William Bodner

Prostate-specific antigen bounce predicts for a favorable prognosis following brachytherapy: a meta-analysis.

Purpose Controversy exists whether the prostate-specific antigen (PSA) bounce phenomenon following definitive radiation for prostate cancer has prognostic significance. Here, we perform a meta-analysis to determine the association between PSA bounce and biochemical control after brachytherapy alone. Material and methods We reviewed Medline, EMBASE, and CENTRAL citations through February 2012. Studies that recorded biochemical failure rates in bouncers and non-bouncers were included. Hazard ratios describing the impact of bounce on biochemical failure were extracted directly from the studies or calculated from survival curves. Pooled estimates were obtained using the inverse variance method. A random effects model was used in cases of significant effect heterogeneity (p < 0.10 using Q test). Results The final analysis included 3011 patients over 6 studies treated with brachytherapy. Meta-analysis revealed that patients experiencing PSA bounce after brachytherapy, conferred a decreased risk of biochemical failure (random effects model HR = 0.42, 95% CI: 0.30-0.59; p < 0.001). Conclusions Our meta-analysis determined that PSA bounce predicts for improved biochemical control following brachytherapy. To our knowledge, this is the first study describing this effect.

An efficient Volumetric Arc Therapy treatment planning approach for hippocampal-avoidance whole-brain radiation therapy (HA-WBRT).

An efficient and simple class solution is proposed for hippocampal-avoidance whole-brain radiation therapy (HA-WBRT) planning using the Volumetric Arc Therapy (VMAT) delivery technique following the NRG Oncology protocol NRG-CC001 treatment planning guidelines. The whole-brain planning target volume (PTV) was subdivided into subplanning volumes that lie in plane and out of plane with the hippocampal-avoidance volume. To further improve VMAT treatment plans, a partial-field dual-arc technique was developed. Both the arcs were allowed to overlap on the in-plane subtarget volume, and in addition, one arc covered the superior out-of-plane sub-PTV, while the other covered the inferior out-of-plane subtarget volume. For all plans (n = 20), the NRG-CC001 protocol dose-volume criteria were met. Mean values of volumes for the hippocampus and the hippocampal-avoidance volume were 4.1 cm(3) ± 1.0 cm(3) and 28.52 cm(3) ± 3.22 cm(3), respectively. For the PTV, the average values of D(2%) and D(98%) were 36.1 Gy ± 0.8 Gy and 26.2 Gy ± 0.6 Gy, respectively. The hippocampus D(100%) mean value was 8.5 Gy ± 0.2 Gy and the maximum dose was 15.7 Gy ± 0.3 Gy. The corresponding plan quality indices were 0.30 ± 0.01 (homogeneity index), 0.94 ± 0.01 (target conformality), and 0.75 ± 0.02 (confirmation number). The median total monitor unit (MU) per fraction was 806 MU (interquartile range [IQR]: 792 to 818 MU) and the average beam total delivery time was 121.2 seconds (IQR: 120.6 to 121.35 seconds). All plans passed the gamma evaluation using the 5-mm, 4% criteria, with γ > 1 of not more than 9.1% data points for all fields. An efficient and simple planning class solution for HA-WBRT using VMAT has been developed that allows all protocol constraints of NRG-CC001 to be met.

Day to day treatment variations of accelerated partial breast brachytherapy using a multi-lumen balloon

Purpose To evaluate the variations of multi-lumen balloon (MLB)-based brachytherapy from simulation day to treatment day and their dosimetric impacts during accelerated partial breast irradiation (APBI). Material and methods A total of 42 CT images scanned from seven patients were evaluated with regards to daily variation due to of: 1) internal uncertainty: size and shape of balloon, seroma volume; 2) geometrical uncertainty-random: length of each catheter was measured for each fraction (total 70); 3) geometrical uncertainty-systematic: virtual systematic errors were tested by offsetting dwell positions. The original plans (as group A) had a mean value of 96.8% on V95 of the PTV_Eval. Plans were rerun (as group B) such that the mean value of the V95 was relaxed to 90.4%. By applying the reference plan to each daily CT image, variations of target coverage under different sources of error were evaluated. Results Shape and size of the balloon had means of < 1 mm decreased in diameter and < 0.4 cm3 decreased in volume; the mean seroma volume increased by 0.2 cm3. This internal variation has a mean of < 1% difference for both V90 and V95. The geometrical uncertainty made a mean deviation of 2.7 mm per root of sum of square. It caused the degradations of V90 and V95 by mean values of 1.0% and 1.2%, respectively. A systematic error of 3 mm and 4 mm would degrade both of V90 and V95 by 4% and 6%, respectively. The degradations on target coverage of the plans in group A were statistically the same as those in group B. Conclusions Overall, APBI treatments with MLB based brachytherapy are precise from day to day. However, minor variation due to daily treatment uncertainties can still degrade tumor bed coverage to an unacceptable coverage when V95 of the original plan is close to 90%.

