bluuebunny/crossref_metadata_2025_split huggingface dataset:
Case-control study of PD-1, PD-L1, and B7-H3 expression in human immunodeficiency virus infected (HIV+) and uninfected patients with head and neck cancers.
Authors: Mainor Candace Barette , Scilla Katherine Ann , Heath Jonathon , Ioffe Olga B. , Cellini Ashley L , Riedel David , Bentzen Soren , Feliciano Josephine Louella , Zandberg Dan Paul 
Published: September 2018

e23194 Background: HIV+patients are typically excluded from immunotherapy trials but there are limited data on co-signaling molecule expression in these patients, including in head and neck squamous cell carcinoma (HNSCC). Methods: A case control study was conducted to evaluate tumor tissue sections for PD-L1, PD-1, and B7-H3 expression in HIV+HNSCC patients (n = 12) and HNSCC controls (n = 12). Cases and controls were matched for age at diagnosis, race, gender, TNM stage, and primary site. Smoking status, HIV RNA viral load (VL), and CD4 count were also recorded. Immunostained tumor sections were analyzed for percent of tumor cells expressing PD-L1 (PD-L1%) and B7-H3(B7-H3%) (Abcam), and percent of tumor infiltrating lymphocytes (TIL) expressing PD-1 (TIL-PD-1%) and PD-L1 (TIL-PD-L1%) (Abcam). Statistical analysis used the non-parametric Mann-Whitney test, chi-square test and Spearman’s rank correlation, Rs. Results: The 12 HIV+ HNSCC cases were predominantly male (67%), black race (67%) and cigarette smokers (100%), with a median age of 50.4 years, median viral load (VL) of 52399 copies/mL, median CD4 count (CD4) of 236cells/uL, predominantly locally advanced (75% Stage III/IVa/IVb), and oropharyngeal primary site (42%). Defining positive expression as > 5%, 42% of HIV+ HNSCC patients tumors were positive for PD-L1, 100% for B7-H3, and 92% had TILs that expressed PD-1 and PD-L1. HIV+ patients had significantly higher B7-H3% (Median 60% vs. 20%, p = 0.03) and TIL-PD-L1% (Median 15% vs. 10%, p = 0.045) compared to controls. There were no differences in PD-L1% or TIL-PD-1%. In HIV+ cases, increased VL correlated with increased TIL-PD-1% (Rs = 0.73, p = 0.011) and increased CD4 count correlated with increased tumor PD-L1% (Rs = 0.62, p = 0.04). There were no other significant correlations between CD4 count or VL and co-signaling molecule expression. Conclusions: HIV+ HNSCC patients had significantly higher tumor B7-H3 and TIL PD-L1 expression, with similar tumor PD-L1 and TIL PD-1 expression, compared to HIV negative HNSCC control patients. These findings support inclusion of HIV+ HNSCC patients in immunotherapy trials with checkpoint inhibitors.
Novel mechanisms-guided treatments for betel-nuts related head and neck squamous cell carcinoma in Taiwan.
Authors: Chen Jo-Pai , Chang Jui-Ying , Kuo Sung Hsin 
Published: September 2018

