Utilizing a novel hybrid brachytherapy technique FINITO (Freehand Interstitial Needles in addition to Tandem and Ovoid) for locally advanced cervical cancer.

PURPOSE: We aimed to assess the clinical feasibility and advantages of using a novel hybrid brachytherapy technique by placing Freehand Interstitial Needles in addition to the Tandem and Ovoid applicator (FINITO) for the treatment of locally advanced cervical cancer (LAC). METHODS AND MATERIALS: A retrospective analysis was performed on two cohorts of patients with LACC treated at our institution: 29 patients in the FINITO group and 17 patients in the control group using T&O only approach. Clinical outcomes of interest included local control (LC), progression-free survival (PFS), overall survival (OS), and rates of acute and late toxicities. Kaplan-Meier methodology was used to estimate OS, PFS, and LC. Wilcoxon signed-rank test was used to compare the median values for dosimetry parameters. A p-value of ≤ 0.05 was considered statistically significant. All statistical analyses were performed using RStudio. RESULTS: At a median of 2 years there was no difference in rates of OS, PFS or LC between the FINITO and the control group of patients. The 2-year OS, PFS, and LC for the FINITO group were 59% (95% CI 34%-100%), 58% (95% CI 38%-89%), and 84% (95% CI 69%-100%), respectively. Late toxicities were significantly lower in the FINITO group for both gastrointestinal and genitourinary symptoms (p = 0.001 and 0.01, respectively) as compared to the T&O group. CONCLUSION: Based on the equivalent LC rate and lower toxicity profile, our FINITO technique appears to be an excellent alternative to the standard intracavitary brachytherapy in patients with advanced disease, especially in resource-limited settings.

Ultrashort courses of adjuvant breast radiotherapy: wave of the future or a fool's errand?

In accelerated partial breast irradiation (APBI), the most commonly used fractionation schemes include 340 or 385 centigrays delivered in a twice daily administration. A further progression of the APBI literature has been the recent interest in extremely short courses of adjuvant radiotherapy, usually delivered by intraoperative radiotherapy techniques. This newer area of single-fraction radiotherapy approaches remains highly contentious. In particular, the recently reported TARGIT trial has been the subject of both praise and scorn, and a critical examination of the trial data and the underlying hypotheses is warranted. Short-term outcomes of the related Italian ELIOT approach have also been reported. Although the assumptions of linear quadratic formalism are likely to hold true in the range of 2 to 8 grays, equating different schedules beyond this range is problematic. A major problem of current single-fraction approaches is that the treatment doses are chosen empirically, or are based on tolerability, or on the physical dose delivery characteristics of the chosen technology rather than radiobiological rationale. This review article summarizes the current data on ultrashort courses of adjuvant breast radiotherapy and highlights both the promise and the potential pitfalls of the abbreviated treatment.

CivaSheet intraoperative radiation therapy for pancreatic cancer.

The treatment of borderline resectable (BR) pancreatic cancer is challenging and requires a multidisciplinary approach with chemotherapy, radiation and surgical resection. Despite using chemotherapy and radiotherapy in the neoadjuvant setting, achievement of negative surgical margins remains technically challenging. Positive margins are associated with increased local recurrences and worse overall survival and there are no standard options for treatment. The CivaSheet is an FDA-cleared implantable sheet with a matrix of unidirectional planar low-dose-rate (LDR) Palladium-103 (Pd-103) sources. The sources are shielded on one side with gold to spare radio-sensitive structures such as the bowel. The sheet can easily be customized and implanted at the time of surgery when there is concern for close or positive margins. The CivaSheet provides an interesting solution to target the region of close/positive margins after pancreatectomy. Here we discuss the physical properties, the dosimetry, clinical workflow and early patient outcomes with the CivaSheet in pancreatic cancer.

Reconstruction of brachytherapy seed positions and orientations from cone-beam CT x-ray projections via a novel iterative forward projection matching method.

