Predictors of castration-resistant prostate cancer after dose-escalated external beam radiotherapy.

BACKGROUND: Castration-resistant prostate cancer (CRPC) is a near uniformly fatal form of prostate cancer; however, information on time to development and predictors for progression to CRPC is limited. We report a detailed longitudinal study for development of CRPC in men initially treated with external beam radiotherapy (EBRT). METHODS: During 1991-2008, 2,478 patients with clinically localized prostate cancer were treated with dose-escalated EBRT at a single institution. The primary objective was to determine predictors of CRPC among men who failed definitive EBRT and progressed to salvage androgen-deprivation therapy (ADT). CRPC was defined as castrate levels of testosterone (<50 ng/dl) with progressive biochemical or radiographic disease. RESULTS: For the entire cohort (n = 2,478), the 10-year cumulative incidence rate for developing CRPC was 9.9%. For those that progressed to salvage ADT (n = 362), the 7-year cumulative incidence rates for developing CRPC from time of salvage ADT was 33.7%. Amongst this cohort, multivariable analysis demonstrated that PSA doubling-time (continuous; hazard ratio [HR], 0.98 [0.97-0.99], P < 0.001), higher Gleason score (HR, 1.96 [1.12-3.43]; P = 0.034), and duration of ADT at time of EBRT (continuous; HR, 1.02 [1.01-1.03]; P = 0.007) were associated with development of CRPC. CONCLUSIONS: This represents the first report of predictors of CRPC for patients treated with modern dose-escalated EBRT. We demonstrate that among the minority of patients not initially cured after EBRT, those treated with longer-course ADT have higher rates of resistance to the re-introduction of ADT. Future trials will need to test this subgroup with more aggressive or alternative forms of salvage therapies.

Clinical trial of proton craniospinal irradiation for leptomeningeal metastases.

BACKGROUND: Leptomeningeal metastases (LM) are associated with limited survival and treatment options. While involved-field radiotherapy is effective for local palliation, it lacks durability. We evaluated the toxicities of proton craniospinal irradiation (CSI), a treatment encompassing the entire central nervous system (CNS) compartment, for patients with LM from solid tumors. METHODS: We enrolled patients with LM to receive hypofractionated proton CSI in this phase I prospective trial. The primary endpoint was to describe treatment-related toxicity, with dose-limiting toxicity (DLT) defined as any radiation-related grade 3 non-hematologic toxicity or grade 4 hematologic toxicity according to the Common Terminology Criteria for Adverse Events that occurred during or within 4 weeks of completion of proton CSI. Secondary endpoints included CNS progression-free survival (PFS) and overall survival (OS). RESULTS: We enrolled 24 patients between June 2018 and April 2019. Their median follow-up was 11 months. Twenty patients were evaluable for protocol treatment-related toxicities and 21 for CNS PFS and OS. Two patients in the dose expansion cohort experienced DLTs consisted of grade 4 lymphopenia, grade 4 thrombocytopenia, and/or grade 3 fatigue. All DLTs resolved without medical intervention. The median CNS PFS was 7 months (95% CI: 5-13) and the median OS was 8 months (95% CI: 6 to not reached). Four patients (19%) were progression-free in the CNS for more than 12 months. CONCLUSION: Hypofractionated proton CSI using proton therapy is a safe treatment for patients with LM from solid tumors. We saw durable disease control in some patients.

Frequency of Large Intrafractional Target Motions During Spine Stereotactic Body Radiation Therapy.

Spine stereotactic body radiation therapy frequently involves the delivery of high doses to targets in proximity to the spinal cord; thus, the radiation must be delivered with great spatial accuracy. Monitoring for large shifts in target and cord position that might occur during dose delivery is a challenge for clinics equipped with a conventional C-arm Linac. Treatment must be halted, then imaging and registration must be done to determine whether a significant shift has occurred. In this retrospective study of 1019 spine SBRT treatments, we investigated the number of target shifts >2 mm in any direction that occurred in carefully immobilized patients. Orthogonal kV images were acquired 3 to 5 times during each session using in an in-room imaging system. Although the likelihood of large intrafractional shifts was found to be very low, they did occur in 6 treatment sessions. Intrafractional monitoring was found to be an important safety component of treatment delivery.

