A competing risk analysis of the patterns and risk factors of recurrence in early-stage non-small cell lung cancer treated with stereotactic ablative radiotherapy.

INTRODUCTION: To assess patterns of recurrence after stereotactic ablative radiotherapy (SABR) in patient ineligible to surgery with early-stage non-small cell lung cancer (ES-NSCLC), report survival and treatment after first recurrence. METHODS: We performed a retrospective analysis on 1068 patients with ES-NSCLC and 1143 lesions. Between group differences were estimated using competing risk analysis and cause-specific hazard ratios were calculated. Overall survival (OS) after first recurrence was calculated. RESULTS: Median follow-up was 37.6 months. Univariate analysis demonstrated that ultra-central location was associated with higher risk of regional recurrence (RR) and distant metastasis (DM) (p = 0.004 and 0.01). Central lesions were associated with higher risk of local recurrence (LR) and RR (p < 0.001). Ultra-central lesions were associated with shorter OS (p = 0.002) compared to peripheral lesions. In multivariate analysis, central location was the only factor associated with increased LR and RR risks (p = 0.016 and 0.005). Median OS after first recurrence was 14.8 months. There was no difference in OS after first recurrence between ultra-central, central, and peripheral lesions (p = 0.83). Patients who received a second SABR course had an OS of 51.3 months, compared to 19.5 months with systemic therapy and 8.1 months with supportive care (p < 0.0001). DISCUSSION: The main prognostic factor for LR and RR risks was central location. Ultra-central and central tumors might benefit from treatment intensification strategies such as dose escalation and/or addition of systemic therapy to improve radiotherapy outcomes. After a first recurrence post SABR, patients with contralateral lung recurrences and those who were eligible to receive a second course of SABR had improved OS.

Corrigendum: MRI-guided focal or integrated boost high dose rate brachytherapy for recurrent prostate cancer.

[This corrects the article DOI: 10.3389/fonc.2022.971344.].

MRI-guided focal or integrated boost high dose rate brachytherapy for recurrent prostate cancer.

Background and purpose: Locally recurrent prostate cancer after radiotherapy merits an effective salvage strategy that mitigates the risk of adverse events. We report outcomes of a cohort enrolled across two institutions investigating MRI-guided tumor-targeted salvage high dose rate brachytherapy (HDR-BT). Materials and methods: Analysis of a prospective cohort of 88 patients treated across two institutions with MRI-guided salvage HDR-BT to visible local recurrence after radiotherapy (RT). Tumor target dose ranged from 22-26 Gy, using either an integrated boost (ibBT) or focal technique (fBT), delivered in two implants over a median of 7 days. Outcome metrics included cancer control and toxicity (CTCAE). Quality of life (QoL-EPIC) was analyzed in a subset. Results: At a median follow-up of 35 months (6 -134), 3 and 5-year failure-free survival (FFS) outcomes were 67% and 49%, respectively. At 5 years, fBT was associated with a 17% cumulative incidence of local failure (LF) outside the GTV (vs. 7.8% ibBT, p=0.14), while LF within the GTV occurred in 13% (vs. 16% ibBT, p=0.81). Predictors of LF outside fBT volumes included pre-salvage PSA>7 ng/mL (p=0.03) and interval since RT less than 5 years (p=0.04). No attributable grade 3 events occurred, and ibBT was associated with a higher rate of grade 2 toxicity (p<0.001), and trend towards a larger reduction in QoL sexual domain score (p=0.07), compared to fBT. Conclusion: A tumor-targeted HDR-BT salvage approach achieved favorable cancer control outcomes. While a fBT was associated with less toxicity, it may be best suited to a subgroup with lower PSA at later recurrence. Tumor targeted dose escalation may be warranted.

Performance of an integrated multimodality image guidance and dose-planning system supporting tumor-targeted HDR brachytherapy for prostate cancer.

