retrospective analysis. Briefly, Tempus xT is a targeted, tumor/normal-matched panel that detects single-nucleotide variants, insertions and/or deletions, and copy number variants in 648 genes, as well as chromosomal rearrangements in 22 genes with high sensitivity and specificity. Tumor mutational burden (TMB) was calculated by dividing the number of nonsynonymous mutations by the megabase size of the panel. Results: Among the 749 patients included, most identified as Non-Hispanic/Latino (NHL) White (n = 570), while 62 identified as NHL Black, 44 as NHL Asian/Pacific Islander (API), 21 as NHL of other races, and 52 as Hispanic/Latino of any race. Age at diagnosis differed between races ( P= 0.009). Oral cavity was the most common subsite in our cohort (N = 306, 41%). TMB also differed among races ( P= 0.018), with Black patients demonstrating the highest TMB (median = 4.6 mut/Mb [3.0-6.2]) and API the lowest (median = 2.3 mut/Mb [1.5-4.2]). Black patients had higher proportions of TP53 (76%), KMT2D (24%), and CTTN (15%) alterations (not significant across races). There were differences in the frequencies of OR4G11P (q = 0.031) and OR4F5 (q = 0.014) aberrations between races, with Black patients showing the highest frequencies (16% and 15%, respectively). The API population demonstrated higher frequencies of RASA1 (16%), MTAP (11%), CDKN2B (32%), and ERCC3 (11%) mutations (not significant across races). Additionally, there were differences in TERT mutations between races (q = 0.01), with API harboring the highest proportion of TERT co-mutations (52%). Conclusions: Overall, these results demonstrate that molecular profiles are heterogeneous across multiple racial/ethnic groups. Many of the alterations described here have been previously associated with outcomes in HNC. Accordingly, future investigations should aim to understand the effects of the activated pathways for clinical utility and investigate biomarkers to drive individualized treatment plans that result in equitable care.
Rapid establishment of patient-derived organoids from treatment-naive head and neck cancer patients for drug and radiosensitivity screening.
Authors: Tinhofer Inge , Fisch Anne-Sophie , Pestana Ana , Doll Christian , Heiland Max , Dommerich Steffen , Obermüller Theresa , Hofmann Veit Maria , Klinghammer Konrad Friedrich , Piwonski Iris , Schallenberg Simon , Zips Daniel 
Published: June 2023

e18043 Background: Patient-derived organoids (PDOs) have been shown to be powerful tools for modeling disease and patient-individualized drug sensitivity screening, opening a novel avenue to precision medicine. A major challenge for guidance of clinical decisions is the extended time frame for establishing these models. Here, we report the feasibility of a refined protocol for PDO generation from head neck squamous cell carcinoma (HNSCC) tumors, suitable to guide personalized treatment decisions in the curative setting. Methods: After informed consent, tumor tissue specimens from 145 newly diagnosed HNSCC patients were collected during diagnostic biopsy or curative surgery. Following mechanic / enzymatic dissociation and initial expansion in 2D cultures, tumor cells were seeded in extracellular matrix (Matrigel) to form PDOs. Primary endpoint of the study was the PDO engraftment rate. In additio, the time needed for ex vivo expansion of PDO cultures for personalized drug/radiosensitivity testing was determined. Interference of patient and tumor characteristics with PDO engraftment was analyzed using SPSS version 27. Results: The PDO engraftment rate in the entire cohort was 51% (n = 74 of 145 patients). Neither tumor stage, grading, anatomical sublocalisation, HPV status nor sample type (biopsy vs. surgical specimen) were significantly associated with PDO establishment. Of note, Kaplan-Meier analysis revealed a trend between successful ex vivo engraftment and reduced overall survival (log-rank: p = 0.09), suggesting preferential engraftment of aggressive poor prognosis tumors. Engraftment rate in the subgroup of patients with recommendation for adjuvant chemoradiation was 58%. Time for expansion of PDO cultures for subsequent drug/radiation screening was 18.5 ± 9.6 days (median ± SD). Expansion was completed before start of adjuvant chemoradiation in all but one cases. Conclusions: Our study suggests feasibility of PDO generation for locally advanced aggressive HNSCC within a timeframe suitable for guiding treatment decisions for adjuvant therapy. Planned future directions include clinical validation of drug testing results for individual patients and clinical study cohorts.
