bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigating survivin as a novel target in black women with breast cancer.
Authors: Walens Andrea , Olsson Linnea T , Van Alsten Sarah , Carey Lisa A. , Troester Melissa A. , Abdou Yara 
Published: June 2021

594 Background: Black women with breast cancer have higher mortality than White women. Differences in tumor biology contribute to racial disparities in breast cancer outcomes. BIRC5 gene encodes survivin, an inhibitor of apoptosis protein, and an independent marker of poor prognosis in breast cancer. Cancer patients have anti-survivin antibodies and circulating survivin-specific T cells, suggesting that survivin may be targetable. Several ongoing antibody-mediated, vaccine strategies that target survivin are being developed. Nevertheless, most survivin studies were conducted in cohorts of White women. To date, the prevalence and/or role of survivin expression in breast tumors from Black women has not been studied. Methods: Associations between BIRC5 expression, clinicopathological and molecular features were measured in the population-based Carolina Breast Cancer Study (CBCS) and The Cancer Genome Atlas (TCGA) breast cancer cohort. Gene expression was measured by Nanostring RNA counting and split into BIRC5 high (4th quartile) and low categories based on log2 gene expression values. Relative frequency differences (RFD) for the association between BIRC5 high and clinicopathologic features were estimated. RNA based p53 mutant status and homologous recombination deficiency (HRD) status were included in RFD analysis. Receiver operating characteristic (ROC) curves were used to illustrate the potential of BIRC5 expression to distinguish patients who achieved pathological complete response (pCR) after receiving neoadjuvant chemotherapy in CBCS (133 Black, 49 non-Black). Results: BIRC5 gene expression was significantly increased in tumors from 966 Black patients compared to 1,497 non-Black (p < 0.00001), adjusting for stage and subtype. BIRC5 high tumors were significantly more expressed in higher stage and basal-like breast cancer subtypes. BIRC5 high tumors were also significantly enriched for expression of genes involved in p53 loss and HRD. Furthermore, in an analysis of 182 CBCS patients, BIRC5 gene expression alone predicted pCR with similar overall AUC to ROR-PT multigene signatures (AUC 0.62 vs 0.64). Conclusions: Our study shows that survivin expression is particularly high in breast tumors from Black women. This was associated with more aggressive clinicopathological features in addition to p53 mutant and HRD status. Black women with breast cancer represent an area of unmet clinical need and could potentially benefit from anti-survivin targetable treatment strategies. Further studies are needed to help close this gap which constitutes the largest disparity among cancer-specific diseases.[Table: see text]
Efficacy of concurrent cetuximab (CTX) and nivolumab (NIVO) in previously untreated recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC).
Authors: Chung Christine H. , Saba Nabil F. , Steuer Conor Ernst , Li Jiannong , Bhateja Priyanka , Johnson Matthew , Masannat Jude , Poole Maria , Hoening Dirk , Song Feifei , Hernandez-Prera Juan C. , Molina Helen , Wenig Bruce , Farinhas Joaquim , Kish Julie Ann , Muzaffar Jameel , Kirtane Kedar , Rocco James William , Schell Michael J. , Bonomi Marcelo Raul 
Published: June 2021

6017 Background: Current standard of care for patients (pts) with previously untreated R/M HNSCC that are incurable is either pembrolizumab (pembro) with/without chemotherapy depending on the Programmed Death-Ligand 1 (PD-L1) combined positive score (CPS). We evaluated the combination of CTX and NIVO for its efficacy. Methods: Pts were treated with CTX 500 mg/m2 IV on Day (D) -14 as a lead-in followed by CTX 500 mg/m2 IV and NIVO 240 mg/m2 IV on D1 and D15 every 28-D cycle (C). Pts with CTX infusion reaction or who did not receive C1D1 for any reason were non-evaluable and replaced. NIVO dose reduction was not allowed. Results: Fifty-four evaluable pts were analyzed. Median age was 62 (42-85). ECOG performance status at baseline was 0 (20, 37%), 1 (30, 56%), and 2 (4, 7%). Primary sites were oral cavity 19 (35%), oropharynx 22 (41%), hypopharynx 3 (6%), larynx 9 (17%), and unknown primary 1 (2%). p16 status is positive 22 (41%), negative 29 (54%), and unknown 3 (6%). PD-L1 CPS is < 1 in 6 (11%), >1 in 26 (48%), and unknown 22 (41%). Median follow up time for overall survival (OS) was 12.2 months. The most common grade 3 treatment-related adverse events (TRAEs) occurring in ≥2 pts were hypomagnesemia 2 (4%), hypophosphatemia 2 (4%), fatigue 4 (7%), and rash-acneiform 4 (7%). The only grade 4 TRAEs were hypomagnesemia in 1 (2%) and CTX infusion reaction in 1 (2%). The most common grade 3 immune-related adverse event (IRAE) occurring in ≥2 was fatigue 2 (4%). No grade 4 IRAEs is observed. Median progression-free survival (PFS) and OS were 7.8 and 14.5 months, while 1-year PFS and 1-year OS were 39% and 61%, respectively. There were no statistically significant differences in either PFS and OS based on tumor p16 or PD-L1 status. Conclusions: The clinical trial met its primary endpoint of 1-year OS. Our data indicate the combination of CTX and NIVO is safe and effective in pts with previously untreated incurable R/M HNSCC. Clinical trial information: NCT03370276.
