Reirradiation + hyperthermia for recurrent breast cancer en cuirasse.

BACKGROUND AND PURPOSE: Patients with irresectable locoregional recurrent breast cancer en cuirasse (BCEC) do not have effective curative treatment options. Hyperthermia, the elevation of tumor temperature to 40-45 °C, is a well-established radio- and chemotherapy sensitizer. A total of 196 patients were treated with reirradiation and hyperthermia (reRT+HT) at two Dutch institutes from 1982-2005. The palliative effect was evaluated in terms of clinical outcome and toxicity. PATIENTS AND METHODS: All patients received previous irradiation to a median dose of 50 Gy. In all, 75% of patients received 1-6 treatment modalities for previous tumor recurrences. ReRT consisted of 8 × 4 Gy given twice a week or 12 × 3 Gy given four times a week. Superficial hyperthermia was added once or twice a week. Tumor area comprised ≥½ of the ipsilateral chest wall. RESULTS: Overall clinical response rate was 72% (complete response [CR] 30%, partial response [PR] 42%, stable disease [SD] 22%, progressive disease [PD] 6%). The local progression-free rate at 1 year was 24%. Median survival was 6.9 months. Forty-three percent of our patients with CR, PR, SD after treatment remained infield progression-free until death or last follow-up. Acute ≥grade 3 toxicity occurred in 33% of patients, while late ≥grade 3 toxicity was recorded in 14% of patients. Tumor ulceration prior to treatment had a negative impact on both clinical outcome and toxicity. CONCLUSION: ReRT+HT provides sustainable palliative tumor control, despite refractory, extensive tumor growth. Compared to currently available systemic treatment options, reRT+HT is more effective with less toxicity.

Rib fractures after reirradiation plus hyperthermia for recurrent breast cancer: Predictive factors.

BACKGROUND: Combining reirradiation (reRT) and hyperthermia (HT) has shown high therapeutic value for patients with locoregional recurrent breast cancer (LR). However, additional toxicity of reirradiation (e.g., rib fractures) may occur. The aim of this study is to determine the impact of potential risk factors on the occurrence of rib fractures. PATIENTS AND METHODS: From 1982-2005, 234 patients were treated with adjuvant reRT + HT after surgery for LR. ReRT consisted typically of 8 fractions of 4 Gy twice a week, or 12 fractions of 3 Gy four times a week. A total of 118 patients were irradiated with abutted photon and electron fields. In all, 60 patients were irradiated using either one or alternating combinations of abutted AP electron fields. Hyperthermia was given once or twice a week. RESULTS: The 5-year infield local control (LC) rate was 70 %. Rib fractures were detected in 16 of 234 patients (actuarial risk: 7 % at 5 years). All rib fractures occurred in patients treated with a combination of photon and abutted electron fields (p = 0.000); in 15 of 16 patients fractures were located in the abutment regions. The other significant predictive factors for rib fractures were a higher fraction dose (p = 0.040), large RT fields, and treatment before the year 2000. DISCUSSION AND CONCLUSION: ReRT + HT results in long-term LC. The majority of rib fractures were located in the photon/electron abutment area, emphasizing the disadvantage of field overlap. Large abutted photon/electron fields combined with 4 Gy fractions increase the number of rib fractures in this study group. However, as these factors were highly correlated no relative importance of the individual factors could be estimated. Increasing the number of HT sessions a week does not increase the risk of rib fractures.

A dosimetric uncertainty analysis for photon-emitting brachytherapy sources: report of AAPM Task Group No. 138 and GEC-ESTRO.

