• 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.

• 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.247-256
• /
• 2008

Purpose: The purpose of this study is to evaluate anal sphincter preservation rates, survival rates, and prognostic factors in patients with rectal cancer treated with preoperative chemoradiotherapy. Materials and Methods: One hundred fifty patients with pathologic confirmed rectal cancer and treated by preoperative chemoradiotherapy between January 1999 and June 2007. Of the 150 patients, the 82 who completed the scheduled chemoradiotherapy, received definitive surgery at our hospital, and did not have distant metastasis upon initial diagnosis were enrolled in this study. The radiation dose delivered to the whole pelvis ranged from 41.4 to 46.0 Gy (median 44.0 Gy) using daily fractions of $1.8{\sim}2.0\;Gy$ at 5 days per week and a boost dose to the primary tumor and high risk area up to a total of $43.2{\sim}54\;Gy$ (median 50.4 Gy). Sixty patients (80.5%) received 5-fluorouracil, leucovorin, and cisplatin, while 16 patients (19.5%) were administered 5-fluorouracil and leucovorin every 4 weeks concurrently during radiotherapy. Surgery was performed for 3 to 45 weeks (median 7 weeks) after completion of chemoradiotherapy. Results: The sphincter preservation rates for all patients were 73.2% (60/82). Of the 48 patients whose tumor was located at less than 5 cm away from the anal verge, 31 (64.6%) underwent sphincter-saving surgery. Moreover, of the 34 patients whose tumor was located at greater than or equal to 5 cm away from the anal verge, 29 (85.3%) were able to preserve their anal sphincter. A pathologic complete response was achieved in 14.6% (12/82) of all patients. The downstaging rates were 42.7% (35/82) for the T stage, 75.5% (37/49) for the N stage, and 67.1% (55/82) for the overall stages. The median follow-up period was 38 months (range $11{\sim}107$ months). The overall 5-year survival, disease-free survival, and locoregional control rates were 67.4%, 58.9% and 84.4%, respectively. The 5-year overall survival rates based on the pathologic stage were 100% for stage 0 (n=12), 59.1% for stage I (n=16), 78.6% for stage II (n=30), 36.9% for stage III (n=23), and one patient with pathologic stage IV was alive for 43 months (p=0.02). The 5-year disease-free survival rates were 77.8% for stage 0, 63.6% for stage I, 58.9% for stage II, 51.1% for stage III, and 0% for stage IV (p<0.001). The 5-year locoregional control rates were 88.9% for stage 0, 93.8% for stage I, 91.1% for stage II, 68.2% for stage III, and one patient with pathologic stage IV was alive without local recurrence (p=0.01). The results of a multivariate analysis with age (${\leq}55$ vs. >55), clinical stage (I+II vs. III), radiotherapy to surgery interval (${\leq}6$ weeks vs. >6 weeks), operation type (sphincter preservation vs. no preservation), pathologic T stage, pathologic N stage, pathologic overall stage (0 vs. I+II vs. III+IV), and pathologic response (complete vs. non-CR), only age and pathologic N stage were significant predictors of overall survival, pathologic overall stage for disease-free survival, and pathologic N stage for locoregional control rates, respectively. Recurrence was observed in 25 patients (local recurrence in 10 patients, distant metastasis in 13 patients, and both in 2 patients). Acute hematologic toxicity ($\geq$grade 3) during chemoradiotherapy was observed in 2 patients, while skin toxicity was observed in 1 patient. Complications developing within 60 days after surgery and required admission or surgical intervention, were observed in 11 patients: anastomotic leakage in 5 patients, pelvic abscess in 2 patients, and others in 4 patients. Conclusion: Preoperative chemoradiotherapy was an effective modality to achieve downstaging and sphincter preservation in rectal cancer cases with a relatively low toxicity. Pathologic N stage was a statistically significant prognostic factor for survival and locoregional control and so, more intensified postoperative adjuvant chemotherapy should be considered in these patients.

