Dynamic contrast-enhanced magnetic resonance imaging of osseous spine metastasis before and 1 hour after high-dose image-guided radiation therapy.

OBJECTIVE High-dose image-guided radiation therapy (HD IGRT) has been instrumental in mitigating some limitations of conventional RT. The recent emergence of dynamic contrast-enhanced (DCE) MRI to investigate tumor physiology can be used to verify the response of human tumors to HD IGRT. The purpose of this study was to evaluate the near-immediate effects of HD IGRT on spine metastases through the use of DCE MRI perfusion studies. METHODS Six patients with spine metastases from prostate, thyroid, and renal cell carcinoma who underwent HD IGRT were studied using DCE MRI prior to and 1 hour after HD IGRT. The DCE perfusion parameters plasma volume (Vp) and vascular permeability (Ktrans) were measured to assess the near-immediate and long-term tumor response. A Mann-Whitney U-test was performed to compare significant changes (at p ≤ 0.05) in perfusion parameters before and after RT. RESULTS The authors observed a precipitous drop in Vp within 1 hour of HD IGRT, with a mean decrease of 65.2%. A significant difference was found between Vp values for before and 1 hour after RT (p ≤ 0.05). No significant change was seen in Vp (p = 0.31) and Ktrans (p = 0.1) from 1 hour after RT to the first follow-up. CONCLUSIONS The data suggest that there is an immediate effect of HD IGRT on the vascularity of spine metastases, as demonstrated by a precipitous decrease in Vp. The DCE MRI studies can detect such changes within 1 hour after RT, and findings are concordant with existing animal models.

Single-dose radiotherapy disables tumor cell homologous recombination via ischemia/reperfusion injury.

Tumor cure with conventional fractionated radiotherapy is 65%, dependent on tumor cell-autonomous gradual buildup of DNA double-strand break (DSB) misrepair. Here we report that single-dose radiotherapy (SDRT), a disruptive technique that ablates more than 90% of human cancers, operates a distinct dual-target mechanism, linking acid sphingomyelinase-mediated (ASMase-mediated) microvascular perfusion defects to DNA unrepair in tumor cells to confer tumor cell lethality. ASMase-mediated microcirculatory vasoconstriction after SDRT conferred an ischemic stress response within parenchymal tumor cells, with ROS triggering the evolutionarily conserved SUMO stress response, specifically depleting chromatin-associated free SUMO3. Whereas SUMO3, but not SUMO2, was indispensable for homology-directed repair (HDR) of DSBs, HDR loss of function after SDRT yielded DSB unrepair, chromosomal aberrations, and tumor clonogen demise. Vasoconstriction blockade with the endothelin-1 inhibitor BQ-123, or ROS scavenging after SDRT using peroxiredoxin-6 overexpression or the SOD mimetic tempol, prevented chromatin SUMO3 depletion, HDR loss of function, and SDRT tumor ablation. We also provide evidence of mouse-to-human translation of this biology in a randomized clinical trial, showing that 24 Gy SDRT, but not 3×9 Gy fractionation, coupled early tumor ischemia/reperfusion to human cancer ablation. The SDRT biology provides opportunities for mechanism-based selective tumor radiosensitization via accessing of SDRT/ASMase signaling, as current studies indicate that this pathway is tractable to pharmacologic intervention.

High-dose, single-fraction image-guided intensity-modulated radiotherapy for metastatic spinal lesions.

PURPOSE: To report tumor control and toxicity for patients treated with image-guided intensity-modulated radiotherapy (RT) for spinal metastases with high-dose single-fraction RT. METHODS AND MATERIALS: A total of 103 consecutive spinal metastases in 93 patients without high-grade epidural spinal cord compression were treated with image-guided intensity-modulated RT to doses of 18-24 Gy (median, 24 Gy) in a single fraction between 2003 and 2006. The spinal cord dose was limited to a 14-Gy maximal dose. The patients were prospectively examined every 3-4 months with clinical assessment and cross-sectional imaging. RESULTS: The overall actuarial local control rate was 90% (local failure developed in 7 patients) at a median follow-up of 15 months (range, 2-45 months). The median time to local failure was 9 months (range, 2-15 months) from the time of treatment. Of the 93 patients, 37 died. The median overall survival was 15 months. In all cases, death was from progression of systemic disease and not local failure. The histologic type was not a statistically significant predictor of survival or local control. The radiation dose was a significant predictor of local control (p = 0.03). All patients without local failure also reported durable symptom palliation. Acute toxicity was mild (Grade 1-2). No case of radiculopathy or myelopathy has developed. CONCLUSION: High-dose, single-fraction image-guided intensity-modulated RT is a noninvasive intervention that appears to be safe and very effective palliation for patients with spinal metastases, with minimal negative effects on quality of life and a high probability of tumor control.

