tbuckley/cabot-search huggingface dataset:
Molecular characterization and clinical features of Chinese pulmonary sarcomatoid carcinoma: analysis of 36 cases.
Authors: Di Wu, Yingying Yu, Jiwei Liu, Wei Liu, Shijie Lan, Qiliang Yin, Zhen Guo, Xuan Wang, Sisi Wang, Yi Zhao, Wenqiu Zhang
Journal: Journal of Clinical Oncology (2018)

e13616 Background: Pulmonary Sarcomatoid Carcinoma (PSC) ) is a group of non-small cell lung cancer(NSCLC) which has poorly differentiated and highly aggressive. It approximately accounts for 0.1–0.4% of all lung cancer, and portend a very poor prognosis. Methods: Thirty-six PSC patients were enrolled in this study. All of them were confirmed by the pathology from operation from June 2011 to June 2017. Next-Generation Sequencing (NGS) technology was performed. The survival rate was analyzed with SPSS22.0 statistical software,P < 0.05 statistically significant. Kaplan-Meier method for univariable survival analysis, Cox regression model for multivariable survival analysis. Results: 13 patients were successfully followed up. Among them, 8 patients died and 5 patients survived. NGS was performed, of which 18 variants were considered hot spot mutations, including the genes TP53 (69.4%) 、PKD1 (38.9%) 、THADA (33.3%) 、KRAS (30.6%) and so on. In univariable analysis that KRAS, BRCA1 and ALK mutations could affect the overall survival(OS) (P = 0.018, P = 0.000, P = 0.038). But there was no significant difference in OS between sex, age, tumor diameter, smoking history and TNM stage (P > 0.05). In multivariable analysis, KRAS (HR, 5.92;95% CI, 1.14–30.66; p = 0.034)was associated with worse survival. Conclusions: The high mutation frequency and new mutation sites will be useful for future diagnosis and molecular targeted therapy. However, in this study, tumor diameter and TNM staging were not correlated with the prognosis. It is different from the previous literature, and may be related to fewer patients were followed up. It needs to be perfected in the future research.
Pilot trial of KD018 with neo-adjuvant concurrent chemo-radiation therapy in patients with locally advanced rectal cancer.
Authors: Benjamin H Kann, Kimberly Johung, Yung-Chi Cheng, Wing Lam, Shwu-Huey Liu, Roy H. Decker, Susan A. Higgins
Journal: Journal of Clinical Oncology (2017)

e15162 Background: Neo-adjuvant chemo-radiation (CRT) is commonly used for rectal cancer, though is associated with gastrointestinal (GI) toxicity. KD018 is a state-of-the-art adaptation of Huang-Qin-Tang, a traditional Chinese medicine used to treat GI ailments. KD018 is a standardized pharmaceutical product subjected to quality-control measures including chemical fingerprinting by liquid chromatography and mass spectroscopy, individual target bioassays, and genomic bioresponse profiling to ensure product consistency. Clinical studies showed the safety of KD018 when given with chemotherapy to reduce GI toxicity. Preclinical study showed that KD018 decreased GI toxicity of abdominal RT without compromising tumor control. Here, we present preliminary results of the first clinical trial to use KD018 in patients receiving RT (neo-adjuvant CRT for rectal cancer). Methods: We conducted a pilot phase I trial of KD018 in patients with biopsy proven rectal adenocarcinoma, clinical stage T3-T4, N0-N2, who received neo-adjuvant CRT. Patients received 3D-conformal pelvic RT to 45 Gy in 1.8 Gy fractions, followed by a 5.4 Gy tumor boost with capecitabine 825mg BID on days 1-5 of RT (weekly) and KD018 800mg PO BID on days 1-4 of RT (weekly). Accrual goal was 24 patients. Primary endpoint was grade 3-4 GI toxicity by CTCAE v4.0 assessed weekly during RT, and until at least 30 days after RT. Secondary endpoint was pathologic response. Results: Of 19 patients enrolled, 16 began treatment, and 14 completed the protocol. Of these, there were no treatment related grade 3-4 GI toxicities (Table 1). Of 11 patients who completed surgery thus far, all had pathologic partial responses. Conclusions: This is the first clinical study of KD018 with concomitant RT and demonstrates the safety and favorable toxicity profile of this regimen compared to historical controls. These preliminary results warrant further study of the efficacy of KD018 as an adjuvant to pelvic CRT or RT to reduce GI toxicity. See table. Clinical trial information: NCT02178644. [Table: see text]
Development and validation of a Medicare health outcomes survey (MHOS) frailty index in multiple myeloma (MM).
