Charn Il Park

Radiotherapy of intracranial germinomas

Between 1980 and 1992, 32 patients with intracranial germinomas were treated with radiation. All patients were confirmed histopathologically prior to treatment. Of the 32 intracranial germinomas reviewed, 14 were located in the suprasellar region, 12 in the basal ganglia and thalamus, four in the pineal, and two in both the pineal and suprasellar regions. Three patients had subarachnoid seeding. Craniospinal irradiation was undertaken for 29 patients. The median dose of 54 Gy was delivered to the tumor bed, 36 Gy to the whole brain and 24 Gy to the spinal axis. Five and 10-year survival rates were 96.9 and 96.9%, respectively. Local control was achieved in all patients except one who died of persistent tumor after 2 months following radiotherapy. No intracranial recurrence or spinal metastasis were found. Tumor site did not relate to the prognosis. One patient developed severe intellectual deterioration, three patients had vertebral growth impairment. The present study confirms the excellent result with radiotherapy alone for patients with germinomas.

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-α, 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 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.

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.

Phase I study of weekly docetaxel and cisplatin concurrent with thoracic radiotherapy in stage III non-small-cell lung cancer

PURPOSE This is the first report of a Phase I study on concomitant weekly cisplatin and docetaxel chemotherapy with thoracic radiation for Stage III non-small-cell lung cancer (NSCLC). The study objectives were to determine the maximum tolerable dose (MTD) and dose-limiting toxicity (DLT) of docetaxel used in this regimen, and to evaluate the feasibility of weekly concurrent chemoradiotherapy. METHODS AND MATERIALS Patients with histologically proven and unresectable Stage III NSCLC were the subjects of this study. Cisplatin was administered at a fixed dose of 20 mg/m2, while the dose of docetaxel was increased from 0 to 30 mg/m2 in increments of 10 mg/m2. Chemotherapy was given on the first day of each week for 6 weeks. The primary tumor and regional lymph nodes were irradiated to 54 Gy, followed by an additional 9 Gy boost to the primary tumor, making the total dose 63 Gy at 1.8 Gy/fraction. RESULTS Sixteen men and 2 women with advanced NSCLC without prior treatment were enrolled. The median age of the group was 58 years (range 49-67). Three patients had Stage IIIa disease and 15 patients had IIIb disease. Dose-limiting Grade 3 esophagitis was encountered at a docetaxel dose level of 30 mg/m2 in 2 of 3 patients. No dose-limiting, nonhematologic toxicity occurred in the other patients and no dose-limiting hematologic toxicity occurred in any patient. CONCLUSION The treatment schedule for NSCLC was feasible, with the DLT being esophagitis. We determined the recommended dose of docetaxel to be 20 mg/m2 for a Phase II study when combined with weekly cisplatin and concomitant thoracic RT.

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

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).

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.

NEOADJUVANT CHEMOTHERAPY AND RADIATION THERAPY COMPARED WITH RADIATION THERAPY ALONE IN ADVANCED NASOPHARYNGEAL CARCINOMA

PURPOSE To analyze the impact of neoadjuvant chemotherapy on the treatment of locoregionally advanced nasopharyngeal carcinoma and to assess the outcomes of patients receiving such treatment. METHODS AND MATERIALS We analyzed 137 previously untreated and histologically confirmed advanced stage nasopharyngeal carcinoma patients treated with either radiation therapy only or combined radiation therapy and chemotherapy at the Seoul National University Hospital between 1984 and 1996. The stage distribution was as follows: AJCC Stage III-21, Stage IV-61 in the radiation therapy group (RT group); AJCC Stage III-1, Stage IV-54 in neoadjuvant chemotherapy and radiation therapy group (CT/RT group). The median follow-up for surviving patients was 48 months. RESULTS The 5-year overall survival (OS) rates were 71% for the CT/RT group and 59% for the RT group (p = 0.04). The 5-year actuarial disease-free survival (DFS) rates were 63% for the CT/RT group and 52% for the RT group (p = 0.04). Distant metastasis (DM) incidence was significantly lower in the CT/RT group. The 5-year freedom from distant metastasis rates were 84% for the CT/RT group and 66% for the RT group (p = 0.01). The incidence of locoregional failures was also lower in the CT/RT group, although this difference did not reach statistical significance (69% vs. 56%, p = 0.09) CONCLUSION While not providing conclusive evidence, historical evidence from this institution suggests that neoadjuvant chemotherapy significantly improves both overall and the disease-free survival of patients with advanced stage nasopharyngeal carcinoma.

Neoadjuvant Chemotherapy and Radiotherapy for the Treatment of Advanced Hypopharyngeal Carcinoma

PURPOSE To evaluate the efficacy of the neoadjuvant chemotherapy and radiation therapy in treatment of patients with advanced hypopharyngeal cancer, which is notorious for its poor prognosis and severe surgical morbidity with functional deficits. MATERIALS AND METHODS Medical records of 62 patients with squamous cell carcinoma of the hypopharynx, Stage III or IV (AJCC, 1992), were retrospectively reviewed. RESULTS Neoadjuvant chemotherapy showed an overall response rate of 87% and a complete remission (CR) rate was 67% following chemotherapy and radiation therapy. The patients who did not show CR after chemotherapy had a high likelihood of treatment failure, even though they achieved CR following subsequent radiotherapy. Thirteen of 30 patients were able to preserve their larynges for more than 3 years by chemotherapy and radiation. CONCLUSION This approach appeared to be as effective as radical surgery with postoperative radiation therapy without comprising survival. To improve the cure rates, we need to develop better strategies to increase CR rates with chemotherapy and determine the best treatment option for patients who are partially or nonresponsive to chemotherapy.

EXPRESSION OF EPIDERMAL GROWTH FACTOR RECEPTOR AND CYCLIN D1 IN PRETREATMENT BIOPSIES AS A PREDICTIVE FACTOR OF RADIOTHERAPY EFFICACY IN EARLY GLOTTIC CANCER

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.