To compare current SBRT and HDR prostate treatment regimens from a disease perspective using the latest published dose-response functions We developed and validated a comprehensive software platform enabling in-silico growth of realistic prostate tumor-like volumes of random shape and morphology within prostate. Published probabilities of disease occurrence in various prostate zonal anatomies, for various disease stages were taken into account when tumorlets were generated. The model used the patient-specific segmented anatomy and dose distributions delivered for 10 patients. 4500 tumorlets, ranging from 0.1 to 10 cm3 were generated. Each tumorlet was overlapped with the dose distribution and the corresponding radiobiological integral parameters (EUBED, gBEUD) were computed. Data from 25 international radiotherapy outcome datasets, stratified by risk and use of ADT, were used to generate dose-response curves, fractionation sensitivity and repopulation. These values then enabled our model to convert integral metrics parameters into a probability of cure (PoC). A large range of radiobiological parameters, α/b = [1.5, 7.7] Gy and α = [0.04, 0.3] Gy-1 were explored in comparing currently accepted regimens (e.g. 7.25Gy x 5 and 13.5Gy x 2). SBRT plans were created using both RTOG 0938 and NRG GU005 criteria. A version of the plan was escalated from 36.25 to 40Gy. The two methods of integrating radio-biological dose effect (EUBED and gBEUD) handle dose inhomogeneity differently. SBRT plans display less dose inhomogeneity and consequently both formalisms produce very similar results. For HDR plans, which have more dose heterogeneity, the two formalisms produce slightly different results but for both, the PoC tends to decrease with the increased disease volume. Similar SBRT and HDR outcomes were observed for a very low α/b (1.5) and only low and intermediate risk disease. For higher α/b values, for all the dose-response curves examined, predictions showed that HDR provided a 5-30% increase in PoC, increasing with increased α/b and risk strata. The NRG plans, requiring higher dose coverage (98% vs 95%), produce, for the same prescription dose, a 1-5% PoC increase. The NRG 40Gy plans restore some of the PoC, when compared to HDR, particularly at large tumor volumes. We are presenting a novel perspective in comparing two treatment modalities or regimens. Our results show that using prescription dose alone in a BED-style equivalence, particularly when accounting for large degrees of variability in planning styles and delivery, has a limited value. The method we are proposing, looking at probabilities of cure at disease level –tumorlets- rather than physical peripheral prescription dose at gland level, has the potential to create a true equivalence between established and time-tested treatments (HDR) and newer modalities (SBRT), while accounting for all existent planning style variability.

Currently, there are no published studies evaluating the comparative cost of image guidance techniques and fractionation schedules for managing prostate cancer. We hypothesized that image guidance with fiducial markers and onboard imaging with daily orthogonal radiographs, rather than daily cone beam CT (CBCT), is significantly less expensive to deliver, even for hypofractionated courses of IGRT. We utilized time-driven activity-based costing (TDABC) to determine the cost of each IGRT technique, based on resources used rather than charges billed to the payer. Process maps were created detailing each activity in our department, from initial referral to post-treatment follow-up visits. Time estimates for each activity was obtained via staff interviews, and the capacity cost rate (CCR) was calculated for all involved personnel, equipment, and clinical space. Total cost was determined from the product of the time required for each process and its CCR. We specifically compared conventionally fractionated IGRT with a dose of 80 Gy, to hypofractionated IGRT with a dose of 60 Gy in 20 fractions, as well as image guidance using fiducial markers versus daily CBCT, for both fractionation schemes. The total cost of prostate IGRT to a dose of 80 Gy with daily CBCT was $10,594, $5,066 of which were personnel costs. The cost of prostate IGRT to 80 Gy with fiducial markers and daily kv imaging was $8,489, of which $4,077 were personnel costs. Thus, the difference between daily CBCT and fiducial markers with conventional fractionation was determined to be $2,135 per patient. Of this difference, the cost of additional physician time to review images contributes $931, or 44% of the added cost. For hypofractionated IGRT to a dose of 60 Gy in 20 fractions, the total cost was $6,024 with daily CBCT, versus $5,237 for fiducial markers, with an absolute difference of $787 per patient; physician time comprises $750 of this difference. When comparing standard fractionation to hypofractionation, the difference was $4,570 with daily CBCT, and $3,222 with fiducial markers, in favor of hypofractionated IGRT. Cost of care will likely play a growing role in treatment decisions, and this analysis shows that hypofractionated IGRT saves thousands of dollars per patient. As hypothesized, IGRT using fiducials is less expensive than IGRT using CBCT. However, the cost savings are only marginal for a hypofractionated course, suggesting that daily CBCT may be utilized for short course IGRT without adversely affecting value.

