tbuckley/cabot-search huggingface dataset:
The correlation of CT volumetry with prognosis in advanced gastric cancer treated with neoadjuvant chemotherapy.
Authors: Chao Chen, Chunhui Shou, Xiaoxiao Shi, Baishu Zhong, Qing Zhang, Xiaosun Liu, Kankai Zhu, Yuan Gao, Qianyun Shen, Zhicheng Zhao, Jiren Yu
Journal: Journal of Clinical Oncology (2018)

e16061 Background: To investigate the feasibility and utility of computer tomography (CT) volumetry in evaluating the tumor response to neoadjuvant chemotherapy(NAC) in advanced gastric cancer (AGC) patients. Methods: AGC patients who treated with NAC and underwent R0 resection (no residual) from January 2006 to December 2012 were retrospectively reviewed. Tumor volumes were measured by software OsiriX according to contrast-enhanced CT scan. The percentage volume reduction rate (VRR) was calculated using the following equation: VRR = [(pre-chemotherapy total volume) - (post-chemotherapy total volume)]/ (pre-chemotherapy total volume) × 100%. The optimal cut-off value of VRR for differentiating favorable from unfavorable prognosis was determined as the point closest to the 0% false-positive and 100% true-positive on the receiver operating characteristic (ROC) curve. Overall survival (OS) was calculated using Kaplan-Meier analysis and values were compared using the log-rank test. Multivariate analysis was determined by the Cox proportional regression model. Results: A total of 117 AGC patients with a median follow-up of 52 months (rang 7-120 months) were enrolled in this study. There were 83 men and 34 women with a median age of 60 years (range 37-80 years). The mean tumor volume of all patients decreased significantly after NAC (53.8 ± 32.6 cm3 vs 35.9 ± 28.4 cm3, p < 0.01). The optimal cut-off value of VRR was determined to be 31.95% based on the ROC analysis, with a sensitivity of 70.4% and a specificity of 71.7%. The area under the ROC curve was 0.76 (95% CI: 0.676-0.851). Thereafter, all patients were divided into VRR-High (VRR≥31.95%, N = 63) and VRR-Low (VRR < 31.95%, N = 54) groups. Five-year OS was significantly higher in the VRR-High group than that in the VRR-Low group (63.2% vs 31.0%, p < 0.01). The Cox regression model indicated that the high VRR is a favorable independent prognostic factor (Hazard ratio = 0.41, 95% CI 0.24-0.72; P < 0.01). Conclusions: Using of CT volumetry for evaluating tumor response to chemotherapy was feasible, and could predict the long-term survival of AGC patients treated with NAC followed by R0 resection.
P01.090 Patterns of care and clinical outcome in patients with glioblastomas without histological verification: a population-based prospective study of 132 consecutive patients
Authors: K Werlenius, B Fekete Rydenhag, M Blomstrand, A S Jakola, A Smits, B Rydenhag
Journal: Neuro-Oncology (2018)

Elderly patients with suspected glioblastomas (GBM) and an accumulation of negative prognostic factors have an extremely short survival and are not always fit for a diagnostic biopsy. This subgroup is thus illdefined and often excluded from clinical trials. This study focuses on the clinical characteristics, patterns of care, and outcome of patients with unverified histological diagnosis to evaluate if it is possible to predict who could be spared from a biopsy. Between November 2012 and June 2016, all patients presenting with suspected GBM in the Western region of Sweden (population 2 million) have been registered in a population-based consecutive prospective study. Individual clinical treatment decisions were made at multidisciplinary team conferences for all patients. During the study period 380 patients presented with a radiological diagnosis of GBM and of these 248 (65%) were histologically verified. The clinical characteristics of the 132 patients (35%; 73 men, 59 women) with histological-unverified GBM were: age ≥ 75 (n=102), tumor in eloquent areas (n=75), extensive tumor infiltration (n=98), significant co-morbidity (n=37) and PS WHO ≥2 (n=93). The median age at the time of diagnosis was 80 years (range 52–90, mean 78 years), compared to 63 years (range 19–82, mean 60 years) in the group of patients with histological-verified GBM. The median survival was 3.6 months, compared to 11.9 months for patients with histological-verified GBM. A total of 46 patients (35%) with histological unverified GBM received oncological treatment. The average WHO performance status in this subgroup was 1.41 compared to 2.52 in those receiving no oncological treatment. Temozolomide (TMZ) as a single agent was the most common treatment (n=45), only 3 patients received a short-course of radiotherapy. The overall radiological response rate to TMZ was 33%. The median survival for the subgroup receiving treatment was 6.5 months. The rate of histological-unverified diagnosis was 35% and this subpopulation consisted of elderly patients with frequent extensive tumor spread in eloquent areas. The varying clinical outcome even within this subpopulation with poor prognosis suggests that at least some patients in this group with better performance status may benefit from treatment with TMZ with feasible side-effects. To guide a more rationale palliative treatment decision, diagnostic biopsy including evaluation of MGMT promotor methylation status for these patients would be preferable.
Disparities in access to breast cancer treatment: An observational study based on insurance status.
Authors: Karthik Kailasam, Mohammad Omaira, Marie Ravichandar, Suceil Sivsammye
Journal: Journal of Clinical Oncology (2017)

