tbuckley/cabot-search huggingface dataset:
Efficacy of abemaciclib (abema) after palbociclib (palbo) in patients (pts) with metastatic breast cancer (MBC).
Authors: Veronica Mariotti, Hung T. Khong, Hatem Hussein Soliman, Ricardo L Costa, Shanel Fisher, David Boulware, Hyo S. Han
Journal: Journal of Clinical Oncology (2019)

e12521 Background: CDK 4/6 inhibitors (Abema and Palbo) have shown efficacy in patients with HR+/HER2- MBC. Abema is distinct from other CDK 4/6 inhibitors and was approved after the approval of Palbo. There is limited data on sequential use or cross resistance. The aim of this study was to analyze the response to Abema based therapy in MBC pts with prior exposure to Palbo. Methods: We queried our EMR database for pts who received Abema from 9/2017-9/2018 after having received prior Palbo. Under IRB approved protocol we retrospectively collected demographics, tumor characteristics, disease status, toxicities and survival. Results: 23 female pts were identified. Four patients discontinued Palbo due to toxicities: two of them remained on Abema for 8 months and the other 2 discontinued Abema due to toxicities. The remaining 19 pts (median age 57 years, range 39-76) received a mean of 5.6 prior therapies (range (1-11) including Palbo in combination with endocrine therapy (fulvestrant 9 in pts and Aromatase inhibitors (AI) in 10 pts) at the time of Abema based therapy. 73.6% had visceral involvement including brain metastasis in 26%. The median progression-free survival (PFS) of Palbo in combination with endocrine therapy was 8 months (range 2.3-14.3). Abema was given in combination with endocrine therapy in 15 pts (9 pts fulvestrant and 6 pts AI) and 4 pts received it as a single agent. The median PFS of Abema based therapy was 7.0 months (range 1.8-12.1). Four pts (21%) had a longer PFS on Abema compared to prior Palbo PFS (table). Abema was discontinued due to toxicities in 15.7%. No partial or complete response was observed but 33% had stable disease. Conclusions: Abema showed response in a significant number of pts previously exposed to Palbo and heavily treated with multiple lines of chemotherapy for widespread metastatic disease. Prospective studies are warranted to better assess the response to Abema after exposure to CDK4/6 inhibitors. [Table: see text]
Quantifying interoperability: An analysis of oncology practice electronic health record data variability.
Authors: Elmer Victor Bernstam, Jeremy Lyle Warner, John C. Krauss, Edward P. Ambinder, Wendy S. Rubinstein, George Anthony Komatsoulis, Robert S. Miller, James Lin Chen
Journal: Journal of Clinical Oncology (2019)

e18080 Background: Implementation of electronic health records (EHRs) has engendered a large quantity of machine-readable data. However, different practices choose different EHR vendors and the same vendor product may be implemented differently at each practice. Motivated by the desire to facilitate appropriate integration of data, our goal was to describe and quantify the consistency and variation of structured data within EHRs. Methods: De-identified and aggregated CancerLinQ data from 47 practices regarding the standards and variability of structured data including race, diagnoses, encounters, cancer staging, selected cancer-relevant medications, lab values and biomarkers were analyzed. EHR represented included ARIA, MOSAIQ, Allscripts, Centricity, Epic, Intellidose, NextGen, and OncoEMR. Results: De-identified EHR implementations included 23 A, 12 B, C and 5 other vendors. Only 6 practices (13%) used non-standard race representation. All practices used ICD-9/10 for diagnoses. There was variability in coding of encounters. Sixteen practices always used CPT, 5 practices always used SNOMED CT and 26 practices used multiple standards. Multiple staging systems were used. An average of 48% (range 11%-; including patients staged more than once) of patient records included coded staging information. Only one practice used a standard (LOINC) for laboratory data. No standards were used for medications ordered/administered or biomarkers. The table shows the number of distinct names for selected lab tests, medications and biomarkers across systems. Conclusions: In this cross-sectional sample, standards are used consistently for diagnoses and encounter data, often for race and rarely for medications, laboratory tests or biomarkers.[Table: see text]
Late toxicities, especially second malignancies, with GWAS analysis in hepatoblastoma cases treated in the Japanese study group for pediatric liver tumor protocol-2.
Authors: Eiso Hiyama, Kenichiro Watanabe, Makiko Mori, Kohmei Ida, Tomoro Hishiki, Michihiro Yano, Yukichi Tanaka, Kenichi Yoshimura, Keiko Hiyama
Journal: Journal of Clinical Oncology (2019)

