tbuckley/cabot-search huggingface dataset:
Safety and efficacy of pyrotinib in patients with NSCLC and other advanced solid tumors with activating <i>HER2</i> alterations: A phase I basket trial.
Authors: Bob T. Li, Tianhong Li, Melissa Lynne Johnson, Saiama Naheed Waqar, Viola Weijia Zhu, Sai-Hong Ignatius Ou, Jessica Jiyeong Lin, Ding Wang, Geoffrey Shapiro, Judy Sing-Zan Wang, Dazhi Liu, Yuqing Ye, Hana Kosar, Angela Hee, Greg Berk, Sean Zhang, Junsheng Wang, Manish R. Patel
Journal: Journal of Clinical Oncology (2020)

3510 Background: Pyrotinib is a potent, irreversible tyrosine kinase inhibitor (TKI) that blocks signal transduction through the erythroblastic leukemia viral oncogene homolog (erbB) receptors, which has previously demonstrated promising antitumor activity in patients (pts) with breast cancers. We studied the safety and efficacy of pyrotinib in pts with non-small cell lung cancer (NSCLC) and other solid tumors with activating human epidermal growth factor receptor 2 ( HER2, ERBB2) alterations. Methods: This is an open-label, multicenter phase 1 dose expansion basket trial of pyrotinib given 400mg oral daily at 28-day cycles. Expansion cohorts included pts with HER2-mutant NSCLC and advanced solid tumors with HER2 mutation or amplification. HER2 testing was conducted using next generation sequencing or fluorescence in situ hybridization. Primary endpoints included toxicities as evaluated by NCI CTCAE v5.0, and overall response rate (ORR) as evaluated by RECIST v1.1. Secondary objectives included progression-free survival (PFS). Results: A total of 62 pts were enrolled. The median age was 67 (range 40 – 86 years), 61% were female and the median lines of prior systemic therapy was 3 (range 1-11). There were no treatment related deaths. The most common adverse events were diarrhea (96.8%), nausea (82.3%) and vomiting (41.9%). The only ≥ grade 3 treatment related toxicity was diarrhea (24.2%). Prophylactic anti-diarrhea treatment was introduced to facilitate continuation of pyrotinib. At the Jan 13, 2020 cut-off, 24 pts with HER2-mutant NSCLC (20, i.e. 65% of which were the A775_G776insYVMA mutation) and 18 pts with HER2-mutant or amplified solid tumors completed end of Cycle 2 imaging scan and were evaluable for tumor responses. The ORR was 19% (8/42, 95% CI 7-31%); confirmed responses include a complete response (CR) and 3 partial responses (PRs) in HER2-mutant NSCLC, and 4 PRs in HER2-amplified cholangiocarcinoma, ovarian, endometrial and salivary gland carcinomas. There were 7 stable disease ≥ 6 months. Median progression-free survival was 5.4 months (95% CI 4.4-7.3). Conclusions: Pyrotinib demonstrated a manageable safety profile and encouraging efficacy in pts with heavily pre-treated HER2-mutant NSCLC. Furthermore, it is the first TKI to produce durable responses in pts with HER2-amplified biliary tract, ovarian, endometrial and salivary gland cancers. These results warrant further clinical development of pyrotinib. Clinical trial information: NCT02500199 .
Multi-antigen active specific immunotherapy induced long-term remission and prevent colorectal cancer relapse.
Authors: Juan Pablo Marquez-Manriquez, Pedro Alejandro Lucero-Diaz, Alejandro Camacho-Hernandez, Dolores Gallardo-Rincon, Martin Orlando Rosas-Delgado, Mario Alberto Perez-Astorga, Daniel Adrian Fernandez-Felix, Jorge Alberto ALBERTO Cisneros-Ruiz, Maria Olga Rocha Banuelos, Alberto Durazo
Journal: Journal of Clinical Oncology (2020)

