bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment and outcome of patients with high-grade advanced ovarian cancer (AOC): Real-world data in Germany (QS Ovar of the AGO Study Group).
Authors: Mahner Sven , Harter Philipp , Du Bois Andreas , Hilpert Felix , Kerkmann Markus , Sehouli Jalid , de Gregorio Nikolaus , Hanker Lars Ch. , Heitz Florian , Marmé Frederik , Woelber Linn Lena , Holtmann Laura , Elser Gabriele , Pfisterer Jacobus ,   AGO Study Group
Published: June 2022

e17613 Background: Outcome of patients with ovarian cancer depends largely on treatment quality and expertise of treating physicians and centers. To assess treatment reality and quality in Germany, we initiated a nationwide quality assurance program. Methods: All German hospitals treating patients with ovarian cancer were asked to document their patients with primary diagnosis of epithelial ovarian cancer in the third quarters of 2012 and 2016. Details of tumor, treatment and outcome were documented in a central database. The current analysis focuses on patients with high-grade AOC stage III/IV. Results: In total, 1010 patients with high-grade AOC were documented. This represents 63% of all patients diagnosed with AOC in Germany in these periods. Median age was 65 years. The majority (774/1010 - 76.6%) were diagnosed with stage III disease and 947/1010 (93.8%) had serous, 34 (3.4%) endometrioid and 29 (2.9%) clear cell histology. 915/1010 (90.6%) had primary cytoreductive surgery. Complete resection was achieved in 434/915 (47.4%) at primary surgery and in 54/95 (56.8%) at interval debulking surgery. Median PFS and OS in patients with primary surgery and complete resection was 29.7 months and 63.1 months compared to 16.8 months and 30.7 months in patients with residual disease (HR PFS 0.46 95% CI 0.22-0.54 HR OS: 0.38 95% CI 0.31-0.45). In patients with neoadjuvant chemotherapy and interval debulking, median PFS and OS were 24.3 and 50.7 months with complete resection, compared to 15.4 and 33.9 months with residual disease (HR PFS 0.61 95% CI 0.38-0.95 HR OS: 0.48 95% CI 0.28-0.83). First-line chemotherapy was carboplatin/paclitaxel (TC) in 919/1010 (91%) of the patients, 627 (62%) also received bevacizumab (TCB) and 544 of these (87%) also received maintenance therapy. Median PFS and OS in patients with TCB was 23.3 months and 46.2 months and 18.5 months and 39.0 months in patients treated with TC (p = 0.049: HR 0.85, 95% CI 0.72-1.00 and p = 0.012: HR 0.79, 95% CI 0.65-0.95). The rate of complete tumor resection at surgery as well as the use of bevacizumab increased between the two periods. Conclusions: Based on this representative cohort of patients with advanced ovarian cancer in Germany, the majority of patients is treated with primary surgery followed by carboplatin/paclitaxel and bevacizumab. Patient outcome regarding PFS and OS was best when complete tumor resection was achieved at primary surgery and patients received combination chemotherapy with maintenance treatment. Supported by Roche, Amgen, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Essex.
Real-world outcomes of niraparib treatment in patients with ovarian cancer: The first observational multicenter study in China.
