tbuckley/cabot-search huggingface dataset:
The clinical features and genomic landscape of elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) in patients with colorectal cancer.
Authors: Ming Huang Chen, Shih-Ching Chang, Jen-Kou Lin, Shung-Haur Yang, Jeng-Kai Jiang, Chien-Hsing Lin, Yuan-Tzu Lan, Chun-CHI Lin, Wen-Yiah Liang, Wei-Shone Chen
Journal: Journal of Clinical Oncology (2018)

e15591 Background: Elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) is another form of microsatellite instability (MSI) at tetranucleotide repeats and has emerged as a new potential biomarker in multiple cancers. In colorectal cancer (CRC), the clinical implications and mutation spectrum of EMAST remain inconclusive. Methods: We evaluated 1,505 CRC cases using five markers (D20S82, D20S85, D8S321, D9S242 and MYCL1) for EMAST and the Bethesda panel for MSI status. Most commonly mutations involved in CRCs were identified by MassArray Assay. DNA repair genes were analyzed by Next-Generation Sequencing (NGS). Clinical characteristics and prognostic relevance were correlated with EMAST. All statistics were assessed by SPSS software (version 16.0). Results: We first identified the optimal definition of EMAST-positive as tumors showing framshifts in at least two tetranucleotide markers. According to this definition, the frequencies of EMAST was 159 (10.6%) out of 1,505 CRC cases with unique clinical features with female predominant (p = 0.017), a higher prevalence in proximal colon (p < 0.001), a tendency of early stage (p = 0.002), poorly differentiated (p < 0.001), mucinous histology (p = 0.001) and highly associated with MSI (p < 0.001). Mutation spectrum in EMAST- positive tumors showed a higher incidence of PI3KCA mutations (p = 0.003), BRAF mutations (p < 0.001), TGFßR mutations (p < 0.001), PTEN mutations (p = 0.001) and AKT1 mutations (p = 0.04) compared with EMAST– negative tumors. Furthermore, Compared with EMAST positive alone or MSI alone tumors, both EMAST positive and MSI-H tumors had higher mutation rates in MSH6, MSH3, PMS2, EXO1 genes (p < 0.001, p = 0.005, p = 0.001, p = 0.027) and MLH1, MSH6, and EXO1 genes (p = 0.019, p = 0.005, p = 0.046). Finally, EMAST-positive tumors was a good prognostic factor in early stage CRC (p = 0.002), but not stage IV CRC (p = 0.920). Patient with both EMAST positive and MSI-H had best outcome compared with other patients (p < 0.001). Conclusions: The EMAST defines a unique molecular subtype of CRC.
TCT-612 Physician Prediction of Mortality Outcomes in the Cardiac Cath Lab: Comparisons to a Validated Risk Score
Authors: Kiran Sarathy, Richard Jung, Alisha Labinaz, Rebecca Rochman, Ian Pitcher, Robert Moreland, Pouya Motazedian, Francisco Ramirez, Pietro Di Santo, Jeffrey Marbach, Paul Boland, Trevor Simard, Saleh Alghofaili, Juan Russo, Etienne Couture, Marino Labinaz, Chris Glover, Benjamin Hibbert
Journal: Journal of the American College of Cardiology (2018)
Association of allograft rejection with reduction of immunosuppression for post-transplant lymphoproliferative disorder: Analysis of a 20-year single-institutional experience.
Authors: Aaron J Franke, Rohit Bishnoi, Ravneet Bajwa, William Paul Skelton, Niraj Patel, William Birdsall Slayton, Nam H. Dang
Journal: Journal of Clinical Oncology (2017)

