tbuckley/cabot-search huggingface dataset:
End of life care for infants, children and young people with life limiting conditions: summary of NICE guidance
Authors: Gemma Villanueva, M Stephen Murphy, David Vickers, Emily Harrop, Katharina Dworzynski
Journal: BMJ (2016)

#### What you need to know

Children and young people can have a wide range of life limiting conditions and may sometimes live with such conditions for many years. This guideline recommends that end of life care be managed as a long term process that begins at the time of diagnosis of a life limiting condition and entails planning for the future. Sometimes it may begin before the child’s birth. It is part of the overall care of the child or young person and runs in parallel with other active treatments for the underlying condition itself.1 Finally, it includes those aspects related to the care of the dying.

This guideline was commissioned with the aim to standardise end of life care for infants, children, and young people living with a life limiting condition, and thus promote equity and consistency. Important themes are to involve children and young people and their parents or carers in decisions about their care, facilitate their care in their preferred location (most likely home), and plan for day and night care.

This article summarises the most recent guidance from the recent National Institute for Health and Care Excellence (NICE) on the planning and management of end of life care in infants, children, and young people.2 For a visual summary, please …
Overall survival effect of lower chemotherapy dosing in extremely obese (BMI ≥ 35) patients with breast cancer based on adjusted BSA.
Authors: P. Sharma, T. A. Samuel, J. C. Wells, E. Mebel, J. T. French, J. A. Crozier, S. W. Looney
Journal: Journal of Clinical Oncology (2011)

1047 Background: Chemotherapy (ctx) treated breast cancer patients (BC pts) w/ BMI ≥ 35 (WHO Class II obese) have significantly lower overall survival (OS) than pts w/ BMI < 35, regardless of race or age, possibly due to use of a lower dosing BSA (dBSA), to avoid ctx toxicity. This retrospective analysis examines discrepancies between calculated BSA (cBSA) & dBSA in BC pts. We further analyzed OS in relation to BMI & BSA discrepancies. Methods: Data obtained from the GHSU tumor registry included BMI, dBSA, cBSA (using Mosteller eq.), & OS data from all BC pts receiving ctx between 1997−2005. For pts w/ BMI ≥ 35, (n = 68) & pts who have BMI < 35 (n = 193), Lin’s coefficient of concordance (r) was used to measure agreement between the BSAs. Results: In pts w/ BMI < 35, agreement between the BSAs was almost perfect (r = 0.95, 95% CI 0.93−0.96). Yet, for pts w/ BMI ≥ 35, agreement between the BSAs was low (r = 0.55, 95% C.I. 0.43−0.66). BSA concordance differed significantly between the two groups (p < 0.001). Bias in BSA measurement was estimated by subtracting the cBSA from the dBSA for each pt. For all pts (n = 261), the mean bias ± SD = −0.06 ± 0.09 (range: −0.51 to 0.45). The mean bias differed significantly between pts w/ BMI > 35 (mean ± SD: −0.15 ± 0.12) & pts w/ BMI < 35, (mean ± SD: −0.027 ± 0.047), p < 0.001. In deceased pts (n = 87), the mean bias ± SD was −0.069 ± 0.078 (range: −0.4 to 0.03). In living pts (n = 174), the mean bias ± SD was −0.055 ± 0.096 (range: −0.51 to 0.45). Bias difference between those who died & those alive was not statistically significant (p = 0.2). Vital status differences are small between groups using odds ratio (OR) adjusted for the bias in BSA. Unadjusted comparison based on logistic regression: OR = 2.05, p = 0.014; adjusted for BSA bias: OR = 2.25, p = 0.028. Results are similar when comparing groups in terms of OS using hazard ratio (HR) adjusted for bias in BSA. Unadjusted comparison using Cox regression: HR = 1.56, p = 0.049; adjusted for BSA bias; HR = 1.65, p = 0.04. Conclusions: Our analyses indicate that there is a significant bias in BSA calculation for ctx dosing in pts w/ BMI ≥ 35. Yet, this bias does not seem to affect OS between BMI groups. The decreased OS seen in pts w/ BMI ≥ 35 is likely related to factors other than lower dBSA.
Implementation of intraoperative radiation therapy (IORT) for breast cancer treatment: An emphasis on radiation and patient safety and quality using a Provonost checklist approach.
Authors: V. E. Arterbery, L. Liang, J. Carethers
Journal: Journal of Clinical Oncology (2011)

