tbuckley/cabot-search huggingface dataset:
Can a surgeon be a good couselor for ovarian and endometrial cancer patients regarding Lynch syndrome and Hereditary Breast and Ovarian Cancer syndrome?
Authors: Soo Hyun Kim, Min Kyu Kim
Journal: Journal of Clinical Oncology (2015)

e12509 Background: Lynch syndrome and hereditary breast and ovarian cancer (HBOC) are the two most common hereditary cancer syndromes. Finding mutation carrier has advantage in cancer prevention and cancer management. There is not much data about effectiveness of early counseling by surgeon among gynecologic malignancy about Lynch syndrome and HBOC. We undertook this study to find it Methods: This study examined 30 patients diagnosed with ovarian and endometrial cancers operated and counseled by a single surgeon prospectively. All patients were provided early genetic counseling based on immunohistochemistry (IHC) of MSH2, MLH1, BRCA1, BRCA2 and family history of cancer after pathology. Additionally, genetic sequencing to verify germ line mutations was performed after patient consent was obtained. Results: There were 19 ovarian and 11 endometrial cancer patients in this study. The number of patients with negative IHC results for MLH1/MSH2/BRCA1/BRCA2 were 0 (0%), 2 (7%), 14 (52%), and 3(11%) respectively. Nine patients refuse approval. There were 3 patients (10%) with germ line mutations (two with HBOC and one with Lynch syndrome). Conclusions: Our data indicate approximately 10% of the patients have a germ line mutation. Gynecologic oncologist can be a better counselor in finding hereditary mutation carrier of Lynch syndrome and HBOC among ovary and endometrial cancer patients.
Salvage therapy with lomustine for temozolomide refractory recurrent anaplastic astrocytoma: A retrospective study.
Authors: Marc C. Chamberlain
Journal: Journal of Clinical Oncology (2015)

e13023 Background: There is no standard therapy for recurrent anaplastic astrocytoma (AA). Assess response and toxicity of lomustine (CCNU) in recurrent AA following prior surgery, radiotherapy and TMZ in a retrospective case series. Methods: 35 adults (18 males; 17 females: median age 42.5 years) with TMZ refractory recurrent AA were treated with lomustine. 7 patients were treated at 1st recurrence and 28 patients were treated at second recurrence. Prior salvage therapy included re-resection in 19, TMZ in 20 and radiotherapy in 7. A cycle of lomustine was defined as 100mg/m2 on day 1 only administered once every 6-8. Success of treatment was defined as progression free survival at 6 months of 40% or better. Results: Grade 3 or 4 toxicities included anemia (14 patients), constipation (1), fatigue (4), lymphopenia (5), nausea/vomiting (2), neutropenia (8) and thrombocytopenia (10). No grade 5 toxicities were seen. The median number of cycles of therapy was 3 (range 1-6). Best radiographic response was progressive disease in 14 (40%), stable disease in 19 (54%) and partial response in 2 (5.7%). Median progression free survival (PFS) was 4.5 months (range 1.5-12 months), 6-month PFS was 40% and 12 month PFS was 11.4%. Median survival after onset of CCNU was 9.5 months (range 2.5-15 months). Median overall survival was 2.7 years (range 1.7-4.3). Conclusions: In this small retrospective series of patients with recurrent AA refractory to TMZ, lomustine appears to have modest single agent with manageable toxicity. Confirmation in a larger series of similar patients is required.
Digital Hemodynamics in the Normotensive and Hypertensive States
Authors: FRANCIS S. CALIVA, RUDOLPH J. NAPODANO, RICHARD H. LYONS
Journal: Circulation (1963)

By use of the technic of rheoplethysmography, it has been demonstrated that the small veins and venules participate in the over-all increase in peripheral resistance in hypertension. An arbitrary grading of the degree of venomotor tone in hypertension has been established.
Abstract P264: Metal Exposures and Preeclampsia in the Boston Birth Cohort
Authors: Tiange Liu, Mingyu Zhang, Eliseo Guallar, Guoying Wang, Xiumei Hong, Xiaobin Wang, Noel T Mueller
Journal: Circulation (2019)

