tbuckley/cabot-search huggingface dataset:
Costs and hazard ratios of commonly used drugs in advanced/metastatic lung cancer at Cancer Free Foundation, Dana Point, California.
Authors: Helmy M. Guirgis
Journal: Journal of Clinical Oncology (2019)

e20508 Background: The American Cancer Society of Clinical Oncology used hazard ratios (HR) in its value framework as indicators of clinical response. Bevacizumab (Bev) and Pemetrexed (Peme) were introduced for non-squamous metastatic lung cancer prior to epidermal growth factor recognition. Objective: Analyze drug costs and HR in 1 st -line advanced/metastatic lung cancer. Methods: Costs of Bev, Peme, Pembrolizumab (Pembro) and Atezolizumab (Atezo) were calculated x one year. Protocols and HR at 95% confidence intervals were quoted. Results: Median drug HR was 0.73. Bev costs were $132,314 and HR 0.79 (A. Sandler, 2006). Peme costs were $97,947, HR 0.63 (M. Zuchin, 2013) and 0.78 (PARAMOUNT). Costs of Pembro 2mg/Kg x 80 Kg were $125,770 compared with $157,313, the currently used 200 mg flat dose. Proportionate savings were noted over the 90-50 Kg weight. Pembro costs x 35 cycles increased to $317,450. In tumor progression score (TPS) &gt; 50% (KEYNOTR-24), Pembro HR was 0.60. In KEYNOTE-042, HR in &gt; 1.0% was 0.81 and improved to 0.69 in 50% with a net benefit of 14%. In squamous cell (KEYNOTE-407), Pembro+chemo HR was 0.64. Pembro+Peme+chemo costs were $255,160. In KEYNOTE-189, irrespective of program death receptor-ligand-1 (PD-L1), HR was 0.49, &lt; 1.0% 0.59 and &gt; 50% 0.42. The net benefit was 28%. Atezo+Bev combination costs were $287,314 and HR 0.78 (IMPOWER 150). In extensive small-cell, Atezo+chemo costs were $150,604 and HR 0.70 (IMPOWER 133). Conclusions: Pembro weight-adjusted dose resulted in significant cost saving over the fit-all 200mg. In 1 st -line advanced/metastatic lung cancer, Pembro-Peme, irrespective of PD-L1, offered incomparable 0.49 HR at yearly costs of $255,160.
Association of single nucleotide polymorphisms within genes in NF-κB, TGF-β, and JNK signaling pathways with the risks of nasopharyngeal carcinoma in Chinese Han.
Authors: Hanyi Zhang, Shun Lu, Jinyi Lang
Journal: Journal of Clinical Oncology (2019)

6053 Background: Nasopharyngeal Carcinoma(NPC) is an Epstein-Barr virus(EBV) associated malignancy with remarkable ethnic and geographical distribution. The EBV oncoprotein latent membrane protein 1 (LMP1) is the primary oncogene of EBV infection through the its signaling cascade and its connections to other pathways including NF-κB, TGF-β and JNK signaling, which plays an important role in the pathogenesis of NPC. In GWASs(Genome-wide association studies) associations these pathways were also identified. Single nucleotide polymorphisms (SNPs) in the regulatory regions may regulate the expression of genes in these pathways, or affect the function of the coded protein. Methods: Altogether 149 SNPs were covered by the 15 SNPs in the TRAF2, TRAF3, NFKBIA, MAP2K4, and CHUK genes were genotyped in a hospital-based case-control study of 350 NPC cases and 587 healthy controls from the Chinese Han. The observed genotype frequencies in the controls were tested for Hardy–Weinberg equilibrium (HWE) using the chi-square test. Odds ratios (ORs) and 95% confidence intervals (95% CIs) for associations between genotypes and NPC risk and tumor characteristics were calculated by logistic regression, and they were adjusted for multiple testing using the SNP spectral deposition (SNPSpD) approach for multilocus analyses. Results: We found one NFKBIA SNP was associated with NPC risk after adjustment for multiple comparisons. Minor allele carriers of the NFKBIA had an increased risk of NPC (P &lt; 0.05). The analyses were adjusted for age and gender. For a polymorphism with a variant allele frequency between 10 %and 50%, the study had greater than 90% power to detect an OR of 1.50 at a significance level of 0.05 (PS—software for power and sample size calculation, http://biostat.mc.vanderbilt.edu/twiki/bin/view/Main/PowerSampleSize). The other genotyped SNPs were not associated with NPC risk. Conclusions: Our data suggests that genetic variation especially in the NFKBIA maybe a useful biomarker for NPC screening and further studies are warranted.
Antibiotic Use in Dentistry—What We Know and Do Not Know
Authors: Emily S. Spivak
Journal: JAMA Network Open (2019)