10043 Background: This study focused on late toxicities, especially second malignancies (SMNs), experienced by patients with hepatoblastoma (HB) treated with CITA (cisplatin and pirarubicin) in the Japanese Study Group for Pediatric Liver Tumor protocol-2 (JPLT-2). Methods: In the JPLT-2, 361 children with HB were eligible for inclusion. We evaluated late effects including ototoxicity, cardiotoxicity and SMN in these patients. PRETEXT I/II patients were typically treated by initial resection at diagnosis followed by CITA. Otherwise, patients received preoperative CITA, followed by surgery and postoperative chemotherapy. Non-responders to CITA received ITEC (ifosfamide, pirarubicin, etoposide, and carboplatin) or intensified chemotherapeutic regimens. In 267 patients whose germline DNA samples were available, genotyping analysis was performed using the Illumina Human Omni Express Exome-8 v.1.3 BeadChip. Associations between single nucleotide polymorphisms (SNPs) and toxicities were assessed using logistic regression analysis. Results: Among the patients (n = 300) who survived more than 5 years, ototoxicity was detected in 61 and cardiotoxicity in 18. The presence of ototoxicity was associated with a significantly higher dose of cisplatin, and the Brock grade of ototoxicity was correlated with the total dose of cisplatin (P &lt; 0.01). SMNs occurred in 13 patients (9 leukemia, 1 myelodysplastic disease, 1 lymphoma, 1 Ewing sarcoma and 1 thyroid tumor). The total dose of pirarubicin in SMN cases was significantly higher than those without SMNs (P = 0.035). The mean age at onset of HB was 13 months in the patients with SMNs and 23.3 months in the other patient (P = 0.12). However, two-way analysis of variance showed that SMN occurrence was significantly correlated with the age of HB onset and the total dose of pirarubicin (P &lt; 0.0001). We identified ten inherited SNPs, including six SNPs associated with ototoxicity such as ACYP2, two SNPs associated with cardiotoxicity and two candidate SNPs associated with SMNs. Conclusions: The total dose of cisplatin was significantly associated with ototoxicity development. A low incidence of cardiotoxicity but high rates of SMTs, which were correlated with a high dose of pirarubicin and younger age at diagnosis, were found in this study. We also identified SNPs associated with SMNs in HB. Our study provides strong evidence that germline mutation may modify the effect of chemotherapy for childhood cancers on late toxicities, especially during early childhood. Clinical trial information: UMIN000001116.
A phase II multicenter biomarker trial to study the predictive value of <i>TMPRSS2-ERG</i> before enzalutamide treatment in chemo-naïve metastatic castration-resistant prostate cancer.
Authors: Enrique Grande, Maria Piedad Fernandez Perez, Daniel Wetterskog, Albert Font Pous, Sergio Vazquez-Estevez, Aránzazu Gonzalez del Alba, Begona Mellado, Ovidio Fernandez Calvo, Maria Jose Mendez-Vidal, Miguel Ángel Climent, Ignacio Duran, Enrique Gallardo Diaz, Angel Rodriguez Sanchez, Carmen Santander, M Isabel Sáez, Javier Puente, Elena Castro, Daniel E. Castellano, Gerhardt Attard, Enrique González-Billalabeitia
Journal: Journal of Clinical Oncology (2019)

5040 Background: TMPRSS2-ERG fusion gene is a common driver of prostate cancer. The PREMIERE study is a phase II, single arm open-label, multicentre, clinical trial designed to analyse the predictive/prognostic value of TMPRSS2-ERG in first-line chemo-naïve mCRPC patients treated with enzalutamide. Methods: We centrally evaluated TMPRSS2-ERG in diagnostic samples using PCR, FISH and IHC for ERG. Among exploratory biomarkers we included plasma DNA, AR copy number by ddPCR and CTC by AdnaTest. PCWG2 criteria were used for outcome evaluation. We correlated TMPRSS2-ERGand other exploratory biomarkers with mCRPC outcomes. Results: Ninety eight patients with median age 77 y (range 59-95), ECOG 0/1 (54/46%) with mts located in bone (82%), LN (48%) and visceral (17%). With a median FU of 37.3 months, PSA response was PSA50: 82% and PSA90: 53%; median PSA-PFS was 13.7m (95%CI 10.2-19.0), Rad-PFS 26.7m (95%CI: 22.0-NA) and OS 37.5m (95%IC: 33.7-NA). TMPRSS2-ERG was detected in 32 pts (33%), AR gain in 11 pts and CTCs in 35 pts. No differences were observed based on TMPRSS2-ERG status for PSA response (PSA50: 81% vs 83%; p=0.8), PSA-PFS (median 12.8 vs 14.7m; HR 0.98; 95%CI 0.58-1.67; p=0.95), Rad-PFS (median 28.4 vs 26.4m; HR 1.02; 95% 0.53-1.96, p=0.95) or OS (median 36.9 vs 38.1m; HR 1.23; 95%CI 0.69-2.21, p=0.48). Plasma AR gain was associated with worse PSA-PFS (median 4.2 vs 14.7 m; p&lt;0.0001), Rad-PFS (median 3.6 vs 28.4m; p&lt;0.0001) and OS (median 12.7 vs 38.1m; p&lt;0.0001). Plasma DNA and CTCs were also associated with worse outcome. Multivariate analyses of exploratory biomarkers are included in the table. Conclusions: The fusion gene TMPRSS2-ERG is not predictive nor prognostic on enzalutamide treatment in first-line chemo-naïve mCRPC patients. Plasma AR gain and CTCs are strong independent biomarkers associated with adverse outcome. Multivariate analysis of exploratory biomarkers. Clinical trial information: NCT02288936. [Table: see text]
The PHACT Study: Population Health and Cancer Testing.
Authors: Mallika Sachdev Dhawan, Silpa Karipineni, Jason Budge, Julie Mak, Alicia Zhou, Kelly Williams, Kyusun Cha, Pamela N. Munster
Journal: Journal of Clinical Oncology (2019)

