tbuckley/cabot-search huggingface dataset:
Update survival analysis from a multicenter, randomized phase 3 study on the optimization of the combination of bevacizumab with FOLFOX/OXXEL in patients with metastatic colorectal cancer (mCRC).
Authors: Antonio Avallone, Guglielmo Nasti, Gerardo Rosati, Chiara Carlomagno, Lucrezia Silvestro, Antonino Cassata, Carmen Romano, Vincenza Granata, Alfonso De Stefano, Salvatore Tafuto, Franco Bianco, Valeria Vicario, Domenico Bilancia, Secondo Lastoria, Antonella Petrillo, Francesco Izzo, Ciro Gallo, Paolo Delrio, Alfredo Budillon, Maria Carmela Piccirillo
Journal: Journal of Clinical Oncology (2018)

3562 Background: Bevacizumab is a humanized anti-vascular endothelial growth factor (VEGF) monoclonal antibody, approved in combination with chemotherapy in the treatment of mCRC. It has been hypothesized that the schedule of administration might be critical and that anticipating bevacizumab to chemotherapy might improve treatment efficacy. Present analysis updates 2016 findings Methods: mCRC pts, ≤ 75 years, ECOG PS ≤1, were randomized (1:1) to receive standard (S) administration of bevacizumab (5mg/kg d1 Q14) with chemotherapy (mFOLFOX/OXXEL regimen for 12 cycles) vs experimental (E) bevacizumab given whenever 4 days before chemotherapy (same dose and cycles number ). Pts could receive maintenance bevacizumab with fluoropyrimidines until disease progression or unacceptable toxicity. Primary end point was the objective response rate (ORR). With 80% power and 2-tailed alpha 0.05, an expected 20% increase in response rate, 230 pts were planned. Analyses were based on the intention to treat. Correlative studies on biomarkers and FDG-PET were also planned. Results: From May 2012 to Dec 2015, 230 pts were randomised to E (n = 115) and S (n = 115) arm. Median age was 62 years (IQ range 53-68), 79% were PS 0, 93% were not pretreated, 53% had a single metastatic site, 71% had a left primary site (71% and 74% in S and E, respectively), 54% were RAS-mutant (47% and 62% in the S and E arm, respectively). ORR was 54% in both arms (p = 0.89). With a median follow-up of 42 months, 209 PFS events and 150 deaths were reported. Median PFS was 10.5 and 11.7 months (HR 0.80, 95% CI: 0.61-1.06; multivariate adjusted p = 0.12) and median OS was 23.8 and 29.1 months (HR 0.70, 95% CI: 0.51-0.97; multivariate adjusted p = 0.03), in the S and E arm, respectively. Distribution of patients receiving treatment after progression was similar across the arms. Conclusions: Anticipating bevacizumab to chemotherapy does not improve ORR and PFS, but results associated with a significantly longer OS. Further studies are required to confirm whether this schedule might improve treatment efficacy in mCRC patients. Supported by the Italian Ministry of Health. Clinical trial information: NCT01718873..
Evaluation of RNA Polymerase I Subunit C gene (<i>POLR1C</i>) as prognostic biomarker in cancer.
Authors: Junior Smith Torres-Roman, Alexandra Prado, Cesar H. Saravia, Luis Usquiano, Jenny Zavaleta, Leny Bravo
Journal: Journal of Clinical Oncology (2018)

e24325 Background: POLR1C is a gene encoding a subunit common to RNA polymerases I and III. Currently, mutations in this gene are known have been associated with Treacher Collins Syndrome and hypomyelinating leukodystrophy. Despite high transcriptional activity is a characteristic of cancer cells, only few works linked its expression to some tumoral aggressiveness features. Our aim in this work was to evaluate the relationship of POLR1C with the outcome in different types of malignant neoplasm. Methods: The association of POLR1C expression with the patients outcome was evaluated in meta-analysis of public datasets of several malignancies. Results: The results of our meta-analysis indicate that high levels of POLR1C expression (over the median) was significantly associated with a shorter overall survival in kidney cancer, HR=1.50 (95%IC: 1.28-1.75); pancreatic cancer, HR=1.43 (95% IC:1.15-1.78), breast cancer, HR=1.37 (95% IC:1.15-1.62), liver cancer, HR=1.35 (IC95%:1.04-1.76), ovarian cancer, HR=1.29 (95% IC:1.15-1.44) and colon cancer HR=1.22 (95%IC:1.04-1.44). Conclusions: POLR1C expression was associated with a shorter overall survival in kidney, pancreatic, breast, liver, ovarian and, colon cancer. Its evaluation as biomarker in these malignancies should be deeply explored.
Discordant breast cancer: Low risk genomic, high risk pathologic.
Authors: Leann Blankenship, Daniel Ezekwudo, Ishmael A. Jaiyesimi, Osama Alassi, Michael J. Stender, Susanna S. Gaikazian
Journal: Journal of Clinical Oncology (2017)

