• Radiation Oncology Journal
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• v.27 no.3
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• pp.133-139
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• 2009

Purpose: This study was designed to analyze the outcome and toxicity of thoracic radiation therapy (TRT) and chemotherapy for patients who suffer with limited-stage small-cell lung cancer (LS-SCLC). Materials and Methods: We retrospectively studied 35 patients with LS-SCLC. TRT was administered once daily (1.8 to 2 Gy per fraction) and it was directed to the primary tumor for a total 50 to 66 Gy in 6 to 7 weeks. The patients received four cycles of etoposide plus cisplatin. TRT was begun on day 1 of the first cycle of chemotherapy in the concurrent arm and after the fourth cycle in the sequential arm. Results: The median progression-free survival time was 16.5 months (95% confidence interval [CI], 9.0 to 24.1 months) for the sequential arm, and 26.3 months (95% CI, 16.6 to 35.9 months) for the concurrent arm. The 2-year progression-free survival rate was 16.0 percent for the sequential arm and 50.0 percent for the concurrent arm (p=0.0950 by log-rank test). Leukopenia was more severe and more frequent in the concurrent arm than in the sequential arm. However, severe esophagitis was infrequent in both arms. The radiotherapy was interrupted more frequently in the concurrent arm than in the sequential arm due to hematologic toxicities (p=0.001). Conclusion: This study suggests that concurrent TRT with etoposide plus cisplatin is more effective for the treatment of LS-SCLC than sequential TRT. However, there is a significant increase in the risk of toxicities, and radiotherapy was frequently interrupted in the concurrent arm due to hematologic toxicities.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.15
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• pp.6595-6597
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• 2015

Objective: To investigate short- and long-term treatment effects and side reactions of lobaplatin plus 5-Fu combined and concurrent radiotherapy in treating patients with inoperable middle-advanced stage esophageal cancer. Methods: Sixty patients with middle-advanced stage esophageal squamous cell cancer were retrospectively analyzed. All patients were administered lobaplatin (50 mg intravenously) for 2 h on day 1, and 5-Fu ($500mg/m^2$) injected intravenously from day 1 to 5 for 1 cycle, in an interval of 21 days for totally 4 cycles. At the same time, late-course accelerated hyperfractionated three-dimensional conformal radiotherapy was performed. Patients were firstly treated with conventional fractionated irradiation (1.8 Gy/d, 5 times/week, a total of 23 treatments, and DT41.4 Gy), and then treated with accelerated hyperfractionated irradiation (1.5 Gy, 2 times/d, a total of 27 Gy in 9 days, an entire course of 6-7 weeks, and DT 68.4Gy). Results: All patients completed treatment, including 10 complete response (CR), 41 partial response (PR), 7 stable disease (SD), and 2 progressive disease (PD). The total effective rate was 85.0% (51/60). Thirty-nine patients had an increased KPS score. One-, 2-, and 3-year survival rates were 85.3%, 57.5%, and 41.7%, respectively. The median survival time was 27 months. The adverse reactions included myelosuppression, which was mainly degree I and II. The occurrence rate of radiation esophagitis was 17.5%. No significant hepatic or renal toxicity was observed. Conclusion: Lobaplatin plus 5-Fu combined with concurrent radiotherapy is safe and effective in treating patients with middle-advanced stage esophageal cancer. However, this result warrants further evaluation by randomized clinical studies.