This report addresses uncertainties pertaining to brachytherapy single-source dosimetry preceding clinical use. The International Organization for Standardization (ISO) Guide to the Expression of Uncertainty in Measurement (GUM) and the National Institute of Standards and Technology (NIST) Technical Note 1297 are taken as reference standards for uncertainty formalism. Uncertainties in using detectors to measure or utilizing Monte Carlo methods to estimate brachytherapy dose distributions are provided with discussion of the components intrinsic to the overall dosimetric assessment. Uncertainties provided are based on published observations and cited when available. The uncertainty propagation from the primary calibration standard through transfer to the clinic for air-kerma strength is covered first. Uncertainties in each of the brachytherapy dosimetry parameters of the TG-43 formalism are then explored, ending with transfer to the clinic and recommended approaches. Dosimetric uncertainties during treatment delivery are considered briefly but are not included in the detailed analysis. For low- and high-energy brachytherapy sources of low dose rate and high dose rate, a combined dosimetric uncertainty <5% (k=1) is estimated, which is consistent with prior literature estimates. Recommendations are provided for clinical medical physicists, dosimetry investigators, and source and treatment planning system manufacturers. These recommendations include the use of the GUM and NIST reports, a requirement of constancy of manufacturer source design, dosimetry investigator guidelines, provision of the lowest uncertainty for patient treatment dosimetry, and the establishment of an action level based on dosimetric uncertainty. These recommendations reflect the guidance of the American Association of Physicists in Medicine (AAPM) and the Groupe Européen de Curiethérapie-European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) for their members and may also be used as guidance to manufacturers and regulatory agencies in developing good manufacturing practices for sources used in routine clinical treatments.

Study of encapsulated 170Tm sources for their potential use in brachytherapy.

PURPOSE: High dose-rate (HDR) brachytherapy is currently performed with 192Ir sources, and 60Co has returned recently into clinical use as a source for this kind of cancer treatment. Both radionuclides have mean photon energies high enough to require specific shielded treatment rooms. In recent years, 169Yb has been explored as an alternative for HDR-brachytherapy implants. Although it has mean photon energy lower than 192Ir, it still requires extensive shielding to deliver treatment. An alternative radionuclide for brachytherapy is 170Tm (Z=69) because it has three physical properties adequate for clinical practice: (a) 128.6 day half-life, (b) high specific activity, and (c) mean photon energy of 66.39 keV. The main drawback of this radionuclide is the low photon yield (six photons per 100 electrons emitted). The purpose of this work is to study the dosimetric characteristics of this radionuclide for potential use in HDR-brachytherapy. METHODS: The authors have assumed a theoretical 170Tm cylindrical source encapsulated with stainless steel and typical dimensions taken from the currently available HDR 192Ir brachytherapy sources. The dose-rate distribution was calculated for this source using the GEANT4 Monte Carlo (MC) code considering both photon and electron 170Tm spectra. The AAPM TG-43 U1 brachytherapy dosimetry parameters were derived. To study general properties of 170Tm encapsulated sources, spherical sources encapsulated with stainless steel and platinum were also studied. Moreover, the influence of small variations in the active core and capsule dimensions on the dosimetric characteristics was assessed. Treatment times required for a 170Tm source were compared to those for 192Ir and 169Yb for the same contained activity. RESULTS: Due to the energetic beta spectrum and the large electron yield, the bremsstrahlung contribution to the dose was of the same order of magnitude as from the emitted gammas and characteristic x rays. Moreover, the electron spectrum contribution to the dose was significant up to 4 mm from the source center compared to the photon contribution. The dose-rate constant lamda of the cylindrical source was 1.23 cGy h(-1) U(-1). The behavior of the radial dose function showed promise for applications in brachytherapy. Due to the electron spectrum, the anisotropy was large for r <6 mm. Variations in manufacturing tolerances did not significantly influence the final dosimetry data when expressed in cGy h(-1) U(-1). For typical capsule dimensions, maximum reference dose rates of about 0.2, 10, and 2 Gy min(-1) would then be obtained for 170Tm, 192Ir, and 169Yb, respectively, resulting in treatment times greater than those for HDR 192Ir brachytherapy. CONCLUSIONS: The dosimetric characteristics of source designs exploiting the low photon energy of 170Tm were studied for potential application in HDR-brachytherapy. Dose-rate distributions were obtained for cylindrical and simplified spherical 170Tm source designs (stainless steel and platinum capsule materials) using MC calculations. Despite the high activity of 170Tm, calculated treatment times were much longer than for 192Ir.

