tbuckley/cabot-search huggingface dataset:
Ipilimumab with anti PD-1 (nivovlumab or pembrolizumab) after progression on first line anti-PD-1 therapy for advanced melanoma.
Authors: Inderjit Mehmi, Jordan Hill
Journal: Journal of Clinical Oncology (2018)

e21552 Background: Metastatic melanoma (MM) continues to present a challenge in clinical oncology. Anti-PD-1 antibodies (nivolumab, pembrolizumab) have improved outcomes for a significant number of patients. Currently available data indicates upfront anti-PD-1 therapy will capture about 40% of MM. Outside of clinical trials, for the remaining options are limited. Ipilimumab (ipi) has retrospective second-line data after anti-PD-1 therapy failure (1). We report a plausible approach for ipi with anti-PD-1 in patients who progress on first-line MM therapy. Methods: From Sept 2015 to Sept 2017, 15 patients were identified with progressive disease after first-line anti-PD-1 therapy. Patients were treated with ipi and anti-PD-1 according to dosing from CHECKMATE 067 or KEYNOTE 029. Four cycles of ipi and anti-PD-1 were planned, followed by imaging to assess response, and maintenance anti-PD-1. Through retrospective chart review, data including age, sex, AJCC disease stage, prior therapies, number of ipi/anti-PD-1 doses completed, response, and adverse events were collected. Results: Evaluated patients had a median age of 62 (range, 47-80); 67% had AJCC stage M1a or b, 33% M1c; median number of prior therapies was 2 (range, 1-3); median number of ipi/anti-PD-1 cycles given was 4 (range, 1-4), 80% received 2 or more cycles, 53% received 4 cycles, 60% started maintenance anti-PD-1. We observed responses in 60% of patients, 27% partial response or stable disease, 33% complete response. 33% of patients had grade 3-4 events (dermatitis, encephalitis, and nephritis) leading to discontinuation of ipi/anti-PD-1. Conclusions: For patients who progress on first-line MM immunotherapy, ipi with anti-PD-1 is a reasonable option based on our small retrospective study. Ref: 1. Long GV, et al. Presented at: 13th Annual Society for Melanoma Research Congress. Boston, MA; November 6-9, 2016
The risk of malnutrition in patients with a colon carcinoma: An analysis of 13239 patients.
Authors: Carl Meissner, Joerg Fahlke, Ronny Otto, Christoph Kahl, Matthias Krueger, Walter Asperger, Henry Ptok, Hans Lippert, Karsten Ridwelski
Journal: Journal of Clinical Oncology (2017)

e15057 Background: The problem of under-nutrition and lack of nutrition is increasingly placed in the focus of operational discipline. Many of them are deficient in malnutrition before being hospitalized. In surgical therapy, the prevention of postoperative complications is of utmost importance. Due to a preoperative condition of malnutrition, the complication rate may increase and thus the associated increased treatment therapy costs per patient. The consequence, of course, is also a diminished postoperative treatment quality of the treating clinic. Methods: Prospective Multicentric Observational Study: "Quality Assurance Study Colorectal Cancer from 2010-2014 of the" An Institute for Quality Assurance in Operational Medicine "at the Otto-von-Guericke-University Magdeburg. The screening for lack of nutrition was carried out with the Nutritional Risk Screening (NRS 2002) Kondrup J et al .. Results: 13239 primary data records from 2010 to 2014 were included. With the help of the NRS screening, a total score in the form of a scoring system is possible. The sum of 3 points or more identifies a patient with a nutrition-related risk and should be a cause for further diagnosis and therapy. The median of all colorectal cancer patients was NRS = 3. 65.4% of the patients had an NRS score of &gt; = 3. In morbidity, the complications in colorectal cancer patients with NRS &gt; = 3 points are significantly increased. Also in the case of general complications (such as pneumonia, urinary tract infection, etc.) the rate increases with a larger NRS score. Conclusions: If the risk of malnutrition is small in patients with a colon carcinoma, the morbidity is low.
Efficacy and safety of bevacizumab in elderly or unfit patients with metastatic colorectal cancer: A systematic review and meta-analysis.
Authors: Lorenzo Antonuzzo, Giuseppe Aprile, Sandro Barni, Evaristo Maiello, Gianluca Masi, Fausto Petrelli, Mario Scartozzi, Valter Torri, Carmine Pinto
Journal: Journal of Clinical Oncology (2016)