e18160 Background: Studies using the 21-gene recurrence score (RS) have shown low risk pathologic features and RS breast cancers do not benefit from systemic chemotherapy (CTx). However, data is lacking for patients with discordant risk factors and which feature, genomic or clinical, plays more of a role in determining outcomes. Methods: Retrospective analysis was conducted to identify breast cancer patients with discordant features, defined as low genomic/high pathologic factors, from 2011 to 2016. Patients were hormone-receptor positive with RS &lt; 18 and had ³ 2 high risk factors: tumor size ³2cm, lymph node (LN) positivity, or grade 2-3 disease. Results: There were 469 patients with low risk RS were identified of whom 118 met discordant risk criteria. Patients management is depicted in Table 1. Of the 118 discordant patients, 22 had breast cancer recurrence as either metastatic (1) or locoregional (21); 11 being ipsilateral while the remainder were contralateral. Patients with ipsilateral recurrences had partial mastectomy and radiotherapy as initial management. CTx was received in 30 patients despite low RS. Recurrences occurred in 31.8% of patients who received adjuvant CTx. The majority of recurrences occurred &gt;5 years after initial diagnosis. Conclusions: Our results show both genomic and pathologic features were important in determining the need for CTx in early stage breast cancer but neither had a greater impact. Thus, we advocate a more comprehensive and individualized approach, taking into account comorbidities, genomic, and pathologic features, for addition of CTx to standard hormonal therapy. Further studies are needed to determine the proper treatment of this unique patient population. [Table: see text]
TCT-34 Effect of Baseline Anemia on Outcomes After PCI and CABG in Patients With Left Main Disease: The EXCEL Trial
Authors: Prakriti Gaba, Patrick Serruys, Joseph Sabik, A. Pieter Kappetein, Shmuel Chen, David Taggart, Marie-Claude Morice, David Kandzari, John Puskas, Ovidiu Dressler, Aaron Crowley, Ori Ben-Yehuda, Roxana Mehran, Gregg Stone
Journal: Journal of the American College of Cardiology (2018)
NRG BN002: Phase I study of checkpoint inhibitors anti-CTLA-4, anti-PD-1, the combination in patients with newly diagnosed glioblastoma.
Authors: Andrew E. Sloan, Mark R. Gilbert, Peixin Zhang, Kenneth D. Aldape, Jing Wu, Lisa R. Rogers, Patrick Y. Wen, Igor J. Barani, Fabio Massaiti Iwamoto, Raju R. Raval, Alfredo Daniel Voloschin, John Frederick De Groot, Minhee Won, Minesh P. Mehta
Journal: Journal of Clinical Oncology (2018)

2053 Background: Glioblastoma (GBM) remains an incurable disease that is associated with impaired immunity. Recently, immune checkpoint inhibitors (ICIs) have demonstrated efficacy in several solid tumors including brain metastases. This study evaluated the safety of anti-CTLA-4 (Ipilimumab; IPI) and anti-PD-1 (Nivolumab; NIVO) ICIs alone or in combination in newly diagnosed GBM during adjuvant temozolomide (TMZ) treatment. Methods: This is a phase I study of IPI (3mg/kg), NIVO (3mg/kg), and the combination (1 mg/kg & 3 mg/kg respectively) followed by an expansion cohort for the combined treatment of adults with confirmed unifocal, supratentorial newly diagnosed GBM after gross or near total resection. Treatment with ICIs started after standard chemo-radiotherapy along with adjuvant TMZ; starting dosing of ICIs were at target with dose reduction planned for toxicity. The primary endpoint was the dose limiting toxicity (DLT) from the start of ICIs to 8 weeks after in each arm. A standard up-and-down design was used, with 6 evaluable patients enrolled at a given dose level. The dose level would be declared safe if no more than 1 of 6 had an DLT. Results: Thirty-two patients were enrolled at 9 institutions, 6 to each arm and 14 to the expansion cohort. One patient was not treated, yielding 31 analyzable. Median age was 54 years (range: 23-74), 68% were male and 84% were white. Overall, treatment was well tolerated with a 16% rate of Grade 4 events; the combination did not have an increased toxicity rate and there was no reported Grade 5 event. One DLT was seen in each single-agent arm; none in the combination arm. Median follow-up time was 7.1 months (range: 0.5-21.3) for all analyzable patients, at which time 10 had progressed (32%) and 8 had died (26%), 7 due to disease progression and 1 due to pulmonary embolism. For the 18 patients who had at least 1-year follow-up, 6 on each arm, 3 died within 1 year, 1 on each arm. Conclusions: IPI and NIVO are safe and tolerable with similar toxicity profiles noted with other cancers when given with adjuavant TMZ for newly diagnosed GBM. These results provide necessary safety data justifying the performance of a subsequent trial to test the efficacy of ICIs in this disease. Clinical trial information: NCT02311920.
Personal goals among women with breast cancer.
Authors: Anu Paul, Sarah Linsky, Celine Croft, Hui Tan, Dena Schulman-Green
Journal: Journal of Clinical Oncology (2016)

