tbuckley/cabot-search huggingface dataset:
Quantifying the health effects of climate change upon pollen allergy: a combined cohort and modelling study
Authors: Iain Lake, Felipe Colon, Natalia Jones
Journal: The Lancet Planetary Health (2018)

BackgroundGlobally, pollen allergy is a major public health problem, but a fundamental knowledge gap exists on the effect of climate change on pollen allergies. The annual herbaceous plant common ragweed (Ambrosia artemisiifolia) is highly invasive; it thrives on disturbed land, with each plant producing up to 62 000 seeds per year. Ragweed is particularly harmful for public health because each plant produces up to 1 billion grains per year. Our study aims to quantify the consequences of climate change on pollen allergy in people in Europe.MethodsWe used a process-based model to estimate the change in the distribution of ragweed plants across Europe under climate change. A second model simulated plant invasion, pollen production, pollen release, and the atmospheric distribution of pollen to estimate current and future ragweed pollen levels. These findings were translated into two different measures of health burden: pollen sensitisation rates and changes in allergy symptoms. Changes in pollen sensitisation rates were estimated using a dose–response curve generated from a systematic review and from current and future population data across Europe (baseline 1986–2005, future 2041–60). Changes in allergy symptoms were modelled by obtaining dose-response relationships between pollen and symptoms from a cohort of 85 sensitised individuals in Croatia. These relationships were then applied to future pollen loads, which considered two different regional climate and pollen models, two greenhouse gas emissions scenarios (representative concentration pathways 4·5 and 8·5), and three different plant invasion scenarios. A second set of health effects (sensitisation rates and allergy symptoms) were obtained from future pollen models.FindingsWe estimated that sensitisation to ragweed will more than double in Europe, from a baseline estimate of 33 million people (1986–2005) to 77 million by 2041–60. According to our projections, sensitisation will increase in countries with an existing ragweed problem (eg, by 27% in Hungary, 26% in Croatia, and 21% in Serbia), but the greatest proportional increases will occur where sensitisation is uncommon (an increase of 235% in Germany, 292% in Poland, and 231% in France). Higher pollen concentrations and a longer pollen season might also increase the severity of symptoms.InterpretationOur quantitative estimates indicate that ragweed pollen allergy will become a common health problem across Europe, expanding into areas where it is currently uncommon. Control of ragweed spread might be an important adaptation strategy in response to climate change.FundingThis project was supported by the European Community Framework programme 7, Atopica.
A model of an advanced practice provider led melanoma survivorship clinic at a NCI-designated cancer center.
Authors: Ro Henderson, Gary C. Doolittle
Journal: Journal of Clinical Oncology (2018)

41 Background: Melanoma cancer survivors present unique challenges for survivorship care due to their increasing numbers as well as the rapidly expanding options for adjuvant treatment including immunotherapy and targeted therapies for which the long term sequelae is relatively unknown. For this reason, the melanoma program at a NCI-designated cancer center elected to create an Advanced Practice Provider (APP) led dedicated Melanoma Survivorship Clinic. Methods: Patients are transferred to the APP led Melanoma Survivorship Clinic following the completion of definitive treatment for their cancer. The surgical and medical oncology specialists dedicated to the management of melanoma at this institution identify and include those requiring surgical intervention only as well as those who have received surgery followed by adjuvant treatment. Results: Patients meet with the APP who reviews the recommended stage specific National Comprehensive Cancer Network (NCCN) guidelines, completes and reviews the survivorship care plan (SCP). The SCP is provided to the patient and primary care provider. Patients continue to follow in the APP led clinic for at least the next 5 years to monitor for disease recurrence and the unique long term and late effects of new immune related and targeted agents. Surveillance includes history taking, physical examination including detailed skin examination, screening for genetic counseling, and Quality of Life tool. Imaging may be indicated if the patient develops symptoms that warrant or in those with higher risk disease . Five year risk of recurrence is calculated and reviewed using on-line tool. In addition, tools have been built in the electronic medical record to support documentation for melanoma survivorship patients as well as the SCP. Conclusions: Since its inception in March 2016, the APP led Melanoma Survivorship Clinic has been a successful collaboration between the APP, medical and surgical oncologists. There have been over 200 new survivorship patient referrals from surgical and medical oncology. Tools are continually modified and updated according to latest evidence, NCCN guidelines and SCP requirements.
Regorafenib tolerance and outcomes in inner-city minority colorectal cancer population.
Authors: Ahmed Tarig Ahmed, Sindhu Janarthanam Malapati, Barbara Yim, Sunny R K Singh, Shweta Gupta
Journal: Journal of Clinical Oncology (2018)

