tbuckley/cabot-search huggingface dataset:
AR101 Oral Immunotherapy for Peanut Allergy
Journal: New England Journal of Medicine (2018)

Peanut allergy, for which there are no approved treatment options, affects patients who are at risk for unpredictable and occasionally life-threatening allergic reactions.In a phase 3 trial, we screened participants 4 to 55 years of age with peanut allergy for allergic dose-limiting symptoms at a challenge dose of 100 mg or less of peanut protein (approximately one third of a peanut kernel) in a double-blind, placebo-controlled food challenge. Participants with an allergic response were randomly assigned, in a 3:1 ratio, to receive AR101 (a peanut-derived investigational biologic oral immunotherapy drug) or placebo in an escalating-dose program. Participants who completed the regimen (i.e., received 300 mg per day of the maintenance regimen for approximately 24 weeks) underwent a double-blind, placebo-controlled food challenge at trial exit. The primary efficacy end point was the proportion of participants 4 to 17 years of age who could ingest a challenge dose of 600 mg or more, without dose-limiting symptoms.Of the 551 participants who received AR101 or placebo, 496 were 4 to 17 years of age; of these, 250 of 372 participants (67.2%) who received active treatment, as compared with 5 of 124 participants (4.0%) who received placebo, were able to ingest a dose of 600 mg or more of peanut protein, without dose-limiting symptoms, at the exit food challenge (difference, 63.2 percentage points; 95% confidence interval, 53.0 to 73.3; P<0.001). During the exit food challenge, the maximum severity of symptoms was moderate in 25% of the participants in the active-drug group and 59% of those in the placebo group and severe in 5% and 11%, respectively. Adverse events during the intervention period affected more than 95% of the participants 4 to 17 years of age. A total of 34.7% of the participants in the active-drug group had mild events, as compared with 50.0% of those in the placebo group; 59.7% and 44.4% of the participants, respectively, had events that were graded as moderate, and 4.3% and 0.8%, respectively, had events that were graded as severe. Efficacy was not shown in the participants 18 years of age or older.In this phase 3 trial of oral immunotherapy in children and adolescents who were highly allergic to peanut, treatment with AR101 resulted in higher doses of peanut protein that could be ingested without dose-limiting symptoms and in lower symptom severity during peanut exposure at the exit food challenge than placebo. (Funded by Aimmune Therapeutics; PALISADE ClinicalTrials.gov number, NCT02635776 .).
Exceptions to the rule: Novel retrospective analysis of a single-center institution of the PSMA PET/CT modality.
Authors: Vipal P. Durkal, Matthew Rettig
Journal: Journal of Clinical Oncology (2019)

e14625 Exceptions to the Rule: Using Pathology as a Gold Standard to Evaluate the Sensitivity of PSMA PET/CT Modality. Background: The experience with the novel Ga-68 PSMA PET/CT imaging and its limitations are described anecdotally in the literature. Cases of false-positive PSMA PET/CT of various benign and malignant etiologies are described in case reports. False-negative PSMA PET/CT results are significantly less well characterized. Our analysis is based on the UCLA Cancer Center experience with patients who underwent PSMA PET/CT and subsequent biopsy of target lesions. Methods: Of 44 evaluable patients, we found four patients with false negative results based on the 'Gold Standard' of pathologic biopsy. In this context, false negative is defined as PSMA PET/CT negative but proven to be PSMA-expressing adenocarcinoma of the prostate using biopsy of target lesions. Results: In our analysis, we found several stark patterns of these false-negative lesions. The vast majority were pulmonary in origin (75%). Their average size was subcentimeter (0.96 cm). The average Gleason Score at diagnosis was relatively high (8.25), while the initial PSA at diagnosis was relatively modest (4.3). A majority (75%) of these patients received radiation to the prostate. In terms of treatment: a majority were on Androgen-Deprivation Therapy (75%); Abiraterone (50%); had received prostatectomy (100%). The average age at diagnosis was 65. Conclusions: False-negative adenocarcinoma of the prostate that has been-biopsy proven to express PSMA has not been described in the literature. This is the first such instance that we can encountered. The implications of this finding are potentially far-reaching, since the lung remains the second most common site of metastasis in prostate cancer after the bone. The average sub-centimeter size of the target lesions that were biopsied suggests that the density of PSMA receptors may have a role in the detection on Ga-68 PSMA PET/CT and correlate with sensitivity.
A phase I open label study evaluating VT1021 in patients with advanced solid tumors.
Authors: Michael Cieslewicz, Devalingam Mahalingam, Wael A. Harb, Amita Patnaik, Joyce F. Liu, Dejan Juric, Andrea J. Bullock, Lei Zheng, Kathleen N. Moore, Manish R. Patel, Robert Guttendorf, Suming Wang, Kathy Kerstein, Gregory Ivan Berk, Jing Watnick
Journal: Journal of Clinical Oncology (2019)

