PURPOSE: To evaluate the predictive value of the early response of 18F-flurodeoxyglucose positron emission tomography (FDG PET) during concurrent chemoradiotherapy (CCRT) for locally advanced non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: FDG PET was performed before and during CCRT for 13 NSCLC patients. Maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured and the changes were calculated. These early metabolic changes were compared with the standard tumor response by computed tomograms (CT) one month after CCRT. RESULTS: One month after the completion of CCRT, 9 patients had partial response (PR) of tumor and 4 patients had stable disease. The percent changes of SUVmax (%DeltaSUVmax) were larger in responder group than in non-responder group (55.7% +/- 15.6% vs. 23.1% +/- 19.0%, p = 0.01). The percent changes of SUVmean (%DeltaSUVmean) were also larger in responder group than in non-responder group (54.4% +/- 15.9% vs. 22.3% +/- 23.0%, p = 0.01). The percent changes of MTV (%DeltaMTV) or TLG (%DeltaTLG) had no correlation with the tumor response after treatment. All the 7 patients (100%) with %DeltaSUVmax > or = 50% had PR, but only 2 out of 6 patients (33%) with %DeltaSUVmax < 50% had PR after CCRT (p = 0.009). Likewise, all the 6 patients (100%) with %DeltaSUVmean > or = 50% had PR, but only 3 out of 7 patients (43%) with %DeltaSUVmean < 50% had PR after CCRT (p = 0.026). CONCLUSION: The degree of metabolic changes measured by PET-CT during CCRT was predictive for NSCLC tumor response after CCRT.
Carcinoma, Non-Small-Cell Lung* ; Chemoradiotherapy* ; Glycolysis ; Humans ; Lung Neoplasms ; Positron-Emission Tomography ; Tumor Burden

We report four cases of spontaneous intracranial hypotension that were investigated by radionuclide cisternography Tc-99m-diethylenetriamine pentaacetic acid radionuclide cisternography of all our patients showed direct sign of cerebrospinal fluid leakage as well as indirect signs of less activity than expected over the cerebral convexities and rapid appearance of bladder activity. The headache of all patients was eventually controlled with bed rest and hydration.
Bed Rest ; Cerebrospinal Fluid ; Headache ; Humans ; Intracranial Hypotension* ; Urinary Bladder

PURPOSE: Flavopiridol enhanced radiation-induced apoptosis of cancer cells in our previous in vitro study. The purpose of this study was to assess if flavopiridol could enhance the radioresponse of mouse mammary tumors in vivo. MATERIALS AND METHODS: Balb/c mice bearing EMT-6 murine mammary carcinoma were treated with flavopiridol only, radiation only, or both for 7 days. Flavopiridol was administered 2.5 mg/kg twice a day intraperitoneally (IP). Radiation was delivered at a 4 Gy/fraction at 24-h intervals for a total dose of 28 Gy. Tumor volume was measured and compared among the different treatment groups to evaluate the in vivo radiosensitizing effect of flavopiridol. Tumors were removed from the mice 20 days after treatment, and TUNEL and Immunohistochemical stainings were performed. RESULTS: Significant tumor growth delay was observed in the radiation only and combined treatment groups, when compared with the control group. However, there was no significant difference between the tumor growth curves of the control and flavopiridol only group or between the radiation only and combination treatment group. Apoptotic cells of different treatment groups were detected by terminal deoxynucleotidyl transferase-medicated nick end labeling (TUNEL) staining. The expressions of Ku70 in tumor tissues from the different groups were analyzed by immunohistochemistry. Similarly, no significant difference was found between the apoptotic rate or Ku70 expression among the different treatment groups. CONCLUSION: Flavopiridol did not show evidence of enhancing the radioresponse of mouse mammary tumors in this study.
Animals ; Apoptosis ; Flavonoids ; Immunohistochemistry ; In Situ Nick-End Labeling ; Mice ; Piperidines ; Radiation-Sensitizing Agents ; Tumor Burden ; Ursidae

