Isodose Volume Research Articles

Predicting the effect of indirect cell kill in the treatment of multiple brain metastases via single-isocenter/multitarget volumetric modulated arc therapy stereotactic radiosurgery.

PurposeDue to spatial uncertainty, patient setup errors are of major concern for radiosurgery of multiple brain metastases (m‐bm) when using single‐isocenter/multitarget (SIMT) volumetric modulated arc therapy (VMAT) techniques. However, recent clinical outcome studies show high rates of tumor local control for SIMT‐VMAT. In addition to direct cell kill (DCK), another possible explanation includes the effects of indirect cell kill (ICK) via devascularization for a single dose of 15 Gy or more and by inducing a radiation immune intratumor response. This study quantifies the role of indirect cell death in dosimetric errors as a function of spatial patient setup uncertainty for stereotactic treatments of multiple lesions.Material and MethodsNine complex patients with 61 total tumors (2‐16 tumors/patient) were planned using SIMT‐VMAT with geometry similar to HyperArc with a 10MV‐FFF beam (2400 MU/min). Isocenter was placed at the geometric center of all tumors. Average gross tumor volume (GTV) and planning target volume (PTV) were 1.1 cc (0.02–11.5) and 1.9 cc (0.11–18.8) with an average distance to isocenter of 5.4 cm (2.2–8.9). The prescription was 20 Gy to each PTV. Plans were recalculated with induced clinically observable patient setup errors [±2 mm, ±2o] in all six directions. Boolean structures were generated to calculate the effect of DCK via 20 Gy isodose volume (IDV) and ICK via 15 Gy IDV minus the 20 Gy IDV. Contributions of each IDV to the PTV coverage were analyzed along with normal brain toxicity due to the patient setup uncertainty. Induced uncertainty and minimum dose covering the entire PTV were analyzed to determine the maximum tolerable patient setup errors to utilize the ICK effect for radiosurgery of m‐bm via SIMT‐VMAT.ResultsPatient setup errors of 1.3 mm /1.3° in all six directions must be maintained to achieve PTV coverage of the 15 Gy IDV for ICK. Setup errors of ±2 mm/2° showed clinically unacceptable loss of PTV coverage of 29.4 ± 14.6% even accounting the ICK effect. However, no clinically significant effect on normal brain dosimetry was observed.ConclusionsRadiosurgery of m‐bm using SIMT‐VMAT treatments have shown positive clinical outcomes even with small residual patient setup errors. These clinical outcomes, while largely due to DCK, may also potentially be due to the ICK. Potential mechanisms, such as devascularization and/or radiation‐induced intratumor immune enhancement, should be explored to provide a better understanding of the radiobiological response of stereotactic radiosurgery of m‐bm using a SIMT‐VMAT plan.

Breast clinical target volume: HU-based glandular CTVs and ESTRO CTVs in modern and historical radiotherapy treatment planning

PurposeThe current study aimed to compare contouring of glandular tissue only (gCTV) with the clinical target volume (CTV) as defined according to European Society for Radiotherapy and Oncology (ESTRO) guidelines (eCTV) and historically treated volumes (marked by wire and determined by palpation and anatomic landmarks) in breast cancer radiotherapy.MethodsA total of 56 consecutive breast cancer patients underwent treatment planning based solely on anatomic landmarks/wire markings (“wire based”). From these treatment plans, the 50% and 95% isodoses were transferred as structures and compared to the following CT-based volumes: eCTV; a Hounsfield unit (HU)-based automatic contouring of the gCTV; and standardized planning target volumes (PTVs) generated with 1‑cm safety margins (resulting in the ePTVs and gPTVs, respectively).ResultsThe 95% isodose volume of the wire-based plan was larger than the eCTV by 352.39 ± 176.06 cm3 but smaller than the ePTV by 157.58 ± 189.32 cm3. The 95% isodose was larger than the gCTV by 921.20 ± 419.78 cm3 and larger than the gPTV by 190.91 ± 233.49 cm3. Patients with larger breasts had significantly less glandular tissue than those with small breasts. There was a trend toward a lower percentage of glandular tissue in older patients.ConclusionHistorical wire and anatomic landmarks-based treatment planning sufficiently covers the glandular tissue and the theoretical gPTV generated for the glandular tissue. Modern CT-based CTV and PTV definition according to ESTRO results in a larger treated volume than the historical wire-based techniques. HU-standardized glandular tissue contouring results in a significantly smaller CTV and might be an option for reducing the treatment volume and improving reproducibility of contouring between institutions.

Gamma Knife radiosurgery as salvage therapy for gangliogliomas after initial microsurgical resection

IntroductionGangliogliomas (GG) are considered WHO grade I rare tumors. While they commonly manifest as temporal lobe epilepsy, they can be located anywhere in the brain. Primary treatment is complete microsurgical resection. Remnant or recurrent GG can benefit from radiation therapy. Here, we present a series of GG who received Gamma Knife radiosurgery (GKR) after initial microsurgery. MethodsBetween October 2009 and February 2020, four patients benefitted from such approach. The median age at surgery was 16 years (mean 17, 11–25) and at the time of GKR was 22.5 years (mean 23, 19–28). Initial clinical symptom was epilepsy in 3 cases and incidental in one. Biopsy was firstly performed in one case. One patient had stereotactic electroencephalography. The respective anatomical locations were right parieto-occipital, sylvian, left paraventricular and left inferior parietal. ResultsGamma Knife radiosurgery was performed after a median time of 3.5 years after initial gross total microsurgical resection (GTR). The median follow-up after GKR was 54 months (mean 58.5, 6–120). The median marginal dose was 18 Gy (mean 17.5, 16–18). The median target volume was 0.5 mL (mean 0.904, 0.228–2.3). The median prescription isodose volume was 0.6 mL (mean 0.9, 0.3–2.4). At last follow-up, GG majorly decreased in 3 patients, remained stable in one. ConclusionGamma Knife radiosurgery is safe and effective for remnant GG after GTR. Primary treatment remains microsurgical resection, especially in cases with symptomatic mass effect or with epilepsy. Single fraction GKR can be a valuable option for remnant or recurrent tumors after initial resection.