Authors: Li Jin , Wu Xiaohua , Shou Huafeng , Zheng Fei , Huang Xiaohong , Liu Fang , Tang Xuedong , Yang Jianhua , Zhang Lin 
Published: June 2022

e17614 Background: Compared with western countries, the application time of PARP inhibitor in China is shorter and the real world outcomes are affected by many factors. The objective of this study was to present the real-world patients’ portrait, and the results of Niraparib treatment in China. Methods: This study included 142 patients treated with Niraparib from 8 hospitals in China between Dec. 2018 and Sep. 2021. Patients’ characteristics were summarized. The efficacy and safety in first-line maintenance (1L-M), platinum-sensitive recurrence maintenance (PSR-M), and treatment for ovarian cancer were evaluated. Survival outcomes and the factors influencing PFS were estimated. Results: 93 patients received Niraparib as 1L-M, 31 as PSR-M and 18 as salvage. BRCA status was wild-type or unknown in 87.3% of patients. With a median follow-up time of 8.7m, the mPFS for 1L-M has not yet been reached, and the mPFS for PSR-M and salvage therapy was 10.5 months (95%CI: 3.9-NE) and 5.7 months (95%CI: 3.0-13.0), respectively. Responses to last chemotherapy (CR vs. PR, P= 0.0077) and CA125 value before taking Niraparib (≤35UI/ml vs. > 35UI/ml, P= 0.0344) were two important factors affecting PFS among 1L and PSR patients. 12.7%(18/142) of patients experienced grade ≥3 hematologic adverse events and 23.2% experienced dose adjustment. It was noteworthy that when the interval of chemotherapy and Niraparib < 21 days, the incidence of Grade ≥ 3 adverse events increased significantly ( P= 0.0355). Conclusions: This was the first and largest observational multicenter study reporting the outcomes of Niraparib treatment for ovarian cancer in real-world setting in China. Generally, Niraparib was effective and well tolerated, which was consistent with the results of prospective trials. However, in real world, it was more inclined to use Niraparib in late-line treatment without genetic testing.
Evaluation of homologous recombination deficiency biomarkers in patients with ovarian cancer treated with PARP inhibitors.
Authors: Campoverde Leticia , Lopes Da Silva Laercio , Silveira Hyan , Coelho Nogueira Wilson , Mina Lida A. , Lopes Gilberto , Batalini Felipe 
Published: June 2022

e17615 Background: Germline BRCA1/2 mutations are associated with response to Poly(ADP-ribose) polymerase inhibitors (PARPi). In addition to BRCA1/2 mutations, there are other Homologous Recombinations Deficiency (HRD) biomarker candidates already available in clinical practice including genome-wide loss-of-heterozygosity (gLOH) and myChoice score. Inconsistencies in biomarkers used in clinical trials with PARPi are a challenge to clinical interpretation. This study aims to compare clinically available HRD biomarkers in terms of benefits from PARPi. Methods: We performed database search for phase II or III randomized clinical trials comparing PARPi versus chemotherapy, and meta-analysis using generic inverse variance and a random-effects model. Patients were classified into three categories according to their HRD status: 1) BRCAmut (patients with BRCA1/2 mutation of germline or somatic origin), 2) non-BRCA HRD (patients BRCA wild-type (wt) with a different HRD biomarker - gLOH or myChoice); and 3) homologous recombination proficiency (HRP) (BRCAwt and without HRD biomarkers). From those that were BRCAwt, we compared myChoice+ with gLOH-high. Results: Eight studies (n = 4372 patients) with PARPi as first-line and recurrence settings were included. BRCAmut had PFS HR 0.29 (95%CI, 0.24-0.35), BRCAwt & HRD 0.43 (95%CI, 0.34-0.53) and HRP 0.74 (95%CI, 0.62-0.89). In a secondary analysis by HRD stratification method, patients with BRCAwt & myChoice > = 42 had PFS HR 0.43 (95%CI, 0.34-0.56), similar to patients with BRCAwt & gLOH-high with PFS HR 0.42 (95%CI, 0.28-0.62). Conclusions: Patients with BRCA mutations benefited the most from PARPi. From patients with BRCA1/2 wild-type, a similar benefit was found in patients with gLOH-high and those myChoice+, which was superior to HRP patients. The clinical development of further HRD biomarkers (i.e. Sig3, HRDetect) may help identify more patients who benefit from PARPi.
Comparison of AYA versus non-AYA ovarian cancer genomic landscape in NCI-MATCH trial.