Authors: Mark A Fiala, Emily Jean Guerard, Mark A. Schroeder, Keith Stockerl-Goldstein, Ravi Vij, Tanya Marya Wildes
Journal: Journal of Clinical Oncology (2017)

e21519 Background: Increasing age is associated with poorer outcomes in MM. However, biological aging (BA) is heterogeneous and does not correlate perfectly with chronological age (CA). A recently developed frailty of CA, functional status, and comorbidities is more predictive of toxicity, progression-free and overall survival (OS) than CA alone (Palumbo et al Blood 2015). We sought to apply the Rockwood Accumulation of Deficits approach to develop and validate a frailty index (FI) for older adults with MM. Methods: MHOS, a random survey of HRQOL (health related quality of life) in Medicare Advantage HMO enrollees, data were obtained from 1,747,042 non-cancer patients (pts) and 340 with newly diagnosed MM 1997-2011 from the SEER-MHOS linked dataset. In creating the FI, we considered only variables available throughout all 4 survey versions used since its initiation in 1998. We identified 34 variables including items related to function/mobility, comorbidities, and mental health. The FI was calculated as the number of deficits present, divided by the number total number of possible deficits, with possible scores ranging from 0 to 1 and higher values indicating more frail. Missing data points were excluded from the FI calculation. Cox regression analysis was performed to determine the association of the FI with OS, controlling for CA, gender, and race. The FI was first derived in the non-cancer cohort then applied in the MM cohort. Results: The median age was 72 for non-cancer pts and 75 for pts with MM; the median FI was 0.308 and 0.368, respectively. Among non-cancer pts, each 10% increase in FI (~3-4 more deficits) was associated with a 35% increased risk for death (aHR 1.352, 95% CI 1.350-1.354, p &lt; 0.001); among pts with MM it was associated with a 15% increased risk (aHR 1.147, 1.065-1.236, p &lt; 0 .001). Median OS for pts with MM in the lowest tertile of FI was 48 months (95% CI 42-56) compared to 23 months (17-33) for the highest tertile. Conclusions: Here we present a MHOS-based FI. The FI was more prognostic among non-cancer pts than among pts with MM, presumably because stage and tumor characteristics also contribute to OS in MM pts. Further exploration of the MHOS-FI in MM and other cancers is warranted.
TCT-677 Multivessel Versus Culprit-Lesion-Only Percutaneous Coronary Intervention in Acute Myocardial Infarction Complicated by Cardiogenic Shock: An Updated Meta-Analysis
Authors: Amartya Kundu, Partha Sardar, Nikolaos Kakouros, Dhaval Kolte, J. Dawn Abbott, Daniel Fisher, Dmitriy Feldman
Journal: Journal of the American College of Cardiology (2018)
Outcomes of diffuse large b-cell lymphoma with MYC and/or BCL2 protein expression treated with intensive chemotherapy.