Image-guided intensity-modulated photon radiotherapy using multifractionated regimen to paraspinal chordomas and rare sarcomas.

PURPOSE: Image-guided intensity-modulated radiotherapy enables delivery of high-dose radiation to tumors close to the spinal cord. We report our experience with multifractionated regimens using image-guided intensity-modulated radiotherapy to treat gross paraspinal disease to doses beyond cord tolerance. METHODS AND MATERIALS: We performed a retrospective review of 27 consecutive patients with partially resected or unresectable paraspinal tumors irradiated to >5,300 cGy in standard fractionation. RESULTS: The median follow-up was 17.4 months (range, 2.1-47.3). Eighteen sarcomas, seven chordomas, and two ependymomas were treated. The median dose to the planning target volume was 6,600 cGy (range, 5,396-7,080) in 180- or 200-cGy fractions. The median planning target volume was 164 cm3 (range, 29-1,116). Seven patients developed recurrence at the treatment site (26%), and 6 of these patients had high-grade tumors. Three patients with recurrence had metastatic disease at the time of radiotherapy. The 2-year local control rate was 65%, and the 2-year overall survival rate was 79%. Of the 5 patients who died, 4 had metastatic disease at death. Twenty-three patients (84%) reported either no pain or improved pain at the last follow-up visit. Sixteen patients discontinued narcotic use after treatment (62.5%). Twenty-three patients (89%) had a stable or improved American Spine Injury Association score at the last follow-up visit. No patient experienced radiation-induced myelopathy. CONCLUSIONS: The dose to paraspinal tumors has traditionally been limited to respect cord tolerance. With image-guided intensity-modulated radiotherapy, greater doses of radiation delivered in multiple fractions can be prescribed with excellent target coverage, effective palliation, and acceptable toxicity and local control.

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.

Stereotactic body radiotherapy for metastatic spinal sarcoma: a detailed patterns-of-failure study.

OBJECTIVE The aim of this study was to report the first detailed analysis of patterns of failure within the spinal axis of patients treated with stereotactic body radiotherapy (SBRT) for sarcoma spine metastases. METHODS Between 2005 and 2012, 88 consecutive patients with metastatic sarcoma were treated with SBRT for 120 spinal lesions. Seventy-one percent of patients were enrolled on prospective institutional protocols. For patients who underwent routine posttreatment total-spine MRI (64 patients, 88 lesions), each site of progression within the entire spinal axis was mapped in relation to the treated lesion. Actuarial rates of local-, adjacent-, and distant-segment failure-free survival (FFS) were calculated using the Kaplan-Meier method. RESULTS The median follow-up for the cohort was 14.4 months, with 81.7% of patients followed up until death. The 12-month actuarial rate of local FFS was 85.9%; however, 83.3% of local failures occurred in conjunction with distant-segment failures. The 12-month actuarial rates of isolated local-, adjacent-, and distant-segment FFS were 98.0%, 97.8%, and 74.7%, respectively. Of patients with any spinal progression (n = 55), only 25.5% (n = 14) had progression at a single vertebral level, with 60.0% (n = 33) having progression at ≥ 3 sites within the spine simultaneously. Linear regression analysis revealed a relationship of decreasing risk of failure with increasing distance from the treated index lesion (R(2) = 0.87), and 54.1% of failures occurred ≥ 5 vertebral levels away. Treatment of the index lesion with a lower biological effective dose (OR 3.2, 95% CI 1.1-9.2) and presence of local failure (OR 18.0, 95% CI 2.1-152.9) independently predicted for distant spine failure. CONCLUSIONS Isolated local- and adjacent-segment failures are exceptionally rare for patients with metastatic sarcoma to the spine treated with SBRT, thereby affirming the treatment of the involved level only. The majority of progression within the spinal axis occurs ≥ 5 vertebral levels away. Thus, total-spine imaging is necessary for surveillance posttreatment.

Multifractionated image-guided and stereotactic intensity-modulated radiotherapy of paraspinal tumors: a preliminary report.

