Cost-Utility Analysis Compared Between Radiotherapy Alone and Combined Surgery and Radiotherapy for Symptomatic Spinal Metastases in Thailand.

OBJECTIVE: To investigate the patient quality of life and cost-utility compared between radiotherapy alone and combined surgery and radiotherapy for spinal metastasis (SM) in Thailand. METHODS: Patients with SM with an indication for surgery during 2018-2020 were prospectively recruited. Patients were assigned to either the combination surgery and radiotherapy group or the radiotherapy alone group. Quality of life was assessed by EuroQol-5D-5L (EQ-5D-5L) questionnaire, and relevant healthcare costs were collected pretreatment, and at 3-month and 6-month posttreatment. Total lifetime cost and quality-adjusted life-years (QALYs) were estimated for each group. RESULTS: Twenty-four SM patients (18 females, 6 males) were included. Of those, 12 patients underwent combination treatment, and 12 underwent radiotherapy alone. At 6-month posttreatment, 10 patients in the surgery group, and 11 patients in the nonsurgery group remained alive for a survival rate of 83.3% and 91.7%, retrospectively. At 6-month posttreatment, the mean utility in the combination treatment group was significantly better than in the radiotherapy alone group (0.804 ± 0.264 vs. 0.518 ± 0.282, respectively; p = 0.011). Total lifetime costs were 59,863.14 United States dollar (USD) in the combination treatment group and 24,526.97 USD in the radiation-only group. The incremental cost-effectiveness ratio using 6-month follow-up data was 57,074.01 USD per QALY gained. CONCLUSION: Surgical treatment combined with radiotherapy to treat SM significantly improved patient quality of life compared to radiotherapy alone during the 6-month posttreatment period. However, combination treatment was found not to be cost-effective compared to radiotherapy alone for SM at the Thailand willingness-to-pay threshold of 5,113 USD/QALY.

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.

Influence of hydrogel spacer placement with prostate brachytherapy on rectal and urinary toxicity.

OBJECTIVE: To determine the influence of rectal hydrogel spacer placement (HSP) on late rectal toxicity outcomes in prostate cancer patients treated with low-dose-rate (LDR) brachytherapy, with or without supplemental external beam radiotherapy (EBRT). PATIENTS AND METHODS: A total of 224 patients underwent LDR brachytherapy with HSP, as monotherapy or combined with EBRT, between January 2016 and December 2019. Dosimetric variables reflecting the extent of rectal sparing and late rectal toxicity outcomes were evaluated. This spacer cohort was retrospectively compared to a similar patient group (n = 139) in whom HSP was not used. RESULTS: Hydrogel spacer placement was associated with significantly reduced rectal doses for all dosimetric variables; the median percentage rectal dose to 1 cc of rectum and rectal dose to 2 cc of rectum of the spacer cohort were all significantly lower compared to the non-spacer cohort. The incidence rates of overall (any grade) and grade ≥2 rectal toxicity were lower in patients with HSP compared to patients who did not undergo HSP: 12% and 1.8% vs 31% and 5.8%, respectively. The 3-year cumulative incidence of overall rectal toxicity was significantly lower with HSP than without (15% vs 33%; P < 0.001), corresponding to an overall rectal toxicity reduction on univariable analysis (hazard ratio 0.45, 95% confidence interval 0.28-0.73; P = 0.001). In this patient cohort treated with prostate brachytherapy, none of the urethral dosimetric variables or the presence or absence of HSP was associated with late urinary toxicity. CONCLUSION: Hydrogel rectal spacer placement is a safe procedure, associated with significantly reduced rectal dose. HSP translates to a decrease in overall late rectal toxicity in patients receiving dose-escalated brachytherapy-based procedures.

Diagnostic performance of 18F-fluciclovine PET/CT in prostate cancer patients with rising PSA level ≤ 0.5 ng/ml after multiple treatment failures.

