Total Target Volume Research Articles

Clinical Outcomes and Relevance of Composite V12 Gy in Patients With Four or More Brain Metastases Treated With Single Fraction Stereotactic Radiosurgery

AimsTissue V12Gy (total brain volume receiving 12Gy including target) can predict for late toxicity in single target benign disease treated with stereotactic radiosurgery (SRS). The value of this metric remains uncertain for multiple brain metastases. This retrospective cohort study reports the outcomes and evaluates the predictors of toxicity in patients with four or more brain metastases treated with single-fraction SRS. Materials and methodsTwo hundred twenty-six patients with 2160 metastases treated from 2014-21 were retrospectively studied. Symptomatic late toxicity (new/progressive neurological symptoms ≥3 months post SRS) with magnetic resonance imaging (MRI) changes suggestive of treatment effect were analysed. Kaplan–Meier and competing risk analysis was used to assess survival and toxicity respectively. Resultsmedian number of metastases/patient was 6 (range: 4-41) and median composite tissue V12Gy (inclusive of planning target volume (PTV)) was 11.3 cc (IQR: 6.1 cc–17.1 cc). Sixteen out of the 226 patients developed symptomatic late radiation adverse event (R-AE), and the cumulative incidence was 4.9% at 1 year and 6.9% at 2 years. The total target volume was significantly predictive of the risk of late R-AE. Volume of the largest lesion, V12Gy and V15Gy did not predict for late R-AE, but plotted graphs showed suggestions of linear relationships between dosimetric parameters and late R-AE. ConclusionWithin the limitations of this study, the cumulative incidence of symptomatic toxicity remains acceptable despite routinely accepting a composite tissue V12Gy in excess of 10 cc to treat multiple brain metastases. Advances in knowledgeV12Gy has limitations as a plan quality metric in multiple brain metastases treated with SRS. There is insufficient evidence to have a defined target limit as <10 cc.

Fractionated Stereotactic Intensity-Modulated Radiotherapy for Large Brain Metastases: Comprehensive Analyses of Dose–Volume Predictors of Radiation-Induced Brain Necrosis

Background: The objective was to explore dosimetric predictors of brain necrosis (BN) in fractionated stereotactic radiotherapy (SRT). Methods: After excluding collinearities carefully, multivariate logistic models were developed for comprehensive analyses of dosimetric predictors in patients who received first-line fractionated SRT for brain metastases (BMs). The normal brain volume receiving an xx Gy biological dose in 2 Gy fractions (VxxEQD2) was calculated from the retrieved dose–volume parameters. Results: Thirty Gy/3 fractions (fr) SRT was delivered to 34 patients with 75 BMs (median target volume, 3.2 cc), 35 Gy/5 fr to 30 patients with 57 BMs (6.4 cc), 37.5 Gy/5 fr to 28 patients with 47 BMs (20.2 cc), and 40 Gy/10 fr to 20 patients with 37 BMs (24.3 cc), according to protocols, depending on the total target volume (p &lt; 0.001). After excluding the three-fraction groups, the incidence of symptomatic BN was significantly higher in patients with a larger V50EQD2 (adjusted odds ratio: 1.07, p &lt; 0.02), V55EQD2 (1.08, p &lt; 0.01), or V60EQD2 (1.09, p &lt; 0.01) in the remaining five- and ten-fraction groups. The incidence of BN was also significantly higher in cases with V55EQD2 &gt; 30 cc or V60EQD2 &gt; 20 cc (p &lt; 0.05). These doses correspond to 28 or 30 Gy/5 fr and 37 or 40 Gy/10 fr, respectively. Conclusions: In five- or ten-fraction SRT, larger V55EQD2 or V60EQD2 are BN risk predictors. These biologically high doses may affect BN incidence. Thus, the planning target volume margin should be minimized as much as possible.

Neoadjuvant radiation target volume definition in esophageal squamous cell cancer: a multicenter recommendations from Chinese experts

BackgroundThis study aimed to establish a consensus on the delineation of target volumes for neoadjuvant radiation therapy (nRT) in esophageal squamous cell carcinoma (ESCC) within China.MethodsFrom February 2020 to June 2021, nine ESCC patients who received nRT were retrospectively selected from Sun Yat-sen University Cancer Center and Shandong Cancer Hospital. A panel from eight cancer radiotherapy centers performed two rounds of nRT target volume delineation for these patients: the first round for cases 1–6 and the second for cases 7–9. Online meetings were held after each delineation round to discuss findings. The consistency of delineations across centers was compared using mean undirected Hausdorff distances (Hmean), dice similarity coefficients (DSC), and total volumes, analyzed with the Mann-Whitney U test.ResultsThe second round of delineations showed improved consistency across centers (total clinical target volume (CTVtotal): mean DSC = 0.76–0.81; mean Hmean = 2.11–3.14 cm) compared to the first round (CTVtotal: mean DSC = 0.63–0.64; mean Hmean = 5.66–7.34 cm; DSC and Hmean: P < 0.050 between rounds), leading to the formation of a consensus and an atlas for ESCC nRT target volume delineation. A proposal was reached through evaluating target volume delineations, analyzing questionnaire survey outcomes, and reviewing pertinent literature.ConclusionsWe have developed guidelines and an atlas for target volume delineation in nRT therapy for ESCC in China. These resources are designed to facilitate more consistent delineation of target volumes in both clinical practice and clinical trials.