e11537 Background: IORT is being evaluated as a novel approach to radiation delivery as part of breast conserving surgery. To improve the quality, patient safety and radiation safety issues with this technology we utilized a checklist approach to streamline treatment delivery. Methods: IORT is delivered as a single-dose Intraoperative radiation treatment. The treatment requires a high level of radiation and surgical expertise. We developed a model of implementation that would improve quality, and radiation safety for patient and staff and reduce the possibility of radiation errors associated with treatment delivery. To achieve this goal, we developed a pre op and Intraoperative “Provonost checklist” approach. We streamlined implementation by developing lists using an “Lean thinking method”. 1) Initial meeting with senior management for OR, Nursing and Physicians, with brainstorming to create checklists, timelines and identify IORT quality and safety issues 2) Communicated IORT quality and safety plan to all involved staff. In-services presentations were designed for the nursing, surgical and anesthesia staff as well as well-designed quizzes 3) Safety checklist for nursing, physics, OR staff and separate “time out” for the Intraoperative radiation portion of the procedure. 4) Two end-to-end dry runs prior to the procedures were performed, modifying the list(s) when necessary. This was found to be a necessary step toward the final goal. 5) Evaluated results of the test run, encouraged feedback 6) stabilized the results and by using evaluations to improve efficiency with IORT procedure. Results: IORT was able to be incorporated as part of our cancer center and operating room practice smoothly and successfully, with all radiation and patient safety procedures followed by staff. Conclusions: We performed a thorough and rigorous implementation program, dedicated to potential quality and radiation safety issues in every aspect of implementing IORT. This allowed for decreased OR time, minimal radiation exposure, to staff and reduced anesthesia time during our implementation of this IORT treatment to our Cancer Center.
Retrospective Analysis of NK/T Cell Lymphoma Prognostic Index (NKPI), EBV-DNA and Soluble IL-2 Receptor (sIL2R) for Extranodal NK/T-Cell Lymphoma, Nasal Type
Authors: Norihito Inoue, Noriko Nishimura, Anna Takahashi, Hirofumi Yamauchi, Yoshiharu Kusano, Kyoko Ueda, Yuko Mishima, Masahiro Yokoyama, Yasuhito Terui, Kiyohiko Hatake
Journal: Blood (2016)
Effect of body mass index on survival outcome among women with early-stage, triple-negative breast cancer.
Authors: S. S. Dawood, X. Lei, J. K. Litton, T. A. Buchholz, G. N. Hortobagyi, A. M. Gonzalez-Angulo
Journal: Journal of Clinical Oncology (2011)

