tbuckley/cabot-search huggingface dataset:
RTHP-31. LOW GRADE GLIOMA MALIGNANT TRANSFORMATION (MT): CLINICAL OUTCOMES AND PROGNOSTIC FACTORS IN TEMOZOLOMIDE ERA
Authors: Erin Murphy, C. Marc Leyrer Leyrer, Michael Parsons, John Suh, Samuel Chao, Jennifer Yu, Xuefei Jia, David Peereboom, Glen Stevens, Manmeet S. Ahluwalia
Journal: Neuro-Oncology (2016)

Data from EORTC 22845 estimates that 2/3rds of low grade gliomas (LGG) will undergo MT regardless of timing of radiotherapy. The factors that influence the rate of MT in the temozolomide era are not well known. This study evaluates the risk factors and outcomes for MT patients treated with temozolomide at a tertiary care setting. We queried our IRB approved LGG database for patients diagnosed with MT. Patient, tumor, and treatment factors were analyzed with respect to outcomes and impact on MT. Univariate and multivariate survival analysis were performed. From a total of 600 patients, 124 underwent MT; 76 (61.3%) were biopsy proven. 95% of MT patients had new enhancement. MT incidence was 0.17 events/person year of follow up and median time to MT from original diagnosis was 143.4 (range, 4.1, 761.6) months. There were no significant differences between the biopsy and non-biopsy patients, except biopsy patients had more presenting neurologic symptoms. Any treatment versus none was a risk factor for MT (p<0.001) and specifically chemotherapy alone compared to radiotherapy alone or both was a risk factor for MT (p=0.001). 94%, 80 out of 85 patients treated with chemotherapy prior to MT received temozolomide. 1p19q status did not impact MT. Median PFS post-MT was 4.09 months. 1-yr PFS:33% (+/- 4.3%), 2-yr:17%(+/-3.4%), 5-yr:8.5%(+/-2.6%). Median OS post-MT was 29.1 months, 1-yr OS:79%(+/- 3.8%); 2-yr:57%(+/- 4.8%) and 5-yr:26.5%(+/- 4.8%).Prospective neurocognitive and quality of life data is available for 17 MT patients. Outcomes of MT LGGs are similar to de novo high grade gliomas, regardless of pathologic confirmation. Our series suggests that temozolomide may increase the risk of MT and 1p19q status is not impactful. These results need to be validated in an independent cohort.
Outcomes of Ibrutinib Therapy By Age in Patients with CLL/SLL: Analyses from Phase 3 Trial Data (RESONATE and RESONATE-2)
Authors: Jennifer A. Woyach, Peter Hillmen, Jennifer R. Brown, Steven E. Coutre, Paul Barr, Susan M. O'Brien, Jacqueline C. Barrientos, Stephen Devereux, Neil E. Kay, Nishitha Reddy, Stephen Mulligan, Alessandra Tedeschi, Cathy Zhou, Joi Ninomoto, Danelle F. James, John C. Byrd, Jan Burger
Journal: Blood (2016)
Active surveillance for prostate cancer: Scottish experience.