e23217 Background: Betel-nuts related HNSCCs in Taiwan will cause (1)strong inflammation, invasion, and angiogenesis; (2)poor response to chemotherapy, radiation, and epidermal growth factor receptor inhibitors. Methods: HNSCC cell lines(SCC4, SCC9, SCC15, SCC25, FaDu, KB, Cal27, SAS, and TW2.6, betel-nuts related) were used to evaluate (1)the in vitro drug sensitivity; (2)synergistic effects of different treatment combinations with MTT assay, colony formation, flow cytometry, and western blotting; (3)invasion capacity by wound healing. TW2.6 had already been proved to possess defective p53, p16 loss, and increased Bcl2. Results: TW2.6 was resistant to chemotherapies, radiation, & EGFR inhibition; but sensitive to PI3K/mTOR dual inhibition(BEZ235), CDK4/6 inhibitor(palbociclib), Bcl2 inhibitor(ABT-199), WEE1 inhibitor(AZD1775), FGFR inhibitor(BGJ398), ALK/IGF-1R inhibitor(ceritinib), & eribulin. Polo-like kinase inhibitor(volasertib) with radiation, resulting in G2/M arrest in flow-cytometry and increased cyclin B levels in western blotting, caused TW2.6 apoptosis. Nintedanib & regorafenib(VEGFR/PDGFR/FGFR inhibitor) and foretinib (VEGFR/c-MET/Axl inhibitor) would suppress HUVEC, block invasion capacity of TW2.6, inhibit TW2.6 growth, and resensitize TW2.6 to docetaxel, afatinib, and volasertib. Western blotting showed (1)mesenchymal markers(Slug, Snail, Axl, Twist, Vimentin, Claudin-1), PI3K/Akt/mTOR signaling(p-Akt & p70S6K), and BMI-1 dropped after nintedanib, regorafenib, and foretinib; (2)PDL1 drop after foretinib use. BYL719, ABT-199, and ceritinib also sensitize TW2,6 to docetaxel. Astragalus polysaccharides, minimally cytotoxic on TW2.6, could inhibit tumor migration, suppress epithelial-mesenchymal transformation & PI3K/AKT/mTOR pathway, and induce PDL1 drop. APS re-sensitizes TW2.6 to afatinib & volasertib. Olaparib(PARP inhibitor) also had poor effect on TW2.6; but volasertib, AZD1775, and foretinib could reverse olaparib resistance. Conclusions: TW2.6 might reflect treatment refractoriness of betel-nuts related HNSCC in Taiwan. Several novel-mechanisms-guided treatment combinations could be developed in the future.
Long-term results of a phase II randomized controlled trial (RCT) of a psychological intervention (Conquer Fear) to reduce clinical levels of fear of cancer recurrence in breast, colorectal, and melanoma cancer survivors.
Authors: Beith Jane McNeil , Thewes Belinda , Turner Jane , Gilchrist Jemma , Sharpe Louise , Girgis Afaf , Smith Allan 'Ben' , Fardell Joanna , Tesson Stephanie , O'Connell Rachel , Asher Rebecca , Butow Phyllis ,   Members of the Conquer Fear Authorship Group
Published: September 2018

LBA10000 The full, final text of this abstract will be available at abstracts.asco.org at 2:00 PM (EDT) on Friday, June 2, 2017, and in the Annual Meeting Proceedings online supplement to the June 20, 2017, issue of the Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Saturday edition of ASCO Daily News.
Adverse health outcomes in relationship to hypogonadism (HG) after platinum-based chemotherapy: A multicenter study of North American testicular cancer survivors (TCS).
Authors: Abu Zaid Mohammad Issam , Menendez Alvaro G. , El Charif Omar , Fung Chunkit , Monahan Patrick O. , Feldman Darren R. , Hamilton Robert James , Vaughn David J. , Beard Clair , Cook Ryan , Althouse Sandra K. , Sesso Howard D. , Ardeshirrouhanifard Shirin , Dinh Paul C , Einhorn Lawrence , Fosså Sophie , Travis Lois B. ,   For the Platinum Study Group
Published: September 2018

LBA10012 The full, final text of this abstract will be available at abstracts.asco.org at 2:00 PM (EDT) on Friday, June 2, 2017, and in the Annual Meeting Proceedings online supplement to the June 20, 2017, issue of the Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Saturday edition of ASCO Daily News.
Overall survival results of a randomized trial assessing patient-reported outcomes for symptom monitoring during routine cancer treatment.
Authors: Basch Ethan M. , Deal Allison Mary , Dueck Amylou C. , Bennett Antonia Vickery , Atkinson Thomas Michael , Scher Howard I. , Kris Mark G. , Hudis Clifford A. , Sabbatini Paul , Dulko Dorothy , Rogak Lauren J. , Barz Allison Emily , Schrag Deborah 
Published: September 2018

LBA2 The full, final text of this abstract will be available at abstracts.asco.org at 7:30 AM (EDT) on Sunday, June 4, 2017, and in the Annual Meeting Proceedings online supplement to the June 20, 2017, issue of the Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Sunday edition of ASCO Daily News.
LATITUDE: A phase III, double-blind, randomized trial of androgen deprivation therapy with abiraterone acetate plus prednisone or placebos in newly diagnosed high-risk metastatic hormone-naive prostate cancer.
Authors: Fizazi Karim , Tran Namphuong , Fein Luis Enrique , Matsubara Nobuaki , Rodríguez Antolín Alfredo , Alekseev Boris Y. , Ozguroglu Mustafa , Ye Dingwei , Feyerabend Susan , Protheroe Andrew , De Porre Peter , Kheoh Thian , Park Youn C. , Todd Mary Beth , Chi Kim N. ,   On Behalf of the LATITUDE Investigators
Published: September 2018

