tbuckley/cabot-search huggingface dataset:
Mobile text messaging to improve adjuvant hormone therapy and side effect management among breast cancer patients: A pilot RCT.
Authors: Kuang-Yi Wen, Lori J. Goldstein, Rita Smith, Suzanne M. Miller
Journal: Journal of Clinical Oncology (2019)

e23061 Background: Substantial evidence reports that adjuvant hormone therapy (AHT) decrease breast cancer (BCa) recurrence and mortality, however, many patients are nonadherent due to troublesome side effects. The goal of this pilot study is to test a novel mobile text messaging-based intervention ( TXT2Adhere) that delivers adherence-promoting and side effect coping tips messages. Methods: 58 BCa patients who were within 1 month of AHT initiation were randomized into the TXT2Adhere group (n = 29) or usual care control group (UC, n = 29). Intervention participants received a daily reminder prompt for medication uptake and two messages addressing the importance of AHT adherence and management for potential side effects for 3 months. Assessments were conducted at baseline, 1-month, 2-month, and 3-month. Results: Participants in the TXT2Adhere group reported higher AHT adherence at 2 months (93% vs. 54%, p &lt; 0.05) but this difference between groups disappeared at 3-month as adherence rate in the TXT2Adhere group greatly declined at month 3. Increase in symptom distress at 3-month was found substantially smaller in the TXT2Adhere group than the UC group, although this difference was not statistically significant. Conclusions: Daily text messages promoting adherence and side-effect management demonstrated feasibility with better short-term adherence. Potential intervention improvement to facilitate greater participant engagement and adherence behaviors as the onset of symptoms (e.g. during month 3) needs to be considered.
Sex Disparities in Receipt of Bystander Interventions for Students Who Experienced Cardiac Arrest in Japan
Authors: Satoshi Matsui, Tetsuhisa Kitamura, Kosuke Kiyohara, Junya Sado, Mamoru Ayusawa, Masahiko Nitta, Taku Iwami, Ken Nakata, Yuri Kitamura, Tomotaka Sobue
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Bystander interventions are a factor for improving survival of out-of-hospital cardiac arrest (OHCA), but it is hypothesized that girls and women experiencing OHCA may be less likely to receive bystander interventions than boys and men. <h3>Objective</h3> To investigate sex disparities in receiving public-access automated external defibrillator (AED) pad application and bystander-initiated cardiopulmonary resuscitation (CPR) among students who experienced OHCA in school settings. <h3>Design, Setting, and Participants</h3> This nationwide cohort study used the Stop and Prevent Cardiac Arrest, Injury, and Trauma in Schools (SPIRITS) database to link databases from 2 nationally representative registries—the Injury and Accident Mutual Aid Benefit System of the Japan Sport Council and the All-Japan Utstein Registry of the Fire and Disaster Management Agency. Students from elementary schools (ages 6-12 years), junior high schools (ages 12-15 years), high schools (ages 15-21 years), and technical colleges (ages 15-21 years) who experienced nontraumatic OHCA involving attempted resuscitation by emergency medical service personnel or bystanders in school settings from April 1, 2008, to December 31, 2015, were included. Data analysis was performed from January 5, 2019, to April 11, 2019. <h3>Exposures</h3> Sex and school level. <h3>Main Outcomes and Measures</h3> Application of public-access AED pads or initiation of CPR by a bystander. <h3>Results</h3> A total of 232 students who experienced OHCA with nontraumatic causes in school settings (mean [SD] age, 14.5 [2.9] years; 175 [75.4%] male) were included. In multivariable analysis of the full cohort of students who experienced OHCA, female sex was associated with significantly lower odds of receiving public-access AED pad application compared with male sex (36 of 57 female students [63.2%] received AED pad application vs 141 of 175 male students [80.6%]; adjusted odds ratio [OR], 0.44; 95% CI, 0.20-0.97;<i>P</i> = .04). In the subgroup analysis of students who experienced OHCA in high schools or technical schools, female sex was associated with significantly lower odds of receiving public-access AED pad application compared with male sex (10 of 18 female students [55.6%] vs 84 of 101 male students [83.2%]; adjusted OR, 0.26; 95% CI, 0.08-0.87;<i>P</i> = .03). Among the full cohort, 48 of 57 female students (84.2%) and 151 of 175 male students (86.3%) received CPR from bystanders (adjusted OR, 0.81; 95% CI, 0.30-2.22), and there were no significant differences in receiving bystander-initiated CPR between sexes, irrespective of school level. <h3>Conclusions and Relevance</h3> Among students who experienced OHCA in schools in Japan, female sex was associated with lower odds of receiving public-access AED pad application compared with male sex.