An empirical method for splitting arcs in VMAT.

We present a new approach to determine the optimal arc split for VMAT beams which is an extension of our recently published algorithm for selecting optimal beam angles in Intensity Modulated Radiation Therapy (IMRT) MATERIAL AND METHODS: The proposed approach uses an objective function based scoring method called "ψ - score" to determine optimal arc splitting strategy. To validate our approach, we applied it in different clinical cases: Abdomen-Para aortic node, Lung, Pancreas and Prostate. Basically, for all clinical cases, two set of plans were created, namely VMAT plan and VMAT_S plan using Pinnacle3 (V16.2, Philips Medical Systems (Cleveland), Inc.). In the VMAT plans, full arc (360°) with 4-degree gantry spacing was used during optimization to compute the "ψ - score". Subsequently the avoidable arc portions were identified and removed using the ψ - score plot followed by the final optimization (VMAT_S). Equivalent or better OAR sparing, and similar target coverage were achieved in VMAT_S plans compared to VMAT plans. VMAT_S reduced the number of control points and monitor units by 24.2% and 12.9% respectively. On the average, beam on time was reduced by 21.9% and low dose volume (5Gy isodose volume) to healthy tissues was reduced by 4.9% in VMAT_S compared to VMAT plans. The results demonstrated that the proposed method is useful for reducing the monitor units, beam on time and low dose volume without significantly compromising plan quality and most useful for non-centrically located targets.

Salvage Radiosurgery for Recurrent Supratentorial Primitive Neuroectodermal Tumors: A Single Institutional Series and Review of the Literature

Introduction: Supratentorial primitive neuroectodermal tumor is a rare, aggressive intrinsic brain tumor with limited treatment options for recurrent disease. SRS as a treatment modality in the recurrent setting was investigated. Methods: A retrospective review of 8 patients treated with SRS for local or distant recurrence of supratentorial PNET from 1999 to 2014 was conducted. Results: Thirty-six tumors were treated in 15 sessions in 8 patients. The median patient age was 22.5 (interquartile range [IQR], 14.75–43.5 years) with a median 21-month period from diagnosis until SRS (IQR, 16–23.75 months). The median prescription isodose volume was 1.85 cm³ (IQR, 1.85–7.02 cm³); median tumor margin dose was 18 Gy (IQR 14–20 Gy); and median isocenters was 2 (range 1–13). No patients experienced adverse radiation effects. All but 1 patient died, and the median overall survival was 32 months (IQR, 26.75–53.5 months) with median overall survival following SRS of 9.5 months (IQR, 5.25–30 months). Univariate analysis failed to demonstrate a statistically significant association between age, number of gamma knife treatments, interval to gamma knife, and margin radiation dose with overall survival. Discussion/Conclusion: This series supports the use of SRS in patients with recurrent supratentorial PNET following multimodal therapy.

Radionecrosis (RN) in patients with brain metastases treated with stereotactic radiosurgery (SRS) and immunotherapy

Objectives Limited data exist regarding radionecrosis (RN) rates when patients receive immunotherapy (IT) and SRS for brain metastases. This study assesses the influence of such treatments on the rate of RN. Methods We retrospectively reviewed 352 lesions from 105 patients with metastatic melanoma or NSCLC treated with SRS and IT from 2012 to 2018. Lesions were excluded from analysis if patients had received WBRT or prior GK to the same lesion, if RN occurred before IT, or if IT had been discontinued >6 months pre-SRS or initiated >1 year post-SRS. IT was delivered concurrently (±30 days of SRS) or sequentially. Overall survival and RN rates were assessed with Kaplan-Meier analysis. Univariate analysis and multivariate analysis were performed to identify characteristics predicting RN. Results Of 195 lesions from 63 patients included in analysis, the median prescription dose, IDL, lesion volume, and maximum tumor dimension (MTD) were 19 Gy, 50%, 0.15 cc and 0.8 cm, respectively. RN rates at 1, 2, and 3 years were 7.3%, 10.4% and 10.4%. On UVA, RN risk increased with, isodose volume (IDV), MTD, and tumor volume (TV) whereas conformity index was associated with a trend toward decreased RN risk. Two-year RN rates increased with TV ≥ 0.3 cc (16% vs 1.1% p = 0.001), MTD ≥ 1.3 cm (19.1% vs 1.8% p < 0.003), and IDV ≥ 1.5 cc (19.6% vs 1.7% p = 0.001). Concurrent vs sequential timing of IT did not predict for RN. Conclusions Patients who received IT and SRS had acceptably low rates of RN. Timing of IT did not predict for RN. Further investigation is warranted to define RN risk with combined SRS and IT.

Treatment outcomes of helical tomotherapy for hepatocellular carcinoma in terms of intermediate-dose spillage.

