tbuckley/cabot-search huggingface dataset:
Development of CMRF-56 blood dendritic cell preparations for immunotherapy of multiple myeloma
Authors: F. Vari, T. Rossetti, D. Munster, D. Hart
Journal: Journal of Clinical Oncology (2006)

17572 Background: Despite advances in therapy for multiple myeloma, such as the use of proteosome inhibitors or stem cell transplantation, it is usually incurable. One promising therapeutic approach is to eradicate residual disease after stem cell transplantation by immune therapy. Method: The CMRF-56 monoclonal antibody detects an antigen expressed on blood dendritic cells (BDC) that is expressed after a short in vitro culture period. With clinical trail applications in mind, we have developed a procedure for isolation of CMRF-56+ BDC using CliniMACS. Cell culture, antibody staining and immunoselection occur in a closed system, compatible with regulatory requirements for cell therapy. Simultaneously, our team has developed of a bioprocess for production of the murine biotinylated CMRF-56 antibody for clinical trials. The bioprocess incorporates components that remove contaminating DNA, host cell proteins, viral particles and endotoxin. Results: Positive immunoselection using this antibody produces a BDC population containing some contaminating CMRF-56 positive B cells and monocytes. CliniMACS selection of PBMC from an apheresis produces enough BDC for a vaccination program with an average recovery of 1%, purity of 38%, yield of 48% and viability of 70%. These CMRF-56 dendritic cell preparations have been used to generate strong T cell responses to influenza matrix peptide and the putative tumour antigen MART-1. In order to discover and validate additional antigens capable of inducing effective immune responses against multiple myeloma, we have tested numerous of potential target antigens. It has been possibe to generate moderate specific immune responses against HM1.24 and mucin 1 peptides in normal HLA A2 donors. Using the CMRF-56 dendritic cell preparation as antigen presenting cells, it is possible to generate strong cytotoxic T cell responses against a lysate of the myeloma cell line U266. Indicating the potential usefulness of a whole cell lysate in generating anti-myeloma T cells for immunotherapy. Conclusions: These studies have provided the necessary pre-clinical data to commence a Phase I Clinical Trial in 2006 using CMRF-56 BDC preparations loaded with myeloma and control antigens in myeloma patients with minimal residual disease. No significant financial relationships to disclose.
Imaging biomarkers of ramucirumab and olaratumab in patients with recurrent glioblastoma.
Authors: Jaishri O'Neill Blakeley, Joy D. Fisher, Frank S. Lieberman, Janine Lupo, Louis B. Nabors, Jason Crane, Patrick Y. Wen, Andre Cote, David M. Peereboom, Qiuting Wen, Timothy Francis Cloughesy, H. Ian Robins, Serena Desideri, Stuart A. Grossman, Xiaobu Ye, Sarah Nelson
Journal: Journal of Clinical Oncology (2013)

2044 Background: VEGF and PDGF receptors are overexpressed in glioblastoma (GBM). Both receptor families may be important therapeutic targets. We explored early biologic markers of VEGFR-2 or PDGFRa inhibition with functional MRI. Methods: A subset of patients (pts) from a multicenter phase II study of monoclonal antibodies to VEGFR-2 (ramucirumab 8mg/kg IV q2wks) or PDGFRa (olaratumab 20mg/kg IV q2wks) in adult patients with recurrent GBM underwent a standardized MRI brain protocol with dynamic contrast enhanced (CE); diffusion tensor; perfusion weighted and routine sequences at -1d, +1d, +28d and every +56d from treatment initiation. ACRIN performed site qualification and imaging QA. Regions of CE and T2w hyperintensity were manually defined; percent change in volumes and change in normalized image intensities was calculated. Results: 28 patients were evaluable. Pts receiving ramucirumab (n=11; 7 male) had a median age of 54 (43-67), KPS 90 (70-100) and Dex dose 2mg (0-8). Pts receiving olaratumab (n=17; 14male) had a median age of 58 (24-72), KPS 80 (70-100) and Dex dose 2mg (0-4mg). KPS and Dex were stable over time. Conclusions: Preliminary results show that within 1 day of ramucirumab, CE volume, relative CE intensity and blood volume decreased and by 28 days, T2 volume and ADC decreased suggesting a potent antiangiogeneic effect. PDGFRa inhibition had no effect on lesion volume, but reduced relative CE intensity and blood volume at 28 days. Clinical efficacy results are anticipated in mid-2013. Clinical trial information: NCT00895180. [Table: see text]
EPIDEMIOLOGY AND INCIDENCE OF INJURY IN ELITE NETBALL PLAYERS – AN INJURY AUDIT OF THE 2016 NETBALL SUPERLEAGUE SEASON
Authors: Gemma Best
Journal: British Journal of Sports Medicine (2017)

