• 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.6 no.2
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• pp.211-226
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• 1988

Among 165 patients of esophagus cancer treated by either radiation alone or postoperative radiation, median survival period was 6.6 months, $16\%$ 3 years and $8\%$ 5years crude survival. In biphasic plotting of survival curve semilogarithmically all nonresponder died within one year regardless of treatments and in responder each 1, 2, 3 years survival rate was $80\%,\;70\%,\;60\%$ in the group of postoperative radiation among 20 patients ($54\%$ of 37 patients) respectively and $62\%,\;38\%,\; 23\%$ each in the group of radiation alone among 61 patients ($48\%$ of 128 patients) respectively, better survival rate of postoperative radiation vs radiation alone in 3 year (P<0.01). The most common cause of death was dysphagia $55\%$, and majority of patients died by failure to control the disease locally $62\%,\;88\%$ of stricture were associated with persistenece of cancer in esophagus. $50\%$ of patients was found to have locoregional metastatc nodes. Preoperative diagnostic failure rate was for metastatic locoregional nodes was $54\%$, for grossly metastatic nodes $29.7\%$, for blood borne organ metastasis $13.5\%$, and for local extent of the disease $14\%$. The residual cancer at surgical margin o. postitive node was not effectively killed by either 5000 to 5500 cGy conventional radiation or 5290 to 5750 cGy with 115 cGy fraction in 2 times daily; hyperfractionated radiation. However hyperfractionation schedule decreased the both acute and late complications in this study.

• Radiation Oncology Journal
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• v.34 no.4
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• pp.239-249
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• 2016

Tumor hypoxia, a common feature occurring in nearly all human solid tumors is a major contributing factor for failures of anticancer therapies. Because ionizing radiation depends heavily on the presence of molecular oxygen to produce cytotoxic effect, the negative impact of tumor hypoxia had long been recognized. In this review, we will highlight some of the past attempts to overcome tumor hypoxia including hypoxic radiosensitizers and hypoxia-selective cytotoxin. Although they were (still are) a very clever idea, they lacked clinical efficacy largely because of 'reoxygenation' phenomenon occurring in the conventional low dose hyperfractionation radiotherapy prevented proper activation of these compounds. Recent meta-analysis and imaging studies do however indicate that there may be a significant clinical benefit in lowering the locoregional failures by using these compounds. Latest technological advancement in radiotherapy has allowed to deliver high doses of radiation conformally to the tumor volume. Although this technology has brought superb clinical responses for many types of cancer, recent modeling studies have predicted that tumor hypoxia is even more serious because 'reoxygenation' is low thereby leaving a large portion of hypoxic tumor cells behind. Wouldn't it be then reasonable to combine hypoxic radiosensitizers and/or hypoxia-selective cytotoxin with the latest radiotherapy? We will provide some preclinical and clinical evidence to support this idea hoping to revamp an enthusiasm for hypoxic radiosensitizers or hypoxia-selective cytotoxins as an adjunct therapy for radiotherapy.

• Radiation Oncology Journal
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• v.21 no.2
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• pp.112-117
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• 2003

