tbuckley/cabot-search huggingface dataset:
Validation of lymphocyte to monocyte ratio in resected small bowel adenocarcinoma as a predictor of survival.
Authors: Brandon M. Huffman, Zhaohui Jin, Siddhartha Yadav, Shruti Patel, Amit Mahipal, Thorvardur Ragnar Halfdanarson
Journal: Journal of Clinical Oncology (2019)

e15799 Background: Lymphocyte to monocyte ratio (LMR) has been described as a prognostic factor in many solid tumors including colorectal adenocarcinoma. LMR has not been investigated as a prognostic factor in small bowel cancers. In this study, we aimed to evaluate prognostic factors in resected small bowel adenocarcinoma including LMR. Methods: Two hundred forty-one patients who underwent resection for stage I-III small bowel adenocarcinoma were retrospectively identified utilizing the pathology database at a single tertiary referral institution from 1994 to 2015. All patients had complete follow up data and were included in the survival analysis. One hundred sixty-nine patients had preoperative peripheral blood counts available for analysis. Plot of martingale residuals against LMR were used to establish best cutoff points for LMR. A training set for LMR included consecutively identified patients from 2006 to 2015, and a validation cohort including patients identified from 1994 to 2005 was used. Overall survival was performed utilizing Kaplan-Meier method, and Wilcoxon tests were used for statistical comparisons. Cox proportional hazards were performed and all tests were two sided. P value of &lt; 0.05 was considered significant. Results: Median overall survival for the entire group was 54.5 months (95% CI: 37.2-81.2 months) with 5- and 10-year overall survival of 48% and 35%. The training set for LMR included 81 patients, and the validation set included 88 patients. The cutoff of 1.56 was chosen based on most significant p value (p = 0.002). When combined, the overall area under the curve (AUC) for LMR was 0.63, p &lt; 0.01, (specificity 37.3%, sensitivity 90.1%, positive predictive value 33.1%, and negative predictive value 92.2%). There were 126 patients with LMR &gt; 1.56 and 43 patients with LMR &lt; 1.56 in the entire cohort. In multivariate analysis, LMR under 1.56 was a negative prognostic factor, HR = 2.20 (95% CI: 1.27-3.84, p &lt; 0.01). In addition to LMR, age &gt; 60 years and advanced T stage were independently negative predictors of overall survival in all patients. Conclusions: Lymphocyte-to-monocyte ratio &lt; 1.56 is a validated negative prognostic factor in resected small bowel adenocarcinoma.
Activity of larotrectinib in TRK fusion cancer patients with brain metastases or primary central nervous system tumors.
Authors: Alexander E. Drilon, Steven G. DuBois, Anna F. Farago, Birgit Geoerger, Juneko E. Grilley-Olson, David S. Hong, Davendra Sohal, Cornelis Martinus van Tilburg, David Simon Ziegler, Nora Ku, Michael Craig Cox, Shivani Nanda, Barrett H. Childs, Francois P. Doz
Journal: Journal of Clinical Oncology (2019)