3138 Background: Clinical effective multi-antigen active immunotherapy for colorectal cancer (CRC) is still limited and most studies have failed. We consider this is because the targets in some of the studies are not oncogenic drivers. This is especially important for patients that progressed to standard of care treatment. Also, most of the studies with Immune checkpoint inhibitors (ICH) have failed in CRC but potentially may impact and provide better outcomes if used as combination therapies. We treated CRC patients with progressive disease in a pilot study n = 15 and found clinical responses that correlate with the CD8, delayed-type hypersensitivity (DTH) and Th1 parameters. After patients achieved remission we used the same peptides to prevent relapse with clinical and statistics significance. Methods: N = 15 CRC patients were enrolled in this pilot trial after approval for the ethic IRB committee from CICS Mexico. Patients were treated with an intradermal vaccine every week for four weeks, every two weeks four times in axillary and inguinal lymph nodes (LN) areas, and finally subcutaneously every month six times in the sites with tumor activity. Previously to the treatment we perform Granzyme B ELISPOT, ELISA, DTH and CT scan as initial controls. We delivered intradermal four peptides from sixteen peptides predicted from four proteins such as Fascin-1, Ape-1, VCP and RCAS1. Results: 86% of the patients had an objective clinical responses and 14% stable disease. All the patients had a correlation with the immunological assays as following. 58% of patients had an increased in the CD8 cells demonstrated by Granzyme B; DTH reactions were gradually increasing and by the first month of treatment the DTH were positive for Fascin-1 (78%), Ape-1 (85%), VCP (95%) and RCAS1 (83%) peptides. The more immunogenic peptides by ELISA were Fascin-1 A (P = 0.001), Fascin-1 D (P = 0.005), Ape-1 C (p = 0.001), VCP A (P = 0.003), RCAS1 A (p = 0.001) and RCAS1 B (P = 0.01). Conclusions: The treatment was effective with CR and SD responses. Once we validate this data we are planning a clinical study combining the treatment with low dose of ICH. Currently all the patients with CR are now under relapse prevention. We are still treating the patients with SD until disease progression. Importantly we believe that this data may impact the PFS and OS in CRC patients who have Karnoksky &gt; to 80% despite progressive disease to standard of care.
Clinical utility of comprehensive genomic profiling and targeted therapy in biliary tract cancers: A real-world experience.
Authors: Mahum Shahid, Mohamed A. Abdallah, Moataz Ellithi, Hafez Mohammad Abdullah, Morgan Nelson, Benjamin Maurice Solomon, Jonathan Bleeker
Journal: Journal of Clinical Oncology (2020)

e16671 Background: Biliary tract cancers (BTC) are a highly aggressive group of malignancies with high mortality and poor prognosis. Chemotherapy is the mainstay of treatment for advanced disease. The role of molecular targeted therapy and immunotherapy using comprehensive genomic profiling (CGP) is evolving. We investigated the role of CGP directed therapy in patients with BTC. Methods: A multi-center retrospective study of CGP done on 35 patients with BTC at Sanford USD Medical Center and Avera McKennan Hospital, Sioux Falls, SD, between 2014 and 2019. 27 patients had cholangiocarcinoma (fifteen intrahepatic, two extrahepatic and ten unclassified), two had gallbladder carcinoma and six had ampullary carcinoma. Results: 22 of 35 BTC (63%) had potentially actionable genetic alterations(GA). Nine of these 22 (41%) received molecular therapy based on CGP. Four patients had microsatellite instability (MSI-H) and two of them received immunotherapy (Table). CDKN2A/B was the most common mutation (23%) followed by PIK3CA (13%), ARID1A (13%) and Tp53(13%). By the end of the follow up period, median overall survival (OS) was 569 days(19 months) for those who received targeted therapy compared to 315 days(10.5 months) for those who did not. (P = 0.051). Conclusions: In this multi-center cohort, 63% of patients had at least one targetable GA. Furthermore, CGP guided treatment decisions in 41% of patients. CGP has the potential to provide clinically meaningful treatment options for patients with BTC. New studies are warranted to further investigate this promising prospect for BTC management. [Table: see text]
APOLLO: A phase I study of adaptive memory natural killer (NK) cells in recurrent ovarian cancer.
Authors: Melissa Ann Geller, Sarah A. Cooley, Mark Wallet, Bahram Valamehr, Deanna Gek Koon Teoh, Todd E. DeFor, Martin Felices, Jeffrey Miller
Journal: Journal of Clinical Oncology (2020)