Efficiency and cost-control in today’s healthcare system has become increasingly important. Accurate analyses to determine the most cost-efficient treatment techniques are essential. Time Driven Activity Based Costing (TDABC) simply and precisely determines costs of a process by accounting for all resources and utilities provided during each step and assigning a cost per time. We applied TDABC to compare Whole Brain Radiotherapy (WBRT) using CT simulation against WBRT using clinical setup. Our hypothesis is that WBRT with clinical setup is more cost-efficient than using CT Simulation for planning. Using the TDABC method, we created process maps to delineate the independent steps in WBRT (30Gy/10fx) for inpatient consultations using CT Simulation for treatment planning versus clinical setup. Through staff interviews and departmental consensus, we estimated the timing of each step from initial consultation through post-treatment billing. Capacity cost rates (CCR, in cost per minute) were determined for personnel, materials, physical space, and equipment. Total cost of each step was computed by multiplying the CCR by time required of each resource during the step. Lastly, total Process Cost was calculated by summating the costs of each step in combination with disposable materials. Clinical setup WBRT resulted in a total cost which was 77% of the total cost using CT Simulation. For CT Simulation, cost comprised of 57% personnel costs, 36% space/equipment costs, and 7% material costs. Clinical setup comprised of 62% personnel costs and 38% space/equipment costs. With CT Simulation, the extra appointment, personnel, planning, and machine usage resulted in a probability weighted time which was 90 minutes longer than using clinical setup. The most expensive activity was attending physician time spent with patient in consultation which was the same between the two pathways. Attending physicians had the highest CCR ($4.28/min). Clinical setup for whole brain radiotherapy resulted in a 23% absolute reduction in total cost compared with CT Simulation for treatment planning. Consideration of cost difference should be given when considering using CT Simulation for inpatient palliative WBRT. Future investigations should use TDABC to better understand expenditures through appropriately accounting for consumed resources.

Purpose— Target delineation in lung cancer radiotherapy using CT and/or PET-CT is affected by large variability. MRI has excellent soft tissue visualization and better spatial resolution than PET-CT. The main purpose of this study is to analyze delineation variability for lung cancer using MRI. Methods and materials— Seven physicians delineated the tumor volumes of ten patients for the following scenarios: (1) CT only; (2) PET-CT fusion images registered to CT (“clinical standard”); and (3) post-contrast T1-weighted MRI registered with diffusion-weighted MRI. To compute interobserver variability, the median surface was generated from all observers’ contours and used as the reference surface. A physician labeled the interface types (tumor to lung, atelectasis (collapsed lung), hilum, mediastinum, or chest wall) on the median surface. Contoured volumes and bidirectional local distances (BLDs) between individual observers’ contours and the reference contour were analyzed. Results— CT- and MRI-based tumor volumes normalized relative to PET-CT-based volumes were31.62±0.76 (mean±SD) and 1.38±0.44, respectively. Volume differences between the imaging modalities were not significant. Between observers, the mean normalized than other interfaces for all modalities combined (p=0.0006). The interfaces with the smallest uncertainties were tumor-lung (on CT) and tumor-mediastinum (on PET-CT and MRI). Conclusions— While MRI-based contouring showed overall larger variability than PET-CT, contouring variability depended on the interface type and was not significantly different between modalities despite of the limited observer experience with MRI. Multimodality imaging and combining different imaging characteristics might be the best approach to define the tumor volume most accurately.

To analyze the dosimetric consequences and acute toxicities associated with the routine injection of a bioabsorbable hydrogel spacer in the perirectal space during permanent low dose rate prostate brachytherapy. A consecutive series of 80 patients implanted with I-125 permanent brachytherapy seeds between August 2013 and October 2014 were evaluated. The most recent 40 patients also underwent a single transperineal injection of polyethylene glycol (5 cc) in the space between the prostate and rectum. This was performed immediately after the implant following hydrodissection of Denonvilliers' fascia with 1-3 cc of radiopaque IV contrast. Postop day 0 CT-based dosimetry was compared between patients with and without hydrogel spacer to evaluate for differences in rectal and prostate dosimetry using a two-tailed unequal variance t-test. There were no differences between baseline factors with regards to mean age (63 years), pre-implant gland size (30 cc), number of seeds implanted (64), or total activity (25 mCi). There were no acute genitourinary or rectal toxicities within the first 3 months that could be attributed to the hydrogel rectal spacer. Comparing patients with and without hydrogel, the mean separation between the prostate and rectum was 14 mm ± 4 mm versus 6 mm ± 3 mm (P<0.0001), respectively. The mean rectal doses to 1 cc, 2 cc, and 5 cc relative to prescription dose were 41% vs 61% (P<0.0001), 44% vs 50% (P<0.0001), and 26% vs 32% (P<0.0009) respectively. There were no statistically significant differences on prostate coverage with or without a hydrogel rectal spacer with V100: 92% vs 91%, V150: 45% vs 48%, D90: 106% vs 106%, respectively. The use of PEG hydrogel significantly and consistently reduced the rectal exposure of radiation in patients undergoing permanent brachytherapy without any adverse effect on acute toxicity or prostate gland coverage.