Introduction: Preeclampsia is a leading cause of maternal and perinatal morbidity and mortality, accounting for 50,000-60,000 deaths per year worldwide. Animal studies have linked metal exposures to its development but epidemiologic studies have had inconsistent findings. We assessed the associations between metal exposures and preeclampsia in a prospective cohort. Methods: A total of 1,346 women from the Boston Birth Cohort (enrolled from 1998 to 2018) had complete data on the exposures and outcome and were free of both chronic and gestational hypertension. Metal exposures, including manganese (Mn), cadmium (Cd), lead (Pb), mercury (Hg), and selenium (Se) were measured from red blood cells (RBCs) collected within 1 to 3 days after delivery. Preeclampsia (including HELLP syndrome) diagnosis was ascertained from medical records. Logistic regression models were fitted for each metal. Covariates adjusted for included age at delivery, race, pre-pregnancy body mass index, education, parity, and smoking status during pregnancy. Results: A total of 119 (8.84%) women developed preeclampsia. A 1 standard deviation (SD) (15.42 μg/L) increase in RBC Mn was associated with a 0.71 (95% confidence interval (CI): 0.56, 0.90) times lower odds of preeclampsia. Compared to the 1 st quintile of RBC Mn, the 5 th quintile was associated with 0.39 (95% CI: 0.20, 0.76) times lower odds of preeclampsia. In contrast, a 1 SD (0.68 μg/L) increase in RBC Cd was associated with a 1.17 (95% CI: 0.94, 1.46) times higher odds of preeclampsia, and the odds for the 5 th quintile of RBC Cd was 2.04 (95% CI: 1.03, 4.04) times higher than the 1 st quintile (Figure) . Null associations were observed for RBC Pb, Hg and Se. Conclusion: RBC Mn was associated with lower odds of preeclampsia, while Cd was associated with higher odds. Findings from this study help elucidate potentially modifiable causes of preeclampsia and inform interventions to reduce the burden of this important pregnancy complication.
Development of cost and quality composites for the 2012 ASCO Choosing Wisely measures: Methods and evidence.
Authors: Melora K Simon, Arnold Milstein, Karma L. Kreizenbeck, Catherine R. Fedorenko, Scott David Ramsey
Journal: Journal of Clinical Oncology (2015)

6512 Background: Oncology clinics, health care systems, and payers are considering how to gauge performance for the ASCO Choosing Wisely (CW) program. We sought to develop a clinic-level composite CW metric that accounts for adherence to the 2012 CW measures. We also measured total cost of care. Methods: SEER cancer registry records for western Washington State from January 2007 to May 2014 were linked with claims from a large regional commercial insurer to develop algorithms to characterize each CW measure and assign patients to their primary oncology provider. In addition, a time-based episode was developed to capture total cost of care related to each CW measure. For each clinic, we looked at the observed to expected ratio across the CW measures and the total cost of care measures, with expected defined as the average clinic rate for each measure. A composite score for each was derived by dividing the weighted observed/expected ratio by the clinic volume. Results: Among the 14 clinics with the highest patient volume, the number of eligible commercially insured patients ranged from 531 to 1532 depending on the CW measure. Clinic scores on the CW measures ranged from 25% to 100%. The observed to expected adherence composite scores ranged from 0.77 to 1.13 (SD-0.11) while the cost composite scores ranged from 0.68 to 1.40 (SD-0.21). Adherence and cost of care were not well-correlated. Three clinics had better than expected composite adherence score and lower than expected costs. We identified these as “high value outliers.” Five clinics had better than expected composite adherence score and higher than expected costs. 3 clinics each had lower than expected composite adherence scores and either higher or lower than expected costs. Conclusions: Identifying high performing clinics using individual CW metrics is complex - clinics vary widely in their adherence across metrics. We intend to assess convergence between the composite score and expert opinion through site visits, while using a similar approach in other geographies to increase our sample. Our composite score approach may assist decision makers in identifying the best clinics. To better gauge value, costs of care should also be considered alongside performance.
Determining viability of using APNG status as a prognostic marker in patients with glioblastoma multiforme.
Authors: Rikke Hedegaard Dahlrot, Sofie Hellwege, Sigurd Fosmark, Kristian Lindstroem Jensen, Jesper Lohse, Helene Derand, Jacob Hjelmborg, Steinbjorn Hansen, Bjarne Winther Kristensen
Journal: Journal of Clinical Oncology (2015)

