Meta-analysis of the efficacy and adverse reactions of fractionated high dose rate brachytherapy as monotherapy for localized prostate cancer / 中华放射肿瘤学杂志

Objective:To conduct a meta-analysis to analyze the efficacy and adverse reactions of fractionated high dose rate brachytherapy (HDR-BT) as monotherapy for localized prostate cancer.Methods:Relevant databases were searched to collect the clinical trials on HDR-BT as monotherapy in patients with localized prostate cancer. Included studies were limited to full-text publications of fractionated HDR-BT as monotherapy with a median follow-up of at least 5 years, and adequate reporting of treatment outcomes and adverse reactions data. Stata 12.0 was used for data analysis.Results:According to the inclusion and exclusion criteria, a total of 11 clinical trials involving 2 683 patients with prostate cancer were included in this meta-analysis. The results of the meta-analysis showed that 5-year biochemical recurrence-free survival (bRFS) rate and overall survival (OS) rate were 94% (95% CI: 93% - 96%) and 96% (95% CI: 94% - 98%), respectively. Long-term (≥5 years) cancer-specific survival (CSS) rate and distant metastasis-free survival (DMFS) rate were 99% (95% CI: 98% - 100%) and 98% (95% CI: 98% - 99%), respectively. Long-term (≥5 years) late grade ≥3 grade gastrointestinal and genitourinary adverse reactions rates were 2% (95% CI: 1% - 3%) and 9% (95% CI: 6% - 13%), respectively. Conclusions:Fractionated HDR-BT as monotherapy is an effective treatment for patients with localized prostate cancer. Its long-term efficacy is encouraging, and the treatment is well tolerated and safe.

Evaluation of clinical efficacy and safety of single-channel intracavitary applicator for uterine cervical cancer: 3-year long-term results of a prospective randomized phase Ⅱ clinical trial / 中华放射肿瘤学杂志

Objective:To evaluate the 3-year survival outcomes and late injury between the self-designed patent single-channel applicator, which was modified from the traditional tandem applicator and wrapped with a oval-shield alloy around the source channel and standard Fletcher-type applicator in the high-dose-rate brachytherapy for cervical cancer.Methods:Patients initially diagnosed with cervical cancer in the Affiliated Hospital of Southwest Medical University from December 2011 to April 2017 were enrolled and randomly assigned into the external beam radiotherapy (EBRT)+ single-channel intracavitary applicator group (the patent single-channel group) and EBRT+ the Fletcher applicator group. The whole pelvis irradiation was delivered with 6-MV photons via a four-field box variant or anterior and posterior parallel fields. Five to six fractions of intracavitary brachytherapy were performed at a dose of 7 Gy at point A once a week after 30 Gy (Equivalent Dose in 2 Gy at point A: 80-90 Gy). Chemotherapy was given with intravenous injection of cisplatin at a dose of 40 mg/m 2 once weekly during EBRT. Clinical efficacy and safety were evaluated after corresponding treatment. Results:In total, 150 eligible cases were assigned into the Fletcher applicator group and 149 cases into the patent single-channel group. Up to December 2020, all patients had been followed up for 3 years, and the median duration of follow-up was 61 months. In the Fletcher group, the 3-year overall survival, progression-free survival and locoregional failure-free survival was 76.3%, 78.1% and 75.4%, and 83.8%, 80.3% and 85.5% in the single-channel group, respectively. In the Fletcher group, the cumulative rate of grade 3-4 late rectal complications was 3.3% and 6.7% in the single-channel group ( P=0.122). The cumulative rate of grade 3-4 bladder complications was 1.3% in the Fletcher group and 0.7% in the single-channel group ( P=1.000). Conclusion:The self-designed patent single-channel intracavitary applicator yields equivalent long-term clinical efficacy and safety to the standard Fletcher-type three-channel applicator in the HDR brachytherapy for uterine cervical cancer.

