tbuckley/cabot-search huggingface dataset:
Affordability of drug treatment in advanced non-small cell lung cancer.
Authors: Yi-Ting Chou, Jennifer Elston Lafata, Joel Farley, Tom Stinchcombe, Amber Proctor, Stacie Dusetzina
Journal: Journal of Clinical Oncology (2018)

e18619 Background: Novel treatments have been approved for advanced non-small cell lung cancer (NSCLC) to improve patient outcomes; however, their high costs could pose significant barriers to their widespread use. We examined changes in drug-specific prices in Medicare from 2010 to 2017 to provide insights into drug affordability in advanced NSCLC for products covered on the medical benefit (Part B) and on the outpatient prescription drug benefit (Part D). Methods: We used the Prescription Drug Pricing file and the Average Sales Price data from the Centers for Medicare & Medicaid Services to obtain price information for Part D (oral drugs) and Part B (mostly infused drugs) drugs, respectively. We identified median point-of-sale drug prices for each drug and year and calculated expected out-of-pocket costs for each drug using the standard Part D benefit design in 2017 or assuming a 20% coinsurance for Part B. Results: Over time higher entry prices at FDA approval were observed for drugs covered under Part D, from $2,293/month in 2010 to $14,079/month in 2017. Older drugs covered under Part D also experienced considerable price hikes (up to 244%). In contrast, Part B drug prices have remained stable over time. Over the study period traditional chemotherapies were priced below $100/month; products with new formulations (e.g., albumin-bound paclitaxel) or newer chemotherapy agents (e.g., pemetrexed) were $8,000/month or more. Prices for novel targeted therapies were high on both Part B and Part D; > $10,000/month (immunotherapy, Part B), $8,000/month (EGFR-targeted agents, Part D), and > $13,000/month (ALK-targeted therapy, Part D). In 2017, expected patient out-of-pocket spending was estimated to range from < $40-$3,000/month for a Part B drug and $1,800-$3,500/month for a Part D drug. Conclusions: Treatment affordability is likely to present continued challenges for advanced NSCLC patients given current plan benefits and ever-increasing drug prices. A sustainable mechanism to control/monitor drug price (e.g., value-based pricing) and provide financial access to these medications is needed to ensure optimal patient outcomes.
An observational study of concomitant immunotherapies and denosumab in patients with advanced melanoma or lung cancer.
Authors: Alexander Liede, Rohini K Hernandez, Sally W Wade, Ronghai Bo, Elizabeth Ahern, William C Dougall, Mark J Smyth
Journal: Journal of Clinical Oncology (2018)