2006 Background: TRK fusions are oncogenic drivers of a variety of cancers, many of which can involve the central nervous system (CNS). Larotrectinib is an FDA-approved selective TRK inhibitor for the treatment of TRK fusion cancer (Drilon et al, NEJM 2018). While larotrectinib has been shown to cross the blood–brain barrier (Ziegler et al, Br J Cancer 2018), its clinical activity in a series of TRK fusion cancers with primary or metastatic intracranial disease has not been described. Methods: Patients (pts) with non-primary CNS solid tumors with brain metastases, or primary CNS tumors harboring a TRK fusion treated with larotrectinib in 2 clinical trials (NCT02637687, NCT02576431) were identified. Larotrectinib was administered until disease progression (PD), withdrawal, or unacceptable toxicity. Disease status was investigator-assessed (RANO and RECIST). Data cutoff: July 30, 2018. Results: 14 pts were identified: 5 non-primary CNS solid tumors (3 lung cancer, 2 thyroid cancer; fusion type: 2 ETV6-NTRK3, 2 SQSTM1-NTRK3, 1 EPS15-NTRK1; age range 25–79 y) and 9 primary CNS tumors (3 glioma, 2 glioblastoma, 1 astrocytoma, 3 NOS; fusion type: 3 BCR-NTRK2, 2 KANK-NTRK2, 1 each of AFAP1-NTRK1, AGTPBP1-NTRK2, ETV6-NTRK3, SPECC1L-NTRK2; age range 2–79 y). In the 5 pts with non-primary CNS tumors, the best objective response to therapy was PR in 3 (60%, 1 pending confirmation), SD in 1 (20%), and not evaluable (NE) in 1 (20%). Duration of response ranged from 9+ to 13 mo. In the 9 pts with primary CNS tumors, disease control was achieved in all evaluable pts (primary PD not observed; 1 pt required dose increase). The best objective response to therapy was PR in 1 (11%; pending confirmation, −55% tumor shrinkage, ongoing at 3.7 mo), SD in 7 (78%; tumor shrinkage range −1% to −24% for pts with measurable disease, 5 had SD &gt; 4 mo), and NE in 1 (11%). Duration of treatment ranged from 2.8–9.2+ mo. Conclusions: Larotrectinib is active in pts with TRK fusion cancers with intracranial disease. Confirmed responses and durable disease control were seen in metastatic disease and primary CNS tumors of various histologies. These results further support expanded testing for TRK fusions across all cancers, including primary CNS tumors. Clinical trial information: NCT02637687 and NCT02576431.
Gastrointestinal symptoms and diagnosis preceding ovarian cancer diagnosis: Delays in diagnosis and resulting effects on treatment allocation.
Authors: Dana Meredith Chase, Brooke Harrow, Jessica Perhanidis, Bradley J. Monk
Journal: Journal of Clinical Oncology (2019)

e18195 Background: Ovarian cancer (OC) has a very poor clinical prognosis, with an average 5-year survival rate of &lt; 50%. Symptoms indicating OC are often nonspecific and overlap with gastrointestinal (GI) diagnosis (eg, gastroesophageal reflux disease [GERD], diverticulosis, irritable bowel syndrome [IBS]). Thus, OC diagnosis can be difficult, with most cases diagnosed at an advanced stage. This study examined whether women with a prior GI diagnosis are more likely to undergo neoadjuvant chemotherapy (CT) as their initial OC treatment modality compared to those without a prior GI diagnosis who may be likely candidates for primary debulking surgery (PDS). Methods: This retrospective study identified patients with newly diagnosed OC in the United States from January 2014–July 2018 using MarketScan Commercial and Medicare Supplemental Databases. Analysis was limited to women with commercial or Medicare coverage for ≥12 months before and ≥1 month after the index date (defined as the earliest date of an OC diagnosis or surgery) who underwent CT or PDS. Patients with GI symptoms were identified by diagnosis codes from claims in the year before the OC index date. Logistic regression analysis was used to test the hypothesis that women with a prior GI diagnosis are diagnosed with more advanced OC as signaled by their initial OC treatment (CT vs PDS) compared to women without a prior GI diagnosis. Results: Of the 5865 patients with OC identified, 23% had a diagnosis of ≥1 of the following GI disorders before their OC diagnosis: IBS, inflammatory bowel disease, diverticulosis, and GERD. Of these patients, 40% and 60% had GI disorders that occurred 6–12 months before and &lt; 6 months before their OC diagnosis, respectively. Women with a GI diagnosis were more likely to undergo CT versus PDS as their first OC treatment (odds ratio [OR], 1.37; P &lt; 0.0001), even when controlled for age, region, insurance plan type, and index year (OR, 1.23; P = 0.0021). Conclusions: In this administrative claims database, nearly one-quarter of women with OC had a prior GI diagnosis within the past year and were at greater odds of being diagnosed with more advanced disease requiring CT prior to surgical intervention.
Assessing real-world outcomes in precision oncology by linking clinical genomic testing to electronic medical records.
Authors: Debajyoti Datta, Theodore Goldstein, Atul Butte
Journal: Journal of Clinical Oncology (2019)