PURPOSE: The use of image-guided and stereotactic intensity-modulated radiotherapy (IMRT) techniques have made the delivery of high-dose radiation to lesions within close proximity to the spinal cord feasible. This report presents clinical and physical data regarding the use of IMRT coupled with noninvasive body frames (stereotactic and image-guided) for multifractionated radiotherapy. METHODS AND MATERIALS: The Memorial Sloan-Kettering Cancer Center (Memorial) stereotactic body frame (MSBF) and Memorial body cradle (MBC) have been developed as noninvasive immobilizing devices for paraspinal IMRT using stereotactic (MSBF) and image-guided (MBC) techniques. Patients were either previously irradiated or prescribed doses beyond spinal cord tolerance (54 Gy in standard fractionation) and had unresectable gross disease involving the spinal canal. The planning target volume (PTV) was the gross tumor volume with a 1 cm margin. The PTV was not allowed to include the spinal cord contour. All treatment planning was performed using software developed within the institution. Isocenter verification was performed with an in-room computed tomography scan (MSBF) or electronic portal imaging devices, or both. Patients were followed up with serial magnetic resonance imaging every 3-4 months, and no patients were lost to follow-up. Kaplan-Meier statistics were used for analysis of clinical data. RESULTS: Both the MSBF and MBC were able to provide setup accuracy within 2 mm. With a median follow-up of 11 months, 35 patients (14 primary and 21 secondary malignancies) underwent treatment. The median dose previously received was 3000 cGy in 10 fractions. The median dose prescribed for these patients was 2000 cGy/5 fractions (2000-3000 cGy), which provided a median PTV V100 of 88%. In previously unirradiated patients, the median prescribed dose was 7000 cGy (5940-7000 cGy) with a median PTV V100 of 90%. The median Dmax to the cord was 34% and 68% for previously irradiated and never irradiated patients, respectively. More than 90% of patients experienced palliation from pain, weakness, or paresthesia; 75% and 81% of secondary and primary lesions, respectively, exhibited local control at the time of last follow-up. No cases of radiation-induced myelopathy or radiculopathy have thus far been encountered. CONCLUSIONS: Precision stereotactic and image-guided paraspinal IMRT allows the delivery of high doses of radiation in multiple fractions to tumors within close proximity to the spinal cord while respecting cord tolerance. Although preliminary, the clinical results are encouraging.

Novel spirometry based on optical surface imaging.

PURPOSE: To evaluate the feasibility of using optical surface imaging (OSI) to measure the dynamic tidal volume (TV) of the human torso during free breathing. METHODS: We performed experiments to measure volume or volume change in geometric and deformable phantoms as well as human subjects using OSI. To assess the accuracy of OSI in volume determination, we performed experiments using five geometric phantoms and two deformable body phantoms and compared the values with those derived from geometric calculations and computed tomography (CT) measurements, respectively. To apply this technique to human subjects, an institutional review board protocol was established and three healthy volunteers were studied. In the human experiment, a high-speed image capture mode of OSI was applied to acquire torso images at 4-5 frames per second, which was synchronized with conventional spirometric measurements at 5 Hz. An in-house matlab program was developed to interactively define the volume of interest (VOI), separate the thorax and abdomen, and automatically calculate the thoracic and abdominal volumes within the VOIs. The torso volume change (TV C = ΔVtorso = ΔVthorax + ΔVabdomen) was automatically calculated using full-exhalation phase as the reference. The volumetric breathing pattern (BPv = ΔVthorax/ΔVtorso) quantifying thoracic and abdominal volume variations was also calculated. Under quiet breathing, TVC should equal the tidal volume measured concurrently by a spirometer with a conversion factor (1.08) accounting for internal and external differences of temperature and moisture. Another matlab program was implemented to control the conventional spirometer that was used as the standard. RESULTS: The volumes measured from the OSI imaging of geometric phantoms agreed with the calculated volumes with a discrepancy of 0.0% ± 1.6% (range -1.9% to 2.5%). In measurements from the deformable torso/thorax phantoms, the volume differences measured using OSI imaging and CT imaging were 1.2% ± 2.1% (range -0.5% to 3.6%), with a linear regression fitting (slope = 1.02 and R(2) = 0.999). In volunteers, the relative error in OSI tidal volume measurement was -2.2% ± 4.9% (range -9.2% to 4.8%) and a correlation of r = 0.98 was found with spirometric measurement. The breathing pattern values of the three volunteers were substantially different from each other (BPv = 0.15, 0.45, and 0.32). CONCLUSIONS: This study demonstrates the feasibility of using OSI to measure breathing tidal volumes and breathing patterns with adequate accuracy. This is the first time that dynamic breathing tidal volume as well as breathing patterns is measured using optical surface imaging. The OSI-observed movement of the entire torso could serve as a new respiratory surrogate in the treatment room during radiation therapy.

