tbuckley/cabot-search huggingface dataset:
Feasibility and safety of cardiopulmonary exercise testing (CPET) in adults newly diagnosed with acute leukemia undergoing induction therapy.
Authors: Ashley Leak Bryant, Brett Phillips, Allison Mary Deal, Mackenzi Pergolotti, Deborah Mayer, William Allen Wood, Anthony Hackney, AnnMarie Walton, Charlotte Bailey, Hyman B. Muss, Bryce B. Reeve, Claudio Battaglini
Journal: Journal of Clinical Oncology (2016)

e18528 Background: Cardiopulmonary exercise testing (CPET) is a sensitive measure to determine how well the cardiac and respiratory systems work when the body is stressed during exercise. Purpose of this study was to determine if CPET, for the assessment of peak oxygen uptake (VO2peak ), can be feasibly and safely administered in the hospital to adults with acute leukemia prior to beginning induction chemotherapy. Methods: Inclusion criteria: >21 years, diagnosed with acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL), receiving induction therapy, and received permission from oncologist. Exclusion criteria: unable to complete CPET due to cardiac, respiratory or bone abnormalities. Adults were randomized to the control (n=9) or intervention (n=9) arm of the Exercise and Quality of Life in Leukemia Adults (EQUAL) trial, UNC Lineberger Comprehensive Cancer Center (NCT02246907). CPET procedures involved cycle erogemetry and indirect calorimetry. Feasibility defined as 100% baseline completion and 50% post-treatment completion. Safety was evaluated based on adverse events. Results: Eighteen patients (mean age 51, range 21-69) completed baseline CPET (see Table). Reasons for not completing post CPET: 6 not interested, 3 timing conflict, 1 functional decline. No adverse events were observed in those who participated in CPET. Conclusions: CPET appears to be a safe evaluation of cardiopulmonary function in newly diagnosed AML and ALL adults who are without cardiac or respiratory conditions. One limitation was difficulty in obtaining a repeat CPET in the control group, so strategies to increase adherence (ie. incentives, one on one follow-up) and improvements in the study design are warranted. CPET was not feasible as it was arranged within the specific context of this study. Clinical trial information: NCT02246907. Pre-Control (n=9) Post Control (n=2) Pre-Intervention (n=9) Post Intervention (n=6) Mean(ml/kg/ min) 17.53 18.62 19.91 19.95 Range(ml/kg/ min) 5.42-25.56 13.2-24.04 15.08-25.44 14.72-26.1 Baseline VO2 completed: (n=18); Post VO2 completed: (n=8). *Average VO2 max for healthy untrained male and female adults range between 25-40 ml/kg/min.
RRM1 expression is verified as a biomarker predicting the drug sensitivity for GEM with in vitro 3D drug sensitivity test in non-small cell lung cancer tumor.
