Prospective study of HDR (192Ir) versus MDR (137Cs) intracavitary brachytherapy for carcinoma of the uterine cervix

PURPOSE: The aim of this study was to compare the results of high-dose rate (HDR) and medium-dose rate (MDR) intracavitary brachytherapy for carcinoma of the uterine cervix on the basis of a prospective study and to determine the dose rate conversion factor (DRCF) from low-dose rate (LDR) to MDR via HDR, because a DRCF of 0.54 from LDR to HDR has been widely accepted. MATERIALS AND METHODS: Between August 1991 and July 1999, 104 patients were entered into this trial to compare results between HDR (n=54) and MDR (n=50). Three patients were excluded from this study, leaving 54 HDR patients and 47 MDR patients eligible. Method and dose of external beam radiotherapy were the same for both groups. For HDR intracavitary brachytherapy, point A dose was adjusted to 32 Gy/4 fractions for stages I and II, to 30 Gy/4 fractions for stage III, and to 22.5 Gy/3 fractions for stage IV. The corresponding values for MDR were 35.6 Gy/4 fractions, 34 Gy/4 fractions, and 25.5 Gy/3 fractions. The average dose rate at point A was 30 Gy/hour (9.0-65.2) for HDR and 1.7 Gy/hour (1.3-2.2) for MDR. We assumed a DRCF of 0.9 from MDR to HDR. RESULTS: The 3-year cause-specific survival rates for HDR were 85%, 83%, 75%, and 0% for stages I, II, III, and IV, respectively. The corresponding figures for MDR were 100%, 82%, 58%, and 40%. Six of the HDR patients (11%) and 2 of the MDR patients (4%) developed Kottmeier's grade 2 or 3 late complications. A DRCF of 0.6 from LDR to MDR could be derived from a DRCF of 0.9 from MDR to HDR and one of 0.54 from LDR to HDR. CONCLUSIONS: There were no statistically significant differences in cause-specific survival and incidence of late complications between HDR and MDR. A DRCF of 0.6 from LDR to MDR could be determined. However, because the results of this trial were preliminary, a further study is needed.     

Intracavitary brachytherapy for carcinoma of the uterine cervix—Comparison of HDR (Ir-192) and MDR (Cs-137)—

Purpose

To compare the results of high dose rate (HDR) (Ir-192) and medium dose rate (MDR) (Cs-137) intracavitary brachytherapy (ICRT) for carcinoma of the uterine cervix.

Materials and Methods

Between May 1991 and March 2001, a total of 206 patients with Stage I-IVA previously untreated cervical cancer were treated with ICRT combined with external beam radiotherapy (EBRT). HDR was administered to a total of 135 patients: 22 patients in Stage I, 49 in Stage II, 56 in Stage III, and eight in Stage IVA. MDR was administered to a total of 71 patients: six patients in Stage I, 27 in Stage II, 33 in Stage III, and five in Stage IVA. The MDR at point A was 30 Gy/hour for HDR and 1.7 Gy/hour for MDR treatment, and the corresponding median follow-up periods for survivors were 55 and 68 months.

Results

For the HDR group, 5-year cause-specific survival rates were 90%, 78%, 53% and 33% for Stages I, II, III, and IVA, respectively. For the MDR group, the corresponding rates were 100%, 76%, 51%, and 40%. In the HDR group, 19 patients (14%) developed Grade 2 or higher late complications, and, in the MDR group, four patients (6%) did.

Conclusions

There was no statistically significant difference in cause-specific survivals between the results of HDR and MDR brachytherapy for cervical cancer. The incidence of late complications tended to be higher for the HDR group than for the MDR group, but did not show a statistically significant difference (p=0.07).     