1130 Background: Recent studies indicate that obesity among women with breast cancer predicts for the development of distant metastases and is an indicator for increased risk of breast cancer related death. The aim of this retrospective study was to look at the prognostic impact of obesity among women with early stage triple receptor negative breast cancer (TN), a subtype of breast cancer known to be associated with poor prognosis. Methods: Women with stageI-III TN breast cancer diagnosed between 1990 and 2010 were identified. The cohort was divided into three groups according to body mass index (BMI): normal/underweight (BMI <25kg/m2), overweight (BMI 25 – 30kg/m2) and obese (BMI >30kg/m2). Distant disease free survival (DDFS) was estimated using the Kaplan-Meier product limit methods and compared across groups using log rank statistic. Cox proportional hazards models were then used to determine the association of DDFS and BMI after adjusting for patient/tumor characteristics. Results: 2311 patients were identified of whom 794 (34.3%), 692 (30%), and 825 (35.7%) had BMI of <25kg/m2, 25 -30kg/m2 and >30kg/m2 respectively. Median follow up was 39 months (range 1 – 233 months). 5-year DDFS was 61%, 62% and 62% among patients with BMI of <25kg/m2, 25 -30kg/m2 and >30kg/m2 respectively. On multivariate analysis compared to patients with BMI < 25kg/m2 patients with BMI 25-30kg/m2 (HR=1.03; 95% CI 0.86-1.24, p=0.75) and those with BMI >30kg/m2 (HR=1.05;95% CI 0.88-1.26, p=0.58) did not have a significant increase in risk of distant metastases. When the models were stratified by menopausal status similar results were obtained. Conclusions: Patients with TN disease have significant rates of disease recurrence associated with poor prognostic outcome. The results of this study indicate that disease recurrence rates are similar across BMI categories and as such obesity does not function as a prognostic indicator among patients with TN disease.
Shared genetic variants suggest common pathways in allergy and autoimmune diseases
Authors: Eskil Kreiner, Johannes Waage, Marie Standl, Susanne Brix, Tune H. Pers, Alexessander Couto Alves, Nicole M. Warrington, Carla M.T. Tiesler, Elaine Fuertes, Lude Franke, Joel N. Hirschhorn, Alan James, Angela Simpson, Joyce Y. Tung, Gerard H. Koppelman, Dirkje S. Postma, Craig E. Pennell, Marjo-Riitta Jarvelin, Adnan Custovic, Nicholas Timpson, Manuel A. Ferreira, David P. Strachan, John Henderson, David Hinds, Hans Bisgaard, Klaus Bønnelykke
Journal: Journal of Allergy and Clinical Immunology (2017)
Retrospective analysis of the effect on overall survival of radiotherapy and chemotherapy sequence as treatment for primary breast cancer.
Authors: E. H. Gort, S. G. Elias, O. Visser, P. H. M. Elkhuizen, S. C. Linn
Journal: Journal of Clinical Oncology (2011)

1127 Background: Primary breast cancer patients with unfavorable prognosis are often treated with both chemotherapy (CT) and radiotherapy (RT). Whereas a delay in start of RT or CT results in increased chance of local and systemic recurrence respectively, the optimal sequence of RT and CT is subject for debate. The effect of RT and CT sequence on overall-survival (OS) was studied using a population-based cancer registry. Methods: Data from all primary breast cancer patients diagnosed in the Netherlands from 1999 to 2008 were obtained from the Netherlands Cancer Registry. Cox regression was used to compare OS in two treatment groups (RT first or CT first), while adjusting for important prognostic variables. Results: Of 131,122 new breast cancer patients registered by the Netherlands Cancer Registry between 1999 and 2008, 22,045 (16.8%) T1-3M0 patients received both CT and RT as treatment for primary breast cancer (9977 (45.3%) received RT first and 12,068 (54.7%) received CT first). During a total of 112,872 years of follow-up (median 4.75 years (range 10.96)), 3,075 patients died. Multivariate analysis with adjustments for age, TNM stage, number of positive lymph nodes, B&R grade and administration of hormone therapy, showed no overall survival difference for CT first compared to RT first (hazard ratio (HR) 0.99; 95%CI 0.91-1.07; p=0.7). Additional adjustment for hormone receptor status, HER2 status and tumor diameter within the subgroup of 9,951 patients diagnosed after 2004, for whom these data were available, did not change the results (HR 1.03; 95%CI 0.84-1.27; p=0.8). Conclusions: The sequence of radio- and chemotherapy as treatment for primary breast cancer was not associated with overall-survival in a large retrospective cohort of patients after a median follow-up of approximately 5 years.
Modeling the risk of secondary lung malignancy in patients treated with breast radiation therapy.
Authors: J. Ng, I. Shuryak, A. Xu, I. Deutsch, R. J. Burri, D. J. Brenner
Journal: Journal of Clinical Oncology (2011)

