Evolving concepts in margin strategies and adaptive radiotherapy for glioblastoma: A new future is on the horizon.

Chemoradiotherapy is the standard treatment after maximal safe resection for glioblastoma (GBM). Despite advances in molecular profiling, surgical techniques, and neuro-imaging, there have been no major breakthroughs in radiotherapy (RT) volumes in decades. Although the majority of recurrences occur within the original gross tumor volume (GTV), treatment of a clinical target volume (CTV) ranging from 1.5 to 3.0 cm beyond the GTV remains the standard of care. Over the past 15 years, the incorporation of standard and functional MRI sequences into the treatment workflow has become a routine practice with increasing adoption of MR simulators, and new integrated MR-Linac technologies allowing for daily pre-, intra- and post-treatment MR imaging. There is now unprecedented ability to understand the tumor dynamics and biology of GBM during RT, and safe CTV margin reduction is being investigated with the goal of improving the therapeutic ratio. The purpose of this review is to discuss margin strategies and the potential for adaptive RT for GBM, with a focus on the challenges and opportunities associated with both online and offline adaptive workflows. Lastly, opportunities to biologically guide adaptive RT using non-invasive imaging biomarkers and the potential to define appropriate volumes for dose modification will be discussed.

Stereotactic Body Radiation Therapy for Sacral Metastases: Deviation From Recommended Target Volume Delineation Increases the Risk of Local Failure.

PURPOSE: Although spine stereotactic body radiation therapy (SBRT) is considered a standard of care in the mobile spine, mature evidence reporting outcomes specific to sacral metastases is lacking. Furthermore, there is a need to validate the existing sacral SBRT international consensus contouring guidelines to define the optimal contouring approach. We report mature rates of local failure (LF), adverse events, and the effect of contouring deviations in the largest experience to date specific to sacrum SBRT. METHODS AND MATERIALS: Consecutive patients who underwent sacral SBRT from 2010 to 2021 were retrospectively reviewed. The primary endpoint was magnetic resonance imaging-based LF with a focus on adherence to target volume contouring recommendations. Secondary endpoints included vertebral compression fracture and neural toxicity. RESULTS: Of the 215 sacrum segments treated in 112 patients, most received 30 Gy/4 fractions (51%), 24 Gy/2 fractions (31%), or 30 Gy/5 fractions (10%). Sixteen percent of segments were nonadherent to the consensus guideline with a more restricted target volume (undercontoured). The median follow-up was 21.4 months (range, 1.5-116.9 months). The cumulative incidence of LF at 1 and 2 years was 18.4% and 23.1%, respectively. In those with guideline adherent versus nonadherent contours, the LF rate at 1 year was 15.1% versus 31.4% and at 2 years 18.8% versus 40.0% (hazard ratio [HR], 2.5; 95% CI, 1.4-4.6; P = .003), respectively. On multivariable analysis, guideline nonadherence (HR, 2.4; 95% CI, 1.3-4.7; P = .008), radioresistant histology (HR, 2.4; 95% CI, 1.4-4.1; P < .001), and extraosseous extension (HR, 2.5; 95% CI, 1.3-4.7; P = .005) predicted for an increased risk of LF. The cumulative incidence of vertebral compression fracture was 7.1% at 1 year and 12.3% at 2 years. Seven patients (6.3%) developed peripheral nerve toxicity, of whom 4 had been previously radiated. CONCLUSIONS: Sacral SBRT is associated with high efficacy rates and an acceptable toxicity profile. Adhering to consensus guidelines for target volume delineation is recommended to reduce the risk of LF.

Magnetic Resonance Imaging Frequency After Stereotactic Body Radiation Therapy for Spine Metastases.

