bluuebunny/crossref_metadata_2025_split huggingface dataset:
Temporal trends among survivors of rhabdomyosarcoma: A report from the Childhood Cancer Survivor Study (CCSS).
Authors: Hingorani Pooja , Wang Mingjuan , Srivastava Deokumar , Nathan Paul C. , Oeffinger Kevin C. , Yasui Yutaka , Leisenring Wendy M. , Howell Rebecca M. , Mueller Emily L. , Gibson Todd M. , Wolden Suzanne L. , Bjornard Kari L. , Meyer William H. , Arndt Carola A. S. , Robison Leslie L. , Green Daniel M. , Armstrong Gregory T. , Ness Kirsten K. 
Published: March 2020

11570 Background: Intergroup Rhabdomyosarcoma Study Group (IRSG) protocols included treatment modifications, which may have ameliorated late health outcomes for rhabdomyosarcoma (RMS) survivors treated in more recent era. Methods: We evaluated chronic health conditions (CHCs) and late mortality ( > 5 years from diagnosis) among survivors treated 1970-1990 (IRSG I-III) and 1991-1999 (IRSG IV), and associations with specific treatments to identify treatment-related factors for adverse outcomes. Associations between treatments and CHCs and mortality were evaluated using Fine and Gray’s proportional hazards method accounting for competing risks. Results: 856 survivors treated 1970-90 (median diagnosis age 5.4 years [0- 20]) and 306 treated 1991-99 (median diagnosis age 5.5 years [0-20]) were included. Significant exposure differences between eras included higher percentage (53% vs. 17%, p < 0.01) receiving ≥ 20gm/m2 cumulative alkylators in 1991-99, but more receiving platinums (13% vs 5%, p < 0.01) and abdomen/ pelvis radiation (29% vs. 23%, p = 0.04) in 1970-90. 20-year cumulative incidence for any (40% vs. 28%, p < 0.01), ≥2 (16% vs. 7%, p < 0.01), and endocrine (8% vs. 2.5%, p < 0.01) grade 3-5 CHCs was higher in 1970-90 compared to 1991-99. The hazard ratio (HR) for any (HR 0.7, 95% Confidence Interval [CI] 0.55-0.9), ≥2 (HR 0.38, 95% CI 0.22-0.66) and endocrine (HR 0.25, 95% CI 0.09-0.67) grade 3-5 CHC was lower for 1991-99 survivors than 1970-90. The effect of era (1991-99 vs 1970-90, HR 0.73; 95% CI 0.59-0.91) on CHC was not attenuated when treatment variables were added to multivariable model. Exposures with increased risk of grade 3-5 CHC included platinums (hearing, HR 2, 95% CI 1.07-3.8), anthracycline ≥250mg/m2 (cardiovascular, HR 2.7, 95% CI 1.2-6) and abdomen/ pelvis radiation (second malignant neoplasms, HR 2.1, 95% CI 1.1-4, gastrointestinal, HR 7.4, 95% CI 3.5-16 and endocrine, HR 2.5, 95% CI 1.4-4.4). Gonadal dysfunction was the most common endocrine CHC. There was no difference in all cause or cause-specific mortality between the two cohorts. Conclusions: RMS survivors from the IRSG IV era are at reduced risk for late onset chronic health conditions compared to previous era.
Ixazomib and dexamethasone in high risk smoldering multiple myeloma: A clinical and correlative pilot study.
Authors: Mailankody Sham , Salcedo Meghan , Tavitian Elizabet , Korde Neha , Lendvai Nikoletta , Hassoun Hani , Lesokhin Alexander M. , Lahoud Oscar Boutros , Smith Eric L. , Hultcrantz Malin , Devlin Sean M. , Landgren Ola 
Published: March 2020

