It is well known that intracavitary radiotherapy (ICR), either alone or in combination with external-beam radiotherapy (EBRT) is an essential component of the radiation treatment of uterine cervical cancer. Although low-dose-rate (LDR) brachytherapy has been successfully applied to the management of such patients, several radiation oncologists have experience of using high-dose-rate (HDR) brachytherapy with promising clinical results over the past 4 decades. However, there has been a considerable reluctance by radiation oncologists and gynecologists in North America to employ the HDR remote afterloading technique instead of the more firmly established LDR treatment modality. In contrast, the HDR-ICR system is rapidly gaining acceptance in Korea since the introduction of the Ralstron, remotely controlled afterloading system using HDR Co-60 sources, at the Yonsei Cancer Center in 1979. According to brachytherapy statistics reported by the Korean Society of Therapeutic Radiology and Oncology, in 1997, brachytherapy was performed upon 1,758 Korean patients with uterine cervical cancer, of whom approximately 83% received HDR brachytherapy. In this review, we present our experiences of HDR-ICR for the treatment of uterine cervical cancer. In addition, we discuss the controversial points, which are raised by those considering the use of HDR-ICR for uterine cervical cancer; these issues include physical and radiobiological considerations, and the prospect of future technical improvements.
Brachytherapy/*methods ; Cervix Neoplasms/*radiotherapy ; Dose Fractionation ; Female ; Human ; Radiotherapy Planning, Computer-Assisted

PURPOSE: The purpose of this study was to describe treatment patterns of radiotherapy (RT) for prostate cancer in Korea. MATERIALS AND METHODS: A questionnaire about radiation treatment technique and principles in 2013 was sent to 83 radiation oncologists and data from 57 hospitals were collected analyzed to find patterns of RT for prostate cancer patients in Korea. RESULTS: The number of patients with prostate cancer treated with definitive RT ranged from 1 to 72 per hospital in 2013. RT doses and target volumes increased according to risk groups but the range of radiation doses was wide (60 to 81.4 Gy) and the fraction size was diverse (1.8 to 5 Gy). Intensity-modulated radiation therapy was used for definitive treatment in 93.8% of hospitals. Hormonal therapy was integrated with radiation for intermediate (63.2%) and high risk patients (77.2%). Adjuvant RT after radical prostatectomy was performed in 46 hospitals (80.7%). Indications of adjuvant RT included positive resection margin, seminal vesicle invasion, and capsular invasion. The total dose for adjuvant RT ranged from 50 to 72 Gy in 24–39 fractions. Salvage RT was delivered with findings of consecutive elevations in prostate-specific antigen (PSA), PSA level over 0.2 ng/mL, or clinical recurrence. The total radiation doses ranged from 50 to 80 Gy with a range of 1.8 to 2.5 Gy per fraction for salvage RT. CONCLUSION: This nationwide patterns of care study suggests that variable radiation techniques and a diverse range of dose fractionation schemes are applied for prostate cancer treatment in Korea. Standard guidelines for RT in prostate cancer need to be developed.
Dose Fractionation ; Humans ; Korea* ; Prostate* ; Prostate-Specific Antigen ; Prostatectomy ; Prostatic Neoplasms* ; Radiotherapy* ; Recurrence ; Seminal Vesicles

