• Title/Summary/Keyword: Brain cancer therapy

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Safety Assessment of Intravenous Administration of Trastuzumab in 100ml Saline for the Treatment of HER2-Positive Breast Cancer Patients

  • Abe, Hajime;Mori, Tsuyoshi;Kawai, Yuki;Tomida, Kaori;Yamazaki, Keiichi;Kubota, Yoshihiro;Umeda, Tomoko;Tani, Tohru
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.8
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    • pp.4843-4846
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    • 2013
  • Background: The infusion rate is considered to affect incidence and severity of infusion reactions (IRs) caused by protein formulations. Trastuzumab (TRS) is approved for 90-minute infusion as the initial dose followed by 30-minute infusion with 250 ml saline. In the study, we evaluated the safety of TRS intravenously administered over 30 minutes with 100 ml saline to reduce burden of patients, safety of infusion with 250 ml saline already being established. Materials and Methods: Women with HER2 positive breast cancer, ${\geq}18$ years and ${\geq}55%$ left ventricular ejection fraction (LVEF), were registered in the study. Patients received 8mg/kg of TRS 250 ml over 90 minutes followed by 6mg/kg of TRS 100ml over 30 minutes in a three-week cycle. Results: A total of 31 patients were recruited, 24 for adjuvant therapy and seven with metastases. The median age was 59 years (range 39 to 82). The total number of TRS doses ranged from 5 to 17 with the median of 15. Mild IR occurred in two patients at the first dose. However, no IR was observed after reducing to 100 ml saline. No decrease of LVEF, increase of serum brain natriuretic peptide or any other adverse events were reported. Conclusions: Intravenous infusion of TRS with 100 ml saline over 30 minutes in breast cancer patients can be considered safe based on results from the study. It can be given on an outpatient basis as with the currently recommended dilution in 250 ml saline.

Dexamethasone Interferes with Autophagy and Affects Cell Survival in Irradiated Malignant Glioma Cells

  • Komakech, Alfred;Im, Ji-Hye;Gwak, Ho-Shin;Lee, Kyue-Yim;Kim, Jong Heon;Yoo, Byong Chul;Cheong, Heesun;Park, Jong Bae;Kwon, Ji Woong;Shin, Sang Hoon;Yoo, Heon
    • Journal of Korean Neurosurgical Society
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    • v.63 no.5
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    • pp.566-578
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    • 2020
  • Objective : Radiation is known to induce autophagy in malignant glioma cells whether it is cytocidal or cytoprotective. Dexamethasone is frequently used to reduce tumor-associated brain edema, especially during radiation therapy. The purpose of the study was to determine whether and how dexamethasone affects autophagy in irradiated malignant glioma cells and to identify possible intervening molecular pathways. Methods : We prepared p53 mutant U373 and LN229 glioma cell lines, which varied by phosphatase and tensin homolog (PTEN) mutational status and were used to make U373 stable transfected cells expressing GFP-LC3 protein. After performing cell survival assay after irradiation, the IC50 radiation dose was determined. Dexamethasone dose (10 μM) was determined from the literature and added to the glioma cells 24 hours before the irradiation. The effect of adding dexamethasone was evaluated by cell survival assay or clonogenic assay and cell cycle analysis. Measurement of autophagy was visualized by western blot of LC3-I/LC3-II and quantified by the GFP-LC3 punctuated pattern under fluorescence microscopy and acridine orange staining for acidic vesicle organelles by flow cytometry. Results : Dexamethasone increased cell survival in both U373 and LN229 cells after irradiation. It interfered with autophagy after irradiation differently depending on the PTEN mutational status : the autophagy decreased in U373 (PTEN-mutated) cells but increased in LN229 (PTEN wild-type) cells. Inhibition of protein kinase B (AKT) phosphorylation after irradiation by LY294002 reversed the dexamethasone-induced decrease of autophagy and cell death in U373 cells but provoked no effect on both autophagy and cell survival in LN229 cells. After ATG5 knockdown, radiation-induced autophagy decreased and the effect of dexamethasone also diminished in both cell lines. The diminished autophagy resulted in a partial reversal of dexamethasone protection from cell death after irradiation in U373 cells; however, no significant change was observed in surviving fraction LN229 cells. Conclusion : Dexamethasone increased cell survival in p53 mutated malignant glioma cells and increased autophagy in PTEN-mutant malignant glioma cell but not in PTEN-wildtype cell. The difference of autophagy response could be mediated though the phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin signaling pathway.

