bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oncologists’ views on Expanded Access and Right-to-Try: The need for education and shared decision-making.
Authors: Master Zubin , Smith Cambray , Stout Jeremiah , Adjei Alex A. , Buckner Jan C. , Tilburt Jon Charles 
Published: June 2021

e13603 Background: Over half of Americans report favoring access to experimental treatments even if they have yet to be proven either safe or effective, yet only 3-5% are enrolled in clinical trials and a fraction of a percent in expanded access. The Expanded Access (EA) program (aka “compassionate use”) and Right-to-Try (RTT) are parallel federal mechanisms that offer qualifying patients access to off-trial experimental treatments. Our study aimed to capture the views and experiences of oncologists on obtaining eligible medicine using the FDA’s EA and is the first to report findings on physician attitudes toward RTT. Methods: We conducted 21 semi-structured interviews and qualitative analysis of oncologists at a major cancer center with 3 main sites across the U.S. Participants were purposely selected to have experience with EA. Results: Oncologists’ considerations for offering EA options to patients were based on a sound scientific rationale, reasonable risk-benefit ratio, functional status of the patient, and patient motivation. Although oncologists’ experience positively correlated with level of ease in navigating EA, most remained largely unfamiliar with RTT. Only 4 oncologists had experience discussing RTT with patients and none had obtained an experimental therapeutic under this pathway. When informed about RTT, oncologists articulated 3 sets of concerns including limited safety and oversight, unclear structure and lack of requirements to collect and report data, and the potential for inflating patient expectations. Published work by others have shown that patients desire experimental options to be offered and report that physicians do not always offer experimental medicine taking into account factors, such as, reimbursement. Given that oncologists may factor in variables such as patient motivation, and potentially affordability or health literacy, when considering whether experimental medicine is appropriate to offer their patient, there may be a need to develop a conversation aid so that clinically relevant options are presented to patients equitably and patient choice is enhanced. Conclusions: Further research to better understand patient perspectives and potential discordant views between patients and oncologists is needed in order to design shared decision-making tools to inform oncologists about off-trial preapproval pathways and help both oncologists and patients navigate the thorny issues of experimental oncology.
National survey on the effect of oncology drug shortages in clinical practice: A Hematology Oncology Pharmacy Association (HOPA) survey.
Authors: Hudson-Disalle Sarah , DeRemer David L. , Buie Larry W , Hamm Mark , Pilz Jeffrey , McBride Ali 
Published: June 2021

e13609 Background: Drug shortages are a clear and growing challenge. Prominent shortages included oncology medications and supportive care products essential for the care of cancer patients. Oncology drug shortages often result in disruptions in the timing of chemotherapy treatments, alterations in the dose or regimen administered, or even missed doses when alternative agents are unavailable. The purpose of this survey was to characterize the impact of oncology drug shortages across the United States, including the experiences of health care organizations, resource implications, and the impact on patient safety, patient care, and clinical trials. Methods: A 34-item online survey was distributed to HOPA membership of the Hematology Oncology Pharmacy Association to gather information on shortages of oncology drugs (i.e., all drugs essential in the care of cancer patients, including supportive care agents. Results: Sixty-eight organizations completed the survey; almost all completed by pharmacists, and analysis completed. Sixty-three percent of institutions reported one or more drugs shortages a month, with a 34.33% increase in 2019 from 2018. Sixty four percent of responded had incurred increased costs from oncology drugs shortages, with 7% noting reimbursement issues when switched to brand name therapies due to shortages. Treatment delays, reduced doses or alternative regimens were reported by 74.63% of respondents. The most common disease states which causes a dose delay of treatment included Acute Lymphocytic Leukemia, Lymphoma and Multiple Myeloma with dose reductions noted in 36.36%, 36.36 and 15.91%. The top five oncology drugs on shortage included epirubicin, flutamide, decitabine, mechlorethamine, dactinomycin with the top 5 supportive care drugs on shortage being noted as hydrocortisone, bivalirudin, promethazine, mycophenolate sodium and scopolamine. Respondents noted medication errors related to oncology drug shortages at 4.48%, with noted errors including incorrect conversion from iv to oral etoposide and incorrect EMR drug builds. Oncology Drug shortages impacted clinical trials in 13.4% of respondents in which 54.55% of respondents noting patients not being enrolled in clinical trials. Conclusions: A survey of US oncology pharmacists and technicians indicated that oncology drug shortages occurred frequently in 2020. Shortages led to delays in chemotherapy and changes in treatment or omission, complicated clinical research and increased the risk of medication errors and adverse outcomes.
Evaluation of the effectiveness of telephone consultations and the level of satisfaction of patients attending the Unidad Docente Asistencial de Mastología [Mastology Care Teaching Unit] using this method during the COVID health emergency.
Authors: Camejo Natalia , Castillo Cecilia , Artagaveytia Nora , Amarillo Dahiana , Vitureira Florencia , Rodriguez Florencia , Delgado Lucia Beatriz 
Published: June 2021