2028 Background: Expression of the enzyme alkylpurine-DNA-N-glycosylase (APNG) has been associated with poor outcome in patients with glioblastoma multiforme (GBM). APNG is part of the base excision repair system, and expression of APNG is related to resistance towards temozolomide (TMZ). This study evaluates the prognostic value of APNG in a population-based cohort of 185 Danish GBM patients diagnosed between 2005 and 2009. Due to GBM’s cellular heterogeneity, APNG contribution from non-tumor cells was excluded. Methods: APNG expression was evaluated using image analysis and a novel quantitative immunohistochemical (IHC) assay (qIHC, Dako), where APNG protein levels were represented through dots. Non-tumor cells, which were found to express APNG, were excluded using an IHC/qIHC double-staining. To verify the qIHC results, APNG was measured in 177 of the patients using a quantitative in-house developed APNG immunofluorescence (IF) assay. MGMT methylation status was obtained in 152 patients by pyrosequencing. Results: Using qIHC, median expression of APNG was 0.31 dots/cell (range 0.099-0.96). An optimal cut-point was identified dichotomizing the patients at an APNG value of 0.24 (25% vs. 75% of the patients). In Cox regression high expression of APNG was associated with better overall survival (OS) (HR 0.53, p = 0.001) adjusting for the effect of age, performance status, tumor crossing midline, treatment and gender. APNG was associated with better OS (HR 0.57, p = 0.012) when adjusting for MGMT status. Retesting the cohort using IF, demonstrated similar results (HR 0.81, p = 0.2). Patients with methylated MGMT promoters and high APNG expression demonstrated a better OS, than with non-methylated MGMT promoters and low APNG expression (HR 0.55, p = 0.04). Conclusions: APNG measured by qIHC was found to be an independent significant prognostic factor for OS in GBMs, This was supported by IF measurements. Removing bias associated with APNG expression in non-tumor cells in both assays has, in this study contributed substantially to analyze the prognostic value of APNG in GBM patients. We expect that APNG qIHC can potentially identify patients who will not benefit from treatment with TMZ.
Abstract P001: Greater Time Spent in Ideal Cardiovascular Health in Adulthood is Associated With Lower Risk of Cardiometabolic Outcomes and Death: the Framingham Heart Study
Authors: Laura Corlin, Meghan I Short, Ramachandran S Vasan, Vanessa Xanthakis
Journal: Circulation (2019)

