tbuckley/cabot-search huggingface dataset:
Mental healthcare use and severe psychiatric diagnoses in adult survivors of childhood cancer: A population-based study using health services data.
Authors: Sumit Gupta, Alex Nachman, Paul Kurdyak, Rinku Sutradhar, Jason D Pole, Paul C. Nathan
Journal: Journal of Clinical Oncology (2017)

10565 Background: Though physical late effects in childhood cancer survivors are well documented, their risk for adverse mental health outcomes is less clear; existing evidence is contradictory. Health services data offer an objective method for measuring population-based mental health outcomes. Methods: Using a provincial registry with detailed patient, disease, treatment, and outcome data, we assembled a cohort of all five-year survivors of childhood cancer diagnosed before age 18 years and treated in an Ontario pediatric cancer centre between 1987-2008. Patients were linked to population-based healthcare data capturing inpatient, outpatient, and emergency department (ED) visits. The primary outcome was the rate of mental healthcare visits (primary care, psychiatrist, ED or hospital). Secondary outcomes included the time to a severe mental health event (ED visit, hospitalization, or suicide) both overall and by psychiatric diagnostic categories. Outcomes were compared between survivors and matched controls using recurrent event and survival analyses, and predictors of adverse outcomes modeled. Results: When compared to 20,269 controls, 4,117 survivors had a significantly higher rate of mental health visits [47.1 vs. 36.1 visits/100 person years; adjusted relative rate (RR) 1.3, 95 % confidence interval (CI) 1.2-1.5]. Higher rates of visits were associated with female gender (RR 1.4, CI 1.1-1.7; p = 0.008) and adolescent age at diagnosis (RR 2.0, CI 1.3-3.0; p = 0.004). Cancer type, treatment intensity or treatments targeting the central nervous system were not significant predictors. The hazard of a severe mental health event did not differ between survivors and controls. Though rare in both groups, survivors were at increased risk of a severe event due to a psychotic disorder (HR 1.8, CI 1.1-2.8; p &lt; 0.05). Conclusions: Childhood cancer survivors experience higher rates of mental health visits than the general population, but are no more likely to experience a severe mental health event. Their risk is not attributable to a specific diagnosis or aspect of treatment. An increased risk of severe psychotic disorders requires confirmation in other cohorts.
Survival benefit of systemic chemotherapy given as adjuvant (ACT) after thoracic surgery for N0-1 non-small cell lung cancer (NSCLC) patients (pts) with synchronous brain metastasis (SBM).
Authors: Sarah Shin, Saikrishna S. Yendamuri, Adrienne Groman, Grace K. Dy
Journal: Journal of Clinical Oncology (2017)

8525 Background: Pts with solitary SBM and otherwise early-stage NSCLC demonstrate prolonged survival with surgical resection of both primary and metastatic disease. The role of “ACT” after thoracic surgery in this circumstance is not well-defined. We seek to determine the effect on overall survival(OS) of ACT after resection of primary tumor in pts with surgically resectable primary NSCLC and SBM. Methods: The National Cancer Database (NCDB) was queried to identify pts who underwent resection of NSCLC as the primary cancer (without other malignancies) from years 2010-2014 (n = 90,518). We then focused on pts who also were diagnosed with SBM (n = 807). Only patients with pathologically confirmed N stage 0 (n = 419) or 1 (n = 101) status were included in the final analysis. Patients who received platinum-based ACT within 3 months after surgery were considered to have received ACT. Associations between treatment groups were analyzed using the Chi-square test for categorical variables and Wilcoxon Rank Sum test for continuous variables. Univariate and multivariate proportional hazards modeling results were used to assess the effect of treatment and the confounding variables on OS. Relative prognosis was summarized using estimates and 95% confidence interval(CI) for the hazard ratio (HR). Unadjusted differences in OS between the treatments are shown using Kaplan-Meier methods. All analyses were performed using SAS version 9.4. Results: There is no imbalance in terms of gender, race, income, nodal status, histology between groups. Non-ACT pts were older (n = 181, median 64 vs 58 years in ACT group, p &lt; 0.001). Age, nodal status, ACT, and histology were associated with OS in both univariate and multivariate analysis, with OS HR 0.51 (95% CI 0.39-0.66) in favor of ACT (n = 339). One- and 5-year survival in ACT group versus non-ACT group was 83% (95% CI 78%-87%) and 33% (25%-40%), versus 57%(95% CI 48%-65%) and 18% (95% CI 11%-26%), respectively. Conclusions: ACT after thoracic surgery for N0-1 NSCLC with SBM is associated with improved OS in this analysis.
TCT-636 International experience with Impella mechanical circulatory support for Takotsubo syndrome with shock
Authors: L Christian Napp, Jacob Møller, Federico Pappalardo, Karim Ibrahim, Jan-Thorben Sieweke, Laurent Bonello, William O'Neill, Daniel Burkhoff, Andreas Schafer, Ralf Westenfeld
Journal: Journal of the American College of Cardiology (2018)
Phase I/III trial of atezolizumab with carboplatin and etoposide in ES-SCLC in first-line setting (IMpower133).
Authors: Leora Horn, Aaron Scott Mansfield, Martin Reck, Tony Mok, Alexander I. Spira, Xiongwen Tang, Sivuonthanh Lam, Fairooz F. Kabbinavar, Ariel Lopez-Chavez, Alan Sandler, Stephen V. Liu
Journal: Journal of Clinical Oncology (2017)