Neoadjuvant trastuzumab (H), pertuzumab (P), and chemotherapy versus trastuzumab emtansine (T-DM1) and P in human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC): Final outcome results from the phase III KRISTINE study.
Authors: Sara A. Hurvitz, Miguel Martin, Kyung Hae Jung, Chiun-Sheng Huang, Nadia Harbeck, Vicente Valero, Daniil Stroyakovskiy, Hans Wildiers, Mario Campone, Jean-Francois Boileau, Matthias W. Beckmann, Karen Afenjar, Gonzalo Spera, Vanesa Lopez Valverde, Chunyan Song, Thomas Boulet, Joseph A. Sparano, William Fraser Symmans, Alastair Mark Thompson, Dennis J. Slamon
Journal: Journal of Clinical Oncology (2019)

500 Background: KRISTINE compared neoadjuvant chemotherapy plus dual HER2- blockade (HP) with T-DM1 plus P (T-DM1+P), a targeted regimen that omits standard chemotherapy. T-DM1+P resulted in a lower pathologic complete response (pCR) rate, but a more favorable safety profile. Here we present the final outcomes from KRISTINE. Methods: KRISTINE (NCT02131064) was a randomized study of T-DM1+P versus docetaxel, carboplatin, and H plus P (TCHP). Patients with HER2-positive stage II–III BC received 6 cycles of neoadjuvant T-DM1+P or TCHP q3w. Patients receiving T-DM1+P continued adjuvant T-DM1+P; patients receiving TCHP received adjuvant HP, for 12 cycles in each arm. Patients in the T-DM1+P arm without pCR were encouraged to receive standard adjuvant chemotherapy before adjuvant T-DM1+P. Secondary endpoints, analyzed with descriptive statistics, included event-free survival (EFS; all events pre- and post-surgery), invasive disease-free survival (IDFS; invasive events post-surgery), overall survival and safety. Results: At median follow-up of 37 months, EFS favored TCHP (HR = 2.61 [95% CI: 1.36–4.98]), due to more locoregional progression events in the T-DM1+P arm before surgery (6.7% vs 0; Table). pCR was associated with reduced risk of an IDFS event (HR = 0.24 [95% CI: 0.09– 0.60]) regardless of treatment arm. There were 5 deaths (2.3%) in the TCHP arm and 6 (2.7%) in the T-DM1+P arm. There were more grade ≥3 AEs with TCHP but a higher rate of AEs leading to treatment discontinuation with T-DM1+P. Conclusions: EFS numerically favors TCHP due to locoregional progression events with T-DM1+P prior to surgery. T-DM1+P was associated with fewer grade ≥3 AEs but increased treatment discontinuation. Clinical trial information: NCT02131064. [Table: see text]
Relationship of liver cancer with LRP1B or TP53 mutation and tumor mutation burden and survival.
Authors: Longrong Wang, Kai Yan, Jiamin Zhou, Ning Zhang, Miao Wang, Jia Song, Jing Zhao, Yuzi Zhang, Shangli Cai, Yiming Zhao, Lu Wang
Journal: Journal of Clinical Oncology (2019)

1573 Background: Liver cancer (LC), one of the most common causes of cancer-related deaths, is a serious medical problem due to the limited treatment options available for this disease. Immune checkpoint inhibitors (ICIs) that are proved to be beneficial in the treatment of advanced LC. Similar to observations in other cancers, these ICIs as monotherapy may benefit only a fraction of HCC patients. Tumor mutation burden (TMB) is an important predictor for efficacy of ICIs in several solid tumors. However, the research on exploring the association between TMB and mutant genes with high frequency of liver cancer is limited. Besides, previous research on prognostic factors primarily focus on pathological features, probing the effects of genetic variations are urgently needed to study. Methods: Whole-exome sequencing data of 377 liver tumors from the Cancer Genome Altas (TCGA) and next generation sequencing (NGS) data of 655 liver tumors from Chinese clinical dataset were analyzed to explore the associated between LRP1B or TP53 gene alteration and TMB. TMB was defined as total number of somatic non-synonymous mutations in coding region. Results: In total, 9.3% (35/377) of hepatic tumors in TCGA and 7.8% (51/655) in clinical cohort harboring LRP1B mutation. LRP1B mutation was significantly associated with higher TMB in both TCGA cohort (P = 0.0003) and clinical cohort (P = 0.0005). The frequency of TP53 mutation was 28.1% (106/377) in TCGA cohort, however, TP53 mutation represented a greater rate of 54.5% (357/655) in Chinese clinical cohort. TP53 mutation was also associated with higher TMB in the two cohort (P = 0.0005 for the TCGA cohort and P = 0.0010 for the clinical cohort). In addition, prognosis analysis was performed on patients in TCGA cohort. LRP1B statue resulted in significantly shorter overall survival (OS, median, 20.9 vs 61.7 months; HR, 2.22; P = 0.0012), and a decreasing trend on progression-free survival (PFS) without significant difference (median, 8.7 vs 16.6 months; HR, 1.28; P = 0.2839). TP53 mutation was an independent risk factors affecting both OS (HR 1.58, P = 0.0109) and PFS (HR 1.59, P = 0.0027), respectively. Conclusions: The results indicated that LRP1B or TP53 mutation was a poor prognostic factor in LC, and patients harboring any of these two gene mutations might easily benefit from the immunotherapy.