e21001 Background: After a case report of a melanoma (MEL) patient (pt) who had profound clinical response after treatment with an immune checkpoint inhibitor (ICI) and RANK-ligand inhibitor denosumab, we identified similar pts treated with concomitant ICI/denosumab from electronic health records (EHR), and described pt characteristics and outcomes to inform further investigations. Methods: This observational study used Flatiron Health's EHR database from ~255 US cancer clinics. Included were advanced MEL or non-small-cell lung cancer (NSCLC) pts who received denosumab within 30 days of ICI start with a minimum of 6 months (mos) of follow up. ICIs were CTLA-4 (ipilimumab) or PD1 (pembrolizumab, nivolumab) inhibitors. Real-world tumor response (rwTR) was analyzed for scans available up to 30 days after final dose of either concomitant therapy. Preclinical experiments evaluated relative sequencing of ICI, denosumab vs monotherapy or control. Results: MEL (n = 66) pts were treated concomitantly with denosumab/ICI for a mean 4.0 mos, and 3.1 mos for NSCLC (n = 241). Two-thirds of pts had best rwTR evaluable, as either complete (CR), partial response (PR), stable disease (SD), or disease progression (PD) (Table). Longer mean duration of concomitant exposure was associated with overall response rate (ORR; CR+PR) in the MEL (p = 0.0172), NSCLC (p < .0001), and combined cohorts (p < .0001). Longer concomitant therapy was associated with increased overall survival, primarily in NSCLC (p < .0001). Preclinical data suggest that optimal use was ICI initiated before or at same time as denosumab. Conclusions: Results provide proof-of-concept that rwTR is associated with concomitant ICI/denosumab. Crude survival analyses supported the association of concomitant therapy and improved outcomes outside of clinical trials, and warrant future comparative study. Tumor type/ Weeks (tertiles) of concomitant use rwTR CR/PR n (%) SD n (%) PD n (%) Melanoma (N = 32) 16 (50.0) 5 (15.6) 11 (34.4) < 10 2 (6.3) 1 (3.1) 2 (6.3) 10-31 5 (15.6) 1 (3.1) 7 (21.9) ≥ 32 9 (28.3) 3 (9,4)) 2 (6.3) NSCLC (N = 178) 61 (34.3) 46 (25.8) 71 (39.9) < 11 5 (2.8) 10 (5.6) 44 (24.7) 11-26 19 (10.7) 15 (8.4) 21 (11.8) ≥ 27 37 (20.8) 21 (11.8) 1 (0.6)
Frequency and outcomes of melanoma subtypes in a diverse population: The Los Angeles County – University of Southern California (LAC-USC) Medical Center experience.
Authors: Gino Kim In, Dongyun Yang, Jacob Stephen Thomas, Anthony Pham, Arnab Basu, Arjun Ajay Mehta, Kimberly Ann Miller, Myles Cockburn, James Hu
Journal: Journal of Clinical Oncology (2017)

e21063 Background: Melanoma is a biologically heterogeneous disease that varies by ethnicity and histology. While superficial spreading (SSM) histology is the most common subtype in non-Hispanic whites (NHW), acral lentiginous (ALM) and other subtypes occur more frequently in Hispanics, Asians and African Americans. There are no known risk factors for ALM, and further investigation is warranted. Methods: We retrospectively reviewed a database of melanoma patients diagnosed between 2001-2016 at LAC-USC. Overall survival (OS) was estimated using Kaplan-Meier methodology, and comparisons performed using log-rank testing. Fisher’s exact test was used to evaluate associations between relevant clinicopathological variables. A p-value &lt; 0.05 was considered statistically significant. Results: Among 272 melanoma patients, there were 140 Hispanics (51.5%), 105 NHW (38.6%), 14 Asians, and 4 African Americans. The most frequent histology among Hispanics was ALM (30.7%), while SSM was the most frequent among NHW (33.3%). BRAF V600 mutations were found in 34.5% (10/29) and 58.8% (10/17) of Hispanics and NHW, respectively. A total of 52 patients with ALM were identified, including 43 Hispanics (82.7%). There was a significant association between no prior history of non-melanoma skin cancer (NMSC) and ALM (p &lt; .0001). Median Breslow thickness for ALM was 4.2 mm, and 32.7% were ulcerated. The rate of BRAF V600 mutations among 13 ALM patients tested was 0%. NRAS mutations were found in 3 ALM patients; KIT amplification/mutations were found in 2 ALM patients. Conclusions: We identified a population enriched for Hispanic patients with ALM. We found an association between no prior NMSC and ALM, suggesting that UV exposure is not a causative risk factor. BRAF mutations are less common amongst Hispanics, and nearly absent in ALM. Survival differences were not statistically significant, but cannot be ruled out due to low number of patients in this early study. [Table: see text]
Window-of-opportunity clinical trial of a PD-1 inhibitor in patients with recurrent glioblastoma.
Authors: John Frederick De Groot, Marta Penas-Prado, Jacob Joseph Mandel, Barbara Jane O'Brien, Shiao-Pei S. Weathers, Shouhao Zhou, Kathy Hunter, Kristin Alfaro-Munoz, Gregory N. Fuller, Jason Huse, Ganesh Rao, Jeffrey S Weinberg, Sujit S. Prabhu, Sherise D. Ferguson, Ying Yuan, Luis M Vence, James Patrick Allison, Padmanee Sharma, Amy B. Heimberger
Journal: Journal of Clinical Oncology (2018)