Salvage permanent low dose rate brachytherapy (LDR-BT) has long been offered at our institution with mpMRI guidance for patients who develop locally recurrent prostate cancer following external beam radiotherapy (EBRT) or prior LDR-BT. It was hypothesized that this approach is associated with a delay and/or avoidance of androgen deprivation therapy (ADT) in the majority of patients, and might be associated with only rare occurrences of severe late toxicities. As part of a quality improvement project, we reviewed the patient, tumor, and treatment characteristics for all patients who underwent a salvage LDR-BT between 2001-2015 at our institution. All patients had undergone a restaging mpMRI scan with T2-weighted imaging, diffusion weighted imaging, and dynamic contrast enhancement with or without spectroscopy (1.5-Tesla with endorectal coil or 3-Tesla with transabdominal phase array coil). Concerning lesions were biopsied via mpMRI-guidance. Salvage LDR-BT plans were developed to encompass the suspicious regions on the mpMRI images and implanted under anesthesia with either I-125 or Pd-103. Post-implant dosimetry was available for all patients except for two who underwent salvage LDR-BT after prior LDR-BT. Genitourinary and gastrointestinal toxicities were retrospectively coded using CTCAE 4.0. The Kaplan-Meier method was used to estimate the time to re-recurrence, which was defined as the post-LDR-BT PSA nadir + 2 ng/mL, or initiation of ADT. A total of 39 patients were identified with a median follow-up time of 55 months. The median age at relapse was 72 (range: 52-91). The initial course of radiotherapy had been EBRT, LDR-BT, or a combination in 77%, 15%, and 8%, respectively. The median time from initial radiotherapy to salvage LDR-BT was 80 months (range: 22 - 156 months). The median rPSA and rPSA doubling times were 5.8 ng/mL (range: 1.2-26.4 ng/mL) and 18.1 months (range: 1.9-36.3 months), respectively. Restaging biopsies with mpMRI guidance were performed in 33 patients and identified Gleason's score (GS) 8-10, GS 7, GS ≤6, PIN and benign changes in 39%, 33%, 6%, 12%, and 9%. Following salvage LDR-BT, the PSA response rate was 100%. The K-M adjusted freedom from re-recurrence was 46% at 55 months. All failures occurred between 3-44 months with a median time to failure of 21.9 months. Four patients developed grade 3 toxicities (incontinence = 2; rectal ulcer = 2). There were no grade 4-5 toxicities. Two patients developed metastasis at 55 and 98 months. Among 13 deceased patients, 1 died as a result of relapse, 5 with recurrence but not from relapse, and 7 died without relapse. Nearly half of all patients who underwent mpMRI-guided salvage LDR-BT had long-term PSA control and avoided ADT. This likely improves patient health, but its impact on metastases, prostate cancer mortality, and overall survival cannot be determined from this retrospective study. Improved ultrasound imaging, planning techniques, and the introduction of injectable rectal spacers over the study period have eliminated grade 3 toxicities. However, our experience provides a reminder that they are to always be discussed with patients whenever offering this treatment.

Purpose:Target delineation in lung cancer radiotherapy has, in general, large variability. MRI has so far not been investigated in detail for lung cancer delineation variability. The purpose of this study is to investigate delineation variability for lung tumors using MRI and compare it to CT alone and PET‐CT based delineations.Methods:Seven physicians delineated the primary tumor volumes of nine patients for the following scenarios: (1) CT only; (2) post‐contrast T1‐weighted MRI registered with diffusion‐weighted MRI; and (3) PET‐CT fusion images. To compute interobserver variability, the median surface was generated from all observers’ contours and used as the reference surface. A single physician labeled the interface types (tumor to lung, atelectasis (collapsed lung), hilum, mediastinum, or chest‐wall) on the median surface. Volume variation (normalized to PET‐CT volume), minimum distance (MD), and bidirectional local distance (BLD) between individual observers’ contours and the reference contour were measured.Results:CT‐ and MRI‐based normalized volumes were 1.61±0.76 (mean±SD) and 1.38±0.44, respectively, both significantly larger than PET‐CT (p<0.05, paired t‐test). The overall uncertainty (root mean square of SD values over all points) of both BLD and MD measures of the observers for the interfaces were not significantly different (p>0.05, two‐samples t‐test) for all imaging modalities except between tumor‐mediastinum and tumor‐atelectasis in PET‐CT. The largest mean overall uncertainty was observed for tumor‐atelectasis interface, the smallest for tumor‐mediastinum and tumor‐lung interfaces for all modalities. The whole tumor uncertainties for both BLD and MD were not significantly different between any two modalities (p>0.05, paired t‐test). Overall uncertainties for the interfaces using BLD were similar to using MD.Conclusion:Large volume variations were observed between the three imaging modalities. Contouring variability appeared to depend on the interface type. This study will be useful for understanding the delineation uncertainty for radiotherapy planning of lung cancer using different imaging modalities.Disclosures: Research agreement with Phillips Healthcare (GH and EW), National Institutes of Health Licensing agreement with Varian Medical Systems (GH and EW), research grants from the National Institute of Health (GH and EW), UpToDate royalties (EW), and none (others). Authors have no potential conflicts of interest to disclose.