BackgroundAlthough helical tomotherapy (HT) tends to increase intermediate-dose spillage by increasing of low-dose region, this has not been fully determined in the clinical setting. Therefore, we investigated treatment outcomes of HT for hepatocellular carcinoma (HCC) with respect to intermediate-dose spillage.MethodsWe retrospectively reviewed 20 HCC patients, who received high-dose radiotherapy (RT) using HT with radical intent between April 2014 and September 2017. In accordance with the Barcelona Clinic Liver Cancer (BCLC) classification, stage was 0 in 7 patients, A in 3 patients, B in 5 patients, and C in 5 patients. Baseline Child-Pugh class was A in 18 patients and B in 2 patients. The median tumor size was 2.5 cm (range, 1–11 cm). Helical intensity-modulated radiotherapy (IMRT) technique was applied in all patients: among these, 13 patients were treated with stereotactic body radiotherapy (SBRT). The median fraction size was 12 Gy (range, 2–15 Gy), and the median total dose was 50 Gy (range, 44–60 Gy). Intermediate-dose spillage was assessed by the Radiation Therapy Oncology Group recommendation from 22 HT planning data, as follows: R50% means the ratio of the 50% prescription isodose volume to the planning target volume (PTV).ResultsThe median follow-up period after HT was 22 months. The local progression-free survival (LPFS) and progression-free survival (PFS) rates were 89% and 59% at 1 year, and 82% and 30% at 2 years, respectively. The overall survival rate was 100% at 1 year and 85% at 2 years, respectively. In terms of intermediate-dose spillage, minor or major deviations were noted in the R50% of 20 HT plans (91%). However, 1 patient (5%) experienced classic radiation-induced liver disease, and severe toxicity ≥ grade 3 was not reported.ConclusionsAlthough HT for HCC tends to increase intermediate-dose spillage, the treatment results were favorable with that reported in other published studies.

P05.14 Dosimetric Impact of Using the Acuros XB for Planning of SBRT of Centrally Located NSCLC

Stereotactic Body Radiation Treatment (SBRT) of lung cancer is applied to a heterogeneous density gradient. Dose modeling is highly dependent on the accuracy of the calculation algorithm. This study aims to assess the dosimetric implications calculated by Acuros External Beam (AXB) instead of the Anisotropic Analytical Algorithm (AAA) in SBRT of centrally located-Non small cell lung cancer (CL-NSCLC). Twelve IMRT plans for SBRT of CL-NSCLC were investigated retrospectively. The prescribed scheme was 50 Gy in 5 fractions every 2 days. The plans originally calculated by AAA aimed to cover 95% PTV by varying prescription isodose lines at 70 to 90%. These plans were recalculated by AXB (Dose to medium) and verified by the benchmark Monte Carlo (MC) method. Dosimetric parameters e.g. V20Gy Lungs, D95%(PTV), D98%(GTV), dose gradient (the ratio of 50% prescription isodose volume to the PTV, R50%), and doses to organs at risk (spinal cord, heart, esophagus, trachea, bronchus, and major vessels) were compared. AAA has generally overestimated the PTV dose compared to AXB and MC. The mean differences for D95%(PTV) and D98%(GTV) is 3.1% and 2.8% higher than that of AXB, respectively. The differences were significant with p-value<0.05. They were further verified by MC method, the results agreed with that of AXB. The agreement between AXB and MC in all PTV parameters were within 1.6% and the differences were not significant. No significant differences were also noted on V20Gy Lungs between the three algorithms but three cases were observed with maximum point dose to the lung tissue 1cm surrounding the PTV increased over 11% after the recalculation of AXB. Moreover, two cases were reported exceeding in heart dose and three cases were found degrading from none to minor deviation in dose gradient R50%. AXB has been investigated intensively and found to perform superiorly to AAA especially in calculating the rapid change in heterogeneous density gradient e.g. in regions of re-buildup in soft tissue after passed through lung/air. Although AXB and MC have two completely different way in solving Linear Boltzmann Transport Equation (LBTE), the agreement between AXB and MC was widely acceptable, AXB provides an accurate but faster alternative to MC method. In this study, a significant under-dosage in PTV and large dose difference in modeling tissue/air interface were observed after remodeled with AXB and MC. Since the PTV of SBRT for NSCLC is relatively small, the PTV missed in AAA may lead to a reduction in treatment outcome. Hence, AXB should be used in preference to AAA to model SBRT for centrally located NSCLC.

Reporting of dose–volume specifications for “Martinez Universal Perineal Interstitial Template–based interstitial high-dose-rate brachytherapy for gynecological cancers” according to International Commission on Radiation Units and Measurements 58 with early clinical outcomes

PurposeThe study is an audit of reporting dose and volume specifications as per the ICRU 58 for MUPIT-based interstitial brachytherapy in gynecological cancers. Correlation between total reference air kerma (TRAK) and isodose surface was also evaluated to understand the intensity of treatment in interstitial brachytherapy. Methods and MaterialsForty-two patients underwent HDR MUPIT-based interstitial brachytherapy 20 Gy in five fractions after EBRT during 2017–2019. Treated volume, high and low-dose regions, mean central dose, Dose Homogeneity Index (DHI), organ at risk doses, and TRAK values were computed. ResultsHigh-dose regions V150 mean was 12.4 cc and V200 was 4.58 cc; and low-dose region was 75.92 cc. The mean treated volume was 59.8 cc. The mean central dose was 3.7 Gy. DHI was 79%. The mean D2cm3 bladder and rectum were 2.9 Gy and 2.8 Gy. The mean TRAK was 0.16 cGy per fraction per hour at 1 m. TRAK values showed significant correlation with various isodose volumes (TRAK and V100: r = 0.943 p < 0.0005; and TRAK and V50: r = 0.953; p < 0.0005). A positive correlation was observed between TRAK and the number of needles (r = 0.746; p < 0.0005). At a median followup of 16 months, 4 of 42 patients (9.5%) had local recurrences. ConclusionsOur study shows compliance with ICRU 58 recommendations along with certain deviations. Local recurrence rate is acceptable. TRAK shows correlation with surface isodose in MUPIT-based brachytherapy and should to be evaluated in future studies.