1531 Background: There is considerable uncertainty on cancer risk and recommendations for genetic testing in various populations. The purpose of this study is to test types and frequencies of cancer risk mutations in large, unaffected multiethnic populations, as well as feasibility and acceptance of general population germline testing. Methods: After consent, germline genetic testing via Color Genomics 30-gene Cancer Risk panel with personal and family cancer history assessment was offered to 500 participants residing in the San Francisco Bay Area. Participants were older than 21 and without a known family history of a cancer risk mutation. Recruitment occurred at random and through various, non-cancer related community events. Genetic counseling through a genetic counselor at UCSF was offered to all participants. Post-participation surveys were sent out to those who completed testing with 195 responses to assess attitudes towards genetic testing. Results: 500 participants completed testing; 35 were found to have a cancer risk mutation (7.0%). The majority of these have been in moderate risk cancer mutations including CHEK2 (1.0%), APC (0.8%), MUTYH (1.4%) and NBN (0.4%); higher risk mutations were found in BRCA1 (0.4%), BRCA2 (0.6%), BRIP1 (0.4%), PMS2 (0.2%) and PALB2 (0.2%). Data via self-reporting and SNP testing via the Color Genomics platform was collected to contextualize the racial, ethnic, and geographic association of these results. Rates of VUS (variants of uncertain significance) differed among the various ethnic groups (p = 0.027) with the lowest rates in Europeans vs. all other ethnicities (16.6% vs. 29%, p = 0.001). 37 (19.8%) out of 187 respondents reported that their genetic testing influenced testing in family members. In those 37 families, 8 additional people were positive for genetic mutations. Cost was the biggest barrier to pursuing prior genetic testing according to most individuals (20% of respondents); others were too busy (12%) or did not feel genetic testing was medically recommended (9%). Conclusions: The PHACT study demonstrates that large population screening of cancer risk mutations is feasible. The number of participants found to have mutations was greater than expected although the majority of these were in moderate risk genes. We found high rates of VUS in non-Europeans, which points to the complexity of population-based genetic testing.
Significant neutrophil accumulation, IL-18 deposition, and active inflammasome in tumor regions of human pancreatic ductal adenocarcinoma.
Authors: Ahmed Khattab, Yesica Garciafigueroa, Brett Phillips, Sunita Patruni, Amir Kamran, Thejus Jayakrishnan, Nazia Khatoon, Nabeeha Mohy-ud-din, Satdarshan P Monga, Stacey Miller, Nick Giannoukakis, Dulabh K. Monga
Journal: Journal of Clinical Oncology (2019)