Low-Dose-Rate versus High-Dose-Rate intracavitary brachytherapy in cervical cancer - Final Results of a Phase III randomized trial

PURPOSEIntracavitary brachytherapy using High-Dose-Rate (HDR) and Low-dose-rate (LDR) in cervical cancer has been utilized. We report the long-term final results of a large randomized trial in terms of toxicities and efficacy.METHODS AND MATERIALSBetween 1996 to 2005, 816 patients were randomized to LDR (n = 441 patients) or HDR brachytherapy (n = 369 patients) stratified by FIGO Stage grouping. Patients with Stage I-II received external irradiation of 40 Gy in 20 fractions (with midline block (MLB)) followed by either 2 LDR Intracavitary applications of 30 Gy to point A (2–3 weeks apart) or 5 HDR Intracavitary applications of 7 Gy to point A once weekly. Patients with Stage III received 50 Gy in 25 fractions (with MLB after 40 Gy) followed by either one application of LDR 30 Gy to point A or three applications of HDR 7 Gy to point A once weekly.RESULTSWith a median follow-up was 64 months (interquartile range [IQR]: 21 - 111), moderate to severe rectal and bladder complications were higher in LDR arm as compared to HDR arm (9.7% vs. 3.6%; p = 0.02) and (10.5% vs. 5.5%; p = 0.06) for Stage I-II. No difference in rectal or bladder complications for Stage III patients. Disease free and overall survivals were similar in both the arms for all stages.CONCLUSIONSHDR intracavitary brachytherapy with 7 Gy per fraction weekly is superior to LDR in terms of late rectal and bladder complications. Local control rates and survivals are similar irrespective of stages.     

Anmerkungen zum Problem der Dosierung in der HDR-Brachytherapie

Background

In HDR brachytherapy activity distributions can be achieved which were unknown in LDR brachytherapy. For this reason the classical dosage systems can only be used with caution in HDR brachytherapy.

Methods

Different simple applications are used to investigate the effect of various activity distributions on dose and integrated reference air kerma.

Results

Within the classical LDR dosage systems dose and integrated reference air kerma were equivalent. Due to the possibility to “opotimize” the activity distribution in HDR brachytherapy this is not longer the case. Different optimization algorithms and different optimization goals may lead to quite different activity distributions and different integrated reference air kerma values even if the source positions are the same. For target volume oriented optimization schemes a dosage system is described which is based on dose-volume-histograms.

Conclusions

A widely accepted dosage system in HDR brachytherapy is missing. The dosage system described in this paper may be useful in solving this problem.     

Late Effects of Post-High-Dose-Rate Brachytherapy for Oropharyngeal Carcinoma: Are They Severer than Post-Low-Dose-Rate?

BACKGROUND:. Late effects by high-dose-rate (HDR) brachytherapy have been believed severer than low-dose-rate (LDR) provided tumor control was constant. Local control of oropharyngeal carcinoma with HDR at Osaka Medical Center was comparable to LDR series from Centre Alexis Vautrin (82%, 79.5%, respectively). To assess the feasibility of HDR brachytherapy, the late effects were compared. PATIENTS AND METHODS:. The data of 29 HDR and 24 LDR patients (median follow-up of 27 and 29.5 months, respectively; p = 0.89) were collected. The HDR schedule was 21 Gy/3.5 fractions/2 days following 46 Gy/23 fractions external beam, while 25 Gy/3 days following 50 Gy/25 fractions external beam was for LDR. Late changes were evaluated using RTOG/EORTC late morbidity scoring scheme. For subclinical late changes, mucosa chapter of Dische score was modified for brachytherapy. Scores were discussed through photos and were agreed on by authors. Late sequelae were estimated, by reviewing charts, concerning frequency, severity, and duration of mucosal damages (erosion and ulcer). RESULTS:. Late changes were of no difference (p = 0.12 for EORTC/RTOG, and p = 0.45, 0.47, 1.00, 0.12, 0.16, 0.95, 0.27, 0.21 for erythema, ulceration, edema, thinning, pallor, telangiectasia, mobility impairment of tongue/faucial pillars, respectively, of the modified Dische score). Late sequelae showed no differences (p = 0.90, 0.12, 0.40 for frequency, severity, duration, respectively, of mucosal damages). CONCLUSION:. The late effects by HDR were not severer than by LDR. HDR oropharyngeal brachytherapy is as safe as LDR.     

