tbuckley/cabot-search huggingface dataset:
Phase I evaluation of an agonist anti-CD27 human antibody (CDX-1127) in patients with advanced hematologic malignancies.
Authors: Stephen Maxted Ansell, Donald W. Northfelt, Ian Flinn, Howard A. Burris, Shira Naomi Dinner, Victor Manuel Villalobos, Branimir I. Sikic, Matthew Hiram Taylor, Lana Pilja, Thomas R. Hawthorne, Michael Jay Yellin, Tibor Keler, Thomas A. Davis
Journal: Journal of Clinical Oncology (2014)

3024 Background: CD27, a member of the TNF receptor superfamily, is a co-stimulatory molecule that regulates T cell activation, survival, and memory responses through interaction with a tightly regulated ligand, CD70. CDX-1127 is an anti-CD27 human antibody shown to activate human T cells when combined with T cell receptor stimulation, and mediate anti-tumor activity in human CD27 transgenic mice challenged with syngeneic tumors. Methods: In a 3+3 dose-escalation (DE), patients (pts) with advanced B-cell lymphoma received CDX-1127 (0.1, 0.3, 1.0, 3.0 or 10 mg/kg IV) as a single dose with 28-day observation, followed by up to 5 treatment cycles (4 weekly doses / Day 85 restaging), until progression. Results: 19 pts (3 Hodgkin (HL), 5 follicular, 9 diffuse large B-cell, 2 unspecified non-Hodgkin) have received CDX-1127. DE has exceeded 3 mg/kg with no DLT; enrollment at 10 mg/kg is ongoing. Treatment-related toxicity, generally Grade 1-2, included fatigue, nausea, decreased appetite and anemia. A pt with Stage IV Hodgkin lymphoma who had previously failed chemotherapy, autologous stem cell transplant, and brentuximab vedotin experienced a complete response (CR) and remains in remission at 8.6+ months. IHC analysis of archived tumor for the 3 HL pts showed CD27-negative reed-sternberg cells and CD27-expressing infiltrating lymphocytes. The highest tumor CD27 expression was noted for the pt who had CR. Three additional pts had stable disease (4.5, 5.6 and 14.0 months), including a pt with follicular lymphoma who has completed 3 cycles of therapy and a pt with marginal zone lymphoma with 36% shrinkage in measurable disease. Response data are pending for the 10 mg/kg dose level. Immune correlates including serum cytokines, soluble CD27 levels, and changes in circulating lymphocyte populations are being investigated. Conclusions: Emerging results suggest that weekly dosing of CDX-1127 is well tolerated with promising biological and clinical activity in pts with B-cell lymphoma. A DE in pts with T cell malignancies is underway. Single agent safety and activity data support planned combination studies with both conventional and immune-based therapies. Clinical trial information: NCT01460134.
Patterns of treatment and outcomes in elderly patients with non-metastatic, unresected gastric adenocarcinoma: A review of the Florida cancer data system.
Authors: Gregory Riccardo Vlacich, Pamela Parker Samson, Hayley Stowe, Samantha Hsieh, Cliff Grant Robinson, Stephanie Mabry Perkins
Journal: Journal of Clinical Oncology (2017)

146 Background: Concurrent chemoradiation is considered definitive treatment for unresected, localized gastric adenocarcinoma, but utilization in the elderly is complicated by increased toxicity risk and limited life expectancy. The benefit of concurrent chemoradiation in this population over non-definitive therapy is not well characterized. Methods: The Florida Cancer Data System was queried for patients ≥ 60 years old diagnosed with non-metastatic gastric adenocarcinoma between 2004 and 2010 who did not undergo primary surgery. Logistic regression was performed to evaluate variables independently associated with treatment and mortality hazard was evaluated using Cox-proportional modeling. The primary aim was to compare overall survival between groups. Results: A total of 1,729 patients were identified with a median and maximum age of 79 and 101 years respectively. The majority received no therapy (68.4%) followed by concurrent chemoradiation (12.0%), chemotherapy alone (10.5%), radiation alone (5.0%), and sequential chemoradiation (4.2%). Median survival with no treatment was 3.7 months (95% CI: 3.3-4.1) and no difference was seen with radiation alone (MS 5.4 months, p = 0.85). However, improved survival was seen with chemotherapy alone (9.1 months), and concurrent (10.5 months) and sequential (12.5 months) chemoradiation, all p &lt; 0.001 compared to no therapy. Despite a modest survival benefit with sequential chemoradiation compared to chemotherapy alone (p = 0.046), this was not seen with concurrent chemoradiation (p = 0.215) or between concurrent and sequential chemoradiation (p = 0.266). On multivariate analysis, age ≥ 80 (OR 0.41, p &lt; 0.001) and African-America race (OR 0.45, p = 0.004) were independently associated with no treatment compared to receiving any chemotherapy. Conclusions: Chemotherapy may improve survival over those not receiving systemic therapy, and the addition of radiation does not appear to provide any added benefit over chemotherapy alone. Advanced age and African-American race are strong predictors against chemotherapy use, however additional factors not accounted for such as performance status may contribute.
Effect of new anti-neoplastic agent, MK615, from Japanese apricot, ume, on growth of breast cancer cells in vitro
Authors: A. Nakagawa, T. Sawada, T. Okada, T. Ohsawa, M. Adachi, K. Kubota
Journal: Journal of Clinical Oncology (2007)

