• Radiation Oncology Journal
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• v.13 no.4
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• pp.303-309
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• 1995

Purpose : The effect of dose escalation of up to 6500 cGy on local control and survial was investigated in locally advanced non-small cell lung cancer. Materials and Methods: Ninety eight patients with biopsy-proven unresec-table non-small cell lung cancer without distant metastases or medically inoperable patients with lower-stage were treated with definitive radio-therapy alone. Group A was treated by thoracic irradiation, 6000 cGy or less in total tumor dose with daily fractions of 180 to 200 cGy; and group B was treated with 6500 cGy of same daily fractions. Results : The actuarial overall survival rate for the entire group was 54% at 1 year, 26.6% at 2 years and 16.4% at 3 years with a median survival time of 13 months. Statistically significant prognostic factors that affect survival rate were stage and N-stage. However, no improvement in local control and survival has been seen with higher dose radiotherapy(group B). Conclusion : Dose escalation of up to 6500 cGy was no effect on local control and survival rate. To increase the survival rate of non-small cell lung cancer hyperfractionated radiotherapy or concurrent chemoradiotherapy should be considered.

• Radiation Oncology Journal
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• v.36 no.3
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• pp.172-181
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• 2018

Successful anticancer strategies require a differential response between tumor and normal tissue (i.e., a therapeutic ratio). In fact, improving the effectiveness of a cancer therapeutic is of no clinical value in the absence of a significant increase in the differential response between tumor and normal tissue. Although radiation dose escalation with the use of intensity modulated radiation therapy has permitted the maximum tolerable dose for most locally advanced cancers, improvements in tumor control without damaging normal adjacent tissues are needed. As a means of increasing the therapeutic ratio, several new approaches are under development. Drugs targeting signal transduction pathways in cancer progression and more recently, immunotherapeutics targeting specific immune cell subsets have entered the clinic with promising early results. Radiobiological research is underway to address pressing questions as to the dose per fraction, irradiated tumor volume and time sequence of the drug administration. To exploit these exciting novel strategies, a better understanding is needed of the cellular and molecular pathways responsible for both cancer and normal tissue and organ response, including the role of radiation-induced accelerated senescence. This review will highlight the current understanding of promising biologically targeted therapies to enhance the radiation therapeutic ratio.

• Analytical Science and Technology
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• v.34 no.2
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• pp.37-45
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• 2021

A rapid and simple LC-MS/MS analytical method in determining Jaspine B has been developed and validated in rat plasma. The standard curve value was 25 - 5000 ng/mL and the linearity, inter-day and intra-day accuracy and precision were within 15.0 % of relative standard deviation (RSD). The mean recoveries of Jaspine B ranged from 87.5 % to 91.2 % with less than 3.70 % RSD and the matrix effects ranged from 91.1 % to 108.2 % with less than 2.6 % RSD. The validated LC-MS/MS analytical method of Jaspine B was successfully applied to investigate the dose-escalated pharmacokinetic study of Jaspine B in rats following an intravenous injection of Jaspine B at a dose range of 1 - 10 mg/kg. The initial plasma concentrations and area under plasma concentration curves showed a good correlation with intravenous Jaspine B dose, indicating the dose independent pharmacokinetics of Jaspine B in rats. In conclusion, this analytical method for Jaspine B can be easily applied in the bioanalysis and pharmacokinetic studies of Jaspine B, including its administration at multiple therapeutic doses, or for making pharmacokinetic comparisons for the oral formulations of Jaspine B in small experimental animals as well as in vivo pharmacokinetic-pharmacodynamic correlation studies.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.24 no.1
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• pp.7-18
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• 2021

Purpose: The long-term efficacy and safety of infliximab (IFX) in children with ulcerative colitis (UC) have not been well-evaluated. Here, we reviewed the long-term durability and safety of IFX in our single center pediatric cohort with UC. Methods: This retrospective study included 20 children with UC who were administered IFX. Results: For induction, 5 mg/kg IFX was administered at weeks 0, 2, and 6, followed by every 8 weeks for maintenance. The dose and interval of IFX were adjusted depending on clinical decisions. Corticosteroid (CS)-free remission without dose escalation (DE) occurred in 30% and 25% of patients at weeks 30 and 54, respectively. Patients who achieved CS-free remission without DE at week 30 sustained long-term IFX treatment without colectomy. However, one-third of the patients discontinued IFX treatment because of a primary nonresponse, and one-third experienced secondary loss of response (sLOR). IFX durability was higher in patients administered IFX plus azathioprine for >6 months. Four of five patients with very early onset UC had a primary nonresponse. Infusion reactions (IRs) occurred in 10 patients, resulting in discontinuation of IFX in four of these patients. No severe opportunistic infections occurred, except in one patient who developed acute focal bacterial nephritis. Three patients developed psoriasis-like lesions. Conclusion: IFX is relatively safe and effective for children with UC. Clinical remission at week 30 was associated with long-term durability of colectomy-free IFX treatment. However, approximately two-thirds of the patients were unable to continue IFX therapy because of primary nonresponse, sLOR, IRs, and other side effects.

