Evaluation of Usefulness of Portal Image Using Electronic Portal Imaging Device (EPID) in the Patients Who Received Pelvic Radiation Therapy

Purpose : To evaluate the usefulness of electronic portal imaging device through objective compare of the images acquired using an EPID and a conventional port film Materials and Methods : From Apr. to Oct. 1997, a total of 150 sets of images from 20 patients who received radiation therapy in the pelvis area were evaluated in the Inha University Hospital and Severance Hospital. A dual image recording technique was devised to obtain both electronic portal images and port film images simultaneously with one treatment course. We did not perform double exposure five to ten images were acquired from each patient. All images were acquired from posteroanterior (PA) view except images from two patients. A dose rate of 100-300 Mu/min and a 10-MV X-ray beam were used and 2-10 MUs were required to produce a verification image during treatment. Kodak diagnostic film with metal/film imaging cassette which was located on the top of the EPID detector was used for the port film. The source to detector distance was 140 cm. Eight anatomical landmarks (pelvic brim, sacrum, acetabulum. iliopectineal line, symphysis, ischium, obturator foramen, sacroiliac joint) were assessed. Four radiation oncologist joined to evaluate each image. The individual landmarks in the port film or in the EPID were rated - very clear (1), clear (2), visible (3), not clear (4), not visible (5). Results : Using an video camera based EPID system. there was no difference of image quality between no enhanced EPID images and port film images. However, when we provided some change with window level for the portal image, the visibility of the sacrum and obturator foramen was improved in the portal images than in the port film images. All anatomical landmarks were more visible in the portal images than in the port film when we applied the CLAHE mode enhancement. The images acquired using an matrix ion chamber type EPID were also improved image qualify after window level adjustment. Conclusion : The quality of image acquired using an electronic portal imaging device was comparable to that of the port film. When we used the enhance mode or window level adjustment. the image quality of the EPID was superior to that of the port film. EPID may replace the port film.ope

Treatment Outcome, Prognostic Factors and Patterns of Failureof Nasopharyngeal Carcinoma

Purpose：The first treatment of choice for nasopharyngeal carcinoma (NPC) is radiotherapy as NPC is more responsive to radiotherapy than any other head and neck cancer. We analyzed the clinical characteristics and prognostic factors of NPC patients treated at the Severance Hospital. Subjects and Method：Charts of 123 patients diagnosed with NPC at the Severance Hospital from 1995 to 2002 were reviewed and retrospectively analyzed. They were staged according to the 1997 AJCC criteria. According to the WHO classification, the type I included 14 cases, type II 44 cases, and type III 65 cases. Sixty-five cases were treated with radiotherapy only and 58 cases were treated with a combined modality of chemotherapy and radiotherapy. Results：The factors for a poor prognosis were age over 47 years' old, histologic findings of WHO type I and advanced T, N stage. The overall 5 year survival rate was 66.22%. According to treatment modality, only the radiotherapy group was 68.6%, while the chemoradiotherapy group was 63.6%. There was no difference in survival (p>0.05). In chemoradiotherapy group, the survival of induction chemoradiotherapy group was 82.1% and the concurrent chemoradiotherapy group was 36.8%. There was significant difference in survival. Conclusions：There was no significant difference in the 5 year survival rate between the patients who were treated with radiotherapy only and those who were treated with both radiotherapy and chemotherapy.ope

Radiosensitivity enhancement by celecoxib, a cyclooxygenase (COX)-2 selective inhibitor, via COX-2-dependent cell cycle regulation on human cancer cells expressing differential COX-2 levels