8051 Background: Patients with high risk smoldering multiple myeloma (HR-SMM) have an increased risk of progression to multiple myeloma (MM)- median time < 2 years. The standard management of these patients currently is close clinical monitoring; however, randomized trials show longer progression-free and overall survival in in HR-SMM patients treated with the oral immunomodulatory drug lenalidomide. We report the use ixazomib, the first oral proteasome inhibitor, in combination with dexamethasone in the setting of HR-SMM. Because proteasome inhibitors can provide deep clinical responses in patients with MM, we set the pre-specified threshold for efficacy high (overall response rate of ≥75%). Methods: In this single arm pilot trial of ixazomib/dexamethasone, patients received 12 4-week cycles of ixazomib/dexamethasone followed by ixazomib maintenance for 24 cycles. The primary endpoint is best overall response after 12 cycles and second objectives include duration of response, safety, and progression free survival. Results: 14 patients with HR-SMM were enrolled between 06/2016 and 03/2018. The median age is 65 years and 10 (71%) of patients were male. 11 (79%) patients were high-risk by the PETHEMA criteria, 2 (14%) by the Mayo Clinic criteria and 1 (7%) by both. At data cut-off (02/07/2019), patients completed a median of 17 cycles and 10 (71%) are continuing treatment. 4 patients have stopped treatment (2 patients for raise in serum markers without progression to MM, and 1 each for toxicities, and co-morbidities unrelated to treatment). 9 (64%) achieved an objective response (8 PR, and 1 VGPR) and no patient has progressed to MM. Non-heme adverse events included 3 grade 1 GI events, 2 grade 3 lung infection, 1 grade 2 acute kidney injury, and 1 had grade 1 fatigue that was possibly related to treatment. Conclusions: Ixazomib/dexamethasone appears well tolerated with high overall response (9/14; 64%) in patients with HR-SMM. Although the trial does not meet our pre-specified threshold for efficacy (i.e. best overall response rate of 75%), with a median follow-up of 17 months, no patient progressed to MM and only 2 patients had serologic progression. These results support further evaluation of ixazomib/dexamethasone alone and in combination with other agents as treatment for patients with HR-SMM. Clinical trial information: NCT02697383.
Association of BAP1 alterations with malignant pleural mesothelioma treated with trimodality therapy.
Authors: Zauderer Marjorie Glass , Rizvi Hira , DuBoff Mariel A. , Adusumilli Prasad S. , Rusch Valerie W. , Sauter Jennifer L. , Ladanyi Marc , Rimner Andreas 
Published: March 2020

8552 Background: Trimodality therapy with pleurectomy/decortication, cytotoxic chemotherapy, and adjuvant pleural intensity modulated radiation therapy (IMPRINT) is an emerging standard of care for locally advanced epithelioid mesothelioma (Rimner, Zauderer et al. JCO 2016). Some patients, however, progress rapidly and we therefore sought to identify potential predictive markers of response to this treatment. Given the putative role of BAP1 in DNA damage repair, we hypothesized that alteration in BAP1 would be associated with improved local control after radiation therapy. Methods: We identified patients previously treated at our institution with IMPRINT to a median dose of 4680cGy in 26 fractions. Targeted next generation sequencing was performed with MSK-IMPACT on archival tissue samples. Chart review was undertaken for clinicopathologic features and outcome data. Results: MSK-IMPACT testing was successfully performed on 58 patients who completed IMPRINT. The majority were male with a median age of 70 years. Ninety-seven percent had epithelioid subtype while 3% were biphasic with predominantly epithelioid histology. Median overall survival was 30.2 months with a median follow-up of 45.3 months, consistent with prior reports. Somatic BAP1 mutations were identified in 34% of the specimens. Those with BAP1 mutant tumors had a median time to local failure of 22.4 months (IQR 10.9 – 36.9 months) while those with BAP1 wild type tumors only had a median of 12.1 months (IQR 8.7-15.85 months) to local failure (p = 0.057). We identified a trend towards improved overall survival among those with BAP1 altered tumors compared to those with BAP1 wild type (HR = 0.61, p = 0.14). Conclusions: BAP1 alteration may be associated with improved duration of local control and improved overall survival after IMPRINT therapy. Further analysis and validation in a large data set is needed and a platform for identifying and validating predictive biomarkers should be included in the planned NRG randomized trial of IMPRINT.
Antitumor activity of TAK-788 in NSCLC with EGFR exon 20 insertions.
Authors: Janne Pasi A. , Neal Joel W. , Camidge D. Ross , Spira Alexander I. , Piotrowska Zofia , Horn Leora , Costa Daniel Botelho , Tsao Anne S. , Patel Jyoti D. , Gadgeel Shirish M. , Bazhenova Lyudmila , Zhu Viola Weijia , West Howard , Vincent Sylvie , Zhu Jian , Li Shuanglian , Riely Gregory J. 
Published: March 2020