Technical Note: A custom-designed flexible MR coil array for spine radiotherapy treatment planning.

PURPOSE: To assess the performance and optimize the MR image quality when using a custom-built flexible radiofrequency (RF) spine coil array fitted between the immobilization device and the patient for spine radiotherapy treatment planning. METHODS: A 32 channel flexible custom-designed receive-only coil array has been developed for spine radiotherapy simulation for a 3 T Philips MR scanner. Coil signal-to-noise performance and interactions with standard vendor hardware were assessed. In four volunteers, immobilization molds were created with a dummy version of the array within the mold, and subjects were scanned using the custom array in the mold. Phantoms and normal volunteers were scanned with both the custom spine coil array and the vendor's FDA-approved in-table posterior coil array to compare performance. RESULTS: The superior-inferior field of view for the custom spine array was ~30 cm encompassing at least 10 vertebrae. A noise correlation matrix showed at least 25 dB isolation between all coil elements. Signal-to-noise ratio (SNR) calculated on a phantom scan at the depth of the spinal cord was a factor of 3 higher with the form-fit spine array as compared to the vendor's posterior coil array. The body coil B1 transmit map was equivalent with and without the spine array in place demonstrating that the elements are decoupled from the body coil. Volunteer imaging showed improved SNR as compared to the vendor's posterior coil array. The custom array permitted a high degree of acceleration making possible the acquisition of isotropic high-resolution 1.1 × 1.1 × 1.1 mm3 three-dimensional data set over a 30-cm section of the spine in less than 5 min. CONCLUSION: The custom-designed form-fitting flexible spine coil array provided enhanced SNR and increased acceleration compared to the vendor's posterior array. Future studies will assess MR-based spinal cord imaging with the custom coil in comparison to CT myelogram.

Palliative Radiation Therapy for Oncologic Emergencies in the Setting of COVID-19: Approaches to Balancing Risks and Benefits.

Palliation of metastatic disease compromises a significant portion of radiation treatments in the United States. These patients present a unique challenge in resource-limited settings, as expeditious treatment is often required to prevent serious morbidity. In order to reduce the risk of infection with severe acute respiratory syndrome coronavirus-2 and maximize the benefit to patients, we present evidence-based recommendations for radiation in patients with oncologic emergencies. Radiation oncologists with expertise in the treatment of metastatic disease at a high-volume comprehensive cancer center reviewed the available evidence and recommended best practices for the treatment of common oncologic emergencies, with attention to balancing the risk of infection with severe acute respiratory syndrome coronavirus-2 and the potential morbidity of delaying treatment. Many prospective trials and national guidelines support the use of abbreviated courses of radiotherapy for patients with oncologic emergencies. As such, in the setting of the current coronavirus disease 2019 pandemic, the use of hypofractionated radiation therapy for patients requiring palliation for oncologic emergencies achieves desirable functional outcomes without compromising care.

Clinical Experience of Automated SBRT Paraspinal and Other Metastatic Tumor Planning With Constrained Hierarchical Optimization.