Authors: Jawaher Ansari, Lillian White, Hilary Glen, Brian McGlynn, Robert Nairn, Margaret Balsitis, Graham Hollins, Kathleen Smith, Biju Nair, Murat Gurun, Brian Little, Robert Meddings, Neil Al-Saffar, Syed A. Hussain, John Glaholm, Rana I. Mahmood
Journal: Journal of Clinical Oncology (2012)

167 Background: Prostate cancer is the second most common malignancy in men worldwide with 910,000 cases registered in 2008. The prognosis for low-risk prostate cancer patients remains excellent and arguably the majority may either not require radical treatment or may benefit from deferred radical treatment. Active surveillance involves serial prostate-specific antigen (PSA) monitoring, digital rectal examinations, and periodic trans-rectal ultrasound guided prostate biopsies. Patients for active surveillance are carefully selected, counselled and actively followed-up. Radical treatment is deferred until there is evidence of biochemical, pathological or clinical disease progression. Methods: Retrospective review of prostate cancer patients enrolled on to the active surveillance program within NHS Ayrshire and Arran Hospitals. Clinical examination and PSA monitoring was undertaken 3-monthly in year 1, 4-monthly in year 2 and 6-monthly thereafter. The protocol stipulates repeat TRUS biopsies at years 1, 4, 7 and every 3 years thereafter. Results: 105 patients with low-intermediate risk prostate cancer with a median age of 68yrs (48–78yrs) were followed for a median duration of 30 months (4–152 months). The median PSA at presentation was 7ng/ml (0.5-31). Repeat biopsies were performed in 82 patients and 37% had no histological evidence of cancer. The median time to re-biopsy was 16 months (10–85 months). Of the patients who received radical treatment; 3 underwent radical prostatectomy and 23 received radical radiotherapy. The indications for radical treatment were pathological progression in 73%, PSA progression in 23% and co-existing bladder cancer in 4%. One patient died due to unrelated medical problems and one patient developed metastatic disease. Conclusions: With appropriate counselling, a significant percentage of men with low-moderate risk prostate cancer choose active surveillance. In this study, active surveillance does not appear to compromise outcomes for patients with low-intermediate risk prostate cancer. Less then 25% of patients needed radical treatment and therefore this approach appears cost-effective and avoids treatment-related morbidity.
The effect of body mass index at diagnosis on clinical outcome in children with newly diagnosed acute lymphoblastic leukemia
Authors: H M Eissa, Y Zhou, J C Panetta, E K Browne, S Jeha, C Cheng, M V Relling, D Campana, C-H Pui, H Inaba
Journal: Blood Cancer Journal (2017)

The impact of body mass index (BMI) at diagnosis on treatment outcome in children with acute lymphoblastic leukemia (ALL) is controversial. We studied 373 children with ALL enrolled on the Total XV study, which prospectively used minimal residual disease (MRD) for risk assignment. MRD on day 19 and at the end of remission induction (day 46), cumulative incidence of relapse/refractory disease (CIR), event-free survival (EFS) and overall survival (OS) were evaluated using sets of four, three and two subgroups based on BMI at diagnosis, along with BMI percentile change during remission induction. Higher BMI was associated with older age and higher treatment risk. There was no association between MRD on days 19 or 46 and BMI for four, three or two BMI subgroups (P>0.1 in all cases), nor was BMI associated with CIR or EFS. Obese patients had worse OS compared with non-obese (P=0.031) due to treatment-related mortality and less salvage after refractory disease or bone marrow relapse. No association between BMI change during remission induction and MRD, CIR, EFS or OS was seen. BMI at diagnosis does not predict poorer response or relapse in a contemporary MRD-directed ALL regimen. Improvements in supportive care and innovative, less-toxic frontline/salvage therapies are needed, especially for obese patients.