Progressive transition from pre-planned to intraoperative optimizing seed implant: post implementation analysis.

Purpose To perform a dosimetric comparison between a pre-planned technique and a pre-plan based intraoperative technique in prostate cancer patients treated with I-125 permanent seed implantation. Material and methods Thirty patients were treated with I-125 permanent seed implantation using TRUS guidance. The first 15 of these patients (Arm A) were treated with a pre-planned technique using ultrasound images acquired prior to seed implantation. To evaluate the reproducibility of the prostate volume, ultrasound images were also acquired during the procedure in the operating room (OR). A surface registration was applied to determine the 6D offset between different image sets in arm A. The remaining 15 patients (Arm B) were planned by putting the pre-plan on the intraoperative ultrasound image and then re-optimizing the seed locations with minimal changes to the pre-plan needle locations. Post implant dosimetric analyses included comparisons of V100(prostate), D90(prostate) and V100(rectum). Results In Arm A, the 6D offsets between the two image sets were θx=−1.4±4.3; θy=−1.7±2.6; θz=−0.5±2.6; X=0.5±1.8 mm; Y=−1.3±−3.5 mm; Z=−1.6±2.2 mm. These differences alone degraded V100 by 6.4% and D90 by 9.3% in the pre-plan, respectively. Comparing Arm A with Arm B, the pre-plan based intraoperative optimization of seed locations used in the plans for patients in Arm B improved the V100 and D90 in their post-implant studies by 4.0% and 5.7%, respectively. This was achieved without significantly increasing the rectal dose (V100(rectum)). Conclusions We have progressively moved prostate seed implantation from a pre-planned technique to a pre-plan based intraoperative technique. In addition to reserving the advantage of cost-effective seed ordering and efficient OR implantation, our intraoperative technique demonstrates increased accuracy and precision compared to the pre-planned technique.

Abstract CT005: FLT3 ligand (CDX-301) and stereotactic radiotherapy for advanced non-small cell lung cancer

Background We previously demonstrated, in a murine model, that localized radiotherapy and fms-like tyrosine kinase 3 (FLT3) ligand can act synergistically to control non-small cell lung cancer (NSCLC). Here we present preliminary results from an ongoing prospective clinical trial testing this combination in patients with advanced NSCLC. Methods Patients with advanced NSCLC that has previously been treated with at least one line of systemic therapy, at least two sites of active disease based on pre-treatment FDG-PET, and ECOG performance status 0-2 are eligible for this trial. Study subjects receive 5 daily subcutaneous injections of CDX-301 (75 µg/kg) concurrent with stereotactic body radiotherapy (SBRT) directed at a single intrathoracic site of disease. SBRT doses may range from 30 to 54 Gy, delivered over one week in 1, 3, or 5 fractions, depending on the target size and location. The primary study endpoint is survival without disease progression four months after treatment (PFS4). We hypothesize that the PFS4 rate will exceed 40%. Secondary endpoints include dose-limiting toxicities (grade ≥3 adverse events observed within 30 days of treatment and attributed to study therapy) and responses on PET based on total glycolytic activity (TGA), which is a volumetric measure of disease burden. Lesions targeted with SBRT are not included in radiographic response assessments. Based on PET Response Criteria in Solid Tumors (PERCIST) guidelines, a reduction in TGA of 45% or greater is classified as a partial response (PR). Results Nine subjects received study therapy between October 2016 and October 2017. Subjects were previously treated with a median of 2.5 courses of systemic therapy (range: 1-3). Seven subjects were previously treated with immune checkpoint inhibitors targeting the PD-1/PD-L1 axis. No dose-limiting toxicities were observed. On PET performed two months after treatment, PR of lesions not targeted with SBRT (“abscopal effect”) was observed in 5/9 subjects. Responses were observed in unirradiated pulmonary, nodal, and osseous lesions. With a median follow-up duration of 5 months (range: 4 to 13 months), five subjects have developed disease progression, and two subjects have died. PFS4 was achieved in 5/9 subjects overall and in 5/5 subjects who demonstrated PR on PET. PR and PFS4 were achieved in 5/7 subjects who were previously treated with immunotherapy and in 0/2 subjects who were not previously treated with immunotherapy. Conclusion The combination of CDX-301 and stereotactic radiotherapy for advanced NSCLC has yielded promising early results, with frequent abscopal effects and a high PFS4 rate. This regimen may be particularly effective for patients who have previously been treated with immune checkpoint inhibitors targeting the PD-1/PD-L1 axis. Enrollment is ongoing to further characterize treatment efficacy and to explore the immunological effects of combining CDX-301 and SBRT. Citation Format: Nitin Ohri, Balazs Halmos, Haiying Cheng, Tony Abraham, Tahir Yahya, Madhur Garg, William Bodner, Rafi Kabarriti, Shalom Kalnicki, Michael J. Yellin, Tibor Keler, Chandan Guha. FLT3 ligand (CDX-301) and stereotactic radiotherapy for advanced non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT005.