6044 Background: Human cytomegalovirus (CMV) infection induces a subset of long-lived CD57 + NKG2C + adaptive NK cells that exhibit enhanced antibody-dependent cellular cytotoxicity and resistance to tumor-suppressive mechanisms. We developed a 7-day culture process using a GSK3 inhibitor and IL-15 to manufacture modulated adaptive NK cells (FATE-NK100) from CMV + haploidentical donors for adoptive transfer. The phase I Apollo trial tests the maximum tolerated dose/maximum feasible dose (MTD/MFD) of FATE-NK100 administered intraperitoneally (IP) to treat platinum-sensitive or -resistant recurrent ovarian, fallopian tube, and primary peritoneal cancer. Methods: FATE-NK100 via IP port was tested using 3 dose cohorts ([DC]; 1 × 10 7 cells/kg; &gt;1 × 10 7 cells/kg to ≤3 × 10 7 cells/kg; or &gt;3 × 10 7 to ≤10 × 10 7 cells/kg) after lympho-conditioning with fludarabine 25 mg/m 2 IV and cyclophosphamide 300 mg/m 2 IV on days −6 and −5. After FATE-NK100 infusion on day 0, rhIL-2 at 6 million IU was given IP 3 times a week for 6 doses for in vivo NK activation. IP fluid and peripheral blood were collected regularly until response assessment (day 28). Patients with stable disease or better were eligible for retreatment. Pre- and post-treatment tumor biopsies were collected. Results: Nine patients were treated with no dose-limiting toxicities (DLTs) to date. Retreatment based on clinical benefit was performed on 3 patients (33%), 2 following stable disease (DC 2) and 1 with partial remission (48% tumor reduction, DC 3). IP samples were collected for PK and functional analysis. FATE-NK100 product was detected by flow cytometry in 5 of 6 patients with evaluable samples (range 4.8%–91.2% donor NK cells at day +5-7). Retreatment samples were available in 1 patient, where FATE-NK100 persisted to day +21, demonstrating that repeated IP dosing did not accelerate clearance of the donor NK cells. In that same patient, measurement of NK cell CD107a degranulation or IFNg production in response to K562 targets demonstrated sustained enhanced in vivo function of FATE-NK100 compared to endogenous patient NK cells (e.g. at Day +12 CD107a + NK were 39.0% vs. 22.5% cycle 1, and 40.3% vs. 18.2% retreatment cycle 2, and IFNg + NK were 12.3% vs. 5.9% cycle 1, and 2.4% vs. 0.2% retreatment cycle 2). Conclusions: IP delivery of FATE-NK100 is safe, with clinical benefit in 3/9 patients treated. The allogeneic product cells persist and have enhanced function compared to patient NK cells for up to 21 days, even after retreatment. This phase I study in recurrent/refractory ovarian cancer shows promise for IP NK cell delivery. Clinical trial information: NCT00652899.
Videos improve patient understanding of misunderstood chemotherapy terms in a rural population.
Authors: Eli Rowe Abernethy, Gavin Paul Campbell, Rachel Hianik, Mary Catherine Thomson, Margie D Dixon, Jeffrey M. Switchenko, Rebecca D. Pentz
Journal: Journal of Clinical Oncology (2020)

7022 Background: Rural communities can have low health literacy, which impacts the adequacy of informed consent, adherence to treatment, and outcomes. We had previously created and tested educational videos about basic chemotherapy terminology for use in an underserved population at our inner-city hospital. This study aimed to determine if these videos increased understanding of these terms in rural communities. Methods: Through patient and provider interviews in an underserved urban setting, 20 basic cancer treatment terms were identified as frequently misunderstood. As a pilot, 6 of these terms were explained in short, animated one-minute videos using VideoScribe (Sparkol).To determine if these videos improved understanding in the rural setting, 50 rural patients, specified as patients living in a county ranked 4-9 on the USDA Rural Urban Continuum Code (RUCC) scale, were asked to define each term before and after viewing the video. All answers were audiotaped and double coded for correctness of definition pre and post video screening, using the video definition as the correct definition. Before video and after video correct definition rates were calculated, along with 95% exact binomial confidence intervals using the Clopper-Pearson method. The videos for all 20 terms can be viewed on CancerQuest ( https://www.cancerquest.org/media-center/videos/cancer-treatment-terms ). Results: Participants were mostly white (79%), female (52%), resided in the more rural counties RUCC ranked 6-9 (62%), had &lt; a high school degree (56%) and had a family income of &lt;$40K (59%). Conclusions: Improving health literacy is a critical component in improving care. Our study establishes that a simple and easily disseminated intervention can significantly increase patient understanding of basic chemotherapy terminology in a rural setting. [Table: see text]
Outpatient cancer rehabilitation to improve patient reported and objective measures of function.
Authors: Mackenzi Pergolotti, Kelley Renee Covington, Ashley N Lightner, Jessica Bertram, Melissa Thess, Julia L Sharp, Matthew B Spraker, Grant Richard Williams, Peter Manning
Journal: Journal of Clinical Oncology (2020)