e13610 Background: In March 2020, a health emergency was decreed due to COVID-19 and this produced changes in the organization of health services. One of the objectives of the reorganization that took place was a reduction in face-to-face consultations (FTFC), and the promotion of telephone consultations (TC). Objective: Evaluate the effectiveness of TC and the level of satisfaction of patients attending the Mastology Unit using this method during the COVID health emergency. Methods: A prospective, cross-sectional study. A survey was used to assess the effectiveness of TC and the level of satisfaction with the method. Results: : Forty-two patients were surveyed, of which 69% were receiving adjuvant treatment and 14.2% palliative treatment. With regard to the effectiveness of TC, 76.1% of those surveyed had their appointment resolved by telephone; 78.6% of patients preferred to do the consultation by telephone; 97.6% believed that sufficient time was spent and that the timing of the appointment was appropriate. The responses showed a high degree of satisfaction with the care received. The medical care met the expectations of all patients, and 83.3% believed that once normalcy was restored, TC would be an option for their situation Conclusions: The TC method was evaluated with a high degree of satisfaction and allowed care to be maintained during the emergency. Although it is early to assess the healthcare impact of TC and the method's capacity to resolve issues, preliminary results show that it is a useful and valuable tool in clinical practice during periods of healthcare emergency.
Telemedicine visits result in a significantly lower rate of cancellations compared to in-person visits for interventional oncology clinic patients.
Authors: Shah Suken , Solomon Stephen Barnett 
Published: June 2021

e13624 Background: Telemedicine allows increased access to specialists, less time in a waiting room and on-demand options with little to no transportation costs. These changes have been accelerated by the COIVD-19 pandemic. The purpose of the study was to test the hypothesis that a virtual telemedicine clinic would significantly decrease no-show rates and cancellations compared to in-person visits for interventional oncology (IO) clinic patients. Methods: Telemedicine visits were performed by a physician or advanced practice provider (PA or NP) at a single institution, academic medical center including 5 regional sites to patients at home in multiple states. Total patients encounters and data from January 2020 to December 2020 were analyzed. Visit types included new visits and follow up visits. Phone only visits were excluded. Primary outcome measures were an analysis of total cancelled visits (both same day and rescheduled visits), completed visits, and total scheduled visits with calculation of the telemedicine and in-person cancellation rates. Results: There was a total of 9,044 IR clinic visits in 2020 from 6,348 unique patients across the MSK Main Campus and Regional Network. Of these clinic visits, 5586 were telemedicine visits and 3458 were in-person visits. There was a significant decrease in no show and cancellation rates for telemedicine patients (6.3%) compared to in-person visits (8.1%) (p-value <0.00001). Conclusions: Telemedicine visits resulted in a significantly lower rate of visit cancellation compared to in-person visits. This reduction in no-show and cancellation rates may yield significant cost savings by eliminating gaps in the interventional oncology clinic schedule to allow for more efficient use of physician time and resources.
Treatment pattern and outcomes of leptomeningeal carcinomatosis in India: CRSF201901 study.
Authors: Goyal Gautam , Singh Ashish , Prasad Manu , Raut Nirmal Vivek , Talreja Vikas , Chandrasekharan Arun , Gupta Kushal , Bhosale Bharat , Kothari Rushabh Kiran , Poladia Bhavesh Pradip , Ghosh Joydeep , Talele Avinash , Shrirangwar Sameer , Karpe Ashay 
Published: June 2021