Purpose: The effects of hypefractionation radiation therapy, such as the failure pattern and survival, on the treatment results in advanced stage head and neck cancer were studied. Materials and Methods: Between September 1990 and October 1998, 24 patients with advanced stage (III, IV) head and neck cancers, were treated using hyperfractionation radiation therapy in the Department of Radiation Oncology at the Keimyung University Dongsan Medical Center. The male to female ratio was 7 : 1, and the age range from 38 to 71 years with the median of 56 years. With regard to the TNM stage, 11 patients were stage III and 13 were stage IV. The sites of primary cancer were the nasopharynx in six, the hypopharynx in 6, the larynx in five, the oropharynx in three, the maxillary sinus in three, and the oral cavity in one patient. The radiotherapy was delivered by 6 MV X-ray, with a fraction size of 1.2 Gy at two fractions a day, with at least 6 hours inter-fractional interval. The mean total radiation doses was 72 Gy, (ranging from 64.4 to 75.8 Gy). Follow-up periods ranged between 3 and 136 months, with the median of 52 months. Results: The overall survival rates at 3 and 5 years in all patients were 66.7$\%$, and 52.4$\%$. The disease-free survival rates at 3 and S years (3YDFS, 5YDFS) in all patients were 66.7$\%$ and 47.6$\%$. The 3YDFS and 5YDFS in stage III patients were 81.8$\%$ and 63.6$\%$, and those in stage IV patients were 53.8$\%$ and 32.3$\%$. Ten patients were alive with no local nor distant failures at the time of analyses. Six patients (25$\%$) died due to distant metastasis and 12.5$\%$ died due to local failure. Distant metastasis was the major cause of failure, but 2 patients died due to unknown failures and 3 of other diseases. The distant metastasis sites were the lung (3 patients), the bone (1 patient), and the liver (2 patients). One patient died of second esophageal cancer. There were no severe late complications, with the exception of 1 osteo-radionecrosis of the mandible 58 months after treatment. Conclusion: Although this study was peformed on small patients group, we considered hypefractionated radiation therapy for the treatment of advanced stage head and neck cancer might improve the disease free survival and decrease the local failure with no increase in late complications despite of the slight Increase in acute complications.

• Radiation Oncology Journal
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• v.13 no.2
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• pp.143-148
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• 1995

Purpose: We tried to evaluate the role of conventional radiotherapy alone or with neoadjuvant chemotherapy in the hypopharyngeal cancer by retrospective analysis. Materials and Methods: Between Jul.1985 and Sep.1992, 42 patients of hypopharyngeal cancer were treated by conventional radiotherapy alone or combined with neoadjuvant chemotherapy. The male to female ratio was 20:1 with a median age of 58 years, Twelve Patients were treated by conventional radiotherapy alone and 30 patients were treated by neoadjuvant chemotherapy and radiotherapy. Results: Seven Patients were Stage I,II and the patients with stage III and IV were 10 and 25, respectively at the time of presentation. The overall survival and disease-specific survival rates at 24 months were $12.9\%$ and $15.5\%,$respectively Two-year survival rates of stage I+II and III+IV patients were $50\%$ and $6.3\%,$ respectively(p(0.05). Sixteen Patients$(38\%)$ revealed CR and 26 patients$(62\%)$ revealed less than CR at the end of radiotherapy and their 2-year survival rates were $31.3\%\;and\;0\%,$ respectively(p(0.05). On univariate analysis, stage, T-stage, N-stage and treatment response were the significant prognostic factors, but only stage and treatment response were significant on multivariate analysis Conclusion : This conventional radiotherapy alone or with neoadjuvant chemotherapy does not seem to be sufficient in the treatment of most advanced hypopharyngeal cancer Therefore other treatment modalities such as hyperfractionation or concurrent chemoradiotherapy should be considered.

• Radiation Oncology Journal
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• v.10 no.1
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• pp.15-20
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• 1992

A total of 20 patients (male: female=10:10, adult:children=8:12) with brainstem tumors had been received radiation therapy in the Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine between 1980 and 1990. Thirteen of 20 patients were treated with conventional radiation therapy (before 1989, 180~200 cGy per fraction, 5 days a week, total dose 4680~5400 cGy), and seven patients were treated with hyperfractionated radiation therapy (in 1990, 100 cGy per fraction, twice daily 10 fractions a week, total dose 7200 cGy). Median follow up Periods for conventional radiation therapy group and hyperfractionated radiation therapy group were 36 months and 10 months, respectively. Four of 20 Patients had histopathologic diagnosis prior to treatment; 3 cases were low grade astrocytoma and 1 case was high grade astrocytoma. Overall 2-year actuarial survival rate was 30%. The prognosis of patients with a longer duration of symptom and sign was better (60%, vs 12%), and the adult (52%) was better than children (14%). There was no significant difference between the focal (29%) and diffuse (26%) type. The initial clinical response was better in the hyperfractionated radiation therapy group. Because of the relatively small number of Patients and short follow up Period in hyperfractionated radiation therapy group, there was no comparison between two group.