LBA3 The full, final text of this abstract will be available at abstracts.asco.org at 7:30 AM (EDT) on Saturday, June 3, 2017, and in the Annual Meeting Proceedings online supplement to the June 20, 2017, issue of the Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Sunday edition of ASCO Daily News.
Second- or third-line nivolumab (Nivo) versus nivo plus ipilimumab (Ipi) in malignant pleural mesothelioma (MPM) patients: Results of the IFCT-1501 MAPS2 randomized phase II trial.
Authors: Scherpereel Arnaud , Mazieres Julien , Greillier Laurent , Dô Pascal , Bylicki Olivier , Monnet Isabelle , Corre Romain , Audigier-Valette Clarisse , Locatelli-Sanchez Myriam , Molinier Olivier , Thiberville Luc , Urban Thierry , Ligeza-poisson Catherine , Planchard David , Amour Elodie , Morin Franck , Moro-Sibilot Denis , Zalcman Gerard ,   French Cooperative Thoracic Intergroup (IFCT)
Published: September 2018

LBA8507 The full, final text of this abstract will be available at abstracts.asco.org at 7:30 AM (EDT) on Monday, June 5, 2017, and in the Annual Meeting Proceedings online supplement to the June 20, 2017, issue of the Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Monday edition of ASCO Daily News.
A multicenter phase 4 geriatric assessment directed trial to evaluate gemcitabine +/- nab-paclitaxel in elderly pancreatic cancer patients (GrantPax).
Authors: Betge Johannes , Haertel Nicolai , Chi-Kern Jing , Belle Sebastian , Schulte Nadine , Maenz Martin , Wedding Ulrich , Ebert Matthias Philip 
Published: September 2018

TPS10124 Background: Nab-paclitaxel/gemcitabine ( nab-P/gem) is an effective 1st line regimen for metastatic pancreatic ductal adenocarcinoma (mPDAC). Elderly mPDAC patients (pts) may as well benefit from nab-P/gem. Geriatric assessments to evaluate the functional reserve of these pts may allow individualization of treatment. Therefore, the aim of this study is to determine whether comprehensive geriatric assessments (CGAs) can predict the benefit from combined nab-P/gem therapy for elderly mPDAC pts in 1st line. A stratified treatment approach shall result in patient groups with a stable or improving CGA performance during the 1st cycle of treatment. Methods: GrantPax (NCT02812992) is a multicenter, open label phase 4 interventional trial with stratified parallel treatment groups (n = 45 per arm). The hypothesis is that individualized assessment directed treatment algorithms identify elderly pts (≥70 yrs), who benefit from combined nab-P/gem therapy. The study uses a CGA to stratify pts as GOGO, SLOWGO or FRAIL. Depending on test outcome, pts receive chemotherapy (GOGO: nab-P/gem; SLOWGO: gem mono) or best supportive care (FRAIL). After 1st cycle of chemotherapy (4 wks) a CGA and safety assessment will be performed to assign pts to their definite treatment arm. The primary objective is that CGA-stratified pts do not decline in their CGA performance in response to chemotherapy, measured as a loss of 5 points or less in Barthels activities of daily living (ADL1 vs. ADL2 during CGA core assessment). The expected proportion of pts with ADL decline in each treatment group is 6%. Under this assumption it shall be shown with 80% power at one-sided significance level alpha of 0.05 that the proportion of pts with functional decline is less than 20% (n = 43 per group; ADL decline: n = 2 per group). Secondary endpoints are CGA scores during the course of therapy (CGA1-4), response rates, safety, survival rates, duration of treatment, cumulative dose, quality of life and discrepancy between CGA strata estimation by the investigator and true CGA assessment. GrantPax is the first trial realizing a CGA-driven treatment to individualize cancer therapy for elderly pts. Clinical trial information: NCT02812992.
A phase II-III, multicenter, randomized, open study evaluating the feasibility and efficacy of a supervised home-based standard physical exercise program for metastatic cancer patients receiving oral targeted therapy: The UNICANCER SdS 01 QUALIOR study (ID-RCB: 2015-A01922-47).
Authors: Joly Lobbedez Florence , Vanlemmens Laurence , Descotes Jean-Marc , Abadie-Lacourtoisie Sophie , Boiron Claude , Garnier-Tixidre Claire , Girre Veronique , Helissey Carole , Houede Nadine , Lefeuvre-Plesse Claudia , Mastroianni Benedicte , Meneveau Nathalie , Oudard Stephane , Plence Valérie , Priou Frank , Salas S Bastien , Stefani Laetitia , Zannetti Alain , Bonnetain Franck , Krakowski Ivan 
Published: September 2018