Interfraction physical dose variations in high-dose-rate brachytherapy for carcinoma cervix based on computed tomography image dataset to find the compatibility of the first fraction plan to treat successive fractions

Context: Due to limited resources and/or affordability by majority of the patients, many centers in low- and middle-income countries are still not able to adapt three-dimensional image-based brachytherapy planning in their routine practice. Aim: The aim of the study was to see the feasibility of using computed tomography (CT)-based plan of the first fraction to treat successive fractions of intracavitary brachytherapy based on the estimation of the physical dosimetric differences between successive applications. Materials and Methods: CT image-based brachytherapy plans of 38 patients who received three insertions of intracavitary application with high-dose-rate brachytherapy have been analyzed. Revised plans for the second and third insertions were generated by adapting dwell time and dwell position of the first insertion plan. The dose to point “A” and maximum doses to 2, 1, and 0.1 cc volumes of the rectum and bladder have been used for dosimetric comparison. Results: The statistical differences of mean point “A” doses were observed insignificant except between original and revised plans for the second insertions. The dosimetric differences between consecutive original and revised plans for the bladder and rectum have not shown any significance except minimum dose to 0.1 cc volume of the rectum for the third insertions. Conclusions: Dosimetric deviation for tumor and organs at risk is within acceptable limit while using CT image-based brachytherapy plan of the first fraction for treating successive fractions

Interdigitated versus sequential high-dose-rate intracavitary brachytherapy with external beam radiotherapy in locally advanced carcinoma cervix

Aims: To decrease overall treatment time (OTT) and to compare the clinical outcome of interdigitated high-dose-rate intracavitary brachytherapy (HDRICBT) versus sequential HDRICBT with external beam radiotherapy (EBRT) in the treatment of locally advanced carcinoma cervix. Methods: Eighty-two patients with histologically confirmed carcinoma of the cervix, untreated International Federation of Gynecology and Obstetrics Stage IIB–IIIB, were included and randomized into two groups. The study group received EBRT 50 Gy/25 fractions with interdigitated HDRICBT 8 Gy/fraction weekly a total of three fractions. Patients in the control group received EBRT 50 Gy/25 fractions with sequential HDRICBT 8 Gy/fraction weekly a total of three fractions. At the end of the study, results of both groups compared in terms of OTT, acute and late toxicities, and response to therapy clinically. Results: A total of 82 patients were enrolled 41 in each arm. Seventy-two patients completed treatment and were analyzed. Mean OTT in study group and control group was 40 and 60 days, respectively. The median follow-up duration was 10 months (3–18). Most of the acute and late toxicities were of Grade 1 and 2 type and comparable in both study and control groups. Treatment interruption due to treatment-related toxicity was slightly higher in the study group than the control group, but it was statistically insignificant. Os negotiability was not found to be a limiting factor for interdigitated HDRICBT. Conclusion: Interdigitated HDRICBT has equivalent response and toxicities as sequential HDRICBT with the advantage of significant reduction in OTT

A study of deformable image registration of high-dose-rate brachytherapy CT image to intensity modulated radiation therapy CT image / 中华放射肿瘤学杂志

Objective To study a novel method for the high-dose-rate brachytherapy (HDR) CT image to the intensity modulated radiation therapy (IMRT) CT image deformable image registration and dose accumulation.Methods The applicator in the HDR CT image is first segmented and removed,then a deflation step is performed on the applicator-free HDR CT image by solving the Navier-Stokes equation.Demons algorithm is utilized to register the deflated HDR CT image to the IMRT CT image,along with the HDR dose.The deformed HDR dose is then added on the IMRT dose and yield the final accumulated dose.Results The HDR CT image and IMRT CT image,as well as the corresponding dose distribution,from five cervical cancer patients are used for evaluation of the proposed algorithm,the results show that the proposed method can effectively get rid of the influence of the applicator and produce an accurate accumulated dose.Conclusions Dose accumulation and supervision is an important step in adaptive radiotherapy for accurate dose delivery and treatment plan re-optimization.The proposed method in this study can effectively accumulate the HDR dose to the IMRT dose domain,and the accuracy is proved to be sufficient for clinical needs.

