• Radiation Oncology Journal
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• v.35 no.1
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• pp.1-15
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• 2017

Locoregional failure is the most frequent pattern of failure in locally advanced head and neck cancer patients and it leads to death in most of the patients. Second primary tumors occurring in the other head and neck region reach up to almost 40% of long-term survivors. Recommended and preferred retreatment option in operable patients is salvage surgical resection, reporting a 5-year overall survival of up to 40%. However, because of tumor location, extent, and underlying comorbidities, salvage surgery is often limited and compromised by incomplete resection. Reirradiation with or without combined chemotherapy is an appropriate option for unresectable recurrence. Reirradiation is carefully considered with a case-by-case basis. Reirradiation protocol enrollment is highly encouraged prior to committing patient to an aggressive therapy. Radiation doses greater than 60 Gy are usually recommended for successful salvage. Despite recent technical improvement in intensity-modulated radiotherapy (IMRT), the use of concurrent chemotherapy, and the emergence of molecularly targeted agents, careful patient selection remain as the most paramount factor in reirradiation. Tumors that recur or persist despite aggressive prior chemoradiation therapy imply the presence of chemoradio-resistant clonogens. Treatment protocols that combine novel targeted radiosensitizing agents with conformal high precision radiation are required to overcome the resistance while minimizing toxicity. Recent large number of data showed that IMRT may provide better locoregional control with acceptable acute or chronic morbidities. However, additional prospective studies are required before a definitive conclusion can be drawn on safety and effectiveness of IMRT.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.10
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• pp.4147-4152
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• 2014

Standard therapy for advanced head and neck cancer consists of a combination of surgery and radiation. However, survival of this patient population has not improved during the past 20 years. Many different multimodality treatment schedules have been proposed, and chemotherapy is often used with the intent of organ preservation. The present study was intended to establish the efficacy of concomitant chemoradiation with a single agent carboplatin in advanced head and neck cancers.The objectives were to investigate the feasibility of concomitant administration of carboplatin, monitor acute toxicity during radiotherapy, and determine subacute side effects, such as wound healing following surgery after chemoradiotherapy. A prospective study was conducted wherein a total of 40 patients with stage III and IV squamous cell carcinomas of oral cavity, oropharynx, hypopharynx and larynx were enrolled. All patients were treated with external beam radiotherapy and weekly carboplatin area under curve (AUC of 5). Radiotherapy was given in single daily fractions of 1.8-2 grays (Gy) to a total dose of 66-72 Gy. Salvage surgery was performed for any residual or recurrent locoregional disease. Neck dissection was recommended for all patients with neck disease showing less than a complete response after chemoradiation. A total of 40 patients were enrolled of whom 32 were males and 8 were females. Highest incidence of cancer was seen in the 5th-6th decades of life with a median age of 47.7 years. Oropharyngeal tumours constituted a maximum of 21 patients followed by hypopharynx in 10, larynx in 7 and oral cavity in 2. 80% of the patients had a neck node on presentation of which 40% had N2-N3 nodal status. TNM staging revealed that 58% of patients were in stage III and 43% in stage IV. Evaluation of acute toxicity revealed that 50% had grade II mucositis, 25% grade III mucositis, 2.5% grade IV mucositis. 50% of patients had grade I skin reactions, 65% of patients had grade I thrombocytopenia, and 24% of patients had grade I anaemia. After completion of treatment 65% of patients had complete response at the primary and regional sites, and 35% of patients had a partial response of whom 23% underwent neck dissection and 5% of them underwent salvage surgery at the primary site. At the end of one year there were six deaths and four recurrences and 70% were free of disease. Concurrent chemoradiation with carboplatin provided good locoregional control for locally advanced head and neck cancers. This regimen, although toxic, is tolerable with appropriate supportive intervention. Primary site conservation is possible in many patients. Chemoradiotherapy appears to have an emerging role in the primary management of head and neck cancers.

• Archives of Reconstructive Microsurgery
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• v.20 no.1
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• pp.57-59
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• 2011

Tongue reconstruction after oncologic resection with free flap is important to conserve function and shape. Vertical rectus myocutaneous free flap is usually used for total tongue reconstruction, but our patient was thin and primary closure after flap elevation seemed hard. So we used anterolateral thigh free flap to reduce donor site morbidity and to maintain bulk of the tongue as much as possible. Deepithelization of both middle side of flap and folding was done to mimic normal tongue base's shape and volume. Flap survived without complication and patient underwent concurrent chemoradiation therapy three weeks after surgery. Anterolateral thigh free flap can be good candidate for total tongue reconstruction especially in thin patient.

