tbuckley/cabot-search huggingface dataset:
Preoperative chemoradiotherapy and the long-term run in curative treatment of locally advanced oesophagogastric junction adenocarcinoma: Update of the POET phase III study.
Authors: Michael Stahl, Jorge Riera-Knorrenschild, Martin Stuschke, Rita Engenhart-Cabillic, Michael Bitzer, Wilfried Budach, Andreas Sandermann, Gunnar Folprecht, Luisa Mantovani Loeffler, Martin K Walz, Hansjochen Wilke
Journal: Journal of Clinical Oncology (2016)

4031 Background: In 2009 we published the results of a German phase III trial comparing preoperative chemotherapy (CT) with preoperative chemoradiotherapy (CRT) in locally advanced esophago-gastric junction adenocarcinoma (EGJ AC) (JCO 27:851). Three-year survival was increased from 28% to 48% by adding radiotherapy, but results did not reach statistical significance (p = 0.07). Methods: Fifty-nine pts vs 60 pts were randomized into preoperative CT vs CRT, respectively. Median observation time reached 10.5 years. Results: The rate of R0-resection was comparable between treatment arms (68% vs 72%). With regard to OS there was a strong trend in favour of CRT: survival rate at 5 years reached 24.4% (group A) and 39.5% (group B) (HR 0.65, 95%CI 0.42-1.01; two-sided log-rank p = 0.055). Moreover, we observed a significant improvement in local PFS after complete resection (R0/R1) by CRT compared to CT (HR 0.42, 0.19-0.93; p = 0.03). Disease free survival after complete resection was also improved by adding radiotherapy to CT (HR 0.61, 0.36-1.01, p = 0.053). Overall, there was no difference in survival between pts with Siewert type I and those with type II cancer, but pts with type II cancer appear to benefit even more from radiotherapy (type I HR 0.71; type II HR 0.60). Conclusions: Our results suggest that long-term survival of pts with locally advanced EGJ AC is best achieved with preoperative CRT. POET remains the single phase III trial comparing chemo- with chemoradiotherapy followed by surgery in this patient population. We urgently need a confirmatory trial to define preoperative CRT as standard treatment.
Genomic approaches for studying crop evolution
Authors: Mona Schreiber, Nils Stein, Martin Mascher
Journal: Genome biology (2018)

Understanding how crop plants evolved from their wild relatives and spread around the world can inform about the origins of agriculture. Here, we review how the rapid development of genomic resources and tools has made it possible to conduct genetic mapping and population genetic studies to unravel the molecular underpinnings of domestication and crop evolution in diverse crop species. We propose three future avenues for the study of crop evolution: establishment of high-quality reference genomes for crops and their wild relatives; genomic characterization of germplasm collections; and the adoption of novel methodologies such as archaeogenetics, epigenomics, and genome editing.
Daily aspirin doesn’t prevent deaths or disability in healthy older people, trial finds
Authors: Susan Mayor
Journal: BMJ (2018)

Daily, low dose aspirin is not associated with a significant reduction in death, dementia, or persistent physical disability in healthy people aged 70 or over, a randomised trial1 that also found increased risk of major haemorrhage has shown.2

“The results provide the most reliable evidence on the balance of risk and benefit of starting aspirin after the age of 70 in healthy people,” said Peter Rothwell, professor of neurology and head of the Centre for the Prevention of Stroke and Dementia at the University of Oxford. He added, “There were too few people in the over 70 age group in previous trials to draw reliable conclusions.”

Several studies have shown the benefits of low dose aspirin for people with a history of coronary heart disease, but the evidence for primary prevention in healthy older people has been inconclusive. Guidelines do not recommend this treatment even though it is widely used by elderly people. …
The ideal interface between oncology and palliative care: Views from the field.
Authors: Risha Gidwani, Douglas W. Blayney, Manali I. Patel, Steven M Asch, P. Adam Kelly, Andrea Nevedal
Journal: Journal of Clinical Oncology (2016)

