tbuckley/cabot-search huggingface dataset:
A nonrandom association of sarcoidosis in patients with gastrointestinal stromal tumor and other sarcomas.
Authors: Andrea Patricia Espejo Freire, Jeremy Ramdial, Breelyn A. Wilky, Darcy Kerr, Jonathan C. Trent
Journal: Journal of Clinical Oncology (2017)

e22521 Background: Sarcoidosis can mimic metastatic cancer. Although sarcoidosis is associated with carcinomas, there are limited data supporting its association with GIST and other sarcomas. Prior reports on cancer related sarcoidosis are inconsistent in terms of prognosis; while some reports link sarcoidosis with a favorable prognosis, others associate it with recurrence and secondary malignancies. Here we describe a series of 7 patients with diagnosis of sarcoma and sarcoidosis seen at a single sarcoma center in South Florida. Methods: Seven patients with diagnosis of both sarcoma and sarcoidosis were identified over the period of 2007 to 2016. Data of presentation, treatment, histology and outcome was tabulated for analysis. The Standardized Incidence Ratio (SIR) was calculated for the state of Florida and for our hospital catchment area. Results: Of the seven patients, 4 cases were GIST, 1 case of unclassified spindled and epithelioid cell sarcoma that coexisted with tenosynovial giant cell tumor, 1 case of uterine leiomyosarcoma, and 1 case of myxofibrosarcoma. Sarcoidosis was diagnosed before sarcoma in 3 patients, after the diagnosis of sarcoma in 3 patients and at the same time of sarcoma diagnosis in 1 patient. All cases of sarcoidosis involved the lungs. From our series, 3 patients have shown no progression of sarcoma, 1 is alive with sarcoma, 2 died due to progression of sarcoma and 1 was lost to follow up. Statistical analyses showed a SIR = 268 (95% CI 106-503), when comparing to the expected incidence in the state of Florida and SIR = 831 (95% CI 329-1562), when comparing to the expected incidence in our catchment area. Conclusions: This case series points to a statistically robust, non-random, association between Sarcoma and Sarcoidosis that has not been previously described. Our study found the lung is not only the most common site of sarcoma metastasis but also the most common site of sarcoidosis. These results infer that patients with presumed metastatic sarcoma should be considered for a biopsy to rule out a benign process such as sarcoidosis. Additionally, the presence of sarcoidosis could be associated with risk of sarcoma. The mechanism of sarcoidosis-associated sarcoma is ongoing.
Why Pulse Oximetry Is Inaccurate in Liver Cirrhosis: Ancient Knowledge
Authors: Sarah Raevens, Isabelle Colle, Anja Geerts, Hans Van Vlierberghe
Journal: Hepatology (2018)

To the Editor: With great interest we read the article by Forde et al., regarding pulse oximetry as a screening tool for hepatopulmonary syndrome (HPS).1 Their results indicate that pulse oximetry is insensitive for HPS detection in patients with liver cirrhosis. We aimed to further clarify the underlying physiologic mechanisms that result in poor correlation between pulse oximetry and arterial oxygenation in this patient population. The oxyhemoglobin dissociation curve (ODC) is a sigmoid curve that plots the relation between oxygen saturation (SO2) and partial pressure of oxygen in the blood. The strength with which oxygen binds hemoglobin is influenced by several factors, which might reshape the ODC. In patients with cirrhosis, the ODC is significantly dispersed relative to normal conditions,2 which might result in normal SO2 readings despite a state of hypoxemia. This dispersion can at least in part be attributed to increased 2,3‐diphosphoglycerate (2,3‐DPG) levels (Fig. 1).3 2,3‐DPG is formed in erythrocytes during glycolysis and represents an adaptive mechanism that enables compensation for several disease states characterized by reduced tissue oxygenation, e.g., a hyperdynamic circulation.3 At least four mechanisms have been identified that enhance 2,3‐DPG production in cirrhosis. First, sodium and water excretion are affected, which most frequently result in hyponatremia and hypokalemia, hyperchloremia, and hyperphosphatemia. These plasma ion disturbances are known to stimulate 2,3‐DBP synthesis,2 which can moreover be influenced by diuretic treatment.2 Second, the rate of glycolysis is increased and 2,3‐DPG phosphatase is decreased, with a resultant increase in 2,3‐DPG, during alkalosis, which is frequent in patients with cirrhosis due to hyperventilation.2 Third, low glucokinase and glucose‐6‐phosphatase activity and high hexokinase have been observed in cirrhosis and stimulate the glycolysis cycle.5 Fourth, erythrocytes increase their 2,3‐DPG content in response to chronic anemia, to ensure proper tissue oxygenation.3Figure 1: Dispersion of the ODC in liver cirrhosis. Abbreviation: PO2, partial pressure of oxygen.Furthermore, mechanisms other than 2,3‐DPG may influence the position of the ODC, including propranolol intake, elevated carbon monoxide levels, and peripheral vasodilation.1 Also, as correctly stated by the authors, SO2 measurements can be normal in HPS patients who have an increased alveolar‐arterial oxygen gradient with preserved partial pressure of oxygen levels, due to hypocapnia from hyperventilation. To conclude, the work by the Pulmonary Vascular Complications of Liver Disease study group not only carries great clinical implications with regard to our current HPS screening program but also highlights the pitfalls of using pulse oximetry in the general population with cirrhosis. Potential conflict of interest Dr. Isabelle Colle consults for Promethera.
Will SPAR be useful in the usual patients with scleroderma?
Authors: Arghya Chattopadhyay, Varun Dhir, Shefali Sharma, Aman Sharma, Sanjay Jain
Journal: Annals of the Rheumatic Diseases (2018)

