tbuckley/cabot-search huggingface dataset:
Predictors of long-term follow-up care (LTFU) among survivors of adolescent and young adult (AYA) cancers: A population-based study in the IMPACT cohort.
Authors: Dalia Kagramanov, Rinku Sutradhar, Zhan Yao, Sumit Gupta, Nancy N. Baxter, Paul C. Nathan
Journal: Journal of Clinical Oncology (2018)

10014 Background: AYA cancer survivors are at elevated risk for developing therapy-related adverse health outcomes and require life-long risk-adapted health care. We determined the location and providers of LTFU care received by a population-based cohort of survivors and explored the demographic, disease and treatment factors that predict care received. Methods: We conducted a retrospective study using multiple linked administrative health databases in Ontario, Canada. Five-year AYA cancer survivors were identified from the IMPACT cohort, which consists of all AYA who were 15-20.9 years of age at diagnosis of one of six specified cancers in Ontario between 1992-2010. We defined four models of care: specialized survivor clinic; general oncology clinic; primary care physician; no regular care. Specialized survivor clinic attendance was only available to those treated at a paediatric cancer centre. Separate Poisson regression models determined attendance rates, adjusting for demographic, disease and treatment characteristics. Results: The cohort consisted of 1574 survivors (1066 treated at adult centres; 508 treated at paediatric centres). Median follow-up from five-year survival was 8.7 years (95% CI, 4.3-13.9 years). Over their follow-up, the highest level of care accessed by survivors was: survivor clinic (16.7%), oncology clinic (47.3%), PCP (9.3%), no regular care (26.7%). Among those eligible for the specialized survivor clinics, greater attendance was observed in females, those younger at diagnosis, living closer to a clinic, and those treated with Bone-Marrow Transplant. Specialized clinic attendance decreased by 19% with every 2-years of follow up. In contrast, the risk of receiving no regular care among all survivors was highest in males and increased by 20% with every 2-years of follow-up. Conclusions: Despite the need for risk-based care, most eligible AYA survivors do not attend specialized clinics, and almost one-third receives no regular care, with lack of care increasing over time. Strategies are needed to ensure that the maximum number of survivors receive life-long risk-based care.
Early molecular response in patients (pts) with chronic myeloid leukemia in chronic phase (CML-CP) treated with dasatinib (DAS) or imatinib (IM) from DASISION.
Authors: Neil P. Shah, Giuseppe Saglio, Andreas Hochhaus, Robyn Bilmes, Li Li, Jorge E. Cortes
Journal: Journal of Clinical Oncology (2016)