10034 Background: The American Society of Clinical Oncology recommends palliative care be provided for patients with advanced cancer, and be provided soon after diagnosis. However, despite a strongly-positive evidence base and support for palliative care, many patients do not receive palliative care, or receive it so late in the course of disease they are not able to fully realize its benefit. There are many potential reasons for this incongruence between the research evidence and the practice of medicine, including system- , provider- and patient-level factors. Here, we evaluate provider-level factors and specifically, provider attitudes towards the role of primary and secondary palliative care in treating patients with advanced cancer. Despite their large role in the provision of these services, there is surprisingly little evidence regarding U.S. oncologists' attitudes towards palliative care. Methods: A pilot study consisting of semi-structured interviews of 31 U.S. based oncologists practicing in Academic Medical Centers, the Veterans Health Administration and the community. Physicians were asked a variety of questions, including the appropriate timing of primary and secondary palliative care, patient candidates for palliative care, the ideal interface between palliative care and oncology, and oncologist training in palliative care. Transcribed interviews were analyzed using matrix and thematic analysis. Results: Oncologists acknowledged the benefit of palliative care, but expressed strongly different views about: the handoff between oncology and palliative care specialists; the appropriate time to provide palliative care, and the discussions of terminal prognosis. For example, some oncologists felt that all palliative care should be handed off to specialists so they could focus on the difficult task of providing appropriate chemotherapy, while others felt that oncologists should provide the majority of palliative care because “good oncologic care is palliative.” Conclusions: Even amongst providers who largely support the use of palliative care, there are a variety of opinions about how to best integrate palliative care providers and/or services into the oncologic care of patients with advanced disease.
Abstract 17251: Indexed Left Atrial Adipose Tissue Area is Associated With Severity of Atrial Fibrillation as Well as Atrial Fibrillation Recurrence Among Patients Undergoing Catheter Ablation
Authors: Saket R Sanghai, Samer Mowakeaa, Barinder Hansra, Aline Iskandar, Seth T Dahlberg, Gerard P Aurigemma, David D McManus, Timothy P Fitzgibbons
Journal: Circulation (2017)

Introduction: Epicardial adipose tissue (EAT) is associated with atrial fibrillation (AF), possibly because of adverse paracrine signaling to adjacent atrial substrate. However, few studies have ex...
Impact of adjuvant chemotherapy in higher risk stage II colon cancer with a deficient mismatch repair (dMMR)/ microsatellite instability-high (MSI-H) profile.
Authors: AMR Mohamed, Renjian Jiang, Philip Agop Philip, Maria Diab, Madhusmita Behera, Christina Wu, Bassel F. El-Rayes, Mehmet Akce
Journal: Journal of Clinical Oncology (2018)

3604 Background: Randomized phase III trials have shown that patients with dMMR/ MSI-H stage II colon cancer (CC) do not benefit from adjuvant chemotherapy. However, a subgroup of stage II patients have a higher risk for recurrence but it is unclear whether those patients who also have dMMR/MSI-high tumors will in fact benefit from adjuvant chemotherapy. Methods: In this retrospective analysis of National Cancer Database (NCDB) we studied the impact of adjuvant chemotherapy in high risk stage II with dMMR/MSI-high CC. Higher risk was defined by at least one of the following criteria: < 12 lymph nodes examined, lymphovascular invasion (LVI), positive surgical margin, T4 tumor, and poorly differentiated/undifferentiated histology. No data were available for obstruction or perforation at diagnosis. Results: Between 2010 and 2013, 3851 CC patients (56.1% females, median age 69, 49.5% clinico-pathologically high risk) were determined to have dMMR/MSI-high status. 24.6% of dMMR/MSI-high patients received adjuvant chemotherapy, of whom 67.8% received multiagent therapy. On univariate analysis no adjuvant chemotherapy, pT4A/B tumor, pathologic stage IIB/C, < 12 lymph nodes, LVI positive, positive margin, and older age at diagnosis were associated with worse overall survival (OS). On multivariable analysis no adjuvant chemotherapy, male sex, stage IIC, positive surgical margin, older age at diagnosis were associated with worse OS. High risk dMMR/MSI-high patients had better OS when given adjuvant chemotherapy, HR 0.50 (0.34-0.74, p < 001). Single and multiagent adjuvant chemotherapy were associated with better OS, HR 0.38 (0.19-0.76, p = 0.006) and 0.58 (0.37-0.90, p = 0.02), respectively. Conclusions: Adjuvant chemotherapy was associated with better OS in stage II CC patients with high-risk features plus dMMR/MSI-high profile. Benefit was observed with both single and multiagent chemotherapy. In the absence of prospective studies, this study supports the consideration of adjuvant chemotherapy in the subgroup of stage II CC patients with dMMR/MSI-high status if they also have high recurrence clinico-pathological features risk.
TCT-332 Serial IVUS Substudy Results from J-LESSON: Japan Unprotected Left Main Coronary Artery Disease PCI Strategy On New Generation Stents
Authors: Akiko Maehara, Nobuaki Kobayashi, Mitsuaki Matsumura, Soo-Jin Kang, Shigeo Saito, Toshiya Muramatsu, Gary Mintz, Masahiko Ochiai, Masato Nakamura
Journal: Journal of the American College of Cardiology (2018)
A phase I/II study of regorafenib (R) plus avelumab (A) in digestive tumors.
Authors: Sophie Cousin, Maud Toulmonde, Sabrina Albert, Carine A. Bellera, Barbara Lortal, Simone Mathoulin-Pélissier, Antoine Italiano
Journal: Journal of Clinical Oncology (2018)

