tbuckley/cabot-search huggingface dataset:
The role of adjuvant chemotherapy according to the status of surgical margin in rectal cancer patients who received preoperative chemoradiation and total mesorectal excision
Authors: S. Sung, J. Lee, S. Kim, J. Lee
Journal: Annals of Oncology (2018)

Introduction: Adjuvant chemotherapy has been recommended for patients who have locally advanced rectal cancer. However, the role of adjuvant chemotherapy in patients with positive surgical margin has not been clarified. We investigated the benefit of adjuvant chemotherapy according to the surgical margin in locally advanced rectal cancer patients who received preoperative chemoradiation (CRT) and total mesorectal excision (TME). Methods: A total of 1801 rectal cancer patients staging cT3-4N0-2M0 were included. The patients were eligible when tumors were pathologically confirmed adenocarcinoma, located within 10cm from anal verge, and staged cT3-4N0-2M0. Before surgery, all patients received radiation therapy at a dose of 50.4 Gy in 28 fractions with concurrent 5-fluorouracil or capecitabine. Curative surgery including TME was performed 4 to 8 weeks after radiotherapy. Adjuvant chemotherapy was performed after 4-6 weeks after surgery. Results: Adjuvant chemotherapy was given to 1531 patients (85.0%). Patients with positive circumferential resection margin or distal resection margin were 205 (11.4%). With patients with positive surgical margin (n = 205), the 5-year recurrence-free survival (RFS) showed a significant difference between adjuvant chemotherapy group and no adjuvant chemotherapy group (50.3% vs. 30.9%, p = 0.01). The 5-year overall survival rate was 72.6% in adjuvant chemotherapy group and 57.2% in no adjuvant chemotherapy group (p = 0.09). With patients with the negative margin (n = 1596), the 5-year RFS rate did not show any difference between two groups (75.6% vs. 76.8%, p = 0.94). On multivariate analysis, adjuvant chemotherapy was significantly associated with RFS in patients who had the positive surgical margin (Hazard ratio (HR): 0.48, 95% confidence interval (CI): 0.25-0.94, p = 0.032). In contrast, there was no significant association between adjuvant chemotherapy and RFS in those with negative surgical margin (HR: 0.99, 95% CI: 0.72-1.35, p = 0.94). Conclusion: Patients who received adjuvant chemotherapy showed a significantly improved 5-year RFS rate compared with those who did not receive adjuvant chemotherapy if the patients had positive surgical margin. The benefit of adjuvant chemotherapy was more remarkable in patients with positive surgical margin compared to those with negative surgical margin.
Decreased mitochondrial respiration in aneurysmal aortas of Fibulin-4 mutant mice is linked to PGC1A regulation
Authors: Ingrid van der Pluijm, Joyce Burger, Paula M van Heijningen, Arne IJpma, Nicole van Vliet, Chiara Milanese, Kees Schoonderwoerd, Willem Sluiter, Lea-Jeanne Ringuette, Dirk H W Dekkers, Ivo Que, Erik L Kaijzel, Luuk te Riet, Elena G MacFarlane, Devashish Das, Reinier van der Linden, Marcel Vermeij, Jeroen A Demmers, Pier G Mastroberardino, Elaine C Davis, Hiromi Yanagisawa, Harry C Dietz, Roland Kanaar, Jeroen Essers
Journal: Cardiovascular Research (2018)

Thoracic aortic aneurysms are a life-threatening condition often diagnosed too late. To discover novel robust biomarkers, we aimed to better understand the molecular mechanisms underlying aneurysm formation.
CRAN-29. CONSERVATIVE SURGERY FOLLOWED BY PROTON THERAPY FOR CRANIOPHARYNGIOMA IN CHILDREN: A PHASE II STUDY TO EXAMINE THE FEASIBILITY OF DOSE ESCALATION
Authors: Claire Alapetite, Stephanie Puget, Catherine Nauraye, Kevin Beccaria, Stephanie Bolle, Paul Lesueur, Hervé Brisse, Nathalie Boddaert, Remi Dendale, François Doz, Christian Sainte Rose, Eric Bouffet, Jean-Louis Habrand
Journal: Neuro-Oncology (2018)

