tbuckley/cabot-search huggingface dataset:
Immune-related adverse events in melanoma: A nationwide analysis 2016.
Authors: Manoj P. Rai, Prabhjot Singh Bedi, Rohanlal Vishwanth, Fawzi Abu Rous, Shiva Shrotriya, Prajwal Dhakal
Journal: Journal of Clinical Oncology (2019)

e18253 Background: Melanoma is an aggressive skin cancer. Immunotherapy is currently used as a first-line treatment for unresectable metastatic disease. Combination immunotherapy has been shown to improve overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) compared to single-agent immunotherapy. However, immunotherapy related adverse events (irAE's) are being increasingly seen. This study analyses the incidence of irAE's and the variation in the length of stay, and mortality. Methods: This is a retrospective cohort analysis of the 2016 NIS database. We identified hospitalizations with either primary or secondary diagnosis of Melanoma. Logistic regression of irAE's such as pneumonitis, colitis, hypophysitis, adrenal insufficiency, encephalitis, myocarditis was performed. We evaluated the association between irAE's and various parameters. Results: We identified 13170 hospitalizations with primary or secondary diagnosis of melanoma. Univariate logistic regression showed pneumonitis (OR: 1.39; p value: &lt; 0.01), hypophysitis (OR: 20.61; p value &lt; 001), adrenal insufficiency (OR: 10.36, p value = &lt; 0.01), colitis (OR 23.94, p value &lt; 001), myocarditis (OR: 1; p value was n/a), encephalitis (OR 1.71; p value was 0.5). Univariate logistic regression for LOS showed colitis (OR 1.23; p value: 0.01), adrenal insufficiency (OR 0.20; p value: 0.748), hypophysitis (OR -2.50; p value: 0), myocarditis no admissions, encephalitis (OR -2.15; p value 0.01). Univariate logistic regression for mortality showed pneumonitis (OR 6.07; p value: &lt; 0.01), colitis (OR 0.86 p value: 0.721), adrenal insufficiency (OR 1; p value: 0.996). Conclusions: The above results suggest that the incidence of colitis is the highest among irAE’s in melanoma patients likely due to immunotherapy. Hypophysitis is the next most common side effect, it’s followed by adrenal insufficiency which can be life-threatening. A high index of suspicion and anticipation of the above complications can lead to their timely detection and treatment.
Abstract 2364: Bivalirudin With And Without Eptifibatide For Elective Stenting: A Pharmacodynamic Study Of Platelet Reactivity And Its Relation To Periprocedural Myocardial Infarction.
Authors: Paul Gurbel, Kevin P Bliden, Joseph Dichiara, Aswani Bassi, William Herzog, Tania Gesheff, Udaya S Tantry
Journal: Circulation (2007)

Background: It has been demonstrated that heparin and eptifibatide produced superior platelet inhibition and less myocardial necrosis than heparin alone in patients treated with clopidogrel (CLP) a...
Genomic analysis of paired <i>IDHwt</i> glioblastoma (GB) to reveal recurrent alterations of <i>MPDZ</i> at relapse after radiotherapy and temozolomide (RTCT).