9007 Background: TAK-788 is an oral investigational EGFR/HER2 inhibitor under evaluation in NSCLC patients (pts) with EGFR exon 20 insertions. We report results of a phase 1/2 open-label, multicenter study (NCT02716116). Methods: Pts with advanced, previously treated NSCLC received daily TAK-788 in dose escalation and expansion cohorts based on tumor genotype. Antitumor activity was determined for pts with EGFR exon 20 insertions who received TAK-788 at the RP2D. Safety is reported for all pts across all doses and at 160 mg. Results: As of 14 Sep 2018, 101 pts (median age, 61 y; female, 70%; ≥2 prior anticancer therapies, 76%; brain metastases, 53%) were treated with TAK-788 at 5–180 mg qd. RP2D was determined to be 160 mg. 28 pts with EGFR exon 20 insertions were treated with 160 mg qd during dose escalation or in expansion cohort 1 (median 3.6 mo on treatment; median 3.8 treatment cycles); 24 pts remain on treatment. Antitumor activity in pts with EGFR exon 20 insertions is shown in Table. At data cutoff, 7/14 responses were confirmed with 6 awaiting confirmation and 1 unconfirmed PR at 160 mg qd; median time to response in these 14 pts was 56 days. 23/24 evaluable pts with EGFR exon 20 insertions treated at 160 mg qd had decreased target lesion measurements (median best percent change, -32.6% [-79.1%, 3.8%]). Rate of treatment discontinuation due to AEs was 10.7% in pts treated at 160 mg. Most common TEAEs (≥20%) in pts treated with 160 mg qd: diarrhea (85%), rash (43%), nausea (41%), vomiting (30%), decreased appetite (28%), and stomatitis (22%); gr ≥3 TEAEs (≥5%) were diarrhea (26%) and hypokalemia, nausea, and stomatitis (7% each). Median dose intensity for pts treated with 160 mg qd was 93%. There is no clear trend that response to TAK-788 is enriched in particular EGFR exon 20 insertion variants. Conclusions: In NSCLC pts with EGFR exon 20 insertions, TAK-788 demonstrated antitumor activity and an AE profile consistent with other EGFR TKIs. Clinical trial information: NCT02716116. [Table: see text]
Safety and preliminary antitumor activity of U3-1402: A HER3-targeted antibody drug conjugate in EGFR TKI-resistant, EGFRm NSCLC.
Authors: Janne Pasi A. , Yu Helena Alexandra , Johnson Melissa Lynne , Steuer Conor Ernst , Vigliotti Michele , Iacobucci Corinne , Chen Shuquan , Yu Channing , Sellami Dalila B. 
Published: March 2020