Katie J. Suda, PharmD, MS; Gregory S. Calip, PharmD, MPH, PhD; Jifang Zhou, MD, MPH; Susan Rowan, DDS; Alan E. Gross, PharmD, BCPS, BCIDP; Ronald C. Hershow, MD; Rose I. Perez, BS; Jessina C. McGregor, PhD; Charlesnika T. Evans, MPH, PhD
Randomization of dose-reduced subcutaneous interleukin-2 (scIL2) in maintenance immunotherapy (IT) with anti-GD<sub>2</sub> antibody dinutuximab beta (DB) long-term infusion (LTI) in front–line high-risk neuroblastoma patients: Early results from the HR-NBL1/SIOPEN trial.
Authors: Ruth Lydia Ladenstein, Ulrike Poetschger, Dominique Valteau-Couanet, Juliet Gray, Roberto Luksch, Walentyna Balwierz, Victoria Castel, Shifra Ash, Maja Beck Popovic, Genevieve Laureys, Godfrey Chi Fung Chan, Ellen Ruud, Kim Vettenranta, Cormac Owens, Henrik Schroeder, Hans Loibner, Peter F Ambros, Sabine Sarnacki, Tom Boterberg, Holger N. Lode
Journal: Journal of Clinical Oncology (2019)

10013 Background: We tested dose-reduced scIL2 in combination with DB-LTI and oral isotretinoin and evaluated toxicity and efficacy in high-risk neuroblastoma patients (EudraCT:2006-001489-17). Methods: High-risk patients (stage 4 ≥1y; stage 4 &lt; 1y with MYCN amplification (MNA); stage 2, 3, 0-21y with MNA) received high intensity induction (rapid COJEC or N5-MSKC and TVD for insufficient response), surgery, high dose therapy with busulfan/melphalan and local radiotherapy. Patients ≤9 months between diagnosis and HDT/SCT who achieved at least a partial response prior to HDT/SCT and without progression thereafter were randomized to receive up to 5 cycles of 100mg/m 2 DB-LTI (d8-17) ± 3x10 6 IU/m 2 scIL2 (d1-5; d8, d10, d12, d14, d16) and 160mg/m 2 oral isotretinoin (d19-32). Results: Between 04/2014 and 06/2018, 408 patients from 18 countries were randomized. Median follow-up is 1.8 years. Stage, age, MNA, induction treatments and remission status were well balanced between randomization arms. The 2yrs-EFS and -OS for DB-LTI (205 pts) vs. DB-LTI&amp;scIL2 (203 pts) was 64%±4%vs63%±5% (p = 0.844) and 83%±3%vs74%±4% (p = 0.337). For patients in CR the 2yrs-EFS was 69%±5% for DB and 66%±6% for DB&amp;scIL2. Patients with evaluable disease prior DB or DB&amp;scIL2, the end of treatment response rate was 57% (26% CR, 31% PR) vs 52% (27% CR, 25% PR) with 2yrs-EFS rates of 58%±7% and 64% ±8%, respectively. Grade 3&amp;4 toxicity was lower in the group with DB vs DB&amp;scIL2 for fever (14%vs31%, p &lt; 0.001) and pain (7%vs18%, p = 0.005), and no significant difference was seen for general condition (17%vs22%,ns), allergy (3%vs3%,ns), capillary leak (4%vs8%,ns), liver enzyme elevation (20%vs27%, ns) and neurological toxicities (2%vs2%,ns). Conclusions: We previously reported grade 3&amp;4 toxicity to DB short-term infusion (STI) ± 10x6x10 6 IU/m 2 scIL2 for general condition (16%vs41%, p = 0.000), fever (14%vs40%, p = 0.000), allergic reaction (10%vs20%, p = p = 0.006), capillary leak (4%vs15%, p = 0.004), liver enzyme elevation (17%vs23%, ns), central neurotoxicity (3%vs8%, p = 0.034) and pain (16%vs26%, p = 0.048). Our results indicate that DB-LTI and dose-reduced scIL2 clearly reduced the toxicity profile, but showed absence of benefits of scIL2. DB-LTI achieved 2yrs-EFS in line with DB-STI (Ladenstein, Lancet Oncology 2018; Yu, NEJM, 2010) and a response rate &gt; 50% supporting its use as standard of care IT. Clinical trial information: EudraCT:2006-001489-17.
Adherence of oral targeted agents in patients with B-cell malignancies.
Authors: Laura S. Samples, Dora M. Banjanin, Booyeon Kim, Solomon A. Graf
Journal: Journal of Clinical Oncology (2019)

