tbuckley/cabot-search huggingface dataset:
A phase II study to evaluate the safety and efficacy of OQL011 on VEGFR inhibitor-associated hand-foot-skin reaction in cancer patients.
Authors: Mario E. Lacouture, Milan J. Anadkat, Omkar Subhash Marathe, Nicholas J. Vogelzang, Elaine Tat Lam, Benjamin Kaffenberger, Jennifer N. Choi, Mark L. Webb, Robert Claude Tyler, Juegang Ju, Hong Tang, Jie Luo, Anisha Patel
Journal: Journal of Clinical Oncology (2021)

TPS12132 Background: Hand-Foot Skin Reaction (HFSR) is frequently associated with the use of multi-targeted tyrosine kinase inhibitors of the vascular endothelial growth factor receptor (VEGFRi) such as cabozantinib, regorafenib, sunitinib, and lenvatinib. HFSR affects the skin on the palms and soles and is manifested as edema, erythema, hyperkeratosis, and bullae, leading to a decrease in quality of life and interruptions in dosing. The incidence of HFSR differs among VEGFRi, ranging from 5-60% (all grades) and 1-18% (grade 3). To date, there is no FDA approved treatment for HFSR, and marginal benefit has been shown with topical urea or steroids. Although not fully elucidated, the pathogenesis of HFSR has been associated with impaired vascular repair mechanisms, caused by inhibition of VEGF signaling pathways. We hypothesize that topical stimulation of VEGFR through OQL011 will decrease the severity of HFSR symptoms via local upregulation of the VEGF/VEGFR related signaling pathways. Methods: NCT04088318 is a phase 2, double-blind, randomized controlled trial to evaluate the safety and efficacy of OQL011 compared to vehicle control in the treatment of moderate to severe HFSR in patients on VEGFRi therapy. Eligible patients will have ≥ grade 2 palmar plantar erythrodysesthesia (PPE). The study is expected to enroll 112 patients in two parts. In the first part, 42 patients will apply 0.2% OQL011 topical ointment or vehicle control (2:1 randomization) TID for six weeks. In Part 2, 70 subjects will be randomized into two additional dose levels or vehicle control in a 2:2:1 ratio. The two dose levels selected will be based on the efficacy and safety results of Part 1. The primary efficacy endpoint is improvement of NCI CTCAE v5.0 PPE to grade ≤1 by week 3. Photographs of the affected areas will be taken at Day 0, 7, 14, 21 and 42 timepoints. Superiority test will be performed to compare treatment groups, and the exposure-response relationship will be explored. In addition, an investigator global assessment (IGA) for HFSR will be used in this trial to specifically assess skin recovery and is proposed to be a new evaluation tool. The validity of IGA criteria will be evaluated by assessing the inter-rater and intra-rater reliability. The correlation between IGA, NCI CTCAE v5.0 for PPE, and patient reported outcomes including Visual Analog Scale of Pain, Hand-foot Quality of Life questionnaire will also be evaluated. This study began enrolling patients in December 2019 and is ongoing. Clinical trial information: NCT04088318.
T-cell receptor pharmacodynamics associated with survival and response to tremelimumab (T) in combination with durvalumab (D) in patients (pts) with unresectable hepatocellular carcinoma (uHCC).
Authors: Patricia McCoon, Young S Lee, Robin Kate Kelley, Violeta Beleva Guthrie, Song Wu, Stephanie A Bien, Alejandra Negro, Philip He, John Kurland, J Carl Barrett, Fernanda Pilataxi, Steven Ching, Ghassan K. Abou-Alfa
Journal: Journal of Clinical Oncology (2021)

