Mean Biological Effective Dose Research Articles

The Effect of Stereotactic Body Radiotherapy (SBRT) Dose-Fraction (fx) Schema on Non-Small Cell Lung Cancer (NSCLC)

Stereotactic body radiotherapy (SBRT) dose-fraction (fx) schema for non-small cell lung cancer (NSCLC) varies at different centers and commonly involves 3 to 5 fx. Additionally, the frequency of treatment per week, or treatment schedules (TS), can also differ. We sought to evaluate and compare the effect of different dose-fx schemas on overall survival (OS). We retrieved data from the National Cancer Database. Patient eligibility included early-stage NSCLC with cT1-2 N0M0 disease treated with SBRT using 3-5f x regimens. Demographics and clinical characteristics were identified. Biologically effective dose (BED) and total dose (TD) were calculated. TD included following: 45-60 Gy for 3 fx, 48-60 Gy for 4 fx, and 50-60 Gy for 5 fx. TS was classified as one of the following: daily, every other day, twice per week, or prolonged (less frequently than twice weekly). Non-prolonged TS was defined as daily, every other day, and twice per week. OS was calculated from the date of end of RT to the date of death and censored at the date of last contact. Kaplan Meier method was used to estimate OS and log-rank tests were used to compare the difference between groups. TS was compared pairwise within each individual fx-group. Univariable Cox proportional models with robust standard errors to account for within institution correlations were used to investigate the association between BED, TD, TS, fx-group and OS. Within each fx-group, BED was also assessed and compared. A total of 3244 patients were identified, with median age 73. 48% were males and 52% females. 601 (19%) patients received 3 fx, 884 (27%) received 4 fx, and 1759 (54%) received 5 fx treatments. For the overall cohort, median and mean BEDs were 112 and 119, respectively. TS did not show a difference in OS among each individual fx group. Overall, prolonged vs non-prolonged schedules also did not show a difference in OS (p = 0.64). OS was superior in the 3 fx group compared to 4 and 5 fx groups, with median survival times of 61.5 vs 53.7 vs 52.6 months, respectively (p = 0.046). Overall, an increase in BED reduced risk of death (HR = 0.97 per 10-units, CI: 0.94-0.99, p = 0.04). When stratified by fx, each 10 unit rise in BED for those treated with 5 fx reduced the risk of death by 8% (HR = 0.92, CI: 0.87-0.97, p<0.01). However, increasing BED was not associated with change in OS for 3 fx (HR = 1.00, CI: 0.93-1.08, p = 0.93) and 4 fx (HR = 1.08, p = 0.08) regimens. Patients who received BED greater than the median (BED>112) had improved OS compared to those receiving BED£112 (HR = 0.86, p = 0.047). When evaluating the 5 fx-group individually, BED >100 (median of 5fx group) had superior OS compared to £100 (HR = 0.80, p = 0.02). Three-fraction regimens have superior OS compared to 4 and 5 fx regimens. Higher BED improves OS in 5 fx regimens. Treatment schedule variations among individual fx-groups does not impact OS.

PD15-03 RADIATION DOSE REQUIRED TO CONTROL PROSTATE CANCER AS DETERMINED BY POST-TREATMENT BIOPSY: LONG TERM RESULTS

You have accessJournal of UrologyCME1 Apr 2023PD15-03 RADIATION DOSE REQUIRED TO CONTROL PROSTATE CANCER AS DETERMINED BY POST-TREATMENT BIOPSY: LONG TERM RESULTS Nelson Stone, Rendi Shue, Barry Rosenstein, and Richard Stock Nelson StoneNelson Stone More articles by this author , Rendi ShueRendi Shue More articles by this author , Barry RosensteinBarry Rosenstein More articles by this author , and Richard StockRichard Stock More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003262.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Radiation therapy for prostate cancer is typically prescribed at a standard dose, 79-81 Gy for external beam irradiation (EBRT) and 145 Gy for iodine-125 brachytherapy (BT). Unlike prostatectomy where the gland is removed at the time of treatment successful radiation treatment relies on the death of all cancer cells in situ. However, the dose requirement for different Gleason grade groups or NCCN risk groups may also differ. We investigated the relationship between the biological effective dose (BED) and local control as determined by post-treatment biopsy (PB) in a large cohort of men who had BT +EBRT. METHODS: 545 men who had BT were followed a median of 11 years (range 2-26) and had PB a mean of 3.2 years (2-17) post-treatment. All PB were performed by one investigator (NNS) and routinely performed at 2 years or later for a rising PSA. Median age, PSA and BED were 66 years (41-85), 7.0 ng/ml (1-189) and 185.5 Gy (15-282). 295 (54.1%) received hormone therapy (HT) for a median of 6 months. Radiation doses were converted post-implant to the BED using an ꭤ/β of 2. Associations with grade, stage, PSA, NCCN status, HT use, BED were compared to the PB results and prostate cancer survival (PCS) using ANOVA, chi-square, linear regression, Kaplan Meier estimates with comparisons by log rank and Cox proportion hazards. RESULTS: 34 (6.2%) of the 545 men had a positive PB which occurred a mean of 5.9 years (range 2-17) after all treatment. BED (p<0.001), stage (p=0.004), PSA (p=0.038) and HT use (p=0.019) were associated with a positive PB but only BED (p<0.001) remained significant on regression analysis. Dichotomizing BED to <140, 160, 180, 200, 220 or greater yielded optimal local control (positive biopsy rate 2% or less) at 180 Gy for all 3 NCCN risk groups (Table). Men with a positive PB had a mean BED of 136.8 vs. 181.3 Gy for negative PB (p<0.001). At <180 Gy 24/229 (10.5%) had local failure compared to 5/392 (1.7%) for higher doses (p<0.001, OR 6.7, 95% CI 2.5-17.9). PCS at 15 and 20 years for negative PB was 94.5 and 94.5% vs. 74.4 and 46.5% for a positive one (p<0.001). PCS was associated with BED (p<0.001), PSA (p=0.028) and stage (p=0.018). CONCLUSIONS: This long-term investigation defined the radiation dose necessary to eradicate prostate cancer and should be considered as the minimal requirement when prescribing and delivering this treatment option. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e419 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Nelson Stone More articles by this author Rendi Shue More articles by this author Barry Rosenstein More articles by this author Richard Stock More articles by this author Expand All Advertisement PDF downloadLoading ...