Authors: Amir Issa, Vishwanath Sathyanarayanan, Michelle A. Fanale, Yasuhiro Oki, Fredrick B. Hagemeister, Sattva Swarup Neelapu, Loretta J. Nastoupil, Nathan Hale Fowler, Francesco Turturro, Mansoor Noorani, Mohamed Amin Ahmed, Richard Eric Davis, Maria Alma Rodriguez, Michael Wang, Lei Feng, Ken H Young, Timothy McDonnell, Chelsea Camille Pinnix, Luis Fayad, Jason R. Westin
Journal: Journal of Clinical Oncology (2016)

7563 Background: Several studies on single and double protein expressing DLBCL (DPL), defined as BCL2 positive in > 70% and MYC positive in > 40%, have identified inferior clinical outcomes when treated with standard RCHOP compared with non-expressing DLBCL. We present the clinical outcomes of patients with single protein expressing and DPL, in comparison with non-expressors of BCL2 or MYC, treated with REPOCH. Methods: We conducted a retrospective review of all consecutive, newly diagnosed DLBCL patients treated with REPOCH at MD Anderson Cancer Center from 2010 to 2014. Eligible patients were ≥ 18 years, had immunohistochemical (IHC) staining for MYC and BCL2, and had available data of demographics, pathology, treatment, and response. The objectives were to analyze demographics, response to therapy, and survival outcomes in comparison with MYC and BCL2 expression. Double hit lymphoma defined as MYC and BCL2 or 6 translocation were excluded from this analysis (Oki et al, British J Hematology 2014). Results: We identified DLBCL patients with IHC data for BCL2 (n = 151), MYC (n = 60), and both (n = 52). The demographic characteristics between the groups were similar (Table). The overall response rates (ORR), one and three year overall survival (OS) rates, and proportion of patients treated with dose adjusted EPOCH were not significantly different between patients with MYC + vs. -, BCL2 + vs. -, and DPL. In addition, ORR and OS were not different between DPL, MYC+BCL2-, MYC-BCL2+, or MYC-BCL2- patients. The median follow up time for censored observations was 2.8 years. Conclusions: In this large retrospective analysis of DLBCL patients treated with REPOCH, we identified that clinical outcomes with overexpression of MYC and/or BCL2 may not be inferior in comparison to DLBCL with lack of overexpression, though prospective studies are needed to confirm these data. Additional analyses are ongoing and will be presented at the ASCO meeting. Variable MYC + / - BCL2 + / - MYC/BCL2 + & + N 29 / 31 106 / 47 16 Median age 56 / 59 61 / 52 66 Male Sex % 69 / 58 59 / 68 69 IPI 3-5 % 55 / 35 51 / 36 63 Dose Adjusted EPOCH % 59 / 48 61 / 89 50 ORR % 93 / 94 91 / 96 88 3 year OS % 88 / 87 83 / 91 75
Induction chemotherapy with paclitaxel liposome, nedaplatin, and fluorouracil in patients with locally advanced nasopharyngeal carcinoma: A phase II study.
Authors: Jing Yan, Ju Yang, Wei Ren, Kongcheng Wang, Bin Huang, Juan Wang, Jie Shen, Li Xie, Juan Liu, Shuangshuang Li, Jinfeng Bao, Shanbao Gao, Xia Zhou, Xiaoping Qian, Baorui Liu
Journal: Journal of Clinical Oncology (2018)

e18024 Background: A previous study found that adding cisplatin, fluorouracil, and docetaxel (TPF) induction chemotherapy to concurrent chemoradiotherapy could improve failure-free survival in patients with locoregionally advanced nasopharyngeal carcinoma (NCT01245959). Paclitaxel liposome may have fewer side effects and work better than paclitaxel. Nedaplatin has been developed to decrease the toxicities induced by cisplatin. In this study, we aimed to evaluate the safety and efficacy of induction chemotherapy with paclitaxel liposome, nedaplatin, and fluorouracil in such patients. Methods: In total we included 46 patients with newly diagnosed and pathologically confirmed stage III-IV nonkeratinized nasopharyngeal carcinoma from 2015 May to 2017 June. Patients were treated with paclitaxel Liposome (135mg/m2), nedaplatin (60mg/m2), and fluorouracil (600mg/m2/day×5days), every 3 weeks for 2 cycles. Radiotherapy plus concurrent chemotherapy with nedaplatin was subsequently given with a total dose of 70Gy-74Gy with 2Gy per fraction in 35-37 fractions. Treatment response was evaluated 1 month after the end of the treatment. Results: Thirty-eight patients completed 3 cycles induction chemotherapy (80.1%, 38/47). Three patients (6.5%, 3/46) developed grade 3 bone marrow suppression. Grade 1 nausea occurred in 3 patients (6.5%, 3/46) and grade 1 malaise occurred in 5 patients (10.9%, 5/46). After the induction chemotherapy, no patients achieved CR, 37 patients (80.4%, 37/46) achieved PR, 8 patients (17.4%, 8/46) were with stable disease (SD) and 2 patients (4.3%, 2/46) developed progressive disease (PD). After induction chemotherapy plus concurrent chemoradiotherapy, all the patients achieved PR or CR. The median follow-up was 16 months (range, 8-33 months). Distant metastases occurred in 9 patients, and only 1 patient had in-field recurrence. Conclusions: Induction chemotherapy with paclitaxel liposome, nedaplatin, and fluorouracil is safe and efficient for patients locally advanced nasopharyngeal carcinoma. This regimen is well tolerated and might be especially helpful for patients with poor performance status. Clinical trial information: ChiCTR-PIN-17011874.
