tbuckley/cabot-search huggingface dataset:
Breast cancer in young women in India.
Authors: Sanjay P Deshmukh, Anupama Dutt Mane
Journal: Journal of Clinical Oncology (2012)

e11506 Background: The incidence of breast cancer is rising in India. It presents at a younger age in Indian population as compared to the western countries. Methods: This is a retrospective review of all breast cancer patients less than 40 years of age treated in single tertiary care center from June 2006 to June 2011. The aim was to assess the factors that may influence clinical outcome and prognosis including demographics, clinical characteristics, surgical and pathological findings and the treatment given. Clinical data was collected from medical records and histopathology reports. Independent variables like age, stage at presentation, surgery type, chemotherapy, radiation, tumour size, grade, nodal status, no. of positive nodes, perinodal extension, lymphovascular extension, ER, PR and Her2 neu were analysed. Results: Out of a total of 613 patients, 91 were under 40 years of age, corresponding to a prevalence of 14.8%. Median age was 35 years with the youngest being 23 years old. Maximum patients were in the age group of 36-40 years. Lymphovascular emboli was positive in 42 patients (48.8%) and perinodal extension was positive in 36 patients (41.8%). 30 patients(34.8%) had ER positivity, while 39 patients (45.3%) had PR positivity. Her 2 neu receptors were positive in 20 patients (23.2%). 39 patients were triple negative (45.3%). The median follow up period for all the patients was 28 months with the DFS being 76.1% and OS being 88.3%. In univariate analysis, factors significantly associated with survival were stage at presentation (p value- 0.026), presence of lymhovascular emboli (p value- 0.019) and presence of perinodal extension (p value- 0.007 ).Grade of the tumour also correlated with survival , however it was not statistically significant (p value- 0.086). Statistical analysis was done with SPSS 17. Conclusions: The incidence of breast cancer in younger women in India is high with increased number of triple negative patients. Overall survival is quite similar to that of the western population. Longer follow up and more studies are required to confirm this finding.
Role of genetics in the prediction of statin-associated muscle symptoms and optimization of statin use and adherence
Authors: Liam R Brunham, Steven Baker, Andrew Mammen, G B John Mancini, Robert S Rosenson
Journal: Cardiovascular Research (2018)

Statin therapy reduces cardiovascular events in patients with, or at risk of, atherosclerotic cardiovascular disease. However, statins are underutilized in patients for whom they are indicated and are frequently discontinued. Discontinuation may be the result of statin-associated muscle symptoms (SAMS), which encompass a broad spectrum of clinical phenotypes from myalgia to severe myopathy. As with many adverse drug reactions (ADRs), inter-individual variability in susceptibility to SAMS is due, at least in part, to differences in host genetics. The genetic basis for SAMS has been investigated in candidate gene studies, genome-wide association studies, and, more recently, studies of multi-omic networks, including at the transcriptome level. In this article, we provide a systematic review of the pharmacogenetic basis of SAMS, focusing on how an understanding of the genetic and molecular determinants of SAMS can be considered in a personalized approach to reduce the incidence of this ADR, optimize statin adherence, and reduce the risk for cardiovascular events.
Abstract 264: p38 Regulates Programmed Myofibroblast Differentiation and Fibrosis
Authors: Darrian Bugg, Natasha Ghearing, Lisa E Dorn, Michelle A Sargent, Ambika Gunajea, Peter Kim, Kinya Otsu, Jeffery D Molkentin, Jennifer Davis
Journal: Circulation Research (2017)

