[Show abstract][Hide abstract] ABSTRACT: This study was done to evaluate the association of cyclooxygenase 2 (COX-2) and brain fatty acid binding protein (BFABP) with tumor grade and outcome of grades I-II meningiomas treated with radiotherapy. From 1996 to 2008, 40 patients with intracranial grades I-II meningiomas were treated with radiotherapy. Immunohistochemical staining for COX-2 and BFABP were performed on formalin-fixed paraffin-embedded tissues. COX-2 expression was significantly associated with BFABP status and both COX-2 (P < 0.01) and BFABP (P = 0.01) expression were stronger in the grade II meningiomas than in grade I tumors. Among the clinicopathologic factors, age and COX-2 status were prognostic in progression-free survival. Patients with moderate or strong COX-2 expression had worse outcome than those with negative or weak COX-2 expression (P = 0.03) after controlling for potential confounders. Our results suggest that the molecular biomarker COX-2 has prognostic significance in intracranial grades I-II meningiomas following radiotherapy.
[Show abstract][Hide abstract] ABSTRACT: The objective of this study was to assess the effect of postoperative radiotherapy on the outcome of esophageal cancer with microscopically positive resection margin by comparing the results with those of patients with negative resection margin.
Medical records of 88 patients treated with macroscopic resection followed by postoperative radiotherapy for stage II or III squamous cell carcinoma of the esophagus from June 1984 to March 2008 were reviewed. Twelve patients had received chemotherapy. Patients were classified into two groups based on resection margin status: negative resection margin (group A, n=66) and microscopically positive resection margin (group B, n=22). Median follow-up duration of living patients was 68 months (range, 18 to 115 months). Median total radiation dose of group A and group B was 51.5 Gy (range, 45 to 69 Gy) and 52.1 Gy (range, 45 to 64 Gy), respectively.
Median overall survival and disease-free survival were 15 and 10 months, respectively. The five-year overall survival, disease-free survival, and local control rates for group A and group B were 15.9% and 16.4%, 13.5% and 9.1%, and 76.3% and 69.6%, respectively. No statistically significant difference in terms of overall survival, disease-free survival, and local control (p=0.295, p=0.209, and p=0.731, respectively) was observed between group A and group B. Seven patients experienced toxicity of grade 3 or higher.
A significant portion of patients with margin involvement reached long term survival after addition of postoperative radiotherapy. These results suggest a potential role of postoperative radiotherapy, especially for patients with margin involvement.
Cancer Research and Treatment 09/2013; 45(3):202-9. · 2.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to assess the clinical outcomes of hypofractionated radiotherapy (HFRT) with three-dimensional conformal technique for medically inoperable patients with early stage non-small-cell lung cancer (NSCLC) and to evaluate prognostic factors.
We performed a retrospective review of 26 patients who underwent HFRT for early stage NSCLC between September 2005 and August 2011. Only clinical stage T1-3N0 was included. The median RT dose was 70 Gy (range, 60 to 72 Gy) and the median biologically equivalent dose (BED) was 94.5 Gy (range, 78.0 to 100.8 Gy). In 84.6% of patients, 4 Gy per fraction was used. Neoadjuvant chemotherapy with paclitaxel and cisplatin was given to 2 of 26 patients.
The median follow-up time for surviving patients was 21 months (range, 13 to 49 months). The overall response rate was 53.9%, and the initial local control rate was 100%. The median survival duration was 27.8 months. Rates of 2-year overall survival, progression-free survival (PFS), local control (LC), and locoregional-free survival (LRFS) were 54.3%, 61.1%, 74.6%, and 61.9%, respectively. Multivariate analysis showed that BED (>90 vs. ≤90 Gy) was an independent prognostic factor influencing PFS, LC, and LRFS. Severe toxicities over grade 3 were not observed.
Radical HFRT can yield satisfactory disease control with acceptable rates of toxicities in medically inoperable patients with early stage NSCLC. HFRT is a viable alternative for clinics and patients ineligible for stereotactic ablative radiotherapy. BED over 90 Gy and 4 Gy per fraction might be appropriate for HFRT.
