Long-Term Outcome of Definitive Radiotherapy for Early Glottic Cancer: Prognostic Factors and Patterns of Local Failure.

PURPOSE: This study evaluates the long-term results of definitive radiotherapy (RT) for early glottic cancer. Clinical and treatment factors related to local control and patterns of failure are analyzed. MATERIALS AND METHODS: We retrospectively reviewed 222 patients with T1-2N0 squamous cell carcinoma of the glottic larynx treated with definitive RT from 1981 to 2010. None of the patients received elective nodal RT or combined chemotherapy. The median total RT dose was 66 Gy. The daily fraction size was < 2.5 Gy in 69% and 2.5 Gy in 31% of patients. The RT field extended from the hyoid bone to the cricoid cartilage. RESULTS: The median age was 60 years, and 155 patients (70%) had T1 disease. The 5-year rates of local recurrence-free survival (LRFS) and ultimate LRFS with voice preservation were 87.8% and 90.3%, respectively. T2 (hazard ratio [HR], 2.30; 95% confidence interval [CI], 1.08 to 4.94) and anterior commissural involvement (HR, 3.37; 95% CI, 1.62 to 7.02) were significant prognostic factors for LRFS. In 34 patients with local recurrence, tumors recurred in the ipsilateral vocal cord in 28 patients. There were no contralateral vocal cord recurrences. Most acute complications included grade 1-2 dysphagia and/or hoarseness. There was no grade 3 or greater chronic toxicity. CONCLUSION: Definitive RT achieved a high cure rate, voice preservation, and tolerable toxicity in early glottic cancer. T2 stage and anterior commissural involvement were prognostic factors for local control. Further optimization of the RT method is needed to reduce the risk of ipsilateral tumor recurrence.

Immunohistochemical analysis of cyclooxygenase-2 and brain fatty acid binding protein expression in grades I-II meningiomas: correlation with tumor grade and clinical outcome after radiotherapy.

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.

Role of postoperative radiotherapy for microscopic margin involvement in the squamous cell carcinoma of esophagus.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Hypofractionated three-dimensional conformal radiotherapy for medically inoperable early stage non-small-cell lung cancer.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Definitive Radiotherapy versus Postoperative Radiotherapy for Tonsil Cancer.

PURPOSE: 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. MATERIALS AND METHODS: Of 124 patients, 67 underwent CRT, and 57 underwent SRT. We compared survival and complication rates in both groups. RESULTS: 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. CONCLUSION: 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.

Definitive radiotherapy with or without chemotherapy for T3-4N0 squamous cell carcinoma of the maxillary sinus and nasal cavity.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Intensity-modulated radiation therapy with simultaneous integrated boost technique following neoadjuvant chemotherapy for locoregionally advanced nasopharyngeal carcinoma.

BACKGROUND: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Fractionated stereotactic body radiation therapy for medically inoperable stage I lung cancer adjacent to central large bronchus.

PURPOSE: 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. MATERIALS: 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). RESULTS: 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. CONCLUSIONS: 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.

Upfront chemotherapy and involved-field radiotherapy results in more relapses than extended radiotherapy for intracranial germinomas: modification in radiotherapy volume might be needed.

PURPOSE: 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. METHODS AND MATERIALS: 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. RESULTS: 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). CONCLUSIONS: 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.

Treatment of patients with clinically lymph node-negative squamous cell carcinoma of the oral cavity.

OBJECTIVE: To evaluate treatment outcome and to determine optimal treatment strategy for patients with clinically lymph node-negative (N0) oral cavity squamous cell carcinoma (SCC). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Expression of epidermal growth factor receptor and cyclin D1 in pretreatment biopsies as a predictive factor of radiotherapy efficacy in early glottic cancer.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Treatment outcomes for radiotherapy alone are comparable with neoadjuvant chemotherapy followed by radiotherapy in early-stage nasopharyngeal carcinoma.

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.

Clinical results of stereotactic body frame based fractionated radiation therapy for primary or metastatic thoracic tumors.

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.

Outcomes of Kimura's disease after radiotherapy or nonradiotherapeutic treatment modalities.

PURPOSE: To evaluate the clinical outcome of Kimura's disease and to identify the optimal treatment regimen for Kimura's disease. METHODS AND MATERIALS: 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. RESULTS: 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. CONCLUSION: These results supports the finding that RT is more effective against Kimura's disease. Simple or immunohistochemical features did not influence the treatment outcome.

Histone deacetylase inhibitor-mediated radiosensitization of human cancer cells: class differences and the potential influence of p53.

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.

Early adjuvant radiotherapy toward long-term survival and better quality of life for craniopharyngiomas--a study in single institute.

OBJECTIVES: 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. METHODS AND MATERIALS: 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. RESULTS: 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. CONCLUSIONS: 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.

Phase II study of radiotherapy with three-dimensional conformal boost concurrent with paclitaxel and cisplatin for Stage IIIB non-small-cell lung cancer.

PURPOSE: To evaluate the efficacy and toxicity of concurrent chemoradiotherapy with paclitaxel/cisplatin for Stage IIIB locally advanced non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS: Radiotherapy was administered to a total dose of 70.2 Gy (daily fraction of 1.8 Gy, 5 days/wk), over an 8-week period, combined with chemotherapy. The chemotherapy consisted of weekly 40 mg/m2 of paclitaxel plus 20 mg/m2 of cisplatin for 8 consecutive weeks. All patients received three-dimensional conformal radiotherapy (3D-CRT), based on computed tomography simulated planning after 41.4 Gy. The median follow-up period of survivors was 24 months. RESULTS: Between January 2000 and October 2002, 135 patients with a median age of 60 years were enrolled and analyzed in this prospective trial. The overall response rate was 75% including 2 cases of complete response. The major patterns of failure were local failure and distant metastasis. The 2-year overall and progression-free survival rates were 37% and 18%, respectively. The median overall and progression-free survival times were 17 months and 9 months, respectively. Hematologic toxicity >Grade 2 was observed in 19% of patients and severe non-hematologic toxicity was infrequent. CONCLUSIONS: Three-dimensional conformal radiotherapy, combined with paclitaxel and cisplatin chemotherapy, was associated with a satisfactory outcome with manageable toxicity. Further investigations are needed to improve the local control.

