bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and tolerability of weekly 40mg/m² cisplatin radiosensitizing modified regimen for locally-advanced head and neck squamous cell carcinoma radical treatment with chemoradiotherapy: A university hospital experience.
Authors: Bighetti Bruna , Neto José Tristão , Pereira Renata do Socorro Monteiro , SOUZA LAÍS CRISTHINE , Santoro Ilka Lopes , Tadokoro Hakaru , Ribas Christian , De Mello Ramon Andrade 
Published: May 2020

e18512 Background: Cisplatin-based chemoradiotherapy (CRT) is a well-established regimen used for adjuvant and/or head-and-neck squamous cell carcinoma (HNSCC) radical treatment. The most classic protocol for chemoradiotherapy remains the administration of Cisplatin 100mg/m² EV D1 q3-week period, 3 cycles. The objective of this study is to assess the efficacy and tolerability of the weekly 40mg/m² cisplatin regimen. Methods: we conducted a retrospective study from 2007-2020 with 102 patients treated at a national reference institution. All of them with HNSCC received concurrent CRT with weekly cisplatin 40mg/m² EV D1. We analyzed the overall survival (OS), local recurrence and tolerability in this scheme. Results: The median cisplatin cumulative dose received by our patients was 240mg/m². Hence, we divided them in two groups for the analysis: Group A (41 patients) received less than 240mg/m² cisplatin total dose and Group B (61 patients) received more or equal 240mg/m² cisplatin total dose. Both groups were equally balanced between sex, clinic stage, histologic grade and clinic status. We found that the Group A experienced 5 deaths (12.2%) while the Group B experienced 6 deaths (9.8%). The mean time to recurrence disease in the Group A was 45.68 months and in Group B 60.22 months (p = 0.958). The estimated overall survival in the Group A was 150 months and in the Group B was 116.4 months (p = 0.443). Conclusions: The weekly cisplatin dose regimen showed to be feasible, more tolerable, and less toxic and with no difference in terms of OS then the classic 3-week cisplatin protocol in the CRT setting. Our group suggests that the 240mg/m² cumulative cisplatin weekly schedule should be a better option for CRT treatments then the classic cisplatin regimen. A phase III clinical trial is warranted to further understanding of this framework. Key-words: head and neck cancer, cisplatin, radiotherapy
Single-institute outcomes of palliative chemotherapy in metastatic head and neck squamous cell carcinoma (HNSCC).
Authors: Parikh Rujul H , Fleming Christopher W , Reddy Chandana A. , Koyfman Shlomo A. , Joshi Nikhil , Woody Neil McIver , Burkey Brian B. , Scharpf Joseph , Lorenz Robert R , Prendes Brandon , Ku Jamie , Lamarre Eric , Schwartzman Larisa , Adelstein David J. , Geiger Jessica Lyn 
Published: May 2020

e18513 Background: Distantly metastatic HNSCC carries a poor prognosis with limited palliative systemic treatment options and a paucity of literature examining factors impacting outcomes of such therapy. We sought to evaluate characteristics conferring more favorable responses to frontline palliative systemic therapy after distant failure (DF). Methods: From an IRB-approved database, we identified 332 pts with metastatic HNSCC treated from 1999 to 2019. Pts with locoregional HNSCC who developed DF and subsequently were treated with palliative systemic therapy were included. Pts were categorized by disease factors, and outcomes were analyzed for progression-free survival (PFS) and overall survival (OS) with Kaplan-Meier curves and log-rank p-values. Results: A total of 85 pts were identified with median age 59.5 years (37-89); 82.4% male, 90.6% Caucasian, 52.9% with > 10 pack-years tobacco use history. Oropharynx primary was the most common site (36.5%) followed by oral cavity (23.5%). All 31 oropharynx cancer pts were HPV-related. Sixty-six pts initially received definitive chemoradiotherapy, with 43 receiving concurrent radiosensitizing cisplatin. Median time to DF was 15 months (m). Thirty pts (35.3%) had concurrent locoregional failure with DF. 62.4% had only one metastatic organ site, with lung-only metastasis in 43.5%. Carboplatin/paclitaxel was the most commonly used frontline palliative chemotherapy (50.6%); 22.4% received frontline nivolumab or pembrolizumab, and 9.4% were treated with frontline platinum/5-FU/cetuximab (9.4%). 63.5% of pts achieved a best response of stable disease or better with frontline therapy. At two years after initial DF, 6 pts (7%) were disease-free. Sixteen pts were alive at last follow-up. After DF, median PFS was 6.5 m and median OS was 10.6 m. On univariate analysis, HPV-related disease was associated with increased PFS (9.5 vs 5.1 m, p < 0.0001) and increased OS (21.1 vs 7.7 m, p < 0.0001). Pts with one metastatic organ site had better OS (11.0 vs 6.2 m, p = 0.047). There was a trend of increased OS with lung-only metastasis (14.4 vs 7.7 m, p = 0.0776), and absence of concurrent locoregional failure (10.8 vs 8.3 m, p = 0.1153). Conclusions: Our results demonstrate that HPV-related metastatic HNSCC is associated with a statistically significant increased PFS and OS. Additionally, there was a trend of increased OS with lower locoregional and distant metastatic burden at DF though statistical significance was not achieved.
Clinicopathological characteristics and survival outcome in oral cavity cancer with masticator space involvement (T4b): A retrospective single-institutional experience.
Authors: K P Abdulla , Geotge Nebu Abraham , M C Hajara , Mohan Raj 
Published: May 2020