e19325 Background: Adults with cancer often struggle with persistent symptoms that negatively impact quality of life (QoL), physical and social function. Cancer rehabilitation delivered by a trained physical and/or occupational therapist (PT/OT) is recommended. However, evidence is lacking regarding the impact of community-based PT/OT on patients' functioning. Methods: We assessed adults (≥ 18 years) who completed cancer-specific visits in routine care at two outpatient rehabilitation clinics. Demographic and clinical data was patient-reported. Patient-Reported Outcomes Measurement Information System (PROMIS) measures included: Global Physical Health (GPH) and Mental Health (GMH) scale (10 item); Physical Function (PF; 4-item), and Ability to Participate in Social Roles and Activities (SRA; 4-item). Hand grip strength (HGS) and the Timed Up and Go (TUG) were administered by PT/OT. We compared outcomes collected during the first and final therapy evaluations using paired samples t-test and calculated effect size using Cohen’s d. We used independent t-test to compare mean pre-post change between patients on active treatment versus post-treatment. Results: Patients (N= 185) were predominantly female (75%), 41-64 years old (57%), and majority receiving cancer treatment (58%). Most (N =115, 62%) completed at least one follow-up evaluation over 6 weeks. From pre to post therapy, a significant (p&lt;.05; d = 0 .35-.21) effect was observed for GPH, SRA, HGS, and TUG. There was no difference in the average improvement between active and post-treatment groups. Conclusions: Community-based cancer-specific PT/OT has a significant impact on the well-being and functioning of adults with cancer. Evidence supports the utilization of community-based, cancer-specific PT/OT throughout the cancer-care continuum. [Table: see text]
4R Care Delivery Program results: Impact of implementation metrics on patient self-management and 4R usefulness.
Authors: Julia Rachel Trosman, Christine B. Weldon, Della F. Makower, Bruce D. Rapkin, Claudia Beth Perez, Swati Kulkarni, Cathleen M. Schaeffer, Kent Hoskins, Christopher Gallagher, Shelly S. Lo, Cathy Grace-Louthen, Alyssa Throckmorton, Editha A. Krueger, Jennifer Van Horn, Brieyona Chardee Reaves, Arliene Ravelo, Elaine Yu, Lidia Schapira, Al Bowen Benson, William John Gradishar
Journal: Journal of Clinical Oncology (2020)

225 Background: We previously proposed a 4R care delivery model that facilitates teamwork and patient self-management (pSM) in cancer care (NCI ASCO Teams Project, Trosman JOP 2016). 4R (Right Info / Care / Patient / Time) enables patient and care team to manage complex care with an innovative 4R Care Sequence. We tested 4R at 10 US sites in a stepwise mode 2016-2019. Methods: Step 1 included 1 academic and 2 nonacademic sites; step 2 included 3 academic and 4 nonacademic sites. Patients with stage 0-III breast cancer received 4R Sequences (4R Cohort). We surveyed 4R and historical control cohorts of patients treated at the same sites pre-4R. We assessed the impact of implementation metrics on usefulness of 4R to the 4R cohort and on improvement of pSM in 4R cohort vs historical control cohort. Results: Survey response rates: 63%, 422/670 (4R cohort); 47%, 466/992 (control cohort). Three of the five implementation metrics significantly impacted patient usefulness of 4R (Table). Patients at step 2 sites; sites with a systematic care process; and sites with small practices reported significantly higher 4R usefulness than patients in the comparison subgroup within respective metrics. 4R usefulness was not affected by practice setting or availability of patient navigators. pSM was significantly improved between control and 4R cohorts along all implementation metrics (p &lt; .001), but the magnitude of incremental improvement between comparison subgroups varied across metrics (Table), with the largest increment associated with the program step metric. Conclusions: 4R is useful to patients across settings, with or without patient navigators. Stepwise design is effective in increasing 4R impact overtime. Future 4R Program will investigate an expanded array of implementation metrics and their influence on 4R outcomes. [Table: see text]
Retrospective analysis of retreatment with Ipilimumab in patients with metastatic melanoma.
Authors: André Alexandre Formozo, Jessica Ribeiro Gomes
Journal: Journal of Clinical Oncology (2020)