PURPOSE: We report on the clinical performance of a fully automated approach to treatment planning based on a Pareto optimal, constrained hierarchical optimization algorithm, named Expedited Constrained Hierarchical Optimization (ECHO). METHODS AND MATERIALS: From April 2017 to October 2018, ECHO produced 640 treated plans for 523 patients who underwent stereotactic body radiation therapy (RT) for paraspinal and other metastatic tumors. A total of 182 plans were for 24 Gy in a single fraction, 387 plans were for 27 Gy in 3 fractions, and the remainder were for other prescriptions or fractionations. Of the plans, 84.5% were for paraspinal tumors, with 69, 302, and 170 in the cervical, thoracic, and lumbosacral spine, respectively. For each case, after contouring, a template plan using 9 intensity modulated RT fields based on disease site and tumor location was sent to ECHO through an application program interface plug-in from the treatment planning system. ECHO returned a plan that satisfied all critical structure hard constraints with optimal target volume coverage and the lowest achievable normal tissue doses. Upon ECHO completion, the planner received an e-mail indicating the plan was ready for review. The plan was accepted if all clinical criteria were met. Otherwise, a limited number of parameters could be adjusted for another ECHO run. RESULTS: The median planning target volume size was 84.3 cm3 (range, 6.9-633.2). The median time to produce 1 ECHO plan was 63.5 minutes (range, 11-340 minutes) and was largely dependent on the field sizes. Of the cases, 79.7% required 1 run to produce a clinically accepted plan, 13.3% required 1 additional run with minimal parameter adjustments, and 7.0% required ≥2 additional runs with significant parameter modifications. All plans met or bettered the institutional clinical criteria. CONCLUSIONS: We successfully implemented automated stereotactic body RT paraspinal and other metastatic tumors planning. ECHO produced high-quality plans, improved planning efficiency and robustness, and enabled expedited treatment planning at our clinic.

Replacing 30 Gy in 10 fractions with stereotactic body radiation therapy for bone metastases: A large multi-site single institution experience 2016-2018.

BACKGROUND: Bone metastases cause significant morbidity in patients with cancer, and radiation therapy (RT) is an effective treatment approach. Indications for more complex ablative techniques are emerging. We sought to evaluate RT trends at a large multi-site tertiary cancer center. METHODS: Patients who received RT for bone metastases at a single institution (including regional outpatient clinics) from 2016 to 2018 were identified. Patients were grouped by RT regimen: single-fraction conventional RT (8 Gy × 1), 30 Gy in 10 fractions, SBRT, and "other". Multinomial logistic regression was performed to assess trends in regimens over time. Binary logistic regression was performed to evaluate factors associated with receipt of SBRT. RESULTS: Between 2016 and 2018, 5,952 RT episodes were received by 2,969 patients with bone metastases. Overall, 76% of episodes were ≤ 5 fractions. The median number of fractions planned for SBRT and non-SBRT episodes was 3 (IQR 3-3) and 5 (IQR 5-10), respectively. Use of SBRT increased from 2016 to 2018 (39% to 53%, p < 0.01) while use of 30 Gy in 10 fractions decreased (26% to 12%, p < 0.01), and 8 Gy × 1 was stable (5.3% to 6.9%, p = 0.28). SBRT was associated with higher performance status (p < 0.01) and non-radiosensitive histology (p < 0.01). Use of SBRT increased in the regional network (19% to 48%, p < 0.01) and at the main center (52% to 59%, p = 0.02), but did not increase within 30 days of death. More patients treated with 8 Gy × 1 than SBRT died within 30 days of treatment (24% vs 3.8%, respectively, p < 0.01). CONCLUSIONS: SBRT is replacing 30 Gy in 10 fractions for bone metastases, especially among patients with high performance status and non-radiosensitive histologies. Better prognostic algorithms could further improve patient-centered treatment selection at the end of life.

Residual Tumor Volume, Cell Volume Fraction, and Tumor Cell Kill During Fractionated Chemoradiation Therapy of Human Glioblastoma using Quantitative Sodium MR Imaging.