Introduction: The AHA ideal cardiovascular health (CVH) metric evaluated on a single occasion is associated with risk of cardiovascular disease (CVD). It is unclear if greater time spent in ideal CVH during midlife influences morbidity and mortality. Hypothesis: We hypothesized that maintenance of ideal CVH for a longer duration in midlife is associated with lower risk of hypertension, diabetes mellitus, chronic kidney disease (CKD), atrial fibrillation, CVD, CVD sub-types (coronary heart disease, stroke, congestive heart failure, and peripheral artery disease), and all-cause mortality. Methods: We evaluated 2609 Framingham Offspring Study participants (mean age 61 years; 54% women) who attended examination cycle 7 [1998-2001]. CVH scores were calculated using smoking status, diet, physical activity, total serum cholesterol, resting blood pressure, body mass index, and fasting blood glucose for a total score of 0-14 (score of 0-7 = poor; 8-11 = intermediate; 12-14 = ideal). We determined time spent in each CVH score category during midlife (using data from examination cycles 5 [1991-1995] through 7 (6426 person-exams). Incident hypertension, diabetes, and CKD were assessed at sequential follow-up examinations whereas incident atrial fibrillation, CVD, CVD sub-types, and mortality were assessed based on continuous surveillance through 2015. Years spent in a given CVH score category were related to each outcome using proportional hazards regression with discrete (for hypertension, diabetes, and CKD) or continuous (other outcomes) time, adjusted for age, sex, and baseline values (e.g., fasting blood glucose for diabetes). Results: At examination 7, participants mostly had poor (40%) or intermediate (54%) CVH scores. For each 5-year duration that participants had poor CVH, they were more likely to develop adverse outcomes (Figure). Conclusions: Maintenance of ideal CVH for a longer duration in midlife may have salutary cardiometabolic benefits and be associated with a lower risk of all-cause mortality.
Venous thrombotic events in patients with glioblastoma.
Authors: Diogo D'Agoretta D'Alpium Santos Costa, Daniel Romeira, Mariana Fernandes Valente, Joao Passos, Susana Esteves, Alexandra Mayer, Ana Azevedo, Jose Bravo Marques
Journal: Journal of Clinical Oncology (2015)

e13059 Background: Venous thrombotic events (VTE) are common throughout the course of disease in glioblastoma (GBM) patients (pts). Postoperative long-term risk of VTE has been reported to be 7%-28% over a 1 year-period. A widerange of factors (individual, tumor, treatment, and humoral) have been associated with increased risk of venous thrombosis. The aim of this study was to describe the occurrence of VTE in pts with GBM being treated in a single tertiary comprehensive cancer care center. Methods: 5-year (2009-2014) retrospective cohort analysis of 100 pts with histologically confirmed GBM. Medical records were reviewed for demographics, location, histopathology, VTE and treatment strategies. Kaplan-Meier analysis was used to estimate survival. Results: Pts median age was 64.8 years [34-87], mostly male (61%), with an initial Karnofsky performance status (PS) of 100-80 (47%), 70-50 (43%) and 40-30 (10%). 5% had long-term anticoagulant prophylaxis (without previous VTE). 33% of pts presented with a tumor size larger than 5 cm (59% less than 5 cm and 5% not specified). Histologically, 3% were GBM with oligodendroglial component; 32% had intraluminal thrombosis. 88% of pts were initially treated with surgery (partial or gross total resection), and 52%, 35%, 1% with adjuvant chemoradiotherapy, radiotherapy and chemotherapy, respectively. The median follow-up, overall survival and progression free survival were 8.33 months, 8.62 months and 5.57 months, respectively. We found 21 VTE, corresponding to 18 pts: 5 pulmonary embolisms and 16 deep vein thrombosis (DVT); 3 pts had recurrent DVT. The median time between GBM diagnosis and VTE was 72 days [0-829]. Comparing these pts with the others without VTE, PS was 10% lower; there were more comorbidities; tumours were not larger ( > 5 cm: 33% versus 31%), but had more intraluminal thrombosis (50% versus 28%), and treatment with bevacizumab was more frequent (17% versus 10%). Conclusions: Further studies are needed to evaluate the impact of the several risk factors for VTE in this population. In the future, it would be useful to validate a simple score system that could individually stratify pts according to their VTE risk, and optimize thromboprophylaxis.
Specific SUV cut-off value with <sup>18</sup>F-FDG PET/CT for the diagnosis of lymph node involvement in penile cancer patients: A proof-of-concept.
Authors: Andre Salazar, Lucas Nogueira, Raul Silva Filho, Joao Paulo Solar Vasconcelos, Paulo GUilherme Oliveira Salles, Guilherme Catizane, Wadson Miconi, Carlos Corradi, Walter Cabral, Marcelo Mamede
Journal: Journal of Clinical Oncology (2015)