Background With England netball announcing that for the first time in its history it will be offering full time, professional contracts there is an increased need to be able to understand why players are getting injured in top level competition. Objective To undertake a prospective epidemiological study of injuries sustained in elite netball. Design A cohort design was used to collect descriptive injury data using superleague netball players. Setting 2016 British Netball Superleague season. Patients (or Participants) 103 players across 8 superleague netball teams were used in the study. Main Outcome Measurements Date of injury, age of player, playing position, activity at time of injury, mechanism of injury, classification of injury at two levels (body location and injury type), predicted time loss and identification of injury being acute, gradual on set or recurrent was recorded. Injuries were recorded by physiotherapists at each netball franchise using a specific injury audit questionnaire designed to suit the characteristics of netball. Results 59 injuries we recorded during one season with an injury incidence rate of 9.08 injuries per 1000 hours exposure. Injuries were more common in competitive match play (71.2%) than in training (28.8%). The ankle was injured most frequently (35.6%). Data revealed a significant association between match quarter and occurrence of injuries χ 2 (3)=9.91, p=0.019. A tendency for injuries to increase throughout the time in match and a peak reached at the third quarter was observed. No significant association was observed between playing position and injury incidence χ 2 (2)=0.917, p=0.632. Overall injury frequency was highest in the first half of the regular 14 week season with 57.6% of all injuries occurring in this time frame. Conclusions Pre-season preparation, half time match strategies and overall physiological conditioning should be considered when addressing injury prevention within elite netball.
Composite assessment of treatment response in patients (pts) with locally advanced basal cell carcinoma (laBCC): Sonidegib efficacy using two sets of response criteria.
Authors: Reinhard Dummer, Vernon K. Sondak, James M Grichnik, Lawrence H. Schwartz, Sven Gogov, Tingting Yi, Manisha Mone, Aldo Trylesinski, Dalila B. Sellami, Michael Robert Migden
Journal: Journal of Clinical Oncology (2015)

e20055 Background: In the pivotal BOLT phase 2 study (NCT01327053), durable responses were observed in pts with advanced BCC treated with sonidegib, a hedgehog pathway inhibitor (HPI). Treatment responses were assessed using a novel composite evaluation, which was more stringent than that used in prior studies of HPIs in BCC. In this analysis, treatment responses in BOLT were evaluated using 2 sets of criteria: BCC-mRECIST (A; used in BOLT) and BCC-mRECIST-like (B; similar to criteria used in other HPI studies with less stringent requirements for complete response [CR]). Methods: Assessments by MRI per RECIST v1.1, photography per WHO guidelines, and histology in multiple biopsies were used to determine a composite overall response (COR) in pts with laBCC treated with sonidegib 200 mg once daily (QD) using criteria A and B. The main distinction between A and B was the level of stringency required to achieve a COR of CR. Criteria B allowed a COR of CR when the response by MRI and/or photography was partial (PR) or stable disease (SD), as long as the histology result was negative; in contrast, in the same cases, COR by criteria A was considered a PR. Objective response rate (ORR), best overall response (BOR), and disease control rate (DCR; CR + PR + SD) were assessed by central review using both criteria. Results: The ORR and DCR were similar with both criteria (Table), but the CR rate was higher with criteria B than with A (20% vs 5%). Conclusions: These data demonstrate a high response to sonidegib and the stringency of the BCC-mRECIST criteria used in BOLT.The higher CR rate with the BCC-mRECIST-like criteria observed in this analysis was due to the less stringent requirement for a COR of CR (ie, negative histology can overrule MRI/photography data that indicate residual disease). Despite the inherent challenges of assessing tumor response in laBCC, both evaluation criteria support the clinical benefit of sonidegib in this difficult-to-treat pt population. Clinical trial information: NCT01327053.Efficacy of sonidegib 200 mg QD in pts with laBCC (n = 66)a Criteria A B ORR, % 58 62 95% CI 45-70 49-74 BOR, % CR 5 20 PR 53 42 SD 33 29 Progressive disease 2 2 Unknown 8 8 DCR, % 91 91 a 12-mo data; cutoff: Dec 31, 2013; median follow-up: 20 mo.
Feasibility of a home-based walking program in female breast cancer patients age 60+ during chemotherapy.
Authors: Kirsten A Nyrop, Allison Mary Deal, Shani Malia Alston, Samara Ann Dixon, Hyman Muss
Journal: Journal of Clinical Oncology (2015)