e18517 Background: Oral cavity cancer with the masticator space involvement is considered as very advanced localised disease and staged as T4b in AJCC 8th edition, along with the involvement carotid artery,base of skull or prevertebral fascia. NCCN treatment guidelines consider this as inoperable disease and advocate non surgical options or palliative treatment. This study intends to compare the different treatment modalities in T4b oral cavity cancer and their impact on survival. Methods: This is a retrospective study of 150 patients with T4b oral cavity ca, from 2013to 2015 and follow up data till 31 st July 2019 were collected. All patients had biopsy proven SCC and CT evidence of masticator space involvement. Results: Total of 150 patients were included. 102 patients had received curative treatment and 48 patients had received palliative treatment. 30% in the curative group and 42% in the palliative group were supra notch disease. In the curative group 84% were treated with surgery and adjuvant treatment and remaining had received RT with or without chemotherapy. 90% patients in the surgically treated group had attained margin negative resection. 4 year OS in the curatively treated group was 58.9% and in the palliative group was 12%. 2 year OS was 69% and 31% respectively, (p=0.001). The survival of supra notch disease was not different from infra notch disease neither in the curative group (61% v/s 57%, p=0.452) nor in the palliative group (10% v/s 14%, p=0.13). The surgically treated patients in the curative arm had significant survival advantage over the patients who had received only RT with or without chemotherapy, (63.5% v/s 34%, p=0.001). Conclusions: Curatively treated oral cavity cancer with masticator space involvement has survival outcome comparable to the published survival data of those without masticator space involvement. Clinicopathological spectrum of supra notch disease is not different from infra notch disease, and their prognosis is similar to infr anotch disease, if margin negative resection is attained. Radical intent treatment, preferably surgery should be offered to all patients with masticator space involvement, if negative margin is anticipated from preoperative imaging.
DNA methylation profiling in patients with head and neck squamous cell carcinoma treated with immune checkpoint inhibitors.
Authors: Starzer Angelika Martina , Heller Gerwin , Tomasich Erwin , Feldmann Katharina , Hatziioannou Teresa , Traint Stefan , Minichsdorfer Christoph , Schwarz-Nemec Ursula , Nackenhorst Maja , Muellauer Leonhard , Preusser Matthias , Berghoff Anna Sophie , Fuereder Thorsten 
Published: May 2020

