bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence and survival of oropharyngeal carcinoma patients and the development of HPV-testing prevalence in North Rhine-Westphalia: A Cancer Registry analysis from 2008-2018.
Authors: Teichler Valentin , Kajüter Hiltraud , Wellmann Ina , Pogorzelski Michael , Lang Stephan , Klussmann Jens Peter , Stang Andreas , Grünwald Viktor 
Published: June 2023

e18070 Background: Oropharyngeal cancer (OPC) is caused by tobacco and alcohol or by HPV infection, which is associated with a better overall survival. A growing incidence of OPC with a decrease in other risk factors suggests a rising proportion of HPV-associated oropharyngeal carcinomas. However, regional differences exist and require further analyses. Therefore we analysed the incidence and the survival of OPC-patients and the test-rate for HPV in the largest European cancer registry in North-Rhine Westphalia (NRW), Germany. Methods: All patients diagnosed with oropharyngeal cancer (ICD-10: C01; C02.4; C05.1; C05.2; C09.0-9; C10.0-9) during 2008-2018 were included in the study. We assumed a carcinoma to be HPV-associated if either p16-IHC-test and/or HPV-DNA-PCR test was positive. In this retrospective study we analysed pseudonymized individual pathology and incidence reports collected by the cancer registry to extract our data. Five-year survival was calculated with the Kaplan-Meier Estimator. Results: A total of 10.652 cases of oropharyngeal cancer were reported in the study period. Age standardized incidence rate was 4.1 (SE 0.041) and constant over time. The majority (M:71.9%;n = 7663/W:28.1%n = 2989) of all cases were men, which is comparable to the distribution for HPV-associated OPC (M:70,3%;n = 786/W:29,7%;n = 332). 1,866 (17.5%) of OPC were tested for HPV. (M:70,4%;1314/W29,6%;552) In 2008 the test rate was 2.3% (n = 20), which increased steadily to 49.3% (n = 490) in 2018. HPV detection rate was 59,9% (n = 1118) in tested cases, which remained stable during the observation period.(M:59,8%; W:60,1%) Five-year survival was better for HPV-associated OPC (0.656; SE 0.023) than for non-HPV-associated OPC (0.430; SE 0.026) and not-HPV-tested OPC (0.468; SE 0.006). Five-year survival was slightly worse for men with OPC (0.466; SE 0.007) than for women (0.531; SE 0.011). The mean age was 63.0 (n = 10,652; HPV+Ø = 62,5; HPV-Ø = 62,7). Conclusions: In line with existing data, HPV-associated OPC achieved a better prognosis in NRW. HPV test rate increased in OPC recently, however, about 50% were still not tested. With relatively constant fractions of HPV-positive OPC in the tested group over the timespan our data does not suggest a rise in the fraction of HPV-associated OPC, which is in contrast to published data. The retrospective analyses, variance in HPV testing as well as the lack of occupational or behavioural hazards captured in the registry limit the interpretation of our data.
Neoadjuvant chemotherapy followed by definitive chemoradiation in technically unresectable oral cavity squamous cancers.
Authors: Trikha Mehak , Patil Vijay Maruti , Noronha Vanita , Menon Nandini Sharrel , Singh Ajaykumar Chandrabhan , Dhanawat Aditya , Chaturvedi Pankaj , Pai Prathamesh S , Chaukar Devendra A , Laskar Sarbani Ghosh , Prabash Kumar 
Published: June 2023

e18073 Background: Definitive Chemoradiation has dismal outcomes in very advanced oral cavity cancers. Surgical resection is the preferred modality of treatment . NACT followed by assessment for surgery is the standard algorithm used in technically unresectable oral cavity squamous cancers. Patients who are not amenable for surgery or not willing for the same are subjected to definitive Chemoradiation. There is very limited data about the outcomes of these patients and hence we have performed this analysis. Methods: This is an institutional review board approved retrospective analysis of a prospectively collected dataset of borderline resectable oral cavity squamous patients who received NACT. Adults patients with an eastern co-operative oncology group (ECOG) performance status (PS) 0-2 who were deemed as technically unresectable in a multi-disciplinary clinic (MDC) were included. These patients received 2-3 cycles of NACT (3-weekly) and underwent a response assessment. Depending on response and general condition, they were re-assessed in MDC and further therapy was decided. Patients who were not amenable to surgery and not willing for the and considered for definitive Chemoradiation were included in this analysis. Overall survival (OS) was calculated from date of diagnosis to date of death. Kaplan-meier method was used for estimation of 5 years OS. Impact of response to neoadjuvant chemotherapy on overall survival was calculated using log-rank method. Results: A total of 429 patients were analysed of which 387 (90.2%) were males The median age was 40 years (IQR; 40-54 years). The baseline ECOG PS was 0 in 163 (38%), 1 in 257 (59.9%) and 2 in 9 (2.1%) patients. The clinical stage at presentation was IVA in 257 (59.9%) patients and IVB in 172 (40.1%). The neoadjuvant regimen received were TPF regimen in 162 (37.8%) patients and two drug Taxane- Platinum regimen in the rest. The response rate to neoadjuvant therapy was 35.9% (N=154). Three thirty nine patients had an event with a median survival of 10 months (95%CI-;8.6-11.4). The five year survival was 15.6 % (Standard error 2%), while the 10 year OS was 9.6% (standard error 2.6%). On multivariate analysis, the only factor impacting the OS was response to neoadjuvant chemotherapy (HR: 0.54, 95% CI; 0.43-0.69; P=0.000). Conclusions: Neoadjuvant Chemotherapy followed by definitive Chemoradiation (who are not amenable for surgical resection or not willing) leads to dismal outcomes and further strategies to improve the outcomes are warranted.