The evolution of brachytherapy treatment planning.

Brachytherapy is a mature treatment modality that has benefited from technological advances. Treatment planning has advanced from simple lookup tables to complex, computer-based dose-calculation algorithms. The current approach is based on the AAPM TG-43 formalism with recent advances in acquiring single-source dose distributions. However, this formalism has clinically relevant limitations for calculating patient dose. Dose-calculation algorithms are being developed based on Monte Carlo methods, collapsed cone, and solving the linear Boltzmann transport equation. In addition to improved dose-calculation tools, planning systems and brachytherapy treatment planning will account for material heterogeneities, scatter conditions, radiobiology, and image guidance. The AAPM, ESTRO, and other professional societies are working to coordinate clinical integration of these advancements. This Vision 20/20 article provides insight into these endeavors.

Phantom investigations on CT seed imaging for interstitial brachytherapy.

BACKGROUND AND PURPOSE: The Braphyqs group (BRAchytherapy PHYsics Quality System, the brachytherapy physicist's task group of GEC-ESTRO) investigated the quality of CT- and X-ray based seed reconstruction procedures using the Kiel-phantom. In this study systematic phantom investigations on CT post-planning and the results of a mailed multi-centre inter-comparison are presented. MATERIALS AND METHODS: The phantom was equipped with a test configuration composed of 17 non-radioactive seeds. To investigate the quality of seed reconstruction CT measurements with varying CT parameters and different seed models were carried out. In a mailed multi-centre approach the phantom was sent to six European seed centres. The centres performed a typical CT- or X-ray based post-planning. The coordinates of the reconstructed sources were compared with the known positions in the phantom. RESULTS: In the systematic study it was found for the used CT scanner and seed models that when the slice thickness or the table index (respectively, an appropriate pitch for helical scans) reaches 4 or 5mm the accuracy of the CT seed reconstruction decreases in longitudinal direction. No influences of scanned field of view, tube current, kV(p), or scan type (axial or spiral) on seed reconstruction accuracy were detected. This finding was confirmed by the multi-centre evaluation. It was demonstrated that the Kiel-phantom is a suitable quality assurance (QA) tool for the assessment of the seed reconstruction accuracy in post-implant procedures and that it is a feasible QA test tool for a mailed multi-centre approach. CONCLUSIONS: QA of seed post-planning is necessary. A trend was observed that when the slice thickness and table index is 4 or 5mm the standard deviation of the reconstructed seeds increases for CT-based post-planning. Individual optimizations can be performed with dedicated phantoms.

Accuracy of volume and DVH parameters determined with different brachytherapy treatment planning systems.

PURPOSE: To determine the uncertainties in dose volume histogram (DVH) analysis used in modern brachytherapy treatment planning systems (TPSs). MATERIALS AND METHODS: A phantom with three different volumes was scanned with CT and MRI. An inter-observer analysis was based on contouring performed by 5 persons. The volume of a standard contour set was calculated using seven different TPSs. For five systems a typical brachytherapy dose distribution was used to compare DVH determination. RESULTS: The inter-observer variability (1SD) was 13% for a small cylindrical volume, 5% for a large cylinder and 3% for a conical shape. A standardized volume for a 4mm CT scan contoured on seven different TPS varied by 7%, 2%, and 5% (1SD). Use of smaller slice thickness reduced the variations. A treatment plan with the sources between the large cylindrical shape and the cone showed variations for D(2cc) of 1% and 5% (1SD), respectively. Deviations larger than 10% were observed for a smaller source to cylinder surface distance of 5mm. CONCLUSIONS: Modern TPSs minimize the volumetric and dosimetric calculation uncertainties. These are comparable to inter-observer contouring variations. However, differences in volume result from the methods of calculation in the first and last slice of a contoured structure. For this situation and in case of high dose gradients inside analyzed volumes, high uncertainties were observed. The use of DVH parameters in clinical practice should take into account the method of calculation and the possible uncertainties.