• Radiation Oncology Journal
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• v.25 no.2
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• pp.101-108
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• 2007

[ $\underline{Purpose}$ ]: To compare radiation therapy alone to combined modality therapy about survival rate and tolerance of elderly patients ($70=or{\geq}$) with non-small-cell lung cancer (NSCLC). $\underline{Materials\;and\;Methods}$: Between 1998 and 2002, 57 patients given radiation therapy due to NSCLC (Stage III) were analysed retrospectively. Radiation therapy alone (RT), concurrent chemoradiation (CRT), and sequential chemoradiation (SCRT) was done to 33, 16 and 8 patients, respectively. Patients' median age was 74 (range $70{\sim}85$). Male and female are 51 patients and 6 patients, respectively. 23 patients were stage IIIa and 34 were stage IIIb. Patients' characteristic distribution of RT and CRT was not significantly different except mass size that RT has a bigger than CRT. The fraction size of radiation therapy was 1.8 Gy in CRT and $1.8{\sim}3\;Gy$ in other groups. Total radiation dose was $51{\sim}63\;Gy$ according to the fraction size. If the prescribed total radiation dose was successfully irradiated, we stated that it was completion of radiation therapy. $\underline{Results}$: 52 patients were dead. Median period of radiation therapy was as follow: RT, 35 days, CRT, 60.5 days and SCRT, 35 days. Overall median survival time (MST) was 10.1 months. The 1 yr- and 2 yr-overall survival rate was 39.8% and 17.6%, respectively. MST of RT, CRT and SCRT was 8.9, 8.2 and 11.7 months, respectively. The 1 yr survival rate of RT, CRT and SCRT was 38.4%, 37.5% and 50% (not significant). Patients given incomplete radiation therapy were 12 (RT, 5 CRT, 6 SCRT, 1). N stage (p=0.081) and the difference of treatment methods (p=0.079) were the factors affecting incompletion of radiation therapy, but it was not significant. In case of combined-agents chemotherapy, 4 of 8 ceased radiation therapy. T stage ($T{\geq}3$), mass size (${\geq}5\;cm$), Karnofsky performance scale (${\leq}70$) and completion of radiation therapy were the prognostic factors in uni- and multi-variate analysis. $\underline{Conclusion}$: In elderly patients with NSCLC, radiation therapy alone was a treatment method with similar survival period compared with other methods. Generally, patients given radiation therapy alone was tolerable to a treatment. Before planning concurrent chemoirradiation in elderly patients with NSCLC, physicians pay attention to a selection of patients and chemotherapy agents considering general condition and toxicity.

• 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.

• Korean Journal of Head & Neck Oncology
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• v.22 no.2
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• pp.123-129
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• 2006

Objective ： This retrospective study was designed to evaluate the anti-tumor efficacy and toxicities of the radiation therapy(RT) combined with cisplatin-based chemotherapy in locally advanced nasopharyngeal cancer(NPC). Materials and Methods ： Fifty three patients with locally advanced NPCs(AJCC stage II, III, IV) received curative RT and cisplatin-based chemotherapy. Duration of follow-up ranged from 5.5 to 201 months(median 50.8 months). Nineteen patients(35.8%) were treated with induction chemotherapy including cisplatin $100mg/m^2$ for 1 day and 5-fluorouracil $1g/m^2$ for 5 days followed by RT(Induction CTx-RT). Another 34 patients (64.2%) were treated with concurrent chemoradiation(CCRT) using cisplatin $100mg/m^2$(D1, 22, 43). Results ： Thirty-six(67.9%) and 11(20.8%) patients achieved clinical complete response and partial response, respectively. The pattern of failure was as follows：14 locoregional recurrence(26.4%) and 7 distant metastasis(13.2%). Among them, two patients(3.8%) had both locoregional and distant failure. Median overall survival(OS) and progression-free survival(PFS) were 85.5 months and 87.5 months, respectively. Five-year OS rate was 57.1%. The stage(AJCC), tumor response to chemoradiation and T stage were significant prognostic factors for OS(p=0.0113, p=0.0362 and p=0.0469). The stage(AJCC), tumor response to chemoradiation were also significant prognostic factors for PFS(p=0.0329, p=0.0424). Compared to each treatment group(Induction CTx-RT vs. CCRT), there were no significant differences in OS and PFS(p=0.7000, p=0.8261). Grade 3-4 mucositis, nausea/vomiting and hematological toxicities were noticed in 35.8%, 11.3% and 13.2%, respectively. Delayed RT over 2 weeks was inevitable in 26.5%. Seventeen patients(50%) successfully completed planned 3 courses of cisplatin in CCRT group. Conclusions ： RT combined with cisplatin-based chemotherapy in locally advanced NPC showed high response rate, good locoregional control, and survival rate. As expected, frequency of acute toxicities increased, and the patient's compliance to treatment was need to be improved. Although our data could not show additional survival benefit of CCRT compare to that of induction chemotherapy followed by RT, patients' accrual and further follow-up are required due to limitation of retrospective study.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.12
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• pp.4857-4860
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• 2014

