tbuckley/cabot-search huggingface dataset:
The influence of chemotherapy induced nausea and vomiting (CINV) on survival: An individual participant data meta-analysis of the North-Eastern German Society of Gynecological Oncology (NOGGO) of 1213 recurrent ovarian cancer patients.
Authors: Hannah Woopen, Rolf Richter, Guelhan Inci, Radoslav Chekerov, Gulten Oskay-Oezcelik, Jalid Sehouli
Journal: Journal of Clinical Oncology (2017)

e17062 Background: Nausea and vomiting are frequent side effects of chemotherapy and are the most feared toxicities of our patients. Aim of this study is to evaluate the potential influence of chemotherapy induced nausea and vomiting (CINV) on survival. Methods: Synthesized raw data of three phase II/III studies (“Tower”, “Topotecan phase III” and “Hector”) of the North-Eastern German Society of Gynecological Oncology (NOGGO) including 1213 patients were analyzed using logistic regression and cox regression analyses. Results: In this analysis 661 patients (54.5%) developed grade I/II and 44 patients (3.6%) grade III/IV nausea. 343 patients (28.3%) had grade I/II vomiting and 33 patients (2.7%) grade III/IV. There were no differences between severity of CINV regarding FIGO, grading, histology and amount of recurrences. Patients &lt;65 years developed more frequently grade III/IV nausea than patients ≥ 65 years (p&lt;0.001, OR 1.29, 95% CI 0.68-2.46). Polypharmacy was also associated with grade III/IV CINV (p&lt;0.001 and p=0.002 respectively). Progression free survival was worse in patients with grade III/IV nausea (p=0.023, HR 1.58, 95% CI 1.14-2.20). Median overall survival (OAS) in patients without nausea was 19.0 months compared to patients with grade III/IV nausea with 11.0 months (p&lt;0.001, HR for grade III/IV 2.35, 95% CI 1.64-3.37). Grade III/IV vomiting was also highly associated with worse OAS (median of 22.0 months in patients without vs. 5.9 months in patients with grade III/IV vomiting, p&lt;0.001, HR for grade III/IV vomiting 3.4, 95% CI 2.32-5.00). However, dose reductions and prior discontinuation of chemotherapy were not more frequent in patients with nausea and vomiting. Conclusions: Patients with nausea and vomiting had a decreased progression and overall survival. This study underlines once again the importance of early best supportive care on survival.
Aqueous humor genomics predicts eye salvage in retinoblastoma.
Authors: Liya Xu, Jesse Berry, James Hicks, Peter Kuhn, Rishvanth Prabakar
Journal: Journal of Clinical Oncology (2018)

10519 Background: Retinoblastoma was one of the first cancers to demonstrate a genetic basis to the development of cancer. However, unlike many cancers, Rb cannot be directly biopsied due to the high risk of extraocular cancer spread. Therefore, unless the eye is enucleated, tumor tissue is not evaluated for genetic and genomic changes and these alterations are not used to inform diagnosis or prognosis for this disease. However, in a recent publication in JAMA Ophthalmology,(Berry JL, Xu L et al. JAMA Ophthalmol, 2017) we demonstrated that tumor-derived cell-free DNA can be extracted from the aqueous humor (AH) of Rb eyes, which is safe to extract even with active intraocular disease. The purpose this current study was to identify somatic chromosomal copy number alterations (sCNA) in tumor-derived cell-free DNA in the AH of Rb eyes and to correlate with clinical outcomes particularly tumor relapse requiring enucleation. Methods: AH was extracted via paracentesis from Rb eyes during intravitreal injection of chemotherapy or enucleation. Shallow whole genome sequencing was performed to assess for cell-free tumor DNA fractions and highly-recurrent sCNAs in Rb which include gain of 1q, 2p, 6p and loss of 13q and 16q. Globe salvage was recorded. Results: 26 patients were included; 3 patients had both eyes included for 29 eyes. From these, 63 samples of AH were analyzed; 5 post-enucleations and 58 during intravitreal chemotherapy injection. Ultimately 13 eyes required enucleation and 16 eyes were salvaged. Follow-up ranged from 8-43 months (median 17 months). 6p gain was the most common sCNA found in 10/13 enucleated eyes (77%) compared to 4/16 (25%) of salvaged eyes (p = 0.009). The mean amplitude of 6p gain was 1.47 in the enucleated group versus 1.07 in the salvaged group (p = 0.001). The presence of a detectable sCNA in enucleated eyes was 92% while in salvaged eyes was 38% (p = 0.022). The probability of globe salvage was improved in eyes without detectable sCNAs (p = 0.0028). Conclusions: This is the first study to correlate globe salvage with highly-recurrent sCNAs in the AH from Rb eyes. This study suggests that not only can the AH serve as a surrogate to tumor biopsy but could contribute to prognostication of tumor response to therapy.
