tbuckley/cabot-search huggingface dataset:
P05.34 Multidisciplinary treatment in patients with leptomeningeal metastasis from gastric cancer in the era of individualized treatment: A single-institution, retrospective study
Authors: K Mitsuya, N Yoko, D Shoichi, N Hayashi, H Yasui, H Harada
Journal: Neuro-Oncology (2018)

Leptomeningeal metastasis (LM) is a devastating complication of systemic cancers. New effective therapies for primary cancers have underscored the clinical significance of LM. We reviewed the outcomes of patients with LM from gastric cancer (LM-G) treated in our institute. Data on patients with LM-G diagnosed by cytological examination or MR images were retrospectively analyzed. Fourteen LM-G patients were treated between January 2005 and December 2016. Patients underwent intrathecal chemotherapy with methotrexate (it-MTX) and whole brain radiotherapy (WBRT) followed by systemic chemo-therapy, if they had KPS more than 40% and life expectancy longer than three months after control of their LM-G. Decision making of treatments was based on clinical manifestations, and was discussed at our cancer board on the individual situation. CSF shunt was indicated for patients with hydrocephalus or uncontrollable intracranial hypertension. Of the 14 patients, 12 (86%) were male, and the median age was 63 years (range, 30–73). The median time from the diagnosis of gastric cancer to the onset of LM-G was 14 months. Symptoms were headache in 12 patients e, and ataxia in 2 patients. The median survival time from the onset of LM-G was 3.5 months. The longest survivor lived for 18 months (n=2). Median survival time was 7 months in patients who underwent all of it-MTX, RT and systemic chemotherapy (n=6) compared to 2 months in patients with it-MTX and RT alone (n=8) (p = 0.003). Most favorable prognostic group was chemotherapy-naïve patients LM-G who completed triple modality treatment, their mOS-LM was 17 months (n=3). Two patients achieved complete response after it-MTX, WBRT and systemic chemotherapy with a regimen of “cisplatin and S-1”. CSF shunt surgery yielded patient palliation effects (n=5). Combination of triple modalities, it-MTX, WBRT and systemic therapy, is a safe and effective strategy in patients with LM-G. Because of palliative nature of the treatments for patients with LM-G, we need to clarify indications of interventional treatments on the basis of multi-institutional cohort.
cfDNA mutation frequency in early stage breast cancer.
Authors: Karthik Joshua Kota, Rekha Gyanchandani, Margaret Quinn Rosenzweig, Adam Brufsky, Shannon Leigh Huggins-Puhalla, Lori Miller, Steffi Oesterreich, Adrian V. Lee
Journal: Journal of Clinical Oncology (2017)

e23047 Background: Though 93% of patient present with early stage breast cancer (EBC), metastatic recurrence is expected in 7-13%. To prevent estrogen receptor (ER) positive disease recurrence, endocrine therapy (ET) is given after local disease. ET guidelines recently extended therapy —specifically tamoxifen—from 5 years to 10 based on ATLAS and aTTom. This pilot study used blood samples from women 6 months post-ET to determine cell free DNA (cfDNA) mutation prevalence in disease-free patients Methods: Patients with EBC and continued follow-up after ET were recruited from the Magee Women’s Breast Cancer Clinic. Inclusion criteria were EBC, ER+, and completion of ET &gt; 6 months prior to visit; the exclusion criterion was active disease. Patients gave 2 blood samples, placed in Streck and EDTA tubes and processed at 2 laboratory sites for cfDNA. Blood from patients with metastatic breast cancer (MBC) served as controls for mutation detection. cfDNA was amplified for ESR1 and PIK3CA genes. Targeted amplifications underwent digital droplet PCR to identify mutations: 4 for ESR1 (D538G, Y537C/N/S), 2 for PIK3CA (E545K, H1047R) Results: Ten EBC patients &gt; 6 months post-ET (post-EBC; 2/5/3 of stage I/II/III) and 10 MBC patients gave samples. cfDNA yield between plasma isolated from EDTA and Streck tubes (including mutation allele frequencies) was not significantly different (p &gt; 0.05); cfDNA yield from patients with MBC was &gt; 2X higher than post-EBC (p &lt; 0.001). MBC cfDNA had 2 monoclonal and 1 polyclonal (2 different) mutations in ESR1, while post-EBC cfDNA had none Conclusions: This pilot study shows cfDNA can be consistently isolated from Streck or EDTA-processed blood from patients with MBC and post-EBC; however, cfDNA levels are significantly higher in MBC. There were no mutations (ESR1 or PIK3CA) in post-EBC samples, though ESR1 mutations were found in MBC. Further studies are needed to determine if mutations in cfDNA can be found in patients without evidence of disease
RNA turbulence by tumor type: Overexpression of actionable mRNA signaling pathways by histology.
Authors: Sandip Pravin Patel, Scott Morris, Young Kwang Chae, Jeffrey Melson Clarke
Journal: Journal of Clinical Oncology (2017)