This retrospective study is to assess the performance of 18F-Fluciclovine PET/CT in prostate cancer (PC) patients with multiple treatment failures and prostate-specific antigen (PSA) ≤ 0.5 ng/mL. PC patients with multiple treatment failures who had PSA level within 2-week interval of 18F-Fluciclovine PET/CT (PSAPET) ≤ 0.5 ng/mL were identified in retrospective review of our institution's database (n=28). Patient, tumor, treatment, PSA and castration characteristics as well as findings on 18F-Fluciclovine PET/CT were collected and compared between positive and negative 18F-Fluciclovine PET/CT subgroups by using Fisher's exact test. The overall detection rate of 18F-Fluciclovine PET/CT was 7 of 28 studies (25%). PSAPET > 0.2 ng/mL was associated with higher detection rates in all (33.3 vs 10%, P=0.172), castration-resistant (CR) (50 vs 20%, P=0.343) and castration-sensitive (CS) (28.6 vs 0%, P=0.179) patients. Sites of recurrence were local 42.9% (3/7), nodal 42.9% (3/7) and bone metastases 14.3% (1/7). Higher Gleason score (GS 8-10) (33.3 vs 14.5%, P=0.396), advanced tumor stage (T3-T4) (35.7 vs 20%, P=0.653), second-line androgen deprivation therapy (ADT) uses (66.7 vs 20%, P=0.145), chemotherapy uses (50 vs 23.1%, P=0.444) and CRPC (33.3 vs 21.1%, P=0.483) related to positivity of 18F-Fluciclovine PET/CT but none reached statistical significance. Performance of 18F-Fluciclovine PET/CT in prostate cancer patients with multiple treatment failures and PSAPET ≤ 0.5 ng/mL was acceptable particularly in patients with PSAPET ≥ 0.3 ng/mL, CRPC, initial GS ≥ 8 or T3-T4.

Outcome comparison of patients who develop leptomeningeal disease or distant brain recurrence after brain metastases resection cavity radiosurgery.

BACKGROUND: To compare the outcomes between patients with leptomeningeal disease (LMD) and distant brain recurrence (DBR) after stereotactic radiosurgery (SRS) brain metastases (BM) resection cavity. METHODS: Twenty-nine patients having single-fraction SRS after BM resection who developed either LMD (n = 11) or DBR (n = 18) as their initial and only site of intracranial progression were retrospectively reviewed. RESULTS: Patients developing LMD more commonly had a metachronous presentation (91% vs 50%, P = .04) and recursive partitioning class 1 status (45% vs 6%, P = .02). There was no difference in the median time from SRS to the development of LMD or DBR (5.0 vs 3.8 months, P = .68). The majority of patients with LMD (10/11, 91%) developed the nodular variant (nLMD). Treatment for LMD was repeat SRS (n = 4), whole-brain radiation therapy (WBRT; n = 5), resection + WBRT (n = 1), and no treatment (n = 1). Treatment for DBR was repeat SRS (n = 9), WBRT (n = 3), resection + resection cavity SRS (n = 1), and no treatment (n = 5). Median overall survival (OS) from time of resection cavity SRS was 15.7 months in the LMD group and 12.7 months in the DBR group (P = .60), respectively. Median OS in salvage SRS and salvage WBRT were 25.4 and 5.0 months in the nLMD group (P = .004) while 18.7 and 16.2 months in the DBR group (P = .30), respectively. CONCLUSIONS: Following BM resection cavity SRS, nLMD recurrence is much more frequent than classical LMD. Salvage SRS may be considered for selected patients with nLMD, reserving salvage WBRT for patients with extensive intracranial disease without compromising survival. Further study with larger numbers of patients is needed.

Does the dural resection bed need to be irradiated? Patterns of recurrence and implications for postoperative radiotherapy for temporal lobe gliomas.