4087 Background: Study 22, a phase 2 clinical study (NCT02519348) evaluating T (anti-CTLA-4) and D (anti-PD-L1) as monotherapies and in combination indicated the best efficacy-safety profile with a novel combination regimen containing a single, priming dose of T (T300+D). Additionally, an expansion of proliferative CD8+ lymphocytes at Day 15 was observed with T300+D that was associated with improved response. Here, an exploratory molecular analysis of peripheral blood T cell receptors is presented. Methods: Immune-checkpoint inhibitor-naïve pts were randomized to 1 of 2 T+D combinations: T300+D (T 300 mg [1 dose] + D 1500 mg, then D every 4 weeks [Q4W]) or T75+D (T 75 mg Q4W + D 1500 mg Q4W [4 doses], then D Q4W); or single agent D (1500 mg Q4W) or T (750 mg Q4W [7 doses] then Q12W). DNA was isolated from PAXgene-preserved whole blood collected at baseline and on Day 29 during the first cycle of Q4W dosing, and then underwent CDR3 sequencing of T-cell receptor β using the immunoSEQ Assay (Adaptive Biotechnologies, Seattle, WA). Associations with objective response rate (ORR) and overall survival (OS) were evaluated. Results: The number of evaluable pts, samples, and overall ORR and OS are provided (Table). Immunosequencing analysis did not reveal significant differences in baseline T-cell clonality across arms. Increased T-cell clonal expansion at Day 29 appeared to be T dose dependent (Table), with no significant difference in the median expansion between the D and T75+D arms. Across all arms, responders had a larger median number of expanded T-cell clones on Day 29 than nonresponders (77.5 vs 40), and this greater expansion trended with longer OS (Table). Further evaluation by arm demonstrated an increase in T-cell clonal expansion in responders vs nonresponders in the T300+D arm. Pts with T-cell expansion above the median in the T300+D and T75+D arms also exhibited longer OS. Both newly expanded and total expanded clones on Day 29 vs Day 1 were associated with improved OS. Conclusions: The observed T dose-dependent increase in T-cell clonal expansion trended with improved ORR and longer OS, with the greatest overall benefit seen with T300+D vs T75+D, D and T. This is consistent with the previously reported observation that T300+D led to the highest median proliferating CD8+ T-cell counts and radiographic response. Further work is needed to differentiate the relative contributions of CD4 and CD8 clonal expansion to increased efficacy. T300+D and D are being evaluated in the phase 3 HIMALAYA study (NCT03298451) in uHCC vs sorafenib. Funding: AstraZeneca. Clinical trial information: NCT02519348. [Table: see text]
Breast Cancer Metastasis Mimicking Meningioma in 68Ga-DOTATOC PET/CT
Authors: Matthias P. Fabritius, Thomas Geyer, Freba Ahmaddy, Nathalie L. Albert, Peter Bartenstein, Reinhold Tiling, Johannes Rübenthaler, Adrien Holzgreve
Journal: Clinical Nuclear Medicine (2021)

Abstract 68 Ga-DOTATOC PET/CT is a reliable imaging modality in the diagnosis and therapy planning of symptomatic meningiomas. We present a case of a 74-year-old woman where a supposed SSTR-positive sphenoid wing meningioma turned out to be a breast cancer metastasis. Our case shows that dural metastases from breast cancer might represent a clinical pitfall in 68 Ga-DOTATOC PET/CT.
Abstract 218: Weekly Exercise Increases Coronary Artery Diameter: A Case Report
Authors: Katsumi Akimoto, Asuka Nakamura, Mana Harada, Sachie Shigemitsu, Hideo Fukunaga, Takeshi Furukawa, Masahiro Ohtsuki, Ken Takahashi, Masahiko Kishiro, Toshiaki Shimizu
Journal: Circulation (2015)

Background: Studies have reported that heparin and exercise may alleviate myocardial ischemia in patients with Kawasaki disease (KD).Moreover, exercise alone can alleviate ischemic heart disease, e.g., cardiac rehabilitation in adult coronary disease. Exercise induces secretion of some growth factors and improves endothelial function. We found that exercise may play a role in physiologically increasing the diameter of the coronary artery(CA) in KD patients with history of coronary aneurysm. Clinical course: We report the case of a 9-year-old boy who had been admitted to our hospital at 6 months of age. He had long-term fever, rash, peripheral edema, conjunctivitis, and strawberry tongue and was diagnosed with KD. We treated him with a high dose of gamma globulin and pulse therapy. Despite these treatments, he developed coronary aneurysms on both sides. In the left descending artery (LAD), the aneurysmal diameter was 8 mm. We initiated treatment with warfarin and aspirin and performed angiography twice in the acute phase and at one year after admission, followed by magnetic resonance coronary angiography every 6 months. At 6 years of age, the aneurysmal changes disappeared. We stopped warfarin and started regular exercise on a weekly basis (1 hour of running and 2 hours of baseball). After initiation of exercise,echocardiography showed that LAD diameter increased from 2.8 mm to 3.5 mm. At 9 years of age, we performed angiography and intravascular ultrasound (IVUS) to determine whether this increase in diameter was due to recurrent aneurysmal change or physiological change. The diameter of the LAD was 3.5 mm (&gt;+2 SD of normal). IVUS showed that there was a small amount of endothelial hypertrophy but no irregularity, calcification, or thrombus. Thus, we concluded that this dilatation was not an inflammatory change but a physiological change. Conclusion: Regular exercise may play a role in improving CA lesions through arterial dilatation and improvement of endothelial function.
Hospitalization at Home for Patients With Acute Exacerbation of Chronic Disease—Further Evidence to Inform Practice
Authors: Jared Conley
Journal: JAMA Network Open (2021)