e23213 Background: Overexpression of mRNA provides an oncogenic mechanism, downstream of DNA level changes detected by sequencing, that can be treated with targeted therapies. It is still unknown why a subset of patients experience substantial responses to targeted therapies, while others experience minimal benefit. We hypothesize that the occurrence of multiple mRNA drivers may segment by cancer type in a similar manner to mutation burden. Methods: We examined results from 2088 patients with the 23 most common histologies that had received molecular testing at Paradigm Diagnostics by a panel of 56 mRNA targets, including 21 from the MAPK pathway, 14 from the P53 pathway, and 18 from the PI3K pathway. We calculated RNA turbulence, defined as the number of mRNA overexpressed in each case, as well as the pathway-specific RNA turbulence for the MAPK, PI3K and TP53 pathways. Results: Significant differences in overall and pathway-specific RNA turbulence across cancer types was observed. Colon and rectal cancers had high turbulence in the MAPK and TP53 pathways, with 87% having multiple putative drivers in the MAPK pathway and 29% having multiple drivers in the PI3K pathway. Small cell lung cancer and kidney cancers had high turbulence in the PI3K pathway, with 33% and 39% having multiple RNA drivers respectively. Overall, pancreatic, kidney and colon cancers had the highest turbulence and GIST, melanoma and cholangiocarcinoma had the lowest. There was a slight inverse relationship in tumor type when ranked by mutation burden vs. RNA turbulence Conclusions: RNA turbulence represents a unique mechanism by which to analyze tumors and correlates with disease type. Multiplex diagnostics assaying DNA, RNA, and protein level tumor changes will likely be needed to guide cancer therapeutics.
Selenium-layered nanoparticles serving for oral delivery of phytomedicines with hypoglycemic activity to synergistically potentiate the antidiabetic effect
Authors: Wenji Deng, Huan Wang, Baojian Wu, Xingwang Zhang
Journal: Acta Pharmaceutica Sinica B (2018)

Diabetes mellitus (DM) remains a great challenge in treatment due to pathological complexity. It has been proven that phytomedicines and natural medicines have prominent antidiabetic effects. This work aimed to develop selenium-layered nanoparticles (SeNPs) for oral delivery of mulberry leaf and Pueraria Lobata extracts (MPE), a group of phytomedicines with significant hypoglycemic activities, to achieve a synergic antidiabetic effect. MPE-loaded SeNPs (MPE-SeNPs) were prepared through a solvent diffusion/in situ reduction technique and characterized by particle size, ζ potential, morphology, entrapment efficiency (EE) and drug loading (DL). The resulting MPE-SeNPs were 120 nm around in particle size with EE of 89.38% for rutin and 90.59% for puerarin, two marker components in MPE. MPE-SeNPs exhibited a slow drug release and good physiological stability in the simulated digestive fluid. After oral administration, MPE-SeNPs produced significant hypoglycemic effects both in the normal and diabetic rats. Ex vivo intestinal imaging and cellular examinations demonstrated that MPE-SeNPs were provided with outstanding intestinal permeability and transepithelial transport aptness. It was also revealed that MPE-SeNPs could alleviate the oxidative stress, improve the pancreatic function, and promote the glucose utilization by adipocytes. Our study provides new insight into the use of integrative nanomedicine containing phytomedicines and selenium for DM treatment.
Low-Calorie Sweetened Beverages and Cardiometabolic Health: A Science Advisory From the American Heart Association
Authors: Rachel K. Johnson, Alice H. Lichtenstein, Cheryl A.M. Anderson, Jo Ann Carson, Jean-Pierre Després, Frank B. Hu, Penny M. Kris-Etherton, Jennifer J. Otten, Amytis Towfighi, Judith Wylie-Rosett
Journal: Circulation (2018)