TPS3158 Background: VT1021 is a cyclic pentapeptide that functions as a potent inducer of thrombospondin-1 (Tsp-1) expression in the tumor microenvironment (TME). By triggering the production of Tsp-1, VT1021 reprograms the TME from one that is immune-suppressive and tumor-promoting, to one that activates the adaptive immune system and is tumor-inhibiting. Tsp-1 reprograms the TME to: (i) induce apoptosis in tumor cells that express CD36 on their cell surface, (ii) convert macrophages from M2 to M1 polarization, which promotes phagocytosis and blunts immunosuppression and (iii) inhibit angiogenesis. Preclinical studies have shown robust anti-tumor activities of VT1021 in animal models of ovarian, pancreatic and breast cancer, including complete tumor regression and reprogramming of the immune TME. These observations led to the initiation of the first-in-human study of VT1021. Methods: This study is a first-in-human, Phase 1, open-label, multicenter, dose escalation (Part 1) study with dose expansion (Part 2) in advanced solid tumors. The primary objectives are to assess the safety and tolerability of VT1021, to assess dose-limiting toxicities (DLT), and to determine the maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D). Secondary objectives include the evaluation of pharmacokinetics (PK) and pharmacodynamic (PD) effects of VT1021 in tumor and tumor microenvironment, and assessment of preliminary antitumor activity. VT1021 is administered intravenously twice weekly. DLTs will be assessed in the first cycle (Days 1-28) of the dose escalation cohort and are defined as grade 3 adverse events related to VT1021. In Part 1 of the study, 24-30 patients will be enrolled to determine the MTD and RP2D for expansion. In Part 2 of the study, 80-100 patients will be enrolled, grouped into cohorts based on disease subtypes (ovarian, pancreatic, Triple-negative breast cancers, and glioblastoma). Blood samples and biopsy samples from patients will be collected to assess PK properties and PD responses systemically as well as in the TME. No formal statistical hypothesis testing will be conducted in this study. This study is currently open for enrollment in the US. Clinical trial information: NCT03364400.
Acute kidney injury in childhood cancer: An insight from Kids' Inpatient Database.
Authors: Eman M Elsabbagh, Shireen Hashmat
Journal: Journal of Clinical Oncology (2019)

e18379 Background: Oncology patients are at high risk for Acute Kidney Injury (AKI). AKI may occur due to direct injury from primary cancer, nephrotoxic effects of chemotherapy, hematopoietic stem-cell transplantation or following comorbidities like sepsis and metabolic disturbance. AKI is associated with prolonged hospital stay, high healthcare cost and increased mortality in critically ill patients. Despite the increased risk and these associations, the national rate and clinical outcome of AKI among pediatric oncology patients is not well described. Objective: Define AKI incidence and health outcomes among pediatric oncology patients in the United States (U.S.). Methods: We performed a retrospective cohort analysis of the Health Cost and Utilization Project (HCUP) Kids’ Inpatient 2000-2012 Database (KID) for patient ≤ 20 years of age. Patients with principal diagnosis of acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic myeloid leukemia (CML), lymphomas (Hodgkin and non-Hodgkin), brain tumor, neuroblastoma, bone tumors (Ewing’s Sarcoma and Osteosarcoma) and hepatoblastoma were reviewed. Encounters for chemotherapy were excluded. Patients with medical diagnosis of AKI were identified using ICD-9-CM codes. We performed descriptive statistics to characterize the cohort in terms of demographic factors (age, race, sex, insurance type), hospital characteristics and comorbidities. Data weights were applied to sampled patients to provide national estimates. The in-hospital mortality rate, total charges, and hospital length of stay (LOS) were compared between cancer patients with and without AKI using bivariable analyses. Results: A total of 266,113 admissions were included for analysis. The cohort was comprised of 4,761 patients with AKI, with an overall incidence 18 per 1,000 admissions. The median age was 13 years. Males (58.45%), and whites (55.4%) were more commonly affected. South and west regions (59%) of the U.S. had higher frequency of AKI. AML was the most common diagnosis associated with AKI (4.1%). Patients with AKI had significantly higher mortality rates (21.78% vs. 1.36%, p &lt; 0.0001), longer median LOS (15 days vs. 4 days, p &lt; 0.0001) and higher median total charges per hospitalization ($132,712 vs $18,856) when compared to patients without AKI. Conclusions: AKI in pediatric oncology patients is significantly associated with increased in-hospital mortality, LOS, and higher healthcare cost in pediatric oncology patients. This area needs focused research and quality improvement initiatives.
Abstract GS5-04: Prediction of occult invasive disease in ductal carcinoma <i>in situ</i> using deep learning features
Authors: JY Lo, LJ Grimm, MA Mazurowski, JA Baker, JR Marks, LM King, CC Maley, E-SS Hwang, B Shi
Journal: Cancer Research (2018)

