tbuckley/cabot-search huggingface dataset:
Circulating tumor (ct) DNA-based comprehensive genomic profiling to identify microsatellite instability (MSI) and defective DNA damage repair (DDR) in prostate cancer (PCa) patients.
Authors: Leylah M. Drusbosky, Lesli Ann Kiedrowski, Kelsey Johnson, Rebecca Nagy, Jennifer Saam, Mehmet Asim Bilen, Niraj K. Gupta, Michael B. Lilly
Journal: Journal of Clinical Oncology (2020)

190 Background: Recent trials in PCa have shown efficacy of PARP inhibitors (PARPi) in patients (pts) with mutations in DDR genes such as BRCA1/2 (TOPARP-B, GALAHAD), as well as efficacy of immunotherapy (IO) in PCa pts with MSI. The combination of PARPi + IO is currently being evaluated in the KEYNOTE-365 trial. This analysis explored the utility of ctDNA in identifying PCa pts who may benefit from PARPi, IO, or a combination. Methods: ctDNA-based comprehensive genomic profiling (Guardant360) of 2,165 PCa pts was performed between 10/2018-08/2019. Frequency of pathogenic somatic BRCA1/ 2 mutations and MSI are reported. Results: Out of 2,165 PCa pts tested, Guardant360 identified 24 (1.1%) and 59 (2.7%) pts harboring pathogenic somatic BRCA1 or BRCA2 variants, respectively; MSI was detected in 40 (1.8%) PCa pts. Of the 40 MSI samples, 9 (22.5%) pts also had a somatic pathogenic BRCA1 and/or BRCA2 mutation . One pt harbored pathogenic somatic mutations in both BRCA1 and BRCA2. The variant allele frequency (VAF) for somatic pathogenic BRCA1 (N=2) ranged from 0.2-0.88%, and BRCA2 (N=8) ranged from 0.05-12.4%. There were no BRCA1/2 mutations at VAFs suspicious for germline in MSI PCa pts. A median of 19 genomic alterations (range 8-28) was identified among the 9 pts with pathogenic BRCA1/2 variants. The most frequent co-occurring aberrations were found in TP53, APC, AR, BRCA2, ARID1A, PTEN, RB1, and PIK3CA. An 82yo male with recurrent metastatic PCa underwent Guardant360 testing which identified BRCA2 T3085fs at 7.9% VAF and MSI. He was treated with pembrolizumab for 3 cycles and remains in remission. Another 51yo with MSI was treated with pembrolizumab for 4 cycles. He also remains in remission. Subsequent analysis shows clearance of ctDNA and MSI. Conclusions: ctDNA-based comprehensive genomic profiling can be used to detect PCa pts eligible to receive PARPi, IO, or a combination, improving clinical treatment decision making and pt outcomes, especially when a tissue biopsy is not feasible or sufficient for comprehensive genomic profiling. PSA and objective responses to IO have been observed in PCa pts with MSI detected by ctDNA.
Autochthonous Chagas Disease — Missouri, 2018
Authors: George Turabelidze, Archana Vasudevan, Christian Rojas-Moreno, Susan P. Montgomery, Molly Baker, Drew Pratt, Susanne Enyeart
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

On December 13, 2017, the Missouri Department of Health and Senior Services (MDHSS) was notified of a suspected case of Chagas disease in a Missouri woman. The patient had donated blood, and laboratory screening revealed antibodies to Trypanosoma cruzi, the parasite that causes Chagas disease. Evaluation by physicians found no clinical symptoms consistent with Chagas disease. The patient had no travel history that would have suggested a significant risk for Chagas disease risk and had no occupational exposure to the disease agent. She had never received a blood transfusion or organ transplant. Confirmatory testing of the patient's serum at CDC for T. cruzi antibody was consistent with infection. These findings raise the possibility that the exposure to T. cruzi occurred locally (autochthonously) in Missouri. Although the insect vector for the parasite T. cruzi, triatomines (commonly known as "kissing bugs"), has been identified previously in Missouri, no locally acquired human cases of Chagas disease have been identified in the state. Health care providers and public health professionals should be aware of the possibility of locally acquired Chagas disease in the southern United States.
Improvement in Patient-Reported Outcomes With Intensity-Modulated Radiotherapy (RT) Compared With Standard RT: A Report From the NRG Oncology RTOG 1203 Study
Authors: Anamaria R. Yeung, Stephanie L. Pugh, Ann H. Klopp, Karen M. Gil, Lari Wenzel, Shannon N. Westin, David K. Gaffney, William Small, Spencer Thompson, Desiree E. Doncals, Guilherme H.C. Cantuaria, Brian P. Yaremko, Amy Chang, Vijayananda Kundapur, Dasarahally S. Mohan, Michael L. Haas, Yong Bae Kim, Catherine L. Ferguson, Snehal Deshmukh, Deborah W. Bruner, Lisa A. Kachnic
Journal: Journal of Clinical Oncology (2020)