BACKGROUND AND PURPOSE: Advances in high-dose-rate brachytherapy to treat prostate cancer hinge on improved accuracy in navigation and targeting while optimizing a streamlined workflow. Multimodal image registration and electromagnetic (EM) tracking are two technologies integrated into a prototype system in the early phase of clinical evaluation. We aim to report on the system's accuracy and workflow performance in support of tumor-targeted procedures. MATERIALS AND METHODS: In a prospective study, we evaluated the system in 43 consecutive procedures after clinical deployment. We measured workflow efficiency and EM catheter reconstruction accuracy. We also evaluated the system's MRI-TRUS registration accuracy with/without deformation, and with/without y-axis rotation for urethral alignment at initialization. RESULTS: The cohort included 32 focal brachytherapy and 11 integrated boost whole-gland implants. Mean procedure time excluding dose delivery was 38 min (range: 21-83) for focal, and 56 min (range: 38-89) for whole-gland implants; stable over time. EM catheter reconstructions achieved a mean difference between computed and measured free-length of 0.8 mm (SD 0.8, no corrections performed), and mean axial manual corrections 1.3 mm (SD 0.7). EM also enabled the clinical use of a non or partially visible catheter in 21% of procedures. Registration accuracy improved with y-axis rotation for urethral alignment at initialization and with the elastic registration (mTRE 3.42 mm, SD 1.49). CONCLUSION: The system supported tumor-targeting and was implemented with no demonstrable learning curve. EM reconstruction errors were small, correctable, and improved with calibration and control of external distortion sources; increasing confidence in the use of partially visible catheters. Image registration errors remained despite rotational alignment and deformation, and should be carefully considered.

Fusion of Intraoperative Transrectal Ultrasound Images with Post-implant Computed Tomography and Magnetic Resonance Imaging.

Purpose To compare the impact of the fusion of intraoperative transrectal ultrasound (TRUS) images with day 30 computed tomography (CT) and magnetic resonance imaging (MRI) on prostate volume and dosimetry. Methods and materials Seventy-five consecutive patients with CT and MRI obtained on day 30 with a Fast Spin Echo T2-weighted magnetic resonance (MR) sequence were analyzed. A rigid manual registration was performed between the intraoperative TRUS and day-30 CT based on the prostate volume. A second manual rigid registration was performed between the intraoperative TRUS and the day-30 MRI. The prostate contours were manually modified on CT and MRI. The difference in prostate volume and dosimetry between CT and MRI were compared. Results Prostate volume was on average 8% (standard deviation (SD) ± 16%) larger on intraoperative TRUS than on CT and 6% (18%) larger than on MRI. In 48% of the cases, the difference in volume on CT was > 10% compared to MRI. The difference in prostate volume between CT and MRI was inversely correlated to the difference in D90 (minimum dose that covers 90% of the prostate volume) between CT and MRI (r = -0.58, P < .001). A D90 < 90% was found in 5% (n = 4) on MRI and in 10% (n = 7) on CT (Fisher exact test one-sided P = .59), but in no patient was the D90 < 90% on both MRI and CT. Conclusions When fusing TRUS images with CT and MRI, the differences in prostate volume between those modalities remain clinically important in nearly half of the patients, and this has a direct influence on how implant quality is evaluated.

Stereotactic body radiotherapy (SBRT) for patients with locally advanced pancreatic cancer: A single center experience.

INTRODUCTION: Despite advances in treatment, notably in systemic therapy, the prognosis of pancreatic adenocarcinoma (PADC) remains dismal. Stereotactic body radiotherapy (SBRT) is an emerging tool in the complex management of PADC. We review outcomes of SBRT for PADC at our institution. METHODS: We reviewed patients treated with SBRT for either unresectable PADC or locally recurrent PADC after surgery. Treatment was delivered using a robotic radiosurgery system with respiratory tracking. The median prescribed dose was 30 Gy (30-35 Gy), delivered in 5-6 fractions. Toxicities were reported as per CTCAE v4.0. Survival was estimated using the Kaplan-Meier method. RESULTS: Between October 2010 and March 2016, 21 patients were treated at our institution. The median follow-up was 7 months (range: 1-28). The 1-year local control rate was 57%. The 1-year overall survival was 25% for locally advanced patients and 67% for those with local recurrences (p = 0.27). Eighty percent of cancer related deaths were due to metastatic progression. Five patients (24%) had Grade I-II gastrointestinal acute toxicity; one patient had fatal gastrointestinal bleeding 6 months after SBRT. CONCLUSION: In PADC, fractionated SBRT dose schedules near 30 Gy may strike the best balance of local control and bowel toxicity. More work is required to integrate pancreatic SBRT with modern systemic therapy.