Fibrosis is the excess collagen deposition that occurs with nearly every form of heart disease. A myriad of different stimuli including mechanical strain, cytokines and neuroendocrine effectors like TGFβ and Angiotensin II induce fibrotic matrix deposition. Current paradigms suggest that the differentiation of resident fibroblasts into myofibroblasts underlies the heart’s fibrotic response through yet unknown molecular mechanisms. Recently the p38 mitogen activated protein kinase (MAPK) signaling axis was implicated as a nodal pathway regulating myofibroblast differentiation in vitro , but never examined in vivo . To tactically address the role of p38 in the heart’s fibrotic response tamoxifen-inducible Cre recombinase knock-in mice (Tcf21 MCM ) were used to excise p38α from cardiac fibroblasts of conditional p38α knockout mice (p38 F/F ) subjected to ischemic injury. Deletion of p38 in fibroblasts reduced scar area by more than 50%, which we ascribe to the significantly reduced number of myofibroblasts in these hearts. Moreover, p38 F/F - Tcf21 MCM mice had markedly improved diastolic function relative to control littermates with intact p38 activity. Conversely, mice with fibroblast-specific expression of a constitutively active MAPK kinase 6 transgene (MKK6 Tg), which directly initiates p38α activity, developed interstitial and perivascular fibrosis at baseline. These mice had severe diastolic dysfunction in comparison to non-transgenic littermates with myofibroblasts present throughout heart. To investigate whether p38 MAPK regulates the fibrotic response in other tissues, p38α was deleted from activated dermal fibroblasts in mice using a tamoxifen-inducible periostin Cre recombinase (Postn MCM ) that were subjected to subcutaneous circular wounds. Mice lacking p38 signaling in activated fibroblasts had significantly delayed wound closure relative to p38 replete littermates, whereas mice expressing the activated MKK6 transgene in activated fibroblasts had accelerated wound closure and scarring suggesting that p38α activity in fibroblasts is universally vital to the fibrotic phase of wound healing. Collectively, these data suggest that p38 inhibition is a viable candidate for anti-fibrotic therapies.
Cost-effectiveness analysis of abiraterone acetate (AA) versus docetaxel (D) for the management of metastatic hormone naïve prostate cancer (mHNPC).
Authors: Chethan Ramamurthy, Andres F Correa, Elizabeth A. Handorf, J Robert Beck, Daniel M. Geynisman
Journal: Journal of Clinical Oncology (2018)

6514 Background: Therapies previously reserved for castration resistant prostate cancer (CRPC) have demonstrated improved progression-free (PFS) and overall survival (OS) in mHNPC. Four randomized trials have provided level 1 evidence for using either D or AA in addition to androgen deprivation therapy (ADT) for mHNPC, but the cost-effectiveness of these options has not been compared. Methods: A Markov cohort model was developed to project cost-effectiveness of each treatment until disease progression. Survival curves for progression/death were abstracted and digitized from the CHAARTED and LATITUDE studies. Clinically or financially significant adverse events (AEs) were modeled (neutropenia, neutropenic fever, and severe fatigue); utility values were obtained from the literature. Drug costs were obtained from a range of sources (Average Wholesale Price; VA costs). Effectiveness was measured in PFS quality adjusted life years (PFS QALYs) and cost-effectiveness was calculated using incremental cost-effectiveness ratios (ICER). Results: Adding D or AA to ADT improved PFS QALYs by 0.26 and 0.54, and increased cost by $12,185 and $208,684, respectively. Resulting ICERs were $46,519/QALY (D vs ADT) and $705,323/QALY (AA vs D). Results were highly sensitive to AA price, although even under lowest prices, the ICER was $404,451/QALY (AA vs DC) (Table 1). AA cost must be reduced by 76% for it to fall below a willingness-to-pay threshold of $150,000/QALY. Conclusions: Addition of AA modestly increases PFS QALYs compared with D, but substantially increases costs. While therapy subsequent to progression will impact the overall cost-effectiveness of the respective frontline options, the relative durations of treatment for CRPC are shorter. Thus, cost-effectiveness of mHNPC therapy is an important consideration given that OS is similar between studies for D and AA. Effect of varying medication costs on ICERs. Cost ($) ICER (AA vs D) ($) ICER (D vs ADT) ($) Base case 705,323 46,519 Abiraterone (cost/30d supply) 9358* LB 5,550 404,450 46,519 UB 11,275 856,743 46,519 Docetaxel (cost/mg) 10* LB 1.6 726,302 24,206 UB 12 700,210 51,958 *Base case; LB = lower bound, UB = upper bound
Perceptions of unintentional weight loss among cancer survivors.
Authors: Alexandra Katherine Zaleta, Shauna McManus, Thomas William LeBlanc, Joanne S Buzaglo
Journal: Journal of Clinical Oncology (2018)