Treatment outcome of angiocentric T-cell and NK/T-cell lymphoma, nasal type: radiotherapy versus chemoradiotherapy.

OBJECTIVE: The purpose of this study was to evaluate the treatment outcome of angiocentric T-cell and natural killer (NK)/T-cell lymphoma, nasal type. METHODS: Between February 1989 and March 2001, 53 patients with newly diagnosed angiocentric T-cell and NK/T-cell lymphoma, nasal type involving the head and neck, were treated with radiation therapy (RT). There were 37 males and 16 females. The median age of the patients was 45 years (range 19-73). Twenty of them were treated with chemoradiotherapy (CRT), while 33 with treated with RT alone. The median follow-up period was 74 months (range 6-173). RESULTS: The 5-year overall survival rate of all patients was 69%. CRT appeared to be inferior to RT alone in terms of 5-year overall survival, though the difference was not statistically significant (59 versus 76%, P = 0.27). CONCLUSIONS: There was no difference in survival between RT and CRT in angiocentric T-cell and NK/T-cell lymphoma, nasal type.

Retrospective analysis of the treatment results for patients with squamous cell carcinoma of tonsil.

PURPOSE: There has been no definitive randomized study to identify the optimal therapeutic regimen for treating squamous cell carcinoma of tonsil. The purpose of this study was to retrospectively evaluate the treatment outcome according to various combinations of surgery, radiation therapy and chemotherapy. MATERIALS AND METHODS: Fifty-six patients with tonsillar carcinoma, who were treated at Seoul National University Hospital from March 1985 to August 2001, were the subjects of this study. Twenty-one patients received surgery followed by radiation therapy (SRT), 16 patients underwent radiation therapy alone (RT), and 19 patients received neoadjuvant chemotherapy and radiation therapy (CRT). The median radiation dose was 66.6 Gy for the SRT group and 70.2 Gy for the RT and CRT groups. Surgery comprised extended tonsillectomy and modified radical neck dissection of the involved neck. Cisplatin and 5-fluorouracil were used every three weeks for 3 cycles in the SRT group. The median follow-up was 73.2 months. RESULTS: The distribution of T-stage was 4 cases of T1, 14 cases of T2, 1 case of T3 and 2 cases of T4 staging in the SRT group, 2 cases of T1, 6 cases of T2, 5 cases of T3 and 3 cases of T4 staging in the RT group and 0 cases of T1, 7 cases of T2, 9 cases of T3 and 3 cases of T4 staging in the CRT group. The distribution of N-stage was 5 cases of N0, 2 cases of N1, 13 cases of N2 and 1 case of N3 staging in the SRT group, 6 cases of N0, 5 cases of N1, 5 cases of N2 and 0 cases of N3 staging in the RT group, and 2 cases of N0, and 7 cases of N1, 9 cases of N2 and 1 case of N3 staging in the CRT group. The five-year overall survival rate (OSR) for all patients was 78%. The five-year OSR was 80% for the SRT group, 71% for the RT group, and 80% for the CRT group (p=ns). The five-year disease-free survival rate was 93% for the CRT group and 71% for the RT group (p=0.017). Four patients developed local failure and one patient failed at a regional site in the RT group, and one patient failed at a primary site in the CRT group. The five-year DFS was 84% for patients who had undergone neck dissection and 76% for patients who had not undergone neck dissection (p=ns). Treatment-related complications of grade 3 or 4 occurred in 15 patients, and the incidence of complication was not different between each of the treatment methods. CONCLUSION: Although the patients with more advanced T stage were included in the RT and CRT groups, the OSR was not statistically different according to the treatment methods. In the radical radiation therapy group, the addition of neoadjuvant chemotherapy showed an improvement in the disease-free survival. Because of the retrospective nature of our study and the small number of patients, this study cannot draw any definite conclusions, but it suggests that radiation therapy with chemotherapy can be a good alternative option for squamous cell carcinoma of tonsil. Controlled randomized study is necessary to confirm this hypothesis.

A histone deacetylase inhibitor, trichostatin A, enhances radiosensitivity by abrogating G2/M arrest in human carcinoma cells.

PURPOSE: Histone deacetylase inhibitors (HDIs) are emerging as potentially useful components in anticancer therapy. In this study, we tried to confirm the radiosensitizing effect of trichostatin A (TSA) on a panel of human carcinoma cell lines and elucidate its mechanism of interaction. MATERIALS AND METHODS: A549, HeLa and Caski cells were exposed to TSA for 18 hr prior to irradiation, and the cell survival then measured using a clonogenic assay. Western blot and flow cytometric analyses, for histone acetylation, and cell cycle and apoptosis, respectively, were also performed. RESULTS: TSA increased the acetylation of histone H3. The pretreatment of TSA consistently radiosensitized all three cell lines. The SF2 (surviving fraction at 2 Gy) of TSA-treated cells was significantly lower than that of mock treated cells. The SER (sensitizer enhancement ratio) increased in all 3 cell lines, in concentration dependent manners. The TSA treated cells showed abrogation of radiation-induced G2/M arrest, in a concentration dependent manner. CONCLUSION: The pretreatment of TSA enhanced the radiosensitivity of a panel of human carcinoma cells, which was attributed, in part, to the abrogation of radiation-induced G2/M arrest.