Tumour and target volumes in permanent prostate brachytherapy: a supplement to the ESTRO/EAU/EORTC recommendations on prostate brachytherapy.

The aim of this paper is to supplement the GEC/ESTRO/EAU recommendations for permanent seed implantations in prostate cancer to develop consistency in target and volume definition for permanent seed prostate brachytherapy. Recommendations on target and organ at risk (OAR) definitions and dosimetry parameters to be reported on post implant planning are given.

Development of a TLD mailed system for remote dosimetry audit for (192)Ir HDR and PDR sources.

BACKGROUND AND PURPOSE: In the framework of an ESTRO ESQUIRE project, the BRAPHYQS Physics Network and the EQUAL-ESTRO laboratory have developed a procedure for checking the absorbed dose to water in the vicinity of HDR or PDR sources using a mailed TLD system. The methodology and the materials used in the procedure are based on the existing EQUAL-ESTRO external radiotherapy dose checks. MATERIALS AND METHODS: A phantom for TLD postal dose assurance service, adapted to accept catheters from different HDR afterloaders, has been developed. The phantom consists of three PMMA tubes supporting catheters placed at 120 degrees around a central TLD holder. A study on the use of LiF powder type DTL 937 (Philitech) has been performed in order to establish the TLD calibration in dose-to-water at a given distance from (192)Ir source, as well as to determine all correction factors to convert the TLD reading into absorbed dose to water. The dosimetric audit is based on the comparison between the dose to water measured with the TL dosimeter and the dose calculated by the clinical TPS. Results of the audits are classified in four different levels depending on the ratio of the measured dose to the stated dose. The total uncertainty budget in the measurement of the absorbed dose to water using TLD near an (192)Ir HDR source, including TLD reading, correction factors and TLD calibration coefficient, is determined as 3.27% (1s). RESULTS: To validate the procedures, the external audit was first tested among the members of the BRAPHYQS Network. Since November 2004, the test has been made available for use by all European brachytherapy centres. To date, 11 centres have participated in the checks and the results obtained are very encouraging. Nevertheless, one error detected has shown the usefulness of this audit. CONCLUSION: A method of absorbed dose to water determination in the vicinity of an (192)Ir brachytherapy source was developed for the purpose of a mailed TL dosimetry system. The accuracy of the procedure was determined. This method allows a check of the whole dosimetry chain for this type of brachytherapy afterloading system and can easily be performed by mail to any institution in the European area and elsewhere. Such an external audit can be an efficient QC method complementary to internal quality control as it can reveal some errors which are not observable by other means.

Overview of brachytherapy resources in Europe: a survey of patterns of care study for brachytherapy in Europe.

BACKGROUND AND PURPOSE: The Patterns of Care for Brachytherapy in Europe (PCBE) study is aimed at establishing a detailed information system on brachytherapy throughout Europe. MATERIALS AND METHODS: The questionnaire was web-based and the analysis used data from each radiotherapy department with brachytherapy. There were three groups: Group I with 19 countries (15 initial European Community (EC) countries plus Iceland, Monaco, Norway and Switzerland -EC+4-), Group II with 10 countries (New European Community countries -NEC-) and Group III with 14 countries (Other European Countries -OEC-). RESULTS: In the European area there are 36 of 43 countries (85%) which achieved data collection from at least 50% of centres, and were included in the analysis. The tumour site that had the largest number of treated patients was gynaecological tumours. Several variations have been found in the mean number of patients treated per consultant radiation oncologist and physicist; and in the proportion of brachytherapy patients with gynaecology, prostate and breast tumours, by country and by European area. The provided data showed that the average number of brachytherapy patients per centre increased by 10% between 1997 and 2002. CONCLUSIONS: A European wide evaluation of brachytherapy practice using a web-based questionnaire is feasible and that there is considerable variation in both patterns of practice and available resources.

