tbuckley/cabot-search huggingface dataset:
QOLP-25. BASELINE QUALITY OF LIFE BURDEN IN PATIENTS WITH CENTRAL NERVOUS SYSTEM (CNS) TUMOURS TREATED WITH PENCIL BEAM PROTON THERAPY AT INDIA’S FIRST PROTON THERAPY CENTRE
Authors: Rakesh Jalali, Srinivas Chilukuri, Roopesh Kumar, Sapna Nangia, Pankaj Kumar Panda
Journal: Neuro-Oncology (2020)

Abstract The aim of this study is to evaluate and assess the impact of baseline quality of life (QOL) in adult patients with central nervous system (CNS) tumours treated with pencil beam proton therapy (PT) seen consecutively at India’s first proton therapy centre. Data sets of 50 consecutive adult patients with histologically proven brain neoplasms (both primary and recurrent) who were planned for proton therapy at our centre were during one full calendar year were considered for this study. The study included detailed neurological assessment, evaluation of QOL using EORTC questionnaire (QLQ-C30) and specific Brain Cancer module (BN20). In the present analysis, QOL scores before starting adjuvant treatment were measured and impact of patient and tumour related factors were analysed. Baseline global QOL data of all patients (available in 50) was 58.3 which is relatively low including in all histological tumour types. Physical function, role function, emotion function, cognitive and social function scores were 77.9, 80, 78.5, 80.3, 69.3 (higher values better), respectively. Domains of visual disorder, motor deficit, communication deficit, headache, seizures and drowsiness scores were 21.5, 20.3, 32.3, 31, 20.4, 32.6 and 14.5 (lower values better), respectively. Elderly patients (&amp;gt; 50 years) had poorer global score (p &amp;lt; 0.05). Patients with lower performance status (KPS &amp;lt; 70) had a lower global QOL (KPS &amp;gt; or = 80 vs. &amp;lt; or= 70; 42 vs. 75; p &amp;lt; 0.05) including in all histological types of high-grade gliomas (HGG) (HGG vs. LGG; 67 vs. 59; p &amp;lt; 0.05). Patients undergoing re-irradiation had poorer global score as compared to ones who had not received any radiation previously (p &amp;lt; 0.05). Patients with malignant, recurrent tumours, poor performance status and patients who had previously been irradiated had significantly lower QOL scores even before starting adjuvant treatment.
A Call to Action: Dismantling Racial Injustices in Preclinical Research and Clinical Care of Black Patients Living with Small Cell Lung Cancer
Authors: Portia L. Thomas, Chioma J. Madubata, Melinda C. Aldrich, Montessa M. Lee, Taofeek K. Owonikoko, John D. Minna, Charles M. Rudin, Julien Sage, Christine M. Lovly
Journal: Cancer Discovery (2020)

Small cell lung cancer (SCLC) is an aggressive disease with dismal survival rates and limited therapeutic options. SCLC development is strongly associated with exposure to tobacco carcinogens. However, additional genetic and environmental risk factors that contribute to SCLC pathogenesis are beginning to emerge. Here, we specifically assess disparities pertaining to SCLC in Black populations. In contrast to non-small cell lung cancer, preliminary data suggest that Black individuals may actually be at a lower risk of developing SCLC relative to white individuals. This difference remains unexplained but urgently needs to be verified in larger data sets, because it could provide important new insights and approaches to understanding this recalcitrant tumor. Importantly, little biological information exists on SCLC in Black individuals, and few patient-derived preclinical SCLC models from diverse ancestries are available in the laboratory. Unfortunately, we note strikingly low numbers of Black participants in clinical trials testing new treatments for SCLC. Evidence further indicates that care for patients with SCLC may vary between communities with a large fraction of Black patients and those without. Together, these observations underscore the need to better investigate genetic, environmental, and socioeconomic factors associated with SCLC development, preclinical research, clinical care, and outcomes.
Knee arthroscopy: evidence for a targeted approach
Authors: Robert F LaPrade, Tim Spalding, Iain R Murray, Jorge Chahla, Marc R Safran, Christopher M Larson, Scott C Faucett, Richard von Bormann, Robert H Brophy, Rodrigo Maestu, Aaron J Krych, Ponky Firer, Lars Engebretsen
Journal: British Journal of Sports Medicine (2020)