PURPOSE: The role of radiotherapy (RT) was largely deserted after the introduction of platinum-based chemotherapy, but still survival rates are disappointingly low. This study focuses on assessing the clinical efficacy of RT in relation to chemotherapy resistance. MATERIALS AND METHODS: From October 2002 to January 2015, 44 patients were diagnosed with epithelial ovarian cancer (EOC) and treated with palliative RT for persistent or recurrent EOC. All patients received initial treatment with optimal debulking surgery and adjuvant platinum-based chemotherapy. The biologically effective dose (BED) was calculated with α/β set at 10. Ninety-four sites were treated with RT with a median BED of 50.7 Gy (range 28.0 to 79.2 Gy). The primary end-point was the in-field local control (LC) interval, defined as the time interval from the date RT was completed to the date any progressive or newly recurring disease within the RT field was detected on radiographic imaging. RESULTS: The median follow-up duration was 52.3 months (range 7.7 to 179.0 months). The 1-year and 2-year in-field LC rates were 66.0% and 55.0%, respectively. Comparisons of percent change of in-field tumor response showed similar distribution of responses among chemoresistant and chemosensitive tumors. On multivariate analysis of predictive factors for in-field LC analyzed by sites treated, BED ≥ 50 Gy (hazard ratio, 0.4; confidence interval, 0.2–0.9; p = 0.025) showed better outcomes. CONCLUSION: Regardless of resistance to platinum-based chemotherapy, RT can be a feasible treatment modality for patients with persistent of recurrent EOC. The specific role of RT using updated approaches needs to be reassessed.
Drug Therapy ; Follow-Up Studies ; Humans ; Multivariate Analysis ; Ovarian Neoplasms* ; Palliative Care ; Radiotherapy ; Survival Rate ; Treatment Outcome

PURPOSE: To see the relationship between the response to chemotherapy and the final outcome of neoadjuvant chemotherapy and radiotherapy in patients with locally advanced hypopharyngeal cancer. METHODS AND MATERIALS: A retrospective analysis was done for thirty-two patients with locally advanced hypopharyngeal cancer treated in the Seoul National University Hospital with neoadjuvant chemotherapy and radiotherapy from August 1979 to July 1997. The patients were treated with Co-60 teletherapy unit or 4MV or 6MV photon beam produced by linear accelerator. Daily fractionation was 1.75 to 2 Gy, delivered five times a week. Total dose ranged from 60.8 Gy to 73.8 Gy. Twenty-nine patients received continuous infusion of cisplatin and 5-FU. Other patients were treated with cisplatin combined with bleomycin or vinblastin. Twenty-four (75%) patients received all three prescribed cycles of chemotherapy delivered three weeks apart. Six patients received two cycles, and two patients received only one cycle. RESULTS: The overall 2-year and 5-year survival rates are 65.6% and 43.0%, respectively. 5-year local control rate is 34%. Organ preservation for more than five years is achieved in 12 patients (38%). After neoadjuvant chemotherapy, 24 patients achieved more than partial remission (PR); the response rate was 75% (24/32). Five patients had complete remission (CR), 19 patients PR, and 8 patients no response (NR). Among the 19 patients who had PR to chemotherapy, 8 patients achieved CR after radiotherapy. Among the 8 non-responders to chemotherapy, 2 patients achieved CR, and 6 patients achieved PR after radiotherapy. There was no non-responder after radiotherapy. The overall survival rates were 60% for CR to chemotherapy group, 35.1% for PR to chemotherapy group, and 50% for NR to chemotherapy group, respectively ( p=0.93). There were significant difference in five-year overall survival rates between the patients with CR and PR after neoadjuvant chemotherapy and radiotherapy (73.3% vs. 14.7%, p< 0.01). The prognostic factor affecting overall survival was the response to overall treatment (CR vs. PR, p<0.01). CONCLUSION: In this study, there were only five patients who achieved CR after neoadjuvant chemotherapy. Therefore the difference of overall survival rates between CR and PR to chemotherapy group was not statistically significant. Only the response to chemo-radiotherapy was the most important prognostic factor. There needs to be more effort to improve CR rate of neoadjuvant chemotherapy and consideration for future use of concurrent chemoradiotherapy.
Bleomycin ; Chemoradiotherapy ; Cisplatin ; Drug Therapy* ; Fluorouracil ; Humans ; Hypopharyngeal Neoplasms* ; Organ Preservation ; Particle Accelerators ; Radiotherapy* ; Retrospective Studies ; Seoul ; Survival Rate

