Maximum Tumor Dose Research Articles

Intraprocedural MRI-based dosimetry during transarterial radioembolization of liver tumours with holmium-166 microspheres (EMERITUS-1): a phase I trial towards adaptive, image-controlled treatment delivery

PurposeTransarterial radioembolization (TARE) is a treatment for liver tumours based on injection of radioactive microspheres in the hepatic arterial system. It is crucial to achieve a maximum tumour dose for an optimal treatment response, while minimizing healthy liver dose to prevent toxicity. There is, however, no intraprocedural feedback on the dose distribution, as nuclear imaging can only be performed after treatment. As holmium-166 (166Ho) microspheres can be quantified with MRI, we investigate the feasibility and safety of performing 166Ho TARE within an MRI scanner and explore the potential of intraprocedural MRI-based dosimetry.MethodsSix patients were treated with 166Ho TARE in a hybrid operating room. Per injection position, a microcatheter was placed under angiography guidance, after which patients were transported to an adjacent 3-T MRI system. After MRI confirmation of unchanged catheter location, 166Ho microspheres were injected in four fractions, consisting of 10%, 30%, 30% and 30% of the planned activity, alternated with holmium-sensitive MRI acquisition to assess the microsphere distribution. After the procedures, MRI-based dose maps were calculated from each intraprocedural image series using a dedicated dosimetry software package for 166Ho TARE.ResultsAdministration of 166Ho microspheres within the MRI scanner was feasible in 9/11 (82%) injection positions. Intraprocedural holmium-sensitive MRI allowed for tumour dosimetry in 18/19 (95%) of treated tumours. Two CTCAE grade 3–4 toxicities were observed, and no adverse events were attributed to treatment in the MRI. Towards the last fraction, 4/18 tumours exhibited signs of saturation, while in 14/18 tumours, the microsphere uptake patterns did not deviate from the linear trend.ConclusionThis study demonstrated feasibility and preliminary safety of a first in-human application of TARE within a clinical MRI system. Intraprocedural MRI-based dosimetry enabled dynamic insight in the microsphere distribution during TARE. This proof of concept yields unique possibilities to better understand microsphere distribution in vivo and to potentially optimize treatment efficacy through treatment personalization.RegistrationClinicaltrials.gov, identifier NCT04269499, registered on February 13, 2020 (retrospectively registered).

Clinical Outcomes and Prognostic Factors of Fractionated Stereotactic Radiosurgery for Brain Metastases ≥20 mm as a Potential Alternative to Surgery

This study investigated the outcomes and prognostic factors of fractionated stereotactic radiosurgery (FSRS) for treatment of brain metastases (BMs) ≥20 mm and determined whether FSRS could replace surgery, the primary treatment for large BMs. Patients with BMs ≥20 mm treated with FSRS were retrospectively examined. Patients who underwent FSRS postoperatively were excluded. Local failure, intracranial failure, and adverse events were evaluated. Overall, 116 lesions in 105 patients were evaluated. The performance status was 0-1, 2-4, and unknown for 86, 28, and 2 patients, respectively. The median maximum tumor diameter was 25 mm, and the median prescribed dose was 35 Gy in 3 fractions. The median follow-up period after FSRS was 8 months. The 1-year local failure, intracranial failure, and overall survival rates were 12.5%, 56.6%, and 49.0%, respectively. A maximum dose of ≥135 Gy (biological equivalent dose [α/β= 10 Gy]) and good performance status were independent favorable prognostic factors for local control. After FSRS, 21 (20%) patients were treated with whole-brain radiotherapy because of multiple intracranial recurrences, and 4 (3.4%) patients underwent surgery because of local recurrence. FSRS for BMs ≥20 mm achieved good local control. Only 3.4% of patients required surgery after FSRS, suggesting that FSRS is a potential alternative to surgery. For FSRS, a higher maximum tumor dose was useful for local control.

Tufts Medical Center Experience With Long-Term Follow-Up of Vestibular Schwannoma Treated With Gamma Knife Stereotactic Radiosurgery: Novel Finding of Delayed Pseudoprogression

