tbuckley/cabot-search huggingface dataset:
Incidence of <i>Neuregulin1</i> (<i>NRG1</i>) gene fusions across tumor types.
Authors: Stephen V. Liu, Rebecca Feldman, Hossein Borghaei, Shirish M. Gadgeel, Patrick C. Ma, Jorge J. Nieva, Alexander I. Spira, Ari M. Vanderwalde, Antoinette J. Wozniak, Sushma Jonna, Edward S. Kim
Journal: Journal of Clinical Oncology (2018)

12084 Background: NRG1 gene fusions are an emerging potential therapeutic target in non-small cell lung cancer (NSCLC). NRG1 is a ligand for the HER3 tyrosine kinase and NRG1 fusions can activate oncogenic HER2/HER3 and PI3K-AKT signaling. The pan-ErbB inhibitor afatinib has been associated with durable response in patients with NRG1+ lung adenocarcinoma. NRG1 fusions and the specific fusion partners have not been well characterized across different tumor types. Methods: Tumor samples submitted for profiling between 01/16 - 01/18 at a CLIA-certified genomics laboratory (Caris Life Sciences, Phoenix, AZ) were assayed with anchored multiplex PCR for targeted RNA sequencing with the ArcherDX fusion assay (Boulder, CO). Novel isoforms and fusions with high reads (defined as > 10% of total reads), high confidence after bioinformatics filtering and considered in-frame are included in this analysis. Results: In a cohort of 14,150 tumors successfully assayed, 31 cases (0.2%) harbored an NRG1 fusion. The incidence of NRG1 fusions varied by tumor type: 0.9% thyroid (1/116), 0.5% ovary (3/574), 0.5% cholangiocarcinoma (1/194), 0.4% pancreas(2/510), 0.3% NSCLC (20/5869), 0.2% breast (2/927), 0.2% sarcoma (1/475), and 1 case in sinonasal teratocarcinoma (SNTC). One of the 20 NSCLC cases (NRG1- SDC4) had squamous histology, the remaining were adenocarcinoma. No NRG1 fusions were detected in colorectal cancer (0/1382) or glioblastoma multiforme (0/1200). In NSCLC, NRG1 fusions were mutually exclusive with oncogenic alterations in EGFR, ALK, ROS1, RET, and KRAS with the exception of one case that co-occurred with a KRAS G12C mutation. Fusion partners are shown below. Conclusions: Gene fusions in NRG1 can be identified in various tumor types though the highest number of events was in NSCLC. Consistent detection of NRG1 fusions will need to account for multiple fusion partners. The optimal treatment of tumors harboring NRG1 fusions needs to be established. Tumor Type NRG1 fusion partners NSCLC CD74 (n = 8), SDC4 (n = 3), ATPB1, DPYSL2, MRPL13, OAS2, PARP8, ROCK1, SLCA3, TNC, WRN (n = 1, each) Ovary ZMYM2, SETD4, TSHZ2 (n = 1, each) Pancreas CDH1, VTCN1 (n = 1, each) Breast ADAM9, COX10-AS1 (n = 1, each) Thyroid TRAF3IP2 Cholangiocarcinoma NOTCH2 Sarcoma WHSC1L1 SNTC HMBOX1
Developing a telemedicine triage system to manage patient flow at a high volume cancer center urgent care.
Authors: Christian Otto, Diane Lauren Reidy, Stutman Robin, Kara Sutton, Erika Dugan, Lee Erickson, Lori Roland-Plonski, Jason Napoli, Danny Joseph, Jeffrey S. Groeger
Journal: Journal of Clinical Oncology (2018)