e14012 Background: Leptomeningeal carcinomatosis (LCM) is a rare event and has a dismal prognosis. Limited data is available from India on LCM. Hence we did this country wise audit of LCM. Methods: This was a retrospective, multicentric audit of adult (age ≥ 18 years) patients with diagnosis of LCM, conducted across India in 2020 for patients treated from 2010 to 2020. Baseline characteristics, previous treatments, cancer sites, LCM diagnosis details, treatment pattern and overall survival (OS) were collected. Descriptive statistics were performed and Kaplan Meier analysis was performed for estimation of OS. Results: We had 84 patients diagnosed with LCM. The diagnosis of LCM was confirmed in 52 (61.9%) and probable 32 (38.1%) patients. The mean age was 51.8 years (SD-10.8) and we had 46 (54.8%) females. The three most common site of malignancy were lung, breast and gastrointestinal with 45 (53.6%), 22 (26.1%) and 9 (10.7%) patients. The ECOG PS at the presentation of LCM was 1, 2 in and 3-4 in 41 (48.8%), 28 (33.3%) and 15 (17.9%) respectively. LCM was seen at diagnosis in 2 patients (2.4%) and at progression in rest. The status of the extracranial disease at the occurrence of LCM was progressive disease in 39 patients (46.1%). The treatment offered was best supportive care in 24 patients (28.6%), systemic therapy only in 27(32.1%), systemic therapy and intrathecal therapy in 22 (26.2%) and only intrathecal therapy in 11(13.1%). Among 33(39.3%) patients receiving IT methotrexate was used in 23 (27.4%) and the combination of methotrexate, AraC and hydrocortisone was used in 10 (11.9%). The CSF clearance rate was assessed in 24 (28.6%) patients and the clearance rate was 13.1% (n=11). The median duration of therapy was 4 weeks (IQR 1-14). The median os was 90 days (95% CI 46.2-133.8). Conclusions: LCM has a grave prognosis and nearly 1/3rd patients are treated with best supportive care. Intrathecal therapy though part of all guidelines is administered in 39% of patients. This data can serve as a benchmark for further improvement to facilitate studies for further improving the outcomes.
Anlotinib alone or in combination with temozolomide in recurrent high-grade glioma: A retrospective study.
Authors: Yang Qun-ying , Guo Cheng-Cheng , He Zhenqiang , Lin Fuhua , Zhang Ji , Guo Xiaoyu , Chen Yinsheng , Jiang Xiaobing , Ke Chao , Chen Zhongping , Mou Yonggao 
Published: June 2021

e14019 Background: High-grade glioma (HGG) is the most common malignant brain tumor and lacks effective treatment regimen. Anlotinib is a multikinase inhibitor blocking angiogenesis and tumor cell proliferation simultaneously. This study was performed to evaluate the efficacy and safety of anlotinib alone or in combination with temozolomide (TMZ) in the treatment of recurrent HGG. Methods: This is a single-center, retrospective study. Eligible patients (pts) were diagnosed with pathologically confirmed high grades (WHO III/IV) glioma and had recurrent or progressive disease on or after prior treatment. Other key eligibility criteria included Karnofsky Performance Status (KPS) ≥ 40, aged 16 ̃75 years and having at least one measurable lesion (RANO criteria). Pts were administrated with anlotinib once daily for 14 days every 3 weeks till disease progression, intolerable toxicities or death. The initial dose was 12mg for younger pts ( < 40 years old) with KPS ≥ 60 and 10 mg for others. Combination treatment was allowed if previous TMZ was effective and tolerable. TMZ was administered on dose-dense schedule (150mg/m2, QD, d1-d7 and d15-d21 every 28 days) or metronomic schedule (25-50mg/m2 QD). The primary endpoint was progression-free survival at 6 months (PFS6m) accessed according to RANO criteria. The second endpoints included overall survival (OS), objective response rate (ORR) and disease control rate (DCR). Results: Between August 2019 and June 2020, 23 pts with HGG (15 grade IV; 8 grade III; 12 males, 11 females) were enrolled. The median age and median KPS was 42 years and 60. 16 pts have multifocal or disseminated disease. 18 pts received ≥2 lines previous treatment. At the data cutoff date on September 2020, the median duration of treatment was 9 weeks (range: 3-33). The PFS6m was 39.1% and the median PFS was 4.2 months (95% CI: 2.8, 5.6). The median OS was not reached (95% CI: NE, NE) and the OS at 12 months (OS12m) was 54.8%. 8 pts observed tumor response and 9 pts had stable disease. The ORR and DCR were 34.8% and 73.9% respectively. The results of survival analysis for subgroups were summarized in table below. Grade 1 or 2 treatment-related adverse events (TRAEs) occurred in 65.2% pts. No ≥ grade 3 TRAE was found. All hematological TRAEs occurred in patients received combination regimen. No TRAE-induced treatment termination occurred. The lower incidence of TRAE may partly attributed to that most pts (18/23) received lower initial dose (10mg) of anlotinib and the relatively shorter treatment duration. Conclusions: This study showed treatment with anlotinib alone or in combination with TMZ had promising efficacy and favorable tolerability in patients with recurrent HGG.[Table: see text]
Integrated genomic and transcriptomic analysis identified KRT18 mutation and MTAP loss as key genetic alterations related to the prognosis of astrocytoma and glioblastoma.
Authors: Li Zhiyong , Jin Yinghui , Zou Qingping , Shi Xiaofeng , Li Kaishu , He Qun , Lin Zhiying , Wang Xiran , Xie Sidi , Gao Lei , Ni Bowen , Zhang Yunxiao , Wang Ziyu , Liu Rui , Liu Yawei , Huang Guanglong , Qi Songtao 
Published: June 2021