The effectiveness of a pneumatic compression belt in reducing respiratory motion of abdominal tumors in patients undergoing stereotactic body radiotherapy.

PURPOSE: Abdominal compression using a pneumatic abdominal compression belt developed in-house has been used to reduce respiratory motion of patients undergoing hypo-fractionated or single fraction stereotactic radio-ablative therapy for abdominal cancers. The clinical objective of belt usage was to reduce the cranial-caudal (CC) respiratory motion of the tumor to 5 mm or less during both CT simulation and treatment. A retrospective analysis was done to determine the effectiveness of the device and associated clinical procedures to reduce the CC respiratory motion of the tumor. MATERIALS AND METHODS: 42 patients treated for tumors in the liver (30), adrenal glands (6), pancreas (3) and lymph nodes (3) using high dose hypofractionated radiotherapy between 2004 and the present were eligible for analysis. All patients had 2-3 radiopaque fiducial markers implanted near the tumor prior to simulation, or had clips from prior surgery. Integral to the belt is an inflatable air bladder that is positioned over the abdomen. The pneumatic pressure was set to a level in consultation with the patient. The CC motion was measured fluoroscopically with and without pneumatic pressure. Pneumatic pressure was used at all treatments to reduce to CC motion to that achieved at simulation. RESULTS: The mean CC motion with the belt in place, but no additional air pressure was 11.4 mm with a range of 5-20 mm. With the pressure applied, the mean CC motion was reduced to 4.4 mm with a range of 1-8 mm (P-value < 0.001). The clinical objective of reducing the CC motion of the tumor to a maximum excursion of 5 mm or less was achieved in 93% of cases. CONCLUSION: The use of a pneumatic compression belt and associated clinical procedures was found to result in a significant and frequently substantial reduction in the CC motion of the tumor.

Insufficiency fractures of the sacrum following stereotactic body radiotherapy for sacral tumors.

INTRODUCTION: There is little data on sacral insufficiency fracture(SIF) incidence following pelvic radiotherapy, with existing studies based on conventional fractionation. Stereotactic body radiotherapy (SBRT), characterized by dose escalation with hypofractionation, may pose even greater risks to sacral integrity. This study aims to define SIF incidence and risk factors following SBRT. METHODS: Records of 43 consecutive patients who underwent sacral SBRT from September 2005-May 2009 were reviewed. Baseline patient information (age, gender, menopausal status, body mass index, use of bone-thinning agents, presence of osteoporosis), tumor characteristics (histology, lesion appearance and extent) and treatment parameters (dose/fractionation, prior radiation/surgery) were documented. Primary end-point was development of new fractures or progression of pre-existing fractures. Secondary end-points included pain scores, analgesic use, functional ability, and local tumor control. RESULTS: Median follow-up was 17months. Common histologies included sarcoma, renal cell, and prostate carcinoma; 47% of lesions were lytic, 37% sclerotic and the remainder mixed. Doses ranged from 18-24Gy/1fraction to 30Gy/5fractions with 45% receiving single fractions.14% had prior radiation (median dose: 30Gy/10fractions).Five patients developed SIF. In four, fractures occurred in the context of controlled local disease. Median time to SIF was 8.2months. Symptoms varied from minimal pain requiring no intervention to severe pain impacting on function. Two patients underwent sacroplasty due to intractable pain, with both obtaining good analgesia. Low event numbers precluded meaningful univariate/multivariate analyses. One-year local tumor control rates were excellent (91.7%). CONCLUSION: In this study, actuarial SIF incidence at one year was 8.2%, suggesting that SIF risk from sacral SBRT is low. However, larger prospective studies with longer follow-up are needed. In addition, novel therapies such as sacroplasty need further study to determine safety, efficacy and indications for use.

No association between excessive wound complications and preoperative high-dose, hypofractionated, image-guided radiation therapy for spine metastasis.

