bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combination therapy with anti-PD-1 or PD-1 antibody alone in pediatric patients with relapsed or refractory cancer.
Authors: Que Yi , Wang Juan , Zhu Jia , Li Na , Huang Junting , Lu Suying , Sun Feifei , Zhang Lian , Zhen Zijun , Zhang Li , Cai Ruiqing , Guo Haixia , Sun Xiaofei , Zhang Yizhuo 
Published: June 2021

e22004 Background: There is limited experience of PD-1 combined with other therapies in children. We aimed to explore the antitumor activity and safety of PD-1 antibody monotherapy or combination with other regimens in relapsed or refractory pediatric cancer. Methods: This was an observational retrospective study performed at two academic medical centers (Sun Yat-sen University Cancer Center and Nanfang Hospital, Southern Medical University) The primary objective of this study was to describe the overall response rate (ORR) and disease control rate (DCR). Secondary objectives included characterizing toxicities according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 as well as describing progression free survival (PFS) and overall survival (OS). Results: Of the 22 pediatric cancer patients who received PD-1 inhibitors, the median follow-up for all patients after the commencement of PD-1 therapy with or without other regimens was 12.3 months (0-43 months). The objective response rate (ORR) and disease control rate (DCR) of the 6 patients with HL were 83.3% (3CR and 2PR) and 100%, respectively. No objective response was observed in patients with melanoma or Burkitt lymphoma evaluated in this study. For patients treated with PD-1 inhibitor combination therapy, PD-1 antibody combined with decitabine showed potential efficacy in advanced pediatric cancer patients. One of the Three of patients who received PD-1 combined with decitabine achieved CR and another two other patients achieved PR. At the data cutoff, 10 of the 13 (76.9%) patients achieved disease control as the best objective response. The median PFS and OS were 90 days (95%CI: 10.733-169.267) and 158 days (95%CI: 131.514-184.486) respectively. There were no severe treatment-related adverse events (TRAEs) directly attributed to PD-1 monotherapy. The severe TRAEs are due to chemotherapy in the combination regimen. Conclusions: PD-1 monotherapy demonstrated antitumor activity in a population of pediatric patients with HL. The regimen of PD-1 inhibitor combined with decitabine showed potential in treating with pediatric cancer patients.
Early cancer detection using low-coverage whole-genome sequencing of cell-free DNA fragments.
Authors: Yang Shunli , Zhihua Pei , Yu Jianing , Zhao Xiuyu , Liu Yiqian , Zhang Yaxi , Chen Geng , Chen Weizhi , He Ji 
Published: June 2021

e22510 Background: Recent advances in circulating cell-free DNA (cfDNA) of plasma have shown that tumor diagnosis based on tumor-specific genetic and epigenetic changes (e.g., somatic mutations, copy number variations, and DNA methylation) is a promising non-invasive method. However, the number of tumor-specific genomic variants identified by whole-genome sequencing (WGS) in early cancer patients is very limited. Moreover, the mutations generated by clonal hematopoiesis in cfDNA can further confound the detection of cancer-specific mutations. It has been shown that ctDNA and cfDNA fragments have differences in length distribution. Compared with a limited number of genomic mutations, cfDNA fragment size index (FSI) is more abundant and easier to be detected. Methods: We designed a novel method for fragment detection of plasma cfDNA based on low-coverage WGS. The fragment length differences between healthy individuals and tumor patients were systematically analyzed. The training dataset includes 50 healthy individuals and 354 patients from eight different cancers. After the data preprocessing, we calculated the weight of fragmental bins and built a model for distinguishing healthy individuals from cancer patients. An independent dataset involving 22 healthy controls and 340 cancer patients was used to validate the model. The performance of our method was measured by the area under the curve (AUC) using the one-versus-all approach. Results: In our analysis, a total of 504 markers were selected from the dataset for model construction. Our model performed well for all cancer types on both training (AUC = 0.804) and validation (AUC = 0.837) datasets. Conclusions: The good performance of our model in large-scale plasma samples demonstrates the potential clinical application of cfDNA fragment analysis in early cancer detection based on low-coverage WGS.
A unique molecular identifier-based and clonal hematopoiesis-aware approach for accurate mutation calling in cell-free DNA assays.
Authors: Xie Hongyu , Zhang Yaxi , Zhihua Pei , Yu Jianing , Liu Yiqian , Zheng Shiqi , Chen Geng , Chen Weizhi , He Ji 
Published: June 2021

