tbuckley/cabot-search huggingface dataset:
Intensified induction therapy with reduced total anthracycline exposure in pediatric low-risk acute myeloid leukemia.
Authors: Katherine Ashley Minson, Caitlin Herring, Jonathan Metts, Himalee Sabnis, Todd Michael Cooper, William G. Woods, Frank G. Keller
Journal: Journal of Clinical Oncology (2017)

10533 Background: Despite advances in risk stratification and therapy, the post-induction disease free survival (DFS) and overall survival (OS) for children with low-risk acute myeloid leukemia (LR-AML) remain low with DFS and OS of 50% and 68%, respectively, on the standard arm of the recent Children’s Oncology Group (COG) trial, AAML1031. Additionally, current therapy for pediatric LR-AML contains anthracycline doses exceeding thresholds known to increase the risk of adverse cardiac effects. In an effort to decrease exposure to cardiotoxic therapy, the Aflac Cancer and Blood Disorders Center adopted an institutional practice to treat LR-AML patients with a regimen of intensified induction therapy with decreased anthracycline exposure (Aflac-AML consisting of ADE10, Mitox/HiDAC, HiDAC/VP, Capizzi II). The aim of this study is to describe the associated toxicities and outcomes of this regimen in pediatric LR-AML. Methods: We retrospectively reviewed medical records of patients diagnosed with de novo LR-AML and treated per the Aflac-AML regimen from 2011-2014. Charts were reviewed for cardiac outcomes, ICU admissions, and the rate of infectious toxicities. DFS and OS were determined using Kaplan-Meier survival analysis. Results: We identified 11 LR-AML patients treated with Aflac-AML therapy. Patients received a planned 317 mg/m 2 cumulative anthracycline dose vs 442 mg/m 2 for those treated on AAML1031. There was no decrease in LVEF with a mean change of +2.17% for Aflac-AML patients from the time of diagnosis to therapy completion (p = 0.23). The primary infectious toxicities observed were febrile neutropenia and bacterial infections with a median of 36.4±6% documented bacterial infections per cycle. Fungal and viral infections were rare as were ICU admissions – median 4.5±4% per cycle – and there were no toxic mortalities. The 3-year DFS and OS from end of induction I for Aflac-AML patients were 72.7% and 90.9%, respectively. Conclusions: The Aflac-AML regimen resulted in short-term toxicities and outcomes comparable to current chemotherapy regimens for pediatric LR-AML but with reduced anthracycline exposure. These data support use of this regimen for pediatric LR-AML patients.
The economic effectiveness of fidaxomicin over vancomycin in treating clostridium difficile infection in cancer patients: A systematic review.
Authors: Omar Khaled Mahmoud Abughanimeh, Laith Al momani, Tyler Morgan, Mouhanna Abu Ghanimeh, Timothy J. Pluard
Journal: Journal of Clinical Oncology (2018)

e18923 Background: Clostridium difficile infection (CDI) is a common health care associated infection. Its incidence has been increasing recently despite all the measures to prevent it. This disease increases annual expenses by 1.5 billion dollars. Cancer patients are at higher risk to acquire CDI, which can be explained by their frequent exposure to the risk factors. Traditionally, metronidazole and vancomycin were considered the gold standard for treating mild and moderate to severe diseases, respectively. Fidaxomicin was approved by FDA for treatment of CDI in 2011. There was a trial that was done on cancer patients that showed the superiority of fidaxomicin over vancomycin in term of cure rates, sustained responses, and fewer recurrences. Till date, fidaxomicin is not a first line treatment, which some have attributed to its higher cost. Herein, we performed a systematic review to evaluate the cost difference between using fidaxomicin vs. vancomycin as a first line treatment in CDI. Methods: We performed a comprehensive literature search using Medline, the Cochrane Central Register Of Controlled Trials, and Pub Med databases. MeSH terms utilized in different combination were “Clostridium difficile”, “cancer/oncology”, “Vancomycin”, “Fidaxomicin” during our search. Studies that evaluated the cost difference between the 2 drugs in cancer patients were incorporated in the review. Results: Total of 5 studies were reviewed. Four studies included total cost savings, while three studies included data regarding saved costs associated with hospitalization. Use of fidaxomicin led to an average total costs savings of $1,356. Use of fidaxomicin led to an average hospitalization costs savings of $2,820. Conclusions: Although initial fidaxomicin cost is higher than vancomycin, our systematic review illustrated that the use of fidaxomicin as a first line for treating CDI in cancer patients has favorable economic results compared to vancomycin. This result need to be validated by a larger clinical trial that assess the difference in cure rate, clinical recurrence and hospitalization cost between the two drugs.
Detection of androgen receptor expression in circulating tumor cells of metastatic breast cancer patients.
Authors: Tanja N. Fehm, Melissa Neubacher, Franziska Meier-Stiegen, Natalia Krawczyk, Hans Neubauer, Wolfgang Janni
Journal: Journal of Clinical Oncology (2018)