9010 Background: Treatment options are limited for EGFRm NSCLC resistant to EGFR TKIs. HER3 is expressed in a majority of NSCLC tumors. U3-1402 is a HER3-targeted antibody drug conjugate with a fully human HER3-targeted antibody, novel cleavable peptide-based linker, and topoisomerase I inhibitor payload. Methods: An ongoing multicenter phase 1 dose escalation and expansion study is assessing U3-1402 safety/tolerability and preliminary activity in metastatic or unresectable EGFRm NSCLC patients (pts) who are T790M negative after disease progression while on erlotinib, gefitinib or afatinib; or develop disease progression while on osimertinib regardless of T790M status. Dose escalation is based on dose-limiting toxicities (DLTs) and guided by the modified Continuous Reassessment Method. U3-1402 is administered via intravenous infusion in 21-day cycles. Pretreatment tumor tissue is required. Results: As of 11 Nov 2018, 15 pts (6 M; 9 F) were enrolled across 3 dose levels (3.2, 4.8, 6.4 mg/kg). Median age was 63 y; 10 pts had EGFR exon 19 deletion and 5 EGFR L858R mutation. Median sum of longest diameters (SLD) at baseline was 69 (range 22–143) mm. All pts had prior EGFR TKIs; 14 had 2nd line or later osimertinib. Six had prior chemotherapy. All 11 evaluable tumors demonstrated HER3 expression (median HER3 membrane H-score 188, range 150–290). Five pts discontinued treatment: 4 due to progressive disease, 1 due to adverse event (AE). All Grade (Gr) treatment-emergent AEs (TEAEs) in ≥20% of pts were nausea (60%), vomiting (40%), fatigue (33%), decreased appetite (27%), and alopecia (20%). Gr≥3 TEAEs were nausea (1/15; Gr3; related), hypoxia (1/15; Gr3; unrelated), and platelet count decreased (2/15; both Gr4 at 6.4 mg/kg and considered DLTs). In 13 evaluable pts, all but 1 had a decrease in SLD (median best change −29%, range +10% to −67%), 2 had confirmed partial response per RECIST v1.1 (best changes −44%, −67%). Conclusions: U3-1402 showed a manageable safety profile and preliminary antitumor activity in EGFR TKI-resistant EGFRm NSCLC. Evaluation of candidate biomarkers, including HER3 expression, which correlate with U3-1402 response is ongoing. Clinical trial information: NCT03260491.
Safety and preliminary clinical activity of repotrectinib in patients with advanced ROS1 fusion-positive non-small cell lung cancer (TRIDENT-1 study).
Authors: Cho Byoung Chul , Drilon Alexander E. , Doebele Robert Charles , Kim Dong-Wan , Lin Jessica Jiyeong , Lee Jeeyun , Ahn Myung-Ju , Zhu Viola Weijia , Ejadi Samuel , Camidge D. Ross , Liu Yuwei Juliet , Stopatschinskaja Shanna , Cui Jingrong Jean , Hyman David Michael , Ou Sai-Hong Ignatius , Shaw Alice Tsang 
Published: March 2020

9011 Background: Repotrectinib is a next-generation ROS1/TRK/ALK TKI inhibiting ROS1 with > 90-fold greater potency than crizotinib. Preclinical studies showed robust kinase inhibitory activity of repotrectinib against all known ROS1 fusion positive resistance mutations, including the most common ROS1 solvent-front mutation (SFM) G2032R. Methods: In this ongoing phase 1 study (NCT03093116), TKI-naïve and TKI-refractory (≥1 TKI) patients (pts) with advanced ROS1/TRK/ALK+ solid tumors received repotrectinib treatment. Endpoints include safety, PK, and confirmed overall response (cORR). Safety analysis for all pts (n = 75) and efficacy analysis for ROS1+ NSCLC pts (n = 28) enrolled on the study was conducted. Results: As of 31-Oct-2018, 75 pts were treated with repotrectinib at dose levels from 40 mg QD to 200 mg BID. Most AEs were manageable and grade (Gr) 1-2. Common ( > 20%) treatment-related AEs were dizziness (49%), dysgeusia (48%), paresthesia (28%), and constipation (20%). Four DLTs (Gr3 dyspnea/hypoxia (n = 1); Gr2 (n = 1) and Gr3 (n = 1) dizziness at 160 mg BID, and Gr3 dizziness (n = 1) at 240 mg QD) occurred and were managed with dose modifications. The MTD has not been reached. Median number of prior TKI treatment was 1 (0-3) with all of TKI naïve and 83% of TKI pre-treated pts received prior chemotherapy. Among 10 evaluable TKI-naïve ROS1+ NSCLC pts, confirmed ORR by Blinded Central Review (BCR) was 90% (95% CI 56 - 100) with median duration of response (DOR) not reached ((range 5.5+ – 14.9+ months (mos)). Among 18 TKI-pretreated pts, confirmed ORR by BCR was 28% (95% CI 10 – 54) with DOR of 10.2 mos. Subgroup analysis showed cORR 44% (95% CI 14 - 79) in 9 prior TKI pts and treated at dose levels of 160 mg QD or above. In 7 pts with measurable target CNS lesions at baseline, the intracranial ORR was 3/3 (100%) with DOR (5.5+; 7.2+; 14.85+ mo) in TKI-naïve pts and 2/4 (50%) with DOR (5.5+;14.8+, mo) in TKI-pretreated pts, respectively. Conclusions: Repotrectinib was well tolerated and demonstrated encouraging overall and intracranial clinical activity in pts with ROS1 fusion-positive NSCLC. Enrollment in phase 1 continues until the RP2D is determined. A global phase 2 study is planned. Clinical trial information: NCT03093116.
Clinical haematological biomarkers: Derived neutrophil-to-lymphocyte ratio (dNLR), platelet-to-lymphocyte ratio (PLR), and prognostic nutritional index (PNI) and their relationship to survival outcomes in non small cell lung cancer (NSCLC) treated with immunotherapy: A multicenter review.
Authors: Dennehy Colum , McMahon Eileen , Power Derek Gerard , O'Reilly Seamus , Collins Dearbhaile Catherine , O'Mahony Deirdre , Horgan Anne M. , O'Connor Miriam , Jordan Emmet , Calvert Paula , Bambury Richard Martin 
Published: March 2020