BACKGROUND: Patterns of recurrence and survival with different surgical and radiotherapy (RT) techniques were evaluated to guide RT target volumes for patients with temporal lobe glioma. METHODS AND MATERIALS: This retrospective cohort study included patients with World Health Organization grades II to IV temporal lobe glioma treated with either partial (PTL) or complete temporal lobectomy (CTL) followed by RT covering both the parenchymal and dural resection bed (whole-cavity radiotherapy [WCRT]) or the parenchymal resection bed only (partial-cavity radiotherapy [PCRT]). Patterns of recurrence, progression-free survival (PFS) and overall survival (OS) were evaluated. RESULTS: Fifty-one patients were included and 84.3% of patients had high-grade glioma (HGG). CTL and PTL were performed for 11 (21.6%) and 40 (78.4%) patients, respectively. Median RT dose was 60 Gy (range, 40-76 Gy). There were 82.4% and 17.6% of patients who received WCRT and PCRT, respectively. Median follow-up time was 18.4 months (range, 4-161 months). Forty-six patients (90.2%) experienced disease recurrence, most commonly at the parenchymal resection bed (76.5%). No patients experienced an isolated dural recurrence. The median PFS and OS for the PCRT and WCRT cohorts were 8.6 vs 10.8 months (P = .979) and 19.9 vs 18.6 months (P = .859), respectively. PCRT was associated with a lower RT dose to the brainstem, optic, and ocular structures, hippocampus, and pituitary. CONCLUSION: We identified no isolated dural recurrence and similar PFS and OS regardless of postoperative RT volume, whereas PCRT was associated with dose reduction to critical structures. Omission of dural RT may be considered a reasonable alternative approach. Further validation with larger comparative studies is warranted.

Predictors for post-treatment biopsy outcomes after prostate stereotactic body radiotherapy.

PURPOSE: To investigate predictors associated with post-treatment biopsy outcomes after stereotactic body radiotherapy (SBRT) for localized prostate cancer. MATERIALS AND METHODS: 257 patients treated with prostate SBRT to dose levels of 32.5 Gy to >40 Gy in 5-6 fractions underwent a post-treatment biopsy performed approximately two years after treatment to evaluate local control status. 73 had% intermediate-risk disease (n = 187) and the remaining 17% (n = 43) and 10% (n = 27) had low-risk and high-risk disease, respectively. RESULTS: The incidence of positive, negative, and treatment-effect post-treatment biopsies were 15.6%, 57.6%, and 26.8%, respectively. The incidence of a positive biopsy according to dose was 37.5% (n = 9/24), 21.4% (n = 6/28), 19.4% (n = 6/31), and 10.9% (n = 19/174) for 32.5 Gy, 35 Gy, 37.5 Gy, and >40 Gy, respectively. In a multivariable model, patients treated with SBRT doses of <40 Gy and those with unfavorable-intermediate-risk or high-risk disease had higher likelihood of a positive post-treatment biopsy. A positive post-SBRT biopsy was associated with a significantly higher likelihood of subsequent PSA relapse at five years (Positive biopsy: 57%, 95% CI: 29-77% compared to negative biopsy: 7%, 95% CI: 3-14%; p < 0.001). CONCLUSION: Based on two-year post-SBRT biopsies, excellent tumor control was achieved when dose levels of 40 Gy or higher were used. Standard SBRT dose levels of 35-37.5 Gy were associated with a higher likelihood of a positive post-treatment biopsy. Two-year positive post-treatment biopsies pre-dated the development of PSA failure in the majority of patients.

Disease control and failure patterns of unresectable hepatocellular carcinoma following transarterial radioembolization with yttrium-90 microspheres and with/without sorafenib.