TPS8584 Background: The first-line standard of care for the majority of patients (pts) with extensive-stage small-cell lung cancer (ES-SCLC) is platinum-based chemotherapy with etoposide, but survival outcomes remain poor (median OS, &lt; 1 year) despite initial response rates ranging from 50-70%. Atezolizumab (atezo), an anti–PD-L1 mAb, prevents the binding of PD-L1 with its receptors PD-1 and B7.1 and restores anticancer T-cell activity. Tolerable safety with promising durability of response has been shown with atezo in pts with ES-SCLC: confirmed ORR was 6% (n = 1/17 [partial response]; DOR of 7 mo) by RECIST v1.1 and 24% by immune-related response criteria (irRC; n = 4/17, with 2 pts on atezo for ≥ 12 mo). Preliminary data also indicate the potential synergy between atezo and platinum-based chemotherapy in NSCLC, whereby durable responses may translate into improved survival over atezo alone. IMpower133 (NCT02763579), a global, Phase I/III, randomized, multicenter, double-blinded, placebo-controlled trial will evaluate the efficacy and safety of 1L atezo + carboplatin + etoposide compared with placebo + carboplatin + etoposide in treatment-naive pts with ES-SCLC. Methods: Pts with measurable (RECIST v1.1) ES-SCLC, who have ECOG PS 0-1 and no prior systemic anticancer treatment, are eligible for the study. Exclusion criteria include untreated CNS metastases and history of autoimmune disease. The study requires submission of tumor tissue, but pts will be enrolled regardless of biomarker status. Pts will be stratified by sex, ECOG PS and presence of treated brain metastases. Eligible pts will be randomized 1:1 to receive four 21-day cycles of atezo (1200 mg IV) or placebo in combination with carboplatin (AUC 5 mg/mL/min IV, d 1) and etoposide (100 mg/m 2 IV, d 1-3), followed by maintenance therapy with atezo or placebo until PD per RECIST v1.1. Pts can continue with treatment until persistent radiographic PD, symptomatic deterioration or unacceptable toxicity. Co-primary endpoints are investigator-assessed PFS per RECIST v1.1 and OS. Secondary efficacy endpoints include investigator-assessed ORR and DOR. Safety and tolerability will also be assessed. Approximately 400 pts will be enrolled. Clinical trial information: NCT02763579.
<i>MET</i> amplification and activating mutation analysis in solid tumors using comprehensive NGS panel.
Authors: Xinghao Ai, Mingming Yuan, Jun Zhao, Liyun Miao, Gen Lin, Xueming Du, Jun Wu, Longbo Zhang, Xiangyang Cheng, Chunwei Xu, Wen-xian Wang, Rongrong Chen, Xuefeng Xia
Journal: Journal of Clinical Oncology (2018)

