The impact of salvage radiotherapy initiation at PSA ≤ 0.5 ng/ml on metastasis-free survival in patients with relapsed prostate cancer following prostatectomy.

BACKGROUND AND PURPOSE: Salvage radiation therapy (SRT) is indicated for biochemical failure after radical prostatectomy. Prior data have shown that initiation of SRT at lower PSA levels improves subsequent biochemical control, yet given the long natural history of prostate cancer questions remain regarding optimal timing of SRT. We analyzed the impact of prostate specific antigen (PSA) level at time of salvage radiotherapy with regard to both biochemical relapse-free (bRFS) as well as metastasis-free survival (MFS) in patients with biochemically recurrent prostate cancer. METHODS: Using prospective institutional tumor registry data, univariate and multivariable-adjusted Cox proportional hazards models were constructed to assess association between outcomes and clinical and pathologic prognostic features, including pre-SRT PSA, interval from prostatectomy to SRT, androgen deprivation therapy (ADT), and adverse pathologic features. RESULTS: We identified 397 patients who received salvage RT between 1985 and 2016: 187 (45.8%) received SRT initiated when pre-RT PSA was ≤0.5 ng/ml; 212 (52.0%) patients had pre-SRT PSA > 0.5 ng/ml. Independent of pathologic risk status and ADT use, pre-SRT PSA ≤ 0.5 ng/ml was the most significant predictor of bRFS (HR 0.39, 95% CI [0.27, 0.56]) as well as MFS (HR = 0.58, 95% CI [0.37, 0.91]). Seminal vesicle invasion was also associated with shorter interval to biochemical failure, HR = 1.79, 95% CI [1.07, 2.98], and eventual metastases, HR = 2.07, 95% CI [1.14, 3.740]. CONCLUSIONS: Initiation of salvage RT while PSA levels remain ≤0.5 ng/ml was associated with improved MFS. Consideration for salvage RT initiation while PSA levels remain low is warranted to minimize risk of future prostate cancer metastasis.

In silico comparison of whole pelvis intensity-modulated photon versus proton therapy for the postoperative management of prostate cancer.

BACKGROUND: Limited data exist comparing intensity-modulated photon (IMRT) and proton (IMPT) radiation therapy when treating the prostate bed and pelvic lymph nodes in the postoperative setting for prostate cancer. The aim of this study was to evaluate dosimetric differences between IMRT and IMPT when treating with whole pelvis radiation therapy (WPRT) postoperatively. MATERIALS AND METHODS: IMRT and IMPT plans were generated for 10 post-prostatectomy patients treated between July and August 2020. The prescription was 50 Gy radiobiologic equivalent (GyE) (proton radiobiological effective dose 1.1) to the pelvis and 70 GyE to the prostate bed in 2 GyE per fraction. Paired 2-sided Wilcoxon signed-rank tests were used to compare clinical target volume (CTV) coverage and dose to organs at risk (OARs). RESULTS: CTV coverage was met for all plans with 99% of CTVs receiving ≥99% of prescription doses. Dose to OARs was significantly higher with IMRT than IMPT for the following endpoints: bladder V5-V65; bowel V5-V45; sigmoid V5-V50; rectum V5-V70; femoral head V40 and maximum dose; bone V5-V65. Select endpoints with significant differences included bladder V30 (63.5 vs. 44.4%, p < .001), bowel V15 (949 vs. 191 cc, p = .001) and V30 (386 vs. 121 cc, p < .001), rectum V40 (81.8 vs. 32.1%, p < .001) and V50 (47.6 vs. 24.9%, p < .001), femoral head maximum doses (46.4-47.1 vs. 38.3-38.6GyE, p < .001), and bone V10 (93.3 vs. 85.4%, p < . 001). Mean doses for all OARs were significantly higher with IMRT, including bladder (41.9 vs. 29.7GyE, p < .001), bowel (21.2 vs. 5.5GyE, p < .001), and rectum (50.8 vs. 27.3GyE, p < .001). Integral dose to 'Body - CTV' was significantly higher with IMRT (32.8 vs. 18.4 J, p < .001). CONCLUSION: IMPT provides comparable target coverage to IMRT when treating prostate cancer with WPRT in the postoperative setting while significantly reducing dose to OARs. These data can inform the future clinical management and delivery of post-prostatectomy irradiation for prostate cancer.