High dose rate (HDR) brachytherapy technique: For carcinoma of uterine cervix using nucletron applicators

This study describes our existing treatment method for high dose rate (HDR) brachytherapy of carcinoma of uterine cervix using Nucletron applicators. Based on our clinical experience with low dose rate (LDR) brachytherapy since 1986, we deliver 40–45Gy by external and 30Gy by internal radiation therapy. The change in regimen using HDR brachytherapy is that internal radiation dose is given in 5 total of 100 treatments done at our center using ring-tandem (R-T) and ovoid-tandem (O-T) applicator combinations. Since O-T applicator has more flexibility of using desired tandem length and reduced rectum and bladder dose due to internal shielding inside the ovoids, we have made the transition from R-T to O-T combination of applicator. The dose volume histogram of the isodose curve indicates that there is an increase in isodose volume with the O-T applicator by as much as 1.5 times as compared to R-T applicator. In majority of the treatments, rectum and bladder doses are less than 70% of target dose, however in very few treatments, the bladder dose has increased to more than the target dose, in which case, the applicators were reseated and added more packing or reduced the dose per fraction, for better tolerance of late responding normal tissues. All our dose calculations are checked with an independent calculation method and agreement was obtained with in 5–7% discrepancy. From 1991 to January 1995, we have treated over 20 patients and there has been no report of any rectal or bladder complications, while better local control has been reported.     

Fractionated high dose rate versus low dose rate regimens for intracavitary brachytherapy of the cervix. I. General considerations based on radiobiology

Intracavitary brachytherapy at low dose rate (LDR), often with the addition of external-beam radiotherapy, has long been considered the treatment of choice for carcinoma of the cervix, maximizing acute damage in the treatment volume, whilst minimizing late effects. In recent years, primarily for reasons of convenience and cost, there has been a move towards treatments involving a few fractions at high dose rate (HDR). Using data from cells of human origin cultured in vitro, we make estimates of the doses that, delivered in 2-12 HDR fractions, produce tumour control and early effects equivalent to intracavitary treatments at LDR. We also show that, for situations where the normal-tissue dose responsible for late effects is significantly smaller than the tumour dose, HDR schemes may be devised which, while yielding early killing comparable with that of LDR, should not result in worse late effects. We suggest that this scenario probably applies to treatment of carcinoma of the cervix.     

Interfractional fluctuation of rectal dose in high dose rate brachytherapy for prostate cancer

Purpose The aim of the study was to explore the cause of the difference in the maximal rectal dose between the first and second high dose rate (HDR) brachytherapy applications by comparing the thickness of the anterior rectal wall. Materials and methods The rectal dose and the thickness of the anterior rectal wall were analyzed in 26 patients with prostate cancer. After undergoing external beam radiation treatment with a total isocenter dose of 50 Gy, they were treated with HDR brachytherapy of 7.5 Gy/fraction, two fractions daily. The interval between the first HDR brachytherapy session and the second was 5 h. The rectal doses were directly surveyed during irradiation of the HDR brachytherapy. Thickening of the anterior rectal wall was measured at the same level by axial computed tomography scans obtained before the first and second HDR brachytherapy applications. Results The maximal surveyed rectal doses during the first and second HDR brachytherapy applications were 188 ± 51 cGy and 220 ± 35 cGy, respectively (P < 0.01). The fluctuation ratio exceeded 1 in each case. The thickness of the anterior rectal wall before the first and second HDR brachytherapy applications was 18.78 ± 4.34 mm and 14.95 ± 4.09 mm (P < 0.01), respectively. The fluctuation difference exceeded 0 in each case. Conclusion The different rectal dose is attributable to thinning of the anterior rectal wall. The total rectal dose is within the range of doses at risk of exerting a toxic effect on the rectum.     