Authors: Sankaran Hari , Kotliarov Yuri , Zhao Yingdong , Temkin Sarah M , Williams Paul M. , Karlovich Chris Alan , Coffey Brent , Das Biswajit , Chang Ting-Chia , Seibel Nita , Tricoli James V. , Best Ana F. , Gray Robert James , Wang Victoria , Wei Zihan , Hamilton Stanley R. , Patton David R. , Chen Alice P. , McShane Lisa 
Published: June 2022

e17617 Background: NCI-MATCH, a signal-finding precision medicine trial, centrally screened tumors from ̃6000 patients age > 18 with refractory/relapsed cancer using Oncomine Comprehensive Assay (OCA) targeted gene panel. Screened cohort included a subset of patients with ovarian cancer age 18-39 yrs, overlapping adolescent and young adult (AYA) range (NCI consensus definition: 15-39 yrs). Objective of this study was to compare tumor genomic features of AYA to non-AYA ovarian cancers. Methods: Patient clinicopathologic, demographic, and tumor mutation (SNVs, Indels, CNVs by central OCA) data from NCI-MATCH were available. Analyses were restricted to mutation profiles generated by OCA version 2 (OCA v2), which assessed 143 genes and was used for most samples. Proportions of cases with mutations in each gene were compared for AYA and non-AYA groups by 2-sided Fisher’s exact tests. For each gene, association between age (continuous independent variable) and presence of mutation (binary dependent variable) was assessed using logistic regression. Benjamini-Hochberg adjusted p-values were computed; false discovery rate (FDR) was controlled at 10%. Results: Data from 455 ovarian cancers (437 epithelial, 18 stromal), including 21 AYA and 434 non-AYA cases, were included in this analysis. Among the 28 genes most frequently (in > 6 patient tumors) mutated and altered, CTNNB1 was mutated in 9.5% of AYA patients compared to 0.9% in non-AYA (unadj. p=0.027) but failed to meet 10% FDR criterion (FDR-adj. p=0.7). KRAS mutation was more frequent in AYA than non-AYA but not significantly after adjustment (FDR-adj. p=0.7). Logistic regression results showed TP53 mutation was significantly associated with older age (FDR-adj. p<0.0001), and ATM mutation was borderline associated with younger age (FDR-adj. p=0.052). No other differences, including in clinically actionable mutations ( BRCA1/2, MSH2), were observed. Table displays selected results. Conclusions: This preliminary study shows that no genes were mutated in significantly different proportion between AYA and non-AYA groups, but modeling age as a continuous variable highlighted known association of TP53 mutation with older age and a trend towards association of ATM mutation with younger age. More comprehensive tumor mutation profiling and analyses of additional tumor types may reveal further insights into rare AYA cancers. [Table: see text]
Efficacy and safety of pembrolizumab in Chinese patients with recurrent/unresectable/metastatic head and neck squamous cell carcinoma.
Authors: Li Jieying , Song Kai , Feng Yuanyong , Shang Wei ,   Affiliated Hospital of Qingdao University
Published: June 2022

e18001 Background: The efficacy and safety of Pembrolizumab in recurrent /unresectable/metastatic head and neck squamous cell carcinoma have been well documented in KEYNOTE-048 and other studies, and the effectiveness of different areas’ population have been shown in related studies. However, there is no native data based on the Chinese population. The purpose of this study was to investigate the efficacy and safety of Pembrolizumab in the treatment of R/U/M head and neck squamous cell carcinoma in Chinese population. Methods: We reviewed patients data from the department of Oral & Maxillofacial Surgery, the Affiliated Hospital of Qingdao University. The patients with R/U/M head and neck squamous cell carcinoma were treated with or without combined chemotherapy / targeted therapy according to their PD-L1 expression status (CPS). Pembrolizumab was infused intravenously with 200mg every 3 weeks for a maximum of 35 cycles. The primary endpoint was Objective Response Rate(ORR). The secondary endpoints were Quality of Life, Safety and Progression Free Survival(PFS). Results: A total of 23 eligible patients with R/U/M head and neck squamous cell carcinoma were included from February 2021 to February 2022, including 18 males (78.26%) and 5 