• Radiation Oncology Journal
• /
• v.22 no.1
• /
• pp.1-10
• /
• 2004

Locally advanced (Stage III) non-small cell lung cancer (NSCLC) accounts for approximately one third of all cases of NSCLC. Few patients with locally advanced NSCLC present with disease amenable to curative surgical resection. Historically, these patients were treated with primary thoracic radiation therapy (RT) and had poor long term survival rates, due to both progression of local disease and development on distant metastases. Over the last two decades, the use of multidisciplinary approach has improved the outcome for patients with locally advanced NSCLC. Combined chemoradiotherapy is the most favored approach for treatment of locally advanced unresectable NSCLC. There are two basic treatment protocols for administering combined chemotherapy and radiation, sequential versus concurrent. The rationale for using chemotherapy is to eliminate subclinical metastatic disease while improving local control. Sequential use of chemotherapy followed by radiotherapy has improved median and long term survival compared to radiation therapy alone. This approach appears to decrease the risk of distant metastases,, but local failure rates remain the same as radiation alone. Concurrent chemoradiotherapy has been studied extensively. The potential advantages of this approach may include sensitization of tumor cells to radiation by the administration of chemotherapy, and reduced overall treatment time compared to sequential therapy; which is known to be important for improving local control in radiation biology. This approach Improves survival primarily as a result of improved local control. However, it doesn't seem to decrease the risk of distant metastases probably because concurrent chemoradiation requires dose reductions in chemotherapy due to increased risks of acute morbidity such as acute esophageal toxicity. Although multidisciplinary therapy has led to improved survival rates compared to radiation therapy alone and has become the new standard of care, the optimal therapy of locally advanced NSCLC continues to evolve. The current issues in the multidisciplinary management of locally advanced NSCLC will be reviewed in this report.

• Korean Journal of Head & Neck Oncology
• /
• v.14 no.2
• /
• pp.182-190
• /
• 1998

Background: Most of the cancers of maxillary sinus are the squamous variety, but various histopathologic types of malignant tumor can occur in the maxillary sinus. These non-squamous cell tumors have quite different patterns of clinical behavior compared with squamous variety, such as invasive characters, route of metastasis, treatment modality, and so on. Objectives: The authors intend to establish the clinical characteristics and treatment modalities of non-squamous cell tumors of the maxillary sinus. Material and Methods: We experienced 16 cases of non-squamous cell tumors arisen from the maxillary sinus during the 10-year period from 1987 to 1996. We analyzed their clinical features, therapeutic modalities and results with review of literatures. Results: According to AJCC TNM system, 13 patients presented with $T_{1-2}$, 3 with $T_{3-}4$, Two patients were treated with surgery after radiotherapy, 3 patients with surgery after chemotherapy and radiotherapy, 4 patients with chemotherapy and radiotherpy, 5 patients with chemotherapy and radiotherapy after surgery. Conclusion: In cases of adenoid cystic carcinoma, adenocarcinoma and sarcoma, we believe that the best form of therapy is wide surgical excision. If there is microscopic evidence of disease at or close to the resection margin, postoperative radiation was used to achieve better local control. In cases of undifferentiated carcinoma, preoperative chemotherapy and radiation therapy showed improved outcomes.