Optimal treatment for pediatric craniopharyngioma remains controversial. Although conservative surgery followed by radiation is favored, particularly when hypothalamic infiltration. Proton beam therapy (PT) offers further sparing of normal tissues exposure compared to photons. The objectives of this study were; To assess the efficacy of limited surgery followed by PT in children with craniopharyngioma; To evaluate feasibility of dose escalation while maintaining risk-adapted dose constraints to the chiasm. The trial included 33 patients (17 males), median age 9.0 years (2.1–15.5) at diagnosis, 9.6 years (3.3–15.8) at radiation. All patients underwent surgery (1–5, median: 2) with measurable residue. Median interval between diagnosis and PT was 7.2 months (2.5–73.6). Median PTV was 31.1 cm3 (12.7–136). Imaging studies during radiation identified increase in size of cystic components in 11 patients, including 2 who required re-planning. Total median dose was 54.4 CGE (52.2–56.1). Based on dosimetric parameters, 5 patients underwent slight dose escalation. Median dose to the chiasm was 52.7 CGE (51.8–54.4). At a median follow-up of 4.3 years (1.3–7.0) since radiation, 32 patients are alive. 3 patients experienced progression. All patients are on hormone replacement, 25/32 patients have normal vision in at least one eye, 17/32 have restricted fields. 24 patients have normal academic status, 8 patients require special schooling. Median BMI is 24.1 (18.7–36.3), 11 patients are overweight and 9 obese. This study supports the use of PT in pediatric craniopharyngioma, although the objective of dose escalation, using passive scattering delivery was not reached, preventing dose effect relationship evaluation.
Combating head and neck cancer metastases by targeting Src using multifunctional nanoparticle-based saracatinib
Authors: Liwei Lang, Chloe Shay, Yuanping Xiong, Parth Thakkar, Ron Chemmalakuzhy, Xuli Wang, Yong Teng
Journal: Journal of Hematology & Oncology (2018)

Inhibition of metastasis of head and neck squamous cell carcinoma (HNSCC) is one of the most important challenges in cancer treatment. Src, a non-receptor tyrosine kinase, has been implicated as a key promoter in tumor progression and metastasis of HNSCC. However, Src therapy for HNSCC is limited by lack of efficient in vivo delivery and underlying mechanisms remain elusive. Src knockdown cells were achieved by lentiviral-mediated interference. Cell migration and invasion were examined by wound healing and Transwell assays. Protein levels were determined by Western blot and/or immunohistochemistry. The Src inhibitor saracatinib was loaded into self-assembling nanoparticles by the solvent evaporation method. An experimental metastasis mouse model was generated to investigate the drug efficacy in metastasis. Blockade of Src kinase activity by saracatinib effectively suppressed invasion and metastasis of HNSCC. Mechanistic assessment of the drug effects in HNSCC cells showed that saracatinib induced suppression of Src-dependent invasion/metastasis through downregulating the expression levels of Vimentin and Snail proteins. In tests in mice, saracatinib loaded into the novel multifunctional nanoparticles exhibited superior effects on suppression of HNSCC metastasis compared with the free drug, which is mainly attributed to highly specific and efficient tumor-targeted drug delivery system. These findings and advances are of great importance to the development of Src-targeted nanomedicine as a more effective therapy for metastatic HNSCC.
DEV-18. ENDONASAL ENDOSCOPIC APPROACH TO PITUITARY ADENOMAS: SINGLE CENTER EARLY EXPERIENCE
Authors: Mohamed M Arnaout, Mohamed G Ammar, Mansour A Mekia, Magdy O Elshiekh, Ismail Elnashar
Journal: Neuro-Oncology (2018)

In the last two decades, the endoscopic endonasal transsphenoidal approach has become an alternative to the transseptal endoscopic approach for pituitary adenomas. Recently, in our center we have shifted from the transseptal to the endonasal approach. MATERIALS AND For the last two years, forty seven patients with pituitary adenomas, who were undergoing trans-nasal endoscopic approach, were prospectively studied. 14 patients (29.8 %) had endocrinological symptoms as the first presentation. Most of tumors were macrodenomas in 42 patients (89.4%). All patients data were collected and surgical complications were analyzed. Most of our patients have been improved in terms of biochemical cure (18 out of 25 functioning adenomas (72%)) and relieve of the main presenting symptom. The most devastating complication is death and it has occurred in only one patient on the third postoperative day due to pulmonary embolism. The most common surgical complication is cerebrospinal fluid leak occurred in 6 cases (12.8%). Reoperation for overlay large fat graft was done in only one case. Immediate postoperative third nerve palsy developed in one patient. (2.1%). Our study results and the literature support endoscopic endonasal surgery for the resection of pituitary adenomas has been established as the standard approach. This approach may have an equivalent if not superior outcome over transseptal and transcranial surgeries in terms of biochemical cure and patient satisfaction. CSF leaks are still a challenge but may improve with the use of fat or fascia lata and middle turbinate flap in large defects.
Uterine Corpus Metastasis From Rectal Adenocarcinoma Detected Using 18F-FDG PET/CT
Authors: Hongxi Wang, Minggang Su, Futao Cui, Xia Wu, Rong Tian
Journal: Clinical Nuclear Medicine (2018)