Background: Colorectal cancer is common in Iran. However our knowledge about survival of rectal cancer in our province is low. The aim of this study is to evaluate this question. Materials and Methods: Patients with documented pathology of adenocarcinoma of the rectum and rectosigmoid junction referred to our center from September 2004 to September 2012 were enrolled in this study. Metastatic and recurrent patients were excluded. A questionnaire including clinicopathologic parameters, quality and sequence of treatment modalities was filled in for each patient. Patients treated with a combination of surgery, chemotherapy and radiation therapy were divided into standard and non-standard treatment groups, according to the sequence of treatment. Results: One hundred and nineteen patients were evaluated. Mean age was 60.8 year. The median overall survival was 62 months and five year survival was 55%. TNM staging system was not possible due to (Nx) in 21 (17.6%) patients. The others were in stage I, 20 patients (16.8%), II, 35 (29%.5) and III, 43(36.1%). According to our definition only 25 patients (21%) had been treated with standard treatment and 79% had not received it. A five year survival in patients with standard treatment was 85% and in the non-standard group it was 52%.Age, sex, stage and grade of tumor did not show any significant relation to survival. Conclusions: Our study showed a five year survival of rectal cancer in our patients was about 10% lower than the rate which is reported for developed countries. Preoperative concurrent chemoradiation significantly improved local control and even overall survival.

• 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.33 no.2
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• pp.155-159
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• 2015

We present a case of cervical cancer treated by concurrent chemoradiation. In radiation therapy part, the combination of the whole pelvic helical tomotherapy plus image-guided brachytherapy with megavoltage computed tomography of helical tomotherapy was performed. We propose this therapeutic approach could be considered in a curative setting in some problematic situation as our institution.

• Radiation Oncology Journal
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• v.21 no.1
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• pp.54-65
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• 2003

Purpose : To analyze the gene expression Profiles of uterine ceulcal cancer, and its variation after radiation therapy, with or without concurrent chemotherapy, using a CDNA microarray. Materials and Methods :Sixteen patients, 8 with squamous ceil carcinomas of the uterine cervix, who were treated with radiation alone, and the other 8 treated w14h concurrent chemo-radiation, were Included in the study. Before the starling of the treatment, tumor biopsies were carried out, and the second time biopsies were peformed after a radiation dose of 16.2$\~$27 Gy. Three normal cervix tissues were used as a control group. The microarray experiments were peformed with 5 groups of the total RNAs extracted individually and then admixed as control, pre-radiation therapy alone, during-radiation therapy alone, pre-chemoradiation therapy, and during-chemoradlation therapy. The 33P-iabeled CDNAS were synthesized from the total RNAs of each group, by reverse transcription, and then they were hybridized to the CDNA microarray membrane. The gene expression of each microarrays was captured by the intensity of each spot produced by the radioactive isotopes. The pixels per spot were counted with an Arrayguage, and were exported to Microsoft Excel The data were normalized by the Z transformation, and the comparisons were peformed on the Z-ratio values calculated. Results : The expressions of 15 genes, including integrin linked kinase (ILK), CDC28 protein kinase 2, Spry 2, and ERK 3, were increased with the Z-ratio values of over 2.0 for the cervix cancer tissues compared to those for the normal controls. Those genes were involved In cell growth and proliferation, cell cycle control, or signal transduction. The expressions of the other 6 genes, Including G protein coupled receptor kinase 5, were decreased with the Z-ratio values of below -2.0. After the radiation thorapy, most of the genes, with a previously Increase expressions, represented the decreased expression profiles, and the genes, with the Z-ratio values of over 2.0, were cyclic nucleotlde gated channel and 3 Expressed sequence tags (EST). In the concurrent chemo-radiation group, the genes involved in cell growth and proliferation, cell cycle control, and signal transduction were shown to have increased expressions compared to the radiation therapy alone group. The expressions of genes involved in anglogenesis (angiopoietln-2), immune reactions (formyl peptide receptor-iike 1), and DNA repair (CAMP phosphodiesterase) were increased, however, the expression of gene involved In apoptosls (death associated protein kinase) was decreased. Conclusion : The different kinds of genes involved in the development and progression of cervical cancer were identified with the CDNA microarray, and the proposed theory is that the proliferation signal stalls with ILK, and is amplified with Spry 2 and MAPK signaling, and the cellular mitoses are Increased with the increased expression oi Cdc 2 and cell division kinases. After the radiation therapy, the expression profiles demonstrated 4he evidence of the decreased cancer cell proliferation. There was no sigificant difference in the morphological findings of cell death between the radiation therapy aione and the chemo-radiation groups In the second time biopsy specimen, however, the gene expression profiles were markedly different, and the mechanism at the molecular level needs further study.