Low doses to the heart in daily practice for treating left-sided breast cancer using accelerated partial-breast irradiation by multicatheter brachytherapy and deep-inspiration breath-hold using a SIB

PurposeThe aim of this study was to analyze the heart dose for left-sided breast cancer that can be achieved during daily practice in patients treated with multicatheter brachytherapy (MCBT) accelerated partial-breast irradiation (APBI) and deep-inspiration breath-hold (DIBH) whole-breast irradiation (WBI) using a simultaneous integrated tumor bed boost (SIB)—two different concepts which nonetheless share some patient overlap.Materials and methodsWe analyzed the nominal average dose (Dmean) to the heart as well as the biologically effective dose (BED) and the equivalent dose in 2‑Gy fractions (EQD2) for an α/β of 3 in 30 MCBT-APBI patients and 22 patients treated with DIBH plus SIB. For further dosimetric comparison, we contoured the breast planning target volume (PTV) in each of the brachytherapy planning CTs according to the ESTRO guidelines and computed tangential field plans. Mean dose (Dmean), EQD2 Dmean, and BED Dmean for three dosing schemes were calculated: 50 Gy/25 fractions and two hypofractionated regimens, i.e., 40.05 Gy/15 fractions and 26 Gy/5 fractions. Furthermore, we calculated tangential field plans without a boost for the 22 cases treated with SIB with the standard dosing scheme of 40.05 Gy/15 fractions.ResultsMCBT and DIBH radiation therapy both show low-dose exposure of the heart. As expected, hypofractionation leads to sparing of the heart dose. Although MCBT plans were not optimized regarding dose to the heart, Dmean differed significantly between MCBT and DIBH (1.28 Gy vs. 1.91 Gy, p < 0.001) in favor of MCBT, even if the Dmean in each group was very low. In MCBT radiation, the PTV–heart distance is significantly associated with the dose to the heart (p < 0.001), but it is not in DIBH radiotherapy using SIB.ConclusionIn daily practice, both DIBH radiation therapy as well as MCBT show a very low heart exposure and may thus reduce long term cardiac morbidity as compared to currently available long-term clinical data of patients treated with conventional tangential field plans in free breathing. Our analysis confirms particularly good cardiac sparing with MCBT-APBI, so that this technique should be offered to patients with left-sided breast cancer if the tumor-associated eligibility criteria are fulfilled.

Stereotactic Body Radiation Therapy Versus Conventional Radiation Therapy in Pain Relief for Bone Metastases: A Systematic Review and Meta-Analysis

This study aimed to investigate the difference in pain relief between stereotactic body radiation therapy (SBRT) and conventional radiation therapy (cRT) for patients with bone metastases. Clinical trials and observational studies comparing SBRT versus cRT for bone metastases were retrieved. The main endpoint was pain relief after radiation therapy; the secondary endpoints were pain score change, local progression-free survival, reirradiation rate, and toxic events. When there was a significant heterogeneity, the random-effects model was applied. Otherwise, the fixed-effects model was used. Analyses of all included studies were performed first, followed by analyses of randomized controlled trials (RCTs) only. Six RCTs, 1 prospective cohort study, and 3 retrospective observational studies were enrolled. Between 2004 and 2019, 448 patients received SBRT, and 445 patients received cRT. All prospective studies defined the lesions as oligometastatic. Pooled results based on all included studies indicated that SBRT was generally associated with a higher overall relief rate (P < .001 at 3 months; P=.015 at 6 months) and complete relief rate (P=.029 at 1 month; P < .001 at 6 months). Pooled results based on RCTs indicated that at 3 and 6 months, SBRT was associated with a higher overall relief rate (P < .001 and P=.017, respectively) and complete relief rate (P < .001 and P < .00, respectively). Subgroup analyses indicated that in more cases, the analgesic advantage of SBRT was more obvious when spinal lesions were irradiated, when the difference in the mean biological effective dose (BED) was less, or when intensity modulated radiation therapy was used to deliver SBRT. Excessive elevation of BED introduces the risk of diminishing the analgesic effect of SBRT. SBRT delivered using intensity modulated radiation therapy is preferred for pain relief in spinal oligometastases. More RCTs are required to determine the most appropriate BED or dose regimen for SBRT.