e22032 Background: The checkpoint inhibitors are effective in the treatment of many types of neoplasia, either being used separately or in combination. Ipilimumab pioneered the treatment of metastatic melanoma and nowadays it has being used in combination with anti-PD1. Retreatment with Ipilimumab has rarely been reported, but it may be an important strategy for the current treatment of metastatic melanoma. In this study we analyzed the patients with metastatic melanoma who were retreated with Ipilimumab. Methods: We evaluated patients with metastatic melanoma who had benefited from the first treatment with Ipilimumab, but eventually had progression of disease. They received Ipilimumab at the same dose as the first treatment (3 mg/kg every 3 weeks for four cycles). The effect was evaluated for progression free survival and clinical benefit. Results: Twenty–two patients were retreated with Ipilimumab in our Oncology Center. Most of them retreated six months or more, after the prior treatment. The progression free survival of the first treatment with Ipilimumab was 9.9 months. The median progression free survival of the retreatment was 6.3 months. Fourteen patients were reported to have clinical benefit (63%). Conclusions: This is a retrospective evaluation about the retreatment with Ipilimumab in patients with metastatic melanoma. It has been rarely reported in the medical literature, especially Ipilimumab at doses of 3 mg/kg. Maybe the next step might be the combined retreatment with Ipilimumab and anti-PD1.
Forecasting global essential childhood cancer drug need and cost: An innovative model-based approach.
Authors: Avram Denburg, Brianna Empringham, Terence Hughes, Anita K. Wagner, Zachary J. Ward, Jennifer Yeh, Sumit Gupta, A. Lindsay Frazier
Journal: Journal of Clinical Oncology (2020)

e19078 Background: Childhood cancer outcomes in low-middle income countries (LMICs) have not kept pace with advances in care and survival in high income countries (HICs). A contributing factor to this survival gap is unreliable access to essential cancer drugs. Lack of data on the aggregate need and cost of essential cancer drugs has hampered rational planning and acquisition in many LMICs. Methods: We created a pediatric-specific tool (FOR x ECAST) that estimates drug quantity and cost for 18 pediatric cancers, customizable to region, regimen, cancer stage distribution, and drug price. We used adapted treatment regimens developed by the International Society of Pediatric Oncology (SIOP), supplemented with input from disease experts, to model treatment approaches reflective of health-system capabilities. FOR x ECAST incorporates incidence data generated through microsimulation estimates of both diagnosed and undiagnosed (total) cases. Results: We created a pediatric-specific tool (FOR x ECAST) that estimates drug quantity and cost for 18 pediatric cancers, customizable to region, regimen, cancer stage distribution, and drug price. We used adapted treatment regimens developed by the International Society of Pediatric Oncology (SIOP), supplemented with input from disease experts, to model treatment approaches reflective of health-system capabilities. FOR x ECAST incorporates incidence data generated through microsimulation estimates of both diagnosed and undiagnosed (total) cases. Conclusions: Our results enable evidence-based forecasting of childhood cancer drug need and cost to inform health system planning in a wide range of countries. The model is adaptable to setting, diagnosis, and treatment approach, allowing decision-makers to generate results specific to their context and needs. Global estimates of essential childhood cancer drug need and cost demonstrate the comparatively small amount of aggregate resources required to treat all cases worldwide, and can help advance innovative procurement strategies with regional and international scale that drive global improvements in childhood cancer drug access.
Characteristics of hospitalized patients with anaphylaxis during different eras at Peking Union Medical College Hospital
Authors: Rui Tang, Ying Diao, Shi Chen
Journal: BMJ (2014)

To analyze the incidence, clinical manifestations and causes of 42 in patients with anaphylaxis from 1990 and follow its change before and after 2005 retrospectively.The mean age was (39±16) years.The ratio of male and female was 1∶2.2.The incidence increased obviously after 2005 (30 vs. 12). A majority of patients were females after 2005 (24 vs. 5). The proportions of patients with impaired nerve system, circulatory system and hypotension decreased after 2005 (P<0.01, P<0.05, P<0.01). Anaphylaxis attacked more often intra-operatively after 2005(43.3% vs.1/12). The most common cause was drug(35/42), especially antibiotics(14/35).


Key words: 
Anaphylaxis; Clinical manifestation
The applicatlon of principal components:analysis in priority analysis of community health care project for elderlies
Authors: Min Xian, Li-kang Wu, Zhen-wen Zhang, Xin-dong Zhang
Journal: BMJ (2008)

A survey was conducted among 121 health care managers and health workers in community health care institutions with questionnaire and interview.Data on health care conditions in the community and health needs of elderly people were collected and analyzed using principle component analysis method.The priority order of 17 community health care projects for elderly people was ranked with this analysis method and the development strategy of community health service was suggested.

Key words: 
Health services for the aged; Evaluation studies