Dietary Protein Restriction Reprograms Tumor-Associated Macrophages and Enhances Immunotherapy
Authors: Ashley Orillion, Nur P. Damayanti, Li Shen, Remi Adelaiye-Ogala, Hayley Affronti, May Elbanna, Sreenivasulu Chintala, Michael Ciesielski, Luigi Fontana, Chinghai Kao, Bennett D. Elzey, Timothy L. Ratliff, David E. Nelson, Dominic Smiraglia, Scott I. Abrams, Roberto Pili
Journal: Clinical Cancer Research (2018)

Diet and healthy weight are established means of reducing cancer incidence and mortality. However, the impact of diet modifications on the tumor microenvironment and antitumor immunity is not well defined. Immunosuppressive tumor-associated macrophages (TAMs) are associated with poor clinical outcomes and are potentially modifiable through dietary interventions. We tested the hypothesis that dietary protein restriction modifies macrophage function toward antitumor phenotypes.Macrophage functional status under different tissue culture conditions and in vivo was assessed by Western blot, immunofluorescence, qRT-PCR, and cytokine array analyses. Tumor growth in the context of protein or amino acid (AA) restriction and immunotherapy, namely, a survivin peptide-based vaccine or a PD-1 inhibitor, was examined in animal models of prostate (RP-B6Myc) and renal (RENCA) cell carcinoma. All tests were two-sided.Protein or AA-restricted macrophages exhibited enhanced tumoricidal, proinflammatory phenotypes, and in two syngeneic tumor models, protein or AA-restricted diets elicited reduced TAM infiltration, tumor growth, and increased response to immunotherapies. Further, we identified a distinct molecular mechanism by which AA-restriction reprograms macrophage function via a ROS/mTOR-centric cascade.Dietary protein restriction alters TAM activity and enhances the tumoricidal capacity of this critical innate immune cell type, providing the rationale for clinical testing of this supportive tool in patients receiving cancer immunotherapies.
A phase I/II clinical trial of autologous CMV-specific cytotoxic T cells (CMV-TC) for glioblastoma: Dose escalation results.