e22515 Background: Given peripheral blood cells (PBCs) matched cell-free DNA (cfDNA), accurate mutation calling in next generation sequencing (NGS)-based assays relies on discriminating artifacts and clonal hematopoiesis mutations from tissue originated somatic mutations. Although clonal hematopoiesis has been considered in previous overall error modeling, it has not been adapted to PBCs without using unique molecular identifiers (UMIs). Moreover, previous studies on background error profiling were mainly based on healthy controls without matched PBC gDNA, which may lead to potential overestimation of the error rates on those sites with clonal hematopoiesis mutations. Additionally, the fraction of tissue cells is also an important influencing factor but is usually ignored. Methods: We performed UMI-assisted capture-based DNA assays on cfDNA samples, matched PBCs, and oral epithelium cells from 150 healthy donors. A site-specific and subtype-specific background error model was first built for PBCs using the SNVs called from PBCs with matched oral epithelium cells to exclude potential clonal hematopoiesis mutations. Then a similar background model was established for cfDNA with the SNVs inferred from cfDNA to exclude clonal hematopoiesis. The SNVs identified in cfDNA and matched PBCs were separately filtered with the cfDNA and PBC background error models. In this study, we used the ultrasensitive liquid biopsy approach to evaluate paired with tissue and blood samples from 56 early-stage NSCLC patients. All samples are sequenced using NGS target-capture panels covering 29 genes. Results: The mutations were detected in 91.1% of tissue and 67.9% were discovered in plasma. The coincidence rate between tissue and plasma of the 56 early-stage NSCLC patients was 66.1%. Conclusions: We have developed a novel method tailored for UMI-assisted capture-based targeted DNA assays, which outperforms currently available methods in terms of modeling background errors and filtering clonal hematopoietic mutations.
Performance characteristics of brief family history questionnaire to screen for Lynch syndrome in women with newly diagnosed ovarian cancers.
Authors: Kim Rachel Soyoun , Tone Alicia , Kim Raymond , Cesari Matthew , Clarke Blaise , Eiriksson Lua Ruhiyyih , Tae Hart , Lytwyn Alice , Maganti Manjula , Gallinger Steven , Bernardini Marcus , Oza Amit M. , Djordjevic Bojana , Lerner-Ellis Jordan , Van de Laar Emily , Vicus Danielle , Pugh Trevor J. , Pollett Aaron , Ferguson Sarah E. 
Published: June 2021

e22525 Background: Ovarian cancer (OC) is the third most common Lynch syndrome (LS)-associated cancer in women but there is no established screening strategy to identify LS in this population. An adequate family history may identify patients suspected of LS, prompting a referral to genetic assessment. We have previously validated the 4-item brief Family History Questionnaire (bFHQ) in endometrial cancers. The objective of this study was to assess whether bFHQ can be used as a screening tool to identify women with OC at risk of LS. Methods: Prospective cohort study recruited women with newly diagnosed non-serous/non-mucinous OC from three cancer centers in Ontario, Canada. Participants completed bHFQ, extended Family History Questionnaire (eFHQ; encompassing Amsterdam II criteria, Society of Gynecologic Oncology 20-25% criteria and Ontario Ministry of Health criteria), immunohistochemistry (IHC) for mismatch repair (MMR) proteins and universal germline testing for LS. The performance characteristics were compared between bFHQ, eFHQ, and IHC. Results: Of 215 participants, 169 (79%) were evaluable with both bFHQ and germline mutation status; 12 of these 169 were confirmed to have LS (7%). Nine of 12 patients (75%) with LS were correctly identified by bFHQ, compared to 6 of 11 (55%) by eFHQ and 11 of 13 (85%) by IHC. The sensitivity, specificity, positive predictive values and negative predictive values of bFHQ were 75%, 66%, 15% and 98%, compared to 55%, 92%, 35% and 96% for eFHQ and 85%, 90%, 39% and 99% for IHC respectively. IHC was the most sensitive and specific approach. The 4-item bFHQ was more sensitive than eFHQ and took less than 10 minutes for each patient to complete. Conclusions: Patient-administered bFHQ may serve as an adequate screening tool to triage women with OC for further genetic assessment for LS, especially in centers without access to universal tumor testing for IHC for MMR.[Table: see text]
The MGMT (O6-methylguanine–DNA methyltransferase) promotes methylation and clinical outcomes of salvage temozolomide and irinotecan chemotherapy in progressive Ewing sarcoma: A preliminary report.
Authors: Salah Samer , Naser Walid , Jaber Omar , saleh yacob , Mustafa Rawan Mohammed Mahmoud , Abuhijlih Ramiz , Abuhijla Fawzi , Yaser Sameer , Sultan Iyad Yasin , Mustafa Nour , Tbakhi Abdelghani 
Published: June 2021