PURPOSE: Spatial and temporal patterns of response of human glioblastoma to fractionated chemoradiation are described by changes in the bioscales of residual tumor volume (RTV), tumor cell volume fraction (CVF), and tumor cell kill (TCK), as derived from tissue sodium concentration (TSC) measured by quantitative sodium MRI at 3 Tesla. These near real-time patterns during treatment are compared with overall survival. EXPERIMENTAL DESIGN: Bioscales were mapped during fractionated chemoradiation therapy in patients with glioblastomas (n = 20) using TSC obtained from serial quantitative sodium MRI at 3 Tesla and a two-compartment model of tissue sodium distribution. The responses of these parameters in newly diagnosed human glioblastomas undergoing treatment were compared with time-to-disease progression and survival. RESULTS: RTV following tumor resection showed decreased CVF due to disruption of normal cell packing by edema and infiltrating tumor cells. CVF showed either increases back toward normal as infiltrating tumor cells were killed, or decreases as cancer cells continued to infiltrate and extend tumor margins. These highly variable tumor responses showed no correlation with time-to-progression or overall survival. CONCLUSIONS: These bioscales indicate that fractionated chemoradiotherapy of glioblastomas produces variable responses with low cell killing efficiency. These parameters are sensitive to real-time changes within the treatment volume while remaining stable elsewhere, highlighting the potential to individualize therapy earlier in management, should alternative strategies be available.

Feasibility of radiosurgery for patients with spinal tumors treated in lateral decubitus position: A case series from Memorial Sloan Kettering Cancer Center.

INTRODUCTION: Often in clinical practice radiation oncologists encounter patients who require treatment to the spine commonly in the setting of metastatic disease. These metastases usually cause pain, immobility, or neurologic deficits mandating expedited therapy to alleviate the suffering of our patients. Spine radiosurgery techniques have been used extensively for palliation purposes; however, given the patients' deteriorating condition or pain and inability to tolerate anesthesia the radiation oncologist is often left with the conundrum of how to best set up his or her patient in preparation for radiosurgery if supine is not a viable option. In the Memorial Sloan Kettering Cancer Center several patients have been treated successfully in the lateral decubitus position to overcome this set-up issue. In this report, the feasibility of the lateral decubitus set-up for patients who benefit from radiosurgery to the spine when and if they cannot tolerate standard supine position is explored. OBJECTIVE: To report on a retrospective case series of three patients with a total of four lesions who were treated with radiosurgery for spinal metastases while set up in the lateral decubitus position. METHODS AND MATERIALS: This is a retrospective case series of 3 patients who were treated with radiosurgery to the spine for palliation of painful metastatic foci. Patients were treated in the lateral decubitus position in 1-5 fractions in order to be eligible for this retrospective case series. Their set-up data, and clinical outcomes were then compared with historic controls. RESULTS: Patients who were treated in the lateral decubitus position were set up reliably and reproducibly. Additionally clinical outcomes on routine follow-up and imaging, and toxicity profiles also corroborated the utility of this treatment set-up. CONCLUSIONS: Routinely employing optical surface tracking during patient setup followed by KVCBCT prior to treatment delivery along with intra-fractional monitoring is safe and effective while utilizing the lateral decubitus position for the treatment of spinal metastases for patients who cannot tolerate the supine position. Finally the patient follow-up also corroborated that treatments were successful thus lending credence to the safety, ease, effectiveness, and feasibility of this patient set-up.

Multicenter, Phase 1, Dose Escalation Study of Hypofractionated Stereotactic Radiation Therapy With Bevacizumab for Recurrent Glioblastoma and Anaplastic Astrocytoma.

PURPOSE: To establish the maximum tolerated dose of a 3-fraction hypofractionated stereotactic reirradiation schedule when delivered with concomitant bevacizumab to treat recurrent high-grade gliomas. METHODS AND MATERIALS: Patients with recurrent high-grade glioma with Karnofsky performance status ≥60, history of standard fractionated initial radiation, tumor volume at recurrence ≤40 cm3, and absence of brainstem or corpus callosum involvement were eligible. A standard 3+3 phase 1 dose escalation trial design was utilized, with dose-limiting toxicities defined as any grade 3 to 5 toxicities possibly, probably, or definitely related to radiation. Bevacizumab was given at a dose of 10 mg/kg every 2 weeks. Hypofractionated stereotactic reirradiation was initiated after 2 bevacizumab doses, delivered in 3 fractions every other day, starting at 9 Gy per fraction. RESULTS: A total of 3 patients were enrolled at the 9 Gy × 3 dose level cohort, 5 in the 10 Gy × 3 cohort, and 7 in the 11 Gy × 3 cohort. One dose-limiting toxicity of grade 3 fatigue and cognitive deterioration possibly related to hypofractionated stereotactic reirradiation was observed in the 11 Gy × 3 cohort, and this dose was declared the maximum tolerated dose in combination with bevacizumab. Although no symptomatic radionecrosis was observed, substantial treatment-related effects and necrosis were observed in resected specimens. The intent-to-treat median overall survival was 13 months. CONCLUSIONS: Reirradiation using a 3-fraction schedule with bevacizumab support is feasible and reasonably well tolerated. Dose-escalation was possible up to 11 Gy × 3, which achieves a near doubling in the delivered biological equivalent dose to normal brain, in comparison with our previous 6 Gy × 5 schedule. Promising overall survival warrants further investigation.

