bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preliminary results of anlotinib and niraparib dual therapy evaluation in platinum-resistant recurrent ovarian cancer.
Authors: Liu Guochen , Liu Jihong , Xian Bingna , Li Jing , Feng Yanling , Huang He , Wan Ting , Huang Qidan , Tu Hua , Gu Haifeng , Liu Zhimin 
Published: June 2021

e17532 Background: Patients with platinum-resistant ovarian cancer have a poor prognosis. Effective treatment options for these patients are limited. Combination of PARP inhibitors and antiangiogenic therapy is reported as an effective antitumor strategy. In this study (ANNIE), we evaluate the activity of niraparib combined with anlotinib in patients with platinum resistant recurrent ovarian carcinoma. Methods: The ANNIE trial (ClinicalTrials.gov identifier NCT04376073) was a multicentre, single-arm, phase 2 study that evaluated the safety and activity of niraparib combined with anlotinib in patients (≥18 & ≤70 years, an Eastern Cooperative Oncology Group performance status of 0 or 1) with recurrent ovarian epithelial, fallopian tube, or primary peritoneal cancer cancer whose disease recurred in less than 6 months after the last administered platinum therapy, and with measurable disease according to the Response Evaluation Criteria in Solid Tumors. Patients received oral niraparib 300mg/200mg once daily continuously and anlotinib 12mg (The initial dose was reduced to 10mg on November 1, 2020) on day 1-14 of each 21-day cycle thereafter until disease progression or intolerable toxicity. The primary objective was to assess objective response rate (ORR; complete plus partial responses) according to RECIST version 1.1. 40 cases are planned to be enrolled. Results: Between May 22, 2020 and February 6, 2021, we enrolled 33 patients (median age, 56 years [range, 37-69 years]). Patients had received a median of six (range, 2-9) previous lines of therapy. The cut-off date of analysis was February 4, 2021, the median follow-up was 4.1 months (range, 0.1–8.1). At data cutoff, all but seven (2 voluntarily withdrew, 5 with progressive disease) of the patients were still on treatment. Twenty-five patients underwent imaging evaluation. The confirmed best overall response assessment showed 12 with partial responses, 12 with stable disease, yielding the ORR of 48.0% (95% CI, 27.0%̃69.0%). The median duration of response and the median PFS were not reached. Drug-related grade 3 or worse treatment-emergent adverse events were occurred in 39.4% patients, including hand-foot skin reaction (3 pts), thrombocytopenia (2 pts), hypertriglyceridemia (2 pts), neutropenia (2 pts), anemia (1 pts) and hypertension (1 pts). The most common treatment emergent adverse events were hand-foot skin reaction (36.4%), hypertension (36.4%), and thrombocytopenia (33.3%). No treatment-related death was recorded. Enrollment was ongoing so far. Conclusions: Niraparib in combination with anlotinib showed promising antitumor activity and tolerable toxicity in patients with platinum resistant recurrent ovarian cancer. The conclusion can be clarified after the research is completed. Clinical trial information: NCT04376073.
Determinants of response to checkpoint inhibition in ovarian cancer.