e15029 Background: Bevacizumab improves progression-free survival (PFS) and overall survival (OS) of metastastic colorectal cancer (mCRC) patients when added to doublets in first-line setting. In the AVEX trial elderly patients exposed to capecitabine and bevacizumab had longer PFS and OS compared to those who received capecitabine alone. However, the use of bevacizumab in older or frail mCRC patients remains a matter of debate. This systematic review aimed to evaluate the efficacy and safety data of bevacizumab combined with monochemotherapy in elderly or unfit mCRC patients. Methods: A literature search for the identification of studies using monochemotherapy plus bevacizumab in unfit patients was performed in PubMed and EMBASE databases up to May 2015; the random-effects model was used to combine effect estimates and the I2 index to quantify the between-study heterogeneity unexplained by sampling error. Results: We screened 1,304 papers and after a double check we considered 56 papers for the full text evaluation; of these 38 were excluded and 10 were considered not evaluable for lack of data on unfit patients. Eight papers including 782 patients were considered eligible for the meta-analysis (3 RCTs, 4 single arm phase II trials and 1 prospective cohort study). Administered monochemotherapy was capecitabine in 531 (67.9%) pts and 5-fluorouracile (5-FU) in 251 (32.1%) pts; 500 (63.9%) pts also received bevacizumab. Median age was 75 years, 441 (56.4%) pts were male, ECOG performance status was 0-1 in 684 (87.7%) pts. The use of bevacizumab produced advantages in terms of both OS (HR 0.79; 95%CI:0.64-0.98 P = 0.03; I2= 0%) and PFS (HR 0.52; 95%CI:0.43-0.64 P < 0.00001; I2= 0%,; pooled effect estimates of RCTs have been previously reported). As expected, higher rates of all grade hypertension (27% vs 4.9%), bleeding (24% vs 6,4%), thromboembolic events (10% vs 5%) and proteinuria (25,6% vs 8,2%) were observed with bevacizumab. Conclusions: These data support the addition of bevacizumab to first-line fluoropyrimidine chemotherapy in daily practice in unfit and elderly patients with mCRC. The favorable safety profile of the antiangiogenic drug was confirmed.
Circulating tumor DNA profiling to reveal heterogeneity of EGFR-TKI resistance mechanisms in lung adenocarcinoma patients.
Authors: Rongrong Chen, Jun Zhao, Xingsheng Hu, Pingping Dai, Yuting Yi, Zhenzhen Zhou, Yanfang Guan, Meiru Zhao, Tao Liu, Ling Yang, Xin Yi, Xuefeng Xia
Journal: Journal of Clinical Oncology (2017)

11527 Background: EGFR-TKI therapy has significantly improved prognosis of NSCLC patients with EGFR sensitive mutation. However, almost all patients ultimately develop PD while receiving TKI treatment. Circulating tumor DNA (ctDNA) is promising as a minimally-invasive liquid biopsy for comprehensive analysis of molecular abnormalities. Methods: A total of 254 advanced lung adenocarcinoma patients with signs of EGFR-TKI resistance were enrolled in the study. ctDNA was analyzed using next-generation sequencing based ER-Seq method, which enables simultaneously assess single-nucleotide variants, insertions/deletions, rearrangements, and somatic copy-number alterations across 59 genes. Results: ctDNA profiling was possible for all patients, 172 patients had ≥ 1 ctDNA alteration(s). Median number of plasma somatic mutations was 2, predominantly located in EGFR and TP53, with MET, ERBB2 and PIK3CA followed. Of that, 30.6% of mutations detected in ctDNA were at a frequency below 1%. In exploring the mechanisms of TKI-resistance, we found TKI-sensitizing mutations were not detected in plasma of 138 patients (54.3%). Known mechanisms such as EGFR T790M/C797S mutation, activating mutations of PI3K- AKT- mTOR signaling, amplification of MET, activating mutation / amplification of ERBB2, activating mutation of KRAS, BRAF or mutations in EGFR EX20 other than T790M/C797S were identified in 59, 16, 8, 7, 3, 2, and 2 patients respectively. T790M/C797S was detected in 50.8% of patients with plasma positive for TKI-sensitizing mutations. Of note, C797S was only detected in patients treated with AZD9291. EGFR amplification were identified in 15 patients, though whether it would result in TKI-resistance was still controversial. Co-occurrence of resistance mechanisms were observed in 22 patients including 13 patients without TKI-sensitizing mutations. Conclusions: There was a high frequency of inter and intra-patient heterogeneity of resistance mechanisms after EGFR TKI therapy. ctDNA can be used as a ‘liquid biopsy’ to facilitate the broad exploration of potential resistance mechanisms.
Detection of actionable genome alterations using hybrid capture based next generation sequencing technology: NEOplus and NEOliquid.
Authors: Lukas C. Heukamp, Roopika Menon, Judith Mueller, Sotirios Lakis, Johannes Schulte, Gunther Wiest, Frank Griesinger, Christoph Salat, Rafal Dziadziuszko, Oliver Gautschi, Christian Grohe, John Crown, Johannes Heuckmann
Journal: Journal of Clinical Oncology (2016)

