Present and future in brachytherapy--from the discovery of radium to the 21st century]

Brachytherapy can deliver high doses of radiation to a tumor with only low doses to the normal tissue. Brachytherapy can be classified as intracavitary, intraluminar and interstitial radiotherapy. It can be also divided into three groups according to dose rate: low (LDR), medium (MDR) and high (HDR) dose rates. In recent years, HDR remotely controlled afterloading systems are widespread in Japan. HDR brachytherapy has solved the problem of radiation exposure for medical staff, and patients need not be isolated in highly sealed rooms. Local control rates of T1 and T2 tongue cancer treated with LDR interstitial radiation using 226Ra and 192Ir were 80% and 67%. A phase III trial of HDR versus LDR interstitial brachytherapy for early tongue cancer revealed the same local control rates between the two groups. For uterine cervix cancer, the cause-specific survival rates of patients treated with HDR intracavitary brachytherapy were almost the same as those treated with LDR. HDR brachytherapy can be applied against recurrent tumors. Almost half of recurrent tumors can be controlled with HDR treatment. Brachytherapy is widely used for prostate cancer in the USA. LDR brachytherapy using 125I seeds is used for prostate cancer. In Japan, 125I seeds can not be used because of the regulation of radioisotopes, so we treat prostate cancer patients with HDR brachytherapy. The two-year biochemical NED rate is 83%. Brachytherapy has a long history of nearly 100 years. In recent years, the development of an HDR remotely controlled afterloading system and treatment planning system allows us to make a precise treatment plan and a uniform dose distribution. In the next century, HDR-brachytherapy will continue to play an important role in the field of radiotherapy.     

Volume-based dose optimization in brachytherapy.

PURPOSE: We address the question of how to optimize the dwell time distribution in brachytherapy with a stepping source if a minimal tumor dose is prescribed within the planning target volume (PTV). METHODS AND MATERIALS: For a given PTV, reference points inside and at the surface of the PTV are generated and dose constraints are prescribed. The dose at these reference points can be calculated if the positions of the sources are known. We determine a set of dwell times such that the dose constraints are fulfilled, and at the same time, the total irradiation time is minimized. The simplex algorithm allows us to find a solution (if any exists) for this problem. RESULTS: The performance of this method has been tested for a geometrically simple PTV. This method gives better results than conventionally used algorithms for dwell time optimization. CONCLUSION: The method described in this paper allows a volume-oriented optimization for brachytherapy dose distribution. The algorithm guarantees finding a dwell time distribution which fulfills the prescribed dose constraints, if any solution exists.     

A simple method of obtaining equivalent doses for use in HDR brachytherapy

PURPOSE: To develop a simple program that can be easily used by clinicians to calculate the tumor and late tissue equivalent doses (as if given in 2 Gy/day fractions) for different high-dose-rate (HDR) brachytherapy regimens. The program should take into account the normal tissue sparing effect of brachytherapy. METHODS AND MATERIALS: Using Microsoft Excel, a program was developed incorporating the linear-quadratic (LQ) formula to calculate the biologically equivalent dose (BED). To express the BED in terms more familiar to all clinicians, it was reconverted to equivalent doses as if given as fractionated irradiation at 2 Gy/fraction. Since doses given to normal tissues in HDR brachytherapy treatments are different from those given to tumor, a normal tissue dose modifying factor (DMF) was applied in this spreadsheet (depending on the anticipated dose to normal tissue) to obtain more realistic equivalent normal tissue effects. RESULTS: The spreadsheet program created requires the clinician to enter only the external beam total dose and dose/fraction, HDR dose, and the number of HDR fractions. It automatically calculates the equivalent doses for tumor and normal tissue effects, respectively. Generally, the DMF applied is < 1 since the doses to normal tissues are less than the doses to the tumor. However, in certain circumstances, a DMF of > 1 may need to be applied if the dose to critical normal tissues is higher than the dose to tumor. Additionally, the alpha/beta ratios for tumor and normal tissues can be changed from their default values of 10 Gy and 3 Gy, respectively. This program has been used to determine HDR doses needed for treatment of cancers of the cervix, prostate, and other organs. It can also been used to predict the late normal tissue effects, alerting the clinician to the possibility of undue morbidity of a new HDR regimen. CONCLUSION: A simple Excel spreadsheet program has been developed to assist clinicians to easily calculate equivalent doses to be used in HDR brachytherapy regimens. The novelty of this program is that the equivalent doses are expressed as if given at 2 Gy per fraction rather than as BED values and a more realistic equivalent normal tissue effect is obtained by applying a DMF. Its ease of use should promote the use of LQ radiobiological modeling to determine doses to be used for HDR brachytherapy. The program is to be used judiciously as a guide only and should be correlated with clinical outcome.     