11105 Background: MK615 is an extract mixture from Japanese apricot, UME. In this study, the anti-neoplastic effects of MK615 against breast cancer cells were investigated. Methods: Two breast cancer cell lines, MDA-MB-468 (MDA) and MCF7, were cultured with (600, 300, 150 μg/ml) or without MK615. After 72 hours of incubation, growth inhibition was evaluated by MTT assay, and the mechanism of the anti-neoplastic effect of MK615 was evaluated by cell cycle- and apoptosis assay. Results: MK615 inhibited the growth of MDA and MCF7 in a dose-dependent manner. The percentage growth inhibition of MDA at dosages of 600, 300, and 150 μg/ml was 59.2%, 52.4%, and 23.3%, respectively, and that for MCF7 was 83.5%, 52.7%, and 16.6%, respectively. Cell cycle analysis showed that MK615 increased the proportion of cells in G2-M phase in both MDA (7.8% to 11.7%) and MCF7 (8.1% to 18.7%), and finally both cell lines became apoptotic. The proportion of apoptotic cells increased with incubation time. Conclusions: MK615 effectively inhibits the growth of breast cancer cells in vitro, possibly by cell cycle modification and apoptosis induction. No significant financial relationships to disclose.
Immune response results of vesigenurtacel-l (HS-410) in combination with BCG from a randomized phase II trial in patients with non-muscle invasive bladder cancer (NMIBC).
Authors: Gary D. Steinberg, Neal D. Shore, Lawrence Ivan Karsh, James L. Bailen, Trinity J. Bivalacqua, Karim Chamie, James S. Cochran, Richard David, Robert L. Grubb, Wael A. Harb, Jeffrey M. Holzbeierlein, Ashish M. Kamat, Edouard John Trabulsi, William Vincent Walsh, Michael Brandon Williams, Fredrick Wolk, Michael Woods, Melissa Leigh Price, Brandon Early, Taylor Houghton Schreiber
Journal: Journal of Clinical Oncology (2017)

319 Background: Vesigenurtacel-L (HS-410) is a vaccine comprised of an allogeneic cell line, selected for high expression from a series of bladder tumor antigens, and transfected with gp96-Ig. Cell-secreted gp96-Ig delivers these cell-derived antigens to a recipient's own antigen presenting cells, activating CD8+ cytotoxic T cells. Here we present the secondary immune outcomes from a randomized Phase 2 trial with HS-410 in combination with BCG in NMIBC. Trial ID NCT02010203. Methods: 78 patients with intermediate- (n=5) or high-risk (n=73) NMIBC who are either BCG-naïve or recurrent, with or without carcinoma in situ (CIS), were enrolled 1:1:1 to one of two doses of HS-410 (either 10 6 or 10 7 cells/dose) or placebo in combination with 6 weeks of induction BCG, followed by 6 more weeks of HS-410 in the induction phase. Maintenance treatment consisted of 3-weekly treatments at the following timepoints: 3 mo., 6 mo., 12 mo. Concurrently, 16 patients (1 int. risk, 15 high-risk) were enrolled in an open-label monotherapy HS-410 arm for patients who did not receive BCG. The primary endpoint was 1-year RFS. Secondary immune evaluations include ELISPOT, tumor IHC, tumor antigen profiling, flow cytometry, urine cytokine analysis, and T cell receptor sequencing. Results: HS-410 treatment was well tolerated; AE profiles were similar across the treatment arms. HS-410 antigen expression showed prominent overlap with patient tumors. IFNγ ELISPOT assay demonstrated a high baseline response to HS-410; responses to overlapping peptide pools of HS-410 derived antigens defined immune responders (doubling of IFNγ-secreting cells). IHC demonstrated that ~60% of NMIBC patient tumor biopsies were TIL negative at baseline (n=84), but that only ~15% of tumor biopsies were TIL negative post treatment (n=40). Thus, TIL status may be further used to define a responder and non-responder population to HS-410. Conclusions: Vesigenurtacel-L is well-tolerated, and immunologic responses consistent with vaccine mechanism of action may correlate with efficacy and suggest future biomarkers. Vesigenurtacel-L warrants further investigation as a potential treatment for NMIBC. Clinical trial information: NCT02010203.
Expression of stem cell markers in pancreatic ductal adenocarcinoma and clinical relevance.
Authors: Kalliopi Andrikou, Luca Faloppi, Cristian Loretelli, Alessandra Mandolesi, Italo Bearzi, Stefano Cascinu
Journal: Journal of Clinical Oncology (2013)

