tbuckley/cabot-search huggingface dataset:
A review of the patterns of prescribing, efficacy and toxicities for patients receiving checkpoint inhibitors.
Authors: Peter Nightingale, Phillip Parente
Journal: Journal of Clinical Oncology (2018)

e15090 Background: Anti-PD1 antibodies are TGA approved for the treatment of melanoma, non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC) with studies progressing in multiple other cancers Immune related adverse events (IRAEs) are widely described Previous publications on toxicity data have not focussed on mode of access used to deliver these agents to patientsMethods: Patients who had treatment with pembrolizumab, nivolumab, ipilimumab or combination therapy between January 2015 and August 2017 at Eastern Health or Epworth Eastern were identified and medical records reviewed retrospectively. Adverse effects were identified and graded based upon documentationResults: 43 (77%) of the melanoma patients accessed through government funding, whereas 13 (23%) accessed via compassionate program. 66 (99%) of lung cancer patients, 10 (100%) renal cancer patients and 9 (41%) other tumour types accessed via compassionate access. The average length of treatment for melanoma patients (8.2 months). The average lengths of treatment for lung, renal and other cancers were 5.4, 3.3 and 4.4 months respectively. There was a clear correlation to increased survival times in those with an IRAE and increased number IRAEs (Table 1) Clinically relevant toxicity rates (Grade 3 or 4 IRAEs) were identified. 7/19 patients who received both ipilimumab and an Anti-PD1 (38%). 12/150 patients who received only an Anti-PD1 agent (8%). When toxicity was stratified by tumour type, 5 (11%) melanoma patients, 9 (17%) lung cancer patients and 1 (11%) renal cancer patient experienced grade 3 or 4 toxicity Conclusions: In Australia, majority Anti-PD1 drugs was via government funding in melanoma patients, and via compassionate access for non-melanoma patients. The average length of treatment was longer for melanoma compared to other tumour types. Toxicity rates were similar across all tumour types, however, higher in those patients who received ipilimumab. More IRAEs correlated with an increase in progression free survival. No of IRAEs Progression free survival (months) 0 4.83 1 8.80 2+ 12.30
Molecular landscape of fibrolamellar carcinoma (FLC): Beyond the DNAJB1-PRKACA chimera.
Authors: Imane Hassan El Dika, Marinela Capanu, Michael F. Berger, Maria E. Arcila, Ryma Benayed, James J. Harding, Matthew Rusek, Emily Valentino, Eileen Mary O'Reilly, Leonard Saltz, Ghassan K. Abou-Alfa
Journal: Journal of Clinical Oncology (2017)

e15668 Background: FLC is a rare cancer arising in non-cirrhotic liver of young adults. A functional chimeric transcript resulting from the in-frame fusion of DNAJB1 with PRKACA genes on chromosome 19 is thought to be universal and unique in FLC. This chimera has possible role in pathogenesis, yet with no determined prognostic or therapeutic value. Methods: Archival FFPE samples from FLC patients who prospectively consented to an IRB-approved protocol from 2014 onward were analyzed using the MSK-IMPACT platform, a hybridization capture based next generation sequencing assay for targeted deep sequencing of all exons and selected introns of &gt; 400 key cancer genes. Tumor and matched normal libraries were sequenced on an Illumina HiSeq 2500. Sequencing output was processed using a custom analysis pipeline. Archer targeted RNAseq was performed in select cases. Demographic, treatment, and outcome data was prospectively collected. Fisher’s exact tests were performed to look for associations between clinical characteristics and genetic alterations. Results: 18 patients were identified. Median age at diagnosis was 18 years and 61% were women. 17 (94%) underwent upfront surgery, and median number of therapies was 5. The DNAJB1-PRKACA fusion transcript was detected in 100% of cases. 7 samples were negative via MSK-IMPACT, (2 false-negatives, and 5 due to an older panel not including the fusion transcript) and were confirmed positive on Archer targeted RNAseq. The second most common genetic mutation was TERT, detected in 4 patients, whereas CIC, NOTCH1, ERBB3, EPHAS, MCL1, PNRC1, NCOR, INPP4B, ARID1A, CHECK1, NKX3-1, TET1, RAD52, DIS3, SF3B1, MDM2, MED12, MPL, KRAS, PAK7, BCOR, HGF, ROS1, MYCL1, CTNNB1, and YAP1 were detected in 1 patient each. 3-year overall survival (OS) was 98%, median OS was not reached. Conclusions: This limited cohort of patients with FLC exhibited universally the DNABJ1-PRKACA chimera, and demonstrated a favorable outcome compared to a 3-year OS approaching 70% previously reported by the Fibrolamellar Consortium. The fusion transcript did not imply a prognostic value considering its expression among all patients with FLC. Other drivers or the lack of may be responsible for the improved outcome in this small cohort
TCT-441 SOCIME + LATIN: Partners for Comprehensive, Nationwide AMI Care in Mexico
Authors: Sameer Mehta, Roberto Botelho, Francisco Fernandez, Mauricio Prudente, Ricardo Cavalcanti, Jamil Cade, Cesar Dusilek, Fausto Feres, Marco Alcocer-Gamba, Alfredo Estrada, Mario Torres, Daniel Rodriguez, Daniel Vieira
Journal: Journal of the American College of Cardiology (2018)
Hope for salivary gland cancer (SGC): EORTC HNCG/UKCRN 1206 randomized phase II study to evaluate the efficacy and safety of chemotherapy (CT) vs androgen deprivation therapy (ADT) inpatients with recurrent and/or metastatic androgen receptor (AR) expressing SGC (NCT01969578).
Authors: Laura Locati, Carmela Aves Caballero, Catherine Fortpied, Federica Perrone, Pasquale Quattrone, Kevin Harrington, Vincent Gregoire, Lisa F. Licitra
Journal: Journal of Clinical Oncology (2018)