Permanent radioactive seed implantation provides highly effective treatment for prostate cancer that typically includes multidisciplinary collaboration between urologists and radiation oncologists. Low dose-rate (LDR) prostate brachytherapy offers excellent tumor control rates and has equivalent rates of rectal toxicity when compared with external beam radiotherapy. Owing to its proximity to the anterior rectal wall, a small portion of the rectum is often exposed to high doses of ionizing radiation from this procedure. Although rare, some patients develop transfusion-dependent rectal bleeding, ulcers or fistulas. These complications occasionally require permanent colostomy and thus can significantly impact a patient's quality of life. Aside from proper technique, a promising strategy has emerged that can help avoid these complications. By injecting biodegradable materials behind Denonviller's fascia, brachytherpists can increase the distance between the rectum and the radioactive sources to significantly decrease the rectal dose. This review summarizes the progress in this area and its applicability for use in combination with permanent LDR brachytherapy.

Head-and-neck (H&N) IMRT treatment plans are characterized by complex, spatially-varying dose distributions with steep dose gradients and critical organs in close proximity to target volumes. Thus, reproducible and accurate daily patient alignment is crucial to ensure target coverage and avoid encompassing critical organs in the high dose regions. Numerous in room imaging systems are available, however studies directly comparing the shifts derived from each are sparse. The purpose of this study is to investigate the correlation of daily H&N shift data from three commercially available in-room imaging systems. Nine patients with biopsy proven H&N tumors were enrolled on an IRB approved imaging protocol. Each patient was treated to 70 Gy in 33-35 fractions with concurrent chemotherapy when indicated. Daily pre-treatment imaging was performed with cone beam CT (CBCT), kV paired orthogonal x-ray and 6d stereoscopic x-ray imaging systems. The daily couch shifts were computed from offline matches and the vertical and lateral shifts were compared using linear regression with correlation being assessed using Pearson’s correlation coefficient (R). Bland-Altman analysis was also performed to assess for trends in the correlations. The best mean shift correlation was observed between stereoscopic x-ray and orthogonal x-ray imaging (vertical R = 0.67, lateral R = 0.72) and orthogonal x-ray and CBCT (vertical R = 0.66, lateral R = 0.76). The CBCT and stereoscopic x-ray vertical shifts exhibited the worst correlation (vertical R = 0.48, lateral R = 0.71). For most patients, the vertical shifts had worse correlation than the lateral shifts. Overall, it was observed that the stereoscopic x-ray shifts were smaller than the CBCT or orthogonal x-ray shifts. We also observed that the shift correlations appeared to be worse in the earliest enrolled patients compared to the more recently enrolled patients. Initial inspection revealed that time on the table between imaging was much shorter for more recent patients as the imaging workflow efficiency was improved. This preliminary analysis revealed that the largest differences in shift information occur between stereoscopic x-ray and CBCT imaging. We generally found that shifts from stereoscopic imaging were smaller than CBCT or orthogonal x-ray, which could be explained by the additional rotational corrections inherent to the stereoscopic system. To date, there is no “gold standard” in terms of on-board imaging and our results confirm that not all imaging systems produce equal shifts when used on the same patient. In addition, our findings reinforce the need for efficient treatment workflows to minimize the risk of patient movement between imaging and treatment.

Purpose: Value in health care is defined as outcomes achieved per dollar spent, and understanding cost is critical to delivering high-value care. Traditional costing methods reflect charges rather than fundamental costs to provide a service. The more rigorous method of time-driven activity-based costing was used to compare cost between whole-breast radiotherapy (WBRT) and accelerated partial-breast irradiation (APBI) using balloon-based brachytherapy. Materials and Methods: For WBRT (25 fractions with five-fraction boost) and APBI (10 fractions twice daily), process maps were created outlining each activity from consultation to post-treatment follow up. Through staff interviews, time estimates were obtained for each activity. The capacity cost rates (CCR), defined as cost per minute, were calculated for personnel, equipment, and physical space. Total cost was calculated by multiplying the time required of each resource by its CCR. This was then summed and combined with cost of consumable materials. Results: The total cost for WBRT was $5,333 and comprised 56% personnel costs and 44% space/equipment costs. For APBI, the total cost was $6,941 (30% higher than WBRT) and comprised 51% personnel costs, 6% space/equipment costs, and 43% consumable materials costs. The attending physician had the highest CCR of all personnel ($4.28/min), and APBI required 24% more attending time than WBRT. The most expensive activity for APBI was balloon placement and for WBRT was computed tomography simulation. Conclusion: APBI cost more than WBRT when using the dose/fractionation schemes analyzed. Future research should use time-driven activity-based costing to better understand cost with the aim of reducing expenditure and defining bundled payments.