PurposeOur purpose was to evaluate the long-term outcomes of patients with vestibular schwannoma (VS) treated with Gamma Knife stereotactic radiosurgery (GKSRS) with modern techniques, with attention to posttreatment tumor growth dynamics, dosimetric predictors, and late toxicities. Methods and MaterialsOne hundred twelve patients with VS were treated with GKSRS with a median dose of 12.5 Gy to the 50% isodose line treated between 2004 and 2015, with patients followed up to 15 years. Target and organ-at-risk doses were recorded, and tumor diameter/volume, audiologic decline, and trigeminal/facial nerve preservation were tracked from treatment onward. ResultsGKSRS yielded local control of 5, 10, and 15 years at 96.9%, 90.0%, and 87.1% respectively. Pseudoprogression was found in 45%, with a novel pattern detected with peak swelling at 31 months. Pseudoprogression was associated with smaller tumor diameter at treatment and fewer treatment isocenters, but not with the development of any toxicity, nor was it predicted by any dosimetric factor. Median time to hearing loss was 3.4 years with actuarial hearing preservation at 2, 5, and 10 years of 66.5%, 43.1%, and 37.6%, with rate of hearing loss correlating with maximum cochlea and modiolus doses. Trigeminal and facial nerve preservation rates were 92.7% and 97.6%, respectively. Increasing maximum tumor dose was associated with facial paresthesia. ConclusionsModern GKSRS is a safe and effective treatment for VS on long-term follow-up, with high levels of facial and trigeminal nerve preservation. A novel pattern of pseudoprogression has been identified suggesting longer imaging follow-up may be needed before initiating salvage in those without symptomatic progression. Several tumor and dosimetric predictors have been suggested for the development of different toxicities, requiring further evaluation.

Determination of Tumor Dose Response Thresholds in Patients with Chemorefractory Intrahepatic Cholangiocarcinoma Treated with Resin and Glass-based Y90 Radioembolization.

To compare the efficacies of glass and resin-based Yttrium-90 microspheres by comparing absorbed tumor dose (TD) with both tumor response (TR) and overall survival (OS) in patients with chemorefractory intrahepatic cholangiocarcinoma (ICC). Post-Y90 treatment bremsstrahlung SPECT/CT of 38 consecutive patients receiving 45 treatments (21 resin microspheres, 24 glass microspheres) were analyzed retrospectively. MIM software v6.9.4 (MIM Software Inc, Cleveland, OH) was used to calculate targeted tumors' dose volume histogram. Modified Response Evaluation Criteria in Solid Tumors was used to evaluate tumor response 3months post-treatment. Kaplan Meier estimation was used for survival analysis. T-test was used to compare the devices on various dosimetric parameters. Thresholds for TD to predict TR with ≥ 80% specificity were as follows: mean TD (Resin: 78.9Gy; Glass: 254.7Gy), maximum TD (Resin: 162.9Gy; Glass: 591Gy), minimum TD (Resin: 53.7Gy; Glass: 149.1Gy). Microsphere type had no effect on survival from first Y90 (Resin: 11.2 mo; Glass 10.9 mo [p = 0.548]). In patients receiving resin microspheres, mean TD ≥ 75Gy or maximum TD ≥ 150Gy was associated with median OS of 20.2 mo compared to 6.5 mo for those receiving less (p = 0.001, 0.002, respectively). For patients treated with glass microspheres, those receiving a mean TD ≥ 150Gy had a median OS of 14.6 mo vs. 2.6 mo for those receiving less (p = 0.031). TD thresholds predictive of TR and OS differ significantly between glass and resin microspheres. However, microsphere type has no impact on survival in patients with chemorefractory ICC. Level 3, Retrospective Study.

Determination of tumour dose response threshold and implication on survival in patients with HCC treated with Y90 radiation segmentectomy: a simple semi-quantitative analysis.

To evaluate the relationship between Yttrium-90 (Y90) tumour dose and response rate in patients with hepatocellular carcinoma (HCC) who undergo Y90 radiation segmentectomy (Y90-RS) and to determine implication on overall survival (OS). Post Y90-RS Bremsstrahlung single-photon emission computed tomography/CT of 105 HCC patients with 110 treatments performed with glass microspheres was retrospectively analysed. The dose-volume histogram of the targeted tumour was determined with commercially available dosimetry software. Tumour response at 3 months was evaluated using modified Response Evaluation Criteria in Solid Tumours. Tumour dose thresholds associated with the objective response with 80% specificity were then used to evaluate implication on OS using Kaplan-Meier estimation and log-rank analysis. Tumour dose thresholds to predict objective response with 80% specificity were the following: maximum tumour dose (748 Gy), mean tumour dose (568 Gy), minimum tumour dose of 30% tumour volume (608 Gy), minimum tumour dose of 50% tumour volume (565 Gy), minimum tumour dose of 70% tumour volume (464 Gy) and minimum tumour dose of 100% tumour volume (213 Gy). These parameters all significantly predicted tumour response with areas under the ROC curve of >0.6. Mean tumour dose of ≥250 Gy predicted median OS of 43.67 vs. 17.87 months for others (P = 0.026). Minimum dose ≥180 Gy to 100% of tumour volume predicted median OS of 44.93 vs. 35.87 months for others (P = 0.043). In patients with HCC undergoing Y90-RS, mean tumour dose ≥250 Gy and minimum tumour dose of ≥180 Gy to 100% of tumour volume are both significantly correlated with higher objective tumour response and prolonged survival.