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study is to analyze treatment outcome of radiotherapy (RT) in patients with stage III-IV tonsil cancer managed by surgery followed by postoperative RT (SRT) and definitive chemoradiotherapy (CRT), and to thereby evaluate the most feasible treatment modality.
Of 124 patients, 67 underwent CRT, and 57 underwent SRT. We compared survival and complication rates in both groups.
The median follow-up time was 57 months (range, 19 to 255 months) for surviving patients. At five years, locoregional progression-free survival (LRPFS) and overall survival (OS) were 88% and 80%, respectively. No significant difference in LRPFS (p=0.491) and OS (p=0.177) was observed between CRT and SRT. In multivariate analysis, old age and higher T stage showed a significant association with poor LRPFS, PFS, and OS; higher N stage showed an association with poor PFS and a trend of poor LRPFS, while no association with OS was observed; treatment modality (CRT and SRT) showed no association with LRFPS, PFS, and OS. Grade 3 or higher mucositis was observed in 12 patients (21%) in the SRT group, and 25 patients (37%) in the CRT group.
Definitive CRT and SRT have similar treatment outcomes for patients with stage III-IV tonsil cancer. Although acute complication rate appears to be higher in the CRT group, it should be noted that not all data on complications were included in this retrospective study. To determine the most feasible treatment modality, not only mucositis and xerostomia, but also emotional aspect and quality of life, should be considered.
Cancer Research and Treatment 12/2012; 44(4):227-34. · 2.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate the efficacy and toxicity of definitive radiotherapy with or without chemotherapy for T3-4 squamous cell carcinoma of maxillary sinus and nasal cavity.
Forty-two patients with T3-4N0 squamous cell carcinoma of maxillary sinus (n = 30) and nasal cavity (n = 12) received definitive radiotherapy. Chemotherapy was used in 34 patients and elective neck irradiation was not used.
The 5-year overall survival/local control rates were 34%/29% for maxillary sinus cancer and 50%/52% for nasal cavity cancer. For maxillary sinus cancers, a performance status of Eastern Cooperative Oncology Group >or=2 (P = 0.012), biologically equivalent dose <68 Gy (P = 0.011) and no use of chemotherapy (P = 0.037) were significant worse predictors for overall survival on log-rank analysis. Biologically equivalent dose <68 Gy was independently associated with poor local control (hazard ratio, 3.32; 95% confidence interval, 1.38-7.97; P = 0.007) and overall survival (hazard ratio, 2.94; 95% confidence interval, 1.23-7.01; P = 0.015). Regional recurrence occurred in only 1 of 30 patients with maxillary sinus cancer and 4 of 12 patients with nasal cavity. Two radiation necrosis in brain, one osteoradionecrosis, and one retinopathy and optic neuropathy occurred.
The treatment outcome was poor and local control was a major problem. High radiation dose, effective chemotherapy and elective neck irradiation for advanced nasal cavity cancers may improve disease control.
Japanese Journal of Clinical Oncology 02/2010; 40(6):542-8. · 1.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Our aim was to evaluate the feasibility and efficacy of intensity-modulated radiation therapy (IMRT) with simultaneous integrated boost (SIB) technique following neoadjuvant chemotherapy for locoregionally advanced nasopharyngeal cancer (NPC).
Between April 2004 and December 2006, 25 patients with stage IIB to IVB NPC underwent 3 cycles of neoadjuvant chemotherapy followed by IMRT using SIB technique. Neoadjuvant chemotherapeutic regimens were 5-fluorouracil and cisplatin in 11 patients; docetaxel, 5-fluorouracil, and cisplatin in 8; and paclitaxel and cisplatin in 6. Dose prescription of IMRT was as follows: 67.5 Gy at 2.25 Gy/fraction to postchemotherapy gross tumor, 54 to 60 Gy at 1.8 to 2 Gy/fraction to subclinical disease, and 48 Gy at 1.6 Gy/fraction to elective neck. Seventeen patients received weekly cisplatin during the course of radiation therapy as well.