Tumor control and radiobiological fingerprint after Gamma Knife radiosurgery for posterior fossa meningiomas: A series of 46 consecutive cases

IntroductionGamma Knife radiosurgery (GKR) can be a valuable treatment option for posterior cranial fossa meningiomas (PCFM). We retrospectively analyzed outcomes of GKR for PCFM. MethodsWere included forty-six patients with 47 PCFM. Primary endpoint was tumor control. Secondary endpoint was clinical improvement. Biologically effective dose (BED) was evaluated in relationship to primary and secondary outcomes. Mean marginal dose was 12.4 Gy (median 12, 12–14). Mean BED was 63.6 Gy (median 65, 49.1–88.3). Mean target volume (TV) was 2.21 cc (range 0.3–8.9 cc). ResultsOverall tumor control rate was 93.6% (44/47) after mean follow-up of 47.8 months ± 28.46 months (median 45.5, range 6–108). Radiological progression-free survival at 5 years was 94%. Higher pretherapeutic TVs were predictive for higher likelihood of tumor progression (Odds ratio, OR 1.448, 95% confidence interval - CI 1.001–2.093, p = 0.049). At last clinical follow-up, 28 patients (71.8%) remained stable, 10 (25.6%) improved and 1 patient (2.6%) worsened. Using logistic regression, the relationship between BED and clinical improvement was assessed (OR 0.903, standard error 0.59, coefficient 0.79–1.027, CI −0.10; 0.01; p = 0.14). The highest probability of clinical improvement corresponded to a range of BED values between 56 and 61 Gy. ConclusionPrimary GKR for PCFM is safe and effective. Higher pretherapeutic TV was predictor of volumetric progression. Highest probability of clinical improvement might correspond to a range of BED values between 56 and 61 Gy, although this was not statistically significant. The importance of BED should be further validated in larger cohorts, other anatomical locations and other pathologies.

A reinforcement learning approach for finding optimal policy of adaptive radiation therapy considering uncertain tumor biological response

Recent studies have shown that a tumor's biological response to radiation varies over time and has a dynamic nature. Dynamic biological features of tumor cells underscore the importance of using fractionation and adapting the treatment plan to tumor volume changes in radiation therapy treatment. Adaptive radiation therapy (ART) is an iterative process to adjust the dose of radiation in response to potential changes during the treatment. One of the key challenges in ART is how to determine the optimal timing of adaptations corresponding to tumor response to radiation. This paper aims to develop an automated treatment planning framework incorporating the biological uncertainties to find the optimal adaptation points to achieve a more effective treatment plan. First, a dynamic tumor-response model is proposed to predict weekly tumor volume regression during the period of radiation therapy treatment based on biological factors. Second, a Reinforcement Learning (RL) framework is developed to find the optimal adaptation points for ART considering the uncertainty in biological factors with the goal of achieving maximum final tumor control while minimizing or maintaining the toxicity level of the organs at risk (OARs) per the decision-maker's preference. Third, a beamlet intensity optimization model is solved using the predicted tumor volume at each adaptation point. The performance of the proposed RT treatment planning framework is tested using a clinical non-small cell lung cancer (NSCLC) case. The results are compared with the conventional fractionation schedule (i.e., equal dose fractionation) as a reference plan. The results show that the proposed approach performed well in achieving a robust optimal ART treatment plan under high uncertainty in the biological parameters. The ART plan outperformed the reference plan by increasing the mean biological effective dose (BED) value of the tumor by 2.01%, while maintaining the OAR BED within +0.5% and reducing the variability, in terms of the interquartile range (IQR) of tumor BED, by 25%.

Gamma Knife surgery for recurrent or persistent Cushing disease: long-term results and evaluation of biological effective dose in a series of 26 patients.

Here we report long-term results after stereotactic radiosurgery (SRS) with Gamma Knife (GKRS) for Cushing disease. We further evaluated the potential role of the biological effective dose (BED) in the cure of this disease. A retrospective review of a prospectively collected database (n = 26) was undertaken at Lille University Hospital, France. The mean follow-up period was 66 months (median 80, range 19&ndash;108). The mean marginal prescribed dose was 28.5 Gy (median 27.5, range 24&ndash;35) and the mean BED was 208.5 Gy2.47 (median 228.1, range 160&ndash;248). We divided patients with endocrine remission into a high BED group (160&ndash;228 Gy2.47, n = 6) and a low BED group (228&ndash;248 Gy2.47, n = 12). Eighteen (69.2%) patients had endocrine remission in the absence of any pharmacological therapy after a mean of 36 months (median 24, range 6&ndash;98). The actuarial probability of endocrine remission was 59% at 3 years and 77.6% at 7 years, which remained stable up to 10 years. There was a tendency to a higher overall probability of biological remission associated with higher BED values (77% versus 66% at last follow-up), although this did not reach statistical significance. Of note, the numbers of patients reflecting this actuarial probability at 12, 24, 36, 51 and 96 months were 21, 15, 11, 7 and 3, respectively. Tumour control was achieved in all cases (mean decrease in size for patients experiencing one was 29.4%, range 0&ndash;100%). Seven patients developed new pituitary insufficiency after GKRS. Gamma Knife radiosurgery offers high rates of tumour control and endocrine remission on a long-term basis for ACTH-secreting pituitary adenomas. In this small series, higher BED values appeared to be associated with better endocrine remission rates. Owing to the limited sample size, such results should be validated in a larger cohort.