Anlotinib in radioiodine-refractory differentiated thyroid carcinoma: A subanalysis based on ALTER01032 study for patients with poor baseline characteristics.
Authors: Chi Yihebali , Gao Ming , Zhang Yuan , Shi Feng , Cheng Ying , Guo Zhuming , Ge Minghua , Qin Jianwu , Zhang Jiewu , Li Zhendong , Zhou Xiaohong , Huang Rui , Chen Xiaohong , Liu Hui , Cheng Ruochuan , Xu Zhengang , Zheng Xiangqian , Li Dapeng , Tang Pingzhang 
Published: June 2021

6022 Background: Anlotinib (anlo), a multikinase inhibitor, has demonstrated a significant survival benefit in treating locally advanced or metastatic radioiodine-refractory differentiated thyroid carcinoma (RAIR-DTC) with a nearly 4 folds prolongation in median progression-free survival (mPFS) (HR = 0.21, p < 0.0001) compared with placebo in a randomized, placebo-controlled phase 2 study (ALTER01032, NCT02586337). Older age, bone metastasis, structural progression within a short time are generally indicated as negative prognostic factors for thyroid cancer. This subanalysis explored the outcomes of patients (pts) enrolled in ALTER01032 study with these poor baseline characteristics. Methods: 113 pts were enrolled, 76 in anlo arm and 37 in placbo arm. The primary endpoint is PFS. Pts with older age (≥ 55), bone metastasis or radiographic documented disease progression within 3 months (mo) before enrollment were selected. The PFS and overall survival (OS) for these pts were estimated and compared. Since 64.9% pts in placebo arm received crossover treatment with open label anlo after progression while only 3 pts in anlo arm received post-study treatment, the penitential bias for OS from imbalance of subsequent treatment was adjusted by a two-stage estimation method. Results: The results of subanalysis were summarized in the table below. Pts with poor baseline characteristics showed higher risk of progression and death. Significant PFS prolongation was shown across all subgroups in pts received anlo compared with their counterparts who received placebo ( P < 0.05). In pts with bone metastasis or structural progression within 3 mo, anlo treatment achieved significant OS benefit ( P < 0.05). Also, in older pts, a trend of OS improvement was observed (HR = 0.85 (95% CI 0.37, 1.97)). Most pts in placebo arm received crossover anlo. After adjustment, a near-significant decrease of death risk was observed in older pts received anlo compared with those received placebo (HR = 0.48 (95% CI 0.20, 1.13)). Conclusions: This subanalysis showed anlo effectively improved both PFS and OS of pts with RAIR-DTC who have poor baseline characteristics above. Interestingly, although most pts in placebo arm received crossover anlo, they still have higher risk of death, indicating the importance of earlier treatment for these pts. Clinical trial information: NCT02586337. [Table: see text]
Phase II trial of combined durvalumab plus tremelimumab with proton therapy to boost the abscopal effect for recurrent or metastatic head and neck squamous cell carcinoma.