Positive margin and advanced depth of invasion as the indicators for assessing the necessity of adjuvant chemoradiotherapy in early-stage oral cavity squamous cell carcinoma.
Authors: Lu Hsueh-Ju , Chiu Yu-Wei , Peng Chih-Yu , Tseng Hsien-Chun , Hsin Chung-Han , Chuang Chun-Yi , Chen Chun-Chia , Wu Ming-Fang , Huang Wei-Shiou , Yang Sung-Fa 
Published: June 2023

e18052 Background: Adjuvant therapy was indicated for patients with a high risk of disease progression after curative therapy, and RTOC 9501/EORTC 22931 were the landmark studies for assessing the necessity of adjuvant therapy in oral cavity squamous cell carcinoma (OCSCC). However, the role of adjuvant therapy in early-staging OCSCC, which was redefined by the 8th edition American Joint Committee on Cancer (AJCC) staging system, was unknown. Methods: A total of 485 early-staging OCSCC patients (pT1-2N0) diagnosed between Jan 2010 and Dec 2019 were retrospectively enrolled. All of them were newly diagnosed and reevaluated to meet the criteria of the 8th edition AJCC staging system. Adjuvant therapy was discussed and concluded in the combined conference of the head and neck multidisciplinary team at Chung Shan Medical University Hospital. And the enrolled patients were divided into the groups with or without adjuvant therapy. The effectiveness of adjuvant therapy and prognostic factor for locoregional recurrence-free survival (LRFS) were analyzed. Results: Nearly one-sixth (16.1%, 78/485) of the enrolled patients received adjuvant therapy. The patients with adjuvant therapy were worse in pathologic T staging ( P < 0.001), histologic grade ( P < 0.001), and pathologic features (depth of invasion [DOI] > 4mm, P < 0.001; perineural invasion, P < 0.001) than those without. Positive margin and advanced DOI ( > 4mm) were the independent factors for LRFS. Adjuvant therapy did not improve LRFS that the 3-year LRFS of the patients with or without adjuvant therapy were 79.7% and 81.5%, respectively ( P = 0.718)(hazard ratio [HR], 95% confidence interval [CI]: 1.10 [0.67-1.80]). However, adjuvant chemoradiotherapy (CRT) indeed prolonged LRFS in some subgroups, such as those with positive margin or advanced DOI (the subgroup with positive margin, 3-year LRFS of those with or without adjuvant therapy, 100% and 58.8%, HR[95% CI]: 0.04[0.00-267.330]; the subgroup with advanced DOI, 3-year LRFS, 83.3% and 73.1%, HR[95% CI]: 0.48[0.16-2.01]). In addition to positive margin, advanced DOI was the most critical correlation coefficient factor among the pathologic features, including pathologic T staging, perineural invasion, lymphovascular invasion, poorly differentiated, and close margin. For the patients eligible for evaluation, forty percent (40.1%, 180/439) of the patients were diagnosed with positive margins or advanced DOI and these patients might be considered to receive adjuvant CRT in the future. Conclusions: Positive margin and DOI were the most important indicators to evaluate the necessity of adjuvant CRT in early-staging OCSCC. Future warranted studies were needed.
Association of patient and tumor characteristics with outcomes in young patients with head and neck squamous cell carcinoma (HNSCC).
