• Radiation Oncology Journal
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• v.25 no.3
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• pp.151-159
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• 2007

Purpose: The purpose of this study is to present the treatment results and to identify possible prognostic indicators in patients with locally advanced hypopharyngeal carcinoma. Materials and Methods: Between October 1985 to December 2000, 90 patients who had locally advanced stage IV hypopharyngeal carcinoma were studied retrospectively. Twelve patients were treated with radiotherapy alone, 65 patients were treated with a combination of chemotherapy and radiotherapy, and 13 patients were treated with surgery and postoperative radiotherapy with or without neoadjuvant chemotherapy. Total radiation dose ranged from 59.0 to 88.2 Gy (median 70 Gy) for radiotherpay alone. Most patients had ciplatin and 5-fluorouracil, and others had cisplatin and pepleomycin or vincristin. Median follow-up period was 15 months. Kaplan-Meier method was used for survival rate and Cox proportional hazard model for multivariate analysis of prognostic factors. Results: Overall 3-and 5-year survival rates were 27% and 17%, respectively. The 2-year locoregional control rates were 33% for radiotherapy alone, 32% for combined chemotherapy and radiotherapy, and 81 % for combined surgery and radiotherapy (p=0.006). The prognostic factors affecting overall survival were T stage, concurrent chemoradiation and treatment response. Overall 3-and 5-year laryngeal preservation rates in combined chemotherapy and radiotherapy were 26% and 22%, respectively. Of these, the 5-year laryngeal preservation rates were 52% for concurrent chemoradiation group (n=11), and 16% for neoadjuvant chemotherapy and radiotherapy (n=54, p=0.012). Conclusion: Surgery and postoperative radiotherapy showed better results than radiotherapy alone or with chemotherapy. Radiotherapy combined with concurrent chemotherapy is an effective modality to achieve organ preservation in locally advanced hypopharyngeal cancer. Further prospective randomized studies will be required.

• Radiation Oncology Journal
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• v.19 no.3
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• pp.237-244
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• 2001

Purpose : To assess the tolerance, complete response rate, bladder preservation rate and survival rate in patients with muscle-invading bladder cancer treated with selective bladder preservation protocol. Method and Materials : From October 1990 to June 1998, twenty six patients with muscle-invading bladder cancer (clinical stage T2-4, N0-3, M0) were enrolled for the treatment protocol of bladder preservation. They were treated with maximal TURBT (transurethral resection of bladder tumor) and 2 cycles of MCV chemotherapy (methotrexate, crisplatin, and vinblastine) followed by $39.6\~45\;Gy$ pelvic irradiation with concomitant cisplatin. After complete urologic evaluation (biopsy or cytology), the patients who achieved complete response were planed for bladder preservation treatment and treated with consolidation cisplatin and radiotherapy (19.8 Gy). The patients who had incomplete response were planed to immediate radical cystectomy. If they refused radical cystectomy, they were treated either with TURBT followed by MCV or cisplatin chemotherapy and radiotherapy. The median follow-up duration is 49.5 months. Results : The Patients with stage T2-3a and T3b-4a underwent complete removal of tumor or gross tumor removal by TURBT, respectively. Twenty one out of 26 patients $(81\%)$ successfully completed the protocol of the planned chemo-radiotherapy. Seven patients had documented complete response. Six of them were treated with additional consolidation cisplatin and radiotherapy. One patient was treated with 2 cycles of MCV chemotherapy due to refusal of chemo-radiotherapy. Five of 7 complete responders had functioning tumor-free bladder. Fourteen patients of incomplete responders were further treated with one of the followings : radical cystectomy (1 patient), or TURBT and 2 cycles of MCV chemotherapy (3 patients), or cisplatin and radiotherapy (10 patients). Thirteen patients of them were not treated with planned radical cystectomy due to patients' refusal (9 patients) or underlying medical problems (4 patients). Among twenty one patients, 12 patients $(58\%)$ were alive with their preserved bladder, 8 patients died with the disease, 1 patient died of intercurrent disease. The 5 years actuarial survival rates according to CR and PR after MCV chemotherapy and cisplatin chemoradiotherapy were $80\%\;and\;14\%$, respectively (u=0.001). Conclusion : In selected patients with muscle-invading bladder cancer, the bladder preservation could be achieved by MCV chemotherapy and cisplatin chemo-radiotherapy. All patients tolerated well this bladder preservation protoco. The availability of complete TURBT and the responsibility of neoadjuvant chemotherapy and chemoradiotherapy were important predictors for bladder preservation and survival. The patients who had not achieved complete response after neoadjuvant chemotherapy and chemoradiotherapy should be immediate radical cystectomy. A randomized prospective trial might be essential to determine more accurate indications between cystectomy or bladder preservation.