Authors: Kim Hana , Ahn Myung-Ju , Oh Dongryul , Park Sehhoon , Jung Hyun Ae , Lee Se-Hoon , Park Keunchil , Ahn Yong Chan 
Published: June 2021

6034 Background: This phase 2 study investigated whether durvalumab plus tremelimumab with proton therapy improves objective response rate (ORR), overall survival (OS), and progression-free survival (PFS) in heavily treated recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) via boosting abscopal effect. Methods: Thirty-one patients who have previously received more than one chemotherapy regimen, including at least one platinum-based regimen and have at least two measurable lesions enrolled at Samsung medical center. Patients received durvalumab 1500mg intravenously (IV) in combined with tremelimumab 75 mg IV every four weeks for four cycles followed by durvalumab 1500mg every four weeks. After one cycle of durvalumab and tremelimumab combination, proton therapy was performed with a total dose of 25 Gy in 5-Gy daily fractions to one of the measurable lesions. We assessed the target lesion response outside the radiation field by RECIST criteria 1.1 to evaluate the abscopal effect. Results: Between March 2018 and July 2020, 31 patients were enrolled. The median age was 59 years, and median two prior chemotherapy regimens were administered. With 24.8 months of follow-up, the median number of cycles of immunotherapy was three. The ORR was 27.3%, including one complete response and five partial responses. Median OS was 6.4 months (95% CI, 1.0 to 11.8), and median PFS was 2.4 months (95% CI, 0.6 to 4.2). Median duration of response was 15.9 months (range 3.7 – 21.2). Grade 3 or higher adverse events were observed in 6 (27.3%) patients; anemia (n = 1), constipation (n = 1), electrolyte imbalance (n = 2), hyperglycemia (n = 1), pneumonia (n = 1). Conclusions: Combination of durvalumab/tremelimuab with proton therapy is well tolerable and shows encouraging anti-tumor efficacy in non-irradiated tumor lesions of heavily treated HNSCC patients. These results suggest that the combination of immunotherapy with proton therapy might enhance the abscopal effect. Clinical trial information: NCT03450967.
Racial and regional differences in incidence of oropharyngeal cancer in the United States during 2001 to 2017.
Authors: Guo Fangjian , Chang Mihyun , Berenson Abbey 
Published: June 2021

6041 Background: The incidence of human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) has been reported to be increasing among both middle-aged and elderly adults in the United States. This study was to assess racial and regional differences in the incidence of OPSCC among adults in the US. Methods: We included 271,037 adult patients ≥ 20 years old diagnosed with potentially HPV-related OPSCC from the US Cancer Statistics 2001–2017 database which essentially covered the entire US population. Incidence of OPSCC was age- adjusted to the US standard population. Annual percentage change (APC) in the incidence was assessed across races/ethnicities and regions of residence. Results: Among these adults with potentially HPV-related OPSCC from 2001-2017, 5.3% were Hispanics, 83.0% were non-Hispanic Whites, and 9.2% were non-Hispanic Blacks, and 79.1% were male. Incidence of OPSCC increased from 3.9 per 100,000 in 2001 to 4.0 per 100,000 in 2017 (APC 0.43, 95% confidence interval (CI) 0.01, 0.85) in Hispanics, increased from 5.3 per 100,000 in 2001 to 8.6 per 100,000 in 2017 (APC 2.97, 95% confidence interval (CI) 2.71, 3.24) in non-Hispanic Whites, and decreased from 6.3 per 100,000 in 2001 to 5.1 per 100,000 in 2017 (APC -1.27, 95% confidence interval (CI) -1.56, -0.99) in non-Hispanic Blacks. The incidence increased from 5.8 per 100,000 in 2001 to 7.8 per 100,000 in 2017 (APC 1.94, 95% confidence interval (CI) 1.67, 2.21) in the South, increased from 5.0 per 100,000 in 2001 to 7.1 per 100,000 in 2017 (APC 2.13, 95% confidence interval (CI) 1.92, 2.34) in the Northeast, increased from 4.9 per 100,000 in 2001 to 6.3 per 100,000 in 2017 (APC 1.85, 95% confidence interval (CI) 1.53, 2.17) in the West, and increased from 4.9 per 100,000 in 2001 to 7.7 per 100,000 in 2017 (APC 2.79, 95% confidence interval (CI) -2.52, 3.07) in the Midwest. The incidence decreased from 0.9 per 100,000 in 2001 to 0.8 per 100,000 in 2017 (APC -0.81, 95% confidence interval (CI) -1.41, -0.20) among adults 20-44 years old, increased from 9.0 per 100,000 in 2001 to 12.7 per 100,000 in 2017 (APC 2.01, 95% confidence interval (CI) 1.66, 2.36) among adults 45-64 years old, and increased from 10.9 per 100,000 in 2001 to 16.7 per 100,000 in 2017 (APC 2.96, 95% confidence interval (CI) 2.75, 3.16) among adults 65+ years old. Conclusions: OPSCC incidence increased across racial/ethnic groups, regions, and age groups from 2001 to 2017, except that the incidence decreased among non-Hispanic Blacks and young people. Underlying causes for the decreasing trend in the incidence of OPSCC among certain groups need further investigation.