The Effect of Prescription Isodose Variation on Tumor Control and Toxicities in Stereotactic Radiosurgery for Sporadic Vestibular Schwannoma: Propensity Score-Matched Case-Control Study.

Objective Vestibular schwannoma (VS) treated with Gamma Knife stereotactic radiosurgery (SRS) was typically performed at 50% isodose line (IDL50); however, the impact of IDL variation on outcomes is poorly understood. This study aimed to compare tumor control (TC) and toxicities between treatment at 40% (IDL40) and 50% (IDL50). Methods Sporadic/unilateral VS patients treated with SRS dose 12 to 14 Gy and prescription isodose volume ≤10cm 3 were included. Propensity score matching was applied to IDL40 cohort to generate an IDL50 companion cohort, adjusting for age and prescription isodose volume. After exclusion of patients with follow-up <24 months, there were 30 and 28 patients in IDL40 and IDL50 cohorts, respectively. Results Median follow-up time was 96 months (24-225 months). Actuarial and radiographic TC rates were 91.8% and clinical TC was 96.2% both at 5 and 10 years. TC was higher in IDL40 cohort but not significant (96.4 vs. 86.7%; p = 0.243). Hearing preservation (HP) rates were 71.9 and 39.2% at 5- and 10-year intervals, with significantly higher rates of HP noted in IDL40 cohort (83.3 vs. 57.1% at 5-year interval; 62.5 vs. 11.4% at 10-year interval; p = 0.017). Permanent facial neuropathy occurred in two patients, both from the IDL50 cohort (3.5%). Rates of post-SRS steroid treatment or shunt placement for hydrocephalus were slightly higher in IDL50 patients (6.9 vs. 17.9%; p = 0.208 and 3.3 vs. 7.1%; p = 0.532). Conclusion For treatment of VS with SRS, dose prescription at IDL40 or IDL50 provides excellent long-term TC and toxicity profiles. IDL40 may be associated with improved long-term HP.

Abstract PS1-12: Factors associated with chronic breast lymphedema after adjuvant radiation in women undergoing breast conservation therapy

Abstract Purpose/Objective(s):Unlike temporary breast edema caused by post-lumpectomy radiation therapy (RT), the edema that persists beyond one year is not well defined and difficult to treat. The aim of this study is to define the incidence and risk factors for the development of chronic breast lymphedema in women undergoing lumpectomy with RT at a large metropolitan cancer center. Materials/Methods:A retrospective chart review was performed on all patients who underwent lumpectomy from 2014 to 2018. Women who did not undergo RT at our institution and those with stage IV disease were excluded from the analysis. Patient demographics, comorbidities, operative data, RT data and postoperative complications were obtained. Chronic breast lymphedema (CBL) was defined as edema that persisted beyond one year post completion of radiation therapy. Breast volumes were determined by contoured breast volumes or, if unavailable, estimated by the 95% isodose volumes from the RT treatment planning system. Using a density curve, the distribution of breast volumes was plotted for patients with and patients without CBL. Univariate analysis was used to evaluate factors associated with CBL. Multivariate regression analysis was used to evaluate factors associated with the risk of CBL while accounting for potential confounding variables as defined by the univariate analysis. Results:A total of 1173 patients were included for analysis. Seventy-four (6.3%) patients developed breast lymphedema beyond one year. For the entire cohort, mean age was 63 years old (SD=11.17), mean BMI was 31.15 kg/m2 (SD=7.17), mean breast volume was 1198.54 cm3 (SD=645.82 cm3), mean total radiation was 59.18 Gy (SD=16.76), and 139 (11.8%) patients underwent ALND. Compared to the cohort that did not develop CBL (n=1099), the CBL cohort (n=74) had a higher median BMI (33.23 kg/m2 vs. 29.81 kg/m2, P&amp;lt;0.001), higher percentage of African Americans (56.8% vs. 37.9%, P=0.004), larger median breast volume (1502.33 cm3 vs. 1083.59 cm3, P&amp;lt;0.001), higher percentage that underwent ALND (23% vs. 11.1%, P=0.005), and larger median size of lumpectomy specimen (128.00 cm3 vs. 94.57 cm3, P=0.002). When accounting for potential confounding variables, multivariate regression analysis revealed when breast volume was evaluated as a continuous variable, for every 1 cm3 increase in breast volume, the risk of breast lymphedema increases by 0.1% (OR=1.001, P&amp;lt;0.001). When breast volume was analyzed as a categorical variable using 1300 cm3 as the optimal cutoff (based on density curve evaluations), patients whose breast volume was greater than 1300 cm3 had nearly 3 times the risk of developing CBL (OR=2.976, P&amp;lt;0.001) compared to those with less than 1300 cm3 breast volume. The multivariate regression also demonstrated that CBL was associated with total radiation dose (OR=1.02, P=0.015) and African American race (OR=1.705, P=0.037). Conclusion:Chronic breast lymphedema presents a clinical concern for women undergoing lumpectomy with postoperative radiation, particularly in women with larger breasts. Further studies should focus on preventative strategies, as well as the psychosocial and economic impact of this morbidity. Citation Format: Sanjay Rama, Cara Canella, Jenna Luker, Kelley Park, Renee Barry, Saheli Ghosh, Simeng Zhu, Yalei Chen, Jessica Bensenhaver, Eleanor Walker, Kenneth Levin, Dunya Atisha, Maristella Evangelista. Factors associated with chronic breast lymphedema after adjuvant radiation in women undergoing breast conservation therapy [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-12.