e15058 Background: Emerging evidence has suggested that malignant tumors are heterogeneous and that are composed of a small subset of distinct cancer cells (usually defined by cell surface marker expression) that are responsible for tumor initiation and propagation, termed cancer stem cells. These cancer stem cells (CSCs), or tumor-initiating cells (TICs), exhibit properties of normal stem cells and are associated with resistance to current therapies. It was found that human pancreatic cancer has shown a population of cancer stem cells that have aberrantly activated developmental signaling pathways, are resistant to standard chemotherapy and radiation, and have up-regulated signaling cascades that are integral for tumor metastasis. The aim of our study is to investigate the prognostic implication of cancer stem cell markers in pancreatic ductal adenocarcinoma. Methods: In 43 histological samples of pancreatic ductal adenocarcinoma were performed molecular biology assessment of CD 24, CD44, CD133, CD166, OCT3/4, LGR5. Results: At univariate analysis patients with an overexpression of CD44, CD133, OCT3/4 showed a worse prognosis in terms of overall survival (respectively: p=0.031; p=0.014; p=0.001). At multivariate analysis OCT3/4 resulted to be independent factor influencing outcome (HR=0.23). Patients with overexpression of all factors seem to have a worse OS compared to patients expressing only two, one or none (8.6 vs. 15.6 vs. 18.0 vs. 59.9 mts; p=0.006). Conclusions: Our data suggest that the presence of cancer stem cells could be linked with tumor aggressiveness and patients’ survival. This finding could drive therapeutic decision towards less or more intensive treatment.
Immunological evaluation of personalized peptide vaccination for metastatic breast cancer patients with triple-negative types.
Authors: Ryuji Takahashi, Uhi Toh, Nobutaka Iwakuma, Hiroko Otsuka, Kazuo Shirouzu, Satoko Matsueda, Shigeki Shichijo, Tetsuro Sasada, Kyogo Itoh
Journal: Journal of Clinical Oncology (2012)

e13046 Background: To develop cancer vaccine, we investigated immune responses of the patients (pts) with metastatic breast cancer (MBC) with triple negative (TN) types to personalized peptide vaccine (PPV). Methods: Thirty-four pts including 8 TN-MBC were enrolled a phase II study of PPV. A maximum of four HLA-class IA (A2, A3s, A24, A26)-matched peptides showing higher antigen-specific IgG responses were administered. Levels of IgG reactive to each of the 31 peptides in the pre- and post-treatment plasma at every 6 times of vaccination were measured using LUMNEX system. Peptide-specific CTL responses were examined by INF-g ELISPOT. Results: All 34 pts had significant pre-existing humoral immunity, whereas only 13 of 31 patients, including 3 of 6 TN cases, showed pre-existing cellular immunity. Thirty-one of 34 pts, including 6 TN cases, achieved more than one cycle (6 times) of vaccination. The augmentation of the IgG responses specific to at least one of the vaccinated peptides was observed in 18 of 31 pts, including 3 of 6 TN cases. CTL responses were augmented in 16 of 31 pts, including 5 of 6 TN cases. IgG responses were boosted to greater levels with 12th vaccination in all 31 pts tested including 6 TN cases. Best clinical responses of 6 TN cases were 1 CR, 0 PR, 5 SD, and 0 PD, while those of the other 25 cases were 1 CR, 1 PR, 17 SD, and 6 PD, respectively. Conclusions: There were no significant differences between TN cases and the other cases of MBC with regard to immunological humoral and/or cellular responses to PPV.
Multicenter Analysis of Elderly Hodgkin Lymphoma (eHL): Outcomes and Prognostic Factors in the Modern Era
Authors: Andrew M. Evens, Irene Helenowski, Chadi Nabhan, Erika Ramsdale, June M McKoy, Annette Larsen, Sarah Miyata, Benjamin Parsons, Reem Karmali, Britt E. Hanson, Leo I. Gordon, Scott E. Smith, Stephanie A. Gregory, Sonali M. Smith
Journal: Blood (2011)
Care cycle on advanced cancer: Reforming a value-based system.
Authors: Hiroshi Tsukuda, Tomohiro Suzumura, Kimio Yonesaka, Masahiro Fukuoka
Journal: Journal of Clinical Oncology (2013)