Radiotherapy doses at special reference points correlate with the outcome of cervical cancer therapy

PURPOSE: The authors analyzed the correlation between radiotherapy doses at reference points on the uterine edge and the rectal wall and both pelvic control and late rectal complications of cervical cancer therapy. METHODS AND MATERIALS: Between 1997 and 2005, 57 patients with Stages IB-IVA cancer of uterine cervix were treated with a combination of external beam radiotherapy and high-dose-rate intracavitary brachytherapy. Their high-dose-rate intracavitary brachytherapy was planned by dose-point optimization at six dose points located on the edge of uterus by computed tomography. A rectal reference point located on the anterior wall of the rectum by computed tomography was also used. The pelvic control rate and the rate of late rectal complications were calculated according to the biologically effective dose (BED) at each point and several clinical parameters. RESULTS: The overall 3-year pelvic control rate was 69.4%. The patients with a BED >80 Gy10 at the point on the edge of the uterine cervix had better pelvic control (78.4% at 3 years) than the patients with a BED < or =80 Gy10 (54.4% at 3 years), and the difference was significant. The difference in the BED (Gy3) at the rectal reference point between the patients with Grade 0-1 late rectal complications (median, 114 Gy) and the patients who developed Grade > or =2 late rectal complications (median, 178 Gy) was significant. Chemotherapy was a borderline significant parameter in regard to correlation with pelvic control and late rectal complications, but there were no correlations with other dosimetric or clinical parameters. CONCLUSIONS: The radiotherapy dose at the reference point on the edge of the cervix affected pelvic control more than the clinical parameters, and the dose at the rectal reference point was more strongly correlated with the occurrence of late rectal complications.     

Locally advanced verrucous carcinoma of the oral cavity

Background

Oral verrucous carcinomas are locally invasive but rarely metastasize. Current treatment options include surgery and external beam radiotherapy (EBRT). In medical inoperable patients or irresectable tumors, high-dose-rate (HDR) brachytherapy is a valid alternative.

Case

We present an 85-year-old man with functionally irresectable cT3N0M0 verrucous carcinoma superficially spreading along the upper alveolar ridge to the retro-alveolar triangle, with infiltration of the left soft and hard palate and buccal mucosa. Using a customized intraoral mold, this patient was treated with HDR brachytherapy delivering a dose of 48 Gy in 12 fractions three times per week. Treatment was well tolerated, and after prolonged confluent mucositis the tumor is in complete remission.

Review of literature and conclusion

The scarce literature on customized mold HDR brachytherapy in maxillary tumors is reviewed and recommendations for other head and neck tumors are given.     

Early results of exclusive radiotherapy in advanced stage cervical carcinoma performed with reference to ICRU Report 38.

BACKGROUND AND PURPOSE: Most of the studies in which medium dose rate (MDR) or high dose rate (HDR) brachytherapy have been used for the treatment of cervical carcinoma were prescribed according to the Manchester system. This study aims to present early results of exclusive radiotherapy, which includes MDR brachytherapy, performed using ICRU 38 recommendations to their full extent. MATERIALS AND METHODS: Between 1994 and 1997, 80 patients with advanced stage (FIGO stages IIA-IVA) cervical carcinoma received external beam therapy (EBT) to the pelvis at a total dose of 46 to 50 Gy and two fractions of MDR (approximately 11.5 Gy/h) brachytherapy delivered to the 60 Gy reference isodose. A dose correction factor of 0.80 was used for dose rate effect. Additionally, 10-14 Gy EBT was given as a parametrial boost. Mean follow-up duration was 25.7 months. RESULTS: Local control (LC) and 3-year overall survival were 63% and 68%, respectively, for all patients. For stages II, III, and IV, LC was 75%, 44%, and 60% and 3-year survival was 75%, 62%, and 50%, respectively. Seven patients had severe late complications (8.7%). CONCLUSIONS: The results of this study encourage the use of ICRU 38 recommendations with MDR or HDR brachytherapy with some additional measures in terms of the radiobiological aspect.     