Pathological and clinical features of non-acral cutaneous melanoma (CM) patients (pts) with <i>TP53</i> and <i>BRAF<sup>Non</sup></i><sup>-<i>V600</i></sup> (<i>NonV600</i>) mutations (muts).
Authors: Dae Won Kim, Lauren Elaine Haydu, Aron Joon, Roland L. Bassett, Alan Siroy, Michael T. Tetzlaff, Alexander Lazar, Scott Eric Woodman, Jeffrey E. Gershenwald, Michael A. Davies
Journal: Journal of Clinical Oncology (2016)

9535 Background: Our previous analysis of advanced CM pts and the TCGA demonstrated that BRAFV600 (V600), NRAS, TP53 and BRAFNon-V600 (NonV600) muts are common in CMs. As V600 and NRAS muts are both significantly associated with CM features, we analyzed a large retrospective cohort of CM pts to identify pt, tumor and clinical features significantly associated with TP53 and NonV600 muts. Methods: Under an IRB-approved protocol clinical and pathological data were collected for a retrospective cohort of CM pts with clinical molecular testing performed by a next gene sequencing panel from April 2012 to November 2014. Muts were assessed for associations with pt demographics, melanoma characteristics, and clinical outcomes. Significance of observed associations were determined by Fisher’s exact, Kaplan Meier and log rank testing. Results: Among 929 CM pts, 43% had V600, 21% had NRAS, 19% had TP53 and 7% had NonV600 muts. TP53 muts were detected in 11% of pts with V600 muts, 19% of pts with NRAS muts and 29% of pts without V600 or NRAS muts (WT). NonV600 muts were detected in 1% of V600 pts, 4% of NRAS, and 15% of WT. TP53 muts were associated with increased age at diagnosis (p = 0.02) and primary tumor site (p = 0.0001), with increased frequency of head and neck tumor location. Pts with TP53 mut had longer overall survival (OS) from stage IV on univariate analysis (p = 0.04), and on multivariate analysis (p = 0.026) that included gender, stage, and LDH. Improved OS with TP53 mutation was not observed in pts with a V600 mut (p = 0.89), and TP53 mut was not associated with outcomes in V600 pts treated with approved BRAF inhibitors. NonV600 muts correlated with older age at diagnosis (p = 0.005), but no other pt demographic, tumor characteristic, or OS from stage IV. None of the NonV600 mut pts treated with approved BRAF inhibitors (n = 11; 1 with concurrent MEK inhibitor) had an objective response. Conclusions: TP53 muts were significantly associated with longer OS from stage IV in this large cohort of CM pts, and should be evaluated other melanoma patient cohorts. BRAF NonV600 mutations were not associated with primary tumor characteristics or OS.
Phase II trial of atezolizumab before and after definitive chemoradiation for unresectable stage III NSCLC.