Selective de-implementation of routine in vivo dosimetry.

As cone-beam computed tomography (CBCT) has become the localization method for a majority of cases, the indications for diode-based confirmation of accurate patient set-up and treatment are now limited and must be balanced between proper resource allocation and optimizing efficiency without compromising safety. We undertook a de-implementation quality improvement project to discontinue routine diode use in non-intensity modulated radiotherapy (IMRT) cases in favor of tailored selection of scenarios where diodes may be useful. After analysis of safety reports from the last 5 years, literature review, and stakeholder discussions, our safety and quality (SAQ) committee introduced a recommendation to limit diode use to specific scenarios in which in vivo verification may add value to standard quality assurance (QA) processes. To assess changes in patterns of use, we reviewed diode use by clinical indication 4 months prior and after the implementation of the revised policy, which includes use of diodes for: 3D conformal photon fields set up without CBCT; total body irradiation (TBI); electron beams; cardiac devices within 10 cm of the treatment field; and unique scenarios on a case-by-case basis. We identified 4459 prescriptions and 1038 unique instances of diode use across five clinical sites from 5/2021 to 1/2022. After implementation of the revised policy, we observed an overall decrease in diode use from 32% to 13.2%, with a precipitous drop in 3D cases utilizing CBCT (from 23.2% to 4%), while maintaining diode utilization in the 5 selected scenarios including 100% of TBI and electron cases. By identifying specific indications for diode use and creating a user-friendly platform for case selection, we have successfully de-implemented routine diode use in favor of a selective process that identifies cases where the diode is important for patient safety. In doing so, we have streamlined patient care and decreased cost without compromising patient safety.

The Peaks and Valleys of Photon Versus Proton Spatially Fractionated Radiotherapy.

Spatially-fractionated radiotherapy (SFRT) delivers high doses to small areas of tumor while sparing adjacent tissue, including intervening disease. In this review, we explore the evolution of SFRT technological advances, contrasting approaches with photon and proton beam radiotherapy. We discuss unique dosimetric considerations and physical properties of SFRT, as well as review the preclinical literature that provides an emerging understanding of biological mechanisms. We emphasize crucial areas of future study and highlight clinical trials that are underway to assess SFRT's safety and efficacy, with a focus on immunotherapeutic synergies. The review concludes with practical considerations for SFRT's clinical application, advocating for strategies that leverage its unique dosimetric and biological properties for improved patient outcomes.

Psoralen: a narrative review of current and future therapeutic uses.

Psoralen is a family of naturally occurring photoactive compounds found in plants that acquire potential cytotoxicity when activated by specific frequencies of electromagnetic waves. Psoralens penetrate the phospholipid cellular membranes and insert themselves between the pyrimidines of deoxyribonucleic acid (DNA). Psoralens are initially biologically inert and acquire photoreactivity when exposed to certain classes of electromagnetic radiation, such as ultraviolet light. Once activated, psoralens form mono- and di-adducts with DNA, leading to marked cell apoptosis. This apoptotic effect is more pronounced in tumor cells due to their high rate of cell division. Moreover, photoactivated psoralen can inhibit tyrosine kinase signaling and influence the immunogenic properties of cells. Thus, the cytotoxicity of photoactivated psoralen holds promising clinical applications from its immunogenic properties to potential anti-cancer treatments. This narrative review aims to provide an overview of the current understanding and research on psoralen and to explore its potential future pharmacotherapeutic benefits in specific diseases.

Comparing Ultra-hypofractionated Proton versus Photon Therapy in Extremity Soft Tissue Sarcoma.