Authors: Brice Chanez, Romain Appay, Arnaud Guille, Arnaud Lagarde, José Adelaide, Emilie Denicolai, Chantal Campello, Aurelie Tchoghandjian, Gregorio Petrirena, Carole Colin, Maryline Barrie, Nathalie Baeza-Kallee, Celine Boucard, Carine Jiguet-Jiglaire, Thomas Graillon, Isabelle Nanni-Metellus, Henry Dufour, Dominique Figarella-Branger, Olivier L. Chinot, Emeline Tabouret
Journal: Journal of Clinical Oncology (2019)

e13535 Background: GB are highly aggressive tumors which systematically relapse. Our objective was to identify disease progression mechanisms and genomic drivers of GB treatment resistance. Methods: Ten paired frozen tumors from initial and recurrent surgery after RTCT were screened by CGH Array. Next, NGS of the selected genes was performed on 19 paired tumors (38 samples). Molecular alterations were correlated with patient data. TCGA was used to characterize the molecular profile of MPDZ. Results: Nineteen IDHwt GB patients with a median age of 54.5 years (37.2-72.8) were included. Using CGH array, unsupervised analysis clustered the whole samples by paired of initial and recurrent tumors. However only 44% of CGH Array alterations were shared between initial and recurrent tumors (amplifications: 55%; deletions: 30%). The new alterations detected at relapse were amplifications in 25% and deletions in 23% of tumors. Two regions corresponding to 171 genes were lost at relapse (p = 0.03): 19q13.33 and 19q13.41. Using DAVID genome, 3/171 genes (related to neutrophil chemotactic factors) were identified: FPR1, FPR2, FPR3. Moreover, 24 genes were lost (including MPDZ) and 2 genes were gained in 20% of recurrent tumors. Totally, 29 genes were analyzed by NGS and 4 genes showed pathogenic mutations shared by initial and recurrent tumors: FPR2, REL, TYRP1 and MPDZ. Only MPDZ showed, at relapse, an increasing rate of mutated variants and a new mutation affecting the splicing site. These alterations were independent from classical prognostic factors (age, sexe, karnofsky performans status, MMS and MGMT status) and from patient survivals. To explore MPDZ expression, we used TCGA initial dataset and observed that a lower RNA expression of MPDZ was associated with IDHwt ( p&lt; 0.001) and grade IV ( p&lt; 0.001) gliomas, reinforcing the potential pejorative impact of MPDZ loss. Conclusions: Our results suggest that MPDZ is frequently altered at initial diagnosis with increased alterations in recurrent IDHwt GB after RTCT, suggesting that MPDZ impairment could contribute to the resistance/relapse mechanisms. Further investigations are needed to validate these results.
Colorectal cancer in young patients: An institutional experience.
Authors: Wissam Hanayneh, Yu Wang, Thomas J. George, Miles Cameron, Sanda Tan, Atif Iqbal, Thomas Read, Carmen Joseph Allegra, Hiral D. Parekh
Journal: Journal of Clinical Oncology (2019)

e15140 Background: The incidence of colorectal cancer (CRC) in young patients (&lt;50 years) is increasing but little is known about disease characteristics and treatment outcomes in this patient population. Methods: CRC patients diagnosed at &lt; 50 years of age (UF registry 2000-2017) constituted the IRB approved study cohort. Statistical methods included descriptive statistics, uni-variable cox proportional hazard regression model, Pearson chi-square exact and Wilcoxon rank-sum test. Results: Young CRC patients (n= 286) comprised 16% of total CRC patients (n= 1806) treated at our institution. (See Table for demographics and tumor characteristics). The median age at diagnosis was 45 years (range 17-50) with 74% diagnosed between age 40-50. One third (35.7%) of patients had rectal primary. DNA mismatch repair gene deficiencies (dMMR) and/or microsatellite instability (MSI) was tested in 60.1%; 10.5% had MSI-H or dMMR tumors and 11 of those had confirmed Lynch syndrome. Next generation sequencing (n= 71) or mutational analysis (n= 79) was performed. Most common mutation was exon 12 of K- ras (40.7%, n = 61) followed by TP53 (7.33%; n = 11) and PIK3CA (5.33%; n = 8). BRAF V600E was seen in 5 patients. Patients who underwent curative resections had better hemoglobin (p=0.005), albumin levels (p &lt;0.001) and lower CEA level (p&lt;0.001). Factors associated with poor survival were low albumin ≤34 g/l, advanced primary tumor (T3/T4), nodal disease (N1/N2) and presence of diffuse metastases. For stage 4 disease, the cancer-specific survival (CSS) at 1 year was 77.2%, 3-year CSS was 46.1% and 5-year CSS was 29%; survival was better (HR=0.4; 95% CI 0.2-0.6, p&lt;0.001) among patients who underwent metastatectomy. Conclusions: Our results reveal that the most young CRC were 40-50 years age group with a female preponderance. Young CRC patients were more likely to be managed in an aggressive manner with a higher proportion of early stage patients receiving perioperative therapy. A suggestion of an improved CSS was seen in advanced stage disease even with similar prognostic factors. Review of larger data sets are warranted. [Table: see text]
A randomized trial of a mercaptopurine (6MP) adherence-enhancing intervention in children with acute lymphoblastic leukemia (ALL): A COG ACCL1033 study.