e24267 Background: Approximately 4-7% of non-small cell lung cancer (NSCLC) patients have abnormal activation of MET, and MET inhibitors have shown promising results. However, the prevalence of MET amplification and/or activating mutations in other solid tumors remains wildly unknown. Methods: MET mutation status were reviewed in 6000 cancer patients who underwent genetic testing at our institute from 2016 to 2017. Mutation profiles were analyzed using hybridization capture based next-generation sequencing (NGS), which enables the simultaneous detection of single-nucleotide variants, insertions/deletions, rearrangements, and copy-number alterations of at least 59 genes (range 59 – 1021 genes). MET amplification, exon 14 skipping and other activating mutations were included for analysis. Results: MET activating mutations were detected in a total of 70 patients among multiple cancer types (details in table 1). Most MET activating mutations occur in lung cancer, including 23 amplification, 20 exon 14 skipping and 10 other mutation cases. Four of 10 other mutation cases were coexistence of multiple MET mutations. On the contrary, MET amplification was identified in multiple cancers, while almost all MET exon 14 skipping was in lung cancer, except for 1 malignant mesothelioma case. Conclusions: Comprehensive NGS sequencing can detect different types of MET activating mutations in multiple solid tumors, which provides a cost-effective strategy to find the potential target for refractory cancer patients. Table 1. The prevalence of MET activating mutations in solid tumors LC HBC CRC CUP GEC MG NB MM EC All Amplification 23 4 3 2 2 2 1 0 1 38 Exon 14 skipping 20 0 0 0 0 0 0 1 0 21 Others 10 1 0 0 0 0 0 0 0 11 All 53 5 3 2 2 2 1 1 1 70 Notes LC, lung cancer; HBC, hepatobiliary cancer; CRC, colorectal cancer; CUP, Carcinoma of unknown primary; GEC, gastroesophageal cancer; MG, malignant glioma; NB, neuroblastoma; MM, malignant mesothelioma; EC, endometrial cancerOthers, known activating mutations in the tyrosine kinase domain or coexistence of multiple MET mutations.
Serial analysis of mutant KRAS in circulation cell-free DNA (cfDNA) of patients with KRAS mutant metastatic colorectal cancer: A translational study of the KRK0207 trial.
Authors: Jens T Siveke, Smiths Lueong, Axel Hinke, Andreas Herbst, Andrea Tannapfel, Anke C. Reinacher-Schick, Frank T Kolligs, Susanna Hegewisch-Becker
Journal: Journal of Clinical Oncology (2018)

e15599 Background: Circulating tumor DNA (ctDNA) is a promising marker for monitoring tumor burden and therapy response in metastatic colorectal cancer (mCRC). The AIO KRK 0207 trial investigated different maintenance strategies after a 24-week standard induction therapy with fluropyrimidine/oxaliplatin/bevacizumab. Here we report analysis of mutant KRAS copies and correlation to prognostic baseline characteristics and survival. Methods: KRAS mutations were quantified in plasma using multiplex droplet digital PCR (ddPCR) and fractional abundance of ctDNA assessed before and 2-3 weeks after treatment initiation in samples with ctDNA from patients defined as eligible and evaluable within the framework of the main analysis of AIO KRK 0207 (Hegewisch-Becker et al, Lancet Oncol 2015). Results: 129 pts with valid baseline measurements (DNAb), 117 pts with valid follow-up (DNAf) measurements (two to three weeks post start of induction therapy and 111 pts with valid fold change (DNAc) were evaluated. High DNAb values are associated with a dissemination to more than one metastatic site, a high baseline CEA, primary tumors located at the right side, and impaired performance status. DNAb is a strong prognosticator for PFS1 (HR = 2.01, 95% CI: 1.25 – 3.22, p = 0.0033). Univariable analysis for overall survival shows a prognostic impact that is numerically larger than for any of the conventional parameters (HR = 1.91, 95% CI: 1.29 – 2.82, p = 0.00096). Neither DNAf nor DNAc show any major impact on PFS1 and OS. Correlation of ctDNA with response to therapy will be presented at the meeting. Conclusions: Data from this post-hoc analyses of ctDNA levels in patients with RAS mutant mCRC show that baseline ctDNA levels show the most robust correlation to prognostic baseline characteristics and survival.
Impact of 1st surgeon recommendation against CPM on patient treatment experiences and satisfaction.
Authors: Steven J. Katz, Monica Morrow, Sarah T. Hawley, Reshma Jagsi
Journal: Journal of Clinical Oncology (2016)