After retrospective evaluation of the SETUP rate change during the treatment of head and neck cancer patient with Helical Tomotherapy (두경부환자의 토모테라피 치료시 SETUP 변화율에 대한 후향적 평가)

  • Ha, Tae-young;Kim, Seung-jun;Hwang, Cheol-hwan;Son, Jong-gi
    • The Journal of Korean Society for Radiation Therapy
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    • v.28 no.1
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    • pp.27-34
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    • 2016
  • Purpose : Retrospective evaluation of setup changes using the corrected position during helical tomotherapy Materials and Methods : Head and neck cancer patients were randomly sampled and summarized into 3 groups: Group 1(32) Brain, Group 2 2(28)Maxillar, Nasal cavity, Group 3 (35) Nasopharynx(NPX), Tongue, Tonsil, and Oropharynx(OPX). In 3 groups, the statistical tests based on repeated measurements among 30 times of the duration of treatment by applying X, Y, Z axis errors, roll, weight changes, and vectors as variables. Results : The statistical test results showed that there was no difference between x-axis (p = 0.458) and y-axis (p=0.986) and in roll (p = 0.037), weight change (p <0.001), and the vector (p <0.001). In addition, the pattern between the three groups based on the fraction revealed no difference in x-axis (p = 0.430) and roll (p = 0.299) but a difference in y-axis (.023), weight change (p = 0.001), and vector (p = 0.028). Conclusion : The results of the retrospective evaluation found the change in the group 3 with respect Y, Z, weight, and vector and a larger random error during the treatment including low neck.

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Differentiation of True Recurrence from Delayed Radiation Therapy-related Changes in Primary Brain Tumors Using Diffusion-weighted Imaging, Dynamic Susceptibility Contrast Perfusion Imaging, and Susceptibility-weighted Imaging (확산강조영상, 역동적조영관류영상, 자화율강조영상을 이용한 원발성 뇌종양환자에서의 종양재발과 지연성 방사선치료연관변화의 감별)

  • Kim, Dong Hyeon;Choi, Seung Hong;Ryoo, Inseon;Yoon, Tae Jin;Kim, Tae Min;Lee, Se-Hoon;Park, Chul-Kee;Kim, Ji-Hoon;Sohn, Chul-Ho;Park, Sung-Hye;Kim, Il Han
    • Investigative Magnetic Resonance Imaging
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    • v.18 no.2
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    • pp.120-132
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    • 2014
  • Purpose : To compare dynamic susceptibility contrast imaging, diffusion-weighted imaging, and susceptibility-weighted imaging (SWI) for the differentiation of tumor recurrence and delayed radiation therapy (RT)-related changes in patients treated with RT for primary brain tumors. Materials and Methods: We enrolled 24 patients treated with RT for various primary brain tumors, who showed newly appearing enhancing lesions more than one year after completion of RT on follow-up MRI. The enhancing-lesions were confirmed as recurrences (n=14) or RT-changes (n=10). We calculated the mean values of normalized cerebral blood volume (nCBV), apparent diffusion coefficient (ADC), and proportion of dark signal intensity on SWI (proSWI) for the enhancing-lesions. All the values between the two groups were compared using t-test. A multivariable logistic regression model was used to determine the best predictor of differential diagnosis. The cutoff value of the best predictor obtained from receiver-operating characteristic curve analysis was applied to calculate the sensitivity, specificity, and accuracy for the diagnosis. Results: The mean nCBV value was significantly higher in the recurrence group than in the RT-change group (P=.004), and the mean proSWI was significantly lower in the recurrence group (P<.001). However, no significant difference was observed in the mean ADC values between the two groups. A multivariable logistic regression analysis showed that proSWI was the only independent variable for the differentiation; the sensitivity, specificity, and accuracy were 78.6% (11 of 14), 100% (10 of 10), and 87.5% (21 of 24), respectively. Conclusion: The proSWI was the most promising parameter for the differentiation of newly developed enhancing-lesions more than one year after RT completion in brain tumor patients.

Study of overlapping setting up of Planning Target Volume for Improving Target Coverage adjacent Organ At Risk (손상위험장기에 인접한 표적 Coverage 개선을 위한 Planning Target Volume 중복 설정에 관한 연구)

  • Lee, Jung Woong;Kim, Bo Kyum;Mun, Jun Ki;Woo, Hun;Lee, Yang Hoon;Jeon, Chang Woo;Lee, Jea Hee
    • The Journal of Korean Society for Radiation Therapy
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    • v.31 no.2
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    • pp.33-41
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    • 2019
  • Purpose: The purpose of this study is to improve the reduction of coverage of PTVs adjacent to organ at risk (OAR) by setting up overlapping Planning Target Volume (PTV) during Volumetric Modulated Arc Therapy(VMAT). Materials and Methods: In patients who received Whole Brain, Gall Bladder and Rectum radiation therapy, We compared the cover change, maximum dose, Homogenicity Index and Conformity Index of PTV and also compared the maximum dose and average dose change of Organ At Risk by organizing treatment plans that are not applied overlaped PTV and treatment plans that are applied overlaped PTV in areas where coverage is insufficient. Results: overage of treatment plans with overlapping PTVs was increased in all patients, and overall coverage was also increased in each of the four patients. The maximum dose for PTV was increased in five patients, and the Homogenicity Index and Conformity Index for all patients did not differ much. The maximum dose of the lens was increased by 1.12 times, and the maximum dose was decreased in two patients for brain stem. The mean dose of the eyeball was increased by a maximum of 1.15 times, and there was no significant difference between both parotid gland. In case of gallbladder cancer patients, the mean dose in the liver and colon was decreased, and the mean dose in the duodenum was increased. In the case of rectal cancer patients, the mean dose was reduced for both femur and bladder set as OARs. The overall MU was shown to be similar in four patients, excluding one. Conclusion: If the critical dose of OAR is considered and used properly, I think it is a useful way to improve coverage of PTV.

