• Journal of Korean Neurosurgical Society
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• v.58 no.2
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• pp.163-166
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• 2015

The prophylactic use of phenytoin during and after brain surgery and cranial irradiation is a common measure in brain tumor therapy. Phenytoin has been associated with variety of adverse skin reactions including urticaria, erythroderma, erythema multiforme (EM), Stevens-Johnson syndrome, and toxic epidermal necrolysis. EM associated with phenytoin and cranial radiation therapy (EMPACT) is a rare specific entity among patients with brain tumors receiving radiation therapy while on prophylactic anti-convulsive therapy. Herein we report a 41-year-old female patient with left temporal glial tumor who underwent surgery and then received whole brain radiation therapy and chemotherapy. After 24 days of continous prophylactic phenytoin therapy the patient developed minor skin reactions and 2 days later the patient returned with generalized erythamatous and itchy maculopapuler rash involving neck, chest, face, trunk, extremities. There was significant periorbital and perioral edema. Painful mucosal lesions consisting of oral and platal erosions also occurred and prevented oral intake significantly. Phenytoin was discontinued gradually. Systemic admistration of corticosteroids combined with topical usage of steroids for oral lesions resulted in complete resolution of eruptions in 3 weeks. All cutaneous lesions in patients with phenytoin usage with the radiotherapy must be evoluated with suspicion for EM.

• Radiation Oncology Journal
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• v.37 no.3
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• pp.156-165
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• 2019

Purpose: Prophylactic cranial irradiation (PCI) is a standard treatment for limited-stage small cell lung cancer (LS-SCLC) showing a response to initial treatment, but many patients do not receive PCI due to comorbidities or refusal. This study aims to define the patient group for whom PCI can be omitted with minimal risk. Materials and Methods: Patients with LS-SCLC who underwent radiotherapy with curative aim at our institution between January 2004 and December 2015 were retrospectively reviewed. Patients who did not receive PCI were evaluated for brain metastasis-free survival (BMFS), progression-free survival (PFS), overall survival (OS), and prognostic factors for survival, and treatment outcomes were compared with a patient cohort who received PCI. Results: A total of 350 patients achieved a response following thoracic radiotherapy, and 190 of these patients did not receive PCI. Stage I-II and a complete response (CR) to initial therapy were good prognostic factors for BMFS and OS on univariate analysis. Patients with both stage I-II and a CR who declined PCI showed comparable 2-year BMFS to those who received PCI (92% vs. 89%). In patients who achieved CR, PCI did not significantly improve OS or PFS. Conclusion: There should be less concern about omitting PCI in patients with comorbidities if they have stage I-II or a CR, with brain metastasis control being comparable to those patients who receive PCI.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.3
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• pp.1233-1239
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• 2014

Background: The incidence of brain metastases (BM) varies in patients with non-small cell lung cancer (NSCLC), calls into question the value of prophylactic cranial irradiation (PCI). It is possible that clinicopathologic characteristics are associated with the development of BM, but these have yet to be identified in detail. Thus, we conducted the present meta-analysis on risk factors for BM and the value of PCI in patients with NSCLC. Methods: Eligible data were extracted and the risk factors for BM and the value of PCI in patients with NSCLC were analyzed by calculating the pooled odds ratio (OR). Heterogeneity was detected using Q and I-squared statistics, and publication bias was tested by funnel plots and Egger's test. Results: Six randomized controlled trials with a focus on the value of PCI and 13 eligible studies with a focus on risk factors for BM were included. PCI significantly reduced the incidence of BM in patients with NSCLC (p=0.000, pooled OR=0.34, 95% confidence interval = 0.37-0.59). Compared with non-squamous cell carcinoma, squamous cell carcinoma was associated with a low incidence of BM in patients with NSCLC (p=0.000, pooled OR=0.47, 95% confidence interval =0.34-0.65). The funnel plot and Egger's test suggested that there was no publication bias in the current meta-analysis. Conclusions: This meta-analysis provides statistical evidence that compared with non-squamous cell carcinoma, squamous cell carcinoma can be used as a predictor for BM in patients with NSCLC, and PCI might reduce the incidence of BM in patients with NSCLC, but does not provide a survival benefit.