6570 Background: Surgeons are increasingly aware of the need to address growing patient interest in contralateral prophylactic mastectomy (CPM) after diagnosis of breast cancer. But they may be concerned that counseling against CPM may upset patients or motivate them to seek another surgeon. Methods: We examined whether patient report of a recommendation against CPM by their first surgeon was associated with lower patient satisfaction with surgical decisions (5 item Likert scale, low vs. higher), or communication with the surgeon (HCCQ Scale, low vs. higher), seeking a 2nd surgical opinion, or getting surgery from a 2nd surgeon. 3781 patients aged 20-79 with early stage breast cancer treated in 2013-14 and reported to Georgia and Los Angeles county SEER registries were identified and surveyed about 2 months after surgical treatment (response rate 69%, n = 2593). We display outcomes (for patients who moderately to strongly considered CPM) by report of surgeon recommendation, adjusted for sampling design, risk of 2nd primary cancer, stage, age, education, and SEER site. Results: One third of patients (n = 897, 35%) moderately to strongly considered CPM and half received it. One quarter (24%) reported that their first surgeon recommended against it, of whom 9% had CPM (vs 67% of others, p < .001). One fifth (20%) sought a 2nd surgical opinion and 11% had surgery performed by a 2nd surgeon. The Table shows adjusted % of the decision outcomes by surgeon recommendation. Conclusions: A minority of patients who considered CPM received a recommendation from their first surgeon against it. Although these patients were much less likely to receive CPM, they did not report lower satisfaction with surgeon communication nor did they more frequently receive surgery from a 2nd surgeon. However, lower satisfaction with surgery decisions in this group reinforces the need for better communication strategies around the growing desire for CPM. Patients who reported: 1st surgeon recommended against CPM Total % p value Yes (%) n = 195 No (%) n = 684 Low satisfaction w/ surgical decision 28.7 15.7 19.4 .001 Low satisfaction w/ surgeon communication 10.0 9.3 10.0 .795 2nd surgical opinion 24.3 18.4 19.5 .116 2nd surgeon performed surgery 12.3 10.1 10.8 .422
Relationship between pre-treatment organ-specific tumor burden (TB) and response to immunotherapy in advanced melanoma (MEL).
Authors: Ryan Campbell Massa, Mark Sparrow, Huang Lin, Yan Lin, David J. Mauro, Art M. Krieg, Heather Kelley, Amy Rose, Yana G. Najjar, John M. Kirkwood, Diwakar Davar
Journal: Journal of Clinical Oncology (2018)

e21507 Background: Prior reports have described an association with hepatic metastases and total TB with reduced response rates to anti-PD-1 treatment in subjects with advanced MEL. We explored baseline organ-specific TB as assessed by volumetric analysis to compare fractional burden of disease to response rates in patients treated on a phase IB study of PD-1 inhibitor pembrolizumab and intratumorally injected Toll-like receptor 9 (TLR9) agonist, CMP-001. Methods: Responders (n = 8) and non-responders (n = 10) were identified among patients with advanced MEL refractory to prior anti-PD-1 therapy treated on a phase IB clinical trial of pembrolizumab/CMP-001 combination. Responders were defined as stable disease, partial response, or complete response for a minimum of 36 weeks as assessed by computed tomography (CT) imaging by RECIST v1.1 criteria. Non-responders were defined as progression of disease at initial CT imaging assessment at 12 weeks. Volumetric assessment of baseline screening CT imaging was performed to assess total TB prior to initiation of treatment. TB was delineated by site of disease (liver, non-liver visceral, lung, lymph node and subcutaneous). Fractional TB was calculated by dividing site-specific tumor burden by total TB. Results: 18 subjects were included in the analysis. High fraction of visceral TB was associated with lack of response to treatment (p = 0.0016) and shorter progression-free survival (PFS, p = 0.001). High fraction of lymph node TB was associated with response to treatment (p = 0.079) and longer PFS (p = 0.029). Conclusions: In subjects treated with the combination of pembrolizumab and CMP-001, high fraction of visceral TB is associated with lack of response to treatment and shorter PFS. Conversely, high fraction of lymph node TB is a favorable feature and is associated with response to treatment and longer PFS. Results suggest that organ-specific TB is a potential prognostic marker in subjects with advanced melanoma treated with immunotherapy.
Novel, simplex and multiplex assays for BRAF mutation detection.
Authors: Samantha Epistolio, Mariann Guldmann-Christensen, Stephen Hamilton-Dutoit, Torben Steiniche, Majbritt Hauge Kyneb, Michael Boergesen, Christina Andersen, Alice Riva, Luca Mazzucchelli, Tine Yde Wolff, Jan Lorenzen, Ulf Bech Christensen, Kristin Feuerlein, Milo Frattini
Journal: Journal of Clinical Oncology (2016)