Authors: Helen J. Ross, David E. Kozono, James John Urbanic, Terence Marques Williams, Carter Dufrane, Ilze Bara, Mayank Gandhi, Katja Schulze, Jane Michelle Brockman, Xiaofei F. Wang, Everett E. Vokes, Tom Stinchcombe
Journal: Journal of Clinical Oncology (2018)

TPS8585 Background: Over 40,000 patients in the US/year are diagnosed with stage III NSCLC, but only ~25% will be cured by standard chemoradiation (CRT). Combining checkpoint inhibition through PD-L1 blockade with CRT may attenuate tumor related immunosuppression via depletion of Tregs and clonal expansion of effector T-cells, thereby improving tumor immunogenicity. Responses to immunotherapy seem to be higher in patients with significant cytoreduction, such as with radiation (RT). Further, CRT may reveal otherwise hidden antigens that can present additional targets to the reconstituting immune system. Whether anti-PD-L1 therapy before CRT will further improve outcomes in this setting is unknown. Methods: This phase II single arm Alliance Foundation Trials study (AFT-16, NCT03102242) will evaluate safety and efficacy of atezolizumab before and after definitive CRT. 63 patients with stage III NSCLC, PS 0-1, no active autoimmune disease and no underlying organ dysfunction will be enrolled at 15 US Alliance sites. Treatment consists of 4 cycles of neoadjuvant atezolizumab 1200 mg IV q 21 days with restaging after cycles 2 and 4. Non-progressing patients undergo carboplatin and paclitaxel (C/P) weekly with 60 Gy RT followed by 2 cycles of C/P consolidation followed by atezolizumab to complete one year of therapy. The primary endpoint of this pilot study is disease control rate (CR+PR+SD) after neoadjuvant atezolizumab. Secondary endpoints include ORR, PFS and OS, safety and QoL assessed by the EORTC QLQ-30. Correlatives include the role of PD-L1 and tumor mutation burden as predictive biomarkers. Tumor tissue will be obtained at study entry, and plasma and immune cells will be isolated at study entry, post neoadjuvant atezolizumab, post CRT, during adjuvant atezolizumab and at study end. Additional potential predictive biomarkers will be to define how atezolizumab affects the proportions of immunologic subtypes and immune activation using flow cytometry and T cell receptor immunophenotyping, multiplex immunohistochemistry and cytokine analysis. The trial was activated on 11/1/17. As of 2/13/18, the trial has been opened at 4 centers and 8 patients have been enrolled. Clinical trial information: NCT03102242.
Subtyping, phenotyping or endotyping rosacea: how can we improve disease understanding and patient care?
Authors: J.P. Thyssen
Journal: British Journal of Dermatology (2018)

Linked Articles:Tan et al. Br J Dermatol 2018; 179:741–746. Gether et al. Br J Dermatol 2018; 179:282–289.
Effect of apalutamide on health-related quality of life in patients with non-metastatic castration-resistant prostate cancer: an analysis of the SPARTAN randomised, placebo-controlled, phase 3 trial
Authors: Fred Saad, David Cella, Ethan Basch, Boris A Hadaschik, Paul N Mainwaring, Stéphane Oudard, Julie N Graff, Kelly McQuarrie, Susan Li, Stacie Hudgens, Joe Lawson, Angela Lopez-Gitlitz, Margaret K Yu, Matthew R Smith, Eric J Small
Journal: The Lancet Oncology (2018)
TCT-625 Five-Year Clinical Outcomes of NOBORI Biolimus-Eluting Stent versus XIENCE Everolimus-Eluting Stent in Diabetic Patients
Authors: Yuichi Tanaka, Shoichi Kuramitsu, Takashi Hiromasa, Makoto Hyodo, Shinichi Shirai, Kenji Ando
Journal: Journal of the American College of Cardiology (2018)
Prophylactic cranial irradiation (PCI) in limited-disease small-cell lung cancer (LD-SCLC) patients with brain imaging.