Purpose: Recent single institution, phase II evidence has demonstrated the feasibility and efficacy of ultra-hypofractionated, preoperative photon therapy in 5 fractions for the treatment of soft tissue sarcoma (STS). Our purpose was to evaluate the dosimetric benefits of modern scanning beam proton therapy compared with conventional photon radiation therapy (RT) for the neoadjuvant treatment of adult extremity STS. Materials and Methods: Existing proton and photon plans for 11 adult patients with STS of the lower extremities previously treated preoperatively with neoadjuvant RT at our center were used to create proton therapy plans using Raystation Treatment Planning System v10.A. Volumes were delineated, and doses reported consistent with International Commission on Radiation Units and Measurements reports 50, 62, and 78. Target volumes were optimized such that 100% clinical target volume (CTV) was covered by 99% of the prescription dose. The prescribed dose was 30 Gy for PT and RT delivered in 5 fractions. For proton therapy, doses are reported in GyRBE = 1.1 Gy. The constraints for adjacent organs at risk (OARs) within 1 cm of the CTV were the following: femur V30Gy ≤ 50%, joint V30Gy < 50%, femoral head V30Gy ≤ 5 cm3, strip V12 ≤ 10%, and skin V12 < 50%. Target coverage goals, OAR constraints, and integral dose were compared by Student t test with P < .05 significance. Results: A minimum 99% CTV coverage was achieved for all plans. OAR dose constraints were achieved for all proton and photon plans; however, mean doses to the femur (10.7 ± 8.5 vs 16.1 ± 7.7 GyRBE), femoral head (2.0 ± 4.4 vs 3.6 ± 6.4 GyRBE), and proximal joint (1.8 ± 2.4 vs 3.5 ± 4.4 GyRBE) were all significantly lower with PT vs intensity-modulated radiation therapy (IMRT) (all P < .05). Integral dose was significantly reduced for proton vs photon plans. Conformity and heterogeneity indices were significantly better for proton therapy. Conclusion: Proton therapy maintained target coverage while significantly reducing integral and mean doses to the proximal organs at risk compared with RT. Further prospective investigation is warranted to validate these findings and potential benefit in the management of adult STS.

Treatment Planning of Bulky Tumors Using Pencil Beam Scanning Proton GRID Therapy.

Purpose: To compare spatially fractionated radiation therapy (GRID) treatment planning techniques using proton pencil-beam-scanning (PBS) and photon therapy. Materials and Methods: PBS and volumetric modulated arc therapy (VMAT) GRID plans were retrospectively generated for 5 patients with bulky tumors. GRID targets were arranged along the long axis of the gross tumor, spaced 2 and 3 cm apart, and treated with a prescription of 18 Gy. PBS plans used 2- to 3-beam multiple-field optimization with robustness evaluation. Dosimetric parameters including peak-to-edge ratio (PEDR), ratio of dose to 90% of the valley to dose to 10% of the peak VPDR(D90/D10), and volume of normal tissue receiving at least 5 Gy (V5) and 10 Gy (V10) were calculated. The peak-to-valley dose ratio (PVDR), VPDR(D90/D10), and organ-at-risk doses were prospectively assessed in 2 patients undergoing PBS-GRID with pretreatment quality assurance computed tomography (QACT) scans. Results: PBS and VMAT GRID plans were generated for 5 patients with bulky tumors. Gross tumor volume values ranged from 826 to 1468 cm3. Peak-to-edge ratio for PBS was higher than for VMAT for both spacing scenarios (2-cm spacing, P = .02; 3-cm spacing, P = .01). VPDR(D90/D10) for PBS was higher than for VMAT (2-cm spacing, P = .004; 3-cm spacing, P = .002). Normal tissue V5 was lower for PBS than for VMAT (2-cm spacing, P = .03; 3-cm spacing, P = .02). Normal tissue mean dose was lower with PBS than with VMAT (2-cm spacing, P = .03; 3-cm spacing, P = .02). Two patients treated using PBS GRID and assessed with pretreatment QACT scans demonstrated robust PVDR, VPDR(D90/D10), and organs-at-risk doses. Conclusions: The PEDR was significantly higher for PBS than VMAT plans, indicating lower target edge dose. Normal tissue mean dose was significantly lower with PBS than VMAT. PBS GRID may result in lower normal tissue dose compared with VMAT plans, allowing for further dose escalation in patients with bulky disease.

Improving Quality Metrics in Radiation Oncology: Implementation of Pretreatment Peer Review for Stereotactic Body Radiation Therapy in Patients with Thoracic Cancer.

