tbuckley/cabot-search huggingface dataset:
Quality indicators at a breast cancer (BC) unit in a Uruguayan university hospital according to the requirements of European Society of Breast Cancer specialists.
Authors: Natalia Camejo, Cecilia Castillo, Lucia Richter, Nora Artagaveytia, Ana laura Hernandez, Lucia Beatriz Delgado
Journal: Journal of Clinical Oncology (2017)

e18209 Background: Although clear guidelines for BC management have been developed and widespread, there are many variations between centers, with impact in clinical outcomes. Quality indicators to assess care allows comparison with standards and monitoring changes post intervention. The objective is to evaluate quality indicators in BC care at our Breast Unit. Methods: Retrospective analysis of women diagnosed and treated for BC from June 2014 through June 2016 .The European Society of Mastology (EUSOMA) guidelines for quality assurance in BC and diagnosis (published in 2010 and up dated in 2013 ) were used in order to asses quality of care Results: 103 patients treated for BC were included in the study. Median age was 54 years old, ductal carcinoma: 76,5 %, histological grade I-II: 74 %; stage 0-II: 72%, axillary metastasis: 39 %, progesterone receptor/estrogen receptors+ (RE/RP+): 64 %, HER2+: 27 %. Quality criteria associated to preoperative diagnosis, pathology analysis, surgical treatment, radiotherapy and oncologic treatment were met. Conclusions: Quality indicators allows BC evaluation from established standards, giving objective and reproducible information, helpful to plan process optimization. Care received by patients seen at the Hospital de Clinicas BC Unit during the referred period met all indicators suggested by the European Society of Mastology. [Table: see text]
Abstract 17088: Less Than Ideal Cardiovascular Health is Associated With Shorter Leukocyte Telomere Length: The National Health and Nutrition Examination Surveys
Authors: Samson Y Gebreab, Zerai G Manna, Rumana J Khan, Pia Riestra, Ruihua Xu, Sharon K Davis
Journal: Circulation (2016)

Introduction: The associations between individual cardiovascular disease (CVD) risk factors and leukocyte telomere length (LTL) have been inconclusive. This study examined the association between g...
Survival disparity and racial differences in the use of neoadjuvant chemotherapy (NAC) compared with primary debulking surgery (PDS) in women with ovarian cancer.
Authors: Eirwen M Miller, Joan Tymon-Rosario, Xianhong Xie, Harriet Olivia Smith, Gary L. Goldberg, Dennis Yi-Shin Kuo, Nicole Suzanne Nevadunsky
Journal: Journal of Clinical Oncology (2017)

e17099 Background: Studies demonstrate racial disparity in ovarian cancer survival though survival differences seem to be mitigated when patients receive similar care. We sought to identify whether racial disparity exists in the use of NAC or PDS for women with ovarian cancer. Methods: After IRB approval, all patients with epithelial ovarian cancer who received primary treatment at our institution from 2005-2016 were identified from our tumor registry. Charts were retrospectively reviewed for clinicopathologic and survival data. Categorical variables were compared with chi-squared and continuous variables with the student t-test. Kaplan-Meier was used to compare survival probabilities. Results: 302 evaluable patients were identified. 240 (79%) patients underwent PDS and 62 (21%) received NAC. Older patients, black patients, and those with stage III/IV disease were more likely to receive NAC. In a multivariate analysis controlling for stage and age, black race remained associated with NAC [OR 3.25 (95% CI 1.41-7.47), p &lt; 0.01]. In a subgroup of advanced disease, stage III patients (n = 138) were more likely than stage IV patients (n = 52) to undergo PDS (78% v 44%, p &lt; 0.01) and black patients were more likely than others to present with stage IV disease (39% v 22%, p = 0.01). NAC was utilized more frequently (48% v 24%, p &lt; 0.01) in black patients compared with all other races. In the advanced stage subgroup analysis, patients that underwent PDS had a longer PFS than those that received NAC [HR 2.21 (95% CI 1.26-3.89), p = 0.01]. Conclusions: Racial disparity exists in the selection of PDS compared with NAC for patients with ovarian cancer and this disparity persists when controlling for stage and age. The choice of NAC or PDS may result in survival disparity. Further investigation is needed to examine other reasons, such as medical co-morbidities and disease distribution, for racial disparity in management. [Table: see text]
Associations of pre- and post-cancer depression with end-of-life cancer care intensity.
Authors: Kathy Cao Doan, Becca Ruth Levy, Cary Philip Gross, Shi-Yi Wang
Journal: Journal of Clinical Oncology (2016)