e15754 Background: Obesity is an established risk factor for cancer and cancer-related mortality. Adipocytes may act as a “damage” signal resulting in the accumulation of innate immune cells, fueling an inflammatory micro-environment. Among the innate immune cells, tumor-associated neutrophils (TANs) are confirmed to accumulate inside the tumor. As obesity is a significant risk factor for a poorer prognosis in pancreatic ductal adenocarcinoma (PDAC), we hypothesize that obesity-driven adipose fuels the progression of PDAC in a TAN and inflammasome-facilitated manner. This may happen through several mechanisms, including genomic instability of aggressive PDAC clonal populations. Methods: Tissue from resected tumors of PDAC patients with a body-mass index (BMI) &gt; 27 (obesity, n = 5) and BMI &lt; 22 (normal, n = 5) were incubated with anti-human IL-18 and CD66b antibodies and detected using Alexa Fluor 488-conjugated donkey anti–mouse and Alexa Fluor 594-conjugated goat anti-rabbit secondary antibodies. Images were acquired in a Zeiss Axioplan microscope workstation and analyzed by ZEN and Metamorph software. Results: We identified the presence of CD66b+ neutrophils and IL-18 in all tissue sections. There is a significantly greater density of CD66b+ neutrophils and IL-18 in the tumor environment when compared to adjacent normal areas and IL-18+ signals appear to be deposited alongside the luminal area in a unique lasso-like pattern. These data suggest an association between BMI and inflammasome accumulation in the tumor environment. There does not appear to be an association between tumor stage and TAN or IL-18 accumulation in the tumor area or the adjacent normal tissue in the tissues. Conclusions: Our data uniquely shows that CD66b+ neutrophils accumulate inside PDAC and this is associated with intra-tumoral active inflammasomes. The novel periductal deposition of IL-18 in the tumor areas may be of mechanistic relevance in understanding how inflammation induces progression of PDAC. A larger cohort of tissues from PDAC obtained from low and high BMI individuals will be needed to test our hypothesis and to begin to decipher the role of obesity on inflammation and PDAC progression.
Comparative performance of Breast Cancer Index (BCIN+) and CTS5 in hormone receptor-positive (HR+) lymph node-positive (N+) breast cancer patients with one to three positive nodes (N1).
Authors: Dennis Sgroi, Yi Zhang, Catherine A. Schnabel
Journal: Journal of Clinical Oncology (2019)

555 Background: Identification of N+ breast cancer patients with a limited risk of recurrence improves selection of those for which chemotherapy and/or extended endocrine therapy (EET) may be most appropriate to reduce overtreatment. BCIN+ integrates gene expression with tumor size and grade, and is highly prognostic for overall (0-10yr) and late (5-10yr) distant recurrence (DR) in N1 patients. Clinical Treatment Score post-5-years (CTS5) is a prognostic model based on clinicopathological factors (nodes, age, tumor size and grade) and significantly prognostic for late DR. The current analysis compares BCIN+ and CTS5 for risk of late DR in N1 patients. Methods: 349 women with HR+, N1 disease and recurrence-free for ≥5 years were included. BCIN+ results were determined blinded to clinical outcome. CTS5 was calculated as previously described (Dowsett et al, JCO 2018; 36:1941). Kaplan-Meier analysis and Cox proportional hazards regression for late DR (5-15y) were evaluated. Results: 64% of patients were &gt; 50 years old, 34% with tumors &gt; 2cm, 79% received adjuvant chemotherapy and 64% received up to 5 years of ET. BCIN+ stratified 23% of patients as low-risk with 1.3% risk for late DR vs those classified as high-risk with 16.1% [HR 12.4 (1.7-90.4), p = 0.0014]. CTS5 classified patients into 3 risk groups: 29% of patients as low-risk (4.2% DR), 37% as intermediate-risk (10.6% DR), and 34% as high-risk (22.1% DR) [HR intermediate vs. low: 2.3 (0.7-7.0), p = 0.16; high vs. low: 5.3 (1.8-15.5), p = 0.002]. In a subset of patients who completed 5 years of ET (N = 223), BCIN+ identified 22% of patients as low-risk with a late DR rate of 2.1%, while CTS5 identified 29% and 37% of patients as low- and intermediate-risk with late DR rates of 5.2% and 10.3%, respectively. Conclusions: BCIN+ classified N1 patients into binary risk groups and identified 20% patients with limited risk of late DR ( &lt; 2%) that may be advised to forego EET and its attendant toxicities/side effects. In comparison, CTS5 classified patients into 3 risk groups, with low- and intermediate-risk of late DR of 4-5% and 10%, wherein the risk-benefit profile for extension of endocrine therapy is less clear.
Induction chemotherapy followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: Long-term results of a phase 3 multicenter randomized controlled trial.
Authors: Ming-Yuan Chen, Qi Yang, Minghuang Hong, Ming-Huang Hong
Journal: Journal of Clinical Oncology (2019)