Authors: Buras Andrea Leigh , Martin Alexandra , Zhou Jun Min , Boulware David C , Conejo-Garcia Jose , Wenham Robert Michael 
Published: June 2021

e17538 Background: Despite evidence that ovarian cancer (OC) is an immunogenic disease, single-agent checkpoint inhibitors have shown limited response. A clinical trial was conducted evaluating dose-dense paclitaxel and pembrolizumab in platinum-resistant OC. Our aim was to evaluate for biomarkers of response to this combination. Methods: Immunohistochemistry was performed to identify PD–L1 and tumor infiltrating lymphocytes (TIL) in pretreatment formalin fixed paraffin embedded tissue. We performed flow cytometry on matched blood to identify presence of immunosuppressive myeloid-derived suppressor cells (MDSCs) in circulation. We performed T-cell receptor (TCR) sequencing on tumor and matched blood to evaluate whether an oligoclonal or polyclonal immune response would be associated with outcomes. On selected patients we assessed peripheral T-cell responses to treatment using an interferon-ɣ enzyme-linked immunospot (IFN-ɣ ELISpot) assay between excellent and poor responders. Cox proportional hazards model was used to estimate hazards ratios (HR) for response in relation to each biomarker. Kaplan-Meier analysis and log-rank test were used to evaluate associations between progression free survival (PFS), overall survival (OS) and each biomarker. Results: Analysis was limited to 34 patients with tumor available and one RECIST response evaluation. Odds of response trended higher (OR = 4.1) in patients with PD-L1 (+) than patients with PD-L1 (-) tumors (p = 0.061). When restricting analysis to best response of CR/PR versus PD, the odds was 13.0 (p = 0.041). Patients with PD-L1(+) tumors had a HR for progression 0.56 (0.26-1.22; p = 0.144). Presence of TILs was classified as 0-3 (0-1 low, 2-3 high). High TIL presence was not associated with response, but was associated with improved OS and trend toward improved PFS; HR 0.29 (0.09-0.90, p = 0.022) and HR 0.47 (0.21-1.05, p = 0.06). Pre- and post-treatment levels of MDSCs were not associated with response or survival, though a trend was noted; a one unit increase in pretreatment MDSCs leads to 5% decrease in the odds of being responder. Immunoseq analysis of TCR repertoire pre- and post-treatment suggested that in increase in productive clonality was associated with increased odds of being a responder; this was not statistically significant. Notably, IFN-ɣ ELISpot assay demonstrated a significant T-cell response against neoantigens post-treatment in patients who had a partial response and long overall survival. Post treatment T-cell response showed a significantly mixed response to neoantigens in the patient analyzed who had progressive disease. Conclusions: Finding biomarkers predicting benefit from checkpoint inhibitors has been challenging. Though inconclusive, these data suggest biomarkers that may be associated with this combination. T-cell response to neoantigens in patients with response to treatment suggests neoantigens as a potential target for therapeutic direction.
Efficacy and safety of weekly paclitaxel in elderly patients with heavily pretreated platinum-resistant ovarian carcinoma.
Authors: Sanchez-Bayona Rodrigo , Tolosa Pablo , Sanchez de Torre Ana , Castelo Alicia , Bernal-Hertfelder Elsa , Lema Laura , Ciruelos Eva M. , Manso Luis 
Published: June 2021

e17552 Background: In platinum-resistant ovarian cancer treatment, single-agent paclitaxel can be used alone or in combination with bevacizumab. We aimed to assess the efficacy and safety profile of a weekly paclitaxel (WP) scheme in heavily pretreated platinum-resistant high-grade serous ovarian carcinoma. Methods: We retrospectively analyzed 30 adult patients with platinum-resistant high-grade serous ovarian carcinoma treated with WP at our institution between 2015 and 2020. Patients with platinum-resistant ovarian, fallopian tube or primary carcinoma of the peritoneum who had received at least 3 doses of WP (80 mg/m2) alone or in combination with bevacizumab until disease progression or unacceptable toxicity were included in the analysis. Progression-free survival was assessed according to the Response Evaluation Criteria in Solid Tumors version 1.1. Information about toxicity was gathered from medical reports and lab tests. Kaplan-Meier curves and Log-rank test were performed for survival estimates. Results: In our sample, the median age was 68 years (IQR: 60-75) and the median number of previous lines of systemic treatment was 3 (range 1-5). 40% of patients received WP in combination with bevacizumab. The disease control rate was 60.7% (42.9% partial response and 17.8% stable disease). In the overall analysis, the median progression-free survival (mPFS) was 5.0 months (95% CI: 2.0-7.1 months). The presence of ascites significantly shortened the mPFS compared to patients without it (1.1 vs 5.1 months, p < 0.001). Even though the addition of bevacizumab to WP improved the mPFS, the difference was not statistically significant compared to WP alone (7.1 vs 4.06 months, p=0.30). Peripheral neuropathy was the most common adverse event (78% all grades, 18% grade 3). No grade 3 hematologic toxicity was registered. Treatment was discontinued in 6 patients (20%) – 4 due to peripheral neuropathy and two because of toxicoderma. Conclusions: In our sample, WP was an active and safe regimen in heavily pretreated platinum-resistant ovarian carcinoma. WP was well tolerated in elderly patients. The presence of ascites was associated to a shorter PFS in patients treated with WP compared to ascites-free patients.
Functional status of patients suffering from ovarian cancer: A cross-sectional study.