Authors: Hsieh Ronan Wenhan , Gooding William E. , Nilsen Marci Lee , Kubik Mark , Kelly Zahra Rahman , Sridharan Shaum , Skinner Heath Devin , Iheagwara Uzoma K. , Zevallos Jose , Duvvuri Umamaheswar , Kim Seungwon , Ferris Robert L. , Zandberg Dan Paul 
Published: June 2023

e18054 Background: HNSCC is increasingly being diagnosed in a younger population, with a variable prognosis. While studies have evaluated outcomes in young compared to older patients, evaluation of prognostic factors specifically in younger patients, that may help guide treatment decisions, is needed. Therefore, we conducted a retrospective study to investigate the association of patient and tumor characteristics with disease specific survival (DSS) in HNSCC patients ≤45 years old (yo). Methods: Patients treated at the University of Pittsburgh Medical Center from January 1, 2007 to June 30, 2020, that were ≤45 yo at time of diagnosis with HNSCC without distant metastatic disease, were included. Those who received treatments at other institutions and who had no follow-up after index treatments were excluded. Patient demographics, social history, tumor pathology and treatment course were collected. The primary endpoint of DSS was defined as the interval between the time of pathologic diagnosis and the time of cancer-related death. Proportional hazards regression was applied separately for surgically and non-surgically treated patients. A multivariate analysis was conducted for surgically treated patients only. Results: 230 patients were included. Median age was 42, 73% male, 45% oral cavity primary, 35% oropharynx (89% Human papillomavirus positive), 14% larynx, 69% were smokers, and 73% received combined modality therapy. 35% of patients had a recurrence with the majority locoregional only (61%). Median DSS was not reached. The 5 year DSS was 73% (95% CI 67% to 80%). There was no difference in DSS between surgically treated (n = 169) and non-surgically treated (n = 61, p = 0.94) patients. For surgically treated patients, univariate analysis showed significantly worse DSS in those with higher pathologic T and N stages, positive margins, perineural invasion (PNI), extranodal extension (ENE), and negative HPV status. For non-surgically treated patients, only negative HPV status was associated with significantly worse DSS (p = 0.034). In the multivariate analysis for surgical treated patients, which included all significant characteristics from univariate analysis, pathologic T and N stage, positive margins, (HR 4.92, 95% CI 1.98-12.25, p = 0.006) and PNI (HR 2.66, 95% CI 1.17-6.08, p = 0.02) were significantly associated with worse DSS. Conclusions: Pathologic T and N stage, positive margins, and PNI are independently associated with significantly worse DSS in surgically treated HNSCC patients aged ≤45. Compared with classic prognostic factors seen in the overall population with HNSCC, PNI may be a uniquely strong prognostic factor in younger-aged HNSCC patients.
Efficacy and safety of immunonutrition in preventing oral mucositis during concurrent chemoradiotherapy in patients with nasopharyngeal carcinoma.
Authors: Qin Yating , Yang Chaolin , Yang Dong , Meng Zhen , Dong Huan , Li Pian , Huang Heqing , Hu Xueying , Zhang Tingting , Shen Meizhu , Liu Kang , Fang Yeying , Wang Rensheng , Kang Min 
Published: June 2023

e18056 Background: To assess the efficacy of immunonutrition on severe radiotherapy-induced mucositis (RIOM) during concurrent chemoradiotherapy (CCRT) in nasopharyngeal carcinoma (NPC). Methods: In total, 30 patients with NPC undergoing CCRT were enrolled in our study. Patients in immunonutrition group (n = 15) receive an immunonutrient formula containing omega-3-fatty acids, arginine, nucleotides from five days before radiotherapy until the end of radiotherapy. Patients in control group (n = 15) receive isocaloric isonitrogenous product. The incidence of grade 3 or 4 RIOM was compared between two groups. Results: Although there was no difference of the incidence of grade 3-4 oral mucositis between the two groups (p = 0.050), the rate of severe mucositis were 13.3% (2/15) in immunonutrients, which was much lower than 53.33% (8/15) in control group. A significant improvement in body fat mass was observed in immunonutrition group than that in control group during the CCRT (3.476, 95CI% 0.015~6.937, P = 0.049) and at the end of CCRT (4.115, 95%CI 0.872~7.359, p = 0.015). And the levels of interleukin 6 (-6.765, 95%CI -16.104~2.573, p = 0.148) and C-reactive protein (CRP) (-7.937, 95%CI -20.395~4.520, p = 0.201) at the end of radiotherapy were lower in immunonutritions even though no statistical difference was reached. In addition, immunonutrition has the potential to improve the life of the patient in the EORTC QLQ-H&N35 scales in painkillers (-13.332, 95%CI -22.612~-4.052, p = 0.007), pain (-15.873, 95%CI -32.131~0.384, p = 0.055), dysphagia (-15.516, 95%CI -34.136~3.104, p = 0.099) and dry mouth (-12.860, 95%CI -31.135~5.415, p = 0.160) at the end of radiotherapy. No patients died of treatment-related causes. Conclusions: Our study indicates that immunonutrition may reduce severe oral mucositis and improved quality of life for patients with NPC during CCRT. Further studies with a larger sample size on the role of immunonutrition in oral mucositis are required to substantiate the result of the study.