Abstract PS1-49: The effect of oncoplastic reduction on the incidence of post-operative breast lymphedema in breast cancer patients undergoing lumpectomy

Abstract Purpose / Objectives: In patients with macromastia, breast conservation surgery (BCS) followed by radiation therapy (RT) for the treatment of breast cancer may be associated with a different complication profile than those without macromastia. General complications of BCS followed by RT includes seroma, infection, wound complications, cosmetic deformity, asymmetry, acute versus long term arm and/or breast lymphedema. Oncoplastic reduction mammoplasty (ORM) aims to reduce breast volume while excising the tumor bed and its margins. Since breast volume was found to be a risk factor for chronic breast lymphedema, this study was performed to determine the impact of ORM on chronic breast lymphedema as well as other complications compared to BCS without ORM. Materials / Methods: We performed a retrospective chart review on patients who underwent lumpectomy with RT from 2014 to 2018. Chronic breast lymphedema (CBL) was defined as swelling that persisted &amp;gt;1 year post-RT. Breast volumes (BV) were determined by contoured breast volumes or, if unavailable, estimated by the 95% isodose volumes from the RT treatment planning system. Univariate analysis was used to evaluate various patient factors and treatment outcomes in women with BV ≥1300 cc compared to &amp;lt;1300 cc. These same factors were compared in women who underwent ORM vs. BCS alone. Multivariate regression analysis was used to evaluate factors associated with ≥1 complication. Logistic regression was performed to identify factors associated with the development of CBL. Results: The total population included 1173 patients, of which 51 (4.3%) underwent ORM and 1122 (95.7%) underwent BCS. 440 (37.5%) patients had BV ≥1300 cc and 733 (62.5%) patients had a BV &amp;lt;1300 cc. Multivariate regression analysis demonstrated that patients with BV ≥1300 cc had a higher BMI (OR=1.200, P&amp;lt;0.001), decreased risk of grade 2 radiation dermatitis (OR=0.457, P=0.002), and increased risk of CBL (OR=2.127, P=0.024) compared to patients with BV &amp;lt;1300 cc. However, oncoplastic reduction was associated with an increased risk of hematoma (OR=5.934, P&amp;lt;0.001), increased risk of wound dehiscence (OR=12.433, P&amp;lt;0.001), and decreased risk of seroma (OR=0.201, P&amp;lt;0.001) compared to BCS patients. Conclusions: Our data demonstrates that patients with breast volume &amp;gt; 1300 cc are at increased risk for developing several complications regardless of the presence of ORM. Those who had ORM experienced an increase in wound complications but having undergone ORM appeared to eliminate the increased risk of CBL associated with macromastia. This suggests that ORM should be considered at the time of BCS to reduce their future risk of CBL as there is no cure for this disease. Citation Format: Jenna Nicole Luker, Cara Canella, Sanjay Rama, Kelley Park, Renee Barry, Saheli Ghosh, Simeng Zhu, Yalei Chen, Jessica Bensenhaver, Eleanor Walker, Kenneth Levin, Maristella Evangelista, Dunya Atisha. The effect of oncoplastic reduction on the incidence of post-operative breast lymphedema in breast cancer patients undergoing lumpectomy [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-49.

Knowledge-based planning in robotic intracranial stereotactic radiosurgery treatments.

PurposeTo develop a knowledge‐based planning (KBP) model that predicts dosimetric indices and facilitates planning in CyberKnife intracranial stereotactic radiosurgery/radiotherapy (SRS/SRT).MethodsForty CyberKnife SRS/SRT plans were retrospectively used to build a linear KBP model which correlated the equivalent radius of the PTV (req_PTV) and the equivalent radius of volume that receives a set of prescription dose (req_Vi, where Vi = V10%, V20% … V120%). To evaluate the model’s predictability, a fourfold cross‐validation was performed for dosimetric indices such as gradient measure (GM) and brain V50%. The accuracy of the prediction was quantified by the mean and the standard deviation of the difference between planned and predicted values, (i.e., ΔGM = GMpred − GMclin and fractional ΔV50% = (V50%pred − V50%clin)/V50%clin) and a coefficient of determination, R2. Then, the KBP model was incorporated into the planning for another 22 clinical cases. The training plans and the KBP test plans were compared in terms of the new conformity index (nCI) as well as the planning efficiency.ResultsOur KBP model showed desirable predictability. For the 40 training plans, the average prediction error from cross‐validation was only 0.36 ± 0.06 mm for ΔGM, and 0.12 ± 0.08 for ΔV50%. The R2 for the linear fit between req_PTV and req_vi was 0.985 ± 0.019 for isodose volumes ranging from V10% to V120%; particularly, R2 = 0.995 for V50% and R2 = 0.997 for V100%. Compared to the training plans, our KBP test plan nCI was improved from 1.31 ± 0.15 to 1.15 ± 0.08 (P < 0.0001). The efficient automatic generation of the optimization constraints by using our model requested no or little planner’s intervention.ConclusionWe demonstrated a linear KBP based on PTV volumes that accurately predicts CyberKnife SRS/SRT planning dosimetric indices and greatly helps achieve superior plan quality and planning efficiency.