We report an unusual case of uterine corpus metastasis from rectal adenocarcinoma detected using F-FDG PET/CT. A 47-year-old woman was diagnosed with rectal adenocarcinoma and treated with surgery and radiochemotherapy 3 years ago. During follow-up, she presented with lower abdomen pain and elevated tumor markers, but ultrasonography findings were unremarkable. We performed an F-FDG PET/CT scan, which showed intense F-FDG avidity in the myometrium of the uterine corpus. Uterine corpus metastasis was suspected, and complementary MRI and diagnostic curettage histopathology confirmed uterine metastasis from rectal adenocarcinoma.
Automated Performance Metrics and Machine Learning Algorithms to Measure Surgeon Performance and Anticipate Clinical Outcomes in Robotic Surgery
Authors: Andrew J. Hung, Jian Chen, Inderbir S. Gill
Journal: JAMA Surgery (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
HGG-36. NFκB AND FOXM1 MEDIATE ANTI-CANCER ACTIVITY OF DUAL HDAC AND PI3K INHIBITION IN PEDIATRIC HIGH GRADE GLIOMA AND DIPG
Authors: Sharmistha Pal, David Kozono, Xiaodong Yang, Whitney Fitts, Jing Ni, John Alberta, Jean Zhao, Kevin Liu, Jie Bian, Nathalene Truffaux, William Weiss, Adam Resnick, Pratiti Bandhopadhayay, Keith Ligon, Steven DuBois, Sabine Mueller, Dipanjan Chowdhury, Daphne Haas-Kogan
Journal: Neuro-Oncology (2018)
Inconsistency between supplement and article?
Authors: Hakan Babaoglu
Journal: Annals of the Rheumatic Diseases (2018)

In their recent article in the Annals of the Rheumatic Diseases , van der Heijde D et al 1 evaluated the effect of certolizumab pegol (CZP) on radiographic progression in patients with ankylosing spondylitis and non-radiographic axial spondyloarthritis (nr-axSpA). They suggested that CZP-treated patients …
HEPANOVA: A phase 2 trial of tumor treating fields concomitant with sorafenib for advanced hepatocellular carcinoma - Trial in progress
Authors: A. Grosu, J. Strouthos, T. Brunner, U. Weinberg
Journal: Annals of Oncology (2018)

Introduction: Tumor Treating Fields (TTFields) are a non-invasive, regional antimitotic treatment modality, which has been approved for the treatment of glioblastoma by the FDA. TTFields predominantly act by disrupting the formation of the mitotic spindle during metaphase. TTFields are delivered at specific frequencies (150 to 200 KHz) to the tumor region through transducer arrays placed on the skin surface. TTFields (200 KHz) are approved for the treatment of patients with recurrent and newly diagnosed glioblastoma. TTFields were effective in multiple preclinical models of hepatocellular carcinoma (HCC), leading to a significant increase in cell death. The optimal TTFields frequency leading to the highest reduction in cell counts was 150 kHz for both HepG2 and Huh-7D12 cells. TTFields at 150 kHz led to 53-64% reduction in cell counts and over 70% reduction in the clonogenic potential. The combined treatment of TTFields and Sorafenib led to a significant reduction in the number of HepG2 and Huh-7D12 cells as compared to each treatment alone. The Phase 2 HEPANOVA study is the first trial of TTFields in HCC patients, and is designed to test the safety and efficacy of adding TTFields to sorafenib in advanced HCC. Methods: Patients (N = 25) with unresectable HCC who are not amenable to any local treatment will be enrolled in this prospective, single-arm study. The study enrolls patients with ECOG score of 0-2 and Barcelona clinic liver cancer (BCLC) stage 0-C. Patients must have a measurable disease per RECIST Criteria. Having implanted electronic devices in the torso is exclusionary. Sorafenib will be administered at standard dose (400 mg daily). TTFields (150 kHz) will be delivered for 18 hours/day until local disease progression per RECIST Criteria. Transducer arrays are placed on the back and front of the patient to deliver the highest field intensities to the hepatic region. Clinical follow-up will be performed q4w, and a CT/MRI scan q12w. Following disease progression in the liver, patients will discontinue TTFields and be followed monthly for survival. Overall response rate will be the primary endpoint and in-field control rate, progression-free survival rate at 12 month (PFS12), OS rate at 1 year and toxicity will all be secondary endpoints. Sample size was calculated using an Exact test for proportions considering the weighted average of ORR of patients who had either complete or partial response per RECIST criteria in historical studies with sorafenib is 4.5%. A sample size of 25 patients was required to achieve a power of approximately 80% at a one-sided alpha level of 0.05 using a single sample Exact test for proportions.
QOL-21. THE EFFECTS OF RADIATION ON COGNITIVE SCORES IN PEDIATRIC PATIENTS WITH MEDULLOBLASTOMA
Authors: Subha Mazzone, Sara McElroy, Sunnye Mayes, Jim Scott, Michael Anderson, Rene McNall-Knapp
Journal: Neuro-Oncology (2018)