Biologically effective dose correlates with linear tumor volume changes after upfront single-fraction stereotactic radiosurgery for vestibular schwannomas

Vestibular schwannomas (VSs) are benign, slow-growing tumors. Management options include observation, surgery, and radiation. In this retrospective trial, we aimed at evaluating whether biologically effective dose (BED) plays a role in tumor volume changes after single-fraction first intention stereotactic radiosurgery (SRS) for VS. We compiled a single-institution experience (n = 159, Lausanne University Hospital, Switzerland). The indication for SRS was decided after multidisciplinary discussion. Only cases with minimum 3 years follow-up were included. The Koos grading, a reliable method for tumor classification was used. Radiosurgery was performed using Gamma Knife (GK) and a uniform marginal prescription dose of 12 Gy. Mean BED was 66.3 Gy (standard deviation 3.8, range 54.1–73.9). The mean follow-up period was 5.1 years (standard deviation 1.7, range 3–9.2). The primary outcome was changes in 3D volumes after SRS as function of BED and of integral dose received by the VS. Random-effect linear regression model showed that tumor volume significantly and linearly decreased over time with higher BED (p < 0.0001). Changes in tumor volume were also significantly associated with age, sex, number of isocenters, gradient index, and Koos grade. However, the effect of BED on tumor volume change was moderated by time after SRS and Koos grade. Lower integral doses received by the VSs were inversely correlated with BED in relationship with tumor volume changes (p < 0.0001). Six (3.4%) patients needed further intervention. For patients having uniformly received the same marginal dose prescription, higher BED linearly and significantly correlated with tumor volume changes after SRS for VSs. BED could represent a potential new treatment paradigm for patients with benign tumors, such as VSs, for attaining a desired radiobiological effect. This could further increase the efficacy and decrease the toxicity of SRS not only in benign tumors but also in other SRS indications.

Biological Effective Dose as a Predictor of Hypopituitarism After Single-Fraction Pituitary Adenoma Radiosurgery: Dosimetric Analysis and Cohort Study of Patients Treated Using Contemporary Techniques.

Hypopituitarism is the most frequent complication after pituitary adenoma stereotactic radiosurgery (SRS) and is correlated with increasing radiation to the pituitary gland. Biological effective dose (BED) is a dosimetric parameter that incorporates a time component to adjust for mechanisms of deoxyribonucleic acid repair activated during treatment. To assess mean gland BED as a predictor of post-SRS hypopituitarism, as compared to mean gland dose, in a contemporary cohort study of patients undergoing single-fraction SRS for pituitary adenoma. Cohort study of 97 patients undergoing single-fraction SRS from 2007 to 2014. Eligible patients had no prior pituitary irradiation, normal pre-SRS endocrine function, and >24mo of endocrine follow-up. Cox proportional hazards analysis was used to assess mean gland dose and BED as predictors of new post-SRS hypopituitarism. Median post-SRS follow-up was 48 mo (interquartile range [IQR], 34-68). A total of 27 patients (28%) developed new hypopituitarism at a median 22 mo (IQR, 12-36). Actuarial rates of new endocrinopathy were 17% at 2 yr (95% CI 10%-25%) and 31% at 5 yr (95% CI 20%-42%). On univariate analysis, sex (P=.02), gland volume (P=.03), mean gland dose (P<.0001), and BED significantly predicted new hypopituitarism (P<.0001). After adjusting for sex and gland volume, BED>45 Gy2.47 and mean gland dose>10Gy were significantly associated increased risk of hypopituitarism (hazard ratio [HR]=14.32, 95% CI=4.26-89.0, P<.0001; HR=11.91, 95% CI=3.54-74.0, P<.0001). BED predicted hypopituitarism more reliably than mean gland dose after pituitary adenoma SRS, but additional studies are needed to confirm these results.

Biological Dose Prediction Model with Deep Neural Networks on Bulky Thoracic Cancer Patients of Partial Stereotactic Ablation Radiotherapy: For Better Therapeutic Evaluation and Risk Assessment