e18527 Background: Biomarkers for response prediction to immune checkpoint inhibitors in head and neck squamous cell carcinoma (HNSCC) patients are needed for a personalized therapy regimen. Therefore, we investigated the predictive potential of inflammatory biomarkers and DNA methylation. Methods: We profiled the methylation status of 850.000 CpG sites in formalin-fixed, paraffin-embedded primary HNSCC samples collected before ICI therapy start using Infinium Methylation EPIC microarrays. Tumor-infiltrating lymphocytes (TILs) and programmed cell death ligand 1 (PD-L1) expression were analyzed employing immunohistochemistry staining. Methylation profile, TIL density and PD-L1 expression were correlated with best radiological response to ICI treatment. Results: 29 patients (median age of 61; range 28-80) years; 8 (27.6%) females, 21 (72.4%) males) with HNSCC were included. Median number of prior systemic therapies was 1 (range 0-3). Median number of ICI applications was 6 (range 1-45). 2/29 (6.9%) patients achieved an objective response (complete response or partial response) under anti-PD-1 therapy. Median progression-free survival (PFS) and median overall survival (OS) were 3.3 months (range 0-28.8) and 7.2 months (range 0-29.4), respectively. 7/29 (24.1%) patients were still alive and one of these patients was still on ICI therapy at data cut-off. Methylation analyses revealed a combination of methylation changes (both hypo- and hypermethylation) that was predictive for response to ICI. 11/27 (40.7%) patients had PD-L1 expressing tumor cells ( > 1% PD-L1 expression). Median density of CD8+ TILs was 423.49 cells/mm2 tumor (range 5.71-11528.43 cells/mm2) and median density of CD3+ TILs was 794.82 cells/mm2 tumor (range 1.68-8811.74 cells/mm2). There was no correlation of PD-L1 expression, density of CD8+ or CD3+ TILs with response or disease control (p > 0.05). Conclusions: In contrast to PD-L1 expression and TIL density, methylation profiles were associated with response to ICI treatment in HNSCC patients.
Multigene profiling to identify clinically relevant actionable mutations in head and neck cancers: An Indian study.
Authors: Kunigal Sateesh S. , Thakur Shalini , Shivkumar Yogesh , M L Sheela , CR Krishna , Bahadur Urvashi , Nayar Ravi , Gopinath Kodaganur S. , Ghosh Mithua , Ajaikumar Basavalinga Sadasivaiah , Rao Vishal Uchila Shishir 
Published: May 2020

e18529 Background: Head and Neck squamous cell carcinoma (HNSCC) represents approximately 5-10% of malignancies worldwide. Despite the advances in treatment modalities there lies a disparity in response, owing to the underlying molecular and genetic make up. In the era of precision medicine, it is important to profile each disease and customise treatment to improve the outcomes by identifying predictive or prognostic indicators at the molecular and genetic level. Methods: 100 patients with HNSCC, diagnosed at our centre from April 2015-17 were profiled by targeted deep sequencing for hotspot mutations in 48 cancer-related genes using Illumina’s TSCAP panel and MiSeq technology. The average coverage across 220 hot spots was greater than 1000X. Data was processed using Strand Avadis NGS. Mutations identified in the tumor were assessed for ‘actionability’ i.e. response to therapy and impact on prognosis. The clinical data for these patients was collected retrospectively and analysed for treatment outcomes with standard therapy. The association of mutations with habits, stage at presentation, poor treatment outcomes and prognosis was also analysed. Results: Somatic variants were detected in 63.1% of cases. Genetic aberrations were identified in major RAS/RAF signalling pathway in 10 % of cases out of which HRAS activating mutations were the most common (n=4). HRAS was co-mutated with PI3KCA (n=3) and PTEN deletions (n=2). Based on the result, Cetuximab was discontinued in 2 patients with metastatic HNSCC. Other targetable mutations included ATM (n=1), STK11 (n=1), RB1 (n=1) and BRAF (n=1). Disruptive and non-disruptive mutations in TP53 alone were found in 43.8% of H&N cancers, varying widely among different histology with variable treatment outcome. Interestingly all metastatic/recurrent patients, with very short progression free survival of 9-12 months (PFS) post Cisplatinum based chemotherapy, were found to have mutated TP53. TP53 was also found to be co- mutated with ATM gene (n=1), an important prognostic marker, indicating poor response to chemotherapy and radiotherapy. The patients with recurrence and poorer prognosis (n =5) showed point mutations in codon regions 173 -273. Conclusions: Indian patients with HNSCC display a wide mutational landscape with specific actionable targets. Although traditional treatment modalities remain the standard of care, specific mutations may be utilised to customise treatment, prognosticate and predict outcomes.
Prognostic value of HER2, PD-L1 and RET mRNA expression in salivary gland tumor.
Authors: Kutukova Svetlana , Imyanitov Evgeny , Raskin Grigory , Ivaskova Julia V. , Beliak Natalia P. , Yaremenko Andrey I. , Razumova Alexandra , Pakhomova Natalia 
Published: May 2020