TPS10126 Background: Fatigue is a frequent side effect with oral targeted therapies (OTT). Physical activity has been reported to improve fatigue and quality of life (QoL). However, few studies focused on metastatic cancer patients and mainly among patients treated with chemotherapy. Furthermore, recent guidelines recommend evaluation and optimization of standardized exercise programs. The aim of our study is to evaluate home-based standard physical exercise program (SPEP) for metastatic cancer patients treated with OTT. Methods: This phase II-III study will randomize (2:1) patients starting first-line OTT for metastatic cancer between an individualized SPEP supervised by a personal coach, and recommended physical exercises via a booklet. Eligible patients will have received ≤2 lines of metastatic chemotherapy, ECOG PS ≤2, controlled pain (VAS < 3/10), and life expectancy ≥3 months. The phase II part (120 patients) will evaluate the feasibility of a 3-month SPEP using the rate of patients performing ≥50% of SPEP (2-stage Fleming: one-sided α = 5%; β = 85%). An interim analysis is planned after the phase II. The phase III will compare the efficacy of an SPEP as opposed to recommendations to reduce fatigue and/or improve physical well-being (PWB) dimensions of QoL (evaluated with FACT-G and FACT-F questionnaires). To show a difference of ≥5 points in PWB and 2.5 for fatigue (α = 2.5%; β = 80%), 312 patients are required in the phase III trial. . Secondary objectives include: PFS, OS, other dimensions of QoL, tolerability and observance of OTT, change in body composition, physical benefits, and a medico-economic study. The SPEP was developed by specialized coaches involved in physical activity and cancer. The study has Ethic committee approval and accrual is planned in 18 French centers in April 2017, for 30 months. This is the first randomized trial dedicated to patients with metastatic cancer treated with OTT evaluating the feasibility and the efficacy of a well design home based SPEP on fatigue and physical well-being.
A randomized, double-blinded, controlled study of tucatinib (ONT-380) vs. placebo in combination with capecitabine (C) and trastuzumab (Tz) in patients with pretreated HER2+ unresectable locally advanced or metastatic breast carcinoma (mBC) (HER2CLIMB).
Authors: Anders Carey K. , Murthy Rashmi Krishna , Hamilton Erika Paige , Borges Virginia F. , Cameron David A. , Carey Lisa A. , Müller Volkmar , Curigliano Giuseppe , Gelmon Karen A. , Hortobagyi Gabriel N. , Krop Ian E. , Loibl Sibylle , Pivot Xavier B. , Pegram Mark D. , Slamon Dennis J. , Hurvitz Sara A. , Tsai Michaela L. , Winer Eric P. 
Published: September 2018

TPS1107 Background: Tucatinib (ONT-380) is a highly selective small molecule inhibitor of HER2 kinase with nanomolar potency. Unlike dual HER2/EGFR agents, it does not inhibit EGFR at clinically relevant concentrations, decreasing the potential for EGFR-related toxicities (severe skin rash and diarrhea). In preclinical studies, tucatinib demonstrated synergistic activity with Tz, and was active in HER2+ models of brain metastases (mets). In a Phase 1b study, tucatinib was combined with C and Tz in pts with HER2+ MBC previously treated with trastuzumab emtansine (T-DM1) and Tz. Objective responses were seen, including in pts with brain mets. The combination was well tolerated, with low rates of Gr 3 diarrhea at the recommended dose (300 mg PO BID, equivalent to the single agent MTD). Based on these data, tucatinib is now being evaluated in a study in combination with C and Tz (HER2CLIMB). Methods: The primary study objective is to assess the effect of tucatinib vs. placebo given with C + Tz on progression-free survival (PFS) based on independent central review. Additional objectives include PFS in patients with brain mets, overall survival, ORR, duration of response, clinical benefit rate, and safety. The study population includes adult patients with progressive HER2+ locally advanced or MBC who have had prior treatment with a taxane, Tz, pertuzumab and T-DM1. Patients with brain mets, including untreated or progressive brain mets, may be enrolled. 480 patients will be enrolled in North America, Europe, Israel, and Australia. Patients are receiving C (1000 mg/mg2 PO BID for 14 days of a 21-day cycle) and Tz (6 mg/kg IV once every 21 days), and are being randomized in a 2:1 ratio to tucatinib 300 mg PO BID or placebo. Patients with isolated CNS progression may continue on study treatment after undergoing local CNS therapy. An independent Data Monitoring Committee is monitoring patient safety. Clinical trial information: NCT02614794.
Phase 2 trial of the novel multi-receptor tyrosine kinase inhibitor sitravatinib in well-differentiated/dedifferentiated liposarcoma.
Authors: Ingham Matthew , Lee Shing Mirn , Patwardhan Parag , Choy Edwin , Chen Isan , Singh-Kandah Shahnaz , Taiclet Lauren , Schwartz Gary K. 
Published: September 2018