Dosimetric impact of dual-energy CT tissue segmentation for low-energy prostate brachytherapy: a Monte Carlo study.

The purpose of this study is to evaluate the impact of a novel tissue characterization method using dual-energy over single-energy computed tomography (DECT and SECT) on Monte Carlo (MC) dose calculations for low-dose rate (LDR) prostate brachytherapy performed in a patient like geometry. A virtual patient geometry is created using contours from a real patient pelvis CT scan, where known elemental compositions and varying densities are overwritten in each voxel. A second phantom is made with additional calcifications. Both phantoms are the ground truth with which all results are compared. Simulated CT images are generated from them using attenuation coefficients taken from the XCOM database with a 100 kVp spectrum for SECT and 80 and 140Sn kVp for DECT. Tissue segmentation for Monte Carlo dose calculation is made using a stoichiometric calibration method for the simulated SECT images. For the DECT images, Bayesian eigentissue decomposition is used. A LDR prostate brachytherapy plan is defined with 125I sources and then calculated using the EGSnrc user-code Brachydose for each case. Dose distributions and dose-volume histograms (DVH) are compared to ground truth to assess the accuracy of tissue segmentation. For noiseless images, DECT-based tissue segmentation outperforms the SECT procedure with a root mean square error (RMS) on relative errors on dose distributions respectively of 2.39% versus 7.77%, and provides DVHs closest to the reference DVHs for all tissues. For a medium level of CT noise, Bayesian eigentissue decomposition still performs better on the overall dose calculation as the RMS error is found to be of 7.83% compared to 9.15% for SECT. Both methods give a similar DVH for the prostate while the DECT segmentation remains more accurate for organs at risk and in presence of calcifications, with less than 5% of RMS errors within the calcifications versus up to 154% for SECT. In a patient-like geometry, DECT-based tissue segmentation provides dose distributions with the highest accuracy and the least bias compared to SECT. When imaging noise is considered, benefits of DECT are noticeable if important calcifications are found within the prostate.

Single-fraction high-dose-rate brachytherapy using real-time transrectal ultrasound based planning in combination with external beam radiotherapy for prostate cancer: dosimetrics and early clinical results.

PURPOSE: To validate the feasibility of a single-fraction high-dose-rate brachytherapy (HDRBT) boost for prostate cancer using real-time transrectal ultrasound (TRUS) based planning. MATERIAL AND METHODS: From August 2012 to September 2015, 126 patients underwent a single-fraction HDRBT boost of 15 Gy using real-time TRUS based planning. External beam radiation therapy (EBRT) (37.5 Gy/15 fractions, 44 Gy/22 fractions, or 45 Gy/25 fractions) was performed before (31%) or after (69%) HDRBT boost. Genito-urinary (GU) and gastro-intestinal (GI) toxicity were assessed 4 and 12 months after the end of combined treatment using the international prostate symptom score scale (IPSS) and the common terminology criteria for adverse events (CTCAE) v3.0. RESULTS: All dose-planning objectives were achieved in 90% of patients. Prostate D90 ≥ 105% and ≤ 115% was achieved in 99% of patients, prostate V150 ≤ 40% in 99%, prostate V200 < 11% in 96%, urethra D10 < 120% for 99%, urethra V125 = 0% in 100%, and rectal V75 < 1 cc in 93% of patients. Median IPSS score was 4 at baseline and did not change at 4 and 12 months after combined treatment. No patients developed ≥ grade 2 GI toxicity. With a median follow-up of 10 months, only two patients experienced biochemical failure. Among patients who didn't receive ADT, cumulative percentage of patients with PSA ≤ 1 ng/ml at 4 and 18 months was respectively 23% and 66%. CONCLUSIONS: Single-fraction HDRBT boost of 15 Gy using real-time TRUS based planning achieves consistently high dosimetry quality. In combination with EBRT, toxicity outcomes appear promising. A longer follow-up is needed to assess long-term outcome and toxicities.

