STUDI ALTERNATIF PERENCANAAAN SISTEM RANGKA PEMIKUL MOMEN KHUSUS (SRPMK) DENGAN KOLOM BULAT PADA KANTOR PUSAT ESTIKES KEPANJEN MALANG

Kolom merupakam elemen vertikal suatu struktur yang berfungsi menahan beban aksial dan momen sebagai akibat beban gravitasi dan beban lateral yang bekerja pada struktur. Oleh karena itu, kolom memegan penampang penting pada keutuhan struktur, apabila kolom mengalami kegagalan akan berakibat pada keruntuhan struktur bangunan atas gedung. perbedaan kolom bulat dan kolom persegi sangkat mendasar. Jika ditinjau dari tulangan sengkang, kolom bulat perpenampang spiral memiliki jarak sengkang yang berdekatan diabnding dengan kolom dengan kolom persegi yang mempunya bentuk sengkang tunggal dan jarak antara yang relatif besaar. Kolom bulat yang menghasilkan kapsitas penampang, gaya – gaya dalam seperti gaya aksial; gaya geser; gaya momen, dan simpangan (maximum displacement) sehingga dalam skripsi ini untuk mengetahui desain kolom bulat yang efisien dan efikas didalam perencanaan. Hasil yang diperoleh dari perenanaan struktur gedung dengan kolom bulat pada gedung kantor pusat stikes kepanjen malang dengan program bantu STAAD PRO V 8, yang ditinjau dari kapasitas penampang dengan luas mutu beton kolom bulat menghasilkan ØPn (aksial nominal) = 3988,690 kN, ØMn ( Momen nominal ) = 478,812 kNm, Vn (Geser nominal) = 681629,848 N. Sehingga kolom bulat memiliki kapasitas penampang yang lebih besar dan efektif. Ditinjau dari rasio dan gaya-gaya dalam struktur, kolom bulat memiliki gaya aksial = 0,021, kekakuan struktur pada kolom bulat memiliki simpangan (maximum displacements) yang lebih besar dari kolom persegi. Sehingga kekakuan pada kolom bulat lebih tinggi dengan kolom persegi

Characterization of molecular pathways for targeting therapy in glioblastoma.

Glioblastoma remains the most common malignant brain neoplasm in adults. The available therapies for treatment have only modestly extended survival. Traditional chemotherapy agents have shown only slight effectiveness in controlling this disease. The use of molecular profiling has allowed personalized medicine options to be explored for the care of these individuals. Targeted therapies have shown significant benefit in numerous other cancer types with survival being extended significantly. In glioblastoma, several promising markers have been identified including vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), and programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1). These targets have been shown to play a critical role in glioblastoma formation and proliferation. The pathways of these receptors have been elucidated in detail. This level of understanding has led to the a more robust understanding of possible mechanism of pathway modification. The targeting of these specific markers has led to the development of several selective therapies with additional therapies being evaluated. The clinical trials validating these markers have been promising but have yet to show a clear benefit in brain tumors. This identification of alternative methods to address these markers or identify additional targets may be the key to the fight against this disease. The molecular targeting of glioblastoma pathways may have significant impact on disease control and patient survival

NCMP-07. CASE SERIES OF REGULARLY SCHEDULED MANNITOL INFUSIONS SHOWING WITH PROLONGED CLINICAL BENEFIT FOR MANAGEMENT OF CEREBRAL EDEMA IN GLIOMAS

Gliomas account for the vast majority of malignant primary tumors arising in the central nervous system. Elevated intracranial pressure (ICP) may be a potentially devastating complication of brain tumors and hydrocephalus. Brain tumors may occupy significant space causing displacement and compression of delicate structures within a finite intracranial compartment. The compliance relationship is nonlinear and decreases as the combined volume of the intracranial contents increases. When these compensatory mechanisms have been exhausted, significant increases in pressure develop with relatively small increases in volume. The diagnosis of elevated ICP is generally based on clinical findings and corroborated by imaging studies and the patient\u27s medical history. The best therapy for intracranial hypertension (ICH) is the resolution of the proximate cause of elevated ICP such as the evacuation of a blood clot, resection of a tumor, or cerebrospinal fluid (CSF) diversion in the setting of hydrocephalus. If these modalities have been exhausted or unavailable, osmotic diuretics such as mannitol can be utilized. This medication reduces brain volume by drawing free water out of the tissue and into the circulation, where it is excreted by the kidneys, thus dehydrating brain parenchyma. The common belief is that effects are usually present within minutes, peak at approximately one hour, and last 4 to 24 hours. We report a series of 33 patients treated for a minimum of 1 month of regularly scheduled maintenance infusions of Mannitol 1g/kg every two weeks, 64% showed improved clinical outcomes or stabilization of edema clinical symptoms. Patients expressed improvements in headaches, dizziness, and cognitive ability. This supports the bi-weekly maintenance use of Mannitol in glioma patients with symptomatic cerebral edema. A controlled trial should be supported. This series also suggest a mechanism of action with a more durable response than osmotic diuresis

Molecularly targeted treatment of recurrent anaplastic astrocytoma - a case report.

