bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of a dedicated institutional tobacco cessation service for thoracic clinic cancer patients.
Authors: Dobson Amato Katharine Ann , Zevon Michael , Hysert Pat , Hysert Robert , Segal Stephanie , Reed Robert , Giovino Gary , Bansal-Travers Maansi , Ochs-Balcom Heather , Nwogu Chukwumere E. , Cummings K. Michael , Mahoney Martin , Hyland Andrew , Reid Mary E. , Warren Graham Walter 
Published: March 2020

1603 Background: Tobacco use by cancer patients is associated with poor therapeutic outcomes including increased toxicity, decreased quality of life, and decreased survival. Though recommendations provide for tobacco assessment and cessation for cancer patients, few oncologists provide cessation support. Presented are data from universal tobacco assessment and cessation program for patients presenting at a thoracic oncology clinic in a NCI Designated Comprehensive Cancer Center. Methods: A standard set of evidence based tobacco assessment questions were incorporated into an automated electronic medical record based system delivered by nursing at initial consult and at follow-up. Patients eligible for tobacco cessation support (i.e. patients self-reporting tobacco use within 30 days) were automatically referred to a dedicated tobacco cessation service. All referred patients are sent a standardized packet of cessation materials with telephone-based follow-up by trained cessation counselors. Results: A total of 980 new thoracic clinic patients were referred to the cessation service from January 2011 and October 2012. Two-thirds of the patients referred (n=728) referred into the system were current smokers and the remainder had quit in the 30 days prior to assessment. Among the 788 patients with contact attempts by the cessation service, 81.2% (n=640) were successfully contacted and only 2.5% (n=20) refused the offer of cessation support. At first contact, 75.6% (n=484) of patients reported continued current tobacco use. Follow-up calls were placed for 53.1% (n=340) of those who participated in the first contact an average of 39 days after the first successful contact. The follow-up had a 93.2% (n=317) participation rate which revealed that 33.3% (n=106) reported not smoking, an 8.9% increase since the first cessation service telephone call. Conclusions: Data demonstrate that an automated tobacco assessment and cessation service for thoracic oncology patients can effectively generate a large mandatory referral base with high patient interest in cessation, and that cessation support can be implemented and maintained in high risk cancer patients.
Comparative impact of treatment on patient reported outcomes (PROs) in patients with glioblastoma (GBM) enrolled in RTOG 0825.
Authors: Armstrong Terri S. , Won Minhee , Wefel Jeffrey Scott , Gilbert Mark R. , Pugh Stephanie L. , Brachman David , Komaki Ritsuko , Crocker Ian R. , Robins H. Ian , Lee R. Jeffrey , Mehta Minesh P. , Wendland Merideth M 
Published: March 2020

2003 Background: RTOG 0825 tested if adding bevicizumab (BEV) to standard chemoradiation improves survival (OS) or progression free survival (PFS) in newly diagnosed GBM. While OS was equivalent, PFS was longer with Bev (Arm 2) than with placebo (Arm 1). Patients completed quality of life and symptom PROs to evaluate clinical benefit. Methods: The M.D. Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT) and the EORTC core Quality of life Questionnaire and brain tumor module (EORTC QLQ-C30/BN20), were completed by pts at baseline (B) and longitudinally (wk 6, 10, 22, 34, and 46) while on study. The difference between treatment arms were compared from B with evaluation in subsequent weeks in those pts without disease progression; and early change (EC) (baseline to wk 10) between those with and without progression as predictors for OS and PFS. Results: 542pts consented to participate on this trial, and 507 randomized pts participated, with completion of forms by 94% at baseline, 75% at wk 10, 61% at wk 22, and 58% at wk 34. There was a trend for all MDASI-BT symptom groupings to be worse in Arm 2, with significant findings in treatment symptoms at wk 22 and wk 34; both affective and generalized disease symptoms were also significantly worse. For EORTCQLQ30/BN20, differential effects varied at each time point, with no persistent differences. For the MDASI-BT, B neurologic symptom grouping and EC in cognitive symptoms were prognostic for both OS and PFS. For the EORTC QLQ30/BN20, global QOL and motor dysfunction at B as well as EC in communication and leg weakness were prognostic for OS; whereas physical function at B and EC in headaches, seizures, and weak legs were prognostic for PFS. Conclusions: The longitudinal collection of PROs in this phase III trial revealed important treatment-related differences as there was overall more deterioration in symptoms and QOL in Arm 2 as compared to Arm 1, with persistent significant differences in treatment associated symptoms. B and EC tumor associated symptoms on both PRO tools were prognostic for OS and PFS. Longitudinal modeling is ongoing to further assess for differential impact of treatment on symptoms and QOL. Support: U10 CA21661, U10 CA37422 and Genentech, Inc. Clinical trial information: NCT00884741.
Contrast-enhanced T1-weighted subtraction maps for response assessment in recurrent glioblastoma treated with bevacizumab.
Authors: Ellingson Benjamin M. , Kim Hyun J. , Woodworth Davis C. , Pope Whitney B. , Cloughesy Jonathan N. , Harris Robert J. , Lai Albert , Nghiemphu Phioanh L. , Cloughesy Timothy F. 
Published: March 2020