Will SPAR be useful in the usual patients with scleroderma?We read with great interest the simplified predictive score 'SPAR model' by Wu et al. 1 A simplified predictive score which can predict 'fast progressors' can be used to target and selectively recruit such patients for drug trials and finally lead to improvement in outcomes in the future.However, certain aspects require clarification.First, the external validity of the patients recruited is unclear.Although early interstitial lung disease (ILD) as defined in the study (<20% CT involvement) would be common, approximately half of the patients of this study could be having forced vital capacity (FVC) >100% (assuming normality).The latter would be a subgroup which would be uncommon.More interestingly, these patients have never been recruited for interventional studies looking at drugs on ILD-both the scleroderma lung studies (refs 2 and 3 ) recruited patients with FVC ≤85%; thus we have no idea whether they (FVC>100%) respond to therapy.In the latter study (SLS2), only 30 out of 198 screened systemic sclerosis were excluded due to pulmonary function test, which could be higher or lower FVC and diffusing capacity of the lung for carbon monoxide-.The authors may like to provide their cohort numbers and how many of them fulfilled the inclusion criteria.Second, the authors found 'arthritis ever' to be significant after multivariate analysis, though a previous study did not show any association of arthritis and ILD progression. 4However, there is no comment on whether arthritis was persistent and erosive, and did it require treatment in their cohort?Was baseline presence of arthritis also significant?In a patient who comes for the first time, history of arthritis would not be available.Third, the best multivariate predictive model in this study (model 3 (SpO2≤94%+arthritis ever)) has a sensitivity of only 44%, thus more than half of the progressors would not be detected.Even in a 0-2 SPAR score, the most common score is 1, and that would only identify one-third of progressors! 1Finally, the authors may like to provide any data on other variables expected to predict progression-baseline extent of ILD on CT (varying from 0% to 20%), oesophageal diameter on high-resolution CT (as shown by other studies 2 5 ) and nail fold capillaroscopy.The latter becomes important as low oxygen saturation after the 6 min walk test, when severe ILD and pulmonary artery hypertension (PAH) are excluded (as in this study), may reflect early microvasculature changes in pulmonary bed, which as expected to be generalised and would be reflected in the nail bed capillaries also.
Association of on-treatment plasma HGF levels with overall survival (OS) in patients (pts) with advanced renal cell carcinoma (RCC) treated with interferon alpha (INF) +/- bevacizumab (BEV): Results from CALGB 90206 (Alliance).
Authors: Daniel J. George, Susan Halabi, Mark D. Starr, Herbert Hurwitz, John C. Brady, Ian Barak, Michael J. Morris, Brian I. Rini, Eric Jay Small, Won Kim, Mary-Ellen Taplin, Andrew B. Nixon
Journal: Journal of Clinical Oncology (2017)