BACKGROUND: Impressive survival outcome of our previous study in unresectable hepatocellular carcinoma (HCC) patients undergoing yttrium-90 glass microspheres transarterial radioembolization (TARE) with/without sorafenib according to individuals' disease burden, i.e., intrahepatic tumor load (IHT) and adverse disease features (ADFs) might partly be confounded by other treatments and underlying hepatic function. Therefore, a dedicated study focusing on treatment response and assessment of failure patterns might be a way to improve treatment outcome in addition to patient selection based on the disease burden. AIM: To assess the tumor response, disease control and patterns of disease progression following TARE with/without sorafenib in unresectable HCC patients. METHODS: This retrospective study was conducted in successful TARE procedures with available pre- and post-treatment imaging studies (n = 169). Three treatment subgroups were (1) TARE only (TARE_alone) for IHT ≤ 50% without ADFs, i.e., macrovascular invasion, extrahepatic disease (EHD) and infiltrative/ill-defined HCC (n = 63); (2) TARE with sorafenib (TARE_sorafenib) for IHT > 50% and/or presence of ADFs (n = 81); and (3) TARE only for patients who could not receive sorafenib due to contraindication or intolerance (TARE_no_sorafenib) (n = 25). Objective response rate (ORR; consisted of complete response (CR) and partial response (PR)), disease control rate (DCR; consisted of CR, PR and stable disease) and failure patterns of treated, intrahepatic and extrahepatic sites were assessed using the modified response evaluation criteria in solid tumors. Time to progression (TTP) was calculated from TARE to the first radiologic progression at any site using Kaplan-Meier method. Identification of prognostic factors for TTP using the univariate Kaplan-Meier method and multivariate Cox proportional hazard model were performed in major population subgroups, TARE_alone and TARE_sorafenib. RESULTS: The median radiologic follow-up time was 4.4 mo (range 0.5-48.8). In treated area, ORR was highest in TARE_sorafenib (53.1%), followed by TARE_alone (41.3%) and TARE_no_sorafenib (16%). In intrahepatic area, DCR remained highest in TARE_sorafenib (84%), followed by TARE_alone (79.4%) and TARE_no_sorafenib (44%). The overall DCR was highest in TARE_alone (79.4%), followed by TARE_sorafenib (71.6%) and TARE_no_sorafenib (40%). Dominant failure patterns were intrahepatic for both TARE_alone (44.5%) and TARE_sorafenib (38.4%). Extrahepatic progression was more common in TARE_sorafenib (32%) and TARE_no_sorafenib (40%) than in TARE_alone (12.7%). TTP was longest in TARE_alone (8.6 mo; 95%CI: 3.4-13.8), followed by TARE_sorafenib (5.1 mo; 95%CI: 4.0-6.2) and TARE_no_sorafenib (2.7 mo; 95%CI: 2.2-3.1). Pre-existing EHD (HR: 0.37, 95%CI: 0.24-0.56, P < 0.001) was a sole prognostic factor for TTP in TARE_sorafenib with no prognostic factor for TTP in TARE_alone. CONCLUSION: TARE with/without sorafenib according to individuals' disease burden provided DCR approximately 70% with intrahepatic progression as dominant failure pattern. Extrahepatic progression was more common in procedures with initially high disease burden.

Survival Outcomes for Yttrium-90 Transarterial Radioembolization With and Without Sorafenib for Unresectable Hepatocellular Carcinoma Patients.

PURPOSE: To assess the overall survival (OS) and progression-free survival (PFS) of unresectable hepatocellular carcinoma (HCC) patients undergoing yttrium-90 glass-microsphere transarterial radioembolization (TARE) with and without concurrent sorafenib. METHODS: OS and PFS were analyzed in 55 patients with an intrahepatic tumor (IHT) ≤50% without advanced or aggressive disease features (ADFs), which was referred to presence of infiltrative/ill-defined HCC, macrovascular invasion, or extrahepatic disease treated with only TARE (TARE_alone) and in 74 patients with IHT ≤50% with ADFs or IHT >50% treated with TARE and sorafenib (TARE_sorafenib). Prognostic factors for OS and PFS were identified using univariate and multivariate analyses. RESULTS: Median OS and PFS of TARE_alone patients were 21.6 (95% CI 6.1-37.1) and 9.1(95% CI 5.2-13.0) months, respectively, and for TARE_sorafenib patients 12.4 (95% CI 9.1-15.6) and 5.1 (95% CI 2.6-7.5) months, respectively. Better OS was associated with serum AFP <400 (HR 0.27, p=0.02) in TARE_alone, and IHT ≤50% (HR 0.39, p=0.004) and AFP <400 (HR 0.5, p=0.027) in TARE_sorafenib. Unilobar involvement (HR 0.43, p=0.029) and AFP <400 ng/mL (HR 0.52, p=0.015) correlated with better PFS in TARE_alone and TARE_sorafenib, respectively. Adverse events (AEs) were more frequent in TARE_sorafenib than TARE_alone (92.4 vs 80.3%), but only 9.3% were grade 3 or higher AEs. CONCLUSION: TARE_alone provided the most prominent survival benefit in IHT ≤50%-without ADF patients who had unilobar HCC and serum AFP <400 ng/mL. TARE and sorafenib yielded the best outcomes in patients with IHT ≤50% and serum AFP <400 ng/mL, with some additional grade 1-2 AEs compared to TARE only.