Like many areas of medicine, the role of arthroscopy is evolving and its use must be guided by critical analysis of the scientific evidence. Data evaluating arthroscopic knee surgery is complex with heterogenous pathology, patient populations and techniques and, therefore, must be interpreted with care. Attention-grabbing headlines and animations can stimulate discussion, but when key aspects of published science are overlooked, they risk oversimplification. We believe a number of articles published in a recent edition of the British Journal of Sports Medicine (BJSM) represent examples where science may be overshadowed by oversimplification. Thus, we offer additional insights to focus the place of arthroscopy in the management of joint problems.

To our interpretation, recent BJSM publications appear to take an emotional stance, indicating that all arthroscopy for conditions that cause joint pain is bad and should be stopped.1 2 Following an article reporting a decline in the rate of arthroscopy in Finland,3 Ardern et al provided a provocative editorial citing reasons for this change as reduced reimbursement, medical overuse and grass roots pressure.1 Scientific evidence was not one of the five reasons given directly.

An editorial by Engebretsen and Moatshe4 in the same edition provides a more balanced discussion on the 5-year results of the Finnish Degenerative Meniscus Lesion Study (FIDELITY) trial also published in the same issue.5 This editorial contends that the conclusion by Sihvonen and colleagues that arthroscopic partial meniscectomy is associated with a greater risk of osteoarthritis is too strong for the data presented.4 They also point out that patients …
MBCL-48. OUTCOMES OF TREATMENT BASED ON THE ST. JUDE MEDULLOBLASTOMA-96 REGIMEN FOR JAPANESE CHILDREN WITH MEDULLOBLASTOMA
Authors: Junya Fujimura, Tomonari Suzuki, Yuko Watanabe, Hidetaka Niizuma, Ryuta Saito, Masayuki Kanamori, Yukihiko Sonoda, Atsuko Watanabe, Ryuhei Tanaka, Megumi Fujiwara, Akinori Yaguchi, Takeshi Ishibashi, Osamu Tomita, Akihide Kondo, Toshiaki Shimizu, Takaaki Yanagisawa, Teiji Tominaga, Ryo NIshikawa, Hajime Arai
Journal: Neuro-Oncology (2020)

Abstract Medulloblastoma is a type of malignant embryonal tumor in childhood that is considered to require multiagent chemotherapy followed by radical resection and craniospinal irradiation (CSI). However, the outcomes of chemotherapy for this tumor in Japan are unclear. Here, we performed a multicenter retrospective study to determine the prognosis of pediatric medulloblastoma patients in Japan treated with the St. Jude medulloblastoma-96 (SJMB96) regimen. Thirty patients with newly diagnosed medulloblastoma received treatment with the SJMB96 regimen at Juntendo University Hospital in Tokyo (n=10), Saitama Medical University International Medical Center in Saitama (n=10), and Tohoku University Hospital in Miyagi (n=10) from 2011 to 2018. All patients underwent tumor resection and CSI, with radiation doses of 23.4Gy for standard-risk patients (n=11) and 39.6Gy for high-risk patients (n=19). Six weeks after radiation therapy, patients received four cycles of high-dose chemotherapy with autologous peripheral blood stem cell transplantation according to the SJMB96 regimen. We found that 5-year overall survival was 80.8% among standard-risk patients and 74.2% among high-risk patients. No treatment-related deaths occurred. Eight patients who experienced recurrence died within 80 months of diagnosis. As these treatment outcomes are comparable to those previously reported outside of Japan, our findings indicate that this regimen is a therapeutic option for medulloblastoma patients in Japan.
Mohankumar Adiseshiah
Authors: Obi Agu, Maria Adiseshiah, Michael Jenkins
Journal: BMJ (2020)