Partial stereotactic ablation radiotherapy(P-SABR) could achieve encouraging local control rates for intractable bulky thoracic cancer. However, the range of ablation may increase the radiation risk of normal tissues surrounded. The purpose of this work was to develop a biological dose prediction model that considers tissue bioreaction in addition to patient anatomy to achieve more comprehensive evaluation for bulky thoracic tumor control and tissue toxicity. A newly developed deep learning architecture, Nestnet, was trained to establish the biological dose prediction model (D-B Nestnet). A database containing images and P-SABR plans of 94 bulky thoracic cancer patients was studied (74 patients for training/validation and 20 patients for testing). Patient-specific parameters of gross tumor ablation boost (GTVb) and other anatomical information, PTV and organs at risk (OAR), were extracted from the structure set. The linear quadratic (LQ)model applied to stereotactic radiotherapy and cell sensitivity for thoracic tissues in hyperfractionation radiotherapy were programmed to transfer the physical dose extracted from plans into biologically effective dose (BED). the training process was completed automatically after the validation loss continued for 100 epochs without fluctuation. We evaluated the model’s accuracy by comparing the minimum BED of GTVb and PTV, the maximum BED and the mean BED of all targets, BED-volume metrics for the predicted biological dose distribution against those of clinical delivered. We also trained a model based on the standard U-net architecture (D-B Unet) and compared the accuracy with the proposed model we mentioned before. The results demonstrate that the B-Nestnet model can predict clinically acceptable biological dose distributions. the average absolute biases of [max, mean] BED for GTVb, PTV are [2.1%, 3.3%] and [2.1%, 4.72%], respectively. Averaging across most of OARs, our proposed model is capable of predicting the errors of the max and mean BED within 6.3% and 6.1%, respectively. The standard D-B Unet performed worse, having averaged max and mean BED prediction errors within 9.9% and 9.7%, respectively. The new developed model, which predicts the biological dose instead of the physical dose, can still predict the distribution with reasonable accuracy. Using this model could provide a more intuitive prediction of tumor ablation and OARs risk. According to the prediction outcomes, clinicalists could modify the range of ablation for enhancing the BED of tumor or decreasing the risk of OARs toxicity. This novel D-B Nestnet model represents a major step forward towards P-SABR planning on bulky thoracic cancer in the real clinical practice.

Influence of Radiosurgery Dose on Pain Relief for Spinal Metastasis

Bone pain from spinal metastatic disease is an important influencer on quality of life in patients with metastatic disease. With advancements in treatment delivery techniques, stereotactic radiosurgery (SRS) is an emerging treatment approach for localized spinal metastases, though the optimal dose remains unclear. We evaluated pain response in patients with spinal metastases who were treated with SRS to determine if dose was a predictor of effective treatment. This was a study of patients from a prospective SRS Registry. Eligible patients received SRS for bone pain, had recorded pain scores before and after treatment, and had adequate follow-up to evaluate pain response. Radiation details including dose and fractionation were collected and converted to a biologically effective dose (BED) using an alpha/beta of 10. An effective treatment was defined as improvement in pain without pain recurrence or radiographic progression of the treated bone metastatic lesion. Ninety-seven patients met the eligibility criteria, with a median follow-up of 8.5 months. The median dose prescribed was 24 Gy (range 6 Gy- 35 Gy) and the median number of fractions used was 3 (range 3-5). The median BED was 41.6 Gy (range 15.7 Gy – 60 Gy). Effective treatment was achieved in 84 patients (86.6%). Seven patients (7.2%) with an initial pain response had either pain recurrence in the treated area or radiographic progression. Six patients (6.2%) did not have pain improvement. Thus, 13 treatments (13.4%) were considered ineffective. The mean BED for ineffective treatments was 35.3 Gy versus 42.0 Gy for effective treatment (p = .025). We found that effective SRS treatments were associated with higher BED. Although emerging randomized data (RTOG 0631) failed to demonstrate a difference in 3-month pain response between SRS and conventionally fractionated external beam radiotherapy, a higher dose on the SRS arm may have improved this outcome.

Gamma Knife radiosurgery for acromegaly: Evaluating the role of the biological effective dose associated with endocrine remission in a series of 42 consecutive cases.

Stereotactic radiosurgery (SRS) is a valuable treatment option for persistent and/or recurrent acromegaly secondary to growth hormone (GH) secreting pituitary adenoma (PA). Here, we assess the role of biological effective dose (BED) received by PA treated with SRS in relation with endocrine remission. Forty-two patients (minimum 6months follow-up) were included. Mean marginal dose was 27.7 (median 28, 20-35), and mean BED received by tumour was 193.1Gy2.47 (median 199.7, 64.1-237.1). Based on the median values, we divided the patients in high tumour BED group (H-BEDtm, 199.7-237.1Gy2.47, n=12) and low BED one (L- BEDtm, 64.1-199.7Gy2.47 , n=10). The two groups did not differ by pretherapeutic IGF-1 levels (p=.1) or by the prescribed dose (p=.6). Mean follow-up period was 62.5months (median 60.5, 9-127). Probability of IGF-1 normalization was 65% at 3years and 72.4% at 4years, remaining stable until last follow-up. Twenty-two (52.4%) patients had complete endocrine remission in absence of any Somatostatin analogues. Actuarial rates were 33% at 3years and 57.4% at 7years, further remaining stable during follow-up course. In univariate analysis, only statistically significant parameter was pretherapeutic serum IGF-1 and IGF-1 index (p=.01). Five patients (5/26, 19.3%) without previous hypopituitarism developed new pituitary insufficiency. H-BEDtm was associated with higher rates of endocrine remission compared with L-BEDtm, with actuarial probability of 70.2% versus 48.2% at 9years, although this did not reach statistical significance (p>.05). Our study confirms that SRS by Gamma Knife is safe and effective for GH-secreting PA. Pretherapeutic serum levels of IGF-1 were only statistically significant parameter for endocrine remission.