e14039 Background: Astrocytoma and glioblastoma (GBM) are two main subtypes of glioma classified by WHO guide of center nervous system (CNS) tumors to different grades. GBM is the most malignant among all CNS tumors with a 5-year survival rate of less than 5%. Although the prognosis of patients with astrocytoma is better than that of GBM in general, astrocytoma patients with IDH wild-type have a similar prognosis as GBM. Exploring the molecular driving force behind the malignant phenotype of astrocytoma and GBM will help explain the diversity of glioma and discover new drug targets. Methods: We enrolled 12 patients with astrocytoma and 12 patients with GBM and performed whole-exome sequencing (WES) and RNA-seq analysis on tumor samples from the patients. Comparative analysis of somatic mutation, copy number variation, cytoband alteration and differently expressed genes were performed between astrocytoma and GBM. Immune cells infiltration was analyzed by CIBERSORT Algorithm with LM22 immune subsets. Results: This study includes 14 male patients and 10 female patients, and the median age was 45.5 (range, 18-68) years old. Seven patients had IDH1 mutation, including 6 patients with astrocytoma and 1 patient with GBM. Somatic mutation of KRT18, which is associated with cell apoptosis and adhesion by interacting with TRADD and Pinin , was significantly enriched in astrocytoma, but rare in GBM. Copy number loss of MTAP, which is a potential drug target and closely related to a poor prognosis of glioma, was found significantly enriched in GBM. Pathway enrichment analysis found that GBM was mainly enriched in tumor-related pathways, such as cell adhesion, cell division, and angiogenesis, but astrocytoma was mainly enriched in pathways with ion transport, cell-cell signaling and neurogenesis. Immune cells infiltration analysis showed that macrophages M0 was significantly enriched in GBM, and activated mast cells, monocytes and plasma cells were significantly enriched in astrocytoma. Conclusions: This study revealed the distinct characteristics of astrocytoma and GBM at the DNA and RNA levels. Somatic mutation of KRT18, which was first reported in glioma, may be closely related to the malignant phenotype of astrocytoma. Copy number loss of MTAP, which was associated with the susceptibility to purine starvation and specific chemotherapy, was a key genetic alterative gene in GBM and had the potential to become the therapeutic target of GBM.
Cutaneous adverse events associated with immune checkpoint blockade: A meta-analysis.
Authors: Han Yiqun , Wang Jiayu , Xu Binghe 
Published: June 2021