e18517 Background: MSKCC sees a high volume of patients with acute presentations at its 21 bed Urgent Care Center (UCC). We examined the incidence and underlying reasons for unplanned inpatient admissions through the UCC. Next, we sought to reduce the number of over-capacity days and improve patient flow by applying telemedicine strategies. Methods: Data for all MSKCC UCC presentations in 2015 were collated and categorized as “walk-in”, or “notified” by patient’s oncology service. Admitted patients were subdivided by disease and staging, presenting symptom(s), and number of inpatient bed days. Results: In 2015 there were 23,087 UCC patient visits; 11,398 were admitted (49.4%). Walk-in patients accounted for 35.4% of admissions (N = 4040). In contrast, 64.6% of admissions (N = 7358) were referred by their oncologist: 58.5% (N = 4307) after speaking with their oncologist’s office by phone, 37.8% (N = 2783) following a visit to their oncologist’s office, and 3.6% (N = 368) were referred from other locations. From home, patients presented to the UCC in 3.2±2.9 hours. From their oncologist’s office patients presented in 1.1±1.2 hours. The mean time in the UCC from time of check-in to an admission was 3.1±2.5 hours, and from check-in to UCC discharge was 4.5±3.2 hours. The 5 most common presenting symptoms were fever N = 1096 (13.7%), pain N = 662 (8.3%), dyspnea N = 446 (5.6%), nausea and vomiting N = 226 (2.8%), and failure to thrive N = 158 (2.0%). Conclusions: A large number of patients present to the UCC acutely with symptoms that could be managed proactively to decrease time to disposition, and to potentially prevent UCC admission. Based on these findings, we are implementing a telemedicine triage program to streamline acute patient care. Upon notification by the patient’s oncologist, UCC providers will contact patients by phone or video to triage care, including: scheduling of imaging where appropriate, and leveraging the MSKCC regional sites by diverting appropriate patients for their required workup.
The negative predictive value (NPV) of FDG-PET/CT in the Head and Neck Squamous Cell Carcinoma (HNSCC) N0 patient, the first report of the ACRIN 6685 trial.
Authors: Brendan C. Stack, Fenghai Duan, JoRean Sicks, Justin Romanoff, Adam Opanowski, Dunstan Horng, Irene Mahon, Christopher S. Hollenbeak
Journal: Journal of Clinical Oncology (2017)

6041 Background: This study evaluated the negative predictive value for node negativity in HNSCC. Methods: Patients were enrolled from 8/10 until 12/16 from 38 centers in the US and 1 center in China. This was a prospective, non-randomized trial. The study was designed to recruit 292 patients; however, 287 were enrolled by study closure. Inclusion criteria were newly diagnosed cT2-T4 SCC patients from the head and neck with one side cN0 who were willing to undergo an elective neck dissection. CN0 was determined by a negative neck CT or MR scan. Exclusions included non-SCC, non-surgical candidates, skin, nasopharynx or sinus primaries. PET/CT imaging reading performed centrally and pathology were analyzed at the neck level (left or right). To estimate confidence intervals, we used a nonparametric bootstrap to account for the correlation of data between sides of neck of the same patient. Correlative data and other image analyses will be reported separately. Results: PET/CT scans and pathology were available for 211 (table) N0 sides of neck for review at last interim analysis. NPV estimate with 95% CI for bilateral necks: 0.896 (0.831, 0.950) and specific to the N0 sides: 0.922 (0.862, 0.973). Conclusions: FDG PET/CT has high NPV for node negativity in HNSCC. This may obviate the need for elective neck dissection in N0 HNSCC patients. This trial was open about three times longer than planned, and a major obstacle to accrual was the generalized assumption among the oncology community that PET/CT had a high NPV. Therefore, patients sent to study centers for further diagnosis and treatment often had their PET/CT scans performed on non-ACRIN certified equipment. This required investigators to forgo offering the trial or the PET/CT was repeated. Our results may suggest application for pre-operative PET/CT nodal imaging of other primaries/lymphatic basins staged cN0. Funding from the National Cancer Institute through the grants U01 CA079778, U01 CA080098, CA180820, CA180794. Clinical trial information: NCT00983697. [Table: see text]
Cost-effectiveness analysis of nivolumab and apatinib in third-line gastric cancer therapy.
Authors: Jiajia Yuan, Lin Shen
Journal: Journal of Clinical Oncology (2018)

e18931 Background: Very few options exist for gastric cancer patients treated with two or more previous chemotherapy regimens. Recent randomized controlled trial ATTRACTION-2 of US Food and Drug Administration-approved anti-PD-1 drug nivolumab demonstrated improved patient outcomes in patients with advanced gastric or gastro-oesophageal junction cancer. Methods: To understand the value of nivolumab better, we developed a Markov model to compare the cost-effectiveness of nivolumab and apatinib for third-line treatment of gastric cancer by estimating costs (2017 RMB) and quality-adjusted life years (QALYs). Rates for drug discontinuation, frequency of adverse events, disease progression, and death obtained from randomized phase III trials were used to determine the likelihood of transition between states. Health states were defined for initial treatment, progression, and death. Results: Compared with the apatinib treatment strategy, nivolumab was associated with incremental costs and benefits of RMB ¥118,809 (USD $18,745) and -0.19 QALYs, respectively. Dominance report suggested that nivolumab third-line treatment strategy is dominated by apatinib. Conclusions: From the perspective of policy makers, a 75% reduction of current price is necessary for anti-PD-1/anti-PD-L1 drugs in third-line gastric cancer therapy according to our prediction. This phenomenon may encourage more medical industry competing in Chinese anti-PD-1/anti-PD-L1 market.
Understanding real-world treatment and outcomes in patients diagnosed with metastatic triple negative breast cancer (mTNBC).
Authors: Karen E Skinner, Mark S. Walker, Amin Haiderali, Lee Steven Schwartzberg
Journal: Journal of Clinical Oncology (2018)