PURPOSE: To generalize and experimentally validate a novel algorithm for reconstructing the 3D pose (position and orientation) of implanted brachytherapy seeds from a set of a few measured 2D cone-beam CT (CBCT) x-ray projections. METHODS: The iterative forward projection matching (IFPM) algorithm was generalized to reconstruct the 3D pose, as well as the centroid, of brachytherapy seeds from three to ten measured 2D projections. The gIFPM algorithm finds the set of seed poses that minimizes the sum-of-squared-difference of the pixel-by-pixel intensities between computed and measured autosegmented radiographic projections of the implant. Numerical simulations of clinically realistic brachytherapy seed configurations were performed to demonstrate the proof of principle. An in-house machined brachytherapy phantom, which supports precise specification of seed position and orientation at known values for simulated implant geometries, was used to experimentally validate this algorithm. The phantom was scanned on an ACUITY CBCT digital simulator over a full 660 sinogram projections. Three to ten x-ray images were selected from the full set of CBCT sinogram projections and postprocessed to create binary seed-only images. RESULTS: In the numerical simulations, seed reconstruction position and orientation errors were approximately 0.6 mm and 5 degrees, respectively. The physical phantom measurements demonstrated an absolute positional accuracy of (0.78 +/- 0.57) mm or less. The theta and phi angle errors were found to be (5.7 +/- 4.9) degrees and (6.0 +/- 4.1) degrees, respectively, or less when using three projections; with six projections, results were slightly better. The mean registration error was better than 1 mm/6 degrees compared to the measured seed projections. Each test trial converged in 10-20 iterations with computation time of 12-18 min/iteration on a 1 GHz processor. CONCLUSIONS: This work describes a novel, accurate, and completely automatic method for reconstructing seed orientations, as well as centroids, from a small number of radiographic projections, in support of intraoperative planning and adaptive replanning. Unlike standard back-projection methods, gIFPM avoids the need to match corresponding seed images on the projections. This algorithm also successfully reconstructs overlapping clustered and highly migrated seeds in the implant. The accuracy of better than 1 mm and 6 degrees demonstrates that gIFPM has the potential to support 2D Task Group 43 calculations in clinical practice.

Localizing intracavitary brachytherapy applicators from cone-beam CT x-ray projections via a novel iterative forward projection matching algorithm.

PURPOSE: To present a novel method for reconstructing the 3D pose (position and orientation) of radio-opaque applicators of known but arbitrary shape from a small set of 2D x-ray projections in support of intraoperative brachytherapy planning. METHODS: The generalized iterative forward projection matching (gIFPM) algorithm finds the six degree-of-freedom pose of an arbitrary rigid object by minimizing the sum-of-squared-intensity differences (SSQD) between the computed and experimentally acquired autosegmented projection of the objects. Starting with an initial estimate of the object's pose, gIFPM iteratively refines the pose parameters (3D position and three Euler angles) until the SSQD converges. The object, here specialized to a Fletcher-Weeks intracavitary brachytherapy (ICB) applicator, is represented by a fine mesh of discrete points derived from complex combinatorial geometric models of the actual applicators. Three pairs of computed and measured projection images with known imaging geometry are used. Projection images of an intrauterine tandem and colpostats were acquired from an ACUITY cone-beam CT digital simulator. An image postprocessing step was performed to create blurred binary applicators only images. To quantify gIFPM accuracy, the reconstructed 3D pose of the applicator model was forward projected and overlaid with the measured images and empirically calculated the nearest-neighbor applicator positional difference for each image pair. RESULTS: In the numerical simulations, the tandem and colpostats positions (x,y,z) and orientations (alpha, beta, gamma) were estimated with accuracies of 0.6 mm and 2 degrees, respectively. For experimentally acquired images of actual applicators, the residual 2D registration error was less than 1.8 mm for each image pair, corresponding to about 1 mm positioning accuracy at isocenter, with a total computation time of less than 1.5 min on a 1 GHz processor. CONCLUSIONS: This work describes a novel, accurate, fast, and completely automatic method to localize radio-opaque applicators of arbitrary shape from measured 2D x-ray projections. The results demonstrate approximately 1 mm accuracy while compared against the measured applicator projections. No lateral film is needed. By localizing the applicator internal structure as well as radioactive sources, the effect of intra-applicator and interapplicator attenuation can be included in the resultant dose calculations. Further validation tests using clinically acquired tandem and colpostats images will be performed for the accurate and robust applicator/sources localization in ICB patients.

Inter-fractional variation of markers and applicators in single-implant high-dose-rate interstitial brachytherapy for gynecologic malignancies.