BACKGROUND/AIMS: This study reports treatment outcomes after helical intensity-modulated radiotherapy (IMRT) in unresectable hepatocellular carcinoma (HCC) patients for whom transarterial chemoembolization (TACE) was considered ineffective or unsuitable. METHODS: From January 2008 to December 2011, 22 unresectable HCC patients received helical IMRT. A daily dose of 1.8 to 4 Gy was delivered at five fractions per week to deliver a total dose of 30 to 60 Gy. The most-prescribed dose fractionation was a total dose of 50 to 57.5 Gy, with a daily dose of 2.3 to 2.5 Gy. RESULTS: In the entire group, the objective response rate of the primary tumor was 72.7%. In the eight patients with portal vein thrombosis (PVT), the objective response rate of PVT was 50.0%. Median disease progression-free survival was 11.8 months, and the 1-year disease progression-free survival rate was 40.2%. The median overall survival was 14.4 months, and the 1- and 2-year overall survival rates were 86.4% and 69.1%, respectively. PVT and Child-Pugh classifications were significant prognostic factors for overall survival in multivariate analyses. CONCLUSIONS: Helical IMRT in patients with unresectable HCC resulted in high treatment response and survival rates. This study suggests helical IMRT is a practical treatment option for HCC patients in whom TACE is unsuitable or ineffective.
Carcinoma, Hepatocellular ; Disease-Free Survival ; Dose Fractionation ; Humans ; Portal Vein ; Radiotherapy, Intensity-Modulated ; Survival Rate ; Thrombosis

To access the result of radiation therapy for 8 years experiences, 21 patients who were treated with superior vena cava syndrome had been analysed according to dose fractionation and toal dose. The results are as follows; 1. In high fractionate dose group, six of eleven patients (54.5%) exhibited relief of symptoms in 1-2 days, and additional three patients of nine (81.7%) within 3-4 days, while standard fractionated dose treatment is not effective to achieve initial relief of symptoms. 2. Graded response by total dose was correlated with total dose rather than dose fractionation. 3. Overall one year survival rate with superior vana cava syndrome was 9.1% and mean survival was 4.2 months.
Dose Fractionation ; Humans ; Radiotherapy ; Superior Vena Cava Syndrome* ; Survival Rate ; Vena Cava, Superior*

The schemes of dose fractionation play an important role in tumor radiotherapy. We used mathematical methods to describe the process of tumor cells evolution during radiotherapy, trying to find how the schemes of dose fractionation affect tumor cells. In clinical radiobiology, linear-quadratic (LQ) model is frequently used to describe radiation effects of tumor cells. We integrated LQ model with effect of oxygen, and with the phenomenon of repopulation and reoxygenation in the theory of radiation biology. While we considered the disappearing progress of doomed cells in tumor, we established the mathematical model of tumor evolution in radiotherapy. We simulated some common treatment schedules, and studied the change role of tumor cells during radiotherapy. These results can serve for the optimization of dose fractionation scheme based on tumor radiobiological characteristics.
Cell Growth Processes ; radiation effects ; Dose Fractionation ; Humans ; Models, Theoretical ; Neoplasms ; pathology ; physiopathology ; radiotherapy ; Radiobiology

Total of 53 patients of unresectable and recurrent rectal cancer treated with neutron beam during the period from Oct. 1987 to Apr. 1992 were analyzed. Dose fractionation for the neutron only group was 1.5 Gy per fraction, 3 fraction per week, 21 Gy/41/2 wks for 42 patients out of 53(76%). Neutron only but modified fractionation schedule (10% more or less of total dose) was applied for 9 patients, and mixed team (neutron boost) was for 4 patients. Complete tumor response was obtained in 40 patients(76% response rate). Local control rate was 28 out of 53(53%). Statistically significant better prognostic factors for local control were age below 49 years old (15/22, 68%) than above 50 years old (13/31, 42%), male (20/32, 63%) than female(8/21, 38%), tumor size less than 5 cm and non-metastatic(16/24, 67%) than size more than 5 cm or metastatic(12/29, 4l%). Major complication had developed in 7 patients (13%). Two year overall survival rate by Kaplan-Meier method was 30%, but it was rised to, 47% when the tumor was less than 5cm non-metastatic.
Appointments and Schedules ; Dose Fractionation ; Humans ; Male ; Middle Aged ; Neutrons* ; Rectal Neoplasms* ; Survival Rate

