tbuckley/cabot-search huggingface dataset:
P14.79 Randomized phase II trial of Tumor Treating Fields plus radiation therapy plus temozolomide compared to radiation therapy plus temozolomide in patients with newly diagnosed glioblastoma
Authors: D Limon, F Bokstein, D Blumenthal, C Ben Harush, Z Ram, R Grossman
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND In last decade, there were numerous attempts to improve the outcome of patients with glioblastoma (GBM), but even after maximal surgical resection, radiation therapy (RT) and temozolomide (TMZ), followed by maintenance TMZ for 6 months the median OS is 14.6 months. In the EF-14 Phase III trial, the addition of Tumor Treating Fields (TTFields) at 200 kHz to maintenance TMZ increased the median OS to 20.9 months, compared with 16.0 months with maintenance TMZ alone (HR, 0.63; 95% CI, 0.53–0.76; p&lt;0.001). Based on these results, the currently accepted standard of care for newly diagnosed GBM (ndGBM) is surgical resection if safely feasible, followed by RT with concomitant TMZ, and then followed by maintenance TMZ in combination with TTFields. Preclinical investigations have shown a radio-sensitizing effect of TTFields on glioma cells, suggesting synergistic effects between TTFields and radiotherapy. In a pilot study of 10 patients with ndGBM, we demonstrated that there was no increased treatment-related toxicity when TTFields were given in combination with RT/TMZ. The only TTFields-related adverse event was skin toxicity below the arrays. Preliminary progression free survival (PFS) data was encouraging. Based on the results of the pilot study, we designed this prospective, randomized Phase II study to further investigate if the addition of TTFields TMZ/RT treatment in ndGBM patients improves treatment efficacy and delays disease progression. MATERIAL AND METHODS Following debulking surgery or biopsy, 60 adult patients (≥18 years) with histologically confirmed GBM, KPS≥70 and life expectancy of at least 3 months will be randomized 1:1 to either a) RT with concomitant TMZ and TTFields (200 kHz) for 6 weeks followed by up to 6 months of maintenance TMZ in combination with TTFields (experimental arm) up to 24 months; or b) RT with concomitant TMZ alone followed by maintenance TMZ in combination with TTFields (control arm). Exclusion criteria: patients with early progressive disease, significant comorbidities precluding maintenance RT or TMZ or patients with an implanted electronic device. The primary endpoint is progression free survival at 12 months (PFS12). Treatment with TTFields will be continued until second progression or 24 months (the earlier of the two). All patients will be followed for survival. Grading and severity of all adverse events will be recorded using CTCAE V5.0. The sample size of 60 patients provides 80% power with a two-sided alpha level of 0.05 to detect a PFS12 of 46.5% with RT/TMZ/TTFields compared to 29.4% with RT/TMZ followed, respectively, by maintenance TMZ/TTFields (calculated from the RT/TMZ followed by maintenance TMZ/TTFields arm of the EF-14 trial). It is forecasted to take 24 months to fully recruit. Follow-up will continue for &gt;12 months from recruitment of the last patient.
P14.30 Treatment outcomes of newly-diagnosed glioblastoma multiforme (GBM) by O6-methylguanine DNA methyltransferase promoter (MGMT) status: a multi-country study
Authors: A Z Fu, J P Hall, A Bailey, J Kemp, G J Thompson, C Lee
Journal: Neuro-Oncology (2019)

Abstract INTRODUCTION This study evaluated the relationship of MGMT status with first-line (1L) treatment outcomes of patients with newly-diagnosed GBM in France, Germany, Italy, Spain, the UK (EU5), and Canada. MATERIALS AND METHODS Medical oncologists and neuro-oncologists across EU5 and Canada completed a point in time, cross-sectional survey for the next 8 GBM patients seen between May and July 2016 within EU5 and Canada. All results apart from time to progression (TTP) were presented for patients receiving 1L active drug treatment. TTP was calculated from initiation of 1L treatment to initiation of second-line treatment. Results presented are statistically significant (p&lt;0.05) unless otherwise specified. Bases vary depending on data availability. RESULTS A total of 241 physicians reported on 