2008 Background: A Phase III study failed to demonstrate a therapeutic benefit of anti-PD-1 therapy in recurrent GBM. This study was initiated to ascertain tumor immune modulatory properties of pembrolizumab in these patients requiring surgery. The primary objectives were to evaluate immune effector function in resected GBM tissue after pembrolizumab treatment and to determine progression-free survival at 6 months (PFS6). Methods: In an open label, single-center, single-arm biomarker-driven Phase 2 trial, 15 patients with GBM, at first or second recurrence who required reoperation for tumor progression were enrolled (NCT02337686). Patients were treated with up to two doses of pembrolizumab prior to surgery and afterwards received pembrolizumab until disease progression or the development of unacceptable toxicities. Recurrent GBM patients receiving standard of care (SOC) were immunologically analyzed (n = 10) as a comparator. Results: 21 patients were screened. 15 were enrolled and received at least one dose of pembrolizumab. The most common adverse event was grade 1 or 2 fatigue in 40% of patients. There were no treatment-related deaths. The median follow-up time for all patients was 12 months (95% CI: 3-31). The longest ongoing duration of response exceeded 34 months in two patients (one IDH1 mutant, one wild-type). Median PFS was 7 months (95% CI: 4-16) and PFS6 was 53% (95% CI: 33%-86%). Median overall survival has not been reached (95% CI: 15 to not reached), with an estimated 1-year overall survival of 72% (95% CI: 52%–99.6%). Analysis with 35 immune markers by mass cytometry revealed that GBM tumors are poorly infiltrated with T cells but are enriched with distinct CD68+ populations. These CD68+ cells are less frequent in pembrolizumab-treated patients (n = 6) relative to those treated with SOC (n = 10; P= 0.01); however, GBM-infiltrating Tregs are more frequent in patients treated with pembrolizumab (P = 0.02). Conclusions: Although pembrolizumab was well tolerated, PFS6 data and immune analysis indicates that anti-PD-1 monotherapy is insufficient for a response in the majority of GBM patients, likely secondary to a marked scarcity of T cells within the tumor microenvironment and a preponderance of CD68+ cells. Clinical trial information: NCT02337686.
The impact of cancer treatment on work productivity of patients and caregivers: A systematic review of the evidence.
Authors: Jordan Randall Covvey, Khalid M Kamal, Ankur A Dashputre, Somraj Ghosh, Christopher Zacker
Journal: Journal of Clinical Oncology (2016)

e18249 Background: Cancer is a leading cause of death with substantial economic burden, including productivity loss. Less is known about the impact of pharmacologic treatments for cancer on patient and caregiver work productivity. To quantify the full economic burden of cancer, a need exists to understand all costs of care, including indirect costs. The study goal was to conduct a systematic literature review to summarize existing evidence and identify knowledge gaps in the impact of cancer treatment on work productivity. Methods: Articles/abstracts were systematically searched from MEDLINE, Cochrane, Scopus and CINAHL, and listings for ISPOR, AMCP and ASCO, up to January 2016. Bibliographies of articles were screened for additional citations. The PRISMA guidelines were utilized for study reporting. Controlled search terminology (alone or in combination) included individual pharmacologic therapies for cancer and terms related to patient/caregiver work productivity, such as absenteeism and presenteeism. Identified studies were screened for study inclusion by two independent reviewers with adjudication by two secondary reviewers during the eligibility phase. Results: Out of 923 potentially relevant citations, 58 articles/abstracts were included in the final synthesis. A total of 43 studies (74.1%) evaluated patient-related productivity, 10 studies focused on caregivers and 5 studies on a combination. Twenty-two studies (37.9%) were conducted in the USA. The most commonly studied cancer was breast (51.7%). A variety of metrics were used to quantify productivity (hours lost, return to work, change of status, activity impairment). The Work Productivity and Activity Impairment questionnaire was the most commonly utilized standardized tool. Conclusions: While it is known that cancer impacts ability to work, less is known about the impact of cancer treatment on work productivity. Additional research is needed to quantify indirect costs, to estimate the full economic burden of cancer and evaluate the potential value of new treatments, including targeted therapies and oral chemotherapy. This may also be valuable to patients as they become more engaged in their care through shared decision-making.
Group acupuncture appointments for cancer-related symptoms: A retrospective review of the first year of experience at the Levine Cancer Institute.
Authors: Wendy G. Brick, Susan I Yaguda, Jonathan Polsky, Chasse Margot Bailey-Dorton, Beth York, Patrick L Meadors
Journal: Journal of Clinical Oncology (2016)