PURPOSE: Stereotactic body radiation therapy (SBRT) is increasingly being used to treat spine metastases. Current post-SBRT imaging surveillance strategies in this patient population may benefit from a more data-driven and personalized approach. The objective of this study was to develop risk-stratified post-SBRT magnetic resonance imaging (MRI) surveillance strategies using quantitative methods. METHODS AND MATERIALS: Adult patients with bony spine metastases treated with SBRT between 2008 and 2021 and who had at least 2 follow-up spine MRIs were reviewed retrospectively. A recursive partitioning analysis model was developed to separate patients into different risk categories for post-SBRT progression anywhere within the spine. Imaging intervals were derived for each risk category using parametric survival regression based on multiple expected spine progression rates per scan. RESULTS: A total of 446 patients and 1039 vertebral segments were included. Cumulative incidence of spine progression was 19.2% at 1 year, 26.7% at 2 years, and 35.3% at 4 years. The internally validated risk stratification model was able to divide patients into 3 risk categories based on epidural disease, paraspinal disease, and Spinal Instability Neoplastic Score category. The 4-year risk of spine progression was 23.4%, 39.0%, and 51.8%, respectively, for the low-, intermediate-, and high-risk groups. Using an expected per-scan spine progression rate of 3.75%, the low-risk group would require follow-up scans every 6.0 months (95% CI, 4.9-7.6) and the intermediate-risk group would require surveillance every 3.1 months (95% CI, 2.6-3.7). At an expected spine progression rate of 5%, the high-risk group would require surveillance every 1.3 months (95% CI, 1.1-1.6) during the first 13.2 months after SBRT and every 5.9 months thereafter (95% CI, 2.8-12.3). CONCLUSIONS: Data-driven follow-up MRI surveillance intervals at a range of expected spine progression rates have been determined for patients at different risks of spine progression based on an internally validated, single-institution risk stratification model.

Dose-Escalated Radiation Therapy Is Associated With Improved Outcomes for High-Grade Meningioma.

PURPOSE: The optimal modern radiation therapy (RT) approach after surgery for atypical and malignant meningioma is unclear. We present results of dose escalation in a single-institution cohort spanning 2000 to 2021. METHODS AND MATERIALS: Consecutive patients with histopathologic grade 2 or 3 meningioma treated with RT were reviewed. A dose-escalation cohort (≥66 Gy equivalent dose in 2-Gy fractions using an α/ß = 10) was compared with a standard-dose cohort (<66 Gy). Outcomes were progression-free survival (PFS), cause-specific survival, overall survival (OS), local failure (LF), and radiation necrosis. RESULTS: One hundred eighteen patients (111 grade 2, 94.1%) were identified; 54 (45.8%) received dose escalation and 64 (54.2%) standard dose. Median follow-up was 45.4 months (IQR, 24.0-80.0 months) and median OS was 9.7 years (Q1: 4.6 years, Q3: not reached). All dose-escalated patients had residual disease versus 65.6% in the standard-dose cohort (P < .001). PFS at 3, 4, and 5 years in the dose-escalated versus standard-dose cohort was 78.9%, 72.2%, and 64.6% versus 57.2%, 49.1%, and 40.8%, respectively, (P = .030). On multivariable analysis, dose escalation (hazard ratio [HR], 0.544; P = .042) was associated with improved PFS, whereas ≥2 surgeries (HR, 1.989; P = .035) and older age (HR, 1.035; P < .001) were associated with worse PFS. The cumulative risk of LF was reduced with dose escalation (P = .016). Multivariable analysis confirmed that dose escalation was protective for LF (HR, 0.483; P = .019), whereas ≥2 surgeries before RT predicted for LF (HR, 2.145; P = .008). A trend was observed for improved cause-specific survival and OS in the dose-escalation cohort (P < .1). Seven patients (5.9%) developed symptomatic radiation necrosis with no significant difference between the 2 cohorts. CONCLUSIONS: Dose-escalated RT with ≥66 Gy for high-grade meningioma is associated with improved local control and PFS with an acceptable risk of radiation necrosis.

30 Gy in 4 Stereotactic Body Radiotherapy Fractions for Complex Spinal Metastases: Mature Outcomes Supporting This Novel Regimen.

