tbuckley/cabot-search huggingface dataset:
Phase I study of ofatumumab (OFA) in Japanese patients (JPN pts) with relapsed or refractory chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL).
Authors: Y. Terui, M. Ogura, K. Tobinai, K. Hatake, T. Suzuki, D. Maruyama, A. Miyazato, K. Katsura, T. Hotta
Journal: Journal of Clinical Oncology (2010)

e18525 Background: OFA is a human IgG1 monoclonal antibody that recognizes a unique epitope encompassing the small and large loop of CD20. OFA was recently approved by the U.S. FDA for treatment of CLL refractory to fludarabine and alemtuzumab based on a pivotal study of a 2,000 mg dose. Methods: We conducted an open-label, nonrandomized, multicenter, phase I study to evaluate the tolerability, safety, efficacy and pharmacokinetics (PK) of OFA monotherapy in JPN pts with CD20-positive, relapsed/refractory CLL, SLL or follicular lymphoma. Pts received 300 mg of OFA at the 1st infusion, followed by 7 weekly infusions of 500 mg (level 1) or 1,000 mg (level 2). The primary endpoint was to determine toxicity including dose-limiting toxicity (DLT). Results: Baseline characteristics are summarized in the Table. All pts completed 8 planned doses. No DLT or serious Adverse Events (AEs) was observed. The investigator reported grade 3-4 AEs were grade 3 lymphopenia (n=1) and neutropenia (n=1). All pts had a grade 1-2 infusion related reaction during the first OFA infusion, which decreased in incidence with subsequent infusions. No pt responded in level 1. All pts in level 2 achieved partial remission (PR); at 9 months after 1st OFA infusion, 2 pts relapsed and the other remained in PR. Plasma concentrations of OFA varied widely between pts and inversely correlated with peripheral blood lymphocyte count. Conclusions: These results demonstrate the efficacy of single-agent OFA in pts with relapsed/refractory CLL and SLL. OFA was well tolerated with no unexpected toxicities. Based on the results of this study and previous phase I/II single agent experience, the tolerability and efficacy of a 2,000 mg dose is being taken forward in future trials of OFA in JPN pts with relapsed/refractory CLL. Baseline characteristics Characteristic Level 1 500 mg (N = 3) Level 2 1,000 mg (N = 3) Male, n (%) 1 (33) 2 (67) Median age, yrs (range) 52 (43–57) 41 (41–61) Disease type, n (%) CLL 1 (33) 1 (33) SLL 2 (67) 2 (67) Ann Arbor, n (%) III 0 1 (33) IV 2 (67) 1 (33) Rai, n (%) II 1 (33) 2 (67) Prior therapies regimen, n (range) 2 (1-3) 2 (1-5) R and F, n (%) 2 (67) 1 (33) R, n (%) 0 1 (33) F, n (%) 0 Abbreviations: R, rituximab; F, fludarabine. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline
Difference-in-Differences Analysis of the Association Between State Same-Sex Marriage Policies and Adolescent Suicide Attempts
Authors: Julia Raifman, Ellen Moscoe, S. Bryn Austin, Margaret McConnell
Journal: JAMA Pediatrics (2017)

Suicide is the second leading cause of death among adolescents between the ages of 15 and 24 years. Adolescents who are sexual minorities experience elevated rates of suicide attempts.To evaluate the association between state same-sex marriage policies and adolescent suicide attempts.This study used state-level Youth Risk Behavior Surveillance System (YRBSS) data from January 1, 1999, to December 31, 2015, which are weighted to be representative of each state that has participation in the survey greater than 60%. A difference-in-differences analysis compared changes in suicide attempts among all public high school students before and after implementation of state policies in 32 states permitting same-sex marriage with year-to-year changes in suicide attempts among high school students in 15 states without policies permitting same-sex marriage. Linear regression was used to control for state, age, sex, race/ethnicity, and year, with Taylor series linearized standard errors clustered by state and classroom. In a secondary analysis among students who are sexual minorities, we included an interaction between sexual minority identity and living in a state that had implemented same-sex marriage policies.Implementation of state policies permitting same-sex marriage during the full period of YRBSS data collection.Self-report of 1 or more suicide attempts within the past 12 months.Among the 762 678 students (mean [SD] age, 16.0 [1.2] years; 366 063 males and 396 615 females) who participated in the YRBSS between 1999 and 2015, a weighted 8.6% of all high school students and 28.5% of students who identified as sexual minorities reported suicide attempts before implementation of same-sex marriage policies. Same-sex marriage policies were associated with a 0.6-percentage point (95% CI, -1.2 to -0.01 percentage points) reduction in suicide attempts, representing a 7% relative reduction in the proportion of high school students attempting suicide owing to same-sex marriage implementation. The association was concentrated among students who were sexual minorities.State same-sex marriage policies were associated with a reduction in the proportion of high school students reporting suicide attempts, providing empirical evidence for an association between same-sex marriage policies and mental health outcomes.
Effect of novel peptide vaccines on secondary recurrences and survivorship.
Authors: Marye Ellen Valentine, Lacey Chance, Peter Todd Gompper, Gavin S. Choy
Journal: Journal of Clinical Oncology (2016)

