• Journal of radiological science and technology
• /
• v.38 no.4
• /
• pp.463-475
• /
• 2015

The standard treatment of locally advanced type of mid-esophageal cancer is concurrent chemoradiation therapy (CRT). We evaluated the feasibility of chemotherapy with adding docetaxel to the classical basic regimens of cisplatin plus 5-fluorouracil (5-FU) and radiotherapy up to 70.2 Gy using dose escalations for esophageal cancer. It was possible to escalate radiation treatment dose up to 70.2 Gy by the respiratory-gated intensity-modulated radiotherapy (gated-IMRT) based on the 4DCT-simulation, with improving target coverage and normal tissue (ex., lung, heart, and spinal cord) sparing. This study suggested that the definitive chemo-radiotherapy with docetaxel, cisplatin, and 5-fluorouracil (i.e., DCF-R) and gating IMRT is tolerable and active in patients with locally advanced mid-esophageal cancer (AEC).

• Progress in Medical Physics
• /
• v.25 no.2
• /
• pp.89-94
• /
• 2014

We investigated whether regional hyperthermia (HT) increased post-surgical complications in patients with locally advanced rectal cancer treated with preoperative concurrent chemoradiotherapy (CCRT). Between 1996 and 2007, 205 patients treated with preoperative CCRT and curative surgery were evaluable for the analysis of acute and late toxicities. A total dose of 39.6 Gy or 45 Gy was delivered concurrently with one or two cycles of chemotherapy (5-fluorouracil, leucovorin). Eighty-eight patients received regional HT twice a week using an 8-MHz radiofrequency capacitive heating device. Surgery was performed 4~6 weeks after the completion of preoperative CCRT. The median age was 59 years (range, 18~83) and the median follow-up period was 61months (range, 2~191). The 5-year overall survival and complication-free survival rate of all patients was 77.4% and 73.7%, respectively. Early leakage, delayed leakage, anastomotic stricture, fistula, and small bowel obstruction occurred in 1.0%, 2.9%, 1.5%, 5.9%, and 17.1%, respectively. HT did not increase all kinds of complications. The 5-year complication-free survival rate was 71.8% in the non-HT group and 76.3% in the HT group (p=0.293). Regional HT did not increase postoperative complications in patients with locally advanced rectal cancer treated with preoperative CCRT followed by curative surgery.

• Radiation Oncology Journal
• /
• v.26 no.4
• /
• pp.213-221
• /
• 2008

Purpose: The objective of this retrospective study was to identify predictive factors for the complete pathologic response and tumor downstaging after preoperative concurrent chemoradiotherapy for locally advanced rectal cancer. Materials and Methods: Between the years 2000 and 2008, 39 patients with newly diagnosed rectal cancer without prior evidence of distant metastasis received preoperative concurrent chemoradiotherapy followed by surgery. The median radiation dose was 50.4 Gy (range, $45{\sim}59.4\;Gy$)). Thirty-eight patients received concurrent infusional 5-fluorouracil and leucovorin, while one patient received oral capecitabine twice daily during radiotherapy. Results: A complete pathologic response (CR) was demonstrated in 12 of 39 patients (31%), while T-downstaging was observed in 24 of 39 patients (63%). N-downstaging was observed in 18 of 28 patients (64%), with a positive node in the CT scan or ultrasound. Two patients with clinical negative nodes were observed in surgical specimens. The results from a univariate analysis indicated that the tumor circumferential extent was less than 50% (p=0.031). Moreover, the length of the tumor was less than 5 cm (p=0.004), while the post-treatment carcinoembryonic antigen (CEA) levels were less than or equal to 3.0 ng/mL (p=0.015) and were significantly associated with high pathologic CR rates. The univariate analysis also indicated that the adenocarcinoma (p=0.045) and radiation dose greater than or equal to 50 Gy (p=0.021) were significantly associated with high T-downstaging, while a radiotherapy duration of less than or equal to 42 days (p=0.018) was significantly associated with N-downstaging. The results from the multivariate analysis indicated that the lesser circumferential extent of the tumor (hazard ratio [HR] 0.150; p=0.028) and shorter tumor length (HR, 0.084; p=0.005) independently predicted a higher pathologic CR. The multivariate analysis also indicated that a higher radiation dose was significantly associated with higher T-downstaging (HR, 0.115; p=0.025), while the shorter duration of radiotherapy was significantly associated with higher N-downstaging (HR, 0.028; p=0.010). Conclusion: The circumferential extent of the tumor and its length was a predictor for the pathologic CR, while radiation dose and duration of radiotherapy were predictors for tumor downstaging. Hence, these factors may be used to predict outcomes for patients and to develop further treatment guidelines for high-risk patients.