TPS11082 Background: Well-differentiated/dedifferentiated liposarcoma (WD/DD LPS) is a sarcoma subtype of adipocytic origin characterized by amplification of cyclin dependent kinase 4 (CDK4) and MDM2. WD/DD LPS is resistant to chemotherapy and success with CDK4 inhibitors is limited. We recently characterized the landscape of activated receptor tyrosine kinases (RTKs) and intracellular signaling pathways finding marked heterogeneity by sarcoma subtype [Patwardhan et al. Oncotarget 2016;7(4)]. In WD/DD LPS cell lines, phosphorylated (p) IGF1-R, MET and PDGFRb are strongly expressed. Selective siRNA knockdown of expression of 1 or more of these RTKs inhibited growth of WD/DD LPS cell lines. Sitravatinib (S) is a novel inhibitor of a broad panel of related RTKs. We showed that S abrogates expression of p-RTKs, including IGF1-R, MET and PDGFRb, at low nanomolar concentrations and potently inhibits proliferation of WD/DD LPS cell lines, where anti-proliferative effects of S were superior to other RTK inhibitors including imatinib, crizotinib and pazopanib. S suppressed tumor growth in vivo in WD/DD LPS . A phase 1 trial of S in solid tumors showed clinical activity in WD/DD LPS. Recommended phase 2 dose was 150 mg/day. As there are no approved RTK inhibitors for adipocytic sarcomas, and based on these findings, we initiated a phase 2 trial of S in WD/DD LPS. Methods: This is a single-arm open-label multi-center Simon 2 stage phase II trial of S in 29 patients (pts) with advanced WD/DD LPS who failed 1 prior therapy and show disease progression before enrollment. Pts receive S 150 mg orally daily continuously. Primary endpoint is the progression free rate at 12 weeks (PFR12) versus historical controls. The design has power of 85% to show improvement in PFR12 from 20% (inactive) to 40% (active) with α = 0.10. Secondary endpoints are ORR, PFS and safety. A subset of pts undergo baseline and on-treatment biopsies and reverse phase protein array used to measure changes in expression of p-RTKs and signaling pathway proteins with confirmation by immunoblot. Genomic landscape of these tumors will be analyzed by next generation sequencing. The study opened in 1/2017. Clinical trial information: NCT02978859.
A phase 3 study of alpelisib (ALP) plus fulvestrant (FUL) in men and postmenopausal women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) ABC progressing on or after aromatase inhibitor (AI) therapy: SOLAR-1.
Authors: Rugo Hope S. , Andre Fabrice , Rubovszky Gabor , Kaufman Bella , Inoue Kenichi , Takahashi Masato , Shimizu Satoru , Ciruelos Eva M. , Campone Mario , Conte Pier Franco , Iwata Hiroji , Loibl Sibylle , Mayer Ingrid A. , Juric Dejan , Longin Anne-Sophie , Mills David , Wilke Celine , Sellami Dalila B. 
Published: September 2018

TPS1111 Background: Patients (pts) with HR+ breast cancer (BC) often havedysregulatedphosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway, which further leads to resistance to endocrine therapy (ET). In a phase 1 study, alpelisib (BYL719), a PI3Kα-specific inhibitor in combination with fulvestrant (FUL) has demonstrated antitumor activity in pts with estrogen receptor-positive, HER2– advanced BC (ABC) with PIK3CA-altered tumors. SOLAR-1 (NCT02437318) aims to assess the efficacy of ALP + FUL in PIK3CA-mutant and non-mutant tumors in HR+, HER2– ABC setting. Methods: SOLAR-1 is a phase 3, randomized, double-blind study conducted in men and postmenopausal women with HR+, HER2– ABC. Pts are randomly (1:1) allocated to oral alpelisib/placebo (300 mg qd) and intramuscular FUL (500 mg) until disease progression or treatment (tx) discontinuation. Stratification factors are presence of liver and/or lung metastases and prior use of CDK4/6 inhibitors. The eligibility criteria for the targeted BC patient population are shown in the Table. The primary endpoint is progression-free survival (PFS; RECIST v1.1; local assessment), while overall survival (OS) is a key secondary endpoint in the PIK3CA-mutant cohort. Other secondary endpoints are PFS and OS in the PIK3CA non-mutant cohort, the association between PFS and baseline PIK3CAstatus in ctDNA, overall response rate, clinical benefit rate, and safety. Recruitment of the planned 560 pts is currently ongoing. Clinical trial information: NCT02437318. [Table: see text]