Intracavitary brachytherapy for carcinoma of the uterine cervix--comparison of HDR (Ir-192) and MDR (Cs-137)

Purpose To compare the results of high dose rate (HDR) (Ir-192) and medium dose rate (MDR) (Cs-137) intracavitary brachytherapy (ICRT) for carcinoma of the uterine cervix. Materials and Methods Between May 1991 and March 2001, a total of 206 patients with Stage I-IVA previously untreated cervical cancer were treated with ICRT combined with external beam radiotherapy (EBRT). HDR was administered to a total of 135 patients: 22 patients in Stage I, 49 in Stage II, 56 in Stage III, and eight in Stage IVA. MDR was administered to a total of 71 patients: six patients in Stage I, 27 in Stage II, 33 in Stage III, and five in Stage IVA. The MDR at point A was 30 Gy/hour for HDR and 1.7 Gy/hour for MDR treatment, and the corresponding median follow-up periods for survivors were 55 and 68 months. Results For the HDR group, 5-year cause-specific survival rates were 90%, 78%, 53% and 33% for Stages I, II, III, and IVA, respectively. For the MDR group, the corresponding rates were 100%, 76%, 51%, and 40%. In the HDR group, 19 patients (14%) developed Grade 2 or higher late complications, and, in the MDR group, four patients (6%) did. Conclusions There was no statistically significant difference in cause-specific survivals between the results of HDR and MDR brachytherapy for cervical cancer. The incidence of late complications tended to be higher for the HDR group than for the MDR group, but did not show a statistically significant difference (p=0.07).     

Brachytherapy provides comparable outcomes and improved cost-effectiveness in the treatment of low/intermediate prostate cancer

PurposeTo evaluate the cost-effectiveness and outcomes of low-dose-rate (LDR) and high-dose-rate (HDR) brachytherapy compared with intensity-modulated radiation therapy (IMRT) in patients with low/intermediate risk of prostate cancer.Methods and MaterialsOne thousand three hundred twenty-eight patients with low or intermediate risk of prostate cancer were treated with LDR (n = 207), HDR with four fractions (n = 252), or IMRT (n = 869) between January 1992 and December 2008. LDR patients were treated with palladium seeds to a median dose of 120 Gy, whereas HDR patients were treated to a median dose 38.0 Gy (four fractions). IMRT patients received 42–44 fractions with a median dose of 75.6 Gy. Clinical outcomes were compared, including biochemical failure, cause-specific survival, and overall survival.ResultsOverall, no differences in 5-year biochemical control (BC) or cause-specific survival were noted among treatment modalities. The calculated reimbursement for LDR brachytherapy, HDR brachytherapy with four fractions, and IMRT was $9,938; $17,514; and $29,356, respectively. HDR and LDR brachytherapy were statistically less costly to Medicare and the institution than IMRT (p < 0.001), and LDR brachytherapy was less costly than HDR brachytherapy (p = 0.01 and p < 0.001). Incremental cost-effectiveness ratios for cost to Medicare for BC with IMRT were $4045 and $2754 per percent of BC for LDR and HDR brachytherapy, respectively. Incremental cost-effectiveness ratio using institutional cost comparing IMRT with LDR and HDR brachytherapy was $4962 and $4824 per 1% improvement in BC.ConclusionsIn this study of patients with low and intermediate risk of prostate cancer, comparable outcomes at 5 years were noted between modalities with increased costs associated with IMRT.     

Computed tomography-guided interstitial high dose rate brachytherapy for centrally located liver tumours: a single institution study

Objectives

To evaluate the clinical outcome of computed tomography (CT)-guided interstitial (IRT) high-dose-rate (HDR) brachytherapy (BRT) in the treatment of unresectable primary and secondary liver malignancies. This report updates and expands our previously described experience with this treatment technique.