• Radiation Oncology Journal
• /
• v.17 no.2
• /
• pp.100-107
• /
• 1999

Purpose: This is to evaluate the acute complication, resection rate, and tumor down-staging after pre-operative concurrent chemoradiotherapy for stage IIIA (N2) non-small cell lung cancer. Materials and Methods Fifteen patients with non-small cell lung cancer were enrolled in this study from May 1997 to June 1998 in Samsung Medical Center. The median age of the patients was 61 (range, 45~67) years and male to female ratio was 12:3. Pathologic types were squamous cell carcinoma (11) and adenocarcinoma (4). Pre-operative clinical tumor stages were cT1 in 2 patients, cT2 in T2, and cT3 in 1 and all were N2. Ten patients were proved to be N2 with mediastinoscopic biopsy and five had clinically evident mediastinal Iymph node metastases on the chest CT scans. Pre-operative radiation therapy field included the primary tumor, the ipsilateral hilum, and the mediastinum. Total radiation dose was 45 Gy over 5 weeks with daily dose of 1.8 Gy. Pre-operative concurrent chemotherapy consisted of two cycles of intravenous cis-Platin (100 mg/m$^{2}$) on day 1 and oral Etoposide (50 mg/m$^{2}$/day) on days 1 through 14 with 4 weeks' interval. Surgery was followed after the pre-operative re-evaluation including chest CT scan in 3 weeks of the completion of the concurrent chemoradiotherapy if there was no evidence of disease progression. Results : Full dose radiation therapy was administered to all the 15 patients. Planned two cycles of chemotherapy was completed in 11 patients and one cycle was given to four. One treatment related death of acute respiratory distress syndrome occurred In 15 days of surgery. Hospital admission was required in three patients including one with radiation pneumonitis and two with neutropenic fever. Hematologic complications and other acute complications including esophagitis were tolerable. Resection rate was 92.3% (12/l3) in 13 patients excluding two patients who refused surgery. Pleural seeding was found in one patient after thoracotomy and tumor resection was not feasible. Post-operative tumor stagings were pT0 in 3 patients, pTl in 6, and pT2 in 3. Lymph node status findings were pN0 in 8 patients, pN1 in 1, and pN2 in 3. Pathologic tumor down-staging was 61.5% (8/13) including complete response in three patients ($23.7%). Tumor stage was unchanged in four patients (30.8%) and progression was in one (7.7%). Conclusions : Pre-operative concurrent chemoradiotherapy for Stage IIIA (N2) non-small cell lung cancer demonstrated satisfactory results with no increased severe acute complications. This treatment shceme deserves more patinet accrual with long-term follow-up.

• Radiation Oncology Journal
• /
• v.23 no.2
• /
• pp.71-77
• /
• 2005

Purpose: This retrospective study was conduced to analyze the treatment results and to evaluate the prognostic factors affecting the survival of nasopharyngeal carcinoma patients. Materials and Methods: From 1987 to 2002, we analyzed 43 patients who had nasopharyngeal carcinomas that were histologically confirmed and who had also completed the planned radiation therapy course at Keimyung University Dongsan Medical Center According to the 6th edition of American Joint Committee on Cancer staging system, 12 patients ($27.9\%$) were at Stage 11, 13 ($30.2\%$) were at Stage III and 18 ($41.9\%$) were at Stage IV Histopathologically, there were 15 ($34.9\%$) squamous cell carcinomas, 8 ($18.5\%$) nonkeratinizing carcinomas, 17 ($39.5\%$) undifferentiated carcinomas, and 3 ($7.0\%$) lymphoepitheliomas. Among the total 43 patients, 31 patients ($72.1\%$) were treated with only radiation therapy. Neoadjuvant chemotherapy was peformed on 7 patients ($16.3\%$) and concurrent chemoradiotherapy was performed on S patients ($11.6\%$). Cisplatin and 5-Fluorouracil were administered to 11 patients for 4 cycles, and Cisplatin and Taxotere were administered to 1 patient for 6 cycles. The range of the total radiation dose delivered to the primary tumor was from 61.2 to 84 Gy (median 70.4 Gy), The follow-up period ranged from 2 to 197 months with median follow-up of 84 months. Results: The local control rate at 6 months after radiation therapy was $90.7\%$. The five year overall survival and disease free survival rates were $50.7\%$ and $48.9\%$, respectively. On the multivariate analysis, the age, T-stage ($T_{1-3}\;vs\;T_4$), N-stage and AJCC stage were the statistically significant prognostic factors affecting survival (p<0.05). The patterns of failure were as follows: local failure only in 3 patients ($7.0\%$), local and systemic failure in 1 patient ($2.3\%$), and distant metastasis only in 11 patients ($25.6\%$). Conclusion: The prognostic factors affecting the outcome of nasopharyngeal carcinoma were age, T-stage (7$T_{1-3}\;vs\;T_4$), N-stage and stage. Because systemic metastasis was the main failure pattern noted for nasopharyngeal carcinoma, systemic chemotherapy is needed to decrease the rate of distant metastasis for nasopharyngeal carcinoma. In audition, research for more effective chemotherapeutical regimens and schedules is also needed.