In oncology trials, the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) is the standard tool for reporting adverse events (AEs), but it may underreport symptoms experienced by patients. This analysis of the NRG Oncology RTOG 1203 compared symptom reporting by patients and clinicians during radiotherapy (RT).Patients with cervical or endometrial cancer requiring postoperative RT were randomly assigned to standard 4-field RT or intensity-modulated RT (IMRT). Patients completed the 6-item patient-reported outcomes version of the CTCAE (PRO-CTCAE) for GI toxicity assessing abdominal pain, diarrhea, and fecal incontinence at various time points. Patients reported symptoms on a 5-point scale. Clinicians recorded these AEs as CTCAE grades 1 to 5. Clinician- and patient-reported AEs were compared using McNemar's test for rates > 0%.Of 278 eligible patients, 234 consented and completed the PRO-CTCAE. Patients reported high-grade abdominal pain 19.1% (P < .0001), high-grade diarrhea 38.5% (P < .0001), and fecal incontinence 6.8% more frequently than clinicians. Similar effects were seen between grade ≥ 1 CTCAE toxicity and any-grade patient-reported toxicity. Between-arm comparison of patient-reported high-grade AEs revealed that at 5 weeks of RT, patients who received IMRT experienced fewer GI AEs than patients who received 4-field pelvic RT with regard to frequency of diarrhea (18.2% difference; P = .01), frequency of fecal incontinence (8.2% difference; P = .01), and interference of fecal incontinence (8.5% difference; P = .04).Patient-reported AEs showed a reduction in symptoms with IMRT compared with standard RT, whereas clinician-reported AEs revealed no difference. Clinicians also underreported symptomatic GI AEs compared with patients. This suggests that patient-reported symptomatic AEs are important to assess in this disease setting.
A review of cutaneous mosaicism
Authors: V.A. Kinsler, O. Boccara, S. Fraitag, A. Torrelo, P. Vabres, A. Diociauti
Journal: British Journal of Dermatology (2020)

Cutaneous mosaicism is a term used for a group of disorders in which a person has two or more genetically different populations of cells existing side by side within the skin. It is an area of dermatology in which there has been an explosion of knowledge within the current decade. This has led to fundamental changes in the understanding of the conditions in this field, and to an ongoing shift in the approach to treating mosaic skin disorders. In this expert review, as part of the European Reference Network project (ERN-Skin), we lay out the general principles of mosaicism as they are currently understood, summarise the known cutaneous mosaic abnormalities of the skin – including signs and symptoms and genetic information – and we review the latest trials of treatments. We also propose guidelines for the general approach to patients thought to have mosaicism. This is a summary of the study: Mosaic abnormalities of the skin: review and guidelines from the European Reference Network for rare skin diseases
Calcium and Vitamin D (Ca&amp;VitD) Intake in Children with Perceived Atopic Disease (PAD) versus Healthy Children and Corresponding Parental/Caregiver (PCs) Attitudes Towards Dairy Products (DPs)
Authors: Alicia Darwin, Michael Carroll, Sara Galvis Noda, Sofia Perez Perez, Rahul Mhaskar, Antoinette Spoto-Cannons, Richard Lockey
Journal: Journal of Allergy and Clinical Immunology (2020)
Surveillance of postchemotherapy subcentimeter residual retroperitoneal mass (RRM) in metastatic nonseminomatous germ cell tumor (mNSGCT).
Authors: Cody Cotner, Susan Hilton, Ronac Mamtani, Thomas J. Guzzo, David J. Vaughn
Journal: Journal of Clinical Oncology (2020)