e19047 Background: Post transplant lymphoproliferative disorder (PTLD) is a rare, but potentially fatal complication of transplantation and therapeutic immunosuppression (IS). The cornerstone of PTLD management is reduction of IS, which carries the risk of allograft rejection. Methods: Retrospective analysis of patients diagnosed with PTLD after solid organ (SOT) or allogeneic stem cell transplant (HSCT) at the University of Florida were identified through a review of individual EMR charts. This analysis focused on rates of allograft rejection and graft failure with RI. Results: Of 138 patients diagnosed with PTLD between 1994 and 2016, 15% (n = 20) experienced allograft rejection during PTLD treatment. The primary organ of transplant and rejection included liver (35%), lung (25%), heart (10%), HSCT (15%) and kidney (15%). Median age at PTLD diagnosis was 14.5 years (range 2-59), males (50%) and median time from transplant to PTLD diagnosis was 25 months (range 0-173). RI was a documented as a component of initial PTLD treatment in 19/20 (95%) patients, with 2/20 (10%) undergoing complete withdrawal of immunosuppression, 13/20 (65%) partial RI (withdraw of one or more drugs) and 3/20 (10%) dose reductions of their established IS regimen. One lung recipient (5%) was transitioned to an alternative agent, and one patient had no documented records of IS adjustment. Treatment for acute rejection included observation 2/20 (10%), pulse steroids 11/29 (55%) or IS increase 12/20 (60%). 7/20 (35%) received combination steroids and increased IS. Allograft failure developed in 5/20 (25%) (1 kidney, 1 lung, 1 heart, 1 liver, 1 BMT). Allograft failure was not shown to correlate with RPI score at diagnosis, organ transplanted, induction therapy at transplant or 3-year OS. Of note 5/5 (100%) of patients received Rituximab as part of initial treatment, versus 5/15 patients whose grafts survived. Conclusions: RI for PTLD is associated with moderate rates of response, however acute graft rejection is common and is associated with high rates of graft failure. PTLD may still have favorable outcomes when combining partial RI with chemotherapy and Rituximab.
P05.71 Acute stroke in cancer patients: do they benefit from reperfusion treatment?
Authors: A Taliansky, M Bakon, Y Schwammenthal, S Mausbach, O Merzlyak, C Granbichler, R Tsabari, J Chapman, D Orion
Journal: Neuro-Oncology (2018)

Thromboembolism is the second leading cause of death in cancer. Stroke is one of thrombotic events that can dramatically change the patient functional status and influence the modality and intensity of oncological treatment. There are no clear guidelines for the treatment of cancer related stroke in general and efficacy of intravascular acute stroke treatment in particular. 21 cancer patients with acute stroke were treated in the department of Neurology at the Sheba Medical Center in Israel. Median age was 68 years (28–85), female/male ratio was 11/10. Decisions on t-PA or endovascular treatment were made according to accepted international guidelines. All patients had common vascular risk factors and 5 of them had atrial fibrillation. 15 patients were not treated with any anti aggregants or anti coagulants on admission, included 3 patients in which such treatments were discontinued because of cancer related complications. 20 patients were within 3 years of cancer diagnosis, 10 of them had metastatic disease of which 3 had brain metastasis. 12 patients were on active oncological treatment, 2-during diagnostic procedures, 7-in active follow up. All patients had significant neurological deficit NIHSS 5–25 (med 18), 15 were admitted within the t-PA window, and 7 of these patients were treated with t-PA first. The other patients and 6-out of the patients within the t-PA window were treated directly with intravascular treatment. Occlusion location was M1-8 patients, M2-4 patients, M3-2 patients, carotid T-2 patients, ICA-2 patients, common carotid-1 patient and VB-2 patients. The median mRS score of patients at discharge was 4, 7 patients were discharged to a home rehabilitation program. There were no patients with significant t-PA or intravascular treatment complications. The 3 month median mRS score was 4. For 9 patients oncological plan was changed because of the neurological condition. Mortality during the follow up period was: 1wk-9%, 1mo-9%, 3mo-14%, 1year-19%. Except for the first week, all mortality was cancer related. Active cancer patients who present with acute stroke can be treated according to general guidelines including intravascular treatment. Cancer patients that have regular vascular risk factors have to be treated for primary and secondary prevention of vascular events if contraindications do not exists.
Evaluation of microarrays for measuring cell cycle progression (CCP) gene expression.
Authors: Steven Stone, Matthew R. Cooperberg, Darl D Flake, John W. Davis, Judd W. Moul, Jonathan David Tward, Michael K. Brawer
Journal: Journal of Clinical Oncology (2017)