• Radiation Oncology Journal
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• v.15 no.3
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• pp.255-262
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• 1997

Purpose : This is retrospective study to compare the results of radiation therapy alone and neoadjuvant chemotherapy and radiation in advanced stage of uterine cervical cancer. Materials and Methods : Seventy-six Patients who were treated with definitive radiation therapy for locally advanced cervical cacinoma between June 1988 and December 1993 at the department of radiation oncology, Keimyung University Dong-san Hospital. Thirty six patients were treated with radiation therapy alone and forty patients were treated with cisplatin based neoadjuvant chemotherapy and radiation therapy. According to FIGO staging system. there were 48 patients in stage IIb, 3 patients in stage IIIa, 23 patients in stage lIIb and two patients in stage IVa with median age of 53 years old. Follow-up periods ranged from 7 to 95 months with median 58 months. Results : Complete response (CR) rate were $86.1\%$ in radiation alone group and $80\%$ in chemoradiation group. There was no statistical difference in CR rate between the two groups. Overall five-year survival rate was $67.3\%$. According to stage, overall five-rear survival rates were $74\%$ in stage IIb, $66.7\%$ in stage IIIa, $49.8\%$ in stage IIb, $50\%$ in stage IVa. According to treatment modality overall five year survival rates were $74.1\%$ in radiation alone and $61.4\%$ in chemoradiation group (P=0.4) Five rear local failure free survival rates were $71.5\%$ in radiation alone group and $60\%$ in chemoradiation group (P=0.17). Five year distant metastasis free survival rates were $80.7\%$ in radiation aione group and $89.9\%$ in chemoradiation group (P=0.42). Bone marrow suppression (more than noted in 3 cases of radiaion alone group and 1 case of chemoradiation group. Grade II retal complication was noted in 5 patients of radiation group and 4 patients In chemoradiation group. Bowel obstruction treated with conservative treatment (1 patient) and bowel perforation treated with surgery (1 patient) were noted in radiation alone group. There was no statistical difference in complication between two groups. Conclusion : There was no statistical difference in survival, failure and complication between neoadjuvant chemotherapy and radiation versus radiation alone in locally advanced uterine cervical carcinoma.

• Radiation Oncology Journal
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• v.24 no.4
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• pp.223-229
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• 2006