TPS6099 Background: SGCs are rare and heterogeneous tumors ( < 1% of all malignancies in Europe). Among more than 20 histotypes, only salivary duct carcinoma (SDC) and adenocarcinoma NOS express AR. These variants are aggressive and associated with poor prognosis. Surgery is the main curative treatment but upon relapse, patients are left with very few options. This study (NCT01969578) aims to evaluate the efficacy and safety of ADT (experimental arm) vs chemotherapy (standard arm) in patients with recurrent and/or metastatic, AR overexpressing SDC and adenocarcinoma, NOS by demonstrating a 15% improvement in Progression Free Survival (PFS) rate at 6 months in favor of ADT. Methods: Trial design: In this multicenter, randomized, phase II intergroup study a total of 76 treatment patients (Cohort A) are planned to be randomized to receive ADT or platinum-based chemotherapy. Patients previously treated with chemotherapy will be enrolled in a separate Cohort B to receive ADT. Patients from Cohort A randomized to chemotherapy can also enter in Cohort B at disease progression. The primary endpoint is PFS for Cohort A and best overall response for Cohort B. AR overexpression is mandatory at study entry. Mechanisms of AR activation and resistance will be studied. This study is led by EORTC Head and Neck Cancer Group with UNICANCER/REFCOR, International Rare Cancer Initiative UK Salivary Gland Cancer Group and RARECARENet. It will run in 35 sites in 10 countries: Austria, Belgium, France, Germany, Greece, Hungary, Italy, Portugal, The Netherlands, and United Kingdom. Sites from the EURACAN European Reference Network are participating. On 9 th February 2018, 54 patients are registered; 27 have been enrolled, of which 17 have been randomized in Cohort A. Identification of AR as a treatment target in SGC can be practice changing. Clinical trial information: NCT01969578.
Molecular profiling of 502 patient cohort with NSCLC using a 27 somatic gene panel.
Authors: Nikolaos Tsoulos, Eirini Papadopoulou, Vasiliki Metaxa-Mariatou, Georgios Tsaousis, Chrisoula Efstathiadou, Georgia Tounta, Katerina Skapeti, Jenny Bourkoula, Paul Zarogoulidis, George E. Pentheroudakis, Stylianos Kakolyris, Ioannis Boukovinas, Pavlos Papakotoulas, Ilias Athanasiadis, Theofanis Floros, Anna Koumarianou, Barbounis Vassilios, George Nasioulas
Journal: Journal of Clinical Oncology (2017)