391 Background: Approximately 30 – 60% of patients with mNSGCT treated with cisplatin-based chemotherapy (CBCT) achieve a complete response (CR), defined as normalization of serum tumor markers with either no RRM or a RRM &lt; 1 cm. While there is universal agreement that patients with a RRM ≥ 1 cm should undergo retroperitoneal lymph node dissection (RPLND), many institutions, including ours, recommend surveillance for patients who achieve a CR. However, studies have not defined which axis of the RRM should be considered when making this decision. Methods: The electronic medical records (2007 – 2017) at the Hospital of the University of Pennsylvania (HUP) were searched to identify good-risk mNSGCT patients treated with CBCT who achieved a CR and underwent surveillance. Consistent with RECIST 1.1, we define a CR as no RRM or a RRM &lt; 1 cm in the transaxial short axis (TSA). We do not consider the transaxial long axis (TLA) or the craniocaudal axis (CCA). A post-hoc review was performed by a blinded radiologist and the RRM dimensions in the TSA, TLA, and CCA were recorded. Differences in the frequency of recurrence between groups with a RRM &lt; 1.0 cm and ≥ 1.0 cm in the TLA and CCA were assessed using the Fischer exact test. Results: 39 patients met study criteria and were included. At a median follow-up of 50.8 months, only 2 patients (5.1%) recurred. Both were successfully treated with RPLND and salvage chemotherapy. Post-hoc review of imaging: median TSA 6 mm (range, 0-11); median TLA 8 mm (range, 0-14); median CCA 11 mm (range, 0-34). Thirteen (33%) and 27 (69%) patients had a RRM ≥ 1 cm in the TLA and CCA, respectively. There were no statistically significant differences in the risk of recurrence between patients with a RRM &lt; 1.0 cm and ≥ 1.0 cm in the TLA (p=0.54) or CCA (p=0.53). Conclusions: Surveillance is an effective strategy in patients with mNSGCT and a post-chemotherapy RRM &lt; 1.0 cm in the TSA. Our study suggests that referencing the TSA and not the TLA or CCA in this decision-making may avoid unnecessary post-chemotherapy RPLND.
Diminished Reactive Hematopoiesis and Cardiac Inflammation in a Mouse Model of Recurrent Myocardial Infarction
Authors: Sebastian Cremer, Maximilian J. Schloss, Claudio Vinegoni, Brody H. Foy, Shuang Zhang, David Rohde, Maarten Hulsmans, Paolo Fumene Feruglio, Stephen Schmidt, Greg Wojtkiewicz, John M. Higgins, Ralph Weissleder, Filip K. Swirski, Matthias Nahrendorf
Journal: Journal of the American College of Cardiology (2020)
Development of a risk calculator of recurrence in inguinal lymph node metastatic (ILNM) patients with surgically resected penile squamous cell carcinoma (PSCC).
Authors: Marco Bandini, Yao Zhu, Dingwei Ye, Antonio Augusto Ornellas, Nick Watkin, Michael Ager, Oliver W. Hakenberg, Axel Heidenreich, Daniele Raggi, Mario Catanzaro, Laura Marandino, Friederike Haidl, Francesco Montorsi, Juan Chipollini, Mounsif Azizi, Maarten Albersen, Roberto Salvioni, Oscar Brouwer, Philippe E. Spiess, Andrea Necchi
Journal: Journal of Clinical Oncology (2020)