7055 Background: An exploratory landmark analysis from DASISION demonstrated improved PFS and OS in newly diagnosed CML-CP pts treated with DAS or IM who achieved BCR-ABL1 ≤ 10% at 3 mo, a milestone achieved by more pts on DAS (DAS: 84%, IM: 64%). Here, we evaluate the impact of EURO (Hasford) risk score on the achievement of this predictive molecular milestone and investigate other predictive factors of survival. Methods: In the phase III DASISION trial, treatment-naive CML-CP pts were randomized to receive DAS 100 mg once daily (n = 259) or IM 400 mg once daily (n = 260). BCR-ABL1 transcript levels were measured on the International Scale. EURO score ≤ 780 is low, > 780 to ≤ 1480 is intermediate, and > 1480 is high risk. Results: Based on EURO scores, 33% of pts in both treatment arms were at low risk, 48% and 47% of pts receiving DAS and IM, respectively, were at intermediate risk, and 19% in both arms were at high risk. Across all 3 risk groups, more pts on DAS had BCR-ABL1 ≤ 10% at 3 mo vs IM (low: 91% vs 73%; intermediate: 80% vs 66%; high: 83% vs 44%). More pts on DAS vs IM also had BCR-ABL1 ≤ 1% at 3 mo (low: 56%, 95% CI [45-68%] vs 20% [12-30%]; intermediate: 48% [38-57%] vs 12% [7-20%]; high: 33% [20-48%] vs 5% [1-16%]). Five-yr PFS and OS rates were higher for pts with BCR-ABL1 ≤ 10% vs > 10% at 3 mo in all risk groups (Table). Multivariate analysis of survival at 5 yrs showed women on DAS were at a lower risk of death than men; there was no association between EURO score or age and survival. Conclusions: In DASISION, a higher proportion of pts on DAS achieved BCR-ABL1 ≤ 10% at 3 mo than pts on IM in all EURO risk score groups, with the most notable difference in high risk pts. The proportion of pts achieving ≤ 1% BCR-ABL1 at 3 mo was statistically significantly higher (at a level of 0.05) on DAS. These data support DAS as a recommended first-line CML-CP therapy for pts in all EURO risk score groups. 5-year Outcomes, % (95% CI) DAS IM BCR-ABL1 at 3 months ≤ 10% > 10% ≤ 10% > 10% Low risk PFS 94 (86-98) 86 (42-100) 95 (86-99) 91 (71-99) OS 97 (90-100) 86 (42-100) 97 (89-100) 100 (85-100) Intermediate/ high risk PFS 91 (85-96) 80 (61-92) 93 (85-97) 79 (67-89) OS 95 (90-98) 87 (69-96) 96 (90-99) 86 (75-93)
Trends related to program participation, implementation, best practices, challenges and resource requests among oncology care model (OCM) participants.
Authors: Daniel Gutkin, Eric Zhao, Karen Phillips, Kristi Cavaliere, Heather Braun, Bryan Powell
Journal: Journal of Clinical Oncology (2018)

6524 Background: The OCM is an alternative payment model (APM), developed by the Center for Medicare & Medicaid Innovation (CMMI) to improve the quality of oncology care. The Patient Outcomes & Policy Regional Executive (POPRE) team was tasked with engaging OCM participants to understand their unique challenges and develop appropriate resources to address their concerns. We examined trends related to participation, implementation, best practices, and resource requests among OCM participants. Methods: Between May and October 2017, the POPRE team conducted interviews at 57 OCM sites, including 30 community, 24 academic, and 3 payer-based accounts. Participants answered questions pertaining to their OCM processes, challenges and needs. Results: The top OCM provider challenges identified were data extraction/analysis, electronic medical record (EMR) integration, and cost of care estimates. Common data extraction/analysis difficulties included labor intensive data collection, entry, and abstraction. EMR integration gaps centered on risk adjustment factors, tumor staging, triage processes, supportive care/pain care plans, among others. Patient & provider education materials, tech/IT tools, and EMR integration tools were the three most common requests from OCM providers. Care coordination solutions, including utilization of pathways, innovative software tools for symptom monitoring, and triage/virtual consults, were among the top OCM Best Practices shared. EMR integration solutions included the adoption of well-known pathways, care and survivorship plans, and symptom screening/risk stratification tools. Conclusions: The majority of participants interviewed experienced difficulties with OCM requirements. Most of those challenges were related to data extraction/analysis and EMR integration issues; however many practices utilized those gaps to innovate, adapt, and request appropriate resources to address these concerns. Resolving common data and solving EMR integration challenges may help improve other critical OCM practice transformations, thus enhancing patient care, providers’ engagement and overall program’s viability.
Radioaerosol Imaging Predicts the Utility of Aerosolized Antifungal Therapy in Allergic Bronchopulmonary Aspergillosis
Authors: Karen Rodriguez, Alan Siegel
Journal: Clinical Nuclear Medicine (2018)