Authors: Marta Penas-Prado, Katayoun Rezvani, Shiao-Pei S. Weathers, Shouhao Zhou, Carlos Kamiya-Matsuoka, Barbara Jane O'Brien, Monica Elena Loghin, Rebecca Anne Harrison, Be Lian Pei, Sandra Ictech, Kathy Hunter, W. K. Alfred Yung, John Frederick De Groot, Elizabeth J. Shpall, Amy B. Heimberger
Journal: Journal of Clinical Oncology (2018)

2035 Background: Cytomegalovirus (CMV) antigens are present in > 90% of GBMs but not in normal brain, and can be targeted as a tumor-specific antigen. CMV-TC present in GBM tumor tissue have their effector function suppressed. Highly functional CMV pp65 specific T cells can be expanded in vitro from peripheral blood (PB) of GBM patients. We have established GMP-compliant conditions for ex vivo expansion of polyclonal CD8+ and CD4+ CMV-TC from GBM patients. Methods: We explored 4 dose levels of autologous CMV-TC (from 5 x 106 cells to 1 x 108 cells) with a 3+3 design. CMV-TC were given after 3 weeks of lymphodepleting dose-dense temozolomide (ddTMZ, 100 mg/m2 for 3 weeks). Treatment was repeated q 6 weeks for a total of 4 cycles. Patients ≥18 years of age with KPS ≥60, CMV seropositivity, receiving ≤ 2 mg of dexamethasone daily, and any number of relapses were eligible. Imaging response was evaluated by MRI q 6 weeks. In vivo persistence and expansion of adoptively-infused CMV-TC was determined by dextramer staining and multiparameter flow cytometry in serially-sampled PB. Results: 27 patients were screened, of whom 15 underwent leukapheresis. Twelve patients (3 at each level) completed cycle 1. Median age 51 (27-65), median KPS 90; 9 were at 1st and 3 at 2nd relapse. MGMT was methylated in 5, unmethylated in 3, indeterminate or unknown in 4. IDH status was wildtype in 7, mutated in 3, unknown in 2. Number of cycles received was 4 in 4 patients, 2 in 3, and 1 in 5. No dose limiting toxicities (DLTs) were observed at any level. Complete radiographic response was observed in 1 patient, partial response in 1 patient, stable disease in 5 patients, and progressive disease in 5. Repeated infusions of CMV-TC were associated with a significant increase in circulating CMV+ CD8+ T-cells. Conclusions: Adoptive infusion of CMV-TC after lymphodepleting therapy with ddTMZ was well tolerated with no DLTs or serious CMV-TC related adverse events. The final dose level is currently being enrolled. Thereafter efficacy will be evaluated in expansion cohorts in newly diagnosed and recurrent GBM. The expansion in recurrent GBM will include correlative studies in tumor tissue after administration of CMV-TC. Clinical trial information: NCT02661282.
Abstract 17100: Cardiotonic Steroids Promote Renal Fibrosis and Dysfunction via NaK-ATPase Profibrotic Signaling in Heart Failure
Authors: Xiaoming Fan, Fatimah K Khalaf, Yiliang Chen, Anuradha Guggilam, Andrew Kleinhenz, Jerry B Lingrel, Jiang Tian, W. H. Wilson Tang, David J Kennedy
Journal: Circulation (2016)

Introduction: Patients with heart failure such as those following myocardial infarction often experience progressive cardio-renal compromise (or “cardio-renal syndrome”), leading to recurrent hospi...
Lowering the <i>P</i> Value Threshold
Authors: Paul Barach, Ronald L. Thomas, Steven E. Lipshultz
Journal: JAMA (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Optimization of PD-L1 algorithm for predicting overall survival (OS) in patients with urothelial cancer (UC) treated with durvalumab monotherapy.
Authors: Magda Zajac, Jiabu Ye, Pralay Mukhopadhyay, Xiaoping Jin, Yong Ben, Joyce Antal, Ashok Kumar Gupta, Marlon Rebelatto, J. Andrew Williams, Jill Walker
Journal: Journal of Clinical Oncology (2018)