1 Background: ILNM PSCC patients (pts) have heterogeneous outcomes. We aimed to identify risk factors of early recurrence in order to optimize the selection of pts for adjuvant (adj) therapies (tx). Methods: In a multicenter database of 924 pts who underwent ILN dissection, we identified 311 ILNM pts. Pts treated with neoadj chemo (CT) and/or radiotherapy (RT) were excluded. Multivariable Cox regression analyses (MVA) tested for predictors of recurrence, after adjusting for adj tx, age, type of surgery of the primary and smoking status. As primary endpoint, a risk calculator predicting early (24-month) risk of recurrence was developed. As secondary endpoint, the overall survival (OS) benefit of adj tx was examined according to the risk calculator-derived tertiles using Kaplan-Meier analysis. Results: Overall, 159 pts (51.1%) had pN1-2 and 203 (65.3%) pT2-4 disease. Overall, 195 (62.7%) and 78 (25.1%) received partial or total penectomy, whereas 6 (1.9%) local excision and 32 (10.3%) other procedures. Median number of removed and positive ILN were 15 (IQR 9-21) and 2 (IQR 1-3). Pelvic LND was performed in 154 (49.5%) pts, and 39% of them had pelvic LNM. In MVA, ILN ratio (HR: 1.01, p= 0.04), pN3 (HR: 2.53, p=0.002) and positive proximal margin of the primary (HR: 2.13, p=0.02) were significantly associated with recurrence. The c-index of our 3-variable risk calculator was 68%, with a net benefit higher that treat-all option from 20% to 90% threshold-probabilities. Within the cohort of adj CT and/or RT (N=127) pts, intermediate-high tertile had similar median OS (NR vs 107m) compared to pts in the low tertile (p=0.1). Conversely, intermediate-high tertile pts who received observation alone had shorter OS (NR vs 40m) compared to the same pts in the lower tertile (p&lt;0.001). Similar results were obtained for CT and RT separately analyzed. Conclusions: We developed and internally validated a risk calculator to predict early recurrence in ILNM surgically-resected PSCC pts. According to our risk-calculator, pts with intermediate/higher risk of early recurrence may benefit from adj tx. Our risk calculator can be used for counseling and enrolment in ongoing studies.
Local Airway Concentration of Anti-Tryptase Antibody (MTPS9579A) Predicts Extent of Tryptase Disruption
Authors: Sharon Rymut, Kenta Yoshida, Siddharth Sukumaran, Fang Cai, Gizette Sperinde, Viyia Sverkos, Prajna Banerjee, Paula Belloni, Joseph Lin
Journal: Journal of Allergy and Clinical Immunology (2020)
Gene Signature for Sorafenib Susceptibility in Hepatocellular Carcinoma: Different Approach with a Predictive Biomarker
Authors: Chang Min Kim, Shin Hwang, Bhumsuk Keam, Yun Suk Yu, Ji Hoon Kim, Dong-Sik Kim, Si Hyun Bae, Gun-Do Kim, Jong Kyu Lee, Yong Bae Seo, Soon Woo Nam, Koo Jeong Kang, Luigi Buonaguro, Jin Young Park, Yun Soo Kim, Hee Jung Wang
Journal: Liver Cancer (2020)

Uniform treatment of hepatocellular carcinoma (HCC) with molecular targeted drugs (e.g., sorafenib) results in a poor overall tumor response when tumor subtyping is absent. Patient stratification based on actionable gene expression is a method that can potentially improve the effectiveness of these drugs. Here we aimed to identify the clinical application of actionable genes in predicting response to sorafenib.Through quantitative real-time reverse transcription PCR, we analyzed the expression levels of seven actionable genes (VEGFR2, PDGFRB, c-KIT, c-RAF, EGFR, mTOR, and FGFR1) in tumors versus noncancerous tissues from 220 HCC patients treated with sorafenib. Our analysis found that 9 responders did not have unique clinical features compared to nonresponders. A receiver operating characteristic curve evaluated the predictive performance of the treatment benefit score (TBS) calculated from the actionable genes.The responders had significantly higher TBS values than the nonresponders. With an area under the curve of 0.779, a TBS combining mTOR with VEGFR2, c-KIT, and c-RAF was the most significant predictor of response to sorafenib. When used alone, sorafenib had a 0.7-3% response rate among HCC patients, but when stratifying the patients with actionable genes, the tumor response rate rose to 15.6%. Furthermore, actionable gene expression is significantly correlated with tumor response.Our findings on patient stratification based on actionable molecular subtyping potentially provide a therapeutic strategy for improving sorafenib's effectiveness in treating HCC.
Performance characteristics of 18F-Fluciclovine positron emission tomography/computed tomography prior to retroperitoneal lymph node dissection.
Authors: Xiaosong Meng, Solomon L. Woldu, Daniel Wong, John T. Lafin, Rashed Ghandour, Vitaly Margulis, Jesse Conyers, Yin Xi, Rathan M. Subramaniam, Aditya Bagrodia
Journal: Journal of Clinical Oncology (2020)