$\underline{Purpose}$: Combined modality therapy including chemotherapy, surgery and radiotherapy is considered the standard of care for the treatment of stage III non-small cell lung cancer (NSCLC). This study was conducted to evaluate the efficacy of paclitaxel and cisplatin with induction chemotherapy followed by concurrent chemoradiotherapy for stage IIIB NSCLC. $\underline{Materials\;and\;Methods}$: Between July 2000 and October 2005, thirty-nine patients with stage IIIB NSCLC were treated with two cycles of induction chemotherapy followed by concurrent chemoradiotherapy. The induction chemotherapy included the administration of paclitaxel ($175\;mg/m^2$) by intravenous infusion on day 1 and treatment with cisplatin ($75\;mg/m^2$) by intravenous infusion on day 1 every 3 weeks. Concurrent chemoradiotherapy included the use of paclitaxel ($60\;mg/m^2$) plus cisplatin ($25\;mg/m^2$) given intravenously for 6 weeks on day 43, 50, 57, 71, 78 and 85. Thoracic radiotherapy was delivered with 1.8 Gy daily fractions to a total dose of $54{\sim}59.4\;Gy$ in $6{\sim}7$ weeks (median: 59.4 Gy). $\underline{Results}$: The follow up period was $6{\sim}63$ months (median: 21 months). After the induction of chemotherapy, 41.0% (16 patients) showed a partial response and 59.0% (23 patients) had stable disease. After concurrent chemoradiotherapy, 10.3% (4 patients) had a complete response, 41.0% (16 patients) had a partial response, and the overall response rate was 51.3% (20 patients). The 1-, 2-, 3-year overall survival rates were 66.7%, 40.6%, and 27.4% respectively, with a median survival time of 20 months. The 1-, 2-, 3-year progression free survival rates were 43.6%, 24.6%, and 24.6%, respectively, with median progression free survival time of 10.7 months. Induction chemotherapy was well tolerated. Among 39 patients who completed the entire treatment including chemoradiotherapy, 46.3% (18 patients) had esophagitis greater than grade 3 and 28.2% (11 patients) had radiation pneumonitis greater than grade 3. $\underline{Conclusion}$: Paclitaxel and cisplatin with induction chemotherapy followed by concurrent chemoradiotherapy for stage IIIB NSCLC seems to be an effective treatment. Occurrence of esophagitis and pneumonitis represents a significant morbidity and suggests a modification of the treatment regimen, either with the chemotherapy schedule or with radiotherapy treatment planning.

• Radiation Oncology Journal
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• v.24 no.4
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• pp.237-242
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• 2006

$\underline{Purpose}$: We evaluated retrospectively the outcome of locally advanced non-small cell lung cancer patients treated with definitive radiotherapy to find out prognostic factros affecting survival. $\underline{Materials\;and\;Methods}$: 216 cases of stage IIIB non-small cell lung cancer were with treated radiotherapy at our Hospital between 1991 to 2002 and reviewed retrospectively. Cases were classified by mode of treatment and response to treatment. Patients showing complete response or partial response to treatment were included in the "response group", while those showing stable or progressive cancer were included in the "non-response group". $\underline{Results}$: 30 patients completed the planned radiotherapy treatments and 39 patients completed combined treatments or chemoradiotherapy. Median survival was 4.6 months for patients treated with radiotherapy and 9.9 months for those undergoing combined radiotherapy and chemotherapy. Survival rates for the first year were 13.3% with radiotherapy and 35.9% with chemoradiotherapy. In the second year, 3.3% of the radiotherapy patients survived and 20.5% of the patients receiving chemoradiotherapy survived. By the third year, 15.4% of the patients receiving the combined treatments survived. None of the patients treated with radiotherapy alone lived to the third year, however. Overall survival was significantly different between the radiotherapy patients and the combined chemoradiotherapy patients (p<0.001). In the response group, median survival was 7.2 months with radiotherapy and 16.5 months with combined therapy. In the non-response group, median survival was 4.4 months with radiotherapy and 6.7 months with combined treatments. Severe acute complications (grade 3) occurred in 2 cases using radiotherapy, and in 7 cases using combined therapy. $\underline{Conclusion}$: When the patients with stage IIIB non-small cell lung cancer received chemoradiotherapy, treatment response rate and overall survival was greater than with radiation alone.

• Radiation Oncology Journal
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• v.16 no.1
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• pp.35-41
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• 1998