Medulloblastoma is treated with radiation therapy but causes late effects including decreased cognitive function (domains of processing speed (PSI) and working memory (WMI) particularly affected). Compared to photon radiation (XRT), proton radiation (PBRT) may decrease these risks; however prior studies assessing IQ (FSIQ) found no difference between the two groups. Specific domains of PSI or WMI have not been assessed. Similarly patients who receive tumor bed boost (TBB) compared to posterior fossa boost (PFB) may also fare better cognitively. To compare cognitive scores in medulloblastoma based on type of radiation and boost radiation. A retrospective single institution review of >300 medulloblastoma patients treated over the last 20 years. 15 patients with medulloblastoma received radiation and had cognitive testing. 10 patients received XRT and 5 patients received PBRT. 8 patients received TBB and 7 received PFB. Percentile scores in WMI, PSI and FSIQ were compared between PBRT vs. XRT patients and TBB vs. PFB patients. There were no statistical differences in WMI, PSI and FSIQ in the PBRT vs. XRT group (p-values 0.24, 0.13, 0.17) or the TBB vs. PFB group (p-values 0.46, 1.00, 0.85). Our data suggests a non-statistical, but potentially clinically significant trend towards superior scores in PSI in the PBRT vs. XRT group (Mean PSI 5.67 vs 23.4, p=0.13). This suggests a clinical benefit to limiting radiation exposure. A larger multi-institutional study would further delineate potential differences.
MBRS-35. COMBINING Chk1/2 INHIBITION WITH RADIATION ENHANCES IN VITRO AND IN VIVO CYTOTOXICITY IN MEDULLOBLASTOMA
Authors: Raelene Endersby, Hilary Hii, Brooke Strowger, Patrick Dyer, Meegan Howlett, Mani Kuchibhotla, Nicholas Gottardo
Journal: Neuro-Oncology (2018)

Medulloblastoma is a heterogeneous disease, comprising four molecular subgroups, termed WNT, SHH, Group 3 and Group 4. Each has distinct clinical, pathological, and molecular features. Surgical resection and craniospinal irradiation followed by chemotherapy are the mainstay of medulloblastoma treatment. Despite treatment intensification, survival has plateaued for the past two decades at around 70%. Certain sub-groups, namely those with SHH with p53 mutations and Group 3 with MYC amplification, have dismal prognoses. Since medulloblastoma patients that relapse are essentially incurable, ergo, the best opportunity to cure medulloblastoma is during frontline therapy. To increase cure rates, we employed an unbiased high-throughput drug screening approach, to identify novel drugs that enhance the effects of current treatments to aid front-line therapy. We identified prexasertib, an inhibitor of the cell cycle checkpoint kinases 1 and 2 (Chk1/2), as a promising candidate. Chk1/2 are critical regulators of the DNA-damage response. Given radiation is a potent inducer of DNA damage, we hypothesised that Chk1/2 inhibition with prexasertib may enhance radiation-induced cytotoxicity in medulloblastoma. In this study, we found that radiation induced a strong DNA damage response in multiple medulloblastoma models. In vitro, prexasertib reduced the colony-forming ability of medulloblastoma cells post-irradiation. In vivo, tumour-targeted radiation therapy and prexasertib each induced modest apoptosis in orthotopically-implanted medulloblastomas, which was significantly increased when co-administered. Importantly, this combination therapy also improved the survival of mice with medulloblastoma. Taken together, these data reveal significant anti-tumour effects when radiation is combined with Chk1/2 inhibition suggesting that this combination therapy may increase treatment efficacy.
LGG-21. LONG-TERM OUTCOME OF PATIENTS WITH PEDIATRIC TECTAL GLIOMA
Authors: Anthony Liu, Julie Harreld, Lisa Jacola, Madelyn Gero, Sahaja Acharya, Jason Chiang, Yahya Ghazwani, Shengjie Wu, Paul Klimo, Amar Gajjar, Ibrahim Qaddoumi
Journal: Neuro-Oncology (2018)