e24096 Background: Predictive relevance of circulating tumor cells (CTCs) in metastatic breast cancer (MBC) patients has been shown in several clinical trials. Moreover identification of predictive biomarkers is of highest importance to stratify patients for targeted therapy. The DETECT studies evaluate the impact of phenotyping of CTCs on therapy decisions for patients with MBC, among others for patients with triple negative (TN) MBC. In DETECT IVb patients with TN MBC or other indications for chemotherapy are receiving Eribulin as monochemotherapy. Associated with this concept is a plethora of translational projects aiming to identify potential predictive biomarkers. The Androgen Receptor (AR) seems to be a promising target as it is expressed in up to 45% of TN tumors. Aim of the project presented here was the characterization of CTC regarding expression of AR using immunofluorescence. Methods: MBC patients with a Her2- primary tumor were screened in the DETECT studies. In a subset of CTC positive patients an additional sample was used to enrich CTCs using CellSearch Profile Kit. Cells were transferred onto slides. Establishment of immunofluorescence staining for AR was performed using prostate cancer cell lines LNCaP and DU145 as positive and negative control, respectively. Staining of pan-cytokeratin (CK) and CD45 was applied to identify nucleated cells as CTCs and to exclude leucocytes. AR expression was specified. Results: Co-staining of AR, CK and CD45 according to the above mentioned workflow was successfully established using cell lines with known AR expression spiked into the blood of healthy donors. For this translational project 75 samples of 66 patients participating in the DETECT studies were analyzed. At least one CTC was detected in 49.3% (37/75). In 40.5% of these samples at least one AR+ CTC was detected (15/37). Overall AR expression in all detected CTCs was shown in 53.3% (8/15). Remaining samples contained AR+ and AR- CTCs (46.7%; 7/15). Conclusions: Expression of AR in CTCs of patients with MBC could successfully been shown. This could serve as a basis for future work exploring the impact of AR as a potential predictive marker for directed or endocrine therapy in patients with TN MBC.
P05.69 Independent risk factors for pre- and postoperative seizures in meningioma patients identified by logistic regression analysis
Authors: L Goertz, C Hamisch, N Erdner, H Muders, R Goldbrunner, N von Spreckelsen, P Stavrinou, B Krischek, M Timmer
Journal: Neuro-Oncology (2018)

To identify independent risk factors of pre- and postoperative seizures in meningioma patients. This is a retrospective single-center analysis of consecutive patients that underwent resection of intracranial meningioma between 2004 and 2017. The impact of patient and tumor characteristics on pre- and postoperative seizures was assessed by univariate and binary logistic regression analysis. Among 729 included patients, pre- and postoperative seizures occurred in 18.9% and 10.0%, respectively. In the univariate analysis, female gender (p = 0.013), preoperative motor deficits (p < 0.001) and peritumoral edema (p < 0.001) were associated with preoperative seizures. Headache (p < 0.001), preoperative sensoric symptoms (p < 0001) and occipital tumor location (p = 0.024) were negatively correlated with preoperative seizures. In the multivariate analysis, preoperative motor deficits (p < 0.001, OR: 3.9, 95% CI: 2.6 - 5.9) and peritumoral edema (p < 0.001, OR: 3.5, 95% CI: 1.8 - 6.7) were independent risk factors of preoperative seizures. In the univariate analysis postoperative seizures were significantly associated with parietal tumor location (p= 0.021), WHO grades 2 and 3 (p < 0.001), presence of multiple meningiomas (p = 0.034), incomplete tumor resection (Simpson grade > 2, p = 0.007) and recurrent meningioma (p = 0.001). Incomplete resection (p = 0.04, OR: 2.6, 95% CI: 1.1 - 6.6) and recurrent meningioma (p = 0.037, OR: 2.6, 95% CI = 1.1 - 6.2) remained as independent risk factors for postoperative seizures in the multivariate analysis. Preoperative motor deficits and peritumoral edema are independent risk factors for preoperative seizures, while incomplete tumor resection and recurrent meningioma are independently associated with postoperative seizures.
Hypereosinophilic syndrome (HES) during rituximab treatment.
Authors: Chinmay Basu
Journal: Journal of Clinical Oncology (2017)