TPS3125 Background: Several preclinical studies have shown that simultaneous blockade of programmed death(PD) 1/PD-L1 and neoangiogenesis induces synergistic anti-tumour effect in vivo. R is a multikinase inhibitor approved for the treatment of metastatic colorectal (CRC) and gastro intestinal stromal tumor (GIST). A is a PD-L1 inhibitor approved for the treatment of Merkel carcinoma. We hypothesized that R in association with A could be synergistic and feasible in patients (pts) with tumors of the digestive tract. Methods: This is a multicenter, prospective phase I/II trial assessing R+A in 4 cohorts of pts with advanced pretreated: A) CRC not MSI-H or MMR-deficient, B) GIST, C) Oesophageal/gastric carcinoma, D) Biliary tract/hepatocellular carcinoma. Primary objectives are to determine the recommended phase II dose (RP2D) of R+A in phase I, and assess the best overall response defined as per RECIST v1.1 with A+R in phase II. In phase I, 2 doses of R will be investigated: 120mg, 160mg, daily, 3 weeks on/1 week off with fixed dose of A: 10mg/kg every 2 weeks. In phase II, all pts will received the RP2D of R with A. Main eligibility criteria are: -adult pts with metastatic, histologically confirmed tumor of 1 of the 4 cohorts, with measurable, progressive disease, after ≥ 1 previous line of systemic therapy. Primary endpoint is toxicity according to NCI-CTCAE v4.0 and incidence rate of DLT at each dose level during the first 28 days (I); antitumor activity in terms of best overall response (II). Secondary endpoints encompass: Objective Response Rate (ORR), Progression Free Survival (PFS), Growth modulation index, 6-months,1-year PFS and Overall Survival, PKs, Pharmacodynamics on (I) mandatory blood samples at baseline/on treatment, archived tumor tissue, (II) on optional biopsy at Baseline/after 4 weeks of R+A focusing on TAM, Lymphocytes infiltrates, PD-L1, VEGFR, PDGFR, HIF1alpha expression. Phase I will follow a classical 3+3 design with 2 dose levels and a maximum of 12 pts. A Bayesian approach will be used in phase II, with a maximum sample size of 50 pts/cohort. At each update of interim analysis, a stopping rule for inefficacy will recommend stopping the trial if there is a high predictive probability (≥80%) that ORR is < or = to the futility bound p0 = 20%. Clinical trial information: NCT03475953.
Telephone-based nutrition coaching decreases insulin resistance in patients undergoing breast cancer treatment.
Authors: Shelby A. Terstriep, Keely Marie Hack, Charissa Quinlan
Journal: Journal of Clinical Oncology (2018)