Technique for Robotic Stereotactic Irradiation of Choroidal Melanoma.

Radiotherapy has a long history in the organ-sparing management of choroidal melanoma. Joining plaque radiotherapy and proton irradiation, stereotactic robotic photon irradiation is a new tool in the radiation oncologist's armamentarium for ocular tumors. The non-coplanar fields with steep dose gradients are well suited to spare uninvolved retina, anterior chamber, and the optic nerve. In our practice, it is the preferred treatment for melanomas that are non-amenable to standard plaque brachytherapy. Since late 2010, we have treated more than 40 patients with our robotic linear accelerator. This case-based technical note outlines the technique used at the University of Montreal, Montreal, Canada.

Severe radiation pneumonitis after lung stereotactic ablative radiation therapy in patients with interstitial lung disease.

PURPOSE: To investigate the incidence and predictive factors of severe radiation pneumonitis (RP) after stereotactic ablative radiation therapy (SABR) in early-stage lung cancer patients with preexisting radiological interstitial lung disease (ILD). METHODS AND MATERIALS: A retrospective analysis of patients with stage I lung cancer treated with SABR from 2009 to 2014 was conducted. Interstitial lung disease diagnosis and grading was based on pretreatment high-resolution computed tomography imaging. A central review of pretreatment computed tomography by a single experienced thoracic radiologist was conducted. Univariate and multivariate analyses were conducted to determine potential predictors of severe RP in patients with ILD. RESULTS: Among 504 patients treated with SABR in this period, 6% were identified as having preexisting ILD. There was a 4% rate of ≥ grade 3 RP in the entire cohort. Interstitial lung disease was associated with increased risk of ≥ grade 3 RP (32% in ILD+ vs 2% in ILD-, P < .001). Five patients (21%) with ILD developed grade 5 RP. Lower forced expiratory volume in 1 second and forced vital capacity, higher V5Gy and mean lung dose, presence of severe radiological ILD, and combined emphysema were significant predictors of ≥ grade 3 RP on univariate analysis; only forced expiratory volume in 1 second remained on multivariate analysis. CONCLUSION: Interstitial lung disease is associated with an increased risk of severe RP after SABR. Chest imaging should be reviewed for ILD before SABR, and the risk of fatal RP should be carefully weighed against the benefits of SABR in this subgroup.

Seed loss in prostate brachytherapy : Operator dependency and impact on dosimetry.

INTRODUCTION: The aim of our study was to review seed loss and its impact on dosimetry as well as the influence of the treating physician on seed loss and dosimetry in patients treated with prostate brachytherapy using permanent loose (125)I implant. PATIENTS AND METHODS: We analyzed 1087 consecutive patients treated by two physicians between July 2005 and April 2015 at a single institution. Pelvic fluoroscopic imaging was done 30 days post implant and a chest X-ray when seed loss was observed. RESULTS: Seed loss occurred in 19.4 % of patients: in 20.0 % of implants done by the most experienced physician and in 17.2 % by the less experienced physician (p = 0.4) and migration to the thorax occurred in 5.9 % (6.9 vs. 2.2 %, p = 0.004). The mean seed loss rate was 0.57 % [standard deviation (SD) 1.39] and the mean rate of seeds in the thorax was 0.14 % (SD 0.65). The most experienced physician had a higher mean number of seeds lost: 0.36 versus 0.25 (p = 0.055), and a higher mean number of seed migration to the thorax: 0.1 versus 0.02 (p < 0.001). When at least one seed was lost, a decrease of 4.2 Gy (p < 0.001) in the D90 and a decrease of 3.5 % (p = 0.002) in the V150 was observed. CONCLUSION: We found a significant decrease in V150 and D90 with the occurrence of seed loss. Furthermore, we found a difference in seed migration among the physicians demonstrating that seed loss is operator dependant.

