tbuckley/cabot-search huggingface dataset:
A Novel, Helper-Dependent, Adenovirus–Retrovirus Hybrid Vector: Stable Transduction by a Two-Stage Mechanism
Authors: Harris Soifer, Collin Higo, Christopher R. Logg, Lily Ja-Lu Jih, Toshiaki Shichinohe, Erik Harboe-Schmidt, Kohnosuke Mitani, Noriyuki Kasahara
Journal: Molecular Therapy (2002)

Panels B and C of Fig. 3 were mistakenly swapped. Below is how they should have appeared in the May 2002 issue of Molecular Therapy. We apologize for this error. A Novel, Helper-Dependent, Adenovirus–Retrovirus Hybrid Vector: Stable Transduction by a Two-Stage MechanismSoifer et al.Molecular TherapyMay, 2002In BriefWe have developed a novel vector system that uses a helper-dependent adenoviral vector as a carrier to deliver a fully functional retrovirus vector. The helper-dependent adenovirus (HDAd) can accommodate large inserts, provide high titers, and infect nondividing as well as dividing cells. However, adenoviral DNA is rarely integrated into the host cell genome, and its episomal expression is transient. Therefore we inserted a replication-competent, ecotropic retrovirus vector containing the green fluorescent protein (GFP) reporter gene as a second-stage component. Full-Text PDF Open Archive
An evaluation of local and systemic immune markers following intratumoral administration of a chimeric adenovirus Ad5/3-D24-GMCSF in refractory cancer patients with solid tumors.
Authors: Sari Anneli Pesonen, Tuuli Ranki, Elke Jäger, Julia Karbach, Claudia Wahle, Timo K. Joensuu, Tuomo Alanko, Kaarina Partanen, Kalevi Kairemo, Riku Turkki, Nina Linder, Johan Lundin, Ari Ristimäki, Mamun Majumder, Ashwini Kumar, Caroline Heckman, Matti Kankainen, Akseli Hemminki, Mikael Von Euler, Magnus Erik Jaderberg
Journal: Journal of Clinical Oncology (2015)

3085 Background: Clinical studies consistently show how adenovirus, unlike other viral vectors, can both prime and boost immune responses. Consequently, adenovirus is used to develop vaccines against various human diseases, such as cancer. Adenoviruses can be armed with transgenes for further enhancement of a tumor-specific immune reaction. We present results from a phase I study describing both local and systemic immune activation following administration of ONCOS-102, a chimeric oncolytic adenovirus, in patients with refractory solid tumors. Methods: A total of 12 patients were treated with up to 9 intratumoral injections of ONCOS-102. Biopsies were collected at baseline, 1 and 2 months after treatment initiation to analyze tumors for the presence of tumor infiltrating lymphocytes (TILs), expression of PD-L1, and gene expression profiles. Peripheral blood mononuclear cells (PBMCs) were collected to assess antigen specificity of CD8+ T cells by IFN-gamma ELISPOT. Results: No dose limiting toxicity was identified. An immediate short-term increase in systemic pro-inflammatory cytokines and an infiltration of innate immune cells into tumors was seen following ONCOS-102. Furthermore, increase in tumor infiltrating CD8+ T cells was seen in 11 out of 12 patients. 10 out of 12 patients showed an increase in PD-L1+ tumor and/or lymphoid cells. Two patients showing the most striking post-treatment increase in TILs showed also a systemic induction of tumor-specific CD8+ T cells (MAGE-A1, MAGE-A3, NY-ESO-1, mesothelin) while none of these tumor-recognizing T cell populations were detected at baseline. These two patients showed high expression levels for genes associated with activated Th1 cells (perforin, granzyme B, granulysin, IFN-gamma) and Th1 type immunoprofile (IRF-1, X3CL1, CXCL9, CXCL10, CCL5, CCL2) in post-treatment biopsies. Conclusions: Concomitant increase in CD8+ TILs and PDL1 expressing cells in tumors suggests that local ONCOS-102 treatment is able to break the immunological ignorance towards tumors by activating the immune system in advanced refractory tumors which were immunologically silent before treatment. Clinical trial information: NCT01598129.
Benign Yellow Dot Maculopathy
Authors: Arundhati Dev Borman, Aleksandra Rachitskaya, Martina Suzani, Robert A. Sisk, Zubair M. Ahmed, Graham E. Holder, Valentina Cipriani, Gavin Arno, Andrew R. Webster, Robert B. Hufnagel, Audina Berrocal, Anthony T. Moore
Journal: Ophthalmology (2017)
Vitamin D levels and its relationship with successful completion of adjuvant chemotherapy and improved survival in early stage colorectal cancer patients.
Authors: Khurram Bilal Tariq, Aaron Gopal, Asha Nayak-Kapoor
Journal: Journal of Clinical Oncology (2017)