9543 Background: National guidelines recommend 150 minutes a week of moderate-intensity physical activity for adults with a cancer diagnosis. Our study investigated the feasibility of a self-directed walking in women age 60 or older undergoing cytotoxic chemotherapy treatment for breast cancer. Feasibility was defined as at least 50% of study participants reporting an average of 150 minutes or more of walking/week for exercise or pleasure during the first 6 weeks of chemotherapy. Methods: Eligibility: Female, age 60+; Stage I-III breast cancer; scheduled for chemotherapy; physician permission to engage in physical activity; English speaking. Intervention: Evidence-based physical activity program for adults with arthritis – “Walk With Ease”. Measures: Patients self-reported the average number of days and number of minutes per day of walking for exercise or pleasure during chemotherapy. Study participants also maintained a daily walking diary throughout the first 6 weeks of chemotherapy. Data analysis: Descriptive statistics. Results: Study sample (N = 22): mean age 68 (60-79), 95% Caucasian, 41% high school degree or less, mean Body Mass Index/BMI 31 (20-50), 50% two or more comorbidities. At baseline (pre-chemotherapy), 29% of participants reported walking at least 150 minutes/week. During chemotherapy, the proportion walking > 150 minutes/week: 41% Week 1, 54% Week 2, 32% Week 3, 45% Week 4, 50% Week 5, 45% Week 6. During chemotherapy, the proportion walking > 100 minutes/week: 68% Week 1, 73% Week 2, 77% Week 3, 64% Week 4, 68% Week 5, 65% Week 6. Conclusions: A home-based, self-directed walking program can encourage older female breast cancer to engage in regular exercise during chemotherapy at a level that is higher than pre-chemotherapy. Achievement of the goal of 150 minutes per week is challenging, and more feasible at a level of 100 minutes per week. This pragmatic physical activity intervention is now being tested in a 4-year efficacy trial with a large sample of female breast cancer patients age 65 or older during chemotherapy treatment, to evaluate the impact of exercise on p16INK4a (biomarker of aging), fatigue and other patient-reported outcomes. Clinical trial information: NCT01789983.
Validation of postoperative adjuvant chemotherapy for elderly patients with stage II/III gastric cancer.
Authors: Tetsuya Kusumoto, Mitsuhiko Ohta, Yasue Kimura, Norifumi Tsutsumi, Masahiko Sugiyama, Eiji Kusumoto, Yoshihisa Sakaguchi, Koji Ikejiri, Hiroshi Saeki, Eiji Oki, Yoshihiko Maehara
Journal: Journal of Clinical Oncology (2015)

e15036 Background: In recent years, the proportion of elderly patients has increased in Japan. Our previous report showed that the elderly patients with non-resectable gastric cancer tolerated intensive chemotherapy, with sufficient efficacy in cases that had neither severe general complications nor organ dysfunctions. We herein examined the clinical significance and validation of postoperative adjuvant S-1 monotherapy following curative gastrectomy for the elderly patients with advanced gastric cancer (AGC). Methods: We conducted a retrospective review of the data of 132 patients with Stage II or III AGC. These patients were categorized into a younger group ( < 75 years old, n = 75, 66 patients received adjuvant chemotherapy and 9 received surgery alone) and an elderly group ( ≥ 75 years old, n = 57, 19 and 38 respectively). The S-1 toxicity, RFS and OS were compared between these 4 groups. Results: In the elderly group, the proportion of AGC patients receiving the adjuvant chemotherapy was 5% and 47% in Stage II and III, respectively. In the adjuvant chemotherapy group, the incidence of adverse events was higher in the elderly group than in the younger group. However, the rates of hematological and non-hematological toxicities of higher than grade 3 in the elderly group, were similar to those found in the younger group. For the survival data, the median RFSs were 893 or 888 days in the elderly patients who received adjuvant chemotherapy or surgery alone, respectively. In Stage III patients, the similar values were 893 and 692 days, respectively, which were not significantly different. Conclusions: Adverse reactions were more frequently reported in the elderly group than in the younger group. However, our study showed that the elderly patients tolerated S-1 monotherapy, with sufficient efficacy. The adjuvant S-1 monotherapy should be considered even for the elderly patients with AGC, in cases that had neither severe general complications nor organ dysfunctions.
A drug-drug interaction study on the combination of cabazitaxel with enzalutamide in patients with metastatic castration-resistant prostate cancer.
Authors: Bodine P.S. Belderbos, Sander Bins, Roelof W.F. van Leeuwen, Esther Oomen De Hoop, Nelly van der Meer, Peter de Bruijn, Paul Hamberg, Esther N.M. Overkleeft, Wendy M. van der Deure, Martijn P. Lolkema, Ronald De Wit, Ron H.J. Mathijssen
Journal: Journal of Clinical Oncology (2017)