BACKGROUND AND OBJECTIVES: We designed a 30 Gy in 4 fractions stereotactic body radiotherapy protocol, as an alternative option to our standard 2-fraction approach, for primarily large volume, multilevel, or previously radiated spinal metastases. We report imaging-based outcomes of this novel fractionation scheme. METHODS: The institutional database was reviewed to identify all patients who underwent 30 Gy/4 fractions from 2010 to 2021. Primary outcomes were magnetic resonance-based vertebral compression fracture (VCF) and local failure per treated vertebral segment. RESULTS: We reviewed 245 treated segments in 116 patients. The median age was 64 years (range, 24-90). The median number of consecutive segments within the treatment volume was 2 (range, 1-6), and the clinical target volume (CTV) was 126.2 cc (range, 10.4-863.5). Fifty-four percent had received at least 1 previous course of radiotherapy, and 31% had previous spine surgery at the treated segment. The baseline Spinal Instability Neoplastic Score was stable, potentially unstable, and unstable for 41.6%, 51.8%, and 6.5% of segments, respectively. The cumulative incidence of local failure was 10.7% (95% CI 7.1-15.2) at 1 year and 16% (95% CI 11.5-21.2) at 2 years. The cumulative incidence of VCF was 7.3% (95% CI 4.4-11.2) at 1 year and 11.2% (95% CI 7.5-15.8) at 2 years. On multivariate analysis, age ≥68 years ( P = .038), CTV volume ≥72 cc ( P = .021), and no previous surgery ( P = .021) predicted an increased risk of VCF. The risk of VCF for CTV volumes <72 cc/≥72 cc was 1.8%/14.6% at 2 years. No case of radiation-induced myelopathy was observed. Five percent of patients developed plexopathy. CONCLUSION: 30 Gy in 4 fractions was safe and efficacious despite the population being at increased risk of toxicity. The lower risk of VCF in previously stabilized segments highlights the potential for a multimodal treatment approach for complex metastases, especially for those with a CTV volume of ≥72 cc.

Stereotactic Body Radiation Therapy for Posterior Element-Only Spinal Metastases: A First Report on Outcomes and Validation of Recommended Clinical Target Volume Delineation Practice.

PURPOSE: Spine stereotactic body radiation therapy (SBRT) results in improved local control and pain response compared with conventional external beam radiation therapy. Consensus exists stipulating that magnetic resonance imaging-based delineation of the clinical target volume (CTV) is critical and based on spine segment sector involvement. The applicability of contouring guidelines to metastases involving the posterior elements alone remains to be validated, and the purpose of this report was to determine the patterns of failure and safety of treating posterior element metastases when the vertebral body (VB) was intentionally excluded from the CTV. METHODS AND MATERIALS: A retrospective review of a prospectively maintained database of 605 patients and 1412 spine segments treated with spine SBRT was performed. Only treated segments involving the posterior elements alone were included for the analyses. The primary outcome was local failure, as per SPINO recommendations, and secondary outcomes included patterns of failure and toxicities. RESULTS: In total, 24 of 605 patients and 31 of 1412 segments were treated to the posterior elements only. Local failure occurred in 11 of 31 segments. The cumulative rate of local recurrence was 9.7% at 12 months and 30.8% at 24 months. Among local failures, the most common histologies were renal cell carcinoma (36.4%) and non-small cell lung cancer (36.4%), and 73% had baseline paraspinal disease extension. A total of 6 of 11 (54.5%) failed exclusively within treated CTV sectors and 5 of 11 (45.5%) with both treated and adjacent untreated sectors. Four of these 5 cases had recurrent disease extending into the VB, but no failure was observed exclusively within the VB. CONCLUSIONS: Posterior element alone metastases are rare. Our analyses support SBRT consensus contouring guidelines such that the VB can be excluded from CTV in spinal metastases confined to the posterior elements.

Dose-Escalated 2-Fraction Spine Stereotactic Body Radiation Therapy: 28 Gy Versus 24 Gy in 2 Daily Fractions.