Authors: Nariyasu Nakashima, Dage Liu, Takayuki Nakano, Yusuke Kita, Xia Zhang, Yoshimasa Tokunaga, Shintaro Tarumi, Natsumi Matsuura, Kazuhito Nii, Tetsuhiko Go, Yoshiyuki Kakehi, Hiroyasu Yokomise
Journal: Journal of Clinical Oncology (2017)

e20054 Background: Ribonucleotide reductase M1 (RRM1) is involved in regulation of cell proliferation and synthesis of deoxyribonucleotides for DNA. It is also a cellular target for gemcitabine (GEM) and overexpression of RRM1 was reported to be associated with the resistance to GEM. Though RRM1 expression has been reported as the biomarkers in predicting the response to chemotherapy clinically, the value of GEM remains inconsistent and controversial. Collagen gel droplet embedded culture-drug sensitivity test (CD-DST) is a newly developed in vitro chemosensitivity test that could directly inspect the anti-cancer drug sensitivity with fresh tumor tissue. With use of CD-DST test, we have verified the predictive value of RRM1 expression to the anti-cancer agent sensitivity for GEM in non-small cell lung cancer (NSCLC) tumor. Here, the predictive value of biomarker RRM1 to GEM was further verified with CD-DST. Methods: Twenty-five patients with primary NSCLC were used in this study. Expression of RRM1 was assessed by immunohistochemistry. For CD-DST test, viable cells were collected from fresh surgical specimen and embed into the collagen gel droplets in 3D condition. Tumor cells were exposed to GEM for 1 hour and further incubated with serum-free culture medium for 7 days. The in vitro sensitivity was expressed as the percentage T/C ratio, where T was the total volume of the treated group and C was the total volume of the control group. Results: 1)Anti-cancer drug sensitivity: The sensitivity for GEM (T/C%) was 76.2 ± 30.5. 2)Expression of biomarkers: RRM1 expression was 39.2 ± 28.2 %. 3) Correlation: The expression of RRM1 significantly correlated with drug sensitivity for GEM (r = 0.446, p = 0.0256). Higher expression of RRM1 indicated worse anti-cancer drug sensitivity for GEM. Conclusions: The significant correlation between the RRM1 expression and sensitivity to GEM was proved with CD-DST in NSCLC tumors. The expression of RRM1 may become a useful biomarker in predicting the drug sensitivity for GEM in NSCLC.
Long-term stroke risk of single-fraction photon-based stereotactic radiosurgery for meningioma.
Authors: Shearwood McClelland, Jeremy N Ciporen, Timur Mitin, Jerry Jeff Jaboin
Journal: Journal of Clinical Oncology (2018)

2021 Background: A recent randomized study of fractionated radiation therapy (RT) examining 44 subtotally resected/recurrent benign meningioma patients revealed that at median follow-up of 17.1 years, the risk of stroke following proton-photon RT was 20.5%; the average stroke developed 5.6 years following RT completion (Sanford et al., 2017). This stroke risk is up to 10 times higher than the 2-6% rate expected for the general population of ages 40-79 (Mozaffarian et al., 2015). The stroke rate following single-fraction stereotactic radiosurgery (SRS) has not been previously studied in meningioma patients. Methods: A PubMed database search for relevant articles examining SRS for meningioma with minimum mean/median follow-up of six years was undertaken. Stroke rate was assessed either from direct description in manuscripts, or from extrapolating post-SRS complications from reported clinical examinations (i.e. hemiparesis/weakness, pituitary dysfunction following treatment of cavernous sinus lesions). Results were then culled to determine an overall stroke rate. Results: Fourteen studies met inclusion criteria; 1,431 patients received photon-based SRS for meningioma with a sufficient long-term follow-up. Median/mean follow-up ranged from 75-144 months. Operative resection prior to SRS occurred in 769/1377 patients (55.8%) for whom surgical history was reported. Twenty-four patients suffered a stroke following SRS, yielding a rate of 1.7%. Conclusions: The long-term stroke rate following single-fraction photon-based SRS for benign meningioma was 1.7%, more than twelve times lower than for fractionated proton-photon RT and comparable to that expected for the general population. The majority of patients underwent resection prior to SRS. These findings indicate that for patients with benign meningioma desiring to avoid the high stroke risk of fractionated proton-photon RT, SRS has a comparable stroke risk profile to observation. Such findings are pertinent for radiation oncology, neuro-oncology, and neurosurgery management of these patients.
Role of neoadjuvant chemotherapy or chemoradiotherapy in oesophageal carcinoma.