With a median follow-up of 29 months for survivors (range, 14-39), the 3-year local progression-free, regional progression-free, and distant metastasis-free survival rates were 89.6%, 87.2%, and 80.4%, respectively. Treatment was well tolerated despite the grade 3 mucositis (16%) and/or pharyngitis (16%). With follow-up, the frequency of xerostomia decreased. At 3 months after IMRT, the proportions of Radiation Therapy Oncology Group grades 0, 1, and 2 xerostomia were 13%, 38%, and 50%, respectively. At 24 months, the corresponding figures were 36%, 46%, and 18%, respectively.
IMRT with SIB technique for locoregionally advanced NPC was feasible and effective regarding locoregional control and development of xerostomia, even after neoadjuvant chemotherapy. Definition of gross tumor volume by postchemotherapy extent of disease was also feasible.
Head & Neck 05/2009; 31(9):1121-8. · 2.83 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To assess the body-framed stereotactic body radiation therapy (SBRT) results and toxicity for medically inoperable stage I lung cancer adjacent to central large bronchus and then compare the results with those of SBRT in peripheral lung tumor in the aspects of survival and SBRT-related pulmonary toxicities.
From June 1999 to May 2006, 32 patients diagnosed as stage I, T1N0 or T2N0, resectable NSCLC were treated with body-frame based fractionated SBRT. Thirty-one patients had several medical problems conflicting surgical procedure. Stereotactic body frame was used for improving setup accuracy. Doses of 10-20 Gy per fraction were delivered to the planning target volume (PTV) up to a total dose of 40-60 Gy with three to four fractions on consecutive days. Centrally located tumor was defined as the tumor within 2 cm apart from large bronchial tree, and was subdivided into bronchial (main/lobar bronchus) and peribronchial (segmental or distal).
Median follow-up was 26.5 months. The 6-month major response rate, including complete or partial response, was 53.1%. One patient showed progressive disease 1 month after SBRT. The 1- and 2-year actuarial local tumor control rates were both 85.3%. Overall survival was 70.9% at 1 year and 38.5% at 2 years, and survival was not correlated with SBRT dose. Of 9 patients with centrally located tumors, three (33%) experienced Grades 3-5 pulmonary toxicities. Eight patients showed partial or complete bronchial stricture and secondary loss of normal lung volume. Median time to bronchial stricture was 20.5 months. Overall survival did not differ by tumor location.
SBRT in this fractionation should not be given to central lung tumors because it can cause the late major airway toxicities in some patients. More protracted hypofractionated treatment regimen may be more safe than that used usually in SBRT for central lung tumors.
Lung cancer (Amsterdam, Netherlands) 02/2009; 66(1):89-93. · 3.14 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BackgroundA Patterns-of-Care Study (PCS) was conducted to determine the patterns of evaluation and treatment for nonmetastatic non— small-cell lung cancer (NSCLC) in Korea.Patients and MethodsA Web-based data system for Korean PCS was developed, and a national survey was conducted. Patients who received thoracic radiation therapy (RT) for clinical or pathologic stage I-III NSCLC without other malignancy in 1998 and 1999 were eligible and randomly selected by power allocation method.ResultsThe records of 446 selected patients from 19 institutions were reviewed, and 10 patients were excluded because of incomplete clinical information. Accordingly, 436 patients were the subjects of this study, with a median age of 62.2 years (range, 33.1–88 years) and male-to-female ratio of 86:14. The histologies were squamous cell carcinoma in 61.2%, adenocarcinoma in 28.4%, large-cell carcinoma in 2.3%, and NSCLC not otherwise specified in 8% of patients, respectively. Bone scan, abdominal ultrasonography or computed tomography (CT), brain CT or magnetic resonsance imaging, and positron emission tomography were examined in 92.5%, 81.5%, 44.8%, and 26.6% of patients, respectively. The clinical stage was I in 8.9%, II in 12.2%, IIIA in 37.4%, and IIIB in 41.5%, respectively. Regarding treatment modalities, RT was used alone in 38.1%; RT combined with operation in 22.9%; RT combined with chemotherapy in 27.1%; and trimodalities including RT, operation, and chemotherapy in 11.9%. The median total dose was 59.4 Gy with daily median fraction size of 1.8 Gy, and the percent delivered dose > 90% was achieved in 87.6%. Most of patients received RT in supine position (99.3%) with beam direction of anterior-posterior/posterior-anterior (95.6%) as their first RT plan and with photon energy of 6 MV (42%) followed by 10 MV (41.7%). The chemotherapy-based planning was used in 2.3 % and 32.6% for their first and second RT plan, respectively. The 3-or-more RT planning was performed in 13.5% of patients. Elective nodal irradiation was used in 87.8% of patients, and the N2 nodal station (48.6%) was most frequently included. The 8% of patients received thoracic RT based on prospective protocol.Conclusion
This study is the first PCS for NSCLC conducted in Korea. We confirmed that various types of RT planning were used according to each institution, but beam delivery techniques were not much different between 1998 and 1999. Another PCS is planned to evaluate changing trends in national practice.