How Does the Number of Brain Metastases Correlate With Normal Brain Exposure in Single-Isocenter Multitarget Multifraction Stereotactic Radiosurgery

PurposeTo investigate the relationship between normal brain exposure in linac-based single-isocenter multi-target multi-fraction stereotactic radiosurgery (SRS) or stereotactic radiotherapy (SRT) and the number or volume of treated brain metastases, especially for high numbers of metastases. Methods and MaterialsA cohort of 44 SRT patients with 709 brain metastases was studied. Renormalizing to a uniform prescription of 27 Gy in 3 fractions, normal brain dose volume indices, including V23Gy (volume receiving >23Gy), V18Gy (volume receiving >18Gy), and mean dose, were evaluated on these plans against the number and the total volume of targets for each plan. To compare with exposures from whole-brain radiotherapy (WBRT), the SRT dose distributions were converted to equivalent dose in 3 Gy fractions (EQD3) using an alpha-beta ratio of 2 Gy. ResultsWith increasing number of targets and increasing total target volume, normal brain exposures to dose ≥18 Gy increases, and so does the mean normal brain dose. The factors of number of targets and total target volume are both significant, though the number of targets has a larger effect on the mean normal brain dose and the total target volume has a larger effect on V23Gy and V18Gy. The EQD3 mean normal brain dose with SRT planning is lower than conventional WBRT. On the other hand, SRT results in higher hot spot (i.e. maximum dose outside of tumor) EQD3 dose than WBRT. ConclusionsBased on clinical SRT plans, our study provides information on correlations between normal brain exposure and the number and total volume of targets. As SRT becomes more greatly utilized for patients with increasingly extensive brain metastases, more clinical data on outcomes and toxicities is necessary to better define the normal brain dose constraints for high-exposure cases and to optimize the SRT management for those patients.

Dosimetric Evaluation of a Novel Non-Metallic Dual Port Expander for Proton Therapy

This study evaluates a novel non-metallic (plastic) dual port expander and clinically utilized single/dual port metallic expanders for intensity modulated proton therapy (IMPT) in order to quantify the dosimetric implications in clinical treatment plans. Four previously treated breast cancer patients (3 left sided, 1 right sided) with tissue expanders were retrospectively planned for IMPT utilizing a treatment planning system. Utilizing the existing CT data sets, models of three Sientra tissue expanders (dual port plastic (DPP), dual port metal (DPM) and single port metal (SPM)) were inserted into the 3D dataset and aligned using the existing patient anatomy. Each patient was planned to a total dose of 50.4 Gy in 28 fractions using 3 incident proton fields and Monte Carlo calculation algorithm. A 5 mm expansion was placed around the metallic portion of the expander to define a beam avoidance region which no proton spots traversed or were placed to minimize dosimetric error. Robust optimization (5mm setup uncertainty, 3.5% range uncertainty) was employed to a total target volume which comprised the CTV chest wall, IMN, axilla and supraclavicular nodes. The subsequent treatment plans were evaluated for target and OAR coverage. Due to the non-metallic construction of the DPP expander, the metallic structure avoidance region was significantly smaller at 4.4cc on average than either the SPM (45cc average) or DPM (63.5cc average). This allowed the IMPT plans to be significantly less modulated, delivering a more uniform dose to the implant volume (SPM 47.1Gy; DPM 45.2 Gy; DPP 50.9 Gy) and thus enabling these plans to be inherently more robust to setup uncertainties. The additional benefit of the reduced avoidance region size is that the hinge angle of the lateral proton beams can be reduced for DPP plans thus reducing dose to the heart and contralateral breast. Average mean heart dose across the four cases presented is 0.68 Gy, 1.03 Gy, and 0.93 Gy, for the DPP, DPM and SPM cases respectively, while average contralateral breast/CW dose is 0.38 Gy, 0.58 Gy and 0.63 Gy. The V20 for the ipsilateral lung was, on average, reduced for the DPP expander at 14.3% across the 4 cases, while 18.8% and 17.0% for the DPM and SPM cases respectively. The minimization of metal in the DPP expander allows for a significantly smaller beam avoidance region, in-turn enabling creation of a more homogeneous plan that can be potentially more robust while also reducing dose to surrounding OARs. Additional work is underway to expand the study to include a larger patient cohort, while also evaluating the impact of different robustness goals on OAR sparing.