PURPOSE: This study was conducted to compare clinical outcomes and treatment-related toxicities after stereotactic body radiation therapy (SBRT) with two different dose regimens for small hepatocellular carcinomas (HCC) ≤3 cm in size. MATERIALS AND METHODS: We retrospectively reviewed 44 patients with liver-confined HCC treated between 2009 and 2014 with SBRT. Total doses of 45 Gy (n = 10) or 60 Gy (n = 34) in 3 fractions were prescribed to the 95% isodose line covering 95% of the planning target volume. Rates of local control (LC), intrahepatic failure-free survival (IHFFS), distant metastasis-free survival (DMFS), and overall survival (OS) were calculated using the Kaplan-Meier method. RESULTS: Median follow-up was 29 months (range, 8 to 64 months). Rates at 1 and 3 years were 97.7% and 95.0% for LC, 97.7% and 80.7% for OS, 76% and 40.5% for IHFFS, and 87.3% and 79.5% for DMFS. Five patients (11.4%) experienced degradation of albumin-bilirubin grade, 2 (4.5%) degradation of Child-Pugh score, and 4 (9.1%) grade 3 or greater laboratory abnormalities within 3 months after SBRT. No significant difference was seen in any oncological outcomes or treatment-related toxicities between the two dose regimens. CONCLUSIONS: SBRT was highly effective for local control without severe toxicities in patients with HCC smaller than 3 cm. The regimen of a total dose of 45 Gy in 3 fractions was comparable to 60 Gy in efficacy and safety of SBRT for small HCC.
Carcinoma, Hepatocellular ; Dose Fractionation ; Follow-Up Studies ; Humans ; Methods ; Radiosurgery ; Retrospective Studies

To evaluate the efficacy of hyperfractionated re-irradiation using a three-dimensional conformal radiotherapy (3-D CRT) technique in patients with locally recurrent carcinoma of the nasopharynx. Four patients with locally recurrent nasopharyngeal cancer were retreated with a hyperfractionated schedule using a 3-D CRT technique. Re-irradiation was delivered in 1.1-1.2 Gy fractions twice per day (BID), with interfraction intervals of more than 6 hours. The total dose ranged from 59.4 to 69.2 Gy. A 3-D CRT technique with 5- or 6-field coplanar and/or non-coplanar beams were employed during the entire treatment procedure. All four patients achieved complete remission of locally recurrent lesions, with marked improvement of subjective symptoms, immediately after re-irradiation. All are alive and well without evidence of disease after limited follow-up periods, which range from 7 to 20 months. So far, there have been no radiation-induced neurologic complications. Four patients with locally recurrent carcinoma of the nasopharynx were successfully treated by hyperfractionated re-irradiation using a 3-D CRT technique. A relatively high re-irradiation dose of more than 60 Gy may be safely delivered with no serious acute or late radiation-induced complications in patients with local recurrences and who were initially treated with doses greater than 70 Gy.
Aged ; Dose Fractionation* ; Human ; Male ; Middle Age ; Nasopharyngeal Neoplasms/radiotherapy* ; Neoplasm Recurrence, Local/radiotherapy* ; Radiotherapy Dosage ; Radiotherapy, Conformal*

