Joan Zatcky

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.

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.

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.

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.

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 patients 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.

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.

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 hypofractionated 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.

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.

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.