4530 Background: PD-L1 expression is a useful biomarker in predicting response to PD-1 and PD-L1 directed immunotherapies in a variety of tumor types. In UC, studies have implicated PD-L1 expression in tumor cells (TC) and tumor-infiltrating immune cells (IC) as having clinical utility, but the relative importance of each cellular compartment and the most predictive algorithm and PD-L1 expression cutoff remain unclear. Methods: PD-L1 expression data (SP263 assay) from 188 patients in the UC cohort from single arm (durvalumab monotherapy) Phase 1/2 Study CD-ON-MEDI4736-1108 (NCT01693562; Oct. 2017 data cutoff) were assessed. Regression models were used to evaluate the impact of PD-L1 expression in TC or IC on OS, progression-free survival (PFS), objective response rate (ORR), best percentage tumor change and tumor shrinkage 15 months after last subject randomization. Kaplan–Meier plots were generated to explore the impact of single biomarker and combined (TC or IC [% PD-L1 positive ICs within IC area]) algorithms on OS. Results: Both IC and TC PD-L1 were linked to higher ORR, and IC PD-L1 was associated with better survival in patients treated with durvalumab. IC PD-L1 had a higher impact on response to durvalumab than TC PD-L1, showing significant (P < 0.05) association with OS, PFS, ORR, and tumor shrinkage. The best outcomes were obtained when TC and IC algorithms were combined, with TC25%/IC25% proving optimal (Table). Conclusions: In UC, the TC25%/IC25% algorithm appears to provide optimal predictive value based on efficacy and prevalence of the biomarker. Additional data from randomized trials are needed to confirm these findings. Clinical trial information: NCT01693562.Cutoff/algorithm ORR, % Median OS, months Prevalence of PD-L1 high pts, % PD-L1 high PD-L1 low PD-L1 high PD-L1 low TC1% 21.6 11.1 8.4 10.9 61.7 TC10% 19.5 16.2 6.9 10.9 41.0 TC25% 23.4 15.6 9.3 10.5 25.0 TC50% 19.4 17.1 9.3 10.5 19.1 IC1% 22.4 5.6 11.6 6.4 71.3 IC10% 22.8 6.6 11.6 6.6 67.6 IC25% 28.4 10.5 22.3 5.5 39.4 IC50% 31.1 13.3 22.3 6.6 23.9 TC1%/IC1% 20.9 0.0 10.8 6.4 84.0 TC10%/IC25% 23.3 7.4 12.5 7.8 63.8 TC25%/IC25% 27.5 5.8 19.8 4.8 54.3 TC50%/IC25% 27.1 7.6 20.0 4.8 51.1 N = 188IC: % PD-L1 positive ICs within IC area
PRECISE: A clinical-grade automated molecular eligibility screening and just-in-time (JIT) physician decision support solution for molecularly-selected oncology trials.
Authors: Jessica Tao, Michael H. Eubank, Erika Pamer, Nicholas Anthony Cangemi, Alexander E. Drilon, James J. Harding, Alison M. Schram, Lillian Mary Smyth, Komal L. Jhaveri, Bob T. Li, Debyani Chakravarty, Ahmet Zehir, Michael F. Berger, Nikolaus Schultz, Alisa Pinkhasik, Stacy B. Thomas, Peter D. Stetson, Stuart M. Gardos, David Michael Hyman
Journal: Journal of Clinical Oncology (2018)

6507 Background: Clinical informatic systems that aid in identifying and matching actionable molecular alterations to the appropriate targeted therapies are critical for ensuring both the delivery of optimal routine care and the successful implementation of precision oncology research programs. We developed DARWIN PRECISE (PRECision Insight Support Engine), a clinical-grade informatics solution that identifies and dynamically tracks patients based on molecular and clinical data. PRECISE also provides JIT notifications to study teams and treating oncologists, facilitating patients’ seamless matching and enrollment to molecularly-selected trials. Methods: Under an IRB-approved study, we prospectively followed all patients identified by PRECISE and subsequently enrolled to molecularly-selected clinical trials at MSKCC between 16-April-2014 and 31-January-2017. Demographic, clinical, and molecular data were abstracted from the institutional data warehouse. Characteristics of therapeutic accruals facilitated by PRECISE were measured using descriptive statistics. Results: Patients treated by 150 unique oncologists and all accruals to 42 therapeutic trials that used PRECISE were included in the analysis. During the study period, a total of 742 patient-accruals occurred across the 42 trials. Of these, PRECISE prospectively identified 327 (44%) of accrued patients. Patients identified and subsequently enrolled by PRECISE harbored a wide variety (n = 32) of molecular alterations; with SNVs, CNAs, or fusions in ERBB2 (23.5%), PIK3CA (18.2%), BRAF (9.3%), and FGFR1/2/3 (6%) occurring most frequently. The median time from initial identification by PRECISE to trial consent was 82 days (IQR: 35-166), and the median time from tumor sequencing to consent was 161 days (IQR: 64-350). Conclusions: PRECISE facilitated the identification and enrollment of 44% (n = 327) of all patients accrued to molecularly-matched studies using this informatic platform. Automated JIT decision-support tools like PRECISE represent a novel and effective method for enhancing patient accrual to molecularly-selected therapies.