4522 Background: Elevated baseline HGF levels were associated with shorter OS in pts treated with BEV+INF. We evaluated on-treatment HGF levels to describe treatment-related changes and associations with outcome. Methods: We analyzed baseline EDTA plasma samples from 310 pts (148 INF; 162 BEV+INF) using an optimized multiplex ELISA platform for HGF at baseline and after 4-weeks (wks) on treatment. Primary endpoint of this analysis was OS. The Kaplan-Meier estimated the OS distribution and the proportional hazards model tested the prognostic importance of change at 4-wks from baseline in HGF levels in predicting OS, adjusting for treatment arm, bone metastases and stratification variables. Results: The median baseline HGF level in 310 pts was 161.4 pg/ml. Elevated HGF at 4-wks (&gt;median) was associated with a worse OS (median OS = 14 vs 27 months; adjusted hazard ratio (HR)= 1.75, p&lt; 0.0001). Only 9/155 pts (5.8%) with baseline HGF levels ≤ median developed elevated HGF (&gt;median) at 4-wks; 66/155 pts (43%) with baseline HGF levels &gt;median lowered HGF (&lt;median) at 4-wks from baseline. Compared to pts with persistently elevated HGF levels, a decline in HGF levels at 4-wks (&lt; median) was associated with improved OS (19 vs 13 months, adjusted HR=1.41, p=0.043). Conclusions: In RCC pts with low baseline HGF levels (&lt; median), levels remain consistently low and are associated with improved OS. Conversely, in pts with high baseline HGF levels results are split; some patients continue to have high levels on treatment and are associated with a worse OS, suggesting that, HGF predicts for therapeutic benefit and represents a potential mechanism of resistance. Support: U10CA180821, U10CA180882. Clinical trial information: NCT00072046 .
The association between atopy and Hodgkin’s lymphoma in teenagers and young adults: A UK nationwide case control study.
Authors: Meena Rafiq, Sara Thomas, Charlotte Warren-Gash, Andrew Hayward
Journal: Journal of Clinical Oncology (2018)

10526 Background: Hodgkin’s Lymphoma (HL) is the commonest cancer in teenagers and young adults (TYAs). Incidence in this age group has been increasing since the early 1990s in the UK, Australia, Canada and several US states. The cause in the majority of cases remains unknown. Previous studies have shown conditions involving impaired immune regulation, including HIV, immunosuppressive treatment and some autoimmune conditions, are associated with increased HL risk. However, few studies have investigated the link between atopy, the commonest form of childhood immune dysregulation, and HL and the results have been conflicting and inconclusive. This study uses large scale, UK data to investigate the association between atopic disease and immunosuppression with development of HL in TYAs. Methods: We conducted a case control study using primary care data from the UK Clinical Practice Research Database linked to hospitalization data. 1,238 cases with HL diagnosed between the ages of 0-49 years were individually matched using concurrent sampling to six controls each by age, sex and follow up time (7,428 controls). Multivariable logistic regression was used to investigate the association between atopic diseases (asthma, eczema, hay fever) and immunosuppression with HL incidence. Results: A prior diagnosis of asthma was associated with 26% increased odds of developing HL (Adjusted Odds Ratio (AOR):1.26, 95%CI 1.08-1.49 p = 0.005). There was weak or no evidence for an association between eczema or hay fever and HL (AOR:1.15, 95%CI 0.98-1.34 p = 0.09; AOR:0.88, 95%CI 0.73-1.05 p = 0.15, respectively) or that HL risk was increased in individuals with more than one atopic diagnosis (p = 0.07). Consistent with previous studies, immunosuppressed individuals had 14 times the odds of developing HL (AOR:13.79, 95%CI 5.67-33.50 p < 0.001). Conclusions: This study has identified asthma as a risk factor for developing HL in early life. These findings add to the growing evidence that immune dysregulation is involved in development of HL in TYAs. Understanding the immune components and pathways underlying this relationship could help uncover markers for HL detection, recurrence and to develop new therapeutic interventions.
Comparison of genomic profiles to reveal heterogenous patterns of tumor evolution in primary and recurrent diffuse gliomas.
Authors: Libuse Lizcova, Karla Svobodova, Halka Lhotska, Hana Cechova, Zdenek Krejcik, Sarka Ransdorfova, Iveta Sarova, Lenka Pavlistova, Silvia Izakova, Filip Kramar, Petr Hrabal, Tomas Jirasek, Kyra Michalova, Zuzana Zemanova
Journal: Journal of Clinical Oncology (2018)