Diagnostic performance of F-18 fluciclovine PET/CT in post-radical prostatectomy prostate cancer patients with rising prostate-specific antigen level ≤0.5 ng/mL.

PURPOSE: The aim of the study was to assess the diagnostic performance of fluciclovine positron emission tomography (PET)/computerized tomography (CT) in post-radical prostatectomy prostate cancer patients with rising prostate-specific antigen (PSA) ≤0.5 ng/mL, and identify the associated predictive factors of positive studies. PATIENTS AND METHODS: From 30 June 2017 to 9 August 2019, patients with post-radical prostatectomy prostate cancer who underwent F-18 fluciclovine PET/CT and had PSA level within 2-week interval (PSAPET) ≤0.5 ng/mL were enrolled into this single-institution retrospective study. Data on tumor characteristics, including Gleason scores, extra-prostatic extension, seminal vesicle invasion, surgical margin and nodal metastasis, PSA after radical prostatectomy, previous hormonal therapy, PSA doubling time (PSADT), scanner type, PSAPET and site of recurrence were collected. Comparison of these factors between groups of positive and negative fluciclovine PET/CT was done by using Mann-Whitney U-test and Fisher's exact test. RESULTS: Of 94 eligible patients with post-radical prostatectomy prostate cancer, 10 patients had positive studies (10.6%). Detection rate at PSAPET 0.1, 0.2, 0.3, 0.4 and 0.5 ng/mL were 0% (0/11), 0% (0/15), 20% (6/30), 4% (1/25) and 23.1% (3/13), respectively. Upon multivariate analysis of clinical factors, only a PSADT <3 months (P = 0.023) was shown to have a statistically significant correlation with a positive study. CONCLUSION: In post-radical prostatectomy prostate cancer patients with rising PSA 0.1-0.5 ng/mL, the sensitivity of F-18 fluciclovine PET/CT for identifying tumor recurrence/metastases is poor with an overall detection rate of 10.6%. Larger prospective studies are required to validate these findings.

Is There Any Role for 18F-Fluciclovine PET/CT in the Presence of Undetectable PSA in Prostate Cancer Patients After Definitive Treatment?

PURPOSE: The aim of this study was to investigate the role of F-fluciclovine PET/CT in the evaluation of prostate cancer (PC) patients after definitive treatment in the presence of undetectable prostate-specific antigen (PSA). PATIENTS AND METHODS: This retrospective study was conducted in PC patients who had undetectable PSA level and underwent fluciclovine PET/CT within a 2-week interval of PSA examination and without interval treatment or other cancer. Patient and tumor characteristics at initial diagnosis, treatment regimens, and findings on fluciclovine PET/CT were collected. Comparisons between groups of positive and negative fluciclovine PET/CT were done by using descriptive statistics. RESULTS: A total of 34 fluciclovine PET/CTs from 34 patients met the inclusion criteria. There were 4 positive (11.8%) and 30 negative fluciclovine PET/CTs (88.2%). All of the patients with positive results had an initial Gleason score of 7 or higher and locally advanced tumor (T3-T4). More common features at the time of diagnosis among positive study patients as compared with negative ones were atypical histologic variants (25% vs 0%) and very high-risk PC (50% vs 30%). Most of the patients with positive study received second-line hormonal therapy (HT) (50%), whereas patients with negative results received first-line HT (53.3%). Chemotherapy naivety was less common among positive patients (75% vs 96.7%). Sites of involvement on positive fluciclovine PET/CTs were pelvic lymph nodes (2/4, 50%), lung and mediastinal lymph node (1/4, 25%), and prostatectomy bed (1/4, 25%). CONCLUSIONS: In the presence of undetectable PSA in PC patients after definitive treatment, fluciclovine PET/CT would benefit most to patients with Gleason score of 7 or higher, high disease burden (T3-T4), and atypical histologic variants at the time of diagnosis, and the ones who have history of second-line HT and/or chemotherapy.