e274 Background: According to the NCI Office of Cancer Survivorship, in 2014, it is estimated there are 14.5 million cancer survivors in the US. By 2024, it is projected there will be 19 million cancer survivors. Peptide-based vaccines are being developed to prevent recurrence in cancer patients following standard of care and increase survivorship by inducing immune responses using antigenic epitopes derived from tumor associated antigens. Two peptide vaccines, nelipepimut-S, a HLA-A2/A3-restricted immunogenic peptide derived from the HER2 protein and E39, a HLA-A2-restricted, folate binding protein (FBP) derived peptide, are being developed to prevent breast cancer and gynecological cancers recurrence, respectively. Methods: Early phase dose finding clinical trials results for both agents have been previously reported by Mittendorf et al. (2014) and Greene et al. (2015). Both agents are concomitantly administered with GM-CSF in the adjuvant setting. Toxicity was monitored and recurrences were documented. Disease free survival (DFS) was analyzed by Kaplan-Myers curves and groups were compared by log-rank test. Results: In the nelipepimut-S Phase 1/2 trial, 97 patients were enrolled in the node positive group. The reported 3-year DFS was 100% in the optimally dosed (1000 mcg vaccine + 250 mcg GM-CSF) vaccinated group vs. 77.8% in the control (p = 0.035, n = 45). In the E39 Phase 1/2 trial, with 9.8 months median follow-up, among optimally dosed (1000 mcg), there is only one recurrence (6.7% vs. 5I% CG, p = 0.01). The 2-year DFS estimate is 19.2% (CG) vs. 85.7% (1000 mcg) (p = 0.09). Nelipepimut-S and E39 were well tolerated. Conclusions: Preliminary results from both Phase 1/2 trials indicate these peptide vaccines derived from the HER2 protein and FBP may be administered chronically, thereby preventing recurrence and increase survivorship in patients with breast, ovarian, and endometrial cancers. Nelipepimut-S is currently being investigated in three ongoing adjuvant clinical trials – 1) single agent in a registrational Phase 3, PRESENT, under a FDA-approved SPA; 2) combination with trastuzumab in IHC 1+/2+ and IHC 3+. Early results of E39 are encouraging and a Phase 2b is being planned in gynecological malignancies. Clinical trial information: NCT00841399, NCT00584789.
Using a disease pathway management (DPM) approach to improve the quality of lung cancer care in Ontario.
Authors: William K. Evans, Yee Ung, Carol Anne Sawka, Nathalie Assouad
Journal: Journal of Clinical Oncology (2012)