• Progress in Medical Physics
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• v.34 no.4
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• pp.41-47
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• 2023

Purpose: This study aimed to dosimetrically compare the technique of three-dimensional conformal radiotherapy (3D CRT), which is a traditional prophylactic cranial irradiation method, and the intensity-modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) techniques used in the last few decades with the dynamic conformal arc therapy (DCAT) technique. Methods: The 3D CRT, VMAT, IMRT, and DCAT plans were prepared with 25 Gy in 10 fractions in a Monaco planning system. The target volume and the critical organ doses were compared. A comparison of the body V₂, V₅, and V₁₀ doses, monitor unit (MU), and beam on-time values was also performed. Results: In planned target volume of the brain (PTV_Brain), the highest D99 dose value (P<0.001) and the most homogeneous (P=0.049) dose distribution according to the heterogeneity index were obtained using the VMAT technique. In contrast, the lowest values were obtained using the 3D CRT technique in the body V₂, V₅, and V₁₀ doses. The MU values were the lowest when DCAT (P=0.001) was used. These values were 0.34% (P=0.256) lower with the 3D CRT technique, 66% (P=0.001) lower with IMRT, and 72% (P=0.001) lower with VMAT. The beam on-time values were the lowest with the 3D CRT planning (P<0.001), 3.8% (P=0.008) lower than DCAT, 65% (P=0.001) lower than VMAT planning, and 76% (P=0.001) lower than IMRT planning. Conclusions: Without sacrificing the homogeneous dose distribution and the critical organ doses in IMRTs, three to four times less treatment time, less low-dose volume, less leakage radiation, and less radiation scattering could be achieved when the DCAT technique is used similar to conventional methods. In short, DCAT, which is applicable in small target volumes, can also be successfully planned in large target volumes, such as the whole-brain.

• Radiation Oncology Journal
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• v.14 no.2
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• pp.137-147
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• 1996

Purpose : This report is the result f retrospective analysis for children who received prophylactic cranial irradiation combined with intrathecal chemotherapy. Materials and Methods : Ninety children with ALL who had got bone marrow remission after induction chemotherapy received PCI. All but 3 children were treated with a dose of 1800 cGy as a standard regimen. While the PCI was given, all patients received intrathecal chemotherapy. Results : Nine of 90 patients experienced CNS relapse during the duration of follow-up ranged from 36 to 96 months (median 60 months). Three children experienced BM relapse prior to CNS relapse. Therefore, CNS relapse rate as the first adverse event was $6.7\%$. Median time interval of CNS relapse was 16 months from the first day of hematologic complete remission. Eighty-nine percent of patients who had CNS relapse were associated with hematologic relapse. and $78\%$ of CNS relpase occurred during maintenance chemotherapy (on-therapy relapse). The CNS RFS at 2 and 5 years are $68\%$ and $42\%$, respectively with median of 43 months. The Prognostic factors affecting CNS RFS are initial WBC count (cut-off point of 50,000/ul), FAB subtype and CALGB risk criteria. The DFS at 2 and 5 years are 61 and $39\%$, respectively with median of 34 months. The prognostic factors affecting DFS are initial WBC count (cut-off point of 50,000/ul), FAB subtype, POG and CALGB risk criteria. Conclusions : In our study, $6.7\%$ of CNS relapse rate as a first adverse event was comparable with other studies. Various risk criteria was based on age at diagnosis and initial WBC count such as POG and CALGB criteria, had prognostic significance for CNS RFS and DFS. Prospective randomized trial according to prognostic subgroup based on risk criteria and systematic study about neuropsychologic function for long term survivors, are essential to determine the most effective and least toxic form of CNS prophylaxis.

• Radiation Oncology Journal
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• v.7 no.2
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• pp.269-277
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• 1989

CNS prophylaxis with 18 or 24 Gy cranial irradiation plus intrathecal methotrexate was given to 134 childhood acute lymphoblastic leukemia patients who had got bone marrow remission (M1) after remission induction chemotherapy from August 1979 to December 1986. The rate of initial total CNS relapse was 14.2% (19/134), the rate of isolated CNS relapse was 5.2% (7/134), and the rate of CNS relapse concomittantly combined with bone marrow relapse or testicular relapse was 9% (12/134). Male sex or older age was accociated with higher CNS relapes and the initial peripheral leukocyte count over 50,000/ul had higher relapse rate. Relapse with radiation dose of 18Gy was somewhat lower than that with 24Gy. Within 4 years after CNS prophylaxis occurred 89% of the total CNS relapses, 100% of the isolated CNS relapses, and 83% of the combined CNS relapses. Adjusted to exposed cases to risk of CNS relapse, the total CNS relapse rate was 11.9% during maintenance chemotherapy and 4.9% after maintenance chemotherapy.