PURPOSE: Stereotactic body radiation therapy (SBRT) for spine metastases improves pain response rates compared with conventional external beam radiation therapy; however, the optimal fractionation schedule is unclear. We report local control and toxicity outcomes after dose-escalated 2-fraction spine SBRT. METHODS AND MATERIALS: A prospectively maintained institutional database of over 600 patients and 1400 vertebral segments treated with spine SBRT was reviewed to identify those prescribed 28 or 24 Gy in 2 daily fractions. The primary endpoint was magnetic resonance imaging based local failure (LF), and secondary endpoints included overall survival and vertebral compression fracture (VCF). RESULTS: A total of 947 treated vertebral segments in 482 patients were identified, of which 301 segments in 159 patients received 28 Gy, and 646 segments in 323 patients received 24 Gy in 2 fractions. Median follow-up per patient was 23.5 months, and median overall survival was 49.1 months. In the 28 Gy cohort, the 6-, 12-, and 24-month cumulative incidences of LF were 3.5%, 5.4%, and 11.1%, respectively, versus 6.0%, 12.5%, and 17.6% in the 24 Gy cohort, respectively (P = .008). On multivariable analysis, 24 Gy (hazard ratio [HR], 1.525; 95% confidence interval, 1.039-2.238; P = .031), paraspinal disease extension (HR, 1.422; 95% confidence interval, 1.010-2.002; P = .044), and epidural extension in either radioresistant or radiosensitive histologies (HR, 2.117 and 1.227, respectively; P = .003) were prognostic for higher rates of LF. Risk of VCF was 5.5%, 7.6%, and 10.7% at 6, 12, and 24 months, respectively, and was similar between cohorts (P = .573). Spinal malalignment (P < .001), baseline VCF (P = .003), junctional spine location (P = .030), and greater minimum dose to 90% of planning target volume were prognostic for higher rates of VCF. CONCLUSIONS: Dose escalation to 28 Gy in 2 daily fractions was associated with improved local control without increasing the risk of VCF. The 2-year local control rates are consistent with those predicted by the Hypofractionated Treatment Effects in the Clinic spine tumor control probability model, and these data will inform a proposed dose escalation randomized trial.

Mature Local Control and Reirradiation Rates Comparing Spine Stereotactic Body Radiation Therapy With Conventional Palliative External Beam Radiation Therapy.

PURPOSE: Stereotactic body radiation therapy (SBRT) improves complete pain response for painful spinal metastases compared with conventional external beam radiation therapy (cEBRT). We report mature local control and reirradiation rates in a large cohort of patients treated with SBRT versus cEBRT enrolled previously in the Canadian Clinical Trials Group Symptom Control 24 phase 2/3 trial. METHODS AND MATERIALS: One hundred thirty-seven of 229 (60%) patients randomized to 24 Gy in 2 SBRT fractions or 20 Gy in 5 cEBRT fractions were retrospectively reviewed. By including all treated spinal segments, we report on 66 patients (119 spine segments) treated with SBRT and 71 patients (169 segments) treated with cEBRT. The primary outcomes were magnetic resonance-based local control and reirradiation rates for each treated spine segment. RESULTS: The median follow-up was 11.3 months (interquartile range, 5.3-27.7 months), and median overall survival in the SBRT and cEBRT cohorts were 21.6 (95% confidence interval [CI], 11.3, upper bound not reached) and 18.9 (95% CI, 12.2-29.1) months (P = .428), respectively. The cohorts were balanced with respect to radioresistant histology and presence of mass (paraspinal and/or epidural disease extension). Risk of local failure after SBRT versus cEBRT at 6, 12, and 24 months were 2.8% (95% CI, 0.8%-7.4%) versus 11.2% (95% CI, 6.9%-16.6%), 6.1% (95% CI, 2.5%-12.1%) versus 28.4% (95% CI, 21.3%-35.9%), and 14.8% (95% CI, 8.2-23.1%) versus 35.6% (95% CI, 27.8%-43.6%), respectively (P < .001). cEBRT (hazard ratio [HR], 3.48; 95% CI, 1.94-6.25; P < .001) and presence of mass (HR, 2.07; 95% CI, 1.29-3.31; P = .002) independently predicted local failure on multivariable analysis. The 1-year reirradiation rates and median times to reirradiation after SBRT versus cEBRT were 2.2% (95% CI, 0.4-7.0%) versus 15.8% (95% CI, 10.4%-22.3%) (P = .002) and 22.9 months versus 9.5 months, respectively. cEBRT (HR, 2.60; 95% CI, 1.27-5.30; P = .009) and radioresistant histology (HR, 2.00; 95% CI, 1.12-3.60; P = .020) independently predicted for reirradiation. Eight of 12 iatrogenic vertebral compression fractures were after SBRT and 4 of 12 after cEBRT; grade 3 adverse fracture effects were isolated to the SBRT cohort (5 of 12). CONCLUSIONS: Risk of local failure and reirradiation is lower with SBRT compared with cEBRT for spinal metastases. Although the iatrogenic vertebral compression fracture rates were within expectations, grade 3 vertebral compression fractures were isolated to the SBRT cohort.