Purpose : To investigate the role of adjuvant chemoradiotherapy in adenocarcinoma of the rectum, we retrospectively compared the treatment results between postoperative adjuvant radiotherapy alone and combined chemoradiotherapy. Material and Methods : From October 1989 to May 1994, 141 patients with rectal carcinoma were treated by postoperative adjuvant therapy in Yonsei Cancer Center. Sixty eight patients were treated by radiation therapy alone. Seventy three patients were treated by combined chemoradiotherapy. Radiation therapy was delivered with 10 MV linear accelerator, 180cGy fraction/5 days per week. Total radiation doses were 5400cGy in the postoperative radiotherapy alone group. Three to twelve cycles of Fluorouracil(mean dose $393.9mg/m^2$) with Leucovorin($20mg/m^2$) and 5040cGy of radiation were delivered in the combined chemoradiotherapy group. Third and 4th cycle of chemotherapy were administrated during the radiation treatment in the combined group. The median follow up was 38 months with a range of 3 to 81 months. Results : The 5 year overall survival rate of radiation alone group and combined group were $60.1\%$ and $66.3\%$, respectively. The 5 year disease free survival rate of radiation aione group and combined group were $54.2\%$ and $65.5\%$, respectively There was no significant difference of overall survival and disease free survival between RT alone group and combined group(p<0.05). But the 5 year Local failure free survival rate of combined group was significantly better than radiotherapy alone group($05.8\%\;vs.\;50.3\%.\;p=0.04$). Conclusion : There was no significant difference in overall survival, disease free survival, and distant metastasis free survival between postoperative adjuvant radiotheray alone group and combinded chemoradiotherapy group. Only the Local failure free survival rate was superior in the combined treatment group. These results confirm the radiosensitizing effect of the chemotherapeutic agent in the combined chemoradiotherapy treatment.

• Radiation Oncology Journal
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• v.25 no.3
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• pp.160-169
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• 2007

Purpose: This study reports the results of the use of preoperative concurrent radiochemotherapy (CRCT) for the treatment of locoregionally advanced esophageal cancer. Materials and Methods: From 1998 through 2005, 61 patients with intrathoracic esophageal cancer at stages II-IVB (without distant organ metastasis and presumed to be respectable) received preoperative CRCT. CRCT consisted of radiotherapy (45 Gy /25 fractions /5 weeks) and FP chemotherapy (5-FU 1 g/$m^{2}$/day, days 1-4 and 29-32, Cisplatin 60 mg/$m^{2}$/day, days 1 and 29). An esophagectomy was planned in $4{\sim}6$ weeks after the completion of CRCT. Results: There were two treatment-related deaths. Among the 61 patients, 53 patients underwent surgery and 17 patients achieved a pathological complete response (pCR). The overall survival (OS) rates of all 61 patients at 2 and 5 years were 59.0% and 38.0%, respectively. The rates of OS and disease-free survival (DFS) of the surgically resected patients at 2 and 5 years were 61.6%, 40.1 % and 53.3%, 41.8%, respectively. By univariate analysis, achieviement of pCR and a clinically uninvolved distant lymph node (cMO) were favorable prognostic factors for OS and DFS. There were 27 patients that experienced a relapse-a locoregional relapse occurred in 5 patients, a distant metastasis occurred in 12 patients and combined failure occurred in 10 patients. Conclusion: The results of the current study are favorable. pCR and an uninvolved distant lymph node were found to be favorable prognostic factors.

• Radiation Oncology Journal
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• v.20 no.3
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• pp.206-214
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• 2002

Purpose : The aim of this study was to assess the effectiveness, survival rate and complications of radiation therapy and chemoradiation treatment in hypopharyngeal cancer. Methods and Materials : From January 1984 to December 1999, 56 patients who had hypopharyngeal carcinoma treated with curative radiation therapy were retrospectively studied. Twenty four patients $(42.9\%)$ were treated with radiation therapy alone (Group I) and $32\;(57.1\%)$ treated with a combination of chemotherapy and radiation (Group II). Total radiation dose ranged from 40.5 to 83. 5 Gy (median 67.9 Gy). Radiotherapy was given with conventional technique in 9 patients $(16.4\%)$, with hyperfractionation I ($1.15\~1.2$ Gy/fr., BID) in 26 $(47.2\%)$, hyperfractionation II (1.35 Gy/fr., BID) in 18 $(32.7\%)$, and accelerated fractionation (1.6 Gy/fr., BID) in 2 $(3.6\%)$. In chemotherapy, 5-FU ($1,000\;mg/m^2$ daily for 5 consecutive days) and cisplatin ($100\;mg/m^2$ on day 1) were administered in a cycle of 3 weeks interval, and a total of 1 to 3 cycles (average 2..3 cycles) were given prior to radiation therapy. Follow up duration was $1\~195$ months (median 28 months). Results : Overall 2 and 5 year survival rates were $40.6\%\;and\;27.6\%;\;50.0\%\;and\;30.0\%$ in Group I, and $36.4\%\;and\;26.3\%$ in Group II, respectively. Complete local control rates in Group I and II were $70.0\%\;and\;67.7\%$, respectively. The response to radiotherapy and nodal stage were statistically significant prognostic factors. The complication rate was increased in Group II and was decreased in hyperfractionation. Conclusion : The response to radiotherapy and nodal stage were valid factors to indicate the degree of control over the hypopharyngeal cancer. The induction cisplatin, 5-Fu chemotherapy was not valid in terms of local control rate and survival rate, but did contribute to an increased complication rate. The use of hyperfractionation was valid to reduce the late radiation complications.