e13116 Background: Treatment options are limited to chemotherapy for patients (pts) diagnosed with mTNBC. Patients with mTNBC are known to have poorer prognosis in clinical trials than other subgroups of metastatic breast cancer, but few studies have evaluated outcomes in real-world pts, including those who do not receive any systemic treatment. Methods: A retrospective chart review of pts with mTNBC from 9 US community oncology practices was conducted. Eligible pts were females age 18 and older who were diagnosed with mTNBC between 1 January 2010 and 31 January 2016. Results: The study included 608 pts: 60.2% White, 33.9% African American, 5.9% Other; mean (standard deviation) age 57.5 (13.5) years. Most pts had ductal carcinomas (82.9%), and over half were postmenopausal (58.2%). Overall, only 505 of the 608 pts (83.1%) received systemic treatment following mTNBC diagnosis. Pts who were treated, on average, were younger than pts who were untreated (mean age 56.6 vs. 61.5, P= .002), and were more likely to be stage IV at initial diagnosis (28.1% vs. 8.7%, P< .001). They were also less likely than untreated pts to have brain metastasis (10.7% vs. 24.3%, P= .001), impaired performance status (ECOG ≥2 or notation of impairment, 8.5% vs. 23.3%, P< .001), or comorbidities (30.5% vs. 40.8%, P= .042). Median first-line progression-free survival was 4.2 months for treated pts. Those who were non-white, had greater comorbidity burden, and > 1 metastatic site were more likely to progress than other pts (HR: 1.25, P= .030; HR: 1.12, P= .024; HR: 1.53, P< .001, respectively). Median overall survival was significantly longer for pts who received treatment than those who did not (12.8 months vs. 4.8 months, P= .030). Pts with impaired performance status and > 1 metastatic site had a higher risk of death than other pts (HR: 1.57, P= .002, HR: 1.61; P< .001, respectively). Conclusions: Nearly 20% of women with mTNBC were not treated, which indicates unmet need. Differences in patient characteristics by treatment status showed an association between poor health status and nontreatment. Overall prognosis remains poor, which highlights the opportunity for newer therapies to address the unmet need of these pts.
Pediatric End-stage Liver Disease Scores as a Method of Assessing Mortality Risk or Prioritization to Transplantability
Authors: Evelyn K. Hsu, Simon P. Horslen, Jorge D. Reyes
Journal: JAMA Pediatrics (2018)

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Single-arm confirmatory trial of laparoscopy assisted total or proximal gastrectomy with nodal dissection for clinical stage I gastric cancer: Japan Clinical Oncology Group study JCOG1401.
Authors: Hitoshi Katai, Junki Mizusawa, Hiroshi Katayama, Chikara Kunisaki, Shinichi Sakuramoto, Noriyuki Inaki, Takahiro Kinoshita, Yoshiaki Iwasaki, Kazunari Misawa, Nobuhiro Takiguchi, Masahide Kaji, Hiroshi Okitsu, Takaki Yoshikawa, Masanori Terashima
Journal: Journal of Clinical Oncology (2018)

