tbuckley/cabot-search huggingface dataset:
Four versus six cycles of docetaxel and cyclophosphamide (TC) in early stage hormone positive breast cancer.
Authors: Aparna Basu, Vrushali S. Dabak, Randa Loutfi
Journal: Journal of Clinical Oncology (2018)

e12576 Background: TC is a regimen commonly used in early stage breast cancer. However, no specific recommendations exist in literature, regarding the number of cycles that can be used. i.e. TC4 vs TC6. Our aim, was to determine if TC4 is non-inferior to TC6 when used in the setting of early stage hormone positive breast cancer. Methods: We retrospectively reviewed 321 patients who were diagnosed with early stage hormone positive breast cancer between 2008 to 2015, at our institution who had Oncotype DX on file. Of these 70 patients were identified, who had received either TC4 or TC6. The number of cycles the patients received were based on provider preference. The two groups (TC4, TC6) were compared in regard to stage of cancer at diagnosis, node positivity, OncotypeDx score, grade of side-effects, compliance with adjuvant hormone therapy, recurrence and death-either from breast cancer or other causes. Median follow up was 4.5 years. Results: In the TC4 group(n = 53), 9(17%) had low oncotype( < 18), 39(73.6%) had intermediate(18-31) and 5(9.4%) had high ( > 31) score. In the TC6 group(n = 17), 3(17.6%) had low, 11(64.7%) had intermediate and 3(17.6%) had a high score. Only 11 of the 70 TC patients (15.7%) were lymph node positive. Among the 11 patients, 7 (63.6%) had TC4 and 4 (36.4%) had TC6 cycles. Regarding adverse effects, 41 patients (77.4%) had adverse events of any grade in the TC4 group and 16 patients (94.1%) had adverse events of any grade in the TC6 arm(p = 0.165). Grade 3 or higher adverse events were higher in the TC6 group as with 5 patients (29.4%) as compared to 5 patients (9.4) in the TC4 group (p = 0.055). Recurrence in the TC4 group was seen 1 patient (1.9%) and 1 (5.9%) patient in the TC6 group(p = 0.514). Death due to breast cancer was seen in 1 patient (1.9%) in the TC4 group and no patients in the TC6 group. Conclusions: In this limited series, TC4 appears to be equally effective to TC6, with fewer side effects of any grade as well as grade 3 and grade 4 side effects. However, a longer follow up and a larger patient base(e.g. SEER Database) is required to be studied to make definitive recommendations.
Mutation signature of patients with ER+ metastatic breast cancer who received endocrine therapy.
Authors: Fei Ma, Yan Zhang, Quchang Ouyang, Pingping Dai, Zongbi Yi, Weiguo Cao, Yidong Zhou, Chenchen Zhu, Yan-Fang Guan, Ling Yang, Xin Yi, Xuefeng Xia
Journal: Journal of Clinical Oncology (2018)

1057 Background: Approximately eighty percent of breast cancer patients are estrogen receptor alpha (ER-α) positive. Although women initially respond well to endocrine therapies, resistance often emerges. In this study we try to analyze the mutations in ER+ metastatic breast cancer patients (MBC) who have received endocrine therapies. Methods: Using next-generation sequencing (NGS)–based gene panel test (NGS), we analyzed the mutation profiling in 194 patients (pts) with MBC who were treated by endocrine therapies. Results: Somatic genomic alterations in ctDNA including copy number variants and point mutations were identified in 179 of 194 patients (92.3%). ESR1 activating point mutations or amplifications were identified in 28.9% (56/194) patients, which has been described to be associated with resistance to tamoxifen and AI therapies in patients with ER+ MBC. The most described hotspot activating mutations Y537C/S/N and D538G were detected in 26 and 21 patients, and other described mutations E380Q (13 pts), S463P (2 pts), L536R/H (2 pts), ESR1 amplifications (2 pts) were also detected. Additionally, nine novel point mutations were identified in ESR1 (including A58T, T311M, P406A, F435L, R436H, H488N, Q580L, V560E, Y526C). Polyclonal ESR1 mutations were identified in 13 patients. Another mechanism of resistance to endocrine therapy FGFR1 amplification was identified in 10 patients and one co-occurring with ESR1 mutation. For other genes associated with target therapies, PIK3CA mutations or PTEN deficiency were more common detected in patients with ESR1 mutation than ESR1 WT (50.0% vs 35.5%, p= 0.01). CDKN2A deficiency/CCND1 amplification were detected in 4 (7.1%) and 15 (10.9%) patients with or without ESR1 mutation. In addition, HER2 amplifications were less common detected in patients with ESR1 mutation than ESR1 WT (3.6% vs 14.5%, p= 0.03). Conclusions: In ER+ MBC patients with endocrine therapies, ESR1 and FGFR1 activating variants were common resistance to endocrine therapies and other targetable variants were also detected. Thus, These patients may benefit from combined treatment, such as endocrine therapies combined with mTOR inhibitors, CDK4/6 inhibitors when other pathways activating together.
Noncigarette Tobacco Products—Gateway or Diversion?—Reply
Authors: Shannon Lea Watkins, Stanton A. Glantz, Benjamin W. Chaffee
Journal: JAMA Pediatrics (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Children and young people with perinatal HIV in Europe: epidemiological situation in 2014 and implications for the future
Journal: Eurosurveillance (2016)