Evaluating Radiation-Related Risk Factors for Pneumonitis in Patients with Stage III NSCLC Receiving Durvalumab after Definitive Chemoradiation

<h3>Purpose/Objective(s)</h3> Concurrent chemoradiotherapy (CCRT) followed by durvalumab consolidation up to 12 mo became the standard of care for patients (pts) with stage III NSCLC after the publication of the PACIFIC trial. Both radiation pneumonitis (RP) and immune checkpoint inhibitor pneumonitis (ICI-p) are serious toxicities that can occur in this population, and radiation and ICI modality individually is known to contribute to pneumonitis risk; when combined, they could work synergistically or additively to increase this risk. We set out to evaluate radiation treatment specific risk factors for symptomatic pneumonitis in pts receiving CCRT followed by durvalumab. We hypothesize that adjuvant ICI (durvalumab) will increase the pneumonitis risk from CCRT predicted by current consensus guidelines. <h3>Materials/Methods</h3> We conducted a retrospective study of pts with stage III NSCLC treated with CCRT followed by durvalumab from 2018 -21. Median follow up time was 18.8 mo from the last day of RT to last contact. RT dose parameters were extracted from each treatment plan. Normal lung volume (NLV) was defined as total lung volume minus clinical target volume (Lung -CTV). Percentage of NLV receiving more than 5, 10, or 20 Gy (V5, V10, V20), and mean lung dose (MLD) were calculated. The primary endpoint was development of symptomatic pneumonitis (≥gr 2), assessed via clinical presentation and available imaging. The association between the % NLV of radiation and the probability of developing pneumonitis was analyzed using logistic regression, and odds ratios (OR) were estimated. <h3>Results</h3> Of the 80 patients included in this study, 21 (26.3%) developed symptomatic pneumonitis following durvalumab initiation. 69 (86.3%) received carboplatin-paclitaxel and 11 (13.8%) received cisplatin-etoposide chemotherapy. 73 (91.2%) had received standard RT dose of 60 Gy, while 7 (8.8%) received an additional 12-16 Gy SBRT boost to the primary tumor on a separate study. We found no significant association between symptomatic pneumonitis and RT dose or type of chemotherapy. However, smaller treatment volumes receiving 5 or 10 Gy were associated with lower pneumonitis risk: V10 < 40%, vs ≥ 40% (OR = 0.347, 95% CI 0.11-1.07, P=0.067) and V5 <65% vs ≥65% (OR = 0.42, 95% CI: 0.15-1.17, P = 0.096). Mean MLD was 14.9 Gy (3.9-21.9 Gy), Mean V20 was 25.7% (4.5-40.1%), both well below current consensus guidelines. We did not identify a notable association between pneumonitis and other known clinical risk factors. <h3>Conclusion</h3> This data is from our institution's first cohort of pts treated as in the PACIFIC study after durvalumab was approved by FDA for this indication. Our data suggest pts with a lower radiation treatment volume at 5 or 10 Gy (V5/V10) prior to durvalumab may have a lower risk of developing pneumonitis when other parameters (MLD, V20) are kept under the current recommended radiation tolerance without adjuvant ICI. Further research with larger study populations is needed to confirm this and inform guideline development.

Radiosurgery for Primary and Metastatic CNS Malignancies in the Pediatric Population

<h3>Purpose/Objective(s)</h3> Safety and efficacy of stereotactic radiosurgery (SRS) are not well described for pediatric patients. This study presents disease control and toxicity outcomes after SRS for malignant CNS lesions in pediatric patients. <h3>Materials/Methods</h3> Retrospective chart review was performed for 31 pediatric patients treated at a single institution with a non-invasive stereotactic radiosurgery instrument for primary or metastatic CNS malignancies between 2000-2020. Analyses were performed with descriptive statistics, Kaplan-Meier, and proportional hazards modeling. <h3>Results</h3> Twenty-five patients were treated with SRS for focal recurrences of primary CNS malignancies, 1 patient was treated in the early adjuvant setting after initial resection, and 5 patients were treated for brain metastases. Primary CNS histologies included ependymoma (n=14), glioma (n=4), medulloblastoma (n=2), and meningioma (n=2). 65% were WHO grade 3 or 4 at the time of diagnosis. Brain metastases were from non-germinomatous germ cell tumors (n=3), papillary thyroid cancer (n=1), and neuroblastoma (n=1). 71% of patients had prior involved-field external beam radiation to the brain (median dose 59.4 Gy in 33 fractions). Median age at SRS was 14 years (range 4-21). SRS was predominantly performed in a single fraction (median dose 17 Gy, range 15-20) to a total of 42 targets among 29 patients, with a median total gross target volume (GTV) of 1.3 cc. Two patients underwent fractionated radiosurgery to 30 Gy in 5 fractions for larger brain metastases (GTVs 8.5 cc & 23.2 cc). Median follow up after SRS was 44 months (interquartile range 20-72). The 3-year actuarial rates of local control, intracranial progression-free survival, and overall survival after SRS were 77.6%, 33.3%, and 74.6%, respectively. 9 patients (29%) had no evidence of intracranial disease after SRS at a median follow up of 39 months. 6 patients (19%) developed local recurrence at a median of 13 months after SRS. 16 patients (52%) developed distant brain recurrence without local failure at a median of 9 months after SRS. Among primary CNS tumors, there was no significant association of histology, grade, or dose with disease control outcomes on univariate analysis. All patients with subsequent CNS recurrence after SRS underwent salvage therapy, including additional radiosurgery (36%), systemic therapy (23%), resection (9%), or combined modality treatment (32%). In total, 4 patients developed CTCAE grade 2-3 toxicity from SRS, all of which were related to radiation treatment effect and occurred within 1 year of SRS. 2 patients received steroids alone, and 2 underwent invasive procedures (1 shunt revision, 1 resection of nonviable tumor). <h3>Conclusion</h3> SRS for malignant CNS lesions in the pediatric population provides effective local control and is generally well-tolerated. Although there remains a substantial risk of distant CNS failures, all patients were able to receive additional salvage therapy after SRS.