PURPOSE: Implanted fiducial markers are a commonly used tool in delineating the CTV in high-dose-rate interstitial brachytherapy (HDR-ISBT) for gynecologic malignancy, but their reliability in gynacological sites is not well understood. These markers and interstitial applicators can experience interfractional motion due to organ swelling or other anatomical changes. The purpose of this study was to evaluate the spatial variation of these features. METHODS AND MATERIALS: The spatial positions of 50 implanted markers and 202 needles were tracked in 15 patients treated over 70 fractions of HDR brachytherapy. Marker and/or needle coordinates were extracted from CT images with contours and dose distributions. Automated analysis determined marker self-consistency and displacements between various elements of the implant. RESULTS: From start to end fraction, the relative positions of the markers experienced an average magnitude displacement of 4.5 ± 3.0 mm while the average displacement of the applicator tips was 11 ± 8 mm, relative to their respective centers of mass (CM). CONCLUSIONS: Markers implanted lateral and superior to the CTV experience greater drift than other implant locations.

First report on the feasibility of a permanently implantable uni-directional planar low dose rate brachytherapy sheet for patients with resectable or borderline resectable pancreatic cancer.

BACKGROUND: Margin negative resection in pancreatic cancer remains the only curative option but is challenging, especially with the retroperitoneal margin. Intraoperative radiation therapy (IORT) can improve rates of local control but requires specially designed facilities and equipment. This retrospective review describes initial results of a novel implantable mesh of uni-directional low dose rate (LDR) Pd-103 sources (sheet) used to deliver a focal margin-directed high-dose boost in patients with concern for close or positive margins. METHODS: Eleven consecutive patients from a single institution with resectable or borderline resectable pancreatic cancer with concern for positive margins were selected for sheet placement and retrospectively reviewed. Procedural outcomes, including the time to implant the device and complications, and clinical outcomes, including survival and patterns of failure, are reported. A dosimetric comparison of the LDR sheet with hypothetical stereotactic body radiotherapy (SBRT) boost is reported. RESULTS: One patient had a resectable disease, and 10 patients had a borderline resectable disease and underwent neoadjuvant treatment. Sheet placement added 15 min to procedural time with no procedural or sheet-related complications. At a median follow up of 13 months, 64% (n = 7) of patients are alive and 55% (n = 6) are disease-free. Compared to a hypothetical SBRT boost, the LDR sheet delivered a negligible dose to kidneys, liver, and spinal cord with a 50% reduction in max dose to the small bowel. CONCLUSION: This is the first report of the use of an implantable uni-directional LDR brachytherapy sheet in patients with resected pancreatic cancer with concern for margin clearance, with no associated toxicity and favorable clinical outcomes.

Clinical application and validation of an iterative forward projection matching algorithm for permanent brachytherapy seed localization from conebeam-CT x-ray projections.

PURPOSE: To experimentally validate a new algorithm for reconstructing the 3D positions of implanted brachytherapy seeds from postoperatively acquired 2D conebeam-CT (CBCT) projection images. METHODS: The iterative forward projection matching (IFPM) algorithm finds the 3D seed geometry that minimizes the sum of the squared intensity differences between computed projections of an initial estimate of the seed configuration and radiographic projections of the implant. In-house machined phantoms, containing arrays of 12 and 72 seeds, respectively, are used to validate this method. Also, four 103Pd postimplant patients are scanned using an ACUITY digital simulator. Three to ten x-ray images are selected from the CBCT projection set and processed to create binary seed-only images. To quantify IFPM accuracy, the reconstructed seed positions are forward projected and overlaid on the measured seed images to find the nearest-neighbor distance between measured and computed seed positions for each image pair. Also, the estimated 3D seed coordinates are compared to known seed positions in the phantom and clinically obtained VariSeed planning coordinates for the patient data. RESULTS: For the phantom study, seed localization error is (0.58 +/- 0.33) mm. For all four patient cases, the mean registration error is better than 1 mm while compared against the measured seed projections. IFPM converges in 20-28 iterations, with a computation time of about 1.9-2.8 min/ iteration on a 1 GHz processor. CONCLUSIONS: The IFPM algorithm avoids the need to match corresponding seeds in each projection as required by standard back-projection methods. The authors' results demonstrate approximately 1 mm accuracy in reconstructing the 3D positions of brachytherapy seeds from the measured 2D projections. This algorithm also successfully localizes overlapping clustered and highly migrated seeds in the implant.

A new development in ultrasound-compatible gynecologic brachytherapy simulators.