A 10-year-old girl with a history of complicated cystic fibrosis was hospitalized for pulmonary exacerbation with allergic bronchopulmonary aspergillosis and severe right upper lobe bronchiectasis diagnosed with chest radiograph and CT. She was started on itraconazole during the hospitalization in attempt to decrease her systemic steroid dose, but she had ongoing coughing and wheezing. The possibility was raised that the right upper lobe bronchiectasis may be a nidus for ongoing aspergillosis. Radioaerosol imaging was performed to determine whether the aerosolized antifungals would reach the area of bronchiectasis.
Effect of hospital volume on mortality rates amongst neutropenic cancer patients within the United States.
Authors: Yaacov Richard Lawrence, Talia Golan, Damien Urban, Liat Hammer, Uri Amit, Raphael Catane, Jair Bar, Jeffrey Goldstein, Zvi Symon, Gavin Urban
Journal: Journal of Clinical Oncology (2016)

6600 Background: Hospital Volume is associated with improved outcomes in cancer surgery, and some aspects of cancer care. The influence of hospital volume on outcomes in neutropenic patients is unknown. Known factors associated with increased mortality include age, race and co-morbidities. We hypothesized that large-volume hospitals would have reduced mortality rates for neutropenic patients compared with small-volume institutions. Methods: We utilized the NIS database of the Healthcare Cost and Utilization Project, focusing on year 2009. All inpatient episodes with a diagnosis of both neutropenia and cancer were included in the study. Hospital volume was defined as the number of neutropenic cancer episodes listed for each institution per year. Mortality was defined as death during admission. Patients were classified into four risk-of-mortality subclasses based upon the 3M APR DRG score. Results: 20,096 hospitalizations from 718 different institutions were analyzed. Median age was 59 years. The overall inpatient mortality was 5.7%. Mortality increased with patient age, for instance amongst those aged 30-39 years it was 3.1% compared to 9.2% for those aged 70-79 years. The average number of neutropenic inpatient episodes in each institution per year ranged from less than one to 548 (median 84). The population was split into four equal groups based upon hospital volume. Mortality was 7.1%, 6.4%, 4.8% and 4.6% for each group (from lowest to highest volume), likewise % discharged home was 77.6%, 82.1%, 88.9% and 91.0% (for both p<0.001). In a logistic regression model incorporating age, race and sex and stratified by 3M APR-DRG, hospital volume remained statistically associated with reduced mortality for 3M APR-DRG risk mortality subclasses 2 and 3 (comprising 78% of the population), but not subclasses 1 and 4. Conclusions: Neutropenic patients hospitalized in large-volume institutions have a substantially lower mortality and a higher likelihood of returning home compared to those hospitalized at low-volume institutions. The 3M APR-DRG risk-mortality score significantly modulates this effect. Our findings imply that the majority of neutropenic patients should be referred onto large volume cancer centers.
Social media interventions for precision public health: promises and risks
Authors: Adam G. Dunn, Kenneth D. Mandl, Enrico Coiera
Journal: npj Digital Medicine (2018)

Social media data can be used with digital phenotyping tools to profile the attitudes, behaviours, and health outcomes of people. While there are a growing number of examples demonstrating the performance of digital phenotyping tools using social media data, little is known about their capacity to support the delivery of targeted and personalised behaviour change interventions to improve health. Similar tools are already used in marketing and politics, using individual profiling to manipulate purchasing and voting behaviours. The coupling of digital phenotyping tools and behaviour change interventions may play a more positive role in preventive medicine to improve health behaviours, but potential risks and unintended consequences may come from embedding behavioural interventions in social spaces.
Outcomes of cetuximab in 1<sup>st</sup>-line therapy for metastatic colorectal cancer (mCRC) according to tumor <i>RAS</i>/<i>BRAF</i> mutation (mt) status in the EREBUS cohort.
Authors: Denis Michel Smith, Magali Rouyer, Eric Francois, Antonio Sa Cunha, Alain Monnereau, Edwige Yon, Emmanuelle Bignon, Cécile Droz-Perroteau, Pernelle Noize, Nicholas Moore, Annie Fourrier-Réglat
Journal: Journal of Clinical Oncology (2018)