Authors: Herui Yao, Yunfang Yu, Qiyun Ou, Ying Wang, Quanlong Gao, Tuping Fu, Dagui Lin, Shaotao Wu
Journal: Journal of Clinical Oncology (2018)

4040 Background: The role of neoadjuvant chemotherapy (NAC) or chemoradiotherapy (NACR) in patients with oesophageal carcinoma continues to be debated. This study aimed to assess the comparative efficacy and safety of NAC or NACR for oesophageal carcinoma. Methods: Randomized clinical trials reporting on NAC or NACR with local operable oesophageal carcinoma were identified. The primary endpoint was overall survival (OS). All trial results were combined and analysised using a fixed or random-effects meta-analysis. Quality of evidence was appraised with GRADE criteria. The PROSPERO registry number is CRD42017072242. Results: 40 trials with 8,393 patients were included. High-quality evidence indicated that NAC was associated with a significant benefit on OS (hazard ratio [HR] 0.86, 95% CI 0.80 to 0.92; P = 0.000) and relapse-free survival (RFS) (HR 0.78, 95% CI 0.72 to 0.84; P = 0.000) versus surgery alone, with an absolute difference at 5 years of 10% (6 to 13), and the treatment effect on survival was especially in favor of adenocarcinoma (HR 0.81, 0.72 to 0.91), but no significant difference in squamous-cell carcinoma (SCC) (HR 0.93, 0.81 to 1.08). High-quality evidence revealed that treatment with NACR, as compared with surgery alone, prolonged OS (HR 0.74, 95% CI 0.67 to 0.81; P = 0.000) and RFS (HR 0.74, 95% CI 0.65 to 0.84; P = 0.000), corresponding to an absolute difference at 5 years of 14% (9 to 20), with similar survival for different histological types of tumor: 0.73 (0.65 to 0.83) for SCC and 0.73 (0.62 to 0.93) for adenocarcinoma. There was moderate-quality evidence that the overall direct and indirect comparison of NACR with NAC showed a survival advantage (HR 0.83, 95% CI 0.73 to 0.94; P = 0.004), with results for SCC (HR 0.74, 0.63 to 0.89) and for adenocarcinoma (HR 0.89, 0.74 to 1.10). Conclusions: This study confirmed that a significant clinical benefit is evident for NACR in both adenocarcinomas and SCC of the esophagus, and NAC in patients with adenocarcinoma of the oesophagus. To our knowledge, this is the first evidence-based finding which provided advantage of NACR over NAC in patients with oesophageal carcinoma.
ASN001, a novel CYP17 lyase inhibitor, in men with metastatic castration-resistant prostate cancer (mCRPC): Safety/tolerability and early activity in a multicenter phase 1/2 trial.
Authors: Niranjan Sathyanarayana Rao, Anthony W. Tolcher, Kyriakos P. Papadopoulos, Drew W. Rasco, Naomi B. Haas, Allan J. Pantuck, Louis J. Denis, Robert Dreicer
Journal: Journal of Clinical Oncology (2016)

e14129 Background: ASN001 is a novel non-steroidal CYP17 lyase inhibitor. In preclinical studies, ASN001 shows potent inhibition of CYP17 lyase with selective inhibition of testosterone synthesis over cortisol synthesis, which may obviate the need for co-administration of prednisone. ASN001 also exhibited high oral bioavailability and low potential for drug-drug interaction, which may support future combination treatment strategies of ASN001 with AR inhibitors and other targeted agents. This multicenter Phase 1/2 clinical trial (NCT02349139) evaluates ASN001 in men with mCRPC. Methods: Eligibility includes progressive mCRPC despite ongoing androgen deprivation therapy. Prior treatment with abiraterone, enzalutamide and chemotherapy was permitted for Phase 1. Up to 90 men will receive oral ASN001 at escalating doses without co-administration of prednisone. Planned dose levels include 50, 100, 200, 300 and 400 mg QD. Endpoints include safety/tolerability, recommended Phase 2 dose, PK, PD (incl. LH/FSH, T/DHT, cortisol and ACTH) and efficacy (PSA and imaging) Results: To date, 11 patients have been enrolled at the 50, 100 and 200 mg QD dose levels. ASN001 was well tolerated, drug-related AEs were CTCAE Gr 1 and 2 incl. myalgia, anorexia, flushing, hot-flashes and presyncope. No DLTs or drug-related serious adverse events have been reported. Stable disease, confirmed by PSA measurement and imaging, of up to 7 months was observed (treatment on-going) despite failure of prior enzalutamide, abiraterone and docetaxel. Excellent systemic exposure was observed at both 50 mg and 100 mg QD regimens (Cmax , Ctrough and AUCτ at 100 mg QD were 3.5 uM, 1.8 uM and 52 uM.h, respectively). There were no dose related changes in cortisol or ACTH levels over the duration of treatment and no need for prednisone administration. Conclusions: The Phase 1 clinical study results to date show that ASN001 is safe and well tolerated at doses up to 100 mg daily. Early data is encouraging as evidence of activity is reflected by disease and PSA stabilization despite failure of standard of care. Updated and detailed results on safety, PK, PD and efficacy will be reported. Clinical trial information: NCT02349139.