e16566 Background: A CCP score has been developed and validated to provide prognostic information in prostate cancer. To date, our studies have exclusively used qRT-PCR to measure CCP gene expression, which is generally considered the ‘gold-standard’ for measuring RNA expression levels. However, qRT-PCR allows for the interrogation of a relatively small number of genes. Because prostate cancer biopsies provide very limited tissue, there is interest in evaluating RNA expression platforms that could simultaneously integrate CCP genes and other less characterized targets that might be clinically useful. Here we evaluate the ability of microarrays to measure CCP gene expression. Methods: CCP scores for 1636 radical prostatectomy samples submitted for commercial testing were generated from the mean expression of 31 CCP genes and 15 housekeeping genes as determined by qRT-PCR. CCP scores were also generated from several publically available Affymetrix microarray expression data sets (Nakagawa et al. 2008, Karnes et al. 2013, Klein et al. 2014, Boormans et al. 2013, Taylor et al. 2013) by averaging the intensities (RMA processed, base 2 log scale) of the 31 CCP genes. Expression data were evaluated by comparing CCP score range and pairwise correlations between CCP genes. Results: The average pair-wise correlation in the commercial cohort using qRT-PCR was 0.67. The pair-wise correlations in the microarray studies were significantly lower, ranging from 0.17 (Klein) to 0.58 (Boormans). Importantly, the data in Boormans et al. was generated from frozen tissue. The CCP score in our commercial cohort ranged from -2 to 3 (base 2 log scale) with a standard deviation (SD) of 0.79. In contrast, the CCP score range in microarray studies was highly truncated with SDs ranging from 0.12 (Nakagawa) to 0.46 (Boormans). Conclusions: Expression of CCP genes as determined by microarrays correlates weakly with expression measured by qRT-PCR, with reduction in normally observed pairwise correlations among CCP genes and the range of CCP scores. This is especially true if the RNA is derived from fixed tissue. As a result, microarray generated CCP scores cannot be assumed to be a valid surrogate for qRT-PCR generated scores for prediction of patient outcome.
Anal cancer outcomes in patients treated with intensity modulated (IMRT) compared to 3-d conformal radiation therapy (3DCRT).
Authors: Gustavo Ferraris, Maria Fernanda Diaz Vazquez, Mario Ferraris, Jorge Palazzo, Eduardo Fernandez
Journal: Journal of Clinical Oncology (2016)

e18088 Background: To evaluate Clinical Outcomes, Toxicities, and Colostomy Free Survival comparing 3DCRT Versus IMRT techniques in anal cancer Methods: This is a multi-center retrospective review of data in 290 patients who were treated with definitive chemoradiation therapy for locoregional anal carcinoma between 1992 and 2010. All of them were preoperatively assessed by a surgeon. 95% underwent chemotherapy. Data recorded included details of treatment, toxicities, disease progression, and whether a colostomy was required during the follow-up period. Overall (OS), progression-free (PFS), and colostomy-free (CFS) survival were calculated with Kaplan-Meier methods. Results: The mean age was 64 years The mean follow-up was 30 months. 90% presented with a squamous cell histology. Lymph nodes were thought to be positive in 16% of patients. 169 patients (60%) received IMRT, and 112 patients (40,%) received 3DCRT. The median total tumor dose was 54 Gy. Most patients (80%) experienced acute complications, and 56 % required a treatment break. The IMRT group had fewer and shorter treatment breaks (48% vs 65%)(p = 0.0261) 19% of patients experienced late complications. Patients who received IMRT had a high significant reduction in all grade 3 acute toxicities versus grade 2 toxicities with respect to skin, hematological and GI symptoms and late GI toxicity, as compared to those treated with 3DCRT. The 3-year OS, PFS and CFS were 68, 78, and 91%, respectively. A univariate analysis showed that performance status, gender, dose and t-stage were statistically significant for OS. Performance status, t-stage, and treatment break predicted for PFS. There were no statistically significant predictors for CFS. On multivariate analysis, t-stage and performance status were significant of OS, t-stage, performance status and age for PFS, and no variable predicted for CFS. Conclusions: In this cohort, one of the largest series directly comparing patients treated with IMRT vs 3DCRT, had similar OS and PFS. Higher radiation doses to the primary and draining lymph nodes and fewer prolonged treatment breaks may contribute to improved outcomes in patients treated with IMRT.
Clear cell ovarian cancer (CCOC): 115 patient (pt) series showing access to experimental therapy may improve response rates in recurrent disease.
Authors: Michael-John Devlin, Dhivya Chandrasekaran, Naveena Singh, Jonathan A. Ledermann, Michelle Lockley, Mary McCormack, Nafisa Wilkinson, Rowan Miller, Rebecca Sophie Kristeleit
Journal: Journal of Clinical Oncology (2018)