Biologically effective dose and prediction of obliteration of unruptured arteriovenous malformations treated by upfront Gamma Knife radiosurgery: a series of 149 consecutive cases.

Arteriovenous malformations (AVMs) present no pathologic tissue, and radiation dose is confined in a clear targeted volume. The authors retrospectively evaluated the role of the biologically effective dose (BED) after Gamma Knife radiosurgery (GKRS) for brain AVMs. A total of 149 consecutive cases of unruptured AVMs treated by upfront GKRS in Lille University Hospital, France, were included. The mean length of follow-up was 52.9 months (median 48, range 12-154 months). The primary outcome was obliteration, and the secondary outcome was complication appearance. The marginal dose was 24 Gy in a vast majority of cases (n = 115, 77.2%; range 18-25 Gy). The mean BED was 220.1 Gy2.47 (median 229.9, range 106.7-246.8 Gy2.47). The mean beam-on time was 32.3 minutes (median 30.8, range 9-138.7 minutes). In the present series, the mean radiation dose rate was 2.259 Gy/min (median 2.176, range 1.313-3.665 Gy/min). The Virginia score was 0 in 29 (19.5%), 1 in 61 (40.9%), 2 in 41 (27.5%), 3 in 18 (12.1%), and 4 in 0 (0%) patients, respectively. The mean Pollock-Flickinger score was 1.11 (median 1.52, range 0.4-2.9). Univariate (for obliteration and complication appearance) and multivariate (for obliteration only) analyses were performed. A total of 104 AVMs (69.8%) were obliterated at the last follow-up. The strongest predictor for obliteration was BED (p = 0.03). A radiosurgical obliteration score is proposed, derived from a fitted multivariable model: (0.018 × BED) + (1.58 × V12) + (-0.013689 × beam-on time) + (0.021 × age) - 4.38. The area under the receiver operating characteristic curve was 0.7438; after internal validation using bootstrap methods, it was 0.7088. No statistically significant relationship between radiation dose rate and obliteration was found (p = 0.29). Twenty-eight (18.8%) patients developed complications after GKRS; 20 (13.4%) of these patients had transient adverse radiological effects (perilesional edema developed). Predictors for complication appearance were higher prescription isodose volume (p = 0.005) and 12-Gy isodose line volume (V12; p = 0.001), higher Pollock-Flickinger (p = 0.02) and Virginia scores (p = 0.003), and lower beam-on time (p = 0.03). The BED was the strongest predictor of obliteration of unruptured AVMs after upfront GKRS. A radiosurgical score comprising the BED is proposed. The V12 appears as a predictor for both efficacy and toxicity. Beam-on time was illustrated as statistically significant for both obliteration and complication appearance. The radiation dose rate did not influence obliteration in the current analysis. The exact BED threshold remains to be established by further studies.

MP53-20 PREDICTING SURVIVAL OUTCOMES AFTER BRACHYTHERAPY USING THE AUA AND PHOENIX DEFINITION OF BIOCHEMICAL FAILURE

You have accessJournal of UrologyProstate Cancer: Localized: Radiation Therapy (MP53)1 Apr 2020MP53-20 PREDICTING SURVIVAL OUTCOMES AFTER BRACHYTHERAPY USING THE AUA AND PHOENIX DEFINITION OF BIOCHEMICAL FAILURE Zeynep G. Gul*, Rollin K. Say, Shirin Razdan, and Nelson N. Stone Zeynep G. Gul*Zeynep G. Gul* More articles by this author , Rollin K. SayRollin K. Say More articles by this author , Shirin RazdanShirin Razdan More articles by this author , and Nelson N. StoneNelson N. Stone More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000915.020AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Biochemical failure (BF) after radiation therapy is defined by the Phoenix definition as the nadir PSA +2. After radical prostatectomy, the AUA definition of BF is a PSA >0.2. The objective of the current study was to compare the AUA and Phoenix definitions of BF as predictors of distant metastasis (DM) and overall survival (OS). METHODS: 2319 men with T1-T4N0M0 prostate cancer were treated with brachytherapy. The mean follow-up was 105 months (8.75 years) and the mean biological effective dose (BED) was 195. Cox regression analysis were performed to determine the associations of AUA BF and Phoenix BF on DM and OS. The other variables included in the analysis were total BED, initial PSA, age at diagnosis, Gleason Score (6 vs 7-10), and clinical stage (T1/T2 vs T3/T4). RESULTS: BF occurred in 413 (17.8%) and 260 (11.2%) men according to the AUA and Phoenix definition, respectively. DM were seen in 71 patients (3.1%). 449 men (19.4%) died during follow up and 65 (2.8%) died from prostate cancer. Both the AUA and Phoenix definitions were significantly associated with DM and OS. CONCLUSIONS: The AUA and Phoenix definitions of BF are similar in their ability to predict DM and OS. Using the AUA definition would allow for better comparisons of outcomes following radical prostatectomy and brachytherapy. Source of Funding: None © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e790-e790 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Zeynep G. Gul* More articles by this author Rollin K. Say More articles by this author Shirin Razdan More articles by this author Nelson N. Stone More articles by this author Expand All Advertisement PDF downloadLoading ...