To characterize the radiation-enhancing effects on human cancer cells and underlying mechanisms of celecoxib, a cyclooxygenase (COX)-2 selective inhibitor, and to ascertain whether its effects are COX-2 dependent. Clonogenic cytotoxicity assays and radiation survival assays after treatment with celecoxib ± radiation were done on four human cancer cell lines that expressed differential COX-2 levels. Stably COX-2 knocked down or overexpressed cell lines were developed, and clonogenic assays, apoptosis assays, or cell cycle change measurements were conducted after treatment with celecoxib ± radiation. Prostaglandin E2 (PGE2) was applied to medium after treatment with celecoxib ± radiation to determine whether the radiation-enhancing effect associated with celecoxib results from reduced generation of prostaglandin. Celecoxib's radiation-enhancing effect was observed in COX-2–expressing A549 and NCI-H460 cells but was not observed in the COX-2 nonexpressing MCF-7 and HCT-116 cells. Celecoxib's radiation-enhancing effects in A549 cells were shown to disappear after the administration of COX-2 knocked down. In contrast, the HCT-116 cells were radiosensitized by celecoxib after being transfected with COX-2 expression vector. The addition of PGE2 after treatment with celecoxib ± radiation had no significant effects on celecoxib's radiation-enhancing effects in A549 and COX-2 transfected HCT-116 cells. Radiation-induced G2-M arrest was enhanced and sustained in the COX-2–overexpressing cells compared with that seen in COX-2 low-expressing cells. Celecoxib or NS-398 effected no changes or attenuated radiation-induced G2-M arrest in the COX-2–overexpressing cells but further enhanced the radiation-induced G2-M arrest in the COX-2 low-expressing cells. Celecoxib's radiation-enhancing effects seem to occur in a COX-2 expression-dependent manner in the cancer cells. This effect does not seem to be the result of reduced PGE2 generation. Celecoxib may exert an inhibitory effect on enhanced radiation-induced G2-M arrest in the COX-2–overexpressing cells, which may allow the arrested cells to enter mitosis and die after radiation, but may also further enhance radiation-induced G2-M arrest in the COX-2 low-expressing cells, by virtue of another mechanism.ope

Mechanism of enhancement of radiation-induced cytotoxicity by sorafenib in colorectal cancer

Sorafenib, an orally available multikinase inhibitor, combined with radiation has shown potential as an anticancer treatment in an in vitro and in vivo colon cancer model. In this study, we investigated the mechanism of enhancement of radiation-induced cytotoxicity by sorafenib in colorectal cancer. The effects of sorafenib on radiation-induced cytotoxicity of DLD-1 and HT-29 were evaluated via clonogenic assay. The impact of sorafenib on radiation-induced cell cycle kinetics and on apoptosis was analyzed using flow cytometry. Cyclin B1 was examined by western blot. As a measure of DNA damage after treatment, γ-H2AX foci and nuclear fragmentation were determined as a function of time after irradiation plus sorafenib combination. Tumor growth delay was used to evaluate the effects of sorafenib on in vivo radiation-induced cytotoxicity. Exposure of each cell line to sorafenib combined with irradiation resulted in an increased radiation-induced cytotoxicity with dose enhancement factors at a surviving fraction of 0.37 ranging from 1.13 to 1.76. Sorafenib strengthened radiation-induced accumulation of tumor cells in the G2-M phase with attenuated expression of cyclin B1, but had no effect on radiation-induced apoptosis. Exposure to sorafenib and radiation resulted in a greater number of remaining γ-H2AX foci and fragmented nuclei than radiation alone. In vivo tumor xenograft study confirmed that administration of sorafenib results in significant tumor growth inhibition when combined with radiation. These results indicate that sorafenib enhances radiation-induced cytotoxicity in colorectal cancer and suggest that the mechanism is associated with delaying repair of radiation-induced DNA damage and down-regulation of cyclin B1.ope

IMRT with simultaneous integrated boost and concurrent chemotherapy for nasopharyngeal cancer: plan evaluation and treatment outcomeoutcome

OBJECTIVE: This study evaluated the outcome of intensity-modulated radiation therapy with simultaneous integrated boost and concurrent chemotherapy for nasopharyngeal cancer. METHODS: We analyzed 53 consecutive nasopharyngeal cancer patients who received definitive treatment using intensity-modulated radiation therapy with simultaneous integrated boost and cisplatin-based concurrent chemotherapy. Forty-six patients were treated with concurrent chemoradiation and seven patients with induction chemotherapy plus concurrent chemoradiation. The gross tumor (PTV(70)) received 69.96 Gy (2.12 Gy/fraction), high-risk subclinical disease (PTV(60)) received 59.4 Gy (1.8 Gy/fraction) and low-risk subclinical disease (PTV(56)) received 56.1 Gy (1.7 Gy/fraction) in 33 fractions. Twenty-eight patients were treated with step-and-shoot intensity-modulated radiation therapy and 25 patients with helical tomotherapy. Dosimetric parameters were compared between the two modalities. RESULTS: The median treatment duration was 49 days (range: 41-65 days). The complete response rate was 92.5%. Three local, two regional, one locoregional and seven distant failures were observed. With the median follow-up of 41 months (range: 8-89 months), the 3- and 5-year local control, locoregional control, disease-free survival and overall survival rates were 91.8 and 91.8%; 87.6 and 87.6%; 77.5 and 70.5%; and 86.4 and 82.1%, respectively. Grade 3 mucositis, dermatitis, leucopenia and grade 4 leucopenia were observed in 10, 1, 2 and 1 patient, respectively. No grade 3 or higher xerostomia occurred. Helical tomotherapy significantly improved dosimetric parameters including the maximum dose, volume receiving >107% of the prescribed dose and uniformity index (D(5)/D(95)). CONCLUSIONS: Intensity-modulated radiation therapy with simultaneous integrated boost with concurrent chemotherapy is a safe and effective treatment modality for nasopharyngeal cancer. Helical tomotherapy has a dosimetric advantage over step-and-shoot intensity-modulated radiation therapy in a clinical setting.ope