4028 Background: Laparoscopy-assisted distal gastrectomy (LADG) for gastric cancer is safe and feasible. Several phase III studies try to confirm non-inferiority of LADG to open surgery for early disease. No prospective study evaluating laparoscopy-assisted total gastrectomy (LATG) and laparoscopy-assisted proximal gastrectomy (LAPG) has been completed yet in terms of both safety and long-term survival. Considering that results of phase III trial to evaluate the long-term outcome of LADG (JCOG0912) would guarantee that of LATG/LAPG, we conducted a single-arm confirmatory trial to evaluate the safety of LATG/LAPG for clinical stage I (T1N0/T1N1/T2N0) proximal gastric cancer. Methods: Laparoscopic operators were limited to credentialed surgeons. The extent of nodal dissection was selected based on the Gastric Cancer Treatment Guidelines in Japan. The mini-laparotomy incision was required to be shorter than 6 cm. The primary endpoint was the proportion of a grade 2 (CTCAE ver. 4.0) or greater esophageal anastomotic leak. Sample size was determined to be 245 considering threshold of 8% and expected value of 3% with one-sided alpha error of 2.5% and statistical power of 90%. Results: Between April 2015 and February 2017, 245 eligible patients were enrolled. LATG/LAPG was performed in 195/50. Among them, only 6 patients (2.4%) converted to open surgery. Clinical T1N0/T1N1/T2N0 was 213/9/24. Extent of dissection was D1 in 0, D1+ in 230, and D2 in 15. Median operation time was 309 minutes (IQR: 265-350). Median blood loss was 30 ml (IQR: 10-85). Grade 2 or greater esophageal anastomotic leak was 2.4% (6/245; 95% CI, 0.9–5.3; one-sided p = 0.0002). The overall proportion of in-hospital grade 3 or 4 adverse events was 29% (71/245). The proportion of intra-abdominal abscess, anastomotic stricture, and pancreatic fistula was 3.7%, 3.3%, and 2.0%, respectively. There were no treatment-related deaths. Conclusions: This trial confirmed the safety of LATG/LAPG. When non-inferiority of LADG is confirmed in our phase III trial, LATG or LAPG will be established as one of the standard treatments for clinical stage I gastric cancer. Clinical trial information: UMIN000017155.
Allogeneic hematopoietic cell transplant (alloHCT) for hematologic malignancies in human immunodeficiency virus infected (HIV) patients (pts): Blood and Marrow Transplant Clinical Trials Network (BMT CTN 0903)/AIDS Malignancy Consortium (AMC-080) trial.
Authors: Richard F. Ambinder, Juan Wu, Brent Logan, Christine Durand, Ryan Shields, Uday R. Popat, Richard F. Little, Deborah Mcmahon, John Watson Mellors, Ernesto Ayala, Lawrence D. Kaplan, Ariela Noy, Alan Howard, Stephen J. Forman, Adam M Mendizabal, Mary M. Horowitz, Willis H. Navarro, Joseph C. Alvarnas
Journal: Journal of Clinical Oncology (2017)

7006 Background: AlloHCT has been regarded as risky in HIV pts, with concern about fatal infection. We set out to assess feasibility and safety of alloHCT in this first prospective multicenter trial. Methods: The primary endpoint was 100-day non-relapse mortality (NRM). Pts had drug-susceptible HIV; age ≥ 15 yr; adequate organ function; acute myeloid leukemia (AML) or acute lymphocytic leukemia (ALL), high risk myelodysplastic syndrome (MDS), or Hodgkin (HL) or non-Hodgkin lymphoma (NHL) beyond first CR; an 8/8 HLA-matched related or at least a 7/8 unrelated donor. Pts received myeloablative (MA) or reduced intensity (RI) regimens. HIV outgrowth assays (VOA) were performed with resting CD4+T-cells in pts who had clinically undetectable HIV plasma RNA at 1 yr. Results: Between 5/2012 and 12/2015, 17 pts underwent alloHCT. Pts were: male (17); white (11), African American (3), Other/Unknown (3); median age 47 yrs (25-64). Associated malignancies were AML (9), ALL (2), MDS (2), HL (1), NHL (3). Median CD4 was 224 (55-833). Conditioning was MA (8) and RI (9). At 100 days there was no NRM, 13 pts were in CR, 4 pts had relapsed/progressive disease; and 8 pts achieved complete chimerism. The cumulative incidence of Grades (Gr) II-IV acute Graft vs Host Disease (GvHD) was 41 % (95%CI: 18 %, 64%). At 6 mo, OS was 82 % (95% confidence interval [CI]: 55%, 94%); 9 pts achieved complete chimerism. At 1 year, OS was 57 % (CI: 31%, 77 %); 8 deaths were from relapsed/progressive disease (5), acute GvHD (1), adult respiratory distress syndrome (1) and liver failure (1). Infections were reported in 11 pts (3 Gr 2, 8 Gr 3). Infectious HIV was detected by VOA in 2 of 3 pts who were mixed chimeras but 0 of 2 who were 100% donor. Median follow up of survivors is 24 mo (7 to 27 ). Conclusions: HIV pts with heme malignancies underwent MA or RI alloHCT without any100-day NRM and there were no infectious deaths at 1 year. AlloHCT should be considered the standard of care for HIV pts who meet usual eligibility criteria. Clinical trial information: NCT01410344.
Chinese doctors' practices regarding fertility preservation in cancer patients.
Authors: Yumei Lin, Fengchun Zhang, Xu Yingchun
Journal: Journal of Clinical Oncology (2018)