1085 Background: The risk of secondary lung malignancy (SLM) is a concern for women treated with breast radiation therapy after breast conserving surgery for early stage breast cancer. The purpose of this study was to estimate the absolute and relative risks of developing secondary lung malignancies in patients treated either with supine or prone whole breast radiotherapy or with Mammosite brachytherapy. Methods: Twenty-two women treated with breast radiotherapy were enrolled in the study. Fifteen patients underwent CT simulation and standard fractionated and hypofractionated whole breast radiation treatment planning in both the prone and the supine positions. Seven patients underwent CT simulation and treatment planning for Mammosite brachytherapy. Dose-volume histograms of the ipsilateral breast and the lungs were calculated and incorporated into a biologically-based mathematical model of spontaneous and radiation-induced carcinogenesis to quantitatively predict the lifetime absolute and relative risks of secondary lung malignancies. Results: The average predicted absolute lifetime risk for SLMs for patients treated in the supine position was higher than that for patients treated in the prone position (4.9% vs. 2.0% respectively, 2-tailed paired t-test, p<0.00001). The risk for SLMs for supine breast irradiation was higher than that for Mammosite patients (4.9% vs. 3.1% respectively, 2-tailed independent two sample t-test, p<0.005). The average predicted absolute lifetime risk of SLMs associated with standard supine breast irradiation was more than three times higher than the predicted background lifetime risk of lung cancer for this population (4.9% vs. 1.3% respectively, 2-tailed independent two sample t-test, p<0.00001). The relative risk increased with younger patient age. Conclusions: Treatment with supine breast irradiation results in a greater predicted risk of developing secondary lung malignancies than treatment with Mammosite brachytherapy or prone breast irradiation. While Mammosite brachytherapy reduces the risk of SLMs, the largest risk reduction is with prone breast irradiation. Prone breast irradiation may reduce the incidence of SLMs in this patient population.
Stereotactic body radiotherapy for treatment of organ-confined prostate cancer: Efficacy and quality of life at 4 years.
Authors: A. J. Katz, M. Santoro
Journal: Journal of Clinical Oncology (2011)

88 Background: The purpose of this study is to assess the efficacy and toxicity of stereotactic body radiotherapy for organ confined prostate cancer patients. Methods: Fifty T1cN0M0 prostate carcinoma patients (42 low- and 8 intermediate-risk) received 5 fractions of 7 Gy SBRT with Cyberknife to a total dose of 35 Gy delivered over 5 consecutive days. Mean patient age was 69.5 years and mean pre-treatment PSA was 5.7 ng/mL. All patients received 1500 mg of amifostine intrarectally prior to each SBRT fraction. Patients were treated to the 83%-87% contour line with 5-mm margins added to the gross tumor volume at all borders except for the rectum where a 3-mm margin was added. During treatment, 4 gold fiducial seeds were continuously tracked. Toxicity was assessed using the Radiation Therapy Oncology Group toxicity scale; biochemical failure was assessed by the Phoenix criteria, and quality of life was assessed with the Expanded Prostate Cancer Index Composite Questionnaire (EPIC). Results: At a median follow-up of 48 months (range, 46-53 months) one biochemical failure has occurred. Three patients died of intercurrent disease. The median PSA at 48 months is 0.10 ng/mL (range, 0.01-3.5 ng/mL). At 42 months, 42 of 47 patients had achieved a PSA of 0.5 ng/mL or less. Toxicity has been minimal with no grade 3+ toxicities. Actuarial 48 month rates for grade 2 urinary and rectal toxicity-free survival were 95.5% and 97.8%, respectively. Mean EPIC bowel and urinary quality of life returned to baseline by 18 months and remain at baseline values at 36 months. Of the 36 patients that were potent prior to treatment 29 (80.5%) maintained potency. Conclusions: At 48 months median follow-up the promising biochemical control, minimal toxicity and the promising potency preservation rates are highly encouraging. [Table: see text]
Risk-specific intensity of surveillance practices in non-muscle-invasive bladder cancer: Results from the BCAN/SUO/AUA/LUGPA electronic survey.
Authors: A. Smith, M. E. Nielsen, J. Ferguson, A. Manvar, R. Pruthi, E. Wallen, Y. Lotan
Journal: Journal of Clinical Oncology (2011)