TCT-507 Increase of coronary lumen area with improved stent apposition after self-expandable stenting in total occlusions: results of the SPACIOUS pilot study
Authors: Selina Vlieger, Cihan Simsek, Esther de Jong-Salentijn, Auke Weevers, David Bouchez, Alexander Ijsselmuiden
Journal: Journal of the American College of Cardiology (2018)
Tumor mutational burden, clinical features, and outcomes to PD-1 mono- and combination therapy in patients with cutaneous and unknown primary melanoma.
Authors: Alexander Noor Shoushtari, Joshua Armenia, Arshi Arora, Jorge Rojas-Zamalloa, Allison Betof Warner, Megan Derr, Michael A. Postow, Margaret K. Callahan, Parisa Momtaz, Daniel G. Coit, Mary Susan Brady, Charlotte Eielson Ariyan, Suresh Nair, Klaus J. Busam, Paul B. Chapman, Nikolaus Schultz, Jedd D. Wolchok
Journal: Journal of Clinical Oncology (2018)

9561 Background: Tumor mutational burden (TMB) in cutaneous and unknown primary (CUP) melanomas is associated with benefit to PD-1 monotherapy (mono), but the impact of TMB on nivolumab plus ipilimumab (combo) is not well established. Few TMB analyses have included standard clinical features in a multivariate analysis (MVA). Methods: All patients (pts) with CUP melanoma who underwent 340+ gene sequencing at Memorial Sloan Kettering Cancer Center and received PD-1 mono or combo as initial checkpoint inhibitor were analyzed. Somatic TMB/megabase (Mb), AJCC 8 stage, ECOG performance status (PS), sites of metastases (mets), lactate dehydrogenase (LDH) elevation, and neutrophil:lymphocyte ratio (NLR) > 4.73 were included in a Cox proportional hazards model and MVA built using backward selection. Overall survival (OS) and time to treatment failure (TTF), the interval until next therapy, clinical progression, or death, were calculated from PD-1 start. Results: 154 pts received PD-1 mono; median follow up was 11 months. 125 pts received combo; median follow up was 19 months. Pts receiving combo vs PD-1 mono were younger (median age 62 vs 71, p < 0.001) and had higher rate of elevated LDH (34% vs 18%, p = 0.04) and stage M1c/d (66% vs 41%). TMB did not vary by combo vs PD-1 mono (median 15.1 vs 18.4 mut/Mb, p = 0.21). Stage was associated with TTF and OS for PD-1 mono and combo (all p < 0.03). On MVA for PD-1 mono, TMB (hazard ratio [HR] 0.98; p = 0.005) and NLR > 4.73 (HR 2.16; p = 0.002) were associated with TTF; PS (ECOG 2+ vs 0, HR 9.86, p < 0.001; 1 vs 0, HR 2.59, p = 0.03) and LDH (HR 3.16, p = 0.005) were associated with poorer OS. TMB was not associated with TTF or OS for combo. On MVA for combo, brain (HR 2.64, p = 0.004) and bone mets (HR 2.28, p = 0.008) were associated with TTF; PS (ECOG 2+ vs 0, HR 5.37, p = 0.009), NLR > 4.73 (HR 2.27, p = 0.037), and bone mets (HR 2.86; p = 0.014) were associated with OS. Conclusions: For patients with cutaneous and unknown primary melanomas, TMB is associated with improved TTF in PD-1 mono but not combo. Performance status, NLR, and bone mets, but not TMB, are associated with OS in PD-1 combo. Models assessing clinical utility of TMB should also include established prognostic features.
A prospective observational multicentric pan India study of lenvatinib in radio-iodine refractory advanced differentiated thyroid cancer.