High-grade astrocytomas are malignant and aggressive, with limited treatment options. Treatment is geared not only toward increasing patient\u27s overall survival but also in delaying or preventing neurological disability, a cause of significant morbidity. Increasingly, targeted and customized treatment approaches, especially for recurrent disease, are being explored. Here we present a successful outcome in a young patient with rapidly progressive disease who responded to targeted treatment based on genetic sequencing and circulating tumor DNA markers, given the inaccessibility of the tissue to biopsy. Molecular testing on tissue, serum or CSF may be helpful in identifying unique targets in these complex patients

CTNI-51. FEASIBILITY AND SAFETY OF NEUROSURGICAL RESECTION AND INTRA-OPERATIVE RADIATION THERAPY USING THE XOFT AXXENT ELECTRONIC BRACHYTHERAPY SYSTEM AND BEVACIZUMAB IN RECURRENT GLIOBLASTOMA

Glioblastoma (GBM) is the most common and aggressive primary brain tumor. External beam radiation therapy (EBRT) is widely recognized as an effective treatment for primary GBM. EBRT applied after GBM resection is associated with an increase in overall survival. Beyond upfront therapy with radiation and temozolomide chemotherapy, there is no standard therapy that has been proven effective. Re-irradiation with ERBT is minimally effective and with significant comorbidities. Our study uses IORT at the time of re-resection in patients who have recurrent, operable GBM after failure of who received primary EBRT and temozolamide in their first course of treatment. IORT allows the delivery of a large effective radiation dose applied directly to the tumor bed at the time of resection. This affords direct radiation to be delivered to the micro- and macroscopic tumor remnants in the vicinity of the resection cavity immediately following gross resection. In contrast, the more distant, surrounding brain tissue does not receive high radiation exposure. This Phase II study continues to accrue subjects with the primary endpoint of overall survival and several secondary endpoints that includes progression free survival, quality of life, and adverse events/safety. To date, five patients have been treated on this protocol. The technical feasibility and safety of administering intraoperative radiation with the Xoft System has been established in this cohort. Preliminary GLIOX Trial findings demonstrate the safety and feasibility of using the Xoft Axxent® Electronic Brachytherapy System to administer intracranial radiation during resection of recurrent glioblastomas. We will report new and expansive study results to include these early findings

QLTI-22. IMPROVING BRAIN CANCER PATIENT ACCESS TO CLINICAL TRIALS ACROSS SEVEN COMMUNITY HOSPITALS, THE PROVIDENCE SOUTHERN CALIFORNIA CLINICAL RESEARCH NETWORK

Despite current FDA approved treatments for glioblastoma (GBM), prognosis remains poor. The rare patient population and limited access to clinical trials are factors in this poor prognosis. Clinical trials need to increase enrollment of patients with glioblastoma and other brain cancers to more rapidly develop more effective treatments. Clinical trials are featured on NCCN guidelines, and are considered “Standard of Care” by many experts. Multiple studies have shown that access to clinical trials is associated with improved survival in GBM, however, less than 25% of patients have access or are offered clinical trials. Access to clinical trials can be even more limited in community hospitals, while a large proportion of brain tumors are treated in smaller centers. Community hospitals care for a significant number of brain tumors annually. We have developed a Clinical Research Network for Neuro-Oncology within the Providence Network involving seven hospitals to date. In the past 3 years, we have grown the number of clinical trials available in outlying cities and counties spanning a distance of 60 miles. Between the seven hospitals in our network, we have 15 clinical trials currently open for brain cancer patients, of which, 3 trials were phase I studies. Over the past 2 years, we have enrolled 104 GBM patients in clinical trials. The ability to enhance access to clinical trials by Neuro-Oncologists treating patients in the community is feasible and promising