Major clinical research advances in gynecologic cancer in 2012 / 부인종양

Ten topics were chosen among major clinical research achievements in gynecologic oncology in 2012. For ovarian cancer, comprehensive review of the history of bevacizumab studies was followed by poly adenosine diphosphate [ADP]-ribose polymerase (PARP) inhibitors and other molecular targeted agents such as epidermal growth factor receptor tyrosine kinase inhibitor and AMG 386. For the development of genomic study in gynecologic cancers, BRCA and DICER1 mutations were covered in epithelial and nonepithelial ovarian cancer, respectively. For endometrial cancer, targeted agents including mammalian target of rapamycin (mTOR) inhibitors and bevacizumab were discussed. Radiation therapy "sandwiched" between combination chemotherapy schedules for the treatment of uterine papillary serous carcinoma was also reviewed. Preoperative prediction of lymph node metastasis, definition of low-risk group, and recurrence and survival outcomes of laparoscopic approaches were addressed. For cervical cancer, we reviewed long-term benefit of human papillomavirus test and efficacy of paclitaxel/carboplatin versus paclitaxel/cisplatin in stage IVB, persistent or recurrent disease. In addition, the effect of three dimensional image-based high-dose rate brachytherapy was also reviewed. For vulvar cancer, the diagnostic value of sentinel lymph node biopsy was discussed. For breast cancer, positive results of three outstanding phase III randomized clinical trials, CLEOPATRA, EMILIA, and BOLERO-2 were introduced. Lastly, updates of major practice guidelines were summarized.

Comparison of Low- and High-dose Rate Brachytherapy in Carcinoma Cervix: Results From a Randomized Study.

Purpose: We are reporting results of a randomized study with the aim to compare the results of low-dose rate (LDR) versus high-dose rate (HDR) brachytherapy in locally advanced carcinoma cervix patients. Material and methods: Sixty cases of carcinoma of uterine cervix in Stage IIB-IIIB (FIGO) were included from a period of January 2002 to March 2003 and were randomized into HDR brachytherapy (6 Gy/fraction for 4 sessions) or LDR brachytherapy (27 Gy/single session) arm after completion of external beam radiotherapy (50 Gy/25#/5 weeks). Results: In HDR arm, 16/30 (53.33%) patients experienced complete response. In LDR arm, complete response was experienced by 13/30 (43.33%) of patients. Locoregional control in HDR group was 54.54%, 57.14% and 71.42% at 6, 9 and 12 months, respectively. Locoregional control in LDR group at 6, 9 and 12 months was 45%, 63.63% and 42.85%, respectively. Conclusion: The results of our study indicate that LDR and HDR groups are similar in locoregional control in the management of carcinoma uterine cervix. HDR brachytherapy can safely substitute LDR brachytherapy applications.

Development of Source Template ICRT Dose Planning Software for Uterine Cervix Using the HDR: 192Ir / 의학물리

The source position and source dwelling time in a given source arrangement in the applicators is very high effect to determine the expose time which in general is derived from the brachytherapy planning system. In high dose rate (HDR) intracavitary radiation therapy (ICRT), the treatment is often performed in based out-patient during the whole fractionation irradiations. However, the patient should be waited on coutch for ICR treatment in first start fraction as unconvinent and immobilized state until perform the dose plannings. In our experiments, the HDR source contributed dose for 55.89+/-4.20% for straight tandem source, 38.14+/-4.46% for the right ovoid soucre on the fornix and 5.97+/-0.50% for left ovoid source. It also showed the 60.33+/-6.53% for the tandem, 33.10+/-6.74% for right ovoid and 6.58+/-0.30% for the left ovoid source in 10 degrees of applicator. The authors designed the source template dose planning software for ICRT of uterine cervix results average -0.55+/-2.15% discrepancy of the full charged brachytherapy dose planning. Developed Source temperate ICRT plaanning software guide a minimized the complains and operating times within a +/-3% of dose discrepancies.

High dose rate brachytherapy in primary and recurrent tongue cancer

Multi-element Ultrasound Applicator for the Treatment of Cancer in Uterus and Cervix / 의학물리

The objective of this study was to construct multi-element ultrasound applicators for the treatment of gynecologic cancer with high dose rate brachytherapy. For the treatment of uterus, piezo-ceramic crystal transducer (PZT-5A) with outer diameter of 4 mm, wall thickness of 1.3 mm, and length of 24.5 mm was selected. For the treatment of cervix or vagina, it should be possible to insert the applicator into the vagina. Thus, a cylindrical PZT-8 material with outer diameter of 24.5 mm, wall thickness of 1.3 mm, and length of 15.2 mm was selected. The operating frequencies determined by vector impedance measurement were 3.2 MHz for the PZT 5A cylinder (OD=4 mm) and 1.7 MHz for the PZT-8 cylinder (OD: 24.5 mm). The ratios of generated acoustic output power to applied electric power were 33% and 61% for the tandem type crystal and the cylinder type crystal, respectively. The radiated acoustic pressure fields from both transducers were calculated using a Matlab code and measured in water using hydrophone. There was good agreement between measured and calculated acoustic pressure field distribution. For a tandem type transducer, the calculated acoustic pressure field decreased from 0.023 MPa at 10 mm to 0.010 Mpa at 30 mm, the reduction of 57%. For the cylinder type transducer which will be used for the treatment of vagina showed 78% reduction at 15 mm and 66% at 25 mm as compared to values at 5 mm from the surface. Based on the characteristics of the transducers, this study demonstrated the possibility of using the crystals as a heating source. Finally, a 3-element and 4-element prototype applicators were constructed. The 3-element applicator is 75 mm long and 4 mm thick and will be used for the treatment of uterus. The 4-element applicator is 61 mm long and 24.5 mm thick and will be used for the treatment of vagina. Using these applicators, it is possible to generate enough power to increase temperature to therapeutic level.