Daily Fluid Intake Behaviors and Associated Health Effects Among Australian and United States Populations.

Minimal data exist exploring intercontinental differences in fluid intake (FI) beliefs and behaviors and the impact on fluid intake practices (i.e., fluid intake volume, beverage type, and timing of fluid intake). Therefore, this study explored the impact that FI beliefs and behaviors had on FI practices among emerging adults living in the United States (USA) and Australia (AUS). A total of 489 individuals (74.5% female; USA, 79.4%; age, 25 ± 6 years completed a 23-item survey between November 2020 and June 2021). Participants detailed their FI practices. FI beliefs were evaluated to determine their contribution to FI behaviors across the day. Multinomial and multiple linear regression analyses explored the association of daily FI beliefs and behaviors across multiple domains. Independent sample t-tests and chi-square analyses were conducted to compare FI practices, beliefs, and behaviors between individuals in the USA and AUS. FI behaviors were significantly different between countries, with the USA more likely to consume fluids to meet a total target volume (β = 1.150, p = 0.036) and consume fluid at the same time as structured daily activities (β = 0.773, p = 0.046) compared to FI alongside food intake. However, there were no differences in the types of beverage consumed (juice, sugar-sweetened beverages, tea, and coffee), total fluid volume, and physical activity (PA) between countries (p > 0.05). Beverage consumption was higher among USA than AUS residents for water, beer, and wine (p < 0.05). Total fluid consumption was greater among males (3,189 ± 2,407 ml) than females (2,215 ± 1,132 ml; β = 3.61, p < 0.001), individuals who regularly consumed fluid during the day to meet a targeted volume (β = 1,728.5, p < 0.001), and those who regularly consumed fluid as a habitual behavior (β = 3.97, p < 0.001) compared to those individuals who only consumed fluid alongside mealtimes (β = 1,041.7, p < 0.001). FI behaviors differed between the USA and AUS; however, total volume consumed, type of beverage consumed, and FI beliefs were similar. FI practices and behaviors appear to be individualized and context-specific among the studied populations.

Systemic Therapy Type and Timing Effects on Radiation Necrosis Risk in HER2+ Breast Cancer Brain Metastases Patients Treated With Stereotactic Radiosurgery.

BackgroundThere is a concern that HER2-directed systemic therapies, when administered concurrently with stereotactic radiosurgery (SRS), may increase the risk of radiation necrosis (RN). This study explores the impact of timing and type of systemic therapies on the development of RN in patients treated with SRS for HER2+ breast cancer brain metastasis (BCBrM).MethodsThis was a single-institution, retrospective study including patients >18 years of age with HER2+ BCBrM who received SRS between 2013 and 2018 and with at least 12-month post-SRS follow-up. Presence of RN was determined via imaging at one-year post-SRS, with confirmation by biopsy in some patients. Demographics, radiotherapy parameters, and timing (“during” defined as four weeks pre- to four weeks post-SRS) and type of systemic therapy (e.g., chemotherapy, HER2-directed) were evaluated.ResultsAmong 46 patients with HER2+ BCBrM who received SRS, 28 (60.9%) developed RN and 18 (39.1%) did not based on imaging criteria. Of the 11 patients who underwent biopsy, 10/10 (100%) who were diagnosed with RN on imaging were confirmed to be RN positive on biopsy and 1/1 (100%) who was not diagnosed with RN was confirmed to be RN negative on biopsy. Age (mean 53.3 vs 50.4 years, respectively), radiotherapy parameters (including total dose, fractionation, CTV and size target volume, all p>0.05), and receipt of any type of systemic therapy during SRS (60.7% vs 55.6%, p=0.97) did not differ between patients who did or did not develop RN. However, there was a trend for patients who developed RN to have received more than one agent of HER2-directed therapy independent of SRS timing compared to those who did not develop RN (75.0% vs 44.4%, p=0.08). Moreover, a significantly higher proportion of those who developed RN received more than one agent of HER2-directed therapy during SRS treatment compared to those who did not develop RN (35.7% vs 5.6%, p=0.047).ConclusionsPatients with HER2 BCBrM who receive multiple HER2-directed therapies during SRS for BCBrM may be at higher risk of RN. Collectively, these data suggest that, in the eight-week window around SRS administration, if HER2-directed therapy is medically necessary, it is preferable that patients receive a single agent.

Non-coplanar volumetric modulated arc therapy for locoregional radiotherapy of left-sided breast cancer including internal mammary nodes.