138 Background: Unintentional weight loss (WL) can be a disruptive symptom of cancer, yet its psychosocial impact is not well understood. We examined cancer survivors’ experiences with unintentional WL. Methods: 320 cancer survivors completed an online survey, provided demographic, health, and unintentional WL history, and rated (0 = not at all; 4 = extremely) 19 statements about WL outcomes. We examined bivariate associations between weight status, unintentional WL, and WL outcomes. Results: Participants were 90% White; mean age = 58.8 years, SD= 11; 41% breast cancer, 23% blood cancer, 8% prostate cancer, mean time since diagnosis = 6.0 years, SD= 5; 18% metastatic, 22% current recurrence/relapse, 51% remission. 55 participants (17%) reported unintentional WL in the past 6 months (mean = 16lbs; range = 2-70; mean BMI = 27.6, SD= 6.3). These participants were less likely to be in disease remission ( p&lt; .05). Participants with unintentional WL tended to underestimate their weight category (e.g., of BMI-classified healthy weight participants, 26% believed they were underweight); κ = -.17, p&lt; .01. 51% of participants felt (somewhat to extremely) positive about WL, 49% said their health care team was supportive of WL; these statements were more strongly endorsed by people describing themselves as overweight ( ps &lt; .05). 27% believed WL caused physical weakness, 23% said WL resulted in lost control over nutrition/eating, 16% said WL made them feel like a burden, 14% said WL caused them to lose their identity; these statements were more strongly endorsed by people describing themselves as underweight ( ps &lt; .01). 20% viewed their WL as a sign of approaching end of life, 13% believed WL meant they would not be able to continue treatment; these views did not differ by perceived weight status. Conclusions: Many cancer survivors experience unintentional weight loss and associate their weight loss with negative outcomes. Survivors also often underestimate their weight status, which is notable given that personal views of one’s weight status, not BMI-derived weight status, is associated with beliefs about the impact of unintentional weight loss. Our findings suggest that people believe unintentional WL meaningfully affects their quality of life.
Liquid Biopsy for Advanced Non-Small Cell Lung Cancer (NSCLC): A Statement Paper from the IASLC
Authors: Christian Rolfo, Philip C. Mack, Giorgio V. Scagliotti, Paul Baas, Fabrice Barlesi, Trever G. Bivona, Roy S. Herbst, Tony S. Mok, Nir Peled, Robert Pirker, Luis E. Raez, Martin Reck, Jonathan W. Riess, Lecia V. Sequist, Frances A. Shepherd, Lynette M. Sholl, Daniel S.W. Tan, Heather A. Wakelee, Ignacio I. Wistuba, Murry W. Wynes, David P. Carbone, Fred R. Hirsch, David R. Gandara
Journal: Journal of Thoracic Oncology (2018)
Alfie Evans case: the good of the patient
Authors: Malcolm L C Smith
Journal: BMJ (2018)

All sides invoke the “good of the patient” in controversies such as the Alfie Evans case.1 Clarifying this term is helpful. The principle of autonomy has replaced what used to be the doctor’s responsibility and prerogative to make life and death decisions. This works well for patients with the capacity to consent to medical treatment. When the …
A robust response to combination immune checkpoint inhibitor therapy in HPV-related small cell cancer: a case report
Authors: Won Jin Ho, Lisa Rooper, Sarah Sagorsky, Hyunseok Kang
Journal: Journal for ImmunoTherapy of Cancer (2018)

<h3>Background</h3> Human papillomavirus-related small cell carcinoma of the head and neck is an extremely rare, aggressive subtype with poor outcomes. Therapeutic options are limited and are largely adopted from small cell lung cancer treatment paradigms. <h3>Case presentation</h3> This report describes a 69-year old male who was diagnosed of HPV-related oropharyngeal cancer with mixed small cell and squamous cell pathology which was clinically aggressive and progressed through multimodal platinum-based therapies. Upon manifestation of worsening metastatic disease, the patient was initiated on a combination of ipilimumab and nivolumab. Within 2 months of starting immunotherapy, a robust partial response was observed. During the treatment course, the patient developed immune-related adverse effects including new diabetes mellitus, colitis, and hypothyroidism. The disease-specific survival was 26&nbsp;months. <h3>Conclusion</h3> Combination immunotherapy may be an attractive option for HPV-related small cell head and neck cancers resistant to other treatment modalities and thus warrants further evaluation.
Consistent Margin-Status Reporting in Soft Tissue Sarcoma Is Essential to Establish Risk-Adapted Strategies Integrating Biology and Histotype in Perioperative Treatments
Authors: Antonin Levy, Sylvie Bonvalot, Dario Callegaro, Angela Botticella, Axel Le Cesne, Alessandro Gronchi, Cécile Le Péchoux
Journal: Journal of Clinical Oncology (2018)
Nitrogen multiple breath washout test for infants with cystic fibrosis
Authors: Václav Koucký, Veronika Skalická, Petr Pohunek
Journal: European Respiratory Journal (2018)