10031 Background: Aggressive end-of-life (EOL) care can result in high costs and is not consistent with patient wishes or linked to better health. Depression also has adverse effects on health outcomes and recovery from cancer. As such, there is rising interest in identifying associations between depression and care quality for cancer patients. This study investigates whether clinically diagnosed depression is associated with EOL care intensity among elderly cancer decedents. Methods: Utilizing the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, we identified decedents ages 66 years or older either with pre-cancer depression, post-cancer depression, or no depression. All decedents had cancer diagnosed from 2004-2011 and died within 3 years of diagnosis as a result of cancer. Using hierarchical generalized linear models, we determined the associations of pre- and post-cancer depression on care quality, adjusting for sociodemographic and clinical characteristics. Results: Our sample consisted of 84,947 Medicare beneficiaries, of whom 6% had pre-cancer depression and 7.9% had post-cancer depression. Compared to decedents without depression, decedents with pre-cancer depression were significantly less likely to have repeated hospitalizations (AOR = 0.91, 95% CI = 0.83-0.99) or ED visits (AOR = 0.89, 95% CI = 0.83-0.94), experience in-hospital death (AOR = 0.83, 95% CI = 0.77-0.89), and receive ICU services (AOR = 0.86, 95% CI = 0.79-0.93) or late chemotherapy (AOR = 0.83, 95% CI = 0.70-0.99), and more likely to use hospice care (AOR = 1.20, 95% CI = 1.12-1.28). Decedents with post-cancer depression had similar care intensity patterns to those with pre-cancer depression, but were more likely to have repeat hospitalizations (AOR = 1.04, 95% CI = 0.97-1.12). Conclusions: Decedents with pre- or post-cancer depression were less likely to receive aggressive EOL care than decedents without depression. Our findings suggest understanding the mechanisms that lead to these patterns may enhance EOL care quality for all decedents. Accurate screening and treatment for depressed patients as well as earlier communication and initiation of hospice for all cancer patients can help improve palliative treatment rates.
Brain metastases treated with immune checkpoint inhibitors: A single center experience.
Authors: Vidhya Karivedu, Roman Jandarov, Trisha Michel Wise-Draper
Journal: Journal of Clinical Oncology (2018)

