• Radiation Oncology Journal
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• v.26 no.1
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• pp.56-64
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• 2008

Purpose: Cathepsin D(CD) is a lysosomal acid proteinase that is related to malignant progression, invasion, and a poor prognosis in several tumors. The aim of this study was to evaluate the prognostic clinical significance of CD and p53 expression in pretreatment biopsy specimens from patients with locally advanced rectal cancer who were treated with preoperative chemoradiation. Materials and Methods: Eighty-nine patients with locally advanced rectal cancer(cT3/T4 or N+) were included in this study. Preoperative chemoradiation consisted of a dose of 50.4 Gy of pelvic radiation and two concurrent cycles of administration of 5-fluorouracil and leucovorin. Surgery was performed six weeks after chemoradiation. CD and p53 expression in pretreatment formalin-fixed paraffin-embedded tumor biopsy specimens were assessed by immunohistochemical staining using a CD and p53 monoclonal antibodies. The threshold value for a positive stain in tumor tissue and stromal cells was 1+ intensity in 10% of the tumors or stromal cells, respectively. Results: Positive CD expression was found in 57(64%) of the tumors and 32(35%) of the stromal cell specimens. There was no association with CD expression of the tumor or stromal cells and patient characteristics. There was a correlation between tumor CD expression with stromal cell CD expression(p=0.01). Overexpression of p53 was not a significant prognostic factor. The 5-year overall survival(OS) and disease-free survival(DFS) rates were not different between tumor CD-negative and positive patient biopsy samples(69% vs. 65%, 60% vs. 61%, respectively). The 5-year OS rates in the tumor-negative/stromal cell-negative, tumor-negative/stromal cell-positive, tumor-positive/stromal cell-negative and tumor-positive/stromal cell-positive biopsy samples were 75%, 28%, 62%, and 73%, respectively. Stromal cell staining only without positive tumor staining demonstrated the worst overall survival prognosis for patients(p=0.013). Conclusion: Overexpression of p53 in rectal biopy tissue was not associated with prognostic significance. In the pretreatment biopsy specimens, an exclusive increase in CD expression in stromal cells without tumor expression was related to poor overall survival in patients with locally advanced rectal cancer treated with preoperative chemoradiation.

• Radiation Oncology Journal
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• v.26 no.4
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• pp.195-203
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• 2008

Purpose: To investigate the treatment outcome and failure patterns after definitive chemoradiation therapy in locally advanced, unresectable esophageal cancer. Materials and Methods: From February 1994 to December 2002, 168 patients with locally advanced unresectable or medically inoperable esophageal cancer were treated by definitive chemoradiation therapy. External beam radiation therapy (EBRT) ($42{\sim}46\;Gy$) was delivered to the region encompassing the primary tumor and involved lymph nodes, while the supraclavicular fossa and celiac area were included in the treatment area as a function of disease location. The administered cone-down radiation dose to the gross tumor went up to $54{\sim}66\;Gy$, while the fraction size of the EBRT was 1.8-2.0 Gy/fraction qd or 1.2 Gy/fraction bid. An optional high dose rate (HDR) intraluminal brachytherapy (BT) boost was also administered (Ir-192, $9{\sim}12\;Gy/3{\sim}4\;fx$). Two cycles of concurrent FP chemotherapy (5-FU $1,000\;mg/m^2$/day, days $2{\sim}6$, $30{\sim}34$, cisplatin $60\;mg/m^2$/day, days 1, 29) were delivered during radiotherapy with the addition of two more cycles. Results: One hundred sixty patients were analyzable for this review [median follow-up time: 10 months (range $1{\sim}149$ months)). The number of patients within AJCC stages I, II, III, and IV was 5 (3.1%), 38 (23.8%), 68 (42.5%), and 49 (30.6%), respectively. A HDR intraluminal BT was performed in 26 patients. The 160 patients had a median EBRT radiation dose of 59.4 Gy (range $44.4{\sim}66$) and a total radiation dose, including BT, of 60 Gy (range $44.4{\sim}72$), while 144 patients received a dose higher than 40 Gy. Despite the treatment, the disease recurrence rate was 101/160 (63.1%). Of these, the patterns of recurrence were local in 20 patients (12.5%), persistent disease and local progression in 61 (38.1%), distant metastasis in 15 (9.4%), and concomitant local and distant failure in 5 (3.1%). The overall survival rate was 31.8% at 2 years and 14.2% at 5 years (median 11.1 months). Disease-free survival was 29.0% at 2 years and 22.7% at 5 years (median 10.4 months). The response to treatment and N-stage were significant factors affecting overall survival. In addition, total radiation dose (${\geq}50\;Gy$ vs. < 50 Gy), BT and fractionation scheme (qd. vs. bid.) were not significant factors for overall survival and disease-free survival. Conclusion: Survival outcome after definitive chemoradiation therapy in unresectable esophageal cancer was comparable to those of other series. The main failure pattern was local recurrence. Survival rate did not improve with increased radiation dose over 50 Gy or the use of brachytherapy or hyperfractionation.