Born in Chennai, the son of the renowned UNESCO educationalist, Malcolm Adiseshiah, Mo graduated from Westminster Hospital Medical School with the surgery prize  Mo trained in the heyday of invasive open aortic surgery for life threatening bleeding, and his most enduring legacy is undoubtedly his pioneering role in the early development of minimally invasive endoluminal stent graft repair, as an alternative to open surgery  Emeritus consultant vascular surgeon University College London Hospitals NHS Foundation Trust (b 1941;q Westminster Hospital Medical School, London, 1965;MA Camb, MS Lond, FRCP Lond, FRCS), died from covid-19 on 24 April 2020
The value of five blood markers in differentiating mycosis fungoides and Sézary syndrome: a validation cohort*
Authors: G. Dobos, C. De Cevins, S. Ly Ka So, F. Jean‐Louis, S. Mathieu, C. Ram‐Wolff, M. Resche‐Rigon, A. Bensussan, M. Bagot, L. Michel
Journal: British Journal of Dermatology (2020)

Clinical and histological diagnosis of Sézary syndrome (SS) and mycosis fungoides (MF) is challenging in clinical routine.We investigated five blood markers previously described for SS (T-plastin, Twist, KIR3DL2, NKp46 and Tox) in a prospective validation cohort of patients.We included 447 patients in this study and 107 patients were followed up for prognosis. The markers were analysed by reverse transcriptase quantitative real-time polymerase chain reaction (RT-qPCR) on peripheral blood leucocytes and CD4+ T cells in a cohort of consecutive patients with early MF, erythrodermic MF and SS and compared with patients presenting with benign inflammatory dermatoses (BID) and erythrodermic BID. The markers were assessed in parallel to gold standard values such as CD4/CD8 ratio, loss of CD7 and CD26 membrane expression and CD4 absolute values. Sensitivity and specificity were analysed by receiver operator characteristic curves. The prognostic value of selected markers was analysed on a subset of patients. This study was conducted in one centre.We defined cut-off values for each marker. T-plastin, Twist and KIR3DL2 had the best validity. SS may be overrepresented. The combination of T-plastin and Twist was able to differentiate between erythrodermic MF or BID and SS. The additional analysis of KIR3DL2 may be useful to predict the prognosis.We propose T-plastin, Twist and KIR3DL2 measured by RT-qPCR as new diagnostic markers for Sézary syndrome.
DIPG-13. TARGETING HYPOXIA AND MITOCHONDRIA WITH REPURPOSED METABOLIC DRUGS AS AN APPROACH TO RADIOSENSITIZATION FOR DIFFUSE INTRINSIC PONTINE GLIOMAS (DIPG)
Authors: Han Shen, Cecilia Chang, Harriet Gee, Kelly McKelvey, Geraldine O’Neill, Victoria Prior, Anneke Blackburn, Eric Hau
Journal: Neuro-Oncology (2020)