Risk stratification of abdominopelvic failure for FIGO stage III epithelial ovarian cancer patients: Implications for adjuvant radiotherapy

OBJECTIVE: To analyze patterns of abdominopelvic failures and to define subgroups for the use of adjuvant radiotherapy in the International Federation of Gynecology and Obstetrics (FIGO) stage III epithelial ovarian cancer (EOC). METHODS: We reviewed 149 patients treated with debulking surgery followed by intravenous taxane and platinum chemotherapy between 1999 and 2008. Patient characteristics, patterns of failure, abdominopelvic failure APF-free survival (APFFS) and overall survival (OS) were analyzed. RESULTS: The median age of the patients was 51 years. Thirty-two patients (21.5%) were found to have residuum >2 cm after surgery. The median pretreatment CA-125 was 604 and 54.4% of patients had a decline in CA-125 ≥90% between pretreatment and at postoperative 1 month. With a median follow-up of 50 months, 79 patients (53.0%) experienced abdominopelvic failure (APF). The 5-year APF-free survival rate was 41.1%. Lymph node metastasis, size of residual disease, and decline in CA-125 were found to be significant prognostic factors for APF upon multivariate analysis. The group of patients in whom abdominopelvic irradiation was indicated as definitive postoperative treatment comprised 55% of the overall patient population and their 5-year survival rate was 68%. CONCLUSION: The stratification was suggested to predict APF based on lymph node metastasis, size of residual tumor, and decline in CA-125. Adjuvant radiotherapy covering the whole abdominopelvis using the intensity modulation technique may be considered to reduce APF in FIGO stage III EOC patients with intermediate risk.ope

Tailored radiotherapeutic strategies for disseminated uterine cervical cancer patients

BACKGROUND: To investigate the role of radiotherapy (RT) in and to suggest radiotherapeutic strategies for patients presenting with disseminated cervical cancer. METHODS: We retrospectively analyzed 50 patients diagnosed as the disseminated cervical cancer with distant lymph nodal or visceral organ metastasis between September 1980 and August 2012. Patients were divided into two subgroups according to visceral organ metastasis: 35 patients diagnosed with distant lymph node metastasis only (group A) and 15 patients with visceral organ metastasis (group B). All patients received external beam RT to the pelvis (median dose 45 Gy) and high-dose rate intracavitary RT (median dose 30 Gy). Thirty-nine patients (78%) received chemotherapy. RESULTS: Median follow-up time was 74 months. The 5-year pelvic control rate (PCR) was 85.8%, and the progression-free survival (PFS), and overall survival (OS) rates were 28.7%, and 36.2%, respectively. The major treatment failure was systemic progression (32 patients, 64%). The 5-year PCRs in groups A and B were 87.4% and 74.7%, respectively (p > 0.05). Meanwhile, PFS and OS rates for group A were significantly better than those for group B (35.3% vs. 13.3%, p = 0.010; and 46.3% vs. 13.3%, p = 0.009, respectively). CONCLUSION: Our data revealed considerable prognostic heterogeneity in disseminated cervical cancer. Even though a high PCR was achieved in patients treated with definitive RT, survival outcomes were dependent on progression of visceral organ metastasis. Therefore, personalized RT and chemotherapy treatment strategies according to the presence of visceral organ metastasis in disseminated cervical cancer patients may help improve clinical outcomes.ope