2055 Background: Antiangiogenic therapy in glioblastoma (GBM) results in decreased enhancement on post-contrast T1w images, which complicates standard response assessment and is likely the reason no studies have found predictive value in enhancing tumor size or change in size. The current study examined whether contrast-enhanced T1-weighted subtraction maps (CE-ΔT1w) calculated from subtracting pre-contrast (T1) from post-contrast T1w images (T1+C) can improve quantification and predict response in GBM patients treated with bevacizumab. Methods: Recurrent GBM patients (n=160) from the BRAIN trial (AVF3708g), a multicenter Phase II trial evaluating bevacvizumab, were used in the current study. CE-ΔT1w maps were calculated 2 weeks before and 6 weeks after the first dose of bevacizumab by: 1) performing registration between T1 and T1+C images, 2) image intensity normalization of T1 and T1+C images, and 3) subtraction of T1 from T1+C images. The volume of tumor regions with positive contrast enhancement after subtraction was retained for analysis. Results: CE-ΔT1w maps greatly improved detectability of subtly enhancing lesions, particularly post-treatment. Results for PFS and OS are summarized in the table below. In all scenarios, CE-ΔT1w maps outperformed conventional tumor segmentation. Results show that size and change in size are both predictive of PFS and OS. Conclusions: CE-ΔT1w maps improve visualization and quantification of contrast enhancing tumor regions in recurrent GBM, allowing for more accurate response assessment. [Table: see text]
Safety analysis of bevacizumab plus NovoTTF-100A in patients with recurrent malignant gliomas.
Authors: Elzinga Grace , Chung Amy T , Wong Eric 
Published: March 2020

2082 Background: Both bevacizumab and the NovoTTF-100A device are treatments approved by the FDA for recurrent glioblastoma. We examined our single-institution experience in using this combination for patients with recurrent malignant gliomas. Methods: We identified retrospectively the side effects experienced by patients while on both bevacizumab and NovoTTF-100A. Overall survival was also tabulated from initiation of this combined modality treatment. Results: There were 14 men and 6 women. Their median age was 54 (range 29-76). All had Karnofsky Performance Status of 60 or above. Fourteen patients received NovoTTF-100A after failure of bevacizumab treatment while the other 6 received both treatments concurrently. The median duration of bevacizumab plus NovoTTF-100A treatments was 2.3 (95% CI 1.8-4.7) months. There were 2 patients who experienced electric shock sensation on the scalp from a poorly-applied transducer array that resulted in minor scalp burns, 3 patients developed scalp rashes (2 moderate and 1 severe), 4 patients experienced liquefied hydrogel from the arrays as a result of high ambient temperature during summer months, 2 experienced vivid dreams of applying the arrays and 3 removed the arrays while periods of sleep or confusion. Only one patient required NovoTTF-100A treatment interruption because of severe scalp rash. No hemorrhage into the malignant glioma or thromboembolism was seen in this cohort. From the time of initiation of bevacizumab plus NovoTTF-100A treatments, the Kaplan-Meier median overall survival was 5.6 (95% CI 4.2-N/A) months. Conclusions: No additive or synergistic side effects were observed when patients were treated with both bevacizumab and NovoTTF-100A. Further evaluation in a prospective manner would be needed to evaluate both side effects and efficacy of this treatment combination.
A phase I study of the first-in-class mitochondrial metabolism inhibitor CPI-613 in patients with advanced hematologic malignancies.
Authors: Pardee Timothy S. , Levitan Denise A. , Hurd David Duane , Ellis Leslie R. , Isom Scott , Harrelson Robin , Manuel Megan , Dralle Sarah , Lyerly Susan , Powell Bayard L. 
Published: March 2020