Current results of brachytherapy for soft tissue sarcoma

Perioperative brachytherapy results in a better local control rate than surgery alone for extremity soft tissue sarcoma. Brachytherapy enables the delivery of a high radiation dose to a limited volume of tissue, allows the reduction of radiation treatment time, enables direct visualization of the tumor bed and surrounding critical structures, and costs less than external beam radiotherapy. The literature seems to regard the effectiveness of brachytherapy as comparable to that of external beam radiotherapy, and the side effect profile is acceptable. Traditional low-dose-rate brachytherapy methods require extended periods of patient isolation, but recent technologic advances may obviate this necessity. Newer high-dose-rate (HDR) brachytherapy delivery methods allow for the fractionation of radiation delivery and outpatient treatment in some cases. Furthermore, with HDR brachytherapy, the radiation dose distribution can be tailored around critical anatomic structures. Although the application of HDR brachytherapy to soft tissue sarcoma is relatively new, it seems to result in a satisfactory local control rate and may replace traditional low-dose-rate techniques.     

High dose rate intracavitary brachytherapy for carcinoma of the cervix: the Madison system: II. Procedural and physical considerations.

The loss in therapeutic ratio accompanying a conversion from low dose-rate (LDR) to high dose-rate (HDR) intracavitary brachytherapy (ICR) requires increased attention to the precision and accuracy of dose distribution calculations and treatment delivery. While the HDR-ICR treatment unit allows better custom-tailored dose distributions compared to LDR, it also requires more attention to detail to achieve the distribution desired. Because the relative biological effectiveness of different isodose levels in a dose distribution varies with the absolute dose (as described in Part 1 of this article), the relative dose distribution used with LDR must be modified for HDR to produce the same expected biological effect. Because of the difference in the radiobiology and physical positioning, simply duplicating applications as performed with LDR misses opportunities for dose distribution improvement as well as opens possibilities for significant complications. Due to differences in positioning the applicator (e.g., retraction of the cervix low in the pelvis instead of packing the applicator high), traditional definitions of points of interest (such as point A) apply poorly with HDR-ICR, compelling new systems of dose specification. With HDR-ICR, irreparable mistakes can happen very quickly, and quality assurance for the treatment plan and calculated dwell times prove much more important than with LDR. Key features of the dose distribution and constant relationships involving doses and dwell times help screen planned treatments for mistakes. This paper details the procedural and physical consideration of the Madison system for HDR-ICR brachytherapy for carcinoma of the cervix.     

The optimal fraction size in high-dose-rate brachytherapy: dependency on tissue repair kinetics and low-dose rate