e20682 Background: In Japan, reconstruction of medical service system for cancer patients is urgent necessity. On medical service system, economist Michael E. Porter and Elizabeth Olmsted Teisberg advocated that value in health care is determined in addressing the patient's particular medical condition over the full cycle of care. In our facility, we adopted their concept to our cancer care system. Methods: In our facility, the cancer care team conducted by medical oncologists provides the best value across the full span of care services. In order to manage our care delivery value chain (CDVC) for advanced cancer, we innovated 'Annshin Card' system. 'Annshin means comfort in Japan. This card functions as a key among the patients, home nursing teams and us. We analyzed 772 patients from the tumor registry of our hospital from 7/12/2010 to 12/31/2012. The following factors were evaluated: (1) the overall incidence rate of emergency visit among patients with an 'Annshin cards', (2) the length of hospitalization and the rate of mortality at our palliative care unit (PCU) as hospitalizing indicators and (3) the medical profession income and expenditure rate as an indicator of cost-benefit. Results: (1) Of 772 patients, 419 patients were adopted 'Annshin card' system. Among patients with an 'Annshin card', the overall incidence rate of an emergency visit was 2.0 visits per 100 patients per month (/100/month). (2) Of 772 patients, 411 patients have been hospitalized in PCU and 748 events of hospitalization to PCU occurred. On 748 events, the average length of hospitalization was 19.8 [ 0-263 ] days; leaving hospital mortality was 274 events (36.6%). (3) On the medical profession income and expenditure rate, before vs. after launching our system, 85.3% vs. 95.8%, respectively. Conclusions: Our CDVC for advanced cancer not only reduced the emergency visit rate, but improved the indicators of hospitalization. Furthermore this system brought cost-benefit. We suppose that the concept of care cycles is effective for cancer patient management.
Randomized phase II study of carboplatin and paclitaxel (CP) versus gemcitabine and vinorelbine (GV) in performance status (PS) 2 patients with advanced non-small cell lung cancer (NSCLC): Preliminary results of West Japan Thoracic Oncology Group 0004
Authors: H. Kaneda, K. Nakagawa, H. Saito, T. Kashii, Y. Iwamoto, N. Katakami, T. Nakano, T. Kurata, M. Fukuoka
Journal: Journal of Clinical Oncology (2006)

7151 Background: A platinum-based chemotherapy is a standard treatment in PS 0–1 patients with advanced NSCLC and a non-platinum doublet is an alternative option. However, the role of combination chemotherapy remains to be defined in PS 2 patients with advanced NSCLC. We have conducted a randomized phase II study to compare the efficacy and safety of CP versus GV in PS 2 patients with NSCLC. Methods: Chemotherapy-naive ECOG PS 2 patients with stage IIIB (malignant effusion) or IV NSCLC were enrolled in this study. Patients were randomized to carboplatin AUC 6 and paclitaxel 200 mg/m 2 day 1 every 3 weeks or gemcitabine 1,000 mg/ m 2 and vinorelbine 25mg/m 2 day 1, 8 every 3 weeks. The primary endpoint was 1-year survival rate and secondary endpoint were response rate, toxicity, time to progression and quality of life. Results: A total of 89 patients were enrolled and 86 were eligible: 42 patients (median age 64 years, male/female 31/11, stage IIIB/IV 7/35) in CP and 44 patients (median age 67 years, male/female 33/11, stage IIIB/IV 7/37) in GV. Of 84 patients evaluable for response, one complete response and 11 partial responses were obtained in CP (29.3%) and 9 partial responses in GV (20.9%). As of 12/05, toxicity data were available in 80 patients. Grade 3/4 toxicity in CP and GV included neutropenia 65.8% vs 63.4%, anemia 13.2% vs 31.7%, thrombocytopenia 7.9% vs 12.2%, liver dysfunction 2.6% vs 9.8%, febrile neutropenia 15.4% vs 12.2%, infection 30.8% vs 22%, nausea/vomiting 15.4% vs 2.4%, constipation 23.1% vs 7.3% pulmonary infiltrates 5.1% vs 12.2% and neuropathy 5.1% vs 0%. Conclusions: CP and GV were feasible and effective in PS 2 patients with advanced NSCLC. GV caused more anemia, thrombocytopenia, liver dysfunction and pulmonary infiltrates, while CP produced more nausea/vomiting, constipation and neuropathy. Response and toxicity data in all pts in each arm will be presented at the meeting. No significant financial relationships to disclose.
National, centralised hospital datasets can inform clinical trial outcomes in prostate cancer: A pilot study in the STAMPEDE trial.
Authors: Harriet Paige Mintz, Felicity Evison, Helen M Parsons, Matthew Robert Sydes, Melissa Ruth Spears, Prashant Patel, Nicholas D. James
Journal: Journal of Clinical Oncology (2017)