e21592 Background: Acupuncture is increasingly being used to treat cancer-related symptoms. Evidence for efficacy of symptom mitigation is lacking, as is volume of evidence for safety in this population. Group acupuncture appointments are an economically prudent and efficient way to provide acupuncture treatments to cancer patients while still allowing for individualized treatment. In this retrospective study, we evaluated the effects (symptom relief and safety) of group acupuncture on cancer related symptoms during the first year of availability at the Levine Cancer Institute. Patient satisfaction with a group format was also evaluated. Methods: Retrospective analysis for self-reported symptoms of pain, neuropathy, hot flashes, anxiety, sleep problems and fatigue for patients receiving group acupuncture by a licensed acupuncturist. At the conclusion of their first group appointment, each patient completed a satisfaction survey. Prior to every visit, patients completed a short symptom questionnaire and rated symptoms on a scale from 1-10. Adverse events were graded using the CTCAE v 3.0. An Independent Samples T-Test was used to compare Baseline to Session 4 and Baseline to Session 8. Results: Of all patients who received at least one group acupuncture treatment, 74% (n = 109) patients completed at least 4 acupuncture treatments and 26% (n = 39) completed at least 8 acupuncture treatments in 2015. All self-reported symptoms (except Neuropathy) decreased significantly between sessions 1 and 4. Only hot flashes decreased significantly between sessions 1 and 8. There were 2 hematomas (Grade 1) and 2 bruises (Grade 1) reported. Conclusions: The results of this study support the use of group acupuncture for cancer-related symptoms and provide evidence that group acupuncture is safe and effective. It is considered valuable to patients as noted by high patient satisfaction scores. Limitations of this study include possible response bias, uncontrolled treatment regimes, and the retrospective review. Future prospective controlled research is needed to further establish the relative efficacy of specific acupuncture treatments for cancer-related symptoms.
Nutritional aspects of cannibalism and other pieces of odd research win Ig Nobel prizes
Authors: Janice Hopkins Tanne
Journal: BMJ (2018)

Cannibalism isn’t very nutritious, roller coasters can remove kidney stones, self colonoscopy is a useful idea, postage stamps can evaluate nocturnal penile erections, human saliva is a good cleaning agent, and other surprising discoveries won Ig Nobel Awards last night at Harvard University in Cambridge, Massachusetts.

The Ig Nobels are for research that first makes people laugh and then makes them think. They are given annually by the science humour magazine Annals of Improbable Research , the Harvard-Radcliffe Science Fiction Association, and the Harvard-Radcliffe Society of Physics Students. The awards were presented before an audience of 1100 cheering, paper aeroplane throwing spectators.

Cannibalism is not an efficient way of getting nutrients, said James Cole, principal lecturer in archaeology at the University of Brighton, who won the Ig Nobel for nutrition. He told The BMJ that he wanted to better understand why humans sometimes eat their fellows. Studies of bones from the paleolithic age showed that the human body is not …
Abstract 17497: Management of Acute Type A Aortic Dissection in an Hybrid Operating Room: - Feasibility and Added Value of Preoperative Angiography and Intravascular Ultrasound
Authors: Rolf A Janosi, Konstantinos Tsagakis, Philipp Kahlert, Eva Kottenberg, Riccardo Gorla, Daniel S Dohle, Ulrich H Frey, Holger Eggebrecht, Rajendra Mehta, Eduardo Bossone, Jürgen Peters, Heinz Jakob, Raimund Erbel
Journal: Circulation (2015)