Authors: Iglesias Campos Marcos , Pajares Bella , Roldán Jiménez Cristina , Bermejo-Perez Maria-Jose , Alba Emilio , Cuesta Vargas Antonio 
Published: June 2021

e17556 Background: Physical activity displays multiple benefits in oncology patients, with the strongest evidence related to breast cancer. But there is little information about patient with ovarian cancer, even less in those who are metastatic. The main objective of this study was to assess and describe the performance´s in patients suffering from ovarian cancer in terms of function and cancer-related fatigue (CRF). Methods: Patients willing to join therapeutic exercise program (TEP) were at the Medical Oncology Unit of the Hospital Virgen de la Victoria, Malaga. A physiotherapist carried out an interview and a baseline assessment. The following outcomes were recorded: number of repetitions (n) performed in 30 seconds sit-to-stand test (30-STS), handgrip strength (Kg), cancer related fatigue (CRF) measured by Piper Fatigue Scale (0-10), upper and lower limb function measured by Upper Limb Functional Index (ULFI) and Lower Upper Limb Functional Index (LLFI), respectively (%). Results: Patients recruited had a diagnosed of an advanced ovarian cancer receiving or not active treatment. All participants had a good performance status (PS) and signed informed consent. 8 women were included, with a mean age of 52.66 (9.53) years and a mean BMI of 27.22 (4.56) kg/m2. Women performed 22 (4.24) repetitions of 30-STS test. Handgrip strength was 22 (2.7) Kg and CRF 5.43 (2.91) points. Patients reported 64.81% (34.65) and 66.83% (37.91) in ULFI and LLFI questionnaires, respectively. Conclusions: At the light of these preliminary results, ovarian cancer patients present a good level of function measured by 30-STS and a good grip strength. However, they report a moderate level of CRF and affected upper and lower limbs function. In additions, patients measured had function enough to participate in a therapeutic exercise program. Given the heterogeneity of the sample and its low number of participants, future studies with a wider sample should be carried out.
Prevalence and variety of HPV types in dependence on gender and age.
Authors: Zykova Tatiana A. , Nikitina Vera P. , Zhenilo Oksana E. , Verenikina Ekaterina V. , Ivanova Viktoria A. , Menshenina Anna P. , Shevchenko Alexey N. , Khomutenko Irina A. , Filatova Elena V. , Shevyakova Elena A. , Velikorodnaya Lilia A. 
Published: June 2021

e17575 Background: Analysis of the typical structure of age, sex and territorial patterns of HPV spread is of interest, since it allows assessing the potential impact of modern immunoprophylaxis. The purpose of the study was to analyze the prevalence and variety of HPV types in dependence on gender and age. Methods: The study included 424 patients (334 women and 90 men) under 45 years of age (228 women and 46 men) and over 46 years old (106 and 44, respectively). Vaginal and cervical swabs were examined in women and urethral swabs in men. DNA extraction was performed by Real-time PCR. Results: HPV DNAs were found in 150(35.4%) patients, including 115(34.4%) women and 35(38.9%) men (p > 0.05). HPV was less frequently detected in older women, and more frequently in older men. Thus, HPV DNAs were found in 85(37.3%) women < 45 years and in 30(28.3%, p = 0.068) women >46 years; in men – 14(30.9%) and 21(47.7%, p = 0.071), respectively. Some HPV types were more frequent in younger patients, compared to older ones: in 26(26.3%) and in 5(9.8%), p = 0.068) of HPV-positive patients, respectively. The most common HPV types were 16(46.7%), 52(16.0%), 56(12.7%), 31(10.7%); HPV16 dominated both in females - 50(50.4%) and males - 12(34.6%). After HPV16, most frequent types in women were: 31-12(11.3%) and 52-13(11.3%), 18-12(10.4%) and 56-119(, 6%); in men - 52-11(31.4%), 56-8(22.9%), 45-4(11.4%) and 18-3(8.6%) types. The total share of two HPV types with the greatest oncogenic potential (types 16 and 18) was 85(56.7%) of all HPV-positive patients, and in women it was higher than in men: 70(60.9) vs. 15(42.9%, p = 0.046), respectively. Conclusions: Simultaneous infection with several HPV types was statistically significantly more often detected in younger patients compared with the older age group among men. HPV16 was the most common type both in men and women; however, the rates of other HPV types differed. Cumulative frequency of types 16 and 18 was statistically significantly higher in women, compared to men.