1747 patients with GBM. 875 were receiving 1L active drug treatment at time of survey. Mean age was 59.7 years (median=61) and 34.6% were women. Mean life expectancy was 14.9 months (median=12) at diagnosis and mean TTP was 8.5 months (median=7.3). Surgery was performed in 62% of patients (n=546) prior to 1L drug treatment; 38% of patients (n=329) had no surgery. Patients with surgery had a higher life expectancy at diagnosis vs patients with no surgery prior to 1L (mean=16.4 vs 12.2 months; median=15.0 vs 12.0). Patients who received corticosteroids (n=524) vs no corticosteroids during radiotherapy (n=64) had a shorter life expectancy at diagnosis (mean=15.0 vs 16.8 months, p=0.07; median=12.5 vs 13.9) and were more likely to have 8 or more inpatient days due to GBM (21% vs 8%, p=0.07) in the last 3 months prior to the survey. 62% of patients (n=541) had an MGMT-status recorded (tested: methylated or unmethylated), and 38% (n=334) were untested/ awaiting results (untested) at 1L. MGMT-tested patients had better life expectancy at diagnosis (mean=16.1 vs 12.9 months; median=15.0 vs 12.0) and longer TTP (mean=8.9 vs 7.8 months; median=7.8 vs 6.4) than untested patients. Among MGMT-tested patients, 58% were methylated and 42% were unmethylated. Methylated patients had similar life expectancy at diagnosis (mean=15.9 vs 16.3 months, p=0.85; median=15.0 vs 15.0) and TTP (mean=9.0 vs 8.8 months, p=0.42; median=8.0 vs 7.5) as unmethylated patients. CONCLUSIONS This analysis provides valuable insights into the 1L treatment outcomes of GBM patients in EU5 and Canada. Patients who did not undergo surgery had worse treatment outcomes. Steroid use appears to be associated with worse outcomes and higher healthcare resource utilization. Patient treatment outcomes varied depending on whether they are MGMT tested.
Photo voice as a participatory approach to influence climate related health policy in the Sundarbans
Authors: Upasona Ghosh, Bonolata Sen, Shibaji Bose
Journal: The Lancet Planetary Health (2019)

The IPCC Fifth Assessment Report highlights community-based strategies to drive effective and ecologically sustainable local adaptation strategies. A climate change hot spot, Sundarbans, India, needs collective action between communities and for local level health and non-health decision makers to find sustainable solutions to combat the impacts of climate change on child health. In our photovoice study, mothers examined mediating factors by which climate change was impacting their child's health. Over 80 mothers with at least one child aged 0–6 years took photographs to document the impact of climate change on factors affecting child health. During facilitated fortnightly group meetings, mothers identified and categorised the major factors affecting their children's health. Participants collectively selected the photographs most reflective of the mediating factors and presented their findings to the local and state health administrations to identify mutually agreeable solutions. Mothers identified five mediating factors. These included food security, livelihood, water and sanitation, accessibility of the health-care system, and breaching of embankments. The findings were presented by the mothers to community-level and state-level policy makers. The interactions resulted in the initiation of resilient road infrastructure, increased human resource availability in primary health centres during floods, and local government representatives demanding long-term adaptation strategies to address climate impacts. Child health is affected by climate change through multiple pathways. Participatory approaches like photo voice can be used effectively to reflect ground level experiences of climate-vulnerable communities, empower them, and provide a collaborative and inclusive platform to design policies and initiatives for the creation of climate resilient health systems and communities. Funding Future Health System Research consortium funded by DFID. Contributors UG drafted the abstract which was modified by BS and SB. UG and SB are the co-investigators of the study. BS is the supervising author. Declaration of interests We declare no competing interests.
Return to work after breast cancer: Comprehensive longitudinal analyses of its determinants.