93 Background: Cancer Care Ontario (CCO) is mandated to oversee quality of cancer care in Ontario and began its Lung Cancer (LC) DPM initiative in 2009. DPM has 4 objectives: align provincial quality improvement (QI) initiatives by disease site; map the patient journey and identify gaps in evidence/quality in clinical practice that impact care or the patient experience; set and manage regional quality indicators across the pathway; and leverage tools to model the impact of policy decisions. Methods: The LC DPM drafted a disease pathway map and established 5 multidisciplinary working groups (WGs) each focussed on a phase of the LC patient journey: prevention, screening, and early diagnosis; diagnosis; treatment; palliative care; the patient experience. WGs held 25 two-hour meetings and developed ideas for 17 QI projects. 8 were selected for discussion at a provincial consensus conference and yielded a Priorities for Action Report. Regional “roadshows” were held in all 14 regions of the province at which region-specific data on incidence, stage at diagnosis, compliance of treatment with guidelines and wait times, amongst other metrics relevant to LC, were shared with the regional care providers. Funding was provided by CCO for regional QI based on the data and identified priorities. Results: Completed diagnostic and treatment pathways are posted on CCO’s website as are educational materials on dyspnea management, including a patient video and a document prepared by patients for patients “Understanding Lung Cancer.” Lung diagnostic assessment units/programs have been initiated in 14 regions. An audit is underway to better understand the barriers to the uniform uptake of evidence-based practices across the province. The percent of LC patients whose symptoms are assessed at least once a month using a standardized symptom assessment instrument (ESAS) has improved. Conclusions: Regional cancer programs are now aware of their performance on a range of LC specific quality metrics. Standardized diagnostic and treatment pathways have been developed and assessment units have been implemented across the province.
Met or EGFR Inhibition in Gastroesophageal Adenocarcinoma (MEGA): FOLFOX alone or in combination with AMG 102 or panitumumab as first-line treatment in patients with advanced gastroesophageal adenocarcinoma: FNCLCC-FFCD-AGEO-GERCOR PRODIGE 17-ACCORD 20 randomized phase II trial.
Authors: D. Malka, S. Gourgou-Bourgade, J. Emile, P. Laurent-Puig, J. Taïeb
Journal: Journal of Clinical Oncology (2011)

TPS178 Background: Advanced gastroesophageal cancers (AGEC) harbour a dismal prognosis (overall survival [OS] < 1 year). EGFR inhibitors showed promising activity in patients (pts) with AGEC. Dysregulation of the HGF/c-Met pathway is a rational therapeutic target in AGEC. This randomised phase II study aims to assess the efficacy and safety of fluorouracil (FU), folinic acid (FA) and oxaliplatin-based chemotherapy (modified FOLFOX6 regimen) alone or combined to either panitumumab, an anti-EGFR monoclonal antibody, or to AMG 102, an anti-HGF monoclonal antibody, as first-line treatment for pts with AGEC. Methods: This multicentre, open-label, randomised phase II trial is ongoing in 30 centres in France. Main eligibility criteria include: histologically proven adenocarcinoma of the stomach, esophagus or gastroesophageal junction; locally advanced or metastatic disease; measurable disease (RECIST 1.1); no known HER2 overexpression; no prior palliative chemotherapy; age > 18 years; ECOG performance status 0 or 1; adequate bone marrow, liver and renal function. Patients are randomised to modified FOLFOX6 (oxaliplatin 85 mg/m², FA 400 mg/m², FU 400 mg/m² bolus then 2400 mg/m² over 46 hr) alone or combined to either panitumumab (6 mg/kg) or AMG 102 (10 mg/kg) every two weeks until unacceptable toxicity or disease progression. Judgment criteria include 4-month progression-free survival rate (primary endpoint), OS, objective response rate, and safety. Ancillary studies aim to identify candidate predictive and prognostic biomarkers among functional of molecular alterations of the EGFR/RAS/RAF and HGF/c-Met pathways, and to monitor circulating tumour cells and circulating immune cells (myeloid derived suppressor cells, NK cells) in sequential blood samples taken at baseline and through the study treatment. A total of 165 pts will be enrolled (Fleming’s one-step design). The first patient enrolled in January 2011.
The JAK2V617F Mutation in Blood Donors with High Haematocrit.
Authors: Giuseppe Tagariello, Rosanna Di Gaetano, Roberto Sartori, Donata Belvini, Paolo Radossi, Renzo Risato, Roberta Salviato, Cristina Tassinari, Nunzio Toffano, Daniela Zanotto
Journal: Blood (2007)
Screen detection of serrated polyps by stool DNA multi-target testing (sDNA-MT): Comparison against fecal immunochemical occult blood testing (FIT).
Authors: Russell I. Heigh, Douglas W. Mahoney, Tracy C. Yab, Julie A. Simonson, Lisa A. Boardman, Michael J. Domanico, Barry M. Berger, Graham P. Lidgard, David A. Ahlquist
Journal: Journal of Clinical Oncology (2013)