• Radiation Oncology Journal
• /
• v.28 no.4
• /
• pp.205-210
• /
• 2010

Purpose: To evaluate the predictive factors for treatment response and prognostic factors affecting survival outcomes after concurrent chemoradiotherapy (CCRT) for patients with anal squamous cell carcinoma. Materials and Methods: Medical records of forty two patients with histologically confirmed analsquamous cell carcinoma, who had complete CCRT between 1993 and 2008, were reviewed retrospectively. Median age was 61.5 years (39~89 years), and median radiotherapy (RT) dose was 50.4 Gy (30.0~64.0 Gy). A total of 36 patients had equal to or less than T2 stage (85.7%). Fourteen patients (33.3%) showed regional nodal metastasis, 36 patients (85.7%) were treated with 5-fluorouracil (5-FU) plus mitomycin, and the remaining patients were treated by 5-FU plus cisplatinum. Results: The median follow-up time was 62 months (2~202 months). The 5-year overall survival, loco regional relapse-free survival, disease-free survival, and colostomy-free survival rates were 86.0%, 71.7%, 71.7%, 78.2%, respectively. Regarding overall survival, the Eastern Cooperative Oncology Group (ECOG) performance status and complete response were found to be significant prognostic factors on univariate analysis. For multivariate analysis, only the ECOG performance status was significant. No significant factor was found for locoregional relapse-free survival or disease-free survival and similarly for treatment response, no significant factor was determined on logistic regression analysis. There were 7 patients who had local or regional recurrences and one patient with distant metastasis. The only evaluable toxicity in all patients was radiation dermatitis of perianal skin (grade 3), which developed in 4 patients (9.5%) and grade 2 in 22 patients (52.4%). Conclusion: This study revealed that patients with a performance score of ECOG 0-1 survived significantly longer than those with a poorer score. Finally, there was no significant predicting factors tested for treatment response.

• Radiation Oncology Journal
• /
• v.27 no.3
• /
• pp.145-152
• /
• 2009

Purpose: We retrospectively studied the outcomes and prognostic factors of patients with locally advanced, unresectable pancreatic cancer who were treated with concurrent chemoradiotherapy (CCRT) or radiotherapy only. Materials and Methods: Fifty-one patients with locally advanced, unresectable pancreatic cancer (stage IIA~III) who recevied radiotherapy ($\geq$30 Gy) between January 1994 and August 2008 were reviewed retrospectively. The median radiation dose was 39 Gy. Chemotherapy consisted of gemcitabine, cisplatin, or 5-FU alone or in various combinations, and was administered concurrently with radiotherapy in 38 patients. Results: The follow-up period ranged from 2~40 months (median, 8 months). The median survival, and the 1-and 2-year overall survival (OS) rates were 7 months, 15.7%, and 5.9%, respectively. Based on univariate analysis, the baseline CA19-9, performance status, and chemotherapy regimen were significant prognostic factors. The median survival was 8 months for CCRT, and 6 months for radiotherapy alone. The patients treated with gemcitabine-containing regimens had longer survival (median, 10 months) than the patients treated with radiotherapy alone (p=0.027). Twenty-three patients were available to evaluate the patterns of failure. Distant metastases (DM) occured in 18 patients and regional recurrences were demonstrated in 4 patients. Local progression developed in 14 patients. We analyzed the association between the time-to-DM and the baseline CA19-9 levels for 18 evaluable patients. The median time-to-DM was 20 months for patients with normal baseline CA19-9 levels and 2 months for patients with baseline CA19-9 levels $\geq$200 U/ml. Conclusion: CCRT with gemcitabine-based regimens was effective in improving OS in patients with locally advanced, unresectable pancreatic cancer. We suggest that the baseline CA19-9 level is valuable in determining the treatment strategy for patients with locally advanced, unresectable pancreatic cancer.