• Radiation Oncology Journal
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• v.26 no.3
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• pp.160-165
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• 2008

Purpose: In cases of locally advanced non-small cell lung cancer (NSCLC), concurrent chemoradiotherapy(CCRT) is the leading therapeutic modality. However, much controversy exists about the chemotherapeutic regimens and radiation methods. Materials and Methods: During concurrent chemoradiotherapy, three or four cycles of gemcitabine ($500\;mg/m^2$) and cisplatin ($30\;mg/m^2$) were administered every two weeks while 50.4 Gy of irradiation was administered in 28 fractions (once/day, 5 treatment days/week) to the tumor site, mediastinum, and the involved lymph node region. In addition, a booster irradiation dose of 18 Gy in 10 fractions was administered to the primary tumor site unless the disease progressed. Two or three cycles of consolidation chemotherapy were performed with gemcitabine ($1,200\;mg/m^2$, $1^{st}$ and 8th day) and cisplatin ($60\;mg/m^2$) every three weeks. Results: A total of 29 patients were evaluable for modality response. Response and treatment toxicities were assessed after concurrent chemoradiotherapy and consolidation chemotherapy, respectively. One patient (4%) achieved a complete response; whereas 20 patients (69%) achieved a partial response after concurrent chemoradiotherapy. Following the consolidation chemotherapy, three patients (10.3%) achieved complete responses and 21 patients (72.4%) achieved partial responses. The median follow-up period was 20 months (range $3{\sim}39$ months) and the median survival time was 16 months (95% CI; $2.4{\sim}39.2$ months). The survival rates in one, two, and three years after the completion of treatment were 62.7%, 43.9%, and 20%, respectively. Complications associated to this treatment modality included grade 3 or 4 esophagitis, which occurred in 15 patients (51.7%). In addition, an incidence of 24% for grade 3 and 14% for grade 4 neutropenia. Lastly, grade 2 radiation pneumonitis occurred in 6 patients (22%). Conclusion: The response rate and survival time of concurrent chemoradiotherapy with biweekly gemcitabine ($500\;mg/m^2$) and cisplatin ($30\;mg/m^2$) were encouraging in patients with locally advanced NSCLC. However, treatment related toxicities were significant, indicating that further modification of therapy seems to be warranted.

• Radiation Oncology Journal
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• v.16 no.4
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• pp.409-423
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• 1998

Purpose : This retrospective study was tried to evaluate the clinical characteristics of patients, patterns of failure, survival rates, prognostic factors affecting survival, and treatment related toxicities when non-small cell lung cancer patients was treated by definitive radiotherapy alone or combined with chemotherapy. Materials and Methods : We evaluated the treatment results of 70 patients who were treated by definitive radiation therapy for non-small cell lung cancer at the Department of Radiation Oncology, Ewha Womans University Hospital, between March 1982 and April 1996. The number of patients of each stage was 2 in stage I, 6 in stage II, 30 in stage III-A, 29 in stage III-B, 3 in stage IV. Radiation therapy was administered by 6 MV linear accelerator and daily dose was 1.8-2.0 Gy and total radiation dose was ranged from 50.4 Gy to 72.0 Gy with median dose 59.4 Gy. Thirty four patients was treated with combined therapy with neoadjuvant or concurrent chemotherapy and radiotherapy, and most of them were administered with the multi-drug combined chemotherapy including etoposide and cisplatin. The survival rate was calculated with the Kaplan-Meier methods. Results : The overall 1-year, 2-year, and 3-year survival rates were 63$\%$, 29$\%$, and 26$\%$, respectively. The median survival time of all patients was 17 months. The disease-free survival rate for 1-year and 2-year were 23$\%$ and 16$\%$, respectively. The overall 1-year survival rates according to the stage was 100$\%$ for stage I, 80$\%$ for stage II, 61$\%$ for stage III, and 50$\%$ for stage IV. The overall 1-year 2-year, and 3-year survival rates for stage III patients only were 61$\%$, 23$\%$, and 20$\%$, respectively. The median survival time of stage III patients only was 15 months. The complete response rates by radiation therapy was 10$\%$ and partial response rate was 50$\%$. Thirty patients (43$\%$) among 70 patients assessed local control at initial 3 months follow-up duration. Twenty four (80$\%$) of these 30 Patients was possible to evaluate the pattern of failure after achievement of local control. And then, treatment failure occured in 14 patients (58$\%$): local relapse in 6 patients (43$\%$), distant metastasis in 6 patients (43$\%$) and local relapse with distant metastasis in 2 patients (14$\%$). Therefore, 10 patients (23$\%$) were controlled of disease of primary site with or without distant metastases. Twenty three patients (46$\%$) among 50 patients who were possible to follow-up had distant metastasis. The overall 1-year survival rate according to the treatment modalities was 59$\%$ in radiotherapy alone and 66$\%$ in chemoirradiation group. The overall 1-year survival rates for stage III patients only was 51$\%$ in radiotherapy alone and 68$\%$ in chemoirradiation group which was significant different. The significant prognostic factors affecting survival rate were the stage and the achievement of local control for all patients at univariate- analysis. Use of neoadjuvant or concurrent chemotherapy, use of chemotherapy and the achievement of local control for stage III patients only were also prognostic factors. The stage, pretreatment performance status, use of neoadjuvant or concurrent chemotherapy, total radiation dose and the achievement of local control were significant at multivariate analysis. The treatment-related toxicities were esophagitis, radiation pneunonitis, hematologic toxicity and dermatitis, which were spontaneously improved, but 2 patients were died with radiation pneumonitis. Conclusion : The conventional radiation therapy was not sufficient therapy for achievement of long-term survival in locally advanced non-small cell lung cancer. Therefore, aggressive treatment including the addition of appropriate chemotherapeutic drug to decrease distant metastasis and preoperative radiotherapy combined with surgery, hyperfractionation radiotherapy or 3-D conformal radiation therapy for increase local control are needed.