BackgroundNon-coplanar volumetric modulated arc therapy (ncVMAT) is proposed to reduce toxicity in heart and lungs for locoregional radiotherapy of left-sided breast cancer, including internal mammary nodes (IMN).Patients and methodsThis retrospective study included 10 patients with left-sided breast cancer who underwent locoregional radiotherapy after breast-conserving surgery. For each patient, the ncVMAT plan was designed with four partial arcs comprising two coplanar arcs and two non-coplanar arcs, with a couch rotating to 90°. The prescribed dose was normalized to cover 95% of planning target volume (PTV), with 50 Gy delivered in 25 fractions. For each ncVMAT plan, dosimetric parameters were compared with the coplanar volumetric modulated arc therapy (coV-MAT) plan.ResultsT here were improvements in conformity index, homogeneity index and V55 of total target volume (PTVall) comparing ncVMAT to coVMAT (p < 0.001). Among the organs at risk, the average V30, V20, V10, V5, and mean dose (Dmean) of the heart decreased significantly (p < 0.001). Furthermore, ncVMAT significantly reduced the mean V20, V10, V5, and Dmean of left lung and the mean V10 and V5 and Dmean of contralateral lung (p < 0.001). An improved sparing of the left anterior descending coronary artery and right breast were also observed with ncVMAT (p < 0.001).ConclusionsCompared to coVMAT, ncVMAT provides improved conformity and homogeneity of whole P TV, better dose sparing of the heart, bilateral lungs, left anterior descending coronary artery (LAD), and right breast for locoregional radiotherapy of left-sided breast cancer with IMN, potentially reducing the risk of normal tissue damage.

RADT-02. FACTORS ASSOCIATED WITH NEW-ONSET SEIZURES AFTER STEREOTACTIC RADIOSURGERY FOR NEWLY DIAGNOSED BRAIN METASTASES

Abstract INTRODUCTION Stereotactic radiosurgery (SRS) is a highly effective therapy for newly diagnosed brain metastases. Risk factors for new-onset seizures after SRS have not been well established. In this study, we aimed to characterize the variables predictive of seizure risk. METHODS Patients treated with SRS for newly diagnosed brain metastases were retrospectively reviewed at a single institution. Data on baseline demographics, radiation parameters, and clinical courses were collected. RESULTS 120 patients without previous seizure history were identified. Median age was 65 years (56-70.8) and baseline KPS 90 (80-90). 16 (13%) patients developed new-onset seizures within 3 months of SRS. In analyses comparing patients with and without new-onset seizures, there was no association between new-onset seizures and baseline KPS(90:80, p=0.48), prior resection (31%:28%, p=0.76), prior WBRT (6%:10%, p=1), immunotherapy or chemotherapy within 1 month (31%:21%, p=0.52 and 56%:57%, p=1), primary tumor site (p=0.07), number of lesions (2.2:3, p=0.21), cerebellar (25%:37%, p=0.41) or brainstem involvement (19%:14%, p=0.71), irradiated maximum target diameter (2.8:2.0cm p=0.191), maximum target volume (7.6:2.9 cm3 p=0.133), total dose of radiation (25:20Gy, p = 0.12), or use of fractionation (56%:35%, p=0.11). However, there was a significant difference in the total irradiated target volume (11.6 vs. 3.8 cm3, p=0.019) and a trend toward increased post-treatment seizures among patients with a total irradiated volume greater than 10cm3 (20%:9%, p=0.11, OR 2.4 [0.85-6.4]). Patients with seizures were also more likely to have received steroids (69%:34%, p=0.012) and AEDs (28%:15%, p=0.021) prior to SRS. CONCLUSIONS Our data suggest that total treatment volume is associated with new-onset seizures within 3 months of SRS. The association between seizures and exposure to steroids or AEDs prior to SRS may be a surrogate for neurologic symptoms at presentation. Patients undergoing SRS to larger volumes and necessitating prophylactic steroids or AEDs may benefit from counseling or intensification of anti-seizure therapy.

A Volumetric Analysis of Stereotactic Radiosurgery Low Dose Volumes in Preventing Future Brain Metastases

Stereotactic radiosurgery (SRS) is now commonly used to treat brain metastases. A primary limitation, compared to whole brain radiotherapy (WBRT) is its inability to prevent development of brain metastases in untreated areas. The purpose of this study is to assess whether low-dose volumes delivered to uninvolved regions of the brain during standard SRS can reduce the risk of developing brain metastases in those regions. Clinical data were collected for 69 patients with brain metastases who were treated with SRS on two or more occasions. Patients who had WBRT prior to or in between rounds of SRS were not included. Tumor volume and dosimetric data were collected from the first round of SRS. The regions of uninvolved brain receiving a high, intermediate, and low dose of incidental radiotherapy were identified. These doses were defined as the absolute volume receiving at least 10, 5, and 2.5 Gy if the prescribed dose was < 25 Gy (1-3 fraction plans) or the absolute volume receiving at least 15, 7.5, and 5 Gy if the prescribed dose was ≥ 25 Gy (5 fraction plans). Tumor volume and location in reference to these three dose levels were collected for metastases that were treated in the second round of SRS. A second-round metastasis was considered to occur within a given dose level if 20% or more of the volume of the tumor was found within that dose level. Progression of treated metastases were not included. Volumetric probabilities were calculated based on the volume of each dose level as a percentage of total brain volume. The sum of these probabilities across all cases was used to calculate the expected number of cases with at least one metastasis occurring in each dose level. P-values were calculated using the chi-square test statistic. Of the 69 patients included in this study, the primary cancer was non-small cell lung cancer for 35%, breast cancer for 32%, and melanoma for 16%. The average number of metastases treated in both the first and second rounds of SRS was two. The mean total clinical target volume (the sum of individual clinical target volumes) was 7.5 cc in the first round and 3.0 cc in the second round. The expected and observed number of cases with at least one second round metastasis occurring in high, intermediate, and low dose levels are displayed in the table below. We observed fewer than expected new metastases within prior SRS low dose levels based on volumetric probabilities, though this difference was only significant for the intermediate dose level. This suggests that low dose volumes from SRS may provide benefit in preventing future regional metastases. Further research is warranted to assess the effects of low dose volumes on future metastases based on cancer type and region of the brain.Abstract 3618; TableNumber of cases with new metastases within prior dose levelsExpectedObservedP-valueHigh dose level200.151Intermediate dose level730.018Low dose level17110.094 Open table in a new tab

Analysis of treatment process time for real-time-image gated-spot-scanning proton-beam therapy (RGPT) system.