• Korean Journal of Head & Neck Oncology
• /
• v.27 no.2
• /
• pp.183-189
• /
• 2011

서 론: 5-FU와 cisplatin 병용항암화학요법은 국소진행성 두경부편평상피암의 유도화학요법으로 널리 사용되고 있는 요법이다. 저자들은 5-FU 대신 경구제재인 S-1을 cisplatin과 병용하는 복합항암요법의 효과와 안전성에 대해 연구하였다. 대상 및 방법: 저자들은 2007년 2월부터 2008년 12월까지 S1과 cisplatin의 복합유도화학요법을 시행받은 3/4기 구인두, 하인두, 후두, 구강 편평상피세포암 환자 52명의 치료결과를 후향적으로 분석하였다. 유도항암화학요법은 제 1일에 cisplatin(75 또는 60mg/$m^2$), 제1일부터 14일까지 S-1(40mg/$m^2$)을 1일 2회, 21일 간격으로 투여하였고 가능한 경우에는 항암방사선동시요법 또는 수술을 뒤이어 시행하였다. 결 과: 전체 52명 중 37명(71.2%)에서 부분반응을 보였으나 완전반응은 관찰되지 않았다. 2년 무진행생존율은 56.9%, 2년 전체생존율은 68.2%였다. 유도항암요법과 관련된 유해반응으로는 호중구감소증(71.2%) 및 빈혈(63.5%) 등과 같은 혈액학적 부작용이 가장 흔했다. 결 론: S-1과 cisplatin의 복합항암화학요법은 국소진행성 두경부편평상피암 환자를 대상으로 한 유도화학요법으로 적용이 가능한 것으로 판단된다.

• Radiation Oncology Journal
• /
• v.16 no.3
• /
• pp.311-323
• /
• 1998

Purpose : Prospective, single arm, Phase I/II clinical trial was performed to assess the efficacy and toxicity of the concurrent chemotherapy and definitive radiotherapy (RT) in patients with previously untreated locally advanced carcinoma of the uterine cervix. Methods and Materials : From Mar 1992 to January 1997, a total of 73 patients with advanced cervical carcinoma were entered on the protocol but 5 patients were excluded in analysis because of patients' refusal of treatment. Their ages ranged from 31 to 77 years, median 58 years. The International Federation of Gynecology and Obstetrics (FIGO) stage distribution was as follows: IIB 46, IIIA 2, IIIB 15 and IVA 5. RT consisted of external beam irradiation to 4,140-5,040 cGy/23-28 fractions plus high dose rate intracavitary treatments to deliver a dose of 30-35 Gy to point A in 6-7 fractions. During the intracavitary treatments parametrial boost was delivered for point B dose of 60 Gy in stage IIB and 65 Gy in stage IIIB. Two cycles of concurrent 5-fluorouracil and cisplatin (FP) chemotherapy (5-fluorouracil 1,000 mg/$m^2$/day continuous infusion for 4 days, day 1-4, 29-32 and cisplatin 20 mg/$m^2$/day intravenous bolus for 3 days day 1-3, 29-31) administered starting on day 1 of RT. Results : The median follow-up was 24 months (range 4-68+). Sixty-four patients were evaluable for survival rate in this protocol: The 5-year actuarial and disease-free survival rate were 52$\%$ and 64$\%$, respectively. The 5-rear actuarial survival for stage IIB and III+IVA patients were 58$\%$ and 36$\%$, respectively The 5-year disease-free survival rate for stage IIB and III+IVA patients were 71$\%$ and 40$\%$, respectively. Of the 68 patients evaluated for patterns of failure, overall recurrence rate was 27.9$\%$ (19/68) : local failure in 5.9$\%$ (4/68), distant metastasis in 10.3$\%$ (7/68) and both in 11.8$\%$ (8/68). Of the 64 patients evaluated for response at one month after the completion of treatment the complete response rate was 78$\%$ (50/64). Concurrent chemoradiation appear to be a well-tolerated regimen but there were two treatment-related deaths. Conclusion : Concurrent chemotherapy of FP with high-dose definitive RT in locally advanced carcinoma of the uterine cervix is feasible and effective with acceptable toxicities. This chemoradiation regimen may offer a modest survival benefit for advanced stage. Further follow-up of these patients will evaluate the impact of this regimen on the long-term local control and their survival.

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