6534 Background: Breast cancer is the second leading cause of cancer death in Caucasians and African-Americans, and the most common cause of cancer death in Hispanic women. Methods: A retrospective analysis was done with data obtained from 1473 hospitals by National cancer database (NCDB) for the years 2004-2014. Patients with breast cancer were analyzed for differences in treatment offered based on their insurance status. Patients in the insurance group were enrolled under either Private, Medicare, Medicaid or other government insurance. Treatments offered were surgery, chemotherapy, radiation therapy or a combination of the above. Patients with unspecified insurance status and those who were on active surveillance were excluded from the analysis. Results: A total of 2,245,259 patients with breast cancer from all age groups were identified from the registry. 47,294 patients did not have insurance; among which 3275 (7.4%) were not offered any treatment. Among 2,093,809 patients with insurance, 58,726 (2.8%) patients were not offered any treatment. Hence, patients without insurance were twice (OR 2.65; CI 2.55-2.75 p &lt; 0.0001) more likely to not receive any first course treatment. Sub-group analysis for different stages of breast cancer showed; carcinoma in-situ (OR 2.44; CI 2.20-2.71 p &lt; 0.0001), stage1 (OR 2.68; CI 2.43-2.96 p &lt; 0.0001), stage2 (OR 2.86; CI 2.61-3.12 p &lt; 0.0001), and stage 3 (OR 2.56; CI 2.25-2.92 p &lt; 0.0001) have similar odds for not being offered any treatment. However, the odds of receiving treatment were better for stage 4 breast cancer (OR 1.44; CI 1.32-1.55 p &lt; 0.0001). Uninsured Caucasians (OR 2.70; CI 2.56-2.85 p &lt; 0.0001) were less likely to receive any treatment compared to uninsured African-Americans (OR 2.16; CI 2.00-2.33 p &lt; 0.0001) and uninsured Hispanics (OR 1.66; CI 1.52-1.82 p &lt; 0.0001) Conclusions: With the recent suggested changes in health care policy, we can expect the number of uninsured patients to rise and therefore more patients might not have access to breast cancer treatment.
Linking pBRD4 and PP2A inhibition in triple negative breast cancer.
Authors: Manuel Pedregal, Ion Cristobal, Francisco Lobo, Yann Izarzugaza, Cristina Carames Sanchez, Victor Moreno, Tatiana Hernández, Jaime Rubio, Sandra Zazo, Blanca Torrejon, Federico Rojo, Jesus Garcia-Foncillas
Journal: Journal of Clinical Oncology (2018)

e13011 Background: It has been recently reported that triple negative breast cancer (TNBC) cells show a preferential sensitivity to BET bromodomain inhibitors (BBI). Moreover, BRD4 hyperphosphorylation was identified as an alteration that confers resistance to BET bromodomain inhibition and PP2A as a main phosphatase that regulates BRD4 phosphorylation levels. However, both PP2A activation status and clinical significance of BRD4 phosphorylation in TNBC remain to be investigated. We report here that BRD4 hyperphosphorylation is a common event that defines a subgroup of TNBC patients with very poor outcome. Methods: We analyzed here BDR4 phosphorylation status in a cohort of 126 TNBC patients, observing BRD4 hyperphosphorylation in 35.4% of cases (44/126). Interestingly, this alteration was found associated with higher tumor grade (p = 0.020) and with the subgroup of cases who relapsed (p = 0.005). Results: Moreover, high BDR4 phosphorylation determined significantly shorter overall (8.5 vs. 22.7 months; p < 0.001) and progression-free survival (13.9 vs. 20.2 months; p < 0.001). Multivariate analyses confirmed its independent prognostic impact. Furthermore, this alteration strongly correlates with a PP2A inhibition status, which clinically supports the previous findings which identified BRD4 as a novel PP2A target. Conclusions: In conclusion, our results highlight that BRD4 hyperphosphorylation is a common event which defines a subgroup of TNBC patients with very poor outcome as well as the potential benefit derived from the clinical use of PP2A activators to anticipate and overcome development of resistance to BBI in TNBC.
Response to Open Peer Commentaries on ‘‘Provider Conscientious Refusal of Abortion, Obstetrical Emergencies, and Criminal Homicide Law’’
Authors: Lawrence Nelson
Journal: The American Journal of Bioethics (2018)