e14500 Background: Dermatological toxicity is the most common immune-related adverse events (irAEs) following immune checkpoint inhibitors (ICIs). A better understanding of this side effect enables early recognition, diagnosis, and management in clinical practice. Methods: We did a meta-analysis of literature published on ClinialTrials.gov, Pubmed, Embase, and Cochrane Library up to April 30, 2020. Randomized controlled trials (RCTs) which reported the cases of cutaneous irAEs following ICIs (anti-PD-1, anti-PD-L1, anti-CTLA-4) were included. We comprehensively assessed the differences in cutaneous irAEs among ICIs, the effect from dosage and combined treatment on the incidence, the correlations of cutaneous irAE with other organ-specific irAEs, and the predictive values for prognosis. This study was prospectively registered in the PROSPERO platform (ID: CRD42020182247). Results: A total of 687 publications were initially identified and 46 eligible RCTs involving 28569 patients were included. Compared with that in patients receiving anti-CLTA-4 antibody, the overall risk of dermatological irAEs tended to be lower in patients receiving anti-PD-1 antibody (RRrash, 0.60; 95%CrI, 0.36-0.99; RRpruritus, 0.51; 95%CrI, 0.22-1.10) and was lower in those receiving anti-PD-L1 antibody (RRrash, 0.63; 95%CrI, 0.43-0.90; RRpruritus, 0.37; 95%CrI, 0.20-0.67). In general, neither treatment in combination nor dosage were estimated to add additional risk to the incidence of cutaneous irAEs. Dermatological toxicity was positively associated with immune-related hepatitis (P = 0.006), neuropathy (P = 0.040) and gastrointestinal dysfunctions (P = 0.038). The cutaneous irAEs was not confirmed as a surrogate predictor for survival with ICIs monotherapy. Conclusions: This study indicates that cutaneous irAEs are dose-independent and agent-specific immune reactions with the highest risk observed in CTLA-4 blockade, and the occurrence is associated with hepatic, neurological, and gastrointestinal disorders. The exploration in the predictive value of cutaneous irAEs for response and survival outcomes will be warranted in the future.
A phase I study to evaluate the safety and effectiveness of neoantigen-based personalized dendritic cell vaccine in patients with advanced solid tumors.
Authors: WU Jianhui , LIU Daoning , Yan Liang , Lv Ang , Tian Xiuyun , CHENG Xudong , Fu Meng , Qiu Hui , Liu Bonan , Liu Qiao , Li Chengpeng , Wang Zhen , Wang Xiaopeng , Hao Chunyi 
Published: June 2021

e14512 Background: Patients with solid tumor may get benefits from neoantigen-based cancer vaccines, which has showed some clinical efficacy data in clinical trials. This study was designed to evaluate the safety and efficacy of a neoantigen-based dendritic cell vaccine in patients with advanced solid tumors Methods: In this single arm study, patient-specific mutation-containing epitopes were detected from patient's tumor tissue. Tumor specimens were processed for whole transcriptome RNA sequencing, whole exome sequencing and HLA typing analysis. Total 10-20 immunogenic neoantigens for each patient were formulated and loaded into patient’s dendritic cells to manufacture the patient-specific anti-cancer vaccines. The patient was administered vaccine injections (Days 0, 14, 35, 56 and 98) into inguinal lymph nodes and intra-cutaneous. Peripheral blood was collected during the treatment (Days 14,15, 35, 36, 56, 57,77, 99 and 120) for safety evaluation and for assessment of the expansion of antigen-specific T cells in vivo. Patients were followed up until confirmed disease progression, withdrawal consent or adverse event intolerance. Results: Between 2019 and 2020, six patients received the neoantigen-based DC vaccine. The tumor types were laryngeal carcinoma, leiomyosarcoma, biliary tract carcinoma and hepatocellular carcinoma. All six enrolled patients had stage III or IV disease and had failed at least one line of systematic therapy at baseline. Preliminary data revealed that 6 pts (5 female and 1 male) with mean age of 44 (41-50) yrs. received ≥3 dose of DC vaccine. Doses ranged from 2×106 cells/ml to 10×106 cells/ml. All observed treatment related Adverse Events were Grade 1 or Grade 2. The most common (≥10%) drug-related adverse events were fatigue (15%), fever (15%), and elevated AST (20%). Five patients received at least one disease assessment post baseline visit. There were no tumor response. The patient with biliary tract carcinoma, laryngeal ca, leiomyosarcoma had SD status for 11 weeks, 30 weeks and 16 weeks respectively. Patients were assessed with the ELISPOT, which showed a CD8 + neoantigen-specific T-cells expansion was detected from each of the six patients’ peripheral blood after the fifth vaccine injection, which demonstrate the preliminary proof of concept for this personalized neoantigen-based dendritic cell vaccine. Conclusions: In this study, neoantigen-based dendritic cell vaccine has showed preliminary activity in advanced solid tumor patients with well-tolerated safety profile, which indicated the neoantigen-targeting DC vaccine has potential to be an effective treatment (with alteration of the immune cell milieu) in solid tumor patients.