Accurate ascertainment of the number of children living with human immunodeficiency virus (HIV) is important to plan paediatric and adolescent health services. In Europe, the first generation of perinatally HIV-infected survivors are transferring to adult care and their health needs are unknown. We undertook an online survey of HIV cohort studies participating in the EuroCoord Network of Excellence to ascertain the number of perinatally HIV-infected (pHIV) patients included, to compare it with those published by the European Centre for Disease Prevention and Control (ECDC) and the World Health Organization (WHO) and to assess the ability of countries to follow up pHIV patients after transfer to adult care. At the end of 2013, 16 countries in EuroCoord reported 8,229 pHIV patients in follow-up in cohorts, compared with 5,160 cumulative diagnoses reported by the ECDC in the same area. Follow-up of pHIV patients after transfer to adult care varied. It is likely that the number of diagnoses of perinatal HIV reported to ECDC is an underestimate, although this varies by country. Further work is needed to refine estimates and encourage follow-up in adult HIV cohorts to investigate long-term outcomes and improve the care of the next generation of children with HIV.
Rare copy number variants analysis identifies novel candidate genes in heterotaxy syndrome patients with congenital heart defects
Authors: Chunjie Liu, Ruixue Cao, Yuejuan Xu, Tingting Li, Fen Li, Sun Chen, Rang Xu, Kun Sun
Journal: Genome Medicine (2018)

Heterotaxy (Htx) syndrome comprises a class of congenital disorders resulting from malformations in left-right body patterning. Approximately 90% of patients with heterotaxy have serious congenital heart diseases; as a result, the survival rate and outcomes of Htx patients are not satisfactory. However, the underlying etiology and mechanisms in the majority of Htx cases remain unknown. The aim of this study was to investigate the function of rare copy number variants (CNVs) in the pathogenesis of Htx.We collected 63 sporadic Htx patients with congenital heart defects and identified rare CNVs using an Affymetrix CytoScan HD microarray and real-time polymerase chain reaction. Potential candidate genes associated with the rare CNVs were selected by referring to previous literature related to left-right development. The expression patterns and function of candidate genes were further analyzed by whole mount in situ hybridization, morpholino knockdown, clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9)-mediated mutation, and over-expressing methods with zebrafish models.Nineteen rare CNVs were identified for the first time in patients with Htx. These CNVs include 5 heterozygous genic deletions, 4 internal genic duplications, and 10 complete duplications of at least one gene. Further analyses of the 19 rare CNVs identified six novel potential candidate genes (NUMB, PACRG, TCTN2, DANH10, RNF115, and TTC40) linked to left-right patterning. These candidate genes exhibited early expression patterns in zebrafish embryos. Functional testing revealed that downregulation and over-expression of five candidate genes (numb, pacrg, tctn2, dnah10, and rnf115) in zebrafish resulted in disruption of cardiac looping and abnormal expression of lefty2 or pitx2, molecular markers of left-right patterning.Our findings show that Htx with congenital heart defects in some sporadic patients may be attributed to rare CNVs. Furthermore, DNAH10 and RNF115 are Htx candidate genes involved in left-right patterning which have not previously been reported in either humans or animals. Our results also advance understanding of the genetic components of Htx.
A brief intervention for chemobrain: Results from a pilot study.
Authors: Jennifer Bennett
Journal: Journal of Clinical Oncology (2018)