OBJECT: Radiation therapy is known to impair wound healing. Higher dose per fraction is believed to increase this risk. This study sought to quantify rates of wound complication in patients receiving preoperative conventionally fractionated radiotherapy (XRT) or high-dose hypofractionated image-guided radiation therapy (IGRT) for spinal metastasis, and to identify predictors of wound complication. METHODS: The records of 165 consecutive patients who underwent spine surgery for metastasis at Memorial Sloan-Kettering Cancer Center between 1999 and 2010, with a history of prior radiation therapy, were reviewed. Patients with primary spine tumors, 2 courses of prior radiation therapy to the surgical site, total dose < 9 Gy, or radiation therapy adjacent to or partially overlapping the surgical site, were excluded. One hundred thirty patients received XRT (≤ 3 Gy/fraction) and 35 received IGRT (> 3 Gy/fraction). The total dose prescribed to the 100% isodose line to treat the planning target volume was 18-30 Gy in 1-5 fractions. Clinical factors evaluated included age, Karnofsky Performance Scale score, body mass index, presence of diabetes, smoking, ambulatory status, prior surgery at same spinal site, preoperative laboratory results (hemoglobin, lymphocyte count, and albumin), perioperative chemotherapy or steroids, estimated blood loss, extent of stabilization hardware, time between radiation therapy and surgery, number of vertebral bodies irradiated, total radiation dose, and dose per fraction of radiation therapy. Wound complication was defined as poor healing, dehiscence, or infection. Potential predictors of wound complication were assessed by univariate analyses using competing-risk methods to adjust for risk of death. results: For XRT patients, median dose was 30 Gy (range 11.5-70 Gy) with 72% of them receiving 3 Gy × 10 fractions. For IGRT patients, 66% received 18-24 Gy × 1 fraction and 23% received 6 Gy × 5 fractions. Groups differed only by the mean number of vertebral bodies treated (4.6 XRT and 1.8 IGRT, p < 0.0001). Wound complications occurred at a median of 0.95 months (range 0.4-3.9 months). A total of 22 wound events occurred in the XRT group and 2 in the IGRT group. The 6-month cumulative incidence of wound complications for XRT was 17% and for IGRT was 6%. There was no significant difference in wound complications between groups (IGRT vs XRT: hazard ratio 0.31, 95% CI 0.08-1.3; p = 0.11). Higher dose per fraction appeared to be associated with a lower risk of wound complication (hazard ratio 0.27, 95% CI 0.06-1.15; p = 0.08), which trended toward significance. Univariate analyses did not reveal any significant predictors of wound complications. CONCLUSIONS: Patients who underwent XRT or IGRT did not have significantly different rates of postoperative wound complications. This finding may be explained by the treatment of fewer vertebral bodies in IGRT patients, or by the low overall number of total events. With a wound complication rate of 6%, preoperative IGRT, a highly conformal treatment, resulted in a very low rate of surgical wound complication.

Delivering a third course of radiation to spine metastases using image-guided, intensity-modulated radiation therapy.

OBJECT: The objective of this study was to investigate the feasibility and safety of delivering a third course of radiation to patients with multiply recurrent metastatic disease to the spine. METHODS: Between 2009 and 2011, 10 patients received a third course of radiation to spinal metastases at Memorial Sloan-Kettering Cancer Center using image-guided intensity-modulated radiation therapy (IMRT). Patient and tumor characteristics, dosimetry details, and outcomes were obtained using retrospective chart review. Spinal imaging was performed prior to treatment and at regular follow-up intervals. The cumulative biologically effective dose (BED) to the spinal cord and cauda equina was calculated and was normalized to 2 Gy equivalents (Gy(2/2)). Toxicity and local control were assessed. RESULTS: The median time between the first and second courses of radiation was 18.5 months and the median time between the second and third courses was 11.5 months. The median follow-up from the third course of radiation was 12 months and the median overall survival was 13 months. Pain or neurological symptoms were improved in 80% of patients. The median spinal cord maximum dose normalized BED (nBED) for the whole cohort was 70.73 Gy(2/2) (range 51.9-101.7 Gy(2/2)). The median dose to 5% of the spinal cord D(05) nBED for the entire cohort was 59.4 Gy(2/2). Acute toxicity was most commonly fatigue and dermatitis, with 1 patient experiencing Grade 3 fatigue and 1 patient Grade 3 dermatitis. Late toxicity was limited to 2 cases of Grade 1 dysphagia. There was 1 case of Grade 1 neuropathy and 1 case of Grade 2 neuropathy. The crude rate of local control was 80% with 1 in-field failure and 1 marginal failure. CONCLUSIONS: In this cohort of patients, a third course of IMRT to the spine was well tolerated with no significant late toxicities. Used as salvage therapy for select patients, a third course of radiation is a safe and effective treatment strategy.