e15547 Background: Poor efficacy of cetuximab has been reported in patients with RAS/BRAF mt. There are few data about cetuximab benefit in real-life according to RAS/BRAF mt status. Methods: EREBUS is a multicenter (n = 65) cohort of KRAS wild-type (wt) unresectable mCRC patients initiating 1st-line cetuximab from 2009 to 2010, followed for 2 years (5 years for vital status). Objective response rate (ORR), metastases resection rate, progression-free survival (PFS) and overall survival (OS) were evaluated according to mt status: RASmt (whatever BRAF status), RASwt/BRAFmt and RASwt/BRAFwt (i.e. 2xWT). Multivariate Cox analyses were used to evaluate the association between mt status and death or progression. Results: 389 patients were included; RAS/BRAF status was known for 310 (80%): 64 RASmt (21%), 33 RASwt/BRAFmt (11%) and 213 2xWT (69%). Respective baseline characteristics were: median age 65, 64 and 63 years, male gender 63%, 64% and 69%, ECOG-PS 0-1 75%, 76% and 79%, liver only metastases 39%, 33% and 40%. ORR was 40.6% 95%CI [28.5-53.6] in RASmt patients, 30.3% [15.6-48.7] in RASwt/BRAFmt patients and 62.4% [55.8-69.0] in 2xWT patients. Metastases resection was performed in 12 RASmt patients (18.8% [10.1-30.5]; 8 radical resections R0/R1/radiofrequency), 2 RASwt/BRAFmt patients (6.1% [0.7-20.2]; 2 radical resections) and 75 2xWT patients (35.2% [28.8-41.6]; 47 radical resections). Median PFS (months) was 8.0 [5.9-9.3] in RASmt patients, 6.0 [2.3-7.2] in RASwt/BRAFmt patients and 10.4 [9.5-11.0] in 2xWT patients. Median OS (months) was 18.4 [10.9-23.3] in RASmt patients, 9.7 [6.9-16.6] in RASwt/BRAFmt patients and 29.3 [26.3-36.1] in 2xWT patients. In multivariate analyses, death (HR 3.13 [2.04-4.79]) and progression (HR 2.69 [1.78-4.07]) were more likely for RASwt/BRAFmt patients vs. 2xWT patients. In reference to 2xWT patients, HR for death was 1.63 [1.13-2.35] for RASmt/BRAFwt patients and HR for progression 1.41 [0.98-2.04] (p = 0.06). Conclusions: EREBUS confirms in real-life the difference in clinical outcomes with tumoral RAS/BRAF mutation in unresectable mCRC treated by 1st-line cetuximab, showing the greatest effectiveness in 2xWT patients.
Comparison of clinicopathological (CP) features and outcome of breast cancers (BC) in <i>BRCA</i>-mutation carriers patients, with a family history without <i>BRCA-</i>mutation and with sporadic disease.
Authors: Stephanie Becourt, Odile Cohen-Haguenauer, Florence Ledoux, Olivia Nguyen, Caroline Cuvier, Sylvie Giacchetti, LaurenceDoidy Cahen-Doidy, Edwige Bourstyn, Marc Espie, Luis Teixeira
Journal: Journal of Clinical Oncology (2018)