• Radiation Oncology Journal
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• v.24 no.2
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• pp.96-102
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• 2006

Purpose: A retrospective study was performed to evaluate the efficiency and feasibility of twice daily radiation therapy plus concurrent chemotherapy for limited-stage small cell lung cancer in terms of treatment response, survival, patterns of failure, and acute toxicities. Materials and Methods: Between February 1993 and October 2002, 76 patients of histologically proven limited-stage small cell lung cancer (LS-SCLC) were treated with twice daily radiation therapy and concurrent chemotherapy. Male was in 84% (64/76), and median age was 57 years (range, 32-75 years). Thoracic radiation therapy consisted of 120 or 150 cGy per fraction, twice a day at least 6 hours apart, 5 days a week. Median total dose was 50.4 Gy (range, 45-51 Gy). Concurrent chemotherapy consisted of CAV ($cytoxan\;1000mg/m^2,\;adriamycin\;40mg/m^2,\;vincristine\;1mg/m^2$) alternating with PE ($cisplatin\;60mg/m^2,\;etoposide\;100mg/m^2$) or PE alone, every 3 weeks. The median cycle of chemotherapy was six (range, 1-9 cycle). Prophylactic cranial irradiation (PCI) was recommended to the patients who achieved a complete response (CR). PCI scheme was 25 Gy/10 fractions. Median follow up was 18 months (range, 1-136 months). Results: Overall response rate was 86%; complete response in 39 (52%) and partial response in 26 (34%) patients. The median overall survival was 23 months. One, two, and three year overall survival rate was 72%, 50% and 30%, respectively. In univariate analysis, the treatment response was revealed as a significant favorable prognostic factor for survival (p<0.001). Grade 3 or worse acute toxicities were leukopenia in 46 (61%), anemia in 5 (6%), thrombocytopenia in 10 (13%), esophagitis in 5 (6%), and pulmonary toxicity in 2 (2%) patients. Of 73 evaluable patients, 40 (55%) patients subsequently had disease progression. The most frequent first site of distant metastasis was brain. Conclusion: Twice daily radiation therapy plus concurrent chemotherapy produced favorable response and survival for LS-SCLC patients with tolerable toxicities. To improve the treatment response, which proved as a significant prognostic factor for survival, there should be further investigations about fractionation scheme, chemotherapy regimens and compatible chemoradiotherapy schedule.

• Radiation Oncology Journal
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• v.27 no.2
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• pp.71-77
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• 2009

Purpose: We investigated the outcome and the prognostic factors of patients with locally advanced esophageal cancer who were treated with concurrent chemo-radiotherapy. Materials and Methods: Two hundred forty six patients with esophageal cancer that were treated by radiotherapy between January 1994 and July 2007. Of these, 78 patients who received radiotherapy of $\geq$45 Gy with concurrent chemotherapy were retrospectively enrolled in this study. We included patients stages IIA, IIB, III, IVA, and IVB with supraclavicular metastasis in the middle/lower esophageal cancer or celiac node metastasis in cervical or upper/middle thoracic esophageal cancer. The median radiation dose was 54 Gy and the combination chemotherapy with 5-FU and cisplatin (FP chemotherapy) was given concurrently with radiotherapy in most patients (88%). Results: The follow-up period ranged from 2 to 117 months (median 14 months). The treatment response of the 54 patients could be evaluated by computerized tomography or endoscopy. A complete response (CR) was observed in 17 patients, whereas a partial response was observed in 18 patients. In patients with a CR, the median recurrence time was 20 months and the first relapse sites constituted a locoregional failure in 3 patients and a distant failure in 7 patients. The 1-, 2-, and 5-year overall survival (OS) rates were 58.9%, 21.7%, and 12.2%, respectively. The median survival period was 14 months. A univariate analysis indicated that the treatment response and cycles of FP chemotherapy were significant prognostic factors for OS. Daily or weekly administration of cisplatin as a radiosensitizer showed a better treatment response than FP chemotherapy. Conclusion: This study has shown that results of concurrent chemo-radiotherapy in patients with locally advanced esophageal cancer is comparable to those of other studies. Daily or weekly cisplatin administration may be considered as an alternative treatment in patients that are medically unfit for FP chemotherapy.