Evaluating which plan quality metrics are appropriate for use in lung SBRT

OBJECTIVE Several dose metrics in the categories-homogeneity, coverage, conformity and gradient have been proposed in literature for evaluating treatment plan quality. In this study, we applied these metrics to characterize and identify the plan quality metrics that would merit plan quality assessment in lung stereotactic body radiation therapy (SBRT) dose distributions. METHODS Treatment plans of 90 lung SBRT patients, comprising 91 targets, treated in our institution were retrospectively reviewed. Dose calculations were performed using anisotropic analytical algorithm (AAA) with heterogeneity correction. A literature review on published plan quality metrics in the categories-coverage, homogeneity, conformity and gradient was performed. For each patient, using dose-volume histogram data, plan quality metric values were quantified and analysed. RESULTS For the study, the radiation therapy oncology group (RTOG) defined plan quality metrics were: coverage (0.90 ± 0.08); homogeneity (1.27 ± 0.07); conformity (1.03 ± 0.07) and gradient (4.40 ± 0.80). Geometric conformity strongly correlated with conformity index (p < 0.0001). Gradient measures strongly correlated with target volume (p < 0.0001). The RTOG lung SBRT protocol advocated conformity guidelines for prescribed dose in all categories were met in ≥94% of cases. The proportion of total lung volume receiving doses of 20 Gy and 5 Gy (V20 and V5) were mean 4.8% (±3.2) and 16.4% (±9.2), respectively. CONCLUSION Based on our study analyses, we recommend the following metrics as appropriate surrogates for establishing SBRT lung plan quality guidelines-coverage % (ICRU 62), conformity (CN or CIPaddick) and gradient (R50%). Furthermore, we strongly recommend that RTOG lung SBRT protocols adopt either CN or CIPadddick in place of prescription isodose to target volume ratio for conformity index evaluation. Advances in knowledge: Our study metrics are valuable tools for establishing lung SBRT plan quality guidelines.

Dosimetric Evaluation of a Flexible Dual Balloon-Constructed Applicator in Treating Anorectal Cancer

Background and Purpose: To assess the dosimetric flexibility of a dual balloon brachytherapy applicator developed for the treatment of anorectal lesions. Materials and Methods: Different amounts of water were infused into the inner and outer balloon separately to study the asymmetrical distribution of the catheter, the radial distance of the active source channel to the inner surface of the global target volume , the space between the active source channels, and their dosimetric impact to target tissues and uninvolved rectum. Results: Increasing inner balloon volume directly increased both the space between the active source channels and the radial distance of the active source channel to the inner surface of the global target volume. The space between the active source channels and the percentage of global target volume received 150% or more of the prescribed dose to target had a strong inverse correlation (−0.881/P = .007, −0.976/P = .001, respectively) with the radial distance of the active source channel to the inner surface of the global target volume. Conformity index, dose to 2 cm3 of rectum, and total reference air kerma were strongly correlated with the radial distance of the active source channel to the inner surface of the global target volume, with values of 0.952 (P = .001), 0.833 (P = .015), and 0.922 (P = .002), respectively. Percentage of global target volume received 150% or more of the prescribed dose was significantly correlated with the space between the active source channels (0.81/P = .022), and conformity index was strongly inversely correlated with the space between the active source channels (−0.833/P = .015). Conclusion: The dual balloon-constructed Anorectal Applicator offers a flexible way to adjust the distances of the active source positions to the target in relation to uninvolved rectal wall. This flexibility simplifies planning which results in a highly conformal dose distribution to the target lesion while minimizing dose to normal rectal tissue.

