OBJECTIVE: Recent studies have suggested that biologically effective dose (BED) is an important correlate of pain relief and sensory dysfunction after Gamma Knife radiosurgery (GKRS) for trigeminal neuralgia (TN). The goal of this study was to determine if BED is superior to prescription dose in predicting outcomes in TN patients undergoing GKRS as a first procedure.
METHODS: This was a retrospective study of 871 patients with type 1 TN from 13 GKRS centers. Patient demographics, pain characteristics, treatment parameters, and outcomes were reviewed. BED was compared with prescription dose and other dosimetric factors for their predictive value.
RESULTS: The median age of the patients was 68 years, and 60% were female. Nearly 70% of patients experienced pain in the V2 and/or V3 dermatomes, predominantly on the right side (60%). Most patients had modified BNI Pain Intensity Scale grade IV or V pain (89.2%) and were taking 1 or 2 pain medications (74.1%). The median prescription dose was 80 Gy (range 62.5-95 Gy). The proximal trigeminal nerve was targeted in 77.9% of cases, and the median follow-up was 21 months (range 6-156 months). Initial pain relief (modified BNI Pain Intensity Scale grades I-IIIa) was noted in 81.8% of evaluable patients at a median of 30 days. Of 709 patients who achieved initial pain relief, 42.3% experienced at least one pain recurrence after GKRS at a median of 44 months, with 49.0% of these patients undergoing a second procedure. New-onset facial numbness occurred in 25.3% of patients after a median of 8 months. Age ≥ 63 years was associated with a higher probability of both initial pain relief and maintaining pain relief. A distal target location was associated with a higher probability of initial and long-term pain relief, but also a higher incidence of sensory dysfunction. BED ≥ 2100 Gy2.47 was predictive of pain relief at 30 days and 1 year for the distal target, whereas physical dose ≥ 85 Gy was significant for the proximal target, but the restricted range of BED values in this subgroup could be a confounding factor. A maximum brainstem point dose ≥ 29.5 Gy was associated with a higher probability of bothersome facial numbness.
CONCLUSIONS: BED and physical dose were both predictive of pain relief and could be used as treatment planning goals for distal and proximal targets, respectively, while considering maximum brainstem point dose < 29.5 Gy as a potential constraint for bothersome numbness.

To recalculate biological effective dose values (BED) for radio-surgical treatments of acoustic neuroma from a previous study. BEDs values were previously overestimated by only using beam-on times in calculations, so excluding the important beam-off-times (when deoxyribonucleic acid repair continues) which contribute to the overall treatment time. Simple BED estimations using a mono-exponential approximation may not always be appropriate but if used should include overall treatment time.
Time intervals between isocenters were estimated. These were especially important for the Gamma Knife Model 4C cases since manual changes significantly increase overall treatment times. Individual treatment parameters, such as iso-center number, beam-on-time, and beam-off-time, were then used to calculate BED values using a more appropriate bi-exponential model that includes fast and slow components of DNA damage repair over a wider time range.
The revised BED estimates differed significantly from previously published values. The overestimates of BED, obtained using beam-on-time only, varied from 0%-40.3%. BED subclasses, each with a BED range of 5 Gy2.47, indicated that revised values were consistently reduced when compared with originally quoted values, especially for 4C compared with Perfexion cases. Furthermore, subdivision of 4C cases by collimator number further emphasized the impact of scheduled gap times on BED. Further analysis demonstrated important limitations of the mono-exponential model. Target volume was a major confounding factor in the interpretation of the results of this study.
BED values should be estimated by including beam-on and beam-off times. Suggestions are provided for more accurate BED estimations in future studies.

OBJECTIVE: The present biological modeling study evaluated possible application of adaptive hypofractionated stereotactic radiosurgery (HSRS), which involves escalation of the prescription dose according to the gradual decrease in the tumor volume between treatment sessions separated by 2- to 3-week intervals, in the management of large brain metastases.
METHODS: To investigate the effects of dose escalation during three-stage adaptive HSRS, a generalized biologically effective dose (gBED) model was applied. Accounting for both a nonuniform dose distribution inside the target and tumor hypoxia was implemented, and normal brain radiation dose distributions were assessed.
RESULTS: In comparison with conventional three-stage HSRS (with an identical prescription dose of 10 Gy at each treatment session), adaptive HSRS resulted in a 30-40% increase in gBED. This effect was especially prominent in late-responding targets (with α/β ratios from 3 to 10 Gy) and in neoplasms containing a high percentage of hypoxic cells. Despite dose escalation in the target, irradiation of the adjacent normal brain tissue was kept within safe limits at a level similar to that applied in conventional three-stage HSRS.
CONCLUSIONS: Adaptive HSRS theoretically results in significant enhancement of gBED in the target and may possibly overcome resistance to irradiation, which is caused by tumor hypoxia. These advantages may translate into higher treatment efficacy in cases of large brain metastases.