<b>Nitrogen multiple breath washout test is a safe, feasible and repeatable method for infants with cystic fibrosis. It may outperform sulfur hexafluoride variant with respect to its better suitability for long time follow up and lower technical demands.</b>http://ow.ly/hqnB30k9REW
Naive B Cells with High-Avidity Germline-Encoded Antigen Receptors Produce Persistent IgM+ and Transient IgG+ Memory B Cells
Authors: Kathryn A. Pape, Robert W. Maul, Thamotharampillai Dileepan, Amanda Schmidt Paustian, Patricia J. Gearhart, Marc K. Jenkins
Journal: Immunity (2018)
De-escalated treatment with trastuzumab-pertuzumab-letrozole in patients with HR+/HER2+ operable breast cancer with Ki67 response after 2 weeks letrozole: Final results of the PerELISA neoadjuvant study.
Authors: Valentina Guarneri, Maria Vittoria Dieci, Giancarlo Bisagni, Antonio Frassoldati, Giulia Valeria Bianchi, Gian Luca De Salvo, Enrico Orvieto, Matteo Curtarello, TomÃ¡s Pascual, Laia Pare, Massimo Ambroggi, Carlo Alberto Giorgi, Gabriella Moretti, Gaia Griguolo, Roberto Vicini, Aleix Prat, Pier Franco Conte
Journal: Journal of Clinical Oncology (2018)

507 Background: Neoadjuvant trials with chemotherapy plus anti-HER2 agents consistently showed a lower rate of pathologic complete response (pCR) in HER2+/HR+ vs HER2+/HR-tumors. Here we report the final results of the PerELISA study, aimed to evaluate the efficacy of a de-escalated, chemotherapy-free neoadjuvant regimen in HER2+/HR+ patients (pts) selected on the basis of Ki67 response after a short course letrozole (L). Methods: PerELISA is a phase II, multicentric, non-profit study for postmenopausal, operable HER2+/HR+ BC pts. Eligible pts received 2 wks window therapy with L, then underwent re-biopsy for Ki67 evaluation. Pts classified as Ki67 responders (relative Ki67 reduction ≥20% from baseline) continued L and started trastuzumab (T) and pertuzumab (P) q21 days for 5 cycles. Pts without Ki67 response discontinued L and started wkly paclitaxel for 13 wks combined with P and T. Primary aim was breast and axillary pCR. At least 8 pCR in 43 Ki67 responders were required to satisfy the study hypothesis in a two-step Simon’s design. Correlative analyses included: PAM50, TILs, PIK3CA. Results: 64 pts from 8 centers were enrolled: median age 63 yrs (49-83 yrs); stage IIA 67%, IIB 23%; IIIA 9%. Median (range) ER, PgR and ki67 expression: 90% (10-100), 14% (0-100); 30% (7-90). Median TILs level 10% (Q1 2%-Q3 15%). PIK3CA mutation was reported in 25% of the cases. 44 pts (69%) achieved a Ki67 response after 2 wks L and underwent surgery after L+T+P (breast conserving 66%; mastectomy 34%). A pCR was observed in 9 cases (20.5%). pCR rate was significantly higher in HER2-E vs other subtypes (45.5% vs 13.8%, p = 0.042). Intrinsic subtype was significantly associated with ki-67 response (p < 0.001).The proportion of pts with a Ki67 response in Luminal vs non Luminal subtypes was 92.6% and 44% respectively. Conclusions: The PerElisa study met its primary aim: a chemotherapy-free regimen for patients with Ki67 response after short term L warrants further investigation. Among Ki67 responders, the HER2-E subtype can identify pts most likely to benefit from de-escalated therapy. Clinical trial information: NCT02411344.
Genetic heterogeneity of primary lesion and metastasis in small intestine neuroendocrine tumors.
Authors: Dirk Walter, Patrick Harter, Florian Battke, Ria Winkelmann, Markus Schneider, Katharina Holzer, Christine Koch, Jörg Bojunga, Stefan Zeuzem, Martin-Leo Hansmann, Jan Peveling-Oberhag, Oliver Waidmann
Journal: Journal of Clinical Oncology (2018)