BACKGROUND AND PURPOSE: Indications of the existence of long repair half-times on the order of 2-4 h for late-responding human normal tissues have been obtained from continuous hyperfractionated accelerated radiotherapy (CHART). Recently, these data were used to explain, on the basis of the biologically effective dose (BED), the potential superiority of fractionated high-dose rate (HDR) with large fraction sizes of 5-7 Gy over continuous low-dose rate (LDR) irradiation at 0.5 Gy/h in cervical carcinoma. We investigated the optimal fraction size in HDR brachytherapy and its dependency on treatment choices (overall treatment time, number of HDR fractions, and time interval between fractions) and treatment conditions (reference low-dose rate, tissue repair characteristics). METHODS AND MATERIALS: Radiobiologic model calculations were performed using the linear-quadratic model for incomplete mono-exponential repair. An irradiation dose of 20 Gy was assumed to be applied either with HDR in 2-12 fractions or continuously with LDR for a range of dose rates. HDR and LDR treatment regimens were compared on the basis of the BED and BED ratio of normal tissue and tumor, assuming repair half-times between 1 h and 4 h. RESULTS: With the assumption that the repair half-time of normal tissue was three times longer than that of the tumor, hypofractionation in HDR relative to LDR could result in relative normal tissue sparing if the optimum fraction size is selected. By dose reduction while keeping the tumor BED constant, absolute normal tissue sparing might therefore be achieved. This optimum HDR fraction size was found to be largely dependent on the LDR dose rate. On the basis of the BED(NT/TUM) ratio of HDR over LDR, 3 x 6.7 Gy would be the optimal HDR fractionation scheme for replacement of an LDR scheme of 20 Gy in 10-30 h (dose rate 2-0.67 Gy/h), while at a lower dose rate of 0.5 Gy/h, four fractions of 5 Gy would be preferential, still assuming large differences between tumor and normal tissue repair half-times and equal overall treatment time. For the same fraction size, an even larger normal tissue sparing can be obtained by prolongation of the HDR overall treatment time. CONCLUSION: Radiobiologic model calculations presented here aim to demonstrate that hypofractionation in HDR might have its opportunities for widening the therapeutic window, but definitely has its limits. For each specific combination of the parameters, a theoretical optimal HDR fraction size with regard to relative or absolute normal tissue sparing can be estimated, but because of uncertainty in the biologic parameters, these hypofractionation schemes cannot be generalized for all HDR brachytherapy indications.     

Radiobiologie de la curiethérapie

Low-dose rate brachytherapy has some radiobiological advantages compared to external beam radiotherapy: subletal damages repair during irradiation leading to a relative protection of healthy tissues; no tumor cell repopulation, cell cycle redistribution and a low oxygen enhancement ratio. High dose rate and pulsed dose rate modalities allow an optimization of dose distribution by varying the dwell times over the different dwell positions. Because of the use of afterloaders, they also offer a better radioprotection of the staff. High dose rate and pulsed dose rate treatments seem to offer the same results as low-dose rate brachytherapy, particularly in cervix carcinoma. For high dose rate brachytherapy, schedules must be designed according to the linear-quadratic model. In pulsed dose rate brachytherapy, pulse dose and time intervals must also be derived from the linear-quadratic model, but half-time repair must be taken into account.     

Optimization in high dose rate brachytherapy for utero-vaginal applications.

BACKGROUND AND PURPOSE: High dose rate (HDR) remote afterloading intracavitary brachytherapy is an effective treatment modality which has some advantages over low dose rate (LDR) techniques for gynaecological cancer. Optimization is one of the possibilities of modern brachytherapy techniques, especially the stepping source technology. The use of the term 'optimization' implies achieving the desired optimum dose distribution by changing some parameters of the treatment. The aim of this study was to theoretically evaluate the optimization possibilities by modifying dwell times and dwell positions of the uterine and vaginal sources. MATERIALS AND METHODS: Working on a virtual utero-vaginal model, the dose distribution variations in the rectum, bladder, mean point B reference points and volume parameters were investigated whilst giving a standard dose to point A in the Manchester system. In this model, the intrauterine tandem consisted of 27 dwell positions for 2.5 mm steps and 14 dwell positions for 5 mm steps. Vaginal colpostats consisted of five dwell positions each for 2.5 mm steps. Using a Nucletron Plato treatment planning system and a Microselectron Ir-192 HDR stepping source unit, the dwell times of the intrauterine (T(u)) and vaginal sources (T(v)) were modified at the ratios of (T(u)/T(v)) 1:1; 1:2; 1:3; 1:4; 1:0.50; 1:0.33; and 1:0.25 for the two different dwell positions, 2.5 and 5 mm steps, of the intrauterine tandem. RESULTS: All evaluated parameters decreased with increasing dwell time ratios of uterine tandem to vaginal colpostats, with the greatest fall in the percentage of rectum reference dose (D(R) %), 23 and 28% for 2.5 and 5 mm dwell positions respectively; in addition, the reference isodose volume decreased by 14 and 17% for 2.5 and 5 mm dwell positions, respectively. All evaluated parameters increased with decreasing dwell time ratios of uterine tandem to vaginal colpostats for both dwell positions. The DR% of 1:1-1:4 (T(u)/T(v)) weightings showed an increase from 40.6 to 58.3 (44%) for 2.5 mm and from 49.2 to 67.5 (37%) for 5 mm dwell positions. The volume was increased by 27 and 37% for 2.5 and 5 mm dwell positions respectively. CONCLUSION: Modern brachytherapy techniques enable the individualization of treatments by optimization procedures in gynaecological brachytherapy applications. By altering the dwell time and position, some important changes in reference points, volume and treatment time can be achieved, whilst maintaining a standard dose to point A.     