females (21.74%) with a median age of 68 years. The primary sites were oral cavity in 16 cases (69.56%), oropharynx in 4 cases (17.39%), hypopharynx in 1 case (4.35%), and larynx in 2 cases (8.70%). P16 status was positive in 4 cases (17.39%), negative in 12 cases (52.17%), and unknown in 7 cases (30.43%). The expression status of PD-L1 in all patients was known. Patients with CPS ≥ 20 were treated with Pembrolizumab monotherapy and patients with CPS < 20 were treated with Pembrolizumab combined with chemotherapy / targeting therapy, of which 22 (95.65%) were treated with first-line therapy and 1 (4.35%) were treated with second-line therapy. The median follow-up period was 6 months. 15 patients were assessed as remission (as of February 2022), of which 4 (17.39%) showed CR, 11 (47.83%) showed PR, 7 (30.43%) showed SD, and 1 (4.35%) showed PD. ORR was 65.22%, DCR was 95.65%. After 4 cycles of treatment, 14 patients (60.87%) achieved tumor remission and control, and the functional status score (KPS) increased from 65 to 85. The incidences of thyroid dysfunction, skin rash, fatigue, neutropenia and immune pneumonia were 2 (8.70%), 3 (13.04%), 2 (8.70%), 1 (4.35%) and 1(4.35%), respectively. Conclusions: This retrospective data have shown excellent efficacy and safety of pembrolizumab in the Chinese population of R/U/M head and neck squamous cell carcinoma, and provide data support for follow-up related research.Due to the short follow-up time, most of the patients have not yet reached PFS, and follow-up will continue.
Nivolumab in squamous cell carcinomas of the head and neck (SCCHN): A real-world outcome study in Ontario, Canada.
Authors: Zereshkian Arman , Shafi Ruaa , Pond Gregory Russell , Hotte Sebastien J. 
Published: June 2022

e18017 Background: The CheckMate-141 trial led to the approval of nivolumab in platinum-resistant metastatic squamous cell carcinomas of the head and neck (SCCHN). We evaluated outcomes of SCCHN patients in Ontario, Canada treated with nivolumab since its funding through the New Drug Funding Program (NDFP) of Cancer Care Ontario (CCO). Methods: Retrospective review using the provincial treatment registry (CCO NDFP) was undertaken. Patient characteristics, reason for treatment, treatment length, and date of death were collected. Kaplan-Meier method was used to estimate overall survival and Cox regression to evaluate prognostic effect of selected factors. Results: 134 patients with SCCHN received nivolumab between March 2017 and March 2019. Median patient age was 63 years with 80.6% male. Nivolumab was used as second-line therapy after disease relapse within 6 months of curative-intent platinum chemotherapy (PC) in 39.6% of patients (Indication 1 – I1), used as second-line therapy post PC in non-curative intent in 42.6% of patients (Indication 2 – I2), and used as first-line therapy in non-curative intent due to contraindication for PC in 17.2% of patients (Indication 3 – I3). Median overall survival (mOS) was 5.8 months (95% confidence intervals (CI) 4.5-7.3), and one-year OS was 28.4% (CI 2.10-36.1). HPV status had no statistically significant impact on OS (p = 0.12). Patients with a lower BSA (< 1.81) had median OS of 3.9 months (CI 3.1-6.7) versus 9.0 months (CI 6.5-14.8) in those with higher BSA, HR = 0.12 (CI 0.04-0.39, p < 0.001). Differences between indications was statistically significant (p < 0.001). Patients who received nivolumab for I1 had mOS 7.2 months (CI 3.8-9.8) versus 11.9 months (CI 6.2-not reached) for I3, HR = 1.73(CI 0.94-3.16). Patients who received nivolumab for I2 had mOS 3.9 months (CI 2.9-5.4) as compared to I3, HR = 3.27(CI 1.80-5.94). Patients who received nivolumab for I2 had poorer mOS as compared to I1 HR = 1.90(CI 1.23-2.92). Conclusions: Real world data in Ontario demonstrates poorer mOS, but similar 1-year survival compared to CheckMate-141 trial. HPV status had no significant impact on mOS. Patients who received nivolumab as first-line therapy in the non-curative setting appeared to have longer mOS than those who received initial PC for non-curative intent followed by nivolumab. Patients who received nivolumab as second-line therapy post PC in non-curative intent setting as compared to within 6 months of curative-intent therapy had poorer mOS.