We developed a synchrotron‐based real‐time‐image gated‐spot‐scanning proton‐beam therapy (RGPT) system and utilized it to clinically operate on moving tumors in the liver, pancreas, lung, and prostate. When the spot‐scanning technique is linked to gating, the beam delivery time with gating can increase, compared to that without gating. We aim to clarify whether the total treatment process can be performed within approximately 30 min (the general time per session in several proton therapy facilities), even for gated‐spot‐scanning proton‐beam delivery with implanted fiducial markers. Data from 152 patients, corresponding to 201 treatment plans and 3577 sessions executed from October 2016 to June 2018, were included in this study. To estimate the treatment process time, we utilized data from proton beam delivery logs during the treatment for each patient. We retrieved data, such as the disease site, total target volume, field size at the isocenter, and the number of layers and spots for each field, from the treatment plans. We quantitatively analyzed the treatment process, which includes the patient load (or setup), bone matching, marker matching, beam delivery, patient unload, and equipment setup, using the data obtained from the log data. Among all the cases, 90 patients used the RGPT system (liver: n = 34; pancreas: n = 5; lung: n = 4; and prostate: n = 47). The mean and standard deviation (SD) of the total treatment process time for the RGPT system was 30.3 ± 7.4 min, while it was 25.9 ± 7.5 min for those without gating treatment, excluding craniospinal irradiation (CSI; head and neck: n = 16, pediatric: n = 31, others: n = 15); for CSI (n = 11) with two or three isocenters, the process time was 59.9 ± 13.9 min. Our results demonstrate that spot‐scanning proton therapy with a gating function can be achieved in approximately 30‐min time slots.

Impact of Air Gap on Intensity-Modulated Proton Therapy Breast Plans

ObjectiveThe primary purpose of this study was to investigate the impact of an air gap (AG) on breast cancer plans that are generated using the intensity-modulated proton therapy technique. MethodsIn this retrospective study, we have included a total of ten female patients with left breast cancer. A total clinical target volume (CTV_Total) was generated by combining breast or chest wall, axillary level I–III nodes, internal mammary nodes, and supraclavicular nodes. Monte Carlo algorithm used within RayStation was used for both the robust plan optimization and dose computation. For each case, intensity-modulated proton therapy breast plan with a 4 cm AG was considered as the base plan. To test the impact of the AG, the base plan (AG = 4 cm) of a given case was copied and recalculated for additional AG of 6, 8, 10, 12, and 14 cm. ResultsAn increase in the AG yielded a decrease in the dosimetric and tumor control probability (TCP) values in all ten patients. As the AG increased from 4 cm to 14 cm, the impact of the AG on the dosimetric indices was the most severe for the target volume received by 95% of the prescription dose (CTV_Total V95%) and dose received by 99% of the target volume (CTV_Total D99%), which showed the average reduction of 7% ± 3% and 6.3% ± 2.8%, respectively. Similarly, the average decrease in dose received by 99% of the volume (CTV_Total D95%), CTV_Total mean dose, Homogeneity Index of CTV_Total, and TCP of CTV_Total were 4.7% ± 1.8%, 2.1% ± 0.6%, 0.03 ± 0.02, and 1.3% ± 0.4%, respectively. ConclusionsIn the present study, an increase in 2 cm AG provided a reduction in the dosimetric and TCP results by ≤1%. An increment of the AG by 4 cm (ie, from 4 cm to 8 cm) resulted in a loss of ≤2% and ≤0.6% in the dosimetric and TCP results, respectively. There was no distinct trend between organ at risk results and variation in the AG.

Correlation of V12 to the Number of Lesions, Total Tumor Volume and Dose Prescription in Multiple Brain Metastases Stereotactic Radiosurgery Treatment