• Radiation Oncology Journal
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• v.27 no.2
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• pp.64-70
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• 2009

Purpose: Concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced unresectable pancreatic cancer. However, the introduction of gemcitabine and the recognition of a benefit in patients with advanced disease stimulated the design of trials that compare chemotherapy alone to concurrent chemoradiation. Therefore, we evaluated role of CCRT for locally advanced unresectable pancreatic cancer. Materials and Methods: We carried out a retrospective analysis of treatment results for patients with locally advanced unresectable pancreatic cancer between January 2000 and January 2008. The radiation was delivered to the primary tumor and regional lymph nodes with a 1~2 cm margin at a total dose of 36.0~59.4 Gy (median: 54 Gy). The chemotherapeutic agent delivered with the radiation was 5-FU (500 mg/$m^2$). The patients who underwent chemotherapy alone received gemcitabine (1,000 mg/$m^2$) alone or gemcitabine with 5-FU. The follow-up period ranged from 2 to 38 months. The survival and prognostic factors were analyzed using Kaplan-Meier method and log-rank test, respectively. Results: Thirty-four patients received concurrent chemoradiotherapy, whereas 21 patients received chemotherapy alone. The median survival time was 12 months for CCRT patients, compared to 11 months for chemotherapy alone patients (p=0.453). The median progression-free survival was 8 months for CCRT patients, compared to 5 months for chemotherapy alone patients (p=0.242). The overall response included 9 partial responses for CCRT and 1 partial response for chemotherapy alone. In total, 26% of patients from the CCRT group experienced grade 3~4 bowel toxicity. In contract, no grade 3~4 bowel toxicity was observed in the chemotherapy alone group. The significant prognostic factors of overall survival were lymph node status, high CA19-9, and tumor location. Conclusion: The response rate and progression-free survival were more favorable in the CCRT group, when compared with the chemotherapy alone group. Therefore, radiation therapy seems to be an effective tool for local tumor control.

• Radiation Oncology Journal
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• v.33 no.2
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• pp.83-88
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• 2015

Purpose: To evaluate the appropriateness of prophylactic inguinal nodal irradiation (PINI), we analyzed patterns of failure in anal cancer patients who were inguinal node-negative at presentation and did not receive PINI. Materials and Methods: We retrospectively reviewed the records of 33 anal cancer patients treated by definitive concurrent chemoradiation therapy (CCRT) between 1994 and 2013. Radiotherapy consisted of a total dose of 44-45 Gy (22-25 fractions in 5 weeks) on the whole pelvis, anus, and perineum. Except inguinal lymphadenopathy was present at initial diagnosis, the entire inguinal chain was not included in the radiation field. In other words, there was no PINI. Results: The median follow-up duration was 50 months (range, 4 to 218 months). Median survival and progression-free survival (PFS) were 57 months (range, 10 to 218 months) and 50 months (range, 4 to 218 months), respectively. Among the survival, the median follow-up duration was 51 months (range, 12 to 218 months). The 5-year overall survival and PFS rates were 93.4% and 88.8%, respectively. Although none of the patients received inguinal node irradiation for prophylactic purposes, there was no inguinal recurrence. Conclusion: Treatment of anal cancer by omitting PINI might be considered in selected patients with clinically uninvolved inguinal nodes.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.2
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• pp.463-466
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• 2016

Glioblastoma (GBM) is the most common and aggressive type of primary brain neoplasm. The current standard therapy for GBM consists of maximal surgical resection within safe limits, followed by radiation therapy (RT) and chemotherapy with temozolomide. Despite advances in treatment, the prognosis of GBM remains poor. Epileptic seizure is one of the most common symptoms in patients with GBM. Valproic acid (VPA), a histone deacetylase inhibitor, is often used as an anti-epileptic drug in patients with brain neoplasms due to its effectiveness and low toxicity profile. Several in vivo and in vitro studies have indicated that VPA has radiosensitizing effects for gliomas and radioprotective influence on normal brain tissue or hippocampal neurons. The results of several retrospective studies have also indicated potential benefit to improve survival of patients with GBM. Moreover, the promising treatment results of a phase 2 trial of concurrent radiation therapy, temozolomide, and VPA for patients with GBM have been recently reported. The use of VPA in patients with GBM has thus recently receiving more attention. In this article, we review the role of VPA in radiation therapy for GBM, focusing on the clinical evidence.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.3
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• pp.1905-1909
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• 2013