e22062 Background: Higher levels of insulin in breast cancer patients at diagnosis correlate with worse prognosis, independent of body mass index (Goodwin, Ennis et al. 2002). Breast cancer patients have an increase in insulin and insulin resistance from pre-surgery to post adjuvant therapy due to multiple factors, including poor nutrition. We evaluated whether telephone-based nutrition coaching with a moderate protein, carbohydrate-controlled diet would decrease the development of insulin resistance throughout breast cancer treatment. Methods: Patients (n = 25) diagnosed with Stage 1-3 breast cancer scheduled to receive primary surgery, adjuvant chemotherapy and radiation were randomized to receive usual care versus weekly telephone-based nutrition coaching by a licensed Registered Dietician. Patients were instructed to follow a macronutrient diet composition of 30% protein, 30% fat, and 40% carbohydrate. Overweight and obese participants were assigned a calorie goal and range based on the NIH weight loss calculator to achieve a weight loss of 10% at six months. HOMA and body composition were the primary outcome measures. Secondary measures were quality of life (via FACT-B), body composition, and metabolic rate changes. Results: Comparing the control and treatment groups at study completion there was a significant decrease in insulin resistance as measured by HOMA (p-value = 0.0261, 3.83 [± 2.65] vs. 1.81 [±0.91] respectively) and fasting insulin (p-value = 0.0369, 12.27 [± 7.72] vs. 7.50 [±3.28] respectively). In addition, the treatment group had a statistically significant improvement in emotional well-being. There were no significant differences in body composition, weight or basal metabolic rate. Conclusions: This pilot study shows that nutrition coaching can improve insulin resistance and insulin levels, which are known negative predictors of survival for breast cancer patients, and is associated with improvement in emotional well-being. Further development of behavioral changes including stress reduction, sleep maximization and exercise should be combined with nutritional changes to maximize efforts to reduce known predictors of negative outcomes.
Can disease activity in patients with psoriatic arthritis be adequately assessed by a modified Disease Activity index for PSoriatic Arthritis (DAPSA) based on 28 joints?
Authors: Brigitte Michelsen, Joseph Sexton, Josef S Smolen, Daniel Aletaha, Niels Steen Krogh, Désirée van der Heijde, Tore K Kvien, Merete Lund Hetland
Journal: Annals of the Rheumatic Diseases (2018)

Objective To test the psychometric performance of a modified Disease Activity index for PSoriatic Arthritis (DAPSA) using 28 instead of 66 swollen/68 tender joint counts (SJC/TJC). Methods We included patients with psoriatic arthritis (PsA) from the Danish national quality registry DANBIO, divided into examination (n=3157 patients, 23987 visits) and validation cohorts (n=3154 patients, 24160 visits). We defined DAPSA28 = (28TJC × conversion factor 1 ) + (28SJC × conversion factor 2 ) + patient global (0–10VAS) + pain (0–10VAS) + C reactive protein (CRP) (mg/dL). Identification of the conversion factors was performed by generalised estimating equations in the examination cohort and evaluation of criterion, correlational and construct validity in the validation cohort. Results We estimated DAPSA28 = (28TJC × 1.6) + (28SJC × 1.6) + patient global (0–10VAS) + pain (0–10VAS) + CRP (mg/dL). Criterion validity: DAPSA/DAPSA28 had comparable discriminative power expressed as standardised mean difference (DAPSA, 0.90; DAPSA28, 0.93) to distinguish between patients in high and low disease activity. Kappa with quadratic weighting of DAPSA/DAPSA28 disease activity states was high: 0.92 (95% CI 0.92 to 0.92). Standardised response means for DAPSA/DAPSA28 were –0.96/–0.92 for visits after biological DMARD-initiation. Correlational validity: Baseline DAPSA/DAPSA28 had high correlation with 28-joint disease activity score with CRP (r=0.87/r=0.93), simplified disease activity index (r=0.92/r=0.99), p&lt;0.001. Bland-Altman plot showed better agreement between DAPSA/DAPSA28 for low than high disease activity. Construct validity: DAPSA/DAPSA28 were similarly correlated to Health Assessment Questionnaire; r=0.60/0.62, p&lt;0.001. DAPSA/DAPSA28 discriminated patients reporting their symptom state as acceptable versus not acceptable equally well: mean (SD) 9.1 (8.7)/8.4 (8.0) and 24.2 (14.9)/22.5 (13.8), respectively. Conclusion Our study suggests that data sets with only 28-joint counts available can be used to calculate DAPSA28, especially in patients with low disease activity. DAPSA28 showed good criterion, correlational and construct validity and sensitivity to change. Still, our results support that 66/68 joint count should be performed and the original DAPSA should be preferred in PsA.
Change of three-dimensional DW-MRI for primary tumor and cervical lymph nodes in head and neck cancer during radiotherapy: A phase II prospective study.
Authors: Mei Feng, Jinyi Lang, Fei Wu, Xiaochun Chen, Peng Xu, Yecai Huang, Lu Li, Jing Ren
Journal: Journal of Clinical Oncology (2017)