e19021 Background: Hypereosinophilic syndrome (HES) is a rare disease defined by organ damage directly attributable to hypereosinophilia of any type. The most commonly involved organ is the lung, followed by the skin. Methods: We report a single-center cohort of patients with NHL (DLBCL). Of these patients, nine had been treated with RCHOP on standard reatment protocol (6 cycle chemotherapy). In a retrospective analysis, data on treatment response, frequency of relapses, adverse events reconstitution were evaluated. Heamotology and biochemistry tests abs analysis were performed after every cycle. Results: All patients had high disease activity before RTX treatment. We found 3 patients who developed severe drug-induced hypereosinophilia with gastrointestinal involvement as a consequence of RCHOP infusion. For the case 1 Full blood count revealed a new mild eosinophilia with eosinophil count of 1 9 109 /l. After the third infusion, the eosinophil count had risen to 7.0 9 109 /L. In case 2, after the 6th infusion, the eosinophil count had risen to 6.4 9 109/L. In case 3 also it occurred in follow up period after 6th infusion and 6.8 9 109 /L. However the finding was not associated with any severe toxicity or other malignancy. No alarming feature was also notice alongside this abnormality Conclusions: Preemptive retreatment with RTX, combined with CHOP, resulted in a sustained treatment response. Hence clinical significant is not clear this stage. Strict post marketing vigilance for evaluating the use of RCHOP was warranted.
PRO labeling for oncology drugs approved by FDA and EMA, 2012-2016.
Authors: Ari Gnanasakthy, Amy Barrett, Emily Evans, Denise D'Alessio
Journal: Journal of Clinical Oncology (2018)

e18730 Background: Although both the FDA and EMA note the importance of patient-reported outcomes (PROs) in oncology drug development, a recently published comparison of new drugs approved by these agencies between 2006 and 2010 found the EMA more likely than the FDA to grant PRO labeling claims (Gnanasakthy et al., 2017). The objective of this review was to compare FDA and EMA labeling for new oncology indications approved by both agencies between 2012 and 2016. Methods: A list of oncology drugs and indications approved between 2012 and 2016 by both the FDA and EMA was identified from the agencies’ websites. PRO-related language and analysis reported in US product labels and drug approval packages (DAPs) and EMA summaries of product characteristics (SmPCs) were then compared for each indication. Results: In total, 49 drugs and 64 indications were reviewed. Of 64 indications, 19 (29.7%) included no PRO data in either regulatory submission. No FDA PRO labeling was identified, but the FDA provided feedback on PRO measures and data in the DAP for 15 of 49 (30.6%) drugs. PRO language was included in the SmPC for 21 (32.8%) indications for 19 products. EORTC and FACT modules were the most frequently used PRO measures in both FDA and EMA submissions, and health-related quality of life, overall health status, and symptoms were the most frequently assessed concepts. Both agencies identified missing values in PRO data as problematic for interpretation; FDA reviewers were also critical of the content validity of the PRO measures used and of single-arm and open-label study designs, where conclusions were seen as unreliable. Conclusions: This review highlights the different evidentiary standards used by the FDA and EMA to assess PRO data from oncology clinical studies to support label claims. PRO data from valid and reliable instruments based on randomized controlled clinical trials without excess missing data may improve the likelihood of labeling based on PRO endpoints for oncology indications.
The reach of a community-based multidisciplinary (MD) thoracic oncology program (P).
Authors: Matthew Smeltzer, Fedoria Elaine Rugless Stewart, Nicholas Ryan Faris, Courtney Foust, Bianca Michelle Jackson, Kristina S. Roark, Laura McHugh, Raymond S Signore, Georgia Oliver, Edward T Robbins, Lisa Klesges, Raymond U. Osarogiagbon
Journal: Journal of Clinical Oncology (2016)