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

• Tuberculosis and Respiratory Diseases
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• v.63 no.2
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• pp.154-164
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• 2007

Background: Irinotecan hydrochloride, a topoisomerase I inhibitor, is effective against small-cell lung cancer. Irinotecan also can act as a potential radiation sensitizer along with cisplatin. To evaluate efficacy and toxicity of irinotecan plus cisplatin (IP) with concurrent thoracic radiotherapy, we conducted a phase II study of IP followed by concurrent IP plus hyperfractionated thoracic radiotherapy in patients with previously untreated limited-stage small-cell lung cancer. Methods: Twenty-four patients with previously untreated small-cell lung cancer were enrolled onto the study since November 2004. Irinotecan $60mg/m^2$ was administered intravenously on days 1 and 8 in combination with cisplatin $60mg/m^2$ on day1 every 21 days. From the first day of third cycle, twice-daily thoracic irradiation (total 45 Gy) was given. Prophylactic cranial irradiation was given to the patients who showed complete remission after concurrent chemoradiotherapy. Restaging was done after second and sixth cycle with chest CT and/or bronchosocpy. Results: Up to November 2004, 19 patients were assessable. The median follow-up time was 12.5 months. A total of 99 cycles (median 5.2 cycles per patient) were administered. The actual dose intensity values were cisplatin $19.6mg/m^2$/week and irinotecan $38.2mg/m^2$/week. Among the 19 patients, the objective response rate was 95% (19 patients), with 9 patients (47%) having a complete response (CR). The major grade 3/4 hematological toxicities were neutropenia (35% of cycles), anemia (7% of cycles), thrombocytopenia (7% of cycles). Febrile neutropenia was 4% of cycles. The predominant grade 3/4 non-hematological toxicities was diarrhea (5% of cycles). Toxicities was not significantly different with concurrent administration of irinotecan and cisplatin with radiotherapy, except grade 3/4 radiation esophagitis (10% of patients). No treatment-related deaths were observed. The 1-year and 2-year survival rate of eligible patients was 89% (16/18) and 47% (9/18), respectively. Conclusion: Three-week schedule of irinotecan plus cisplatin followed by concurrent IP plus hyperfractionated thoracic radiotherapy is an effective treatment for limited disease small-cell lung cancer, with acceptable toxicity.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.4
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• pp.1699-1702
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• 2014