Radiation therapy of cervical cancer: Current status in Korea and recent developments / 부인종양

Brachytherapy is an essential part of the radiotherapy for uterine cervical cancer. Since 1979, high dose rate (HDR) brachytherapy has been used for the treatment of uterine cervical cancer in Korea; the number of institutions employing HDR has been increasing. At 40 radiation oncology departments out of 53 in Korea, HDR brachytherapy was practiced in 2004. Approximately in 1,000 of patients, brachytherapy was done annually and among these, HDR proportions were 75-80%. In Korea, treatment results for HDR are comparable with the low dose rate (LDR) system series and appear to be a safe and effective alternative to LDR for the treatment of cervical carcinoma. The studies from the major centers report the five-year survival rate of cervical cancer as, 78-86% for Stage I, 68-85% for stage II, and 38-56% for Stage III. In conclusion, HDR intracavitary radiotherapy is increasingly practiced in Korea and an effective treatment modality for cervical cancer. To determine the optimum radiation dose and fractionation schedule, a nation-wide prospective study is necessary in Korea. Recently a three-dimensional conformal radiotherapy (3DCRT) or an intensity-modulated radiotherapy (IMRT), which allow for a high degree of conformity to the target volume have been used for the uterine cervical cancer. Several studies have reported the superiority of IMRT, over the conventional technique, in reducing the small bowel dose. The author will introduce the small bowel displacement system (SBDS)-assisted IMRT for cervical cancer patients. Positional changes of the uterus during radiotherapy, which can degrade the accuracy of 3DCRT and IMRT, will be discussed.

Optimum Radiotherapy Schedule for Uterine Cervical Cancer based-on the Detailed Information of Dose Fractionation and Radiotherapy Technique / 대한방사선종양학회지

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.

Optimum Radiotherapy Schedule for Uterine Cervical Cancer based-on the Detailed Information of Dose Fractionation and Radiotherapy Technique / 대한방사선종양학회지

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.

Radical Radiotherapy for Locally Advanced Cancer of Uterine Cervix / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This study was performed to evaluate the treatment results, prognostic factors and complication rates in patients with locally advanced cancer of uterine cervix after radiotherapy with high-dose rate (HDR) brachytherapy. MATERIALS AND METHODS: One hundred and twenty patients with a locally advanced (stages IIB~IVA according to FIGO classification) carcinoma of the uterine cervix were treated with radiotherapy at the Department of Radiation Oncology, Samsung Medical Center between September 1994 and December 2001. The median age of the patients was 61 years (range 29 to 81). Sixty-one, 56 and 3 patients had FIGO stage IIB, III, and IV diseases, respectively. All patients were given external beam radiotherapy over the whole pelvis (median 50.4 Gy) and HDR intracavitary brachytherapy, with a median of 4 Gy per fraction, to point A. Twenty-one patients received chemotherapy, of which 13 and 21 received neoadjuvant chemotherapy and concurrent chemotherapy, respectively, during the first and fourth weeks of external beam radiotherapy. The chemotherapy was not randomly assigned and the median follow-up time was 28.5 months (range: 6~100 months). RESULTS: The three- and 5-year overall survival (OS) and disease-free survival (DFS) rates were 64.4 and 57.0%, and 63.7 and 60.2%, respectively. The 5-year OS and DFS rates of the patients at stages IIB, III and IV were 602, 57.9 and 33.3%, and 57.4, 65.4 and 33.3%, respectively. Univariate analysis indicated that the FIGO stage, overall treatment time (OTT) and treatment response were significant variables for the OS (p=0.035, p=0.0649 and p=0.0009) and of the DFS (p=0.0009, p=0.0359 and p=0.0363). Multivariate analysis showed that the treatment response was the only significant variable for the OS (p=0.0018) and OTT for the DFS (p=0.0360). The overall incidence of late complications in the rectum and bladder were 11.7 and 6.7%, respectively. In addition, insufficiency fractures were observed in 7 patients (5.8%). CONCLUSION: The results of this study suggest that radical radiotherapy with HDR brachytherapy was appropriate for the treatment of locally advanced uterine cervix cancer. Also, the response after treatment and OTT are significant prognostic factors.