• Archives of Obesity and Metabolism
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• v.1 no.2
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• pp.78-82
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• 2022

Liraglutide (Saxenda^R) is prescribed to induce and sustain weight loss in obese patients. The starting dose of liraglutide is 0.6 mg/day for 1 week, which is increased by 0.6 mg/day every week until the full maintenance dose of 3 mg/day is achieved. Such dose titration is needed to prevent side effects, which primarily include gastrointestinal problems such as nausea, diarrhea, constipation, vomiting, dyspepsia, and abdominal pain. A 35-year-old, reportedly healthy obese man receiving liraglutide treatment for obesity visited the emergency room complaining of generalized weakness and dizziness accompanied by repeated diarrhea and vomiting. He reported over 20 episodes of diarrhea starting the day after liraglutide dose escalation from 1.2 mg/day to 1.8 mg/day. Laboratory findings suggested pre-renal acute kidney injury, including serum creatinine 4.77 mg/dl, blood urea nitrogen (BUN) 37 mg/dl, estimated glomerular filtration rate (eGFR) 15 ml/min/1.73 m², and Fractional excretion of sodium 0.08. After volume repletion therapy, his renal function recovered to a normal range with laboratory values of creatinine 1.08 mg/dl, BUN 14 mg/dl, and eGFR 88 ml/min/1.73 m². This case emphasizes the need for caution when prescribing glucagon-like peptide-1 receptor agonists, including liraglutide, given the risk of serious renal impairments induced by volume depletion and dehydration through severe-grade diarrhea and vomiting.

• Radiation Oncology Journal
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• v.22 no.4
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• pp.237-246
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• 2004

Purpose: To investigate the effects of radiation dose-escalation on the treatment outcome, complications and the other prognostic variables for glioblastoma patients treated with 3D-conformal radiotherapy (3D-CRT). Materials and Methods: Between Jan 1997 and July 2002, a total of 75 patients with histologically proven diagnosis of glioblastoma were analyzed. The patients who had a Karnofsky Performance Score (KPS) of 60 or higher, and received at least 50 Gy of radiation to the tumor bed were eligible. All the patients were divided into two arms; Arm 1, the high-dose group was enrolled prospectively, and Arm 2, the low-dose group served as a retrospective control. Arm 1 patients received $63\~70$ Gy (Median 66 Gy, fraction size $1.8\~2$ Gy) with 3D-conformal radiotherapy, and Arm 2 received 59.4 Gy or less (Median 59.4 Gy, fraction size 1.8 Gy) with 2D-conventional radiotherapy. The Gross Tumor Volume (GTV) was defined by the surgical margin and the residual gross tumor on a contrast enhanced MRI. Surrounding edema was not included in the Clinical Target Volume (CTV) in Arm 1, so as to reduce the risk of late radiation associated complications; whereas as in Arm 2 it was included. The overall survival and progression free survival times were calculated from the date of surgery using the Kaplan-Meier method. The time to progression was measured with serial neurologic examinations and MRI or CT scans after RT completion. Acute and late toxicities were evaluated using the Radiation Therapy Oncology Group neurotoxicity scores. Results: During the relatively short follow up period of 14 months, the median overall survival and progression free survival times were $15{\pm}1.65$ and $11{\pm}0.95$ months, respectively. The was a significantly longer survival time for the Arm 1 patients compared to those in Arm 2 (p=0.028). For Arm 1 patients, the median survival and progression free survival times were $21{\pm}5.03$ and $12{\pm}1.59$ months, respectively, while for Arm 2 patients they were $14{\pm}0.94$ and $10{\pm}1.63$ months, respectively. Especially in terms of the 2-year survival rate, the high-dose group showed a much better survival time than the low-dose group; $44.7\%$ versus $19.2\%$. Upon univariate analyses, age, performance status, location of tumor, extent of surgery, tumor volume and radiation dose group were significant factors for survival. Multivariate analyses confirmed that the impact of radiation dose on survival was independent of age, performance status, extent of surgery and target volume. During the follow-up period, complications related directly with radiation, such as radionecrosis, has not been identified. Conclusion: Using 3D-conformal radiotherapy, which is able to reduce the radiation dose to normal tissues compared to 2D-conventional treatment, up to 70 Gy of radiation could be delivered to the GTV without significant toxicity. As an approach to intensify local treatment, the radiation dose escalation through 3D-CRT can be expected to increase the overall and progression free survival times for patients with glioblastomas.