"Response to Open Peer Commentaries on ‘‘Provider Conscientious Refusal of Abortion, Obstetrical Emergencies, and Criminal Homicide Law’’." The American Journal of Bioethics, 18(9), pp. W9–W10
Impact of tumor-infiltrating lymphocytes on response to neoadjuvant chemotherapy in triple-negative early breast cancer: Translational subproject of the WSG-ADAPT TN trial.
Authors: Cornelia Liedtke, Friedrich Feuerhake, Madlen Garke, Matthias Christgen, Ronald E. Kates, Eva-Maria Grischke, Helmut Forstbauer, Michael Wilhelm Braun, Mathias R. Warm, Christoph Hackmann, Christoph Uleer, Bahriye Aktas, Claudia Schumacher, Sherko Kummel, Rachel Wuerstlein, Ulrike Nitz, Hans Heinrich Kreipe, Oleg Gluz, Nadia Harbeck
Journal: Journal of Clinical Oncology (2018)

12102 Background: In triple-negative breast cancer (TNBC), pathological complete response (pCR, ypT0/is/ypN0) is associated with improved prognosis. The randomized prospective WSG-ADAPT TN phase II trial showed higher pCR with Nab-paclitaxel / Carboplatin (NP/C) compared to paclitaxel / gemcitabine (NP/G) as 12-week neoadjuvant therapy. Presence of tumor-infiltrating lymphocytes (TILs) is associated with increased pCR rates after neoadjuvant chemotherapy, but the role of TIL dynamics during (specific) chemotherapy regimens is still unknown. Methods: This pre-planned translational analysis focuses on semi-quantitative TIL measurements in ADAPT-TN among tumor samples at baseline (TIL-0) and after 3 weeks of chemotherapy (TIL-3). Associations of continuous TIL-0 and TIL-3 levels with pCR, with chemotherapy arm and with other clinical / pathological measurements were analyzed using logistic regression, rank correlations, t and chi-square statistics. Results: 336 patients were enrolled. TIL-0 and TIL-3 were available among 311 (92.6%) and 223 (66.4%) patients, respectively. "Low cellularity" in 3-week biopsies (tumor necrosis, lack of invasive tumor cells) was recorded in 82 patients. TIL-0 and TIL-3 were strongly correlated (0.64, p < .001); average relative increase was about 30%. TIL-0 was significantly associated with baseline tumor grade, clinical tumor size, and nodal status. TIL-3 was significantly associated with nodal status and grade in both biopsies. In all patients, higher levels of both TIL-0 (p < .001) and TIL-3 (p = .002) were associated with pCR. Higher TIL-0 was also significantly associated with pCR in both arms separately. "Low cellularity" was also associated with pCR in all patients (OR = 3.9, 95%-CI: 2.3-6.8) and in both arms separately (NP/G: OR = 3.6, 95%-CI: 1.7 to 7.9; NP/C: OR = 4.2, 95%-CI: 1.9-9.3). Conclusions: In TNBC patients, higher levels of tumor-infiltrating lymphocytes were associated with pCR, both at baseline and after 3 weeks of neoadjuvant chemotherapy. "Low-cellularity" at week 3, which indicates extensive response to chemotherapy, was itself strongly associated with response to therapy.
Metastatic stomach cancer: Real world scenario from a developing country.
Authors: Sandip Ganguly, Bivas Biswas, Joydeep Ghosh, Prasad E, Sudeep Banerjee, Mohandas K. Mallath, Suvadip Chatterjee, Deepak Dabkara
Journal: Journal of Clinical Oncology (2017)