5581 Background: 10 year survival for ovarian cancer (OC) in the UK has improved from 18% (1971) to a predicted survival of 35% (2011). Historical data show pts with advanced CCOC have worse survival compared to other histological subtypes of epithelial OC. We sought to determine treatment type and outcome of CCOC pts at 2 UK gynaecological cancer centres. Methods: Medical records of pts with CCOC treated between 2002 and 2017 were reviewed. Data collected comprised pt and tumour characteristics, treatment and outcome. Results: 115 pts, median age 56 (29-86) years (y) with CCOC were identified: stage (S) I (62), II (16), III (23), IV (8) and unknown (6). 91 pts had pure CCOC and 24 had mixed histopathology: endometrioid (83%), serous (12%), other (5%). Endometriosis co-existed in 43 (37%) pts; 34 pure CCOC, 8 mixed endometrioid. BRCA mutations were present in 4/19 tested and MMR loss in 2/8 tested. 21/23 pts with a thromboembolic event and 9/10 pts with hypercalcaemia (2.72-3.63mmol/L) had advanced or recurrent disease. 19 pts had a prior or synchronous malignancy, most commonly endometrial (8) or breast (6). Primary refractoriness to first line treatment occurred in S I (3%), III (13%) and IV (100%) CCOC with median overall survival (OS) of 224 days (d). Recurrence rates were 22% (S I), 38% (S II) and 61% (S III). Molecular targeted agents (MTA) were used in 29 treatments; bevacizumab (45%), nintedanib (17.5%), PARP combination (10%), PI3K/mTOR inhibitor (10%), other novel agent (17.5%).33pts had 2nd line treatment with overall response rate (ORR) of 30% and progression free survival (PFS) 258d. 12/33pts treated with a regimen containing a MTA had PFS 358d vs 228d for those without. ORR in the 3rd line was 14% with PFS 185d. The OS rate at 1y was 98% (S I), 100% (S II), 86% (S III) and 0% (S IV) and at 5y was 81% (S I), 50% (S II) and 23.5% (S III). Conclusions: Late stage CCOC has a phenotype distinct to early stage with a propensity to be treatment resistant, recur, have paraneoplastic manifestations and poor survival. The 2nd line ORR of 30% in our cohort is higher than expected and may reflect increased MTA use. 21% and 25% pt had a BRCA variant or MSI loss suggesting benefit of testing CCOC.
P05.49 Extra-neural metastases from a sacro-coccygeal myxopapillary ependymoma: a case report
Authors: F Bruno, F Franchino, C Chiavazza, A Pellerino, R Soffietti, R Rudà
Journal: Neuro-Oncology (2018)

Myxopapillary ependymoma (MPE) is a subtype of ependymal tumour of grade I WHO arising in the conus medullary, cauda equina and filum terminale. The prognosis is relatively favourable, although MPE may recur and spread in the leptomeninges. Extra-neural metastases are rare, but occasionally described. Here, we report a unique case of subcutaneous and lung metastases from a MPE of the sacro-coccygeal region who underwent multiple lines of therapy. A 53 year-old woman was diagnosed with a sacro-coccygeal MPE in 1997. She underwent subtotal resection and adjuvant radiotherapy with residual tumour stabilization until 2012, when she experienced lumbar pain and the MRI showed signs of local progression. CT showed multiple lung lesions, without FDG (fluoro-deoxy-glucose) PET positivity, that were considered too small for a biopsy. Therefore, chemotherapy with temozolomide was started, based on literature data in ependymomas. A good clinical and radiologic disease control was obtained, both at the primary site and the lung level for 18 months, when temozolomide was stopped. 6 months after interrupting temozolomide, we observed a local sacro-coccygeal recurrence and the appearance of a subcutaneous nodule in the gluteus, with stable lung lesions on CT and FDG-PET. The biopsy of the cutaneous nodule confirmed the diagnosis of MPE localization. Intensified temozolomide was started with further disease progression both in the sacro-coccygeal site and lung with multiple active lesions, associated with symptomatic and drug resistant chronic cough. A CT-guided biopsy of lung nodules confirmed the diagnosis of MPE. Thus, the patient started II line chemotherapy with an association of platinum and lomustine, of which 8 cycles have been administered with radiologic stabilization of all lesions. To date, no further recurrences have been observed. We present a case of late multiple extra-neural metastatic MPE that displayed a successful stabilization following chemotherapy.
NBTXR3, hafnium oxide nanoparticles in the treatment of liver cancer: A phase I/II trial.
Authors: Enrique Chajon, Marc Pracht, Thierry De Baere, France Nguyen, Jean-Pierre Bronowicki, Veronique Vendrely, Anne-Sophie Baumann, Valérie Croisé-Laurent, Emmanuel Rio, Yan Rolland, Samuel Le Sourd, Pierre Gustin, Christophe Perret, Francoise Mornex, Didier Peiffert, Philippe Merle, Eric Deutsch
Journal: Journal of Clinical Oncology (2018)