Refining prostate seed brachytherapy: Comparing high-, intermediate-, and low-activity seeds for I-125 permanent seed prostate brachytherapy.

PURPOSE: To analyze the difference in prostate coverage and dose to the rectum in men with prostate carcinoma treated with permanent seed brachytherapy with different seed activities. METHODS: Forty-nine patients treated with iodine-125 permanent seed prostate brachytherapy with low-activity seeds of 0.30-0.37 mCi were identified. For each of these patients, 2 patients with similar prostate volume (±2 cc) were paired: one treated with intermediate seed activity (0.44-0.46 mCi) and one with high seed activity (0.60-0.66 mCi). The doses to prostate and rectum were compared using CT on Day 30. RESULTS: A total of 147 patients divided into the three seed activity groups were analyzed. Mean prostate volume was 35.7 cc (standard deviation [SD], 11.70). Compared with low-activity seeds, implants with high-activity seeds consisted of an average of 22 seeds and 4.7 needles less. The dose to the prostate (prostate volume receiving 100% of the prescribed dose [V100], prostate volume receiving 150% of the prescribed dose, and minimal dose covering 90% of the prostate volume expressed in Gy) was not higher on Day 30 (p = 0.58-0.97). The mean volume (in cubic centimeters) of rectal wall receiving 100% of the prescribed dose (V100) increased with activity: low activity, 0.34 cc (SD, 0.49), intermediate activity, 0.47 cc (SD, 0.48), and high activity, 0.72 cc (SD, 0.79) (p = 0.009). There was a trend (p = 0.073) toward a higher frequency of clinically unfavorable rectal dosimetry (V100 > 1.3 cc) in patients with high-activity seeds (16.7%) compared with low-activity (6.3%) or intermediate-activity (4.2%) seeds. CONCLUSION: High-activity seeds do not result in a higher dose to the prostate but in a higher dose to the rectum.

Predictive parameters of CyberKnife fiducial-less (XSight Lung) applicability for treatment of early non-small cell lung cancer: a single-center experience.

PURPOSE: To determine which parameters allow for CyberKnife fiducial-less tumor tracking in stereotactic body radiation therapy (SBRT) for early-stage non-small cell lung cancer. METHODS AND MATERIALS: A total of 133 lung SBRT patients were preselected for direct soft-tissue tracking based on manufacturer recommendations (peripherally located tumors ≥1.5 cm with a dense appearance) and staff experience. Patients underwent a tumor visualization test to verify adequate detection by the tracking system (orthogonal radiographs). An analysis of potential predictors of successful tumor tracking was conducted looking at: tumor stage, size, histology, tumor projection on the vertebral column or mediastinum, distance to the diaphragm, lung-to-soft tissue ratio, and patient body mass index. RESULTS: Tumor visualization was satisfactory for 88 patients (66%) and unsatisfactory for 45 patients (34%). Median time to treatment start was 6 days in the success group (range, 2-18 days) and 15 days (range, 3-63 days) in the failure group. A stage T2 (P=.04), larger tumor size (volume of 15.3 cm(3) vs 6.5 cm(3) in success and failure group, respectively) (P<.0001), and higher tumor density (0.86 g/cm(3) vs 0.79 g/cm(3)) were predictive of adequate detection. There was a 63% decrease in failure risk with every 1-cm increase in maximum tumor dimension (relative risk for failure = 0.37, CI=0.23-0.60, P=.001). A diameter of 3.6 cm predicted a success probability of 80%. Histology, lung-to-soft tissue ratio, distance to diaphragm, patient's body mass index, and tumor projection on vertebral column and mediastinum were not found to be predictive of success. CONCLUSIONS: Tumor size, volume, and density were the most predictive factors of a successful XSight Lung tumor tracking. Tumors >3.5 cm have ≥80% chance of being adequately visualized and therefore should all be considered for direct tumor tracking.