Concurrent EGFR wild-type tongue squamous cell carcinoma and EGFR-mutant lung adenocarcinoma and response to osimertinib.
Authors: Wu Fang , Hu Chunhong , Zhang Sujuan , Wang Shuxing , Pan Yue , He Fengjiao , Lu Can , Fu Yucheng , Zeng Yue , Liu Junqi , Shi Shenghao , Peng Yurong , Xiao Chaoyue 
Published: June 2023

e18074 Background: Epidermal growth factor receptor (EGFR) mutation is most commonly oncogenic driver in lung adenocarcinoma with 50% incidence in Asians.Osimertinib is the third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), which has been widely used in metastatic EGFR-mutant non-small cell lung cancer (NSCLC) and has significantly improved outcomes. At present, the treatment of HNSCC mainly relies on surgery or chemoradiotherapy. EGFR is overexpressed in more than 90% of head and neck squamous cell carcinoma (HNSCC). Targeted therapy for HNSCC is mainly monoclonal antibodies, while the application of small molecule inhibitors is limited. The EGFR-TKI can only be applied in subsequent-line, when disease progression on or after platinum therapy. However, the efficacy of EGFR-TKI in patients with both NSCLC and HNSCC remains unclear. Methods: We searched all patients with EGFR-mutation metastatic non-small cell lung cancer and HNSCC who used EGFR-TKI in the Second Xiangya Hospital. Tumor sections were assessed immunohistochemically using PD-L1 and EGFR expression. EGFR amplification was detected by fluorescence in situ hybridization (FISH). We collected clinical characteristics and treatment histories for all patients including time to progression on EGFR-TKI. Time to progression on EGFR-TKI was defined as time from start of EGFR-TKI to time of radiographic RECIST progression. The efficacy and prognosis were evaluated based on the RECIST (version 1.1). Results: We found an advanced lung adenocarcinoma patient who harbored an EGFR-mutation and concurrently had tongue squamous cell carcinoma with EGFR wild-type.The tongue tumor tissue sample for EGFR expression was positive by immunohistochemistry and EGFR amplification was negative by FISH. NGS showed inactive mutation of patched1 (PTCH1) and EGFR wild-type.PET-CT scans demonstrated a partial response (PR) of the lung tumor and tongue cancer after two months of treatment of osimertinib. The lung tumor maintian partial response until now (nearly 30 months). And the tongue tumor reached the first progression- free survival (PFS) at 21 months. Conclusions: The patient with NSCLC and tongue cancer who exhibited objective response to EGFR-TKI, osimertinib monotherapy. The result indicates a clear response of tongue cancer to osimertinib and the potential for the use of osimertinib in tongue cancer. However, with the specific mechanism largely unknown, it is necessary to study further the effect of osimertinib on HNSCC.
Treatment patterns and clinical outcomes of newly diagnosed locally advanced head and neck squamous cell carcinoma (LA HNSCC): A retrospective cohort analysis of national real-world data in England.