390 Background: There is no reliable way to differentiate between fibrosis/necrosis, teratoma, and viable germ cell tumor in patients receiving post-chemotherapy retroperitoneal lymph node dissection (RPLND) for non-seminomatous germ cell tumor (NSGCT). Functional imaging, including 18 F-FDG positron emission tomography/computed tomography (PET/CT), has been disappointing. Due to the need for better imaging modalities, our prospective, pilot study aims to investigate the accuracy of 18 F-Fluciclovine PET/CT in detecting residual tumor prior to RPLND. Methods: From Mar 18 – May 19, 10 eligible patients underwent pre-operative 18 F-Fluciclovine PET/CT prior to undergoing bilateral full template RPLND or excision of mass (for one re-do retroperitoneal lymph node dissection) in a prospective phase II study. Correlation between PET/CT findings and pathology were evaluated on per patient level. Results: A total of 10 patients underwent 18 F-Fluciclovine PET/CT prior to surgery. 9/10 patients received chemotherapy prior to RPLND. Correlation between 18 F-Fluciclovine PET/CT and RPLND pathology was seen in 3/10 patients. 5/10 patients with negative anti- 18 F-FACBC PET/CT were found to have residual disease/teratoma on RPLND. Compared to the reference standard of RPLND, 18 F-Fluciclovine PET/CT demonstrated 29% sensitivity and 33% specificity. Conclusions: Current management of NSGCT is heavily reliant on sub-optimal imaging modalities that are unable to accurately distinguish between post-chemotherapy necrosis/fibrosis versus residual disease and/or teratoma. Despite a different mechanism of action from 18 F-FDG, 18 F-Fluciclovine has low sensitivity and specificity for residual teratoma in the retroperitoneum. Clinical trial information: NCT03426865. [Table: see text]
Clinical investigation of neuroendocrine differentiation in prostate cancer.
Authors: Tatsuya Shimomura, Takashi Kurauchi, Keigo Sakanaka, Takahiro Kimura, Shin Egawa
Journal: Journal of Clinical Oncology (2020)

138 Background: Neuroendocrine prostate cancer (NEPC) is a lethal disease subset with median overall survival of less than 1 year from time of detection. The treatment strategy against NEPC is not yet established and some clinical trials are ongoing now. Recently, clinical trial (RADIIANT4) showed that treatment with everolimus was associated with significant improvement in survival in patients with progressive lung or gastrointestinal neuroendocrine tumors. In this study we evaluated the neuroendocrine differentiation of prostate cancer and we tried to introduce everolimus against pathologically proven NEPC and investigated the clinical outcomes of this agent. Methods: Total of 193 prostate cancer cases were included in this study. We tested serum neuroendocrine markers, including (NSE and pro-GRP). And we evaluated positive rate of these markers. Eleven cases were pathologically proven neuroendocrine prostate cancer (NEPC) in this cohort. Seven out of eleven NEPC cases were introduced everolimus 10mg daily. We investigated the change of serum neuroendocrine markers (NSE and pro-GRP), radiologic examination and survival. Results: The positive rate of serum neuroendocrine markers (at least one of the markers increasing above normal limit) were 23.5% in hormone sensitive prostate cancer (HSPC), 59.5% in castration resistant prostate cancer (CRPC), and 100% in neuroendocrine prostate cancer (NEPC). There were significant differences in each other (HSPC vs. CRPC: p=0.0001, CRPC vs. NEPC: p=0.0109). We introduced everolimus in seven cases out of eleven NEPC cases. The median follow up period was 18 months. Neuroendocrine markers decreased in five of seven (71.4%) cases after introduction of everolimus. Median decreasing rate were 67.1% in NSE and 65.5% in pro GRP. 24M progression free survival rate was 57.1% and 24M overall survival rate was 57.1%. Conclusions: There is a possibility that the incidence of NEPC is higher than expected, and treatment against prostate adenocarcinoma accelerate neuroendocrine differentiation. Everolimus showed efficacy against NEPC. Although this study was retrospective and number of cases was limited, everolimus would be a one of the treatment options against NEPC.
Incidental Detection of Hypothyroidism on 68Ga-PSMA-HBED-CC PET/CT Imaging
Authors: Apurva Sood, Shelvin Kumar Vadi, Rajender Kumar, Harmandeep Singh, Bhagwant Rai Mittal
Journal: Clinical Nuclear Medicine (2020)