Purpose/Objective(s)Studies of late radiation toxicity beyond the typical 5 years of follow-up after prostate brachytherapy are often limited by a loss of patients to follow-up, dependence on mailed surveys, and/or reliance on billing codes that may not accurately capture clinical data. Since Veterans typically seek their care indefinitely within the Veterans Healthcare Administration, it was hypothesized that the availability of clinical encounters in the Computerized Patient Record System (CPRS) may detect a higher rate of late urinary and/or rectal toxicities, than previously believed, emerging only after this initial surveillance period.Materials/MethodsIndividual patient records were reviewed in CPRS for a cohort of patients who underwent permanent low-dose rate brachytherapy between January 2004 and December 2007. The CTCAE v4.0 was used to score urinary and rectal toxicities.ResultsA total of 245 patients were evaluated. Follow-up clinical records were available for 100%, including 95.1% of patients within one year of this study, or death. The median follow-up was 7.5 years, with 88.6% followed ≥ 5 years. Post-implant dosimetry was available for 95.5%. The median d90, v150, v200, and R100 were 103.3%, 59.4%, 30.1%, and 0.5cc. Supplemental external beam radiation therapy (EBRT) was administered to 33.5% of patients before implant. The overall rates of grade ≥ 2 and ≥ 3 urinary toxicities were 23.2% and 0.4%, and grade ≥ 2 and ≥ 3 rectal toxicities were 6.9% and 2.9%, respectively. Six out of the 7 patients with a grade ≥ 3 rectal toxicity received EBRT. Severe radiation toxicities leading to an abdominoperineal resection and suprapubic catheter occurred in only one patient at 1.3 years, and another at 1.8 years, respectively. No patients required a cystectomy. After the initial 5 years, new grade 2 urinary and rectal toxicities occurred in 5.7% and 0.4% of patients, whereas there were no new grade ≥ 3 urinary or rectal toxicities.ConclusionsThe Veterans Healthcare Administration CPRS captures indefinite follow-up clinical encounters for almost all patients treated in this integrated healthcare system. These records provide an accurate resource for studying late radiation toxicities. Beyond the typical 5 years of follow-up after prostate brachytherapy, grade ≥ 2 toxicities are rare, and grade ≥ 3 toxicities even less common. Purpose/Objective(s)Studies of late radiation toxicity beyond the typical 5 years of follow-up after prostate brachytherapy are often limited by a loss of patients to follow-up, dependence on mailed surveys, and/or reliance on billing codes that may not accurately capture clinical data. Since Veterans typically seek their care indefinitely within the Veterans Healthcare Administration, it was hypothesized that the availability of clinical encounters in the Computerized Patient Record System (CPRS) may detect a higher rate of late urinary and/or rectal toxicities, than previously believed, emerging only after this initial surveillance period. Studies of late radiation toxicity beyond the typical 5 years of follow-up after prostate brachytherapy are often limited by a loss of patients to follow-up, dependence on mailed surveys, and/or reliance on billing codes that may not accurately capture clinical data. Since Veterans typically seek their care indefinitely within the Veterans Healthcare Administration, it was hypothesized that the availability of clinical encounters in the Computerized Patient Record System (CPRS) may detect a higher rate of late urinary and/or rectal toxicities, than previously believed, emerging only after this initial surveillance period. Materials/MethodsIndividual patient records were reviewed in CPRS for a cohort of patients who underwent permanent low-dose rate brachytherapy between January 2004 and December 2007. The CTCAE v4.0 was used to score urinary and rectal toxicities. Individual patient records were reviewed in CPRS for a cohort of patients who underwent permanent low-dose rate brachytherapy between January 2004 and December 2007. The CTCAE v4.0 was used to score urinary and rectal toxicities. ResultsA total of 245 patients were evaluated. Follow-up clinical records were available for 100%, including 95.1% of patients within one year of this study, or death. The median follow-up was 7.5 years, with 88.6% followed ≥ 5 years. Post-implant dosimetry was available for 95.5%. The median d90, v150, v200, and R100 were 103.3%, 59.4%, 30.1%, and 0.5cc. Supplemental external beam radiation therapy (EBRT) was administered to 33.5% of patients before implant. The overall rates of grade ≥ 2 and ≥ 3 urinary toxicities were 23.2% and 0.4%, and grade ≥ 2 and ≥ 3 rectal toxicities were 6.9% and 2.9%, respectively. Six out of the 7 patients with a grade ≥ 3 rectal toxicity received EBRT. Severe radiation toxicities leading to an abdominoperineal resection and suprapubic catheter occurred in only one patient at 1.3 years, and another at 1.8 years, respectively. No patients required a cystectomy. After the initial 5 years, new grade 2 urinary and rectal toxicities occurred in 5.7% and 0.4% of patients, whereas there were no new grade ≥ 3 urinary or rectal toxicities. A total of 245 patients were evaluated. Follow-up clinical records were available for 100%, including 95.1% of patients within one year of this study, or death. The median follow-up was 7.5 years, with 88.6% followed ≥ 5 years. Post-implant dosimetry was available for 95.5%. The median d90, v150, v200, and R100 were 103.3%, 59.4%, 30.1%, and 0.5cc. Supplemental external beam radiation therapy (EBRT) was administered to 33.5% of patients before implant. The overall rates of grade ≥ 2 and ≥ 3 urinary toxicities were 23.2% and 0.4%, and grade ≥ 2 and ≥ 3 rectal toxicities were 6.9% and 2.9%, respectively. Six out of the 7 patients with a grade ≥ 3 rectal toxicity received EBRT. Severe radiation toxicities leading to an abdominoperineal resection and suprapubic catheter occurred in only one patient at 1.3 years, and another at 1.8 years, respectively. No patients required a cystectomy. After the initial 5 years, new grade 2 urinary and rectal toxicities occurred in 5.7% and 0.4% of patients, whereas there were no new grade ≥ 3 urinary or rectal toxicities. ConclusionsThe Veterans Healthcare Administration CPRS captures indefinite follow-up clinical encounters for almost all patients treated in this integrated healthcare system. These records provide an accurate resource for studying late radiation toxicities. Beyond the typical 5 years of follow-up after prostate brachytherapy, grade ≥ 2 toxicities are rare, and grade ≥ 3 toxicities even less common. The Veterans Healthcare Administration CPRS captures indefinite follow-up clinical encounters for almost all patients treated in this integrated healthcare system. These records provide an accurate resource for studying late radiation toxicities. Beyond the typical 5 years of follow-up after prostate brachytherapy, grade ≥ 2 toxicities are rare, and grade ≥ 3 toxicities even less common.