722 Background: Regorafenib (REG) is an oral multikinase inhibitor used for treatment of metastatic colon cancer after progression on fluorouracil, oxaliplatin and irinotecan therapy. The FDA approval was based on CORRECT trial showing improvements in progression-free survival (PFS) and overall survival (OS). Another trial (CONCUR) showed similar results. However, these trials included predominantly Whites and Asians. Our study aimed to evaluate treatment outcomes in the underserved, mainly African Americans and Hispanics. Methods: Cook County hospital is the 3rd largest public hospital in the US. All patients with an order for REG were identified from our pharmacy database. Charts were retrospectively reviewed for cancer stage, age, ethnicity, previous treatments, PFS and OS. Patients with non-colorectal cancer, incomplete data, no evidence of REG usage were excluded. Statistical analysis was done by t-test on subgroups. Results: A total of 42 patients were screened and 30 were included in the study. A comparison of outcomes with CORRECT and CONCUR trials is presented in Table 1. Our study patients, despite being less heavily pre-treated, had a worse OS compared to the clinical trials, with similar PFS. There was a trend towards better PFS and OS in women in our study of 4.3 and 4.8 months compared to men with 1.9 and 3.3 months respectively (p = NS). Six (20%) patients discontinued REG due to intolerance within a median of 1.2 months. The intolerant patients had a significantly higher median BMI of 31 compared to 24.9 for patients who continued the medication to progression (p = 0.019). Conclusions: Compared to CORRECT and CONCUR trials, population of predominantly AA and Hispanics showed a trend towards worse OS despite being less heavily pre-treated indicating worse outcomes in minorities treated with REG. Women showed better PFS and OS compared to men in our study. Patients unable to tolerate REG had significantly higher BMI, indicating a need to study dosing in this subgroup. [Table: see text]
A novel method for high precision aortic constriction that allows for generation of specific cardiac phenotypes in mice
Authors: Arne O Melleby, Andreas Romaine, Jan Magnus Aronsen, Ioanni Veras, Lili Zhang, Ivar Sjaastad, Ida G Lunde, Geir Christensen
Journal: Cardiovascular Research (2018)

Generation of reproducible cardiac disease phenotypes in mice is instrumental for investigating mechanisms leading to heart failure (HF). For decades, suture-based thoracic aortic constriction has been the preferred method for increasing left ventricular (LV) afterload in rodents, but the degree of stenosis resulting from this method is variable. In an effort to improve this methodology, we subjected mice to constriction of the ascending aorta using o-rings with fixed inner diameters (IDs).Mice of C57BL/6J and FVB/N background were subjected to constriction of the ascending aorta using o-rings with fixed IDs of 0.71, 0.66, and 0.61 mm. O-ring aortic banding resulted in 98.7% survival 2 weeks post-surgery, with very low intra- and inter-surgeon variation. When using the narrowest o-ring (0.61 mm), mice developed hypertrophy within 1 week. Over 20 weeks, the mice gradually developed reduced LV ejection fraction (LVEF) and dilatation with increased left atrial dimensions and lung weight, indicating congestion. When using o-rings with IDs of 0.66 mm and 0.71 mm, the mice developed hypertrophy, but maintained a compensated state with stabilized LVEF 8-20 weeks post-surgery. The up-regulation of signature genes associated with HF, hypertrophy, fibrosis, and the level of activation of MAPK and NFAT signalling pathways corresponded to the degree of stenosis.Here, we introduce a novel method for high precision aortic constriction in mice with high intra- and inter-surgeon reproducibility and low post-operative mortality that allows generation of specific cardiac disease phenotypes.
Association of clinical/pathological parameters with axillary involvement in early breast cancer in patients with limited sentinel node involvement (&lt; 3 LK) after neoadjuvant chemotherapy (NACT).
Authors: Hans-Christian Kolberg, Cornelia Liedtke, Ingo Bauerfeind, Tanja N. Fehm, Barbara Fleige, Maik Hauschild, Gisela Helms, Annette Lebeau, Sabine Schmatloch, Peter Schrenk, Lukas Schwentner, Annette Staebler, Gunter Von Minckwitz, Sibylle Loibl, Michael Untch, Thorsten Kühn
Journal: Journal of Clinical Oncology (2018)