Authors: Black Chris M. , Kong Anthony , Chiu Gavin , Bolodeoku John , Massey Olivia , Patel Amisha , Ford Alexander , Holbrook Tim 
Published: June 2023

e18075 Background: LA HNSCC (stage III-IVb) is a potentially curable disease. However, many patients experience recurrence and metastasis, resulting in poorer prognoses. The multimodal approach to treating LA HNSCC makes the evaluation of treatment regimens difficult. This study aimed to describe the real-world treatment patterns, clinical outcomes and HCRU of LA HNSCC patients in England. Methods: This retrospective cohort study involved the use of data from the National Cancer Registration and Analysis Service databases (Cancer Registry, Systemic Anti-Cancer Therapy, Hospital Episode Statistics [HES], National Radiotherapy Dataset and Diagnostic Imaging Dataset). Adults with a first record of primary LA HNSCC between 01/01/2015 and 31/12/2018 were indexed. Treatment pathways and clinical outcomes were investigated over a maximum of 5-years follow-up period extending to 31st December 2020. Results: 12,790 patients were included within the cohort. 52.1% (n = 6,665) received chemotherapy at some point during follow-up as part of their combination treatment with surgery and/or radiotherapy. Within the chemotherapy receiving cohort, 21.2% (n = 1,413) received induction chemotherapy prior to surgery or radiotherapy, 92.2% (n = 6,145) received concurrent chemo-radiotherapy and 11.8% (n = 787) received chemotherapy following surgery or radiotherapy, suggesting palliative treatment. The majority of chemotherapy regimens used were platinum-based. Of those receiving surgery (n = 5,292), the most common type of surgery was transoral surgery, occurring in 51.3% of the resectable patients. 40.2% of the overall cohort received salvage surgery during follow-up. 50.1% and 12.4% of patients experienced locoregional or distant metastatic progression, respectively and 39.2% of the cohort died. The 5-year overall survival (OS) was ~59% and ~55% for resected and unresected patients respectively. For event free survival (EFS), the 5-year median survival time post event free state index for the overall cohort was 12.32 months. Median survival time for the different tumour sites ranged from 19.4 and 2.6 months, with the nasopharynx and ‘other’ site group representing these range ends respectively. The highest HCRU/costs were incurred within the first 3 months following diagnosis; mean number of HNSCC-related inpatient stays were 2.93 (SD = 4.05), costing a total of £57,781,497 (per patient: £4,855.18 [£5872.05], mean[SD]). Conclusions: This is the first real world study using the UK NCRAS datasets to assess the treatment pathway and outcomes of the LA HNSCC population in England. Survival outcomes varied across site of primary tumour and patients diagnosed at stage 4 experienced poorer outcomes, highlighting the need for improved treatment plans and clinical outcomes for this patient population.
Impact of pre-treatment anemia on survival in locally advanced head neck squamous cell carcinomas treated with radiation with or without concurrent chemotherapy.
Authors: Shah Minit Jalan , Patil Vijay Maruti , Noronha Vanita , Menon Nandini Sharrel , Singh Ajaykumar Chandrabhan , Jobanputra Kunal Naishadh , Peelay Zoya Ravish , Prabhash Kumar 
Published: June 2023

e18079 Background: Locally advanced head neck squamous cell carcinomas (LAHNSCCs) are treated either with surgery followed by radiation (RT) alone, surgery followed by concurrent chemoradiation (CTRT) or definitive CTRT. Patients receiving RT need to have an optimal hemoglobin (Hb) level, however there is limited data on what is an optimal pre-treatment Hb level required during RT/CTRT in these patients. Hence we performed this analysis. Methods: This data is a pooled analysis of 3 major randomized studies (RCT) performed in the field of chemoradiation over the last decade. These include, a RCT comparing weekly versus (vs) 3 weekly cisplatin in LAHNSCC‘s, weekly cisplatin vs weekly cisplatin plus nimotuzumab in the definitive setting in LAHNSCC‘s and in cisplatin ineligible patients, a comparison of radiation vs docetaxel plus radiation. The baseline demographics, Hb levels, and outcomes were collected and used for analysis. To ensure unanimity, anemia was defined as < 12g/dL in both males and females. Univariate (UVA) and multivariate analysis (MVA) evaluated the factors affecting anemia. The impact of anemia on locoregional control (LRC), disease free survival (DFS) and overall survival (OS) was studied. Kaplan meier analysis was used for estimation of time to event parameters and log rank test was used for comparison. Cox proportional hazards model was used to test the importance of anemia in presence of other important parameters like age, gender, T and N stage, concurrent chemotherapy including its pattern (weekly vs 3 weekly) and site of disease. Results: We studied 1192 patients. Anemia of any grade was seen in 417 patients (35.0%), with the median Hb levels of the entire cohort being 12.8g/dL (IQR 11.6-13.9). Grade 3 or higher anemia (Hb < / = 8g/dL) was seen in only 2 patients (0.2%). Female gender, oral cavity disease, patients with stage IV disease and those receiving adjuvant CTRT significantly impacted anaemia on UVA (p = 0.000 for all). MVA confirmed advancing age (p = 0.001), female gender (p = 0.000), patients with stage III and IV disease (p = 0.009) and those treated with adjuvant CTRT (p = 0.011) to significantly impact anemia. The LRC in patients with or without anaemia was 12.9 months (95%CI 7.8-18.0) and 23.5 months (95%CI 17.8-29.2) respectively (p = 0.000). Similarly the DFS and OS in anemic and non anemic patients were 9.6months (95%CI 6.0-13.2) vs 18.5months (95%CI 12.4-24.7, p = 0.022) and 21.5months (95%CI 16.3-26.8) vs 39.9months (95%CI 31.0-48.9, p = 0.000) respectively. Conclusions: Pre-treatment anemia in LAHNSCC‘s leads to a decrement in treatment outcomes (LRC, DFS and OS) and is an independent prognostic factor.