e18091 Background: With an ever-widening array of targeted therapies for cancer patients, clinical genomic testing has expanded rapidly in recent years. Tumor molecular profiling by next-generation sequencing is now considered a cornerstone of precision oncology, with the potential to offer patients with advanced cancers new therapeutic options. However, the overall impact of this testing remains unclear, and evidence demonstrating improvement in patient outcomes is lacking. The objective of this study is to assess the utility of clinical sequencing on the management of cancer patients. Methods: We present the development of a database that combines results of tumor mutation profiling using various next-generation sequencing panels (both external commercial tests and our institution’s internal sequencing panel), with a variety of data points from a de-identified representation of our institution’s electronic medical record (EMR). Assembling this data from different sources into a common relational database permits efficient retrospective analysis of real-world outcomes in patients with advanced cancers. Results: This study included over 3000 patients seen at UCSF Comprehensive Cancer Center since 2013. With this linked data set we analyzed the rate at which tumor molecular profiling affected clinical decision making, identified barriers to the efficient use of testing, and assessed for disparities in utilization. For example, by measuring patient survival relative to the clinical intervention of genomic testing for the subset of patients with a date of death recorded in our EMR, we found that a small fraction of patients died before results returned and any action could be taken, especially in cases of pancreatic cancer. Conclusions: We demonstrate that a common relational database combining clinical sequencing results with real-world EMR data provides insights into the optimal clinical use of tumor molecular profiling. This provides new opportunities for advancing precision oncology initiatives and improving patient care, such as identifying which cancer patients should get genomic testing and efficiently matching patients to clinical trials.
Systematic review and network meta-analysis of first-line treatments in mRCC.
Authors: Barbara Elizabeth Ratto, Sutirtha Chakraborty, Harini Chinthapatla, Manik Kalra
Journal: Journal of Clinical Oncology (2019)

e16086 Background: The approval of newer agents in metastatic renal cell carcinoma (mRCC) has changed the treatment paradigm in first-line settings. The aim of this review was to compare pazopanib against current first-line treatments in RCC. Methods: A systematic review was conducted that assessed pazopanib against first-line agents in treatment naïve patients with mRCC. Relevant databases and conferences were searched to identify randomized controlled trials (RCTs) assessing treatment naïve adult patient (≥18 years). Frequentist mixed treatment comparison (MTC) method was applied for the pairwise comparisons among treatments for ITT population and favorable, intermediate, and poor risk subgroups. Results: Twenty-three RCTs met the eligibility criteria. The MTC results showed that pazopanib was comparable to sunitinib in terms of progression free survival (PFS) and overall survival (OS) in ITT population. Cabozantinib was significantly better compared to pazopanib for PFS; however, there was heterogeneity in the patient population. Pazopanib was comparable to nivolumab + ipilimumab when assessed for PFS in ITT population; although, favorable risk patients treated with pazopanib achieved significantly higher PFS compared to nivolumab + ipilimumab (HR: 0.46, 95% CI: [0.37, 0.57]). Atezolizumab + bevacizumab and avelumab + axitinib were associated with significantly higher PFS compared to pazopanib. Cabozantinib and nivolumab + ipilimumab were associated with better OS compared to pazopanib. Conclusions: The newer agents i.e. cabozantinib and nivolumab + ipilimumab are approved for intermediate/poor risk patients. The results suggests that pazopanib is still a reliable option for treatment of patients in first-line settings, especially for favorable/intermediate risk patients.[Table: see text]
Efficacy and safety of intensified platinum-based neoadjuvant chemotherapy in locally advanced triple-negative breast cancer: Preliminary results of non-randomized phase II study.
Authors: Elena Glazkova, Mona Frolova, Marina Stenina, Ekaterina Ignatova, Alexey Rumyantsev, Alexander Petrovsky, Olga Krohina, Sergei Tjulandin
Journal: Journal of Clinical Oncology (2019)