e21554 Background: Goal-setting can help match patients’ goals and values to their health care. Little is known about the nature of goals among cancer patients. Our purpose is to describe goals among a sample of breast cancer patients. Methods: We identify goals as part of an ongoing randomized controlled trial testing a cancer self-management intervention. Eligible participants are women aged 21+ with stage I-IV breast cancer receiving any kind of treatment, who have > 6 month prognosis, speak English, and reside in Connecticut. We seek potential participants through Smilow Cancer Hospital. At baseline data collection, we ask participants to identify 3 goals for their health or life for the coming 3 months. We report data from participants enrolled 7/2014-10/2015. Two reviewers independently code goals using content analysis; a third reviewer settles disagreements. Results: To date, participants’ (n=66) mean age is 51.3 (range 33-75 years). The sample is about half White (47%) and half minority (53%). Most are well-educated (74.2%) and 48.4% work full- or part-time. Over half are very spiritual (56.1%). Participants are well distributed with regard to cancer stage. Most are receiving chemotherapy (80.3%). We identified 8 categories of personal goals: Healthy Lifestyle, Cancer Management, Social, Emotional, Leisure, Family, Spiritual, and Altruism (Table). Conclusions: Participants’ goals span a range of health and life goals, but most commonly focus on healthy lifestyle behaviors. Although our work is limited by a small sample, this preliminary categorization informs the literature on goal-setting during cancer self-management. Clinicians should discuss personal goals with patients over time to consistently align personal and treatment goals and to ensure adequate support Clinical trial information: NCT02148575.Participants’ (n=66) baseline goals. Category Subcategory Healthy Lifestyle N=63 Weight n=8 Exercise n=30 Diet n=20 Maintain health n=5 Cancer Management N=42 Treatment n=15 Manage side effects n=17 Be cancer-free n=7 Follow physician’s advice n=3 Social N=30 Get organized n=7 Work/school n=20 Living situation n=3 Emotional N=21 Maximize life n=4 Stay positive n=8 Normalcy n=9 Leisure N=14 Visiting places n=9 Social relationships/activities n=5 Family N=5 Spiritual N=4 Altruism N=3
Impact of early progression on prognosis for non-small cell lung cancer patients with EGFR mutation.
Authors: Kanako Yoshitsugu, Hirotsugu Kenmotsu, Katsuhiro Omae, Shota Omori, Kazuhisa Nakashima, Kazushige Wakuda, Akira Ono, Tateaki Naito, Haruyasu Murakami, Toshiaki Takahashi
Journal: Journal of Clinical Oncology (2017)