ACTR-23. COMBINED IMMUNOCHEMOTHERAPY, R-MPV-A, WITH REDUCED OR DEFERRED RADIOTHERAPY FOR PCNSL IMPROVES SURVIVAL WITH FAVORABLE PERFORMANCE AND COGNITIVE FUNCTION
Authors: Motoo Nagane, Keiichi Kobayashi, Kuniaki Saito, Nobuyoshi Sasaki, Satoshi Kume, Yuki Yamagishi, Saki Shimizu, Kaori Suzuki, Yoshiaki Shiokawa
Journal: Neuro-Oncology (2016)

R-MPV-A (rituximab plus high-dose methotrexate (MTX), procarbazine, vincristine followed by high-dose cytarabine) is an active regimen for primary central nervous system lymphoma (PCNSL). A high complete response (CR) rate by the R-MPV induction phase is expected to reduce or omit neurotoxic whole brain radiotherapy (WBRT). Here we report our single institution experience of treating PCNSL with R-MPV-A with special interests in preservation of neurocognitive function along with radiological findings, and potential prognostic factors. Twenty-six cases with newly diagnosed PCNSL treated with R-MPV-A since 2012 and followed up more than 6 months were eligible (mean age 71.4, 54% were 70 or older, median KPS 70). The standard R-MPV was used for 5 to 8 cycles. CR cases received either 24 Gy WBRT (< 70 yo) or no WBRT (>=70), followed by cytarabine. KPS, MMSE, and Fazekas score were recorded longitudinally. CR/CRu to R-MPV was achieved in 81%, there were only 6 (23%) progressions and 3 (12%) deaths with median follow up for 23.1 months (6.0–51.8). These outcomes were significantly better than those with previously used HD-MTX monotherapy plus WBRT. WBRT was either omitted or reduced in 13 (50%) or 9 (35%), respectively. Univariate analysis for PFS reveals single lesion (p=0.033), resection (vs. biopsy, p=0.038), age (<70, p=0.092), MMSE (>=24, p=0.089), Fazekas (1, p=0.117), MGMT methylated (p=0.140) as favorable factors. MYD88 L265P mutation status was not associated with PFS. KPS improved in 73% and was maintained in 24, while MMSE and Fazekas score were improved or maintained in 20/23 (87%) and 21/26 (81%), respectively. No cases with WBRT omission experienced worsening of Fazekas score except for one with progression. R-MPV-A confers a high CR rate even in elderly patients with improvement and preservation of daily activity, neurocognitive and radiological status. Further exploration may be needed for prognostic factors.
Characterizing the Function of an RNA Binding Protein, IGF2BP3, in Hematopoiesis
Authors: Tiffany M Tran, Jayanth Kumar Palanichamy, Jonathan Howard, Jorge R. Contreras, Thilini Fernando, Giuseppe Basso, Martina Pigazzi, Jeremy R Sanford, Dinesh S. Rao
Journal: Blood (2015)
The impact of metastatic sites in metastatic colorectal cancer at initial diagnosis (MCCID)
Authors: B. A. Leone, J. A. Lacava, A. O. Zwenger, J. Iturbe, J. E. Perez, M. R. Machiavelli, A. O. Romero, C. T. Vallejo, M. E. Dominguez, R. Rodriguez
Journal: Journal of Clinical Oncology (2007)

14536 Background: The role of metastatic site in MCCID is unclear. The goal of this study is to evaluate if metastatic site influence survival in this setting of patients (P). Methods: Analyses were based on individual data of 300 P with MCCID treated with biochemical modulation of 5- Fluorouracil by Methotrexate regimens in different prospective trials conducted at GOCS Institutions since May 1984 to Aug 2000. P with surgical resection of liver metastases were not included in the analyses. 38 P were excluded for incomplete data. P were grouped according to metastatic sites into group A= Liver metastases only (n=161), group B= Liver and other metastatic sites (n=61) and group C= Non liver metastases (n=40) (lung, peritoneal, others). Different prognostic variables were considered: age, sex, PS, weight loss, size of liver metastases, unilateral or bilateral liver involvement, number of liver metastases, histologic differentiation of primary tumor, location of primary tumor, lactate dehydrogenase, alkaline phosphatase, ALT, AST and hemoglobin. Overall survival (OS) was analyzed since date of diagnosis by means of Kaplan-Meier and the Log-rank test was used to assess the differences. Results: The average follow-up time was 14.4 months (0–73.4). Clinical, laboratory and tumor characteristics were similar among groups A, B and C respectively. However P in group A had bigger size of liver metastases, higher number of them and more bilateral liver involvement respect to group B (p=0.02, p=0.03, p=0.05 respectively). Median OS in group A=21.0 months, group B=13.1 months and group C=15 months (p= 0.02). Statistical difference in OS was observed between group A and group B (p= 0.015). No difference was observed between groups A plus B vs the heterogeneous group C (p= 0.83) Conclusions: P with liver only metastatic site had better prognosis respect to those with other coexisting site of metastases despite presenting higher tumor burden in the liver. No factors analysed in the study explaine this difference. The subset of P with liver only metastatic site would be considered as a distinctive group and deserve further molecular studies. No significant financial relationships to disclose.