Prediction of Late Rectal Complication Following High-dose-rate Intracavitary Brachytherapy in Cancer of the Uterine Cervix / 대한방사선종양학회지

PURPOSE: Although high-dose-rate intracavitary radiotherapy (HDR ICR) has been used in the treatment of cervical cancer, the potential for increased risk of late complication, most commonly in the rectum, is a major concern. We have previously reported on 136 patients treated with HDR brachytherapy between 1995 and 1999. The purpose of this study is to upgrade the previous data and confirm the correlation between late rectal complication and rectal dose in cervix cancer patients treated with HDR ICR. MATERIALS AND METHODS: A retrospective analysis was performed for 222 patients with cervix cancer who were treated for curative intent with external beam radiotherapy (EBRT) and HDR ICR from July 1995 to December 2001. The median dose of EBRT was 50.4 (30.6~56.4) Gy with a daily fraction size 1.8 Gy. A total of six fractions of HDR ICR were given twice weekly with fraction size of 4 (3~5.5) Gy to A point by Iridium-192 source. The rectal dose was calculated at the rectal reference point using the barium contrast criteria. in vivo measurement of the rectal dose was performed with thermoluminescent dosimeter (TLD) during HDR ICR. The median follow-up period was 39 months, ranging from 6 to 90 months. RESULTS: Twenty-one patients (9.5%) experienced late rectal bleeding, from 3 to 44 months (median, 13 months) after the completion of RT. The calculated rectal doses were not different between the patients with rectal bleeding and those without, but the measured rectal doses were higher in the complicated patients. The differences of the measured ICR rectal fractional dose, ICR total rectal dose, and total rectal biologically equivalent dose (BED) were statistically significant. When the measured ICR total rectal dose was beyond 16 Gy, when the ratio of the measured rectal dose to A point dose was beyond 70%, or when the measured rectal BED was over 110 Gy3, a high possibility of late rectal complication was found. CONCLUSION: Late rectal complication was closely correlated with measured rectal dose by in vivo dosimetry using TLD during HDR ICR. If data from in vivo dosimetry shows any possibility of rectal bleeding, efforts should be made to reduce the rectal dose.

High-Dose-Rate Brachytherapy for Uterine Cervical Cancer : The Results of Different Fractionation Regimen / 대한방사선종양학회지

PURPOSE: Although high-dose-rate (HDR) brachytherapy regimens have been practiced with a variety of modalities and various degrees of success, few studies on the subject have been conducted. The purpose of this study was to compare the results of local control and late complication rate according to different HDR brachytherapy fractionation regimens in uterine cervical cancer patients. METHODS AND MATERIALS: From November 1992 to March 1998, 224 patients with uterine cervical cancer were treated with external beam irradiation and HDR brachytherapy. In external pelvic radiation therapy, the radiation dose was 45~54 Gy (median dose 54 Gy) with daily fraction size 1.8 Gy, five times per week. In HDR brachytherapy, 122 patients (Group A) were treated with three times weekly with 3 Gy to line-A (isodose line of 2 cm radius from source) and 102 patients (Group B) underwent the HDR brachytherapy twice weekly with 4 or 4.5 Gy to line-A after external beam irradiation. Iridium-192 was used as the source of HDR brachytherapy. Late complication was assessed from grade 1 to 5 using the RTOG morbidity grading system. RESULTS: The local control rate (LCR) at 5 years was 80% in group A and 84% in group B (p=0.4523). In the patients treated with radiation therapy alone, LCR at 5 years was 60.9% in group A and 76.9% in group B (p=0.2557). In post-operative radiation therapy patients, LCR at 5 years was 92.6% in group A and 91.6% in group B (p=0.8867). The incidence of late complication was 18% (22 patients) and 29.4% (30 patients), of bladder complication was 9.8% (12 patients) and 14.7% (15 patients), and of rectal complication was 9.8% (12 patients) and 21.6% (22 patients), in group A and B, respectively. Lower fraction sized HDR brachytherapy was associated with decrease in late complication (p=0.0405) (rectal complication, p=0.0147; bladder complication, p=0.115). The same result was observed in postoperative radiation therapy patients (p=0.0860) and radiation only treated patients (p=0.0370). CONCLUSION: For radiation only treated patients, a greater number of itemized studies on the proper fraction size of HDR brachytherapy, with consideration for stages and prognostic factors, are required. In postoperative radiation therapy, the fraction size of HDR brachytherapy did not have much effect on local control, yet the incidence of late complication increased with the elevation in fraction size. We suggest that HDR brachytherapy three times weekly with 3 Gy could be an alternative method of therapy.