Abstract Background: Deep learning, especially deep convolutional neural network (CNN), has emerged as a promising approach for many image recognition or classification tasks, demonstrating human or even superhuman performance. Used as feature extractor, some pre-trained CNN models can match or surpass the performance of domain-specific, “handcrafted” features. In this study, we aim to determine whether deep features extracted from digital mammograms using a pre-trained deep CNN are prognostic of occult invasive disease for patients with ductal carcinoma in situ (DCIS) on core needle biopsy. Materials and Methods: In this retrospective study, we collected digital mammography magnification views for 99 subjects with DCIS at biopsy, 25 of which were subsequently upstaged to invasive cancer. We utilized a deep CNN model that was pre-trained on non-medical images (e.g., animals, plants, instruments) as the feature extractor. Through a statistical pooling strategy, we extracted deep features at different levels of convolutional layers from the lesion areas, without sacrificing the original resolution or distorting the underlying topology. A multivariate classifier was then trained to predict which tumors contain occult invasive disease. This was compared to the performance of traditional “handcrafted” computer vision (CV) features previously developed specifically to assess mammographic calcifications. The generalization performance was assessed using Monte Carlo cross validation and receiver operating characteristic (ROC) curve analysis. Results: Deep features were able to distinguish DCIS with occult invasion from pure DCIS, with an area under the ROC curve (AUC-ROC) equal to 0.70 (95% CI: 0.68-0.73). This performance was comparable to the "handcrafted" CV features (AUC-ROC = 0.68, 95% CI: 0.66-0.71) that were designed with prior domain knowledge. Conclusion: In spite of being pre-trained on only non-medical images, the deep features extracted from digital mammograms demonstrated comparable performance to "handcrafted" CV features for the challenging task of predicting DCIS upstaging. Acknowledgments: This work was supported in part by NIH/NCI R01-CQA185138 and DOD Breast Cancer Research Program W81XWH-14-1-0473. Citation Format: Lo JY, Grimm LJ, Mazurowski MA, Baker JA, Marks JR, King LM, Maley CC, Hwang E-SS, Shi B. Prediction of occult invasive disease in ductal carcinoma in situ using deep learning features [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr GS5-04.
Comprehensive genomic profiling identifies novel genetic predictors of response to anti-PD-(L)1 therapies in NSCLC.
Authors: Wenfeng Fang, Yuxiang Ma, Jiani Yin, Shaodong Hong, Huaqiang Zhou, Ao Wang, Fufeng Wang, Hua Bao, Xue Wu, Yunpeng Yang, Yan Huang, Hongyun Zhao, Yang Shao, Li Zhang
Journal: Journal of Clinical Oncology (2019)