e18301 Background: Oral targeted agents (OTAs) are rapidly changing the management of B-cell malignancies (BCM) and introducing challenges in prescribing practices and communication between patients, their clinicians, and pharmacists. Emerging data suggests dose interruptions impair OTA efficacy in BCM. However, infrastructure to ensure best practices may be outstripped by increasing OTA use in some clinics. We evaluated adherence to OTAs for BCMs at the Veterans Affairs Puget Sound Health Care System to identify opportunities for quality improvement in prescribing practices and patient education. Methods: Consecutive patients treated with OTAs for BCMs from 2014 to 2018 were examined by detailed chart review and included if they used an OTA uninterrupted for ≥ 30 days. OTA adherence was assessed by 1) identification of medication gaps ≥ 8 days not attributable to medication toxicity or disease progression and 2) ReComp, a validated electronic pharmacy refill adherence algorithm in which a value of 1 corresponds with perfect adherence and deviations from 1 correlate linearly with either over- or under- supply. Logistic regression modeling assessed for independent predictors of adherence. Results: Fifty patients were evaluated and 39 met inclusion criteria. They were prescribed 42 unique OTAs, including ibrutinib, venetoclax, idelalsib, and acalabrutinib over a total of 33,655 days, with a median duration of 420 days (range 60 to 1687). Twenty-three patients (59%) had at least one medication adherence gap ≥ 8 days. Five patients (13%) had ≥ 3 eight-day gaps. The study population had a mean ReComp value of 1.02 (median 0.99, standard deviation 0.15). Medication over-supply was identified in 46% and a quarter of patients were adherent &lt; 93% of the time. No statistically significant correlations were identified between either measure of adherence and examined factors related to socio-demographics and comorbidities. Conclusions: In our institution, a significant percentage of patients prescribed OTAs for BCMs experienced suboptimal adherence. These data identify opportunities to improve disease-related outcomes and costs. Initiatives to improve education and automated monitoring of OTA refills are under evaluation.
No relationship of axillary total tumor load (TTL) by PCR (OSNA) in early breast cancer and local and distant clinical outcomes.
Authors: Jose Ales-Martinez, Raquel Tur, Juan Parra, Jaime Ceballos, Elena Filipovich, Beatriz Segovia, Rafael Revestido, ANA De Castro, Paz Blanco, María José Velasco, Maria Rocio Martin
Journal: Journal of Clinical Oncology (2019)