• Radiation Oncology Journal
• /
• v.15 no.2
• /
• pp.113-119
• /
• 1997

Purpose : Radical gastrectomy is main treatment of gastric cancer. But the result is not satisfactory with surgery alone. Most of pattern of failure remain locoregional recurrence. To improve 5 year survival postoperative chemotherapy with or without radiotherapy has been used. We analyzed patients with stage III and IV stomach cancer who had radical operation and received postoperative radiation therapy combined with or without chemotherapy retrospectively. Material and Method : From March 1985 to June 1993, 68 patients treated with curative resection and received postoperative adiuvant radiotherapy with 36Gy or more were evaluated. Median age was 60 years(range 28-66 yrs) . Patients were followed from 3 to 133 months with median follow up of 48 months. Thirty seven patients had non signet ring adenocarcinoma, 29 signet ring cell, 2 other cell. Patients with stage IIIA, IIIB, IV disease were 19, 25 and 24 respectively Chemotherapy was given to all patients except two. Results : Five-year overall survival and disease-free survival rate were 36.6% and 33.6%, respectively. Prognostic factor affecting survival were assessed. High ratio of jnvolved/dissected Iymph node, signet ring histology showed Poor Prognosis with statistical significance. Presence of residual tumor after surgery, stageIV. split course of radiation therapy, age, number of involved Iymph node, number of Iymph node dissection and grade of tumor affected survival without statistical significance, Type of chemotherapy did not affect survival. Recurrence was documented in 34 patients. High recurrence was seen in omentum and peritoneum with 23.5%, and remnant stomach, anastomosis site, A-loop and I-loop had also high recurrence with 13.2%. In field locoregional recurrence was 20.7% and total distant metastases were 39.7%. Total intraabdominal failure was 47.1% and extraabdominal failure was 13.2%. Treatment toxicity was considered to be acceptable. 22.1% of patients had grade 3 and only 1 patient had grade 4 leukopenia. Six Patients(8.8%) had weigh loss more than 10%. Conclusion : Treatment toxicity was acceptable with combined treatment with chemotherapy and radiotherapy. Locoregional recurrence was relatively low compared to distant failure with addition of irradiation. Peritoneal and omental seeding was high Five-rear surival was increased with combined modality. Radiation may eradicate minimal residual disease and improve survival, To evaluate role of radiation Prospective randomized study employing chemotherapy alone and chemotherapy plus radiation is necessary. Futhermore to reduce intraabdominal failure, role of intraabdominal chemotherapy in addition to combined chemotherapy plus radiation has to be explored.

• Radiation Oncology Journal
• /
• v.15 no.2
• /
• pp.105-111
• /
• 1997

group($22\%\;vs.\;38\%$, p=0.24). The 5YSRs of 21 patients of primary tumor extension to adjacent sites and the other 13 patients of tonsillar proper site were $28\%\;and\;38\%$, respectively but the difference was not significant statistically(p=0.52) There was a statistically significant difference in 5YSRs between the groups of the Patients who received radiotherapy in less than 61days vs more than 60days($60\%\;vs.\;18\%$, p=0.027). All living Patients without any tumor progression(n=11) had suffered from serious late sequelae such as xerostomia, edentia, dental caries and one patient had the osteoradionecrosis of mandible. On univariate analysis. the duration of radiotherapy and T-stage were the significant prognostic factors affecting 5YSR. On multivariate analysis, also the duration of radiotherapy was the only significant Prognostic factor(p=0.01). Conclusion : There was no survival difference between the radiotherapy alone and with neoadiuvant chemothe groups. Although it was a retrospective study, the role of conventional radiotherapy alone could be effective as the local treatment modality only for the early stage of tonsillar carcinomas. But for the purpose of more improved survivals and better quality of lives of living patients, other altered fractionation such as hyperfractionated radiotherapy with shorter treatment time and smaller fraction size rather than conventional radiotherapy might be beneficial and these prospective studies are needed.