e20536 Background: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of many different cancer types, including non-small-cell lung cancer (NSCLC). However, our understandings of the molecular and immunologic determinants of response to ICIs remain incomplete. Methods: We performed whole-exon sequencing (WES) in 73 patients with advanced NSCLC who underwent anti-PD-(L)1 therapies to further explore predictive biomarkers for treatment efficacy. Novel somatic mutations and copy number alterations were identified to be predictive of response or resistance to anti-PD-(L)1 therapies. Results: We confirmed that high tumor mutation burden (TMB) was associated with improved clinical outcomes. Quantification of TMB by targeted next-generation sequencing using a customized panel including 422 cancer-relevant genes (Geneseeq) was strongly correlated with WES results (Spearman's Rho = 0.81, p &lt; 0.001). Patients whose tumour harbored FAT1 mutant had higher durable clinical response (DCB) and objective response rate (ORR) compared with wild-type (62.5% vs 20%, p = 0.02, and 50% vs 12.3%, p = 0.02, respectively), whereas patients with activating mutations in EGFR or ERBB2 had significantly shorter mPFS compared with other patients (51 vs 70.5 days, p = 0.0037, HR = 2.47 [95% CI, 1.33-4.62]). Furthermore, We found copy number loss in specific 3p segments (mPFS, 61.5 vs 65 days; survival rates at 6 months, 0% vs 31%, p = 0.012, HR = 2.08 [95% CI, 1.09-4.00]), which contain the tumor suppressor ITGA9 (mPFS, 36.5 vs 64 days, p &lt; 0.0001, HR = 9.09 [95% CI, 2.91-27.78]) and several chemokine receptor pathway genes, were highly predictive of poor clinical outcome. These findings were further validated in two independently published datasets comprising multiple cancer types. Conclusions: Our findings suggest that comprehensive profiling of TMB and the aforementioned novel genetic alterations could result in greater predictive power of response in NSCLC patients treated with ICI therapies.
Growth factor use and rate of neutropenic complications in breast cancer patients treated with dose-dense paclitaxel: A 5-year experience from a safety net hospital.
Authors: Racha Halawi, Kavi Patel, Ethan Tobias, Samira K. Syed, Nisha Unni, Hsiao Ching Li, Navid Sadeghi
Journal: Journal of Clinical Oncology (2019)

6527 Background: The NCCN guidelines recommend growth factor (G-CSF) support to reduce the risk of febrile neutropenia and maintain dose density in patients receiving dose dense chemotherapy. We retrospectively reviewed growth factor utilization with dose dense paclitaxel (ddT) in breast cancer patients treated at our institution. Methods: Electronic medical records of patients treated at Parkland Health and Hospital System between 2012-2017 for breast cancer with dose dense adriamycin and cyclophosphamide (ddAC) followed by ddT were reviewed. Data on patient characteristics as well as G-CSF use and neutropenic complications were collected. Results: Two-hundred sixty eight patients received a total of 1019 cycles of ddT. Only one physician in the practice routinely prescribed G-CSF after ddT. The majority of ddT cycles were administered without G-CSF support (781 vs 238 cycles). There were no episodes of neutropenic fever in either group. The rate of grade 3/4 neutropenia was 2.1 % with G-CSF support (all grade 3), and 2.7% without G-CSF support (85% grade 3), p = 0.61. Treatment delays were longer in patients who did not receive G-CSF support, but this difference was not statistically significant (mean of 4 vs 2.2 days, p = 0.07). The number of cycles needed to treat to prevent 1 episode of grade 3/4 neutropenia was 167. Based on Medicare average sales price (ASP) for pegfilgrastim, routine use of G-CSF in our patient population would have added over $3.6M to the cost of care over the study period. Conclusions: Our results show a similarly low rate of neutropenic complications in patients receiving dose dense paclitaxel with or without G-CSF support. Therefore routine use of G-CSF with this regimen is not warranted. Judicious use of expensive medications such as G-CSF would reduce the cost of care and financial toxicity to patients, and promote high value care.
Nab-paclitaxel plus S-1 as first line treatment for advanced or metastatic biliary tract adenocarcinoma: A phase 2 study.
Authors: Yongkun Sun, Ai-Ping Zhou, Wen Zhang, Lin Yang, Chengxu Cui, Zhichao Jiang
Journal: Journal of Clinical Oncology (2019)