BACKGROUNDS/AIMS: To investigate survival rates and prognostic factors of patients with gallbladder cancer who were treated with surgery and postoperative radiation therapy. METHODS: Seventeen gallbladder cancer patients who received surgery and postoperative radiotherapy from October 1989 to April 1998 were included in this retrospective study. Five patients had stage II, 8 patients had stage III, and 4 patients had stage IV disease according to the 1997 American Joint Committee on Cancer (AJCC) staging. All patients received > or =40 Gy of postoperative radiotherapy with a daily dose of 2.0 Gy/fraction and 15 patients received concurrent chemotherapy. An analysis was performed for the endpoints of overall and disease-free survival. RESULTS: Of the 17 patients, 13 had no residual disease (R0), 1 had microscopic residual disease (R1), and 3 had macroscopic residual disease (R2) after surgery. Among patients with no residual disease, 4 had locoregional recurrences during the follow-up period. One patient with microscopic residual disease had local recurrence. The 5-year overall survival rate was 38.2%. The median overall survival time was 21 months and the median disease-free survival time was 12 months. Old age (> or =60 years old), female gender, a high pathological stage (> or =IVA), and the presence of residual disease after surgery were significant prognostic factors for disease-free survival. CONCLUSIONS: Despite a high proportion of patients with advanced disease and macroscopic residual disease, the prognosis of gallbladder patients who had postoperative radiotherapy is encouraging. Additional investigation to improve the loco-regional control of gallbladder cancer patients with adverse prognostic factors is warranted.
Disease-Free Survival ; Female ; Follow-Up Studies ; Gallbladder ; Gallbladder Neoplasms ; Humans ; Joints ; Prognosis ; Recurrence ; Retrospective Studies ; Survival Rate

PURPOSE: To determine the effects of combinations of radiation and flavopiridol, an inhibitor of cyclin-dependent kinases and global transcription, in a human uterine cervix cancer cell line. MATERIALS AND METHODS: Human uterine cervix cancer cells (HeLa), cultured to the mid-log phase, were exposed to X-rays, flavopiridol, and combinations of X-rays and flavopiridol in various sequences. The end point in this study was the clonogenic survival, which was measured via clonogenic assays. In order to determine the intrinsic cytotoxicity of flavopiridol, 0, 5, 12.5, 25, 37.5, 50 and 100 nM of flavopiridol were added to cell culture media. In the combination treatment, four different schedules of flavopiridol and irradiation combinations were tested: treatment of flavopiridol for 24 hours followed by irradiation, simultaneous administration of flavopiridol and irradiation, and irradiation followed by flavopiridol (for 24 hours) at intervals of 6 and 24 hours. The fraction of cells surviving after the combination treatment with 2 Gy of radiation (SF2) was compared with that of the fraction of cells surviving after treatment with irradiation alone. RESULTS: The cytotoxicity of flavopiridol was found to be dose-dependent, with an IC50 of 80 nM. No cytotoxic enhancements were observed when flavopiridol and radiation were administered simultaneously. Flavopiridol, administered either 24 hours before or 6 hours after irradiation, exerted no sensitizing effects on the cells. Only one protocol resulted in a radiosensitizing effect: the administration of flavopiridol 24 hours after irradiation. CONCLUSION: Flavopiridol enhanced the effects of radiation on a uterine cervix cancer cell line in vitro, and this enhancement was both sequence- and time-dependent.
Appointments and Schedules ; Cell Culture Techniques ; Cell Line ; Cervix Uteri* ; Cyclin-Dependent Kinases ; Female ; Humans ; Inhibitory Concentration 50 ; Radiation Effects* ; Radiation-Sensitizing Agents