Spine Stereotactic Body Radiotherapy for Prostate Cancer Metastases and the Impact of Hormone Sensitivity Status on Local Control.

BACKGROUND: Stereotactic body radiotherapy (SBRT) is used to deliver ablative dose of radiation to spinal metastases. OBJECTIVE: To report the first dedicated series of spine SBRT specific to prostate cancer (PCa) metastases with outcomes reported according to hormone sensitivity status. METHODS: A prospective database was reviewed identifying patients with PCa treated with spine SBRT. This included those with hormone-sensitive PCa (HSPC) and castrate-resistant PCa (CRPC). The primary end point was MRI-based local control (LC). RESULTS: A total of 183 spine segments in 93 patients were identified; 146 segments had no prior radiation and 37 had been previously radiated; 27 segments were postoperative. The median follow-up was 31 months. At the time of SBRT, 50 patients had HSPC and the remaining 43 had CRPC. The most common fractionation scheme was 24-28 Gy in 2 SBRT fractions (76%). LC rates at 1 and 2 years were 99% and 95% and 94% and 78% for the HSPC and CRPC cohorts, respectively. For patients treated with de novo SBRT, a higher risk of local failure was observed in patients with CRPC (P = .0425). The 1-year and 2-year overall survival rates were significantly longer at 98% and 95% in the HSPC cohort compared with 79% and 65% in the CRPC cohort (P = .0005). The cumulative risk of vertebral compression fracture at 2 years was 10%. CONCLUSION: Favorable LC rates were observed after spine SBRT for PCa metastases; strategies to improve long-term LC in patients with CRPC require further investigation.

Prognostic Factors Associated With Surviving Less Than 3 Months vs Greater Than 3 Years Specific to Spine Stereotactic Body Radiotherapy and Late Adverse Events.

BACKGROUND: Patient selection is critical for spine stereotactic body radiotherapy (SBRT) given potential for serious adverse effects and the associated costs. OBJECTIVE: To identify prognostic factors associated with dying within 3 mo, or living greater than 3 yr, following spine SBRT, to better inform patient selection. METHODS: Patients living ≤3 mo after spine SBRT and >3 yr after spine SBRT were identified, and multivariable regression analyses were performed. We report serious late toxicities observed, including vertebral compression fractures (VCF) and plexopathy. RESULTS: A total of 605 patients (1406 spine segments) were treated from 2009 to 2018. A total of 51 patients (8.4%) lived ≤3 mo, and 79 patients (13%) survived >3 yr. Significant differences in baseline features were observed. On multivariable analysis, nonbreast/prostate primaries (odds ratio [ORs]: 28.8-104.2, P = .0004), eastern cooperative oncology group (ECOG) ≥2 (OR: 23.7, 95% CI: 3.2-177, P = .0020), polymetastatic disease (OR: 6.715, 95% CI: 1.89-23.85, P = .0032), painful lesions (OR: 3.833-8.898, P = .0118), and paraspinal disease (OR: 2.874, 95% CI: 1.118-7.393, P = .0288) were prognostic for ≤3 mo survival. The 3- and 5-yr rates of VCF were 10.4% and 14.4%, respectively, and 3- and 5-yr rates of plexopathy were 2.2% and 5.1%, respectively. A single duodenal perforation was observed, and there was no radiation myelopathy events. CONCLUSION: Shorter survival after spine SBRT was seen in patients with less radiosensitive histologies (ie, not breast or prostate), ECOG ≥2, and polymetastatic disease. Pain and paraspinal disease were also associated with poor survival. Fractionated spine SBRT confers a low risk of late serious adverse events.