A comparative study of small field total scatter factors and dose profiles using plastic scintillation detectors and other stereotactic dosimeters: the case of the CyberKnife.

PURPOSE: Small-field dosimetry is challenging, and the main limitations of most dosimeters are insufficient spatial resolution, water nonequivalence, and energy dependence. The purpose of this study was to compare plastic scintillation detectors (PSDs) to several commercial stereotactic dosimeters by measuring total scatter factors and dose profiles on a CyberKnife system. METHODS: Two PSDs were developed, having sensitive volumes of 0.196 and 0.785 mm(3), and compared with other detectors. The spectral discrimination method was applied to subtract Cerenkov light from the signal. Both PSDs were compared to four commercial stereotactic dosimeters by measuring total scatter factors, namely, an IBA dosimetry stereotactic field diode (SFD), a PTW 60008 silicon diode, a PTW 60012 silicon diode, and a microLion. The measured total scatter factors were further compared with those of two independent Monte Carlo studies. For the dose profiles, two commercial detectors were used for the comparison, i.e., a PTW 60012 silicon diode and Gafchromics EBT2. Total scatter factors for a CyberKnife system were measured in circular fields with diameters from 5 to 60 mm. Dose profiles were measured for the 5- and 60-mm cones. The measurements were performed in a water tank at a 1.5-cm depth and an 80-cm source-axis distance. RESULTS: The total scatter factors measured using all the detectors agreed within 1% with the Monte Carlo values for cones of 20 mm or greater in diameter. For cones of 10-20 mm in diameter, the PTW 60008 silicon diode was the only dosimeter whose measurements did not agree within 1% with the Monte Carlo values. For smaller fields (<10 mm), each dosimeter type showed different behaviors. The silicon diodes over-responded because of their water nonequivalence; the microLion and 1.0-mm PSD under-responded because of a volume-averaging effect; and the 0.5-mm PSD was the only detector within the uncertainties of the Monte Carlo simulations for all the cones. The PSDs, the PTW 60012 silicon diode, and the Gafchromics EBT2 agreed within 2% and 0.2 mm (gamma evaluation) for the measured dose profiles except in the tail of the 60-mm cone. CONCLUSIONS: Silicon diodes can be used to accurately measure small-field dose profiles but not to measure total scatter factors, whereas PSDs can be used to accurately measure both. The authors' measurements show that the use of a 1.0-mm PSD resulted in a negligible volume-averaging effect (under-response of ≈1%) down to a field size of 5 mm. Therefore, PSDs are strong candidates to become reference radiosurgery detectors for beam characterization and quality assurance measurements.

Impact of concurrent androgen deprivation on fiducial marker migration in external-beam radiation therapy for prostate cancer.

PURPOSE: To determine the extent of gold fiducial marker (FM) migration in patients treated for prostate cancer with concurrent androgen deprivation and external-beam radiation therapy (EBRT). METHODS AND MATERIALS: Three or 4 gold FMs were implanted in 37 patients with prostate adenocarcinoma receiving androgen deprivation therapy (ADT) in conjunction with 70-78 Gy. Androgen deprivation therapy was started a median of 3.9 months before EBRT (range, 0.3-12.5 months). To establish the extent of FM migration, the distance between each FM was calculated for 5-8 treatments once per week throughout the EBRT course. For each treatment, the distance between FMs was compared with the distance from the digitally reconstructed radiographs generated from the planning CT. A total of 281 treatments were analyzed. RESULTS: The average daily migration was 0.8 ± 0.3 mm, with distances ranging from 0.2 mm-2.6 mm. Two of the 281 assessed treatments (0.7%) showed migrations >2 mm. No correlation between FM migration and patient weight or time delay between ADT and start of EBRT was found. There was no correlation between the extent of FM migration and prostate volume. CONCLUSION: This is the largest report of implanted FM migration in patients receiving concomitant ADT. Only 0.7% of the 281 treatments studied had significant marker migrations (>2 mm) throughout the course of EBRT. Consequently, the use of implanted FMs in these patients enables accurate monitoring of prostate gland position during treatment.