Image-guided intensity-modulated radiotherapy improves short-term survival for abdominal lymph node metastases from hepatocellular carcinoma.

Radiotherapy (RT) is an effective treatment for hepatocellular carcinoma (HCC) patients with lymph node metastasis (LNM), which is a rare clinical situation with a poor prognosis. We evaluated the responses and toxicities in HCC patients with abdominal LNM treated with either image-guided intensity-modulated radiotherapy (IG-IMRT) or non-IG-IMRT. Retrospective review of the records of HCC patients with regional LNM treated with IG-IMRT (n=43) or non-IG-IMRT (n=42). The tumor responses, local control rates (LCRs), overall survival (OS) rates, and toxicities were evaluated. The mean biological effective dose with α/β =10 Gy (BED10) delivered to IG-IMRT group was 67.23±8.48 vs. 63.43±5.01 Gy delivered to non-IG-IMRT group (P=0.008). OS in IG-IMRT group vs. non-IG-IMRT group was 15.3 vs. 9.7 months (P=0.098). The one-year survival of IG-IMRT group was superior (69% vs. 38.1% for non-IG-IMRT, P=0.006). Whereas two-year survival was not significantly different. Negative independent prognostic factors included ≥2 positive lymph nodes and previous treatment without surgery, while BED10 ≥65 Gy was a protective factor. Toxicities were mild for both groups, while IG-IMRT group showed less late hepatotoxicity. The therapeutic dose delivered by IG-IMRT is slightly higher than non-IG-IMRT which was more effective and showed superior short-term survival and local control in HCC patients with LNM.

Surgical Resection With Radiation Treatment Planning of Spinal Tumors.

The clinical paradigm for spinal tumors with epidural involvement is challenging considering the rigid dose tolerance of the spinal cord. One effective approach involves open surgery for tumor resection, followed by stereotactic body radiotherapy (SBRT). Resection extent is often determined by the neurosurgeon's clinical expertise, without considering optimal subsequent post-operative SBRT treatment. To quantify the effect of incremental epidural disease resection on tumor coverage for spine SBRT in an effort to working towards integrating radiotherapy planning within the operating room. Ten patients having undergone spinal separation surgery with postoperative SBRT were retrospectively reviewed. Preoperative magnetic resonance imaging was coregistered to postoperative planning computed tomography to delineate the preoperative epidural disease gross tumor volume (GTV). The GTV was digitally shrunk by a series of fixed amounts away from the cord (up to 6 mm) simulating incremental tumor resection and reflecting an optimal dosimetric endpoint. The dosimetric effect on simulated GTVs was analyzed using metrics such as minimum biologically effective dose (BED) to 95% of the simulated GTV (D95) and compared to the unresected epidural GTV. Epidural GTV D95 increased at an average rate of 0.88±0.09 Gy10 per mm of resected disease up to the simulated 6 mm limit. Mean BED to D95 was 5.3 Gy10 (31.2%) greater than unresected cases. All metrics showed strong positive correlations with increasing tumor resection margins (R2: 0.989-0.999, P<.01). Spine separation surgery provides division between the spinal cord and epidural disease, facilitating better disease coverage for subsequent post-operative SBRT. By quantifying the dosimetric advantage prior to surgery on actual clinical cases, targeted surgical planning can be implemented.

Clinical Results of Mean GTV Dose Optimized Robotic-Guided Stereotactic Body Radiation Therapy for Lung Tumors.

We retrospectively evaluated the efficacy and toxicity of gross tumor volume (GTV) mean dose optimized stereotactic body radiation therapy (SBRT) for primary and secondary lung tumors with and without robotic real-time motion compensation. Between 2011 and 2017, 208 patients were treated with SBRT for 111 primary lung tumors and 163 lung metastases with a median GTV of 8.2 cc (0.3-174.0 cc). Monte Carlo dose optimization was performed prioritizing GTV mean dose at the potential cost of planning target volume (PTV) coverage reduction while adhering to safe normal tissue constraints. The median GTV mean biological effective dose (BED)10 was 162.0 Gy10 (34.2-253.6 Gy10) and the prescribed PTV BED10 ranged 23.6-151.2 Gy10 (median, 100.8 Gy10). Motion compensation was realized through direct tracking (44.9%), fiducial tracking (4.4%), and internal target volume (ITV) concepts with small (≤5 mm, 33.2%) or large (>5 mm, 17.5%) motion. The local control (LC), progression-free survival (PFS), overall survival (OS), and toxicity were analyzed. Median follow-up was 14.5 months (1-72 months). The 2-year actuarial LC, PFS, and OS rates were 93.1, 43.2, and 62.4%, and the median PFS and OS were 18.0 and 39.8 months, respectively. In univariate analysis, prior local irradiation (hazard ratio (HR) 0.18, confidence interval (CI) 0.05-0.63, p = 0.01), GTV/PTV (HR 1.01-1.02, CI 1.01-1.04, p < 0.02), and PTV prescription, mean GTV, and maximum plan BED10 (HR 0.97-0.99, CI 0.96-0.99, p < 0.01) were predictive for LC while the tracking method was not (p = 0.97). For PFS and OS, multivariate analysis showed Karnofsky Index (p < 0.01) and tumor stage (p ≤ 0.02) to be significant factors for outcome prediction. Late radiation pneumonitis or chronic rip fractures grade 1-2 were observed in 5.3% of the patients. Grade ≥3 side effects did not occur. Robotic SBRT is a safe and effective treatment for lung tumors. Reducing the PTV prescription and keeping high GTV mean doses allowed the reduction of toxicity while maintaining high local tumor control. The use of real-time motion compensation is strongly advised, however, well-performed ITV motion compensation may be used alternatively when direct tracking is not feasible.