CTNI-32. CASE SERIES OF BRAF INHIBITORS FOR THE TREATMENT OF BRAFV600E GLIOBLASTOMA

Glioblastoma is the most common and aggressive primary brain tumor. Beyond upfront therapy with radiation and temozolomide chemotherapy there is no standard therapy that has been effective. Inhibitors of BRAF and MEK, a downstream protein immediately following BRAF, have been shown to have survival benefit for patients with other BRAF V600E mutant neoplasm including advanced melanoma. We describe our experience using this combined target therapy for two patients with BRAF V600E mutant glioblastoma. Two adult patients with pathologically diagnosed glioblastoma presented with radiographic evidence of tumor progression after prior treatment with chemotherapy or immunotherapy. Neither had received radiation therapy within 3 months of starting treatment. Molecular characterization was performed though Caris which showed evidence of BRAF V600E mutation. BRAF inhibitors were initiated in combination with standard therapy options. MRI imaging was obtained to monitor for disease progression. BRAF inhibitors were tolerated well without any side effects not previously reported. Partial objective response was seen in both patients on subsequent MRI imaging within 8 weeks of starting treatment. Progression free survival and overall survival have not been reached in either case. BRAF inhibition may have therapeutic benefit in BRAF mutated glioblastoma. Partial response was seen in this case series. The molecular profile of glioblastoma may suggest treatment options beyond standard chemotherapy options. This series supports the use of BRAF inhibitors for the treatment of BRAFV600E glioblastoma A controlled trial should be supported

Activity of pemetrexed in pre-clinical chordoma models and humans.

Chordomas are rare slow growing tumors, arising from embryonic remnants of notochord with a close predilection for the axial skeleton. Recurrence is common and no effective standard medical therapy exists. Thymidylate synthase (TS), an intracellular enzyme, is a key rate-limiting enzyme of DNA biosynthesis and repair which is primarily active in proliferating and metabolically active cells. Eighty-four percent of chordoma samples had loss of TS expression which may predict response to anti-folates. Pemetrexed suppresses tumor growth by inhibiting enzymes involved in folate metabolism, resulting in decreased availability of thymidine which is necessary for DNA synthesis. Pemetrexed inhibited growth in a preclinical mouse xenograft model of human chordoma. We report three cases of metastatic chordoma that had been heavily treated previously with a variety of standard therapies with poor response. In two cases, pemetrexed was added and objective responses were observed on imaging with one patient on continuous treatment for \u3e 2 years with continued shrinkage. One case demonstrated tumor growth after treatment with pemetrexed. The two cases which had a favorable response had a loss of TS expression, whereas the one case with progressive disease had TS present. These results demonstrate the activity of pemetrexed in recurrent chordoma and warrant a prospective clinical trial which is ongoing (NCT03955042)

Response to OKN-007 and NAC in a Patient with Unilateral Hearing Loss and Chronic Tinnitus from Vestibular Schwannoma

Background: Tinnitus is the perception of sound in the absence of external acoustic stimulation. Being one of the most common diseases of the ear, it has a global prevalence ranging from 4.1 to 37.2%. To date, it has been difficult to treat tinnitus as its pathophysiology is poorly understood and there are limited treatment options. Objective: To investigate the effect of OKN-007 (also known as HPN-07), a nitrone-based investigational drug, in combination with oral N-acetylcycsteine (NAC), for the treatment of hearing loss and chronic tinnitus under an individual expanded access protocol. Patient Case: We report the case of a patient who presented with left-sided ear fullness, mild tinnitus, and mild high frequency sensorineural hearing loss with 100% word recognition. A large enhancing mass seen on MRI revealed a vestibular schwannoma. He underwent subtotal resection of the tumor resulting in a moderate-to-profound sensorineural hearing loss and catastrophic tinnitus. The patient was treated with intravenous OKN-007 at 60 mg/kg dosed three times per week and oral NAC 2500 mg twice daily. Results: Post-treatment audiometric testing revealed an average of 16.66 dB in hearing threshold improvement in three frequencies (125, 250 and 500 Hz) with residual hearing in the affected left ear. His tinnitus loudness matching improved from 90 dB to 19 dB post-treatment. His Tinnitus Handicap Inventory improved from 86/100 (Catastrophic) to 40/100 (Moderate). He also experienced improvements in sleep, concentration, hearing, and emotional well-being, and reported significantly decreased levels of tinnitusrelated distress. Conclusions: This case report highlights the feasibility and therapeutic potential of the combination of OKN-007 and NAC in treating hearing loss and tinnitus that warrants further investigation. Keywords: Tinnitus, Hearing loss, OKN-007