Palbociclib (P) in patients (pts) with head and neck cancer (HNC) with CDKN2A loss or mutation: Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) study.
Authors: Pisick Evan P. , Rothe Michael , Mangat Pam K. , Garrett-Mayer Liz , Worden Francis P. , Bauman Jessica R. , Fu Siqing , Leidner Rom S. , Balmanoukian Ani Sarkis , Calfa Carmen , Carrizosa Daniel R. , D'Andre Stacy D. , Nabell Lisle , Park Min S. , Powell Steven Francis , Thota Ramya , Schilsky Richard L. 
Published: June 2021

6043 Background: TAPUR is a phase II basket study evaluating anti-tumor activity of commercially available targeted agents in pts with advanced cancers with genomic alterations. Results in a cohort of HNC pts with CDKN2A loss or mutation treated with P are reported. Methods: Eligible pts had advanced HNC, no standard treatment options, measurable disease, ECOG PS 0-2, and adequate organ function. Genomic testing was performed in CLIA-certified, CAP-accredited site selected labs. Pts received P at 125 mg orally once daily for 21 days, followed by 7 days off until disease progression. Pts matched to P had CDKN2A loss or mutation and no RB mutations. Simon 2-stage design tested the null disease control (DC) - defined as partial (PR), complete response (CR) or stable disease at 16+ weeks (SD 16+) - rate of 15% vs. 35% (power = 0.85; α = 0.10). If ≥2 of 10 pts in stage 1 have DC, 18 more pts are enrolled. If ≥7 of 28 pts have DC, the null DC rate is rejected. Secondary endpoints are progression-free survival (PFS), overall survival (OS) and safety. Results: 28 pts (64% male) with HNC with CDKN2A loss (20 pts) or mutation (8 pts) were enrolled from June 2016 to Sept 2019. All were eligible for efficacy and toxicity. Demographics and outcomes are summarized in Table. No objective response (OR) and 10 pts with SD16+ (9 with CDKN2A loss, 1 with mutation) were observed for a DC rate of 37% (95% CI: 21%, 50%); the null DC rate of 15% was rejected (p=0.005). 14 pts had at least one grade 3-5 adverse or serious adverse event (AE/SAE) at least possibly related to P with the most common being low WBC/platelets. Other grade 3-4 AEs included anemia, fatigue, hypocalcemia, and syncope. There was one pt with grade 5 respiratory failure likely due to extensive lung metastases and aspiration but P-related pneumonitis could not be ruled out. Conclusions: Monotherapy P demonstrated modest anti-tumor activity and clinically significant AEs in heavily pre-treated pts with HNC with CDKN2A loss or mutation. Additional study is warranted to confirm the efficacy of P in pts with HNC with CDKN2A loss or mutation. Clinical trial information: NCT02693535. [Table: see text]
Capecitabine maintenance therapy after induction chemotherapy in newly diagnosed metastatic nasopharyngeal carcinoma: An open-label, randomized, controlled, phase trial.