171 Background: Up to 75 percent of breast cancer survivors (BCS) who were treated with chemotherapy report difficulty with cognition, including word finding problems and an inability to attend or multitask. The phenomenon of chemotherapy-related cognitive impairment is often referred to as “Chemobrain.” Chemobrain negatively affects one’s family and social and professional lives. In addition, anxiety and depression – commonly found in breast cancer survivors –negatively affect one’s cognition. An intervention for chemobrain needs to also address these psychological disorders in order to increase the quality of life of BCS. Methods: BCS who completed chemotherapy in the past 5 years and complained of subsequent cognitive decline were recruited for an intervention that included mindfulness and cognitive rehabilitation. Mindfulness has been shown to help with attention and to decrease depression and anxiety. The intervention was given in a class setting and met once/week for 1.5 hours for 6 weeks. Participants completed a brief neuropsychological battery pre- and post-intervention. Results: Immediately post-intervention, all participants (n = 11, mean age = 53.7 years, 100% female) reported increased cognitive functioning as measured by FACT-Cognitive Function, with a mean increase of 27.7 points (p &lt; 0.01, d= 1.82). Ninety-one percent of participants reported decreased depression as measured by PHQ-9, with a mean decrease of 4.7 points (p = 0.02, d= 0.82). These improvements were sustained 3 months post-intervention in cognitive functioning (p &lt; 0.01, d= 2.04) and depression (p &lt; 0.01, d = 1.39). Improved performance was also found in verbal fluency (p = 0.02, d= 0.87) and executive functioning as measured by Trail Making Test B (p = 0.02, d= 0.82). No improvement was detected in verbal learning or processing speed. Conclusions: Breast cancer survivors with chemobrain can recover cognitive functioning and decrease levels of depression relatively quickly with an intervention that combines mindfulness and cognitive rehabilitation. This recovery can be sustained for at least 3 months post-intervention. Additional research is needed to investigate how long recovery can be maintained and if the same intervention can help other cancer survivors.
Reply to J.-E. Bibault et al, B. Tombal, and C. Cattrini et al
Authors: Piet Ost, Dries Reynders, Karel Decaestecker, Valérie Fonteyne, Nicolaas Lumen, Bieke Lambert, Louke Delrue, Gert De Meerleer
Journal: Journal of Clinical Oncology (2018)
Treatment effect of palbociclib (PAL) plus endocrine therapy (ET) by prognostic and intrinsic subtype: A joint analysis of PALOMA2 and PALOMA3.
Authors: Richard S. Finn, Massimo Cristofanilli, Johannes Ettl, Karen A. Gelmon, Shailendra Verma, Marco Colleoni, Carla Giorgetti, Eric Roland Gauthier, Yuan Liu, Dongrui (Ray) Lu, Cynthia Huang Bartlett, Dennis J. Slamon, Nicholas C. Turner, Hope S. Rugo
Journal: Journal of Clinical Oncology (2018)

1023 Background: PAL + ET showed significant progression-free survival (PFS) benefit vs ET alone in patients (pts) with HR+/HER2- advanced breast cancer (ABC) in PALOMA2 (PAL2) and PALOMA3 (PAL3). Exploratory analyses were conducted on pts who received neo/adjuvant therapy to evaluate the effect of initial disease-free interval (DFI) in PAL3 or treatment-free interval (TFI) in PAL2 on PFS outcomes. Other analyses assessed luminal (Lum) subtype on PAL efficacy. Methods: Pre/postmenopausal pts whose disease has progressed after prior ET (PAL3; N = 521) and postmenopausal pts previously untreated for ABC (PAL2; N = 666) were randomized 2:1 to receive ET (fulvestrant [F] 500 mg or letrozole [L] 2.5mg/d, respectively) + PAL (125 mg/d, 3 wk on/1 wk off) or placebo (PBO). Median follow up was 14 mos (PAL3; 23Oct2015) and 37 mos (PAL2; 31May2017). DFI in PAL3 was calculated as time between first diagnosis of BC and disease recurrence and TFI in PAL2 as time between end of any neo/adjuvant therapy and relapse. Subpopulation treatment effect pattern plot (STEPP) analysis evaluated the association between DFI/TFI and PFS outcomes of PAL+ET vs PBO+ET for each study. In PAL3 and PAL2, 226 and 364 pts respectively provided FFPE tissue from recurrent or de novo disease where Lum subtype was determined. Gene expression profiling used HTG Molecular's EdgeSeq OBP to assess Lum A/B subtype. Results: In PAL3 and PAL2, 355 and 334 pts, respectively, received adjuvant therapy (232/347 PAL + F and 123/174 F + PBO; 219/444 PAL + L and 115/222 L + PBO). Median DFI in PAL3 was 49.2 mo in PAL + F and 52.0 mo in F + PBO; > 80% of pts had DFI > 2 y. Median TFI in PAL2 was 48.9 mo in PAL + L and 44.9 in L + PBO; ~70% of pts had TFI > 2 y. STEPP analyses suggest no impact on PFS outcomes from baseline DFI in PAL3 and TFI in PAL2. Both Lum A and B pts benefited more from PAL +ET than PBO+ET in PAL2 (Lum A HR [95% CI], 0.546 (0.385-0.773); Lum B: 0.508 [0.335-0.768]) and PAL3 (Lum A: 0.408 [0.253-0.659]; Lum B 0.642 [0.379-1.089]). Conclusions: Adding PAL to ET showed a significant increase in PFS regardless of the length of initial TFI/DFI and of Lum subtype. Sponsor: Pfizer Clinical trial information: NCT01740427, NCT01942135.
Ascertaining cancer survivors in Ontario using the Ontario Cancer Registry and administrative data.
Authors: Munaza Chaudhry, Catherine Chan, Sue Su-Myat, Stefanie De Rossi, Victoria Zwicker, Jillian Ross, Jonathan Sussman
Journal: Journal of Clinical Oncology (2018)