2516^ Background: Altered metabolism is a hallmark of cancer, including hematologic malignancies. This altered metabolism is a possible therapeutic target. The lipoate derivative CPI-613 is a first in class agent that targets pyruvate dehydrogenase complex.This trial was designed to determine the maximally tolerated dose (MTD), safety, and efficacy of CPI-613 given as a single agent by IV infusion. Methods: CPI-613 was given over a 2 hour infusion on days 1 and 4 for 3 weeks every 28 days with a starting dose of 420 mg/m2. The dose was escalated in 6 cohorts to a final dose of 3780 mg/m2. Treatment could be continued if the patient experienced clinical benefit. Results: A total of 26 patients with advanced relapsed or refractory hematologic malignancies were enrolled. Patients were heavily pretreated with a median of 3 previous therapies (range 1-11). CPI-613 was well tolerated when infused over 2 hours, with no worsening of cytopenias at any dose level. After the dose was escalated to 2940 mg/m2 the protocol was amended to a 1 hour infusion. When infused over 1 hour, 2 patients developed grade 3 renal failure. Infusion time was then returned to 2 hours and dose escalation resumed. At a dose of 3780 mg/m2, one patient experienced prolonged grade 3 nausea and one patient grade 3 renal failure, defining this dose as above the MTD. Renal failure resolved in all but one patient who opted for hospice care. A total of 6 patients were treated at a dose of 2940 mg/m2over 2 hours with no DLTs observed, establishing this as the MTD. Of the 21 patients evaluable for a response, eight achieved a response of stable disease or better for a response rate of 38%. Responses included a complete remission maintained over 27 cycles in one AML patient and clearance of marrow blasts in another, sustained partial response in both a Burkitt's and a cutaneous T cell lymphoma patient maintained over 17 and 8 cycles respectively, and stable disease in 2 multiple myeloma and 2 myelodysplasia patients. Conclusions: To our knowledge this is the first report of an agent with activity in aggressive hematological malignancies that is not myelosuppressive. The therapeutic index appears high suggesting CPI-613 should be further studied in phase II trials. Clinical trial information: NCT01034475.
Phase Ib dose-escalation trial of the AKT inhibitor (AKTi) MK2206 in combination with paclitaxel (P) and trastuzumab (H) in patients (pts) with HER2-overexpressing (HER2+) cancer.
Authors: Chien Amy Jo , Truong Thach-Giao , Melisko Michelle E. , Moasser Mark M. , Kelley Robin Katie , Korn Michael , Ko Andrew H. , Pantoja Norma , Reinert Anne , Grabowsky Jennifer A. , Magbanua Mark Jesus M , Rugo Hope S. , Munster Pamela N. 
Published: March 2020