Authors: Agnes Dumas, Ines Maria Vaz Duarte Luis, Thomas Bovagnet, Antonio Di Meglio, Mayssam El-Mouhebb, Sandrine Pinto, Cecile Charles, Sarah Dauchy, Charles Coutant, Paul H. Cottu, Anne Lesur, Florence Lerebours, Olivier Tredan, Laurence Vanlemmens, Christelle Levy, Jerome Lemonnier, Christel Mesleard, Patrick Arveux, Fabrice Andre, Gwenn Menvielle
Journal: Journal of Clinical Oncology (2019)

11564 Background: The interplay between breast cancer (BC) late effects, psychosocial and work-related factors in return to work (RTW) is not well understood. Previous reports were retrospective and did not combine all these features. Methods: We used data of a French prospective cohort study (CANTO, NCT01993498) of stage I-III BC patients (pts) including detailed clinical data of 1,874 pts working at diagnosis (dx) and ≥5 years younger than legal retirement age. The outcome was non-RTW 2 years after dx. Multivariable regressions were conducted to identify correlates of non-RTW. First, we examined the independent effect of treatments, toxicities (Common Toxicity Criteria Adverse Events), and patient reported outcomes (EORTC BR23 and FA12; Hospital Anxiety and Depression Scale) collected shortly after end of primary treatment. Then, in a restricted sample of 1,003 pts with working conditions (WC) information available, we fitted models to account for detailed pre-dx WC including type of contract, working hours, strenuous postures, supportive environment, degree of autonomy and perception of work. All models were adjusted for age, stage, marital status, socioeconomic status and comorbidities. Results: Two years after dx, 21% of pts did not work. Adjusted odds of non-RTW were increased among pts treated with combinations of chemotherapy (CT) and trastuzumab (TR) (e.g. OR of CT-TR = 2.20 [95% CI 1.24-3.88] and OR of CT-TR-hormonotherapy (HT) = 1.72 [1.13-2.63] vs. treated only with CT-HT), who had severe arm morbidity (OR = 1.73 [1.27-2.36] vs. no), severe emotional fatigue (OR = 1.55 [1.03-2.32] vs. no), anxiety (OR = 1.51 [1.02-2.23] vs. no), or depression (OR = 2.23 [1.27-3.94] vs no). In addition, we also found that the odds of non-RTW were increased among pts who had shift working hours (OR = 2.23 [1.32-3.76] vs. no), who did not work in a supportive environment before dx (OR = 2.24 [1.44-3.50] vs. supportive) and who perceived their job as boring (OR = 3.57 [1.71-7.46] vs. not boring). Conclusions: More than 1/5 of pts did not RTW 2 years after dx, with treatment (trastuzumab), clinical, psychological and work-related factors being associated with job reintegration. Multidisciplinary strategies are needed to support BC survivors.
Communication challenges among medical oncologists in Mexico.
Authors: Alejandra Platas, Ariel Jasqui, Claudia Pineda, Alan Fonseca, Ana Platas, Marisol García-García, Fernanda Mesa-Chavez, Cynthia Villarreal-Garza
Journal: Journal of Clinical Oncology (2019)

e23190 Background: Communication in oncology practice presents numerous challenges. Patients may react to the diagnosis and treatment information with unpredictable and difficult to manage emotions, which may distress clinicians and affect patient-physician relationships. An effective communication has shown a beneficial effect on satisfaction from both patients and providers, as well as on quality of health care provision and patients’ adherence, decision-making processes and outcomes. Aim: To identify the most important and hardest topics to discuss during consultation that pose a challenge for Mexican medical oncologists during their clinical practice. Methods: Physicians were reached out by a messaging platform to complete a survey that addressed the most relevant and difficult issues for discussion and the frequent challenges they face during information exchange. Results: A total of 115 oncologists completed the survey. Most of them identified treatment objectives, prognosis and treatment selection as important issues to discuss with patients. They coincided that the hardest matters to disclose were palliative care referral, treatment objectives, prognosis and recurrence. Also, oncologists reported that the most important challenges they face when communicating with patients are being honest without being hopeless (43%) and responding to patients’ emotions (21%). 92% expressed that they would like to receive formal training in communication skills. Conclusions: The issues regarded as highly important to discuss with patients were also the most difficult ones to address, possibly due to barriers related to patients’ emotional reactions when receiving bad news. The incorporation of a psychologist could promote calmness and trust, aid in information assimilation, and provide support to partners and relatives, as needed. Also, results showed the interest of oncologists in receiving formal training in communication skills, which reinforces the need to include this training as part of the medical oncology curriculum to ease transmission and comprehension of information. [Table: see text]
Image Gallery: Cutaneous ulcers in anti‐ <scp>MDA</scp> 5 dermatomyositis successfully treated with sildenafil
Authors: C. Collantes‐Rodríguez, D. Jiménez‐Gallo, L. Ossorio‐García, I. Villegas‐Romero, M. Linares‐Barrios
Journal: British Journal of Dermatology (2019)

E‐mail: cris.collantes.rguez@gmail.com Funding sources: no external funding. Conflicts of interest: none to declare. Dear Editor, A man in his 30s with a history of anti‐MDA5 dermatomyositis (DM) with refractory skin ulcers (Fig. 1a) was successfully treated with sildenafil (Fig. 1b). Figure 2 shows a timeline of the clinical course of his disease. Nowadays, there is no treatment approved for skin ulcers in DM. These ulcers reflect a severe underlying vasculopathy. We hypothesize that sildenafil, which has vasodilator properties, may have helped with pain relief and ulcer healing. On the other hand, it did not show any effect on pulmonary clinical improvement, probably given the advanced fibrosis of the lung parenchyma in our patient. ...