Clinical Lung Cancer 09/2008; 9(5):304. · 3.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To retrospectively compare the outcome of upfront chemotherapy plus radiotherapy (CRT) and the outcome of the use of extended radiotherapy (RT) only for intracranial germinoma.
Of 81 patients with tissue-confirmed intracranial germinoma, 42 underwent CRT and 39 underwent RT only. For CRT, one to five cycles of upfront chemotherapy was followed by involved-field or extended-field RT, for which the dose was dependent on the M stage. For RT only, all 39 patients underwent craniospinal RT alone. The median follow-up was 68 months.
The 5- and 10-year overall survival rate was 100% and 92.5% for RT alone and 92.9% and 92.9% for CRT, respectively. The 5-year recurrence-free survival rate was 100.0% for RT and 88.1% for CRT (p = 0.0279). No recurrences developed in patients given RT, but four relapses developed in patients who had received CRT -- three in the brain and one in the spine. Only one patient achieved complete remission from salvage treatment. The proportion of patients requiring hormonal replacement was greater for patients who received RT than for those who had received CRT (p = 0.0106).
The results of our study have shown that the better quality of life provided by CRT was compensated for by the greater rate of relapse. The possible benefit of including the ventricles in involved-field RT after upfront chemotherapy, specifically for patients with initial negative seeding, should be addressed in a prospective study.
International Journal of Radiation OncologyBiologyPhysics 08/2008; 71(3):667-71. · 4.18 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate the prognostic value of the expressions of epidermal growth factor receptor (EGFR) and cyclin D1 in early glottic cancer treated with radiotherapy only.
One hundred fifty-one patients with T1-2, N0 glottic cancer who had been treated with radiotherapy at Seoul National University Hospital since 1992 through 2004. Immunohistochemical staining for EGFR and cyclin D1 were performed on the formalin-fixed paraffin-embedded tissues of 25 patients who developed local recurrence and on the tissues of 25 matched patients free from disease. Patterns and degrees of expression were compared between these 2 groups.
High EGFR (p = .047) and high cyclin D1 (p = .040) expressions were both found to be significantly associated with a poor prognosis. No association was found between EGFR and cyclin D1 status (p = .158), but EGFR and cyclin D1 status in combination were found to be significantly associated with local control. The patients with both high EGFR and high cyclin D1 expression had the poorest outcome compared with the others (14 months vs 29 months of median time to progression). Patterns of EGFR and cyclin D1 expression changed after recurrence, but these changes were not found to alter the ultimate prognosis.
The molecular biomarkers, EGFR and cyclin D1 have a prognostic significance in early glottic cancer. These markers in combination seem to play an important role in tumor relapse and may be useful for selecting patients with a poor outcome after radiotherapy.
Head & Neck 08/2008; 30(7):852-7. · 2.83 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate treatment outcome and to determine optimal treatment strategy for patients with clinically lymph node-negative (N0) oral cavity squamous cell carcinoma (SCC).