In the United States, 32% of beverages consumed by adults and 19% of beverages consumed by children in 2007 to 2010 contained low-calorie sweeteners (LCSs). Among all foods and beverages containing LCSs, beverages represent the largest proportion of LCS consumption worldwide. The term LCS includes the 6 high-intensity sweeteners currently approved by the US Food and Drug Administration and 2 additional high-intensity sweeteners for which the US Food and Drug Administration has issued no objection letters. Because of a lack of data on specific LCSs, this advisory does not distinguish among these LCSs. Furthermore, the advisory does not address foods sweetened with LCSs. This advisory reviews evidence from observational studies and clinical trials assessing the cardiometabolic outcomes of LCS beverages. It summarizes the positions of government agencies and other health organizations on LCS beverages and identifies research needs on the effects of LCS beverages on energy balance and cardiometabolic health. The use of LCS beverages may be an effective strategy to help control energy intake and promote weight loss. Nonetheless, there is a dearth of evidence on the potential adverse effects of LCS beverages relative to potential benefits. On the basis of the available evidence, the writing group concluded that, at this time, it is prudent to advise against prolonged consumption of LCS beverages by children. (Although water is the optimal beverage choice, children with diabetes mellitus who consume a balanced diet and closely monitor their blood glucose may be able to prevent excessive glucose excursions by substituting LCS beverages for sugar-sweetened beverages [SSBs] when needed.) For adults who are habitually high consumers of SSBs, the writing group concluded that LCS beverages may be a useful replacement strategy to reduce intake of SSBs. This approach may be particularly helpful for persons who are habituated to a sweet-tasting beverage and for whom water, at least initially, is an undesirable option. Encouragingly, self-reported consumption of both SSBs and LCS beverages has been declining in the United States, suggesting that it is feasible to reduce SSB intake without necessarily substituting LCS beverages for SSBs. Thus, the use of other alternatives to SSBs, with a focus on water (plain, carbonated, and unsweetened flavored), should be encouraged.
Short, full-dose neoadjuvant chemotherapy in localized high-risk adult soft tissue sarcomas (STS): An exploratory subgroup analysis on responding patients in a randomized controlled trial comparing 3 neoadjuvant versus 3 neoadjuvant + 2 adjuvant cycles of full dose anthracycline and ifosfamide chemotherapy at a 10yr median FU.
Authors: Silvia Stacchiotti, Sara Pizzamiglio, Antonella Messina, Carlo Morosi, Paola Collini, Antonio Llombart-Bosch, Javier Martin Broto, Alessandro Comandone, Josefina Cruz, Giovanni Grignani, Vittorio Quagliuolo, Piero Picci, Antonino De Paoli, Angelo Paolo Dei Tos, Paolo Verderio, Paolo Giovanni Casali, Alessandro Gronchi
Journal: Journal of Clinical Oncology (2018)

11558 Background: We already reported (Cancer 2012;118:5857) the correlation of Choi criteria (Choi) and RECIST with outcome of pts affected by high-risk STS entering a multicentric Italian/Spanish Phase 3 trial comparing 3 vs 5 cycles of (neo)adjuvant CT with full-dose epirubicin + ifosfamide (JCO 2012;30:850; Ann Oncol 2016; 27:2283). We investigated whether the non inferiority of 3 vs 5 cycles held also in the subgroup of patients responsive to preoperative treatment. Methods: Patients were randomized to receive 3 cycles of preoperative CT with epirubicin 120 mg/m2 and ifosfamide 9 g/m2 (Arm A) or to receive the same 3 cycles of preoperative CT followed by 2 further cycles of post-operative CT (Arm B). Radiotherapy could be delivered in the preoperative or in the post-operative setting. Non-inferiority of the primary end-point, overall survival (OS), was assessed by the confidence interval of the hazard ratio (HR; Arm A/Arm B) derived from Cox model. Response was assessed by RECIST and Choi. Results: Between January 2002 and April 2007, 160 pts were assigned to Arm A and 161 to Arm B, 158 patients received preoperative RT (Arm A = 77; Arm B = 81). At a median FU of 117 months (IQR 103-135 months), 123 deaths were recorded, 58 in Arm A and 65 in Arm B. Ten-year OS was 61% for the entire group of patients, 64% in Arm A and 59% in Arm B (HR 0.92, 90% confidence interval [CI] :0.68–1.23). Of 243 patients evaluable for RECIST, 208 achieved a partial response (PR) or stable disease (SD), 93 in Arm A and 115 in Arm B. Ten year OS was 62% in Arm A and 59% in Arm B (HR 1.02; 90% CI 0.70-1.48). Of 166 pts evaluable for Choi, 135 achieved a PR, 60 in Arm A and 75 in Arm B. Ten-year OS was 60% in Arm A and 66% in Arm B (HR 1.29; 90% CI 0.80-2.07). Conclusions: In this (neo)adjuvant trial, the non inferiority of 3 vs 5 cycles of full dose anthracycline and ifosfamide /neo)adjuvant chemotherapy was confirmed also in the subgroup of patients with evidence of radiologic response to the preoperative treatment Clinical trial information: 2004-003979-36.
Impact of different risk factors on survival of malignant pleural mesothelioma.
Authors: Elisabeth Morin, Normand Blais, Mustapha Tehfe, Marie Florescu
Journal: Journal of Clinical Oncology (2018)