Purpose: Traditional peer reviews occur weekly, and can take place up to 1 week after the start of treatment. The American Society for Radiation Oncology peer-review white paper identified stereotactic body radiation therapy (SBRT) as a high priority for contour/plan review before the start of treatment, considering both the rapid-dose falloff and short treatment course. Yet, peer-review goals for SBRT must also balance physician time demands and the desire to avoid routine treatment delays that would occur in the setting of a 100% pretreatment (pre-Tx) review compliance requirement or prolonging the standard treatment planning timeline. Herein, we report on our pilot experience of a pre-Tx peer review of thoracic SBRT cases. Methods and Materials: From March 2020 to August 2021, patients undergoing thoracic SBRT were identified for pre-Tx review, and placed on a quality checklist. We implemented twice-weekly meetings for detailed pre-Tx review of organ-at-risk/target contours and dose constraints in the treatment planning system for SBRT cases. Our quality metric goal was to peer review ≥90% of SBRT cases before exceeding 25% of the dose delivered. We used a statistical process control chart with sigma limits (ie, standard deviations [SDs]) to access compliance rates with pre-Tx review implementation. Results: We identified 252 patients treated with SBRT to 294 lung nodules. When comparing pre-Tx review completion from initial rollout to full implementation, our rates improved from 19% to 79% (ie, from 1 sigma limit [SDs]) below to >2 sigma limits (SDs) above. Additionally, early completion of any form of contour/plan review (defined as any pre-Tx or standard review completed before exceeding 25% of the dose delivered) increased from 67% to 85% (March 2020-November 2020) to 76% to 94% (December 2020-August 2021). Conclusions: We successfully implemented a sustainable workflow for detailed pre-Tx contour/plan review for thoracic SBRT cases in the context of twice-weekly disease site-specific peer-review meetings. We reached our quality improvement objective to peer review ≥90% of SBRT cases before exceeding 25% of the dose delivered. This process was feasible to conduct in an integrated network of sites across our system.

Evaluating Proton Dose and Associated Range Uncertainty Using Daily Cone-Beam CT.

Purpose: This study aimed to quantitatively evaluate the range uncertainties that arise from daily cone-beam CT (CBCT) images for proton dose calculation compared to CT using a measurement-based technique. Methods: For head and thorax phantoms, wedge-shaped intensity-modulated proton therapy (IMPT) treatment plans were created such that the gradient of the wedge intersected and was measured with a 2D ion chamber array. The measured 2D dose distributions were compared with 2D dose planes extracted from the dose distributions using the IMPT plan calculated on CT and CBCT. Treatment plans of a thymoma cancer patient treated with breath-hold (BH) IMPT were recalculated on 28 CBCTs and 9 CTs, and the resulting dose distributions were compared. Results: The range uncertainties for the head phantom were determined to be 1.2% with CBCT, compared to 0.5% for CT, whereas the range uncertainties for the thorax phantom were 2.1% with CBCT, compared to 0.8% for CT. The doses calculated on CBCT and CT were similar with similar anatomy changes. For the thymoma patient, the primary source of anatomy change was the BH uncertainty, which could be up to 8 mm in the superior-inferior (SI) direction. Conclusion: We developed a measurement-based range uncertainty evaluation method with high sensitivity and used it to validate the accuracy of CBCT-based range and dose calculation. Our study demonstrated that the CBCT-based dose calculation could be used for daily dose validation in selected proton patients.

Variations in referral patterns for hypophysectomies among pediatric patients with sellar and parasellar tumors.

PURPOSE: It has been shown that patients admitted to high-volume hospitals for resection of sellar and parasellar lesions experience reduced mortality and morbidity. It remains unknown what preoperative factors influence admission to high-volume centers. We report a nationwide analysis of patients <18 years of age undergoing neurosurgical intervention for these lesions. METHODS: A retrospective analysis of the Nationwide Inpatient Sample was performed with additional factors from the Area Resource File. International Classification of Diseases, 9th Revision diagnosis/procedural codes were used to identify patients undergoing resection of tumors from the pituitary gland or related structures. Patients >or=18 years old were excluded. Covariates included age, gender, race, and insurance status. Multivariate analysis was performed using multiple logistic regression models. A p value <0.05 was considered statistically significant. RESULTS: In total, 1,063 patients were identified. Most (69.8%) were seen at low-volume centers. Mean (median) patient age was 13.7 (15) years. The majority of patients were female (54.8%), white (61.9%), and insured (90.3%). Hispanics were 44% less likely (odds ratio (OR) 0.56, 95% confidence interval (CI) 0.34-0.92, p < 0.05) to be seen at high-volume centers than their Caucasian counterparts. Each increase in 2-year patient age category was associated with greater access to high-volume centers (OR 1.12, 95% CI 1.03-1.23, p < 0.05), relative to 0-2 years old. Female gender, insurance status, county poverty, neurosurgeon density, and calendar year were not significantly associated with admission to high-volume centers. CONCLUSIONS: Age and racial disparities play a significant role in access neurosurgical care, affecting admission of pediatric patients to high-volume neurosurgical centers across the USA.