NIMG-32. 3D SHORT AND LONG ECHO TIME 1H MRSI IN PATIENTS WITH NON-ENHANCING GLIOMAS
Authors: Yan Li, Tracy Luks, Jason Crane, Sarah Nelson, Tracy McKnight
Journal: Neuro-Oncology (2016)

The purpose of this study was to evaluate the metabolite profiles obtained with short and long echo time (TE) magnetic resonance spectroscopic imaging (MRSI) for patients with non-enhancing gliomas. Thirty-five patients with suspected non-enhancing gliomas were studied before surgical resection. Tumors were graded by histological examination of tissue samples from the surgery. There were 14 patients with grade 2 oligodendroglioma (OD), 7 with grade astrocytoma (AS), 1 with grade 3 OD and 13 with grade 3 AS. For spectra data acquired using short TE MRSI, the levels of Glu/Cr were significantly higher in OD relative to AS (p=0.027, N=15 vs. 20) in the T2 hyperintensity lesion (T2L), while NAA/Cr was significantly lower in grade 3 AS compared to grade 2 AS (p=0.046, N=13 vs. 7). The NAA/Cr from long TE MRSI was significantly higher in patients with OD relative to AS (p=0.023, N=15 vs. 20), and in lesions that were 1p19q co-deleted versus those that were 1p19q intact (p=0.032, N=14 vs. 5), respectively. The median metabolite ratios from short TE MRSI between normal appearing white matter and the T2L were significantly different for Cho/Cr (p<0.001), NAA/Cr (p<0.001), myo-Insitol/Cr (p<0.011), Lipid at 1.3ppm (p<0.025) and 0.9ppm (p<0.007). The differences in Cho/Cr/NAA between long/short TE acquisitions reflect the variations in relaxation times that were consistent with previous findings and indicated that the levels of tumor marker, Cho/NAA, would be higher at long TE. No metabolite parameter was found to be significant between IDH-mutant and IDH-wild type gliomas in this study, which may have been due to the small number of wild type lesions (7/33 with known IDH status, 2 unknown). Future studies will perform a more detailed analysis that combines information from ex vivo tissue samples.
Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with peritoneal carcinomatosis arising from gastric cancer.
Authors: P. Piso, G. Glockzin, H. J. Schlitt
Journal: Journal of Clinical Oncology (2011)

132 Background: Peritoneal carcinomatosis is a common sign of advanced tumor stage or disease recurrence in patients with gastric cancer. The prognosis of these patients is poor. There is some evidence that CRS and HIPEC may improve the oncological outcome of a highly selected part of patients with peritoneal carcinomatosis arising from gastric cancer. Nevertheless, the use of CRS and HIPEC as an additional therapeutic option is still controversial. Methods: Between 01/2005 and 09/2009 16 out of 256 patients underwent CRS and HIPEC for peritoneal carcinomatosis arising from gastric cancer at the University of Regensburg Medical Center. The mean age of patients at the time of surgery was 52 years (range 32-69). Four patients were female (25%). The mean follow-up time was 16.3 months. Results: Thirteen patients (81.25%) underwent complete macroscopic cytoreduction (CC-0/1). HIPEC was performed in all patients. The median hospital stay was 19.5 days (range 8-44) and the median stay on ICU 1 day (range 0-14), respectively. The median operating time was 342 minutes (range 49- 510). The perioperative grade 3/4 morbidity rate was 37.5%. Postoperative complications were pneumonia (2), pancreatitis (2), pneumothorax (2), intraabdominal abscess (2), renal insufficiency (1), urine bladder dysfunction (1) and wound infection (1). There was no operative mortality in our series. The 1-year survival rate was 68.7%. The mean survival of the ten patients that died during follow-up was 14.1 months (range 3.4-44.8). Conclusions: In highly selected patients with gastric cancer and peritoneal carcinomatosis CRS and HIPEC may lead to prolonged survival rates. However, the therapy should be integrated in an interdisciplinary multimodality treatment concept. Further prospective randomized trials are required to determine the role of CRS and HIPEC in the treatment of patients with gastric cancer. No significant financial relationships to disclose.