Assessment Of The Outcomes And Prognostic Factors Of Fractionated Stereotactic Radiation Therapy For Large Brain Metastases As Potential Alternative To Surgery

Stereotactic radiation therapy (SRT) for brain metastases (BM) has been known for excellent local control with preservation of cognitive function. Recently, fractionated SRT(FSRT) has been shown to be superior to single fraction SRT in reducing the risk of radiation necrosis (RN), while maintaining or improving the rates of local control, especially in large BM. The purpose of this study was to clarify the outcomes and prognostic factors of FSRT for large BM and to evaluate whether FSRT could be an alternative to surgery. Patients who met the following criteria were retrospectively reviewed from our institutional database; 1) diagnosed with a BM by computed tomography or magnetic resonance imaging, 2) treated with FSRT, 3) no history of surgical resection for target lesion before FSRT and 4) maximum diameter of BM was 2 cm or greater. Local control (LC), intracranial control (ICC), overall survival (OS) and adverse events (AEs) were evaluated. AEs were evaluated based on Common Terminology Criteria for Adverse Events 5.0. Among 821 lesions, 131 lesions in 122 patients were selected from our database between February 2012 and December 2019 and the following data were extracted: median age, 67 (range, 39-93) years; performance status (PS), 0-1/2-4/unknown, 79/41/2; primary disease, lung/breast/colorectal/others, 81/13/10/18; median tumor maximum diameter, 25 (range, 20-50) mm; median tumor volume, 7.2 (range, 1.7-39.1) cm3; number of BM; 1/2 or more, 50/81; median prescription dose, 35 Gy in 3 fractions (range, 22.7-41.5 Gy in 3-5 fractions). Twenty-eight lesions (21.3%) with tumor diameter greater than 30 mm were included. Twenty-three lesions (17.6%) had a history of whole-brain radiation therapy (WBRT) before FSRT. The median follow-up after FSRT was 7 (range, 0-53) months. The 1-year LC rate, ICC rate and OS rate were 79.1%, 28.4% and 41.8%, respectively. In univariate analysis of LC, Dmax for planning target volume (PTV) calculated in biologically effective dose using α/β = 10 Gy (BED10) more than 135 Gy (p = 0.0032), Dmean for PTV calculated in BED10 more than 100 Gy (p = 0.019), PS 0-1 (p = 0.00083) and systemic therapy after FSRT (p = 0.0057) were associated with a significant better prognosis. The prescribed dose was not a significant factor for LC. In multivariate analysis, Dmax for PTV calculated in BED10 more than 135 Gy, PS 0-1 and systemic therapy after FSRT were independent prognostic factors. Seventeen lesions (12.9%) received WBRT following FSRT. Surgery for targeted lesion was performed in 3 lesions (2.9%) after FSRT. RN, including suspicious RN, were observed in 5 lesions (3.8%). Grade 2 intracranial hemorrhage were observed in 2 lesions (1.5%). FSRT for large BM has the potential to be an alternative to surgery, especially in patients with good PS who can receive systemic therapy following FSRT. FSRT with a higher maximum tumor dose might be improve LC.

Verification of a method to detect glass microspheres via micro-CT.

The ability to determine the microscopic distribution of glass microspheres in 90 Y radioembolization has important applications in post-treatment microdosimetry and cluster analysis. Current methods are time-intensive and labor-intensive and thus are typically only applied to small samples. A high-resolution micro-CT image with a voxel size of 8.74µm was acquired of phantoms containing ~25µm-diameter glass microspheres embedded in tissue-equivalent materials that were optically transparent, which allowed true microsphere locations to be determined using transmission light microscopy. A 3-stage algorithm was developed to estimate the number and locations of microspheres in tissue regions. The stages are thresholding the CT image and discarding regions with insufficient voxels, estimating the number of microspheres in each region using the values of the detected and neighboring region voxels and estimating locations for each microsphere using the outputs of the previous two stages. Two different methods for estimating the number of microspheres in each region were derived, as were five methods for localizing microspheres. Metrics for each stage were computed, and the mean absolute error (MAE) between the dose to 72µm voxels of the true and estimated dose maps created from the microsphere locations was used as the figure of merit for overall algorithm performance. Microsphere locations identified in the optical micrograph were used as the gold standard for the metrics of all stages. The method's utility was then demonstrated using a specimen from a human neuroendocrine tumor (NET) treated with glass 90 Y microspheres. The stage detecting regions containing microspheres found 100% of microspheres inside regions. The number of incorrectly detected regions without microspheres was 1.5% of the total number of regions. In stage 2, with these parameters, nearly 94% of the actual number of spheres in each region was correctly counted, and only 5% of the estimated sphere quantities in each region were false positives. The MAE between the true dose maps and dose maps estimated using the full algorithm with optimal parameter and method choices was 4.2%. A total of 5,713 glass microspheres were identified as being distributed heterogeneously in the NET specimen with a maximum tumor dose of >2500Gy and 46% of the specimen receiving <20Gy. This work developed and evaluated a method to detect and estimate the three-dimensional locations of glass microspheres in whole tissue samples that require less manual effort than traditional methods. This method could be used to gain important insights into the heterogeneity of microsphere distributions that would be useful for improving radioembolization treatment planning.