Intensity-modulated radiotherapy in high-grade gliomas: clinical and dosimetric results.

PURPOSE: To report preliminary clinical and dosimetric data from intensity-modulated radiotherapy (IMRT) for malignant gliomas. METHODS AND MATERIALS: Fifty-eight consecutive high-grade gliomas were treated between January 2001 and December 2003 with dynamic multileaf collimator IMRT, planned with the inverse approach. A dose of 59.4-60 Gy at 1.8-2.0 Gy per fraction was delivered. A total of three to five noncoplanar beams were used to cover at least 95% of the target volume with the prescription isodose line. Glioblastoma accounted for 70% of the cases, and anaplastic oligodendroglioma histology (pure or mixed) was seen in 15% of the cases. Surgery consisted of biopsy only in 26% of the patients, and 80% received adjuvant chemotherapy. RESULTS: With a median follow-up of 24 months, 85% of the patients have relapsed. The median progression-free survival time for anaplastic astrocytoma and glioblastoma histology was 5.6 and 2.5 months, respectively. The overall survival time for anaplastic glioma and glioblastoma was 36 and 9 months, respectively. Ninety-six percent of the recurrences were local. No Grade IV/V late neurologic toxicities were noted. A comparative dosimetric analysis revealed that regardless of tumor location, IMRT did not significantly improve target coverage compared with three-dimensional planning. However, IMRT resulted in a decreased maximum dose to the spinal cord, optic nerves, and eye by 16%, 7%, and 15%, respectively, owing to its improved dose conformality. The mean brainstem dose also decreased by 7%. Intensity-modulated radiotherapy delivered with a limited number of beams did not result in an increased dose to the normal brain. CONCLUSIONS: It is unlikely that IMRT will improve local control in high-grade gliomas without further dose escalation compared with conventional radiotherapy. However, it might result in decreased late toxicities associated with radiotherapy.

CT image-guided intensity-modulated therapy for paraspinal tumors using stereotactic immobilization.

PURPOSE: To design and implement a noninvasive stereotactic immobilization technique with daily CT image-guided positioning to treat patients with paraspinal lesions accurately and to quantify the systematic and random patient setup errors occurring with this method. METHODS AND MATERIALS: A stereotactic body frame (SBF) was developed for "rigid" immobilization of paraspinal patients. The inherent accuracy of this system for stereotactic CT-guided treatment was evaluated with phantom studies. Seven patients with thoracic and lumbar spine lesions were immobilized with the SBF and positioned for 33 treatment fractions using daily CT scans. For all 7 patients, the daily setup errors, as assessed from the daily CT scans, were corrected at each treatment fraction. A retrospective analysis was also performed to assess what the impact on patient treatment would have been without the CT-based corrections (i.e., if patient setup had been performed only with the SBF). RESULTS: The average magnitude of systematic and random errors from uncorrected patient setups using the SBF was approximately 2 mm and 1.5 mm (1 SD), respectively. For fixed phantom targets, the system accuracy for the SBF localization and treatment was shown to be within 1 mm (1 SD) in any direction. Dose-volume histograms incorporating these uncertainties for an intensity-modulated radiotherapy plan for lumbar spine lesions were generated, and the effects on the dose-volume histograms were studied. CONCLUSION: We demonstrated a very accurate and precise method of patient immobilization and treatment delivery based on a noninvasive SBF and daily image guidance for paraspinal lesions. The SBF provides excellent immobilization for paraspinal targets, with setup accuracy better than 2 mm (1 SD). However, for highly conformal paraspinal treatments, uncorrected systematic and random errors of 2 mm in magnitude can result in a significantly greater (>100%) dose to the spinal cord than planned, even though the planned target coverage may not change substantially. With daily CT guidance using the SBF, we showed that the maximal spinal cord dose is ensured to be within 10-15% of the planned value.