Tectal glioma (TG) is an uncommon pediatric low-grade tumor with limited data on long-term outcome. A retrospective review of TG diagnosed in patients ≤ 21 years at our center between 1986 and 2013 identified 19 patients (males=13; median age at diagnosis=10 years [yrs]; range, 0.01-19.99). All patients were diagnosed based on MRI. Initial CSF diversion was necessary in 16 patients (ventriculoperitoneal [VP] shunt= 10; endoscopic third ventriculostomy=6). Ommaya reservoir was inserted in 5 patients. VP shunt revisions (1-12 times) were required in 7 patients; while 2 patients had subdural hematoma due to over-shunting. Biopsy or resection was performed in 7 patients (upfront=5, at progression=2), with histology showing pilocytic astrocytoma (n=6) or low-grade glioma, NOS (n=1). Duplication of chromosome 7q34, marker of KIAA1549-BRAF fusion, was detected in 2 of 4 patients tested. Adjuvant therapy was delivered in 8 patients mostly upon progression, and included focal radiation (n=4), systemic therapy (n=3), or a combination (n=1). The median duration of follow-up was 9.57 yrs (range, 3.64-16.98): 7 experienced progression at median of 0.68 yrs (range, 0.28-8.98), including 2 with metastases. One patient each died due to suicide, obstructive hydrocephalus, and suspected shunt malfunction. Respective 5- and 10yr overall-survival were 92.9 ± 6.9% and 85.1 ± 9.7%. Long-term morbidities included persistent headache (n=8) and visual symptoms (n=7). Significant impairments were seen on measures of intelligence (n=2/9; 22%), working memory (n=2/7; 29%), and processing speed (n=6/6; 100%). Long-term survival of children with TG is satisfactory. Regular follow-up is recommended due to risks of shunt failure, progression, and long-term morbidities.
DIPG-09. HDAC INHIBITION IN THALAMIC AND SPINAL CORD H3K27M+ DIFFUSE MIDLINE GLIOMA
Authors: Sara Kreimer, Grant Lin, Pamelyn Woo, Michelle Monje-Deisseroth
Journal: Neuro-Oncology (2018)

Diffuse midline gliomas (DMG), including diffuse intrinsic pontine gliomas (DIPG), are the leading cause of brain tumor-related deaths in children. There are no effective treatments and median survival remains dismal. Genomics identified a mutation in the majority of DMGs, a lysine to methionine substitution (K27M) in histones 3.1 and 3.3, which causes changes in gene expression that promote gliomagenesis. Panobinostat, a multiple histone deacetylase (HDAC) inhibitor, was one of the most effective agents against patient-derived DIPG cell cultures and xenograft models in previous studies and is presently in clinical trial for DIPG. HDAC inhibition with panobinostat may also exhibit activity against H3K27M+ DMG of the thalamus and spinal cord. Patient-derived thalamic and spinal cord H3K27M+ DMG cell cultures were treated with single agent panobinostat at a range of concentrations. Cell viability was evaluated using the CellTiter-Glo assay. Panobinostat was systemically administered to murine models of luciferase-expressing spinal cord H3K27M+ DMG. Response to panobinostat was evaluated with IVIS in vivo imaging. HDAC inhibition with panobinostat significantly decreases cell proliferation with an IC50 of 30 nM and 41 nM in the spinal cord and thalamic glioma patient-derived cell cultures respectively. Panobinostat slowed tumor growth in spinal cord glioma orthotopic xenografts compared to vehicle controls. This study suggests that HDAC inhibition with panobinostat may also be beneficial for thalamic and spinal cord H3K27M+ DMG.