341 Background: Precursors to 1/3 of colorectal cancer (CRC), serrated polyps have historically been underdetected by screening due to their inconspicuous, nonhemorrhagic, and proximal nature. New generation sDNA-MT show high sensitivity for both CRC and advanced adenomas (Gastroenterology 2012;142:248), but screen detection of serrated polyps by this approach requires further validation. Aim: To assess and compare noninvasive detection of sessile serrated polyps &gt;1cm (SSP) by sDNA-MT and a commercial quantitative FIT. Methods: In a blinded prospective study, a single stool sample used for both tests was collected from 456 asymptomatic adults prior to screening or surveillance colonoscopy (criterion standard). All 29 patients with SSP were included as cases and all 232 with no neoplastic findings as controls. Buffered stool samples were processed and frozen on receipt; Exact Sciences performed sDNA-MT in batches using optimized analytical methods (Gastroenterology 2012;142:S770). The sDNA-MT panel targets methylated BMP3 (mBMP3) and NDRG4, mutant KRAS, β-actin, and hemoglobin. FIT (Polymedco OC-FIT Check) was performed in separate lab &lt;2 days post defecation and evaluated at cutoffs of 50 (FIT-50) and 100 ng/ml (FIT-100). Results: Age/sex distributions were similar in cases and controls: 40% vs 45% &gt; 65 years and 51% vs 59% women, p=NS respectively. SSP median size was 1.2cm (range 1-3cm), 93% were proximal, and 64% had synchronous diminutive polyps. Among sDNA-MT markers, mBMP3 proved highly discriminant for SSP detection (AUC=0.87, p&lt;0.00001); other DNA markers were less informative and provided no incremental sensitivity. Hemoglobin alone showed no discrimination (AUC=0.50, p=NS). At matched specificities, SSP detection by stool mBMP3 was significantly greater than by either FIT-50 or FIT-100 (Table). Conclusions: From a screening and surveillance setting, SSP can be detected noninvasively by stool assay of exfoliated DNA markers, especially mBMP3. FIT appears to have no value in SSP detection. [Table: see text]
A fall prevention and detection project: Preliminary results.
Authors: Elvira De Marino, Cristina Chesta, Elisabetta Rugge, Paola Ferrari, Teresa Posca, Sara Lattuada, Renata Torazzo, Sabrina Rossetti, Alessandra Di Cola
Journal: Journal of Clinical Oncology (2014)

142 Background: Falls often causes serious injury to cancer patients (PTS) and hospital costs account for two thirds of the total. Fall prevention and detection (FAPRE) project was planned to develop a new technology in three steps: first to identify potential high risk fallers (HRF) by Timed Up and Go (TUG) test; second to compare TUG with Conley Scale and third to hospitalize HRF in monitoring room equipped with a network of smart sensors that can identify person’s location, fall or lack of balance and posture connected by smartphone alerting watch nurse. Aim of this study is to describe general characteristic of HRF by TUG and to determine how new test instruments can identify them. Methods: A nurse performed TUG in ambulatory room equipped with pressure sensors on the floor (intelligent carpet), webcam, home gateway, WI-FI router and smartphone. PTS were required to sign informed consent. HRF were identified by TUG test &gt;12 seconds. Results: From January to March a series of 99 consecutive PTS enter the trial, performance status ECOG &lt; 2, age: median 73, range 34-87, 50 males and 49 females. All PTS underwent TUG and were evaluable. There were 11 hematologic (H) and 88 solid tumors (ST); 45/88 ST had metastatic disease; 97/99 were treating by chemotherapy, 2 by palliative care. Six PTS had brain metastasis and 9 bone; 33/99 had previous pathological fractures. Comorbidity: 14/99 diabetes and 33/99 hypertension 10/99 were taking psychoactive drugs, 22 were treated with opiate and 5 both. HRF identified by TUG were 44%; there were 27% H, 46% ST and 75% were older then 70 years. Previous pathological fracture in long bone were 14/33; bone metastasis (BM) 7/9; brain metastasis 3/6. HRF taking only psychoactive drugs were 5//10 and 17/22 opiate; 5/5 both. Conclusions: TUG detected HFR more frequently in ST, elderly with BM and previous long bone fractures treating by opiate and hypertension. Identify HRF by new integrated room automation FAPRE infrastructure seems a simple, reliable and manageable approach at preliminary data. Trial is ongoing and carrying on next step.
Tumor response in the CLARINET study of lanreotide depot vs. placebo in patients with metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs).
Authors: Alexandria T. Phan, Arvind Dasari, Nilani Liyanage, David Cox, Susan Pitman Lowenthal, Edward M. Wolin
Journal: Journal of Clinical Oncology (2016)