e15630 Background: Lymph node involvement is the main prognostic factor in penile cancer patient. CT scan, a morphologic-based changes imaging, is used to evaluate LN enlargement with limited clinical applicability due to micrometasis and LN proliferative reaction. 18F-FDG PET/CT has been used to evaluate lymphatic involvement in penile cancer patient with promising results. However, inflammatory reaction can reduce accurate metastatic LN detection. Thus, the present study was aimed to evaluate the accuracy of 18F-FDG PET/CT (PET) to diagnose histopathologic confirmation of LN involvement using an specific SUV cut-off value versus contrast enhanced CT (ceCT). Methods: Forty patients with histopathologic confirmation of SCC penile cancer whom underwent PET and ceCT from Oct/2012 to Oct/2014 were analyzed. Metastatic LN with PET was assessed using a cut-off value of SUVlbm > 7.1 based on the ROC analyses (AUC = 0.769, sensibility = 62.3% and specificity = 83.9%). As for ceCT, LN involvement was considered positive with a short axis greater than 10mm. Results: Among the 40 selected patients, 20 underwent LNs dissection for histopatologic confirmation. Thirty-eight lymph node chain dissections were included in the present study. ceCT identified 11/12 of LN+ and 13/26 of LN-, resulting in a sensibility, specificity, PPV, NPV and accuracy of 91.7%, 50.0%, 45.8%, 92.9% and 63.2%, respectively. PET with a cuf-off value of SUV > 7.1 showed better results with 12/12 LN+ and 20/26 LN-, resulting in a sensibility, specificity, PPV, NPV and accuracy of 100.0%, 76.9%, 66.7%, 100.0% and 84.2%, respectively. Conclusions: LN morphometric changes by ceCT are useful but not reliable imaging technique for detection of LN involvement. 18F-FDG PET/CT is an emerging methodology in penile cancer. The present study is a prove-of-concept where, by using 18F-FDG PET/CT with an specific cut-off value (SUV > 7.1), we were able to improve LN detection in a prospective study compare to ceCT.
Analysis of overall survival (OS) based on early tumor shrinkage in the phase III METEOR study of cabozantinib (cabo) versus everolimus (eve) in advanced renal cell carcinoma (RCC).
Authors: Ignacio Duran, Pablo Maroto, Cristina Suárez, Daniel E. Castellano, Xavier Garcia del Muro, Luis Costa, Lidia Martin-Couce, Fawzi Benzaghou, Stephane Thomas, David W. Markby, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2019)