Local control and patterns of failure for "Radioresistant" spinal metastases following stereotactic body radiotherapy compared to a "Radiosensitive" reference.

PURPOSE: The concept of a radioresistant (RR) phenotype has been challenged with use of stereotactic body radiotherapy (SBRT). We compared outcomes following SBRT to RR spinal metastases to a radiosensitive cohort. METHODS: Renal cell, melanoma, sarcoma, gastro-intestinal, and thyroid spinal metastases were identified as RR and prostate cancer (PCA) as radiosensitive. The primary endpoint was MRI-based local failure (LF). Secondary endpoints included overall survival (OS) and vertebral compression fracture (VCF). RESULTS: From a prospectively maintained database of 1394 spinal segments in 605 patients treated with spine SBRT, 173 patients/395 RR spinal segments were compared to 94 patients/185 PCA segments. Most received 24-28 Gy in 2 fractions (68.9%) and median follow-up was 15.5 months (range, 1.4-84.2 months). 1- and 2-year LF rates were 19.2% and 22.4% for RR metastases, respectively, which were significantly greater (p < 0.001) than PCA (3.2% and 8.4%, respectively). Epidural disease (HR: 2.47, 95% CI 1.65-3.71, p < 0.001) and RR histology (HR: 2.41, 95% CI 1.45-3.99, p < 0.001) predicted for greater LF. Median OS was 17.4 and 61.0 months for RR and PCA cohorts, respectively. Lung/liver metastases, polymetastatic disease and epidural disease predicted for worse OS. 2-year VCF rates were ~ 13% in both cohorts. Coverage of the CTV V90 (clinical target volume receiving 90% of prescription dose) by ≥ 87% (HR: 2.32, 95% CI 1.29-4.18, p = 0.005), no prior spine radiotherapy (HR: 1.96, 95% CI 1.09-3.55, p = 0.025), and a greater Spinal Instability Neoplasia Score (p = 0.013) predicted for VCF. CONCLUSIONS: Higher rates of LF were observed after spine SBRT in RR metastases. Optimization strategies include dose escalation and aggressive management of epidural disease.

Adverse Radiation Effect After Hypofractionated Stereotactic Radiosurgery in 5 Daily Fractions for Surgical Cavities and Intact Brain Metastases.