Mammalian Target of Rapamycin Complex 1 Signaling Is Required for the Dedifferentiation From Biliary Cell to Bipotential Progenitor Cell in Zebrafish Liver Regeneration
Authors: Jianbo He, Jingying Chen, Xiangyong Wei, Hui Leng, Hongliang Mu, Pengcheng Cai, Lingfei Luo
Journal: Hepatology (2019)

The liver has a high regenerative capacity. Upon two-thirds partial hepatectomy, the hepatocytes proliferate and contribute to liver regeneration. After severe liver injury, when the proliferation of residual hepatocytes is blocked, the biliary epithelial cells (BECs) lose their morphology and express hepatoblast and endoderm markers, dedifferentiate into bipotential progenitor cells (BP-PCs), then proliferate and redifferentiate into mature hepatocytes. Little is known about the mechanisms involved in the formation of BP-PCs after extreme liver injury. Using a zebrafish liver extreme injury model, we found that mammalian target of rapamycin complex 1 (mTORC1) signaling regulated dedifferentiation of BECs and proliferation of BP-PCs. mTORC1 signaling was up-regulated in BECs during extreme hepatocyte ablation and continuously expressed in later liver regeneration. Inhibition of mTORC1 by early chemical treatment before hepatocyte ablation blocked the dedifferentiation from BECs into BP-PCs. Late mTORC1 inhibition after liver injury reduced the proliferation of BP-PC-derived hepatocytes and BECs but did not affect BP-PC redifferentiation. mTOR and raptor mutants exhibited defects in BEC transdifferentiation including dedifferentiation, BP-PC proliferation, and redifferentiation, similar to the chemical inhibition. Conclusion: mTORC1 signaling governs BEC-driven liver regeneration by regulating the dedifferentiation of BECs and the proliferation of BP-PC-derived hepatocytes and BECs.
Risk of depression following prostate cancer work-up: A nationwide study.
Authors: Anne Sofie Friberg, Klaus Brasso, Elisabeth Wreford Andersen, Signe Benzon Larsen, John Thomas Helgstrand, Martin Andreas Røder, Christoffer Johansen, Susanne Oksbjerg Dalton
Journal: Journal of Clinical Oncology (2019)

5061 Background: Little is known about the psychological impact of undergoing evaluation for prostate cancer (PCa). We investigated the risk of developing a depression following PCa work-up with benign and malignant findings, respectively, compared with cancer-free men. Methods: A nationwide cohort of men who underwent prostate needle biopsies in Denmark from 1997–2011 was identified through the Danish Prostate Cancer Registry. Primary outcome was indication of moderate to severe depression defined as hospital contact for depression or first redemption of a prescribed antidepressant. For comparison, we selected a minimum of five age-matched cancer-free men per man who had undergone PCa specific diagnostic work-up. We excluded men with other cancer, major psychiatric disorder or use of antidepressants up to three years before study entry. Information on outcome and covariates (age, period, cohabitation status, income quintile and comorbidity) were retrieved from National Danish registries. We illustrated the risk of depression by cumulative incidence functions. Data were analyzed using Cox models adjusted for possible confounders. Results: We identified 54,766 men who underwent work-up including transrectal biopsies of the prostate, among these, 21,419 biopsy sets were benign and 33,347 men were diagnosed with PCa. We found an increasing cumulative incidence of depression in all groups. However, men diagnosed with PCa had a significantly higher risk throughout up to 18 years of follow-up. The adjusted hazard ratio (HR) of depression in men diagnosed with PCa was increased throughout follow-up with the highest risk in the two years following diagnosis (HR 2.77, 95% CI 2.66–2.87). After undergoing biopsies, men with benign results had an increased risk of depression (HR 1.22, 95% CI 1.14–1.31) in the first two years compared with cancer-free men; hereafter, we found no difference. Conclusions: We found an increased risk of depression in men following diagnostic work-up for PCa compared with a matched background population. In men diagnosed with PCa, the risk remained increased throughout the study period. Future studies are needed to further analyze the impact of stage and treatment modalities.
