tbuckley/cabot-search huggingface dataset:
OS4.4 Interventions to help support caregivers of people with a brain or spinal cord tumour - a Cochrane systematic review
Authors: F W Boele, A G Rooney, H Bulbeck, P R Sherwood
Journal: Neuro-Oncology (2018)

Family caregiving in neuro-oncology is linked to considerable burden and distress. Meeting the support needs of family caregivers is critical to maintain their emotional and physical health, enabling them to continue their caregiving activities for longer. Although support for caregivers is becoming more widely available, large-scale implementation is hindered by a lack of high-quality evidence for its effectiveness in the neuro-oncology caregiver population. We performed a Cochrane systematic review to assess the effectiveness of supportive interventions at improving the wellbeing of caregivers of people with a brain or spinal cord tumour. In March 2017, we searched for studies in CENTRAL, MEDLINE and Embase. We also handsearched relevant conference abstracts published (past 5 years), publications in the two main journals in the field (past year), searched for ongoing trials via ClinicalTrials.gov, and contacted research groups in this field. We included all randomised studies where caregivers of neuro-oncology patients constituted >20% of the sample and which evaluated changes in caregiver wellbeing following any supportive intervention. Two review authors independently selected studies and carried out risk of bias assessments. We aimed to extract data on the outcomes of psychological distress, burden, mastery, quality of patient-caregiver relationship, quality of life, and physical functioning. In total, 1666 records were identified, of which 122 were reviewed in full-text. We could include five studies (four ongoing trials were also identified). Three interventions focused on patient-caregiver dyads and two were aimed specifically at the caregiver. Heterogeneity of populations and methodologies precluded meta-analysis. Risk of bias varied, but all studies included only small numbers of neuro-oncology caregivers (n range= 13 - 56). Some evidence was found for positive effects of caregiver support on psychological distress and mastery (GRADE quality of evidence: low to very low). No studies reported significant effects on caregiver burden, quality of life, or quality of patient-caregiver relationship (GRADE quality of evidence: low to very low). Caregiver physical functioning was not assessed in the studies. The five small-scale studies included employed different methodologies across different populations, with a low quality of evidence overall. It is not currently possible to draw reliable conclusions regarding the effectiveness of supportive interventions aimed at improving neuro-oncology caregiver wellbeing. More high-quality research is needed on support for family caregivers of patients diagnosed with a brain or spinal cord tumour.
National Cancer Institute Breast Cancer Steering Committee Working Group Report on Meaningful and Appropriate End Points for Clinical Trials in Metastatic Breast Cancer
Authors: Andrew D. Seidman, Louise Bordeleau, Louis Fehrenbacher, William E. Barlow, Jane Perlmutter, Lawrence Rubinstein, Suparna B. Wedam, Dawn L. Hershman, Jennifer Fallas Hayes, Lynn Pearson Butler, Mary Lou Smith, Meredith M. Regan, Julia A. Beaver, Laleh Amiri-Kordestani, Priya Rastogi, Jo Anne Zujewski, Larissa A. Korde
Journal: Journal of Clinical Oncology (2018)

To provide evidence-based consensus recommendations on choice of end points for clinical trials in metastatic breast cancer, with a focus on biologic subtype and line of therapy.The National Cancer Institute Breast Cancer Steering Committee convened a working group of breast medical oncologists, patient advocates, biostatisticians, and liaisons from the Food and Drug Administration to conduct a detailed curated systematic review of the literature, including original reports, reviews, and meta-analyses, to determine the current landscape of therapeutic options, recent clinical trial data, and natural history of four biologic subtypes of breast cancer. Ongoing clinical trials for metastatic breast cancer in each subtype also were reviewed from ClinicalTrials.gov for planned primary end points. External input was obtained from the pharmaceutic/biotechnology industry, real-world clinical data specialists, experts in quality of life and patient-reported outcomes, and combined metrics for assessing magnitude of clinical benefit.The literature search yielded 146 publications to inform the recommendations from the working group.Recommendations for appropriate end points for metastatic breast cancer clinical trials focus on biologic subtype and line of therapy and the magnitude of absolute and relative gains that would represent meaningful clinical benefit.