Radiation-induced nasopharyngeal necrosis in locally-recurrent nasopharyngeal carcinoma patients after re-radiotherapy.
Authors: Huang Runda , Miao Jingjing , Zhang Lu , Peng Yinglin , Huang Shaomin , Han Fei , Wang Lin , Deng Xiao-Wu , Zhao Chong 
Published: June 2023

e18063 Background: Re-radiotherapy (re-RT) is the main treatment for locally recurrent nasopharyngeal carcinoma (lrNPC) patients, and commonly led to radiation-induced nasopharyngeal (NP) necrosis, which was lethal but rare study has focused on it. The aim of this study was to evaluate the cause and impact of radiation-induced NP necrosis in lrNPC patients who received re-RT. Methods: Totally 252 lrNPC patients who received re-RT between January 2013 and December 2020 were retrospectively collected. The inclusion criteria were as follows: (1) no NP necrosis before re-RT; (2) complete medical records, including treatment, clinical and dosimetric information; (3) conventional fractionated radiotherapy. All patients received intensity-modulated radiotherapy ± chemotherapy. Radiation-induced NP necrosis was diagnosed by magnetic resonance imaging and/or electronic nasopharyngoscopy. Dosimetric factors of the planning target volume of primary tumor (PTVp) were extracted from the dose-volume histogram (DVH), which was rescaled to an equivalent dose of 2 Gy per fraction (EQD 2 Gy) using a linear quadratic model. Logistic regression was used to identify the independent prognostic factors for generating the nomogram. Results: With a median follow-up of 44.63 months (inter-quartile range [IQR], 27.70 – 69.20 months), 47.6% of patients (120/252) occurred radiation-induced NP necrosis, which mostly happened within 1 year post re-RT (median [IQR], 5.83 [3.37 – 11.57] months). The 3-year overall survival was 83.0% vs 39.7% ( P＜0.001) in lrNPC patients with or without radiation-induced NP necrosis. Except for the fractionated dose, other dosimetric factors of PTVp were not significantly different between two groups, including D98 (dose to 98% of PTVp), D50, D2 and homogeneity index (Table). Furthermore, multivariate analysis showed that continuous variable age (HR [95%CI]: 1.04 [1.02 – 1.07], P = 0.003) and tumor volume (HR [95%CI]: 1.02 [1.01 – 1.03], P＜0.001), and fractionated dose > 2.22 Gy (HR [95%CI]: 2.36 [1.32 – 4.21], P = 0.004) were independent factors in predicting radiation-induced NP necrosis, which yielded a C-index of 0.742 (95% CI, 0.682 - 0.803) for OS in the nomogram. Conclusions: The incidence of radiation-induced NP necrosis was high in lrNPC patients who received re-RT. Patients with older age, larger tumor volume or receiving fractionated dose over 2.22 Gy were more easily to suffer NP necrosis, which need to explore novel treatment strategies to improve patients’ survivals. [Table: see text]
Occult lymph node metastasis in cN0 tongue squamous cell carcinoma: A prospective observational study.