Five-year outcomes following hypofractionated stereotactic radiotherapy delivered in five fractions for acoustic neuromas: the mean cochlear dose may impact hearing preservation.

The aim of this study was to assess the clinical outcomes of acoustic neuromas (ANs) treated with hypofractionated stereotactic radiotherapy (hypo-FSRT) prescribed at a uniform dose. Forty-seven patients with a unilateral AN were treated consecutively with hypo-FSRT between February 2007 and March 2012. Nineteen patients maintained a serviceable hearing status at the beginning of hypo-FSRT. The prescribed dose was 25Gy delivered in five fractions per week to the isocenter, and the planning target volume was covered by the 80% isodose line. The median follow-up and audiometric follow-up periods were 61 and 52months, respectively. The estimated tumor control rate at 5years was 90% (95% CI 76-96). The existence of the cystic component before hypo-FSRT had a significantly worse impact on tumor control (p = 0.02). The estimated hearing preservation rates at 1, 3 and 5years were 68% (95% CI 42-84), 41% (95% CI 20-62) and 36% (95% CI 15-57), respectively. A borderline significant difference was identified in the mean biological effective dose with an α/β value of 3Gy (BED3) to the ipsilateral cochlea between the preserved hearing and hearing loss groups (19Gy vs. 28Gy) (p = 0.08). Hypo-FSRT delivered in five fractions for unilateral ANs may achieve excellent tumor control with no severe facial or trigeminal complications. The mean BED3 in the cochlea may impact the hearing preservation rate. Therefore, the cochlear dose should be as low as possible.

Derivation of mean dose tolerances for new fractionation schemes and treatment modalities

Avoiding toxicities in radiotherapy requires the knowledge of tolerable organ doses. For new, experimental fractionation schemes (e.g. hypofractionation) these are typically derived from traditional schedules using the biologically effective dose (BED) model. In this report we investigate the difficulties of establishing mean dose tolerances that arise since the mean BED depends on the entire spatial dose distribution, rather than on the dose level alone.A formula has been derived to establish mean physical dose constraints such that they are mean BED equivalent to a reference treatment scheme. This formula constitutes a modified BED equation where the influence of the spatial dose distribution is summarized in a single parameter, the dose shape factor. To quantify effects we analyzed 24 liver cancer patients for whom both proton and photon IMRT treatment plans were available.The results show that the standard BED equation—neglecting the spatial dose distribution—can overestimate mean dose tolerances for hypofractionated treatments by up to 20%. The shape difference between photon and proton dose distributions can cause 30–40% differences in mean physical dose for plans having identical mean BEDs. Converting hypofractionated, 5/15-fraction proton doses to mean BED equivalent photon doses in traditional 35-fraction regimens resulted in up to 10 Gy higher doses than applying the standard BED formula.The dose shape effect should be accounted for to avoid overestimation of mean dose tolerances, particularly when estimating constraints for hypofractionated regimens. Additionally, tolerances established for one treatment modality cannot necessarily be applied to other modalities with drastically different dose distributions, such as proton therapy. Last, protons may only allow marginal (5–10%) dose escalation if a fraction-size adjusted organ mean dose is constraining instead of a physical dose.

Lower mean heart dose with deep inspiration breath hold-whole breast irradiation compared with brachytherapy-based accelerated partial breast irradiation for women with left-sided tumors

PurposeFor left-sided breast cancer, radiation to the heart is a concern. We present a comparison of mean heart and coronary artery biologically effective dose (BED) between accelerated partial breast irradiation (APBI) and whole breast irradiation with deep inspiration breath-hold technique (DIBH-WBI). Methods and materialsA total of 100 patients with left-sided, early-stage breast cancer were identified. Fifty underwent single-entry catheter-based APBI and 50 underwent DIBH-WBI. The heart, left anterior descending/interventricular branch, left main, and right coronary artery were delineated. BEDs were calculated from APBI treatment plans (34 Gy in 3.4 Gy twice daily fractions) and for 4 separate plans generated for each DIBH-WBI patient: 50 Gy in 25 fractions (50/25), 50/25 + 10/5 boost, 40/15, and 40/15 + 10/5 boost. ResultsBED to the heart and coronary vessels were statistically significantly higher with APBI than with any of the DIBH-WBI dose/fractionation schedules. ConclusionsFor women with left-sided early-stage breast cancer, DIBH-WBI resulted in statistically significantly lower mean BED to the heart and coronary vessels compared with APBI. This is likely due to increased physical separation between the heart and tumor bed afforded by the DIBH-WBI technique. Long-term assessment of late effects in these tissues will be required to determine whether these differences are clinically significant.