The EQUAL-ESTRO audit on geometric reconstruction techniques in brachytherapy.

BACKGROUND AND PURPOSE: A geometric check procedure of the reconstruction techniques used in brachytherapy treatment planning systems was developed by the EQUAL (European Quality Laboratory) Laboratory in the framework of the ESTRO's (European Society for Therapeutic Radiology and Oncology) project 'ESQUIRE' (Education Science and QUality assurance In Radiotherapy in Europe [Baumann M, Brada M. Towards equity in turbulent Europe ESTRO, European cooperation and the European Commission. Radiother Oncol 2005;75:251-2. Heeren G. The bright but ephemeral life of a rainbow. A chronical of seventeen years of intensive ESTRO-EU cooperation. Radiother Oncol 2005;75:253-7]) by the task group Braphyqs (Brachytherapy physics quality system). PATIENTS AND METHODS: The check is performed by using the so-called 'Baltas' phantom, mailed to the participating centres in order to check the local technique of geometric reconstruction used in dose calculation. RESULTS: To validate the procedures, the check was first tested among the members of the Braphyqs Network. Since November 2002, the system is open to other centres. Until now 152 reconstructions have been checked. Eighty-six percent of the results were within an acceptance level after the first check. For the remaining 14%, a second check has been proposed. The results of the re-checks are in most cases within an acceptance level, except for 2% of the reconstructions. CONCLUSIONS: The geometric check is available from the EQUAL Laboratory for all the brachytherapy centres. The decrease of the deviations observed between the two checks demonstrates the importance of this kind of external audit as some errors were revealed, which were not discovered before with techniques used in clinical quality control routines.

Broad-beam transmission data for new brachytherapy sources, Tm-170 and Yb-169.

The characteristics of the radionuclides (170)Tm and (169)Yb are highly interesting for their use as high dose-rate brachytherapy sources. The introduction of brachytherapy equipment containing these sources will lead to smaller required thicknesses of the materials used in radiation protection barriers compared with the use of conventional sources such as (192)Ir and (137)Cs. The purpose of this study is to determine the required thicknesses of protection material for the design of the protecting walls. Using the Monte Carlo method, transmission data were derived for broad-beam geometries through lead and concrete barriers, from which the first half value layer and tenth value layer are obtained. In addition, the dose reduction in a simulated patient was studied to determine whether transmission in the patient is a relevant factor in radiation protection calculations.

Modelling second malignancy risks from low dose rate and high dose rate brachytherapy as monotherapy for localised prostate cancer.

BACKGROUND AND PURPOSE: To estimate the risks of radiation-induced rectal and bladder cancers following low dose rate (LDR) and high dose rate (HDR) brachytherapy as monotherapy for localised prostate cancer and compare to external beam radiotherapy techniques. MATERIALS AND METHODS: LDR and HDR brachytherapy monotherapy plans were generated for three prostate CT datasets. Second cancer risks were assessed using Schneider's concept of organ equivalent dose. LDR risks were assessed according to a mechanistic model and a bell-shaped model. HDR risks were assessed according to a bell-shaped model. Relative risks and excess absolute risks were estimated and compared to external beam techniques. RESULTS: Excess absolute risks of second rectal or bladder cancer were low for both LDR (irrespective of the model used for calculation) and HDR techniques. Average excess absolute risks of rectal cancer for LDR brachytherapy according to the mechanistic model were 0.71 per 10,000 person-years (PY) and 0.84 per 10,000 PY respectively, and according to the bell-shaped model, were 0.47 and 0.78 per 10,000 PY respectively. For HDR, the average excess absolute risks for second rectal and bladder cancers were 0.74 and 1.62 per 10,000 PY respectively. The absolute differences between techniques were very low and clinically irrelevant. Compared to external beam prostate radiotherapy techniques, LDR and HDR brachytherapy resulted in the lowest risks of second rectal and bladder cancer. CONCLUSIONS: This study shows both LDR and HDR brachytherapy monotherapy result in low estimated risks of radiation-induced rectal and bladder cancer. LDR resulted in lower bladder cancer risks than HDR, and lower or similar risks of rectal cancer. In absolute terms these differences between techniques were very small. Compared to external beam techniques, second rectal and bladder cancer risks were lowest for brachytherapy.