Preliminary results of high-dose single-fraction radiotherapy for the management of chordomas of the spine and sacrum.

BACKGROUND: En bloc wide-margin excision significantly decreases the risk of chordoma recurrence. However, a wide surgical margin cannot be obtained in many chordomas because they arise primarily in the sacrum, clivus, and mobile spine. Furthermore, these tumors have shown resistance to fractionated photon radiation at conventional doses and numerous chemotherapies. OBJECTIVE: To analyze the outcomes of single-fraction stereotactic radiosurgery (SRS) in the treatment of chordomas of the mobile spine and sacrum. METHODS: Twenty-four patients with chordoma of the sacrum and mobile spine were treated with high-dose single-fraction SRS (median dose, 2400 cGy). Twenty-one primary and 3 metastatic tumors were treated. Seven patients were treated for postoperative tumor recurrence. In 7 patients, SRS was administered as planned adjuvant therapy, and in 13 patients, SRS was administered as neoadjuvant therapy. All patients had serial magnetic resonance imaging follow-up. RESULTS: The overall median follow-up was 24 months. Of the 24 patients, 23 (95%) demonstrated stable or reduced tumor burden based on serial magnetic resonance imaging. One patient had radiographic progression of tumor 11 months after SRS. Only 6 of 13 patients who underwent neoadjuvant SRS proceeded to surgery. This decision was based on the lack of radiographic progression and the patient's preference. Complications were limited to 1 patient in whom sciatic neuropathy developed and 1 with vocal cord paralysis. CONCLUSION: High-dose single-fraction SRS provides good tumor control with low treatment-related morbidity. Additional follow-up is required to determine the long-term recurrence risk.

Tumor control outcomes after hypofractionated and single-dose stereotactic image-guided intensity-modulated radiotherapy for extracranial metastases from renal cell carcinoma.

PURPOSE: To report tumor local progression-free outcomes after treatment with single-dose, image-guided, intensity-modulated radiotherapy and hypofractionated regimens for extracranial metastases from renal cell primary tumors. PATIENTS AND METHODS: Between 2004 and 2010, 105 lesions from renal cell carcinoma were treated with either single-dose, image-guided, intensity-modulated radiotherapy to a prescription dose of 18-24 Gy (median, 24) or hypofractionation (three or five fractions) with a prescription dose of 20-30 Gy. The median follow-up was 12 months (range, 1-48). RESULTS: The overall 3-year actuarial local progression-free survival for all lesions was 44%. The 3-year local progression-free survival for those who received a high single-dose (24 Gy; n = 45), a low single-dose (<24 Gy; n = 14), or hypofractionation regimens (n = 46) was 88%, 21%, and 17%, respectively (high single dose vs. low single dose, p = .001; high single dose vs. hypofractionation, p < .001). Multivariate analysis revealed the following variables were significant predictors of improved local progression-free survival: 24 Gy dose compared with a lower dose (p = .009) and a single dose vs. hypofractionation (p = .008). CONCLUSION: High single-dose, image-guided, intensity-modulated radiotherapy is a noninvasive procedure resulting in high probability of local tumor control for metastatic renal cell cancer generally considered radioresistant according to the classic radiobiologic ranking.

Impact of dose on local failure rates after image-guided reirradiation of recurrent paraspinal metastases.