e23257 Background: BRAF gene mutations play key roles in colorectal cancer (CRC) and in malignant melanoma (MM). In CRC, BRAF mutation is associated with poorer prognosis and may be a marker for new targeted therapies. In MM, BRAF mutations are predictive of the efficacy of BRAF-targeted therapies. In CRC, only the V600E change is observed regularly, while in MM different BRAF mutations may occur. To improve the identification of BRAF mutations, we developed novel simplex and multiplex real-time PCR-based assays (SensiScreen) and compared them with Direct Sequencing (DS), Mutant-Enriched PCR (ME-PCR) and Cobas. Methods: SensiScreen assays (PentaBase, Denmark) comprise SuPrimers (DNA primers with increased specificity), BaseBlockers (suppressing amplification of wild-type genes) and HydrolEasy probes (hydrolysis probe with increased S/N ratio and sensitivity). Sensitivity studies on plasmids and extracted cell line DNA were performed. Two cohorts of patients were analysed: 100 CRC patients used for comparison of the V600E SensiScreen assay, DS and ME-PCR; and 100 MM patients used for comparison between SensiScreen assays (simplex and multiplex) and Cobas. Results: Our sensitivity studies gave superimposable results for both simplex and multiplex assays. In plasmids and cell lines experiments, DS had a limit of detection of 10%, ME-PCR of up to 0,5% and SensiScreen of < 0,1%. In 100 CRC cases, we found 7 (7%) BRAF mutated patients by DS, 9 (9%) by ME-PCR and 10 (10%) by SensiScreen. In 100 MM patients, we found 51 (51%) BRAF mutations by Cobas and 55 (55%) by SensiScreen. Simplex and multiplex SensiScreen assays identified the same mutations. Conclusions: SensiScreen simplex and multiplex assays are novel, rapid, easy-to-use and highly sensitive methods for BRAF mutation analysis in CRC and in MM. Indeed, it enables the detection of additional BRAF alterations in CRC and MM patients compared with widely used methodologies.
Results of an educational tool for residents and referring physicians on palliative radiation for bone metastases.
Authors: Nina Desai, Malcolm David Mattes, Eric Bonar, Grant Robertson, Candice Aitken Johnstone
Journal: Journal of Clinical Oncology (2018)

82 Background: Palliative radiation therapy (RT) for painful bone metastases is underutilized in the United States (U.S.), perhaps due to inappropriate use of multi-fraction (MF) regimens over more convenient, less costly, and equally effective single fraction (SF) regimens. Practice patterns may change with improved knowledge of radiation oncology residents (ROR) and non-radiation oncology physicians who refer patients for palliative RT. The aim of this study was to provide evidence-based educational content to these groups, and assess knowledge and views before and after. Methods: In April - June 2017, an electronic educational tool was sent to medical oncology and palliative care physicians, and ROR in the U.S. Multiple choice questions assessed knowledge, and were followed by evidence supporting the correct answer. Likert and sliding scales gaged tool impact. Chi-square and Mann-Whitney tests compared groups and pre/post-test responses. Results: Responses were obtained from 109 (2%) referring physicians (RP) and 135 (21%) ROR. ROR had higher scores than RP for 8 of 9 objective questions. RP were less likely to know that SF and MF are equivalent in terms of pain response (64 v. 91%, p &lt; 0.01) and subsequent analgesic use (86 v. 95%, p = 0.02), or that SF is associated with a higher retreatment rate (27 v. 93%, p &lt; 0.01). ROR were less likely to know that SF and MF are equivalent for patients with a high likelihood of long term survival (25 v. 56%, p &lt; 0.01). After viewing the content, ROR felt more knowledgeable [ mdn 3 (IQR 3 - 4) v. 4 (IQR 3 - 4), p &lt; 0.01], and RP felt more empowered [ mdn 3 (IQR 2 - 4) v. 4 (IQR 3 - 4), p &lt; 0.01]. RP found the survey more helpful, and knew less of the data prior [ mdn 50 (IQR 25 - 75%) v. 80% (IQR 66.3 - 90%), p &lt; 0.01]. Despite knowing the data, ROR preferred SF less than RP at completion (67 v. 85%, p &lt; 0.01). Conclusions: This study demonstrates a need for educational content for multidisciplinary providers on appropriate palliation of bone metastases. Despite ample knowledge, the bias of practicing radiation oncologists for MF is being passed onto residents. Greater knowledge may translate into more effective referral patterns and patient advocacy by RP, and potentially improve utilization of palliative RT in the U.S.