550 Background: In the phase 3 METEOR study (NCT01865747), cabo improved OS (median 21.4 vs 16.5 mo; HR, 0.66; 95% CI, 0.53–0.83), progression-free survival and objective response rate compared with eve in patients (pts) with previously treated advanced RCC (Choueiri 2016). Retrospective studies have shown that early tumour shrinkage (eTS), based on target lesion reduction from baseline to first post-baseline scan, has predictive value for targeted therapies in RCC (Grunwald 2015; Grunwald 2016); here we evaluate its impact on OS in METEOR. Methods: In total, 658 pts were randomized 1:1 to receive cabo (60 mg qd) or eve (10 mg qd), stratified by MSKCC risk group and number of prior VEGFR TKIs. Target lesion size was assessed by independent radiology review using CT/MRI scans at baseline, every 8 wk for the first 12 mo and every 12 wk thereafter. Median OS was estimated for pts with ≥30% eTS, any eTS or no eTS at first post-baseline scan (week 8); data cutoff, 2 October 2016 (Motzer 2018). Results: Median follow-up was 28 mo (IQR 25, 30). Median (range) time to objective response was 1.91 (1.6, 11.0) mo with cabo and 2.14 (1.9, 9.2) mo with eve, and corresponded to the time to the first post-baseline scan. A greater proportion of pts had ≥30% eTS with cabo (20%) than with eve (5%) and the rate of any eTS was higher in the cabo arm (73%) than with eve (47%; Table). Median OS with cabo vs eve for pts with ≥30% eTS was not reached (NR; 95% CI, 23.7–NR) vs 10.2 mo (95% CI, 3.9–NE), respectively (stratified HR, 0.45; 95% CI, 0.21–0.95; p&lt;0.05). Median OS with cabo vs eve for pts with any eTS was 23.7 (95% CI, 21.7–27.7) vs 17.3 mo (95% CI, 15.4–20.8), respectively; (stratified HR, 0.62; 95% CI, 0.48–0.80; p&lt;0.05). OS was similar for cabo and eve for pts with no eTS. Conclusions: Cabo demonstrated a higher rate and greater magnitude of eTS at first post-baseline scan compared with eve, and eTS was associated with prolonged OS in pts treated with cabo. Clinical trial information: NCT01865747. [Table: see text]
A microparticle platform for STING-targeted immunotherapy enhances natural killer cell- and CD8+ T cell-mediated anti-tumor immunity
Authors: Rebekah Watkins-Schulz, Pamela Tiet, Matthew D. Gallovic, Robert D. Junkins, Cole Batty, Eric M. Bachelder, Kristy M. Ainslie, Jenny P.Y. Ting
Journal: Biomaterials (2019)
Preoperative chemoradiotherapy for locally advanced rectal cancer: Multicenter phase II clinical trial.
Authors: Takahiro Hiratsuka, Tomonori Akagi, Shinichiro Empuku, Kentaro Nakajima, Yoshitake Ueda, Manabu Tojigamori, Hidefumi Shiroshita, Tsuyoshi Etoh, Shigeo Ninomiya, Kazuaki Hiroishi, Fumitaka Yoshizumi, Yu Takeuchi, Atsushi Sasaki, Koichiro Tahara, Kyuzo Fujii, Akio Shiromizu, Koichi Ishikawa, Toshifumi Matsumoto, Toshio Bando, Masafumi Inomata
Journal: Journal of Clinical Oncology (2015)

e14612 Background: Fluorouracil-based chemoradiotherapy (CRT) is regarded as a standard perioperative treatment in locally advanced rectal cancer. We investigated the efficacy and safety of substituting fluorouracil with the oral prodrug TS-1. Methods: A multi-institutional (17 specialized centers), interventional phase II trial, was conducted from April 2009 to August 2011.This study is registered with UMIN-CTR, number C003396. For inclusion, patients must fulfill the following requirements before neoadjuvant CRT: (i) histologically proven rectal carcinoma; (ii) tumor located in the rectum (upper, lower); (iii) cancer classified as T3-4, N0–3 and M0; Two cycles of neoadjuvant CRT with TS-1 (100 mg/m2 on days 1-5, 8-12, 22-26, and 29-33) is administered, and irradiation (total 45Gy/25fr, 1.8Gy/day, on days 1-5, 8-12, 15-19, 22-26, and 29-33) is performed. Total mesorectal excision with D3 lymphadenectomy is performed during the 4th and 8th week after the end of the neoadjuvant CRT. The primary endpoint is rate of complete treatment of neoadjuvant CRT. Secondary endpoints are response rate of neoadjuvant CRT, short-term clinical outcomes, rate of curative resection, and pathological response (grade2/3). Results: This trial included 37 patients. A complete treatment of neoadjuvant CRT was found in 86.5% of patients (95%CI;75.5`97.5%), and an adverse event (grade 3/4) occurred in 4 patients(11.1%). Response rate (PR/CR;RECIST 1.0) was 56.8% (95%CI; 40.8`72.7%), and pathologic response rate (grade2/3) was 48.6% (95%CI; 32.5`64.8%). The median operating time was 448.5 min (IQR 340.5-505.5), and median blood loss was 422.5 mL (IQR 182.5-1125). Grade 3-4 postoperative complications occurred in 6 (16.7%) patients. The most common grade 3 or 4 postoperative complication was anastomotic leakage (2 [5.6%]). Conclusions: Our prospective phase-II study demonstrated that a neoadjuvant-synchronus TS-1+RT for locally advanced rectal cancer is feasible in terms of pathological response and adverse events. Clinical trial information: 03396.