PURPOSE: To examine the impact of dose on local failure (LF) rates in the re-treatment of recurrent paraspinal metastases with image-guided intensity-modulated radiotherapy (IG-IMRT). METHODS AND MATERIALS: The records of patients with in-field recurrence after previous spine radiation (median dose, 30 Gy) who received salvage IG-IMRT with either five 4-Gy (20-Gy group, n = 42) or five 6-Gy (30-Gy group, n = 55) daily fractions between January 2003 and August 2008 were reviewed. Institutional practice was 20 Gy before April 2006, when it changed to 30 Gy. A total of 47 cases (48%) were treated adjuvantly, after surgery to decompress epidural disease. LF after IG-IMRT was defined radiographically. RESULTS: The median follow-up was 12.1 months (range, 0.2-63.6 months). The 1-year cumulative incidences of LF after 20 Gy and 30 Gy IG-IMRT were 45% and 26%, respectively (p = 0.04). Of all treatment characteristics examined (20-Gy vs. 30-Gy dose group, dose to 95% of the planned and gross target volume, tumor size, histology, receipt of surgery, and interval between first and second radiation), only dose group had a significant impact on actuarial LF incidence (p = 0.04; unadjusted HR, 0.51; 95% CI, 0.27-0.96). There was no incidence of myelopathy. CONCLUSIONS: A significant decrease in LF after IG-IMRT with five 6-Gy fractions compared with five 4-Gy fractions was observed without increased risk of myelopathy. Until prospective data comparing stereotactic hypofractionated and single-fraction regimens become available, when reirradiating recurrent paraspinal metastases with IG-IMRT, administration of five 6-Gy daily fractions is reasonable.

Predictors of local control after single-dose stereotactic image-guided intensity-modulated radiotherapy for extracranial metastases.

PURPOSE: To report tumor local control after treatment with single-dose image-guided intensity-modulated radiotherapy (SD-IGRT) to extracranial metastatic sites. METHODS AND MATERIALS: A total of 126 metastases in 103 patients were treated with SD-IGRT to prescription doses of 18-24 Gy (median, 24 Gy) between 2004 and 2007. RESULTS: The overall actuarial local relapse-free survival (LRFS) rate was 64% at a median follow-up of 18 months (range, 2-45 months). The median time to failure was 9.6 months (range, 1-23 months). On univariate analysis, LRFS was significantly correlated with prescription dose (p = 0.029). Stratification by dose into high (23 to 24 Gy), intermediate (21 to 22 Gy), and low (18 to 20 Gy) dose levels revealed highly significant differences in LRFS between high (82%) and low doses (25%) (p < 0.0001). Overall, histology had no significant effect on LRFS (p = 0.16). Renal cell histology displayed a profound dose-response effect, with 80% LRFS at the high dose level (23 to 24 Gy) vs. 37% with low doses (≤22 Gy) (p = 0.04). However, for patients who received the high dose level, histology was not a statistically significant predictor of LRFS (p = 0.90). Target organ (bone vs. lymph node vs. soft tissues) (p = 0.5) and planning target volume size (p = 0.55) were not found to be associated with long-term LRFS probability. Multivariate Cox regression analysis confirmed prescription dose to be a significant predictor of LRFS (p = 0.003). CONCLUSION: High-dose SD-IGRT is a noninvasive procedure resulting in high probability of local tumor control. Single-dose IGRT may be effectively used to locally control metastatic deposits regardless of histology and target organ, provided sufficiently high doses (> 22 Gy) of radiation are delivered.

Clinical outcomes after reirradiation of paraspinal tumors.

OBJECTIVE: We present our experience with reirradiation of locally recurrent paraspinal tumors using image-guided intensity modulated radiotherapy (IG-IMRT). METHODS: We performed a retrospective review of 37 patients who were reirradiated using IG-IMRT for recurrent paraspinal tumors between 2000 and 2005. We evaluated radiation dose to the spinal cord or cauda equina in first and second radiation treatments, time to first recurrence, and clinical outcomes after reirradiation including second recurrence, survival, pain, functional status, and toxicity. RESULTS: Median time to local failure after first radiation was 13 months. All patients underwent salvage reirradiation, postoperatively or with IG-IMRT alone. Median radiation dose to the planning target volume (PTV) was 2000 cGy; median spinal cord or cauda equina dose was 990 cGy. Median cumulative spinal cord or cauda equina dose was 4198 cGy. Local control probability at a median follow-up of 8 months was 60%; median interval to second failure was 13 months. Survival probability at a median follow up of 12 months was 72%; median survival was 18 months. Thirty-four patients (91%) reported stable or improved pain after second radiation, and 26 (70%) had a stable or improved functional status. Mild acute toxicity occurred in 3 patients (8%). No long-term toxicity has been identified. CONCLUSIONS: Reirradiation using IG-IMRT is safe and achieves a meaningful interval of local control with improved symptoms. Further studies with more patients and longer follow up are needed to evaluate toxicity, predictors of failure, and timing of radiation after surgical salvage.