Methods

Forty-one patients with 50 tumours adjacent to the liver hilum and bile duct bifurcation were treated in 59 interventions of CT-guided IRT HDR BRT. The tumours were larger than 4 cm with a median volume of 84 cm³ (38–1,348 cm³). The IRT HDR BRT delivered a median total physical dose of 20.0 Gy (7.0–32.0 Gy) in twice daily fractions of median 7.0 Gy (4.0–10.0 Gy) in 19 patients and in once daily fractions of median 8.0 Gy (7.0–14.0 Gy) in 22 patients.

Results

With a median follow-up of 12.4 months, the local control for metastatic hepatic tumours was 89 %, 73 % and 63 % at 6, 12 and 18 months respectively. The local control for primary hepatic tumours was 90 %, 81 % and 50 % at 6, 12 and 18 months respectively. Severe side effects occurred in 5.0 % of interventions with no treatment-related deaths.

Conclusions

CT-guided IRT HDR BRT is a promising procedure for the radiation treatment of centrally located liver malignancies.

Key points

? Interstitial high-dose-rate brachytherapy (IRT HDR BRT) is a promising treatment for central liver tumours ? CT-guided IRT HDR BRT is safe for treating extensive tumours ? CT-guided IRT HDR BRT could play a role in managing unresectable hepatic malignancies     

Low-dose-rate vs. high-dose-rate intracavitary brachytherapy for carcinoma of the cervix: The University of Alabama at Birmingham (UAB) experience

PURPOSE: To review the clinical outcome retrospectively of cervical cancer patients treated definitively with either high-dose-rate (HDR) or low-dose-rate (LDR) brachytherapy. METHODS AND MATERIALS: One hundred sixty patients (44 Stage I, 83 Stage II, and 33 Stage III) were treated from 1990 to 2000 with curative intent for carcinoma of the cervix. One hundred three LDR patients were compared to 57 HDR patients. Two groups were treated during the same period. An external beam dose of 45 Gy to the entire pelvis was delivered at 1.8 Gy per fraction to most patients before the first intracavitary insertion in both groups. Brachytherapy was delivered in one to two LDR implants or four to five HDR implants at 6 Gy per fraction. The prescribed dose to Point A for LDR was at least 80-85 Gy. Patient characteristics were similar for each cohort. Point A doses were similar for each stage. The primary endpoints assessed were survivals and failure sites. Endpoints were estimated using the Kaplan-Meier method and comparisons between treatment groups were performed using the log-rank test. RESULTS: The median followup was 48 months for the LDR group and 59 months for the HDR group. For all stages combined and stage for stage in both groups, there was no statistically significant difference in locoregional control, cause-specific survival, and overall survival for LDR compared with HDR. Locoregional control and overall survival were 78% and 60% for LDR compared to 76% and 55% for HDR at 3 years, respectively (p = 0.96 and p = 0.48). Median cause-specific survival values for LDR vs. HDR were 71 and 81 months, respectively (p = 0.62). The cause-specific survival for LDR patients was 62% compared with 59% for HDR patients at 3 years. For Stage IB2, II, and III LDR patients, cause-specific survival rates were 62%, 67%, and 45%, compared to 67%, 57%, and 33% for HDR at 3 years, respectively (p = 0.75, p = 0.95, and p = 0.48). For patients with a recorded site of first failure, the most common site was locoregional (56%) and then distant metastases (26%). Eight patients who were cancer free developed late complications requiring surgical intervention. Two patients were in the HDR group (3.5%) and 5 in the LDR group (4.8%). CONCLUSIONS: Similar outcome was observed for LDR compared with HDR intracavitary brachytherapy for the entire cohort. In this review, HDR group was not inferior to LDR group in advanced stages. This is likely because our patients were treated with brachytherapy after a high dose of external pelvic radiotherapy in both LDR and HDR patients.     