P14.51 Brain mapping for mentalizing in GBM patient
Authors: D Chung, W Yoon
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Glioblastoma is a disease with very poor outcome. Most patients underwent maximal safe resection, especially focusing in the preservation of motor and language function. However, many caregivers were suffered from the blockage of emotion communication with patients. So the definition of maximal safe resection must include the preservation of cognition and mentalizing of patients. Here we present the experience of brain mapping in awake surgery to preserve mentalizing. MATERIAL AND METHODS A 61-year-old male patient with headache was transferred to our hospital because of brain tumor on CT scan checked in another hospital. On the initial MRI, multi-septate cystic tumor was shown on left medial prefrontal area. The patient was recommended the surgical resection, but patient discharged with the denial of the operation. Ten days later, patient visited our hospital again with slowness of response by the enlargement of tumor size. The tumor extensively involved left cingulum and corpus callosum at anterior part. On diffusion tensor image, tumor located at mediosuperior part of inferior fronto-occipital fasciculus (IFOF). The patient showed deficit of visual and verbal memory, generative naming ability, and phonemic generative naming ability on preoperative neuropsychological test (SNSB-II). Pyramid and palm tree test (PPTT) and ‘Reading the Mind in the Eyes’ test (RMET) were also performed to evaluate the semantic association function and mentalizing preoperatively. RESULTS The patient underwent awake surgery with asleep-awake-asleep technique. The tumor was resected until identification of incorrect response to PPTT or RMET on subcortical stimulation (Ojeman stimulator, 1.5mA, 60Hz, biphasic). The histopathologic diagnosis was glioblastoma. Small part of tumor was remained on cingulum, but patient was discharged without change of mentalizing. CONCLUSION Although the patients with glioblastomas show poor outcome, we think that it is important to consider the cognition and mentalizing of patients for emotion communication with caregivers. With awake surgery, mentalizing can be preserved in selective patients.
P10.02 Differentiating microglia and tumour associated macrophages in high grade glioma
Authors: Z Woolf, M Swanson, T Park, A Brooks, M Dragunow
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Glioblastoma multiforme (GBM) is the most common primary brain tumour that affects adults. This aggressive tumour is invariably fatal, carrying a rapid progression and a dismal median survival period of only 15 months despite multimodal treatment approaches. Central to GBM pathogenesis is the immunosuppressive profile of these tumours. The two cell types that are highly abundant in these tumours and play critical roles in the immunosuppressive niche are the brain’s resident microglia and their peripheral counterparts - tumour associated macrophages (TAMs). Despite microglia and TAMs being ontogenetically distinct, these cells have largely been grouped together in research owing to the previous lack of cell-specific markers. Recent evidence has suggested that although TAMs may hold a predominantly pro-tumoral role, microglia may adopt a more anti-tumoral phenotype. Therefore, the differentiation of these two cell types is critical in elucidating the potentially characteristic roles of these two cell types in GBM pathogenesis. MATERIAL AND METHODS Tissue sections from resected low- and high-grade glioma tumours, along with epilepsy tissue (control), were used for immunohistochemistry (IHC) staining of macrophage pan-makers (Iba1, CD45, PU.1) and microglial-specific markers (TMEM119, P2RY12). Marker co-localisation was then used to differentiate microglia from TAMs. We further investigated a wider subset of cell-specific markers using multicolour flow cytometry and immunocytochemical staining of isolated cells from patient tissue samples. RESULTS Immunofluorescent staining of glioma and epilepsy tissue revealed two clear populations of cells; one population displayed long processes and co-labelling for both pan- and microglial-specific markers, whilst the other population displayed an amoeboid phenotype with only pan-maker staining. Preliminary analysis comparing microglia/TAM populations in low-grade, high-grade and epilepsy tissue suggests a clear difference in the proportions of these cells. CONCLUSION Our work complements RNA-Seq studies, showing that TMEM119 and P2RY12, alongside other markers, can indeed identify two distinct myeloid cell populations within glioma tissue. This provides a strong basis for further study where we aim to elucidate the respective roles of microglia and TAMs within tumours. Ultimately, this may hold the potential for differential targeting of these cells using immunotherapies.