Proton radiotherapy for incurable recurrent or metastatic cancers of the head and neck by the RTOG 8502 hypofractionated palliative schedule.
Authors: Benjamin H. Lok, Jingfeng Zong, Stanley I Gutinov, Xin Cai, Carl Deselm, Paul Bernard Romesser, Ryan Michael Lanning, Marina Shcherba, Han Xiao, Eric Jeffrey Sherman, C. Jillian Tsai, Nadeem Riaz, Sean Matthew McBride, Oren Cahlon, Nancy Y. Lee
Journal: Journal of Clinical Oncology (2016)

e21699 Background: To report the palliative response and early toxicity data of proton hypofractionated radiotherapy (RT) in incurable recurrent or metastatic malignancies of the head and neck using the RTOG 8502 regimen. Methods: From September 2013 to September 2015, a total of 26 patients with recurrent or metastatic cancers were treated with palliative proton radiotherapy to the head and neck by the RTOG 8502 regimen (3.7 Gy twice daily over 2 consecutive days at 4 week intervals per cycle). Patient characteristics, symptoms response, tumor response and survival data were obtained for retrospective analysis with all outcomes calculated from start of palliative RT. Results: With a median follow-up of 10.2 and 9.1 months for living patients and all patients, respectively, 65% of all patients received at least three RTOG 8502 cycles and 88% of patients had prior RT to the head and neck. Palliative systemic therapy was given for 12 patients (46%) and the sequence was concurrent in 5 (19%) and induction–concurrent–adjuvant in 7 (27%) with 7 patients receiving targeted agents (cetuximab, pembrolizumab, cabozantinib; n = 5, 1, 1, respectively) and the remaining 5 with methotrexate or carboplatin/paclitaxel. The overall palliative and tumor response rates were 73% and 61%, respectively. Progression-free survival (PFS) within the irradiated field was 8.1 months. The increasing number of RTOG 8502 cycles was not only significantly correlated with palliative and tumor response (p < 0.001 and p = 0.001) but also statistically affected OS and PFS independently (p = 0.003 and p= 0.001). The most common acute toxicity was Grade 1 fatigue (n = 8) and dermatitis (n = 6). Grade 2 acute dermatitis and mucositis occurred in one patient each. No acute Grade 3-5 toxicity was observed. One patient with bulky recurrent cutaneous carcinoma developed late Grade 3 fibrosis. Conclusions: Proton therapy with the RTOG 8502 regimen provides favorable palliative response and survival outcomes. A favorable toxicity profile for patients with incurable malignant disease in the head and neck was observed, even in patients that had received previous RT and concurrent palliative systemic therapy.
Comparative double-blind randomized trial of 2 rituximab products in patients with CD20+ diffuse large B-cell lymphoma (DLBCL).