188 Background: Cabazitaxel and enzalutamide are effective single agent treatment options for metastatic castration resistant prostate cancer (mCRPC). Preclinical studies suggest enhanced efficacy of the combination of a taxane with enzalutamide. Recently, Morris et al. (CCR 2016) reported on an interaction study between docetaxel and enzalutamide: docetaxel mean exposure decreased by 12% during a short period of co-treatment with enzalutamide, probably due to enzyme (CYP3A4) induction. Since cabazitaxel is a CYP3A4 substrate, we investigated the influence of enzalutamide on cabazitaxel pharmacokinetics (PK) and toxicity during 3 chemotherapy cycles. Methods: We performed a cross-over study in 14 evaluable mCRPC patients who were treated with i.v. cabazitaxel Q3W (25 mg/m 2 ). PK-sampling (over 24h) was conducted on day 1 of each cycle during 3 consecutive cabazitaxel cycles. From day 8 (±1) of the first cycle until day 8 (±1) of the third cycle, enzalutamide (160 mg/day) was administered concomitantly. Primary endpoint was the difference in geometric mean area under the curve (AUC 0-24h ) between the first and third cycle. Secondary endpoints included safety parameters and PSA response. Results: The AUC was 22% (95%CI 9-34%) lower during the third cycle (181 ng*h/mL, 95%CI 150-219 ng*h/mL) than during the first cycle (234 ng*h/mL, 95%CI 209-261 ng*h/mL; p = 0.005). No relevant adverse events occurred due to the drug combination. Nine patients (64%) received the full dose of cabazitaxel during the 3 study cycles. No enzalutamide dose reductions took place, and the combination was well tolerated. PSA response ( ≥ 50% decrease of baseline PSA ) was observed in 10 patients (71%). Conclusions: Cabazitaxel exposure is both statistically and clinically significantly reduced by concomitant enzalutamide use. Since the PROSELICA study (De Bono et al, ASCO 2016) may lead to an adapted standard cabazitaxel dose of 20 mg/m 2 , the clinical relevance of this interaction may be extensive, since it is likely to result in suboptimal exposures. We stimulate clinical studies with this combination, but these should include monitoring of the PK of cabazitaxel, and appropriate dose adaptations. Clinical trial information: NTR5164.
Impact of antithymocyte globulin (ATG)-containing conditioning regimens on patients undergoing allogeneic stem cell transplantation (allo-CST) for poor risk cytogenetic IPSS myelodysplastic syndrome (PRC-MDS): A report from the French Society of Stem Cell Transplantation and Cell Therapy (SFGM-TC).
Authors: Ibrahim Yakoub-Agha, Gandhi Laurent Damaj, Marie Robin, Stephane Vigouroux, Alice Garnier, Mauricette Michallet, Jean El Cheikh, Bruno Lioure, Jacques-Olivier Bay, Nathalie Contentin, Natacha Maillard, Eric Deconinck, Alain Duhamel, Mohamad Mohty
Journal: Journal of Clinical Oncology (2012)

6542 Background: Due to a risk of relapse of underlying disease in patients with PRC-MDS, the use of ATG, incorporated within the conditioning regimen prior to allo-SCT, is still controversial. Methods: Inclusion criteria included patients aged over 18 (n=101) who received allo-SCT transplanted between 1999 and 2009 from either a sibling (n=68) or HLA-allele-MUD (10/10) (n=33) for PRC-MDS. HLA matching was double-checked by the national Bone Marrow Donor Registry. Results: According to the FAB/WHO classification at diagnosis, 22 pts had RA/RARS/RCMD, 40 RAEB1, 30 REAB2 and 9 RAEB-t/AML. 34 pts had progressed to a more advanced disease before allo-SCT. At diagnosis, 89 patients had an IPSS int-2 or higher. At transplant, 36 pts were responders (CR, PR, CRm) and 62 with progressive disease (relapsed/refractory, untreated or stable disease without hematological improvement). Median age at transplantation was 54 years (range, 22-69). Pts received myeloablative conditioning (n=46) and nonmyeloablative (n=55). In this series, 48 patients received ATG as part of conditioning ('ATG' group), whereas 53 did not ('no-ATG’ group). As of April 1st 2011, 44 patients died of relapse and 22 of TRM. 3-year relapse, overall and event-free survival rates were not significantly different between the two groups. In contrast, the cumulative incidence of grade 2-4 acute GVHD was 48% in the no-ATG group and 30% ATG group (P &lt;.005). Although the cumulative incidence of chronic GVHD was similar in the no-ATG and ATG groups, a trend for a lower TRM was observed in the ATG group (p=.06). In multivariate analysis, the absence of use of ATG was associated with an increased risk of acute grade 2-4 [HR = 1.92, p=.044]. Conclusions: The addition of ATG to the conditioning regimen resulted in a decreased incidence of acute GVHD without increasing relapse rates and compromising survival of patients undergoing allo-SCT for poor risk cytogenetic MDS.
POWER-remote: A randomized study evaluating the effect of a remote-based weight loss program on biomarkers in women with early-stage breast cancer.
Authors: Cesar Augusto Santa-Maria, Amanda Blackford, Gerald J Jerome, Janelle Coughlin, Claire Frances Snyder, Arlene Dalcin, Christina Shehata, Stacie Jeter, Colleen Schreyer, Brandon Luber, Lawrence J Appel, Vered Stearns
Journal: Journal of Clinical Oncology (2014)