e23193 Background: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and a tumor with broad spectrum of targeted therapies already available or in clinical trials. Thus, molecular characterization of the tumor using the Next Generation Sequencing (NGS) technology, has become a key tool for NSCLC patients’ treatment decision and clinical management. Methods: The performance of a custom 23 gene multiplex amplification hot spot panel, based on Ion AmpliSeq Technology, was evaluated for the analysis of tumor DNA extracted from FFPE (Formalin Fixed Parraffin Embedded) tissue. Furthermore the Ion AmpliSeq™ RNA Fusion Lung Cancer Research Panel was used for fusion RNA transcript analysis. Tumors’ mutation spectrum was determined in a cohort of 502 patients with NSCLC using the aforementioned targeted gene panels. Results: The panel used for tumor DNA analysis in this study exhibit high rates (100%) of sensitivity, specificity and reproducibility at a mutation frequency of 3%. At least one DNA mutation was detected in 374 patients (74.5%) and an RNA fusion was identified in 16 patients, (3.2%). In total, alterations in a cancer driver gene were identified (including point mutations, gene rearrangements and MET amplifications) in 77.6% of the tumors tested. Among the NSCLC patients, 13.5% (68/502) presented a mutation in a gene with approved targeted therapy (EGFR, ALK ROS1) and 9.4% had an alteration in a gene related to emerging targeted therapies according the NCCN guidelines. These alterations include ERBB2, BRAF and MET mutations, MET amplification and RET rearrangements. The remaining 51.6% of the patients had a mutation in a gene that could be related to an off label therapy or give them access to a clinical trial. Conclusions: Thus the NGS panel validated is a reliable approach of clinical applicability for tumor molecular profile detection in NSCLC patients.
The impact of mild left ventricular dysfunction on trastuzumab use and oncologic outcomes in early stage breast cancer therapy.
Authors: Jordan Gibson, Ren Jie Yao, Margot Davis, Christine E. Simmons
Journal: Journal of Clinical Oncology (2017)

e18148 Background: Trastuzumab (T) significantly reduces the risk of breast cancer recurrence, but may be associated with an increased incidence of heart failure. The intention of this study was to assess how T therapy was managed after the development of mild left ventricular ejection fraction (LVEF) drop in a non-trial setting and to evaluate the cardiovascular and oncologic outcomes. Methods: Patients (pts) who received adjuvant T therapy in British Columbia for breast cancer between September 2005 and December 2013 were identified. Pts were eligible if they had a drop in LVEF to 40-49% after starting T. Charts were reviewed for demographic information. Pts were divided into 2 cohorts: those who continued T without interruption, and those who had any interruption or discontinuation. Breast cancer outcomes and cardiac outcomes were compared in each of these groups. Results: Of the 2401 pts who were screened, 261 (10.9%) pts had a drop in LVEF to 40-49%. Of these, 229 (87.7%) had an interruption in T, while 32 (12.3%) did not have an interruption in therapy. The number of pts who experienced a cancer relapse in the T interruption and continuous groups were 38 (16.6%) and 2 (6.25%), respectively (P = 0.19). Even amongst those who received a full 17 cycles of therapy, there was a 11.25% absolute increase in the risk of breast cancer recurrence (17.5% vs 6.25%) in those who had an interruption in their course of treatment compared to those who did not have an interruption (p = 0.15). Cardiac outcomes (subsequent LVEF drop &lt; 40% or CHF) were higher in the group of pts who had treatment interrupted compared to those who had continuation of T (14.8% vs 0%). Conclusions: Interrupting T after the development of mild left ventricular dysfunction was associated with a 10.35% (p = 0.19) absolute increase in breast cancer recurrence. Continuing T was not associated with an increased risk of long term cardiovascular events. While these results are not statistically significant, they are concerning and warrant further investigation.
Comparison of comprehensive genomic profiling (CGP) and hotspot next generation sequencing (NGS) assays in identifying treatment options for care of patients with metastatic cancer in in the community setting.
Authors: Ricardo H. Alvarez, John W Thomas, Zachary Rockow Chalmers, Alexa Betzig Schrock, Carolina alvarez Tapias, Garrett Michael Frampton, Kim Kramer, Vincent A. Miller, Siraj Mahamed Ali, Bradford A. Tan, Maurie Markman
Journal: Journal of Clinical Oncology (2016)