MPTH-01. ARE MUTATIONS IN MISMATCH REPAIR (MMR) GENES OUR NEXT BIOMARKER OF ALKYLATING AGENT INDUCED HYPERMUTATOR PHENOTYPE? PRELIMINARY RESULTS FROM THE IVY PRECISION TRIAL
Authors: John Kuhn, Ricky Chen, Jennifer Clarke, Susan Chang, Tim Cloughesy, Howard Colman, Patrick Wen, Ingo Mellinghoff, Keith Ligon, John de Groot, Tracy Batchelor, Antonio Omuro, Jennie Taylor, Nicholas Butowski, Rebecca Halperin, Nhan Tran, John Carpten, David Craig, Sara Byron, Michael Berens, Michael Prados
Journal: Neuro-Oncology (2016)

Mutations in the MMR gene MSH6 have been shown to confer resistance to alkylating agents and unleash accelerated mutagenesis, manifesting as recurrent progressive glioma with hypermutator phenotype. The IVY precision trial (IRB# 144-13086) tested the feasibility of using molecular profiling to guide treatment in patients with recurrent GBM from which we identified two patients with the hypermutator phenotype. A total of 15 recurrent GBM tumors were analyzed (Ashion Analytics, CAP/CLIA Lab) by whole-exome sequencing for relevant single nucleotide substitutions (SNS)/deletions, focal deletions/amplification and structural break-points across 20,536 genes. Two (M/F, 40/60 year of age) of 15 patients’ (13%) genotypes expressed the hypermutator phenotype. Prior therapy included RT + TMZ. Each tumor was MGMT methylated, had MSH6 mutations/loss, one with an additional MLH1 (G67E) mutation and one with an IDH1 (R132H) mutation. Neither specimen had polymerase mutations. SNS mutational loads for the 2 tumors were 1538 & 2786 compared to the average of 58 (SD ± 25.5) for the other 13 tumors without MMR mutations. Treatment with an Anti-PD-1 mAb was recommended by the IVY tumor board for both patients. In contrast to the two hypermutator phenotype patients, two additional TMZ-treated patients with IDH1 mutations, MGMT methylation+ and no MMR alterations had SNS mutational loads of 150 and 80. Thus, MGMT status and IDH1 mutations were not concordant with the hypermutator phenotype in this small sample. Mutations/loss in MMR genes appear to be a biomarker for alkylator-induced hypermutator phenotype. Testing for IDH1 mutation and MGMT methylation alone may be insufficient to predict accelerated mutagenesis. Hypermutator phenotypes associated with high neoantigen loads may represent a therapeutic opportunity for ­tumor-specific immunotherapy. Prospective screening for MMR mutations prior to TMZ may be therapeutically indicated. The IVY early clinical trial consortium will test this hypothesis in our upcoming immunotherapy precision bucket trial.
Clinical Characteristics and Treatment Outcome of Refractory Cytopenia of Childhood (RCC): A Prospective Registration Through the Japanese Society of Pediatric Hematology
Authors: Daisuke Hasegawa, Xiaojuan Chen, Shinsuke Hirabayashi, Yasushi Ishida, Shizuka Watanabe, Yuji Zaike, Masahiro Tsuchida, Atsuko Masunaga, Ayami Yoshimi, Asahito Hama, Seiji Kojima, Masafumi Ito, Tatsutoshi Nakahata, Atsushi Manabe
Journal: Blood (2011)
Surprising Lack of Correlation between CD38 and Time to First Treatment in Chronic Lympocytic Leukemia.