Dosimetric evaluation of SBRT treatment plans of non-central lung tumours: clinical experience

AbstractObjectives:Lung cancer is the most commonly diagnosed cancer in Canada and the leading cause of cancer-related mortality in both men and women in North America. Surgery is usually the primary treatment option for early-stage non-small cell lung cancer (NSCLC). However, for patients who may not be suitable candidates for surgery, stereotactic body radiation therapy (SBRT) is an alternative method of treatment. SBRT has proven to be an effective technique for treating NSCLC patients by focally administering high radiation dose to the tumour with acceptable risk of toxicity to surrounding healthy tissues. The goal of this comprehensive retrospective dosimetric study is to compare the dosimetric parameters between three-dimensional conformal radiation therapy (3DCRT) and volumetric-modulated arc therapy (VMAT) lung SBRT treatment plans for two prescription doses.Methods:We retrospectively analysed and compared lung SBRT treatment plans of 263 patients treated with either a 3DCRT non-coplanar or with 2–3 VMAT arcs technique at 48 Gy in 4 fractions (48 Gy/4) or 50 Gy in 5 fractions (50 Gy/5) prescribed to the planning target volume (PTV), typically encompassing the 80% isodose volume. All patients were treated on either a Varian 21EX or TrueBeam linear accelerator using 6-MV or 10-MV photon beams.Results:The mean PTV V95% and V100% for treatment plans at 48 Gy/4 are 99·4 ± 0·6% and 96·0 ± 1·0%, respectively, for 3DCRT and 99·7 ± 0·4% and 96·4 ± 3·4%, respectively, for VMAT. The corresponding mean PTV V95% and V100% at 50 Gy/5 are 99·0 ± 1·4% and 95·5 ± 2·5% for 3DCRT and 99·5 ± 0·8% and 96·1 ± 1·6% for VMAT. The CIRI and HI5/95 for the PTV at 48 Gy/4 are 1·1 ± 0·1 and 1·2 ± 0·0 for 3DCRT and 1·0 ± 0·1 and 1·2 ± 0·0 for VMAT. The corresponding CIRI and HI5/95 at 50 Gy/5 are 1·1 ± 0·1 and 1·3 ± 0·1 for 3DCRT and 1·0 ± 0·1 and 1·2 ± 0·0 for VMAT. The mean R50% and D2cm at 48 Gy/4 are 5·0 ± 0·8 and 61·2 ± 7·0% for 3DCRT and 4·9 ± 0·8 and 57·8 ± 7·9% for VMAT. The corresponding R50% and D2cm at 50 Gy/5 are 4·7 ± 0·5 and 65·5 ± 9·4% for 3DCRT and 4·7 ± 0·7 and 60·0 ± 7·2% for VMAT.Conclusion:The use of 3DCRT or VMAT technique for lung SBRT is an efficient and reliable method for achieving dose conformity, rapid dose fall-off and minimising doses to the organs at risk. The VMAT technique resulted in improved dose conformity, rapid dose fall-off from the PTV compared to 3DCRT, although the magnitude may not be clinically significant.

In Silico Ventilation Within the Dose-Volume is Predictive of Lung Function Post-radiation Therapy in Patients with Lung Cancer

Lung cancer is a leading cause of death worldwide. Radiation therapy (RT) is one method to treat this disease. A common side effect of RT for lung cancer is radiation-induced lung damage (RILD) which leads to loss of lung function. RILD often compounds pre-existing smoking-related regional lung function impairment. It is difficult to predict patient outcomes due to large variability in individual response to RT. In this study, the capability of image-based modelling of regional ventilation in lung cancer patients to predict lung function post-RT was investigated. Twenty-five patient-based models were created using CT images to define the airway geometry, size and location of tumour, and distribution of emphysema. Simulated ventilation within the 20 Gy isodose volume showed a statistically significant negative correlation with the change in forced expiratory volume in 1 s 12-months post-RT (p = 0.001, R = − 0.61). Patients with higher simulated ventilation within the 20 Gy isodose volume had a greater loss in lung function post-RT and vice versa. This relationship was only evident with the combined impact of tumour and emphysema, with the location of the emphysema relative to the dose-volume being important. Our results suggest that model-based ventilation measures can be used in the prediction of patient lung function post-RT.

Dosimetric Impact of Deep Inspiration Breath Hold Uncertainty on Pancreas Stereotactic Body Radiotherapy

Deep inspiration breath hold (DIBH) is often used to immobilize pancreatic tumor for SBRT. Geometric reproducibility of tumor positioning between breath hold have been reported, but the corresponding dosimetric impact is not well understood. We evaluated dosimetric reproducibility of tumor coverage and OAR doses for inter-breath hold variation at treatment. Ten pancreatic cancer patients who underwent DIBH SBRT with 660cGy x 5 fractions (Rx) were selected for the study. The implanted fiducial markers were used as tumor motion surrogate at treatment. At CT sim, the contrast planning CT was acquired with 2-mm slice thickness, immediately followed by three additional CT sets. The patient specific breath-hold variation measured from the four sim CT sets was added as a margin to GTV in addition to a 2-mm set-up margin. At treatment, 4.6 ± 1.5 breath-hold CBCTs were acquired for each patient and each fraction. The first CBCT of each fraction was used as the reference to quantify the geometric and dosimetric inter-breath hold variations on the subsequent CBCT sets in the treatment planning system. The geometric variation of the GTV was quantified as the variation of fiducial centroids. The metrics used for the dosimetric variation were GTV D95 ≥ Rx, PTV D95 ≥ Rx, PTV Dmax < 4290 cGy (130% Rx), Paddick conformity index (pCI), and the ratio of the volume of the 50% isodose volume and the PTV volume (R50%) for tumor, V20Gy < 20% for duodenum, stomach and bowel, V12% < 50% for liver, and V12% < 25% for combined kidneys, in addition to Dmax for each OAR. The tumor position showed an average variation of 0.0 ± 1.6 mm, -0.3 ± 1.5 mm, and -0.4 ± 2.6 mm in the LR, AP, and SI directions, respectively. The GTV D95, PTV D95, and PTV Dmax were changed by 0.8 ± 5.3%, -3.1 ± 14.0%, and -0.1 ± 3.5%. The pCI and R50% varied by 1.7 ± 6.5% and 1.3 ± 10.8%. The V20Gy of duodenum, stomach, and bowel varied by -0.2 ± 3.1%, -0.3 ± 2.5%, and -0.2 ± 4.8%. There was no sizable difference with V12% for liver and combined kidneys. The Dmax for duodenum, stomach, bowel, liver, and combined kidneys were changed by -0.7 ± 4.8%, -0.4 ± 8.2%, 0.8 ± 5.6%, 0.4 ± 4.3%, and -0.6 ± 3.5%, respectively. Inter-breath hold variation in pancreatic tumor position affects tumor coverage, dose conformity, dose fall-off and OAR doses, more significantly for Dmax of duodenum, stomach and bowel which are closely located to the tumor. Future work is to evaluate whether a robust optimization can account for the inter-breath hold variation to minimize the corresponding dosimetric deviations.