OBJECTIVE: The present proof-of-principle study investigated radiobiological effects of redistributing central target dose hot spots across different treatment fractions during hypofractionated stereotactic radiosurgery (HSRS) of large intracranial tumors.
METHODS: Redistribution of central target dose hot spots during HSRS was simulated, and its effects were evaluated in eight cases of brain metastases. To assess dose variations in the target across N number of treatment fractions, a generalized biologically effective dose (gBED) was formulated. The gBED enhancement ratio was defined as the ratio of gBED in the tested treatment plan (with central target dose hot spot redistributions across fractions) to gBED in the conventional treatment plan (without central target dose hot spot redistributions).
RESULTS: At a median α value of 0.3/Gy, the tested treatment plans resulted in average gBED increases of 15.6 ± 3.5% and 8.3 ± 1.8% for α/β ratios of 2 and 10 Gy, respectively. In comparison with conventional treatment plans, the differences in the Paddick conformity index and gradient index did not exceed 2%.
CONCLUSIONS: Redistributing central target dose hot spots across different treatment fractions during HSRS may be considered promising for enhancing gBED in the target. It may be beneficial for management of large intracranial neoplasms; thus, it warrants further clinical testing.

Stereotactic radiosurgery (SRS) is a safe and effective treatment for acromegaly.
To improve understanding of clinical and dosimetric factors predicting biochemical remission.
A single-institution cohort study of nonsyndromic, radiation-naïve patients with growth hormone-producing pituitary adenomas (GHA) having single-fraction SRS between 1990 and 2017. Exclusions were treatment with pituitary suppressive medications at the time of SRS, or <24 mo of follow-up. The primary outcome was biochemical remission-defined as normalization of insulin-like growth factor-1 index (IGF-1i) off suppression. Biochemical remission was assessed using Cox proportional hazards. Prior studies reporting IGF-1i were assessed via systematic literature review and meta-analysis using random-effect modeling.
A total of 102 patients met study criteria. Of these, 46 patients (45%) were female. The median age was 49 yr (interquartile range [IQR] = 37-59), and the median follow-up was 63 mo (IQR = 29-100). The median pre-SRS IGF-1i was 1.66 (IQR = 1.37-3.22). The median margin dose was 25 Gy (IQR = 21-25); the median estimated biologically effective dose (BED) was 169.49 Gy (IQR = 124.95-196.00). Biochemical remission was achieved in 58 patients (57%), whereas 22 patients (22%) had medication-controlled disease. Pre-SRS IGF-1i ≥ 2.25 was the strongest predictor of treatment failure, with an unadjusted hazard ratio (HR) of 0.51 (95% CI = 0.26-0.91, P = .02). Number of isocenters, margin dose, and BED predicted remission on univariate analysis, but after adjusting for sex and baseline IGF-1i, only BED remained significant-and was independently associated with outcome in continuous (HR = 1.01, 95% CI = 1.00-1.01, P = .02) and binary models (HR = 2.27, 95% CI = 1.39-5.22, P = .002). A total of 24 patients (29%) developed new post-SRS hypopituitarism. Pooled HR for biochemical remission given subthreshold IGF-1i was 2.25 (95% CI = 1.33-3.16, P < .0001).
IGF-1i is a reliable predictor of biochemical remission after SRS. BED appears to predict biochemical outcome more reliably than radiation dose, but confirmatory study is needed.

BACKGROUND: There is a lack of data on the biologically effective dose and the efficacy of stereotactic body radiotherapy in hepatocellular carcinoma patients, and this study was conducted to explore the relation between BED and efficacy.
METHODS: This study is designed as a mono-center study. The participants are randomized into three group, and received the following recommended schedule: 49Gy/7f, 54Gy/6f and 55Gy/5f with BED10 in correspondence to 83.3Gy, 102.6Gy and 115.5Gy. The primary outcome measures are to calculate local control rates (LC), overall survival rates (OS) and progression-free survival rates (PFS). The secondary outcome measures are to observe radiation-induced liver injury (RILD) rates, Child-Pugh score and indocyanine green retention rate at 15 min (ICG-R15) value before and after CK-SBRT. Moreover, gastrointestinal toxicities are also observed.
CONCLUSIONS: There is no uniform standard for CK-SBRT dose schedule of hepatocellular carcinoma. We propose to conduct a study determining the optimal CK-SBRT schedule of hepatocellular carcinoma patients (≤5 cm). The trial protocol has been approved by the Institutional Review Board of 302 Hospital of PLA (People\'s Liberation Army). The Ethics number is 2017111D.
BACKGROUND: Clinical trails number: NCT03295500. Date of registration: November, 2017.