e20704 Background: Efficient use of immunotherapy in non-small-cell lung cancer (NSCLC) has been limited by the lack of a definitive predictive biomarker. Recently considerable efforts have been invested to develop biomarkers to predict which patients should receive immune checkpoint inhibitors. This retrospective cohort study aimed to determine whether clinical factors and inflammation-based biological markers such as pre-treatment derived neutrophils to lymphocytes (dNLR) ratio, platelets to lymphocytes (PLR) ratio and prognostic nutritional index (PNI) were associated with outcomes in NSCLC patients treated with immunotherapy. Methods: This study was a multicentered, retrospective systematic review. Clinical and electronic records were retrospectively examined from metastatic NSCLC patients treated with immunotherapy from August of 2015 to September 2018 in 2 regional cancer centers and a total of 69 patients were enrolled. NLR ≥5 and PLR ≥260 were defined as elevated and PNI ≤35 was defined as reduced. Results: Approximately, 57% of patients had NLR ≤ 5 and 51% had PLR ≤260. We found utilising univariant analysis, that pretreatment NLR ≤ 5 was independently associated with superior OS (median 12.4 vs. 6.8 months; HR 2.13, 95% CI 1.66-2.6; p = 0.007) and PFS (median 3.55 vs. 2.6 months; HR 1.75, 95% CI 1.18-2.32; p = 0.024). Results were similar when examining PLR ≤260 median OS 13.64 vs. 7.36 months; HR 1.92, 95% CI 1.1-3.5; p = 0.028) The optimal cutoff for PNI was designated to be 35. The majority (87%) had PNI > 35. NSCLC patients with PNI > 35 were found to have significantly higher median OS compared to patients with PNI ≤35 (11.11 vs. 2.4 months; HR 5.36, 95% CI ; p = 0.001). Conclusions: Immunotherapy is considered as an effective new method to treat advanced NSCLC. In this cohort of patients pretreatment NLR < 5,PLR < 260 and PNI > 35 were associated with superior outcomes. It is unclear whether these markers are predictive or prognostic or both.
Transarterial chemoembolization for pulmonary or mediastinal metastases from hepatocellular carcinoma
Authors: Hori Atsushi , Ohira Ryosuke , Nakamura Tomoyuki , Kimura Yasushi , Ueda Shota , Torii Masahiro , Kennoki Norifumi , Hori Shinichi 
Published: March 2020

Objective:
To evaluate the feasibility, efficacy and safety of transcatheter arterial chemoembolization (TACE) with HepaSphere for patients with pulmonary or mediastinal metastases from hepatocellular carcinoma (HCC).

Methods:
Between June 2009 and January 2018, 14 patients with pulmonary or mediastinal metastases from HCC were treated with TACE with a combination of 1–3 chemotherapeutic drugs followed by HepaSphere embolization. As first end point, local tumor response and adverse events were evaluated after the first session of TACE, with Response Evaluation Criteria In Solid Tumors v. 1.1 and Common Terminology Criteria for Adverse Events v. 4 criteria, respectively. Overall survival was evaluated as secondary end point. TACE was repeated on-demand.