PURPOSE: Limited data exist quantifying the risk of adverse radiation effect (ARE) specific to hypofractionated stereotactic radiosurgery (HSRS). We present our analyses of the risk of ARE after 5 daily fractions of HSRS to surgical cavities and intact metastases. METHODS AND MATERIALS: One hundred and eighty-seven consecutively treated patients with 118 surgical cavities and 132 intact metastases were retrospectively reviewed. All patients were treated with 5 daily fractions with a 2 mm planning target volume applied. Clinical and dosimetric variables were assessed to identify predictors of ARE. RESULTS: The median total prescribed dose was 30 Gy (range, 20-35 Gy) and median follow-up was 12 months. One hundred forty-four patients (77%) received treatment to a single target. Median planning target volumes for resection cavity and intact metastases were 24.9 cm3 and 7.7 cm3, respectively. ARE and symptomatic ARE were observed 21.2% and 10.8% of targets, respectively, and the median time to ARE was 8 months. Time to ARE was <6 months for 38%, 6 to 12 months for 43%, and >12 months for 19% of targets. Multivariable analysis identified intact metastases versus cavities (odds ratio [OR], 3.65; 95% confidence interval [CI], 1.33-10) as a significant predictor of symptomatic ARE. Specific to cavity HSRS, prior whole brain radiation therapy (OR 7.73; 95% CI, 1.67-35.69) and prior stereotactic radiosurgery (OR 8.66; 95% CI, 1.14-65.7) were significant predictors of symptomatic ARE. For intact metastases, the total brain minus gross tumor volume (GTV) receiving 30 Gy (BMC30) was a significant predictor of symptomatic ARE (OR, 1.21; 95% CI, 1.02-1.43), and a volume-based BMC30 threshold of 10.5 cm3 was significant with an OR of 7.21 (95% CI, 1.31-39.45). CONCLUSIONS: The risk of ARE was greater for intact metastases compared with cavities after HSRS. For intact lesions, the BMC30 was predictive for symptomatic necrosis, and a threshold of 10.5 cm3 may guide treatment planning.

Stereotactic Body Radiotherapy for Spinal Metastases at the Extreme Ends of the Spine: Imaging-Based Outcomes for Cervical and Sacral Metastases.

BACKGROUND: The unique anatomy and biomechanical features of the cervical spine and sacrum may impact treatment outcomes following spine stereotactic body radiotherapy (SBRT). Current data for spine metastases are not specific for these locations. OBJECTIVE: To report imaging-based SBRT outcomes to cervical and sacral metastases. METHODS: We retrospectively reviewed our prospective spine SBRT database for cervical and sacral metastases. Patients were followed at 2- to 3-mo intervals with a clinical visit and full spine magnetic resonance imaging (MRI) and we report overall survival (OS), vertebral compression fracture (VCF), and MR imaging-based local control (LC) rates. RESULTS: Fifty-two patients and 93 treated spinal segments were identified. Fifty-six segments were within the cervical spine and 37 within the sacrum, the median follow-up was 14.4 and 19.5 mo, and the median total dose/number of fractions was 24 Gy/2, respectively. Cumulative LC at 1 and 2 yr were 94.5% and 92.7% for the cervical cohort, and 86.5% and 78.7% in the sacral cohort, respectively. Lack of posterior spinal element involvement in the cervical spine (P < .0001) and absence of epidural disease (hazard ratio 0.275, 95% confidence interval 0.076-0.989, P = .048) in the sacral cohort predicted LC. Median OS was 16.3 and 28.5 mo in the cervical spine and sacrum cohorts, respectively. Two cases of sacral VCF, 1 brachial plexopathy, and 1 lumbar-sacral plexopathy were observed. CONCLUSION: Although high rates of LC were observed, strategies specific to the sacrum may require further optimization.

A retrospective review of phyllodes tumours of the breast: A single institution experience.

BACKGROUND: Phyllodes tumours are rare and histologically diverse, posing challenges in prognosis and treatment. Due to their rarity, they have seldom been studied. PURPOSE: The purpose was to investigate clinical practices in the management of phyllodes tumours, as well as patient outcomes to contribute to the limited body of knowledge surrounding these tumours. METHODS: A retrospective review was conducted on all patients with phyllodes tumours at a single institution. Descriptive analyses were conducted on demographic, disease and treatment (breast-conserving surgery, mastectomy, surgical re-excision, adjuvant/palliative radiation, palliative chemotherapy) information. Overall and disease-free survivals were analyzed, and the cumulative incidence of recurrence and metastases was compared. RESULTS: 79 patients with phyllodes tumours of the breast were included in the study. Tumours were classified as malignant, borderline, or benign in 67.1%, 21.5%, and 11.4% of patients, respectively. There were no statistically significant differences in overall or disease-free survival between patients with benign, borderline or malignant disease. Only patients with malignant disease developed recurrence or metastases. Those with malignant disease who received mastectomies had a lower 10-year cumulative incidence of recurrence; however this was not statistically significant (p = 0.69). All patients had negative surgical margins due to a re-excision or mastectomy following margin-positive breast conserving surgery. Of all risk factors assessed, necrosis was significantly associated with increased incidence of recurrence (local or distant) in patients with malignant disease (p = 0.03). CONCLUSION: The presence of tumour necrosis is a significant negative prognostic factor. Breast-conserving surgery may be adequate in providing local control, given negative surgical margins.

