tbuckley/cabot-search huggingface dataset:
Experience of 22 patients with ROS mutated lung adenocarcinoma treated with crizotinib at a tertiary care center in India
Authors: V. Talreja, N. Pande
Journal: Annals of Oncology (2018)

Background: ROS1 hence became recognized as a distinct molecular target in NSCLC.Like ALK rearrangements ROS1 fusions are also found more in never smokers but define a distinct molecular subgroup with both rarely occurring together in same patient Crizotinib, a highly effective inhibitor of ROS1 kinase activity, is now FDA-approved for the treatment of patients with advanced ROS1-positive NSCLC .We report our experience in a tertiary cancer care centre in ROS-1 positive patients. Methods: The present study was a retrospective analysis of a prospectively maintained lung cancer registry in whom the ROS1 mutation status was determined.Genetic Assessments for ROS1 and ALK rearrangements were identified by using FISH.All statistical analyses were carried out using the SPSS software version 22.0. Results: Between January 2015 and December 2017 there were 22 patients who were positive for ROS gene rearrangement. A total of 16 patients took Crizotinib either in first or second line.There were 13 male(60%) and 9 females(40%) in the cohort whose median age was 54 years.The median follow up in Crizotinib received arm was 322 days and 244 days in non-Crizotinib arm.Among the 16 patients who received Crizotinib, 2(12.5%) achieved (CR) as their best response and continue to remain in CR at follow up.13(81.2%) had (PR) as best response and of which on follow up 5 have progressed while 8 continue to maintain response.The median follow-up was 244 days.The estimated medianPFS for the entire cohort of patients was 4 months(95%CI:2.5–5.5 months).The estimated median PFS for the ROS mutant patients was significantly longer at 573 Days(95%CI:318-544 days) as compared to the estimated median PFS for ROS negative patients which was 79 days(95%CI:43-201 days),p=0.00.The estimated median OS for all patients was 13 months(95% CI:10.7–15.3months).The estimated median OS for ROS positive patients was not achieved (95%CI:2.4–25.6 months), while that for ROS negative patients was 79 days (95%CI:7.4–12.6months),p = 0.001. Conclusions: ROS1 rearrangement with incidence of 4% of lung adenocarcinoma represents a important targetable driver mutation in Indian population. Crizotinib is effective treatment option with acceptable side effects in our population. Legal entity responsible for the study: Tata Memorial Hospital. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Variations in Influenza Vaccination by Clinic Appointment Time and an Active Choice Intervention in the Electronic Health Record to Increase Influenza Vaccination
Authors: Rebecca H. Kim, Susan C. Day, Dylan S. Small, Christopher K. Snider, Charles A. L. Rareshide, Mitesh S. Patel
Journal: JAMA Network Open (2018)

<h3>Importance</h3> Influenza vaccination rates in the United States are suboptimal near 40%, but little is known about variations in care based on clinic appointment time. <h3>Objectives</h3> To compare differences in influenza vaccination rates by clinic appointment time and to evaluate the association of an active choice intervention in the electronic health record with changes in vaccination rates. <h3>Design, Setting, and Participants</h3> Retrospective, quality improvement study of 11 primary care practices at the University of Pennsylvania Health System from September 1, 2014, to March 31, 2017. Participants included adults eligible for influenza vaccination. Data analysis was conducted from October 20, 2017, to March 9, 2018. <h3>Interventions</h3> During the 2016 to 2017 influenza season, 3 primary care practices at the University of Pennsylvania Health System implemented an active choice intervention in the electronic health record that prompted medical assistants to ask patients about influenza vaccination during check-in and template vaccination orders for clinicians to review during the visit. <h3>Main Outcomes and Measures</h3> Influenza vaccination rates. <h3>Results</h3> The sample comprised 96 291 patients with a mean (SD) age of 56.2 (17.0) years; 41 865 (43.5%) were men, 61 813 (64.2%) were white, and 23 802 (24.7%) were black. Among all practices across all 3 years, vaccination rates were approximately 44% from 8amto 10am, declined to 41.2% by 11amand 38.3% at noon, increased to 40.2% at 1 pm, and then declined to 34.3% at 3pmand 32.0% at 4pm(<i>P</i> &lt; .001 for adjusted linear trend). For the 3 years, vaccination rates were 46.9%, 47.2%, and 45.6% at control practices and 49.7%, 52.2%, and 59.3% at intervention practices, respectively. In adjusted analyses, compared with control practices over time, the active choice intervention was associated with a significant 9.5–percentage point increase in vaccination rates (95% CI, 4.1-14.3;<i>P</i> &lt; .001). Vaccination rates increased similarly across times of the day. <h3>Conclusions and Relevance</h3> Influenza vaccination rates significantly declined as the clinic day progressed. The active choice intervention was associated with a significant increase in influenza vaccination rates that were similar in magnitude throughout the day.
Detection of autoantibodies against alpha-enolase (ENO1) as potential biomarkers improving immunodiagnosis in human osteosarcoma by serological proteome analysis.
Authors: Jitian Li, Manyu Huang, Zhiping Guo, Junyan Teng, Wuyin Li, Jian-Ying Zhang
Journal: Journal of Clinical Oncology (2018)