Brain metastases resection cavity radio-surgery based on T2-weighted MRI: technique assessment.

PURPOSE: Stereotactic radiosurgery (SRS) is commonly performed after surgical resection of brain metastases to reduce the chance of local tumor recurrence while maintaining cognitive function. Target delineation in these cases is typically based off T1-weighted post-gadolinium MRI (T1Gd). In this study, we report outcomes for patients having postoperative SRS in which the planning target volume (PTV) was based on T2-weighted MRI (T2W). METHODS: Sixty-two consecutive patients having single-fraction SRS after brain metastases resection were retrospectively reviewed. Excluded were patients with prior whole brain radiation therapy, multiple resection cavities, and small cell pathologies. RESULTS: The median time from surgery to SRS was 11 days; 26 patients (42%) had SRS ≤ 7 days. The median PTV was 8.0 cm3; the median margin dose was 18 Gy. The crude rates of local tumor control (LC), leptomeningeal disease (LMD), distant brain recurrence (DBR), and radiation necrosis (RN) were 85%, 19%, 37%, and 2%, respectively. The 1-year LC, LMD, DBR, and RN rates were 88%, 25%, 36%, and 0%, respectively. No tumor or dosimetric factor was associated with LC. Sub-total tumor resection was a risk factor for LMD (HR 5.11, P = 0.003), whereas patients with multiple brain metastases had a greater risk of DBR (HR 2.88, P = 0.01). The median PTV was smaller compared to the median PTV based off the consensus guidelines utilizing T1Gd MRI (8.0 cm3 vs. 9.1 cm3, P = 0.004). CONCLUSION: T2W MRI provided accurate resection cavity delineation even in the early postoperative period and was associated with decreased PTV compared to T1Gd MRI in the majority of cases.

Dose-escalated intensity-modulated radiotherapy and irradiation of subventricular zones in relation to tumor control outcomes of patients with glioblastoma multiforme.

BACKGROUND: Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor with high relapse rate. In this study, we aimed to determine if dose-escalated (DE) radiotherapy improved tumor control and survival in GBM patients. METHODS: We conducted a retrospective analysis of 49 and 23 newly-diagnosed histology-proven GBM patients, treated with DE radiotherapy delivered in 70 Gy (2.33 Gy per fraction) and conventional doses (60 Gy), respectively, between 2007 and 2013. Clinical target volumes for 70 and 60 Gy were defined by 0.5 and 2.0 cm expansion of magnetic resonance imaging T1-gadolinium-enhanced tumor/surgical cavity, respectively. Bilateral subventricular zones (SVZ) were contoured on a co-registered pre-treatment magnetic resonance imaging and planning computed tomography dataset as a 5 mm wide structure along the lateral margins of the lateral ventricles. Survival outcomes of both cohorts were compared using log-rank test. Radiation dose to SVZ in the DE cohort was evaluated. RESULTS: Median follow-up was 13.6 and 15.1 months for the DE- and conventionally-treated cohorts, respectively. Median overall survival (OS) of patients who received DE radiotherapy was 15.2 months (95% confidence interval [CI] =11.0-18.6), while median OS of the latter cohort was 18.4 months (95% CI =12.5-31.4, P=0.253). Univariate analyses of clinical and dosimetric parameters among the DE cohort demonstrated a trend of longer progression-free survival, but not OS, with incremental radiation doses to the ipsilateral SVZ (hazard ratio [HR] =0.95, 95% CI =0.90-1.00, P=0.052) and proportion of ipsilateral SVZ receiving 50 Gy (HR =0.98, 95% CI =0.97-1.00, P=0.017). CONCLUSION: DE radiotherapy did not improve survival in patients with GBM. Incorporation of ipsilateral SVZ as a radiotherapy target volume for patients with GBM requires prospective validation.