Measurement of Neutron Flux and Gamma Dose Rate Distribution Inside a Water Phantom for Boron Neutron Capture Therapy Study at Dalat Research Reactor

Exposure dose rate to the tumor and surrounding cells during neutron beam irradiation in Boron Neutron Capture Therapy (BNCT) comes not only from heavy charged particles produced from the 10B(n,α)7Li nuclear reaction, but also from neutron-induced reactions with other biological elements in living tissue, as well as from gamma rays leaked from the reactor core. At Dalat Research Reactor, Vietnam, the neutron and gamma dose rate distribution inside a water phantom were measured by using activation method and Thermoluminescent Dosimeter (TLD) detector, respectively. The results showed that effective thermal neutron dose rate along the center line of the water phantom had a maximum value of 479 mSv h-1 at 1 cm in phantom and then decreases rapidly to 4.87 mSv h-1 at 10 cm. The gamma dose rate along the center line of the water phantom also reach its maximum of 4.31 mSv h-1 at 1 cm depth and decreases to 1.16 mSv h-1 at 10 cm position. The maximum biological tumor dose rate was 1.74 Gy-eq h-1, not high enough to satisfy the treatment requirement of brain tumors. However, the results of this work are important in supporting of BNCT study in the upcoming stages at Dalat Research Reactor.

Hearing Outcomes After Stereotactic Radiosurgery for Jugular Paraganglioma.

To describe audiometric outcomes following stereotactic radiosurgery (SRS) for jugular paraganglioma (JP). Retrospective review. Tertiary referral center. Patients with pretreatment serviceable hearing (American Academy of Otolaryngology-Head and Neck Surgery [AAO-HNS] Class A or B) and serial post-SRS audiometric follow-up who underwent Gamma Knife SRS for JP between 1990 and 2017. Gamma Knife SRS. Progression to nonserviceable hearing; correlation between baseline hearing and treatment parameters with audiometric outcomes. Of 85 patients with JP who underwent SRS during the study period, 35 (66% female, median age 53) had pretreatment serviceable hearing and serial post-treatment audiometry available for review. Median tumor volume at the time of treatment was 7,080 mm, median cochlear point dose was 5.8 Gy (interquartile range [IQR] 4.1 to 7.3 Gy), and median marginal and maximum tumor doses were 16 and 32 Gy, respectively. After a median follow-up of 37 months (IQR 16 to 77 mo), the median change in pure-tone average and speech discrimination score in the treated ear was -1.2 dB HL/yr (IQR -4.5 to 0.3) and 0%/yr (IQR 0-3.5%), compared with 0.07 dB HL/yr (IQR -0.03 to 0.12) and 0 %/yr (IQR 0 to 0%) in the contralateral untreated ear. Seven patients developed nonserviceable hearing (AAO-HNS Class C or D) at a median of 13.2 months following SRS (IQR 4.8 to 24 mo). Among those who maintained serviceable hearing, median audiometric follow-up was 42 months (IQR 18 to 77 mo). The Kaplan-Meier estimated rates of serviceable hearing at 1, 3, and 5 years following SRS were 91%, 80%, and 80%, respectively. Sixty percent of patients with pulsatile tinnitus who underwent SRS experienced varying levels of symptomatic improvement following treatment. The short- and intermediate-term risk of progression to nonserviceable hearing following SRS for JP is low. Data regarding the impact of cochlear dose from the vestibular schwannoma literature should not be freely applied to JP, since the impact of SRS parameters on hearing preservation seems to be less significant.