e18045 Background: MD care is a recommended strategy for improving lung cancer outcomes, but access may be skewed away from the highest risk populations. We compared the demographics of patients seen within an MD Program to those across a large healthcare system spanning five states in a high US lung cancer mortality zone. Methods: Lung cancer providers within a healthcare system were encouraged to refer patients for discussion in a weekly MD conference with or without referral to a weekly co-located MD clinic in the same healthcare system. The RE-AIM evaluation framework assessed the reach and representativeness of our MD program. In 2014-2015, MD participants were compared on key generalizability characteristics with the potentially eligible population of the: 1) Memphis metropolitan (metro) area and 2) entire mid-south region from 2014. P-values comparing MD clinic and the mid-south region were calculated using chi-square and t tests. Results: 550 patients were presented at MD conference and 265 attended MD clinic. Compared to regional and metro demographics, MD patients were younger and more likely to be female (p<0.01); a higher percentage were African-American (p<0.01). In patients <65 years old, MD care had over twice the percentage of uninsured patients compared to regional and metro (p<0.01). In patients >= 65 years old, MD care had a higher percentage of commercial insurance (30% vs. 7%) and a lower percentage of Medicare (60% vs. 91%) (p<0.01). Conclusions: The MDP effectively reached two traditionally underserved populations, uninsured and racial minorities. Medicare only patients >= 65 were under-represented, indicating an area to improve the reach of the MDP. The more extensive, co-located MD clinic model was successful in reaching similar patients compared with the MD conference-only model. Our results demonstrate that both levels of MD care can be implemented in a way that is inclusive of all potential participants. Mid-South Region (N=2279)/ Metro (N=999) MD Conference (N=550) MD Clinic (N=265) % African American (p<.01) 71 / 67 64 60 % Female (p<.01) 48 / 51 56 56 Insurance, Age < 65 (p<.01) % Medicare 29 / 27 9 12 % Medicaid 22 / 20 15 15 % Commercial 41 / 44 56 54 %None 8 / 9 20 19 Mean (SD) Age (p<.01) 69(10) / 69 (10) 64 (12) 65 (12)
Abstract 18994: Incidence and Predictors of Adverse Cardiovascular Outcomes in Hematopoietic Stem Cell Transplant Recipients
Authors: Nael H Aldweib, Abdullah Haddad, Manik Veer, Gina Berteotti, John Lister, Indu Poornima
Journal: Circulation (2016)

Introduction: Hematopoietic stem cell transplant (HSCT) has revolutionized the treatment of malignant hematologic disorders but morbidity and mortality in this population is influenced by cardiovas...
Multifocal adenocarcinoma of the lung: Factors predictive for local therapy.
Authors: Meghan Mooradian, Melissa C Price, Alona Muzikansky, Inga Tolin Lennes, Michael Lanuti, Henning Willers, Subba Digumarthy, Lecia V. Sequist
Journal: Journal of Clinical Oncology (2017)

e20041 Background: Multifocal Adenocarinoma (MAC) of the lung is a clinical entity of multiple synchronous or metachronous, often ground-glass opacities (GGO) on CT scan, typically indolent-behaving cancers. There is a paucity of clinical data to guide treatment decisions. MACs are often monitored via serial imaging with local therapy (radiation, surgery) employed at the discretion of the clinician. We sought to examine factors predictive of local therapy (Tx) at our institution, to develop standardized objective radiolographic parameters to guide treatment. Methods: We retrospectively reviewed pts seen in the MGH Thoracic Oncology Clinic from 2009-15. 39 pts with MAC were identified and serial CT scans were reviewed, assessing up to 5 nodules per pt. We excluded pts presumed to have MAC by imaging but without confirmatory pathology, those with calcified nodules and &lt; 3 yrs of imaging. Demographics and clinical information were collected and univariant and multivariable logistic regression models were fit to assess correlation with Tx. Results: Among the 39 pts, 84% were female and 92% were smokers (18% active, 51% former &gt; 10pkyr, 23% former &lt; 10pkyr). 149 nodules were identified with median size 11mm (range 5-55mm); the majority of pts had ≥3 nodules (36/39). 66 (44%) nodules received Tx (10 RT, 56 surgery). Radiographic variables significantly associated with Tx were baseline nodule size (p = 0.02) and solid density (p &lt; 0.001). Nodules &gt; 2.5cm at baseline had Tx 77% of the time, while those ≤ 0.7cm had Tx 41%. Median length of monitoring before Tx was 2.1yrs for solid nodules, 3.5yrs for subsolid nodules, and &gt; 11yrs for pure GGOs. Other observations included discordant genotypes between nodules within 1 pt and an overall pattern of nodule contraction just prior to growth acceleration. Conclusions: Lung MAC cases can be successfully managed with serial observation and intervention on growing solid or subsolid nodules. Those with GGO components can often be surveilled for yrs, or if pure GGO, for a decade or more. Larger size at baseline and solid density significantly correlate with the use of Tx. Examples of nodule contraction with concurrent enlargement of the solid component will be presented at ASCO, as this may be an important clinical warning sign.
P01.062 Probability maps of glioblastoma indicate variation in surgical decisions between twelve surgical teams
Authors: D Müller, P Robe, W van den Brink, H Ardon, B Idema, F Kloet, M Wagemakers, F Barkhof, P Vandertop, L Bello, M Conti Nibali, M Rossi, T Sciortino, G Widhalm, B Kiesel, S Han, E Mandonnet, M Berger, P de Witt Hamer
Journal: Neuro-Oncology (2018)