Authors: Sandip Shah, Auro Viswabandya, Asis Mukhopadhyay, Rajnish Vasant Nagarkar, Sonica Sachdeva Batra, Luis Lopez Lazaro, Suresh Kankanwadi, Alok Srivastava
Journal: Journal of Clinical Oncology (2017)

7550 Background: DRL-Rituximab (T) is a proposed biosimilar of the innovator reference rituximab (USA: Rituxan; EU: MabThera). Physicochemical analyses and nonclinical studies have shown T to be comparable with innovator Rituximab. This study evaluated the pharmacokinetics (PK), pharmacodynamics (PD), efficacy, safety and immunogenicity of T with EU sourced MabThera (R) in DLBCL patients. Methods: Multicentre randomized double-blind 2-arm parallel study conducted in patients aged 18-60 yrs, with a centrally confirmed newly diagnosed CD20+ DLBCL, as first line of treatment. Patients received 6 cycles (C), every 21 days, of either T or R at 375 mg/m 2 + CHOP. Primary objective was to compare C1 PK (AUC 0-21d &amp; C max ). Overall Response Rate (ORR) was the key secondary objective, with C6 PK parameters, PD parameters (B-cells measured as CD19+ positive cells in peripheral blood- depletion &amp; repletion), treatment-emergent adverse events (TEAEs), and anti-drug antibodies (ADA) as other secondary objectives. PK similarity criterion was 90% CI of geometric mean ratios (GMRs) of AUC 0-21d and C max in C1, within 80-125%. Results: 151 patients were randomized (T, 76; R, 75). PK similarity criterion was met. The GMR T/R ratios with 90% CIs for AUC 0-21d &amp; C max were 100.0% (87.7, 114.0) &amp; 96.2% (88.7, 104.4), respectively. Per protocol, ORR with 95% CI was 82.1% (69.6, 91.1) with T and 87.1% (76.1, 94.3) with R. Trough concentration (C5/C6) GMR (90% CI) of 91.3% (86.3, 96.7) for T &amp; 94.0% (88.9, 99.5) for R indicated steady state. C6 AUC 0-21d &amp; C max GMR (T/R [90% CI]) were 88.9% (80.3, 98.5) and 94.6% (88.1, 101.7), respectively. T and R led to comparable B-cell depletion and repletion. Incidence of all grades of TEAEs were comparable. TEAEs ≥Grade 3 were 80.3% in T (n = 61) and 88.0% R (n = 66). Neutropenia was the most common TEAE (overall: T, 75.0%; R, 73.3% &amp; ≥ grade 3: T, 64.5%; R, 64.0%). No neutralizing antibodies were observed in either of the arms. Conclusions: These data demonstrate that DRL-Rituximab has comparable PK, PD, efficacy, safety and immunogenicity to MabThera. MabThera already has an established efficacy in longer term follow-up. Clinical trial information: CTRI/2012/11/003129.
Long-term patient reported outcomes following radiation therapy for oropharyngeal cancer: A symptom assessment study in patients &gt;65 years old.
Authors: Salman Ali Eraj, Mona K Jomaa, Crosby Douglas Rock, Abdallah Mohamed, Adam S. Garden, Erich M. Sturgis, Kate A. Hutcheson, Charles Lu, Steven J. Frank, William H. Morrison, David Ira Rosenthal, Clifton David Fuller, Gary Brandon Gunn
Journal: Journal of Clinical Oncology (2017)

e21611 Background: Given the potential for older patients (pts) to experience exaggerated toxicity and symptoms, this study was performed to characterize pt reported outcomes (PROs) in older pts following definitive radiation therapy (RT) for oropharyngeal cancer (OPC). Methods: Disease-free head and neck cancer survivors ( &gt; 6 mos. since tx) were eligible for participation in a questionnaire-based study. Participants completed the MD Anderson Symptom Inventory-Head and Neck module (MDASI-HN). Those who had been treated for OPC with definitive RT (w/ or w/o systemic therapy) and were &gt; 65 y/o at time of RT were included. Individual and overall symptom severity and clinical variables were analyzed. Results: Of the 79 participants analyzed, 82% were male, 95% white, 41% T3/4 disease, 39% RT alone, 27% induction chemotherapy, 52% concurrent, and 18% both, and 96% IMRT. Median age at the time of RT was 71 yrs. (range: 65-85); median time from end of RT to MDASI-HN completion was 46 mos. (2/3 &gt; 24 mos.). The top 5 MDASI-HN items rated most severe in terms of mean (±SD) ratings (0-10 scale) were dry mouth (3.48±2.95), taste (2.81±3.29), swallowing (2.59±2.96), mucus in mouth/throat (2.04±2.68), and choking (1.30±2.38) reported at moderate to severe levels (≥5) by 35, 29, 29, 18, and 13%, respectively. Thirty-nine % reported none (0) or no more than mild (1-4) symptoms across all 22 MDASI-HN symptoms items, and 38% had at least one item rated as severe (≥7). Hierarchal cluster analysis resulted in 3 patient groups: 1) ~75% with generally no to moderate symptom burden, 2) ~25% with moderate to severe ratings for a subset of classically RT-related symptoms (e.g. dry mouth, mucus, swallow, taste), and 3) only 2 pts with severe ratings of nearly all items. Subgroup comparisons will be presented. Conclusions: The overall long-term symptom burden seen in this older OPC cohort was largely favorable, yet a higher symptom group (~25%) with a distinct pattern of mostly local symptoms was identified. We have implemented the routine use of symptom assessment tools as part of OPC survivorship programs and plan to explore age-dose-modeling of symptoms identified and associated normal structures.