The smart options of induction therapy for locally advanced betel-nuts related HNSCC in Taiwan.
Authors: Chen Jo-Pai , Lu Wei-Chen , Chiang Keng-Man , Chen Hsing-wu , Huang Huai-Cheng , Chang Chen-Han , Kuo Sung-Hsin 
Published: June 2023

e18080 Background: The treatment of HNSCC in Taiwan is still very challenging and might be related to betel-nuts use. Betel nut chewing might contribute to strong angiogenesis/invasion and treatment refractoriness. In western countries where HPV+ oropharyngeal cancer prevalence is high, induction TPF (TAX323/324) response rate in locally advanced HNSCC is around 70%; Erbitux and TP (Argiris in JCO2008) induction response rate is 86%. In the analysis from KGMH in Taiwan, induction chemotherapy response for locally advanced HNSCC was 55% in betel-nuts chewers compared with 75% in non-users ( p=0.038; From Su in World Journal of Surgical Oncology 2016). In further studies from Taiwan, Avastin-PF induction benefit (ORR 80%) was also prominent from NTUH (Huang in ESMO Asia2016); Erbitux-TPF induction response rate was 88% from VGH by Lu in Head & Neck2019. Neoadjuvant biochemotherapy seemed to bring more benefits in betel-nuts related HNSCC. In the era of incorporating immunotherapy to neoadjuvant setting of HNSCC, triple therapy of bio-chemoimmunotherapy deserves more attention. Methods: From 2012 to 2022, 111 unresectable stage IVA & IVB betal-nuts related HNSCC patients (OSCC 69, Hypopharynx 26, OPC 13) had ever received induction Bio-chemotherapy or triple therapy (Bio-chemoimmunotherapy) in Yun-lin Branch of National Taiwan University Hospital. We have reviewed basic characteristics, therapeutic regimens, induction response, and final outcomes of these patients. Results: See table. Conclusions: Induction TPF response in locally advanced betel-nuts related HNSCC in Taiwan was not so prominent. Flexible chemotherapy backbones, such as TP/DP-HDFL(weekly docetaxel or paclitaxel with cisplatin and 24-hr high dose 5-fluorouracil/leucovorin infusion), might produce acceptable response rates with less toxicity. Bio(EGFR or VEGFR-targeting)-chemotherapy or Bio-chemoimmunotherapy has brought encouraging induction response with favorable toxicity profiles to conversion surgery or definite CCRT. Further investigation and clinical trials will be urgently warranted. [Table: see text]
tRNA-derived fragments (tRFs) as regulators of oncogenes and tumor suppressor genes in head and neck squamous cell carcinoma.
Authors: Uzelac Matthew , John Daniel , Chakladar Jaideep , Li Wei Tse , Ongkeko Weg M. 