Treatment Results of Radical Radiotherapy in Uterine Cervix Cancer / 대한방사선종양학회지

PURPOSE: This study was conducted to evaluate the treatment results, prognostic factors, and complication rates after high dose rate (HDR) brachytherapy in patients with uterine cervix cancer who were treated with curative aim. MATERIALS AND METHODS: Of 269 cervix cancer patients treated at the department of radiation oncology, Samsung Medical Center from September 1994 to July 1998, the 106 who were treated with radical radiotherapy were analyzed. The median age was 61 years (range 22 to 89). All patients except 4 with carcinoma in situ (CIS) were given external beam radiotherapy (range 30.6~50.4 Gy to whole pelvis) and HDR brachytherapy. The common regimens of HDR brachytherapy were a total dose of 24~28 Gy with 6~7 fractions to point A at two fractions per week. The median overall treatment time was 55 days (range 44 to 104) in patients given both external beam radiotherapy and HDR brachytherapy. RESULTS: Early responses of radiotherapy were evaluated by gynecologic examination and follow-up MRI 1 month after radiotherapy. Treatment responses were complete remission in 72 patients, partial response in 33 and no response in 1. The overall survival (OS) rate of all patients was 82%, and 73%, and the disease free survival (DFS) rate was 72%, and 69%, at 3, and 5 years, respectively. The pelvic control rate (PCR) was 79% at both 3 and 5 years. According to the FIGO stage, 3 and 5 year OS were 100% and 50% in CIS/IA, 100% and 100% in IB, 83% and 69% in IIA, 87% and 80% in IIB, and 62% and 62% in III, respectively. The 3 year OS in 4 patients with stage IVA was 100%. Three-year DFS were 80% in CIS/IA, 88% in IB, 100% in IIA, 64% in IIB, 58% in III, and 75% in IVA. Three-year PCR were 100% in CIS/IA, 94% in IB, 100% in IIA, 84% in IIB, 69% in III, and 50% in IVA. By univariate analysis, FIGO stage and treatment response were significant factors for OS. The significant factors for DFS were age, FIGO stage, treatment response and overall treatment time (OTT). For pelvic control rate, treatment response and OTT were significant factors. By multivariate analysis, FIGO stage had a borderline significance for OS (p=0.0825) and treatment response had a borderline significance for DFS (p=0.0872). A total of 14 patients (13%) experienced rectal bleeding, which occurred from 3 to 44 months (median, 13 months) after the completion of radiotherapy. CONCLUSION: HDR brachytherapy protocol of Samsung Medical Center combined with properly optimal external beam pelvic irradiation is a safe and effective treatment for patients with uterine cervix cancer. The authors found that OTT of less than 55 days had a positive impact on pelvic control and survival rate.

Design of a New Applicator for High-Dose Rate Vaginal Brachytherapy / 영남의대학술지

PURPOSE: This study was aimed to develop a new vaginal applicator(Shin's Applicator) for 2-channel high-dose rate vaginal brachytherapy to evaluate uniformity of surface dose, and to present 3-dimensional dose distribution of the applicator. METHODS: Shin's Applicator was inexpensively constructed using human soft tissue equivalent acrylic bar. We evaluated dose uniformity along the applicator surface using film densitometer and performed vaginal intracavitary brachytherapy after insertion of the applicator using HDR brachytherapy planning software and brachytherapy unit(Ralstron-20B). RESULTS: Shin's Applicator allows improved dose distribution than the existing 1-channel cylinder and achieves diminished urinary bladder and rectal dose by 20%. CONCLUSIONS: From the above results, it can be concluded that Shin's Applicator may be an improved form of a vaginal applicator. Furthermore, it can be suggested that this applicator has an advantage, for it prevents vaginal stenosis after radiation therapy and can be used as a disposable vaginal dilator. Further follow up examination with radiological study may be helpful to evaluate the therapeutic efficacy of this applicator.