Seed migration in prostate brachytherapy depends on experience and technique.

PURPOSE: To determine seed loss and pulmonary migration rate over time in permanent seed prostate brachytherapy. METHODS AND MATERIALS: We analyzed the first 495 patients treated in our department. All patients were treated with loose (125)I seeds with automated seed delivery system and real-time intraoperative planning. Pelvic fluoroscopic imaging was done 30 days after the implant. Patients were divided into five groups of 100 patients according to the order they were treated, and groups were compared using χ(2) test and one-way analysis of variance. RESULTS: A total of 22.8% of patients lost at least one seed. The highest percentage of patients losing any number of seeds was in the first 100. Thirty-eight percent lost at least one seed. This number decreased gradually and was only 9% in Patients 400-499. The mean total seed loss rate (number of seeds lost/number seeds implanted) changed significantly over time (p<0.001). There was a continuous significant (p<0.001) decline after the first 100 patients (1.25% for the first 100 patients) followed by a rise in Patients 300-399, followed by another decline (0.21% for the last 100 patients). The seed loss rate to the thorax changed significantly over time (p=0.009). It rose after an initial rate of 0.25-0.42% in Patients 200-299 and 300-399 and declined later to a rate of 0.21% in the last 100 patients. CONCLUSIONS: We found a learning curve for seed migration. Avoiding implanting seeds outside of the capsule and modern transrectal ultrasound imaging can help decrease migration.

Analysis of seed loss and pulmonary seed migration in patients treated with virtual needle guidance and robotic seed delivery.

PURPOSE AND BACKGROUND: To determine whether automated seed delivery system and real-time intraoperative (IO) virtual needle guidance reduce seed loss and pulmonary seed migration. PATIENTS AND METHODS: We analyzed 279 patients with low and intermediate risk prostate cancer treated in our institution with radioactive iodine (I-125) permanent seed implants. Loose seeds were exclusively used. To account for lost seeds, pelvic fluoroscopic imaging from 3 different angles was done 30 days after the implant. Posteroanterior and lateral chest x-rays were done when seed loss was confirmed. Patients were compared using the χ(2) test and Fisher exact test. RESULTS: At least 1 seed was lost in 31.5% of patients with a migration rate of 1.02%; 9.3% of patients had at least 1 seed in the lung with a migration rate of 0.22%. The population was divided into 3 groups according to the order in which they were treated. Seed loss (P=0.02) and pulmonary seed embolization (P=0.008) were significantly lower in the second hundred than in the first hundred patients. No difference was noted between groups 1 and 3 (patient, 201-279). Peri- or extracapsular seed placement was not correlated to seed loss (P=0.780 and P=0.092, respectively). No serious complications from seed migration were reported. Seed loss did not influence dosimetry parameters (V100, V150, and D90). CONCLUSION: Our pulmonary seed migration and total seed loss rates are comparable to the ones reported in the literature. Virtual needle guidance and automated seed delivery system are in our hand as accurate as the manual technique.

Migration of intraprostatic fiducial markers and its influence on the matching quality in external beam radiation therapy for prostate cancer.