Modulation of lateral positions of Bragg peaks via magnetic fields inside cancer patients: Toward magnetic field modulated proton therapy

This work investigated whether the Bragg peak (BP) positions of proton beams can be modulated to produce uniform doses and cover a tumor under the magnetic fields inside cancer patients, and whether magnetic field modulated proton therapy (MMPT) is effective in vital organ protection. The authors initially constructed an ideal water phantom comprising a central tumor surrounded by cuboid organ regions using GEANT4. Second, we designed the proton beams passing through the gap between two adjacent organ regions during beam configuration. Third, we simulated the beam transports under magnetic fields inside the phantom through GEANT4. Then, the beams were discarded, which did not stop in the tumor. Fourth, the authors modulated the intensities of the remaining beams to produce uniform tumor doses. Subsequently, the calculated MMPT doses were compared with those of traditional methods, such as single, opposing, orthogonal, and box fields. Moreover, the authors repeated the above research procedures for abdominal anatomies comprising tumors at the pancreatic tail and liver to evaluate whether MMPT is effective for the human anatomy. For the water phantom, the vital organ doses were approximately 50%, 30%, 30%, and 15% for the single, opposing, orthogonal, and box fields, respectively. As the vital organ doses decreased, the organ volume receiving proton irradiations for the opposing, orthogonal, and box fields increased by two, two, and four times compared with that for the single field. The vital organ volume receiving proton irradiations were controlled to a fairly low level through MMPT, whereas the BP positions of the proton beams were properly modulated through the magnetic fields inside the phantom. The tumor was sufficiently covered by a 95% dose line, and the maximum tumor doses were smaller than 110%. For the pancreatic tumor case, the proton beams were curved and bypassed the kidney to generate uniform doses inside the tumor through MMPT. In the liver tumor case, the liver volume receiving proton irradiations was reduced by approximately 40% through MMPT compared with traditional methods. The BP positions can be intentionally modulated to produce uniform tumor doses under the magnetic fields inside cancer patients. In some special cases, the vital organs surrounding the tumor can almost be exempted from proton irradiations without sacrificing tumor dose coverage through MMPT. For the tumors inside parallel organs, the parallel organ volume receiving proton irradiations was largely reduced through MMPT. The results of this study can serve as beneficial implications for future proton therapy studies with reduced vital organ damage and complications.

Dose painting by numbers in a standard treatment planning system using inverted dose prescription maps

ABSTRACTBackground. Dose painting by numbers (DPBN) is a method to deliver an inhomogeneous tumor dose voxel-by-voxel with a prescription based on biological medical images. However, planning of DPBN is not supported by commercial treatment planning systems (TPS) today. Here, a straightforward method for DPBN with a standard TPS is presented.Material and methods. DPBN tumor dose prescription maps were generated from 18F-FDG-PET images applying a linear relationship between image voxel value and dose. An inverted DPBN prescription map was created and imported into a standard TPS where it was defined as a mock pre-treated dose. Using inverse optimization for the summed dose, a planned DPBN dose distribution was created. The procedure was tested in standard TPS for three different tumor cases; cervix, lung and head and neck. The treatment plans were compared to the prescribed DPBN dose distribution by three-dimensional (3D) gamma analysis and quality factors (QFs). Delivery of the DPBN plans was assessed with portal dosimetry (PD).Results. Maximum tumor doses of 149%, 140% and 151% relative to the minimum tumor dose were prescribed for the cervix, lung and head and neck case, respectively. DPBN distributions were well achieved within the tumor whilst normal tissue doses were within constraints. Generally, high gamma pass rates (> 89% at 2%/2 mm) and low QFs (< 2.6%) were found. PD showed that all DPBN plans could be successfully delivered.Conclusions. The presented methodology enables the use of currently available TPSs for DPBN planning and delivery and may therefore pave the way for clinical implementation.

Gamma Knife surgery for facial nerve schwannomas.

The aim of this study was to evaluate the tumor control rate and functional outcomes after Gamma Knife surgery (GKS) among patients with a facial nerve schwannoma. The authors reviewed the radiological data and clinical records for 14 patients who had consecutively undergone GKS for a facial nerve schwannoma. Before GKS, 12 patients had facial palsy, 7 patients had hearing disturbance, and 5 patients had undergone partial or subtotal tumor resection. The mean and median tumor volumes were 3707 mm(3) and 3000 mm(3), respectively (range 117-10,100 mm(3)). The mean tumor margin dose was 13.2 Gy (range 12-15 Gy), and the mean maximum tumor dose was 26.4 Gy (range 24-30 Gy). The mean follow-up period was 80.7 months (range 2-170 months). Control of tumor growth was achieved in all 12 (100%) patients who were followed up for longer than 2 years. After GKS, facial nerve function improved in 2 patients, remained unchanged in 9 patients, and worsened in 3 patients. All patients who had had serviceable hearing at the preliminary examination maintained their hearing at a useful level after GKS. Other than mild tinnitus reported by 3 patients, no other major complications developed. GKS for facial nerve schwannomas resulted in excellent tumor control rates and functional outcomes. GKS might be a good primary treatment option for patients with a small- to medium-sized facial nerve schwannoma when facial nerve function and hearing are relatively preserved.