e18534 Background: The objective of our study was to evaluate the cytologically, morphologically and IGH detection of salivary gland (SGT), expression of HER2 and PD-L1, CPS and determine these associations with patient survival. Methods: The study included 59 patients with a confirmed diagnosis of salivary gland cancer (stage II-IVA) by cytology, morphology and IGH analyses. After that HER2, in tumor and tumor infiltrating immune cell PD-L1 expression (with CPS) was determined using IHC-testing. RET mRNA gene expression calculated with using real-time PCR. Results: Aspiration biopsies results: only in 22 (37.29%) cases the malignant tumor was cytologically confirmed. An IHC study showed the proportion of high-grade tumors significantly exceeded 3.82 times the proportion of low-grade tumors (p < 0.00001). Low grade SGT were 2 times more often recorded by morphological studies (p = 0.0172), high grade SGT - 1.37 times more often by IHC study (p = 0.0176). HER2 expression: (0) – 29(60.42%), (1+) – 11(22.92%), (2+) – 4(8.33%), (3+) – 4(8.33%). Median OS HER2-neg pp was 170.25±24.49 mo (95% CI 125.25-218.26), median OS of 8 pp (16.33%) with HER2 (2+,3+) was 41,00 mo (95%CI 4.50-72.00) (HR 0,07; 95% CI 0,01-0,38; p = 0.00715). Median PFS HER2-neg pp was 168.00 mo (95% CI 75.00-168.00), median PFS of 8 pp (16.33%) with HER2 (2+,3+) was 19,00 mo (95%CI 1.00-31.00) (HR 0,23; 95% CI 0.04-1.22; p = 0.01641). PD-L1 expression was: in tumor cells 0-90% in 11/49 pp (22.45%), in immune cells 0-50% in 26/49 pp (53.06%) (p = 0.0006). CPS was 0-100, median CPS 5 (95% CI 0.03-10.00). Median OS pp with CPS > 1 was 72.00 mo (95% CI 19.5-72.00); with CPS < 1 hasn’t yet been achieved (OR 0.26; 95% CI 0.09-0.75; p = 0.0124). RET mRNA expression was detected in 13 of 48 cases (27.08%). The expression level ranged from 0 to 0.205. The median PFS in the RET mRNA-positive pp was 168.00 mo (95% CI 16.00-168.00) and tended to exceed the median TTP in the RET mRNA-naive patient group. Conclusions: The results suggest that the understanding the receptor status of salivary gland cancer can be effective prognostic factors.
Mechanism of sensitivity to TPF chemoagents and its potential alternative of erbB2 in oral cancer with GDF15 overexpression.
Authors: Zhong Lai-Ping , Zhao Tong-chao , Ju Wu-tong , Liang Si-yuan , Wang Li-zhen , Li Jiang , Zhu Dong-wang , Zhang Zhi-yuan 
Published: May 2020

e18542 Background: To explore the mechanism of sensitivity to docetaxel, cisplatin, and 5-fluorouracil (TPF) chemoagents in patients with oral squamous cell carcinoma (OSCC) and growth differentiation factor 15 (GDF15) overexpression recruited in a TPF induction chemotherapy trial; and to explore potential alternative agents for patients who might not benefit from TPF induction chemotherapy. Methods: GDF15-overexpression and silenced OSCC cells were used to investigate sensitivity to TPF chemoagents in vitro and in vivo. Immunoprecipitation combined with mass spectrometry was used to screen out the possible receptor for GDF15, and associated signaling pathways were detected after intervention with the possible receptor of GDF15. The efficacy of an inhibitor of the phosphorylation of the possible GDF15 receptor was evaluated by treatment of GDF15-overexpression OSCC cells in vitro and in vivo. Results: Overexpression of GDF15 in OSCC cell lines and xenografts lead to an increase of chemotherapeutics sensitivity on apoptosis effects induced by docetaxel, cisplatin and 5-fluorouracil, through a caspase -dependent pathway. Immunoprecipitation combined with mass spectrometry revealed that the erbB2 protein was a potential binding protein of GDF15, as verified by coimmunoprecipitation. When GDF15 was overexpressed, the phosphorylation of erbB2 and downstream PI3K/AKT and MAPK/ERK pathways was significantly upregulated, but was downregulated when GDF15 expression was interfered. The erbB2 phosphorylation inhibitor CI1033 significantly inhibited the proliferation and colony-forming ability of GDF15-overexpression OSCC cells as well as the growth of xenografts. CI1033 might be used as a potential targeted drug or alternative of TPF chemoagents for OSCC patients with GDF15 overexpression. Conclusions: OSCC with GDF15 overexpression exhibit sensitivity to TPF chemoagents through a caspase-dependent pathway. ErbB2 phosphorylation inhibitors might be used as potential targeted drugs or an alternative of TPF chemoagents for OSCC patients with GDF15 overexpression.
Incidence of hypothyroidism in head and neck squamous cell carcinoma patients receiving radiotherapy with and without immune checkpoint inhibitors.
Authors: Leddon Jennifer , Chirra Martina , Agrawal Arushi , Roof Logan , Trotier Danny , Shaikh Hira , Stone Timothy , Jandarov Roman , Takiar Vinita , Wise-Draper Trisha Michel 
Published: May 2020