Radiobiological equivalent of low/high dose rate brachytherapy and evaluation of tumor and normal responses to the dose

Purpose The aim of this study was to compare the biological equivalent of low-dose-rate (LDR) and high-dose-rate (HDR) brachytherapy in terms of the more recent linear quadratic (LQ) model, which leads to theoretical estimation of biological equivalence. Materials and methods One of the key features of the LQ model is that it allows a more systematic radiobiological comparison between different types of treatment because the main parameters α/β and μ are tissue-specific. Such comparisons also allow assessment of the likely change in the therapeutic ratio when switching between LDR and HDR treatments. The main application of LQ methodology, which focuses on by increasing the availability of remote afterloading units, has been to design fractionated HDR treatments that can replace existing LDR techniques. Results In this study, with LDR treatments (39 Gy in 48 h) equivalent to 11 fractions of HDR irradiation at the experimental level, there are increasing reports of reproducible animal models that may be used to investigate the biological basis of brachytherapy and to help confirm theoretical predictions. This is a timely development owing to the nonavailability of sufficient retrospective patient data analysis. Conclusions It appears that HDR brachytherapy is likely to be a viable alternative to LDR only if it is delivered without a prohibitively large number of fractions (e.g., fewer than 11). With increased scientific understanding and technological capability, the prospect of a dose equivalent to HDR brachytherapy will allow greater utilization of the concepts discussed in this article.     

Influence of brachytherapy applicators geometry on dose distribution in cervical cancer

Aim

Although the relationship between the dose delivered to adjacent organs (urinary bladder and rectum) and the frequency and severity of treatment complications has been reported in many series, the factors influencing pelvic dose distribution are not well defined. The aim of the study was to assess retrospectively the influence of the size of cervical cancer brachytherapy applicators (ovoids and uterine tandems) on pelvic dose distribution and the impact of various therapy-dependent factors on patient anatomy and on dose distribution in particular applications.

Patients and Method

The subject of this study were 356 cervical cancer patients treated with Selectron LDR as a part of their radical radiotherapy. Analysed factors included preceding external beam radiotherapy (EBRT) or brachytherapy applications, use of general anaesthesia for application and the system of pellet loading.

Results

Significant correlation was found between the size of applicators and doses to bladder, rectum and points B: larger vaginal applicators produced lower dose in bladder and rectum and higher dose in point B (all p<0.0001), longer uterine tandems produced lower dose in rectum and higher dose in point B (both p<0.0001). Significant decrease in the frequency of use of large applicators (ovoids: p<0.0001, tandems: p=0.055) and worsening of dose distribution, i.e. higher doses to critical organs (respectively: bladder p=0.0012, rectum p=0.02) and lower point B dose (p=0.0001) were observed at consecutive brachytherapy applications. Similar situation occurred in patients, who received EBRT prior to brachytherapy (ovoids: p<0.001, tandem: p=0.04, bladder dose: p=0.009, rectal dose: p=0.073, point B dose: p=0.059). Vaginal applicators were larger (p=0.026) and the dose distribution was better (bladder: p=0.023, rectum: p=0.002, point B: p=0.0001) in patients who had their insertions performed under general anaesthesia. The comparison of 2 consecutively used systems of pellet loading revealed more favourable dose distribution: lower dose for bladder (p=0.014) and higher dose for point B (p<0.0001) for the system, which utilised more sources in ovoids and in the distal part of the uterine tandem, in spite of more frequent use of smaller applicators in this group of patients. In multivariate analysis ovoid size was related to preceding external beam radiotherapy (p=0.025). Uterine tandem length was dependent on the number of preceding intracavitary applications (p<0.001) and preceding external beam radiotherapy (p=0.007). Bladder dose was related to preceding brachytherapy (p=0.011) and the pattern of pellet loading (p=0.031). Rectal dose was dependent only on the use of general anaesthesia during application (p=0.001) and point B dose was dependent on the pattern of pellet loading (p<0.001) and marginally — on the use of preceding external beam radiotherapy (p=0.06).