Authors: S.P. Somashekhar, Amit Rauthan, Amit Agarwal, Keechilat Pavithran, Papaiah Susheela Sridhar, Boman Nariman Dhabhar, Hari Goyal, Ashish Singh, Sameer Kaul, Satheesh Chiradoni Thungappa, Chandragouda Dodagoudar, Rohit C Kumar
Journal: Journal of Clinical Oncology (2018)

e18106 Background: Management of advanced differentiated thyroid cancer refractory to radio-iodine (RAI) has taken a new turn with the results of SELECT trial. Physicians are learning to use lenvatinib with experience and data from all over the world. However data from Asian subcontinent is very limited. We report here experience of using lenvatinib in Indian patients. Methods: This was a prospective observational multi-centric study involving institutions distributed all over India . Patients who were diagnosed of differentiated thyroid cancer with disease refractory to radio-iodine treatment & also patients who had already received first line tyrosine kinase inhibitors were enrolled in the study. The toxicity profile, response rates were recorded by the treating physician. Results: Out of 450 patients, 300 were males and 150 females. Mean age group was between 50-70 years.270 (60%) patients had received prior TKI for mean duration of 7 months. Distant metastasis were documented in lung, lymph nodes, bone, liver and brain (95%, 80%, 55%, 15% and 10% respectively). 422 (93.3%) were started at 20mg and 28 (6.66%) at 14mg dose, dose modification was done in 245 (53.3%) of the patients. Final dose taken was 20mg in 184 patients, 14mg in 174 patients and 10 mg in 92 patients. Median duration of treatment was 11.73 months, with a median follow up of 8 months. Best response noted was partial response in 248 (55%), stable disease in 154 (34%). Disease progression was noted in 49 (11%) of patients.G3, G2, G1 morbidity were noted in 154(34.2%), 238(53.3%) and 58(13.3%) respectively. Most common adverse events were mucositis (93.3%), hypertension (86.6%), diarrhoea (80%), fatigue (45.5%) and rashes (33.3%). Conclusions: Our results show that lenvatinib has reasonable clinical activity in Indian patients with RAI-refractory thyroid cancer with nearly half of patients showing clinical benefit. The toxicity profile of lenvatinib in our patients is same as that of rest of the world and is manageable with gain of experience.
Colorectal cancer with mucinous component compared to clinicopathological and molecular features as mucinous adenocarcinoma.
Authors: Liu Yang, Yue Cai, Jianwei Zhang, Huabin Hu, Wang Wenjing, Zehua Wu, Ru Deng, Yanhong Deng
Journal: Journal of Clinical Oncology (2017)

e15166 Background: CRC can be divided into 3 groups: regular adenocarcinoma (RA), mucinous adenocarcinoma (MA), and adenocarcinoma with mucinous component (MC, mucin formation &lt;50 % ). MA is distinct from RA, however, little is known about MC. We aimed to compare the clinicopathological and genetic features of 3 groups. Methods: A retrospective chort of consecutive CRC patients with available gene status was enrolled. KRAS,NRAS,BRAF,PIK3CA gene, MSI(IHC method) status were analyzed. Results: A total of 1454 patients were enrolled, including 1179 RA, 106 MA and 169 MC. Similar to MA, MC patients were younger, tended in proximal colon, had more advanced T stage ,higher nodal and peritoneal metastasis compared to RA. MSI-H were more occurred in MA and MC than RA (18.9%, 15.1% vs.3.9%). MC and MA had identical mutation frequency.They had higher KRAS (62.1%,62.3% vs.41.4%), BRAF(10.1%,9.4% vs.1.9%) and PIK3CA(21.3%,21.7% vs.9.4%) mutation than RA. Among MA or MC patients, almost 80% had at least one mutation, 17% had double mutation,and the mutation rates between left and right colon was similar, which is distinguish from RA. Conclusions: MC has comparable patholgical and molecular features as MA, which is distinct from RA. We should consider mucinous histology and the genetic features into future clinical practice. [Table: see text]