BACKGROUND: The best dose-fractionation regimen of the definitive radiotherapy for cervix cancer remains to be clearly determined. It seems to be partially attributed to the complexity of the affecting factors and the lack of detailed information on external and intra-cavitary fractionation. To find optimal practice guidelines, our experiences of the combination of external beam radiotherapy (EBRT) and high-dose-rate intracavitary brachytherapy (HDR-ICBT) were reviewed with detailed information of the various treatment parameters obtained from a large cohort of women treated homogeneously at a single institute. MATERIALS AND METHODS: The subjects were 743 cervical cancer patients (Stage IB 198, IIA 77, IIB 364, IIIA 7, IIIB 89 and IVA 8) treated by radiotherapy alone, between 1990 and 1996. A total external beam radiotherapy (EBRT) dose of 23.4~59.4 Gy (Median 45.0) was delivered to the whole pelvis. High-dose-rate intracavitary brachytherapy (HDR-ICBT) was also performed using various fractionation schemes. A Midline block (MLB) was initiated after the delivery of 14.4~43.2 Gy (Median 36.0) of EBRT in 495 patients, while in the other 248 patients EBRT could not be used due to slow tumor regression or the huge initial bulk of tumor. The point A, actual bladder & rectal doses were individually assessed in all patients. The biologically effective dose (BED) to the tumor (alpha/beta=10) and late-responding tissues (alpha/beta=3) for both EBRT and HDR-ICBT were calculated. The total BED values to point A, the actual bladder and rectal reference points were the summation of the EBRT and HDR-ICBT. In addition to all the details on dose-fractionation, the other factors (i.e. the overall treatment time, physicians preference) that can affect the schedule of the definitive radiotherapy were also thoroughly analyzed. The association between MD-BED Gy3 and the risk of complication was assessed using serial multiple logistic regression models. The associations between R-BED Gy3 and rectal complications and between V-BED Gy3 and bladder complications were assessed using multiple logistic regression models after adjustment for age, stage, tumor size and treatment duration. Serial Coxs proportional hazard regression models were used to estimate the relative risks of recurrence due to MD-BED Gy10, and the treatment duration. RESULTS: The overall complication rate for RTOG Grades 1~4 toxicities was 33.1%. The 5-year actuarial pelvic control rate for all 743 patients was 83%. The midline cumulative BED dose, which is the sum of external midline BED and HDR-ICBT point A BED, ranged from 62.0 to 121.9 Gy10 (median 93.0) for tumors and from 93.6 to 187.3 Gy3 (median 137.6) for late responding tissues. The median cumulative values of actual rectal (R-BED Gy3) and bladder point BED (V-BED Gy3) were 118.7 Gy3 (range 48.8~265.2) and 126.1 Gy3 (range: 54.9~267.5), respectively. MD-BED Gy3 showed a good correlation with rectal (p=0.003), but not with bladder complications (p=0.095). R-BED Gy3 had a very strong association (p=<0.0001), and was more predictive of rectal complications than A-BED Gy3. B-BED Gy3 also showed significance in the prediction of bladder complications in a trend test (p=0.0298). No statistically significant dose-response relationship for pelvic control was observed. The Sandwich and Continuous techniques, which differ according to when the ICR was inserted during the EBRT and due to the physicians preference, showed no differences in the local control and complication rates; there were also no differences in the 3 vs. 5 Gy fraction size of HDR-ICBT. CONCLUSION: The main reasons optimal dose-fractionation guidelines are not easily established is due to the absence of a dose-response relationship for tumor control as a result of the high-dose gradient of HDR-ICBT, individual differences in tumor responses to radiation therapy and the complexity of affecting factors. Therefore, in our opinion, there is a necessity for individualized tailored therapy, along with general guidelines, in the definitive radiation treatment for cervix cancer. This study also demonstrated the strong predictive value of actual rectal and bladder reference dosing therefore, vaginal gauze packing might be very important. To maintain the BED dose to less than the threshold resulting in complication, early midline shielding, the HDR-ICBT total dose and fractional dose reduction should be considered.
Appointments and Schedules* ; Brachytherapy ; Cohort Studies ; Dose Fractionation* ; Female ; Humans ; Individuality ; Logistic Models ; Pelvis ; Radiotherapy* ; Recurrence ; Urinary Bladder ; Uterine Cervical Neoplasms*