The aim of glioblastoma surgery is to maximize the extent of resection, while preserving functional integrity. Standards are lacking for surgical decision-making and consequently surgical strategies may differ between neurosurgical teams. In this study we quantitated and compared surgical decision-making throughout the brain between neurosurgical teams for patients with a glioblastoma using probability maps. All adults with first-time glioblastoma surgery in 2012–2013 from twelve tertiary referral centers for neuro-oncological care were included in this study. For each patient, pre- and postoperative tumor were manually segmented on MRI and aligned to standard brain space. Resection probability maps and biopsy probability maps were constructed in 1 mm resolution for each team’s cohort. Brain regions with differential biopsy and resection results between teams were identified. The study cohort consisted of 1085 patients of whom 305 received a biopsy and 780 a resection. Biopsy probability maps demonstrated differences between teams in biopsy rate per brain location, such as for the right caudate nucleus, indicating variation in biopsy decisions. Resection probability maps demonstrated differences between teams in residual tumor rate per brain location, such as for the left sagittal striatum and neighboring posterior corpus callosum, indicating variation in resection decisions. Biopsy and resection probability maps indicate treatment variation between teams for patients with a glioblastoma. This conveys useful objective arguments for quality of care discussions between surgical teams for these patients.
Improved survival among children and adolescent and young adults with acute lymphoblastic leukemia (ALL) treated at specialized cancer centers in California.
Authors: Elysia Marie Alvarez, Marcio H. Malogolowkin, Qian Li, Lori S. Muffly, Theodore Wun, Theresa Keegan
Journal: Journal of Clinical Oncology (2018)

10502 Background: We previously demonstrated that adolescent and young adult (AYA) patients who received induction treatment at specialized cancer centers (SCC; versus community hospitals) had lower early mortality within 60 days of diagnosis. However, the effect of location of treatment on long term survival has not yet been evaluated at the population-level. Methods: Using the California Cancer Registry linked to a statewide hospitalization database, we identified children (0-18 years) and AYAs (19-39 years) with first primary ALL who received inpatient treatment, 1991-2014 (n = 7,724). Patients were classified as receiving all or part/none of their treatment at a SCC (Children’s Oncology Group or National Cancer Institute-designated cancer center) within 3 years of diagnosis. Propensity scores were created for treatment at an SCC in each age-group. Inverse probability of treatment-weighted, multivariable Cox regression models estimated the magnitude of associations between location of treatment, sociodemographic and clinical factors with leukemia-specific survival. Results are presented as hazard ratios (HRs) and 95% confidence intervals (CI). Results: Overall, 21.3% of children and 42.6% of AYAs died over the study period (median follow-up time: 11.6 years). Seventy-eight percent (n = 4511) of children and 19% of AYAs (n = 356) received all their treatment at SCCs. In multivariable models, receiving all treatment at a SCC (vs part/no care) was associated with better leukemia-specific survival (HR 0.86, CI 0.75-0.99) in children and AYAs (HR 0.83, CI 0.72-0.97). In both age groups, worse survival was associated with older age, Hispanic and African American race/ethnicity (vs non-Hispanic white), public insurance (vs private) and comorbidities. Conclusions: Our results demonstrate that treatment at a SCC through end of therapy is associated with better leukemia-specific survival in children and AYAs. In contrast to AYAs, the majority of children receive care at a SCC, but both age groups benefit from care at a SCC. This highlights the need for these patients to be referred to and treated at SCCs.