549 Background: Vitamin D deficiency is associated with increased colorectal cancer (CRC) risk and decreased colorectal cancer survival. The purpose of this study was to determine the effect of colorectal cancer adjuvant treatment on the vitamin D status in CRC. Methods: 102 patients at the GCC with Stage I-III CRC were selected between 2009 -2011. A retrospective analyses of baseline vitamin D in these patients was made to determine if vitamin D level predicts survival. Those patients who have received neoadjuvant treatment were excluded. Only patients who had a baseline vitamin D level drawn at baseline were included. Vitamin D sufficiency was defined as serum level of 30ng/ml or greater, insufficiency as 20 to 29ng/ml and deficiency as less than 20ng/ml. Results: Mean age of the patients was 76.4 years. 45 % were Stage I , 35% comprised Stage II and 25% were Stage III. 25OHD Level was insufficient in 85% and deficient in 10% and sufficient in only 5% of the patients. In the patients who received chemotherapy (45% ), those with sufficient vitamin D levels had a statistically longer survival than those with deficient levels (p&lt;0.002). Also the patients with sufficient levels, they were more likely to complete the 6 months of chemotherapy than those with deficient levels (p&lt;0.006). The median Vitamin D level for all 102 patients was 22.8ng/ml. Patients with sufficient vitamin D levels were more likely to have lower body mass index (p&lt;0.01). There was no correlation between race and level of vitamin D. Patients with a sufficient vitamin D Level (25 patients), had a survival which was significantly more than those with deficient levels (p&lt;0.001). Patients with sufficient vitamin D levels were more likely to have stage I and II disease than stage III ( p &lt;0.04). For each stage of CRC, patients with sufficient vitaminD levels had a better overall survival than those with deficient vitamin D level(p&lt;0.01). Conclusions: Patients with sufficient levels of vitamin D are associated with better overall survival in early stage CRC. Whether aggressive vitamin D repletion would improve the outcome in vitamin D deficient CRC patients remains unknown.
Phase II trial of preoperative carboplatin (carbo)/pemetrexed (pem) in patients (pts) with select stage IB-IIIA nonsquamous non-small cell lung cancer (NS-NSCLC).
Authors: David Michael Waterhouse, John D. Hainsworth, Kent C. Shih, Ralph V. Boccia, Victor M. Priego, Michael McCleod, Donald C. Townsend, Fred J. Kudrik, R. Brian Mitchell, Howard A. Burris, F Anthony Greco, David R. Spigel
Journal: Journal of Clinical Oncology (2014)

e18510 Background: Adjuvant platinum-based chemotherapy is standard treatment (tx) in select early stage NSCLC. Adjuvant cisplatin/pem was safe, less toxic, and easier to deliver than vinorelbine/cisplatin in a randomized phase II trial (Kreuter Ann Onc 2013). Potential benefits of preoperative tx are earlier tx of micrometastatic NSCLC and better tx tolerance. This is a phase II trial of preoperative carbo/pem in select stage IB-IIIA NS-NSCLC. Methods: Eligible pts had potentially resectable T2 N0 (>4cm), T1-2 N1-N2 (1 N2 zone, biopsy proven), and T3-T4 N0-1 (not superior sulcus) NS-NSCLC (TNM 6th Ed.). Pts received carbo AUC 6 and pem 500mg/m2 IV D 1 q21 D x 4, followed by imaging, surgery, and routine follow-up (f/u). The primary aim was to assess 3-yr overall survival (OS); and secondary aims to assess response, progression-free survival (PFS), and safety. Results: 46 pts were enrolled: stage IB (11%), II (37%), and IIIA (52%); median age 65 yrs (42-82); 61% female; and 93% smokers. Median f/u: 16 mos (2-41); and median tx cycles: 4 (2-4). Best response: partial response, 19 pts (41%); stable disease, 24 pts (52%); and progressive disease (PD), 3 pts (7%). 27 pts (59%) were resected (Table); pathologic responses: 2 pts (7%), microscopic residual (<1cm); 25 pts (93%), macroscopic (≥ 1 cm). Median time to recurrence, PFS, and OS for IIIA were: 16, 12, and 29 mos, respectively (IA and II not reached). 3-yr OS was 42% (95% CI 15-68%). Grade 3/4 toxicity (≥ 5%): thrombocytopenia (41%), neutropenia (35%), anemia (15%), fatigue (7%), and dyspnea (7%). Surgical complications: 2 arrhythmias; 1 air leak; and no tx-related deaths. Conclusions: Preoperative carbo/pem was safe and well-tolerated in pts with IB-IIIA NS-NSCLC, resulting in radiographic and pathologic responses. However, a high proportion of pts did not have surgery, largely due to pt selection and PD. A randomized trial of preoperative v. adjuvant carbo/pem is required to best define this regimen’s role in IB-IIIA NS-NSCLC. Clinical trial information: NCT00193427.
Immunoglobulin Variable Region Family Usage and Outcomes of Patients with Systemic Light Chain Amyloidosis
Authors: Taxiarchis Kourelis, Surendra Dasari, Paul J Kurtin, Marina Ramirez-Alvarado, Steven R Zeldenrust, Jason D Theis, Morie A Gertz, Ahmet Dogan, Angela Dispenzieri
Journal: Blood (2014)
Preoperative concomitant chemo-radiotherapy (CT-RT) in non small cell lung cancer patients with superior sulcus tumor (SST): A single institution experience
Authors: A. G. Favaretto, L. Loreggian, F. Rea, M. Stefani, L. Bortolotti, R. Marchi, S. Aversa, G. Sotti, S. Monfardini
Journal: Journal of Clinical Oncology (2004)