Authors: Smita Bhatia, Lindsey Hageman, Yanjun Chen, Florence Lennie Wong, Leo Mascarenhas, David Robert Freyer, Nkechi Mba, Paula Aristizabal, David Walterhouse, Glen Lew, Pamela Kempert, Thomas Russell, Rene McNall-Knapp, Shana S. Jacobs, Ha Dang, Elizabeth A. Raetz, Mary V. Relling, Wendy Landier
Journal: Journal of Clinical Oncology (2019)

10007 Background: We previously reported that &gt; 40% of children with ALL are non-adherent to 6MP, and &gt; 52% of ALL relapses are attributable to 6MP non-adherence. The most common barrier is forgetting to take 6MP; the most common facilitator is parental vigilance. These observations informed a randomized trial to enhance 6MP adherence (COG-ACCL1033, #NCT01503632; 89 COG sites). Results are described here. Methods: The Intervention Package (IP) consisted of: i) Education; ii) 6MP schedules; iii) daily personalized text message reminders from physician to patient and caregiver, to prompt iv) directly supervised therapy (DST), with text back response by patient/caregiver. Baseline adherence was measured for 4 wks, followed by intervention for 16 wks to examine the impact of IP vs. Edu (education) on 6MP adherence (measured electronically by MEMs Cap) in all patients, ≥12yo, &lt; 12yo. Longitudinal binomial logistic regression using generalized estimating equations was used. Missing data were handled by multiple imputation. Results: 444 patients were randomly assigned to IP (n = 230) or Edu (n = 214). Baseline characteristics (age at study: 8.6y vs 7.5y; males: 67% vs 69%; non-Hispanic whites: 40% vs 42%) and adherence rates (92% vs 94%) were comparable (except paternal education: 49% vs 38%, p = 0.04). No study arm*time interaction was found; thus, the 16-week overall mean fitted adherence rates were compared between IP and Edu, adjusting for baseline adherence, time on study, parental education. All patients: Adherence rates were marginally higher on IP (94% vs 92.5%, p = 0.09). On IP, for times with a record of text response, adherence rates were higher (94%) when compared with times with no response (89%), p = 0.002. &lt; 12yo: Adherence rates were comparable (IP: 94.4% vs Edu: 93.7%, p = 0.5). ≥12yo: Adherence rates were significantly higher on IP (93.1% vs 90.0%, p = 0.037). ≥12yo with baseline adherence &lt; 90%: IP had the highest impact for this subgroup (83.4% vs 74.6%, p = 0.008). Conclusions: A 16-week comprehensive intervention resulted in higher 6MP adherence rates in children with ALL who were 12y or older at study. IP was most impactful in adolescents with baseline non-adherence. Clinical trial information: #NCT01503632.
Impact of bridging chemotherapy on clinical outcome of CD19 CAR T therapy in adult ALL.