251 Background: The ideal surveillance regimen for patients with non-muscle-invasive bladder cancer (NMIBC) is uncertain. Given different grade- and stage-specific risks of recurrence and progression, there is some question whether it might be acceptable to pursue less intensive surveillance practices for patients with lower risk disease, and there is a paucity of data on current patterns of care in this area of practice. Methods: An electronic survey was developed by the Bladder Cancer Advocacy Network (BCAN) to elicit self-reported practices of cystoscopy, cytology, and radiographic testing in the setting of surveillance for patients with a history of NMIBC. The survey was circulated to urologists via the AUA, SUO and LUGPA distribution lists. 512 respondents completed the survey. Results: Among respondents, 66% report performing cystoscopy every 3 months on all patients for at least the first two years following diagnosis of NMIBC. The remaining 33% report performing surveillance cystoscopy less frequently, 95% of whom report doing so in the setting of low grade pathology. Similarly, 51% report using cytology with every cystoscopy, 23% do so for all high grade cases, and 30% report not using cytology with every cystoscopy. In the absence of recurrence for patients with an initial high grade diagnosis, upper tract reimaging is performed annually in 48%, biannually in 37% and never in 3%. The corresponding figures for patients with an index diagnosis of low grade disease are 14%, 37% and 28%, respectively. In the event of a recurrence in the bladder, 80% of respondents report reimaging the upper tracts for patients with high grade disease, versus 45% in the event of a low grade recurrence. Conclusions: A substantial number of urologists responding to a survey report using relatively less intensive surveillance practices in patients with lower risk NMIBC. These results suggest a lack of consensus on the ideal intensity of evaluation in this setting, and provide a basis for prospective studies to validate the safest and most cost-effective strategies for surveillance. No significant financial relationships to disclose.
Trends in First Line Prescribing Preferences Among US-Based Hematology-Oncology Physicians for Patients with Multiple Myeloma Who Are Not Candidates for or Elect Not to Undergo Stem Cell Transplant
Authors: Joel H Schwartz, Joanne Willey, Arden Buettner, Mitch Scharf, Maria Lankford, Mark R. Green, Katarzyna Puto
Journal: Blood (2014)
Neoadjuvant MDM2 antagonist RG7112 for well-differentiated and dedifferentiated liposarcomas (WD/DD LPS): A pharmacodynamic (PD) biomarker study.
Authors: I. L. Ray-Coquard, J. Blay, A. Italiano, A. Le Cesne, N. Penel, J. Zhi, A. Beryozkina, F. Heil, R. Rueger, G. L. Nichols, B. Bui Nguyen
Journal: Journal of Clinical Oncology (2011)