e12116 Background: patients with locally-advanced triple negative breast cancer (TNBC) have dismal prognosis with current standard of care therapy. Pathologic complete response (pCR) is the most important prognostic factor for long-term survival of these patients. Methods: this was non-randomized prospective single-center phase II study. Key inclusion criteria were histologically verified locally advanced TNBC, non-eligibility for primary surgical treatment (ie, TNM stage Т 2-4 N 2-3 M 0 ) and no evidence of metastatic disease. Patients were treated with 8 cycles of neoadjuvant doxorubicine, paclitaxel and cisplatin chemotherapy (ATP; doxorubicine 40 mg/m2 day 1, paclitaxel 160 mg/m2 day 1 and cisplatin 50 mg/m2 day 1 every two weeks) with G-CSF support (filgrastim 5 mcg/kg day 2-6). After 8 cycles of chemotherapy patients were referred for surgical treatment; adjuvant radiation therapy was prescribed to all patients. Primary end point was pCR assessed in modified intention-to-treat population (ie, in patients who underwent surgical treatment). Key secondary endpoints were disease-free survival (DFS) and pCR rate according to BRCA status. Results: we enrolled 80 patients, 79 (98.7%) of them underwent surgical treatment and were included in the analysis. Median age was 46 years (25-68), 22 (27.1%) patients had BRCA1 mutations, 5382insC was the most common mutation (17 [77.2%] of patients); 1 (1.2%) patient had CHEK2 mutation. pCR was achieved in 51 (64.5%) patients. In with BRCA1-mutation carriers pCR rate was 61.9%, in patients with 5382insC – 81.2%. 2-year DFS was 77.3%; 2-year overall survival was 91.0% . Most common grade 3-4 adverse events were anemia (29.3%), neutropenia (17.8%), neuropathy (4.9%), stomatitis (3.7%) and thrombocytopenia (1.8%). Conclusions: the ATP regimen was effective in treatment of locally-advanced TNBC, especially in patients with founder 5382insC BRCA1 mutation for Slavic population and deserves further investigation.
Predictors of falls and fractures in patients (pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC) treated with apalutamide (APA) plus ongoing androgen deprivation therapy (ADT).
Authors: YaoYao Guan Pollock, Matthew Raymond Smith, Fred Saad, Simon Chowdhury, Stephane Oudard, Boris A. Hadaschik, David Olmos, Paul N. Mainwaring, Ji Youl Lee, Hiroji Uemura, Amitabha Bhaumik, Anil Londhe, Oliver Brendan Rooney, Angela Lopez-Gitlitz, Suneel Mundle, Shinta Cheng, Eric Jay Small
Journal: Journal of Clinical Oncology (2019)