Results:
TACE with HepaSphere was well tolerated with acceptable safety profile and no 30 day mortality. 1 month objective response and disease control rate were calculated to be 7.1 and 100%, respectively. Mean tumor size reduction rate was 15.6±9.5% at the first month. Two Grade 3 cytopenia events were seen (14.3 %), however none of the Grade 2 or more post-embolization syndrome was observed. The median overall survival time was 15.0 months and the 1 year, 3 year and 5 year survival rate were, 57.1%, 28.6%, 19.1%, respectively.

Conclusion:
Early experience showed that the transarterial treatment with HepaSphere is safe and effective treatment for patients with pulmonary or mediastinal metastases from HCC.

Advances in knowledge:
Currently, the effects of molecular targeted drugs on HCC metastases are limited and side-effects are relatively frequent. In the present study, transarterial treatment might be a promising treatment for HCC metastasis.
Measurement of total and visceral fat mass in young adult women: a comparison of MRI with anthropometric measurements with and without bioelectrical impedance analysis
Authors: Froelich Matthias F. , Fugmann Marina , Daldrup Charlotte Lütke , Hetterich Holger , Coppenrath Eva , Saam Tobias , Ferrari Uta , Seissler Jochen , Popp Daniel , Lechner Andreas , Sommer Nora Narvina 
Published: March 2020

Objective:
MRI is established for measurement of body fat mass (FM) and abdominal visceral adipose tissue (VAT). Anthropometric measurements and bioelectrical impedance analysis (BIA) have been proposed as surrogates to estimation by MRI. Aim of this work is to assess the predictive value of these methods for FM and VAT measured by MRI.

Methods:
Patients were selected from cohort study PPS-Diab (prediction, prevention and subclassification of Type 2 diabetes). Total FM and VAT were quantified by MRI and BIA together with clinical variables like age, waist and hip circumference and height. Least-angle regressions were utilized to select anthropometric and BIA parameters for their use in multivariable linear regression models to predict total FM and VAT. Bland–Altman plots, Pearson correlation coefficients, Wilcoxon signed-rank tests and univariate linear regression models were applied.

Results:
116 females with 35 ± 3 years and a body mass index of 25.1 ± 5.3 kg/m2 were included into the analysis. A multivariable model revealed weight (β = 0.516, p &lt; 0.001), height (β = −0.223, p &lt; 0.001) and hip circumference (β = 0.156, p = 0.003) as significantly associated with total FM measured by MRI. A additional multivariable model also showed a significant predictive value of FMBIA (β = 0.583, p &lt; 0.001) for FM. In addition, waist circumference (β = 0.054, p &lt; 0.001), weight (β = 0.016, p = 0.031) in one model and FMBIA (β = 0.026, p = 0.018) in another model were significantly associated with VAT quantified by MRI. However, deviations reached more than 5 kg for total FM and more than 1 kg for VAT.

Conclusion:
Anthropometric measurements and BIA show significant association with total FM and VAT.

Advances in knowledge:
As these measurements show significant deviations from the absolute measured values determined by MRI, MRI should be considered the gold-standard for quantification.
Persuasion Through Selective Disclosure: Implications for Marketing, Campaigning, and Privacy Regulation
Authors: Hoffmann Florian , Inderst Roman , Ottaviani Marco 
Published: March 2020

This paper models how firms or political campaigners (senders) persuade consumers and voters (receivers) by selectively disclosing information about their offering depending on individual receivers' preferences and orientations. We derive positive and normative implications depending on the extent of competition among senders, whether receivers are wary of senders collecting personalized data, and whether firms are able to personalize prices. We show how both senders and receivers can benefit from selective disclosure. Privacy laws requiring senders to obtain consent to acquire personal information that enables such selective disclosure increases receiver welfare if and only if there is little or asymmetric competition among senders, if receivers are unwary, and if firms can price discriminate. This paper has been accepted by Joshua Gans, business strategy.