Phase I trial of dose-escalated stereotactic radiosurgery (SRS) boost for unfavorable locally advanced oropharyngeal cancer.

BACKGROUND AND PURPOSE: Patients with locally advanced oropharynx squamous cell carcinoma have suboptimal outcomes with standard chemoradiation. Here, we evaluated toxicity and oncologic outcomes of dose escalation using radiosurgical boost for patients with unfavorable oropharynx squamous cell carcinoma. MATERIALS AND METHODS: Between 2010-2017, Thirty four patients with intermediate- or high-risk oropharynx squamous cell carcinoma were enrolled onto this prospective phase I trial. Each patient received concurrent cisplatin and fractionated radiotherapy totaling 60 Gy or 66 Gy followed by radiosurgery boost to areas of residual gross tumor: single fraction of 8 Gy or 10 Gy, or two fractions of 5 Gy each. Primary endpoint was treatment toxicity. Secondary endpoints were local, regional, and distant disease control. RESULTS: Eleven, sixteen and seven patients received radiosurgery boost with 8 Gy in 1 fraction, 10 Gy in 1 fraction, and 10 Gy in 2 fractions respectively. Acute toxicities include 4 patients with tumor necrosis causing grade 3 dysphagia, of which 3 developed grade 4 pharyngeal hemorrhage requiring surgical intervention. At 24 months after treatment, 7%, 9%, and 15% had grade 2 dysgeusia, xerostomia, and dysphagia, respectively, and two patients remained feeding tube dependent. No grade 5 toxicities occurred secondary to treatment. Local, regional, and distant control at a median follow up of 4.2 years were 85.3%, 85.3% and 88.2%, respectively. Five patients died resulting in overall survival of 85.3%. CONCLUSIONS: This study is the first to report the use of radiosurgery boost dose escalation in patients with unfavorable oropharynx squamous cell carcinoma. Longer follow-up, larger cohorts, and further refinement of boost methodology are needed prior to implementation in routine clinical practice. TRIAL REGISTRATION: Northwell Health Protocol #09-309A (NCT02703493) ( https://clinicaltrials.gov/ct2/show/NCT02703493 ).

Prophylactic Cranial Irradiation for Resectable Small-Cell Lung Cancer.

After definitive chemoradiation for small-cell lung cancer (SCLC), prophylactic cranial irradiation (PCI) has been established as standard of care in patients whose tumors respond to treatment. In the modern era, however, a subset of patients might receive upfront resection for SCLC, yet the role of PCI in these patients has not been elucidated. In this review, we examine the literature to better define the role of PCI in this subset of patients. For patients with ≥ T2 disease, incomplete resection, or those not receiving adjuvant chemotherapy, PCI is expected to offer a clinical benefit. For patients with T1 tumors treated with R0 resection, however, the rate of intracranial metastasis might be < 10%. In these patients, deferral of PCI might be appropriate because it would avoid known neurocognitive sequelae of cranial irradiation.

Radiation therapy for oropharyngeal squamous cell carcinoma: Executive summary of an ASTRO Evidence-Based Clinical Practice Guideline.

PURPOSE: To present evidence-based guidelines for the treatment of oropharyngeal squamous cell carcinoma (OPSCC) with definitive or adjuvant radiation therapy (RT). METHODS AND MATERIALS: The American Society for Radiation Oncology convened the OPSCC Guideline Panel to perform a systematic literature review investigating the following key questions: (1) When is it appropriate to add systemic therapy to definitive RT in the treatment of OPSCC? (2) When is it appropriate to deliver postoperative RT with and without systemic therapy following primary surgery for OPSCC? (3) When is it appropriate to use induction chemotherapy in the treatment of OPSCC? (4) What are the appropriate dose, fractionation, and volume regimens with and without systemic therapy in the treatment of OPSCC? RESULTS: Patients with stage IV and stage T3 N0-1 OPSCC treated with definitive RT should receive concurrent high-dose intermittent cisplatin. Patients receiving adjuvant RT following surgical resection for positive surgical margins or extracapsular extension should be treated with concurrent high-dose intermittent cisplatin, and individuals with these risk factors who are intolerant of cisplatin should not routinely receive adjuvant concurrent systemic therapy. Induction chemotherapy should not be routinely delivered to patients with OPSCC. For patients with stage IV and stage T3 N0-1 OPSCC ineligible for concurrent chemoradiation therapy, altered fractionation RT should be used. CONCLUSION: The successful management of OPSCC requires the collaboration of radiation, medical, and surgical oncologists. When high-level data are absent for clinical decision-making, treatment recommendations should incorporate patient values and preferences to arrive at the optimal therapeutic approach.