Guidelines by the AAPM and GEC-ESTRO on the use of innovative brachytherapy devices and applications: Report of Task Group 167.

Although a multicenter, Phase III, prospective, randomized trial is the gold standard for evidence-based medicine, it is rarely used in the evaluation of innovative devices because of many practical and ethical reasons. It is usually sufficient to compare the dose distributions and dose rates for determining the equivalence of the innovative treatment modality to an existing one. Thus, quantitative evaluation of the dosimetric characteristics of innovative radiotherapy devices or applications is a critical part in which physicists should be actively involved. The physicist's role, along with physician colleagues, in this process is highlighted for innovative brachytherapy devices and applications and includes evaluation of (1) dosimetric considerations for clinical implementation (including calibrations, dose calculations, and radiobiological aspects) to comply with existing societal dosimetric prerequisites for sources in routine clinical use, (2) risks and benefits from a regulatory and safety perspective, and (3) resource assessment and preparedness. Further, it is suggested that any developed calibration methods be traceable to a primary standards dosimetry laboratory (PSDL) such as the National Institute of Standards and Technology in the U.S. or to other PSDLs located elsewhere such as in Europe. Clinical users should follow standards as approved by their country's regulatory agencies that approved such a brachytherapy device. Integration of this system into the medical source calibration infrastructure of secondary standard dosimetry laboratories such as the Accredited Dosimetry Calibration Laboratories in the U.S. is encouraged before a source is introduced into widespread routine clinical use. The American Association of Physicists in Medicine and the Groupe Européen de Curiethérapie-European Society for Radiotherapy and Oncology (GEC-ESTRO) have developed guidelines for the safe and consistent application of brachytherapy using innovative devices and applications. The current report covers regulatory approvals, calibration, dose calculations, radiobiological issues, and overall safety concerns that should be addressed during the commissioning stage preceding clinical use. These guidelines are based on review of requirements of the U.S. Nuclear Regulatory Commission, U.S. Department of Transportation, International Electrotechnical Commission Medical Electrical Equipment Standard 60601, U.S. Food and Drug Administration, European Commission for CE Marking (Conformité Européenne), and institutional review boards and radiation safety committees.

Reirradiation and hyperthermia for irresectable locoregional recurrent breast cancer in previously irradiated area: Size matters.

BACKGROUND/PURPOSE: Treatment options for irresectable locoregional recurrent breast cancer in previously irradiated area are limited. Hyperthermia, elevating tumor temperature to 40-45°C, sensitizes radio-and-chemotherapy. Four hundred and fourteen patients treated with reirradiation+hyperthermia (reRT+HT) in the AMC(n=301) and the BVI(n=113), from 1982 to 2005 were retrospectively analyzed for treatment response, locoregional control (LC) and prognostic factors for LC and toxicity. PATIENTS/METHODS: All patients received previous irradiation (median 50 Gy). reRT consisted of 8 × 4 Gy-2/week (AMC) or 12 × 3 Gy-4/week (BVI). Hyperthermia was added once (AMC)/twice (BVI) a week. RESULTS: Overall clinical response rate was 86%. The 3-year LC rate was 25%. The number of recurrence episodes, distant metastases (DM), tumor site, tumor size, time to recurrence and treatment year were significant for LC. Acute ⩾ grade 3 toxicity occurred in 24% of patients. Actuarial late ⩾ grade 3 toxicity was 23% at 3-years. In multivariable analysis reRT fraction dose was significantly related to late ⩾ grade 3 toxicity. CONCLUSION: reRT+HT is an effective curative and palliative treatment option for patients with irresectable locoregional recurrent breast cancer in previously irradiated area. Early referral, treatment of chest wall recurrences ⩽ 5 cm in the absence of distant metastases, provided the highest local control rates. The cumulative effects of past and present treatments should be accounted for by adjusting treatment protocol to minimize toxicity.