e14012 Background: We conducted a retrospective study to analyze the overall survival (OS) and progression free survival (PFS) among patients with brain metastases (BM) from Melanoma, Non-small cell Lung Carcinoma (NSCLC), Small cell lung cancer (SCLC), Head and neck squamous cell carcinoma (HNSCC) treated with immunotherapy (Nivolumab, Pembrolizumab, Ipilimumab or a combination, Atezolizumab, or Durvalumab). Methods: After IRB approval, we retrospectively evaluated patients with BM treated at our institute from 2012-2017 who received either immunotherapy alone or immunotherapy and one or more of the following: stereotactic radiosurgery (SRS), whole brain radiation therapy (WBRT), and/or surgery. Univariate analysis was utilized to analyze OS and PFS. Results: A total of 51 patients were identified, median age at diagnosis of BM was 61 years (range 33-84). 32 (63%) patients were male. 43 (84%) patients had a good performance score (KPS 70-100) at the time of BM diagnosis; 36 patients had supratentorial BM, 15 had both infra and supratentorial BM. 17 patients had > 3 BM, 13 had 2-3 BM, and 21 had single BM. 21 patients had asymptomatic BM while 30 patients had symptomatic BM. The median OS from the start of immunotherapy was 7.6, 7.2, 6.2 and 4 months for Melanoma, NSCLC, SCLC and HNSCC respectively. On univariate analysis, patients who received immunotherapy alone as primary BM treatment had worse survival compared to combination with radiotherapy or surgery (95% CI 0.03-0.95, p = 0.04) and patients who had partial intra cranial response with immunotherapy had better survival compared to those with stable disease (95% CI 1.77-239, p = 0.01). Conclusions: Immune check point inhibitors alone in treatment of BM is associated with worse survival outcomes compared to combination with radiotherapy or surgery. Further analysis is needed to validate these results. Primary Cancer No. Patients Median OS from start of immunotherapy Median PFS from start of immunotherapy Melanoma 24 7.6 5.1 NSCLC 18 7.2 2.0 SCLC 5 6.2 6.2 HNSCC 4 4 3.9 P-Value (Log-Rank Test) 0.08 0.40
A Phase II Study of the Dual mTOR Inhibitor MLN0128 in Patients with Metastatic Castration-Resistant Prostate Cancer (mCRPC).
Authors: Dana E. Rathkopf, Susan F. Slovin, Karen A. Autio, Anthony Delacruz, Gregory Shelkey, Katherine Pisano, Melanie Hullings, Mia DeNunzio, Michael J. Morris, Howard I. Scher
Journal: Journal of Clinical Oncology (2016)

e16529 Background: MLN0128 is a first-in-class, dual mTOR inhibitor that has the potential to overcome resistance seen with standard rapalogs through inhibition of both TORC1 and TORC2. This phase II study was designed to evaluate the anti-tumor activity of MLN0128 in mCRPC . Methods: Patients (pts) with mCRPC previously treated with abiraterone acetate (AA) and/or enzalutamide (ENZ). Prior docetaxel (Doc) was allowed. 5 pts started MLN0128 at 5 mg po once daily (qd), all were dose reduced once to 4mg po qd and 2 pts subsequently dose reduced again to 3mg po qd. 4 pts were started on MLN0128 at 4 mg po qd with no dose reductions. The primary endpoint was progression-free survival at 6 months as defined by the Prostate Cancer Working Group 2 with a planned accrual of 21-42 pts. Results: 9 pts (8 post AA and ENZ, 1 post ENZ, 4 post Doc) were enrolled with a median time on treatment of 11 weeks (3-30 weeks). 1 out of 9 pts (11%) achieved the trial endpoint. The best response was stable disease. All pts had a rise in PSA on treatment with a median of 159% increase from baseline (range of 12-620%) and 5 pts (56%) had an immediate PSA decline following discontinuation of drug. Pts had an average baseline circulating tumor cell count of 51.4 cells/7.5ml (2-401), none of which converted ≤ 5 post treatment. 7 out of 9 pts had matched biopsies, analysis is ongoing. The most common grade ≤ 2 adverse events were: fatigue (89%), anorexia (78%), and maculopapular rash (67%). The most common serious adverse events related to treatment were grade 3 dyspnea and rash. All 5 pts who started on 5mg of study drug daily were dose reduced to 4mg daily due to rash, fatigue, oral mucositis or diarrhea. 8 of the 9 pts discontinued treatment before the trial endpoint due to radiographic progression (n = 2), grade 3 toxicity (n = 4) and investigator discretion (n = 3). Conclusions: All 9 pts were heavily pretreated. Due to limited response and tolerance at the recommended phase 2 dose of 5 mg, and PSA kinetics suggestive of AR activation in response to dual mTOR inhibition, we elected to close this trial and focus on reciprocal feedback activation with combined AR/PI3K therapy in mCRPC. Supported by Millennium Pharmaceuticals, SPORE CA092629. Clinical trial information: NCT02091531.
P05.17 Dorsal solid cervicomedullary hemangioblastomas: surgical results in seven patients
Authors: J Hwang, K Park, S Yoon, S Hwang
Journal: Neuro-Oncology (2018)