e23506 Background: Osteosarcoma (OS), characterized by the production of osteoid material by malignant osteoblastic cells, is the most common highly malignant primary bone-tumor. Despite its relatively low incidence rate among overall cancers, it remains one of the most harmful primary malignant tumors in childhood and adolescence. It is now evident that serum autoantibodies against tumor-associated antigens (TAAs) could be used as serological cancer biomarkers in types of cancers. Methods: Serological proteome analysis (SERPA) approach was implemented for the identification of TAAs that induce antibody responses in OS. Sera from OS, Osteochondroma (OC) and Normal Human Sera (NHS) were probed by immunoblotting against cellular proteins extracted from U2-OS and Saos-2 cell lines, with OS sera showing stronger immunoreactivity. MALDI-TOF/TOF Mass Spectrometry (MS) analysis of immunoreactive protein spots revealed that several OS sera contained autoantibodies to a number of proteins, particularly to alpha-enolase (ENO1). Results: The immunoseroproteomics profiling led to the identification of 20 potential TAAs of 56 protein spots targeted by serum autoantibodies in OS patients compared with the NHS pool. Especially, ENO1 (11 of 12) had a higher immunoreactive frequencies in sera with OS. Analysis of 172 serum samples from patients with OS, OC and NHS by ELISA showed higher frequency of anti-ENO1 autoantibodies in OS sera compared to others. The results of ROC curves analysis of anti-ENO1 autoantibody indicate it predominately discriminate the OS group from OC as well as can differentiate OC patients from normal individuals. The expression of ENO1 in Osteosarcoma tissues was evaluated by immunohistochemistry in tumor microarray. Conclusions: Taken together, our results suggested that the autoantibody to ENO1 might be considered as a potential serological biomarker for OS. Key words: Osteosarcoma (OS), Tumor-associated antigen (TAA), Serological proteome analysis, ENO1, Immunodiagnosis.
TCT-871 Stratification of the coronary flow impairment in non-infarcted-related arteries according to the coronary flow capacity (CFC)
Authors: Hernan Mejia-Renteria, Joo Myung Lee, Nina van der Hoeven, Guus de Waard, Nieves Gonzalo, Pilar Jimenez-Quevedo, Luis Nombela-Franco, Ivan Nuñez-Gil, Pablo Salinas, Maria Del Trigo, None Tania Rodriguez Gabella, Niels van Royen, Paul Knaapen, Bon-Kwon Koo, Carlos Macaya, Antonio Fernandez-Ortiz, Javier Escaned
Journal: Journal of the American College of Cardiology (2018)
Tumor flare reaction (TFR) in cancer treatments: A systematic review.
Authors: Amina B. Taleb
Journal: Journal of Clinical Oncology (2017)

e18258 Background: In the last decade, TFR was described as a side-effect associated with immunomodulatory agents IMiDs (thalidomide and lenalidomide), and as a specific condition to chronic lymphocytic leukemia (CLL). However, this phenomenon is seen with the use of new immunotherapy (checkpoints inhibitors) in solid tumors, in addition, cases of TFR were reported in advanced gynecologic, prostate cancer and lymphoid malignancies. TFR is defined as an increase of lesion size related to treatment which simulates disease progression. This phenomenon that occurs after initiating cancer therapy is poorly understood and incidence is under-estimated, since not captured by Recist. It has been suggested that TFR may be the results of immune system activation and may precede tumor shrinkage. TFR is associated with morbidity, severe cases were reported, some of them life-threatening or leading to death. So, early recognition and initial management of patients presenting with TFR, is critical. Methods: From 1985 to 2016, a search was performed in the Pubmed, ASCO and ASH abstracts to identify publications reporting TFR or pseudoprogression. Results: The incidence of all grades of TFR in CLL, ranged from 28% in a study to 58% in another trial. In CLL, painful lymph nodes and/or spleen enlargement were reported with a sudden onset after the first dose. Following initial progression (TFR), tumor response in patients treated beyond progression, was reported inmelanoma trials: 9.7% with ipilimumab, 10% with nivolumab, 6.7% and 12% with pembrolizumab, and in renal cell carcinoma 69% with nivolumab. Even if rare cases of life-threatening or fatal TFR were reported, symptoms are usually mild. While correct diagnosis and adequate management are critical, it is important to better recognize TFR, and avoid an effective treatment discontinuation. Some studies showed that treating patients beyond progression yielded tumor responses, considering TFR as predictive of response. Conclusions: Treatment with immunomodulatory agents is associated with TFR. This is likely to be misinterpreted as progression, hence the need to identify appropriate clinical benefit criteria and the use of immune-related RECIST (irRC) in prospective trials for a better understanding.
P05.05 Gamma knife radiosurgery for foramen magnum meningiomas: a single centre study
Authors: K Abdel Karim, A M N El Shehaby, W A Reda, A Nabeel, R Emad, S R Tawadros
Journal: Neuro-Oncology (2018)