BACKGROUND: The best dose-fractionation regimen of the definitive radiotherapy for cervix cancer remains to be clearly determined. It seems to be partially attributed to the complexity of the affecting factors and the lack of detailed information on external and intra-cavitary fractionation. To find optimal practice guidelines, our experiences of the combination of external beam radiotherapy (EBRT) and high-dose-rate intracavitary brachytherapy (HDR-ICBT) were reviewed with detailed information of the various treatment parameters obtained from a large cohort of women treated homogeneously at a single institute. MATERIALS AND METHODS: The subjects were 743 cervical cancer patients (Stage IB 198, IIA 77, IIB 364, IIIA 7, IIIB 89 and IVA 8) treated by radiotherapy alone, between 1990 and 1996. A total external beam radiotherapy (EBRT) dose of 23.4~59.4 Gy (Median 45.0) was delivered to the whole pelvis. High-dose-rate intracavitary brachytherapy (HDR-ICBT) was also performed using various fractionation schemes. A Midline block (MLB) was initiated after the delivery of 14.4~43.2 Gy (Median 36.0) of EBRT in 495 patients, while in the other 248 patients EBRT could not be used due to slow tumor regression or the huge initial bulk of tumor. The point A, actual bladder & rectal doses were individually assessed in all patients. The biologically effective dose (BED) to the tumor (alpha/beta=10) and late-responding tissues (alpha/beta=3) for both EBRT and HDR-ICBT were calculated. The total BED values to point A, the actual bladder and rectal reference points were the summation of the EBRT and HDR-ICBT. In addition to all the details on dose-fractionation, the other factors (i.e. the overall treatment time, physicians preference) that can affect the schedule of the definitive radiotherapy were also thoroughly analyzed. The association between MD-BED Gy3 and the risk of complication was assessed using serial multiple logistic regression models. The associations between R-BED Gy3 and rectal complications and between V-BED Gy3 and bladder complications were assessed using multiple logistic regression models after adjustment for age, stage, tumor size and treatment duration. Serial Coxs proportional hazard regression models were used to estimate the relative risks of recurrence due to MD-BED Gy10, and the treatment duration. RESULTS: The overall complication rate for RTOG Grades 1~4 toxicities was 33.1%. The 5-year actuarial pelvic control rate for all 743 patients was 83%. The midline cumulative BED dose, which is the sum of external midline BED and HDR-ICBT point A BED, ranged from 62.0 to 121.9 Gy10 (median 93.0) for tumors and from 93.6 to 187.3 Gy3 (median 137.6) for late responding tissues. The median cumulative values of actual rectal (R-BED Gy3) and bladder point BED (V-BED Gy3) were 118.7 Gy3 (range 48.8~265.2) and 126.1 Gy3 (range: 54.9~267.5), respectively. MD-BED Gy3 showed a good correlation with rectal (p=0.003), but not with bladder complications (p=0.095). R-BED Gy3 had a very strong association (p=<0.0001), and was more predictive of rectal complications than A-BED Gy3. B-BED Gy3 also showed significance in the prediction of bladder complications in a trend test (p=0.0298). No statistically significant dose-response relationship for pelvic control was observed. The Sandwich and Continuous techniques, which differ according to when the ICR was inserted during the EBRT and due to the physicians preference, showed no differences in the local control and complication rates; there were also no differences in the 3 vs. 5 Gy fraction size of HDR-ICBT. CONCLUSION: The main reasons optimal dose-fractionation guidelines are not easily established is due to the absence of a dose-response relationship for tumor control as a result of the high-dose gradient of HDR-ICBT, individual differences in tumor responses to radiation therapy and the complexity of affecting factors. Therefore, in our opinion, there is a necessity for individualized tailored therapy, along with general guidelines, in the definitive radiation treatment for cervix cancer. This study also demonstrated the strong predictive value of actual rectal and bladder reference dosing therefore, vaginal gauze packing might be very important. To maintain the BED dose to less than the threshold resulting in complication, early midline shielding, the HDR-ICBT total dose and fractional dose reduction should be considered.
Appointments and Schedules* ; Brachytherapy ; Cohort Studies ; Dose Fractionation* ; Female ; Humans ; Individuality ; Logistic Models ; Pelvis ; Radiotherapy* ; Recurrence ; Urinary Bladder ; Uterine Cervical Neoplasms*