e20570 Background: For epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) patients, EGFR-tyrosine kinase inhibitors (TKIs) improve progression free survival compared with cytotoxic chemotherapy. However, some patients show early progression (EP) in first-line EGFR-TKI treatment, and their prognosis is still unclear. This study aimed to examine the implications of EP for prognosis of EGFR mutant NSCLC patients. Methods: Advanced EGFR mutant NSCLC patients treated with gefitinib (GEF) as first-line between 2005 and 2015 at Shizuoka Cancer Center were retrospectively reviewed. EP on GEF was defined as disease progression before 180 days according to the Jackman criteria. Results: Forty-five of 198 patients treated with GEF as first-line, showed EP. Patient characteristics was as follows (with EP/ without EP) : median age (range), 69 (32-88)/ 70 (35-92) years; male, 40/ 28%; ECOG performance status (PS) 0-1, 64/ 79%; deletion in exon 19 (del 19), 36/ 53%; L858R in exon 21, 53/ 43%; never smoker, 44/ 65%; liver metastasis, 27/ 12%; brain metastasis, 44/ 37%. The median overall survival was 395 days (95% CI: 267-547 days) for patients with EP and 979 days (95% CI: 808-1124 days) for those without EP. Post progression survival after treatment with GEF was significantly shorter in patients with EP (median: 254 days vs. 420 days, HR: 0.55 (95% CI: 0.39-0.79), P &lt; 0.05). Among patients with EP, 56% received subsequent chemotherapy (patients without EP: 71%). In univariate analysis, EP was significantly associated with four factors; liver metastasis, smoking history, PS 2-4, absence of del 19. In multivariate analysis, smoking history (OR: 0.38, 95% CI: 0.18-0.80), PS 2-4 (OR: 0.43, 95% CI: 0.19-0.98), and del 19 (OR: 2.15, 95% CI: 1.04-4.45) were significantly correlated (P &lt; 0.05) with EP. Conclusions: Patients with EP during first-line GEF therapy for advanced EGFR mutant NSCLC showed poor prognosis. Since smokers, patients with PS 2-4, or absence of del 19 tend to show EP, improving first-line treatment is necessary to improve their prognosis.
Distribution of lymph node metastases and impact on survival benefit of oxaliplatin-containing chemotherapy in stage III colon cancer.
Authors: Byung Woog Kang, In Teak Woo, Gi Yong Hwang, Dong Won Baek, In Hee Lee, Soo Jung Lee, Yee Soo Chae, Jong Gwang Kim, Jun Seok Park
Journal: Journal of Clinical Oncology (2018)

e15683 Background: This study investigated the effect of oxaliplatin-containing adjuvant chemotherapy according to the distribution of lymph node (LN) metastases for patients with stage III colon cancer (CC). Methods: Among 1554 patients with CRC who underwent surgical resection between 2010 and 2014, 254 patients were diagnosed with stage III CC, and adjuvant chemotherapy was administered. LN distribution was classified on the basis of the Japanese classification of colorectal carcinoma. The patients were grouped into two categories: PLN (pericolic LN-positive, metastases adjacent to the colon or along the vascular arcades of the marginal arteries) and ELN (extrapericolic LN-positive, metastases along the major vessels or around the roots of the major vessels). Results: Among the 254 patients enrolled in this study, 175 belonged to the PLN group, whereas the remaining 79 patients to the ELN group. The PLN group was also divided into two groups based on the regimen: 79 patients were included in the non-oxaliplatin-containing chemotherapy group, while 96 in the oxaliplatin-containing chemotherapy group. The characteristics were similar between two groups, except for age and body mass index. During the median follow-up duration of 48.5 months (range 4.7-94.0), the estimated DFS and OS at 3 years was 82.8% and 90.1%, respectively. In the univariate analysis, oxaliplatin chemotherapy was not significantly associated with DFS (p = 0.457) and OS (p = 0.147). In the multivariate analysis, the addition of oxaliplatin showed no prognostic significance on DFS (p = 0.073) and OS (p = 0.594). In particular, the subgroup analysis in the PLN group with less than two positive LNs also revealed no association in terms of DFS and OS. Conclusions: In conclusion, oxaliplatin-containing adjuvant chemotherapy was not found to have a significant effect on survival for stage III CC patients with only PLN, suggesting hypothesis of non-oxaliplatin-based adjuvant chemotherapy for those subgroup. Accordingly, the current study can provide a novel strategy for subgroups with limited LNs distribution, considering that the state of the LN distribution is a critical factor for therapeutic success.
Effectiveness of icotinib against non–small-cell lung cancer with uncommon EGFR mutations.
Authors: Shengyu Zhou, Xingsheng Hu, Yan Wang, Li Junling, Liqiang Zhou, Xuezhi Hao, Yutao Liu, Yuankai Shi
Journal: Journal of Clinical Oncology (2018)