Abstract DIPG is the leading cause of brain tumor-related death in children. Currently, radiation is the only treatment that offers transient benefit. Compared to normal brain tissue, DIPGs are hypoperfused with tumors being exposed to hypoxia, a potent barrier to effective radiotherapy. Biguanides are hypoglycemic agents that can reduce the oxygen consumption rate (OCR) in mitochondria, thereby reducing hypoxia. Our previous study has shown that metformin significantly improves the radiosensitivity of DIPG and extends survival in a patient-derived xenograft (PDX) model. In the present study, phenformin, a second biguanide derivative, demonstrated even greater anti-DIPG activity and radiosensitising effect in vitro. As a single agent, phenformin dose-dependently inhibited OCR and increased extracellular acidification rate (ECAR). Low-dose phenformin reduced mitoATP/glycoATP ratio, whereas high doses significantly suppressed net ATP production. To attenuate the phenformin-induced ECAR, phenformin was combined with dichloroacetate (DCA), a clinically relevant pyruvate dehydrogenase kinase inhibitor that can suppress the elevated glycolytic rate of cancers. This combination significantly blocked the phenformin-induced ECAR and killed DIPG cells synergistically by inducing apoptosis, DNA damage and metabolic catastrophe. Moreover, protein expression of HIF-1α and c-Myc, two master regulators that collaboratively enhance the metabolic capacity of tumor cells through increased glycolysis thereby contributing to radioresistance, were also suppressed by phenformin-DCA treatment in vitro. This combination therapy upregulated genes inhibiting cell proliferation while downregulating genes for DNA repair. The triple combination of phenformin, DCA and irradiation demonstrated the most potent efficacy in vitro and is currently being tested in our PDX cohort in vivo.
LINC-23. PRE-OPERATIVE AND POST-OPERATIVE INTERVENTIONS REDUCE RATES OF VENTRICULITIS IN PEDIATRIC BRAIN TUMOR PATIENTS: A PILOT STUDY
Authors: Laura Melissa Stephanie Diamante - San, Marciel Pedro, Ana Patricia Alcasabas, Marissa Lukban, Kathleen Khu, Gerardo Legaspi, Ibrahim Qaddoumi, Daniel Moreira
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND The Philippine General Hospital, a public national referral center, sees 60–80 pediatric brain tumor cases per year. Historically, the rate of post-operative ventriculitis has been high, resulting in treatment delays and poor outcomes. Starting in July 2019, as a means to decrease infections, patients were provided standardized bathing and wound care kits and caregivers were trained to follow a bathing and wound care protocol. METHODS This quality improvement study included patients younger than 18 years who underwent craniotomy at PGH were enrolled. The type of surgery, length of surgery, existence of post-operative CNS infection, length of stay and total cost of care was collected. The outcome of these interventions are analyzed 6 months after implementation. RESULTS Thirty-two 32 patients were included, with mean age of 7 years (1–16). The surgeries performed were: tumor resection (n=20), ventriculo-peritoneal shunt insertion (VPS) (n=3), endoscopic third ventriculostomy (n=3), resection with tube ventriculostomy (n=3), Ommaya reservoir placement (n=2), and resection with shunt (n=1). Median surgery time was 4 hours (1–10). Three patients (9.4%) developed ventriculitis. No surgical site infections occurred. Compared to historical controls, a lower rate of infections was noted (9.4% vs. 15.5%, runchart analysis). Patients without post-operative infections had a shorter length of stay (median 14 vs 48 days, p&amp;lt;0.05) and a lower cost of care (median $1098 vs. $2425 USD, p&amp;lt;0.05). CONCLUSION Implementation of simple hygiene interventions effectively lowered post-operative CNS infections and hospital costs in a public hospital setting. Incorporation of these into standard clinical practices is urgently needed.
Re: J. Alfred Witjes, Harman Max Bruins, Richard Cathomas, et al. European Association of Urology Guidelines on Muscle-invasive and Metastatic Bladder Cancer: Summary of the 2020 Guidelines. Eur Urol 2021;79:82–104
Authors: Gladell P. Paner, Rodolfo Montironi
Journal: European Urology (2020)
RARE-16. SEVEN CASES OF RETINOBLASTOMA WITH CNS INVOLVEMENTS
Authors: Chikako Kiyotani, Masahiro Sugawa, Yukihiro Matsukawa, Yoshihiro Gocho, Kenichi Sakamoto, Noriyuki Azuma, Takako Yoshioka, Yoshiyuki Tsutsumi, Hiroshi Fuji, Kenichi Usami, Hideki Ogiwara, Keita Terashima, Kimikazu Matsumoto
Journal: Neuro-Oncology (2020)