Quality control of brachytherapy equipment in the Netherlands and Belgium: current practice and minimum requirements.

BACKGROUND AND PURPOSE: Brachytherapy is applied in 39 radiotherapy institutions in The Netherlands and Belgium. Each institution has its own quality control (QC) programme to ensure safe and accurate dose delivery to the patient. The main goal of this work is to gain insight into the current practice of QC of brachytherapy in The Netherlands and Belgium and to reduce possible variations in test frequencies and tolerances by formulating a set of minimum QC-requirements. MATERIALS AND METHODS: An extensive questionnaire about QC of brachytherapy was distributed to and completed by the 39 radiotherapy institutions. A separate smaller questionnaire was sent to nine institutions performing intracoronary brachytherapy. The questions were related to safety systems, physical irradiation parameters and total time spent on QC. The results of the questionnaires were compared with recommendations given in international brachytherapy QC reports. RESULTS: The answers to the questionnaires showed large variations in test frequencies and test methods. Furthermore, large variations in time spent on QC exist, which is mainly due to differences in QC-philosophy and differences in the available resources. CONCLUSIONS: Based on the results of the questionnaires and the comparison with the international recommendations, a set of minimum requirements for QC of brachytherapy has been formulated. These guidelines will be implemented in the radiotherapy institutions in The Netherlands and Belgium.

Second primary cancers after radiation for prostate cancer: a systematic review of the clinical data and impact of treatment technique.

The development of a radiation induced second primary cancer (SPC) is one the most serious long term consequences of successful cancer treatment. This review aims to evaluate SPC in prostate cancer (PCa) patients treated with radiotherapy, and assess whether radiation technique influences SPC. A systematic review of the literature was performed to identify studies examining SPC in irradiated PCa patients. This identified 19 registry publications, 21 institutional series and 7 other studies. There is marked heterogeneity in published studies. An increased risk of radiation-induced SPC has been identified in several studies, particularly those with longer durations of follow-up. The risk of radiation-induced SPC appears small, in the range of 1 in 220 to 1 in 290 over all durations of follow-up, and may increase to 1 in 70 for patients followed up for more than 10 years, based on studies which include patients treated with older radiation techniques (i.e. non-conformal, large field). To date there are insufficient clinical data to draw firm conclusions about the impact of more modern techniques such as IMRT and brachytherapy on SPC risk, although limited evidence is encouraging. In conclusion, despite heterogeneity between studies, an increased risk of SPC following radiation for PCa has been identified in several studies, and this risk appears to increase over time. This must be borne in mind when considering which patients to irradiate and which techniques to employ.

Review of clinical brachytherapy uncertainties: analysis guidelines of GEC-ESTRO and the AAPM.