Immunotherapy with nivolumab in metastatic renal cell carcinoma in resource constraint settings: Impact of increasing intervals between standard doses, and stopping treatment early in responding patients.
Authors: Amit Rauthan, Poonam Patil, Nitin Yashas, Shriniwas Subhash Kulkarni, Tanvi Sood, Gaurav Nigade, S.P. Somashekhar, Shabber Zaveri
Journal: Journal of Clinical Oncology (2019)

e16078 Background: Nivolumab is now a standard 2 nd line treatment for patients of metastatic Renal cell cancer (mRCC) who progress on 1 st line Sunitinib or Pazopanib. Most western centers use Nivolumab for either 2 years duration, or indefinitely, or till severe side effects. Due to high drug cost and lack of insurance, it is difficult for most of our Indian patients to afford this duration of treatment. So, we decided to study the impact of increasing intervals between standard doses of Nivolumab, and stopping treatment early in responding patients of mRCC. Methods: This is a single centre, retrospective study of mRCC patients. Nivolumab was given at either 3 mg/kg or 240mg at 2 weekly intervals for the initial 6 cycles. If the patient were found to have either Complete Response (CR), Partial Response (PR) or stable disease, the interval between cycles was extended to 3 weeks (at same dose). After 9 months, the doses were extended to 4 weekly intervals (at same dose). The treatment was stopped at 18 doses in patients with CR or PR. The endpoints were objective response rate (ORR), overall survival (OS) and adverse events (AE). Results: Between May 2016 and Dec 2018, 28 patients received Nivolumab. 24 patients had received oral TKIs initially- 13 Sunitinib, 10 Pazopanib, and 1 Sorafinib. 4 patients received Nivolumab as 1 st line therapy (2 as single agent, 2 with oral TKI). Response was assessed by RECIST criteria. 3 patients (11%) achieved CR, 7(25%) achieved PR, 7 (25%) had stable disease and 11(39%)had progressive disease. Treatment was stopped after 18 doses in the 3 patients who had CR. The duration of followup after stopping treatment ranges from 8 months to 18 months, and all 3 patients continue to be in CR. 3 patients with stable disease have received more that 18 cycles (1 at 22 cycles, 2 at 19 cycles). OS at 1 year is 60% and median OS has not been reached. Conclusions: In our experience, Nivolumab is an effective agent in mRCC, even when the dosage intervals are increased, and when the treatment is stopped early in responding patients. An ORR of 36% and a OS at 1 year of 60% is the best we have seen. Long-lasting responses, even after discontinuing therapy, have been seen. This enables us to reduce the cost of treatment without possibly losing efficacy, and this could be an important step forward for treating more patients with Nivolumab in our resource constraint setting.
Interest of short hormonotherapy (HT) associated with radiotherapy (RT) as salvage treatment for metastatic free survival (MFS) after radical prostatectomy (RP): Update at 9 years of the GETUG-AFU 16 phase III randomized trial (NCT00423475).