Phase I/II trial of a long peptide vaccine (LPV7) plus toll-like receptor (TLR) agonists for resected stage IIB-IV melanoma.
Authors: Sapna Pradyuman Patel, Gina R. Petroni, Elizabeth Mary Gaughan, William W. Grosh, Sacha Gnjatic, Patrick Hwu, Craig L. Slingluff
Journal: Journal of Clinical Oncology (2018)

e15171 Background: We designed a first-in-human clinical trial to evaluate safety and immunogenicity of LPV7, administered in vaccine adjuvant combinations of incomplete Freund's adjuvant (IFA) and agonists for TLR3 (polyICLC, pICLC) and TLR7/8 (resiquimod, resiq). We hypothesized that T cell responses to minimal epitopes would be enhanced compared to prior work with short peptides, and that T cell responses would be improved with TLR agonists, compared to IFA alone. Methods: Patients (pts) with resected stage II-IV melanoma were vaccinated with LPV7 plus a tetanus helper peptide restricted by Class II MHC (Tet). LPV7 is comprised of 29-31-mer peptides from tyrosinase, gp100, MAGE-A1, MAGE-A10, and NY-ESO-1, each containing a minimal epitope for CD8 T cells. Pts received LPV7 in one of 7 adjuvants. Accrual was sequentially initiated to groups with increasing numbers of adjuvants in an adaptive design. Vaccine was given weeks 0, 1, 2, 5, 8, and 11; injection sites were rotated and biopsied d8 and d22. Antibody (Ab) and T cell responses were measured with ELISA and IFNγ ELIspot assay ex vivo, respectively. Results: Fifty eligible pts were adaptively assigned to 7 study groups (4-16 pts per arm, Table). There was one dose limiting toxicity: Group E (grade 3 injection site reaction, ISR). All other AEs were grades 1-2; most common were ISR (90%), fatigue (62%), skin induration (56%), chills (48%), fever, myalgia, and headache (30% each), and were similar across groups, but lower in group C. T cell responses to LPV7 were mostly CD4+, and were most prevalent for groups A, B, E, and G, as were responses to tetanus peptide. CD8 responses to minimal peptides were lower than in prior trials with short peptides, but were highest for groups A and E (Table). Ab responses to peptides (not shown) were highest for Groups E and G. Conclusions: The LPV7 vaccine is safe and immunogenic. Immunogenicity is supported more by IFA than by TLR agonists alone, and may be enhanced by pICLC plus IFA, with or without resiq. Clinical trial information: NCT02126579. Adjuvants Study Group A B C D E F G IFA pICLC Resiq pICLC + resiq IFA + pICLC IFA + resiq IFA + pICLC + resiq N 5 7 4 6 16 6 6 T cell immune response rate (%) LPV7 40 29 0 17 31 17 67 CD8 epitopes 40 14 0 0 25 17 17 Tetanus (CD4) 80 43 0 17 50 17 50
Phase II clinical trial of the 1<sup>st</sup> line combination therapy of eribulin and trastuzumab for advanced or recurrent HER2-positive breast cancer.