434 Background: In the CLARINET study, significant improvement in progression-free survival (primary endpoint) was reported in patients (pts) treated with lanreotide depot (LAN), a long-acting somatostatin analog, for moderately- or well-differentiated, nonfunctioning, locally advanced or metastatic GEP-NETs. A favorable safety profile was also observed. This retrospective analysis presents tumor response from CLARINET. Methods: Pts were randomized to LAN 120 mg (n=101) or PBO (n=103) once every 28 days for 96 weeks. Tumor response was evaluated centrally using RECIST version 1.0. Pts’ tumors were measured by sum of the longest diameter (SLD) of target lesions (TLs). Change was calculated for each pt’s SLD from baseline to last available post-baseline assessment. Tumor response was classified as complete response (CR): disappearance of all TLs and non-target lesions (NTLs) and no new lesions; partial response (PR): ≥30% decrease in SDL and no progressive disease (PD); stable disease (SD): not meeting criteria for CR/PR or PD; PD: ≥20% increase in SLD from baseline or nadir, unequivocal progression of NTLs or appearance of new lesions. The remaining pts were not evaluable (NE) for response. Results: 101 pts treated with LAN and 103 pts treated with PBO were assessed for tumor response. Among pts receiving LAN, 64% (65/101) demonstrated SD compared to 43% (44/103) of pts receiving PBO (Table). An additional 2 pts in the LAN group achieved a PR. Similar trends were observed in pts with pancreas and midgut origin tumors. Conclusions: A clinical benefit (defined as CR+PR+SD) of 66% (67/101) was observed with single agent LAN vs 43% (44/103) with PBO in the CLARINET population, further supporting the clinical efficacy of LAN. Clinical trial information: NCT00353496. [Table: see text]
Expected benefits versus actual outcomes in oncology phase III randomized controlled trials (RCTs).
Authors: H. K. Gan, B. You, G. R. Pond, E. X. Chen
Journal: Journal of Clinical Oncology (2011)

2562 Background: The expected benefit of the experimental over the standard arm (δ) in a RCT is estimated based on current evidence and investigators’ experience. Overestimation of δ can lead to inadequately powered studies, wasted resources, and patient exposure to harmful treatments. A systemic review was conducted to compare δ and actual outcomes (Δ) in oncology RCTs. Methods: RCTs evaluating systemic anti-cancer therapy in adults reported from 2005-2009 were included. Two investigators independently extracted study characteristics and outcomes data (δ, Δ, and p value associated with the primary endpoint [PE]). Data were compared by Kruskal-Wallis and χ2 tests. Results: 315 RCTs were identified. Most common tumor sites were breast (86), thoracic (66) and colorectal cancers (42). RCTs were mainly in metastatic (208) and adjuvant (88) settings.187 RCTs were industry sponsored. Of 253 RCTs with adequate information, δ is consistently overestimated (Table). Overestimation occurred in all subgroups investigated. Only 37% of RCTs were positive studies, i.e., beneficial outcomes (Δ>0) and significant p values. In 20% of cases, δ was totally incorrect as the experimental arm had a detrimental effect (Δ<0). 62 RCTs (20%) could not be adequately assessed (31 did not provide δ, Δ or the p-value for the PE; 23 negative studies were underpowered i.e. recruited <90% of required patient/events; 7 lacked sample size information; 1 had conflicting PE data). Such RCTs were more often associated with lower impact factor (<10) journals (31% vs 16%, p=0.005) and no industry sponsor (31 vs 13%, p=0.001). Authors’ conclusions about these 62 studies were that, compared to control, the experimental arm was superior (16%), not superior (68%), equivalent (7%), or unclear (9%). Conclusions: Investigators consistently overestimate δ when designing oncology RCTs, contributing to frequent negative RCTs. This problem is compounded by poor reporting in a substantial minority of RCTs. Median (min, max) Benefit in PE Expected Observed P value Relative (%) increase (n=123) 31.0 (9, 93) 17.0 (−74, 100) <0.0001 Absolute (%) increase (n=87) 15.0 (5, 30) 5.2 (−11, 36) <0.0001 Absolute (mo) increase (n=43) 2.8 (1, 12) 1.5 (−4, 11) <0.0001