Long-term survival and toxicity in patients treated with high-dose intensity modulated radiation therapy for localized prostate cancer.

PURPOSE: To report long-term survival and toxicity outcomes with the use of high-dose intensity modulated radiation therapy (IMRT) to 86.4 Gy for patients with localized prostate cancer. METHODS AND MATERIALS: Between August 1997 and December 2008, 1002 patients were treated to a dose of 86.4 Gy using a 5-7 field IMRT technique. Patients were stratified by prognostic risk group based on National Comprehensive Cancer Network risk classification criteria. A total of 587 patients (59%) were treated with neoadjuvant and concurrent androgen deprivation therapy. The median follow-up for the entire cohort was 5.5 years (range, 1-14 years). RESULTS: For low-, intermediate-, and high-risk groups, 7-year biochemical relapse-free survival outcomes were 98.8%, 85.6%, and 67.9%, respectively (P<.001), and distant metastasis-free survival rates were 99.4%, 94.1%, and 82.0% (P<.001), respectively. On multivariate analysis, T stage (P<.001), Gleason score (P<.001), and >50% of initial biopsy positive core (P=.001) were predictive for distant mestastases. No prostate cancer-related deaths were observed in the low-risk group. The 7-year prostate cancer-specific mortality (PCSM) rates, using competing risk analysis for intermediate- and high-risk groups, were 3.3% and 8.1%, respectively (P=.008). On multivariate analysis, Gleason score (P=.004), percentage of biopsy core positivity (P=.003), and T-stage (P=.033) were predictive for PCSM. Actuarial 7-year grade 2 or higher late gastrointestinal and genitourinary toxicities were 4.4% and 21.1%, respectively. Late grade 3 gastrointestinal and genitourinary toxicity was experienced by 7 patients (0.7%) and 22 patients (2.2%), respectively. Of the 427 men with full potency at baseline, 317 men (74%) retained sexual function at time of last follow-up. CONCLUSIONS: This study represents the largest cohort of patients treated with high-dose radiation to 86.4 Gy, using IMRT for localized prostate cancer, with the longest follow-up to date. Our findings indicate that this treatment results in excellent clinical outcomes with acceptable toxicity.

Timing of surgery and radiotherapy in the management of metastatic spine disease: a systematic review.

The last decade has witnessed a dramatic change in management of metastatic spine disease, with an increased role for surgery and emerging use of stereotactic radiotherapy, often in combination. Patients may be treated with radiotherapy followed by surgery, or have surgery and then adjuvant radiotherapy. In both cases, the surgeon and oncologist need to select the optimal timing for surgery and radiotherapy to minimize wound complications while obtaining maximum oncolytic effects. The purpose of this review was to determine the optimal timing of surgery and radiotherapy in patients surgically treated for spinal metastases. A systematic review utilizing Medline, Embase, Paper First, Web of Science, Google Scholar, and the Cochrane Database of Systematic Reviews was performed. References were screened to further identify relevant studies and basic science literature reviewed. A total of 46 reports discussing the timing of surgery after radiotherapy, describing experience in 5836 patients, were identified. Only one retrospective study addressed the research question and suggested that surgery within seven days of radiation increases the rate of postoperative wound complications. Timing of adjuvant radiotherapy following surgery was addressed in 51 reports describing 7090 patients. None of the studies specifically answered the research question. The time interval between radiotherapy and surgery was reported as 5-21 days in nine studies. Based on this systematic review together with the understanding of general principles of wound healing and effects of radiation on wound healing, the optimal radiotherapy-surgery/surgery-radiotherapy time interval should be at least one week to minimize wound complications.