Geneviève Arsenault-Lapierre, PhD; Mary Henein, MSc; Dina Gaid, PhD; Mélanie Le Berre, MSc; Genevieve Gore, MLIS; Isabelle Vedel, MD, PhD
Palliative care for cancer in Turkey: A comprehensive review of the literature.
Authors: M. Tezer Kutluk, Fahad Ahmed, Mustafa Cemaloğlu, Burca Aydin, Meltem Sengelen, Meral Kirazlı, Sema Yurduşen, Richard Sullivan, Richard Harding
Journal: Journal of Clinical Oncology (2021)

e24088 Background: Palliative care is patient and family-centered care provided to optimize the quality of life in serious illness, and is an essential health service under Universal Health Coverage. Given the burden of cancer and other chronic disease diseases along with demographic changes, the need for palliative care is growing in Turkey. This study aimed to review of the available scientific literature on palliative cancer care needs, models and outcomes Turkey. Methods: A comprehensive literature review was conducted with English and Turkish keywords in PubMed, Scopus, Embase, ScienceDirect, Web of Science, Google Scholar, The Turkish Academic Network and Information Centre databases, Turkish Ministry of Health documents, Turkish Council of Higher Education’s doctoral thesis, and renowned national and international palliative care as well as cancer conferences 01/ 2000 to 07/ 2020. Results: Out of 27489 papers identified, 320 met the criteria for inclusion. The main focus of these studies was; historical development in palliative care, legislative regulation, professional training, use of opioids, symptom management, care for patients, palliative care centers, public awareness, psychosocial support, and end of life ethics. The majority of this literature used descriptive design, although a few case-control, cohort, and randomized control trials were also found. Our analysis showed that the development of PC in Turkey can be divided into three period. The first (early initiatives, before 2000), the second (dissemination phase, 2000-2010), and the third stage (government &amp; societial engagement, after 2010). Several studies also analyzed the barriers such as low public &amp; professional awareness, disconnection from cancer care, the opioidfobia and the lack of trained palliative care providers. The lack of integration of palliative care to cancer care is a major challenge for palliative care implementation. Conclusions: This review presents the evidence of the significant progress in PC during the last 20 years and the opportunities for further progress. Bringing research into practice is needed for shaping the integration of palliative care to cancer care in Turkey. The stakeholders and policy makers should not neglect the need for PC under the current pressure of COVID-19 pandemic on health and economy.
Bilateral Chilblain-like Lesions of the Toes Characterized by Microvascular Remodeling in Adolescents During the COVID-19 Pandemic
Authors: Valentina Discepolo, Andrea Catzola, Luca Pierri, Massimo Mascolo, Francesca Della Casa, Maria Vastarella, Grace Smith, Antonio Travaglino, Alessandra Punziano, Paola Nappa, Stefania Staibano, Eugenia Bruzzese, Gabriella Fabbrocini, Alfredo Guarino, Maria Alessio
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Chilblain-like lesions have been one of the most frequently described cutaneous manifestations during the COVID-19 pandemic. Their etiopathogenesis, including the role of SARS-CoV-2, remains elusive. <h3>Objective</h3> To examine the association of chilblain-like lesions with SARS-CoV-2 infection. <h3>Design, Setting, and Participants</h3> This prospective case series enrolled 17 adolescents who presented with chilblain-like lesions from April 1 to June 30, 2020, at a tertiary referral academic hospital in Italy. <h3>Main Outcomes and Measures</h3> Macroscopic (clinical and dermoscopic) and microscopic (histopathologic) analysis contributed to a thorough understanding of the lesions. Nasopharyngeal swab, serologic testing, and in situ hybridization of the skin biopsy specimens were performed to test for SARS-CoV-2 infection. Laboratory tests explored signs of systemic inflammation or thrombophilia. Structural changes in peripheral microcirculation were investigated by capillaroscopy. <h3>Results</h3> Of the 17 adolescents (9 [52.9%] male; median [interquartile range] age, 13.2 [12.5-14.3] years) enrolled during the first wave of the COVID-19 pandemic, 16 (94.1%) had bilaterally localized distal erythematous or cyanotic lesions. A triad of red dots (16 [100%]), white rosettes (11 [68.8%]), and white streaks (10 [62.5%]) characterized the dermoscopic picture. Histologic analysis revealed a remodeling of the dermal blood vessels with a lobular arrangement, wall thickening, and a mild perivascular lymphocytic infiltrate. SARS-CoV-2 infection was excluded by molecular and serologic testing. In situ hybridization did not highlight the viral genome in the lesions. <h3>Conclusions and Relevance</h3> This study delineated the clinical, histologic, and laboratory features of chilblain-like lesions that emerged during the COVID-19 pandemic, and its findings do not support their association with SARS-CoV-2 infection. The lesions occurred in otherwise healthy adolescents, had a long but benign course to self-resolution, and were characterized by a microvascular remodeling with perivascular lymphocytic infiltrate but no other signs of vasculitis. These results suggest that chilblain-like lesions do not imply a concomitant SARS-CoV-2 infection. Ongoing studies will help clarify the etiopathogenic mechanisms.
Retrieval of vector integration sites from cell-free DNA
Authors: Daniela Cesana, Andrea Calabria, Laura Rudilosso, Pierangela Gallina, Fabrizio Benedicenti, Giulio Spinozzi, Giulia Schiroli, Alessandra Magnani, Serena Acquati, Francesca Fumagalli, Valeria Calbi, Maximilian Witzel, Frederic D. Bushman, Alessio Cantore, Pietro Genovese, Christoph Klein, Alain Fischer, Marina Cavazzana, Emmanuelle Six, Alessandro Aiuti, Luigi Naldini, Eugenio Montini
Journal: Nature Medicine (2021)
Interim results of viagenpumatucel-L (HS-110) plus nivolumab in previously treated patients (pts) with advanced non-small cell lung cancer (NSCLC) in two treatment settings.
Authors: Roger B. Cohen, George Earl Peoples, Toana Kawashima, Bill Arana, Xiaoxing Cui, Lyudmila Bazhenova, Rachel E. Sanborn, Wael A. Harb, Nathan A. Pennell, Daniel Morgensztern
Journal: Journal of Clinical Oncology (2021)