Authors: Koichi Sakaguchi, Katsuhiko Nakatsukasa, Tetsuya Taguchi
Journal: Journal of Clinical Oncology (2018)

e13016 Background: Eribulin mesylate is approved to treat patients with advanced or reccurent breast cancer who have received at least two previous chemotherapy regimens. CLEOPTRA demonstrated the efficacy of combination therapy of trastuzumab, pertuzumab, and docetaxel as a 1st line regimen for advanced or recurrent HER2-positive breast cancer. On the other hand, the toxicity of this combination therapy is remarkable. The purpose of our study is to assess the efficacy and safety of eribulin with trastuzumab as 1st line therapy for advanced or metastatic HER2-positive breast cancer. Methods: This study was carried out as a multicenter, phase II, single-arm study. Untreated advanced or reccurent HER2 positive breast cancer patients received eribulin at 1.4 mg/m2 intravenously (I.V.) on days 1 and 8 of each 21-day cycle with an initial trastuzumab dose of 8 mg/kg I.V. on day 1, followed by 6 mg/kg of trastuzumab on day 1 of each subsequent cycle. The primary end point was response rate (RR), and secondary end points were progression free survival (PFS), overall survival(OS), duration of response(DOR), and safety. Results: Twenty-eight patients (median age: 62.5 years) were enrolled. Patients received a median of 12 cycles of eribulin with trastuzumab (2-53 cycles). The RR was 53.6% (CR 4, PR 11) with median PFS of 344 days. The clinical benefit rate was 64.0%. Grade 3/4 adverse events were observed in 12 (42.9%) patients. For details, neutropenia in 8 (28.6%) patients, peripheral neuropathy in 2 (7.2%) patients, interstitial pneumonia in 1 (3.6%) patient, ALT elevation in 1 (3.6%) patient, osteomyelitis of the jaw in 1 (3.6%) patient, and fatigue in 1 (3.6%) patient. The patient with osteomyelitis received denosumab, too. No LVEF decline or symptomatic congestive heart failure were observed. Conclusions: Combination therapy of eribulin with trastuzumab is acceptable in efficacy and safety, and a capable option for 1st line advanced or reccurent HER2-positive breast cancer. Clinical trial information: UMIN000009890.
Abstract 18814: Psoriasis Does Not Increase the Mortality in Acute Myocardial Infarction Patients: A Nationwide Analysis
Authors: Rupak Desai, Upenkumar Patel, Rushik Bhuva, Gautam Kumar
Journal: Circulation (2017)

Background: Severe psoriasis increases cardiovascular risk but there is limited data comparing overall mortality and outcomes in AMI (acute myocardial infarction) patients with versus without Psori...
Development of non-Hodgkin lymphoma as a second primary cancer in patients with chronic hepatitis C virus infection.
Authors: Minas P. Economides, Parag Mahale, Francesco Turturro, Jeff Hosry, Bruno Palma Granwehr, Harrys A. Torres
Journal: Journal of Clinical Oncology (2016)

e19059 Background: Hepatitis C virus (HCV) is carcinogenic. Infected patients (pts) are at increased risk of developing hepatocellular carcinoma (HCC) and non-Hodgkin’s lymphomas (NHL). HCC can present as a second primary cancer (SPC). However, reports on HCV-infected pts who develop NHL as a SPC are lacking. Methods: Records of HCV-infected pts who were seen at MD Anderson Cancer Center, between 01/2008 - 11/2015 were reviewed. Infected pts (detectable HCV RNA) who developed HCV-associated NHL in the setting of a different first primary cancer (FPC) (cases) were, based on the FPC, matched 1:3 to HCV-infected pts who did not develop NHL as SPC (controls). NHL was classified according to the 2008 WHO criteria. HCV-associated NHL were identified as previously described (Iqbal T., et al., Int J Cancer2016). Sustained virological response (SVR) was defined as absence of HCV RNA in serum 24 weeks after completion of antiviral therapy (AVT). Results: During