Two hundred and twenty-seven patients with oral cavity SCC received radiotherapy with curative intent. We retrospectively analyzed 69 patients with clinically N0 disease. Forty-three patients were treated with surgery followed by radiotherapy (S+EBRT) and 26 with radiotherapy alone (EBRT). The median doses administered were 63.0 Gy for S+EBRT and 70.2 Gy for EBRT.
The rates of occult metastasis were 60% for T1, 69% for T2, 100% for T3 and 39% for T4, respectively, among patients who underwent neck dissection. A contralateral occult metastasis occurred only in two patients. The median follow-up was 39 months (range, 6-170 months). The 5-year overall survival (OS), disease-free survival (DFS), local control (LC) and regional control (RC) rates for all patients were 56, 50, 66 and 79%, respectively. The 5-year OS, DFS, LC and RC rates were 67/39% (P < 0.01), 66/24% (P < 0.01), 87/30% (P < 0.01) and 73/89% (P = 0.11) for S+EBRT/EBRT, respectively.
The risk for occult neck metastasis is high in patients with oral cavity SCC; therefore, elective neck treatment should be considered. Excellent RC for subclinical disease can be achieved with radiotherapy alone. However, external beam radiotherapy alone to primary tumor resulted in poor LC and combined treatment with surgery and radiotherapy appeared to be a better treatment strategy.
Japanese Journal of Clinical Oncology 07/2008; 38(6):395-401. · 1.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objectives: To analyze the impact of neoadjuvant chemotherapy (CT) on the treatment of early-stage nasopharyngeal carcinoma (NPC) as compared with radiotherapy (RT) alone.Methods: We analyzed retrospectively the outcome of 60 previously untreated and histologically confirmed early-stage NPC patients treated with either RT alone or with neoadjuvant CT followed by RT (CT/RT) at the Seoul National University Hospital between 1986 and 2004. Neoadjuvant CT consisted of three cycles with 5-fluourouracil and cisplatin. RT was given to the nasopharynx and neck nodes. The median dose to the primary site, involved nodes, and elective nodes was 70.2 Gy, 63 Gy, and 45 Gy, respectively. According to the 1997 American Joint Committee on Cancer staging system, 9 patients had stage I or IIA disease, and 22 patients had stage IIB disease in the RT group. For the CT/RT group, 8 patients had stage I or IIA disease, and 21 patients had stage IIB disease. The median follow-up for all patients was 124.5 (range, 5–239) months.Results: The 5-year locoregional failure-free (LRFF), distant metastasis-free (DMF), disease-free survival (DFS), and overall survival (OS) rate was 84%, 93%, 81%, and 84% for the RT group and 77%, 86%, 71%, and 79% for the CT/RT group, respectively. There were no significant differences in LRFF (P = .728), DMF (P = .433), DFS (P = .562), and OS (P = .625) rates between the RT and CT/RT groups. Multivariate analysis revealed that delaying RT for more than 81 days was significantly associated with an increased risk of locoregional failure in the subgroup of patients with stage IIB disease (P = .044).Conclusions: In our retrospective analysis, the use of neoadjuvant CT showed no additional benefit to treatment with RT alone. Neoadjuvant CT may cause deleterious effect on stage IIB disease by delaying RT.
The Laryngoscope 03/2008; 118(4):663 - 670. · 2.03 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate the clinical outcome of Kimura's disease and to identify the optimal treatment regimen for Kimura's disease.
Between 1984 and 2003, 14 patients with Kimura's disease were treated with radiotherapy (RT) and 9 patients were treated with local excision or systemic steroids. The radiation doses ranged from 20 to 45 Gy. Immunohistochemical studies were performed in 13 cases.
At RT completion, a marked response in terms of tumor size was noted in most cases. The median follow-up was 65 months. Local control was obtained in 9 (64.3%) of the 14 in the RT group and in 2 (22.2%) of the 9 in the non-RT group. No secondary malignancies were observed in the RT group.