Evaluation of anatomy-based dwell position and inverse optimization in high-dose-rate brachytherapy of prostate cancer: a dosimetric comparison to a conventional cylindrical dwell position, geometric optimization, and dose-point optimization.

BACKGROUND AND PURPOSE: To compare treatment planning methods in high-dose-rate (HDR) brachytherapy of prostate cancer. In particular, to assess quantitatively the dosimetric superiority, if any, of the anatomy-based dwell position (ABDP) and inverse optimization (IO) over the conventional cylindrical dwell position (CDP), geometric optimization (GO), and dose-point optimization (DO) in terms of the determination of dwell positions and dwell times. PATIENTS AND METHODS: Between September 2002 and April 2003, 10 cases of treatment-planning CT images were taken for external radiotherapy for prostate cancer. Treatment planning computer software and the CT data were used to create hypothetical HDR brachytherapy applicator needles, which were properly implanted in the prostate. Six different plans including IO with ABDP (IO(ABDP)), IO with CDP (IO(CDP)), GO with ABDP (GO(ABDP)), GO with CDP (GO(CDP)), DO with ABDP (DO(ABDP)), and DO with CDP (DO(CDP)) were made for each case, that is, 60 plans in total. All plans were normalized so that the D(95) should be equal to 100% of the prescribed dose. Dose-volume histograms from all 60 plans were analyzed, and multiple implant quality indices, including CI, EI, DNR, %V(R 75), %V(B 75), and %V(U 150) for each plan, were extracted and compared. Then, the best settings for IO(ABDP) regarding dwell position and dose limit were sought for. RESULTS: ABDP showed a statistically significantly lower EI (P<0.001), %V(R 75) (P=0.002), and %V(B 75) (P=0.015) than CDP. IO showed a statistically significantly lower %V(U 150) than GO (P=0.009), or than DO (P<0.001). Given a definition that a figure exceeding three-fold of the minimum figure of the index is clinically unacceptable, only in IO(ABDP) all index figures were clinically acceptable, while in the other five plans at least one index figure was unacceptable. CONCLUSIONS: In the CT-based treatment planning for prostate HDR brachytherapy, ABDP is useful to achieve a high conformity, which leads to a reduction of the doses to the bladder, rectum, and surrounding normal tissue. IO is useful to lower the urethral dose without sacrificing conformity. IO(ABDP) is recommended on the basis of the current study. However, this conclusion has been drawn from the idealized hypothetical settings, and some possibility remains that this conclusion is not always applicable to the real implants.     