e23181 Background: Advances in the area of molecular cancer genomics has led to the identification of an increasing number of tumor-driven genetic alterations, with many being already candidates for tailor-made targeted therapies. NEO is a comprehensive molecular diagnostics platform capable of detecting genomic alterations including mutations, copy number alterations and translocations in both liquid biopsy (NEOliquid) and tumor tissue (NEOplus) samples to support cancer treatment decisions. Methods: We have developed a hybrid capture based next generation sequencing assay capable of detecting clinically relevant genomic alterations, such as point mutations, small insertions and deletions, gene fusions and copy number alterations. The NEOliquid assay is specifically designed for liquid biopsies and covers a panel of more than 30 genes. The NEOplus panel is specifically designed for FFPE tumor tissue covering more than 90 clinically relevant cancer genes. Results: Following signed patient consent, a series of lung cancer patient samples were examined using NEOliquid or NEOplus analysis. The spectrum of actionable genomic alterations that were detected, included oncogenic alterations (e.g. ARAF p.S214F, MET exon 14 skipping, BRAF p.N486_A489 deletion, microsatellite instability detection), resistance mutations (e.g. EGFR p.T790M), gene fusions (e.g. ALK-CARS, EML4-ALK, EGFR-KDD), and copy number alterations (e.g. ERBB2 amplifications) These cases are presented in their clinical context and treatment recommendations and outcome are discussed. Conclusions: Using the NEOplus and NEOliquid assays, we have identified a broad spectrum of therapeutically relevant genomic alterations with high sensitivity and specificity that resulted in concrete therapeutic recommendations. In comparison to standard diagnostics that require several methodologies for different types of genomic alterations, such as sequencing and FISH the NEO assays efficiently detect all relevant alterations in a single assay, thereby conserving both tissue and processing time.
Genomic history of the Sardinian population
Authors: Charleston W. K. Chiang, Joseph H. Marcus, Carlo Sidore, Arjun Biddanda, Hussein Al-Asadi, Magdalena Zoledziewska, Maristella Pitzalis, Fabio Busonero, Andrea Maschio, Giorgio Pistis, Maristella Steri, Andrea Angius, Kirk E. Lohmueller, Goncalo R. Abecasis, David Schlessinger, Francesco Cucca, John Novembre
Journal: Nature Genetics (2018)
Are radiologists reading mammograms for multiple facilities less likely to meet radiologist quality benchmarks?
Authors: Anne Marie Murphy, Dominique Sighoko, Harika Mathi, Bethliz Irizarry, Ariel J Thomas, Garth H Rauscher
Journal: Journal of Clinical Oncology (2016)

e18172 Background: Illinois Medicaid established a mammography quality program run by the Metropolitan Chicago Breast Cancer Task Force (MCBCTF). MCBCTF uses a set of established quality benchmarks including those related to radiologist quality (e.g., cancer detection rates, recall rates, proportion of cancers detected that are minimal/early stage). This analysis’ goal was to determine if radiologists’ ability to meet benchmarks was associated with the number of facilities they interpreted mammograms at. Methods: Retrospective data were collected for calendar year 2013 (CY13). We tabulated radiologists by number of facilities they read mammograms at, estimated the percentage meeting each benchmark, and obtained p-values from Chi-squared tests of association. We modeled the number of facilities as an ordinal independent variable against each binary benchmark separately to obtain Wald p-values for tests of trend. Results: 102 radiologists were linked to 27 corresponding facilities for CY13. The percentage of radiologists reading at a single facility who met benchmarks was greater than for those reading at 3+ facilities for cancer detection rate (96% vs. 75%), recall rate (84% vs. 50%), PPV1 (98% vs. 59%), and PPV3 (65% vs. 22%). Likewise, in trend tests, the probability of meeting benchmarks decreased with increasing number of contracted facilities for cancer detection rate, PPV1, PPV3, and recall rate(p < 0.05 ). There was no association for number of facilities with meeting benchmarks for proportion of breast cancers diagnosed as early stage and minimal. Conclusions: Mammography is a team process initiated by a mammography technologist taking an image to be read by radiologist. Authors’ prior research shows substantial variation in image quality in particular related to technologist associated issues. Close communication is needed between radiologists and technologists to ensure the best images are taken. Radiologists reading at multiple facilities may be less likely to maintain the level of communication/collaboration across facilities to ensure high quality mammography. They may be more likely to read mammograms off-site further hindering communication and feedback to the technologist.
Should MMMT of the endometrium/ovary be treated with anthracycline instead of taxane based chemotherapy?
Authors: Viola A. Heinzelmann-Schwarz, Kenneth Russell, Siti Omar, Andreas Schoetzau, Kerstin Hoeck, Marcus Vetter, Daniel A. Fink, Michael Friedlander, Neville F. Hacker
Journal: Journal of Clinical Oncology (2017)