These results supports the finding that RT is more effective against Kimura's disease. Simple or immunohistochemical features did not influence the treatment outcome.
International Journal of Radiation OncologyBiologyPhysics 08/2006; 65(4):1233-9. · 4.18 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Histone deacetylase inhibitors (HDI) are emerging as potentially useful components of the anticancer armamentarium and as useful tools to dissect mechanistic pathways. HDIs that globally inhibit histone deacetylases (HDAC) have radiosensitizing effects, but the relative contribution of specific HDAC classes remains unclear. Newly characterized HDIs are now available that preferentially inhibit specific HDAC classes, including SK7041 (inhibits class I HDACs) and splitomicin (inhibits class III HDACs). We investigated in human cancer cells the relative radiosensitizations that result from blocking specific HDAC classes. We found that trichostatin A (TSA; inhibitor of both class I and II HDACs) was the most effective radiosensitizer, followed by the class I inhibitor SK7041, whereas splitomicin (inhibitor of class III) had least effect. Interestingly, radiosensitization by TSA in cell lines expressing p53 was more pronounced than in isogenic lines lacking p53. Radiosensitization of cells expressing p53 by TSA was reduced by pifithrin-alpha, a small-molecule inhibitor of p53. In contrast, the radiosensitization by TSA of cells expressing low levels of p53 was enhanced by transfection of wild-type p53-expressing vector or pretreatment with leptomycin B, an inhibitor of nuclear export that increased intracellular levels of p53. These effects on radiosensitization were respectively muted or not seen in cells treated with SK7041 or splitomicin. To our knowledge, this may be among the first systematic investigations of the comparative anticancer effects of inhibiting specific classes of HDACs, with results suggesting differences in the degrees of radiosensitization, which in some cell lines may be influenced by p53 expression.
Clinical Cancer Research 03/2006; 12(3 Pt 1):940-9. · 8.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to evaluate the treatment outcomes of stereotactic body radiation therapy for treating primary or metastatic thoracic tumors using a stereotactic body frame. Between January 1998 and February 2004, 101 lesions from 91 patients with thoracic tumors were prospectively reviewed. A dose of 10-12 Gy per fraction was given three to four times over consecutive days to a total dose of 30-48 Gy (median 40 Gy). The overall response rate was 82%, with 20 (22%) complete responses and 55 (60%) partial responses. The one- and two-year local progression free survival rates were 90% and 81%, respectively. The patients who received 48 Gy showed a better local tumor control than those who received less than 48 Gy (Fisher exact test; p = 0.004). No pulmonary complications greater than a RTOG toxicity criteria grade 2 were observed. The experience of stereotactic body frame based radiation therapy appears to be a safe and promising treatment modality for the local management of primary or metastatic lung tumors. The optimal total dose, fractionation schedule and treatment volume need to be determined after a further follow-up of these results.
[Show abstract][Hide abstract] ABSTRACT: The objective of the study is to compare survival and quality of life (QoL) by the delivery time of adjuvant radiotherapy (RT), early or late, for craniopharyngiomas.
Fifty patients received RT between 1985 and 2002. Early RT (n=25) was delivered within 3 months after initial surgery, whereas late RT (n=25) was combined with or without reoperation after progression or relapse. Radiation dose ranged from 45 to 55.8 Gy with a median of 54 Gy. The median follow-up was 130 months.
Progression-free survival rates at 5 and 10 years were 95.9 and 91.2%, respectively. The overall or progression-free survival was not influenced by RT time. Initial tumor size was the only prognostic factor (p=0.034) for progression-free survival in univariate analysis. Better visual acuity or field was maintained, and diabetes insipidus was partly improved with early RT, but all were deteriorated as tumor progressed without early RT. Visual functions were not worsened after late RT.
The survival was excellent with adjuvant RT, early or late. Poor QoL with late RT resulted from relapsed tumor and repeated surgery but was not associated with RT itself. Thus, early RT with precision technique is highly recommended for better QoL and excellent survival, unless contraindicated.
Child s Nervous System 09/2005; 21(8-9):799-807. · 1.16 Impact Factor