Hemangioblastomas are highly vascular, but rare tumors, which account for only 1.5–2.5% of intracranial neoplasms. They are predominantly found in posterior fossa and spinal cord. Cerebellar hemangioblastomas usually have ‘cyst with mural nodule’ appearance and dorsal cervicomedullary solid tumors are occasionally found. Total resection of tumor may lead to cure of the lesion, but the surgical resection of large solid hemangioblasoma is challenge for neurosurgeons due to their association with critical neurovascular structures and rich vascularity. We present surgical experience of dorsal solid cervicomedullary hemangioblastomas. Among 32 patients with surgically resected infratentorial hemangioblastomas between 1998 and 2017, seven cases (5 males and 2 females) presented dorsal solid cervicomedullary hemangioblastomas. The clinical data were analyzed retrospectively. The follow-up ranged from 2 to 149 months with an average of 40.1 months. Mean age was 39.0 years (range, 30–50). The common presenting symptoms were headache in 4 patients, posterior neck pain and arm weakness in 3 patients respectively. Two cases presented with an acute intracranial hemorrhage and the other two patients had von Hippel-Lindau disease. Mean maximal diameter of solid nodule was 3.5 cm and 4 patients showed a large-sized mass over 4.0 cm. Ventricular enlargement and syrinx formation in upper cervical cord were noted in 5 and 3 cases respectively. Preoperative embolization of tumor was performed in four cases. All hemangioblastomas were radically removed without significant morbidity except one patient who showed a prominent peri-tumoral edema on preoperative MR imaging and insufficient preoperative tumor embolization. The syrinx disappeared immediately after operation on imaging and two patients received radiation as an adjuvant therapy during follow-up period. No patients required the permanent CSF shunt procedure. The dorsal solid cervicomedullary hemangioblastomas can be resected with good surgical outcome in most cases. Better understanding of the vascular pattern of tumor, careful preoperative embolization and en bloc excision should be required for total tumor resection without morbidity especially in the cases of large-sized cervicomedullary hemangioblastoma.
Prognostic impact of tumor budding in stage II colon cancer: A prospective study (SACURA trial).
Authors: Hideki Ueno, Megumi Ishiguro, Eiji Nakatani, Toshiaki Ishikawa, Hiroyuki Uetake, Kenta Murotani, Shigeyuki Matsui, Naohiro Tomita, Yasuhiro Shimada, Keiichi Takahashi, Kenjiro Kotake, Masahiko Watanabe, Hidetaka Mochizuki, Satoshi Teramukai, Kenichi Sugihara
Journal: Journal of Clinical Oncology (2017)

3609 Background: Growing number of studies indicate tumor budding is a significant prognostic factor in colorectal cancer (van Wyk, et al. Cancer Treat Rev 2015), but this has been shown only in retrospective studies. We prospectively evaluated prognostic factors in stage II colon cancer to determine their prognostic value in a multi-institutional phase III study (SACURA trial, ASCO2016 abst#3617). Methods: A total of 991 patients with curatively resected stage II colon cancer (2006–2010; 136 institutions) were included in the study. Tumor budding was defined as an isolated cancer cell or a cluster composed of fewer than five cells in the invasive frontal region, and was graded based on its number within a microscopic field of a 20x objective lens (0.785 mm 2 ) in the hotspot. Tumors with &lt; 5, 5–9, and ≥10 budding foci were classified as grades G1, G2, and G3, respectively. All clinical and pathological data including the grade of budding were prospectively recorded and prognostic analyses were performed at 5 years after the completion of registration. Results: According to budding grading, 376, 331 and 284 tumors were classified as G1, G2, and G3, and 5-year relapse-free survival (RFS) rate was 90.9%, 85.1%, and 74.4%, respectively ( P &lt; 0.0001). Budding grade was significantly associated with the incidence of recurrence in the liver, lung, lymph node, and peritoneum ( P &lt; 0.0001–0.01). Among conventional factors, T stage and the serum CEA levels were associated with RFS, however, tumor grade, lymphatic and venous invasions, and the number of lymph node examined were not significant factors. Multivariate analysis for RFS showed budding, along with T stage, exerted an independent influence on prognostic outcome. Budding grade surpassed T stage and tumor grade in the ability to stratify patients by RFS (Harrell’s c-index, 0.63, 0.59, and 0.54, respectively). Conclusions: Our prospective study indicates that the grade of tumor budding is more informative for prognostic prediction than conventional prognostic factors in stage II colon cancer. The role of this prognostic factor should be highlighted in the adjuvant treatment setting, and conversely, some of prognostic factors adopted in clinical guidelines may need to be reconsidered. Clinical trial information: NCT00392899.
Abstract 238: S-nitrosoglutathione Reductase (GSNOR) Plays a Critical Role in Placental Vascularization Working Through the VEGF-NO Pathway
Authors: Shathiyah Kulandavelu, Michael A Bellio, Julia Fritsch, Wayne Balkan, Joshua M Hare
Journal: Circulation Research (2017)