Patients with brain metastases (BM) present with variable parameters in terms of number, size and location of lesions. In single-fraction stereotactic radiosurgery (SRS) for patients with multiple BM, smaller total tumor volume, higher prescription dose, and lower volume of normal brain receiving >12 Gy (V12) were associated with increased survival rate. V12 larger than 10 cc has been reported to relate to radiation brain necrosis. In this study, we investigated the correlation of V12 to the number of lesions, total tumor volume and dose prescription in multiple BM SRS treatment using Gamma Knife ICON. The dose fall off near the target periphery follows the power-law relationship of D(r, n) ∼ 1/rp(n) (1), where D is the peripheral dose near the target, r is the distance from center of target to a spherical surface surrounding the target, n is the number of targets being treated, and p(n) is the power of the dose fall off. By assuming all the targets to be spheres, the dose of x Gy encompassed volume (Vx) is derived as (Vx/(VT*CI))=(Dp/Dx)γ(n) (2). Here γ(n) = 3/p(n) (3), VT: total target volume, CI: conformity index and Dp: prescription dose. Furthermore, by derivative equation (2), the change of V12 with number of targets and dose prescription are derived respectively as δV12 = VT*CI*(Ln(Dp/12))*(Dp/12)γ(n) δγ(n) (4) and δV12 = VT*CI*γ(n)*(Dp/12)(γ(n)-1) δDp (5). Therefore, we hypothesize that γ(n) increases with number of targets and total target volumes; V12 increases with increasing number of targets and dose prescriptions. In order to prove the above, five single fraction mask-based Gamma Knife treatment plans with numbers of lesions of 3, 13, 8, 3+13=16 and 3+13+8=24 (3 consecutive courses treated for one patient in 2 years) were analyzed and power fitted based on the derived equation (2) and γ(n) was determined for different target number. A significant positive correlation between γ(n) and number of targets was found (R2 = 0.7455), but no strong correlation between γ(n) and total target volume (R2 = 0.4356). A significant positive correlation between increased V12 (δV12) and number of targets were determined (R2 = 0.9998) and the relationship between V12-VT and γ(n) were established (R2 = 0.5174). The results can help clinicians in making decisions about which prescription to choose and what maximum number of targets can be treated to avoid potential complication in brain. The results are listed in the Table below. In this study, we developed a model to correlate V12 in terms of a higher number of targets and dose prescription. The model was derived from clinical multiple BM cases treated with the Gamma Knife ICON in our institution. Our findings can be used as additional clinical guidelines in treatment planning strategy and plan evaluation.Abstract 3851; Table 1n38131624γ(n)1.6321.8941.8441.8082.162VT (cc)7.9438.3261.3579.31817.644Average Dp (Gy)18.615.416.61716.5V12 -VT (cc)7.2313.2862.91211.64125.824V12 (cc)15.17411.6124.26920.95943.468 Open table in a new tab

Radiobiological and dosimetric impact of RayStation pencil beam and Monte Carlo algorithms on intensity-modulated proton therapy breast cancer plans.

PurposeRayStation treatment planning system employs pencil beam (PB) and Monte Carlo (MC) algorithms for proton dose calculations. The purpose of this study is to evaluate the radiobiological and dosimetric impact of RayStation PB and MC algorithms on the intensity‐modulated proton therapy (IMPT) breast plans.MethodsThe current study included ten breast cancer patients, and each patient was treated with 1–2 proton beams to the whole breast/chestwall (CW) and regional lymph nodes in 28 fractions for a total dose of 50.4 Gy relative biological effectiveness (RBE). A total clinical target volume (CTV_Total) was generated by combining individual CTVs: AxI, AxII, AxIII, CW, IMN, and SCVN. All beams in the study were treated with a range shifter (7.5 cm water equivalent thickness). For each patient, three sets of plans were generated: (a) PB optimization followed by PB dose calculation (PB‐PB), (b) PB optimization followed by MC dose calculation (PB‐MC), and (c) MC optimization followed by MC dose calculation (MC‐MC). For a given patient, each plan was robustly optimized on the CTVs with same parameters and objectives. Treatment plans were evaluated using dosimetric and radiobiological indices (equivalent uniform dose (EUD), tumor control probability (TCP), and normal tissue complication probability (NTCP)).ResultsThe results are averaged over ten breast cancer patients. In comparison to PB‐PB plans, PB‐MC plans showed a reduction in CTV target dose by 5.3% for D99% and 4.1% for D95%, as well as a reduction in TCP by 1.5–2.1%. Similarly, PB overestimated the EUD of target volumes by 1.8─3.2 Gy(RBE). In contrast, MC‐MC plans achieved similar dosimetric and radiobiological (EUD and TCP) results as the ones in PB‐PB plans. A selection of one dose calculation algorithm over another did not produce any noticeable differences in the NTCP of the heart, lung, and skin.ConclusionIf MC is more accurate than PB as reported in the literature, dosimetric and radiobiological results from the current study suggest that PB overestimates the target dose, EUD, and TCP for IMPT breast cancer treatment. The overestimation of dosimetric and radiobiological results of the target volume by PB needs to be further interpreted in terms of clinical outcome.

P175] Simultaneous boost in breast radiotherapy requires increased margins or revised match strategy