564 Background: The study of sentinel lymph nodes (SLN) assessed by One Step Nucleic Acid Amplification (OSNA, Sysmex, Kobe, Japan) creates a new variable, Total Tumor Load (TTL). This variable is defined as the total number of CK19 mRNA copies in all positive SLN (copies/microL). The latest edition of the Spanish Oncological Gynecology Society (SEGO) Guideline (2017) proposes a complete axillary lymph node dissection (ALND) when TTL is 15,000 copies or more in early breast cancer. In our center we are using OSNA to ascertain if there is axillary node involvement but the decision to proceed to ALND is based on Z0011 criteria. We want to determine if there is a correlation between clinical outcomes and TTL values, between TTL and pathological variables and if TTL is a useful tool to decide when to complete an ALND. Methods: Clinicopathological and follow up data were obtained from all patients with invasive breast cancer and SLN assessed by OSNA between 2011 and 2017 at our center. Results: A total of 321 patients underwent SNB assessed by OSNA with an average follow-up of 56 months. 320 were female and 1 male. Age range 27-89 years (mean 58.9). 85 % were ductal, 10 % lobular and 5 % other. 53.5% were luminal A, 28.66% luminal B, 7.78%, triple negative, 4.3%, Her2 positive and 4.3%. luminal B-Her2 positive.TTL was equal to 0 in 183 cases and greater than zero in 138 cases.71 cases showed a TTL higher than 15,000 copies. Only 21 cases met Z0011 criteria and had ALND. As of now, 3 patients have had locoregional relapse and 8 metastatic disease. 12 have died, only two from metastatic breast cancer. Conclusions: Using Z0011 criteria, we have adequate clinical outcomes with a low rate of ALND; If we had based the axillary management on TTL values we would have multiplied the number of ALND by a factor of 3.3 (from 21 to 71); We have observed a tendency to higher TTL in luminal phenotypes and to lower TTL in HER2 positive and triple negative subtypes; Work is in progress to increase our sample size.
Clinical outcomes of postoperative intraperitoneal chemotherapy for patients with early-stage high-grade serous ovarian cancer (HGSC) treated at British Columbia cancer agency.
Authors: Joohyun Lee, Anna Tinker
Journal: Journal of Clinical Oncology (2019)

e17105 Background: Intraperitoneal (IP) chemotherapy has been shown to prolong overall survival in optimally debulked stage III ovarian cancer in randomized trials. In British Columbia, we extrapolated this benefit of IP chemotherapy to early stage HGSC patients for the last 10 years, as these patients are optimally debulked at surgery but still have a high rate of recurrence. We conducted a retrospective study of clinical outcomes associated with IP/IV chemotherapy compared to IV chemotherapy for optimally debulked stage I HGSC cases. Methods: This was a retrospective cohort study of women with stages IA-IC HGSC who had primary surgery between 2007-2015, and received either IV or IP/IV chemotherapy post-operatively. We compared progression-free survival (PFS) and overall survival (OS) outcomes between these 2 groups. Kaplan-Meier method evaluated chemotherapy delivery route with progression free survival (PFS) and overall survival (OS), using the statistical program R. Results: We identified 99 patients; 80 (81%) received IV chemotherapy and 19 (19%) received IP/IV chemotherapy. Among IP/IV cohort, 2/19 (11%) discontinued IP therapy during treatment due to abdominal pain at IP port site or hypersensitivity reaction to IV paclitaxel. 5-year PFS was 88.4% (74.5-100%) and 69.7% (58.7-82.7%) among the IP/IV and IV cohorts, respectively (p = 0.549). There was a trend for higher 5-year OS for the IP/IV group; however, this did not reach statistical significance (100% vs. 71.4%; p = 0.182). Conclusions: In our study, IP/IV chemotherapy for stage I HGSC patients was associated with a trend for higher 5-year PFS and OS compared to IV chemotherapy. This observation warrants further prospective investigation.
Chemotherapy in combination with immune checkpoint inhibitors for the first-line treatment of patients with advanced non-small cell lung cancer: A systematic review and literature-based meta-analysis.
Authors: Alfredo Addeo, Giuseppe Luigi Banna, Giulio Metro, Massimo Di Maio
Journal: Journal of Clinical Oncology (2019)