TCT-173 Racial Disparities in Patients Undergoing Transcatheter Aortic Valve Replacement: Insights of the Healthcare Cost and Utilization Project's National Inpatient Sample
Authors: Dagmar Hernandez-Suarez, Nicole Yordan-Lopez, Pedro Villablanca, Lorena González-Sepúlveda, Jose Wiley, Abiel Roche-Lima, Brenda Nieves-Rodriguez, Angel Lopez-Candales, Pedro Cox, Harish Ramakrishna
Journal: Journal of the American College of Cardiology (2018)
Frequency of efficacy, toxicity and cost as the deciding factor when determining clinical pathways.
Authors: Stephanie McCutcheon, Peter G. Ellis, Regis Hess, Melinda Krebs, Kathleen Lokay
Journal: Journal of Clinical Oncology (2016)

e18169 Background: The cost of cancer care has been of increasing concern to patients, payers and providers. There is general agreement that, when clinical outcomes are comparable, the least costly therapy should be offered to the patient. Via Oncology Disease Committees utilize this same philosophy when deciding which regimens should be incorporated into the Via Pathways (VP). Cost is only considered when two or more regimens are deemed to be comparable both in terms of efficacy and toxicity. The distribution of recommendations between efficacy, toxicity and cost as of January 2016 are examined below using the evidence reviews from each Disease Committee meeting. Methods: Each patient presentation for all VP diseases have a Disease Committee Evidence Review that describes the thought process and resulting consensus decision of that Disease Committee for that particular treatment recommendation, including whether the final recommendation was based on efficacy, toxicity or cost. We reviewed the current Evidence Reviews for all medical oncology VP and tabulated the instances of recommendations based on efficacy, toxicity or cost. Results: As of January 2016, the distribution of Disease Committee recommendations for select diseases was as seen in the Table. Efficacy was the deciding factor for all recommendations (n = 202) in CML, Gastroesophageal, Head and Neck, MDS, Mesothelioma, Myeloma, Pancreatic, Renal Cell, and Thyroid. Additional diseases included in the total count were Bladder (n=15), Small Cell Lung (n=6), and Testicular (n=25). None had a treatment recommendation with a deciding factor of cost. Conclusions: The Via Oncology Disease Committees make pathway recommendations based on the efficacy demonstrated in published trials in 86% of patient presentations. Toxicity of therapy is the deciding factor in 9% of patient presentations. Cost of therapy is the deciding factor for recommendation in only 5% of patient presentations. Disease (# of Recommendations) Deciding Factor Efficacy (%) Toxicity (%) Cost (%) Breast (117) 97 3 0 Colorectal (33) 76 18 6 Lymphoma and CLL (86) 93 6 1 Melanoma (28) 36 0 64 Non-Small Cell Lung (63) 54 33 13 Ovarian (22) 77 14 9 Prostate (22) 82 14 5 Uterine (52) 81 19 0 Total for all VP Diseases (671) 86 9 5
P04.55 Efficacy of Tumor Treating Fields (TTFields) and aurora B kinase inhibitor
Authors: D Krex, P Bartmann, A Temme, R Schneiderman, T Voloshin, M Giladi, A Kinzel, E Kirson, U Weinberg, Y Palti
Journal: Neuro-Oncology (2018)

Tumor Treating Fields (TTFields) are an effective anti-neoplastic treatment modality delivered via noninvasive application of low intensity, intermediate frequency, alternating electric fields. TTFields is approved for the treatment of both newly diagnosed and recurrent glioblastoma. A promising approach to enhance the efficiency of TTFields is the use of drugs which extend metaphase-anaphase transition and telophase. Specifically, inhibitors or drugs interfering with components of the chromosomal passenger complex, in particular affecting Aurora B kinase, are potential candidates for combinatorial use with TTFields. The goal of the present study is to test the hypothesis that TTFields effect on tumor cells can be exaggerated by an additional inhibition of cytokinesis through chemical inhibition of Aurora B kinase. Efficacy of the combined treatment of TTFields and Aurora B kinase inhibitors (AZD1152) was tested in two sets of experiments comprising glioma cell lines: U87-MG, U87-MGshP53 and U-251 in the first