the study period, 21 HCV infected pts developed NHL as SPC and were analyzed as cases. Most cases were men (14; 66%), Caucasians (16; 76%) and had genotype 1 infection (7; 58%). Types of NHL among cases, included diffuse large B cell (12; 57%), marginal zone (5; 24%), mantle cell (3; 14%) and lymphoplasmacytic (1; 5%) lymphomas. The majority of FPC were solid tumors (17; 81%), mostly involving the genitourinary (38%) and respiratory (19%) tracts. NHL developed at a median of 5 years after diagnosis of FPC. Surgery (76%) and chemotherapy (42%) were the main treatment modalities for FPC. When compared to controls, more cases had progression of their FPC (43% vs 29%, p = 0.23). More cases than controls received AVT (66% vs 48%, p = 0.77); however, SVR rate was higher in the controls (40% vs 29%, p = 0.04). Duration of HCV infection after the diagnosis of FPC was higher in the cases (median of 10 vs 3 years, p = 0.02). Conclusions: NHL may develop as a SPC in selected HCV infected pts with a different FPC. In addition to HCC screening, surveillance for the development of NHL should be considered in HCV-infected pts with another underlying cancer, especially among those with persistent viremia. Eradication of HCV may potentially reduce the risk of NHL development as a SPC.
Doxorubicin plus dacarbazine (DTIC) in advanced solitary fibrous tumor (SFT): An Italian retrospective case series analysis.
Authors: Maristella Saponara, Bruno Vincenzi, Giuseppe Badalamenti, Carlo Morosi, Silvana Pilotti, Gianpaolo Dagrada, Salvatore Provenzano, Michela Libertini, Rossella Bertulli, Vittoria Colia, Angelo Paolo Dei Tos, Paolo Giovanni Casali, Silvia Stacchiotti
Journal: Journal of Clinical Oncology (2016)

11042 Background: The reported response rate to chemotherapy (CT) in SFT is low both with anthracycline-based regimens ( ≤ 20%) and with trabectedin ( < 10%). DTIC can be active. We report on the combination of doxorubicin + DTIC in a retrospective case-series analysis of SFT patients (pts) treated within 3 Italian sarcoma referral centers. Methods: We singled out metastatic SFT pts treated with CT from February 2012 to December 2015 at Fondazione IRCCS Istituto Nazionale Tumori - Milan, University Campus Bio-Medico - Rome and University Hospital “P. Giaccone” - Palermo, reviewing those receiving doxorubicin + DTIC. Pathologic diagnosis on last available tumor sample was centrally reviewed, distinguishing typical, malignant (MSFT) and dedifferentiated (DSFT) subtypes. Pts were treated until unacceptable toxicity or progression. All pts who received at least 1 cycle of chemotherapy were considered. Response was assessed by RECIST. Results: 13 cases were retrospectively identified (male/female: 9/4; mean age: 53 years, range 31-71; front-line/further-line: 11/2; MSFT/DSFT: 8/5). All pts were evaluable for response. Treatment was stopped in 11 cases (disease progression: 6 - maximum tolerated dose: 3 - surgery of residual disease: 2), while 2 pts are still on therapy. The mean number of cycles was 5 (3-6). There was no unexpected toxicity. Best response by RECIST was partial response (PR) = 6 (46%) - stable disease (SD) = 2 (15%) - progressive disease (PD) = 5 (39%). At a median follow-up of 19.2 months, median PFS was 6.3 months (range 2-32), with 3 pts being progression-free at 12 months. PR was detected in 3/8 MSFT e 3/5 DSFT, with a median PFS of 6.3 and 9.8 months in MSFT and DSFT, respectively. Median OS was 18.7 months (range 3-33). Conclusions: This small retrospective series suggests that doxorubicin + DTIC can be active in SFT. A higher response rate was observed in DSFT in comparison to MSFT (and pts with MSFT may have had an unsampled aggressive evolution). A prospective Phase 2 study on doxorubicin + DITC vs trabectedin in advanced SFT is under evaluation.