4089 Background: Gemcitabine plus cisplatin or S-1 can be used as first-line treatment for advanced or metastatic biliary tract adenocarcinoma. Multiple phase 2 studies found that gemcitabine, oxaliplatin, capecitabine, S-1 were not superior to gemcitabine plus cisplatin. Nab-paclitaxel plus S-1 was effective and well-tolerated in pancreatic cancer. Methods: Patients with pathological confirmed advanced or metastatic biliary tract adenocarcinoma (gallbladder carcinoma, intrahepatic cholangiocarcinoma ICC, extrahepatic cholangiocarcinoma ECC) were treated with Nab-paclitaxel plus S-1(Nab-paclitaxel 120mg/m 2 , d1 and d8; S-1 80-120mg/d, d1-14; q21d). Patients that received PR or SD (RECIST1.1)after 6 cycles were given S-1 maintenance treatment. The primary endpoint was ORR. The study used Simon’s Two Stage design. Results: From March 2016 to September 2018, we recruited 54 patients, with 27 males (50%). The median age was 58(34-73yrs). As of Dec 31 2018, the median treatment cycle was 4(1-6 cycles). 51 patients were evaluable for efficacy: PR 14(27.5%), SD 22 (DCR=PR+SD: 70.6%), PD 15 (29.4%). The median PFS was 6 months, and the median OS was 13.2 months. The response rate varied in different tumor location: gallbladder carcinoma 53.8% (7/13), ICC 18.2% (6/33), ECC 20% (1/5).Common grade 3/4 AEs were: leucopenia 17 (31.5%), hyperbilirubinemia 5(9.3%), Mucositis 4 (7.4%), neurotoxicity 2 (3.7%), diarrhea 2 (3.7%), omit 1(1.9%), fatigue 1 (1.9%), thrombocytopenia 1 (1.9%), ALT increase 1 (1.9%). Conclusions: Nab-paclitaxel plus S-1 as first line treatment for advanced or metastatic biliary tract adenocarcinoma was effective and well-tolerated, especially for gallbladder carcinoma (ORR 53.8%). This regimen need further exploration. Clinical trial information: NCT03830606.
Adoption of immuno-oncology in NSCLC, a real-world study in EU5.
Authors: Alejandra Martinez De Pinillos, Isabel Ricote Lobera, Cristina Martinez, Caroline Anger, Filippo Guglielmetti, Roberto Jorge Bitton
Journal: Journal of Clinical Oncology (2019)

e20631 Background: To date, there are no robust studies in real world practice describing the use of IO (immuno-oncology) treatments in advanced/metastatic (adv/m) NSCLC. The available evidence in Europe is limited to observational studies of small size. This study aims to understand the impact of IO in adv/mNSCLC and study the profile of patients currently receiving these treatments. Methods: 20,157 cases of 1 st and 2 nd line adv/mNSCLC patients between October 2016 and September 2018 in EU5 (France, Germany, Spain, Italy, UK) were identified within Oncology Dynamics, an IQVIA oncology syndicated cross sectional survey collecting anonymized patient-level data. Patient profile was described, and two groups were created to assess differences in the use of IO treatments (nivolumab, pembrolizumab, atezolizumab, ipilimumab, durvalumab) across 2 time periods: #1 October 2016 - September 2017 (n = 9,310); #2 October 2017 - September 2018 (n = 10,847). Results: IO treatments increased 15% in 1 st line adv/mNSCLC (13% in non-squamous and 23% in squamous histology) and 11% in 2 nd line across periods; reaching treatment shares of 20.3% and 67.9% in 1 st line and 2 nd line in Period 2. Within IO-treated patients, 9.5% in 1 st line and 13.6% in 2 nd line had ECOG ≥2, and 27% were &gt; 71 years old. The use of IO in 1 st line patients without mutations (EGFR/ALK/ROS1/BRAF) increased by 24%, while standard chemotherapy decreased by 21%. Conclusions: IO treatments had a rapid adoption in Europe last year, influenced by its approval in 1 st line adv/mNSCLC and by clinical guidelines recommendations. Ongoing clinical trials may suggest a growing trend in the future that could potentially impact in healthcare systems. In addition, real world patients treated with IO are older and have a worse performance status than those widely included in clinical trials. An evaluation of these results sheds light into IO treatments in NSCLC and may contribute to the design of real-world studies to generate new evidence and optimize the use of these class of drugs in clinical practice.[Table: see text]