e20565 Background: Checkpoint inhibitors plus platinum-based chemotherapy have shown superiority compared to chemotherapy alone as first-line therapy in advanced non–small cell lung carcinoma (NSCLC),To evaluate the relative benefit in term of Overall Survival (OS) and Progression-free Survival (PFS) of checkpoint inhibitors plus chemotherapy versus chemotherapy alone, overall and in subgroups defined by PDL1 expression we have performed a meta-analysis Methods: This meta-analysis searched PubMed and checked references of the selected English language articles to identify further eligible trials. Furthermore, proceedings of the main International meetings (American Society of Clinical Oncology [ASCO] annual meeting, European Society of Medical Oncology [ESMO] annual meeting, International Association for the Study of Lung Cancer [IASLC] World Conference on Lung Cancer), were searched from 2010 onwards for relevant abstracts. Data collection for this study took place from October 1 to October 24, 2018. Results: In total, 8 trials involving 4646 patients with advanced NSCLC, 3.314 (71%) and 1.332 (29%) with a non-squamous and squamous histology, respectively, were included in this meta-analysis. Four trials used atezolizumab, 3 pembrolizumab and 1 nivolumab, accounting for 2.985 (64%), 1.298 (28%) and 363 (8%) of patients, respectively. Checkpoint inhibitors plus chemotherapy were associated with prolonged OS, compared with chemotherapy in the ITT population (HR, 0.74; 95% CI, 0.64-0.87; p = 0.0002, with significant heterogeneity among trials). Within the PDL1 low group (1-49) there was a significant heterogeneity (p = 0.06) between type of drug and efficacy: the combination of chemotherapy plus pembrolizumab showed an OS benefit (HR, 0.56; 95% CI, 0.40-0.78; P&lt; .00007) unlike the atezolizumab backbone trials (HR, 0.92; 95% CI, 0.62-1.37; P&lt; 0.69). However, checkpoint inhibitors plus chemotherapy were associated with prolonged PFS in the ITT (HR, 0.61; 95% CI, 0.56-0.66; P &lt; 0.00001) and across PDL1 subgroups. Conclusions: Checkpoint inhibitors plus chemotherapy compared with chemotherapy, are associated with significantly prolonged OS and PFS in first-line therapy in NSCLC. In the low PDL1 subgroups the benefit was statistically significant only in the pembrolizumab backbone trials.
Prognostic significance of amplifications of stemness genes in primary luminal breast cancer depending on the response to neoadjuvant chemotherapy.
Authors: Polina Kazantseva, Elena Slonimskaya, Nicolay Litviakov, Matvey Tsyganov, Marina Ibragimova
Journal: Journal of Clinical Oncology (2019)

e14655 Background: Neoadjuvant chemotherapy (NAС) is one of the treatment options for breast cancer (BC). However, chemotherapy is known can cause intratumoral changes that increase the risk of metastasis. We have previously found that the appearance of new amplifications in the chromosomal regions harboring stemness genes (3q, 5p, 6p, 7q, 8q, 9p, 9q, 10p, 10q21.1, 13q, 16p, 18Chr, 19p) is associated with the development of hematogenous metastases in 100% of cases. In our study, we evaluated the prognostic significance of amplifications stemness genes in primary BC depending on the NAC response. Methods: The study included 104 patients with stage II-III luminal B (Her2Neu -) breast cancer. All patients received 4-8 courses of NAС followed by surgery and hormone therapy. The follow-up period was 4-10 years. Amplifications in primary tumor DNA were determined using Affymetrix high density microarrays. Metastasis-free survival was estimated using the Kaplan-Meier method. Results: Zero or only 1 amplification was identified in tumor tissue of 42 patients (41%) (group 1). Two or more amplifications were identified in tumor tissue of 60 patients (59%) (group 2). We evaluated metastasis-free survival separately in each group, depending on the NAС response. It was found that in group 1, the median survival time was 122 months in cases with partial or complete regression (PR + pCR, and 63 months in cases with stable disease or disease progression (S + P), p &gt; 0.05. In group 2, the median survival of patients with PR + pCR was not reached, and it was 63 months in patients with S + P, p = 0.025. Conclusions: Achievement of partial or complete regression in breast cancer patients, whose primary tumors displayed 2 or more amplifications of stemness genes, was associated with the increased rates of metastasis-free survival and can be considered as a positive prognostic criterion. However, the response to NAC did not impact survival of patients with 0-1 amplification of stemness genes.
Oral vinorelbine as a second-line chemotherapy option in advanced malignant pleural mesothelioma.
Authors: Raul Rogelio Trejo Rosales, Jose Gustavo Nuñez Cerrillo, Juan Carlos Silva Godinez, Rodrigo Fernando Riera Sala, Maritza Peña Campos
Journal: Journal of Clinical Oncology (2019)