Conclusions

The results of this study allow for identification of treatment-related factors determining pelvic dose distribution in cervical cancer brachytherapy and may potentially enable optimisation of this distribution in particular clinical situation.     

High-Dose-Rate Interstitial Brachytherapy for the Treatment of Penile Carcinoma

BACKGROUND: Interstitial low-dose-rate (LDR) brachytherapy allows conservative treatment of T1-T2 penile carcinoma. High dose-rate (HDR) is often considered to be dangerous for interstitial implants because of a higher risk of complications, but numerous reports suggest that results may be comparable to LDR. Nevertheless, there are no data in the literature available regarding HDR interstitial brachytherapy for carcinoma of the penis. CASE REPORT: A 64-year-old man with T1 N0 M0 epidermoid carcinoma of the glans is reported. Interstitial HDR brachytherapy was performed using the stainless hollow needle technique and a breast template for fixation and good geometry. The dose delivered was 18 x 3 Gy twice daily. RESULTS: After 232 days from brachytherapy, the patient was without any evidence of the tumor, experienced no serious radiation-induced complications, and had a fully functional organ. CONCLUSION: HDR interstitial brachytherapy is feasible in selected case of penis carcinoma, when careful planning and small single fractions are used.     

Combined treatment of inoperable carcinomas of the uterine cervix with radiotherapy and regional hyperthermia

Aim

The disappointing results for inoperable, advanced tumors of the uterine cervix after conventional radiotherapy alone necessitates improving of radiation therapy. Simultaneous chemotherapy or altered radiation fractionation, such as accelerated regimen, increase acute toxicity and treatment is often difficult to deliver in the planned manner. The purpose of this phase II study was to investigate the toxicity and effectiveness of a combined approach with radiotherapy and regional hyperthermia.

Patients and Methods

From January 1994 to October 1995 18 patients with advanced carcinomas of the uterine cervix were treated in combination with radiotherpay and hyperthermia. The patients were treated with 6 to 20 MV photons delivered by a linear accelerator in a 4-field-box technique to a total dose of 50.4 Gy in 28 fractions. In the first and fourth week 2 regional hyperthermia treatments were each applied with the Sigma-60 applicator from a BSD-2000 unit. After this a boost to the primary tumor was given with high-dose-rate iridium-192 brachytherapy by an afterloading technique with 4×5 Gy at point A to a total of 20 Gy and for the involved parametrium anterioposterior-posterioanterior to 9 Gy in 5 fractions.

Results

The acute toxicity was low and similar to an external radiotherapy alone treatment. No Grade III/IV acute toxicity was found. The median age was 47 years (range 34 to 67 years). In 16 of 18 patients a rapid tumor regression was observed during combined thermo-radiotherapy, which allowed the use of intracavitary high-dose-rate brachytherapy in these cases. Complete and partial remission were observed in 13 and 4 cases, respectively. One paitent die not respond to the treatment. The median follow-up was 24 months (range 17 to 36 months). The local tumor control rate was 48% at 2 years. Median T20, T50 and T90 values were 41.7°C (range 40.3 to 43.2°C), 41.1°C (range 39.2 to 42.5°C) and 39.9°C (range 37.7 to 41.9°C), respectively. Cumulative minutes of T90>40°C (Cum40T90) and cumulative minutes, which were isoeffective to 43°C, were calculated (CEM43T90, CEM43T50, CEM43T20). CEM43T90 was found to be a significant parameter in terms of local tumor control for the 4 hyperthermia treatments (p=0.019).

Conclusion s

This treatment modality has proved to be feasible and well tolerable. The rapid tumor shrinkage in the combined approach of radiotherapy with hyperthermia before beginning brachytherapy seems to be a good prerequisite for improving of the disappointing results in cure of advanced cancer of the uterine cervix.