PURPOSE: Gynecologic brachytherapy is an essential component in the curative treatment of cervical cancer. With the decline in brachytherapy utilization, gynecologic brachytherapy simulators are being used to provide a mechanism to enhance proficiency-based resident training. However, most models that have been used lack procedural fidelity as they are either repurposed from OB/GYN basic models or from physics phantoms. Therefore, we set out to develop a high-fidelity, ultrasound- and CT-compatible gynecologic brachytherapy training simulator. METHODS AND MATERIALS: Based on prior experience with gynecologic training simulators on the market, we developed a wish list for an ultrasound-compatible brachytherapy training model. A custom simulator was developed based on an existing pelvic ultrasound trainer. Features included a cervical os and endometrial canal as well as a palpable and hypoechoic cervical tumor. RESULTS: The model took about 3 months from the initial meeting with the developer to completion. The properties of the material were equivalent to water for ultrasound, CT, and also MRI and the model did not show signs of degradation after multiple tandem insertions. CONCLUSIONS: A high-fidelity ultrasound-compatible simulator was effectively developed and utilized to improve resident training to perform brachytherapy implants with a derivative benefit in the long term of improving survival for women with advanced gynecologic malignancies through having access to more proficient brachytherapists. Future directions include enhancing the model to allow for repetitive needle insertion and suturing for interstitial training as well as creating variations in anatomy (e.g., retroverted uterus, bulky tumors, etc.) for more advanced technical training.

Effectiveness of Breast-Conserving Surgery and 3-Dimensional Conformal Partial Breast Reirradiation for Recurrence of Breast Cancer in the Ipsilateral Breast: The NRG Oncology/RTOG 1014 Phase 2 Clinical Trial.

IMPORTANCE: Mastectomy is standard for recurrence of breast cancer after breast conservation therapy with whole breast irradiation. The emergence of partial breast irradiation led to consideration of its application for reirradiation after a second lumpectomy for treatment of recurrence of breast cancer in the ipsilateral breast. OBJECTIVES: To assess the effectiveness and adverse effects of partial breast reirradiation after a second lumpectomy and whether the treatment is an acceptable alternative to mastectomy. DESIGN, SETTING, AND PARTICIPANTS: The NRG Oncology/Radiation Therapy Oncology Group 1014 trial is a phase 2, single-arm, prospective clinical trial of 3-dimensional, conformal, external beam partial breast reirradiation after a second lumpectomy for recurrence of breast cancer in the ipsilateral breast after previous whole breast irradiation. The study opened on June 4, 2010, and closed June 18, 2013. Median follow-up was 5.5 years. This analysis used all data received at NRG Oncology through November 18, 2018. Eligible patients experienced a recurrence of breast tumor that was less than 3 cm and unifocal in the ipsilateral breast more than 1 year after breast-conserving therapy with whole breast irradiation and who had undergone excision with negative margins. INTERVENTIONS: Adjuvant partial breast reirradiation, 1.5 Gy twice daily for 30 treatments during 15 days (45 Gy), using a 3-dimensional conformal technique. MAIN OUTCOMES AND MEASURES: The main outcomes of the present study were the predefined secondary study objectives of recurrence of breast cancer in the ipsilateral breast, late adverse events (>1 year after treatment), mastectomy incidence, distant metastasis-free survival, overall survival, and circulating tumor cell incidence. RESULTS: A total of 65 women were enrolled, with 58 evaluable for analysis (mean [SD] age, 65.12 [9.95] years; 48 [83%] white). Of the recurrences of breast cancer in the ipsilateral breast, 23 (40%) were noninvasive and 35 (60%) were invasive. In all 58 patients, 53 (91%) had tumors 2 cm or smaller. All tumors were clinically node negative. A total of 44 patients (76%) tested positive for estrogen receptor, 33 (57%) for progesterone receptor, and 10 (17%) for ERBB2 (formerly HER2 or HER2/neu) overexpression. Four patients had breast cancer recurrence, with a 5-year cumulative incidence of 5% (95% CI, 1%-13%). Seven patients underwent ipsilateral mastectomies for a 5-year cumulative incidence of 10% (95% CI, 4%-20%). Both distant metastasis-free survival and overall survival rates were 95% (95% CI, 85%-98%). Four patients (7%) had grade 3 and none had grade 4 or higher late treatment adverse events. CONCLUSIONS AND RELEVANCE: For patients experiencing recurrence of breast cancer in the ipsilateral breast after lumpectomy and whole breast irradiation, a second breast conservation was achievable in 90%, with a low risk of re-recurrence of cancer in the ipsilateral breast using adjuvant partial breast reirradiation. This finding suggests that this treatment approach is an effective alternative to mastectomy.

Skin and chest wall dose with multi-catheter and MammoSite breast brachytherapy: Implications for late toxicity.