34 Background: The number of cancer survivors in Ontario has grown rapidly due to increasing incidence and advances in screening, diagnostic technologies and treatment. However, there is a lack of information to plan, monitor and improve follow-up care. Using the Ontario Cancer Registry (OCR) and health services administrative data, we developed a cohort of cancer survivors from which we could determine demographic characteristics, where follow-up care was received, and concordance with guideline-recommended surveillance testing. Methods: Individuals were included in the cumulative survivor cohort if they had at least one diagnosed incident malignant cancer from 1964 to 2017 in the OCR. Patients were considered survivors upon completion of treatment (surgery, chemotherapy, radiation therapy). Treatment was ascertained from clinical and administrative data using a data-driven approach combined with clinical expert input. In the absence of recurrence data, a treatment-based proxy was developed. Stage IV and complex malignant haematology cancer patients were excluded. We did a cross-sectional analysis of survivors in the cohort in 2016. We produced descriptive statistics and also determined the year of survivorship. For those who were in their first to fifth year of survival, we calculated the proportion who saw a medical or radiation oncologist (MO/RO) in 2016 stratified by year of survivorship. Results: As of December 31, 2016, there were 414,134 cancer survivors in the cohort, roughly 3% of the Ontario population. Ninety-three percent of survivors had a single primary cancer diagnosis, 66% were aged 65 or older, and slightly more were female (55%). Also, 22% had been diagnosed with breast cancer, 22% with prostate, and 12% with colorectal cancer. For those in their first year of survivorship, roughly 50% saw a MO/RO; whereas, for those in their fifth year of survival, 36% had seen a MO and 27% had seen an RO. Conclusions: The development of a cancer survivor cohort has enabled us to produce timely data on a previously unidentified patient population. Linking this cohort with existing administrative data will enable further examination of visit trajectories as well as cancer and non-cancer health outcomes.
Brief Report: Interleukin‐17 Blockade With Secukinumab in Peripheral Spondyloarthritis Impacts Synovial Immunopathology Without Compromising Systemic Immune Responses
Authors: Leonieke J. J. van Mens, Marleen G. H. van de Sande, Silvia Menegatti, Sijia Chen, Iris C. J. Blijdorp, Henriette M. de Jong, Inka A. Fluri, Talia E. Latuhihin, Arno W. R. van Kuijk, Lars Rogge, Nataliya G. Yeremenko, Dominique L. P. Baeten
Journal: Arthritis & Rheumatology (2018)