e21083 Background: Epidermal growth factor receptor (EGFR) gene mutations other than 19 Del and 21 L858R have not been fully described due to their rarity. Here we present a retrospective study to evaluate the efficacy of icotinib, an EGFR TKI in non-small-cell lung cancer patients with uncommon EGFR mutations. Methods: We retrospectively reviewed the clinical-pathological and effectiveness data for 100 consecutive patients with advanced NSCLC who were responsive to icotinib treatment. Patients with 19 Del alone, or EGFR 21 L858R alone were chosen as comparison. Results: Among 100 patients, 85 and 15 had common and uncommon mutations, respectively. Four patients had a single mutation in 18 or 20 exon, and 11 had a complex mutation with del-19 or L858R. There was no significant association between the presence of different mutation type and the type of any clinical and pathological characteristics. Prolonged but not significant progression-free survival (PFS) was noted in patients with common EGFR mutations [18.07 (14-26.23) vs 12.9 (8.43-23.27), p = 0.056]. Patients without brain metastases had increased PFS to icotinib than those with brain metastases (18.07 [95%CI14.77-27.03] vs 13.17 [8.63-22.63], p = 0.038). Conclusions: Our findings suggested that patients with uncommon mutations, especially complex mutations, had favorable clinical benefits from icotinib. However, the heterogeneous sensitivity to EGFR TKI of uncommon EGFR mutations should be considered when making clinical decision.
Abstract 20288: Prognosis of Patients With Fulminant Myocarditis Requiring Mechanical Circulatory Support
Authors: Naoki Nakayama, Katsutaka Hashiba, Kiwamu Iwata, Masayoshi Kiyokuni, Naohiro Komura, Manabu Nitta, Teruyasu Sugano, Kazuo Kimura
Journal: Circulation (2016)

Introduction: Fulminant myocarditis is a rapidly progressive life-threatening disease and requires acute mechanical circulatory support. Venoarterial extracorporeal membranous oxygenation (V-A ECMO...
Abstract 16382: Comparison of Provocative Maneuvers to Demonstrate Latent Obstruction in Hypertrophic Cardiomyopathy
Authors: Chadi Ayoub, Jeffrey B Geske, Carolyn M Larsen, Christopher G Scott, Kyle W Klarich, Patricia A Pellikka
Journal: Circulation (2016)

Introduction: Exercise stress echocardiogram (ESE) is recommended for patients with hypertrophic cardiomyopathy (HCM) if a 50 mmHg gradient is not present at rest or provoked with Valsalva or amyl ...
TCT-181 Early Changes in Quality of Life after Transcatheter Aortic Valve Replacement: Results from the 3M-TAVR Trial
Authors: Sandra Lauck, David Wood, Janarthanan Sathananthan, None suzanne baron, Karin Humphries, Julie Park, Yinshan Zhao, Anita Asgar, Richard Cook, Dale Murdoch, Vinod Thourani, Susheel Kodali, Harindra Wijeysundera, Robert Welsh, Madhu Natarajan, Jean-Bernard Masson, Tamim Nazif, Marian Hawkey, Patricia Keegan, Danny Dvir, John Cairns, Martin Leon, John Webb, David Cohen
Journal: Journal of the American College of Cardiology (2018)
eXalt3: A phase III study of ensartinib (X-396) in anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC).
Authors: Leora Horn, Yi-Long Wu, Martin Reck, Chris Liang, Fenlai Tan, Kimberly Harrow, Vance Oertel, Gary Dukart, Tony Mok
Journal: Journal of Clinical Oncology (2017)

TPS8578 Background: Ensartinib is a novel, potent anaplastic lymphoma kinase (ALK) small molecule tyrosine kinase inhibitor (TKI) with additional activity against MET, ABL, Axl, EPHA2, LTK, ROS1 and SLK. Ensartinib has demonstrated activity in ALK treatment naïve and previously treated patients and has a generally well tolerated safety profile. Methods: eXalt3 (NCT02767804) is a global, randomized, open-label phase III study comparing the efficacy and safety of ensartinib to crizotinib in ALK- positive TKI naïve non-small cell lung cancer (NSCLC) patients. It is being conducted in &gt; 100 sites in North America, South America, Europe, and the Asia/Pacific region. Enrollment began in 2016. The primary efficacy endpoint is progression free survival (PFS) assessed by independent radiology review. Secondary efficacy endpoints include overall survival, response rates (overall and central nervous system [CNS]), PFS by investigator assessment, time to response, duration of response, and time to CNS progression. Approximately 270 patients with ALK+ NSCLC who have received no prior ALK TKI and up to one prior chemotherapy regimen will be randomized 1:1 to ensartinib 225 mg QD, or crizotinib 250 mg BID, with stratification based on prior chemotherapy, ECOG performance status (PS), CNS metastases and geographic region. Eligibility includes patients ≥ 18 years of age, stage IIIB or IV ALK+ NSCLC. Patients are required to have measurable disease per RECIST 1.1, adequate organ function, and an ECOG PS of ≤2. Adequate tumor tissue (archival or fresh biopsy) must be available for central testing. The study has &gt; 80% power to detect a superior effect of ensartinib over crizotinib in PFS at a 2-sided alpha level of 0.05. Clinical trial information: NCT02767804.