6004 Background: Initial 3-year results from our clinical trial in locoregionally advanced nasopharyngeal carcinoma (NPC) patients showed that induction chemotherapy (IC) with cisplatin and fluorouracil (PF) resulted in improved disease-free survival (DFS) with a marginally significant effect on distant metastasis-free survival (DMFS), but the effect of IC on locoregional relapse-free survival (LRRFS) and overall survival (OS) did not differ significantly. Here, we present 5-year follow-up results. Methods: Our trial was a randomized, open-label phase 3 trial comparing IC followed by concurrent chemoradiotherapy (CCRT) versus CCRT alone in patients with stage III-IVB (except T3N0-1) NPC. The IC followed by CCRT group received cisplatin (80 mg/m² d1) and fluorouracil (800 mg/m² d1-5) every three weeks for two cycles before CCRT. Both groups were treated with 80 mg/m² cisplatin every three weeks concurrently with radiotherapy. The primary endpoints were DFS and DMFS. We did efficacy analyses in the 476 randomized patients (intention-to-treat population). Results: After a median follow-up of 82.6 months, the 5-year DFS rate was 73.4% (95% confidence interval (CI) 67.7-79.1) in the IC followed by CCRT group and 63.1% (95% CI 56.8-69.4) in the CCRT alone group (P = 0.005). The 5-year DMFS rate was also significantly higher in the IC followed by CCRT group (82.8%, 95% CI 77.9-87.7) than in the CCRT alone group (73.1%, 95% CI 67.2-79.0, P = 0.013). Our updated analysis revealed an OS benefit of IC: the 5-year OS rate was 80.8% in the IC followed by CCRT group versus 76.8% in the CCRT alone group (P = 0.045). There were no significant differences in the rate of grade 3–4 late adverse events during follow-up between the two groups. Conclusions: IC followed by CCRT provides long-term DFS, DMFS, and OS benefits compared with CCRT alone in locoregionally advanced NPC and, therefore, can be recommended for these patients. Clinical trial information: NCT00705627.
G-CSF for Extensive STEMI
Authors: Felice Achilli, Gianluca Pontone, Beatrice Bassetti, Lidia Squadroni, Jeness Campodonico, Elena Corrada, Camilla Facchini, Luca Mircoli, Giovanni Esposito, Daniele Scarpa, Stefano Pidello, Stefano Righetti, Filiberto Di Gennaro, Marco Guglielmo, Giuseppe Muscogiuri, Andrea Baggiano, Alberto Limido, Laura Lenatti, Giuseppe Di Tano, Cristina Malafronte, Federica Soffici, Martina Ceseri, Stefano Maggiolini, Gualtiero I. Colombo, Giulio Pompilio
Journal: Circulation Research (2019)

In the exploratory Phase II STEM-AMI (Stem Cells Mobilization in Acute Myocardial Infarction) trial, we reported that early administration of G-CSF (granulocyte colony-stimulating factor), in patients with anterior ST-segment-elevation myocardial infarction and left ventricular (LV) dysfunction after successful percutaneous coronary intervention, had the potential to significantly attenuate LV adverse remodeling in the long-term.The STEM-AMI OUTCOME CMR (Stem Cells Mobilization in Acute Myocardial Infarction Outcome Cardiac Magnetic Resonance) Substudy was adequately powered to evaluate, in a population showing LV ejection fraction ≤45% after percutaneous coronary intervention for extensive ST-segment-elevation myocardial infarction, the effects of early administration of G-CSF in terms of LV remodeling and function, infarct size assessed by late gadolinium enhancement, and myocardial strain.Within the Italian, multicenter, prospective, randomized, Phase III STEM-AMI OUTCOME trial, 161 ST-segment-elevation myocardial infarction patients were enrolled in the CMR Substudy and assigned to standard of care (SOC) plus G-CSF or SOC alone. In 119 patients (61 G-CSF and 58 SOC, respectively), CMR was available at baseline and 6-month follow-up. Paired imaging data were independently analyzed by 2 blinded experts in a core CMR lab. The 2 groups were similar for clinical characteristics, cardiovascular risk factors, and pharmacological treatment, except for a trend towards a larger infarct size and longer symptom-to-balloon time in G-CSF patients. ANCOVA showed that the improvement of LV ejection fraction from baseline to 6 months was 5.1% higher in G-CSF patients versus SOC (P=0.01); concurrently, there was a significant between-group difference of 6.7 mL/m2 in the change of indexed LV end-systolic volume in favor of G-CSF group (P=0.02). Indexed late gadolinium enhancement significantly decreased in G-CSF group only (P=0.04). Moreover, over time improvement of global longitudinal strain was 2.4% higher in G-CSF patients versus SOC (P=0.04). Global circumferential strain significantly improved in G-CSF group only (P=0.006).Early administration of G-CSF exerted a beneficial effect on top of SOC in patients with LV dysfunction after extensive ST-segment-elevation myocardial infarction in terms of global systolic function, adverse remodeling, scar size, and myocardial strain.URL: https://www.clinicaltrials.gov. Unique identifier: NCT01969890.