e17522 Background: DW-MRI become more important, recent study find it help to discriminate metastatic lymph node and distinguish recurrent tumor. However, we still poorly understand the dynamic change of it during treatment, especially for 3D-apparent diffusion coefficient (ADC). It is urgent to study the dynamic change of 3D-ADC for head and neck cancer during radiotherapy, and to investigate the correlation between the ADC change, radiation dose and volume reduction. Methods: 60 head and neck cancer patients treated with image guided IMRT were enrolled. DW-MRI were performed on 3.0T MRI (b = 0, 500, 800 s/mm 2 ) at pre-radiation, the 15 th , the 25 th and post-radiation. Region of interest was primary tumor (GTV-T) and cervical lymph node (GTV-N). The volumes and the maximum, mean and minimum of 3D-ADC value were automatically measured by MIM software. Pearson analysis was used to assess the correlation between 3D-ADC values, delivered radiation dose and tumor volume reduction. Results: All the patients exhibited the mean 3D-ADC increase in GTV-T (0.64±0.24 x10 -3 mm 2 /s) and GTV-N (0.35±0.09 x10 -3 mm 2 /s), with the mean increased ratios of 0.50±0.20 and 0.44±0.08 between pre- and post-radiation. However, the changes of the maximum and minimum 3D-ADC values for GTV-T and GTV-N had no correlation with delivered dose and volume reduction. The maximum, mean and minimum 3D-ADC changes in spinal cord were almost invisible (≤ 0.04 x10 -3 mm 2 /s). The increased mean ADC had a strong positive correlation with the increased radiation delivered dose for GTV-T and GTV-N respectively (r = 0.977, p= 0.023; r = 0.974 , p= 0.026), and a significantly negative correlation with the volume reduction (r = -0.989, p= 0.011; r = -0.969 , p = 0.031) . Conclusions: The mean 3D-ADC value of primary tumor and cervical lymph node can be increased greatly for head and neck cancer during radiotherapy. It had a strong negative correlation with the volume reduction, and a positive correlation with the increased delivered dose. Dynamic 3D-ADC changes during radiotherapy might be an early indicator to assess the treatment response and helps to make treatment strategy for head and neck cancer.
<i>PIK3CA</i> mutations are distinctive genetic features in non-small cell lung cancer (NSCLC) with chronic obstructive pulmonary disease (COPD): A comprehensive mutational analysis from multi-institutional cohort.
Authors: Kenji Sawa, Tomoya Kawaguchi, Yasuhiro Koh, Satoshi Kambayashi, Kazuhisa Asai, Shigeki Mitsuoka, Tatsuo Kimura, Naruo Yoshimura, Akihito Kubo, Hideo Saka, Akihide Matsumura, Noritoshi Nishiyama, Kazuto Hirata
Journal: Journal of Clinical Oncology (2017)

e20060 Background: A mutual developmental mechanism has been proposed between NSCLC and COPD; however, the association is not fully understood. We previously reported that the mutations in PI3K/AKT/mTOR pathway and NFE2L2 were frequently observed and co-existed in NSCLC patients with COPD (Kawaguchi T, J Clin Oncol 34, 2016 [suppl; abstr 8526]). To further validate this finding, a new cohort was added and merged into the original cohort’s study. Methods: A total of 197 surgical specimens of early stage NSCLC including 90 newly added from Osaka City University hospital were collected between 2010 and 2013. Extracted DNAs were deep-sequenced using NGS technologies for somatic mutations in 72 cancer-associated genes for a molecular profiling in NSCLC patients with COPD. We defined COPD as presence of FEV1/FEV &lt; 0.7 and classified the severity based on the Global Initiative for Chronic Obstructive Lung Disease. Results: The COPD group (N = 77) including 56 mild, 21 moderate/severe diseases, had 58 squamous cell carcinoma (SQ) and 19 adenocarcinoma (AD), with 70 smokers. The non-COPD group (N = 120) had 53 SQ, 64 AD and three others, with 78 smokers. The frequency of PIK3CA mutations was higher in COPD (10.4 %) than non-COPD (1.7 %), while in AD KRAS mutations were more frequent in COPD (21.1%) than non-COPD (9.4%). Notably, the frequency of PIK3CA mutations increased parallel to the COPD severity (p &lt; 0.001). Meanwhile, NFE2L2 mutations were observed only in SQ, and no difference in the frequency was observed between the two groups (17.2% vs. 17.0%) unlike our previous analysis. In the multivariate logistic regression model, significantly more PIK3CA mutations were observed in the presence of COPD (Odds ratio = 5.47, 95%CI: 1.04-28.85, p = 0.045) with consideration of age, smoking dose, histology and pathological stage. The most frequent base substitution pattern in PIK3CA mutations was C &gt; T change, suggesting the association with APOBEC-mediated mutagenesis. Conclusions: PIK3CA mutations are distinctive genetic features in NSCLC with COPD, regardless of age, smoking dose, histology and pathological stage.