Objective: To evaluate clinical efficacy of a dose escalating schedule of paclitaxel concurrent with radiotherapy in treating patients with locally advanced non-small cell lung (NSCLC). Methods: Patients with locally advanced NSCLC were treated with conventional fractionated radiotherapy or three dimensional conformal radiotherapy (3 DCRT), concurrently with a dose escalating schedule of paclitaxel. All patients were divided into three groups, A with paclitaxel $30mg/m^2$, B with paclitaxel $60mg/m^2$ and C with paclitaxel $90mg/m^2$. Paclitaxel was repeated every week for a total of 4 or 6 weeks. Results: Among 109 patients, response rates were 68.8%, 71.1% and 71.8% (p>0.05) for group A (n=32), B (n=38), and C (n=39) respectively. Accordingly, disease control rates were 81.3%, 81.6% and 82.1% (p>0.05). Progression-free survival time was $8.0{\pm}5.0$ months, $11.6{\pm}6.1$ months, and $14.8{\pm}7.9$ months (p<0.05), respectively. Overall survival time was $15.4{\pm}7.6$ months, $18.2{\pm}8.0$ months, and $22.0{\pm}7.6$ months (p<0.05), one-year survival rates were 62.5%, 73.1% and 90.0% (p>0.05) and two-year survival rates were 31.3%, 38.5% and 50.0% (p<0.05). Main side-effects were bone marrow suppression, radiation related esophagitis and gastrointestinal reaction. Conclusion: In treating patients with NSCLC, concurrent chemoradiotherapy with paclitaxel improves early response compared with conventional fractionated radiotherapy or 3 DCRT. The survival rate was improved with the addition of paclitaxel, but there was an increase in adverse reactions when the dose of paclitaxel was increased.

• Journal of Chest Surgery
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• v.33 no.8
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• pp.662-668
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• 2000

Background: Many recent results of clinical trials show that pre-operative concurrent chemoradiotherapy and surgical resection could increase the survival of N2 positive stage IIIA non-small cell lung cancer. This study was performed to assess the feasibility, toxicity, and affect rates of concurrent chemoradiotherapy and surgical resection in N2 positive stage IIIA non-small cell lung cancer. Material and Method: Thirty-one patients who underwent preoperative concurrent chemoradiotherapy for N2 positive stage IIIA non-small-cell lung cancer from May 1997 to April 1999 were entered into the study. Mean age was 61 yrs(43∼70 yrs), There were 24 men and 7 women. The confirmation of N2 disease were achieved through mediastinoscopic biopsy(24) and CT scans(7). Induction was achieved by two cycles of cisplatin and etoposide(EP) plus concurrent chest radiotherapy to 45 Gy. Resections were done at 3 weeks after the complection of preoperative concurrent chemoradiotherapy. Resections were performed in 23 patients, excluding 5 refusals and 3 distant metastasis. Result: All patients were compled the thoracic radiotherapy except one who had distant metastasis. Twenty three patients were completed the planned 2 cycles of EP chemotherapy, and 8 patients were received only 1 cycle for severe side effects(6), refusal(1), and distant metastasis(1). There was one postoperative mortality, and the cause of death was ARDS. Three patients who had neutropenic fever and one patient who had radiation pneumonitis were required admission and treatment. Esophagitis was the most common acute side effect, but relatively well-tolerated in most patients. The complection rate of concurrent chemoradiotherapy was 74%, resection rate was 71%, pathologic complete remission rate was 13.6%, and pathologic down-staging rate was 68%. Conclusion: Morbidity related to each treatment was acceptable and many of the patients have benefited down staging of its disease. Further prospective, preferably randomized, clinical trials of larger scale may be warranted to confirm the actual benefit of preoperative concurrent chemoradiotherapy and surgical resection in N2-positive stage IIIA non-small cell lung cancer.