Authors: Liu Guo-Ying , Li Wang-Zhong , Wang De-Shen , Liang Hu , Lv Xing , Ye Yan-Fang , Zhao Chong , Ke Liang-Ru , Qiang Mengyun , Cao Xun , Lv Shu-Hui , Lu Nian , Bei Wei-Xin , Cai Zhuocheng , Chen Xi , Xie Jun-Zhi , Liang Chixiong , Guo Xiang , Xia Weixiong , Yanqun Xiang 
Published: June 2021

6044 Background: Capecitabine maintenance therapy improves outcomes in various tumor types, but minimal data are available on the effect of capecitabine maintenance therapy in metastatic nasopharyngeal carcinoma (NPC). We aimed to investigate whether capecitabine maintenance therapy would prolong the progression-free survival (PFS) of newly diagnosed metastatic NPC, in comparison to best supportive care (BSC). Methods: This was an open-label, randomized, controlled, phase trial. Eligible patients for maintenance randomisation were aged 18-65 years old with newly diagnosed metastatic NPC at the Sun Yat-Sun University Cancer Center (SYSUCC), had completed 4 to 6 cycles of induction chemotherapy as per protocol and had achieved disease control to protocol treatment, including capecitabine. Patients were randomly assigned 1:1 to capecitabine maintenance (oral 1,250 mg/m2/day on days 1-14 every 21 days) for up to 24 months with BSC or BSC alone. The primary endpoint was PFS. The secondary endpoints included overall survival, duration of response, objective response rate and adverse effects. Analyses were done by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT02460419 and is ongoing and no longer recruiting new patients. Results: Between May 16th, 2015, and January 9th, 2020, 140 metastatic NPC patients were screened, and 104 eligible patients were randomly assigned to capecitabine maintenance plus BSC (n = 52) or BSC alone (n = 52). After a median follow-up of 33.1 months (IQR, 21.5-50.7 months), median PFS was 35.2 months in the capecitabine maintenance group and 9.1 months in the BSC group (HR: 0.426; 95%CI: 0.248-0.731, P = 0.001). The most commongrade 3 or 4 adverse events during maintenance therapy were hand-foot syndrome (10.0%), nausea/vomiting (6.0%), fatigue (4.0%), and mucositis (4.0%). Totally 37 deaths occurred during follow-up, 14 (26.9%) in the capecitabine maintenance group and 23 (44.2%) in the BSC group. Overall survival data was immature. No deaths in the capecitabine maintenance group were deemed treatment related. Conclusions: Capecitabine maintenance significantly improved PFS in patients with newly diagnosed metastatic NPC who achieved disease control after induction chemotherapy compared to BSC and exhibited low grade and manageable toxicities. Clinical trial information: NCT02460419.
Refining TNM-8 M1 categories with anatomic subgroups for previously untreated de novo metastatic nasopharyngeal carcinoma.
Authors: Chan Sik-Kwan , Lin Cheng , Huang Shao Hui , Chau Tin Ching , Guo Qiaojuan , O'Sullivan Brian , Lam Ka-On , Chau Sze Chun , Chan Ann SY , Tong Chi-Chung , Vardhanabhuti Varut , Kwong Dora LW , So Tsz Him , Ng Sherry CY , Leung To Wai , Luk Mai-Yee , Lee Anne WM , Choi Cheuk-Wai , Pan Jianji , Lee Victor Ho-Fun 
Published: June 2021

6046 Background: The eighth edition TNM (TNM-8) classified de novo metastatic (metastatic disease at presentation) nasopharyngeal carcinoma (NPC) as M1 without further subdivision. However, survival heterogeneity exists and long-term survival has been observed in a subset of this population. We hypothesize that certain metastatic characteristics could further segregate survival for de novo M1 NPC. Methods: Patients with previously untreated de novo M1 NPC prospectively treated in two academic institutions (The University of Hong Kong [n = 69] and Provincial Clinical College of Fujian Medical University [n = 114] between 2007 and 2016 were recruited and re-staged based on TNM-8 in this study. They were randomized in 2:1 ratio to generate a training cohort (n = 120) and validation cohort (n = 63) respectively. Univariable and multivariable analyses (MVA) were performed for the training cohort to identify the anatomic prognostic factors of overall survival (OS). We then performed recursive partitioning analysis (RPA) which incorporated the anatomic prognostic factors identified in multivariable analyses and derived a new set of RPA stage groups (Anatomic-RPA groups) which predicted OS in the training cohort. The significance of Anatomic-RPA groups in the training cohort was then validated in the validation cohort. UVA and MVA were performed again on the validation cohorts to identify significant OS prognosticators. Results: The training and the validation cohorts had a median follow-up of 27.2 months and 30.2 months, respectively, with the 3-year OS of 51.6% and 51.1%, respectively. Univariable analysis (UVA) and multivariable analysis (MVA) revealed that co-existing liver and bone metastases was the only factor prognostic of OS. Anatomic-RPA groups based on the anatomic prognostic factors identified in UVA and MVA yielded good segregation (M1a: no co-existing liver and bone metastases and M1b: co-existing both liver and bone metastases; median OS 39.5 and 23.7 months respectively; P =.004). RPA for the validation set also confirmed good segregation with co-existing liver and bone metastases (M1a: no co-existing liver and bone metastases and M1b: co-existing liver and bone metastases), with median OS 47.7 and 16.0 months, respectively; P =.008). It was also the only prognostic factor in UVA and MVA in the validation cohort. Conclusions: Our Anatomic-RPA M1 stage groups with anatomical factors provided better subgroup segregation for de novo M1 NPC. The study results provide a robust justification to refine M1 categories in future editions of TNM staging classification.