Authors: Karlo Perica, Jessica Flynn, Kevin Joseph Curran, Xiuyan Wang, Elizabeth Halton, Claudia Diamonte, John Pineda, Yvette Bernal, Mithat Gonen, Isabelle Riviere, Michel Sadelain, Renier J. Brentjens, Jae Hong Park
Journal: Journal of Clinical Oncology (2019)

2520 Background: Autologous chimeric antigen receptor (CAR) T cell therapy has shown to be effective in CD19+ relapsed or refractory (R/R) B-ALL but requires a 2-4 week period of cell processing and manufacture. During this “bridging period,” patients are vulnerable to disease progression and complications. We sought to characterize bridging strategies in our published study of CD19 CAR T cell therapy in adults with R/R ALL (Park et al., NEJM, 2018). Methods: We performed a retrospective review of adult patients with R/R ALL treated with 19-28z CAR T therapy at MSKCC. Bridging therapy was defined as any therapy given from trial enrollment to cell infusion and classified as either high intensity (remission-inducing or myelosuppressive regimens, eg hyper-CVAD or high-dose cytarabine based regimens) or low intensity (maintenance and/or less myelosuppressive regimens, eg POMP, Blinatumomab, TKI). Results: Of 53 patients who received CAR T cell infusion, 19 were bridged with a high intensity regimen and 34 with a low intensity regimen. There was no difference in number of prior therapies, pre-bridging chemotherapy disease burden, and prior transplant status between groups. High intensity therapy was associated with a higher rate of Gr3-4 infectious complications during the bridging period (78% vs 32%, p &lt; 0.002 by Fisher’s Exact) but not with response to bridging or CAR T cell therapy, relapse free survival, post-CAR Gr3-4 cytokine release syndrome (CRS) or neurotoxicity (NT). Patients in both groups who converted from morphologic to molecular disease during bridging (n=9) had a decreased rate of eventual severe CRS (0% vs 41%, p=0.01) or NT (0% vs 55%, p &lt;0.01) compared to patients with persistent morphologic disease. In all patients enrolled on trial (n=83), use of high compared to low intensity bridging was not associated with higher rates of successful CAR T cell infusion (63% vs 79%, p&gt;0.05) or a combined endpoint of CAR T cell infusion or alternative therapy including transplant (80% vs 86%, p&gt; 0.05). Conclusions: High intensity bridging therapy is associated with a high risk of infectious complications without a clear benefit in outcome in R/R ALL receiving CD19 CAR T cells. Selection of bridging regimen therefore requires consideration of previous treatments and patient status to maximize the efficacy and safety. Clinical trial information: NCT01044069.
Burden of copy number alterations predicts outcomes in immune checkpoint blockade treated gastrointestinal cancer patients.
Authors: Zhihao Lu, Huan Chen, Shuang Li, Xi Jiao, Lihong Wu, Henghui Zhang, Lin Shen
Journal: Journal of Clinical Oncology (2019)

e14068 Background: Despite the great achievements made in immune checkpoint blockade (ICB) in cancer therapy, how to identify patients who may benefit from ICB still remains one of the central questions, especially in gastrointestinal (GI) cancer. Methods: To address this, we analyzed FFPE tumor specimens from 73 patients with metastatic GI cancers who were treated with ICB. All patients were randomly assigned into discovery (60%) and validation (40%) cohorts. Overall, tumor mutation burden (TMB) and copy number alterations (CNAs) were determined by using the whole-exome sequencing platform. FFPE samples of 65 patients were analyzed via a multiplex RNA immune oncology sequencing panel. Results: Here we show that lower burden of copy number alteration (CNA) was observed in responders to immunotherapy in both discovery and validation cohorts. More importantly, lower burden of CNA in GI cancers were associated with improved objective response, clinical benefit and overall survival. Efficacy also correlated with the higher TMB. Of note, a combinatorial biomarker of TMB and burden of CNA may better stratify responders from patients received immunotherapy. In addition, patients with lower burden of CNA revealed increased IFNγ and expanded immune signatures in our GI patient cohort and TCGA cohorts as well. Conclusions: Our results suggest that burden of CNA may expand the predictive and prognostic value of genomic determinants in identifying potential responders with GI cancer to immune checkpoint blockade therapy.
Social media for oncology clinical trial recruitment: Oncologists’ attitudes and perceptions.