Introduction: Acute type A aortic dissection (ATAAD) is rapidly lethal and requires comprehensive tactics and decision making. To refine our respective approach we retrospectively analyzed our patients undergoing urgent surgery in our hybrid operating room over a 10 year period for the impact of immediate preoperative coronary angiography (CA), aortography, and/or intravascular ultrasound (IVUS) for the detection of coronary artery disease (CAD) and/or arterial malperfusion. Methods: 136 patients (mean age: 60.6 y ± 13; 63% male, March 2004-February 2014) underwent preoperative CA with or without IVUS. We assessed the time interval from preoperative CA to surgery and the impact for concomitant coronary artery bypass grafting (CABG) or endovascular interventions. Results: The delay to proceed with surgery due to preoperative catheterization averaged 32 min ± 26 (Fig. 1) in the setting of the hybrid OR. CA revealed CAD in 47/136 (35%) patients, with CABG consequently performed in 38 (28%). In 12 (9%) patients, CABG was necessary due to ostium obstruction by the dissection. 30-day mortality more than doubled in patients with concomitant CAD (27.7% vs. 11.2%, respectively, p&lt;0.01). However in patients with confirmed CAD, mortality was less 19% (6/31), in those undergoing CABG, compared to 44% (7/16) for isolated aortic repair (p=0.08). Conclusions: In a hybrid operating room setting, preoperative coronary and aortic angiography do not unduly delay surgery, facilitate diagnosis of coronary malperfusion, and allowing concomitant CABG in as much as 28% of patients.
Updated data from a phase II dose finding trial of single agent isatuximab (SAR650984, anti-CD38 mAb) in relapsed/refractory multiple myeloma (RRMM).
Authors: Joshua Ryan Richter, Thomas G. Martin, Ravi Vij, Craig Cole, Djordje Atanackovic, Jeffrey A. Zonder, Jonathan L. Kaufman, Joseph Mikhael, William Bensinger, Meletios A. Dimopoulos, Todd M. Zimmerman, Nikoletta Lendvai, Parameswaran Hari, Enrique M. Ocio, Cristina Gasparetto, Shaji Kumar, Corina Oprea, Eric Charpentier, Stephen Anthony Strickland, Jesus San Miguel
Journal: Journal of Clinical Oncology (2016)

8005 Background: Isatuximab (ISA) is a humanized anti-CD38 monoclonal antibody with multiple modes of action for killing tumor cells through direct tumor targeting and immune cell engagement. Here, we report updated data from an ongoing Phase II dose finding study of ISA monotherapy in patients (pts) with RRMM (NCT01084252). Methods: Pts with RRMM (≥3 lines of anti-MM therapy or refractory to immunomodulatory drugs [IMiDs] and proteasome inhibitors [PIs]) were randomized to ISA 3 mg/kg Q2W, 10 mg/kg Q2W x 2 cycles then Q4W, or 10 mg/kg Q2W. Randomization stratified by prior pomalidomide and/or carfilzomib therapy. Emerging PK data prompted enrollment of a 4th treatment arm at 20 mg/kg QW x 4 doses then Q2W. 1 cycle = 28 days. Primary objective: evaluation of ISA activity (overall response rate [ORR; IMWG]). Results: 97 pts treated: median age, 62.5 (38–85) y; median time from diagnosis, 5.9 (1.2–24.1) y; ISS stage 3, 37%; median prior lines of therapy, 5 (2–14); 86%, 61%, 80%, 57%, 88% refractory to lenalidomide, pomalidomide, bortezomib, carfilzomib, or IMiD+PI, respectively. 24/56 cytogenetics-evaluable pts (43%) had t(4;14) and/or del(17p). Median treatment duration, 13.1 wks; 22 pts remain on treatment (cut-off Nov 2015). ORR: 9% (2/23), 20% (5/25), 29% (7/24) & 24% (6/25) at ISA 3 Q2W, 10 Q2W/Q4W, 10 Q2W, & 20 mg/kg QW/Q2W, respectively; 14/20 responders continue without progression. At ≥10 mg/kg: ORR was 24% (18/74), similar in subgroups (age, CrCl, prior lines of therapy), and 44% (8/18) in pts with abnormal cytogenetics. Median time to 1st response, 1.35 mo; median duration of response at data cut-off, 6.6 mo. Most common adverse events (AEs) were nausea (33%), fatigue (30%), dyspnea (26%), and cough (24%), which were typically grade ≤2. Infusion-associated reactions (IARs) occurred in 49% of pts, mostly grade ≤2, 94% during the 1st infusion. 6 pts discontinued therapy due to AEs, 2 due to IARs. Conclusions: ISA monotherapy is active and generally well tolerated in heavily pretreated RRMM, with efficacy greatest at ≥10 mg/kg (ORR 24%). ORR was similar in subgroups, including high-risk cytogenetics. Progression-free survival and overall survival data will be presented. Clinical trial information: NCT01084252.
Correlation between local 18F-fluorodeoxyglucose PET/CT and T cell exhaustion for predicting treatment response in patients with advanced melanoma treated with checkpoint inhibitor mono-therapy.
Authors: Miguel Hernandez Pampaloni, Lorenzo Nardo, Alain Patrick Algazi, Katy K. Tsai, Kimberly Loo, Luca Facchetti, Susana Ortiz-Urda, Adil Daud
Journal: Journal of Clinical Oncology (2016)