Penpulimab plus gemcitabine in combination with cisplatin or anlotinib as first-line treatment for metastatic nasopharyngeal carcinoma (M NPC): A phase II study.
Authors: Huang Shuang , Chen Xiaozhong , Qu Song , Qu Shenhong , Han Yaqian , Yang Kunyu , Huang Shiting , Li Min , Zhang Lin , Ding Qian 
Published: June 2022

e18032 Background: Cisplatin (P)-based combination regimen is the backbone in the first-line treatment of M NPC while the toxicity limited its usage. This study investigated the efficacy and safety of penpulimab (an anti-programmed death-1 antibody) plus gemcitabine (G) in combination with cisplatin (P) or anlotinib (a multikinase inhibitor) as first-line treatment of these pts. Methods: This is a multicenter, three cohorts, randomized, phase II study (NCT04736810). Pts with histologically confirmed regional or distant M NPC who had measurable lesions per RECIST 1.1 and received no systemic treatment for metastatic lesions were enrolled. Other inclusion criteria included 18-75 years old and ECOG PS 0-1. Pts in cohort A, B and C were given G + P + penpulimab + anlotinib; G + P + penpulimab or G + penpulimab + anlotinib, respectively. G (1000mg/m2, d1, d8) and P (80mg/m2, d1) were given intravenously for 4 to 6 cycles, 3 weeks per cycle. Penpulimab (200mg, d1) and anlotinib (12mg, qd, d1-14) were given intravenously and orally respectively until confirmed disease progression, or unacceptable toxicities, or up to 2 years, whichever occurred firstly. Pts who developed disease progression but still had clinical benefit could receive penpulimab and anlotinib continuously based on the decision of physicians. The primary endpoint was objective response rate (ORR). Here we report the preliminary results of this study. Results: Between March 2021 and September 2021, 17 pts were randomly assigned to cohort A (n = 5), B (n = 5) or C (n = 7), and the median age was 52, 49 and 52 years old, respectively. Nearly half (7/17, 41.2%) had liver metastasis and the majority (5/7, 71.4%) was in the cohort C. At the data cutoff date on January 17, 2022, the median treatment cycles were 6, 8, 8 across three cohorts. All pts received tumor response and the confirmed ORR was 80.0%, 80.0% and 100%. The details of tumor response were summered in followed table. Notably, in cohort C, 1 pts achieved confirmed complete response (CR) and all others had confirmed partial response (PR). Replacement of cisplatin with anlotinib seemed to show better safety profile that ≥ grade 3 adverse events (AEs) occurred in 6 pts (85.7%) in cohort A, 5 (100%) in cohort B while only 4 (57.1%) in group C. Moreover, the overall incidence of serious AEs was 28.6%, 20%, 14.3% across three cohorts. The most common ≥ grade 3 AEs were white blood cell decreased and neutrophil count decreased. Conclusions: This preliminary analysis indicated that penpulimab plus gemcitabine and anlotinib had promising efficacy and favorable tolerance profile as first-line treatment for M NPC. Further investigate is ongoing. Clinical trial information: NCT04736810. [Table: see text]
Establishment of a visualized mouse orthotopic model of nasopharyngeal carcinoma.