2605 Background: AKT plays a key role in the survival, resistance, and overall aggressive pathogenesis of HER2+ malignancies, suggesting that AKTis may be of therapeutic value. MK2206 is a selective allosteric AKTi that has demonstrated synergy in combination with both H and P in preclinical studies. Methods: We conducted a phase 1b study of MK2206 in combination with weekly P 80 mg/m2 and H 2 mg/kg in pts with HER2+ solid tumors. MK2206 was given orally at a starting dose of 135 mg once a week (QW). Dose escalation was performed using a modified Ji method. The maximum tolerated dose (MTD) was defined as the dose level resulting in 3 or fewer dose limiting toxicities (DLTs) in 11 pts, then confirmed in 4 additional pts. Circulating tumor cells and PK samples were collected for all pts. Results: A total of 17 pts were enrolled, and 15 pts were evaluable for toxicity. All pts had HER2+ tumors (11 breast, 3 gastric, 1 esophageal). Based on interim toxicity data from other studies, the dose of MK2206 was not escalated beyond 135 mg QW. All 15 pts were treated at this dose level which was determined to be tolerable. Two DLTs were observed including grade 3 rash and grade 3 neutropenia resulting in a >7 day treatment delay. There were no severe adverse events (AEs) related to study treatment. Other grade 3/4 AEs were neutropenia (6 pts), febrile neutropenia (1 pt), peripheral neuropathy (1 pt), and depression (1 pt). The most common all-grade AEs include rash (13 pts), hyperglycemia (13 pts), neutropenia (13 pts), peripheral neuropathy (10 pts), diarrhea (9 pts), fatigue (9 pts), anorexia (9 pts), stomatitis (7 pts). Of the 14 pts evaluable for response, 9 pts (64%) had tumor response (2 CR, 7 PR), and 4 pts had SD. The median duration of response was 5.5 months. Pts were heavily pretreated (median lines of prior therapy 3, 11 prior taxane, 12 prior H). Conclusions: MK2206 at a dose of135 mg QW in combination with weekly P and H is safe and well-tolerated. 135 mg QW is the recommended phase 2 dose for this combination. Preliminary data indicate significant clinical activity in pts with HER2+ tumors despite extensive prior therapy. MK2206 is now being tested in the neoadjuvant ISPY2 trial. Clinical trial information: NCT01235897.
Use of tumor growth rate (TGR) to provide useful clinical information in phase I trials and reveal clear drug-specific profiles.
Authors: Ferte Charles , Fernandez Marianna , Hollebecque Antoine , Koscielny Serge , Levy Antonin , Bahleda Rastislav , Massard Christophe , Soria Jean-Charles 
Published: March 2020

3010 Background: The evaluation of treatment response by RECIST does not take into account the tumor growth kinetics along the treatment sequence and may induce misleading information regarding the evaluation of the drug activity. TGR incorporates the time between the tumor evaluations and allows for a dynamic and quantitative evaluation of the tumor kinetics. How TGR is modified along the introduction of experimental therapeutics and is associated with outcome in phase I patients remains unknown. Methods: Medical records from all patients (n=304) prospectively treated at Institut Gustave Roussy in 19 phase I trials between 2009 and 2011 were analyzed. TGR was computed both during the pre-treatment period (REFERENCE) and between baseline and first evaluation (EXPERIMENTAL). TGR is defined as: log 10 (Vt/V0)/dt and is represented as a percentage increase of tumor volume per month for clinical relevance. The associations between TGR, RECIST, the most commonly used prognostic scores (ECOG, RMH score, PFS ratio) and the outcome (OS, PFS) were computed (multivariate analysis). The effect of treatment, prognostic scores, histology, and the number of previous treatment lines on TGR were assessed. Results: Overall, we observed a reduction of TGR between the REFERENCE vs. EXPERIMENTAL periods (11.5 vs. 1.5, P<.0001). Although most of the patients were classified as stable disease (57%) or progressive disease (28%) by RECIST at the first evaluation, 88% and 69% of them exhibited a decrease in TGR, respectively. TGR reveals clear drug specific profiles along the 19 experimental regimens tested, allowing for an early evaluation of the drug activity. The TGR decrease was associated with both PFS (P=.004) and OS (P=.001) and remained significant even after adjustment to the other prognostic scores for phase I patients. Conclusions: Adding TGR assessment in phase I patients is simple and provides clinically relevant information: (i) It allows for an early and precise assessment of the tumor growth, (ii) It reveals drug-specific profiles, suggesting its potential use for the early assessment of drug activity, (iii) TGR is independently associated with prognosis in phase I patients.
Ipilimumab in the real world: The U.K. expanded access programme (EAP) experience in advanced melanoma.
Authors: Ahmad Saif , Qian Wendi , Ellis Sarah Gabrielle , Khattak Muhammad Adnan , Gupta Avinash , Thillai Kiruthikah , Board Ruth E. , Nobes Jenny , Dalgleish Angus , Grumett Simon Aird , Maraveyas Anthony , Danson Sarah , Talbot Toby , Marples Maria , Plummer Ruth , Kumar Satish , Middleton Mark R. , Larkin James M. G. , Ottensmeier Christian , Corrie Philippa 
Published: March 2020