• Radiation Oncology Journal
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• v.24 no.4
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• pp.230-236
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• 2006

$\underline{Purpose}$: To analyze the response, toxicity, patterns of failure and survival rate of patients with locally advanced non-small cell lung cancer who were treated with concurrent chemoradiotherapy with weekly paclitaxel. $\underline{Materials\;and\;Methods}$: Twenty-three patients with locally advanced non-small cell lung cancer patients who received radical chemoradiotherapy from October 1999 to September 2004 were included in this retrospective study. Patients received total $55.4{\sim}64.8$ (median 64.8) Gy (daily 1.8 Gy per fraction, 5 days per weeks) over $7{\sim}8$ weeks. 50 or $60\;mg/m^2$ of paclitaxel was administered on day 1, 8, 15, 22, 29 and 36 of radiotherapy. Four weeks after the concurrent chemoradiotherapy, three cycles of consolidation chemotherapy consisted of paclitaxel $135\;mg/m^2$ and cisplatin $75\;mg/m^2$ was administered every 3 weeks. $\underline{Results}$: Of the 23 patients, 3 patients refused to receive the treatment during the concurrent chemoradiotherapy. One patient died of bacterial pneumonia during the concurrent chemoradiotherapy. Grade 2 radiation esophagitis was observed in 4 patients (17%). Sixteen patients received consolidation chemotherapy. During the consolidation chemotherapy, 8 patients (50%) experienced grade 3 or 4 neutropenia and one of those patients died of neutropenic sepsis. Overall response rate for 20 evaluable patients was 90% including 4 complete responses (20%) and 14 partial responses (70%). Among 18 responders, 9 had local failure, 3 had local and distant failure and 2 had distant failure only. Median progression-free survival time was 9.5 months and 2-year progression-free survival rate was 19%. Eleven patients received second-line or third-line chemotherapy after the treatment failure. The median overall survival time was 21 months. 2-year and 5-year survival rate were 43% and 33%, respectively. Age, performance status, tumor size were significant prognostic factors for progression-free survival. $\underline{Conclusion}$: Concurrent chemoradiotherapy with weekly paclitaxel revealed high response rate and low toxicity rate. But local failure occurred frequently after the remission and large tumor size was a poor prognostic factor. Further investigations are needed to improve the local control.

• Tuberculosis and Respiratory Diseases
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• v.57 no.3
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• pp.257-264
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• 2004

Background : There are many combinations of treatment for locally advanced non-small cell lung cancer (NSCLC). Recent studies have showed the efficacy of concurrent chemoradiotherapy (CCRT) in NSCLC. At present, however, there is no consensus about the optimal dosages and timing of radiation and chemotherapeutic agents. The aims of study were to determine the feasibility, toxicity, response rate, and survival rate in locally advanced NSCLC patients treated with doxetaxel and cisplatin based CCRT. Method : Sixteen patients with unresectable stage III NSCLC were evaluated from May 2000 until September 2001. Induction chemoradiotherapy consisted of 3 cycles of docetaxel (75 $mg/m^2/IV$ on day 1) and cisplatin (60 $mg/m^2/IV$ on day 1) chemotherapy every 3 weeks and concomitant hyperfractionated chest irradiation (1.15 Gy/BID, total dose of 69 Gy) in 6 weeks. Patient who had complete or partial response, and stable disease were applied consolidation chemotherapy of docetaxel and cisplatin. Results : All patients showed response to CCRT. Four patients achieved complete response (25%), partial responses in 12 patients (75%). The major common toxicities were grade III or more of neutropenia (87.3%), grade III esophagitis (68.8%), pneumonia (18.8%) and grade III radiation pneumonitis (12.5%). Thirteen patients were ceased during follow-up period. Median survival time was 19.9 months (95% CI; 4.3-39.7 months). The survival rates in one, two, and three years are 68.7%, 43.7%, and 29.1%, respectively. Local recurrence was found in 11 patients (66.8%), bone metastasis in 2, and brain metastasis in 1 patient. Conclusion : The response rate and survival time of CCRT with docetaxel/cisplatin in locally advanced NSCLC were encouraging, but treatment related toxicities were high. Further modification of therapy seems to be warranted.