Authors: Kang Min , Chen Wei , Chen Sixia , Jiang Li , Shu Gege , Yin Yuanxiu , Quan Zhipeng , Zhou Ziyan , Shen Mingjun , Qin Yating , Yang Chaolin , Su Xuejin , Chen Weimin 
Published: June 2022

e18048 Background: Nasopharyngeal carcinoma, one of the most common head and neck tumors, is particularly prevalent in Southeast Asia and is characterized by high rates of metastasis and recurrence. Although mouse orthotopic tumor models are commonly employed in studies investigating the mechanisms underlying tumor development and progression, as well as preclinical treatment, currently no such model exists for nasopharyngeal carcinoma. The aim of the current study is to, therefore, establish an orthotopic murine model for nasopharyngeal carcinoma. Methods: To this end, human nasopharyngeal carcinoma C666-1-luc cells, stably expressing the firefly luciferase gene, were injected subcutaneously into the right axilla of BALB/C nude mice. Four weeks later, the resulting subcutaneous tumors were cut into small blocks and grafted into the nasopharynx of immunodeficient BALB/C nude mice to induce tumor formation. Tumor growth was monitored by bioluminescence imaging and small animal magnetic resonance imaging. The histological and immunological antigen expression associated with orthotopic nasopharyngeal carcinoma were analyzed by tissue section analysis and immunohistochemistry (IHC). Results: The tumor formation rate was over 90%. Fluorescence signal detection, micro-magnetic resonance imaging and hematoxylin and eosin staining revealed the successful growth of tumors in the nasopharynx of nude mice. Moreover, IHC analysis detected positive CK, CK5/6, P40 and P63 expression in the mouse orthotopic tumors, which is consistent with the reported antigen expression in the nasopharyngeal tumors of patients. Conclusions: Hence, we successfully established a mouse orthotopic model of nasopharyngeal carcinoma that is highly reproducible, and simple in operation, with low mortality and high tumor formation rates. Moreover, this model facilitates real-time monitoring of tumor growth via in vivo imaging technology, thus, providing a platform for researching nasopharyngeal carcinoma that is more conducive to preclinical research.
A novel drug combination strategy that redesigns the pharmacological management of oral cancer.
Authors: Chakraborty Rajdeep , Darido Charbel , Hu Honghua , Vickery Karen , Ranganathan Shoba 
Published: June 2022

e18053 Background: Biofilm formation is a continuous process in oral cancer patients, despite proper extirpation/elimination of a bacterial plaque via a surgical procedure or antibiotic treatment. Also, elimination of a bacterial plaque does not necessarily remove extant bacterial antigen-stimulated oral cancer cells. Therefore, combination drug treatment may be an appropriate approach to elucidate the confounding effects of bacterial antigens on anti-cancer drugs. Methods: Our drug combination strategy addressed both Gram-positive (Lipoteichoic acid [LTA]) and Gram-negative (Lipopolysaccharide [LPS]) bacterial antigens, to determine the effect of anti-cancer drugs on LPS/LTA/LPS+LTA-stimulated preclinical oral cancer models (SCC4, SCC9, SCC25, and Cal 27). The drug combination strategy was designed in six phases of treatment. In phase 1, plated cells were treated with different combinations of bacterial antigens in combination with anti-cancer drugs. In the phases 2 and 3, inhibitory drugs were introduced in the presence of bacterial antigens after 24 hours and 72 hours of bacterial antigen stimulation. In phases 4 and 5, inhibitory drugs were added after 24 hours and 72 hours of bacterial antigen stimulation. In phase 6, inhibitory drugs were applied in the absence of, and without stimulation with, bacterial antigens. Metabolic assays, reverse transcription quantitative PCR, Western blot, Proteome Profiler, apoptotic and ELISA assays were performed to validate the novel drug combination strategy. Results: Anti-cancer drug treatment on preclinical oral cancer models resulted in 43.6% ± 3.3% of precancerous models being apoptotic. To mimic pre-existing unhygenic conditions in oral cancer patients, prior stimulation of preclinical model with LPS+LTA 72 hours before drug treatment, reduced apoptosis to 32.2% ± 1.1% of cells. Apoptosis was almost annulled (2.98% ± 0.3%; p < 0.01) when drug treatment was carried out along with bacterial antigens. Treatment with drugs in the absence of bacterial antigens resulted in significantly more apoptotic cells than in presence of bacterial antigens (p < 0.0001). Metabolic and viability assay showed similar results like apoptotic assay. Conclusions: Bacterial antigens mimic the presence of Gram-negative and Gram-positive bacteria and thus severely affect the efficacy of anti-cancer drugs. The novel drug combination strategy redesigns the pharmacological management of oral squamous cell carcinoma.