9100 Background: Viagenpumatucel-L (HS-110) is an allogeneic cell therapy derived from a human lung adenocarcinoma cell line incorporating multiple cancer testis antigens and transfected with a gp96-Ig fusion protein. Methods: We report interim results of cohort A (previously treated pts who had not received a checkpoint inhibitor [CPI]) and cohort B (pts who progressed after CPI treatment) in an ongoing phase 2 trial evaluating HS-110 plus nivolumab (NIVO) in advanced NSCLC pts (NCT02439450). Pts received HS-110 (1×10 7 cells) intradermally QW for 18 wk and NIVO Q2W until tumor progression. Stratified analyses were performed by injection site reaction (ISR), yes (+) or no (–); baseline blood tumor mutational burden (bTMB), bTMB-L (&lt;10 mutations/ megabase [mut/Mb]) or bTMB-H (≥10 mut/Mb) by FoundationACT test; and baseline PD-L1 expression, – (&lt;1%) or + (≥1%). Results: As shown in the Table, median progression-free survival (PFS) in cohort A (n=47) was 1.8 mo (95% CI 1.8-7.8) and median overall survival (OS) was 24.6 mo (95% CI 11.7-36.0) after a median follow-up (MFU) of 19.5 mo. We observed significantly longer PFS and OS in ISR+ pts (hazard ratio [HR] 0.43, p=0.01; HR 0.23, p&lt;0.001) and longer OS in PD-L1+ pts (HR 0.25, p=0.02). In cohort B (n=68), median PFS was 2.8 mo (1.8-3.9) and median OS was 11.9 mo (9.7-16.3) after a MFU of 11.9 mo. We observed significantly longer OS in ISR+ pts (HR 0.48, p=0.03) and a trend toward extended OS in bTMB-L pts (HR 0.58, p=0.20). HS-110 TEAEs were reported in 21 (44.7%) pts in cohort A and 18 (26.5%) pts in cohort B. TEAEs in &gt;5% of pts included fatigue, maculopapular rash, nausea, diarrhea, and pruritus. Few HS-110–related TEAEs led to discontinuation of treatment [cohort A, 5 (10.6%); cohort B, 3 (4.4%)], and no serious AEs were considered related to HS-110. Conclusions: HS-110 was well tolerated when administered in combination with NIVO. In previously treated pts with advanced NSCLC, we observed (1) significantly longer PFS and OS in ISR+ pts in both CPI naïve and CPI progressor cohorts; (2) significantly longer OS in PD-L1+ patients in the CPI naïve cohort; and (3) a trend of improved OS in bTMB-L pts in the CPI progressor cohort. Further clinical evaluation of HS-110 is warranted in both CPI naïve and CPI progressor NSCLC patients. Clinical trial information: NCT02439450. [Table: see text]
Pilot study of nivolumab in pediatric patients with hypermutant cancers.
Authors: Daniel A. Morgenstern, Natalie Bucheimer Collins, Rebecca Deyell, Rina Dvir, Melissa Edwards, Cecile Faure-Conter, Timothy E. Hassall, Lauren Sambira, Emily L. Taylor, Uri Tabori, Eric Bouffet
Journal: Journal of Clinical Oncology (2021)