We performed a case-control study to characterize the dose-volume relationship and other variables leading to hypothyroidism after head and neck (H&N) cancer radiation therapy (RT) in a homogenous Veterans Affairs (VA) population. All records of patients receiving RT for various H&N cancers at a single VA medical center between 2007 and 2013 (n = 143) were screened for post-RT thyroid stimulating hormone (TSH) levels (n = 77). The thyroid gland was contoured on each slice of the planning computed tomography scan when available (hypothyroid: n = 18; euthyroid > 2 years: n = 16), and dose-volume histograms based on physical dose and biologically equivalent dose (BED) were compared systematically to find the significant dose-volume thresholds that distinguish the patients who developed clinical hypothyroidism. Dosimetric and clinical variables were considered in univariate and multivariate analysis. Preirradiation prevalence of hypothyroidism was 8 of 143 (5.6%). After RT, 36 of 77 (47%) screened patients had abnormally high TSH, of which 22 of 36 (61%) had clinical hypothyroidism after 1.29 ± 0.99 years. The median follow-up durations were 3.3 years and 4.7 years for euthyroid and hypothyroid patients, respectively. Compared with the euthyroid cohort (n = 41), these hypothyroid patients displayed no significant difference in age, gender, primary tumor site, thyroid volume, hypertension, diabetes, or use of chemotherapy, surgery, or intensity-modulated radiation therapy (IMRT). They were more likely to have had stage 3 or 4 cancer than euthyroid patients (86.5% vs 73.2%, p = 0.01). The odds ratios of hypothyroidism for stage 3 + 4 cancers and V50Gy < 75% were 5.0 and 0.2, respectively (p < 0.05). Equivalent BED threshold of V75Gy3 < 75% gave an odds ratio of 0.156 for developing hypothyroidism (p = 0.02). The prevalence of post-RT clinical hypothyroidism was relatively high for patients with H&N cancers and warrants routine surveillance, especially in those with higher stage malignancy. V50Gy < 75% may be a useful guideline to avoid hypothyroidism. We also show BED data which could be used for unconventionally fractionated schemes, and V75Gy3 < 75% may be a useful guideline.

BACKGROUND: This study aimed to highlight the type of tumor thrombus and identify the prognostic factors influencing the long-term survival outcomes in patients with hepatocellular carcinoma (HCC) having a tumor thrombus. A tumor thrombus in HCC is associated with poor prognosis.
METHODS: Eighty patients diagnosed with HCC having a tumor thrombus between May 2006 and April 2014 were enrolled in this study. Age, gender, clinical characteristics, laboratory findings, Child-Pugh classification, performance status (ECOG), types of tumor thrombi, radiotherapy method, biologically effective dose (BED), and primary treatment method were analyzed to identify the prognostic factors associated with the overall survival (OS) rates. Statistical analyses were performed using SPSS version 19.0.
RESULTS: The median follow-up duration was 24 months (range 6-90). The 1-, 3-, and 5-year OS rates of the patients were 77.6%, 37.6%, and 18.8%, respectively. On univariate analysis, gender, radiotherapy method, BED, types of tumor thrombi, Child-Pugh classification, ECOG, and total bilirubin were associated with OS (P < 0.001, P = 0.001, P = 0.016, P = 0.003, P < 0.001, P < 0.001, P = 0.039, respectively). The prognostic factors for OS in multi-variate analyses were gender (P < 0.001), BED (P = 0.044), Child Pugh classification (P = 0.020), performance status (ECOG) (P = 0.004), and types of tumor thrombi (P = 0.001). The median OS for the high-BED group was better than that for the low-BED groups (42 months vs. 19 months, P = 0.016).
CONCLUSIONS: Gender, BED, performance status (ECOG), Child-Pugh classification, and types of tumor thrombi seemed to affect OS, and a stepwise decrease in survival was observed with the types of tumor thrombi ranging from I to IV. High-BED palliative radiotherapy might improve the long-term outcomes for patients with HCC having a tumor thrombus.

The aim of this study was to examine the applicability of the linear-quadratic (LQ) model to single and fractionated irradiation in EMT6 cells. First, the α/β ratio of the cells was determined from single-dose experiments, and a biologically effective dose (BED) for 20 Gy in 10 fractions (fr) was calculated. Fractional doses yielding the same BED were calculated for 1-, 2-, 3-, 4-, 5-, 7-, 15- and 20-fraction irradiation using LQ formalism, and then irradiation with these schedules was actually given. Cell survival was determined by a standard colony assay. Differences in cell survival between pairs of groups were compared by t-test. The α/β ratio of the cells was 3.18 Gy, and 20 Gy in 10 fr corresponded to a BED3.18 of 32.6 Gy. The effects of 7-, 15- and 20-fraction irradiation with a BED3.18 of 32.6 Gy were similar to those of the 10-fraction irradiation, while the effects of 1- to 5-fraction irradiation were lower. In this cell line, the LQ model was considered applicable to 7- to 20-fraction irradiation or doses per fraction of 2.57 Gy or smaller. The LQ model might be applicable in the dose range below the α/β ratio.