e18551 Background: Treatment for locally advanced head and neck squamous cell carcinoma (HNSCC) involves a combination of surgery, chemotherapy, and radiotherapy (RT). RT for HNSCC is a known risk factor for the development of hypothyroidism. Recently, anti-PD1 therapies have been approved for recurrent and metastatic HNSCC and are moving to the forefront of HNSCC care. Similarly, thyroid dysfunction is a common immune-related adverse event following anti-PD1 therapy. Whether the addition of anti-PD1 to RT increases the likelihood of developing hypothyroidism remains unknown. Methods: The rate of hypothyroidism in HNSCC patients receiving RT (+/- chemotherapy and surgery) was compared to HNSCC patients receiving RT + anti-PD1 therapy either concurrently or after RT. Exclusion criteria were preexisting thyroid dysfunction, RT dose < 45 Gy and patients with incomplete treatment records. We defined clinical hypothyroidism as an elevation of TSH with low T3, T4 or elevation of TSH with symptoms requiring levothyroxine initiation. Hypothyroidism incidence was compared using Fisher’s exact test. Results: 153 patients were evaluated. In the RT group (N = 103), patients received RT +/- surgery or chemotherapy. 82/103 (80%) were male, median age was 57 and primary tumor groups included oropharynx 62/103 (60%), larynx 29/103 (28%), oral cavity 9/103 (9%) and other 3/103 (3%). In the RT + anti-PD1 group (N = 50), 36/50 (72%) were males, median age was 57 and primary tumor groups included oral cavity 19/50 (38%), oropharynx 17/50 (34%), larynx 8/50 (16%), and other 6/50 (12%). In the RT group, median follow up after RT was 801 days. In the RT+ anti-PD1 group, median follow up was 595 days from RT and 388 days from anti-PD1. The rate of hypothyroidism was significantly higher in the RT group 22.3% (23/103) versus 6% (3/50)after anti-PD1 therapy (p = 0.011). Multinomial logistical regression found no significant difference in hypothyroidism based on age, sex, or BMI. Larynx as primary tumor location was an independent risk factor for development of hypothyroidism (OR 4.74, p = 0.002). Conclusions: The addition of anti-PD1 therapy to standard HNSCC treatments does not significantly increase the risk of developing hypothyroidism. In fact, this study finds a lower incidence of hypothyroidism in HNSCC patient receiving RT + PD1 therapy which may be due to shorter duration of follow up and lower proportion of laryngeal cancer patients who are at relatively higher risk for surgical hypothyroidism.
Factors impacting use of adjuvant therapy in lip and oral cavity squamous cell carcinoma: A NCDB analysis.
Authors: Ramadas Poornima , Wang Dongliang , Huang Danning , Sivapiragasam Abirami 
Published: May 2020

e18556 Background: Two trials followed by a combined analysis of the trials in head and neck squamous cell carcinoma (SCC) established that the benefit of adjuvant chemotherapy concurrent with radiation (CRT) was only noted in patients with extracapsular extension of nodal disease (ECE) and positive resection margins (PM). Despite this recommendation, other high-risk pathological features including pT3 or pT4 disease, positive lymph nodes, perineural involvement, vascular tumor embolism and level IV or V lymph node involvement have been noted to increase the risk of recurrence and adjuvant chemotherapy has been utilized for these patients. We report an observational study to evaluate the factors impacting use of CRT in patients with oral cavity and lip SCC. Methods: We conducted a retrospective study of patients with oral cavity and lip SCC who underwent resection of primary tumor with or without neck dissection in the reporting hospital in the NCDB database. We compared demographic, clinical and pathological characteristics of patients who received adjuvant CRT versus radiation alone. Multivariate analysis was performed using logistic regression model. Results: Out of the 58,481 patients reported to have surgery in NCDB from 2004 to 2016, 11,413 patients received adjuvant therapy. In univariate analysis, patients who received CRT were most likely less than 65 years of age, males, patients with no insurance or private insurance, lower Charlson Deyo score, Stage IVA, pT4, grade 2 or higher, tumor size > 4cm, positive lymph nodes, involvement of level IV and V nodes, lymphovascular invasion, ECE and PM. In multivariate analysis, factors which influenced receiving CRT were age between 40 and 65 years, males, Stage IVA (compared to Stage I to III), positive nodes, ECE and PM. A total of 984 patients received CRT without having ECE or PM. Conclusions: In addition to ECE and PM, positive lymph nodes was the major pathological factor in patients receiving CRT compared to RT alone.