Published: June 2023

e18082 Background: Roughly 50,000 individuals are diagnosed with head and neck cancers in the United States yearly. Though risk factors and common therapeutic strategies are well-established, early detection of head and neck cancers remains challenging. One strategy for early detection is high-throughput analysis of both coding and noncoding RNA transcripts, which has become increasing implicated in cancer pathogenesis. One such noncoding transcript is tRNA-derived fragments (tRFs), which are the products of enzymatic cleavage of precursor tRNAs. Though tRFs have been suggested to play important roles in the regulation of mRNA translation (similar to other noncoding RNAs), their utility as cancer biomarkers is not well-known. Methods: In this study, we investigate tRFs for correlation to cancer prevalence with specific consideration of translational regulation of oncogenes (OG) and tumor suppressor genes (TSG). tRF read counts were obtained for 499 head and neck squamous cell carcinoma tumor tissue samples and 44 adjacent normal samples. Results: The read counts between both groups were compared to identify tRFs dysregulated in tumor samples, which may be pertinent biomarkers for diagnosis. Ten tRFs were found to be significantly dysregulated in cancer samples. These tRFs were further assessed for correlation to expression of OGs and TSGs using the COSMIC database. Due to the mRNA-degrading nature of tRFs, we analyzed tRF abundance for inverse correlation to gene expression. Four tRFs upregulated in tumor samples showed significant anticorrelation to select TSG expression (ATP2B3, CSMD3, LZTR1, NTHL1, PTPRC), and three tRFs downregulated in tumor samples showed anticorrelation to OG expression (A1CF, MPL, SALL4, TNC). Notably, LeuCAG 5’ tRF was associate with high binding affinity for the TSGs CSMD3 and LZTR1, supporting the likelihood of tRF-mediated degradation. Interestingly, this tRF was inversely correlated with patient survival length. LeuCAG 5’ was also of significantly lesser abundance in patients who experienced complete or partial remission following chemotherapy treatment, further indicating this tRFs’ clinical relevance in HNSCC, potentially as an oncogenic-related agent. Conclusions: Investigation into these tRFs may reveal their potential for use in early diagnosis. High abundance of this tRF may be indicative of oncogenesis. In exploring tRFs’ for their potential as biomarkers of cancer, they may prove useful in allowing earlier diagnosis. Moreover, studying tRFs may provide additional considerations for patient care and treatment.
Ceruminous adenocarcinoma: A National Cancer Database study of demographic characteristics.
Authors: Hsia Beau , Keirns Darby , Silberstein Peter T. , Wu Xinxin 
Published: June 2023

e18084 Background: Ceruminous adenocarcinoma (CA) is a rare form of malignancy that originates from the ceruminous glands located in the external auditory canal. Despite its rarity, 25% of CA patients succumb to the disease within two years of diagnosis. Radiation treatment improves the 10-year survival rate to 60%, up from 30% without radiation treatment. Due to the rarity of CA, the diagnostic trend of the disease could offer valuable insight into its epidemiology. The National Cancer Database (NCDB) database was analyzed to determine the demographic factors in patients diagnosed with CA. Methods: A retrospective cohort analysis utilizing the 2004–2020 National Cancer Database (NCDB) included patients with a histologically-confirmed diagnosis of CA (N = 37). Demographic factors (age, sex, race, Hispanic status, educational attainment, insurance status, facility type, distance from facility, and Charles/Deyo score) were analyzed by descriptive statistics and incidence trends were interpreted in regression analysis. Results: A total of 37 patients were identified in the database with a confirmed diagnosis of CA between 2004 – 2020 with a steady incidence of patients diagnosed per year (R2 = 0.0). The average age of diagnosis was 59.7 years (SD = 16.5, range = 14 – 90 years). The top primary site was the external ear (89.2%), although primary sites on other areas of the skin did occur. Most individuals (89.2%) had Charlson/Deyo comorbidity scores of 0. The majority of the patients were Non-Hispanic White (89.1%). More patients were in the top quartile of income earners (35.5.%) compared to those in the second, third, or fourth quartiles. A higher percentage of patients were privately insured (51.4%) than those who were uninsured or insured by Medicare/Medicaid. More patients lived in metropolitan counties with a population greater than 1 million (43.2%) than in other metropolitan counties (35.1%). Fewer patients were treated in an academic/research program (40.5%) than in a non-academic program (46.0%). Patients lived an average of 43.3 miles (SD = 74.7, range = 1.8 – 370) from the treatment facility. No patients received palliative care. Conclusions: This is the first NCDB analysis on CA to the best of our knowledge and thus addresses a significant knowledge gap on the topic. The majority of CA patients tend to be non-Hispanic and White with a primary site diagnosis presenting at the external ear, similar to earlier descriptions in case reports. This is the first time the socioeconomic factors of CA patients have been described in the literature: CA patients are more likely to be in the top income quartile, live in densely-populated metropolitan areas, and be treated in a non-academic program. Further research is needed to better understand the impact of demographic and socioeconomic factors on the diagnosis of, treatments utilized against, and overall survival of patients with CA.