• Clinical and Experimental Pediatrics
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• v.46 no.6
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• pp.566-571
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• 2003

Purpose : Leukoencephalopathy(LE) is one of the most serious complications in children with hematologic malignancies during the course of treatment. Early recognition is important to reduce the impact and sequelae from LE. We therefore investigated the clinical features of LE following central nervous system(CNS) prophylaxis in children with hematologic malignancies and evaluated the significance of regular check-ups of brain MRI. Methods : We retrospectively reviewed children with hematologic malignancies who had CNS prophylaxis including intrathecal(IT) methotrexate(MTX) and/or cranial irradiation at the Department of Pediatrics, Kyungpook National University Hospital from Oct. 1995 to May 2002. Fifteen cases of acute leukemia and one case of lymphoma who experienced LE following CNS prophylaxis were included in the study. Clinical data were analyzed from the medical records and brain MRIs were reviewed by neuroradiologists. Results : The ages ranged from 1 to 13 years(median age=5.2 years), and the male to female ratio was 3 : 1. The time interval from the beginning of chemotherapy to the time of diagnosis of LE ranged from 2 to 17 months. They all had IT MTX two to 15 times and ten underwent cranial irradiation(1,800 rads). At the time of diagnosis, ten of them had neuropsychiatric symptoms including seizures, personality changes, headache, etc. After the change of treatment modality, four cases showed significant improvement on follow-up MRIs, six cases had no significant changes and two had worsening of LE. Four patients died of infection and bone marrow relapse. Conclusion : CNS prophylaxis with IT therapy and cranial irradiation may cause leukoencephalopathy during the course of treatment. As a result, regular brain MRI check-up is recommended for the early detection and reducing the incidence of LE, along with changes in the treatment modality.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.15
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• pp.6263-6267
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• 2014

Background: It is standard treatment to combine chemotherapy (CT) and thoracic radiotherapy (TRT) in treating patients with limited stage small cell lung cancer (LS-SCLC). However, optimal timing of TRT is unclear. We here evaluated the survival impact of early versus late TRT in patients with LS-SCLC. Materials and Methods: Follow-up was retrospectively analyzed for seventy consecutive LS-SCLC patients who had successfully completed chemo-TRT between January 2006 and January 2012. Patients received TRT after either 1 to 2 cycles of CT (early TRT) or after 3 to 6 cycles of CT (late TRT). Survival and response rates were evaluated using the Kaplan-Meier method and comparisons were made using the multivariate Cox regression test. Results: Median follow-up was 24 (5 to 57) months. Carboplatin+etoposide was the most frequent induction CT (59%). Median overall, disease free, and metastasis free survivals in all patients were 15 (5 to 57), 5 (0 to 48) and 11 (3 to 57) months respectively. Late TRT was superior to early TRT group in terms of response rate (p=0.05). 3 year overall survival (OS) rates in late versus early TRT groups were 31% versus 17%, respectively (p=0.03). Early TRT (p=0.03), and incomplete response to TRT (p=0.004) were negative predictors of OS. Significant positive prognostic factors for distant metastasis free survival were late TRT (p=0.03), and use of PCI (p=0.01). Use of carboplatin versus cisplatin for induction CT had no significant impact on OS (p=0.634), DFS (p=0.727), and MFS (p=0.309). Conclusions: Late TRT appeared to be superior to early TRT in LS-SCLC treatment in terms of complete response, OS and DMFS. Carboplatin or cisplatin can be combined with etoposide in the induction CT owing to similar survival outcomes.