Objective Secukinumab (anti–interleukin‐17A [anti–IL‐17A]) is an effective therapy for ankylosing spondylitis and psoriatic arthritis, the prototypical forms of spondyloarthritis (SpA). We undertook this study to determine whether secukinumab modulates the immunopathology of target lesions without blunting systemic immune responses, using peripheral SpA as a model. Methods Twenty patients with active peripheral SpA were included in a 12‐week open‐label trial with secukinumab (300 mg once weekly from baseline to week 4 and then every 4 weeks thereafter). Outcomes included clinical response, cytokine production by peripheral blood cells using TruCulture technology, and histologic and real‐time quantitative polymerase chain reaction analysis of synovial biopsy samples before and after treatment. Results All patients completed the 12‐week study without severe adverse events (AEs) or severe treatment‐related AEs. The efficacy end point, the number of patients meeting the American College of Rheumatology 20% improvement criteria (achieving an ACR20 response) at 12 weeks, was achieved by 13 of the 20 patients, of whom 8 achieved an ACR50 response and 5 achieved an ACR70 response, with rapid and significant improvements in all clinical disease activity measures. Clinical improvement in joint counts was associated with a histologic decrease in synovial sublining macrophages ( P = 0.028) and neutrophils ( P = 0.004), both of which are sensitive synovial biomarkers of inflammatory response in peripheral SpA, as well as with decreased synovial expression of IL‐17A messenger RNA (mRNA) ( P = 0.010) but not of tumor necrosis factor mRNA. Systemically, secukinumab treatment decreased the C‐reactive protein level and the erythrocyte sedimentation rate (both P &lt; 0.01), and also decreased matrix metalloproteinase 3 production in the TruCulture system ( P &lt; 0.05). However, with the exception of IL‐17A itself, the capacity of peripheral blood cells to produce a broad panel of cytokines and chemokines upon stimulation with microbial antigens was not affected. Conclusion This mechanism‐of‐action study in peripheral SpA indicates that clinical improvement with secukinumab treatment is paralleled by immunomodulation of inflamed target tissues without compromising systemic immune responses.
Comparison of outcomes for AJCC 8th Anatomic and Prognostic staging in contemporary triple negative breast cancer (TNBC) multisite registry.
Authors: Rajvi H. Shah, Yen Y. Wang, Karissa Finke, Rachel Yoder, Anne O'Dea, Lauren Elizabeth Nye, Sheshadri Madhusudhana, Marc Steven Hoffmann, Manana Elia, Gregory James Crane, Jennifer R. Klemp, Qamar J. Khan, Bruce F. Kimler, Priyanka Sharma
Journal: Journal of Clinical Oncology (2018)

555 Background: Eighth edition of the AJCC TNM staging system incorporates biological prognostic factors along with the traditional anatomical factors and currently Prognostic (P) stage must be used for reporting of all cancer patients in the US. Comparison of patient distribution between P and Anatomic staging and outcomes associated with the P stages in a contemporary TNBC population are not known. Methods: 574 patients with stage I-III TNBC were enrolled in an IRB approved multisite prospective registry between 2011 and 2017. Patients were followed for recurrence and survival. AJCC 8th edition Anatomic (A) Stage and clinical Prognostic (P) stage groups were applied to all patients. Recurrence free survival (RFS) (STEEP criterion) was estimated according to the Kaplan-Meier method and compared among groups by log-rank test. Results: Median age was 53 years (23-85). 96% of patients received neo/adjuvant chemotherapy. 82% (468/574) of patients were upstaged on P compared to A staging. Significantly lower numbers of patients were categorized within P stage II (36%) compared to A stage II (51%) (p = 0.001). Conversely, higher number of patients were categorized within P stage III (29%) compared to A stage III (14%) (p = 0.0001), with largest relative increase in stage IIIC (3% to 13%). Table 1 provides 5 years RFS for all A and P stages. Compared to A stage IIIAB, P stage IIIAB was associated with better RFS (HR = 0.42 [0.21-0.86]; p = 0.013), whereas P and A stages IIIC had similar RFS. This suggests appropriate upstaging of TNBC patients to IIIC on P staging. Conclusions: 82% of TNBC patients are upstaged on P staging compared to A staging. Knowledge of outcomes associated with various P stages can guide prognostic counselling for TNBC patients who plan to undergo standard local and systemic treatment. N = 574 Stage P value 5 year RFS (Est) Anatomic Prognostic Anatomic Prognostic Stage I 200 (35%) 199 (35%) NS 86% 87% IA 197 (34%) 3 (1%) 0.001 86% 100% IB 3 (1%) 196 (34%) 67% 87% Stage II 293 (51%) 207 (36%) 0.001 85% 86% IIA 205 (35%) 80 (14%) 0.0001 87% 91% IIB 88 (15%) 127 (22%) 80% 83% Stage III 81 (14%) 168 (29%) 0.0001 57% 70% IIIAB 66 (12%) 94 (16%) 0.0001 59% 83% IIIC 15 (3%) 74 (13%) 55% 54%
Paul Vincent Briffa
Authors: Norman Briffa
Journal: BMJ (2018)

Paul Vincent Briffa grew up in Malta during the second world war. He was a hardworking and ambitious student who went to extraordinary lengths at university to ensure he acquired as comprehensive a knowledge as possible in all subjects. While studying anatomy, he managed to obtain a human skeleton, which he articulated himself by using copper wire, and he painted by hand the origins and insertions of every muscle in the body.

As was the custom at the time in colonial Malta he moved to the UK after qualifying. He joined the British Army and obtained his commission as captain …