Authors: Matthew S. Kaufman, Rajendra Damle, Nina Kohn, Christina Johnson, Nancy Driscoll, Angelica Caramanica, Yehuda Lebowicz, Kai Tsao, Nicholas Chiorazzi, Kanti Rai
Journal: Blood (2007)
TMIC-22. ENRICHMENT OF GLIOBLASTOMA STEM CELLS IN PNIPAAm SCAFFOLDS
Authors: John Heffernan, Sara Bowen, Sabine Borwege, Emily Szeto, James McNamara, Brent Vernon, Nader Sanai, Shwetal Mehta, Rachael Sirianni
Journal: Neuro-Oncology (2016)

Glioblastoma (GBM), the most common and lethal classification of primary adult brain tumor, is maintained by a subpopulation of GBM stem-like cells (GSCs) that exhibit a capacity for indefinite self-renewal and are capable of multipotent differentiation. GSCs are also more tumorigenic, invasive, and resistant to clinical therapies than differentiated GBM cells. Like neural stem cells, it is well-appreciated that GSCs are maintained by a local niche microenvironment that regulates stem-like phenotypes via soluble signaling factors and interactions with components of the extracellular matrix. GSCs are typically propagated in vitro as neurospheres that tend to grow a heterogeneous population of stem and non-stem cells due to poor diffusion of soluble factors through the multicellular spheres. Although these simplified culture conditions are useful for expanding GSC populations, they present limited opportunities for studying how the microenvironment influences regulation and maintenance of GSCs. Previously, we reported the design and implementation of poly(N-isopropylacrylamide-co-Jeffamine® acrylamide) copolymers, termed PNJ copolymers, as temperature-responsive scaffolds to enable serial 3D culture and expansion of immortalized GBM cell lines. We recently discovered that some of these biomaterials are capable of selectively enriching GSC phenotypes, specifically in vitro self-renewal capacity, in multiple patient derived cultures. When compared to standard neurosphere conditions, we observed that 3D PNJ cultures significantly decreased variability in neurosphere sizes and also maintained GSCs in a multipotent state. Cells cultured in 3D demonstrated increased expression of GSC marker proteins (Nestin, EGFR and CD44) as well as increased resistance to radiation treatment. Together, these findings indicate that PNJ scaffolds not only regulate GSC phenotypes, but are also a useful tool for studying relevant GSC-niche interactions. The long term goal of this project is to utilize these scaffolds to identify essential microenvironmental mediators of GSC regulation as potential targets for therapy.
Last-line treatment of luminal metastatic breast cancer: which factors influence the therapeutic choice?
Authors: M. Cinausero, L. Gerratana, M. Bonotto, D. Iacono, C. Bozza, D. Basile, G. Pelizzari, M.G. Vitale, C. Fontanella, V. Fanotto, C. Andreetta, A.M. Minisini, S. Moroso, E. Poletto, S. Russo, M. Mansutti, G. Fasola, F. Puglisi
Journal: Annals of Oncology (2016)
Prediction of long-term survival in metastatic gastrointestinal stromal tumour: analysis of a large, single-institution patient cohort
Authors: I. Hompland, Ø.S. Bruland, J.P. Poulsen, S. Stoldt, T. Hølmebakk, K.S. Hall, K. Boye
Journal: Annals of Oncology (2016)
Chemotherapy extravasation: a survey within the Oncology Network of Piedmont and Valle d'Aosta
Authors: P. Giuliano, M. Beltramo, M. Bruno Franco, A. De Luigi, A. Pertino, E. Ponticelli, F. Savia, D. Scarlata, C. Toma, M. Viale, O. Bertetto
Journal: Annals of Oncology (2016)
Impact of Finding of Low Level Kinase Domain Mutations Using Ultra Deep Next Generation Sequencing in Patients with Chronic Phase CML
Authors: Aytug Kizilors, Elena Crisa, Nicholas Lea, Steven Best, Mian Syed, Robin M. Ireland, Maadh Aldouri, Christopher Pocock, Timothy Corbett, Emily Elizabeth Bart-Smith, Richard Gale, Clare Wykes, Simon Weston-Smith, Donal McLornan, Antonio Pagliuca, Ghulam J. Mufti, Hugues de Lavallade
Journal: Blood (2015)