Clinically evident fat necrosis in women treated with high-dose-rate brachytherapy alone for early-stage breast cancer

PURPOSE: To investigate the incidence of and variables associated with clinically evident fat necrosis in women treated on a protocol of high-dose-rate (HDR) brachytherapy alone without external-beam whole-breast irradiation for early-stage breast carcinoma. METHODS AND MATERIALS: From 6/1997 until 8/1999, 30 women diagnosed with Stage I or II breast carcinoma underwent surgical excision and postoperative irradiation via HDR brachytherapy implant as part of a multi-institutional clinical Phase I/II protocol. Patients eligible included those with T1, T2, N0, N1 (< or = 3 nodes positive), M0 tumors of nonlobular histology with negative surgical margins, no extracapsular lymph-node extension, and a negative postexcision mammogram. Brachytherapy catheters were placed at the initial excision, re-excision, or at the time of axillary sampling. Direct visualization, surgical clips, ultrasound, or CT scans assisted in delineating the target volume defined as the excision cavity plus 2-cm margin. High activity (192)Ir (3-10 Ci) was used to deliver 340 cGy per fraction, 2 fractions per day, for 5 consecutive days to a total dose of 34 Gy to the target volume. Source position and dwell times were calculated using standard volume optimization techniques. Dosimetric analyses were performed with three-dimensional postimplant dose and volume reconstructions. The median follow-up of all patients was 24 months (range, 12-36 months). RESULTS: Eight patients (crude incidence of 27%) developed clinically evident fat necrosis postimplant in the treated breast. Fat necrosis was determined by clinical presentation including pain and swelling in the treated volume, computed tomography, and/or biopsy. All symptomatic patients (7 of 8 cases) were successfully treated with 3 to 12 months of conservative management. Continuous variables that were found to be associated significantly with fat necrosis included the number of source dwell positions (p = 0.04), and the volume of tissue which received fractional doses of 340 cGy, 510 cGy, and 680 cGy (p = 0.03, p = 0.01, and p = 0.01, respectively). Other continuous variables including patient age, total excised tissue volume, tumor size, number of catheters, number of days the catheters were in place, planar separation, dose homogeneity index (DHI), and uniformity index (UI) were not significant. Discrete variables including the presence/absence of DCIS, sentinel versus full axillary nodal assessment, receptor status, presence/absence of diabetes, and the use of chemotherapy or hormone therapy were not found to have a significant association with the risk of fat necrosis. CONCLUSIONS: In this study of HDR brachytherapy of the breast tumor excision cavity plus margin, treatment was planned and delivered in accordance with the dosimetric parameters of the protocol resulting in a high degree of target volume dose homogeneity. Nonetheless, at a median follow-up of 24 months, a high rate of clinically definable fat necrosis occurred. The overall implant volume as reflected in the number of source dwell positions and the volume of breast tissue receiving fractional doses of 340, 510, and 680 cGy were significantly associated with fat necrosis. Future dosimetric optimization algorithms for HDR breast brachytherapy will need to include these factors to minimize the risk of fat necrosis.     

Pulsed dose rate brachytherapy

Pulsed dose rate (PDR) is a new modality for dose delivery in brachytherapy. It uses modern afterloading technology (miniaturized source, cable driven, software controlled), with source activities in the range of 1 Ci, which is actually one tenth of the normal activity used for high dose rate (HDR) brachytherapy. Modern technology allows dose optimization, and source strength in the above-mentioned range creates a new dose rate condition. For small fractions (pulses) with short interpulse intervals, PDR mimics the radiobiology of high dose rate brachytherapy, whereas for bigger doses per fraction, dose adjustments are needed to compensate for the loss of therapeutic ratio. Clinical series showed good figures for local control and toxicity. Almost every clinical site has been reported to have been treated with PDR, with some thousand of patients having been reported. Technical difficulties in some body sites can be overcome by slightly modifying the implant technique. PDR brachytherapy is an ideal environment for the development of new dose fractionation schedules. It creates unique conditions in which to operate. Knowledge of tissue repair kinetics is extremely important for adequate selection of dose per pulse and interpulse interval. Therapeutic ratio can be improved by adjusting interpulse intervals to the repair half-times for normal tissues. On the other hand, superfractionated schedules with low dose per pulse can be explored in conditions of tumor hypoxia, thanks to the predicted hypersensitivity at low dose per fraction. The use of chemical agents (nicotinamide and others) in concomitance with this superfractionated schedules is foreseen in controlled clinical trials. In conclusion, PDR brachytherapy can be considered a new paradigm for dose delivery. It is safe and reliable, can be used in the setting of image-guided radiation therapy, and exploit the differential effect of ionizing radiations by a thorough knowledge of tissue kinetics for an improved therapeutic ratio.     