Inhibition of polo-like kinase 1 in glioblastoma multiforme induces mitotic catastrophe and enhances radiosensitisation.

Glioblastoma multiforme (GBM) is the most common primary brain tumour in the United States of America (USA) with a median survival of approximately 14 months. Low survival rates are attributable to the aggressiveness of GBM and a lack of understanding of the molecular mechanisms underlying GBM. The disruption of signalling pathways regulated either directly or indirectly by protein kinases is frequently observed in cancer cells and thus the development of inhibitors of specific kinases has become a major focus of drug discovery in oncology. To identify protein kinases required for the survival of GBM we performed a siRNA-based RNAi screen focused on the human kinome in GBM. Inhibition of the polo-like kinase 1 (PLK1) induced a reduction in the viability in two different GBM cell lines. To assess the potential of inhibiting PLK1 as a treatment strategy for GBM we examined the effects of a small molecule inhibitor of PLK1, GSK461364A, on the growth of GBM cells. PLK1 inhibition arrested cells in the mitotic phase of the cell cycle and induced cell kill by mitotic catastrophe. GBM engrafts treated with GSK461364A showed statistically significant inhibition of tumour growth. Further, exposure of different GBM cells to RNAi or GSK461364A prior to radiation resulted in an increase in their radiosensitivity with dose enhancement factor ranging from 1.40 to 1.53 with no effect on normal cells. As a measure of DNA double strand breaks, γH2AX levels were significantly higher in the combined modality as compared to the individual treatments. This study suggests that PLK1 is an important therapeutic target for GBM and can enhance radiosensitivity in GBM.

Factors involved in maintaining prolonged functional independence following supratentorial glioblastoma resection. Clinical article.

OBJECT: The median survival duration for patients with glioblastoma is approximately 12 months. Maximizing quality of life (QOL) for patients with glioblastoma is a priority. An important, yet understudied, QOL component is functional independence. The aims of this study were to evaluate functional outcomes over time for patients with glioblastoma, as well as identify factors associated with prolonged functional independence. METHODS: All patients who underwent first-time resection of either a primary (de novo) or secondary (prior lower grade glioma) glioblastoma at a single institution from 1996 to 2006 were retrospectively reviewed. Patients with a Karnofsky Performance Scale (KPS) score ≥ 80 were included. Kaplan-Meier, log-rank, and multivariate proportional hazards regression analyses were used to identify associations (p < 0.05) with functional independence (KPS score ≥ 60) following glioblastoma resection. RESULTS: The median follow-up duration time was 10 months (interquartile range [IQR] 5.6-17.0 months). A patient's preoperative (p = 0.02) and immediate postoperative (within 2 months) functional status was associated with prolonged survival (p < 0.0001). Of the 544 patients in this series, 302 (56%) lost their functional independence at a median of 10 months (IQR 6-16 months). Factors independently associated with prolonged functional independence were: preoperative KPS score ≥ 90 (p = 0.004), preoperative seizures (p = 0.002), primary glioblastoma (p < 0.0001), gross-total resection (p < 0.0001), and temozolomide chemotherapy (p < 0.0001). Factors independently associated with decreased functional independence were: older age (p < 0.0001), coexistent coronary artery disease (p = 0.009), and incurring a new postoperative motor deficit (p = 0.009). Furthermore, a decline in functional status was independently associated with tumor recurrence (p = 0.01). CONCLUSIONS: The identification and consideration of these factors associated with prolonged functional outcome (preoperative KPS score ≥ 90, seizures, primary glioblastoma, gross-total resection, temozolomide) and decreased functional outcome (older age, coronary artery disease, new postoperative motor deficit) may help guide treatment strategies aimed at improving QOL for patients with glioblastoma.