e15569 Background: Data on epidemiology and outcome in metastatic stomach carcinoma patients from resource poor country is scarce. We aimed to evaluate clinical features and treatment outcome in patients treated at our center. Methods: This is a single institutional review of metastatic stomach carcinoma patients treated between May’2011 and October’2016. Patients with past history of adjuvant treatment were also included when they developed metastasis. Progression-free survival (PFS) was calculated from date of diagnosis of metastasis to date of disease progression. Patients who received at least one cycle of chemotherapy were included for a modified intent-to-treat survival analysis. Results: Total 143 patients were diagnosed with metastatic stomach carcinoma with median age of 56 years (range: 29-86) and male:female ratio of 92:51. Twenty-five (17%) patients received prior adjuvant therapy before developing metastasis. Commonest symptoms were abdominal pain in 112 (78%), weight loss in 72 (50%) and gastric outlet obstruction in 33 (24%) patients. Primary sites were proximal stomach in 44 (30%), body in 81 (57%) and distal stomach-pyloric region in 18 (13%) patients. Site of metastasis was peritoneum in 86 (60%), liver in 62 (43%), lung &amp; pleura in 22 (15%), ovary in 14 (10%), and bone in 12 (8%) patients, and 104 (75%) patients had &gt; 1 site of metastasis. Seventy-one (50%) patients were eligible for survival analysis. Common chemotherapy regimens were capecitabine-cisplatin in 27 (38%) and EOX in 22 (31%) patients. Survival status couldn’t be assessed in 29 (41%) patients who lost to follow-up. After a median follow-up 9.7 months (range: 0.5-37.7), median PFS was 7.9 months (range: 0.5 – 23.9) and median OS was 12.2 months (range: 0.5-37.7). ECOG performance status (PS) ≥2 and presence of linitis plastica showed a trend towards inferior PFS (p = 0.052 and 0.053, respectively) only in univariate analysis. Female sex and ECOG PS≥2 predicted inferior OS in both univariate and multivariate analysis (p = 0.012, 0.02 and 0.03 &amp; 0.05, respectively). Conclusions: Platinum based doublet chemotherapy was used in majority of patients. Overall outcome was comparable to that of the available literature. Female sex and ECOG PS≥2 predicted inferior outcome.
How do patterns of progression influence treatment selection after chemohormonal therapy in patients with metastatic hormone sensitive prostate cancer?
Authors: Carlos Aguado De La Rosa, Iciar Garcia Carbonero, Guillermo De Velasco, Teresa Alonso, Maria L. Villalobos, Maria Garrido, Isabel Gallegos, Almudena Martin, Alvaro Pinto, Constanza Maximiano Alonso, Jf Rodriguez-Moreno, Laura Rodriguez, Maria Sereno, Carmen Perezagua, David Marrupe, Alejandro Riquelme, Javier Cassinello, Enrique Grande, Javier Puente, Pablo Gajate
Journal: Journal of Clinical Oncology (2017)

e16504 Background: In the CHAARTED and STAMPEDE clinical trials, Docetaxel combined with androgen-deprivation therapy (ADT) increased overall survival in mHSPC patients. Despite the increasing use of this strategy in clinical practice, there is a lack of information about the best treatment choice after progression. Methods: We retrospectively analyzed 96 patients with mHSPC treated with Docetaxel plus ADT in 18 Spanish centers (July 2014 to December 2016). The objectives of the study were to describe baseline and progression characteristics, as well as second-line treatment choice and its outcomes. Results: The median age was 66.7 years. 33.3% patients had visceral metastases at diagnosis and 81% had a Gleason Score 8-10. After a median follow-up of 12.2 months, 35.4% of patients developed castration-resistant prostate cancer (CRPC). The median time to CRPC was 15.4 months. 36.3% of patients had visceral progressive disease. 27 patients received subsequent treatment after progression: 9 (33.3%) were treated with chemotherapy (2 docetaxel, 6 cabazitaxel, 1 carboplatin-etoposide), and 18 (66.6%) received androgen receptor axis-targeted agents (12 enzalutamide, 6 abiraterone). Median progression-free survival was similar with hormonal therapies (4.3 months) than chemotherapy (3.5 months) as second line. Treatment choice was influenced by pattern of progression (visceral vs non visceral) and time to develop CRPC (≤ 12 vs &gt; 12 months). Hormonal therapies were more frequent for non-visceral disease (75% vs 25%) or patients with longer time to develop CRPC (89% vs 11%). Chemotherapy was preferred in patients with visceral progressive disease (83.3% vs 16.7%). In patients with a time to CRPC less than 12 months both treatments were used equally (44.5 vs 55.5%). Conclusions: In our cohort, androgen receptor axis-targeted agents were used more frequently than chemotherapy after progression to chemo-hormonal therapy. Despite the low number of patients that received treatment at progression, our results suggest that the characteristics at the time of progression, such as pattern of progression and time to develop CRPC, could influence treatment choice.
Abstract 13742: PDE3 Inhibitor, Cilostazol, Ameliorates Ischemic Hindlimb Through cAMP and PPARγ Activation
Authors: Fumihiro Sanada, Yoshiaki Taniyama, Jyun Muratsu, Yuka Ikeda-Iwabu, Rei Otsu, Hiromi Rakugi, Ryuichi Morishita
Journal: Circulation (2015)