3018 Background: Since publication of the registration trial in 2010 (Hodi et al, NEJM 2010;363:711-23), real world use of ipilimumab (Ipi) in previously treated advanced melanoma patients has extended beyond the specific trial entry criteria of ECOG PS 0-1. We undertook a review of UK patients (pts) treated in the international EAP prior to European licensing of Ipi in August 2011, to compare real world survival outcomes. Methods: UK clinicians registered in the EAP provided anonymised data using pre-specified variable fields for all pts. The EAP stipulated pts should have previously treated, unresectable stage III or IV metastatic melanoma and receive Ipi 3 mg/kg, 3 weekly IV, for up to 4 cycles. Response using RECIST criteria was assessed 12 weekly. Grade ≥3 adverse events (AEs) using CTCAE v3.0 were collected. Results: To date, information on 162 pts has been received from 16 UK sites. Primary sites were: 78% cutaneous, 4% ocular, 1% mucosal, 17% unknown. 78% pts had M1c disease, 14% had brain metastases. No prior therapies ranged from 0-4, 72% pts received 1 prior therapy. Median age was 60 years, men>women (1.6:1). ECOG PS was: 38% 0, 47% 1, 14% 2, 1% 3. BRAF status was known in 38% cases and WT in 75% of these. 19% pts were on steroids at baseline. No cycles delivered was 4 in 52%, 3 in 13%, 2 in 16%, 1 in 17% pts. Most frequent reason for stopping early was clinical evidence of disease progression (71%), death (16%) or unacceptable AE (12%). 32% pts experienced a grade ≥3 AE, the most common being diarrhoea (13%) and fatigue (8%). Complete and partial responses were reported in 1% and 21% of treated pts. At median follow-up of 17 months, median progression free survival and overall survival (OS) were 2.8 and 5.7 months, 1 year OS was 30%. Comparing outcomes of various pt subgroups, the strongest prognostic factor for OS was ECOG PS at the start of treatment (p<0.0001). For pts with PS 0 or 1, median OS was 8.8 months (compared with 10 months in the registration trial). More detailed safety and efficacy data on pt subgroups will be presented. Conclusions: This review, representing the largest Ipi EAP UK dataset, reports overall poorer survival outcomes than in the registration trial, but pts with similar characteristics to the trial population lived longer.
Clinical guideline on the prophylactic use of G-CSF on neutropenia by chemotherapy.
Authors: Rivera-Luna Roberto , Gonzalez-Garay Alejandro G , Velasco-Hidalgo Liliana , Mayorga-Butron Jose Luis 
Published: March 2020

3050 Background: Febrile neutropenia (FN) is common in patients with chemotherapy. It requires conventional treatment, however, many studies have reported that G-CSF reduces the incidence of FN; the results were not clear and the physicians use it at their discretion. In this guideline we evaluated the efficacy and safety of the prophylactic use of G-CSF. Methods: We analyzed controlled trials (G-CSF, pegylated form or placebo) given to adult or pediatric patients with chemotherapy for leukemia (LEU), lymphoma and solid tumors (L&ST) or stem cell transplant (SCT), without infections and large radiation ports. Two independent reviewers applied CONSORT to determine the methodological quality; for ranking the evidence we used GRADE and the recommendations were developed by Delphi method. We developed subgroups according to age and type of intervention to analyze the outcomes (risk, duration, severity of FN and adverse events). We performed random-effects or fixed-effects meta-analysis methods according to their heterogeneity. Results: Of 1,776 studies,112 were included. For the risk of FN between C-GSF or pegylated form vs placebo found that G-CSF reduces the risk in adults with LEU (RR 0.89, 95% CI 0.81-0.98; p=0.024), L&ST (RR 0.758, 95% CI 0.68-0.84; p=0.000) and SCT (RR 0.85, 95% CI 0.74–0.97, p=0.017). The risk of developing severe neutropenia reduces in the adults with L&ST with the factor (RR 0.79, 95% CI 0.71-0.88; p=0.000) and pediatric patients with LEU (RR 0.789, 95% CI 0.71-0.88; p=0.000). While the duration of neutropenia in children with L&ST the time reduces with the factor (SMD -0.559; 95% CI -0.841 to -0.28; p=0.000). The G-CSF vs pegylated form, the evidence was inconclusive. Conclusions: When the risk and duration of neutropenia is present we suggest the use of G-CSF in adult and pediatric patients. For adults, we suggest the use of pegylated form, but for pediatric patients we do not have a specific suggestion because the evidence is nonexistent, so it is necessary to carry out clinical trials to obtain evidence.