The Effect of Oncoplastic Reduction on The Incidence of Post-Operative Lymphedema in Breast Cancer Patients Undergoing Lumpectomy

In patients with macromastia, breast conservation surgery (BCS) followed by radiation therapy (RT) may be associated with increased radiation exposure and a different complication profile than those without macromastia. The oncoplastic reduction mammoplasty (ORM) procedure includes breast reduction at the time of BCS. The purpose of this study is to determine if women with macromastia who undergo ORM have a different complication profile compared to those who undergo BCS followed by RT. We performed a retrospective chart review on patients who underwent lumpectomy with RT from 2014 to 2017. Chronic breast lymphedema (CBL) was defined as swelling that persisted >1-year post-RT. Breast volumes (BV) were determined by contoured breast volumes or, if unavailable, estimated by the 95% isodose volumes from the RT treatment planning system. Univariate analysis was used to evaluate various patient factors and treatment outcomes in women with BV ≥1300 cc compared to <1300 cc. These same factors were compared in women who underwent ORM vs. BCS. Multivariate regression analysis was used to evaluate factors associated with ≥1 complication. Logistic regression was performed to identify factors associated with the development of CBL. The total population included 785 patients, of which 28 (3.6%) underwent ORM and 757 (96.4%) underwent BCS. The total population was stratified into two groups, in which 289 (36.8%) patients had BV ≥1300 cc and 496 (63.2%) patients had a BV <1300 cc. Compared to patients with BV<1300 cc, those with BV ≥1300 cc had a higher percentage of African Americans (52.6% vs. 41.5%, P = 0.002), higher median BMI (34.96 vs. 27.87, P<0.001), higher incidence of diabetes (39.8% vs. 27.2%, P<0.001), higher incidence of hypertension (75.4% vs. 63.1%, P<0.001), and higher incidence of CBL (12.5% vs. 4.2%, P<0.001). Compared to BCS patients, ORM patients with BV ≥1300 cc had increased incidence of CBL (36.4% vs. 11.5%, P = 0.035). Logistic regression showed that the incidence of ≥1 complication was associated with BMI, presence of SLNB, and the number of lymph nodes removed in either SLNB or ALND. However, factors such as ORM and BV were not associated with an increased risk of ≥1 complication. Logistic regression demonstrated that having a BV ≥1300 cc was associated with 2.5 times increased odds of CBL compared to those with BV <1300 cc. Even though those who underwent ORM did not change the risk for CBL for the entire cohort, ORM patients with BV ≥1300 had a higher risk of CBL. Ultimately, logistic regression demonstrates that ORM does not increase the risk of CBL when adjusting for BV. In conclusion, axillary surgery contributed most significantly to the incidence of having ≥1 complication. However, BV was associated with an increased risk of CBL, regardless of the presence of ORM. Therefore, women with BV ≥1300 cc should be offered ORM at the time of lumpectomy in order to reduce their future risk of CBL.

Evaluating Clinical Outcomes in 3D vs. 2D Vaginal Brachytherapy

Vaginal brachytherapy (VB) for early stage endometrial cancer (EC) has technologically evolved with the incorporation of 3D imaging into treatment planning. When our institution transitioned from phantom-based 2D template planning to 3D CT-based planning, we implemented selective optimization of standard dwell times for cases with bowel adhered to the vaginal apex. Our hypothesis was that optimizing 3D plans with unfavorable bowel dosimetry would result in no detriment to local control and potentially improve treatment tolerability. We reviewed records of patients with stage I-II EC treated with VB at our institution from 1/2017-6/2019 (3D group). We compared patient, tumor, and treatment characteristics to a historic cohort treated at our institution between 2011-2015 (2D group). Patients had minimum 6 months follow-up. Patients with stage III-IV disease, prior or concurrent pelvic radiation, or synchronous pelvic primary were excluded. Recurrence-free survival (RFS), local control, and treatment tolerability (any acute toxicity recorded prospectively on treatment) were analyzed. Statistical analyses were performed in Stata and included Chi-square and Wilcoxon Rank Sum tests to compare between-group characteristics and Cox proportional hazards analysis to assess RFS. A total of 403 patients were included (n = 99/3D and n = 304/2D). The 3D vs. 2D groups were similar in age, weight, gravidity, cylinder sizes, histology, and chemotherapy, though differed in race (p = 0.004) and % stage IA/IB/II (p = 0.022). VB dose was similar, with majority receiving either 18Gy/3 fractions (46% vs. 46%) or 21Gy/3 fractions (40% vs. 38%) to 5mm depth. In the 3D cohort, however, the proportion of vagina treated was less (3D median 50%, IQ range 43-56% vs. 2D median 60%, IQ range 50-67%; p<0.001). and standard dwell times were decreased to improve bowel dosimetry in 21%. Median follow-up times were 524 and 903 days in the 3D and 2D groups, respectively. There was no significant difference in RFS (HR 0.48, 95% CI 0.19-1.22, p = 0.122). Vaginal recurrence occurred in 1 and 2 patients, respectively, with recurrence distal to treated mucosa in all cases. There were no significant differences between groups in rates of acute GI (14.1% vs. 10.9%, p = 0.376), GU (8.1% vs. 11.2%, p = 0.380), or vaginal (20.2% vs. 19.4%, p = 0.827) toxicities. All toxicities were mild (grade 1-2). In the 3D patients, there were no significant differences (p>0.05) in bowel, rectal, or bladder Dmax or D2cc values between those with vs. without symptoms on treatment. 3D vs. 2D planning maintained excellent local control despite selectively reducing the volume of prescription isodose overlapping with bowel. Treatment tolerability was favorable in both groups with no benefit observed in the short term, however, longer follow-up is needed to compare late outcomes.