PURPOSE: Accelerated partial breast irradiation (APBI) continues to increase in popularity. Up to 14% of patients treated with the MammoSite (MS) report some degree of chronic pain, which may be related to chest wall toxicity. Reports from several institutions using the multicatheter (MC) technique have not shown associated elevated chest wall toxicity. Additionally, a recent investigation has suggested that increased toxicity may occur with the MS when the dose to the chest wall exceeds 125% of the prescribed dose. This investigation compares the skin and chest wall doses of a cohort of patients treated with the MC technique to a group treated with the MS. METHODS AND MATERIALS: The dosimetric data for 43 patients treated with the MC technique and 83 patients treated with the MS at Virginia Commonwealth University were reviewed. This cohort represents consecutively treated patients from our most recent experience to minimize any learning curve effect on dosimetry. Plans were generated using 3D software (Brachyvision, Varian Medical Systems, Inc., Palo Alto, CA). Multiple dwell positions were used for all MS patients to optimize dose delivery. The minimum distances from the planning target volume to the skin and chest wall were calculated, as well as the maximum doses delivered to the skin and chest wall. RESULTS: The mean skin distances for patients treated with the MC technique and the MS were 0.5 and 0.9cm, respectively (p<0.002). Despite the significantly smaller mean skin distance, the mean skin dose for the MC technique was only 2.3Gy per fraction (67% of prescription dose). The mean skin dose for the MS was 3.2Gy per fraction (94% of prescription dose, p<0.001). The mean chest wall distance was 0.9cm for the MC technique and 1.0cm for the MS (p=0.55). Again, the mean chest wall dose for the MC technique was only 2.3Gy per fraction (67% of prescription dose). The mean skin dose for the MS was 3.6Gy per fraction (105% of prescription dose, p<0.001). The percentage of patients receiving skin doses in excess of 125% for the MC and MS were 0% and 9.6%, respectively. The percentage of patients receiving chest wall doses in excess of 125% for the MC and MS were 0% and 38.6%, respectively. CONCLUSION: The MC technique results in more conformal dose delivery, with significantly lower mean skin and chest wall doses. Treatment with the MS was associated with significantly more patients receiving doses to the skin or chest wall in excess of 125% of the prescription. Given the limited followup available for the MS, and the significant dose delivered to the chest wall, the use of this device may be associated with a higher incidence of late chest wall toxicity than previously expected.

The vaginal cylinder: Misunderstood, misused, or trivial? An in-depth dosimetric and multiinstitutional outcome investigation.

PURPOSE: The purpose of the study was to investigate the impact on dose distribution and radiobiological metrics of common high-dose-rate vaginal brachytherapy treatment parameters and to analyze multiinstitutional data for clinically significant impact on outcomes in early-stage endometrial cancer. METHODS AND MATERIALS: Treatment plans were created for all combinations of prescription parameters and used to quantify the dosimetric impact of each parameter and to estimate the dose delivered using common voxel-integrated radiobiological metrics. A rating system, based on risk grouping from GOG and PORTEC trials, was used to consolidate staging information into a cancer "aggressiveness" measure. Correlations between the rating, toxicity, disease recurrence, and plan parameters were investigated. RESULTS: When prescribing to 5 mm depth, the variation caused by the diameter was very large across all dose metrics, ranging from 51% to 175% increase with the most divergence in BEDmax. For surface prescription, changing the cylinder diameter from 4 cm to 2 cm caused the dose metrics of BEDmin, Dmin, and gBEUD (a = -3) to increase by 117%, 67%, and 52%, respectively. Prescription to 5-mm depth caused changes across all dose metrics of 260% compared with surface prescription for a 2-cm cylinder. Deeper prescription point (p = 0.005) and longer treatment length (p = 0.01) were correlated with increased stenosis rates. No correlation between recurrence and any plan parameter was found. CONCLUSIONS: Dramatic differences in dose distributions arise by small variations of plan parameters, with large impact on rates of vaginal stenosis, but no clear relation with local recurrence. To help radiation oncologists interpret the magnitude of these effects for their patients, we created a tool that allows comparison between dose and fractionation parameters.

Proficiency-based cervical cancer brachytherapy training.