SU-E-T-629: Feasibility Study of Treating Multiple Brain Tumors with Large Number of Noncoplanar IMRT Beams

Purpose: To study the feasibility of treating multiple brain tumors withlarge number of noncoplanar IMRT beams. Methods: Thirty beams are selected from 390 deliverable beams separated by six degree in 4pi space. Beam selection optimization is based on a column generation algorithm. MLC leaf size is 2 mm. Dose matrices are calculated with collapsed cone convolution & superposition method in a 2 mm by 2mm by 2 mm grid. Twelve brain tumors of various shapes, sizes and locations are used to generate four plans treating 3, 6, 9 and 12 tumors. The radiation dose was 20 Gy prescribed to the 100% isodose line. Dose Volume Histograms for tumor and brain were compared. Results: All results are based on a 2 mm by 2 mm by 2 mm CT grid. For 3, 6, 9 and 12 tumor plans, minimum tumor doses are all 20 Gy. Mean tumor dose are 20.0, 20.1, 20.1 and 20.1 Gy. Maximum tumor dose are 23.3, 23.6, 25.4 and 25.4 Gy. Mean ventricles dose are 0.7, 1.7, 2.4 and 3.1 Gy.Mean subventricular zone dose are 0.8, 1.3, 2.2 and 3.2 Gy. Average Equivalent uniform dose (gEUD) values for tumor are 20.1, 20.1, 20.2 and 20.2 Gy. The conformity index (CI) values are close to 1 for all 4 plans. The gradient index (GI) values are 2.50, 2.05, 2.09 and 2.19. Conclusion: Compared with published Gamma Knife treatment studies, noncoplanar IMRT treatment plan is superior in terms of dose conformity. Due to maximum limit of beams per plan, Gamma knife has to treat multiple tumors separately in different plans. Noncoplanar IMRT plans theoretically can be delivered in a single plan on any modern linac with an automated couch and image guidance. This warrants further study of using noncoplanar IMRT as a viable treatment solution for multiple brain tumors.

Quantitative Dosimetry for Yttrium-90 Radionuclide Therapy: Tumor Dose Predicts Fluorodeoxyglucose Positron Emission Tomography Response in Hepatic Metastatic Melanoma

PurposeTo assess a new method for generating patient-specific volumetric dose calculations and analyze the relationship between tumor dose and positron emission tomography (PET) response after radioembolization of hepatic melanoma metastases. Methods and MaterialsYttrium-90 (90Y) bremsstrahlung single photon emission computed tomography (SPECT)/computed tomography (CT) acquired after 90Y radioembolization was convolved with published 90Y Monte Carlo estimated dose deposition kernels to create a three-dimensional dose distribution. Dose-volume histograms were calculated for tumor volumes manually defined from magnetic resonance imaging or PET/CT imaging. Tumor response was assessed by absolute reduction in maximum standardized uptake value (SUVmax) and total lesion glycolysis (TLG). ResultsSeven patients with 30 tumors treated with 90Y for hepatic metastatic melanoma with available 90Y SPECT/CT and PET/CT before and after treatment were identified for analysis. The median (range) for minimum, mean, and maximum dose per tumor volume was 16.9 Gy (5.7–43.5 Gy), 28.6 Gy (13.8–65.6 Gy) and 36.6 Gy (20–124 Gy), respectively. Response was assessed by fluorodeoxyglucose PET/CT at a median time after treatment of 2.8 months (range, 1.2–7.9 months). Mean tumor dose (P = .03) and the percentage of tumor volume receiving ≥ 50 Gy (P < .01) significantly predicted for decrease in tumor SUVmax, whereas maximum tumor dose predicted for decrease in tumor TLG (P < .01). ConclusionsVolumetric dose calculations showed a statistically significant association with metabolic tumor response. The significant dose-response relationship points to the clinical utility of patient-specific absorbed dose calculations for radionuclide therapy.

Increasing maximum tumor dose to manage range uncertainties in IMPT treatment planning

The accuracy of intensity modulated proton therapy (IMPT) is sensitive to range uncertainties. Geometric margins, as dosimetric surrogates, are ineffective and robust optimization strategies are needed. These, however, lead to increased normal tissue dose. We explore here how this dose increase can be reduced by increasing the maximum tumor dose instead. We focus on range uncertainties, modeled by scaling the stopping powers 5% up (undershoot) or down (overshoot) compared to the nominal scenario. Robust optimization optimizes for target dose conformity in the most likely scenario, not the worst, while constraining target coverage for the worst-case scenario. Non-robust plans are also generated. Different maximum target doses are applied (105% versus 120% versus 140%) to investigate the effect on normal tissue dose reduction. The method is tested on a homogeneous and a lung phantom and on a liver patient. Target D99 of the robust plans equals the prescription dose of 60 GyE for all scenarios, but decreases to 36 GyE for the non-robust plans. The mean normal tissue dose in a 2 cm ring around the target is 11% to 31% higher for the robust plans. This increase can be reduced to −8% and 3% (compared to the non-robust plan) by allowing a maximum tumor dose of 120% instead of 105%. Thus robustness leads to more normal tissue dose, but it can be compensated by allowing a higher maximum tumor dose.