Authors: Mina S. Sedrak, Arti Hurria, Virginia Sun, Daneng Li, Jennifer Liu, Kevin George, Andrew R. Wong, Simran Padam, Vani Katheria, Supriya Gupta Mohile, James Ross Waisman, William Dale, Joanne E. Mortimer, Don S. Dizon
Journal: Journal of Clinical Oncology (2019)

e18066 Background: Social media may be an effective strategy to improve public awareness of oncology clinical trials and increase accrual. How oncologists perceive the role of social media in clinical trials now and in the future remains unknown. We explored oncologists’ attitudes and perceptions related to social media and clinical trial recruitment. Methods: Semi-structured interviews were conducted with 44 medical oncologists at City of Hope from March to June 2018. Primary measures were oncologists’ self-reported benefits, concerns, and future interventions to leverage social media for trial recruitment. Secondary measures were facilitators and barriers to social media use for professional purposes. Responses were recorded digitally, transcribed, and de-identified. Data was managed using NVivo v12. Two analysts coded interview data using thematic content analysis (kappa = 0.7). Results: Of the 44 participants, 55% were academic and 45% were community oncologists, 36% were women, and 68% had &gt; 10 years of experience. The most commonly cited benefit was increased awareness and visibility (63%). The most commonly cited concerns were: lack of time or support (31%), misinformation or oversimplification (31%), and lack of guidance (regulatory/ethical oversight) (28%). Oncologists reported a desire for an institutional-level intervention (e.g., personnel support with social media expertise) to facilitate trial recruitment using social media (50%). Oncologists’ perceptions of the facilitators to social media use for professional purposes were centered on networking (40%) and staying up to date in the field (33%). Perceived barriers were clustered around lack of comfort, training, time (38%), and lack of evidence of benefit (25%). No differences were identified between academic and community oncologists. Conclusions: Oncologists are hopeful that social media can increase awareness and visibility of cancer clinical trials. However, they have numerous concerns about the application of social media in clinical trials due to lack of time, support, and risk of misinformation. Further research is needed to examine whether social media can facilitate recruitment to oncology clinical trials.
NRG Oncology CC001: A phase III trial of hippocampal avoidance (HA) in addition to whole-brain radiotherapy (WBRT) plus memantine to preserve neurocognitive function (NCF) in patients with brain metastases (BM).
Authors: Vinai Gondi, Snehal Deshmukh, Paul D. Brown, Jeffrey Scott Wefel, Wolfgang Tome, Terri Armstrong, Deborah Bruner, Joseph A Bovi, Cliff Grant Robinson, Deepak Khuntia, David R Grosshans, Andre A. Konski, David Roberge, Vijayananda Kundapur, Kiran Devisetty, Sunjay A Shah, Kenneth Usuki, Bethany Marie Anderson, Minesh P. Mehta, Lisa A. Kachnic
Journal: Journal of Clinical Oncology (2019)

2009 Background: NRG CC001, a phase III trial of WBRT plus memantine (WBRT+M) with or without HA, sought to evaluate the neuro-protective effects of lowering the hippocampal radiation dose. Methods: Patients (pts) with BM were stratified by RPA class and prior radiosurgery/surgery and randomized to WBRT+M or HA-WBRT+M (30Gy/10 fractions). Standardized NCF tests were performed at baseline, 2, 4, 6, and 12 months (mos). The primary endpoint was NCF failure, defined as decline using the reliable change index on Hopkins Verbal Learning Test-Revised, Trail Making Test, or Controlled Oral Word Association. Cumulative incidence estimated NCF failure (death without NCF failure was competing risk); between-arms differences tested using Gray’s test. Deterioration at each collection time point was tested using a chi-square test. Patient-reported symptoms were assessed using the MD Anderson Symptom Inventory Brain Tumor module and analyzed using mixed effects models and t-tests. Results: From 7/2016 to 3/2018, 518 pts were randomized. Median follow-up was 7.9 mos. HA-WBRT+M was associated with lower NCF failure risk (adjusted hazard ratio (HR) = 0.74, p = 0.02) due to lower risk of deterioration in executive function at 4 mos (p = 0.01) and encoding (p = 0.049) and consolidation (p = 0.02) at 6 mos. Age≤61 predicted lower NCF failure risk (HR = 0.60, p = 0.0002); non-significant test for interaction indicated independent effects of HA and age. Patient-reported fatigue (p = 0.036), difficulty speaking (p = 0.049) and problems remembering things (p = 0.013) at 6 mos favored the HA-WBRT+M arm. Imputation models accounting for missing data also favored the HA-WBRT+M arm for patient-reported cognition (p = 0.011) and symptom interference (p = 0.008) at 6 mos. Treatment arms did not differ in toxicity, overall survival, or intracranial progression. Conclusions: HA during WBRT+M for BM better preserves NCF and patient-reported symptoms, while achieving similar intracranial control and survival. Supported by grants UG1CA189867 (NCORP), U10CA180868 (NRG Oncology Operations), DCP from the National Cancer Institute. Clinical trial information: NCT02360215.