Model assessment of individual tumor control rate and adverse effects in comparing locally advanced cervical cancer treatment using intracavitary with and without interstitial brachytherapy

Purpose This study assessed the modeled probability of tumor control and organ at risk toxicities in locally advanced cervical cancer in patients treated by external beam radiation plus brachytherapy using intracavitary combined with interstitial brachytherapy (IC/IS) vs. intracavitary brachytherapy (IC) alone. Material and methods Twenty cervical cancer patients with a mean HR-CTV volume of 47.4 cm3 and a mean width of 54 mm were planned with both IC/IS and IC brachytherapy alone. A probit model was utilized to model 3-year (3-yr) local control rate (LC), 3-yr cancer specific survival rate (CSS), and the adverse effect (AE) of the organ at risk by using a modeled data set from multiple institutions. Modeling results were used to estimate the LC, CSS, and AE of the treatments in this study. Results Using the IC/IS technique, an EQD2 increase of 12.3 Gy to D90 (from 76.1 Gy to 88.3 Gy) of HR-CTV is expected to increase 3-yr LC and 3-yr CSS by 12.5%, and 11.0%, respectively. Comparing IC/IS to IC alone, the expected G2+ AE were 7.7% vs. 7.9% for the bladder, and 5.9% vs. 6.8% for the rectum. Conclusions The IC/IS technique improved dose coverage to the HR-CTV without significantly increasing dose to 2 cm3 of the organ at risk (OAR) surrounding it. With different regimens of EBRT combined with BT, IC/IS can be used to increase the probability of LC and CSS, or decrease the risk of AE.

TU‐F‐18C‐09: Mammogram Surveillance Using Texture Analysis for Breast Cancer Patients After Radiation Therapy

PURPOSE To study the feasibility of applying cancer risk model established from treated patients to predict the risk of recurrence on follow-up mammography after radiation therapy for both ipsilateral and contralateral breast. METHODS An extensive set of textural feature functions was applied to a set of 196 Mammograms from 50 patients. 56 Mammograms from 28 patients were used as training set, 44 mammograms from 22 patients were used as test set and the rest were used for prediction. Feature functions include Histogram, Gradient, Co-Occurrence Matrix, Run-Length Matrix and Wavelet Energy. An optimum subset of the feature functions was selected by Fisher Coefficient (FO) or Mutual Information (MI) (up to top 10 features) or a method combined FO, MI and Principal Component (FMP) (up to top 30 features). One-Nearest Neighbor (1-NN), Linear Discriminant Analysis (LDA) and Nonlinear Discriminant Analysis (NDA) were utilized to build a risk model of breast cancer from the training set of mammograms at the time of diagnosis. The risk model was then used to predict the risk of recurrence from mammogram taken one year and three years after RT. RESULTS FPM with NDA has the best classification power in classifying the training set of the mammogram with lesions versus those without lesions. The model of FPM with NDA achieved a true positive (TP) rate of 82% compared to 45.5% of using FO with 1-NN. The best false positive (FP) rates were 0% and 3.6% in contra-lateral breast of 1-year and 3-years after RT, and 10.9% in ipsi-lateral breast of 3-years after RT. CONCLUSION Texture analysis offers high dimension to differentiate breast tissue in mammogram. Using NDA to classify mammogram with lesion from mammogram without lesion, it can achieve rather high TP and low FP in the surveillance of mammogram for patient with conservative surgery combined RT.

Timing of postseed imaging influences rectal dose–volume parameters for cesium-131 prostate seed implants

PURPOSE To study the influence of timing of postseed implant imaging on rectal dose-volume parameters for cesium-131 ((131)Cs) seed prostate implants. METHODS AND MATERIALS Fifteen patients were treated in our institution with combination (131)Cs brachytherapy followed by pelvic external beam radiation therapy for intermediate to high-risk prostate cancers. For all patients, CT scans were scheduled at 7 days (CT(7)) and again at 2 months for external beam radiation therapy simulation purpose (CT(60)) postseed implantation. Comprehensive postseed implant dosimetry was performed for both CT(7) and CT(60) scans. In each case, dose-volume histogram parameters, rectal separation (the distance between the center of posterior most seed and most anterior rectal wall), and posterior row activity (the total activity implanted within 2-4mm anterior to the posterior wall of the prostate) data were collected. The absolute rectal volumes receiving 100% and 110% prescription dose were also collected. RESULTS Rectal dose correlated strongly with rectal separation (p<0.001). The mean change in rectal separation between CT(7) and CT(60) scans was 1.1 (±1.7) mm, and the corresponding change in 0.1-cc rectal dose was 18 (±26.5) Gy. Posterior row activity did not correlate with rectal dose (p=0.51). The mean volume of rectum that receives between 100% and 110% of the prescription dose (RV(100) and RV(110)) increased twofold, between CT(7) and CT(60) evaluations (0.03 [±0.06] cc vs. 0.07 (±0.05) cc, respectively, p=0.06). CONCLUSIONS Our study has demonstrated that rectal doses after (131)Cs seed implants are influenced by the timing of postseed imaging. This may be a consequence of prostatic and periprostatic edema resolution.