Evaluation of the hybrid-dynamic conformal arc therapy technique for radiotherapy of lung cancer

  • Kim, Sung Joon;Lee, Jeong Won;Kang, Min Kyu;Kim, Jae-Chul;Lee, Jeong Eun;Park, Shin-Hyung;Kim, Mi Young;Lee, Seoung-Jun;Moon, Soo-Ho;Ko, Byoung-Soo
    • Radiation Oncology Journal
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    • v.36 no.3
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    • pp.241-247
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    • 2018
  • Purpose: A hybrid-dynamic conformal arc therapy (HDCAT) technique consisting of a single half-rotated dynamic conformal arc beam and static field-in-field beams in two directions was designed and evaluated in terms of dosimetric benefits for radiotherapy of lung cancer. Materials and Methods: This planning study was performed in 20 lung cancer cases treated with the VERO system (BrainLAB AG, Feldkirchen, Germany). Dosimetric parameters of HDCAT plans were compared with those of three-dimensional conformal radiotherapy (3D-CRT) plans in terms of target volume coverage, dose conformity, and sparing of organs at risk. Results: HDCAT showed better dose conformity compared with 3D-CRT (conformity index: 0.74 ± 0.06 vs. 0.62 ± 0.06, p < 0.001). HDCAT significantly reduced the lung volume receiving more than 20 Gy (V20: 21.4% ± 8.2% vs. 24.5% ± 8.8%, p < 0.001; V30: 14.2% ± 6.1% vs. 15.1% ± 6.4%, p = 0.02; V40: 8.8% ± 3.9% vs. 10.3% ± 4.5%, p < 0.001; and V50: 5.7% ± 2.7% vs. 7.1% ± 3.2%, p < 0.001), V40 and V50 of the heart (V40: 5.2 ± 3.9 Gy vs. 7.6 ± 5.5 Gy, p < 0.001; V50: 1.8 ± 1.6 Gy vs. 3.1 ± 2.8 Gy, p = 0.001), and the maximum spinal cord dose (34.8 ± 9.4 Gy vs. 42.5 ± 7.8 Gy, p < 0.001) compared with 3D-CRT. Conclusions: HDCAT could achieve highly conformal target coverage and reduce the doses to critical organs such as the lung, heart, and spinal cord compared to 3D-CRT for the treatment of lung cancer patients.

Beta Dosimetry for Applying $^{166}Ho$-chitosan Complex to Cystic Brain Tumor Treatment : Monte Carlo Simulations Using a Spherical Model ($^{166}Ho$-chitosan 복합체를 이용한 낭성뇌종양 치료를 위한 베타선의 흡수선량 평가 : 구형 모델을 이용한 Monte Cairo 모사계산)

  • Kim, Eun-Hee;Rhee, Chang-Hun;Lim, Sang-Moo;Park, Kyung-Bae
    • The Korean Journal of Nuclear Medicine
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    • v.31 no.4
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    • pp.433-439
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    • 1997
  • $^{166}Ho$-chitosan complex, or $^{166}Ho$-CHICO, is a candidate pharmaceutical for intracavitary radiation therapy of cystic brain tumors because of the desirable nuclear characteristics of $^{166}Ho$ for therapeutic use and the suitable biological and chemical characteristics of chitosan, not to mention its ready producibility The amount of $^{166}Ho$-CHICO to be administered to obtain the goal therapeutic effect can be suggested by predicting the dose to the cyst wall for a varying pharmaceutical dose. When $^{166}Ho$-CHICO is infused into the cyst, the major part of the energy delivery by beta particles emitted from $^{166}Ho$ occurs in the cyst wall within 4mm in depth from the cyst wall surface. Also, realizing the attachment of $^{166}Ho$-CHICO to the cyst wall surface would change the predictions of dose to the cyst wall.