312 Background: Data on intratumoral heterogeneity of small intestine neuroendocrine tumors (SI-NETs) and related liver metastasis is limited. Further investigation might have impact on development of targeted therapy regimens. The aim of the study was to characterize genetic heterogeneity of 5 patients suffering from SI-NETs. Methods: Formalin-fixed, paraffin-embedded tissues samples of primary and metastatic lesion as well as benign liver of five patients with synchronously metastasized, well or moderately differentiated SI-NETs were analyzed with whole exome sequencing. For one patient, chip based 850k whole DNA methylome analysis was performed of primary and metastatic tumor tissue as well as control tissue. Alterations that occurred only in one tumor site were defined as private, whereas mutations present in both metastasis and primary lesion were regarded as common. Results: 156 single nucleotide variants (SNVs) in 150 genes were identified and amount of mutations/per sample ranged from 9-34 (mean 22). The degree of common (0-94%) and private mutations/per sample was strongly varying (6-100%). In all patients, copy number variations (CNV) were found and the degree of intratumoral heterogeneity of CNVs corresponded to SNV analysis. DNA methylation analysis of a patient without common SNVs revealed are large overlap of common methylated CpG sites. Conclusions: SI-NET primary and metastatic lesions show a highly varying degree of intratumoral heterogeneity. Driver events might not be detectable with exome analysis.
Behavioral treatment of insomnia in cancer survivors: Early results of a stepped-care trial.
Authors: Christopher J. Recklitis, Ann H. Partridge, Alexis L. Michaud, Eric Zhou
Journal: Journal of Clinical Oncology (2018)

140 Background: Insomnia is a burdensome late-effect for up to 30% of long-term survivors. Behavioral insomnia treatments are highly effective, but are not available to most affected survivors. Treatment barriers include lack of trained clinicians and resource demands for standard treatment of 6-8 individual sessions. To address these barriers we investigated the efficacy of delivering insomnia treatment in a stepped-care trial (NCT02756390); low intensity treatment was delivered to all participants, and more intense treatment reserved for non-responders. Methods: 43 survivors (91% female; mean ge = 55 yrs; mean time since diagnosis = 11 yrs) participated. They were primarily breast (63%) and blood cancer (26%) survivors, all with clinically elevated ( &gt; 12) Insomnia Severity Index (ISI) scores at baseline. Participants first received a single education session addressing basic sleep hygiene and were reassessed 4 weeks later. Those with an elevated ISI ( &gt; 12) at 4-week follow-up were offered more intense treatment: a 3-session CBT group program developed for cancer survivors. Participants completed the ISI again prior to CBT and 4-weeks post-treatment. Results: Survivors reported significant reductions in insomnia after a single education session; mean ISI scores fell 5.8 points (p &lt; .001), and 23 of 43 survivors (54%) no longer had clinically elevated ISI scores. Of the 20 survivors with persistent insomnia, 9 have received CBT to date and shown similar improvement; their mean ISI scores fell 6.4 points (p = .006), and 6 (67%) no longer had clinically elevated ISI scores. Both treatments had large effect sizes (d = 1.2). Conclusions: Results support a stepped-care approach to treating survivors’ insomnia. A brief sleep hygiene intervention has important dissemination implications, as it may be delivered by non-specialists or as a mobile intervention. For survivors needing more intensive treatment, a short-duration group CBT intervention is effective while requiring fewer resources than standard CBT insomnia treatment. This ongoing trial will investigate how treatment gains in both groups are maintained over three-month follow-up, and explore what factors may predict response to low-intensity treatment. Clinical trial information: NCT02756390.
Theranostics: Excitation‐Dependent Theranostic Nanosheet for Cancer Treatment (Adv. Healthcare Mater. 10/2018)
Authors: Shanyue Guan, Di Yang, Yangziwan Weng, Heng Lu, Xiangmin Meng, Xiaozhong Qu, Shuyun Zhou
Journal: Advanced Healthcare Materials (2018)

A novel nanosheet for tumor theranostics via either in vivo photoluminescence imaging of the hypoxia condition, or a subsequent topical killing of cancer cells by the generation of 1O2, is developed by Shuyun Zhao and co-workers in article 1701123. The two functions are switchable by just changing the wavelength of the excitation light.