e20073 Background: Malignant pleural mesothelioma (MPM) is an infrequent entity with a poor prognosis. Standard first line chemotherapy therapy is based on pemetrexed and cisplatin, however, there is no established standard second-line therapy. We report our experience with patients treated at a third-level referral center in Mexico, making emphasis in the use of oral vinorelbine. Methods: We conducted a retrospective cohort study of MPM patients treated between 2012 and 2018 at the Centro Médico Nacional Siglo XXI, a third-level referral center in Mexico City. Our objective was to evaluate the effectiveness of different second-line chemotherapy schemes in MPM patients. Results: A total of 143 patients were included. There were 47 women (32.8%) and 96 men (67.1%). Median age was 64 (range 39 - 86). The histological subtypes comprised of 73.4 % epitheloid, 9 % with a sarcomatoid component and 17.4% not otherwise specified. The majority of patients presented with advanced disease 32.1 stage III and 63.6 stage IV. 72% of patients had performance status 0-1, however 9.7% of patients had performance status 3-4 at diagnosis, and received only palliative care as treatment. A total of 125 patients received first-line chemotherapy, and 40 patients underwent second-line therapy. Usual schemes were based on pemetrexed, paclitaxel, gemcitabine and oral vinolrebine. Overall, partial response rate was 5% and stable disease was 35%. There were no statistical differences in response rates between schemes (p = 0.75). The most usual second-line scheme was oral vinolrebine. Progression-free survival was 4 months in vinolrebine-treated patients vs 2 months (HR 1.04, 95% CI 0.86 – 1.25, p = 0.63) as compared with patients treated with other schemes. Conclusions: Our results are comparable with similar series in the second-line scenario. Oral-vinolrebine treatment progression-free survival was similar to other, more toxic drugs. However, we included few patients. More work is needed to identify the characteristics of benefitting patients.
Building a data foundation: How MD Anderson and Palantir are partnering to accelerate research and improve patient care.
Authors: Kristin Alfaro-Munoz, Gemma Hallatt, Jamie Sookprasong, John Frederick De Groot, Bryan Lari, Emily Yu, Jeff Jin, Andrew Futreal, Vinod Ravi
Journal: Journal of Clinical Oncology (2019)

e18077 Background: MD Anderson (MDA) strives to maximize learning from the &gt; 44,000 patients seen annually. This has historically been challenging due to the diverse, often unstructured, and siloed nature of patient data. To begin addressing these challenges, MDA constructed an institutional data warehouse and developed Natural Language Processing (NLP) capabilities. This allowed technical users to extract specific cohorts but proved challenging for many non-technical users. In 2018, MDA conducted a proof of concept with Palantir Technologies to integrate disparate data sources into a single cloud-based platform enabling both technical and non-technical users to directly access and analyze data. Methods: Through a highly iterative, collaborative process between clinical/research users, IT experts and Palantir engineers, 150 deidentified datasets were integrated from the existing data warehouse, NLP, molecular reports, public data and manually curated data, representing data from &gt; 1.5 million patients. Data integration was validated and feedback from clinical users gathered. Results: In addition to centralizing data, the platform was found to: (1) Make data accessible to non-technical users by mapping data to real-world concepts, (2) Create reports backed by live data, with clear visibility into inputs, analysis and history, (3) Create templates for common analytical workflows (e.g. KM curve), and (4) Support increased collaboration through transparent, secure access controls. This resulted in dramatic acceleration of cohort identification, data extraction, and outcomes analyses. Conclusions: Integrating siloed data exposed gaps and errors arising from the unstructured nature of medical data and use of NLP. In response, we are piloting a combination of (1) Purposeful structured data capture at the time of care, (2) Use of logic to suggest commonly uncaptured but critical patient events such as progression, and (3) Auditing functionality to allow users to manually fill in gaps and correct data in a transparent manner. Expanding the data foundation unlocks the potential for more advanced research, fueling scientific discovery, while enhancing the quality and safety of patient care.