7372 Background: SST is an uncommon tumor, usually resected after induction RT. In the recent years some experiences with preoperative chemo-radiotherapy were published. Methods: CT was platinum-based: Carboplatin AUC 5 on days 1 and 22, combined to Mitomycin-C 8 mg/m2, d.1 & 22, and Vinblastine 4mg/m2 dd.1, 8, 22 & 29 (MVC, from 1994 to 1999) or combined to Navelbine 25mg/m2 dd.1, 8, 22 & 29 (NC, from 2000 to 2003). RT was administered 5 dd/week, 30Gy in 10 fractions from dd. 22 to 35 (in the period 1994–96), or 44Gy in 22 fractions, dd.22 to 52 (in the period 1997–2003). Surgery was planned after 2–3 weeks from the end of RT. Results: since 1994 26 pts were treated with induction CT-RT, 1 with induction RT M/F ratio was: 23M/4F, median age 61 years/ range (43–77yrs), median PS was 80 (range 50–80), Histology subtypes were: squamous 11 (41%), adeno 10 (37%), not specified (NSCLC) 6 (21%); stage: 17 had stage IIIa according to TNM-1986 and stage IIb according to TNM-1997, 3 stage IIIa N+, and 7 stage IIIb; 4 pts had a weight loss>5%, 4 pts had a weight loss<5%. 18 pts had shoulder pain irradiated to the arm, 3 pts had the Horner Syndrome. Induction CT: 13 pts had MVC and 13 NC; 8 pts were treated with the 30Gy/10fx RT schedule, 7 had MVC as concurrent CT, 1 had not CT; 19 pts were treated with the 44Gy/22fx RT schedule, 7 had MVC and 12 NC as concurrent CT. Hematologic toxicity of induction CT-RT was mild: out of 52 cycles we observed 3 gr.4 and 2 gr.3 neutropenia; 7 gr.3 leukopenia; 1 gr.4 and 1 gr.3 thrombocytopenia; 2 gr.3 and 3 gr.2 anemia. Non-Hematologic toxicity was: constipation in 9 pts, oesophagitis in 5 pts, N/V in 4 pts; 14 partial and 3 minimal responses were observed.. Surgery: 22 upper lobectomies (15 right, 7 left) and 2 segmentectomies, with chest wall resections, were performed (89% resection rate); 3 pts were not operated: 2 for unresectability 1 for early death during induction CT-RT. Two pathologic complete remissions were seen. 17 pts had improvement of shoulder/arm pain. Median survival was 167 weeks. Conclusions: in SST, concurrent CT-RT was active and feasible without major toxicities, and resulted in a high resectability rate. No significant financial relationships to disclose.
Phase I trial of enzalutamide, gemcitabine, and nab-paclitaxel as a first-line treatment for advanced pancreatic cancer.
Authors: Amit Mahipal, Gregory M. Springett, Nancy Burke, Anthony Neuger, Khaldoun Almhanna, Georgine Wapinsky, Barbara Bertels, Richard D. Kim
Journal: Journal of Clinical Oncology (2015)