Biologic treatment planning for high-dose-rate brachytherapy

PURPOSE: Interstitial brachytherapy treatment plans are conventionally optimized with respect to total target dose and dose homogeneity, which does not account for the biologic effects of dose rate. In an HDR implant, with a stepping source, the dose rate dramatically changes during the course of treatment, depending on location, as the source moves from dwell position to dwell position. These widely varying dose rates, together with the related sequencing of the dwell positions, may impart different biologic effects at points receiving the same total dose. This study applies radiobiologic principles to account for the potential biologic impact of dose delivery at varying dose rates within an HDR implant. METHODS AND MATERIALS: The model under study uses a generalized version of the linear-quadratic (LQ) cell kill formula to calculate the surviving fraction of cells subjected to HDR irradiation. Using a planar interstitial HDR implant with the dwell times optimized to produce a homogeneous dose distribution along a reference plane parallel to the implant plane, surviving fractions were compared at selected reference points subjected to the same total dose. Biologic effect homogeneity was compared to dose homogeneity by plotting the effects at the reference points. The effects were examined with LQ parameters alpha, beta, and sublethal repair time T(1) varied over a range typical of human cells. RESULTS: In a region in which dose is relatively uniform, surviving fraction for some values of the model parameters are found to vary by as much as an order of magnitude due to differences in the HDR irradiation profiles at different dose points. This effect is more pronounced for shorter repair times and smaller alpha/beta ratios, and increases with increasing total irradiation time. CONCLUSION: Conventional HDR treatment planning currently considers dose distribution as the primary indicator of clinical effect. Our results demonstrate that plans optimized to maximize homogeneity within a target volume may not reflect the effect of the sequential nature of HDR dose delivery on cell kill. Biologic effect modeling may improve our understanding and ability to predict the adverse effects of our treatment, such as fat necrosis and fibrosis. Accounting for irradiation history and repair kinetics in the evaluation of HDR brachytherapy plans may add an important new dimension to our planning capabilities.     

Advances in brachytherapy--focusing on the permanent implant for early prostate carcinoma

Even in the modern era of advanced external radiotherapy, brachytherapy is an important and useful modality of radiotherapy. In North America and Europe, it has been noted that the proportion of prostate cancer patients treated by HDR or LDR interstitial brachytherapy is rapidly increasing, as it offers several practical and theoretical advantages over external radiotherapy. HDR treatment with 192Ir remote afterloader provides an optimized dose distribution controlled by an accurate dwell time and position of 192Ir source. LDR brachytherapy is a simple, minimally invasive, and outpatient based procedure that avoids hospitalization and allows the patient an early recovery and rapid return to normal activities. It has produced good 10-year outcome with relatively low morbidity. Although in Japan this treatment was behind North America and Europe, the 125I-seed source was approved by the Japanese FDA and a rule for patient discharge was developed recently. The first case was treated in September 2003 and this treatment is expected to become an important option for early prostate cancer. Several areas of brachytherapy including treatment planning, choice of radionuclide, treatment procedure, and treatment outcome are discussed in this paper.     

Optimization of high dose-rate cervix brachytherapy; Part I: Dose distribution

Computer controlled high dose-rate (HDR) brachytherapy afterloading machines are equipped with a single, miniaturized, high activity Ir-192 source that can be rapidly moved in fine increments among several channels. Consequently, by appropriate programming of source dwell positions and times, the dose distribution can be optimized as desired. We have explored the optimization potential of this new technology for two applications: (a) cervix brachytherapy, and (b) transvaginal irradiation. Cervix brachytherapy with a gynecologic ring applicator was simulated by 48 sources of relative activities ranging from 0.17 to 1.00 that were equally distributed between the tandem and the ring. The results confirmed that the optimized distribution of physical doses are superior to those achievable with standard brachytherapy sources and applicators. For example, with five-point optimization, the relative dose-rate in the rectum was only 47% of that in point A; for standard application the dose rate was 47% higher. For transvaginal application 27 sources of relative activities between 0.07-0.79 were placed in the ring and a single source of unit strength in the tandem. Using dose distribution homogeneity as an optimization criterion, the results (+/- 2.5%) were again superior to those obtained for commonly used double ovoid (+/- 15%), linear cylinder (+/- 27%), or a "T" source (31%).     