After prostatectomy, salvage radiation therapy traditionally targets a volume defined by anatomic landmarks. Multiparametric MRI (Mp-MRI) can detect locally recurrent tumor nodules with high sensitivity and specificity after prostatectomy. We report our institutional experience in targeting these nodules using simultaneous integrated boost (SIB) technique. Seven patients with detectable PSA after radical prostatectomy underwent Mp-MRI and were found to have tumor nodules in the prostate surgical bed. Using a 1.5T magnet and endorectal coil, Mp-MRI scans (T2, diffusion weighted and dynamic contrast enhanced images) were obtained through the prostate surgical bed. Recurrent nodules were identified on the basis of abnormal T2 signal intensity, rapid contrast wash in and wash out, and sometimes diffusion restriction. The MR images were fused manually with the planning CT using rigid image registration. The recurrent nodule GTV was contoured on the MRI with a 0 mm expansion to define the nodule PTV (PTVn). A uniform expansion of 5-7 mm (3 mm posteriorly) was added to the prostate bed to define its PTV. The prostate bed received a median dose of 66 Gy (range, 63-66 Gy) in 30-33 fractions at 2-2.1 Gy/fraction. The PTVn received an SIB to a dose of 72-74.25 Gy at 2.18-2.4 Gy/fraction. All patients were treated with IMRT, and setup verification was performed daily. Toxicity was measured on the RTOG scale. Median age was 66 years (range, 53-76 years). Margins were positive in 2 patients, negative in 4 patients, and unknown for 1 patient. Median Gleason score was 7 (range, 6-8), and no patients had positive lymph nodes. Two patients had extracapsular extension. Median pre-radiation PSA was 0.4 ng/mL (range, 0.2-1.7 ng/mL). The recurrent nodules ranged from 3-11 mm (median 6 mm), and median PTVn volume was 1.18 cc (range, 0.55-15.43 cc). Median rectal V70 was 0.26 cc (range, 0-1.46 cc) and median bladder V70 was 1.13 cc (range, 0-20.2). Median follow-up from completion of therapy is 1.1 years. One patient experienced grade 3 acute toxicity (hematuria), and 1 patient with urinary continence prior to RT became incontinent. Of the 5 patients whose PSA has been checked following treatment, only one has had a biochemical failure, and one remains on adjuvant androgen deprivation (median follow-up 1.4 years). Salvage radiation therapy using SIB to recurrent nodules detected on Mp-MRI is safe and was well tolerated. Prospective trials are warranted to evaluate therapeutic efficacy and potential dose escalation.

Purpose: Many automated Deformable Image Registration (DIR) validation methods are based on comparisons of deformed and observer contours. However, contour‐based comparisons are not sufficient to assess the dosimetric accuracy of a DIR algorithm. There is also potential for large dosimetric discrepancy when DVH accumulation is performed with different DIR algorithms. In this work, we compare the accumulated doses obtained with two different DIR algorithms in Head and Neck (H&N) cancer. Methods: Eight H&N patients who had weekly FBCT scans were included. Small Deformation Inverse‐Consistent Linear Elastic (SICLE) registration was used was used to estimate the displacement vector fields (DVFs) that simultaneously matched the CT intensity from the source (planning CT) image to weekly FBCT (target) images. In addition to intensity‐based matching (SICLE_I), contour‐based (SICLE_C) and intensity plus contour‐based (SICLE_I+C) matching was also performed. GTV, parotids, larynx and esophagus were used to drive SICLE_C registrations. The SICLE registrations were also compared to ITK Diffeomorphic Demons (ITKDD) registration algorithm. Finally, the accumulated dose was calculated for both adaptive and non‐adaptive scenarios and evaluated using dose‐volume constraints. Results: For non‐adaptive scenario, there was hardly any difference in the accumulated dose for target coverage using SICLE_I, SICLEC, SICLEI+C and ITKDD. Using adaptive replanning, however, PTV1 D98 improved by 1.5% using SICLEI+C. The maximum accumulated dose to the brainstem (D2) was also reduced by 12% by adaptive. On the average, the left parotid D50 also decreased by 32% using adaptive replanning. The maximum dose to the cord did not have a significant change using adaptive replanning‐based dose accumulation using all DIR algorithms. Conclusion: Intensity driven DIR algorithms used in this work produced fairly similar accumulated dose results in H&N cases. Overall, the dose accumulation based on adaptive replanning and utilizing intensity + contour driven registration resulted in better target coverage and critical structure sparing.