• Radiation Oncology Journal
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• v.9 no.2
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• pp.221-225
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• 1991

Twenty five patients with unresectable non-small cell carcinoma of the lung have been treated with hyperfractionated radiotherapy with concomitant boost technique since September, 1989. Those patients with history of previous surgery or chemotherapy, pleural effusion or significant weight loss (greater than $10\%$ of body weight) were excluded from the study. Initially, 27 Gy were delivered in 15 fractions in 3 weeks to the large field. Thereafter, large field received 1.8 Gy and cone down boost field received 1.4 Gy with twice a day fractinations up to 49.4 Gy. After 49.4Gy, only boost field was treated twice a day with 1.8 and 1.4 Gy. Total tumor doses were 62.2 Gy for 12 patients and 65.4 Gy for remaining 13 patients. Follow up period was ranged from 6 to 24 month. Actuarial survival rates at 6, 12, and 18 month were $88\%,\;62\%,\;and\;38\%$, respectively. Corresponding disease free suwival rates were $88\%,\;41\%,\;and\;21\%$, respectively. Actuarial cumulative local failure rates at 9, 12 and 15 month were $36\%,\;43\%,\;and\;59\%$, respectively. No significant increase of acute or late complications including radiation pneumonitis was noted with maximum follow up of 24 month. Although the longer follow up is needed, it is worthwhile to try the prospective randomized study to evaluate the efficacy of hyperfractionated radiotherapy with concomitant boost technique for unresectable non-small cell lung cancers in view of excellent tolerance of this treatment. In the future, further increase of total radiation dose might be necessary to improve local control for non-small cell lung cancer.

• Radiation Oncology Journal
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• v.15 no.3
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• pp.243-249
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• 1997

Purpose : In radiation therapy, NTCF is very importart indicator of selecting the optimal treatment plan. In our study, we tried to find out usefullness of NTCP in lung cancer by comparng the incidence of radiation pneumonitis with NTCP. Materials and Methods : From August 1993 to December 1994, thirty six patients with locally advanced non=small cell lung cancer were treated by concurrent chemoradiation therapy. Total dose of radiation therapy was 6480cGy (120cGy, bid) and chemotherapeutlc agents were mitomycin C. vinblastion, cisplatin (2 cycles, 4 weeks interval). We evaluated the development of raniation pneumonitis by CT scan, chest x-rar and clinical symptoms. We used grading system of South Western Oncology Group (SWOG) for radiation pneumanitis. Dose Volume Histograms (DVH) were analyzed for ipsilateral and whole lung, Non uniform DVH was translated to uniform DVH by effective volume method. With these data, we calculated NTCP for ipsilateral and whole lung. Finally we compared the clinical results to NTCP. Results : Eight of thrity six patients developed radiation pneumonitis. Of these 8 patients , 6 had grade I severity and 2 had grade II. The average NTCP value cf the patients who showed radiation pneumonitis was significantly higher than that uf the patients without pneumonitis $(66\%\;vs.\;26.4\%)$. But the results of pulmonary function test was not correlated with NTCP. Conclusion : NTCP of lung is very good indicator for selecting rival treatment planning in lung cancer. According to the results of NTCP, it may be possible to adjust target volume and optimize target dose. In the near future, we are going to anaiyze the effect of hyperfractionation and concurrent chemotherapy in addition to NTCP.

• Radiation Oncology Journal
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• v.26 no.1
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• pp.24-34
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• 2008