set, and U87-MG, and two primary glioblastoma cell lines (HT16360, HT18503) in the confirmatory set. TTFields (1.6 V/cm RMS, 200 kHz) were applied for 72 hours using the inovitro system. AZD1152 was added to the media in concentrations of up to 100 nmol/L. Cell counts, cell cycle and clonogenic potential were determined at the end of treatment. Formation of multinuclear cells was determined using microscopic images of cells stained with crystal violet. The combined treatment of TTFields and AZD1152 led to a significant reduction in the number of U251, U-87 MG and U-87 MGshP53 cells (2-way ANOVA, p<0.001 in all three cell lines) as compared to each treatment alone. The overall effect taking into account, not just the cytotoxic effect at the end of treatment, but also the clonogenic potential, demonstrated a significant reduction in U87-MG, U87-MGshP53 and U-251 cells (2-way ANOVA, p<0.001 in all 3 cell lines) as compared to each treatment alone. Microscopy images of U87-MG and U87-MGshP53 cells stained with crystal violet after treatment, revealed high prevalence of multi nuclear cells in cells exposed to TTFields and AZD1152 (25nM) as compared to cells treated with AZD1152 (25nM) alone. Cells treated with TTFields and higher doses of AZD1152 (50-100nM) demonstrated increased rates of pyknosis. Data could be confirmed in primary tumor-cell lines. The results presented in this work demonstrate that the combination of TTFields and AZD1152 can be an effective treatment against glioma cells. Based on the above, there is a strong rational to continue exploring the potential of combining TTFields and AZD1152 in the clinical settings.
Professional development improves geriatric focused oncology activities in settings across the nation.
Authors: Denice Economou, Peggy Burhenn, Heeyoung Kim, Can-Lan Sun, Chris Okamoto, Anait Arsenyan, Elsa Roberts, Carolina Uranga, Vani Katheria, Arti Hurria
Journal: Journal of Clinical Oncology (2018)

11003 Background: Although older adults represent the majority of patients with cancer, oncology nurses receive little training in the care of older patients. In an effort to bridge this knowledge gap, an NCI-funded R25 grant supported the development and implementation of an educational curriculum in geriatrics for oncology nurses. Methods: Competitively chosen 3-person nursing teams (manager, educator, and clinical provider) from cancer settings across the nation participated in a 2 ½ day course in geriatrics for oncology nurses. Teams developed 3 goals aimed to improve geriatric oncology care in their settings. Goals were coded into detailed subcategories by PI and Co-Is. Code categories included: research-focused, clinical care, education, geriatric assessment, symptom focused, caregiver-related, infrastructure/team building, and other. Progress in implementing the goals was tracked at 6, 12, and 18 months post course. Goal completion rate over time was analyzed using generalized estimating equation for repeated measure. Results: 99 nurses (34 teams) participated in the 1st conference. A single goal may have had 2-3 codes applied and therefore 3 goals per 34 teams yielded a total of 181 codes. The most common goals focused on improving geriatric oncology clinical care (23%; N = 41 codes), professional education (23%; N = 41), geriatric assessment (9%; N = 16), infrastructure/team building (8%; N = 14) and resource development (7%; N = 13). Overall goal achievement at 6, 12, and 18 months was categorized as never started (29%, 7%, 4%), stopped (2%, 10%, 15%), stalled (9%, 20%, 13%), in process (48%, 38%, 30%) and completed (13%, 25%, 37%). Fourteen (8%) of the 41 clinical care goals and 8 (4%) of the education goals had stopped or stalled. Four teams had goals that were not started by 18 months. Goal completion rate increased significantly from 6 to 18 months (P < .0001). By 18 months, 67% of the goals were either in process or completed. Conclusions: An education curriculum in geriatrics for oncology nurses was implemented. Over the subsequent 18 months, nurses enacted goals to improve geriatric oncology care in their institutions. Continued follow-up and support is needed post course to foster goal completion.