e15250 Background: Sex steroid hormones may play an important role in the growth and progression of pancreatic cancer. In the Phase Ia portion of this trial, we evaluated the safety and tolerability of the combination of enzalutamide, a novel androgen receptor (AR) antagonist with gemcitabine and nab-paclitaxel in pts with metastatic pancreatic cancer as a first-line treatment. Methods: Standard 3+3 dose escalation design was used to evaluate 2 dose levels of enzalutamide: 80 mg and 160 mg daily. Gemcitabine (1000 mg/m2) and nab-paclitaxel (125 mg/m2) was administered IV on days 1, 8 and 15 of a 28-day cycle. The dose limiting toxicity (DLT) period was 28-days or until the beginning of the second cycle. A full PK profile was evaluated for nab-paclitaxel after the initial dose through 48 hours post dose while enzalutamide was tested on day 1 at 1 and 2 hours post dose along with levels every 7 days to follow achievement of steady state by day 29 (C2D1). Results: Twelve patients with stage IV pancreatic cancer were enrolled in phase 1a part, 5 patients at the first dose level and 7 patients at the second dose level. The median age was 60 years (50-80 years). Common site of metastases were liver (9), LN (7) and lung (2). Two pts were non-evaluable for DLT. No DLTs were observed. Grade 3/4 treatment related AEs include febrile neutropenia (1), Neutropenia (4), ALT elevation (1), pneumonitis (1), fever (1), anemia (1) and hypoxia (1). Common grade 1/2 related AEs included thrombocytopenia (8), anemia (7), nausea (6), fatigue (6), and ALT elevation (5). Among the 10 evaluable patients, 1 pt had a partial response and 9 pts had stable disease. All patients had decreased CA 19-9 levels. Nine pts are on treatment. PK analysis suggests that the combination therapy does not impact the kinetics of either drug evaluated. Enzalutamide reached steady state levels between day 22 and 29 and the mean half-life of nab-paclitaxel was 19.6 ± 4.7 hours. Conclusions: Enzalutamide at the dose of 160 mg daily is safe to administer in combination with gemcitabine and nab-paclitaxel. No unexpected toxicity has been observed. Preliminary signals of efficacy were observed with this combination. Patients with AR+ tumors are being enrolled in the phase Ib part. Clinical trial information: NCT02138383.
Race- and health-related quality of life among patients newly diagnosed with multiple myeloma.
Authors: Chris L Pashos, Brian G. Durie, Robert M. Rifkin, Rafat Abonour, Rafael Fonseca, Cristina Gasparetto, Jayesh Mehta, Mohit Narang, Jatin J. Shah, Howard R. Terebelo, Sachdev P. Thomas, Kathleen Toomey, Arlene S Swern, Gale Harding, Kristen Sullivan, Thomas Street, Zeba M. Khan
Journal: Journal of Clinical Oncology (2012)

e18556 Background: Studies in the United States (US) have identified variation in incidence and survival of multiple myeloma (MM) patients of different races, and noted that MM is the most common hematologic cancer among African Americans. This analysis evaluated whether health-related quality of life (HRQOL) of patients in the US varies by race as they initiate treatment having been newly diagnosed with active, symptomatic MM. Methods: Data were collected in Connect MM, a prospective US observational registry begun in September 2009. Data on patient demographics and clinical characteristics were provided by clinicians. HRQOL was reported by patients at enrollment within 2 months of diagnosis. Patients completed the Brief Pain Inventory (BPI), EQ-5D, and Functional Assessment of Cancer Therapy-Multiple Myeloma (FACT-MM). Mean reported scores for BPI, EQ-5D and FACT-MM were analyzed by patient race. Statistical significance was ascertained by ANOVA using SAS 9.1. Results: Baseline HRQOL data were reported by 1144 patients (enrolled in 228 centers) of whom 82% were White, 13% Black, and 6% Other race. The cohorts did not differ statistically by ECOG status or by multiple myeloma stage (assessed by either the International Staging System or the Durie and Salmon system). Compared to non-Blacks, Black patients reported less anxiety/depression on the EQ-5D (p=0.030) and better emotional well-being on the FACT-MM (p=0.003). No other statistically significant differences were noted between cohorts on the BPI, other EQ-5D domains (mobility, self care, usual activities, pain/discomfort), or other FACT-MM domains (physical, social/family, functional, and MM-specific considerations). Conclusions: Initial results from the Connect MM Registry indicate that baseline HRQOL prior to initiation of treatment may vary by patient race with respect to emotional well-being, and specifically anxiety/depression. These results serve as a baseline reference for future analyses. As patients in the Connect MM Registry proceed through therapy, analyses should be conducted of patients by race, among other characteristics and factors, to determine whether it may be associated with subsequent clinical outcomes and HRQOL over time.
Updated outcome with long-term follow-up of imatinib for the treatment of progressive or recurrent aggressive fibromatosis (desmoid tumor): A FNCLCC/ French Sarcoma Group phase II trial
Authors: A. Dufresne, N. Penel, S. Salas, A. Le Cesne, D. Perol, B. Bui, E. Brain, I. Ray-Coquard, M. Jimenez, J. Blay
Journal: Journal of Clinical Oncology (2009)