tPA and PAI-1 in malignant tissues of gastric adenocarcinoma can be tumor-associated.
Authors: Nikolay S. Samoylenko, Oleg I. Kit, Elena M. Frantsiyants, Larisa S. Kozlova, Natalya V. Soldatkina, Sergey V. Tumanyan, Yuriy A. Gevorkyan, V. I. Aleynov, Anton G. Milakin, Sergey I. Poluektov, Maksim N. Duritskiy
Journal: Journal of Clinical Oncology (2019)

e15533 Background: Plasminogen regulator system is considered to be involved in migration, invasion and proliferation of malignant cells. The role of tissue plasminogen activator (tPA) and PAI-1 in cancer is still discussed. Our purpose was to study the antigen and active forms of tPA and PAI-1 (tPA-Ag, tPA-act and PAI-1-Ag, PAI-1-act) in tissues of gastric adenocarcinoma (GA), greater omentum and peritoneum with and without metastases (mts). Methods: We studied tissues of patients with GA T 3-4 а N 0-3 M 1 (n = 21, 10 men, 11 women) and T 3-4 а N 0-3 M 0 (n = 24, 15 men, 9 women) aged 61.23±4.8 years. Control group included 17 non-cancer patients aged 39.1±3.2 years (6 men, 11 women). Levels of tPA-act, tPA-Ag, PAI-1-act and PAI-1-Ag were measured by ELISA using standard test systems. Statistical analysis was performed using the SPSS 11.5 software package for Windows. Results: Levels of both forms of tPA and PAI-1 in GA with and without mts were 1-2 orders of magnitude higher than in resection line tissues. Levels of tPA-Ag and PAI-1-Ag in GA without mts were 1.7 and 2.5 times higher than in GA with mts, while levels of tPA-act and PAI-1-act were similar. In tissues of the greater omentum, levels of tPA-Ag with mts exceeded that in tissues without mts and in controls by 5.0 and 1.7 times, respectively; levels of tPA-act were similar to controls, while without mts they were 1.6 times lower than in controls. PAI-1-Ag with mts was 3.2 and 4.5 without mts and in controls, respectively; PAI-1-act with mts was 1.8 and 1.5 times higher than in controls and without mts, respectively. In tissues of the peritoneum, tPA-Ag with mts was 1.6 and 1.4 times higher than without mts and in controls, respectively; tPA-act with and without mts was 1.4 (p = 0.0412) and 1.5 times lower than in controls. PAI-1-Ag in the peritoneum with and without mts 1.4 times (p = 0.0428) exceeded control, and PAI-1-act was higher than in controls by 1.6 and 2.8 times, respectively. The results demonstrated that GA with and without mts secreted PAI-1 and tPA, and levels of tPA-Ag and both forms of PAI-1 were elevated in tissues of the peritoneum and omentum with and without mts. Conclusions: Levels of tPA-Ag and both forms of PAI-1 in the greater omentum and peritoneum without mts indicate possible formation of a pre-metastatic niche.