559 Background: The association between pathological complete remission (pCR) in the breast and clinical/pathological parameters is well established, whereas the association of clinical/pathological parameters and residual axillary involvement after NACT is still not sufficiently defined. We used data from the SENTINA trial to analyze this association in a patient population with limited sentinel lymph node (SLN) involvement. Methods: Patients were included if before NACT they presented with a clinically negative axilla but showed involvement of SLNs prior to NACT (Arm B). Analysis was restricted to patients with < 3 involved SLNs before NACT. All patients received SLNB and axillary dissection after NACT. Univariate and multivariate analyses were carried out to evaluate the association between clinical/pathological parameters and axillary involvement after NACT. Results: Arm B of the SENTINA study contained 360 patients, 265 of which were evaluable with respect to the above parameters. After NACT 66/265 (24.9%) patients had involved SLNs or non-SLNs after NACT; 71/265 (26.8%) achieved a pCR in the breast. We observed a significant association between pCR in the breast and ER negativity (p < 0.0001), PR negativity (p < 0.0001) and triple negative (TN) status (p = 0.001). However, no statistically significant association between residual axillary involvement after NACT and clinical/pathological parameters ER (p = 0.381), PR (p = 0.52), HER2 (p = 0.771), TN status (p = 0.937), grade (G) 1 (p = 0.081), G 2 (p = 0.335), G 3 (p = 0.747), age (p = 0.789), tumor size before NACT (p = 0.761) and pCR in the breast (p = 0.136) could be demonstrated. Conclusions: Our analysis demonstrates that patients enrolled in the SENTINA trial with clinically negative axilla but limited SLN involvement show positive axillary nodes in 24.9% of cases after NACT. We found no association between residual axillary involvement after NACT and clinical/pathological parameters. We could not identify a subset of patients in this cohort for whom axillary surgery after NACT could be safely omitted.
Are women with head and neck cancer undertreated?
Authors: Annie Park, Amy Albaster, Hanjie Shen, Loren K. Mell, Jed Abraham Katzel
Journal: Journal of Clinical Oncology (2018)

LBA6002 Background: Generalized competing event (GCE) models have been used to stratify patients with cancer according to their relative hazard for cancer death versus death from other causes. We evaluated outcomes for head and neck cancer (HNC) patients treated at Kaiser Permanente Northern California (KPNC) based on demographic data and comorbidities using a GCE model. Methods: We identified 884 HNC patients diagnosed 2000-2015 from the KPNC cancer registry, age 18-85 and stage II-IVB by AJCC 7 th edition. Using the GCE proportional relative hazards model, controlling for age, sex, tumor site, and Charlson comorbidity index (CCI), we identified associations between these factors and the relative hazard for HNC-specific mortality (ω+ ratio, ‘gcerisk’ package in R). Death, disenrollment, and end of study (12/31/2016) were used as censoring events. Logistic regression models estimated the odds of receiving intensive treatment (platinum based regimen), adjusting for the same covariates plus stage, smoking, and alcohol abuse history. Results: With a median follow-up of 2.9 years, 271 patients died of cancer, and 93 of non-cancer causes. Compared to male, females were less likely to receive intensive chemotherapy (35% vs. 46%, p = 0.006) and radiation (60% vs. 70%, p = 0.008). On GCE analysis, female patients had an increased relative hazard ratio (RHR) for death from HNC vs. other causes (adjusted RHR 1.92; 95% CI 1.07-3.43), indicating they may be relatively undertreated. Conclusions: Female patients in our cohort may be undertreated in clinical practice, potentially missing the opportunity to aggressively treat their HNC. This study supports the use of a GCE methodology to objectively identify patients more likely to benefit from treatment intensification. These findings may help guide future research in health disparities.[Table: see text]
Procalcitonin-guided antibiotic therapy in patients with fever in a general emergency department population: a multicentre non-inferiority randomized clinical trial (HiTEMP study)
Authors: Y. van der Does, M. Limper, K.E. Jie, S.C.E. Schuit, H. Jansen, N. Pernot, J. van Rosmalen, M.J. Poley, C. Ramakers, P. Patka, E.C.M. van Gorp, P.P.M. Rood
Journal: Clinical Microbiology and Infection (2018)
Prevalence and predictors of androgen receptor (AR) and programmed death-ligand 1 (PD-L1) expression in <i>BRCA1</i>-associated and sporadic triple negative breast cancer (TNBC).
Authors: Nadine M. Tung, Judy Ellen Garber, Vanda Torous, Michele R Hacker, Gordon James Freeman, Scott J. Rodig, Emily Poles, Brian Michael Alexander, Larissa Janeen Lee, Laura C. Collins, Stuart J. Schnitt
Journal: Journal of Clinical Oncology (2015)