TU‐E‐141‐08: Dosimetric Impact of Partial Volume Correction On PET‐Based Targeted Radionuclide Therapy Planning

Purpose: Partial volume effects have been shown to introduce a significant error in positron emission tomography (PET) quantitation. In this study, we investigated the impact of PET partial volume correction (PVC) on the dosimetry of PET‐based targeted radionuclide therapy (TRT) planning. Methods: Five tumor‐bearing nude mice were injected with ∼230 μCi of a 124I‐CLR1404, a small‐molecule, phospholipid ether analog featuring selective retention and accumulation in malignant cells. PET/CT data were acquired at 1, 6, 12, 24, 36, 48, 60, 72, 96, 120, 168, and 240 hours post injection and reconstructed with and without PVC using an OSEM3D algorithm. Assuming identical uptake between 124I‐CLR1404 and its therapeutic analog, 131I‐CLR1404, absorbed doses of 131I‐CLR1404 were modeled by applying a piecewise trapezoidal integration to the 124I‐CLR1404 kinetics. Dose volume histograms (DVHs) and normalized differential DVHs (dDVHs) were used to quantify the impact of PVC on PET‐based TRT planning. Results: Partial volume corrected PET images showed higher tumor uptake, increased the recovery of tumor heterogeneity structures, and a generally improved recovery of small normal tissue structures such as the heart ventricles. In tumors, the mean and maximum 124I‐CLR1404 standardized uptake value at peak drug concentration increased by 1.95±0.86% and 34.97±9.36%, respectively. DVHs of planned 131I‐CLR1404 doses showed an increase in maximum tumor dose levels by 15.63±3.53% due to PVC. Tumor dDVHs confirmed a shift towards higher therapeutic doses with an average increase of 13.09±1.21 mGy per mCi of injected 131I‐CLR1404 activity. Conclusion: PVC of PET data more accurately recovered the biodistribution of 124I‐CLR1404 and thus further improved TRT planning and delivery by increasing the quantitative accuracy. PVC will especially benefit the identification of cold spots in the target volume and the dose estimation in dose limiting organs. JJG and JPWare affiliated with Novelos Therapeutics, Inc., which owns the licensing rights to CLR1404 and related compounds.

Dose Escalation, Not “New Biology,” Can Account for the Efficacy of Stereotactic Body Radiation Therapy With Non-Small Cell Lung Cancer

Dose Escalation, Not “New Biology,” Can Account for the Efficacy of Stereotactic Body Radiation Therapy With Non-Small Cell Lung Cancer

Long-term follow-up studies of Gamma Knife surgery with a low margin dose for vestibular schwannoma

The aim of this study was to assess long-term clinical outcomes in patients who underwent Gamma Knife surgery (GKS) with a low margin dose-14 Gy or less-to treat vestibular schwannoma (VS) unrelated to neurofibromatosis Type II. Between December 1994 and December 2001, 200 patients with VSs underwent GKS, which was performed using the Leksell Gamma Knife model B. More than 10 years of follow-up is available in these patients. One hundred ninety patients (88 male and 102 female patients) were followed up using MRI (follow-up rate 95%). The mean age of these patients was 50.6 years (range 10-77 years). Gamma Knife surgery was the primary treatment for VS in 134 cases (70.5%) and was an adjunctive management approach in 56 cases (29.5%). The median tumor margin dose was 13.0 Gy (range 6.0-14.4 Gy), and the median maximum tumor dose was 28.0 Gy (range 15.0-60.0 Gy). The median tumor volume was 3.6 cm(3) (range 0.3-27.3 cm(3)). The median duration of follow-up in these patients was 109 months (range 8-195 months). In the 190 patients, the latest follow-up MRI studies demonstrated tumor regression in 122 patients (64.2%), stable tumor in 48 patients (25.3%), and tumor enlargement in 20 patients (10.5%). The total rate of tumor control was 89.5%. Using the Kaplan-Meier method, the authors found the estimated 3-, 5-, 10-, and 15-year tumor control rates to be 95%, 93%, 86%, and 79%, respectively; and the estimated 3-, 5-, and 10-year hearing preservation rates to be 96%, 92%, and 70%, respectively. Twenty-six patients (13.7%) exhibited transient mild facial palsy or facial spasm, and 2 patients (1.1%) suffered persistent mild facial palsy. Thirty-nine patients (20.5%) had transient trigeminal neuropathy, and 5 patients (2.6%) suffered from persistent mild facial numbness. The incidence of persistent severe facial and trigeminal neuropathy was 0.0%. With a low prescribed margin dose of 14 Gy or less, GKS was confirmed to provide long-term tumor control for small to medium-sized VSs and largely to prevent cranial nerves from iatrogenic injury. Based on the findings of this study, GKS is also a reasonable option for the treatment of large, heterogeneously enhancing tumors without symptomatic brainstem compression. Gamma Knife surgery can preserve a high quality of life for most patients with VS who do not have symptomatic brainstem compression. Long-term follow-up is required because of the risk of delayed recurrence of VS.