5025 Background: SPARTAN, a phase 3 study of APA vs placebo (PBO) added to ongoing ADT in pts with nmCRPC, demonstrated that APA significantly prolongs metastasis-free survival, time to symptomatic progression, and second progression free survival (Smith et al. NEJM 2018), with no decline in health-related quality of life (Saad et al. Lancet Oncol 2018). SPARTAN pts who received APA, vs PBO, with ongoing ADT had higher rates of falls (15.6% vs 9.0%) and fractures (11.7% vs 6.5%). An analysis was performed to identify clinical characteristics associated with falls and fractures in APA-treated SPARTAN pts. Methods: Of 1207 pts enrolled, 806 were randomized to APA. Univariate Cox proportional hazards model (UVA) assessed the association of 47 baseline clinical characteristics (demographics, comorbidities, and medication use, including bone-sparing agents) with time to fall or time to fracture. Characteristics with p values &lt; 0.10 were included in a multivariate Cox proportional hazards model (MVA) to determine independent factors associated with these outcomes (p &lt; 0.05). Results: Factors associated with time to both fall and fracture on UVA (p &lt; 0.10) included older age, low serum albumin, and poor ECOG performance status (PS). Additional factors associated with time to fall were cerebrovascular accidents/transient ischemic attacks, neuropathy, depression, α-blocker use, and antidepressant use. On MVA, older age, poor ECOG PS, history of neuropathy, and α-blocker use were independently associated with falls; older age and low serum albumin were independently associated with fractures (Table). Conclusions: At initiation of APA added to ongoing ADT, nmCRPC pts with higher risk of falls and fractures can be identified and are candidates for intervention to reduce the risk for these events. Clinical trial information: NCT01946204. [Table: see text]
Thermoregulation via Temperature-Dependent PGD2 Production in Mouse Preoptic Area
Authors: Tongfei A. Wang, Chin Fen Teo, Malin Åkerblom, Chao Chen, Marena Tynan-La Fontaine, Vanille Juliette Greiner, Aaron Diaz, Michael T. McManus, Yuh Nung Jan, Lily Y. Jan
Journal: Neuron (2019)
Abstract 14777: Transcription of Select Homeobox Genes Increases in Patients with Heart Failure-Reduced Ejection Fraction Who Have Improvements in Left Ventricular Ejection Fraction on β-blocker Therapy
Authors: David P Kao, Elaine Epperson, Anis Karimpous-Fard, Edward M Gilbert, Brian D Lowes, Lawrence E Hunter, Michael R Bristow
Journal: Circulation (2012)

Introduction: In patients with heart failure-reduced ejection fraction the mechanisms of left ventricular reverse-remodeling in response to β-blocker therapy are not fully understood. We used netwo...
Trend in the use of neo-adjuvant chemotherapy for the management of muscle invasive bladder cancer at a major tertiary care hospital in Pakistan.
Authors: Adnan Abdul Jabbar, Muhammad Asad Maqbool, Muhammad Bilal Mirza
Journal: Journal of Clinical Oncology (2019)

e16033 Background: Although the use of Neoadjuvant Chemotherapy (NAC) has now become the standard of care for Muscle Invasive Bladder Cancer (MIBC) in the world, most patients in lower- middle-income countries (LMIC), like Pakistan, are still undergoing upfront surgery despite being ideal candidates for chemotherapy. Multi-disciplinary tumor boards have been critical in the change of this trend in the developed world. We aimed to assess the trends in the use of NAC for patients with muscle invasive bladder cancer before undergoing definitive surgery. Methods: We included patients who underwent surgery for ≥ cT2 MIBC without distant metastasis between 2011 and 2015 at a tertiary care hospital in Karachi, Pakistan. We retrospectively assessed the trends in NAC compared to upfront surgery in these patients. Results: Among the 171 patients included in our study, only 4 (2.34%) received NAC, whereas the other 167 (97.67%) underwent upfront surgery without NAC. Out of the 90 patients who underwent surgery for MIBC between 2011 and 2013, none of them received NAC and underwent upfront surgery. Among the 81 patients with MIBC in 2014 and 2015, 4 patients received NAC before surgery whereas the other 77 underwent upfront surgery. Conclusions: The adoption of NAC for MIBC remains a challenge in lower- middle-income countries such as Pakistan. Introduction of a multidisciplinary tumor board in our hospital since 2014 has shown a slight change in this trend. Better communication between different departments remains the key in significantly changing the trend of a much desired standard of care.
Mogamulizumab-Associated Cutaneous Granulomatous Drug Eruption Mimicking Mycosis Fungoides but Possibly Indicating Durable Clinical Response
Authors: Lu Chen, Kenneth R. Carson, Karl W. Staser, Neha Mehta-Shah, András Schaffer, Ilana S. Rosman, Amy Musiek
Journal: JAMA Dermatology (2019)