e23120 Background: Targeted therapy can benefit advanced cancer patients in the context of a clinically relevant genomic alteration (CRGA) (Schwaederle, 26304871). Comprehensive genomic profiling (CGP) may facilitate this approach by assaying all classes of genomic alterations (GA) across many cancer related genes; in contrast focused (‘hotspot’) NGS assesses only specific changes in select genes. We reviewed the records of 57 consecutive advanced solid tumor patients assayed with both CGP and hotspot testing (Caris) via clinical care. Methods: > 50 ng of DNA per specimen was extracted from 57 formalin-fixed paraffin-embedded clinical tumor samples and CGP (hybrid capture-based NGS) was performed on adaptor ligation based libraries to high, uniform coverage ( > 500x) for all exons of 182/236 genes and 14/19 genes frequently rearranged in cancer. Hotspot testing was conducted on selected exons of 44 genes using an Illumina Truseq Amplicon panel, as well as IHC and FISH.. Results: The median age of the patients was 53 (range 21-85). Tumor types studied: breast carcinoma 17 cases (30%), colon cancer 10 cases (18%), and carcinoma of unknown primary 6 cases (11%) , and others. When tested by hotspot, 44 cases (77%) had at least one GA; 13 (22%) had no GA.When assayed with CGP, all but one case (98%) harbored at least one GA. For cases without GA on hotspot, CGP identified CRGA including three instances of PTEN GA, two each of CCND1 and FGFR1 amplifications, and an IDH1 mutation in all but one such case. In 17 breast cases, the most commonly studied tumor type, 108 GA were identified by CGP ( ≥ 1 in 17/17) , and 19 GA by hotspot testing ( ≥ 1 in 12/17). Strikingly, CGP in breast patients identified ESR1 mutations (n = 3 pts), FGFR1 amplifications (n = 2), CCND1 amplification (n = 1), and a PALB2 mutation (n = 1), all missed by hotspot testing. Conclusions: CGP in the course of clinical care identifies more CRGA than hotspot assays, as of cases negative for GA by hotspot testing, 76% had CRGA. For breast cancer cases, avenues of benefit were identified from targeted therapies such as PARP inhibitors, palbociclib, and various investigational agents.
PD.1.04 A Comprehensive Description of the Molecular Epidemiology of Somatic Mutations in Actionable Genes in NSCLC Chilean Patients
Authors: A. Blanco, G. Sepúlveda-Hermosilla, R. Lizana, L. Ramos, M. Freire, M. Spencer, S. Chernilo, C. Fernández, O. Aren, P. Perez, R. Armisen
Journal: Journal of Thoracic Oncology (2018)
Indirect treatment comparison of blinatumomab versus inotuzumab ozogamicin for the treatment of adult patients with relapsed or refractory acute lymphoblastic leukemia receiving zero or one prior salvage therapy.
Authors: Jinlin Song, Qiufei Ma, Wei Gao, Ze Cong, Jipan Xie, Zachary Franklin Zimmerman, Laura Belton, Janet Franklin, Stephen Palmer
Journal: Journal of Clinical Oncology (2018)

e19000 Background: Blinatumomab (BLIN) and inotuzumab ozogamicin (INO) have demonstrated improved outcomes against standard of care (SOC) among adult patients with relapsed or refractory acute lymphoblastic leukemia (R/R ALL) in phase 3 clinical trials. In the absence of head-to-head studies, indirect comparisons provide valuable information to guide the appropriate use of alternative therapies. Methods: Matching-adjusted indirect comparisons were conducted using patient-level data from the BLIN trial (TOWER) and published aggregated data from the INO trial (INO-VATE). Patients with 2+ prior salvage therapies from TOWER were excluded since these patients were not included in INO-VATE. To ensure balance in the remaining patients, TOWER population was reweighted to match the average baseline characteristics in INO-VATE, including sex, age, race, performance status, bone marrow blast, previous salvage therapy, previous allogeneic transplantation, complete remission with complete hematologic recovery (CR) to most recent induction therapy, and duration of first remission. The endpoints were overall survival (OS) and CR. Relative restricted mean survival time (RMST) at 12 months was also estimated. Results: After excluding patients with 2+ prior salvage therapies, 310 patients in TOWER were included (BLIN: 203; SOC: 107). After reweighting, all baseline characteristics listed above were balanced between the two trials. The median OS was 9.3 months for BLIN and 7.7 months for INO (weighted log-rank test p = 0.4). The RMST at 12 months was 1.6 months longer for BLIN than for INO (95% CI = [0.1, 3.2], p < 0.05). The CR rates were similar (anchor-based difference = -2.8%, 95% CI = [-17.5%, 11.9%], p = 0.7). Conclusions: After adjusting for heterogeneities in patient characteristics, BLIN demonstrated a potential survival benefit versus INO among adult patients with R/R ALL receiving zero or one prior salvage therapy. Our findings indicate potentially important differences in efficacy which help to inform treatment choices. Additional head-to-head studies would help to confirm our findings.
Lung cancer screening findings in academic versus community imaging centers.
Authors: Katherine Janssen, Abbie Begnaud
Journal: Journal of Clinical Oncology (2018)