Abstract Treatment strategy for trilateral retinoblastoma (TRb: very rare RB with brain tumor) or retinoblastoma with central nervous system (CNS) involvement is not established yet. We retrospectively reviewed our seven cases of these rare almost fatal tumors. Their ages at diagnosis are 0y3m-1y10m (median 1y3m) (Male 4, Female 3). Only one had RB family history. Their affected eyes were bilateral 3, unilateral 3 and no 1. Their CNS involvements were suprasellar tumor 4, pineal tumor 1 and cerebrospinal fluid (CSF) cytology positive 2. Three of the suprasellar tumor patients had spinal metastasis. Four of the seven patients were TRb and one were genetically classified suprasellar retinoblastoma. All of them were treated with chemotherapy and four received high-dose chemotherapy. Three brain tumors of four TRb almost disappeared with chemotherapy. Two of them also received radiotherapy but relapsed. Although one radiation-free long-term TRb survivor developed secondary osteosarcoma, he got remission again and live 5 more years. One CSF positive Rb patient with chiasm invasion died of disease 11 months later. The other patient had no chiasm invasion nor CSF involvement at diagnosis, but his CSF cytology turned to positive after his second cycle of chemotherapy. He got remission with radiotherapy and high-dose chemotherapy, and alive without disease for 4 years. 2-year RFS and 2-year OS of all patients were 40% and 60%. Although our TRb patients responded to chemotherapy, it was difficult to avoid radiotherapy except one. Data accumulation is necessary for better treatment of these cancer-predisposed patients.
NIMG-06. GUILLAIN BARRE MIMICKING LEPTOMENINGEAL SPREAD IN CANCER PATIENTS: REPORT OF TWO CASES AN REVIEW OF LITERATURE
Authors: Alexandra Benouaich-Amiel, Orly Yariv, Hadar Goldvaser, Vadim Khasminsky, Elena Cogan, Tali Siegal, And Shlomit Yust-Katz
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Guillain-Barre syndrome (GBS) is an immune acute polyradiculoneuropathy usually presented as an ascending peripheral paresis with absent tendon reflex and albumino-cytologic dissociation on cerebrospinal fluid (CSF) exam.We describe two oncologic patients with GBS who presented with atypical symptoms. RESULTS The first patient was a 35 years old woman with newly diagnosed grade 3 invasive breast ductal carcinoma. During the sixth courses of neo-adjuvant chemotherapy she complained at back pain and within 24 hours developed progressive severe bilateral proximal paraparesis with a D10 sensory level. Spine MRI demonstrated diffuse leptomeningeal enhancement. Since leptomeningeal spread (LMD) is uncommon at this stage of breast cancer CSF was obtained. CSF sample revealed albumin-cytologic dissociation (4 cells, protein level 340 mg/dl). EMG showed acute demyelinating neuropathy consistent with GBS. Intravenous immunoglobulins (IVIG) therapy was initiated with clinical improvement. The second patient was a 45 years old woman with newly diagnosed T-Cell lymphoma. Before initiating chemotherapy she presented with a rapidly progressive tetraparesis, hyperreflexia and cervical sensory level. Spine MRI was intact. CSF showed 22 cells without atypia, FACS negative, protein level was 74 mg/dl. The patient worsened clinically. A second CSF sample was obtained and demonstrated an albumin-cytologic dissociation (8 cells without atypia, protein level 115 mg/dl) raising the possibility of GBS. EMG showed acute axonal polyneuropathy consistent with AMSAN variant of GBS. The patient was treated with IVIG with partial recovery. CONCLUSION Atypical presentation of GBS could be challenging among oncologic patients and could lead to misdiagnosis and delay in treatment.
MUC1-C Activates the BAF (mSWI/SNF) Complex in Prostate Cancer Stem Cells
Authors: Masayuki Hagiwara, Yota Yasumizu, Nami Yamashita, Hasan Rajabi, Atsushi Fushimi, Mark D. Long, Wei Li, Atrayee Bhattacharya, Rehan Ahmad, Mototsugu Oya, Song Liu, Donald Kufe
Journal: Cancer Research (2020)