• Progress in Medical Physics
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• v.31 no.3
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• pp.71-80
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• 2020

This paper provides a brief review of the advanced technologies for carbon ion radiotherapy (CIRT), with a focus on current developments. Compared to photon beam therapy, treatment using heavy ions, especially a carbon beam, has potential advantages due to its physical and biological properties. Carbon ion beams with high linear energy transfer demonstrate high relative biological effectiveness in cell killing, particularly at the Bragg peak. With these unique properties, CIRT allows for accurate targeting and dose escalation for tumors with better sparing of adjacent normal tissues. Recently, the available CIRT technologies included fast pencil beam scanning, superconducting rotating gantry, respiratory motion management, and accurate beam modeling for the treatment planning system. These techniques provide precise treatment, operational efficiency, and patient comfort. Currently, there are 12 CIRT facilities worldwide; with technological improvements, they continue to grow in number. Ongoing technological developments include the use of multiple ion beams, effective beam delivery, accurate biological modeling, and downsizing the facility.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.1
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• pp.319-323
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• 2012

Objective: To explore the feasibility of shrinking field technique after 40 Gy radiation through 18F-FDG PET/CT during treatment for patients with stage III non-small cell lung cancer (NSCLC). Methods: In 66 consecutive patients with local-advanced NSCLC, 18F-FDG PET/CT scanning was performed prior to treatment and repeated after 40 Gy. Conventionally fractionated IMRT or CRT plans to a median total dose of 66Gy (range, 60-78Gy) were generated. The target volumes were delineated in composite images of CT and PET. Plan 1 was designed for 40 Gy to the initial planning target volume (PTV) with a subsequent 20-28 Gy-boost to the shrunken PTV. Plan 2 was delivering the same dose to the initial PTV without shrinking field. Accumulated doses of normal tissues were calculated using deformable image registration during the treatment course. Results: The median GTV and PTV reduction were 35% and 30% after 40 Gy treatment. Target volume reduction was correlated with chemotherapy and sex. In plan 2, delivering the same dose to the initial PTV could have only been achieved in 10 (15.2%) patients. Significant differences (p<0.05) were observed regarding doses to the lung, spinal cord, esophagus and heart. Conclusions: Radiotherapy adaptive to tumor shrinkage determined by repeated 18F-FDG PET/CT after 40 Gy during treatment course might be feasible to spare more normal tissues, and has the potential to allow dose escalation and increased local control.

• Radiation Oncology Journal
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• v.20 no.1
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• pp.68-72
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• 2002

This study was done to implement intensity-modulated radiation therapy (IMRT) for the treatment of primary prostate cancer and to compare this technique with conventional treatment methods. A 72-year-old male patient with prostate cancer stage T2a was treated with IMRT delivered with dynamic multi-leaf collimation. Treatment was designed using an inverse planning algorithm, which accepts dose and dose-volume constraints for targets and normal structures. The IMRT plan was compared with a three-dimensional (3D) plan using the same 6 fields technique. Lower normal tissue doses and improved target coverage were achieved using IMRT at current dose levels, and facilitate dose escalation to further enhance locoregional control and organ movement during radiotherapy is an important issue of IMRT in prostate cancer.

• Radiation Oncology Journal
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• v.30 no.3
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• pp.146-151
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• 2012

Purpose: This treatment planning study was undertaken to evaluate the impact of beam angle configuration of intensity-modulated radiotherapy (IMRT) on the dose of the normal liver in hepatocellular carcinoma (HCC). Materials and Methods: The computed tomography datasets of 25 patients treated with IMRT for HCC were selected. Two IMRT plans using five beams were made in each patient; beams with equidistance of $72^{\circ}$ (Plan I), and beams with a $30^{\circ}$ angle of separation entering the body near the tumor (Plan II). Both plans were generated using the same constraints in each patient. Conformity index (CI), homogeneity index (HI), gamma index, mean dose of the normal liver (Dmean_NL), Dmean_NL difference between the two plans, and percentage normal liver volumes receiving at least 10, 20, and 30 Gy (V10, V20, and V30) were evaluated and compared. Results: Dmean_NL, V10, and V20 were significantly better for Plan II. The Dmean_NL was significantly lower for peripheral (p = 0.001) and central tumors (p = 0.034). Dmean_NL differences between the two plans increased in proportion to gross tumor volume to normal liver volume ratios (p = 0.002). CI, HI, and gamma indices were not significantly different for the two plans. Conclusion: The IMRT plan based on beams with narrow separations reduced the irradiated dose of the normal liver, which would allow radiation dose escalation for HCC.