• Radiation Oncology Journal
• /
• v.18 no.1
• /
• pp.17-25
• /
• 2000

Purpose : To evaluate the side effects, pattern of failure, and survival rate according to the sequence of postoperative adjuvant radiotherapy and chemotherapy, patients with stages II and III rectal cancer who had undergone curative resection were randomized to 'early radiotherapy group (arm I)' or' late radiotherapy group (arm II)', then we intend to determine the most effective sequence of the radiotherapy and chemotherapy. Materials and Methods . From January 1996 to March 1999, 313 patients with curatively resected stages II and III rectal cancer have been randomized to' early' or' late' radiation therapy group and received combined chemotherapy (5-FU 375 mg/m$^{2}$/day, ieucovorin 20 mg/m$^{2}$, IV bolus daily Dl-5, 8 cycles) and radiation therapy (whole pelvis with 45 Gy/25 fractions/s weeks). Arm I received radiation therapy from day 1 with first cycle of chemotherapy and arm II received radiation therapy from day 57 with third cycle of chemotherapy after completion of first two cycles. Preliminary analysis was peformed with 228 patients registered up to Jun 1998. Two out of the 228 patients were excluded because of double primary cancer. Median follow-up period was 23 months. Results :Local recurrence occurred in 11 patients (9.7$\%$) for arm I and 9 patients (8$\%$) for arm 11. There was no significant difference between both groups ( p=0.64). However, distant metastasis was found in 22 patients (19.5$\%$) for arm I and 35 patients (31.0$\%$) for arm II and which showed statistically significant difference between the two groups ( p=0.046). And neither 3-year disease-free survival (70.2$\%$ vs 59.2$\%$, p=0.2) nor overall survival (89.4$\%$ vs 88.0$\%$, p=0.47) showed significant differences. The incidence of leukopenia during radiation therapy and chemotherapy was 78.3$\%$ and 79.9$\%$ respectively but leukopenia more than RTOG grade 3 was only 2.1$\%$ and 6.0$\%$ respectively. The incidence of diarrhea more than 10 times per day was significantly higher in the patients for arm I than for arm II (71.2$\%$ vs 41.6$\%$, p=0.02) but this complication was controlled with supportive cares. Conclusion : Regardless of the sequence of postoperative adjuvant radiation therapy and chemotherapy after curative resection for rectal cancer, local recurrence rate was low with combined chemoradlotherapy. But distant metastasis rate was lower in early radiation therapy group than in late radiation therapy group and the reason is unclear. Most patients completed these treatments without severe complication, so these were thought to be safe treatments but the treatment compliance should be improved.

• Radiation Oncology Journal
• /
• v.20 no.1
• /
• pp.53-61
• /
• 2002

Purpose : To determine the optimal scheme of postoperative chemoradiotherapy in rectal cancer by comparing survival, Patterns of failure, toxicities in early and late radiotherapy groups using a Phase III randomized prospective clinical trial. Materials and Methods : From January 1996 to March 1999, 307 patients with curatively resected AJCC stage II and III rectal cancer were assigned randomly to an 'early (151 patients, arm 1)' or a 'late (156 patients, arm II)' and were administered combined chemotherapy (5-FU $375\;mg/m^2/day$, leucovorin $20\;mg/m^2$, IV bolus daily, for 3 days with RT, 5 days without RT, 8 cycles with 4 weeks interval) and radiation therapy (whole pelvis with 45 Gy/25 fractions/5 weeks). Patients of arm I received radiation therapy from day 1 of the first cycle of chemotherapy and those of arm II from day 57 with a third cycle of chemotherapy. The median follow-up period of living patients was 40 months. Results : Of the 307 patients enrolled, fifty patients did not receive scheduled radiation therapy or chemotherapy. The overall survival rate and disease free survival rate at 5 years were $78.3\%\;and\;68.7\%$ in arm I, and $78.4\%\;and\;67.5\%$ in arm II. The local recurrence rate was $6.6\%\;and\;6.4\%$ (p=0.46) in arms I and II, respectively, no significant difference was observed between the distant metastasis rates of the two arms ($23.8\%\;and\;29.5\%$, p=0.16). During radiation therapy, grade 3 diarrhea or more, by the NCI common toxicity criteria, was observed in $63.0\%\;and\;58.2\%$ of the respective arms (p=N.S.), but most were controlled with supportive care. Hematologic toxicity (leukopenia) greater than RTOG grade 2 was found in only $1.3\%\;and\;2.6\%$ of patients in each respective arm. Conclusion : There was no significant difference in survival, patterns of failure or toxicities between the early and late radiation therapy arms. Postoperative adjuvant chemoradiation was found to be a relatively safe treatment but higher compliance is needed.

• 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.