Purpose: We evaluated clinical outcomes of high-risk prostate cancer patients receiving external beam radiotherapy (EBRT) or radical prostatectomy (RP). Materials and Methods: Patients were classified as high-risk prostate cancer and received definitive treatment between 2005 and 2015. Patients with previous pelvic radiotherapy, positive lymph node or distant metastasis were excluded. The primary outcomes were prostate cancer-specific survival (PCSS) and distant metastasis-free survival (DMFS). Results: Of 583 patients met the inclusion criteria (77 EBRT and 506 RP). The estimated 10-year PCSS was 97.0% in the RP and 95.9% in the EBRT (p = 0.770). No significant difference was seen in the DMFS (p = 0.540), whereas there was a trend in favor of RP over EBRT in overall survival (OS) (p = 0.068). Propensity score matching analysis with confounding variables was done, with 183 patients (66 EBRT and 117 RP) were included. No significant difference in DMFS, PCSS or OS was found. Conclusion Our data demonstrated similar oncologic PCSS, OS, and DMFS outcomes between EBRT and RP patients.

Purpose: We evaluated clinical outcomes of high-risk prostate cancer patients receiving external beam radiotherapy (EBRT) or radical prostatectomy (RP). Materials and Methods: Patients were classified as high-risk prostate cancer and received definitive treatment between 2005 and 2015. Patients with previous pelvic radiotherapy, positive lymph node or distant metastasis were excluded. The primary outcomes were prostate cancer-specific survival (PCSS) and distant metastasis-free survival (DMFS). Results: Of 583 patients met the inclusion criteria (77 EBRT and 506 RP). The estimated 10-year PCSS was 97.0% in the RP and 95.9% in the EBRT (p = 0.770). No significant difference was seen in the DMFS (p = 0.540), whereas there was a trend in favor of RP over EBRT in overall survival (OS) (p = 0.068). Propensity score matching analysis with confounding variables was done, with 183 patients (66 EBRT and 117 RP) were included. No significant difference in DMFS, PCSS or OS was found. Conclusion Our data demonstrated similar oncologic PCSS, OS, and DMFS outcomes between EBRT and RP patients.

PURPOSE: To investigate the flavopiridol effect on radiation-induced apoptosis and expression of apoptosis- related genes of human laryngeal and lung cancer cells. MATERIALS AND METHODS: A human laryngeal cancer cell line, AMC-HN3 and a human lung cancer cell line, NCI-H460, were used in the study. The cells were divided into four groups according to the type of treatment: 1) control groups; 2) cells that were only irradiated; 3) cells treated only with flavopiridol; 4) cells treated with flavopiridol and radiation simultaneously. The cells were irradiated with 10 Gy of X-rays using a 4 MV linear accelerator. Flavopiridol was administered to the media at a concentration of 100 nM for 24 hours. We compared the fraction of apoptotic cells of each group 24 hours after the initiation of treatment. The fraction of apoptotic cells was detected by measurement of the sub-G1 fractions from a flow cytometric analysis. The expression of apoptosis-regulating genes, including cleaved caspase-3, cleaved PARP (poly (ADP-ribose) polymerase), p53, p21, cyclin D1, and phosphorylated Akt (protein kinase B) were analyzed by Western blotting. RESULTS: The sub-G1 fraction of cells was significantly increased in the combination treatment group, as compared to cells exposed to radiation alone or flavopiridol alone. Western blotting also showed an increased expression of cleaved caspase-3 and cleaved PARP expression in cells of the combination treatment group, as compared with cells exposed to radiation alone or flavopiridol alone. Treatment with flavopiridol down regulated cyclin D1 expression of both cell lines but its effect on p53 and p21 expression was different according to each individual cell line. Flavopiridol did not affect the expression of phophorylated Akt in both cell lines. CONCLUSION: Treatment with flavopiridol increased radiation-induced apoptosis of both the human laryngeal and lung cancer cell lines. Flavopiridol effects on p53 and p21 expression were different according to the individual cell line and it did not affect Akt activation of both cell lines.
Apoptosis* ; Blotting, Western ; Caspase 3 ; Cell Line ; Cyclin D1 ; Humans* ; Laryngeal Neoplasms ; Lung Neoplasms* ; Lung* ; Particle Accelerators ; Phosphotransferases