PURPOSE: To assess the influence of fiducial marker (FM) migration on the matching quality in external beam radiation therapy (EBRT) for prostate cancer. MATERIALS AND METHODS: The position of FMs were identified using on-board kV imaging (OBI) and their 3-D position established using an in-house reconstruction algorithm for 31 patients with prostate adenocarcinoma. To carry out the match, the positions were overlaid on the digitally reconstructed radiographs (DRR) generated from the planning CT. The distance between each FM was calculated for seven treatments throughout the EBRT course. Four radiotherapy technologists were asked to independently perform and rate the match from OBI to DRR which was then correlated to the extent of FM migration. RESULTS: All the matches were rated by at least three radiotherapy technologists as "very easy" ("easy" subgroup) for 24 patients (77%), while the other seven patients had their match rated less than "very easy" and considered the "not easy" subgroup. The average daily FM migration was 0.93+/-0.34 mm for the "easy" subgroup vs. 1.82+/-0.75 mm for the latter. An average migration >2 mm was seen in five/seven patients in the "not easy" subgroup as compared to none in the "easy" subgroup. There was a trend towards less FM migration and better matching if the planning CT was done later than the day of the FM implant (p=0.093). CONCLUSIONS: FM migration >2 mm predicts for a more difficult matching process; PTV margins might have to be adjusted or the planning CT repeated.

Clinical implementation of a digital tomosynthesis-based seed reconstruction algorithm for intraoperative postimplant dose evaluation in low dose rate prostate brachytherapy.

PURPOSE: The low dose rate brachytherapy procedure would benefit from an intraoperative postimplant dosimetry verification technique to identify possible suboptimal dose coverage and suggest a potential reimplantation. The main objective of this project is to develop an efficient, operator-free, intraoperative seed detection technique using the imaging modalities available in a low dose rate brachytherapy treatment room. METHODS: This intraoperative detection allows a complete dosimetry calculation that can be performed right after an I-125 prostate seed implantation, while the patient is still under anesthesia. To accomplish this, a digital tomosynthesis-based algorithm was developed. This automatic filtered reconstruction of the 3D volume requires seven projections acquired over a total angle of 60 degrees with an isocentric imaging system. RESULTS: A phantom study was performed to validate the technique that was used in a retrospective clinical study involving 23 patients. In the patient study, the automatic tomosynthesis-based reconstruction yielded seed detection rates of 96.7% and 2.6% false positives. The seed localization error obtained with a phantom study is 0.4 +/- 0.4 mm. The average time needed for reconstruction is below 1 min. The reconstruction algorithm also provides the seed orientation with an uncertainty of 10 degrees +/- 8 degrees. The seed detection algorithm presented here is reliable and was efficiently used in the clinic. CONCLUSIONS: When combined with an appropriate coregistration technique to identify the organs in the seed coordinate system, this algorithm will offer new possibilities for a next generation of clinical brachytherapy systems.

Dosimetric impact and theoretical clinical benefits of fiducial markers for dose escalated prostate cancer radiation treatment.

PURPOSE: To assess the impact of fiducial markers and daily kilovoltage imaging (FM-kV) on dose-volume histogram (DVH) parameters and normal tissue complication probabilities (NTCPs) for the rectum and bladder during prostate cancer radiotherapy. METHODS AND MATERIALS: Two different setup scenarios were compared for 20 patients treated with three-dimensional conformal radiotherapy (3D-CRT) for localized prostate cancer to a total dose of 76 Gy: a traditional setup with planning target volume (PTV) margins associated with skin mark alignment vs. another setup using FM-kV. Various DVH parameters were compared, including Radiation Therapy Oncology Group (RTOG) dose-volume constraints for the rectum and bladder. Analysis of NTCPs was also performed according to the Lyman model. RESULTS: With the traditional setup, 85% of patients had rectal V70(Gy) >25% compared with 45% with FM-kV. Moreover, 30% of patients with traditional setup vs. 5% with FM-kV did not fulfill at least 3 RTOG constraint parameters for the rectum. Mean rectal and bladder dose were 4.7 Gy and 6.7 Gy less, respectively, with FM-kV. The NTCP for the rectum was 11.5% with the traditional setup and 9% with FM-kV. This indicates that with FM-kV, the prescription dose could be increased by 2.1 Gy while keeping the same level of late rectal toxicity as with the traditional setup. CONCLUSIONS: Use of FM-kV is an efficient way of lowering the proportion of patients not fulfilling RTOG rectal and bladder dose-volume constraints. The results of the NTCP analysis suggest that the PTV margin reduction allowed by FM-kV should decrease the rate of late rectal toxicities or may allow moderate dose escalation.