257 Background: Hospital Episode Statistics (HES) are routinely collected data describing National Health Service (NHS) hospital visits in England, with procedure &amp; disease codes. This study, embedded in STAMPEDE, aimed to build a model using HES, linked to primary medical records &amp; trial case report forms (CRFs) to identify progressive disease events (PDEs), including skeletal-related events (SREs). Methods: Analysis of 5 STAMPEDE patients (pts) in 2 stages (data to Jul 16). 1: Detailed manual note review of 3 pts’ PDEs were compared to HES &amp; CRFs to build model. 2: Used model to use HES to identify possible PDEs in 2 pts, verified by note review &amp; compared to CRFs. Created algorithm rules to identify PDEs per 8 week interval plus further analysis of HES coding to find SREs. Results: Prostate cancer PDEs coincided with clustering of HES events. HES found 4 PDEs omitted from CRFs but missed 2 (total PDEs: HES 10, CRFs 8). HES found a false positive CRF PDE. Compared with note review HES missed 4 PDEs (false negatives), with 2 missed &amp; 2 upgraded to PDEs post-standard query procedures, plus HES found 3 false positives (1 STAMPEDE treatment &amp; 2 delayed treatments post-PDE). Hence HES found 71% of PDEs in note review (HES 10, note review 14).CRFs found 57% of PDEs compared to note review (CRFs 8, note review 14). Hence HES found 14% more PDEs than were recorded in CRFs compared to note review. HES identified 4 additional SREs not recorded in CRFs but missed 2. Conclusions: Hospital record review revealed site staff may miss reporting major clinical efficacy outcome events on CRFs, especially nearer end-of-life. HES successfully identified most PDEs (often found as a cluster of SREs), plus additional trial events not reported on CRFs compared to note review and as predicted HES &amp; CRFs found less PDEs. PDEs &amp; SREs missed from CRF recording can be identified in HES.This confirmed use of HES to detect PDEs is feasible. HES-identified events have potential as a primary data source when subsequently verified by standard data queries. Future work will test this model prospectively in the forthcoming BladderPath trial. It may offer a superior, cost-effective method of primary data collection compared to traditional CRF recording.
Comprehensive genomic profiling (CGP) of esophageal and tubular GI tumors to identify frequencies of ErbB family member amplification with therapeutic implications.
Authors: Mark Bailey, Siraj Mahamed Ali, Alexa Betzig Schrock, Samuel Jacob Klempner, Ben George, Doron Lipson, Jie He, Vincent A. Miller, Phil Stephens, Jeffrey S. Ross
Journal: Journal of Clinical Oncology (2017)

8 Background: As described in the MyPathway study, amplification and other mutations in ErbB-family proteins are actionable events across solid tumors. Targeting ERBB2 amplifications (amp) in tubular GI cancers (TGC) improves patient outcomes. ErbB family comparisons across anatomic sites is lacking and here we describe the largest known series in TGC. Methods: DNA was extracted from 12,685 FFPE clinical TGC specimens, including 1,720 esophageal CA*. CGP was performed on hybrid-capture, adaptor ligation based libraries to a mean coverage depth of 720X for up to 315 genes plus 47 introns from 19 genes frequently rearranged in cancer. Results: Across all TGC cases, amp was the most frequent genomic alteration among ErbB members at 8.7%. ERBB2 amp was 2.3x as common as EGFR amp across TGC. Across TGC sites, EGFR amp was most frequent in esophageal SCC (13.7%) and ERBB2 amp was most common in gastroesophageal junction adenoCA (21%) compared with overall frequencies of 2.7% and 5.5% respectively. ERBB3 and ERBB4 amp were rare, and most common in gastroesophageal adenoCA relative to other TGC. Clinical support with outcomes for patients treated with anti-ErbB targeted therapy across TGC will be presented, including profiling from cases of acquired resistance to anti-ErbB targeted therapy. Conclusions: Among TGC, esophageal CA harbored the most ErbB family member amp with variation by histology. Profiling across ErbB proteins in TGC suggests biologic differences and may affect response to treatment. CGP can expand the population who may benefit from anti-ErbB directed therapies and refine treatment choices. Further research is warranted. [Table: see text]