e23507 Background: There remains an unmet need to identify prognostic and predictive molecular biomarkers in advance Ewing sarcoma (ES). We sought to assess the influence of MGMT promoter methylation status on response rate, time to progression (TTP), and overall survival (OS) following salvage irinotecan and temozolomide (IT) chemotherapy. Methods: Data of advanced ES patients, treated with IT chemotherapy from Jan, 2014 to Jan, 2020 were retrospectively collected. Patients were required to have previously received and progressed after vincristine, doxorubicin, and cyclophosphamide alternating with ifosfamide and etoposide (VDC-IE). MGMT promoter methylation status was assessed by Methylation Sensitive Restriction Enzyme quantitative-PCR (MSRE-qPCR) on non-decalcified Formalin-fixed paraffin embedded (FFPE) tissue using internally developed primers and the OneStep qMethyl Kit (ZYMO RESEARCH CORP). Responses were assessed by response evaluation criteria in solid tumors (RECIST v. 1.1). TTP and OS were assessed by the Kaplan-Meier method. Survival comparisons were performed by the Log-rank test. Results: Herein, we present data of the preliminary analysis of the first 18 patients who underwent MGMT promoter methylation testing. Patients had a median age of 18 years (range: 5-34 years), and were predominantly male ( n=11; 61%). The primary tumor was located in the pelvis in 9 patients (50%), femur in 3 (17%), tibia in 2 (11%), kidney in 2 (11%), chest wall in one (6%), and scapula in one patient (6%). IT was given in a second ( n=15) or third-line setting ( n=3). At the time of initiation of IT, 13 patients (72%) had distant metastasis, and 5 (28%) had unresectable local progression in the pelvis ( n=4) or chest wall ( n=1). The mean percentage of MGMT promoter methylation was 29% (range: 3-98%). Five patients (28%) had methylated MGMT promoter, whereas the remaining had partially methylated ( n=6; 33%) or unmethylated ( n=7;39%) promoter. Five patients (28%) had objective response, with no observed difference according to MGMT promoter methylation ( p=0.58 for comparison between methylated and unmethylated/ partially methylated). Median TTP was 4.9 and 2.2 months for patients with methylated and partially methylated/ unmethylated MGMT respectively; p=0.76. The corresponding median OS was 69.4 and 14.3 months in favor of the methylated group; p=0.3. Conclusions: This preliminary data suggests a possible prognostic role for MGMT promoter methylation, with a markedly extended median OS for the methylated group. Nevertheless, the median OS difference did not reach statistical significance in this preliminary analysis. We plan to report data of the final analysis after finalizing MGMT testing for the rest of our study patients.
Epidemiology, clinical features, and histopathology of sarcomas managed in a Haitian cancer clinic.
Authors: Bernard Joseph , Alcindor Thierry , Alexis Lynn Gabrielle , Gilbert Doukens Patrick , DeGennaro Vincent 
Published: June 2021

e23515 Background: Sarcomas are among the least described cancers diagnosed in Haiti. Suboptimal surgery and the unavailability of radiation therapy make their management challenging. The main objective of this study was to present the epidemiology, clinical features and histopathology of sarcomas in the Haitian setting. Methods: A seven-year retrospective study was conducted in the cancer program of Innovating Health International (IHI). We included all patients with clinical or histological diagnosis of sarcoma enrolled from January 1, 2014 to December 31, 2020. Date of first visit, age, gender, stage, anatomical site, histology, outcome as of December 31, 2020 and date of death were the main variables selected for this chart review. Mortality rate and overall survival were also evaluated. Results: One hundred and twenty-two (122) patients with sarcomas were diagnosed and treated during the study period. Their mean age was 43.3 years [range: 15-88] and the sample was 62.3% women and 37.7% men. 49.2% of the patients were less than 40 years of age. Among the cases of sarcomas, 86.9% were soft tissue sarcomas and 13.1% bone sarcomas. The lower limbs (36.9%), abdomen (14.8%), head and neck (13.1%), upper limbs (12.3%) and breasts (7.4%) were the most common locations of the sarcomas. 81% of abdominal/pelvic sarcoma cases (n=21) were in women. The most common histological types (n=94) were fibrosarcoma (15.2%), liposarcoma (10.9%), dermatofibrosarcoma protuberans (8.7%), malignant histiocytofibroma (6.5%), rhabdomyosarcoma (5.4%) and gastrointestinal stromal tumor (5.4%). 19.6% of the patients had metastatic disease. The mortality rate for the study period was 53.3% and 17.2% of the patients were lost to follow-up. The median overall survival was 7.2 months for the cohort and 18.4 months for the treated patients (n=70). Conclusions: The sarcomas seen in this Haitian medical clinic mainly affect the soft tissues of limbs, abdomen and head and neck. There is a strong predominance of female patients and about half of the patients are aged less than 40. Despite a low metastatic presentation rate, the prognosis is poor, likely reflecting both the aggressiveness of this group of diseases and the disparities of outcomes between high-income and low-and-middle-income countries.
A phase II study of epirubicin combined with anlotinib followed by anlotinib in the first-line treatment of advanced unresectablesoft tissue sarcoma.
Authors: Zhou Yuhong , Wang Zhiming , Zhuang Rongyuan , Guo Xi , Zhang Chenlu , You Yang , Chen Lisha , Liu Wenshuai , Zhang Yong , Lu Weiqi 
Published: June 2021