Surgical treatment of foramen magnum meningiomas is challenging because of the proximity to critical vascular and neural structures such as the medulla and lower cranial nerves. In addition to the morbidity and mortality associated with surgery, complete resection is not always feasible. Gamma knife radiosurgery may provide a safe alternative or adjuvant to surgery after neural decompression. To evaluate the feasibility, efficacy and safety of the treatment of meningiomas involving the foramen magnum by gamma knife radiosurgery. Between December 2007 and April 2016, 23 patients with meningiomas involving foramen magnum were treated by gamma knife radiosurgery. Of these, 18 patients were available for follow up. There were 17 females and one male. The mean age at the time of gamma knife treatment was 51 years (36–71 years). Nine patients had previous surgery (5 were residual tumors after surgery and 4 were a tumor recurrence). Twenty-two sessions were performed for 18 tumors (4 tumors were volume-staged). The mean target volume was 5.2 cc (0.7–13.5 cc) and the mean dose was 10.7 Gy (10–12 Gy). The mean follow up was 35 months (12–88 months). One died 5 years after treatment from comorbidity. The tumors remained stable in 13 (72%), regressed in 4 (22%) and progressed in one (6%). The overall tumor control was 94%. Seventeen patients were symptomatic before treatment and one was accidentally discovered. Clinical improvement was observed in 8 patients (44%), while remaining patients were clinically stable. No patients suffered adverse radiation effects. Gamma knife radiosurgery appears to be an effective and safe treatment option for meningiomas involving the foramen magnum. It can be utilized as an adjuvant to surgery or as a primary treatment in small tumors and in larger tumors in patients with comorbidities, using volume-staging technique.
Is there a benefit of re-induction therapy in adult patients with AML with &lt;20% blasts?
Authors: Kavya Kannamma Kannan, Paz Vellanki, Scott Isom, Bernard Tawfik, Allison Marie Winter, Heidi D. Klepin, Leslie R. Ellis, Rupali Roy Bhave, Dianna Howard, Megan Manuel, Sarah Dralle, Susan Lyerly, Bayard L. Powell, Timothy S. Pardee
Journal: Journal of Clinical Oncology (2018)