Whole Genome Analyses of Chinese Population and <i>De Novo</i> Assembly of A Northern Han Genome
Authors: Zhenglin Du, Liang Ma, Hongzhu Qu, Wei Chen, Bing Zhang, Xi Lu, Weibo Zhai, Xin Sheng, Yongqiao Sun, Wenjie Li, Meng Lei, Qiuhui Qi, Na Yuan, Shuo Shi, Jingyao Zeng, Jinyue Wang, Yadong Yang, Qi Liu, Yaqiang Hong, Lili Dong, Zhewen Zhang, Dong Zou, Yanqing Wang, Shuhui Song, Fan Liu, Xiangdong Fang, Hua Chen, Xin Liu, Jingfa Xiao, Changqing Zeng
Journal: Genomics Proteomics & Bioinformatics (2019)

Abstract To unravel the genetic mechanisms of disease and physiological traits, it requires comprehensive sequencing analysis of large sample size in Chinese populations. Here, we report the primary results of the Chinese Academy of Sciences Precision Medicine Initiative (CASPMI) project launched by the Chinese Academy of Sciences, including the de novo assembly of a northern Han reference genome (NH1.0) and whole genome analyses of 597 healthy people coming from most areas in China. Given the two existing reference genomes for Han Chinese (YH and HX1) were both from the south, we constructed NH1.0, a new reference genome from a northern individual, by combining the sequencing strategies of PacBio, 10× Genomics, and Bionano mapping. Using this integrated approach, we obtained an N50 scaffold size of 46.63 Mb for the NH1.0 genome and performed a comparative genome analysis of NH1.0 with YH and HX1. In order to generate a genomic variation map of Chinese populations, we performed the whole-genome sequencing of 597 participants and identified 24.85 million (M) single nucleotide variants (SNVs), 3.85 M small indels, and 106,382 structural variations. In the association analysis with collected phenotypes, we found that the T allele of rs1549293 in KAT8 significantly correlated with the waist circumference in northern Han males. Moreover, significant genetic diversity in MTHFR, TCN2, FADS1, and FADS2, which associate with circulating folate, vitamin B12, or lipid metabolism, was observed between northerners and southerners. Especially, for the homocysteine-increasing allele of rs1801133 (MTHFR 677T), we hypothesize that there exists a “comfort” zone for a high frequency of 677T between latitudes of 35–45 degree North. Taken together, our results provide a high-quality northern Han reference genome and novel population-specific data sets of genetic variants for use in the personalized and precision medicine.
Prognosis of adenosquamous carcinoma of the pancreas: A matched case-control study.
Authors: Hiroshi Imaoka, Kenji Yamao, Susumu Hijioka, Kazuo Hara, Nobumasa Mizuno, Tsutomu Tanaka, Shinya Kondo, Masahiro Tajika, Takeshi Ogura, Tomohiko Obayashi, Yasumasa Niwa, Yasuhiro Shimizu
Journal: Journal of Clinical Oncology (2012)

e14540 Background: Adenosquamous carcinoma of the pancreas (ASC), which accounts for only 1-4% of exocrine pancreatic malignancies, is a variant of pancreatic ductal adenocarcinoma (PDAC). However, the prognosis of ASC is still unclear because these reports were based on only case studies and small surgical series with early stage cancers. The purpose of the present study was to clarify the prognosis of ASC using a matched case-control study. Methods: Pathological and clinical records of ASC cases between 2001 and 2011 in our institution were examined. All ASC cases were diagnosed pathologically by a surgical or endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) specimen. First, to examine the efficacy of EUS-FNA for the diagnosis of ASC, the pathological findings of EUS-FNA were compared with the surgical findings in the resected cases of ASC. Next, to clarify the prognosis of ASC, the clinical characteristics of ASC were evaluated. As a control group, PDAC cases matched with ASC cases by sex, age, pretreatment ECOG-PS, location, initial therapy, and the AJCC TNM staging for pancreatic cancer were also included in this study. Results: Of the 914 cases of pancreatic neoplasms, 28 cases of ASC were identified (3.06%), and 56 cases of PDAC were matched as controls. Of 28 cases of ASC, 6 cases underwent curative resection, and 22 cases were unresectable. Of the 6 resected cases of ASC, 5 cases were diagnosed preoperatively by EUS-FNA (κ, 0.83; positive predictive value [PPV], 100%). Overall survival (OS) was significantly worse for ASC than for PDAC, with a hazard ratio (HR) of 1.94 (95% CI, 1.07 to 3.51; p=0.026; median 8.38 months vs. 15.75 months). Of the 22 unresected cases, the OS of ASC was significantly worse than that of PDAC, with an HR of 2.39 (95% CI, 1.27 to 4.51; p=0.007; median 4.67 months vs. 12.36 months). Conclusions: In the present study, EUS-FNA had a high PPV for the diagnosis of ASC, and ASC was found to be more aggressive than PDAC.