e14060 Background: Diffuse gliomas represent heterogeneous group of tumors with highly variable biological behavior. Despite of radical surgical resection and intensive therapy, recurrent lesions with new acquired genetic properties appear in majority of patients. Nature of tumor genome evolution in these cases remains poorly understood and is often neglected. Methods: We compared genomic profiles of 11 paired primary and recurrent gliomas - diffuse astrocytoma (6x), anaplastic astrocytoma (3x) and glioblastoma (2x). The biopsies taken from primary and recurrent tumors were analyzed using SNP array (Illumina), I-FISH (Abbott Molecular, MetaSystems) and MLPA (MRC-Holland) to assess copy number variations and IDH1 mutations status. Methylation of MGMT and MLH3 promoters was investigated by MS-MLPA. Results: The frequency of genomic changes such as loss of chromosome 10, gains on chromosomes 7 and 19 and losses on 9p and 13q as well as 17p LOH and IDH1 mutation was typical for diffuse gliomas and these markers were present in primary and recurrent lesions. In 7/11 recurrent tumors the genetic profile showed additional chromosomal imbalances compared to primary tumor. In 4/11 pairs the profiles were divergent, i.e. the recurrent tumors included additional changes but missed some of the original ones. Losses of chromosomal regions 6p21.33, 6q27, 9q21.13 and 11p11.2 and hypermethylation of MGMT and/or MLH3 were repeatedly detected in recurrent tumors. The progression to a higher grade of glioma occurred in five of 11 patients. Conclusions: We provided a direct example of heterogenous patterns of genomic changes in 11 paired gliomas. Recurrence may be driven by proliferation of cells with additional genomic imbalances to those detected in primary tumor or by one or more subclones, which were present within the primary tumor in addition to the major tumor clone and may have shared some of its genomic imbalances. We suppose that recurrent gliomas are genetically and/or epigenetically different tumors from their corresponding primaries, and thus may benefit from different treatment approaches. Supported by RVO-VFN64165 and GACR-P302/12/G157.
A phase Ib/II, open-label, dose escalation study to evaluate the safety, pharmacokinetics, and efficacy of SM88 in patients with prostate cancer.
Authors: Giuseppe Del Priore, Steve Hoffman, Daniel W. Nixon
Journal: Journal of Clinical Oncology (2017)

TPS2615 Background: Non-hormonal treatments for biochemically recurrent non-metastatic prostate cancer (nmPC) are limited. SM88 is a novel combination of proprietary tyrosine isomer (TI) and other repurposed agents (CYP3a4 inducer, mTOR inhibitor and catalyst) designed to selectively increase metabolic oxidative stress in cancer cells. Early data reported SM88 activity in solid tumors without significant toxicity (Hoffman et al J Clin Oncol 2013; e22095, Hoffman et al Ann Onc 2016: vi551). Methods: This is an open-label multi-center, dose escalating, dose expansion study in nmPC who have failed or refused androgen deprivation. The study includes a dose escalation phase Ib and dose expansion phase 2. The primary objectives are to determine the effect of SM88 on circulating tumor cells (CTC), and progression-free survival. Secondary objectives are: LDH, bone-specific alkaline phosphatase, urinary N-telopeptide, neutrophyll/llymphocyte ratio, cutaneous hyper-pigmentation correlation, PSA doubling times, safety, and patient reported outcomes. As of Jan ‘17, Phase 1b cohorts 1 and 2, with TI and component PK evaluations, have completed enrollment with adequate numbers to establish the Phase 2 dose without DLT. Phase 2 has begun, with 33 patients planned for at least 6 cycles (@28d) to reach the desired power. This would be followed by a pivotal Phase 3 study in the same group of patients. We propose to conduct a pivotal randomized phase 3 of SM88 in rising PSA, nmPC versus patient’s and clinician’s choice, limited to 2 options i.e. observation or ADT therapy. Inclusion would include doubling time &lt; 9 months, elevated CTCs and recurrent disease after localized curative intent therapy (the same population as our completed Phase I and ongoing phase II). Outcomes will include delay of radiographic PFS, and delay of time to subsequent toxic therapy i.e. cytotoxic systemic chemo and/or radiation therapy. We proposed this pivotal trial will lead to a successful NDA for an indication in this population of patients. Rapid accrual is expected at several institutions because of the urgent need for less toxic alternatives to androgen deprivation therapy.
Curative intent of local excision alone for stage I anal canal squamous cell carcinoma (ACSCC).
Authors: Zhaohui Jin, Sakti Chakrabarti, Brandon M Huffman, Christopher Leigh Hallemeier, Joleen Marie Hubbard, Axel Grothey, Amit Mahipal
Journal: Journal of Clinical Oncology (2018)