10011 Background: Responses to immune checkpoint inhibitors (ICI) in unselected pediatric solid tumors have been disappointing. We hypothesized that pediatric cancers with an increased tumor mutation burden (TMB) and/or replication repair deficiency (RRD) may be uniquely susceptible to ICI therapy. Methods: OZM-075 (NCT2992964) is a multicenter pilot study in patients (pts) aged 1-25 yrs with relapsed/refractory cancers (including CNS tumors). Pts were eligible only if tumor showed evidence of RRD (based on immunohistochemistry showing loss of expression of relevant RR protein) or elevated TMB &gt; 5mut/Mb determined by gene panel DNA sequencing. Pts with measurable or evaluable disease were eligible. Enrolment began in May 2017 and was completed in Nov 2020. Pts received programmed death-1 (PD-1) inhibitor nivolumab (NIVO) at a fixed dose of 3mg/kg every 2 weeks. Primary objective was objective response rate (ORR) by iRECIST or iRANO for those with measurable disease. Tumor tissue and serial blood samples were collected for analysis of biomarkers of response and survival. Results: As of 26Jan2021, 6 male and 5 female patients aged 9-18 yrs received treatment with NIVO (5 glioblastoma (GBM), 2 anaplastic astrocytoma (AA), 2 neuroblastoma, 1 colorectal adenocarcinoma (CRC), 1 adrenocortical carcinoma). 3pts had TMB 5-10mut/Mb, 5pts had TMB &gt; 10mut/Mb (range 14-837, median 64), 3 pts enrolled on basis of RRD. Time on treatment ranged from 0-21 months and 2 pts remain on therapy. Best OR was partial response (PR) in 2 pts (both GBM), with an additional patient with CRC achieving pathological CR. Remarkably one of the pts with PR showed early evidence of progression on imaging and elected to discontinue NIVO. Without further therapy, subsequent imaging 7 months later showed PR. Best response of stable disease was demonstrated in 5 further pts, lasting ≥5 months in 3 pts. Median overall survival (OS) not reached. Of 7 patients with relapsed GBM/AA, 5 were alive for ≥12 months following start of NIVO including 4 pts with confirmed TMB &gt; 10mut/Mb. Conclusions: This pilot study showed evidence of impressive clinical benefit particularly for relapsed GBM/AA patients for whom median survival is typically ̃6 months (JCO 1995 13(1):112-). These data contrast previous pediatric data and suggest that in the context of RRD and hypermutation ICI therapy may provide profound long-term response and survival for these children. Analysis of other correlative biomarkers is ongoing. Clinical trial information: 2992964.
How Would You Manage This Patient With Nonvariceal Upper Gastrointestinal Bleeding?
Authors: Zahir Kanjee, Akwi W. Asombang, Tyler M. Berzin, Risa B. Burns
Journal: Annals of Internal Medicine (2021)

Nonvariceal upper gastrointestinal bleeding is common, morbid, and potentially fatal. Cornerstones of inpatient management include fluid resuscitation; blood transfusion; endoscopy; and initiation of proton-pump inhibitor therapy, which continues in an individualized manner based on risk factors for recurrent bleeding in the outpatient setting. The International Consensus Group released guidelines on the management of nonvariceal upper gastrointestinal bleeding in 2019. These guidelines provide a helpful, evidence-based roadmap for management of gastrointestinal bleeding but leave certain management details to the discretion of the treating physician. Here, 2 gastroenterologists consider the care of a patient with nonvariceal upper gastrointestinal bleeding from a peptic ulcer, specifically debating approaches to blood transfusion and endoscopy timing in the hospital, as well as the recommended duration of proton-pump inhibitor therapy after discharge.