Temporal-Spatial Dose Pattern in Vaginal Cylinder Applicator for High Dose Rate (HDR) Brachytherapy

High Dose Rate (HDR) brachytherapy delivery patterns have been described by the dwell energy density distribution index (DEDDI). For simplification, the DEDDI was computed for HDR Brachytherapy with vaginal cylinder applicator for GYN patient as an investigation of potential clinical advantage through optimization of dose delivery pattern. For this study, five cases of cylinder applicator GYN HDR brachytherapy were selected. Each patient was accomplished for a course of three fractions with each fraction prescription dose at 500cGy, 600cGy or 700cGy at vaginal surface and at 0.5 cm depth. The single channel cylinder diameters range to 2.5cm to 3.5cm, the delivery time ranged from 290 to 350 seconds, and the considered volumes were 100%, 90%, 80%, 50%, 30% prescription isodose volume (PIV), and the volume of cylinder with 5 mm expansion. The values of DEDDI were computed for all these PIVs by subtracting the volume of cylinder. The source decay effect for different fractions was also computed with the DEDDI to estimate the variation for time factor for treatment course. At nominal source activity, based on the volume of cylinder applicator, 100%, 90%, 80%, 50%, and 30% of PIV, the average values in Cis/cc of DEDDI were 0.741, 0.886, 0.806, 0.836, and 0.948 with standard deviation at 0.509, 0.594, 0.542, 0.578, and 0.621. The corresponding fraction average values in Cis/cc of DEDDI were 0.854, 1.030, 0.873, 1.238, and 2.039 with standard deviation at 3.8%, 3.8%, 3.8%, 3.3% and 2.4%. Quantitative values of dose delivery pattern for HDR Brachytherapy is calculable, and the simplicity of single channel cylinder applicator provides advantage of initial clinical optimization when large cohort of patient outcome data are available.

Radiomic Features Predict Rib Fracture after Stereotactic Body Radiotherapy for Early Stage Non-Small Cell Lung Cancer

Dose to the chest wall is a well-established predictor of rib fracture after stereotactic body radiation therapy (SBRT), but even with a high dose to the chest wall most patients will not develop a fracture. Discovering other predictors that are independent from dose will improve our ability to predict which patients will develop a rib fracture. Radiomic analysis of the chest wall can provide an opportunity to find such features on imaging. A retrospective analysis was conducted of 73 patients with early stage NSCLC who were treated with SBRT. Quantitative radiomic feature extraction using PyRadiomics was performed on the 4D treatment planning scans of all patients. A total of 236 radiomic features were extracted, all of which were based on a Boolean overlap of the 20 Gy isodose volume and the chest wall. A 10-fold cross validation based Elastic Net Cox regression was completed for variable selection and used to identify the lambda (regularization parameter) value that produced the lowest cross-validated error. Variables that remained in the final model were then evaluated independently with univariate Cox regression hazard ratios and in a multivariate model built with and without the radiomic features and compared based on concordance indexes that were averaged across a Monte Carlo cross-validation scheme with 10 resamples. Correlation between predictors was evaluated using Pearson’s correlation coefficient. Twenty-nine patients with radiation induced rib fractures were identified retrospectively and compared to 44 patients with no rib fracture. The Elastic Net Cox regression model with the lowest cross-validated error included 6 predictors: three clinical and three radiomic. The clinical variables included volume of overlap between the PTV and chest wall (HR 2.49, p < 0.01), volume of chest wall receiving 50 Gy (HR 2.23, p < 0.01) and volume of rib receiving 50 Gy (HR 2.14, p < 0.01). Radiomic variables included shape elongation (HR 0.64, p = 0.03), Gray Level Size Zone Matrix (GLSZM) Large Area Low Gray Level Emphasis (LALGLE; HR 2.24, p < 0.01) and Neighboring Gray Tone Difference Matrix (NGTDM) busyness (HR 2.36, p < 0.01). A multivariate model that included only the clinical variables had a concordance index of 0.69 (95% CI 0.61-0.77) while inclusion of the radiomic variables increased the concordance index to 0.79 (95% CI 0.76 to 0.82). Of the 3 identified radiomic features, shape elongation was the least correlated with the clinical variables. The Pearson correlation coefficient comparing shape elongation to chest wall V50 was 0.03 (95% CI -0.20 to 0.25, p = 0.824). Radiomic feature extraction from the chest wall can provide insight into a patient’s risk of a rib fracture after SBRT. Of the radiomic features found to persist in the final multivariate model, shape elongation was the only variable not correlated with chest wall dose. This provides evidence for a predictor of rib fracture after SBRT that is independent of chest wall dose.