Hearing preservation after low dose linac radiosurgery for acoustic neuroma depends on initial hearing and time

PurposeTo assess long term outcomes and factors determining hearing preservation after low dose linac stereotactic radiosurgery (SRS) for acoustic neuroma (AN) at the Royal Adelaide Hospital using prospectively collected data. Material and methodsBetween 1994 and 2010, 102 patients had SRS for AN. Five patients had neurofibromatosis type 2, six sporadic cases had relapsed after surgery, and the remaining 91 sporadic cases had primary SRS. Dose was 12 or 14Gy. Sustained changes ⩾2mm in any diameter were deemed significant, and useful hearing was defined as inter-aural pure tone average (PTA)⩽50dB. Possible prognostic factors for hearing retention were tested by dividing the patients at pre-specified cutpoints: age (60years), maximum tumour diameter (20mm), initial PTA (20dB) and dose (12 vs 14Gy). ResultsEighty-four of the 91 sporadic primary SRS cases were evaluable for tumour control with at least one post-treatment MRI. Their median follow-up was 65mo (range 10–184mo). Eighty-two (97.6%) were controlled, the remaining two requiring salvage surgery for progression at 5.75 and 9.75years. Also, one of the post-operative cases required surgery at 2.1years after SRS. For the 50 sporadic primary SRS patients with initially useful hearing, median age was 56 (range 21–76), median initial PTA 16dB (range −11 to +45dB) and median tumour diameter 21mm (range 10–33mm). Four received 14Gy, the rest 12Gy. After SRS, 19 patients (38%) retained useful hearing. The Kaplan–Meier estimated preservation rate at 5years was 50% (95% CI 36–64%) but by 10years, this had fallen to 23% (95% CI 12–41%). On univariate analysis, the only significant factor was initial PTA (P<0.0001). The estimated risk of hearing loss after SRS for patients with initial PTA⩾20dB was 5.0 (95% CI 2.2–11.2) times that with PTA<20dB. ConclusionsTumour control was excellent (99/102=97% freedom from surgical salvage). Hearing preservation was strongly dependent on initial PTA, but there was a steady fall-off in hearing out to at least 10years.

SU‐D‐110‐06: Delineation of Target Volume Based on FDG PET‐CT Images and Its Effect on Tumor and Normal Tissue Doses

Purpose: To evaluate the effect of FDG PET‐CT imaging on target volume definition, inter and intra observer perceptions, and on tumor and normal tissue doses. Methods: The positron emission tomography with fluorine‐18‐ fluorodeoxyglucose (18F‐FDG) radiopharmaceutical and computed tomography (CT) combined provide structural and functional information for the definition of tumor and radio‐resistant regions that can be treated to high doses. This study uses data from twenty patients who had CT and PET imaging for treatment plan preparation. Treatment plans used non‐opposing co‐planar beams of four to seven fields. The prescribed dose was 70.2 Gy in 39 fractions. Physicians H and T independently delineated tumor volumes on CT and PET‐CT images and treatment plans were generated. Doses to CT contoured structures were obtained from plans that were originally planned based on contoured PET‐CT fused images. Tumor volumes of PET‐ CT and CT were compared by an index of agreement (IA). The intra and inter observer variations on tumor delineation, mean, minimum and maximum tumor doses, and percent differences in uninvolved lung doses were compared. Results: The mean intra observer IA value was approximately 0.50 for both physicians. The mean inter observer IA value was 0.45 and 0.52 for CT and fused PET‐CT tumor outlining respectively. The percent differences in average minimum and mean tumor doses for PET‐CT and CT plans were 60.1% and 8.1% respectively for physician H, and 78.4% and 11.7% respectively for physician T. The uninvolved lung mean dose variations for PET‐CT and CT plans were 5.6% and 1.9% for physicians H and T respectively, and between both physicians the differences were 9.6% and 12.7% for PET‐CT and CT plans respectively. Conclusions: The volumes created on PET‐CT images by two experienced physicians were greatly different compared to volumes created on CT only, resulting in extreme differences in calculated doses.