• Tuberculosis and Respiratory Diseases
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• v.63 no.2
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• pp.154-164
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• 2007

Background: Irinotecan hydrochloride, a topoisomerase I inhibitor, is effective against small-cell lung cancer. Irinotecan also can act as a potential radiation sensitizer along with cisplatin. To evaluate efficacy and toxicity of irinotecan plus cisplatin (IP) with concurrent thoracic radiotherapy, we conducted a phase II study of IP followed by concurrent IP plus hyperfractionated thoracic radiotherapy in patients with previously untreated limited-stage small-cell lung cancer. Methods: Twenty-four patients with previously untreated small-cell lung cancer were enrolled onto the study since November 2004. Irinotecan $60mg/m^2$ was administered intravenously on days 1 and 8 in combination with cisplatin $60mg/m^2$ on day1 every 21 days. From the first day of third cycle, twice-daily thoracic irradiation (total 45 Gy) was given. Prophylactic cranial irradiation was given to the patients who showed complete remission after concurrent chemoradiotherapy. Restaging was done after second and sixth cycle with chest CT and/or bronchosocpy. Results: Up to November 2004, 19 patients were assessable. The median follow-up time was 12.5 months. A total of 99 cycles (median 5.2 cycles per patient) were administered. The actual dose intensity values were cisplatin $19.6mg/m^2$/week and irinotecan $38.2mg/m^2$/week. Among the 19 patients, the objective response rate was 95% (19 patients), with 9 patients (47%) having a complete response (CR). The major grade 3/4 hematological toxicities were neutropenia (35% of cycles), anemia (7% of cycles), thrombocytopenia (7% of cycles). Febrile neutropenia was 4% of cycles. The predominant grade 3/4 non-hematological toxicities was diarrhea (5% of cycles). Toxicities was not significantly different with concurrent administration of irinotecan and cisplatin with radiotherapy, except grade 3/4 radiation esophagitis (10% of patients). No treatment-related deaths were observed. The 1-year and 2-year survival rate of eligible patients was 89% (16/18) and 47% (9/18), respectively. Conclusion: Three-week schedule of irinotecan plus cisplatin followed by concurrent IP plus hyperfractionated thoracic radiotherapy is an effective treatment for limited disease small-cell lung cancer, with acceptable toxicity.

• Tuberculosis and Respiratory Diseases
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• v.49 no.3
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• pp.323-331
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• 2000

Purpose: Brain metastases are present in approximately 10-16% of small cell lung cancer patients at diagnosis. Brain metastasis is an important clinical problem associated with increasing the survival rate, with a cumulative incidence of up to 80% in patients surviving 2 years. Prophylactic cranial irradiation(PCI) reduces the incidence of brain matastasis and may prolong survival in patients with limited small-cell lung cancer who achieved complete remission. This study was performed to analyze the incidence of brain metastasis, survival and clinical aspects after PCI in patients with limited small-cell lung cancer who achieved complete remission. Methods : Between 1989 and 1999, forty-two patients with limited small-cell lung cancer who achived achieved complete remission after therapy were enrolled into this study retrospectively. All patients received etoposide and cisplatin(VPP) alternating with cytoxan, adriamycin, and vincristine(CAV) every 3 weeks for at least 6 cycles initially. All patients received thoracic radiotherapy: concurrent(38.1%) and sequential(61.9%). All patients received late PCI. Results : Most patients(88.1%) were men, and the median age was 58 years. The median follow-up duration was 18.1 months. During the follow-up period, 57.1% of the patients developed relapse. The most frequent site of relapse was chest(35.7%), followed by brain(14.3%), liver(11.9%), adrenal gland(44%), and bone(2.2%). With the Kaplan-Meier method, the average disease-free interval was 1,090 days(median 305 days). The average time to development of brain relapse after PCI and other sites relapse(except brain) were 2,548 days and 1,395 days(median 460 days), respectively. The average overall survival was 1,233 days(median 634 days, 21.1 months), and 2-year survival rates was 41.7%. The average overall survival in the relapse group was 642 days(median 489 days) and in the no relapse group was 2,622 days(p<0.001). The average overall survival in the brain relapse group was 928 days(median 822 days) and in the no brain relapse group was 1,308 days(median 634 days)(p=0.772). In most patients(85.7%), relapse(except brain) or systemic disease was the usual cause of death. Brain matastasis was the cause of death in 14.3% of the cases. Conclusions : We may conclude that PCI reduces and delays brain metastasis in patients with limited small cell lung cancer who achieved complete remission. We found decreased survival in relapse group but, no significant survival difference was noted according to brain matastasis. And relapse(except brain) or systemic disease was the usual cause of death. In order to increase survival, new treatment strategies for control methods for relapse and systemic disease are required.