e16194 Background: Hepatocellular carcinoma (HCC) is the most widespread primary liver cancer. Liver metastasis (mets) are even more common with a wide range of malignancies. Management of both liver affections is a challenging task regarding toxicity toward liver functions. In response, NBTXR3, innovative injectable hafnium oxide nanoparticles activated by radiotherapy, was developed to increase the local deposit of energy within the tumor cells without negatively affecting the liver. It is currently evaluated in a phase I/II clinical trial to introduce the use of NBTXR3 with stereotactic body radiation therapy (SBRT) in patients with HCC or liver mets [NCT02721056]. Methods: So far, eleven patients (pts) with HCC with/without with Portal Vein Tumor Thrombosis or liver mets were treated with a single intralesional or intraarterial injection of NBTXR3 followed by SBRT (45Gy / 3 fractions / 5 to 7 days). A 3+3 dose escalation design was implemented with five dose levels equivalent to 10%, 15%, 22%, 33% and 45% of the baseline tumor volume. Primary endpoints were the determination of the Recommended Dose and of Dose Limiting Toxicities (DLTs). Secondary endpoints included the local assessment on target lesions by mRECIST via MRI. Pts are followed until disease progression or study cut-off date. Results: Enrollment is currently at the third dose level at 22% (1 pt) and completed for the first two levels at 10% (6 pts) and 15% (4 pts). The treatment resulted with no early DLTs, no adverse events (AE) related to NBTXR3 and no serious AE related to the injection or to SBRT. Dispersion and permanence assessments by CT scan confirmed NBTXR3 to stay within the tumor without negatively impacting liver functions nor the reliability of the image-guided radiation therapy. Conclusions: Overall, current results observed a safe and well tolerated profile for NBTXR3 indicating an encouraging perspective in pts highly vulnerable to liver complications. This multidisciplinary study brought together the successful complex cooperation of several centers and of different medical disciplines to treat two types of liver affections with an innovative approach. Clinical trial information: NCT02721056.
Endocrine and metabolic diseases among colorectal cancer survivors in a population-based cohort.
Authors: Makenzie Hawkins, Sean Patrick Soisson, Brenna Blackburn, Kerry G. Rowe, Vikrant Deshmukh, Michael Newman, Yuan Wan, Alison M Fraser, Ken R Smith, Cornelia M Ulrich, Patricia A. Ganz, Niloy Jewel Samadder, Mia Hashibe
Journal: Journal of Clinical Oncology (2017)

10074 Background: Colorectal cancer is the third most common cancer among men and women in the United States. As of 2016, there were an estimated 1.4 million colorectal cancer survivors. Research on endocrine and metabolic diseases over the long term in colorectal cancer survivors is limited. Obesity is a risk factor for colorectal cancer, thus it is of interest to investigate diseases that may share this risk factor such as diabetes for long term health effects among survivors. Methods: A total of 7,077 colorectal cancer patients who were diagnosed between 1997 to 2012 were identified in the Utah Population Database. A general population cohort of 35,354 individuals was matched on birth year, sex, birth state and follow-up time as a comparison group. Late effects were identified using electronic medical records and statewide ambulatory and inpatient data and were assessed over three time periods of 1-5 years, 5-10 years, and &gt; 10 years. Cox proportional hazard models were used to estimate the risk of late effects after adjusting for matching factors, race, baseline body mass index, and the baseline Charlson Comorbidity Index. Results: Across all three time periods, late effects risk for endocrine diseases and metabolic disorders was significantly greater for colorectal cancer survivors compared to the general population cohort. Risk for diabetes mellitus with complications was significantly increased for survivors and risk was greatest for uncontrolled diabetes (HR = 5.04, 99%CI = 2.38, 10.67) and diabetes with neurological manifestations (HR = 4.10, 99%CI = 2.08, 8.26). Higher risk was also observed for thyroid disorders (HR = 3.09, 99%CI = 2.34, 4.08) and nutritional deficiencies (HR = 4.98, 99%CI = 3.47, 7.17). The risk of obesity in survivors was greatest 1-5 years post cancer diagnosis (HR = 5.04, 99%CI = 2.91, 8.75), but remained significantly increased at all follow-up time periods. Conclusions: Endocrine and metabolic diseases were significantly higher in colorectal cancer survivors across the follow-up periods. As the number of colorectal cancer survivors increases, understanding the long term multimorbidity trajectory is critical for improved survivorship care.