Purpose In radiotherapy simultaneous boost compared to sequential boost allows shortening of the overall treatment time. Challenges remain in obtaining good image match concurrently within the boost volume and total target volume. The present study evaluated the difference between match based on boost volume and total target volume, with the overall aim to suggest treatment margins if treating both boost and total target volume using the same registration. Methods A total of 358 cone-beam CT (CBCT) s from 55 patients were analysed retrospectively. Of these 250 CBCTs were performed before each fraction on 16 patients receiving radiotherapy after breast conserving surgery and with lymph node involvement, and 39 patients receiving radiotherapy after breast conserving surgery without lymph node involvement were scheduled for CBCT once a week, and reached a total of 108 CBCTs. Two matches were performed with each CBCT: A chest wall-match where CBCTs were auto-registered to the planning CT, lymph nodes included if relevant (a match on the total volume). Further a boost specific match using manual registration of surgical clips. Results Based on the systematic (Σ) and random errors (σ) between the chest wall-match and the boost match the CTV-to-PTV margins of the boost volume were calculated. Margins needed for the boost volume to receive the prescribed dose using a match based on the total target volume are (lateral, longitudinal, vertical) = (7.3, 8.4, 8.5) mm and (5.1, 7.5, 4.3) mm, for the patients with lymph node involvement and without lymph node involvement data, respectively. Conclusions CTV-to-PTV margin for the boost area are normally set to 5 mm when using a sequential boost strategy. Our study suggests that with simultaneous boost radiotherapy larger margins are required. Further, patients with lymph node involvement compared to patients with only the breast involved requires a larger CTV-to-PTV margin. Another solution can be to use an adaptive protocol for daily IGRT which can reduce the required CTV to PTV margin for the boost region by re-scanning and re-matching the boost region for patients where the two regions differ by more than a pre-set threshold.

How to improve obliteration rates during volume-staged stereotactic radiosurgery for large arteriovenous malformations.

The management of large-volume arteriovenous malformations (AVMs) with stereotactic radiosurgery (SRS) remains challenging. The authors retrospectively tested the hypothesis that AVM obliteration rates can be improved by increasing the percentage volume of an AVM that receives a minimal threshold dose of radiation. In 1992, the authors prospectively began to stage anatomical components in order to deliver higher single doses to AVMs > 15 cm3 in volume. Since that time 60 patients with large AVMs have undergone volume-staged SRS (VS-SRS). The median interval between the first stage and the second stage was 4.5 months (2.8-13.8 months). The median target volume was 11.6 cm3 (range 4.3-26 cm3) in the first-stage SRS and 10.6 cm3 (range 2.8-33.7 cm3) in the second-stage SRS. The median margin dose was 16 Gy (range 13-18 Gy) for both SRS stages. AVM obliteration after the initial two staged volumetric SRS treatments was confirmed by MRI alone in 4 patients and by angiography in 11 patients at a median follow-up of 82 months (range 0.4-206 months) after VS-SRS. The post-VS-SRS obliteration rates on angiography were 4% at 3 years, 13% at 4 years, 23% at 5 years, and 27% at 10 years. In multivariate analysis, only ≥ 20-Gy volume coverage was significantly associated with higher total obliteration rates confirmed by angiography. When the margin dose is ≥ 17 Gy and the 20-Gy SRS volume included ≥ 63% of the total target volume, the angiographically confirmed obliteration rates increased to 61% at 5 years and 70% at 10 years. The outcomes of prospective VS-SRS for large AVMs can be improved by prescribing an AVM margin dose of ≥ 17 Gy and adding additional isocenters so that ≥ 63% of the internal AVM dose receives more than 20 Gy.

Investigation of irradiated volume in linac-based brain hypo-fractionated stereotactic radiotherapy

BackgroundEmerging techniques such as brain hypo-fractionated radiotherapy (HF-RT) involve complex cases with limited guidelines for plan quality and normal tissue tolerances. The purpose of the present study was to statistically parameterize irradiated volume independently of dose prescription, or margin to determine what spread in achievable irradiated volume one may expect for a given case.MethodsWe defined EXT as the total tissue within the external contour of the patient (including the target) and we defined BMP as the contour of the brain minus PTV. Irradiated volumes of EXT and BMP at specific doses (i.e. 50, 60%, etc., of the prescribed dose) were extracted from 135 single-target HF-RT clinical cases, each planned with a single-arc, homogeneous (SAHO) approach in which target maximum dose (Dmax) was constrained to <130% of the prescribed dose. Irradiated volumes were subsequently measured for cases involving 2 targets (N = 29), 3 targets (N = 7) and >3 targets (N = 10) to investigate the effect of target number. We also examined the effect of shape complexity. A series of best fit curves with confidence and prediction intervals were generated for irradiated volume versus total target volume and the resulting model was subsequently validated on a subsequent set of 23 consecutive prospective cases not originally used in curve-fitting. A subset of 30 HF-RT cases were re-planned with a well-published four-arc, heterogeneous (FAHE) radiosurgery planning approach (Dmax could exceed 130%) to demonstrate how technique affects irradiated volume.ResultsFor SAHO, strong correlation (R2 > 0.98) was found for predicting irradiated volumes. For a given total target volume, irradiated-volume increased by a range of 1.4–2.9× for >3 versus single-targets depending on isodose level. Shape complexity had minor impact on irradiated volume. There was no statistical difference in irradiated volumes between validation and input data (p > 0.2). The FAHE-generated irradiated volumes yielded curves and prediction and confidence bands that agreed well with published data indicating that the proposed approach is feasible for cross-institutional comparisons.ConclusionsA description of irradiated volume for linac-based HF-RT is proposed based on population data. We have demonstrated that the proposed approach is feasible for inter and intra-institutional comparisons.

Accurate Prediction of Total Radiation Time Based on the Correlation Between Total Reference Air Kerma and Clinical Target Volume in CT-Based HDR Prostate Brachytherapy

Accurate Prediction of Total Radiation Time Based on the Correlation Between Total Reference Air Kerma and Clinical Target Volume in CT-Based HDR Prostate Brachytherapy