Introduction: Preeclampsia (PE), a leading cause of maternal and fetal mortality and morbidity, is characterized by increased levels of reactive oxygen species (ROS) and S-nitrosylated protein, and decreased levels of the antioxidant, ascorbate (Asc), which is required for the release of nitric oxide (NO) from nitrosylated proteins. Mice lacking S-nitrosoglutathione reductase (GSNOR –/– ), a denitrosylase that regulates protein S-nitrosylation, exhibit a PE-like phenotype including maternal hypertension, cardiac concentric hypertrophy and impaired placental vascularization. We hypothesized that impaired placental vascularization, one of the primary causes of preeclampsia is mediated by alteration in S-nitrosylation of the VEGF-NO pathway, and ascorbate treatment rescues this pathologic phenotype. Methods: Pregnant GSNOR –/– and control (WT) mice (n=5-7) were studied at late pregnancy (day 17.5). Ascorbate was provided in drinking water beginning at day 0.5. Fetoplacental capillary density was determined from isolectin staining and reactive nitrosative stress determined from nitrotyrosine staining in placental sections. S-nitrosylation of VEGF was determined using SNO-Rac and eNOS levels by Western blot analysis. Results: Fetoplacental capillary density was reduced 19% in GSNOR –/– fetuses compared to WT (P&lt;0.001). GSNOR –/– placentas exhibited higher nitrotyrosine staining than WT placentas, indicating the presence of nitrosative stress. These increases were associated with reduced level of eNOS protein (P&lt;0.05) and decreased S-nitrosylation of VEGF (P&lt;0.05) in the GSNOR –/– placentas as compared to WT. Ascorbate treatment decreased nitrotyrosine staining, and increased fetoplacental capillary density ~10% (P&lt;0.001), eNOS protein levels (P&lt;0.05) and S-nitrosylation of VEGF (P&lt;0.05) in the GSNOR –/– placentas as compared to WT. Conclusion: These findings suggest that GSNOR plays an essential role in promoting placental vascularization in part working through the VEGF-NO pathway. Ascorbate treatment rescued the nitrosative stress and improved placental vascularization, suggesting that it can be used therapeutically to treat or prevent preeclampsia.
Sentinel Surveillance for Congenital Rubella Syndrome — India, 2016–2017
Authors: Manoj Murhekar, Ashish Bavdekar, Asha Benakappa, Sridhar Santhanam, Kuldeep Singh, Sanjay Verma, Gajanan N. Sapkal, Nivedita Gupta, Valsan Philip Verghese, Rajlakshmi Viswanathan, Asha Mary Abraham, Shyama Choudhary, Gururajrao N. Deshpande, Suji George, Garima Goyal, Parul Chawla Gupta, Ishani Jhamb, Deepa John, Swetha Philip, Sandeep Kadam, Ravinder Kaur Sachdeva, Praveen Kumar, Anjali Lepcha, S. Mahantesh, S. Manasa, Urvashi Nehra, Sanjay Kumar Munjal, Vijaya Lakshmi Nag, Sadanand Naik, Naga Raj, Jagat Ram, R.K. Ratho, C.G. Raut, Manoj Kumar Rohit, R. Sabarinathan, Sanjay Shah, Pratibha Singh, Mini P. Singh, Ashish Tiwari, Neelam Vaid
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