• Radiation Oncology Journal
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• v.13 no.2
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• pp.181-189
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• 1995

Pupose: Radiation therapy(RT) is conventionally standard treatment for locally advanced stage for uterine cervix cancer. Recently to improve treatment results, combined chemotherapy and radiation therapy was tried We retrospectively analysed our experience of 122 patients. Comparision of the results in 45 patients treated with RT alone and 77 patients treated with RT plus chemotherapy was made Materials and Mathods: From January 1985 to December 1991 122 patients with cervix cancer were treated with whole pelvic external RT and ICR(34 1 ICR, 77 2 ICR, 11 high dose rate ICR) in our department. Forty five patients were treated with RT alone, and 77 patients were treated with combined RT plus chemotherapy Mean age was 58 years(range:29-81). Histologic types were 111 squamous cell carcinoma, 5 large cell carcinoma, 3 adenocarcinoma, and 2 adenosquamous cell carcinoma. According to the FIGO stage 6 had stage $IA(4.9\%),$ 11 had $IIA(9.0\%),$ 37 had $IIB(30.3\%),$ 3 had $IIIA(2.5\%),$ 63 had $IIIB(51.6\%).$ and 2 had stage $IV(1.6\%).$ In 77 patients with RT Plus chemotherapy, 36 patients were treated with VBP(vinblastin, bleomycin, cisplatinum) , 39 patients with cisplatinum plus 5-FU and 2 patients with 5-FU. Results: Complete response after external RT (3960cGy-5500cGy) was achieved in 61 patients$(50\%).$ The actuarial 5 year and 9 rear survival rate was $57.8\%\;and\;53.9\%,$ respectively. Five rear actuarial survival rate was $63.1\%$with RT alone(n=45) and $55.9\%$ with RT plus chemotherapy(n=77). The 5 rear survival rate was $35.5\%$ for 1 course of ICR and $67\%$ for 2 courses of ICR. There was statistically significant advantage of survival with RT alone group who were treated with 2 courses of ICR and dose to the A Point)=8000cGy (4/25 died). In RT plus chemotherapy group, dose response was not seen and there was no difference in 5 year survival between 1 course and 2 course of ICR $(50\%\;vs\;56.8\%),$ and dose to point A less than 8000 cGy and more than 8000 $cGy(55.6\%\;vs\;55.7\%).$ There was no significant difference in survival between RT alone and RT plus chemotherapy for patients with tumor size greater than 3cm in size. Five year survival rate for early stage (Stage IB and IIA) with RT alone group and with RT Plus chemotherapy group was $60\%\;and\;77.0\%,$ respectively In advanced stage (stage IIB, IIIA, IIIB, IVA) the 5 year actuarial survival rate were $62.6\%,$ for RT alone group vs $53.6\%$ for RT plus chemotherapy group. Conclusion: Present study demonstrates that there is no survival advantage with adding chemotherapy in advanced stage of uterine cervix cancer. RT alone is considered as treatment of choice for patients with locally advanced cervix cancer. There was increased survival in RT alone group treated with RT dose above 8000 cGy to point A and 2 course of ICR. but 2 course of ICR and RT dose above 8000 cGy to point A did not affect survival advantage in RT plus chemotherapy group.

• 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.