The Effects of High Dose Rate Brachytherapy in Recurrent Obstructive Bronchogenic Cancer after External Irradiation Therapy / 결핵

BACKGROUND: Patients with centrally recurred bronchogenic carcinoma make a complaint of many symptoms like hemoptysis, cough & dyspnea. At these conditions, the goal of treatment is only to relieve their symptoms. High dose rate brachytherapy(HDR-BT) is the palliative treatment modality of centrally located endobronchial tumor regardless of previous external irradiation(XRT) on the same site in symptomatic patients. METHOD: We studied the effects of HDR-BT in 26 patients with symptomatic recurrent lung cancer. Patients(male: 24, mean age: 54yrs)were treated with HDR-BT underwent bronchoscopic placement of 192Ir HDR after loading unit(Gammamed(R), Germany) to deliver 500cGY intraluminal irradiation at a depth of 1cm every 1wk on 3 occasions. Evaluation at base line and 4wks after HDR brachytherapy included chest X-ray, bronchscopy, symptoms (Standadized Scale for dyspnea, cough, hemoptysis), and Karnofsky performance scale. RESULTS: Endobronchial obstruction was improved in 11/26 patients(37%). Atelectasis in chest X-ray was improved in 5/15 patients(33%). Hemoptysis, dyspnea & cough were improved in 5/10 patients (50%), 5/8 patients (62%) & 10/18 patients (56%) respectively. Karnofsky performance status was changed from 76.4 scores in pretreatment to 77.6 scores after treatment. During HDR-BT, massive hemoptysis (2 patients) and pneumothorax(1 patient) were occurred as complications. CONCLUSION: We concluded that HDR-BT gave additional benefits for the control of symptoms and general performance and endobronchial obstruction & atelectasis. And HDR-BT will be an additional treatment for the recurrent and endobronchial obstructive lung cancer.

Current Status of High Dose Rate Brachytherapy in Cervical Cancer in Korea and Optimal Treatment Schedule / 대한방사선종양학회지

Brachytherapy is an essential part of radiotherapy for uterine cervical cancer. The low dose rate (LDR) regimen has been the major technique of intracavitary therapy for cervical cancer. However, there has been an expansion in the last 20 years of high dose rate (HDR) machines using Ir-192 sources. Since 1979, HDR brachytherapy has been used for the treatment of uterine cervical cancer in Korea. The number of institutions employing HDR has been increasing, while the number of low dose rate system has been constant. In 1995, there was a total 27 HDR brachytherapy units installed and 1258 cases of patients with cervical cancer were treated with HDR. Most common regimens of HDR brachytherapy are total dose of 30-39 Gy at point A with 10-13 fractions in three fractions per week, 24-32 Gy with 6-8 fractions in two fractions per week, and 30-35 Gy with 6-7 fractions in two fractions per week. The average fractionation regimen of HDR brachytherapy is about 8 fractions of 4.1 Gy each to Point A. In Korea, treatment results for HDR brachytherapy are comparable with the LDR series and appears to be a safe and effective alternative to LDR therapy for the treatment of cervical carcinoma. Studies from the major centers report the five-year survival rate of cervical cancer as, 78-86% for Stage I, 68-85% for stage II, and 38-56% for Stage III. World-wide questionnaire study and Japanese questionnaire survey of multiple institutions showed no survival difference in any stages and dose-rate effect ratio (HDR/LDR) was calculated to be 0.54 to 0.58. However, the optimum treatment doses and fractionation schemes appropriate to generate clinical results comparable to conventional LDR schemes have yet to be standardized. In conclusion, HDR intracavitary radiotherapy is increasingly practiced in Korea and an effective treatment modality for cervical cancer. To determine the optimum radiotherapy dose and fractionation schedule, a nation-wide prospective study is necessary in Korea. In addition, standardization of HDR application (clinical, computer algorithms, and dosimetric aspects) is necessary.