Peripheral arterial disease (PAD) is highly prevalent in the elderly and subjects with atherosclerotic risk factors. Approximately 2-4% of those affected with PAD commonly complain of intermittent claudication (IC) that is a strong indicator for the development of systemic atherosclerosis. Cilostazol (CSZ) has been shown to be of benefit in improving pain-free walking distance and quality of life in patients with IC. CSZ may be the most clinically effective pharmacologic option for IC. However, the underlying mechanism for amelioration of IC by CSZ remains largely unclear. Here, we demonstrate that CSZ increases expression of hepatocyte growth factor (HGF) in vascular smooth muscle cells (SMCs) via two distinct pathways, PPAR γ and cAMP pathway. Activation of PPAR γ and cAMP activates HGF promoter leading to increase in capillary density and improvement of perfusion in mouse ischemic hind limb model. Enhancement of angiogenesis by CSZ involves Akt/eNOS activation in endothelial cells by HGF secreted from SMCs. However, this process was essentially absent in aspirin treatment group and CSZ with HGF neutralizing antibody treatment group. As CSZ also increases HGF protein production in interstitial area of skeletal muscle where satellite cells reside, we postulated that CSZ stimulates myogenesis. To proof this hypothesis, BrdU was injected every day for 7days in mouse hind limb model, and animals were sacrificed at day 7 and 28. Embryonic form of myocyte heavy chain (eMHC), BrdU positive myocyte, and nuclear centralization was measured. As predicted, CSZ increases the number of newly formed myocyte in ischemic leg compared to control and Aspirin treated mouse. This beneficial effect of CSZ was blunted by the administration of HGF neutralizing antibody. Additionally, Heart specific HGF overexpression mouse in which serum level of HGF is 4-5 times higher than wild type mouse were generated to proof the role of HGF in angiogenesis and myogenesis. Similar to the data obtained from CSZ treated mouse, HGF Tg mouse ameliorates ischemic hind limb via both angiogenesis and myogenesis. Altogether, our date demonstrates that CSZ improves ischemic hind limb via angiogenesis and myogenesis. This results may account for the beneficial effect of CSZ in PAD patients with IC.
Patients with metastatic melanoma treated with vemurafenib as monotherapy or in combination with cobimetinib.
Authors: Janja Ocvirk, Martina Rebersek, Marko Boc, Tanja Mesti
Journal: Journal of Clinical Oncology (2017)

e21016 Background: This is a retrospective analysis of patients (pts) with metastatic melanoma (mM) designed to evaluate the efficacy and safety of vemurafenib as monotherapy (V) in comparison with vemurafenib in combination with cobimetinib (V+C) in routine clinical practice. Methods: Baseline characteristics, treatment-related adverse events, and efficacy data were collected from 58 mm pts who were treated with V and 32 mm pts treated with V+C. Cobimetinib was given within approved pre-approval access program. Results: In 39-month period, 241 pts were diagnosed with unresectable or mm and in 137 pts (57%) tumor tissue was positive for BRAF V600E/K mutation (89% BRAF V600E and 11% BRAF V600K). 58 BRAF-positive pts were treated with V (median age 55.1, 66% males, 62% pts with elevated LDH level, 74% M1c) and 32 BRAF-positive pts with V+C (median age 54.5, 69% males, 31% pts with elevated LDH level, 81% M1c). V was given as first, second or third line treatment to 49 (85%), 6 (10%) and 3 (5%) pts respectively, while V+C was given only as first line treatment. In pts with assessable disease (88% in V and 100% in V+C group) the overall response rate (ORR) was 41% in V group and 56% in V+C group. Disease control rate (DCR) was 69% in V group and 91% in V+C group. Complete responses (CR) were reported in 4 pts (7%) in V group and in 1 pts (3%) in V+C group. Partial responses (PR) were more frequent in V+C group (53%) than in V group (29%). Median progression-free survival (PFS) was 5.0 months (95% CI, 2.8-7.2) in V group and 7.9 months (95% CI, 6.1-9.7) in V+C group. Median overall survival (OS) was 6.7 months (95% CI, 4.0-9.4) in V group and 9.7 months (95% CI, 7.6-11.8) in V+C group. At the time of analysis 16% of pts are alive in V group and 41% in V+C group. The best outcomes had subgroup of pts with normal LDH level in V+C group (DCR = 95%), with 50% pts alive at the time of data analysis. Adverse events (AEs) were reported in 83% of pts in V group and 63% in V+C group and 83% and 94% of reported AEs were grade 1-2 respectively. Dose reduction was required in 50% of pts in V group and in 28% of pts in V+C group. Conclusions: Vemurafenib in combination with cobimetinib has shown meaningful efficacy and managable safety profile in real-world setting.