7021 Background: Decision on re-induction (RI) therapy in adult patients with newly diagnosed acute myeloid leukemia (AML) who have received induction chemotherapy (ICT) when there are less than 20% blasts on day 14 nadir bone marrow biopsy (NBMB), is difficult due to the lack of efficacy data and the toxicity associated with RI. We sought to determine the utility of RI in this group of patients. Methods: We identified 270 adults with AML treated at Wake Forest Baptist Health with ICT between 2002-2009. We excluded 37 patients who did not have a NBMB. NBMB were classified as negative ( < 5% blasts), suspicious ( < 5% blasts with morphological suspicion for residual disease or 5-20% blasts) and positive ( > 20% blasts) for residual disease. Complete remission (CR) was achieved if recovery BM had < 5% blasts along with platelet recovery to at least 100,000 cells/microliter and absolute neutrophil count of at least 1000 cells/microliter. A CRi was defined as having either platelet or neutrophil recovery but not both. Kaplan Meier estimation was used to calculate the median OS and survival estimates at 1, 2, and 3 years post induction. Results: Of the 233 patients, 106 (45.5%) had NBMB findings suspicious for residual disease (sRD). Of these patients, 66 (62.3%) underwent RI and 40 (37.7%) did not. Of those who received RI, 52 of 66 (78.8%) achieved a CR/CRi. In the patients who did not receive RI, 32 of 40 (80.0%) achieved a CR/CRi. There was no statistical difference in median OS with and without re-induction in patients with sRD overall and when sub classified into favorable, intermediate and poor cytogenetic categories. Conclusions: Our retrospective analysis raises questions of the utility of RI in adult patients with AML with less than 20% blasts on nadir marrow. This finding warrants prospective trials for further validation. sRD(106) RI (66) No RI (40) Demographics Age < 60 27 (40.9%) 20 (50.0%) > or equal to 60 39 (59.1%) 20 (50.0%) Gender Male (57.5%) 40 (60.6%) 21 (52.5%) Female (42.5%) 26 (39.4%) 19 (47.5%) Cytogenetic risk Favorable (16%) 11 (16.7%) 6 (15.0%) Intermediate (71.7%) 46 (69.7%) 30 (75.0%) Poor (12.3%) 9 (13.6%) 4 (10.0%) Median OS in months (p-0.7484) 16.9 20.1 Favorable (p-0.4415) NA* NA* Intermediate (p-0.5018) 16.9 20.1 Poor (p-0.4839) 6.4 5.2
Mutation profile of drug resistant gastrointestinal stromal tumor (GIST) patients (pts) enrolled in the phase 1 study of DCC-2618.
Authors: Suzanne George, Michael C. Heinrich, Albiruni Ryan Abdul Razak, Ping Chi, Michael S. Gordon, Kristen N. Ganjoo, Margaret von Mehren, Neeta Somaiah, Jonathan C. Trent, Ying Su, Rodrigo Ruiz-Soto, Oliver Rosen, Filip Janku
Journal: Journal of Clinical Oncology (2018)

11511 Background: GIST is driven by primary and secondary driver mutations in KIT/PDGFRα and cell-free tumor (ct) DNA may provide the opportunity to assess disease status and response to therapy. The pan-KIT/PDGFRα switch control inhibitor DCC-2618 has demonstrated durable disease control in heavily pre-treated GIST pts in the ongoing Phase 1 study (NCT02571036). Methods: Pts with advanced GIST were treated in either the escalation stage or in expansion cohorts of the Phase 1 study with oral DCC-2618. Tissue and liquid biopsies were performed and tested via next generation sequencing (NGS) of tumor tissue and/or plasma ctDNA. Results: A total of 136 2nd to 7th line (median of 3 prior therapies) GIST pts (KIT or PDGFRα mutations by local testing) were enrolled as of January 18, 2018 and treated with doses of ≥100 mg per day. 132 patients had a ctDNA sample available for baseline assessment by NGS. To date, activating mutations in KIT or PDGFRα were identified in 71% of baseline ctDNA analyzed from 77 pts. In the 53 confirmed KIT mutant GIST pts, exon 13/14 mutations were detected in 16 patients (30%); while exon 17/18 mutations were detected in 33 patients (62%). Notably, multiple patients had mutations in both exons 13/14 and 17/18. 92 GIST patients had at least one additional ctDNA sample available at first restaging. The correlation between tumor tissue and ctDNA, and the change in KIT/PDGFRA mutant allele frequency for GIST pts following the first 2 cycles of treatment with DCC-2618 will be presented. 76% of 136 pts are still on treatment. In 99 GIST pts with ≥1 on-study tumor assessment, the overall response rate (ORR) was 16%. Conclusions: Identification of ctDNA by NGS in the majority of patients in this cohort was feasible. The mutation profile of GIST in both tumor and plasma suggests the need for a pan-KIT inhibitor across various lines of therapy. DCC-2618 is being tested in a pivotal, randomized phase 3 study, INVICTUS, (NCT03353753) in the 4th+ line population with plans to be tested in a second Phase 3 study in 2nd line GIST. ctDNA in this patient population deserves further study as a non-invasive marker of disease heterogeneity and response assessment. Clinical trial information: NCT02571036.
Effect of HLA-DQ presentation on SEG/SEI superantigenic reactivity to a CD4+-mediated anti-tumor response devoid of autoimmune or allogeneic effects.
Authors: Peter Knopick, Katherine Benedict, Travis Alvine, Matthew Nilles, John Ballantyne, David Terman, David Bradley
Journal: Journal of Clinical Oncology (2016)