MVX-ONCO-1 in advanced refractory cancers: Safety, feasibility, and preliminary efficacy results from all HNSCC patients treated in two ongoing clinical trials.
Authors: Fernandez Eugenio , Vernet Remi , Charrier Emily , Migliorini Denis , Joerger Markus , Belkouch Marie-Claude , Urwyler Muriel , Von Rohr Olivier , Saingier Valentin , Ancrenaz Virginie , Grandjean Nicole , Lavalliere Emmanuel , Lafferma Elisabeth , Rubin Olivier , Villard Jean , Grogg Julien , Mach Nicolas 
Published: June 2021

e18005 Background: MVX-ONCO-1 is an active, personalized cancer immunotherapy combining irradiated autologous tumor cells and encapsulated, genetically engineered allogeneic cells producing GM-CSF. The immunostimulant cytokine is released locally in a sustained manner over one week at the immunization site. All cancer types are potential candidates and more than 40 patients have been treated in two clinical trials. Here we report the data on all HNSCC patients treated, as of 31st January 2021. Methods: Eleven (11) patients with locally advanced/metastatic HNSCC relapsing after at least one line of systemic therapy were enrolled in 2 open-label, single-arm clinical trials (NCT02193503 and NCT02999646) evaluating the safety, feasibility and efficacy of MVX-ONCO-1. All patients were treated with at least 5 administrations of MVX-ONCO-1 over 8 weeks (W1,2,3,4,6,8). Each administration consists of the subcutaneous implantation in healthy skin of 2 capsules containing each 8x105 cells, producing > 20ng/24h of GM-CSF, and an injection of 4x106 irradiated autologous tumor cells between the 2 capsules. Results: Eleven (11) patients are evaluable for safety and feasibility. Ten patients (91%) with at least 6 months, respectively 9 patients (82%) with 12 months follow-up are evaluable for efficacy analysis. Eight patients (80%) failed both Cisplatin based chemotherapy and anti-PD1 therapies prior to enrolment. The most common treatment-related adverse event (AE) was local hematoma at implantation site in 3 patients (27%). None experienced > grade 2 treatment-related AE. Overall Survival is 70% (7/10pts) at 6 months, and 56% (5/9pts) at 12 months. Eight patients (80%) presented some degree of disease control with 4SDs, 2PRs and 2CRs. Both CRs are longstanding, with both patients not any longer on anticancer therapy for 24 and 6 months respectively. While 1 PR was observed on MVX-ONCO-1, 1PR and 1CR were observed on subsequent Nivolumab therapy (both CPS0), and 1 CR was observed after carboplatin-cetuximab. Two patients had progressive disease as best overall response. Conclusions: Treatment with MVX-ONCO-1 is feasible, safe and well tolerated. Preliminary efficacy data shows an encouraging rate of tumor control including prolonged CR in patients subsequently treated with nivolumab or chemotherapy. Efficacy of the concurrent use of anti-PD-1 and MVX-ONCO will be assessed in a planned clinical trial. Clinical trial information: NCT02999646.
A multiparameter model for prediction of pathological nodal status in clinically early stage oral cancer using machine learning.
Authors: Mallick Indranil , Saha Saheli , Chatterjee Sanjoy , Roy Paromita 
Published: June 2021

e18025 Background: The current approach to neck treatment in clinical T1-2 oral cancers is to offer elective nodal dissection to all patients, despite the fact that the majority of patients are pathologically node negative. This is due to the poor predictive ability of clinico-radiological assessment and subsequently poorer survival in those in whom neck dissection is omitted based on this. A robust prediction model for pathological nodal status may allow individualized decisions for neck dissection. Our aim was to develop a multiparameter prediction model to identify pathological node-negative status using machine learning. Methods: We identified 497 patients with cT1-2 oral cancer from a single institutional database from 2011-2018 who underwent primary resection and neck dissection. We compared the sensitivity, positive predictive value and accuracy of prediction of pathologically negative neck from clinico-radiological staging alone vs. a model created from multiple parameters including clinical features (clinico-radiological nodal status, ages, sex, subsite of primary lesion) and pathological features of the resected primary tumor (maximum dimension, depth of invasion, lymphovascular invasion, perineural invasion, grade and margins of resection). The multiparameter model was built from a training dataset of the first 400 patients using an ensemble of logistic regression, random forests and support vector machines. A cohort of 97 patients was used for independent validation. Results: In this cohort 232 (47%) were clinico-radiologically node negative, while 307(62%) were pathologically node negative. The sensitivity, positive predictive value and accuracy of the clinico-radiologically assigned nodal status was 56%, 74% and 61%, while that of the multiparameter machine learning model was 87%, 89% and 89% respectively. The area under curve (AUC) of the clinico-radiological prediction was 0.62 whereas that of the multiparameter predictive model was 0.91. In the validation dataset, 58/62 pathologically node negative patients were predicted correctly by the model. The accuracy of the model on the external validation dataset was 82%. Conclusions: The performance of the multiparameter predictive model was considerably superior to clinico-radiological neck staging for prediction of pathological node negative neck. This could be validated on an independent dataset. This could be considered for prospective clinical evaluation of individualized neck dissection.