5563 Background: Carcinosarcomas of endometrial (MMMT-E) and ovarian (MMMT-O) origin are rare biphasic tumors, associated with poor prognosis and thought to be epithelial in origin. In view of this, there has been a shift towards carboplatin and paclitaxel rather than anthracycline based chemotherapy regimens which were used when they were treated as “sarcomas”. The purpose of this large retrospective study is to determine whether this change in chemotherapy is associated with better outcomes. Methods: Firstly, clinicopathological features of patients with all stages of MMMT-E (n=103) and -O (n=17) were compared to patients with adenocarcinoma of the endometrium (n=172) and ovary (n=189) in a case-controlled study. Clinicopathological characteristics, FIGO stage, first-line regimens and patient outcomes were analyzed. Secondly, primary tumor specimens of high grade serous ovarian cancers (HGSOC, n=1290) and MMMT-O (n=450) from an independent cohort were analyzed using immunohistochemistry and next generation sequencing to predict response to chemotherapeutic agents. Results: MMMT have a poor prognosis, however, there was a plateau in survival of MMMT-E after 2.5 years in patients with FIGO stage I/II disease, with no recurrence/cancer deaths observed beyond this. There was a statistically significant worse relapse-free survival in patients with MMMT-E treated with carboplatin and paclitaxel compared to carboplatin and anthracyclines (p=0.0011). In the second independent prospective cohort comparing HGSOC versus MMMT-O, both were driven predominantly by p53 mutations. MMMT-O expressed statistically more commonly PI3KCA and KRAS (p=0.015 and 0.018), respectively. Of particular interest, both HGSOC and MMMT-O showed a higher percentage of probability of responding to a combination of carboplatin/anthracyclins (71.2 vs. 73.9%) than carboplatin/taxanes (58.4 vs 39.4%). Conclusions: Patients with MMMT-E and stage I/II have an excellent prognosis if there is no recurrence by 2.5 years. Platinum/anthracyclines regimens appear to be associated with a better outcome than platinum/taxane in MMMT-E and MMMT-O. This could be tested in an international prospective randomized controlled trial.
Incidence of T3a upstaging and survival after partial nephrectomy: Size-stratified rates and implications for prognosis.
Authors: Arnav Srivastava, Hiten Patel, Max Kates, Zeyad Schwen, Gregory Joice, Alice Semerjian, Phillip M. Pierorazio, Michael A. Gorin, Mohamad Allaf
Journal: Journal of Clinical Oncology (2017)