e21047 Background: SEG and SEI are 3rd generation superantigens (SAgs) derived from the enterotoxin gene cluster (egc) of Staphylococcus aureus. In a recent study, 14 patients with stage IIIB NSCLC with pleural effusion (PE) were treated with a S. aureus filtrate containing SEG and SEI resulting in resolution of PE with minimal toxicity. SEG/SEI elicit robust T cell proliferation and anti-tumor cytotoxicity and humans do not exhibit seroreactive neutralizing antibodies against them. The presence of the latter is the major deterrent to successful use of SAgs to treat human cancer. Methods: Here we test recombinant SEG/SEI against aggressive B16-F10 melanoma in transgenic DQ8 (HLA-DQA1*0301, HLA-DQB1*0302) and C57BL/6 mice. HLA class II isotypes control the magnitude and quality of the immune response to superantigens. Although SEG/SEI bind naturally to HLA-DR1, we selected HLA-DQ for these studies because a related SAg, SPEA (streptococcal pyrogenic exotoxin A), induced greater protection against septic death in humans when presented from DQ compared to DR. Results: B16-F10 melanoma was implanted intraperitoneally and SEG/SEI were subsequently injected 6 and 9 days post implant resulting in a median survival of 27 days in C57BL/6 mice while HLA-DQ8 mice treated with the identical regimen show 100% survival for more than 70 days post implant. HLA-DQ8 mice, which are prone to autoimmune polychondritis, showed no evident signs of autoimmune or graft versus host disease. Splenocytes from HLA-DQ8 mice demonstrated a stronger T cell proliferation relative to C57BL/6 mice (p < 0.01). Cytotoxicity assays revealed a significant increase in CD4+-mediated cytotoxicity in SEG/SEI treated DQ8 mice compared to similarly treated C57BL/6 mice (p < 0.01). CD8+-mediated cytotoxicity was comparable in both groups. Conclusions: These results unveil a hitherto unrecognized role of DQ8 in activating a potent, predominantly CD4+-mediated, SEG/SEI-anti-tumor response devoid of autoimmunity. Collectively, these findings suggest SEG/SEI presented via a DQ platform as a promising new candidate, devoid of neutralizing antibodies, for translation to patients with advanced melanoma.
Outcome of gastrointestinal cancer patients (pts) after ICU admission: The Abington Memorial Hospital (AMH) experience.
Authors: Faizan Malik, Naveed Ali, Syed Imran Mustafa Jafri, Mary Naglak, Rajeshkumar Patel, Christian Fidler, Steven J. Cohen
Journal: Journal of Clinical Oncology (2017)

e18108 Background: Based on prior studies, cancer pts admitted (atd) to ICU have poor outcome but gastrointestinal(GI) cancers have not been studied separately. We evaluated outcomes of GI cancer pts receiving active therapy (Rx) who were admitted to the ICU with the goal of informing physicians and pts regarding goals of care. Methods: We retrospectively evaluated pts with GI cancer on active chemo Rx in past 6 months who were admitted to the ICU from 2011-2016. Out of 375, 115 pts met the inclusion criteria. (85 = CRC, 30 = other GI malignancy). Results: The mean age was 71 (51% males). 75% stage 4, 42% had liver, 28% peritoneal, and 21% lung mets. The median duration of the last chemo dose was 2 wks. The median ICU length of stay was 3 days. 25% had neutropenia on admission. 64% had prior cancer related surgery, and 31% had prior radiation. 23% were atd due to cancer progression (CP), 19% due to potentially reversible cancer complications (pRCC), and 57% due to therapy complications (TC).Most common admitting diagnoses were: pneumonia (25.9%), abdominal infection (27%), PE/DVT/MI (20%), febrile neutropenia (10%). During ICU stay, 29% had ventilator dependent respiratory failure (VDRF), 53% had sepsis, 43% had renal failure (RF) and 17% had liver failure(LF). Median survival after ICU admit was 2 weeks (0-75). 15.5% were DNR at ICU admission and 82.8% were full code. 55.2% had palliative talk. After DC, 38.8% went back on Rx and 41% chose hospice. Readmission was 15.5%. In-hospital mortality (IHM) was 24.1% overall, and highest in those with LF (50%, p = .008), sepsis, and RF (34% each, p = .048). IHM was 33% in pts with CP (p value-0.201), 31% in patients with a pRCC (p-value 0.204), 18% in pts with a TC(p-value 0.092), and 52% in pts with VDRF(p-value 0.000). Overall, 56% were dead at 30 days, 65% at 90-days and 73% at 180 days. Conclusions: Our study suggests that in-hospital, 30-, 90- and 180-day mortality in GI cancer patients on active Rx admitted to the ICU was high, particularly in patients admitted with progressive cancer and/or with organ dysfunction. Most patients were full code and had not had prior documented GOC discussions. These results highlight the importance of early realistic GOC discussions for this population.