PURPOSE: Although brachytherapy increases the local control rate for cervical cancer, there has been a progressive decline in its use. Furthermore, the training among residency programs for gynecologic brachytherapy varies considerably, with some residents receiving little to no training. This trend is especially concerning given the association between poor applicator placement and decline in local control. Considering the success of proficiency-based training in other procedural specialties, we developed and implemented a proficiency-based cervical brachytherapy training curriculum for our residents. METHODS AND MATERIALS: Each resident placed tandem and ovoid applicators with attending guidance and again alone 2 weeks later using a pelvic model that was modified to allow for cervical brachytherapy. Plain films were taken of the pelvic model, and applicator placement quality was evaluated. Other evaluated metrics included retention of key procedural details, the time taken for each procedure and presession and postsession surveys to assess confidence. RESULTS: During the initial session, residents on average met 4.5 of 5 placement criteria, which improved to 5 the second session. On average, residents were able to remember 7.6 of the 8 key procedural steps. Execution time decreased by an average of 10.5%. Resident confidence with the procedure improved dramatically, from 2.6 to 4.6 of 5. Residents who had previously never performed a tandem and ovoid procedure showed greater improvements in these criteria than those who had. All residents strongly agreed that the training was helpful and wanted to participate again the following year. CONCLUSIONS: Residents participating in this simulation training had measurable improvements in the time to perform the procedure, applicator placement quality, and confidence. This curriculum is easy to implement and is of great value for training residents, and would be particularly beneficial in programs with low volume of cervical brachytherapy cases. Simulation programs could also be created for other technically challenging radiation oncology procedures.

Neural stem cell-preserving external-beam radiotherapy of central nervous system malignancies.

PURPOSE: Recent discoveries have implicated neural stem cells (NSC) as the source of plasticity and repair in the mature mammalian brain. Treatment-induced NSC dysfunction may lead to observed toxicity. This study evaluates the feasibility of NSC-preserving external beam radiotherapy. METHODS AND MATERIALS: A single computed tomography (CT) dataset depicting a right periventricular lesion was used in this study as this location reflects the most problematic geometric arrangement with respect to NSC preservation. Conventional and NSC preserving radiotherapy (RT) plans were generated for the same lesion using two clinical scenarios: cerebral metastatic disease and primary high-grade glioma. Disease-specific target volumes were used. Metastatic disease was conventionally treated with whole-brain radiotherapy (WBRT) to 3,750 cGy (15 fractions) followed by a single stereotactic radiosurgery (SRS) boost of 1,800 cGy to gross disease only. High-grade glioma was treated with conventional opposed lateral and anterior superior oblique beams to 4,600 cGy (23 fractions) followed by a 1,400 cGy (7 fractions) boost. NSC preservation was achieved in both scenarios with inverse-planned intensity modulated radiotherapy (IMRT). RESULTS: Cumulative dose reductions of 65% (metastatic disease) and 25% (high-grade glioma) to the total volume of the intracranial NSC compartments were achieved with NSC-preserving IMRT plans. The reduction of entry and exit dose to NSC niches located contralateral to the target contributed most to NSC preservation. CONCLUSIONS: Neural stem cells preservation with current external beam radiotherapy techniques is achievable in context of both metastatic brain disease and high-grade glioma, even when the target is located adjacent to a stem cell compartment. Further investigation with clinical trials is warranted to evaluate whether NSC preservation will result in reduced toxicity.

A Multi-institution, Retrospective Analysis of Cervix Intracavitary Brachytherapy Treatments. Part 1: Is EQD2 Good Enough for Reporting Radiobiological Effects?

PURPOSE: When brachytherapy doses are reported or added, biologically effective dose (BED) minimum dose covering 90% of the volume (D90) is used as if dose is delivered uniformly to the target. Unlike BED(D90), equivalent uniform BED (EUBED) and generalized biologically equivalent uniform dose (gBEUD) are quantities that integrate dose inhomogeneity. Here we compared BED(D90) and equivalent uniform BED (EUBED)/gBEUD in 3 settings: (1) 2 sites using tandem and ovoid (T&O) but different styles of implants; (2) 2 sites using different devices-T&O and tandem and ring (T&R)-and different styles; and (3) the same site using T&O and T&R with the same style. METHODS AND MATERIALS: EUBED and gBEUD were calculated for 260 fractions from 3 institutions using BED(α/ß = 10 Gy). EUBED uses an extra parameter α with smaller values associated with radioresistant tumors. Similarly, gBEUD uses a, which places variable emphasis on hot/cold spots. Distributions were compared using the Kolmogorov-Smirnoff test at 5% significance. RESULTS: For the 2 sites using T&O, the distribution of EUBED-BED(D90) was not different for values of α = 0.5 to 0.3 Gy-1 but was statistically different for values of α = 0.15 to 0.05 Gy-1 (P=.01, .002). The mean percentage differences between EUBED and BED(D90) ranged from 20% to 100% for α = 0.5 Gy-1 to 0.05 Gy-1. Using gBEUD-BED(D90), the P values indicate the distributions to be similar for a = -10 but to be significantly different for other values of a (-5, -1, 1). Between sites and at the same site using T&O versus T&R, the distributions were statistically different with EUBED/gBEUD irrespective of parameter values at which these quantities were computed. These differences indicate that EUBED/gBEUD capture differences between the techniques and applicators that are not detected by the BED(D90). CONCLUSIONS: BED(D90) is unable to distinguish between plans created by different devices or optimized differently. EUBED/gBEUD distinguish between dose distributions created by different devices and styles of implant and planning. This discrepancy is particularly important with the increased use of magnetic resonance imaging and hybrid devices, whereby one has the ability to create dose distributions that are significant departures from the classic pear.