e23536 Background: Anlotinib, a multi-target TKI,showed well efficiency and tolerance for the treatment of recurrent or metastatic soft tissue sarcoma (STS). Moreover, the synergistic activity of anlotinib plus epirubicin on the sarcoma PDX modelwas confirmed in our previous preclinical study. This phase II clinical study was designed to assess the efficacy and safety of epirubicin combined with anlotinib followed by anlotinib in the first-line treatment of advanced unresectable STS. Methods: This study is an open-label, prospective, single-arm phase II clinical study. Patients (pts) with locally advanced or metastatic soft tissue sarcomas confirmed by histopathology and not suitable for surgery were recruited, and treated with 6 cycles of anlotinib and epirubicin (epirubicin 90mg/m2 CIV for 48 hours on day 1 and anlotinib 12 mg QD on day1-14, 21 days per cycle), followed by anlotinib alone unless the pts experienced progression or intolerance. Tumor imaging evaluations and echocardiography were performed every 2 cycles during combined therapy, and were performed every 3 cycles during the sequential anlotinib treatment. The primary end point was the progression-free rate at 12 weeks (PFR12w) and 6 months (PFR6m), secondary endpoints included ORR, PFS, safety, DCR and OS. Results: 33 eligible pts were enrolled from June 2019 to August 2020, and 3 pts dropped out without completing one cycle of treatment. Of 30efficacy-evaluable pts,10 were man, median age was 48 (range 18-74). The main subtypes included 10 leiomyosarcoma, 8 fibrosarcoma, 5 dedifferentiated liposarcoma, 4 synovial sarcoma, 2 undifferentiated pleomorphic sarcoma, and 1 epithelioid sarcoma. The average number of combined treatment cycle is 4.7 (range 2-6), 13 pts had entered into anlotinib maintenance treatment. The PFR12w, PFR6m, ORR, DCR were 70%,53.8%, 13.3%, and 80%,respectively. Median PFS was 11.5 months (95%CI: 5.0-NA), median OS has not been reached. As cut-off on Jan 20th 2020, 6 pts are still in treatment. The other pts discontinued trial due to disease progression (16/24), adverse events (AEs) (3/24), changes in treatment strategy because of tumor shrinkage (3/24), cytoreductive surgery (1/24), and opt-out (1/24). The main AEs were grade III-IV neutropenia (8/30, 26.7%), and 7 of them were febrile neutropenia (7/30, 23.3%). Until now, no cardiac-related AEswere observed. Conclusions: Advanced unresectable STS pts could benefit from epirubicin combined with anlotinib followed by anlotinibtreatment in first line. And it is generally well tolerated especially with no short-term cardiac toxicity. Clinical trial information: ChiCTR1900024928.
Participation of older patients with advanced gastroesophageal cancer in clinical trials: A systematic review of age-restrictive inclusion criteria over the last 25 years.
Authors: Hennessy Maeve , Hamid Munzir , Goggin Caitriona , Nay Myo Oo , Carrigan Marie , Mockler David , O'Donovan Anita G. , Horgan Anne M. 
Published: June 2021