Adaptive radiotherapy (ART) has been shown to improve dosimetric parameters of head and neck (HN) IMRT by accounting for anatomic changes seen on fan beam CT (FBCT). However, the utility of cone beam CT (CBCT) scans in ART has not been well studied. This study aims to investigate the potential role of CBCT in adaptive IMRT planning for HN tumors and to quantify changes in target and normal tissue volumes over the course of treatment.

Purpose/Objective(s)Adaptive radiation therapy (ART) is of substantial interest in head and neck (H&N) IMRT as changes in weight, tumor, and normal tissue can compromise the accuracy of the original treatment plan. The aim of this study is to investigate the daily setup uncertainty over the course of treatment using multiple image techniques and multiple factors that alter patient setup integrity.Materials/MethodsThirteen patients with biopsy proven H&N tumors were enrolled under an IRB approved imaging protocol. Each patient was treated to 70 Gy in 33-35 fractions with concurrent chemotherapy. Pre-treatment imaging with cone beam CT, kV orthogonal on-board imaging, and patient motion-tracking system was performed daily and fan beam CT imaging was performed weekly. Preliminary data focuses on the patient motion-tracking system, which is the imaging modality used to align patients for H&N IMRT in our clinic. In this preliminary data analysis of the first 5 successfully enrolled patients, the daily shifts are grouped by treatment week to observe trends over time. The daily pre-treatment shift magnitudes were averaged over each week to quantify the mean shift distance. The standard deviation of the daily shifts was calculated for each week to quantify the random setup uncertainty.ResultsSetup uncertainly over the time of treatment showed two trends. Patients with increasing shift trends were not treated with a bite block (N = 2) whereas those without an increasing trend were treated with a bite block (N = 3). One patient without a bite block had a mean 3D vector shift distance of 2.5 mm (week 1 of imaging), which increased to 6.9 mm (week 7) with a clear increasing trend throughout. The mean vertical shift distance increased from 0.6 mm (week 1) to 2.9 mm (week 7). The random vertical setup uncertainty increased from 0.9 mm (week 1) to 3.6 mm (week 7). There were no appreciable trends in mean lateral shift distance. However, the random lateral setup uncertainty increased from 0.2 mm (week 1) to 3.6 mm (week 7). For the 3 patients treated with a bite block there were no clear increasing time trends in mean shift distance or random setup uncertainty. Mean 3D vector shift distance decreased by 0.1 mm from week 1 to week 7, random lateral setup uncertainty decreased 0.4 mm, and random lateral setup uncertainty decreased 1.7 mm.ConclusionsThe results of this preliminary analysis reinforce the use of a bite block for H&N patients. Even with significant weight loss, the bite block allowed the patient to be more consistently aligned day-to-day over the course of treatment. We have used this preliminary data in our clinic to recommend bite blocks for all patients receiving H&N IMRT. Analysis of the data from this imaging protocol is ongoing in support of identifying optimal ART strategies. Purpose/Objective(s)Adaptive radiation therapy (ART) is of substantial interest in head and neck (H&N) IMRT as changes in weight, tumor, and normal tissue can compromise the accuracy of the original treatment plan. The aim of this study is to investigate the daily setup uncertainty over the course of treatment using multiple image techniques and multiple factors that alter patient setup integrity. Adaptive radiation therapy (ART) is of substantial interest in head and neck (H&N) IMRT as changes in weight, tumor, and normal tissue can compromise the accuracy of the original treatment plan. The aim of this study is to investigate the daily setup uncertainty over the course of treatment using multiple image techniques and multiple factors that alter patient setup integrity. Materials/MethodsThirteen patients with biopsy proven H&N tumors were enrolled under an IRB approved imaging protocol. Each patient was treated to 70 Gy in 33-35 fractions with concurrent chemotherapy. Pre-treatment imaging with cone beam CT, kV orthogonal on-board imaging, and patient motion-tracking system was performed daily and fan beam CT imaging was performed weekly. Preliminary data focuses on the patient motion-tracking system, which is the imaging modality used to align patients for H&N IMRT in our clinic. In this preliminary data analysis of the first 5 successfully enrolled patients, the daily shifts are grouped by treatment week to observe trends over time. The daily pre-treatment shift magnitudes were averaged over each week to quantify the mean shift distance. The standard deviation of the daily shifts was calculated for each week to quantify the random setup uncertainty. Thirteen patients with biopsy proven H&N tumors were enrolled under an IRB approved imaging protocol. Each patient was treated to 70 Gy in 33-35 fractions with concurrent chemotherapy. Pre-treatment imaging with cone beam CT, kV orthogonal on-board imaging, and patient motion-tracking system was performed daily and fan beam CT imaging was performed weekly. Preliminary data focuses on the patient motion-tracking system, which is the imaging modality used to align patients for H&N IMRT in our clinic. In this preliminary data analysis of the first 5 successfully enrolled patients, the daily shifts are grouped by treatment week to observe trends over time. The daily pre-treatment shift magnitudes were averaged over each week to quantify the mean shift distance. The standard deviation of the daily shifts was calculated for each week to quantify the random setup uncertainty. ResultsSetup uncertainly over the time of treatment showed two trends. Patients with increasing shift trends were not treated with a bite block (N = 2) whereas those without an increasing trend were treated with a bite block (N = 3). One patient without a bite block had a mean 3D vector shift distance of 2.5 mm (week 1 of imaging), which increased to 6.9 mm (week 7) with a clear increasing trend throughout. The mean vertical shift distance increased from 0.6 mm (week 1) to 2.9 mm (week 7). The random vertical setup uncertainty increased from 0.9 mm (week 1) to 3.6 mm (week 7). There were no appreciable trends in mean lateral shift distance. However, the random lateral setup uncertainty increased from 0.2 mm (week 1) to 3.6 mm (week 7). For the 3 patients treated with a bite block there were no clear increasing time trends in mean shift distance or random setup uncertainty. Mean 3D vector shift distance decreased by 0.1 mm from week 1 to week 7, random lateral setup uncertainty decreased 0.4 mm, and random lateral setup uncertainty decreased 1.7 mm. Setup uncertainly over the time of treatment showed two trends. Patients with increasing shift trends were not treated with a bite block (N = 2) whereas those without an increasing trend were treated with a bite block (N = 3). One patient without a bite block had a mean 3D vector shift distance of 2.5 mm (week 1 of imaging), which increased to 6.9 mm (week 7) with a clear increasing trend throughout. The mean vertical shift distance increased from 0.6 mm (week 1) to 2.9 mm (week 7). The random vertical setup uncertainty increased from 0.9 mm (week 1) to 3.6 mm (week 7). There were no appreciable trends in mean lateral shift distance. However, the random lateral setup uncertainty increased from 0.2 mm (week 1) to 3.6 mm (week 7). For the 3 patients treated with a bite block there were no clear increasing time trends in mean shift distance or random setup uncertainty. Mean 3D vector shift distance decreased by 0.1 mm from week 1 to week 7, random lateral setup uncertainty decreased 0.4 mm, and random lateral setup uncertainty decreased 1.7 mm. ConclusionsThe results of this preliminary analysis reinforce the use of a bite block for H&N patients. Even with significant weight loss, the bite block allowed the patient to be more consistently aligned day-to-day over the course of treatment. We have used this preliminary data in our clinic to recommend bite blocks for all patients receiving H&N IMRT. Analysis of the data from this imaging protocol is ongoing in support of identifying optimal ART strategies. The results of this preliminary analysis reinforce the use of a bite block for H&N patients. Even with significant weight loss, the bite block allowed the patient to be more consistently aligned day-to-day over the course of treatment. We have used this preliminary data in our clinic to recommend bite blocks for all patients receiving H&N IMRT. Analysis of the data from this imaging protocol is ongoing in support of identifying optimal ART strategies.