4588 Background: The use of partial nephrectomy (PN) to treat renal cell carcinoma has grown in the past decade, with expansion to larger tumors. Performing PN for larger tumors may increase the number of patients up-staged to pT3a after surgery, who may have underwent radical nephrectomy (RN), if known preoperatively. We aimed to estimate the proportion of patients up-staged to T3a disease after PN, stratified by size. We also compared size-stratified survival of up-staged pT3a patients to those with T1a, T1b, or T2 disease. Methods: From 1998 – 2013, we identified patients undergoing PN or RN from the Surveillance Epidemiology and End Results registries. The proportion of patients receiving PN found to have pT3a disease was quantified by size. Cox proportional hazards models compared cancer-specific (CSS) and overall survival (OS) for PN patients with pT1a, pT1b, and pT2 disease to size-stratified pT3a patients. Also, we compared PN patients with pT3a disease to RN patients with pT3a disease. Results: From the 28,854 patients undergoing PN, the estimated proportion up-staged to pT3a increased along with tumor size: 4.2% for T1a, 9.5% for T1b, and 19.5% for T2. Among those receiving PN, survival analysis showed worse CSS for up-staged pT3a patients versus stratified pT1a (HR = 1.87, p = 0.02), pT1b (HR = 1.91, p = 0.01), and pT2 (HR = 2.33, p = 0.01) patients. When assessing OS, only in tumors &lt; 4cm did the pT3a cohort demonstrate worse OS (HR = 1.25, p = 0.04). Comparing PN and RN for pT3a disease, size-adjusted analysis revealed no difference in CSS or OS. Lastly, among pT3a patients undergoing PN, patients with larger tumors, measuring 4 – 7cm (OS: HR = 1.44, p = 0.04) or 7 – 16cm (OS: HR = 2.64, p &lt; 0.01), had worse survival than those with tumors &lt; 4cm. Conclusions: A greater proportion of patients experience T3a up-staging after PN with increasing initial T stage. Up-staged pT3a patients have worse CSS after PN compared to those with similarly sized localized tumors. Also, pT3a patients after PN showed similar survival to pT3a patients after RN. However, pT3a patients undergoing PN had worse survival with increasing tumor size, reinforcing the need for improvements in identifying patients at risk of up-staging.
TCT-679 The impact of complete revascularization in STEMI patients with left ventricular dysfunction
Authors: Jeehoon Kang, Kyung Woo (KW) Park, You Jeong Ki, Tae-Min Rhee, Chengbin Zheng, Jung-Kyu Han, Han-Mo Yang, Hyun-Jae Kang, Bon-Kwon Koo, Hyo-Soo Kim
Journal: Journal of the American College of Cardiology (2018)
Open Atrial Transcatheter Mitral Valve Replacement in Patients With Mitral Annular Calcification
Authors: Hyde M. Russell, Mayra E. Guerrero, Michael H. Salinger, Melissa A. Manzuk, Amit K. Pursnani, Dee Wang, Hassan Nemeh, Rahul Sakhuja, Serguei Melnitchouk, Ashish Pershad, H. Kenith Fang, Sameh M. Said, James Kauten, Gilbert H.L. Tang, Gabriel Aldea, Ted E. Feldman, Vinnie N. Bapat, Isaac M. George
Journal: Journal of the American College of Cardiology (2018)
P04.42 Utilising whole transcriptome profiling to increase understanding of mechanisms driving IDH-mutant glioma progression and recurrence
Authors: A Cho, A L Hudson, E K Colvin, S A Hayes, H R Wheeler, V M Howell
Journal: Neuro-Oncology (2018)

Gliomas are the most common primary brain tumours in adults. IDH-mutated low-grade gliomas of astrocytic lineage (astrocytomas) have a relatively indolent clinical course; however, over time they progress to a higher grade. Molecular studies revealed recurrent tumours harbour more mutations upon malignant progression when treated with chemotherapy and/or radiotherapy compared to treatment-naïve tumours, however, genes which promote progression and recurrence in these tumours are unknown. This study aims to ascertain the natural history and treatment-induced effects of progressive IDH-mutated astrocytomas using whole transcriptome profiling. This study compared differences in the whole transcriptome profiles of 6 matched pairs of primary lesions with their higher-grade recurrent lesion. Tumour specimens from three patients who presented with grade 2 lesions and received no treatment following resection were collected. Tumours from another three patients who presented with grade 3 lesions and received radiotherapy alone following surgery were also collected. The recurrent high grade tumour of each patient that was collected from the second surgery was also analysed. RNA was extracted from frozen specimens and following quality control, analysed with the Illumina Next-Generation Sequencing platform (HiSeq HT paired end, TruSeq Kit). Comparison of primary and recurrent specimens identified 2042 differentially expressed genes (Fold Change ≥2) for the no-treatment group and 2066 differentially expressed genes for the radiotherapy group. Several differentially expressed gene families, including HLAs corresponding to MHC class II, cytokine families (IL, CXC, CC, TNF) and metalloproteinase families (ADAM, MMP), were associated with immune response and modification of the tumour microenvironment. The identification of these key gene families suggests the importance of the immune response and the tumour microenvironment to promote glioma progression. The identification of differentially expressed genes will improve our understanding of the mechanisms driving recurrence and progression of gliomas and may also reveal potential novel targets for additional therapies for this deadly cancer.