American Brachytherapy Society consensus report for accelerated partial breast irradiation using interstitial multicatheter brachytherapy.

PURPOSE: To develop a consensus report for the quality practice of accelerated partial breast irradiation (APBI) using interstitial multicatheter brachytherapy (IMB). METHODS AND MATERIALS: The American Brachytherapy Society Board appointed an expert panel with clinical and research experience with breast brachytherapy to provide guidance for the current practice of IMB. This report is based on a comprehensive literature review with emphasis on randomized data and expertise of the panel. RESULTS: Randomized trials have demonstrated equivalent efficacy of APBI using IMB compared with whole breast irradiation for select patients with early-stage breast cancer. Several techniques for placement of interstitial catheters are described, and importance of three-dimensional planning with appropriate optimization is reviewed. Optimal target definition is outlined. Commonly used dosing schemas include 50 Gy delivered in pulses of 0.6-0.8 Gy/h using pulsed-dose-rate technique and 34 Gy in 10 fractions, 32 Gy in eight fractions, or 30 Gy in seven fractions using high-dose-rate technique. Potential toxicities and strategies for toxicity avoidance are described in detail. Dosimetric constraints include limiting whole breast volume that receives ≥50% of prescription dose to <60%, skin dose to ≤100% of prescription dose (≤60-70% preferred), chest wall dose to ≤125% of prescription dose, Dose Homogeneity Index to >0.75 (>0.85 preferred), V150 < 45 cc, and V200 < 14 cc. Using an optimal implant technique coupled with optimal planning and appropriate dose constraints, a low rate of toxicity and a good-to-excellent cosmetic outcome of ≥90% is expected. CONCLUSIONS: IMB is an effective technique to deliver APBI for appropriately selected women with early-stage breast cancer. This consensus report has been created to assist clinicians in the appropriate practice of APBI using IMB.

NRG Oncology-Radiation Therapy Oncology Group Study 1014: 1-Year Toxicity Report From a Phase 2 Study of Repeat Breast-Preserving Surgery and 3-Dimensional Conformal Partial-Breast Reirradiation for In-Breast Recurrence.

PURPOSE: To determine the associated toxicity, tolerance, and safety of partial-breast reirradiation. METHODS AND MATERIALS: Eligibility criteria included in-breast recurrence occurring >1 year after whole-breast irradiation, <3 cm, unifocal, and resected with negative margins. Partial-breast reirradiation was targeted to the surgical cavity plus 1.5 cm; a prescription dose of 45 Gy in 1.5 Gy twice daily for 30 treatments was used. The primary objective was to evaluate the rate of grade ≥3 treatment-related skin, fibrosis, and/or breast pain adverse events (AEs), occurring ≤1 year from re-treatment completion. A rate of ≥13% for these AEs in a cohort of 55 patients was determined to be unacceptable (86% power, 1-sided α = 0.07). RESULTS: Between 2010 and 2013, 65 patients were accrued, and the first 55 eligible and with 1 year follow-up were analyzed. Median age was 68 years. Twenty-two patients had ductal carcinoma in situ, and 33 had invasive disease: 19 ≤1 cm, 13 >1 to ≤2 cm, and 1 >2 cm. All patients were clinically node negative. Systemic therapy was delivered in 51%. All treatment plans underwent quality review for contouring accuracy and dosimetric compliance. All treatment plans scored acceptable for tumor volume contouring and tumor volume dose-volume analysis. Only 4 (7%) scored unacceptable for organs at risk contouring and organs at risk dose-volume analysis. Treatment-related skin, fibrosis, and/or breast pain AEs were recorded as grade 1 in 64% and grade 2 in 7%, with only 1 (<2%) grade ≥3 and identified as grade 3 fibrosis of deep connective tissue. CONCLUSION: Partial-breast reirradiation with 3-dimensional conformal radiation therapy after second lumpectomy for patients experiencing in-breast failures after whole-breast irradiation is safe and feasible, with acceptable treatment quality achieved. Skin, fibrosis, and breast pain toxicity was acceptable, and grade 3 toxicity was rare.