Authors: Huang Sanqian , Li Feiping , Wang Sunbin , Wu Zheng , Li Yiting , Zhou Yujuan , Huang Wenxiao , Wang Hui , Han Yaqian , Zhang Hailin 
Published: June 2023

e18066 Background: Tongue squamous cell carcinoma (TSCC) is prone to occult lymph node metastasis, and preoperative evaluation of cervical nodes is critical for determining treatment strategies. There is scarce report of detecting occult lymph node metastasis in TSCC by using multi-parameter magnetic resonance imaging (mpMRI), spectral computed tomography (spectral CT) or other diagnostic functional imaging. In this study, we aimed to analyze the incidence and risk factors of occult lymph node metastasis in cN0 TSCC by comparing preoperative imaging with postoperative pathology results. Methods: This study prospectively enrolled newly-diagnosed cN0 TSCC patients admitted to the Hunan Cancer Hospital between May, 2022 and December, 2022. All patients underwent primary resection and selective dissection of cervical lymph nodes. MpMRI and spectral CT scan of oral cavity and neck were performed prior to surgery. Preoperative evaluation of lymph node metastasis was conducted by two senior radiologist independently. The location of cervical lymph nodes was assigned based on the 2013 consensus guidelines. Results: A total of 26 cN0 TSCC patients (6 cT1 stage, 13 cT2 stage, and 7 cT3 stage) were enrolled. The median age was 53 (range, 36-64), and there were 25 males. Among all patients, 13 patients underwent unilateral cervical lymph node dissection, while 13 patients underwent bilateral cervical lymph node dissection. A total of 208 lymphatic drainage areas were resected, and 1003 lymph nodes were removed. There were 7 of pT1, 12 of pT2, 7 of pT3 based on postoperative pathological stages. Besides, there are 21 cases staged pN0, 2 cases staged pN1, 2 cases staged pN2, and 1 case staged pN3. Among the 26 patients, 5 (19.23%) cases had occult lymph node metastasis. A total of 8 metastatic lymph nodes (4 in ipsilateral Ib level, 1 in contralateral Ib level, 3 in IIa level ipsilateral side) were detected in the whole group. No lymph node metastasis was detected in level IIb, III and IV. The median maximum diameter of metastatic lymph nodes was 12 mm (range 5 to 15 mm), and 1 extra-nodal extension was observed. Moreover, all occult lymph node metastases occurred in patients with a primary invasion depth of ≥ 5 mm (29.41%, 5/17). Conclusions: The incidence of occult lymph node metastasis in cN0 TSCC remains high under functional imaging diagnostic technology. Preventive neck dissection is necessary for patients with cN0 disease, especially those with primary tumor invasion depth exceeding 5 mm.
Hearing loss related outcomes post-lateral temporal bone resection and other oncologic treatment.
Authors: Jivani Shirin , Hutcheson Kate A. , Nader Marc-Elie , Pratihar Rajarshi , White Claudia Karina , Gidley Paul 
Published: June 2023

e18069 Background: Lateral temporal bone resection (LTBR) is used to treat malignancies originating from the auricle, periauricular skin, external auditory canal, parotid gland, or temporal bone. LTBR is the workhorse of otologic cancer surgery; however, few studies have described audiologic outcomes in a large sample of patients. The current literature focuses on overall survival rates post-surgery; however, hearing loss-related outcomes after surgery and adjuvant therapy are lacking in the literature. Following surgery, patients are expected to have maximal conductive hearing loss in the affected ear which can be augmented by ototoxic effects of adjuvant treatment such as radiation and systemic therapy. This type of hearing loss significantly impacts quality of life, making it difficult to understand speech directed to the surgically closed ear, localize sounds, and understand conversational speech in noisy environments. Less is known about the rate and severity of sensorineural hearing loss (SNHL) following LTBR. Methods: A retrospective chart review was conducted among 252 patients who underwent LTBR at single tertiary care center from 2010 to 2020. We evaluated changes in ipsilateral bone conduction (BC) hearing thresholds after LTBR ± adjuvant therapy, including head and neck radiation, chemotherapy, and immunotherapy. Patients who completed at least 1 preoperative and 1 postoperative audiogram within 2 years of surgery were included. Patients who had preoperative chemotherapy, immunotherapy, or temporal bone radiation were excluded. Of 252 patients reviewed, 94 met the eligibility criteria. Audiometric data included pure tone average (PTA) for BC thresholds. A significant decline in hearing was defined as an increase in PTA ≥ 10 decibels (American Academy of Otolaryngology-Head and Neck Surgery). Three treatment subgroups were analyzed, including LTBR only, LTBR and radiation therapy, and LTBR with radiation and systemic therapy. Results: Among all patients, BC PTA increased on average by 7dB after treatment (p<0.001); 30% of patients had ≥ 10dB shift. Patients undergoing LTBR with adjuvant therapy had a higher rate of hearing loss compared to patients undergoing LTBR alone (22/69, 32% vs. 5/25, 20%, respectively). Conclusions: LTBR can cause significant long-term decline in BC hearing that is worsened with the addition of adjuvant therapy. Therefore, it is critical to systematically obtain preoperative and post-treatment audiologic testing to monitor and rehabilitate hearing loss over time. The findings of this study may help patients understand realistic expectations of long-term treatment outcomes related to hearing loss, as an initial step to help improve quality of life with hearing rehabilitation such as osseointegrated bone conduction devices.