BACKGROUND AND PURPOSE: A substantial reduction of uncertainties in clinical brachytherapy should result in improved outcome in terms of increased local control and reduced side effects. Types of uncertainties have to be identified, grouped, and quantified. METHODS: A detailed literature review was performed to identify uncertainty components and their relative importance to the combined overall uncertainty. RESULTS: Very few components (e.g., source strength and afterloader timer) are independent of clinical disease site and location of administered dose. While the influence of medium on dose calculation can be substantial for low energy sources or non-deeply seated implants, the influence of medium is of minor importance for high-energy sources in the pelvic region. The level of uncertainties due to target, organ, applicator, and/or source movement in relation to the geometry assumed for treatment planning is highly dependent on fractionation and the level of image guided adaptive treatment. Most studies to date report the results in a manner that allows no direct reproduction and further comparison with other studies. Often, no distinction is made between variations, uncertainties, and errors or mistakes. The literature review facilitated the drafting of recommendations for uniform uncertainty reporting in clinical BT, which are also provided. The recommended comprehensive uncertainty investigations are key to obtain a general impression of uncertainties, and may help to identify elements of the brachytherapy treatment process that need improvement in terms of diminishing their dosimetric uncertainties. It is recommended to present data on the analyzed parameters (distance shifts, volume changes, source or applicator position, etc.), and also their influence on absorbed dose for clinically-relevant dose parameters (e.g., target parameters such as D90 or OAR doses). Publications on brachytherapy should include a statement of total dose uncertainty for the entire treatment course, taking into account the fractionation schedule and level of image guidance for adaptation. CONCLUSIONS: This report on brachytherapy clinical uncertainties represents a working project developed by the Brachytherapy Physics Quality Assurances System (BRAPHYQS) subcommittee to the Physics Committee within GEC-ESTRO. Further, this report has been reviewed and approved by the American Association of Physicists in Medicine.

Second primary cancers after radiation for prostate cancer: a review of data from planning studies.

A review of planning studies was undertaken to evaluate estimated risks of radiation induced second primary cancers (RISPC) associated with different prostate radiotherapy techniques for localised prostate cancer. A total of 83 publications were identified which employed a variety of methods to estimate RISPC risk. Of these, the 16 planning studies which specifically addressed absolute or relative second cancer risk using dose-response models were selected for inclusion within this review. There are uncertainties and limitations related to all the different methods for estimating RISPC risk. Whether or not dose models include the effects of the primary radiation beam, as well as out-of-field regions, influences estimated risks. Regarding the impact of IMRT compared to 3D-CRT, at equivalent energies, several studies suggest an increase in risk related to increased leakage contributing to out-of-field RISPC risk, although in absolute terms this increase in risk may be very small. IMRT also results in increased low dose normal tissue irradiation, but the extent to which this has been estimated to contribute to RISPC risk is variable, and may also be very small. IMRT is often delivered using 6MV photons while conventional radiotherapy often requires higher energies to achieve adequate tissue penetration, and so comparisons between IMRT and older techniques should not be restricted to equivalent energies. Proton and brachytherapy planning studies suggest very low RISPC risks associated with these techniques. Until there is sufficient clinical evidence regarding RISPC risks associated with modern irradiation techniques, the data produced from planning studies is relevant when considering which patients to irradiate, and which technique to employ.

Patient positioning based on a radioactive tracer implanted in patients with localized prostate cancer: a performance and safety evaluation.

PURPOSE: To evaluate the performance and safety of a radiation therapy positioning system (RealEye) based on tracking a radioactive marker (Tracer) implanted in patients with localized prostate cancer. METHODS AND MATERIALS: We performed a single-arm multi-institutional trial in 20 patients. The iridium-192 ((192)Ir)-containing Tracer was implanted in the patient together with 4 standard gold seed fiducials. Patient prostate-related symptoms were evaluated with the International Prostate Symptom Score (IPSS) questionnaire. Computed tomography (CT) was performed for treatment planning, during treatment, and after treatment to evaluate the migration stability of the Tracer. At 5 treatment sessions, cone beam CT was performed to test the positioning accuracy of the RealEye. RESULTS: The Tracer was successfully implanted in all patients. No device or procedure-related adverse events occurred. Changes in IPSS scores were limited. The difference between the mean change in Tracer-fiducial distance and the mean change in fiducial-fiducial distance was -0.39 mm (95% confidence interval [CI] upper boundary, -0.22 mm). The adjusted mean difference between Tracer position according to RealEye and the Tracer position on the CBCT for all patients was 1.34 mm (95% CI upper boundary, 1.41 mm). CONCLUSIONS: Implantation of the Tracer is feasible and safe. Migration stability of the Tracer is good. Prostate patients can be positioned and monitored accurately by using RealEye.