10518 Background: We present updated results from a previously reported phase II trial assessing clinical efficacy of imatinib in progressive or recurrent aggressive fibromatosis (Fayette et al. ASCO 2007) Methods: Patients with aggressive fibromatosis not amenable to radiotherapy or non-mutilating surgery were eligible and received imatinib 400mg daily (increased to 800mg daily in case of progression) up to 1 year then stopped. The primary end point was non-progressive disease rate at 3 months. Independent radiological committee reviewed responses. The number of patients was calculated according to a optimal 2-stages design. Results: Forty patients were included between September 2004 and October 2005 in 15 centers. The median follow up is 33 months [95% CI: 32–35]. Toxicity of imatinib is similar to that previously reported. At 3 months, the nonprogression rate was 91% [95% CI: 77–96] with 1 (2%) complete and 3 (8%) partial confirmed responses observed. The non progression rates at 6, 9, and 12 months were 80%, 69% and 66% respectively. The median time to progression was 9.5 months. The 2-year progression-free survival (PFS) was 55%. No plateau was observed. The 2-year-overall survival was 95%. Two patients with mesenteric aggressive fibromatosis died from progressive disease. In multivariate analysis including clinical factors, only previous radiotherapy was associated with reduced progression free survival. None of the biological factors tested using IHC on TMA (PDGFR α, PDGFR β, β catenin, c-kit, E cadherine, MCSFR, cycline D1 and Erk) were found correlated to response, progression free or overall survival. Conclusions: With a 2.8 years median follow up, this is the largest study which confirms the high efficacy of imatinib (400 mg daily) in patients presenting with aggressive fibromatosis failing local treatment and with documented evidence of progressive disease before imatinib treatment. [Table: see text]
Randomized phase III trial of stereotactic radiosurgery (SRS) versus observation for patients with asymptomatic cerebral oligo-metastases in non-small cell lung cancer (NSCLC).
Authors: Sung Hee Lim, Ji Yun Lee, Min-Young Lee, Donghoon Han, Sungmin Kim, Hyun Ae Jung, Moonjin Kim, Jong-Mu Sun, Jin Seok Ahn, Keunchil Park, Sang-Won Um, Hojoong Kim, O Jung Kwon, Jung-Il Lee, Myung-Ju Ahn
Journal: Journal of Clinical Oncology (2014)

8037 Background: In patients with non-small cell lung cancer (NSCLC) with asymptomatic cerebral oligo-metastases, it is unclear whether treating brain metastasis before starting systemic chemotherapy is beneficial effects on survival compared with upfront systemic chemotherapy. This study was aimed to determine if early treatment with stereotactic radiosurgery (SRS) improve overall survival (OS) in NSCLC patients with asymptomatic oligo-brain metastases. Methods: We undertook a randomized controlled trial of 105 patients with asymptomatic oligo (1 to 4) brain metastases, each less than 3 cm in diameter, enrolled at Samsung Medical Center between 2008 and 2013. Patients older than 18 years with NSCLC and synchronous asymptomatic brain metastasis were randomly assigned to receive SRS initially (53 patients) followed by systemic chemotherapy or upfront systemic chemotherapy alone group (52 patients). The primary end point was OS and secondary end points included time to CNS disease progression, salvage brain treatment. Results: The median age of all patients was 58 years (range, 29-85) with good ECOG performance status(0,1), and most patients had adenocarcinoma (87%). The median overall survival time was 15.8 months (95% CI, 8.1-23.5) in SRS group and 17.6 months (95% CI, 12.4-22.8) for observation group (P=0.346). There was no significant difference in time to CNS disease progression (median, 9.4 months vs. 8.7 months, P=0.579). Salvage treatment for progression of CNS disease was required more frequently in observation group (52.8%) than SRS group (47.2%) which did not show statistical significance (P=0.201). The multivariate analysis revealed that higher extra-cranial disease activity, number of brain metastases (≥2), age older than 65 years, non-adenocarcinoma histology were independent risk factors associated with poor OS. Conclusions: These results suggest that SRS treatment followed by systemic chemotherapy did not improve overall survival in asymptomatic oligo-brain metastases NSCLC patients compared with upfront chemotherapy alone.