Rubella infection during pregnancy can result in miscarriage, fetal death, stillbirth, or a constellation of congenital malformations known as congenital rubella syndrome (CRS). The 11 countries in the World Health Organization (WHO) South-East Asia Region are committed to the elimination of measles and control of rubella and CRS by 2020. Until 2016, when the Government of India's Ministry of Health and Family Welfare and the Indian Council of Medical Research initiated surveillance for CRS in five sentinel sites, India did not conduct systematic surveillance for CRS. During the first 8 months of surveillance, 207 patients with suspected CRS were identified. Based on clinical details and serologic investigations, 72 (34.8%) cases were classified as laboratory-confirmed CRS, four (1.9%) as congenital rubella infection, 11 (5.3%) as clinically compatible cases, and 120 (58.0%) were excluded as noncases. The experience gained during the first phase of surveillance will be useful in expanding the surveillance network, and data from the surveillance network will be used to help monitor progress toward control of rubella and CRS in India.
Novel porcupine (PORCN) inhibitor RXC004: Evaluation in models of RNF43 loss of function cancers.
Authors: Inder Bhamra, Nick Adams, Richard Armer, Matilda Bingham, Helen McKeever, Caroline Phillips, Ben Thompson, Simon Woodcock
Journal: Journal of Clinical Oncology (2017)

e14094 Background: Wnt signalling initiates oncogenic pathways involved in tumour initiation, growth, differentiation and metastasis. 1 Targeting the Wnt pathway is an attractive approach to cancer treatment. Porcupine (PORCN) is a membrane-bound O-acyltransferase dedicated to the palmitoylation of Wnt ligands, an essential step in the processing of Wnt into active ligands. 2 A PORCN inhibitor may benefit patients with cancers in which Wnt signalling is implicated. It has been shown that PORCN inhibition is efficacious in cell lines with upstream mutations in this pathway, eg RNF43 loss of function. 3 Methods: Analysis of TCGA data was carried out to identify cancer types harbouring RNF43 mutations. 4 Redx PORCN inhibitor RXC004 was evaluated in vitro for Wnt pathway inhibition and anti-proliferative effects using assays previously described for early lead compounds. 5 Anti-tumour effects of RXC004 were evaluated using a pancreatic CAPAN-2 xenograft in SCID Bg. mice and a gastric PDX model in nu/nu mice. Both models have RNF43 loss of function mutations. Results: TCGA data revealed that both gastric cancer and pancreatic cancer exhibit mutations in the RNF43 gene (18% and 4% respectively), 4 expected to result in loss of function. RXC004 showed activity in preclinical models of cancers with this genetic background. RXC004 significantly inhibited tumour growth in a CAPAN-2 pancreatic cancer xenograft and in a gastric cancer PDX model when dosed orally once or twice daily. Conclusions: Taken together, these data indicate that RXC004 is a potent inhibitor of tumour growth in RNF43 loss of function preclinical cancer models. RXC004 will be evaluated in a first in human Phase 1 study in 2017. Phase 1a aims are to characterise the safety profile and PK/PD relationship in cancer patients and establish a Phase 1b dose. The efficacy of RXC004 in gastric and pancreatic cancer patients prospectively selected for RNF43 loss of function mutations will be the focus of Phase 1b expansion groups. 1 . Nat. Rev. Cancer, 2013, 13 (1): 11-26.2. J. Biol. Chem., 2012, 287 (27): 23246-23254. 3. PNAS, 2013, 110 (31): 12649-12654 4. Sci. Signal, 2013, 269 (6): 1-34; Cancer Discov., 2012, 2 (5): 401-404 5. AACR Annual Meeting, 2015, 75 (15): abs. 5071.