1005 Background: TNBC comprise 15% of breast cancers and are more common in women with germline BRCA1 mutations. However, considerable heterogeneity exists among TNBC. While most have basal cell gene expression signatures, others resemble luminal tumors with expression of AR-related genes. In addition, a subset of TNBC expresses the immunoinhibitory protein PD-L1. Given the availability of clinical trials evaluating AR-targeted and immune therapies in TNBC, determining predictors of AR and PD-L1 expression and whether expression differs by BRCA1 status is of interest. Methods: We studied 197 TNBC: 78 (39.6%) from women with germline BRCA1 mutations (BRCA1+) and 119 (60.4%) from women without a BRCA1 mutation (sporadic). Histologic type, grade, lymphovascular invasion (LVI), and lymphocytic infiltrates (LI) were evaluated on H and E sections. Tissue microarrays were constructed (three 0.6mm cores/tumor) and sections were immunostained for AR, PD-L1, CK5/6, CK14 and EGFR (to define basal features). Adjusted odds ratio (OR) are presented. Results: Among 194 TNBC with AR results, 18.0% were AR-positive (AR+; ≥ 1% nuclei staining) and 11.3% strongly AR+ ( ≥ 10% nuclei staining). Among 193 TNBC with PD-L1 results, 26% were PD-L1+ ( ≥ 1% cancer cells staining). BRCA1+ TNBC were less often AR+ than sporadic TNBC (9.2% vs 23.7%; p = 0.01). There was no significant difference in PD-L1 positivity between BRCA1+ and sporadic TNBC (p = 0.35). LI were more common in BRCA1+ than sporadic TNBC (OR, 3.0; 95% CI, 1.1-8.0). PD-L1+ TNBC were more likely to be AR+ (OR, 2.6; 95% CI, 1.1-6.1). Grade 1 or 2 TNBC (OR, 4.6; 95% CI, 1.1-19.7) and TNBC in older women (OR, 1.3; 95% CI 1.03-1.7 for each 5 years of age) were more likely to be strongly AR+. Both LI (OR, 3.3; 95% CI, 1.1-10.4) and AR positivity (OR, 3.2; 95% CI, 1.4-7.5) were associated with PD-L1 positivity, while TNBC with LVI (OR, 0.41; 95% CI, 0.18-0.92) were less likely to be PD-L1+. Conclusions: BRCA1+ TNBC are significantly less often AR+ than sporadic TNBC. The frequency of PD-L1+ TNBC does not differ by BRCA1 status. These results confirm the heterogeneity of TNBC and highlight differences between BRCA1+ and sporadic TNBC.
BYLieve: A phase II study of alpelisib (ALP) with fulvestrant (FUL) or letrozole (LET) for treatment of <i>PIK3CA</i> mutant, hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2<i>–</i>) advanced breast cancer (aBC) progressing on/after cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) therapy.
Authors: Hope S. Rugo, Giulia Valeria Bianchi, Stephen K. L. Chia, Nicholas C. Turner, Dejan Juric, William Jacot, Manuel Ruiz Borrego, Linnea I. Chap, Ursa Abigail Brown-Glaberman, Carolyn C. Nienstedt, Nikos Sophos, Antonia Ridolfi, Chinjune Lin, Eva Ciruelos
Journal: Journal of Clinical Oncology (2018)