High-dose-rate brachytherapy may be radiobiologically superior to low-dose rate due to slow repair of late-responding normal tissue cells

BACKGROUND AND PURPOSE: Recent analysis of morbidity for patients treated with the continuous hyperfractionated accelerated radiotherapy (CHART) regimen demonstrates that repair half-times for late-reacting normal tissue cells are of the order of 4-5 h, which is considerably longer than previously believed. This would reduce repair of these tissue cells during a course of low-dose rate (LDR) brachytherapy, but have no effect at high-dose-rate (HDR), where there is no repair during, and full repair between fractions, regardless of repair half-time. The effect this has upon radiobiologic comparison of LDR and HDR is the topic of this paper. METHODS AND MATERIALS: The linear-quadratic (L-Q) model is used to compare late-effect biologically effective doses (BEDs) of LDR and HDR, for constant BED (tumor). The effects of dose rate (for LDR), fractionation (for HDR), and geometrical sparing of normal tissues are all considered. Repair half-times observed in the CHART study are used to investigate the potential impact of long repair times on the comparison of LDR and HDR. RESULTS: It is demonstrated that, for a repair half-time of 1.5 h for tumor cells, if the half-time for repair of late-reacting normal tissue cells exceeds about 2.5 h, LDR becomes radiobiologically inferior to HDR. Even with the least HDR-favorable combinations of parameters, HDR at over about 5 Gy/fraction ought to be radiobiologically superior to LDR at 0.5 Gy/h, so long as the time between HDR fractions is long compared to the repair half time. It is also shown that any geometrical sparing of normal tissues will benefit HDR more than LDR. CONCLUSION: The previously held belief that LDR must be inherently superior radiobiologically to HDR is wrong if the long repair times demonstrated in the recent CHART study are applicable to other late-reacting normal tissues. This could explain why HDR has been so successful in clinical practice, especially for the treatment of cervical cancer, despite previous convictions of radiobiologic inferiority of this modality.     

The American Brachytherapy Society recommendations for high-dose-rate brachytherapy for head-and-neck carcinoma

To develop recommendations for use of high-dose-rate (HDR) brachytherapy in patients with head-and-neck cancer.

A panel consisting of members of the American Brachytherapy Society (ABS) performed a literature review, added information based upon their clinical experience, and formulated recommendations for head-and-neck HDR brachytherapy.

The ABS recommends the use of brachytherapy as a component of the treatment of head-and-neck tumors. However, the ABS recognizes that some radiation oncologists are reluctant to employ brachytherapy in the head-and-neck region because of the complexity of the postoperative management and concerns about radiation safety. In this regard, HDR eliminates unwanted radiation exposure and thereby permits unrestricted delivery of clinical care to these brachytherapy patients. The ABS made specific recommendations for previously untreated and recurrent head-and-neck cancer patients on patient selection criteria, implant techniques, target volume definition, and HDR treatment parameters (such as time, dose, and fractionation schedules). Suggestions were provided for treatment with HDR alone and in combination with external beam radiation therapy. It should be recognized that only limited experiences exist with HDR brachytherapy in patients with head-and-neck cancers. Therefore, some of these suggested doses have not been extensively tested in clinical practice. Hence, these guidelines will be updated as significant new outcome data are available. Any clinician following these guidelines is expected to use clinical judgment to determine an individual patient’s treatment.

Little has been published in the clinical literature on HDR brachytherapy in head-and-neck cancer. Based upon the available information and the clinical experience of the panel members, general and site-specific recommendations were offered. Areas for further investigations were identified.     