Abstract 68 Ga-labeled prostate-specific membrane antigen (PSMA) ligand PET/CT is a rapidly evolving imaging modality for prostate cancer. However, with the widespread use of 68 Ga-PSMA PET/CT, various reports of nonprostatic uptake of 68 Ga-PSMA in both benign and malignant lesions have also appeared. We report a recently diagnosed case of prostate cancer demonstrating diffuse 68 Ga-PSMA expression in both the lobes of thyroid gland, which on further clinical and biochemical investigations was established as hypothyroidism.
ARCTIC: durvalumab with or without tremelimumab as third-line or later treatment of metastatic non-small-cell lung cancer
Authors: D. Planchard, N. Reinmuth, S. Orlov, J.R. Fischer, S. Sugawara, S. Mandziuk, D. Marquez-Medina, S. Novello, Y. Takeda, R. Soo, K. Park, M. McCleod, S.L. Geater, M. Powell, R. May, U. Scheuring, P. Stockman, D. Kowalski
Journal: Annals of Oncology (2020)

Many patients with metastatic non-small-cell lung cancer (mNSCLC) experience disease progression after first- and second-line treatment; more treatment options are required for these patients. ARCTIC, a phase III, randomized, open-label study, assessed durvalumab ± tremelimumab versus standard of care (SoC) as ≥ third-line treatment of mNSCLC.ARCTIC comprised two independent sub-studies. Study A: 126 patients with ≥25% of tumor cells (TCs) expressing programmed cell death ligand-1 (PD-L1) were randomized (1 : 1) to durvalumab [up to 12 months 10 mg/kg every 2 weeks (q2w)] or SoC. Study B: 469 patients with PD-L1 TC <25% were randomized (3 : 2 : 2 : 1) to durvalumab + tremelimumab (12 weeks durvalumab 20 mg/kg + tremelimumab 1 mg/kg q4w then 34 weeks durvalumab 10 mg/kg q2w), SoC, durvalumab (up to 12 months 10 mg/kg q2w), or tremelimumab (24 weeks 10 mg/kg q4w then 24 weeks q12w). Primary end points: overall survival (OS) and progression-free survival (PFS) for durvalumab versus SoC (study A; descriptive only) and durvalumab + tremelimumab versus SoC (study B).Study A: median OS 11.7 (durvalumab) versus 6.8 (SoC) months {hazard ratio (HR) 0.63 [95% confidence interval (CI), 0.42-0.93]}; median PFS 3.8 (durvalumab) versus 2.2 (SoC) months [HR 0.71 (95% CI, 0.49-1.04)]. Study B: median OS 11.5 (durvalumab + tremelimumab) versus 8.7 (SoC) months [HR 0.80 (95% CI, 0.61-1.05); P = 0.109]. Median PFS of 3.5 months for both groups [HR 0.77 (95% CI, 0.59-1.01); P = 0.056]. Treatment-related grade 3/4 adverse events: 9.7% (durvalumab) and 44.4% (SoC; study A) and 22.0% (durvalumab + tremelimumab) and 36.4% (SoC; study B).In heavily pretreated patients with mNSCLC, durvalumab demonstrated clinically meaningful improvements in OS and PFS versus SoC (patients with PD-L1 TC ≥25%); numerical improvements in OS and PFS for durvalumab + tremelimumab versus SoC were observed (patients with PD-L1 TC <25%). Safety profiles were consistent with previous studies.Clinicaltrials.gov identifier: NCT02352948.
Molecular Patterns of IgE Sensitization to Storage Mites in Persistent Asthma Under Subtropical Weather Conditions
Authors: Ruperto Gonzalez Perez, Fernando Pineda de la Losa, Paloma Poza Guedes, Miriam Castillo, Martina Aumayr, Cristina Alava Cruz, Peter Forstenlechner, Victor Matheu, Elena Mederos Luis, Inmaculada Sanchez-Machin
Journal: Journal of Allergy and Clinical Immunology (2020)