Hypofractionated high-dose intensity-modulated radiotherapy (60 Gy at 2.5 Gy per fraction) for recurrent renal cell carcinoma: A case report

A patient with renal cell carcinoma (RCC) developed synchronous bone metastasis with metachronous relapses to the bone and renal fossa. The primary lesion was initially removed surgically, and the metastatic bone lesions and locally recurrent tumours were treated by a high-fractional dose and high-total-dose intensity-modulated radiotherapy (IMRT, 60 Gy at 2.5 Gy per fraction) without significant side effects. All the grossly relapsed tumors underwent complete remission (CR) within a short time after IMRT. To date, CR has been maintained for more than two years. This case study reports the successful treatment of radioresistant RCC using a new scheme that involves a fractionation regimen with a high precision radiotherapyope

Synchronous Coexpression of Epidermal Growth Factor Receptor and Cyclooxygenase-2 in Carcinomas of the Uterine Cervix - A Potential Predictor of Poor Survival

PURPOSE: To evaluate the potential of the new prognostic information gained by analyzing the coexpression of epidermal growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) in cervical cancer patients. EXPERIMENTAL DESIGN: Sixty-eight patients with International Federation of Gynecology and Obstetrics stage IIB squamous cell carcinoma of the uterine cervix, who underwent concurrent chemoradiotherapy between 1993 and 1996, were divided into the following four groups according to their immunoreactivities for EGFR and COX-2 in paraffin-embedded sections: (a). the EGFR-negative/COX-2-negative group (n = 11); (b). the EGFR-negative/COX-2-positive group (n = 8); (c). the EGFR-positive/COX-2-negative group (n = 27); and (d). the EGFR-positive/COX-2-positive group (n = 22). The clinical features, patterns of treatment failure, and survival data in the four groups were compared. RESULTS: Positive immunoreactivity for EGFR and COX-2 was observed in 49 of 68 (72%) and 19 of 68 (28%), respectively. However, no strong correlation was found between the levels of EGFR and COX-2 immunopositivity (R(2) = 0.05, P = 0.07). Patients in the EGFR-positive/COX-2-positive group had a higher likelihood of locoregional recurrence than those in the other three groups (P = 0.02). Of the patients in the four groups, patients positive for both oncoproteins were found to have the worst prognosis with an overall 5-year disease-free survival rate of 55% compared with 91% for the EGFR-negative/COX-2-negative patients, 88% for the EGFR-negative/COX-2-positive patients, and 69% for the EGFR-positive/COX-2-negative patients (P = 0.05, log-rank test). In addition, the synchronous coexpression of the EGFR and COX-2 oncoproteins was found to be an independent prognostic factor by univariate and multivariate analyses (relative risk = 4.0, P = 0.03). CONCLUSIONS: Given these observations, we conclude that the coexpression of EGFR and COX-2 immunoreactivity may be used as a potent molecular risk factor for predicting the poor survival of patients with the International Federation of Gynecology and Obstetrics stage IIB squamous cell carcinoma of the uterine cervix.ope

Pattern of failure in bladder cancer patients treated with radical cystectomy: rationale for adjuvant radiotherapy

Thus far, the role of adjuvant radiotherapy (RT) after radical cystectomy (RC) in urinary bladder cancer patients has yet to be defined. The purpose of this study is to analyze patterns of failure, and suggest the rationale for RT. Between 1986 and 2005, a total of 259 patients treated with RC and pelvic lymph node dissection was enrolled. The age range was 27-82 yr (median, 62 yr). Node positivity increased according to tumor staging. Patients were divided into the following two groups based on pathologic analysis: organ-confined disease group (n=135) and extravesical/lymph node-positive disease group (n=80). Pelvic failures (PF) were observed in 8 (4.9%) in organ-confined disease group, and 21 (21.7%) in extravesical/lymph node-positive disease group. Five-year PF-free survival rates were 91.2% in organ-confined disease group and 68.0% in extravesical/lymph node-positive disease group. Five-year cancer-specific survival rates were 86.2% in organ-confined disease group and 53.9% in extravesical/lymph node-positive disease group. In conclusion, a relatively high PF rate was observed in extravesical lymph node-negative and lymph node-positive disease patients in this study. Adjuvant pelvic RT may be considered to reduce pelvic failures in extravesical lymph node-positive bladder cancer. Future prospective trials are required to test the clinical benefit of adjuvant RT.ope