A potential survival impact of blood immune cells in patients with locoregionally advanced nasopharyngeal carcinoma treated with concurrent chemoradiotherapy.
Authors: Yang Li , Xu Zhiyuan , Lee Victor Ho-Fun , Lee Anne W. M. 
Published: June 2021

e18027 Background: To exam the changes of blood immune cells during concurrent chemoradiotherapy (CCRT) and explore their effects on survival in patients with locoregionally advanced nasopharyngeal carcinoma. Methods: Study population included stage III-IVA (TNM-8th edition) locoregionally advanced nasopharyngeal carcinoma (NPC) patients treated with induction chemotherapy followed by CCRT from January 2015 to October 2019. Patients received induction PX (cisplatin: 80mg/m2 on day 1 + capecitabine: 1000mg/m2 twice daily from day 1 to 14 every 3 weeks for 3 cycles) followed by CCRT (cisplatin: 100mg/m2 every 3 weeks for a total of 2-3 cycles or 40mg/m2 weekly for a total of 6 weeks concurrent with intensity-modulated radiation therapy [IMRT]). IMRT with doses of 70Gy, 63Gy and 56Gy were delivered to 3 levels of planning target volumes (PTV) (high, intermediate and low risk) respectively and simultaneously in 35 fractions/7 weeks. All had complete blood counts with differentials at baseline and before each chemotherapy. The primary endpoint was progression-free survival (PFS). “Immune cells” of our interest included lymphocytes, neutrophils and platelets. Results: A total of 139 patients were eligible and recruited. The median follow-up was 34 months (range 4-72). All immune cells decreased significantly during CCRT; the rate of grade 3/4 lymphopenia, neutropenia and thrombocytopenia during CCRT were 96.4%, 25.2% and 9.4%, respectively. The median (interquartile range, IQR) time to nadir from the start of CCRT were 40 (32-44), 26 (20-42) and 30 (15-39) days for lymphocytes, neutrophils and platelets, respectively. The median PFS was not reached and estimated 2-year PFS was 90.2%. Patients with lymphocyte nadir ≤ 0.2×109/L had better PFS compared with those with lymphocyte nadir > 0.2×109/L（2-yr PFS 95.5% vs. 87.5%, P=0.048). Patients with platelet nadir < 100×109/L had better PFS compared with those with platelet nadir ≥ 100×109/L(2-yr PFS 96.9% vs. 84.2%, P=0.011). Neutrophil nadir was not associated with PFS in univariate analysis. Multivariate analysis including prognostic variables in univariate analysis showed that platelet nadir (< 100 × 109/L vs ≥ 100 × 109/L, hazard ratio [HR] 0.279, 95% confidence interval [CI] 0.091-0.857, P=0.026), stage (III vs IVA, HR 0.321, 95% CI 0.115-0.901, P=0.031) and cumulative concurrent cisplatin dose (< 180mg/m2 vs ≥ 180mg/m2, HR 3.422, 95% CI 1.366-8.577, P=0.009) were prognostic of PFS by adjusting lymphocyte nadir and baseline hemoglobin. Conclusions: Blood immune cells decreased during CCRT and thrombocytopenia was prognostic of PFS in patients with LANPC. Longer follow-up is warranted to identify prognostic factors of overall survival.