e15574 Background: Definitive chemoradiotherapy (CRT) is the standard of care for localized or locally advanced ACSCC, while surgery is typically reserved for salvage therapy. Outcome of treatment with local excision alone is unknown and is currently not recommended by NCCN. We retrospectively analyzed outcome of the patients with small (T1 lesion) incidentally found ACSCC who were treated with local excision alone. Methods: On retrospective analysis, a cohort of 13 patients with pathologically confirmed stage I ACSCC treated at Mayo Clinic between 1990 and 2016 was identified who were managed with local excision alone. Baseline as well as follow up data were obtained by chart review. Results: Median age of the patients at diagnosis was 64 years (range: 36-89 years) and majority were females (12 out of 13, 92%). Median follow-up duration was 106 months. Of the 13 patients, 3 patients did not receive standard CRT due to co-morbid conditions and other 10 patients chose surveillance over CRT because of small size of the lesion. There were only 2 patients who had disease recurrence, 1 at 21 months and the other at 97 months. Both patients were salvaged with CRT and remained alive and disease free 123 months and 264 months out from diagnosis, respectively. There were 3 deaths, all unrelated to ACSCC. Of the patients who had at least 5 years of follow up after diagnosis, 77% were alive and disease free. Conclusions: Local excision as a single modality of treatment may be safe and effective for highly selected small stage I ACSCC patients. Further clinical study is warranted to accurately define the patient population who can be treated with local excision alone, potentially sparing them long term toxicities of CRT.
Abstract 16060: Usefulness of Magnetic Resonance Feature Tracking to Measure Both Systolic and Diastolic Cardiac Function: Comparison With Pressure Volume Loop Analysis in Animal Study
Authors: Hideto Ozawa, Shigeru Miyagawa, Satsuki Fukushima, Akima Harada, Emiko Ito, Atsuhiro Saito, Takayoshi Ueno, Koichi Toda, Toru Kuratani, Yoshiki Sawa
Journal: Circulation (2014)

Background: The noninvasive evaluation of cardiac function remains a challenge. A new modality, feature tracking (FT), offers a novel method of measuring myocardial strain and velocities from cardiovascular MR (CMR) images. We aimed to quantify the left ventricular diastolic and systolic function by using FT- CMR cine acquisitions in comparison with values from cardiac catheterization. Methods: Porcine ischemic heart models were obtained by using LAD occlusion methods. We subjected 13 porcine models that had both CMR and cardiac catheterization. LV long axis CMR cines were analyzed using FT-CMR software (TomTec, Germany). Myocardial mechanics (diastolic function(DF): peak of early diastolic dv/dt, strain rate, systolic function(SF): peak of negative dv/dt, %strain and strain rate) which obtained from FT-CMR were compared with catheterization parameters (DF: EDP, Tau, EDPVR, peak of negative dp/dt, SF: ESPVR, peak of positive dp/dt). We also examined the correlation with the DF and SF with the %fibrosis an...
Evaluation of selected molecular parameters in two types of endometrial cancer.
Authors: Janina Markowska, Anna Markowska, Pawel Knapp, Monika Pawalowska, Jakub Zurawski, Stefan Sajdak, Andrzej Bienkiewicz, Anita Olejek, Wiesława Bednarek, Anna Grybos, Andrzej Marszalek, Violetta Filas, A. Roszak, Katarzyna Wojcik-Krowiranda, Wojciech Kuncman, Radoslaw Madry, Marcin Jozwik
Journal: Journal of Clinical Oncology (2016)

e17118 Background: Multiple factors linked to etiology, clinical course and prognosis in two types of endometrial cancer (endometrioid type I and non-endometrioid type II cancer) have been recognised .These include alterations in concentrations of estrogen and progesterone hormones, mutations in MMR (mismatch repair) genes, PTEN, TP53, beta-catenin, disturbed signalling pathways (e.g. PI3K/AKT). However, in several studies, including the data of Epidemiology of Endometrial Cancer Consortium, endometrial cancers and those of type II (serous carcinoma and clear-cells carcinoma) in particular proved to be more heterogenous than expected (1),(2),(3). Methods: The study manifested a multi-centre character. Using sections of paraffin-embedded preparations and immunocytochemistry with application of specific antibodies, in 115 patients with EC type I and in 31 patients with EC type II, the expression of ER ß1, ER ∂, PR and BRCA1 was estimated. Results: Expression of ER ß1 was augmented in USC (type II ), in cancers of a poor differentiation(G3), it was more pronounced in cancers of an increased clinical advancement according to FIGO. Expression of ER ∂ was detected in the endometrioid type I cancer manifesting good histological differentiation (G1or G2) and a low clinical degree of advancement according to FIGO. In over 50% cases of EC type II a mutation was detected in BRCA1, associated with a decreased expression of ER ∂. Conclusions: An augmented expression of ER ß1 in EC was linked to poor prognosis in type II EC. Higher expression of ER ∂ in type I EC of increased maturity was associated with a good prognosis. It seems that type II EC is partially connected to BRCA1 mutation.