e24017 Background: Cancer is a disease of aging, however older patients are underrepresented in the clinical trials that determine the standards of care for oncological treatment. We conducted a review to identify whether there have been age-restrictive inclusion criteria in clinical trials over the last twenty five years. We focused on patients with metastatic gastroesophageal cancer. Methods: A search strategy was developed encompassing Embase, Pubmed and The Cochrane Library databases. All completed Phase III randomised controlled trials evaluating systemic anti-cancer therapies in metastatic gastroesophageal malignancies for the period 01.01.95 to 18.11.20 were identified. Reference management software (Covidence; Veritas Health Innovation Ltd) was used to screen for inclusion/exclusion. The following details were extracted from trial protocols: country of study, date of publication, patient number, age inclusion and exclusion criteria. The median age of participants and the percentage of older patients enrolled in each study was collected. A linear probability model was used to estimate the change over time in the proportion of studies using an upper age exclusion. Results: 363 phase III studies were identified. 152 studies were eligible for full text review, 86 were excluded, leaving 66 trials for final analysis. 86% (n = 56) included Gastric, 9% (n = 6) Oesophageal and 5% (n = 3) Oesophagogastric malignancies. Asian studies represented 48% (n = 32) of trials, 29% (n = 19) were worldwide and 23% (n = 15) were European. The median age of trial participants was 62, (range 18-94). No clear trend in the ages of study participants over the time period was identified. 32% (n = 21) of studies specified an upper age limit for inclusion and 57% of these were Asian studies. The median age of exclusion was 75 years (range 65-80). All studies starting before 2003 used an upper age exclusion (n = 12); whereas only 9 of the 52 that started in 2003 or later did (17%). Among these later studies, there was a very modest downward yearly-trend in the proportion of studies using an upper age exclusion (-0.02 per year; 95%CI -0.05 to 0.01; p = 0.31). 52% (n = 34) of studies specified the proportion of their study population who were over 65 years. Older patients represented only 36% of the trial populations in these studies (range 7-60%). Our search of currently enrolling trials on clinicaltrials.gov yielded 11 active studies, none of which specified an upper age limit. Conclusions: Recent years have seen improvements in clinical trial protocols, with many no longer specifying restrictive age criteria. Reasons for poor representation of older patients are complex and ongoing efforts are needed to broaden eligibility criteria and prioritise the inclusion of older adults in clinical trials.
Prevalence and risk factors for vasomotor symptoms in Hispanic female breast cancer survivors, 0-3 years post-treatment: Results of a single-center retrospective analysis.
Authors: Morin Lisellet , Zanville Noah , Guest Rosalind , Rubens Muni , Currier M. Beatriz 
Published: June 2021

e24038 Background: Early detection and a growing complement of treatment options have led to improved survival among women with breast cancer in the U.S. Vasomotor symptoms (VMS) such as hot flashes and night sweats are among the most common side effects reported by breast cancer survivors (BCS) following treatment. These symptoms may affect quality of life and increase the risk of non-adherence to anti-hormonal therapies. Hispanics are one of the fastest growing ethnic populations in the U.S. However, research exploring whether Hispanic BCS report VMS at similar rates as their non-Hispanic counterparts remains an important gap in the science. The purpose of this study was to compare the prevalence and risk factors for VMS between Hispanic and non-Hispanic BCS following cancer treatment. Methods: Data for this single-center, retrospective study came from a database of self-reported symptom data collected at survivorship visits. Results: Over a 2.8-year period, 815 female BCS were evaluated for VMS (Hispanic: 63.0% (n=513) vs. Non-Hispanic: 37.0% (n = 302)). Mean age of the sample was 58.4 + 11.7 (range 24.2 - 91.8).Approximately four in ten (42.9%) BCS reported VMS at their initial survivorship visit, 0-3 years post-treatment. Results found virtually no difference in VMS prevalence between Hispanic and non-Hispanic BCS, (42.5% vs 43.7%, p = 0.735). BCS who reported VMS after treatment were 6.5 years younger, on average, than BCS who did not report VMS (54.7 ±11.0 vs. 61.2 ±11.3, p < 0.001). Multivariate logistic regression models using age, race, stage of cancer, chemotherapy, radiation and hormone therapy as predictors showed that only age was associated with reporting VMS. For every one-year increase in age, the odds of reporting VMS fell by approximately 5.3% (OR: 0.947, 95% CI: 0.933-0.963, p < 0.0001). Conclusions: Results found no difference in VMS prevalence between Hispanic and non-Hispanic BCS. VMS were reported by over 40 % of BCS in the study. In addition, symptoms were more prevalent in younger BCS. Given the potential impact of VMS on quality of life and mediation adherence, studies validating these findings as well as exploring the prevalence and risk factors for VMS in Hispanic BCS from distinct nationalities and cultures are needed.