e18915 Background: Widespread adoption of lung cancer screening (LCS) with low-dose computed tomography (LDCT) is an opportunity to save lives. However, one risk of screening is undergoing unnecessary testing to evaluate false positive findings, including incidental findings (IF). Many screening exams will detect findings unrelated to lung cancer that result in additional testing. There is minimal published data about real-world occurrence of incidental findings the screening population. Our goal is to compare and to characterize the common LCS findings among screened patients at academic and community imaging centers. Methods: This is a retrospective registry review of 1718 who underwent lung cancer screening exams from December 1, 2013 through July 17, 2017. This registry includes patients screened at academic and community imaging centers. Information collected included patient age, gender, co-morbidities, smoking history, and incidental findings, if any, on their CT scan. Descriptive statistics were used to characterize the incidence and type of IF. Results: 701 of 1718 exams (41%) were performed at academic imaging centers. Each center had similar proportions of abnormal findings related to lung cancer (LungRADS 3, 4A, 4B or 4X) but drastically different proportions of exams with incidental findings. 61% of exams performed at an academic medical center those reported incidental findings compared to 25.2% of community-performed imaging exams. CAC was the most common incidental finding in exams from both academic and community imaging centers (25.1% vs 16.8% respectively), followed by ILA (22.2% vs 2.6%). Conclusions: The value of LCS is both in its ability to detect lung cancer early but also to optimize the non-cancer related risks and benefits of screening. Incidental findings are common but substantial variability is seen between academic and community imaging centers in the same health system in Minnesota. It is unclear is if this represents different reporting approaches or different patient populations. Further investigation is necessary to identify factors which contribute to these differences.
Systemic immune-inflammation index is prognostic in testicular germ cell tumors with PD-L1 expressing tumor infiltrating lymphocytes.
Authors: Michal Chovanec, Zuzana Cierna, Vera Miskovska, Katarina Machalekova, Katarina Kalavska, Katarina Rejlekova, Daniela Svetlovska, Dusan Macak, Stanislav Spanik, Karol Kajo, Pavel Babal, Jozef Mardiak, Michal Mego
Journal: Journal of Clinical Oncology (2017)

e16042 Background: Systemic immune-inflammation index (SII) and programmed death-ligand 1 (PD-L1) are prognostic in various types of malignancies. Recently we have shown a prognostic value of PD-L1 expression on tumor cells and tumor infiltrating lymphocytes (TILs) in testicular germ cell tumors (GCT). This study aimed to evaluate prognostic role of SII in a GCT population of patients expressing PD-L1 on TILs. Methods: SII was calculated using platelet (P), neutrophil (N) and lymphocyte (L) counts measured prior to chemotherapy (SII = P x N/L). SII was calculated in our discovery set of 216 patients with GCT treated at National Cancer Institute and St. Elisabeths' Cancer Institute between 1999 and 2015. A model with median obtained from the discovery data was tested in an independent validation set of 181 patients that were included in a retrospective study evaluating PD-L1 on TILs in GCT. PD-L1 on TILs was detected by immunohistochemistry and scored semiquantitatively by weighted histoscore method. SII was dichotomized into low and high categories based on median value. Results: Low SII ( &lt; 1003) was found in 133 patients (73.5%) as opposed to 48 patients (26.5%) with high SII (≥ 1003). Ten (5.5%) and 171 patients (94.5%) from the validaton set had low (HS &lt; 150) and high (HS ≥ 160) expression of PD-L1 on TILs, respectively. Discovery group of patients with high SII had significantly shorter PFS (HR = 4.48, 95% CI 2.44 – 8.23, p = 0.0000) and OS (HR = 6.10 95% CI 3.11 – 11.95, p = 0.0000) opposite to patients with low SII. PFS from validation set confirmed shorter PFS (HR = 3.03, 95% CI 3.86 – 7.46, p = 0.0062) and OS (HR = 6.49 95% CI 2.10 – 20.03, p = 0.0001) in patients with high versus low SII. A combined prognostic value of PD-L1 TILs and SII uncovered three prognostic groups. The best prognosis was observed in patients with low SII and high PD-L1 on TILs, the worst prognosis was seen in patients with high SII and low PD-L1 on TILs. Patients with SII and PD-L1 on TILs both values high or low had intermediate prognosis. Conclusions: SII was prognostic in our patients with GCT independently of international germ cell cancer collaborative group criteria, suggesting involvement of immune mechanisms in the behavior of GCT.
TCT-25 Radial artery access and outcomes for left main stem PCI: an analysis of 19,482 cases from the British Cardiovascular Intervention Society national database
Authors: tim kinnaird, Richard Anderson, Alexander Sirker, Peter Ludman, Mark de Belder, Keith Oldroyd, Nick Curzen, Adrian Banning, Mamas Mamas
Journal: Journal of the American College of Cardiology (2018)