Objective: The aim of the current study was to evaluate changes in treatment outcomes in terms of health-related quality of life (HRQoL) and symptom burden at zero, one, three, and six months after an initial diagnosis of colorectal cancer. The demographic and clinical characteristics that account for outcome changes in patients were investigated using a repeated measures framework. Methods and Materials: A cohort study was performed of 134 colorectal cancer patients followed from diagnosis to 6 months post-treatment in Central Taiwan. HRQoL and symptoms were assessed at diagnosis and one, three, and six months thereafter. The Functional Assessment of Cancer Therapy-Colon (FACT-C) questionnaire, VAS pain, and the Memorial Symptom Assessment Scale (MSAS) were used for data collection. A generalized estimating equation (GEE) was applied for statistical analysis. Results: The majority of the patients were male (55%) and married (91.5%). The mean age was 60.4 years (SD = 11.71). Most were diagnosed stage III and IV colorectal cancer (54.5%). All underwent surgery; some also received chemotherapy (CT) or concurrent chemoradiation therapy (CCRT). The results of the GEE showed that overall, the HRQoL, pain, and symptoms of the patients significantly improved over the treatment period. Patients with stage IV disease who had received surgery and CCRT showed the worst HRQoL. Females, patients with comorbidity, and stage IV patients had higher pain scores over time. Female and stage IV patients had more severe physical symptoms, whereas stage II and IV patients had worse psychological symptoms over time. Conclusion: The patients' HRQoL, pain, and symptoms significantly improved over the 6-month treatment period. Certain patient and clinical variables accounted for changes in treatment outcomes regarding HRQoL and symptom burden in colorectal cancer patients.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.4163-4167
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• 2012

Aims: To prospectively assess the efficacy and safety of moderately hypofractionated conformal radiotherapy in patients with thoracic esophageal cancer. Methods and Materials: From Sept. 2002 to Oct, 2005, 150 eligible patients with T2-4N0-1M0 stage thoracic esophageal squamous cell cancers were enrolled to receive either conventional fractionated radiation (CFR) or moderately hypofractionated radiation (MHR) with a three-dimensional conformal radiation technique. Of the total, 74 received moderately hypofractionated radiation with total dose of 54-60Gy/18-20fractions for 3.5-4 weeks in the MHR arm, and 76 received conventional radiation with total dose of 60Gy/30 fractions for 6 weeks in the CFR arm. Concurrent chemotherapy comprised of paclitaxel and cisplatin. Safety was evaluated, and local control and overall survival rates were calculated. Results: Statistically significant differences between the CFR versus MHR arms were observed in local/regional failure rate (47.3% v 27.0%, P=0.034) and the percentage of patients with persistent local disease (26.3% v 10.8%, P=0.012). But 3 and 5-year overall survival rates (43.2%, 38.8% v 38.2%, 28.0%, respectively) were not different between the two arms (P=0.268). There were no significant differences in the incidences of grade 3 or higher acute toxicities (66.3% v 50.0%) and late complications rates (27.0% v 22.4%) between the MHR and CFR arms. Conclusions: Moderately hypofractionated, three-dimensional radiation treatment could improve the local control rate of esophageal cancer and potentially increase patients' survival.

• Radiation Oncology Journal
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• v.29 no.4
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• pp.269-276
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• 2011

Purpose: To determine the incidence, risk factors, and clinical characteristics of pelvic insufficiency fracture (PIF) in patients with cervical cancer. Materials and Methods: Between July 2004 and August 2009, 235 patients with non-metastatic cervical cancer were treated with definitive chemoradiation or postoperative radiotherapy. Among 235 patients, 117 (49.8%) underwent the first positron emission tomography/computed tomography (PET/CT) within 1 year after radiotherapy. The median radiation dose was 55 Gy (range, 45 to 60 Gy). Medical charts and imaging studies, including PET/CT, magnetic resonance imaging (MRI), CT. bone scintigraphy were reviewed to evaluate the patients with PIF. Results: Among 235 patients, 16 developed PIF. The 5-year detection rate of PIF was 9.5%. The 5-year detection rate of PIF in patients who underwent the first PET/CT within a year was 15.6%. The median time to development of PIF was 12.5 months (range, 5 to 30 months). The sites of fracture included 12 sacroiliac joints, 3 pubic rami, 3 iliac bones, and 1 femoral neck. Eleven of 16 patients having PIF complained of hip pain requiring medications. One patient required hospitalization for pain control. The significant risk factors of PIF were old age, body mass index less than 23, bone mineral density less than -3.5 SD, and the first PET/CT within a year after radiotherapy. Radiation dose and concurrent chemotherapy had no impact on PIF rate. Conclusion: PIFs were not rare after pelvic radiotherapy in cervical cancer patients in the era of PET/CT. Timely diagnosis and management of PIF can improve quality of life in patients with cervical cancer, in addition to reducing unnecessary medical expenses.