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3-Dimensional Conformal Radiation Therapy in Carcinoma of The Nasopharynx (비인강암의 3차원 입체조형치료에서 등가선량분포에 관한 연구)

  • Keum Ki Chang;Kim Gwi Eon;Lee Sang Hoon;Chang Sei Kyung;Lim Jihoon;Park Won;Suh Chang Ok
    • Radiation Oncology Journal
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    • v.16 no.4
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    • pp.399-408
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    • 1998
  • Purpose : This study was designed to demonstrate the potential therapeutic advantage of 3-dimensional (3-D) treatment planning over the conventional 2-dimensional (2-D) approach in patients with carcinoma of the nasopharynx. Materials and Methods : The two techniques were compared both qualitatively and quantitatively for the boost portion of the treatment (19.8 Gy of a total 70.2 Gy treatment schedule) in patient with T4. The comparisons between 2-D and 3-D plans were made using dose statistics, dose-volume histogram, tumor control probabilities, and normal tissue complication probabilities. Results : The 3-D treatment planning improved the dose homogeneity in the planning target volume. In addition, it caused the mean dose of the planning target volume to increase by 15.2$\%$ over 2-D planning. The mean dose to normal structures such as the temporal lobe, brain stem, parotid gland, and temporomandibular joint was reduced with the 3-D plan. The probability of tumor control was increased by 6$\%$ with 3-D treatment planning compared to the 2-D planning, while the probability of normal tissue complication was reduced. Conclusion : This study demonstrated the potential advantage of increasing the tumor control by using 3-D planning. but prospective studies are required to define the true clinical benefit.

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Medulloblastoma in the Molecular Era

  • Kuzan-Fischer, Claudia Miranda;Juraschka, Kyle;Taylor, Michael D.
    • Journal of Korean Neurosurgical Society
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    • v.61 no.3
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    • pp.292-301
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    • 2018
  • Medulloblastoma is the most common malignant brain tumor of childhood and remains a major cause of cancer related mortality in children. Significant scientific advancements have transformed the understanding of medulloblastoma, leading to the recognition of four distinct clinical and molecular subgroups, namely wingless (WNT), sonic hedgehog, group 3, and group 4. Subgroup classification combined with the recognition of subgroup specific molecular alterations has also led to major changes in risk stratification of medulloblastoma patients and these changes have begun to alter clinical trial design, in which the newly recognized subgroups are being incorporated as individualized treatment arms. Despite these recent advancements, identification of effective targeted therapies remains a challenge for several reasons. First, significant molecular heterogeneity exists within the four subgroups, meaning this classification system alone may not be sufficient to predict response to a particular therapy. Second, the majority of novel agents are currently tested at the time of recurrence, after which significant selective pressures have been exerted by radiation and chemotherapy. Recent studies demonstrate selection of tumor sub-clones that exhibit genetic divergence from the primary tumor, exist within metastatic and recurrent tumor populations. Therefore, tumor resampling at the time of recurrence may become necessary to accurately select patients for personalized therapy.

A Phase II Trial of Combination Chemotherapy with Cisplatin & Etoposide in Small Cell Lung Cancer (소세포폐암에 대한 Cisplatin과 Etoposide(PVP) 복합화학요법의 효과)

  • Cheon, Eun-Mee;Kim, Hyung-Gun;Son, Tae-Young;Yuh, Young-Jin;Lee, Sang-Goo;Lee, Choon-Taek;Kim, Young-Hwan;Lee, Jhin-Oh;Kang, Tae-Woong
    • Tuberculosis and Respiratory Diseases
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    • v.41 no.6
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    • pp.632-643
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    • 1994
  • Background: The objective responses of cisplatin and etoposide (PVP) combination chemotherapy as second-line therapy following CAV was high (40~50%) and, in several reports, PVP yields survival results that are at least as good as those obtained with cyclophosphamide or doxorubicin-based regimens and with less host-related toxicity in chemotherapy-naive patients. We conducted a phase II study to evaluate the effect of a combination of cisplatin and etoposide as a fitst-line therapy in patients with small cell lung cancer. Methods: Sixty-one previously untreated small cell lung cancer patients with measurable lesion (s) received cisplatin(30 $mg/m^2$ IV, day 1~3) and etoposide(100 $mg/m^2$ IV, day 1~3). In patients with limited disease, after completion of 6 cycles of PVP chemotherapy, chest and prophylatic brain irradiation was performed in case of complete responder, chest irradiation on1y in partial responder. Results: 1) Of 55 evaluable patients, 13(24%) had a complete response and 29(53%) had a partial response. 2) The median survival time was 55.8 weeks for all patients(N=55), 61.1 weeks for limited disease(N=31), 51.3 weeks for extensive disease(N=24). 3) The response duration was 29.1 weeks for responders(N=42). 4) There was no significant prognostic factors influencing response rates. 5) The toxicity was tolerable and there was no treatment-related deaths. Conclusion: The PVP combination chemotherapy as a first-line therapy was effective and well-tolerated in patients with small cell lung cancer.

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