TPS9657 Background: The majority of women diagnosed with breast cancer are overweight or obese, and gain weight with treatment, leading to inferior survival outcomes. The Practice-based Opportunities for Weight Reduction (POWER) investigators reported that, in an obese population with cardiovascular risk factors, a scalable remote-based weight loss intervention was equally effective to an in-person intervention (Appel NEJM 2011). We have adapted the remote intervention for breast cancer survivors. Methods: Randomized phase II single-blinded trial. Participants are women with stage 0-III breast cancer and a BMI ≥ 25 who have completed local therapy and adjuvant chemotherapy. Objectives:1.) Compare the proportion of participants who lose ≥5% of their baseline body weight after 6 and 12 months in the POWER-remote and self-directed (control) arms; 2.) Investigate the effects of weight loss on a panel of biomarkers relevant to obesity, inflammation, and breast cancer risk (insulin, IGF-1, hsCRP, IL-1, IL-6, TNF-α, leptin, adiponectin, estradiol, and telomere length); 3.) Investigate the effects of weight loss on patient-reported outcomes (PROs), particularly physical function. Statistical Approach: We hypothesize that the proportion of women who experience ≥5% weight loss after 6 months will be greater in POWER-remote and will be similar to the results of the original POWER study (38.2% and 18.8% ≥5% weight loss in the remote and control groups, respectively). An interim futility analysis is planned after the first 80 patients are evaluable for the primary endpoint. The final analysis will conclude a significant benefit from POWER-remote if the one-sided p value is greater than 0.10 by Fisher’s exact test. Changes in biomarkers and PROs from baseline to 6 months will be calculated and tested for differences by treatment arm and by response. We have enrolled 16 of the planned 200 patients. Future Directions: Results will be used to implement clinically based weight loss programs, and biomarker data will improve our understanding of energy dynamics in breast cancer survivors, leading to future studies investigating weight loss for primary and secondary breast cancer prevention. Clinical trial information: NCT01871116.
CRS-207 vaccine plus chemotherapy as front-line treatment for subjects with malignant pleural mesothelioma (MPM).
Authors: Raffit Hassan, Scott J. Antonia, John J. Grous, Aimee Murphy, Anish Thomas, Andrew Miller, Thomas Dubensky, Dirk G. Brockstedt
Journal: Journal of Clinical Oncology (2013)

TPS7607 Background: CRS-207 is a live-attenuated Listeria monocytogenes (Lm) vaccine expressing the tumor-associated antigen mesothelin which is overexpressed in MPM. CRS-207 was well tolerated and induced Lm- and mesothelin-specific T cell immunity in a phase 1 study in adults with mesothelin-expressing cancers (Le et al., Clin. Cancer Res. 2012). Preclinical and clinical studies suggest that vaccines and chemotherapies work synergistically and augment anti-tumor effectiveness of subsequent chemotherapies. Methods: This phase 1B study is evaluating the safety and induction of mesothelin-specific immune responses by CRS-207 plus chemotherapy with pemetrexed (P) and cisplatin (C) in adults with newly diagnosed, unresectable MPM. Two doses of 1×10 9 colony forming units (CFU) CRSE207 are administered intravenously two weeks apart followed two weeks later by up to six cycles of P (500 mg/m2) and C (75 mg/m2) given every 3 weeks. Two booster vaccinations of CRS-207 are administered three weeks apart 4 weeks after completing PC. Secondary and exploratory endpoints will assess objective tumor response, time to progression, overall survival and immune correlates. This is one of the first trials to assess the synergy between vaccines and chemotherapy in newly diagnosed patients with MPM. Sponsor: Aduro BioTech, Inc. ClinicalTrials.gov ID: NCT01675765. Clinical trial information: NCT01675765.