TPS1107 Background: Endocrine therapy (ET) is the standard of care for treatment of HR+, HER2– aBC. However, ET resistance occurs frequently due to dysregulation of the PI3K/AKT/mTOR pathway, specifically mutations in PIK3CA, the gene encoding the p110alpha subunit of PI3K. In a phase 1 study, ALP, a PI3Kα-specific inhibitor, in combination with FUL has shown antitumor activity in patients (pts) with PIK3CA mutant, HR+, HER2– aBC. The ongoing phase 3 SOLAR-1 trial (NCT02437318) is evaluating ALP + FUL combination in HR+, HER2– aBC. The present BYLieve study aims to assess the efficacy and safety of ALP + FUL/LET in PIK3CA-mutant, HR+, HER2– aBC progressing on/after prior CDK4/6i combination therapy. Methods: BYLieve is a phase 2, multicenter, open-label, 2-cohort, non-comparative study. Men and women (pre-menopausal and post-menopausal; ≥18 years) with PIK3CA-mutant, HR+, HER2− locally advanced or metastatic breast cancer that has progressed on/after prior CDK4/6i combination therapy are eligible. Other eligibility criteria include ≥1 measurable lesion (RECIST v1.1) or predominantly lytic bone lesion; ECOG PS ≤2; ≤1 line of prior chemotherapy in the advanced setting; and no prior PI3K inhibitor therapy. Pts are allocated to 2 cohorts; cohort A (pts who had received CDK4/6i + aromatase inhibitor): oral ALP (300 mg QD) + intramuscular FUL (500 mg) and cohort B (pts who had received CDK4/6i + FUL): oral ALP (300 mg QD) + oral LET (2.5 mg QD). The primary end point is the proportion of pts who are alive without disease progression at 6 months (RECIST v1.1; local assessment), and will be evaluated separately in each cohort. Evidence of treatment effect will be demonstrated if the lower bound of the 90% CI is greater than 30% with a planned sample size of 80 pts in each cohort. Secondary end points include progression-free survival (PFS), PFS on next-line treatment (PFS2), overall response rate, clinical benefit rate, duration of response, safety, and tolerability. Recruitment of the planned 160 pts is currently ongoing. Clinical trial information: NCT03056755.
Effect of cytoreductive surgery and HIPEC on survival in comparison to palliative chemotherapy for biliary carcinoma with peritoneal metastasis: A multi-institutional cohort from PSOGI and BIG RENAPE groups.
Authors: Frederic Mercier, Iris Amblard, David L. Bartlett, Edward Allen Levine, Dario Baratti, Pompiliu Piso, David L. Morris, Beate Rau, Antonios Apostolos K Tentes, Jean-Jacques Tuech, Francois Quenet, Eduardo Hiroshi Akaishi, Marc Pocard, Yutaka Yonemura, Gerard Lorimier, Delphine Delroeux, Laurent Villeneuve, Olivier Glehen, Guillaume Passot
Journal: Journal of Clinical Oncology (2018)

418 Background: Peritoneal metastasis from biliary carcinoma (PMC) is associated with poor prognosis when treated with chemotherapy. The objective was to evaluate the impact on survival of cytoreduction surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), and compare with conventional palliative chemotherapy for patients with PMC. Methods: A prospective multicenter international database was retrospectively searched to identify all patients with PMC treated with a potentially curative CRS/HIPEC (CRS/HIPEC group). The overall survival (OS) was compared to patients with PMC treated with palliative chemotherapy (systemic chemotherapy group). Survival was analyzed using Kaplan-Meier method and compared with Log-Rank test. Results: Between 1995 and 2015, 34 patients were included in the surgical group, and compared to 21 in the medical group. In the surgical group, median peritoneal cancer index was 9 (range 3-26), macroscopically complete resection was obtained for 25 patients (73%). There was more gallbladder localization in the surgical group compared to the medical group (35% vs. 18%, p= 0.001). Median OS was 21.4 and 9.3 months for surgical and medical group, respectively (p =0.007). Three-year overall survival was 30% and 10% for surgical and medical group, respectively. Conclusions: Treatment with CRS and HIPEC for cholangiocarcinoma with peritoneal metastasis is feasible and may provide survival benefit when compared to palliative chemotherapy.