Dosimetric effects of seed anisotropy and interseed attenuation for 103Pd and 125I prostate implants.

A Monte Carlo study is carried out to quantify the effects of seed anisotropy and interseed attenuation for 103Pd and 125I prostate implants. Two idealized and two real prostate implants are considered. Full Monte Carlo simulation (FMCS) of implants (seeds are physically and simultaneously simulated) is compared with isotropic point-source dose-kernel superposition (PSKS) and line-source dose-kernel superposition (LSKS) methods. For clinical pre- and post-procedure implants, the dose to the different structures (prostate, rectum wall, and urethra) is calculated. The discretized volumes of these structures are reconstructed using transrectal ultrasound contours. Local dose differences (PSKS versus FMCS and LSKS versus FMCS) are investigated. The dose contributions from primary versus scattered photons are calculated separately. For 103Pd, the average absolute total dose difference between FMCS and PSKS can be as high as 7.4% for the idealized model and 6.1% for the clinical preprocedure implant. Similarly, the total dose difference is lower for the case of 125I: 4.4% for the idealized model and 4.6% for a clinical post-procedure implant. Average absolute dose differences between LSKS and FMCS are less significant for both seed models: 3 to 3.6% for the idealized models and 2.9 to 3.2% for the clinical plans. Dose differences between PSKS and FMCS are due to the absence of both seed anisotropy and interseed attenuation modeling in the PSKS approach. LSKS accounts for seed anisotropy but not for the interseed effect, leading to systematically overestimated dose values in comparison with the more accurate FMCS method. For both idealized and clinical implants the dose from scattered photons represent less than 1/3 of the total dose. For all studied cases, LSKS prostate DVHs overestimate D90 by 2 to 5% because of the missing interseed attenuation effect. PSKS and LSKS predictions of V150 and V200 are overestimated by up to 9% in comparison with the FMCS results. Finally, effects of seed anisotropy and interseed attenuation must be viewed in the context of other significant sources of dose uncertainty, namely seed orientation, source misplacement, prostate morphological changes and tissue heterogeneity.

Recommendations of the American Association of Physicists in Medicine regarding the impact of implementing the 2004 task group 43 report on dose specification for 103Pd and 125I interstitial brachytherapy.

In March 2004, the recommendations of the American Association of Physicists in Medicine (AAPM) on the interstitial brachytherapy dosimetry using 125I and 103Pd were reported in Medical Physics [TG-43 Update: Rivard et al., 31, 633-674 (2004)]. These recommendations include some minor changes in the dose-calculation formalism and a major update of the dosimetry parameters for eight widely used interstitial brachytherapy sources. A full implementation of these recommendations could result in unintended changes in delivered dose without corresponding revisions in the prescribed dose. Because most published clinical experience with permanent brachytherapy is based upon two widely used source models, the 125I Model 6711 and 103Pd Model 200 sources, in this report we present an analysis of the dosimetric impact of the 2004 TG-43 dosimetry parameters on the history of dose delivery for these two source models. Our analysis indicates that the currently recommended prescribed dose of 125 Gy for Model 200 103Pd implants planned using previously recommended dosimetry parameters [AAPM 103Pd dose prescription: Williamson et al., Med. Phys. 27, 634-642 (2000)] results in a delivered dose of 120 Gy according to dose calculations based on the 2004 TG-43 update. Further, delivered doses prior to October 1997 varied from 113 to 119 Gy for a prescribed dose of 115 Gy compared to 124 Gy estimated by the AAPM 2000 report. For 125I implants using Model 6711 seeds, there are no significant changes (less than 2%). Practicing physicians should take these results into account when selecting the clinically appropriate prescribed dose for 103Pd interstitial implant patients following implementation of the 2004 TG-43 update dose-calculation recommendations. The AAPM recommends that the radiation oncology community review this report and consider whether the currently recommended dose level (125 Gy) needs to be revised.