10007b Background: WD/DD LPS are a prominent subset (15%) of sarcomas, where cytotoxic treatments have limited activity. MDM2 gene amplifications (and MDM2 overexpression) are potential molecular drivers. We report a neoadjuvant study of RG7112, a small molecule MDM2 antagonist, in chemotherapy-naive primary or relapsed LPS patients (pts) eligible for tumor resection. Methods: Pts with WD/DD LPS were treated orally at 1440 mg/m2 (Ph 1 MTD) QD for 10 days on a 28 day cycle. 3 cycles were planned, followed by complete resection. PK was collected d1 and d8 in cycle 1 (C1), with tumor biopsies collected at baseline and d8. Tumor p53 mutation (AmpliChip), MDM2 amplification (SISH) and expression (PCR), apoptosis (TUNEL) and proliferation (Ki67) were compared pre-treatment and at d8, along with serum MIC-1 (macrophage inhibitory cytokine-1), a p53 transcriptional target. Results: Between June-Dec 2010, 20 pts (12 M/8 F, med. 62y) completed pre-treatment and d8 biopsy. 12 pts had WD and 8 DD LPS. 9 were untreated, 1 metastatic. To date, 13 of 14 evaluable pts had MDM2 amplification, 2/19 had p53 mutations. 13 pts completed > 1 course (med 3); 6 received only C1. High grade adverse events included vomiting (G3-4, n=2), neutropenia (Gr 3-4 n= 3), and thrombocytopenia (Gr 3-4 n=5). Platelet nadir was highly correlated to exposure (R=0.85 and 0.86 for Cmaxss and AUCss, respectively). Increase in serum MIC-1 was also highly associated with exposure (R=0.77). Preliminary tumor analyses are available on 18/20 pts. 9/14 pts had increased TUNEL activity, 9/13 decreased Ki67 by IHC. 2 pts progressed. 7 pts have been resected with 3 patients still on treatment. Conclusions: This neoadjuvant biomarker study of RG7112, a novel MDM2 antagonist in WD/DD LPS, required sequential biopsies, was feasible, and achieved rapid completion of accrual. Preliminary data are consistent with induction of apoptosis and/or decrease in proliferation after treatment with RG7112. Treatment and assessments are ongoing. Biomarker analyses (including evidence of p53 activation by RG7112), PK clinical response data will be presented and updated with biomarker data from tumors obtained at debulking surgery.
Standard Versus High Dose Lenograstim in Adults with Hematological Malignancies for Peripheral Blood Progenitor Cell Mobilization: Results of a Retrospective Study on Behalf of Rome Transplant Network.
Authors: Azzurra Anna Romeo, Anna Chierichini, Diana Giannarelli, Alessandra Spagnoli, Barbara Anaclerico, Mariangela Vittori, Michele Vacca, Maria Gozzer, Antonio Spadea, Luciana Annino, Maria Concetta Petti, Andrea Mengarelli, William Arcese
Journal: Blood (2008)
Proteomic Profiling In CD34+CD38- Stem Cells and CD34+ Cells From 185 Myelodysplasia Patients Using Reverse Phase Proteins Arrays (RPPA) Reveals Recurrent Proteins Expression Signatures with Prognostic Implications
Authors: Steven M. Kornblau, Yi Hua Qiu, Nianxiang Zhang, Kevin R Coombes, David Graber, Guillermo Garcia-Manero, Hagop M. Kantarjian
Journal: Blood (2010)
Unrelated Donor Nonmyeloablative/Reduced Intensity (NST/RIC) Hematopoietic Stem Cell Transplantation (HCT) for Patients with Relapsed and Refractory Hodgkin’s Lymphoma (HL).
Authors: Marcel P. Devetten, Parameswaran Hari, Jeanette Carerras, Brent R. Logan, Koen van Besien, Julie M. Vose, Hillard M. Lazarus, Paolo Anderlini
Journal: Blood (2006)
Deubiquitinase USP13 maintains glioblastoma stem cells by antagonizing FBXL14-mediated Myc ubiquitination
Authors: Xiaoguang Fang, Wenchao Zhou, Qiulian Wu, Zhi Huang, Yu Shi, Kailin Yang, Cong Chen, Qi Xie, Stephen C. Mack, Xiuxing Wang, Angel M. Carcaboso, Andrew E. Sloan, Gaoliang Ouyang, Roger E. McLendon, Xiu-wu Bian, Jeremy N. Rich, Shideng Bao
Journal: The Journal of Experimental Medicine (2016)

Glioblastoma is the most lethal brain tumor and harbors glioma stem cells (GSCs) with potent tumorigenic capacity. The function of GSCs in tumor propagation is maintained by several core transcriptional regulators including c-Myc. c-Myc protein is tightly regulated by posttranslational modification. However, the posttranslational regulatory mechanisms for c-Myc in GSCs have not been defined. In this study, we demonstrate that the deubiquitinase USP13 stabilizes c-Myc by antagonizing FBXL14-mediated ubiquitination to maintain GSC self-renewal and tumorigenic potential. USP13 was preferentially expressed in GSCs, and its depletion potently inhibited GSC proliferation and tumor growth by promoting c-Myc ubiquitination and degradation. In contrast, overexpression of the ubiquitin E3 ligase FBXL14 induced c-Myc degradation, promoted GSC differentiation, and inhibited tumor growth. Ectopic expression of the ubiquitin-insensitive mutant T58A–c-Myc rescued the effects caused by FBXL14 overexpression or USP13 disruption. These data suggest that USP13 and FBXL14 play opposing roles in the regulation of GSCs through reversible ubiquitination of c-Myc.