This case series report of mogamulizumab-associated cutaneous granulomatous drug eruption (CGDE) describes 12 patients with mycosis fungoides (MF) whose CGDE mimicked the MF but was followed by durable clinical MF response.
Aircraft Cabin Hypoxia and Adverse Medical Events—Reply
Authors: Christian Martin-Gill, Thomas J. Doyle, Donald M. Yealy
Journal: JAMA (2019)

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ROR1-targeted delivery of miR-29b induces cell cycle arrest and therapeutic benefit in vivo in a CLL mouse model
Authors: Chi-Ling Chiang, Swagata Goswami, Frank W. Frissora, Zhiliang Xie, Pearlly S. Yan, Ralf Bundschuh, Logan A. Walker, Xiaomeng Huang, Rajeswaran Mani, Xiaokui M. Mo, Sivasubramanian Baskar, Christoph Rader, Mitch A. Phelps, Guido Marcucci, John C. Byrd, L. James Lee, Natarajan Muthusamy
Journal: Blood (2019)
A randomized phase 0 trial of the mitochondrial inhibitor ME344 or placebo added to the antiangiogenic (Aa) bevacizumab in early HER2-negative breast cancer (E-HERNEBC).
Authors: Miguel Quintela-Fandino, Serafin Morales, Alfonso Cortes Salgado, Luis Manso, Juan V Apala, Javier Cortes, Juan Antonio Guerra, Eduardo Caleiras, Francisca Mulero, Silvana Andrea Mouron
Journal: Journal of Clinical Oncology (2019)

3100 Background: We have shown that when Aas induce vascular normalization (VN), tumors escape upregulating mitochondrial metabolism. Mitochondrial inhibition with ME344 induced synergy with various Aas. We also found that VN could be traced by showing a 10% decrease in tumor FDG-PET SUV from day (d) 0 to d8 of Aa. We studied the activity of adding ME344 or placebo to Bev (Ki67 decrease) in E-HERNEBC in a phase 0 randomized trial. As a secondary objective we measured the activity of the combination in patients (Pts) showing VN according to FDG-PET. Methods: Untreated E-HERNEBC Pts with T &gt; 1cm, any N, M0 underwent a baseline FDG-PET (d1) and received a single dose of Bev (15mg/kg) prior to randomization (1:1) to arm A (FDG-PET on d8 followed by ME344 10 mg/kg IV on d8, d15 and d21) or Arm B (FDG-PET on d8 followed by placebo on d8, d15 and d21). Tumors were biopsied on d0 and 28. A 40 Pts sample size was powered to detect a 30% relative difference between arms in digitally acquired Ki67 decrease from d0 to d28 (alpha 0.05, beta 0.2). Results: Arm A: 20 Pts; Arm B: 21 Pts. Baseline characteristics were in arm A vs B: age 58.4(41.5-75.3) vs 53.6(39-82.8); T1(30%)/T2(60%)/T3(10%) vs T1(52%)/T2(48%)/T3(0%); N0(80%)/N1(20%) vs N0(81%)/N1(19%); ER+(75%)/TNBC(25%) vs ER+(71.4%)/TNBC(28.6%); Ki67 31.6% (3.6%-70%) vs 25.2% (1.2% - 81.5%). PET-SUV decreased &gt; 10% from d0 to d8 in 6/20 (arm A) and 6/21 (arm B) Pts. Two G3 adverse events (blood pressure) were reported (1/arm) and deemed related to Bev. Results of the primary endpoint: table. Conclusions: ME344 showed significant biologic activity, enhancing the effect in Ki67 decrease vs placebo when added to Bev in E-HERNEBC. The activity was greater in TNBC. A trend for greater activity in patients experiencing VN according to FDG-PET was observed. Clinical trial information: NCT02806817. [Table: see text]