e20561 Background: Asbestos exposure is main risk factor for pleural mesothelioma. We decided to look to the impact of different risk factors (Tabaco, obesity, sex, stage, histology, prior radiation, cancer family history) and treatment on survival of inoperable mesothelioma. Methods: Using our SARDO database, we retrospectively analyzed 79 patients diagnosed with inoperable malignant pleural mesothelioma diagnosed at CHUM from 2006 to 2016. Asbestos exposure was established either on working history or presence of pleural plaques at the time of diagnostic. Results: The 27 patients (39%) in asbestos-exposed group were younger (median age 67y) and more men but well balanced for other characteristics compared with the control group (n = 52) (median age 75y). Younger the 65y old patients had an overall better mOS at 18m compared to 7mo for patients older than 65y (p = 0.0001). In consequence, the asbestos-exposed patients had a significant better median survival 13mo compared to non-exposed patients 7mo (p = 0,047). Moreover, the exposed group was significantly more treated 55% receiving chemotherapy compared to only 8% in non-exposed group (p = 0,016). Standard chemotherapy treatment was the main independent factor to impact on survival. The treated asbestos-exposure group had a worse 18 mos mOS compared to 24mos in treated control group (p = 0.016). No difference in survival was seen according to sex (p = 0,096), clinical stage (p = 0,417), smoking history (p = 0,069), histology (p = 0.084) and body mass index (p = 0,415). Conclusions: Asbestos exposure had negative impact on survival when controlled for treatment. The mesothelioma treatment is the only independent factor to positively impact on survival in our 79 homogeneous treated patients. Younger age at diagnostic had also a favorable outcome on survival. No impact on survival was seen with tobacco use, obesity, stage, histology and sex in this analysis. The asbestos-exposed group was significantly more treated which is hypothesis generating.
Perioperative lung protective ventilation
Authors: Brian O’Gara, Daniel Talmor
Journal: BMJ (2018)

ABSTRACT Perioperative lung injury is a major source of postoperative morbidity, excess healthcare use, and avoidable mortality. Many potential inciting factors can lead to this condition, including intraoperative ventilator induced lung injury. Questions exist as to whether protective ventilation strategies used in the intensive care unit for patients with acute respiratory distress syndrome are equally beneficial for surgical patients, most of whom do not present with any pre-existing lung pathology. Studied both individually and in combination as a package of intraoperative lung protective ventilation, the use of low tidal volumes, moderate positive end expiratory pressure, and recruitment maneuvers have been shown to improve oxygenation and pulmonary physiology and to reduce postoperative pulmonary complications in at risk patient groups. Further work is needed to define the potential contributions of alternative ventilator strategies, limiting excessive intraoperative oxygen supplementation, use of non-invasive techniques in the postoperative period, and personalized mechanical ventilation. Although the weight of evidence strongly suggests a role for lung protective ventilation in moderate risk patient groups, definitive evidence of its benefit for the general surgical population does not exist. However, given the shift in understanding of what is needed for adequate oxygenation and ventilation under anesthesia, the largely historical arguments against the use of intraoperative lung protective ventilation may soon be outdated, on the basis of its expanding track record of safety and efficacy in multiple settings.
PTEN and cetuximab resistance in head and neck squamous cell carcinoma (HNSCC).
Authors: Alexandre Andre B. A. Da Costa, Felipe D'Almeida Costa, Andrea Cruz Ferraz de Oliveira, Carlos Stecca, Audrey Oliveira, Ana Caroline Fonseca Alves, Marcos Pedro Guedes Camandaroba, Daniel Vilarim Araujo, Larissa Machado, Vladmir Claudio Cordeiro De Lima
Journal: Journal of Clinical Oncology (2017)