11572 Background: Development of biomarkers to evaluate prolonged systemic treatment response is crucial for optimizing individual checkpoint inhibitor therapies. Glucose consumption rates assessed by 18F-FDG PET/CT have been used to stage and monitor the response to therapy in patients with melanoma. We aim to explore whether local 18F-FDG uptake can predict systemic response and how it correlates with intratumoral infiltration measured by the proportion of “exhausted” antigen experienced T cells (TEx)/Total CD8+ cells. Methods: Following core biopsies or surgical excision, freshly isolated tumor samples were digested and tumor infiltrating lymphocytes (TILs) were extracted and stained with T cell myeloid and activation markers, and analyzed with 14 color FACS. Patients were treated with either Nivolumab 3 mg/kg q2 week or Pembrolizumab 2 mg/kg q3 week. TEx was calculated as % CD8+, PD-1+, CTLA-4+ cells divided by total CD8+ T cells in the tumor sample. Thirty-nine patients (23 males) with measurable advanced melanoma were included. The closest in time, (49 ± 22 days), standard of care whole-body 18F-FDG PET/CT to the biopsy was used for analysis. Uptake was measured by maximum standardized uptake value (SUVmax) at the biopsied lesion. Treatment response was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST), for a period of 14±9 months. Results: Of the 18 patients with high TEx (more than 24%), 11 were in CR or PR at follow-up with a SUVmax of 15.8 an, compared to an SUVmax of 10.7 for the 7 patients in PD or SD. Nine of the 21 patients with low TEX (less than 24%) were in PR or CR with an SUVmax of 4.9, significantly lower than the SUVmax of the 12 patients in PD or SD, 10.4. Conclusions: When associated with TEx, local glucose utilization measured by 18F-FDG may be of help for predicting systemic response to check inhibitor mono-therapy. Variations in local increased glucose consumption may reflect several pathophysiologic pathways including different concentrations of activated lymphocyte populations, non-homogenous melanocytic tumoral densities and local inflammatory cellular migrations.
Abstract 19670: Association Between Myocardial T1-Mapping and Left Ventricular Mechanics in Patients With Repaired Tetralogy of Fallot
Authors: Christopher M Haggerty, Abba Mejia-Spiegeler, Jonathan D Suever, Gregory J Wehner, Esther Kim, Brandon K Fornwalt, Mark A Fogel
Journal: Circulation (2016)

Introduction: Patients with repaired tetralogy of Fallot (TOF) have progressive, adverse ventricular remodeling, leading to abnormal contractile mechanics. Defining the mechanisms underlying this d...