Abstract The Brg/Brahma-associated factor (BAF, mSWI/SNF) chromatin remodeling complex is of importance in development and has been linked to prostate oncogenesis. The oncogenic MUC1-C protein promotes lineage plasticity in the progression of neuroendocrine prostate cancer (NEPC), however, there is no known association between MUC1-C and BAF. We report here that MUC1-C binds directly to the E2F1 transcription factor and that the MUC1-C→E2F1 pathway induces expression of embryonic stem cell–specific BAF (esBAF) components BRG1, ARID1A, BAF60a, BAF155, and BAF170 in castrate-resistant prostate cancer (CRPC) and NEPC cells. In concert with this previously unrecognized pathway, MUC1 was associated with increased expression of E2F1 and esBAF components in NEPC tumors as compared with CRPC, supporting involvement of MUC1-C in activating the E2F1→esBAF pathway with progression to NEPC. MUC1-C formed a nuclear complex with BAF and activated cancer stem cell (CSC) gene signatures and the core pluripotency factor gene network. The MUC1-C→E2F1→BAF pathway was necessary for induction of both the NOTCH1 effector of CSC function and the NANOG pluripotency factor, and collectively, this network drove CSC self-renewal. These findings indicate that MUC1-C promotes NEPC progression by integrating activation of E2F1 and esBAF with induction of NOTCH1, NANOG, and stemness. Significance: These findings show that MUC1-C, which promotes prostate cancer progression, activates a novel pathway that drives the BAF remodeling complex, induces NOTCH1 and NANOG, and promotes self-renewal of prostate cancer stem cells.
EPCT-07. DEBIO1347, AN ORAL FGFR INHIBITOR: RESULTS FROM A SINGLE CENTER STUDY IN RECURRENT/REFRACTORY FGFR ALTERED PEDIATRIC GLIOMAS
Authors: Sameer Farouk Sait, Stephen Gilheeney, Ira Dunkel, Matthias Karajannis
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Oncogenic driver alterations in FGFR are present in a subset of pediatric gliomas. Debio1347 is an orally available, highly selective FGFR 1–3 inhibitor that had a favorable safety profile and encouraging preliminary clinical activity in an adult phase 1 study. METHODS Five children with progressive/refractory CNS tumors harboring an FGFR gene alteration following prior chemotherapy were treated with Debio1347 at Memorial Sloan Kettering Cancer Center on single patient use protocols. Patients were treated using the 20 mg tablet formulation at the adult recommended phase 2 dose (80 mg/1.73 m2 * BSA once daily). Toxicities were graded using CTCAEv5.0 and imaging response assessments were performed every 8–12 weeks. RESULTS All AEs were grade 1–2. Most common treatment-related adverse events were ALT increased, hypoalbuminemia and hyperphosphatemia (4 patients). Two patients met criteria for partial response and two patients had stable disease. A 13 month-old patient with a spinal cord high-grade glioma harboring two FGFR1 mutations (V592M, K687) had tumor reduction of 91.7% maintained for 12 months. A 26-month-old patient with a pilomyxoid astrocytoma harboring an FGFR1-TACC1 fusion had a tumor reduction of 74.5% maintained for 9 months. Prolonged disease stabilization was noted in an eight year-old patient with metastatic suprasellar pilomyxoid astrocytoma harboring an FGFR1 mutation (9 months) and in a 14 year-old patient with posterior fossa glioneuronal tumor harboring an FGFR3-TACC3 fusion (18 months and ongoing). CONCLUSIONS Debio1347 demonstrated tolerable toxicity and promising anti-tumor efficacy in pediatric patients with refractory FGFR altered gliomas. Further studies in this population are warranted.