Patient preference for stereotactic radiosurgery plus or minus whole brain radiotherapy for the treatment of brain metastases.

BACKGROUND: Optimal management for limited, non-resectable brain metastases is an evolving area in radiation oncology. Previous data show no difference in survival between stereotactic radiosurgery (SRS) and SRS plus whole-brain radiotherapy (WBRT). Neurocognitive toxicities, treatment duration and tumor recurrence differ and therefore patient values play an important role in decision making. We aim to elicit patient preferences and understand factors important in deciding which treatment to pursue. METHODS: Patients were recruited from 2 centers in North America. Eligibility criteria included ≤4 intracranial lesions and physician judgment that either treatment was appropriate. Those with prior treatment for brain metastases were excluded. A decision board presented the treatments and summarized evidence regarding disease control and toxicity. An option to either take an active or passive role was offered. If taking a passive role, treatment was left to the clinician. If an active role was taken, patients made a decision about whether to receive SRS alone, or in combination with WBRT. A debriefing questionnaire to rank important factors in decision making was then completed. Descriptive statistics summarized findings. RESULTS: A total of 23 patients were enrolled. The majority of patients were male (15/23; 65.2%), had primary lung cancer (15/23; 65.2%) and the mean age was 65.5 years. All patients took an active role in deciding their treatment. The majority of patients (21/23) chose to receive SRS alone. The highest ranked factors were quality of life (9.4/10), ability to maintain functional independence (9.3/10) and influence of treatment on survival (9.2/10). The least important factor was number of trips required to the cancer center (5.0/10). CONCLUSIONS: A patient centered approach to decision making in brain metastases is feasible. Most patients will take an active role in management if relevant information is presented in a clear, understandable manner. When informed, most patients prefer SRS alone rather than SRS + WBRT and identify quality of life, ability to maintain functional independence and influence of treatment on survival as highly important factors in making their decision.

Palliative treatment of metastatic phyllodes tumors: a case series.

Up to 20% of malignant phyllodes tumors (PT) metastasize, most frequently to the lungs, bone, and brain. Descriptions of metastatic PT are limited in the literature. In this series, we present three cases of malignant PT metastatic to various unusual sites including the peritoneum, soft tissue of the thigh, and scalp. All three patients initially received surgical resections, and two underwent adjuvant radiation. All three patients developed lung metastases first. Several palliative modalities were used including surgical resection, gamma-knife stereotactic radiosurgery, external beam radiation, and chemotherapy. All three patients died within 3 years of the initial diagnosis.

Bilateral Blindness Following Chemoradiation for Locally Advanced Oropharyngeal Carcinoma.

Wernicke's encephalopathy is a life-threatening neurologic complication of thiamine deficiency. Though the presentation of symptoms can vary widely, the classical triad is founded on ophthalmoplegia, alteration of mental status, and gait disturbance. We describe a case of Wernicke's encephalopathy in an oncology patient shortly after concurrent 5-fluorouracil, carboplatin, and radiotherapy for locally advanced oropharyngeal cancer, presenting as complete bilateral blindness, ataxia, nystagmus, and confusion. Thiamine was given based on clinical suspicion and rapid improvement of clinical findings occurred. An MRI performed later supported the diagnosis of Wernicke's encephalopathy. A multifactorial etiology of thiamine deficiency from nutritional deficits and neurotoxic effects of chemotherapy are hypothesized.