e18864 Background: The aim of this study was to explore the current practice of Chinese doctors with different clinical specialties regarding fertility preservation (FP) of cancer patients and to determine the relative barriers to these practices. Methods: A study was conducted in doctors with different clinical specialties assisting cancer patients through a structured self-report questionnaire between January 2017 and December 2017, and 179 medical oncologists, 77 radiation oncologists and 79 surgeons were included. Results: There were 88 male and 247 female doctors with a median age of 35.94±6.27 years in the current study. Although 96.4% of the doctors reported knowing that chemo-radiation with impairment of fertility and 85.1% of them thought it was necessary to recommend fertility preservation, but only 28.1% of them have ever discussed the reproductive issues with their patients and referred their patients to fertility experts.The oncologists and surgeons, female physicians, and those with higher professional titles and education background were more likely to make the FP recommendation. Among the 63.3% clinicians who reported informing about male FP, only 37.9% and 21.2% noted the exact methods and place for FP, respectively. Similarly, for the 65.1% participants who informed about female FP, the percentage was 49.9% and 24.5%, respectively. As far as “which kinds of cancer should be offered FP” was concerned, 52.8% of the doctors support breast cancer, then 49.3% for gynecologic tumor, 48.4% for head and neck cancer, 46.9% for gastrointestinal carcinoma, 46.3% for urogenital neoplasms, and 43.0% for hematological and lymphatic systemic disease. When it comes to the barriers of FP decision-making, 32.8% of the oncologists reported their concern on whether cancer patients were suitable to reproduce. 27.6% of the physicians honestly admitted that they lacked expertise in fertility preservation and 22.7% of them worried about delayed cancer treatment. Conclusions: The results of this study confirm that it is important to help the doctors to establish the perceptions of reproductive issues for cancer patients in China. And it is also urgent to overcome the barriers that emerged as being relevant to oncologists' FP practices.
Targeted sequencing identified JAK/STAT pathway alteration in KRAS mutated metastatic colorectal cancer.
Authors: Shu-Jen Chen, Tan Kien Thiam, Shang-Yun Liu, Hua-Chien Chen, David Chung, Hung-Chih Hsu
Journal: Journal of Clinical Oncology (2016)

e15113 Background: KRAS is frequently mutated in patients with metastatic colorectal cancer (mCRC). However, no effective treatment strategy has been developed for KRAS mutated mCRC patients. The aim of this study was to compare genomic alteration patterns between KRAS wild-type (WT) and KRAS mutated (MT) colorectal cancers and to identify potentially actionable genomic alterations that could be targeted with approved agents. Methods: Seventy-seven archived primary tumor tissues of stage IV mCRC cancer were analyzed, including 49 KRAS-WT and 28 KRAS-MT tumors. We assessed all coding exons in 409 cancer-related genes for base substitutions, indels, and copy number alterations. The average sequencing depth was > 1,000×. Results: We observed 513 genomic alterations in 203 genes in all tumors (mean 10.8, range 3 – 57). The average number of genomic alterations was similar in KRAS-WT (10.5, range 3 - 57) and KRAS-MT (11.4, range 6 - 18) (p = .57) tumors. The most common mutations were PT53, APC and SYNE1 in both groups. FBXW7 and BRAF mutations were only detected in KRAS-WT tumor while CARD11, PTPRD, CDH11 and EML4 mutations were only detected in KRAS-MT tumors. Copy number analysis found that MYC is the most frequently amplified gene while GNA11, TCF3 and FLT4 were frequently deleted. Interestingly, TCF3, FLT4 and TSC2 deletion were more frequently detected in KRAS-WT tumor whereas BIRC5 and SEPT9 deletions were more frequent in KRAS-MT tumors. Notably, mutations in genes involved in JAK/STAT signaling, including PTPRD, PTPRT, JAK1 and JAK3, were significantly enriched in KRAS-MT tumors (42.8% vs 10.2%, p = .0015). In contrast, genomic alterations in PI3K/AKT/mTOR pathway involving TSC2, AKT1, AKT2, MTOR, PTEN andPIK3RI, were more frequent in KRAS-WT tumors. Conclusions: Our study discovered that mCRC tumors harbored different mutation patterns depending on their KRAS genotype. As both JAK/STAT and PI3K/AKT/mTOR pathways have approved targeted agents, the difference in genomic alteration may be translated into treatment strategy.