6061 Background: Platinum-based chemotherapy in association to cetuximab is the standart first-line treatment for metastatic HNSCC. There is no established biomarker for cetuximab efficacy in HNSCC. We have previously shown that PTEN loss of expression is a bad prognostic factor for patients treated with platinum-based chemotherapy and cetuximab. The aim of the present study was evaluate the prognostic impact of PTEN loss of expression in patients treated with or without cetuximab and to evaluate its predictive value to cetuximab benefit. Methods: One hundred and nineteen patients with metastatic or locally recurrent HNSCC were included. Clinical data on treatment and outcomes was retroespectively colected from medical charts. Tissue micro-array was constructed to evaluate PTEN protein expression through immunohistochemistry. Citoplasmatic staining was evaluated using H-score. Tumors with H-score &lt; 10 were considered to present PTEN loss of expression. Results: From the 119 patients 72 were treated with chemotherapy plus cetuximab while 47 were treated with chemotherapy alone. Median overall survival (mOS) was 9.2 months and median progression free survival (PFS) was 4.6 months. Patients treated with cetuximab compared to those who were not treated with cetuximab had a mOS of 11.4 vs 7.0 months (p = 0.770) and a median PFS of 6.2 vs 3.0 months (p = 0.249). Patients with PTEN loss of expression had a worse OS and PFS with mOS of 5.8 vs 10.5 months (p = 0.002) months and mPFS of 3.2 vs 5.2 (p = 0.015). On multivariate analysis including PTEN loss of expression and ECOG performance status both remained independently associated to survival with HR 2.25 (CI95% 1.28-3.97, p = 0.005) for PTEN loss of expression and a HR 1.63 (CI95% 1.07-2.50, p = 0.023) for ECOG. Negative prognostic impact of PTEN loss of expression was seen only in the cetuximab treated patients (mOS 7.3 vs 13.0 months; p = 0.002) but not in the chemotherapy only group (mOS 3.2 vs 7.5 months; p = 0.051). Interaction test for treatment group and PTEN loss of expression showed a p = 0.418. Conclusions: The present study confirms PTEN as a prognostic factor for metastatic HNSCC and suggests PTEN expression should be studied in larger cohorts to evaluate its predictive value to cetuximab response.
P05.60 Management of adult patients with medulloblastoma at Skane University Hospital between 1994 and 2017
Authors: K Lideke, M Åström, S Kinhult
Journal: Neuro-Oncology (2018)

We report our experience in the management of adult patients with medulloblastoma, exploring prognostic factors important for survival and disease control. Between 1994 and 2017, 23 consecutive patients with medulloblastoma and age ≥ 18 years old were treated. Sixteen were men and 7 women, median age at diagnosis was 26 years (range 18–62 years). Median follow-up time was 16 years (range 0, 3–24 years). Gross total resection (GTR) was performed in 12 patients, subtotal resection (STR) (≥ 1, 5 cm2 residual disease) in 10 patients and biopsy in 1 patient. Staging according to the Chang classification showed that 20 patients had T2, 1 patient T3a and 2 patients had unknown T stage. M staging showed 20 patients without metastases (M0) and 3 patients with seeding in the spinal subarachnoid space (M3). Twelve patients were assigned to the average-risk group (any T stage, GTR and M0) and 11 to the high-risk group (residual tumour and or metastases). All patients underwent surgery and postoperative craniospinal irradiation (CSI). Vincristine was given weekly concomitantly with CSI in 10 patients. Adjuvant chemotherapy was given to 16 patients. The 5- and 10-year overall survival (OS) rates for the present study were 76% (95% CI 53% -100 %) and 60% (95% CI 28 -92 %), respectively. The 5- and 10 years progression-free survival was 59% (95% CI 35 -82 %) and 47% (95% CI 21–72 %), respectively. Normal approximation confidence interval and Fisher′s exact test was used to analyse outcome. Ten years OS was significantly (p=0.0111) correlated with extent of resection (patients with GTR had a better outcome). Patient gender, age, hydrocephalus that required VP-shunt, tumour location, T-stage, M-stage, time interval between surgery and start of CSI, time interval between end of CSI and start of adjuvant chemotherapy, concomittant vinkristin and adjuvant chemotherapy did have overlapping confidence interval which strongly indicate differences in OS not being significant. Ten patients had tumour recurrence with a median time to recurrence of 15 months. Nine out of ten relapses occurred locally in the posterior fossa. Late recurrences were not rare, two patients relapsed more than 5 years after diagnosis. Generally, the results of salvage therapy for recurrent disease have been poor, with only one patient with long term survival after recurrence. At last follow up, three patients were fully recovered with no deterioration. Five patients suffered from cognitive impairment or substantial fatigue, three from pituitary insufficiency and one from hearing and vestibular dysfunction. Long-term survival is possible in adults treated for medulloblastoma. Late relapse is common and long-term follow-up is important. Our results confirm complete resection as important prognostic factor in this population based clinical patient sample.