e13522 Background: BRCA-1 and 2 are two major susceptibility genes for BC. We compared CP features and outcome in (i) BRCA (1/2)-mutation carrier's patients, (ii) patients with a family history suggesting hereditary breast cancer (HBC) without BRCA mutation (Eisinger score ⩾ 5) and (iii) patients with sporadic disease. Methods: We retrospectively reviewed clinical and pathological data of 64 BRCA- mutation carriers (33 BRCA1 - 31 BRCA2), 59 HBC patients and 112 sporadic BC patients, treated in Saint-Louis hospital between 1987 and 2016. Sporadic BC patients were free from family history of cancer and randomly extracted from our database. We recorded age, CP characteristics of breast tumors (tumor size, nodal status, tumor grade, hormone receptor and c-erbB2 status), treatment type, ipsilateral relapse, contralateral BC and outcome (disease-free and overall survival). Results: BRCA-mutated patients and HBC patients were significantly younger at diagnosis than sporadic BC patients (mean age 38 years (i) (35 for BRCA1, 40.5 for BRCA2), 40 years (ii) and 54 years (iii), p < 0.05). 75% of BRCA1-mutated patients tumors were triple-negative, and 66% of grade 3, whereas the other groups presented mostly tumors of luminal subtype (84% of BRCA2-mutated patients, 70% of HBC patients and 74% of patients with sporadic disease). Interestingly, BRCA1-mutated tumors were more sensitive to chemotherapy than in the two other groups, with a higher rate of pathological complete response to neo-adjuvant chemotherapy (65%, p = 0.03). BRCA-mutated patients presented a higher incidence of contralateral breast cancer than the two other groups (30% (i) vs 17% (ii) and 14% (iii), p = 0.02) and a poorer overall survival (14% of death (i) vs 0% (ii) and 4% (iii), p < 0.05). HBC patients presented a lower rate of relapse than the other groups (18% (ii) vs 25% (i) and 28% (iii), p < 0.05). Conclusions: CP characteristics and outcome of HBC patients are similar to those of BRCA2-mutated patients. Ongoing multi-gene panel testing in this population will probably identify mutations in other relevant genes providing new insights in genotype-phenotype correlation.
Global collaborative software solution to match patients to trials and real-time sharing of clinical experience.
Authors: Christian Diego Rolfo, Csongor Lengyel, Csilla Hegedus, Zsofia Binder, Marc Peeters, Istvan Petak
Journal: Journal of Clinical Oncology (2016)

e23166 Background: It has become evident that both pathological and molecular genetic disease stratification has major impact on therapeutic decisions and outcomes. However, combination of such cancer-specific parameters generates rare and distinct cancer subtypes, investigation of which by prospective randomized trial or even basket trial design is hampered by the extremely low expected frequencies of such disease entities. We have developed a software solution to enable matching of patient cancer parameters with relevant therapies, including on-label, off-label and trial options; and also a platform for the instant sharing of therapeutic response. Methods: We present a case as an example. A 58-gene hot spot targeted re-sequencing NGS and a selected FISH analysis panel was used to determine the molecular profile of a renal pelvis squamous cell carcinoma patient. The molecular profile was interpreted with a three-step algorithm linking the detected driver alterations to targets and drugs according to the highest available evidence. Results: MET amplification was identified as a driver genetic alteration and the patient was referred from Hungary to Belgium to a phase 1b clinical trial testing a MET inhibitor. The patient achieved partial response. Conclusions: The incidence of renal pelvis cancer is 3.7%, (SEER database), the frequency of squamous cell histology in this tumor type is 0.5% and the prevalence of MET amplification is currently unknown in this histology but ranges between an average 2-5% in solid tumors. This estimates that the frequency of this combination of tumor type-histology-driver will be approximately 6 in a million. Matching all patients with the right effective targeted therapy needs a global solution and real-time clinical experience sharing.
An open-source clinical knowledgebase featuring the ability to match patient somatic mutational profiles to eligible clinical trials.
Authors: Susan M. Mockus, Sara E. Patterson, Cara Statz, Anuradha Lakshminarayana, Daniel Durkin
Journal: Journal of Clinical Oncology (2016)