Purpose: To assess the efficacy of the use of accelerated hyperfractionated radiotherapy(AHRT) for locally advanced uterine cervix cancers. Materials and Methods: Between May 2000 and September 2002, 179 patients were identified with FIGO stage IIB, IIIB, and IVA cancers. Of the 179 patients, 45 patients were treated with AHRT(AHRT group) and 134 patients were treated with conventional radiotherapy(CRT group), respectively. Patients undergoing the AHRT regimen received a dose of 30 Gy in 20 fractions(1.5 $Gy{\times}2$ fractions/day) to the whole pelvis. Subsequently, with a midline block, we administered a parametrial boost with a dose of 20 Gy using 2 Gy fractions. Patients also received two courses of low-dose-rate brachytherapy, up to a total dose of 85{\sim}90 Gy to point A. In the CRT group of patients, the total dose to point A was $85{\sim}90$ Gy. The overall treatment duration was a median of 37 and 66 days for patients that received AHRT and CRT, respectively. Statistical analysis was calculated by use of the Kaplan-Meier method, the log-rank test, and Chi-squared test. Results: For patients that received cisplatin-based concurrent chemotherapy and radiotherapy, the local control rate at 5 years was 100% and 79.2% for the AHRT and CRT group of patients, respectively(p=0.028). The 5-year survival rate for patients with a stage IIB bulky tumor was 82.6% and 62.1% for the AHRT group and CRT group, respectively(p=0.040). There was no statistically significant difference for severe late toxicity between the two groups(p=0.561). Conclusion: In this study, we observed that treatment with AHRT with concurrent chemotherapy allows a significant advantage of local control and survival for locally advanced uterine cervix cancers.

• Radiation Oncology Journal
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• v.13 no.3
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• pp.215-223
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• 1995

Purpose : The aim of this study was to assess the effectiveness, survival rate and complication of radiation in nasopharyngeal cancer. Materials and Methods : From January 1980 to May 1989. Fifty patients who had nasopharyngeal carcinoma treated with curative radiation therapy at Kosin Medical Center were retrospectively studied. Thirty seven patients($74{\%}$) were treated with radiation therapy alone(Group I) and 13 patients ($26{\%}$) treated with combination of chemotherapy and radiation (Group II). Age distribution was 16-75 years(median : 45.8 years). In histologic type, squamous cell carcinoma was in 30 patients($60{\%}$), undifferentiated carcinoma in 17 patients($34{\%}$), and lymphoepithelioma in 3 patients($6{\%}$). According t AJCC staging system. 4 patients($8{\%}$) were in $T_1$, 13 patients($26{\%}$) in $T_2$. 20 patients($40{\%}$) in $T_3$, 13 patients($26{\%}$) in $T_4$ and 7 patients($14{\%}$) in $N_0$, 6 patients($12{\%}$) $N_1$, 23 patients($46{\%}$) in $N_2$, 14 patients($28{\%}$) in $N_3$. Total radiation dose ranges were 5250-9200cGy(median : 7355 cGy) in Group I and 5360-8400cGy(median : 6758cGy) in Group II Radiotherapy on 4-6MV linear accelerator and/or 6-12MeV electron in boost radiation was given with conventional technique to 26 patients($52{\%}$), with hyperfractionation(115-120cGy/fr., 2times/day) to 16 patients($32{\%}$), with accelerated fractionation(160cGy/fr., 2 times/day) to 8 patients($16{\%}$). In chemotherapy, 5 FU 1000mg daily for 5 consecutive days, pepleomycin 10mg on days 1 and 3, and cisplatin 100mg on day 1 were administered with 3weeks interval, total 1 to 3 cycles(average 1.8cycles) prior to radiation therapy. Follow up duration was 6-140 months(mean : 58 months). Statistics was calculated with Chi-square and Fisher's exact test. Results : Complete local control rates in Group I and II were $75.7{\%},\;69.2{\%} Overall 5 year survival rates in Group I and II were $56.8{\%},\;30.8{\%}$. Five year survival rates by histologic type in Group I and II were $52.2{\%},\;14.3{\%}$ is squamous cell carcinoma and $54.5{\%},\;50{\%}$ in undifferentiated carcinoma. Survival rates in Group I were superior to those of Group II though there were not statistically significant. In both group, survival rates seem to be increased according to increasing total dose of radiation up to 7500cGy, but not increased beyond it. There were not statistically significant differences in survival rates by age, stage, and radiation techniques in both group. Twenty four patients($48{\%}$) experienced treatment failures. Complications were found in 12 patients($24{\%}$). The most common one was osteomyelitis(4 patients, $33.3{\%}$) involving mandible (3 patients) and maxilla(1 patient). Conclusion : Chemotherapy in combination with radiotherapy was found to be not effective to nasopharyngeal cancer and the survival rate was also inferior to that of radiation alone group though it was statistically not significant due to small population in chemotherapy combined group.