Authors: Nobuaki Mamesaya, Kazushige Wakuda, Mie Kotake, Takumi Fujiwara, Haruki Kobayashi, Takahisa Kawamura, Kazuhisa Nakashima, Shota Omori, Akira Ono, Hirotsugu Kenmotsu, Tateaki Naito, Haruyasu Murakami, Toshiaki Takahashi
Journal: Journal of Clinical Oncology (2017)

e20010 Background: PCI is recommended for patients with LD-SCLC who have a good response to initial therapy. But this recommendation has been made based on studies in which brain imaging was not a standard component of initial staging or follow-up. The aim of this study was to evaluate the efficacy of PCI for LD-SCLC patients with brain MRI immediately before PCI administration. Methods: This single-center, retrospective study included patients with LD-SCLC who achieve a good response to initial therapy without BM confirmed by MRI between 09/2002 and 06/2015. Responses were classified as CR and PR, according to RECIST. We categorized these patients into three groups: C: patients who achieved CR and received PCI; P: patients who achieved PR and received PCI; N: patients who did not receive PCI, regardless of responses. We compared OS, progression free survival (PFS), and the cumulative incidence of BM at 3 years (3yBM) among these groups. Results: A total of 79 patients were included in this study. At baseline, age and PS differed significantly between C and N. In P, patients were also younger than N. Although there were no statistical significances in OS and PFS between C and N, differences in 3 years OS rate and median PFS were numerically large. The 3yBM in C revealed marginal significance compared with N. However, No differences were observed with OS, PFS, and 3yBM between P and N. Conclusions: PCI may not add clinical benefit to LD-SCLC patients who did not achieve CR after initial therapy if absence of BM could be confirmed by MRI immediately before PCI administration. [Table: see text]
P04.78 Ultrarapid FGFR3 immunostaining for diagnosis of gliomas harboring FGFR3 gene fusions
Authors: S Mäntylä, J Haapasalo, J Ilvesaro, K Nordfors, J Isola, H Haapasalo, M Nykter, K Granberg
Journal: Neuro-Oncology (2018)

Fibroblast growth factor receptor 3 (FGFR3) gene fusion with transforming acidic coiled coil 3 (TACC3) has been detected in a subset of diffuse gliomas and other malignancies. Tumors with FGFR3:TACC3 fusion are typically aggressive isocitrate dehydrogenase (IDH) wild-type tumors and are more commonly observed in female patients. Strong FGFR3 staining has been shown to be an indicator of FGFR3 fusions and is also associated with worse survival of patients. Different FGFR inhibitors are currently being clinically tested for various cancer types harboring FGFR alterations, and tumors with FGFR3 fusions have shown promising treatment responses. Intraoperative screening of FGFR3 fusion in gliomas could be beneficial due to the possibility of therapeutic FGFR inhibition. High to moderate FGFR3 staining is a prognostic marker and could be thus informative when the extent of the resection is considered. Intraoperative FGFR3 staining could also enable the targeted administration of FGFR-inhibitors into the tumor cavity. Therefore, we aimed to investigate whether a rapid immunohistochemical staining could be used intraoperatively to predict FGFR3 fusion status of tumors on frozen tissue sections. Ultrarapid FGFR3 immunohistochemical staining was performed on frozen tissue sections from 34 astrocytomas (grades II-IV), five oligodendrogliomas (grades II-III) and two ependymomas (grades II and III). Results were histologically graded and cases with moderate to strong FGFR3 staining were selected for further analysis. Staining protocol was simple and practical to carry out. The protocol can be performed in under ten minutes, which makes it suitable for the use in intraoperative setting. Ultrarapid-FGFR3 immunostaining would be beneficial for the diagnosis of FGFR3 fusion positive gliomas and other malignancies when carried out intraoperatively, since it is quick to perform and it nicely separates tissues with moderate to high staining. Intraoperatively this protocol could provide valuable information on the extent of the resection required to achieve the best treatment outcome in combination with targeted inhibitory treatment.