e23242 Background: Clinical trials in precision oncology generally require the presence or absence of specific mutations as part of the criteria for patient eligibility. Identification of these trials is hampered by the lack of open clinical trial registries with systematic methods to capture and search mutational eligibility requirements. Methods: We have built a Clinical Knowledgebase (CKB) to support our own internal clinical NGS pipeline and have now launched CKB as an open-source tool to assist others traversing similar hurdles. CKB is a manually curated resource that contains data attributes on gene variants, targeted therapies, efficacy evidence, and clinical trials; all curated through interoperable controlled vocabularies and HGVS and HGNC nomenclature standards. The clinical trial component systematically captures mutational profiles that are required or excluded from trial eligibility criteria. A nightly script updates the recruitment status for each trial, enabling searching in real-time. Results: Content in CKB currently contains 16,836 gene variants, 1250 targeted therapies, 3715 efficacy evidences, and 3193 clinical trials. A web interface allows users to browse any of the data attributes or to run specific clinical reporting queries based on the patient’s indication and somatic mutational profile. The clinical trial component currently contains 944 trials with mutational requirements and new trials are regularly curated through backend tools that enable triaging of clinicaltrials.gov query retrievals through bulk gene or targeted therapy lists. Examples of the searchable clinical trial content in CKB include 11 trials recruiting on EGFR T790M, 4 trials excluding patients with BRAF V600 mutations, and 3 trials requiring TP53 mutations. Inputting the patient’s indication through a drop down list of cancer terms from the Disease Ontology further refines trial results. Conclusions: We have created and launched a web-enabled open-source clinical knowledgebase for sharing content, disseminating methods, and fostering community development of interpretation of somatic mutations and clinical trial identification in precision oncology.
Osimertinib compared to docetaxel-bevacizumab as third-line treatment in EGFR T790M mutated non-small cell lung cancer.
Authors: Keke Nie, Zhongfa Zhang, Xiao Zou, Chunling Zhang, Xingjun Zhuang, Zhuang Yu, Ketao Lan, Youxin Ji
Journal: Journal of Clinical Oncology (2017)

9017 Background: Osimertinib, an oral irreversible EGFR tyrosine kinase inhibitor, had promising results in patients with EGFR T790M resistance mutation of non-small-cell lung cancer (NSCLC). This study compared efficacy and toxicities of osimertinib versus docetaxel -bevacizumab as third-line treatment in EGFR T790M mutated NSCLC. Methods: In this phase 3, open-label, three-center study, we randomly assigned previously treated with TKI-chemotherapy or chemotherapy-TKI recurrent or metastatic advanced non-squamous lung cancer patients who had acquired EGFR T790M resistance mutation confirmed by tumor tissues or serum genetic test. Patients were randomly assigned in a ratio of 1:1 to receive oral osimertinib (80mg/day) or receive intravenous infusion docetaxel (75mg/m2) and bevacizumab (7.5mg/kg) until disease progression or unacceptable toxic effects. Docetaxel -bevacizumab group patients might crossover to osimertinib group after disease progression. The primary end-point of this study was progression-free survival and the secondary end-point were response rates, toxicities and OS. Results: A total of 147 patients were treated. Among them, 74 enrolled in the osimertinib group and 73 in the docetaxel-bevacizumab group. The median progression-free survival was 10.20 months and 2.95 months in the osimertinib group and docetaxel -bevacizumab group respectively (Hazard ratio 0.23; 95% confidence interval, 0.12 to 0.38; P &lt; 0.0001). The overall response rate and disease control rate was 61.6% or 87.6% in osimertinib group 8.3% or 43.0% in docetaxel-bevacizumab group respectively. The median overall survival time was not reached. The main grade 3 or 4 toxic effects were diarrhea (2.7%) and interstitial lung disease (1.2%) in the osimertinib group and alopecia (15.1%), anorexia (12.3%), neutropenia (9.6%) and nausea (8.6%) in docetaxel -bevacizumab group. Conclusions: Response rate and progression-free survival of osimertinib group were superior to docetaxel-bevacizumab group in third-line treatment of EGFR T790M positive NSCLC. There was no survival difference between patients with EGFR 19 Del-T790M mutation and EGFR L858R-T790M mutation. Clinical trial information: NCT02959749.