Pharmacokinetics (PK), pharmacodynamics (PD) and immunogenicity of moxetumomab pasudotox (Moxe), an immunotoxin targeting CD22, in adult patients (Pts) with relapsed or refractory hairy cell leukemia (HCL).
Authors: Kemal Balic, Nathan Standifer, Linda Santiago, Denison Kuruvilla, Nai-Shun Yao, Robert J. Kreitman, Ira Pastan, Xia Li, Meina Liang, Inna Vainshtein, Chih-Ming Tseng, Raffaella Faggioni, Lorin Roskos
Journal: Journal of Clinical Oncology (2018)

7061 Background: Moxe is a recombinant immunotoxin that specifically binds to CD22 on the B cell surface and internalizes leading to cell death. The PK, PD, and immunogenicity of moxe were evaluated in a pivotal study (NCT01829711) in pts with HCL. Methods: Eighty pts were enrolled and received moxe (40 µg/kg IV) on days 1, 3, and 5 of each 28-day cycle. Samples were collected for assessments of PK, circulating CD19+ B cell counts and immunogenicity. PK parameters were estimated by non-compartmental approach. B cell counts were evaluated by flow cytometry. Immunogenicity testing utilized a tiered strategy: screen, neutralization followed by characterization of domain specificity (Pseudomonas exotoxin A [PE38], CD22) and titer. Results: Moxe concentrations peaked shortly after infusion followed by rapid elimination in a monophasic fashion (half-life = 1.38 hr; clearance = 44.6 mL/hr/kg). PK exposure increased from Dose 1 to Dose 3, likely due to post-treatment depletion of B cells expressing CD22. Moxe caused rapid and sustained depletion of circulating CD19+ B cells (mean 89% reduction from baseline on day 8). PK exposure revealed an inverse relationship with baseline CD19+ B cells. Higher PK exposures were significantly associated with low baseline CD19+ B cell counts. After dosing, CD19+ B cells were almost fully depleted and a weakened relationship with PK was observed. Anti-drug antibody (ADA) incidence and prevalence rates were 66% and 88%, respectively. Neutralizing antibodies (Nab) were detected in 84% of total pts. Among Nab+ pts, 99% and 54% of ADA exhibited specificity to PE38 and CD22 binding domains, respectively. Median titers were generally low at baseline but increased with time. Reduced PK exposure was observed at later cycles (≥ Cycle 3), consistent with increasing titer levels. Conclusions: Moxe exhibited rapid clearance and was highly immunogenic, as expected for a bacterial immunotoxin. This CD22 targeted therapy elicited rapid and potent B cell depleting activity in pts with HCL. Overall, these properties support moxe as a promising new approach for the treatment of relapsed/refractory HCL. Clinical trial information: NCT01829711.
Targeting Withdrawal Symptoms in Men Addicted to Methamphetamine With Transcranial Magnetic Stimulation
Authors: Ying Liang, Lei Wang, Ti-Fei Yuan
Journal: JAMA Psychiatry (2018)

This randomized clinical trial examines the use of transcranial magnetic stimulation targeting the left dorsal-lateral prefrontal cortex to modulate withdrawal symptoms in men addicted to methamphetamine.