PURPOSE DIR algorithms differ by physical principles employed in their design which in turn determines complexity of the transformation that the algorithm allows. Indiscriminate application of different algorithms without regard for their limitations may lead to significant discrepancies in research results and in clinical procedures. We compare two different algorithms in Head and Neck (H&N) patients to assess what aspects of DIR use are most sensitive to differences between algorithms. METHODS H&N patients are enrolled in a protocol which acquires weekly FBCT and daily double CBCT. Each FBCT study is contoured by the same physician. Two DIR algorithms are compared: Small Deformation Inverse-Consistent Linear Elastic (SICLE), and the ITK Diffeomorphic Demons (ITKDD) as implemented in the ITK package. Both algorithms employ significantly different physical principles in their design and consequently impose different restrictions on the complexity of transformation they allow. We compare Jacobian Volume Histograms (JVH), Spatial Discrepancy Volume Histograms (SDVH), BED and physical dose accumulation results and resulting plan evaluation indices. RESULTS Analysis of mean Jacobian shows that both algorithms are able to detect changes in structure volumes, though they differ quantitatively from one another and from the ground truth as established by the analysis of changes in contours. Width of Jacobian distributions is very different indicating that Jacobian should not be used as a measure of volume change at a voxel level without independent validation. Analysis of SDVHs shows that dose lookup points implied by both algorithms are separated by 5mm - 10mm over approximately 30% of most volumes. These differences translate into clearly visible though not very significant differences in BED and dose accumulation. We further observe that physical dose accumulation in external beam H&N patients is a good proxy for direct BED accumulation. CONCLUSIONS Different DIR algorithms may have to be applied selectively in different areas of treatment planning. Acknowledgments: Supported by NIH Grant P01 CA11602.