Real-time intraoperative computed tomography assessment of quality of permanent interstitial seed implantation for prostate cancer.

OBJECTIVES: To evaluate the use of real-time kilovoltage cone-beam computed tomography (CBCT) during prostate brachytherapy for intraoperative dosimetric assessment and correcting deficient dose regions. METHODS: A total of 20 patients were evaluated intraoperatively with a mobile CBCT unit immediately after implantation while still anesthetized. The source detector system was enclosed in a circular CT-like geometry with a bore that accommodates patients in the lithotomy position. After seed deposition, the CBCT scans were obtained. The dosimetry was evaluated and compared with the standard postimplantation CT-based assessment. In 8 patients, the deposited seeds were localized in the intraoperative CBCT frame of reference and registered to the intraoperative transrectal ultrasound images. With this information, a second intraoperative plan was generated to ascertain whether additional seeds were needed to achieve the planned prescription dose. The final dosimetry was compared with the postimplantation scan assessment. RESULTS: The mean differences between the dosimetric parameters from the intraoperative CBCT and postimplant CT scans were < .5% for percentage of volume receiving 100% of the prescription dose, minimal dose received by 90% of the prostate, and percentage of volume receiving 150% of the prescription dose. The minimal dose received by 5% (maximal dose) of the urethra differed by 8% on average and for the rectum an average difference of approximately 18% was observed. After fusion of the implanted seed coordinates from the intraoperative CBCT scans to the intraoperative transrectal ultrasound images, the dosimetric outcomes were not significantly different from the postimplantation CT dosimetric results. CONCLUSIONS: Intraoperative CT-based dosimetric evaluation of prostate permanent seed implantation before anesthesia reversal is feasible and might avert misadministration of dose delivery. The dosimetric measurements using the intraoperative CBCT scans were dependable and correlated well with the postimplant diagnostic CT findings.

Risk of fracture after single fraction image-guided intensity-modulated radiation therapy to spinal metastases.

PURPOSE: Single-fraction image-guided intensity-modulated radiation therapy (IG-IMRT) allows for tumoricidal treatment of traditionally radioresistant cancers while sparing critical adjacent structures. Risk of vertebral fracture after IG-IMRT for spinal metastases has not been defined. PATIENTS AND METHODS: We evaluated 62 consecutive patients undergoing single fraction IG-IMRT at 71 sites for solid organ metastases. A neuroradiologist and three spine surgeons evaluated prospectively obtained magnetic resonance/computed tomography (CT) imaging studies for post-treatment fracture development and tumor recurrence. RESULTS: Fracture progression was noted in 27 vertebrae (39%). Multivariate logistic regression analysis showed that CT appearance, lesion location, and percent vertebral body involvement independently predicted fracture progression. Lesions located between T10 and the sacrum were 4.6 times more likely to fracture than were lesions above T10 (95% CI, 1.1 to 19.7). Lytic lesions were 6.8 times more likely to fracture than were sclerotic and mixed lesions (95% CI, 1.4 to 33.3). As percent vertebral body involvement increased, odds of fracture also increased. Patients with fracture progression had significantly higher narcotic use, change in Karnofsky performance score, and a strong trend toward higher pain scores. Local tumor progression occurred in seven patients and contributed to one fracture. Obesity, posterior element involvement, bisphosphonate use, and local kyphosis did not confer increased risk. CONCLUSION: Vertebral fracture is common after single fraction IG-IMRT for metastatic spine lesions. Lytic disease involving more than 40% of the vertebral body and location at or below T10 confer a high risk of fracture, the presence of which yields significantly poorer clinical outcomes. These results may help clinicians identify high-risk patients who would benefit from prophylactic vertebro- or kyphoplasty.