Authors: Christian Carrie, Nicolas Magné, Patricia Burban-Provost, Paul Sargos, Igor Latorzeff, Stephane Supiot, Yazid Belkacemi, Didier Peiffert, Nedla Allouache, Bernard M. Dubray, Stephanie Servagi Vernat, Jean-Philippe Suchaud, Gilles Crehange, Stéphane Guerif, Meryem Brihoum, Nicolas Barbier, Pierre Graff-Cailleaud, Alain Ruffion, Sylvie Chabaud
Journal: Journal of Clinical Oncology (2019)

5001 Background: RT is the standard salvage treatment after RP. The role of HT is not formally demonstrated to date. This trial assessed the efficacy of RT alone vs RT+HT in terms of progression-free survival (PFS), metastase-free survival (MFS) and overall survival (OS) in patients with biological relapse (BR) after RP. After a median follow-up (FU) duration of 5.3 years, we previously reported [Carrie C, Lancet Oncol 2016] a benefit in PFS (80% vs 62% PFS free at 5 years; p &lt; 0.0001) in the combined arm, whatever the risk subgroups. Methods: Patients (pts) were randomized (1:1) to RT alone or RT+HT (goserelin, for 6 months). The randomization was stratified according to radiotherapy modality and risk group. Low risk was defined as Gleason score &lt; 8, surgical margins+, psa doubling time &gt; 8 months and no seminal vesicle involment. Assuming a 45% 5-year PFS of 45% in the RT arm, the trial required 369 pts per arm to detect an improvement of 12% on PFS in RT+HT arm (90% power and 5% bilateral alpha risk), possibly translating into a 10% gain in OS (75% to 85% with 80% power). Biological relapse (BR) was defined according to ASTRO-consensus. Results: At the time of data cutoff (March 2019), the median duration follow-up was 112 months. We confirm the benefit of RT+HT on PFS (HR = 0.54 [CI95% = 0.43-0.68] ; p &lt; 0.0001) whatever the risk subgroup (HR = 0.47 [CI95% = 0.28-0.80] and 0.56 [CI95% = 0.44-0.73] for low and high risk patients, respectively. Metastatic free survival (MFS) is significantly improved in the combined arm (HR = 0.73 [CI95% = 0.54-0.98] ; p = 0.034) with 69% [CI95% = 63-74] versus 75% [CI95% = 70-80] of MFS at 10 years for RT alone and RT+HT, respectively. Conclusions: Salvage radiotherapy combined with short term HT significantly improved 10-years metastatic free survival compared with salvage radiotherapy alone. GETUG-16 considered in the context of previously published results from RTOG-9601, confirm that this strategy can be considered as the new standard for salvage treatment after radical prostatectomy. Clinical trial information: NCT00423475.
Exosomes as novel prognostic biomarker in potentially resectable colorectal cancer liver metastatic (CCLM) patients.
Authors: Ina Valeria Zurlo, Mariantonietta Di Salvatore, Donatella Lucchetti, Filomena Colella, Claudio Ricciardi Tenore, Luigi Perelli, Massimo Ferrucci, Michele Basso, Maria Vellone, Maria Alessandra Calegari, Lisa Salvatore, Carmelo Pozzo, Felice Giuliante, Alessandra Cassano, Alessandro Sgambato, Giampaolo Tortora
Journal: Journal of Clinical Oncology (2019)

3558 Background: Target therapies and new surgical strategies deeply modify the history of CCLM patients (pts). Several prognostic scoring systems have been developed but no one is able to identify pts who should be excluded from a potentially useless surgery. Currently research is committed in identifying early biomarkers able to discern pts who could benefit from an aggressive approach. Exosomes are arising as promising biomarkers in cancer. The aim of this pivotal study was to analyze the association among exosome levels during CCLM-pts treatment, clinical outcomes and the KRAS status. Methods: We enrolled 22 pts with CCLM candidate to preoperative chemotherapy (pCT) and subsequent liver surgery. A blood sample was collected before pCT, after surgery, monthly during follow-up and at progression (PD). Exosomes were isolated by ultracentrifugation and characterized by standard methods. Exosomes concentration was assessed by Bradford assay. We adopted ddPCR™ KRAS G12/G13 Screening Kit to evaluate the KRAS status in exosomal DNA (e-DNA). Results: 22 CCLM pts received pCT and underwent liver surgery: 5 major hepatectomies and 17 multiple liver resections. Changes in exosomes plasma levels were found to correlate with each treatment step,resulting reduced after pCT and surgery and increased at PD, respectively (p = 0.0026). Pts with higher baseline exosome levels experimented shorter PFS than those with lower levels (p = 0.0033 HR 0.2). No association was found between exosome levels after liver surgery and disease free interval nor overall survival. KRAS status on e-DNA was evaluated on 10 pts in baseline, in pCT, after surgery, and in PD samples. In 8 out of 10 pts e-DNA displayed the same mutational status than the one detected on tumor DNA. Changes in e-DNA KRAS copies were found statistically significant in pCT vs surgery and pCT vs PD (p = 0.039; p = 0.04). Conclusions: Our study suggests a prognostic role of exosome levels in CCLM pts. Moreover, we showed that KRAS mutational status could be monitored during the post-surgery follow up by analyzing e-DNA. Overall, our data confirm the potential role of exosomes in liquid biopsy tool to monitor molecular changes during the treatment of CCLM pts.