Treatment planning for MRI assisted brachytherapy of gynecologic malignancies based on total dose constraints

PURPOSE: To develop a method for treatment planning and optimization of magnetic resonance imaging (MRI)-assisted gynecologic brachytherapy that includes biologically weighted total dose constraints. METHODS AND MATERIALS: The applied algorithm is based on the linear-quadratic model and includes dose, dose rate, and fractionation of the whole radiotherapy setting, consisting of external beam therapy plus high-dose-rate (HDR), low-dose-rate (LDR) or pulsed-dose rate (PDR) brachytherapy. Biologically effective doses (BED) are converted to more familiar isoeffective (equivalent) doses in 2-Gy fractions. For individual treatment planning of each brachytherapy fraction, the algorithm calculates the physical dose per brachytherapy fraction that corresponds to a predefined isoeffective total dose constraint. Achieved target dose and sparing of organs at risk of already delivered brachytherapy fractions are incorporated. RESULTS: Since implementation for use in clinical routine in 2001, MRI assisted treatment plans of 216 gynecologic patients (161 HDR, 55 PDR brachytherapy) were prospectively optimized taking into account isoeffective dose-volume histogram-based total dose constraints for high-risk clinical target volume (HR CTV) and organs at risk (bladder, rectum, sigmoid). The algorithm is implemented in a spreadsheet and the procedure is fast and efficient. An uncertainty analysis of the isoeffective total doses based on variations of tissue parameters shows that confidence intervals are larger for PDR compared with HDR brachytherapy. For common treatment schedules, overall uncertainties of high-risk clinical target volume and organs at risk are within 8 Gy, except for the bladder when using the PDR technique. CONCLUSION: The presented method to respect total dose constraints is reliable and efficient and an essential tool when aiming to increase local control and minimize side effects.     

Low-dose-rate brachytherapy is superior to high-dose-rate brachytherapy for bladder cancer

PURPOSE: To determine the efficacy and safety of a high-dose-rate (HDR) brachytherapy schedule in the treatment of bladder cancer and to investigate the impact of different values of repair half-times and alpha/beta ratios on the design of the HDR schedule. METHODS AND MATERIALS: Between 2000 and 2002, 40 patients with T1G3 and T2 bladder carcinoma were treated with 30 Gy external beam radiotherapy followed by interstitial HDR brachytherapy to a total dose of 32 Gy in 10 sessions of 3.2-Gy fractions in two fractions daily with a 6-h interfraction interval. The local control rate and toxicity were compared with a historical group of 108 patients treated with 30 Gy external beam radiotherapy followed by 40-Gy interstitial low-dose-rate (LDR) brachytherapy. The HDR schedule was designed to be biologically equivalent to the previously used LDR schedule with the linear-quadratic model, including incomplete mono-exponential repair. RESULTS: The local control rate at 2 years was 72% for HDR vs. 88% for LDR brachytherapy (p = 0.04). In the HDR group, 5 of 30 evaluable patients encountered serious late toxicity: 4 patients developed a contracted bladder with inadequate capacity (<100 mL), and 1 patient required cystectomy because of a painful ulcer at the implant site. In the LDR group, only 2 of 84 assessable patients developed serious late toxicity. One patient developed a persisting vesicocutaneous fistula and the other a urethral stricture due to fibrosis. The difference in observed late toxicity for HDR vs. LDR was statistically significant (p = 0.005). The increased late toxicity with the HDR schedule compared with the LDR schedule suggests a short repair half-time of 0.5-1 h for late-responding normal bladder tissue. CONCLUSION: Local control of HDR brachytherapy for bladder cancer was disappointing and late toxicity unexpectedly high. The increase in late toxicity suggested a short repair half-time of 0.5-1 h for late-responding normal bladder tissue, which would not support HDR brachytherapy in the treatment of bladder cancer. The analysis demonstrated that the calculation of equivalent HDR schedules on the basis of the LDR schedules used in clinical practice might be hazardous.